Why in the News?

A recent study published in the ‘Nature’ has shown that Extrachromosomal DNA (ecDNA) is present in approximately 50% of cancer types, playing a significant role in tumor evolution and genetic heterogeneity.

What is ecDNA?

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Recent research by scientists at the University of Nottingham’s has found that a chemical produced by a fungus growing on caterpillars may slow cancer cell growth.

What is Caterpillar fungus?

• Cordyceps militaris, also known as caterpillar fungus, is a parasitic fungus that primarily infects caterpillars and other insects.
• Found in the Himalayan region and parts of Asia, it is valued in traditional Asian medicine for its health benefits, including immune support, anti-inflammatory properties, and energy enhancement.
• It is considered a delicacy in some Asian cultures and has long been used for its purported wellness effects.

How it can slow down growth of cancer cells?

• Researchers from the University of Nottingham’s School of Pharmacy have identified cordycepin, a compound produced by Cordyceps militaris, as potentially effective in slowing cancer cell growth.
• Cordycepin works by interrupting overactive cell growth signals in cancer cells, which prevents rapid multiplication and allows for more targeted treatment.
• This approach may be less harmful to healthy tissues compared to conventional cancer treatments, offering a promising direction for targeted cancer therapies.

Other observations and significance of the species

• In addition to its traditional uses, Cordyceps militaris is significant for its role in ecological balance, helping control insect populations in forest ecosystems.
• Advances in research have enabled large-scale studies on cordycepin’s effects, with future studies focusing on derivatives of cordycepin for potentially enhanced anti-cancer properties.
• The fungus illustrates how natural compounds can contribute to sustainable medical practices, offering less toxic alternatives for disease treatment, especially in oncology.

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Recent research conducted by scientists at McGill University has shed light on the critical role of vitamin D in maintaining thymus health and its implications for immune function.

What is Vitamin D?

• Vitamin D is a fat-soluble vitamin crucial for the body’s ability to absorb calcium, magnesium, and phosphate, which are essential for bone health.
• It supports muscle movement, nerve function, and immune system responses. Due to its synthesis in the skin upon exposure to sunlight, it is often called the ‘sunshine vitamin’.
• The body naturally produces Vitamin D when skin is exposed to ultraviolet B (UVB) rays from sunlight.
• Sources of Vitamin D:
  • Fish: Salmon, mackerel, tuna, and sardines are rich in Vitamin D.
  • Cod liver oil: A concentrated source, providing 400–1,000 IU per teaspoon.
  • Mushrooms: Varieties like portobello contain Vitamin D if exposed to UV light.
  • Fortified Foods: Milk, yogurt, orange juice, and cereals often have added Vitamin D.
  • Egg yolks: Contain a small amount of Vitamin D.
  • Common forms include Vitamin D2 (ergocalciferol) and Vitamin D3 (cholecalciferol), especially useful in autumn and winter when sunlight exposure is limited.

Significance of Vitamin D

• Bone Health: Essential for calcium absorption, which strengthens bones and prevents osteoporosis.
• Muscle and Nerve Function: Supports muscle contractions and nerve signaling between the brain and body.
• Immune System: Enhances immune defenses, helping to fight off infections by viruses and bacteria.
• Brain Health: May play a role in maintaining cognitive health, especially with aging.
• Inflammation and Pain: Helps regulate the body’s response to inflammation and pain.
• Blood Pressure: Linked to regulating blood pressure; deficiency is associated with hypertension.

Impacts of Vitamin D Deficiency

• Increases the risk of rickets in children (softening of bones) and osteoporosis in adults.
• Low levels of Vitamin D are linked to autoimmune conditions like rheumatoid arthritis, lupus, and multiple sclerosis.
• Recent studies indicate that Vitamin D deficiency can accelerate thymus aging, leading to immune dysfunction and a higher risk of autoimmune diseases.
• Deficiency has been associated with cancer, cardiovascular disease, diabetes, depression, and chronic pain.
• Can include fatigue, muscle weakness, bone pain, and depression.
• In severe cases, deficiency may cause impaired bone growth and fracture susceptibility.

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Indian researchers have developed a predictive model based on the Gompertz Model to estimate a newborn’s birth weight using routine pregnancy scans.

What is the Gompertz Model?

• It is a mathematical model developed by English mathematician Benjamin Gompertz in the early 19th century.

• • It was originally designed to model population growth in a constrained environment, such as a specific geographic region.
  • The model uses an S-shaped (sigmoid) curve to represent growth patterns that start slowly, accelerate, and then slow again as they approach a plateau.

• Applications:

• • Biology: The Gompertz Model is used to study tumor growth and cell population dynamics, reflecting constrained growth in biological systems.
  • Epidemiology: Applied in predicting the spread of infectious diseases like COVID-19, capturing how transmission rates slow with interventions.
  • Ecology: Useful for modelling species population growth in habitats with limited resources, aiding conservation and ecosystem management.
  • Healthcare: Recently adapted to predict foetal birth weight, helping identify potential risks associated with low or high birth weight.
  • Aging Research: Employed to analyze mortality rates and lifespan patterns, contributing to studies on aging and longevity.

Recent Research and Significance

• Recent research has applied the Gompertz Model in predicting foetal birth weight using routine scans, as shown by researchers from IISER Pune and IMSc Chennai, offering a non-invasive alternative for maternal health.
• The model is used in tumor growth studies, allowing researchers to understand and predict cancer progression.
• Its predictive accuracy under constrained conditions makes it useful for biological systems, including population growth and cell dynamics.
• In healthcare, it supports early detection and intervention for conditions impacted by growth patterns, such as low or high birth weight risks.

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• A team of researchers has discovered the genetic mechanisms that allow a newly identified tardigrades species—Hypsibius henanensis—to withstand high levels of radiation.

About Tardigrades

• Tardigrades, often called “water bears” or “moss piglets,” are tiny, water-dwelling microorganisms known for their remarkable ability to survive extreme conditions.
• They can withstand environments that would be lethal for most life forms, including:
  • Extremely high and low temperatures (from near absolute zero to over 150°C),
  • High levels of radiation and vacuum conditions found in space,
  • Extreme dehydration (losing nearly all water in their bodies),
  • High pressures (up to six times that of the ocean’s deepest trenches).
• This adaptability makes them a subject of interest for scientists, especially in understanding survival mechanisms in extreme conditions.

How Tardigrades resist High Radiations?

The researchers identified 2,801 genes involved in DNA repair. Three key factors contributing to radiation tolerance include:

• DNA Repair Protein (TRID1): Enabled the species to repair double-strand DNA breaks due to radiation.
• Gene Activation for Mitochondrial Proteins: Radiation exposure activated a gene that produced two proteins vital for mitochondrial synthesis and DNA repair.
• Antioxidant Pigments (Betalains): These pigments neutralize harmful chemicals generated by radiation within cells.

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Researcher have successfully mapped the entire brain of an adult fruit fly, marking the first time researchers have created such a detailed map of an adult animal’s brain.

Key findings

• Scientists identified more than 50 million connections between 139,000 neurons (brain nerve cells).
• They classified the cells into 8,453 distinct types, making it the largest catalogue of cell types in any brain.
• The research gave insights into how different types of cells function and how the fruit fly’s eyes process motion and color.
• A group of “hub neurons” was discovered, which may help speed up information flow.

Significance of the Work

• Although the human brain is more complex, the logic of how neurons communicate is similar between fruit flies and humans.
• Fruit flies are a valuable model system for neuroscience. Their brains solve many of the same problems that human brains do.
• It could help in understanding and treat mental health conditions like Parkinson’s and depression.
• The mapping of the fruit fly’s brain raises hopes that scientists will eventually be able to map the entire human brain.

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Angelina Jolie’s case highlighted hereditary breast and ovarian cancer (HBOC) after she underwent preventive surgeries due to a BRCA1 gene mutation.

What is BRCA Testing?

• BRCA testing is a genetic test that looks for mutations in the BRCA1 and BRCA2 genes.
• These genes normally help repair DNA, but when they are mutated, they increase a person’s risk of developing certain cancers, particularly breast and ovarian cancers.
• BRCA testing identifies whether a person has inherited these mutations, which can lead to Hereditary Breast and Ovarian Cancer (HBOC) and other cancers.
• The test is done using a blood or saliva sample, which is collected and sent to a laboratory for analysis.
• In the lab, next-generation DNA sequencing or other genetic analysis methods are used to examine the BRCA1 and BRCA2 genes for harmful mutations.
• The test results can show whether a person has inherited a harmful mutation in these genes.
  • If the result is positive, it means they are at a higher risk for developing certain cancers.

Issues with BRCA Testing

• BRCA testing in India is expensive, costing between ₹15,000 to ₹30,000, which makes it unaffordable for many, particularly in lower-income populations.
• Testing is often only offered to individuals with a family history of cancer, which misses about 50% of people who may have the mutations but no known family history.

Significance for India

• Breast cancer is the most common cancer among women in India, accounting for 27% of all cancer cases.
• Women with BRCA mutations have up to a 72% risk of developing breast cancer.
  • Early identification allows for preventive measures, such as regular screenings or surgeries, which can reduce cancer incidence by up to 100%.
• By increasing access to population-wide BRCA testing, India can improve early detection and reduce the burden of cancer on its healthcare system.
  • Early identification can also lower treatment costs and improve outcomes.

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Mumbai-based Entod Pharmaceuticals has announced that the Drug Controller General of India (DCGI) has approved its new eye drop, PresVu, aimed at reducing the dependency on reading glasses for individuals with presbyopia.

How does PresVu work? 

• The active ingredient in PresVu is pilocarpine, a compound that contracts the iris muscles, controlling the size of the pupil and helping individuals focus better on nearby objects.
• PresVu also uses an advanced dynamic buffer technology to adapt to the pH levels of tears, ensuring consistent efficacy and safety for extended use over the years.
• However, PresVu’s effects are temporary, typically lasting between four to six hours, and it is prescription-only.

• PresVu should not be used by individuals with iris inflammation.
• Regular use may lead to side effects such as:
  • Itching and redness
  • Eyebrow pain
  • Muscle spasms in the eyes

Is this a Novel Therapy?

• Although Entod claims PresVu is novel, the main compound, pilocarpine, has been available in India for decades and is commonly used as a first-line therapy for cataracts.
• Pilocarpine’s ability to temporarily improve the depth of focus has been explored in other countries, including the United States, where the FDA approved a pilocarpine eye drop for presbyopia in 2021.
• In India, the government regulates the ceiling price of pilocarpine in 4% and 2% concentrations, whereas PresVu contains 1.25%.

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Recent research reveals that FD&C Yellow 5, a common food dye, can temporarily make tissue transparent, with potential implications for cancer treatment and medical procedures.

About Yellow Food Dye 

• FD&C Yellow 5, also known as Tartrazine, is a widely used synthetic food dye found in various snacks, drinks, and processed foods.
• Approved by the FDA, it is commonly used to give products a vibrant yellow color.

How does it work?

• The dye has the ability to make tissue transparent is based on its interaction with light, specifically through the Kramers-Kronig relations, a principle in physics.
• It absorbs blue light, leaving only the red-orange spectrum visible.
• This alters the refractive index of water, causing it to match the refractive index of fats and proteins in tissue.
• When the refractive indices match, light can pass through tissue with less scattering, creating the appearance of transparency.

Potential Medical Applications of Yellow Food Dye

• Cancer Treatment: By making tissues transparent, FD&C Yellow 5 could enhance photodynamic and photothermal therapies, allowing laser light to reach deeper tissues and target cancerous cells more effectively.
• Vein Visibility: Transparent tissues could help make veins more visible, aiding in procedures like venepuncture for blood draws or injections, particularly in patients with hard-to-see veins.
• Non-invasive Diagnostics: The dye could allow doctors to visualize internal organs and structures without the need for invasive procedures like biopsies or expensive imaging technologies like CT scans or MRIs.

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Why in the News?

• These medical tools—thermometers, stethoscopes, weighing scales, and sphygmomanometers—are essential for diagnosing and monitoring basic health parameters.
  • Each tool has its own function and specific way of operation, which helps healthcare professionals make informed decisions about patient care.

Here is the list of tools used in a Doctor’s Diagnosis:

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Leonard Hayflick, the renowned biomedical researcher who made a discovery about the limits of cell division in somatic cells (Hayflick Limit) has passed away at 98.

What is the Hayflick Limit?

• In the early 1960s, Hayflick discovered that somatic (non-reproductive) cells have a finite number of divisions, typically between 40-60 times.
• This phenomenon, the ‘Hayflick limit’ suggests that aging occurs because cells eventually stop dividing.
  • This leads to the accumulation of senescent cells that contribute to the aging process.
• The “ultimate Hayflick limit” for humans is estimated to be around 125 years.
• Beyond this, no amount of lifestyle changes or medical interventions can extend the human lifespan.

• Hayflick’s discovery has been applied to cells from various animals, revealing different Hayflick limits based on species’ lifespans.
• Ex. Galapagos turtles, have cells that can divide approximately 110 times, whereas laboratory mice have a much lower limit of around 15 divisions.

Broader Implications and Research

• Hayflick’s discovery led to the discovery of telomeres in the 1970s.
  • Telomeres are protective DNA sequences at the ends of chromosomes, which shorten with each cell division.
• When telomeres reach a critical length, cell division stops, which correlates with the Hayflick limit.
• In the 1980s, scientists discovered telomerase, a protein capable of replenishing telomeres, which is naturally active in cancer cells, allowing them to bypass the Hayflick limit.

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• “Osteoporosis” is a condition where bones become weak and brittle, with over 10 million cases annually in India.
  • It predominantly affects ageing women due to decreased oestrogen levels post-menopause.

Role of Oestrogen in Bone Growth

• Oestrogen is crucial for bone growth and formation, acting as a manager signaling the bone construction crew.
• During breastfeeding, oestrogen production drops to focus on milk production, which should weaken bones.
• Contrary to expectations, mothers’ bones become stronger to meet their babies’ high calcium demands.

How does the ‘Hidden’ Hormone Keep Mice Mothers’ Bones Healthy?

• During breastfeeding, the body suppresses oestrogen production to focus on milk production, which should weaken bones.
• Despite low oestrogen, mothers’ bones strengthen.

Experimental Findings:

• In experiments with genetically modified mice, those lacking the oestrogen receptor alpha still maintained healthy bones due to CCN3.
• When CCN3 was introduced to skeletal stem cells, it significantly increased bone formation, showing its potential to strengthen bones independently of oestrogen.

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Research suggests that around 8% of the human genome is composed of Endogenous Retroviruses (ERVs) often referred to as ‘zombie’ regions.

What are Endogenous Retroviruses (ERVs)?

• ERVs are remnants of ancient viral infections that have integrated into the genome of the host species.
• When these retroviruses infect germ cells (sperm or egg cells), their genetic material can be passed down to the next generation, becoming a permanent part of the host’s DNA.
• Zombie Regions:
  • They refer to inactive viral sequences within the genome that no longer produce functional viruses but remain as embedded genetic fossils.
  • These regions are a result of retrovirus integration that has lost its ability to replicate and produce proteins, yet they persist in the host’s DNA.

Evolutionary Significance of ERVs:

• In the life cycle of a retrovirus, reverse-transcribed DNA is integrated into the host’s DNA with the help of integrase.
• The viral DNA, called a provirus, hijacks human cells, turning them into virus-making factories.
• Over tens of thousands of years, many retroviruses have left genomic elements in human genome, contributing to evolutionary processes.
• Example:
  • Syncytins are genes thought to have descended from ERVs and are crucial for placental development. These genes originally came from viruses and were acquired during mammalian evolution.

Their Contribution to Human Biology

• ERVs are highly expressed in the placenta and may influence conditions like preeclampsia.
• Researchers found that a particular RNA derived from an ERV is dysregulated in early-onset preeclampsia, suggesting it could be used as a biomarker for the condition.
• ERVs play a role in cell-type differentiation during embryo development.
• A protein called MERVL-gag is derived from an ERV. This transition is crucial for producing pluripotent stem cells capable of forming different cell types.
• Researchers also found that a human ERV element LTR10 affects tumour formation in colorectal cancer.

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• In the farmlands of central Thailand, thousands of pythons are raised in a warehouse for their diamond-patterned skins, which are sold to high-end European fashion houses.
  • Some scientists and industry insiders believe the true value of these snakes lies in their meat.

Python Farming in Asia

• Researchers estimate that China and Vietnam alone have at least 4,000 python farms, producing several million snakes primarily for the fashion industry.
• A study published in Nature highlighted python farming as a flexible and efficient response to global food insecurity.

Benefits of Python Farming

• Pythons can survive for months without food or water and maintain their condition.
• They were fed waste chicken and wild-caught rodents, offering a more efficient feed-to-meat ratio than poultry, beef, and even crickets.
• Female pythons can lay between 50 and 100 eggs annually, leading to rapid reproduction.

Advantages of Python Meat

• Pythons offer a more efficient feed-to-meat ratio than poultry, beef, and even crickets.
• They can survive without food and water for months without losing condition.
• Python meat has a chicken-like texture and is low in saturated fats.
• It could provide a sustainable protein source with a lower environmental impact compared to traditional meat.

Challenges and Market Acceptance

• Despite the advantages, the market is limited for python meat.
• Python farmers struggle to convince people to consume snake meat, resulting in most of it being discarded or sold to fish farms.

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There have been four cases, including three deaths, of the rare, but fatal brain-eating primary amoebic Meningoencephalitis (PAM) in Kerala in the last two months.

What is Primary Amoebic Meningoencephalitis (PAM)?

• PAM is a rare brain infection caused by Naegleria fowleri, a free-living amoeba found in warm freshwater and soil worldwide.
  • An amoeba is a type of cell or unicellular organism with the ability to alter its shape, primarily by extending and retracting pseudopods.
  • Higher temperatures of up to 115°F (46°C) are conducive to its growth and it can survive for short periods in warm environments.
• The amoeba enters the body through the nose, typically during activities like swimming, and travels to the brain, causing severe damage.
• PAM is also non-communicable.
• Symptoms: Headache, fever, nausea, vomiting, stiff neck, confusion, seizures, hallucinations, and coma.
  • According to the US Centers for Disease Control and Prevention (CDC), most people with PAM die within 1 to 18 days after symptoms begin. It usually leads to coma and death after 5 days.

Diagnosis and Treatment:

• Currently, there are no established effective treatments for PAM.
• Diagnosis involves PCR tests of cerebrospinal fluid, though detection can be challenging due to the rarity of PAM.
• Treatment follows CDC guidelines, including miltefosine, Azithromycin, and Amphotericin B, with miltefosine recently procured by the State Health Department from Germany.
  • Medical interventions typically involve a combination of drugs, including amphotericin B, azithromycin, fluconazole, rifampin, miltefosine, and dexamethasone.

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• The AMRSense Project of the IIIT-Delhi has won the joint second prize in Trinity Challenge’s competition focused on combating Antimicrobial resistance (AMR).
  • The project shares the £600,000 joint second prize with ‘OASIS: OneHealth Antimicrobial Stewardship for Informal Health Systems,’ also from India.

What is the AMRSense Project?

• The AMRSense is aimed at addressing the critical issue of Antimicrobial Resistance (AMR) through a comprehensive and proactive approach.
• The project focuses on empowering communities, particularly Community Health Workers (CHWs), with tools and strategies to enhance AMR surveillance and management.
• It seeks to bridge the gap in data collection and evidence-based interventions at the community level in India.
• Collaborators: The project involves collaboration with CHRI-PATH, 1mg.com, and the Indian Council of Medical Research (ICMR).

Four Components of AMRSense:

1. Community Engagement: AMRSense empowers CHWs with AI-assisted tools for accurate and simplified data collection related to AMR. This helps in improving the quality and reliability of AMR data gathered from local communities.
2. Data Integration: The project integrates various sources of AMR-related data, including antibiotic sales, consumption patterns, and WHONet-compliant surveillance data. This integration is facilitated through open-source tools and APIs, aiming to create a unified AMR data ecosystem.
3. Predictive Analytics: AMRSense employs federated analytics across the OneHealth ecosystem. This approach provides integrated insights into AMR trends, facilitating proactive decision-making and interventions to manage and mitigate AMR risks.
4. AMRaura Scorecard: This tool is designed to monitor and evaluate AMR trends over time. It helps in assessing the effectiveness of interventions and guiding targeted strategies to combat AMR effectively.

Impact and Future Prospects

• AMRSense aims to fill gaps in CHW awareness, training, and motivation, enhancing community-level AMR data collection and management in India.
• The project’s comprehensive approach seeks to foster proactive AMR surveillance and management practices.

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• India is close to developing a gene therapy using CRISPR-Cas9, a gene-editing tool for sickle cell disease (SCD).
  • SCD is a genetic blood disorder prevalent among the Scheduled Tribes.

What is Sickle Cell Disease?

• Sickle cell disease (SCD) is a group of inherited blood disorders caused by a genetic mutation in the hemoglobin-β gene located on chromosome 11.
• This mutation results in defective hemoglobin, which forms rod-like structures after releasing oxygen.
• As a result, red blood cells become rigid and assume a sickle shape.
• The disease is inherited in an autosomal recessive pattern, meaning both parents must carry the abnormal gene for a child to inherit it.
• Symptoms may not manifest immediately in newborns but can include extreme tiredness, fussiness, swollen hands and feet, and jaundice.

• Implications:

• • • The mis-shapen RBCs can block small blood vessels, leading to impaired blood flow and causing chronic anaemia.
    • Individuals with SCD often experience acute pain episodes, severe bacterial infections, and tissue damage due to inadequate blood supply.

• Treatment:

• • Presently treatment includes medications for pain relief, regular blood transfusions to replace damaged red blood cells.
  • In rare cases, a bone marrow or stem cell transplant, which carries significant risks, is recommended.

Eliminating Sickle Cell Disease: Global and National Context

• This progress follows the approval of CRISPR-Cas9 technology by the U.S. Food and Drug Administration for a cell-based gene therapy to treat sickle cell disease in December 2023.
• One of the main challenges for India is to develop a cost-effective therapy, as part of its mission to eradicate sickle cell disease by 2047, launched by Prime Minister in July 2023.
• The mission aims to conduct over 7 crore screenings among vulnerable tribal populations across 17 States and Union Territories, with three crore screenings completed so far.

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Researchers at the Duke Human Vaccine Institute have successfully induced broadly neutralising antibodies (bNAbs) against HIV (human immunodeficiency virus) through vaccination for the first time.

N332-GT5 and eOD-GT8: The New Vaccines in Making

• N332-GT5: This vaccine candidate targets a specific region on the surface of the HIV virus known as the N332 glycan site. By engaging B-cells that have the potential to produce bNAbs against this site, N332-GT5 aims to stimulate the immune system to generate a protective response against a wide range of HIV strains.
• eOD-GT8: Similarly, eOD-GT8 is designed to target another region on the HIV virus, known as the eOD protein. By leveraging nanoparticles as carriers, eOD-GT8 aims to enhance the immune system’s ability to recognize and neutralize HIV, ultimately leading to the production of bNAbs.

What are Broadly Neutralizing Antibodies (bNAbs)?

• In the 1990s, scientists discovered that some HIV-infected individuals produced bNAbs, which neutralize many viral strains.
• bNAbs target viral protein areas crucial for infectivity, making them less likely to change.
• Despite their effectiveness, bNAbs take years to develop, by which time HIV has often evolved to escape them.

Developing bNAb-Based Vaccines

• The goal is to make the immune system produce bNAbs quickly in response to a vaccine.
• Germline targeting involves three steps:
  1. Identify and engage B-cells capable of producing bNAbs.
  2. Use a booster to guide these cells to produce stronger bNAbs.
  3. Refine bNAbs to neutralize a wide range of HIV strains.

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“Klebsiella pneumoniae” bacteria might employ a newly discovered protein called “Neo” to halt bacteriophage infections.

About Neo Protein

• Discovery Details: Researchers, led by Stephen Tang and Samuel Sternberg, reported the discovery of Neo in a 2023 preprint paper on bioRxiv, while investigating Klebsiella pneumoniae.
• Neo’s Defense Strategy: Bacteria employ diverse immune systems to fend off viral infections, including defense-associated reverse transcriptase (DRT) systems, which Neo is a part of.
  • DRT-2 System: This system involves de novo gene synthesis via rolling-circle reverse transcription (RT) of a non-coding RNA (ncRNA).
  • Operational Process: In uninfected cells, the ncRNA and RT enzyme catalyze the synthesis of a repetitive single-stranded cDNA.
  • Activation by Phage: Phage presence triggers the synthesis of the second-strand cDNA, resulting in long double-stranded DNA.
  • Role of Neo Protein: The translation of this double-strand cDNA produces the Neo protein, which induces potent growth arrest (cell dormancy), thereby protecting the bacterial population from phage proliferation.

Biotechnological and Medical Implications

• Potential Applications: Neo represents a promising tool for controlling viral infections, holding significance in both biotechnology and medicine.
• Evolutionary Connections: Neo’s discovery sheds light on the shared evolutionary history and functional mechanisms of retroelements in the human genome and bacterial reverse transcriptases.
• Technological Influence: Bacterial reverse transcriptases, predecessors of their eukaryotic counterparts, share analogous mechanisms and have revolutionized molecular biology research methods.

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• Fish oil supplements, highly regarded for their high omega-3 fatty acid content, have long been associated with heart health benefits.
  • A recent study has caused controversy by raising the possibility that these supplements may be as harmful as previously thought.

What are Omega-3 Fatty Acids?

• Omega-3 fatty acids (omega-3s) are polyunsaturated fats that perform important functions in the human body.
• There are three main types of omega-3 fatty acids:
  • EPA (eicosapentaenoic acid). EPA is a “marine omega-3” because it’s found in fish.
  • DHA (docosahexaenoic acid). DHA is also a marine omega-3 found in fish.
  • ALA (alpha-linolenic acid). ALA is the form of omega-3 found in plants.

• • When we get ALA from food, the human body can turn some of the ALA into EPA and subsequently to DHA. However, this process provides just a small amount of EPA and DHA. So, dietary sources of EPA and DHA (like fish) are essential.

Functions of Omega-s fatty acids:

• • They help to provide structure and supporting interactions between cells.
  • Omega-3s are concentrated in high levels in cells in human eyes and brain.
  • They provide the human body with energy (calories) and support the health of many body systems.  These include the human cardiovascular system and endocrine system.

Significance of Omega-3 fatty acids:

• Omega-3 fatty acids have many potential benefits for human cardiovascular health.
• One key benefit is that they help lower human triglyceride levels.
  • Too many triglycerides in human blood (hypertriglyceridemia) raise human risk of atherosclerosis, and through this, can increase human risk of heart disease and stroke. So, it’s important to keep triglyceride levels under control.
• Omega-3s may help us by raising human HDL (good) cholesterol and lowering human blood pressure.
  • Some studies show omega-3s may lower human risk for Cardiovascular disease (CVD), and hence lowering the sudden death caused by an abnormal heart rhythm (arrhythmia), and blood clots.
• Beyond heart health, omega-3s may help lower the human risk of developing some forms of cancer, including breast cancer, Alzheimer’s disease, and dementia, age-related macular degeneration (AMD), research continues to investigate these and other possible benefits.

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The recent passing away of Richard Slayman, the first recipient of a modified pig kidney transplant, has drawn attention to xenotransplantation—an innovative medical procedure with the potential to revolutionise organ transplantation.

What is Xenotransplantation?

• It involves transplanting live cells, tissues, or organs from nonhuman animal sources into human recipients.
• It seeks to address the critical gap between organ demand and supply.
• Xenotransplantation, pioneered in the 1980s with heart transplants, has emerged as a promising solution to alleviate the organ shortage crisis, particularly prevalent in kidney transplantation.

Examples:

• Chimpanzee-to-Human Transplants: In the 1960s, there were attempts at chimpanzee-to-human kidney transplants, heart transplants, and liver transplants.
• Pig-to-Human Heart Transplant: In 2022, a groundbreaking milestone was achieved with the first successful transplantation of a pig heart into a human with end-stage heart disease

Procedural Details

• Xenotransplantation involves genetic modifications to animal organs, like 69 CRISPR-Cas9 edits to a pig kidney, removing pig genes and adding human genes for compatibility.

Why is the Pig a Preferred Source?

• Anatomical Resemblance: Pigs are favoured for xenotransplantation due to their physiological similarities to humans, facilitating successful integration. Pig organs, like heart valves, have been used in human medicine for over 50 years.
• Breeding Advantages: Extensive pig farming ensures a readily available and cost-effective supply of organs, with diverse breeds offering size-matching opportunities.

Challenges associated

• The main challenge is preventing organ rejection. Innovative methods, such as embedding the pig’s thymus gland under the kidney’s outer layer, help manage immune responses.
• There are also significant concerns regarding potential infections from both recognised and unrecognised infectious agents that could affect not only the recipient but also the wider population.
• Retroviruses present in the animal organs pose a risk of cross-species infection, which could remain latent and cause diseases years after the transplantation.

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Why in the news?

Researchers at Princeton University found that Caenorhabditis elegans can inherit the ‘knowledge’ to avoid a disease-causing bacterium, Pseudomonas vranovensis, across several generations after initially consuming it.

About C. Elegans Worm

• C. elegans, or Caenorhabditis elegans, is a small, transparent nematode (roundworm) widely used in scientific research.
• It is about 1 mm in length, making it easy to study under a microscope.
• It has a simple body plan, which simplifies many types of biological research.
• C. elegans was the first multicellular organism to have its entire genome sequenced in 1998.

Key Features of C. Elegans Worm

• Short lifespan and quick regeneration: It has a short lifespan of about 2-3 weeks and develops from an egg to an adult in just 3-5 days. This allows for quick generation turnover and facilitates studies on genetics and developmental biology.
• Transparency:  It allows researchers to easily observe its internal structures and developmental processes in real time.
• Genetic information: This has provided a wealth of genetic information and made it a powerful tool for genetic studies.
• Consistent Somatic Cell Count: Adult C. elegans have exactly 959 somatic cells, and their lineage has been fully mapped, providing a consistent model for studying cell development and death.

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Why in the news?

• Magnetic Resonance Imaging (MRI) revolutionized medical diagnostics, offering non-invasive insights into soft tissues.
• The pioneering efforts of Paul Lauterbur and Peter Mansfield led to its commercialization, earning them the Nobel Prize in Medicine in 2003.

What is MRI?

• Magnetic resonance imaging (MRI) is a non-invasive diagnostic procedure used to obtain detailed images of soft tissues within the body.
• It is particularly valuable for imaging sophisticated structures like the brain, cardiovascular system, spinal cord, joints, muscles, liver, and arteries.
• MRI is instrumental in diagnosing and monitoring various conditions, including cancer, neurological disorders (such as Alzheimer’s and stroke), and cardiovascular diseases.
• Functional MRI (fMRI) can also assess brain activity by monitoring changes in blood flow.

Working Principle:

• MRI utilizes the magnetic properties of hydrogen atoms (one proton with one electron around it), which are abundant in water and fat molecules found throughout the body.
• The MRI machine generates a powerful magnetic field, aligning hydrogen atoms within the body.
• Radiofrequency pulses are then applied, causing hydrogen atoms to absorb energy and emit signals.
• These emitted signals are detected by sensors and processed by a computer to create detailed images of the body’s internal structures.

Components of an MRI Machine:

The MRI machine consists:

• Superconducting Magnet: Large magnet (superconducting magnet) that produces a powerful and stable magnetic field.
• Gradient Coils: Gradient magnets produce smaller magnetic fields with varying strengths and directions, allowing for precise imaging of specific body areas.
• Radiofrequency Coils: This emit radiofrequency pulses to excite hydrogen atoms in the body. The frequency of pulse the ‘excess’ atoms have to absorb is called the Larmor frequency.
• Detectors: It capture emitted signals from hydrogen atoms and convert them into image data for analysis.

Advantages of MRI:

• High-Resolution Imaging: MRI offers high-resolution imaging with excellent tissue contrast, allowing for accurate diagnosis and treatment planning.
• Versatile Viewing Angles: It can visualize structures from various angles without the need for repositioning, providing comprehensive information.
• Safety and Non-Invasiveness: MRI scans are non-invasive and do not involve ionizing radiation, making them safe for repeated use.
• Enhanced Image Quality: Contrast agents can enhance image quality by highlighting specific tissues or abnormalities.

Limitations of MRI:

• High Costs: MRI machines are expensive to purchase and maintain, resulting in high healthcare costs for patients.
• Requirement for Patient Stillness: Patients undergoing MRI scans must remain still for extended periods to prevent image distortion, which can be challenging for some individuals.
• Discomfort or Anxiety: The strong magnetic fields and loud noises produced during MRI scans may cause discomfort or anxiety for patients.
• Limitations with Metallic Implants: Certain metallic implants or objects can interfere with MRI scans, limiting their use in individuals with such implants.

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Why in the news?

• Researchers at the Fred Hutchinson Cancer Center in the US have identified specific subtypes of Fusobacterium nucleatum associated with colorectal cancer (CRC) tumors.
• These subtypes, particularly Fusobacterium nucleatum animalis (Fna), have been found in relatively higher quantities in CRC tumors.

About Fusobacterium nucleatum

• Fusobacterium nucleatum is a species of bacteria commonly found in the human mouth.
• It is a gram-negative anaerobic bacterium, meaning it does not require oxygen for growth.
• While typically residing in the oral cavity, it has been associated with various diseases and conditions, including periodontal diseases and colorectal cancer.

Association with Colorectal Cancer (CRC):

• In cases of colorectal cancer (CRC), Fusobacterium nucleatum has been found within tumors in the gut.
• Studies have shown that this bacterium can aid cancer cells in evading the immune system and promoting metastasis, or the spread of cancer to other parts of the body.
• Its presence in CRC tumors has led to investigations into its potential role in the development and progression of colorectal cancer.

Impact:

• Assisting cancer cells in evading the immune system.
• Promoting inflammation and creating an environment conducive to tumor growth.
• Facilitating metastasis by interacting with cancer cells and promoting their spread to other tissues.

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Why in the news?

• The Kerala government disclosed the re-emergence of West Nile fever cases in Thrissur, Malappuram, and Kozhikode districts.
• West Nile fever was first detected in Kerala in 2011, with a fatal case recorded in 2019 involving a six-year-old from Malappuram.

What is West Nile Fever?

• West Nile fever is caused by a West Nile Virus (WNV) transmitted through bites from infected Culex mosquitoes.
• The WNV is a mosquito-borne, single-stranded RNA virus.
• According to the WHO, it is a member of the flavi-virus genus and belongs to the Japanese Encephalitis antigenic complex of the family Flaviviridae.

How does it spread?

• It is transmitted by infected mosquitoes between and among humans and animals, including birds, which are the reservoir host of the virus.
• Mosquitoes become infected when they feed on infected birds, which circulate the virus in their blood for a few days.
• The virus eventually gets into the mosquito’s salivary glands.
• During later blood meals (when mosquitoes bite), the virus may be injected into humans and animals, where it can multiply and possibly cause illness.
• WNV can also spread through blood transfusion, from an infected mother to her child, or through exposure to the virus in laboratories.
• It is not known to spread by contact with infected humans or animals.

Symptoms of WNV infection:

• The disease is asymptomatic in 80% of the infected people.
• The rest develop what is called the West Nile fever or severe West Nile disease.
• In these 20% cases, the symptoms include fever, headache, fatigue, body aches, nausea, rash, and swollen glands.

Back2Basics: Type of Viruses 

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Why in the news?

• Researchers from Kerala reported 15 cases of Membranous Nephropathy (MN) linked to the regular application of fairness creams.
• These creams contained high levels of mercury, sometimes exceeding the safe limit by 10,000 times.

Mercury Contamination in Hair Cream

• Blood and urine screenings of affected individuals unveiled alarmingly high levels of mercury, a well-known toxic element.
• The fairness creams contained mercury levels up to 10,000 times above the permissible limit of 1 ppm under Minamata Convention (2013).
• Most cases were PLA2R (phospholipase A2 receptor) negative, indicating a different cause.
• Cases of MN linked to Neural epidermal growth factor-like protein 1 (NELL-1) have been identified.
• NELL-1 has been associated with MN caused by traditional medicines containing high mercury levels.

Understanding Membranous Nephropathy

• Membranous Nephropathy (MN) is a nephrotic syndrome, characterized by excessive protein leakage into urine, eventually leading to kidney failure. Symptoms such as fatigue, edema, and proteinuria were found to have a history of regular fairness cream usage.

Impact of Mercury:

• Mercury in fairness creams inhibits melanin formation, resulting in lighter skin. Consumers perceive higher mercury levels as more effective for skin whitening.
• Mercury, a potent heavy metal found in these creams, penetrates the body through various channels, including sweat glands and hair follicles, causing systemic toxicity.
• Chronic exposure to mercury can result in kidney damage, neurological disorders, and a myriad of other health complications.

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Why in the news?

After multiple rounds of screening, researchers have identified an antibody, 95Mat5 that showed promising results in making a potent antidote against various snake venoms.

What is 95Mat5?

• 95Mat5 is a universal antivenom developed to neutralize the toxins present in snake venoms.
• Development Process:

1. The scientists first synthesized variants of a toxin called long-chain 3FTxs (3FTx-L), which are found in the venoms of various snakes, including cobras, kraits, mambas, and monocled cobras.
2. They then screened billions of human antibodies expressed on the surface of yeast cells to find antibodies that bound best to the synthesized toxins.
3. After multiple rounds of screening, they identified a shortlist of antibodies that broadly reacted with most of the 3FTx variants used in the study.
4. The selected antibodies were further tested in vitro in human cells to determine which ones could best neutralize the toxins.

Mechanism of Action

• 95Mat5 specifically targets α-neurotoxins, which are a specific class of 3FTxs that prevent nerve and muscle cells from responding to acetylcholine, a neurotransmitter involved in carrying messages from neurons to muscles.
• By binding to the toxins, 95Mat5 prevents toxins from interacting with the receptors in human nerve and muscle cells, thereby blocking their ability to induce paralysis and other deadly effects.
• In animal experiments, 95Mat5 demonstrated efficacy in neutralizing the toxins present in the venoms of various snake species, protecting the animals from death.

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Why in the news?

• A significant health concern in Tamil Nadu is found through ingestion of Rat poison containing Yellow Phosphorus, leading to liver toxicity.
  • Since December 2017, the team at CMC Vellore introduced Plasma Exchange, (a cost-effective treatment) for acute liver failure caused by rat poison ingestion.

What is Plasma Therapy (Plasmapheresis)?

• Plasma exchange, also known as plasmapheresis, is a medical procedure used to treat various conditions by removing and replacing plasma from the blood.
• During Plasma Exchange, the patient’s blood is circulated through a machine that separates plasma from other blood components, such as red and white blood cells and platelets.

Working procedure:

• The plasma, which may contain harmful substances or antibodies, is discarded.
• The remaining blood components are mixed with replacement plasma or a plasma substitute and returned to the patient’s bloodstream.

Usage of Plasmapheresis:

• In Autoimmune diseases: Conditions such as Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus, and certain forms of vasculitis.
• In Neurological disorders: Conditions such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, and certain types of encephalitis.
• In Toxicological emergencies: Poisoning or overdose with substances such as drugs, chemicals, or toxins that can be removed from the bloodstream through plasma exchange.

Benefits observed in TN’s Case

• The treatment significantly improved survival rates, with 63.9% of patients treated in 2022-2023 successfully discharged.
• Retrospective studies at CMC Vellore demonstrated promising outcomes, with survival rates of 75% among children and 80.2% among adults treated with plasma exchange.

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Why in the news?

• Dr. Daniel Belsky from Columbia University introduced the concept of “Geroscience” and develops a blood test, termed “gerozyme,” to measure aging pace by studying DNA methylation.
• Various research groups explore drugs like Metformin and Rapamycin to target aging and enhance immunity in the elderly.

What is Geroscience?

• Geroscience refers to the interdisciplinary field focused on understanding the biological mechanisms of ageing and age-related diseases.
• It involves studying various factors, including DNA methylation, enzyme activity (such as the gerozyme), socio-economic influences, and lifestyle interventions like nutrition, exercise, and music therapy.
• It aims to develop strategies, such as drug interventions targeting specific ageing-related processes, to promote healthy ageing and combat age-related conditions like dementia.

Drug Interventions in Geroscience

• Metformin and TORC1 inhibitors show promise in targeting aging and improving immune response in seniors.
• Research proposes rapamycin’s potential in extending longevity and combating age-related diseases.

Impact of Socio-Economic Factors in Ageing

• Dr. Belsky’s research reveals the influence of socioeconomic status on DNA methylation levels, highlighting the role of disadvantage in ageing.
• Columbia Aging Centre emphasizes the role of a balanced diet in supporting brain health and reducing inflammation.
• Healthline.com advocates for proteins, healthy fats, and antioxidant-rich foods to promote healthy ageing, crucial for India’s ageing population.

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In the news

• The human brain, composed of billions of neurons, orchestrates intricate processes that sustain life and enable complex cognitive functions.
• Understanding these neural interactions is paramount, and scientists have achieved this through the concept of the connectome.

What is Connectome?

• Definition: The Connectome serves as a comprehensive map of neuronal connections, akin to a cartogram illustrating the intricate network of synapses transmitting electrical and chemical signals within the brain.
• Neural Communication: Neurons communicate through synapses, where dendrites receive chemical signals converted into electrical impulses transmitted along the axon. Subsequently, the cell releases chemicals into synapses based on electrical inputs, facilitating communication with neighbouring neurons.

Applications in Neuroscience

• Functional Insights: Mapping the connectome provides invaluable insights into brain function, shedding light on processes underlying cognitive functions and elucidating the impact of neurological disorders such as attention deficit hyperactivity disorder (ADHD) and Alzheimer’s disease.
• Drug Development: By unravelling cellular connections, researchers gain crucial knowledge about cognitive processes and associated disorders, informing the development of novel therapeutic interventions for conditions affecting neurological health.

Challenges and Progress

• Complexity of the Brain: The intricate nature of the brain and the vast amount of data it processes present significant challenges in mapping the connectome.
• Simplified Understanding: Despite these challenges, the connectome has revolutionized scientists’ comprehension of the brain, offering a clearer understanding of neurological health and paving the way for advancements in neuroscience research.

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In the news

• Cannabis (Cannabis sativa) has long intrigued psychiatrists due to its impact on mood and cognition, prompting research into its potential therapeutic applications for conditions like schizophrenia and mood disorders.

What is Cannabis?

• Cannabis, also known as marijuana, weed, pot, or ganja, is a genus of flowering plants that belongs to the Cannabaceae family.
• It is primarily known for its psychoactive properties due to the presence of compounds such as tetrahydrocannabinol (THC).
• This THC interacts with the brain’s cannabinoid receptors, resulting in various effects including relaxation, euphoria, altered perception of time, and increased appetite.
• The plant contains over 100 different cannabinoids, with THC and cannabidiol (CBD) being the most well-known and studied.

Why discuss this?

• Researchers at the University of British Columbia initiated a clinical trial to explore the efficacy of cannabidiol (CBD) in treating bipolar depression, offering promise for addressing depressive episodes in bipolar disorder.
• While delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis, CBD has garnered attention for its potential antipsychotic and neuroprotective effects.

Understanding the Cannabinoid System

• Receptor Mechanisms: The human cannabinoid system, comprising CB1 and CB2 receptors, plays a crucial role in modulating various bodily functions, including pain, memory, and appetite, with THC exerting acute effects on motor control and memory.
• Endo-cannabinoid System (ECS): The ECS, governed by endogenous molecules, regulates neurotransmitter activity, influencing mood and cognitive processes.

Therapeutic Applications  

• Medical Uses: THC and synthetic cannabinoids are utilized to stimulate appetite, alleviate nausea, and manage pain associated with conditions like HIV-AIDS and cancer.
• Addiction and Withdrawal: Debate surrounds the addictive potential of THC, with animal studies suggesting addictive responses and withdrawal symptoms upon cessation of heavy use.

Psychiatric Implications

• Mood Effects: Cannabis’ impact on mood is multifaceted, with reports suggesting associations with depression and bipolar disorder, although rigorous scientific scrutiny is lacking.
• Psychotic Risks: Individuals with psychotic illnesses, including schizophrenia, exhibit heightened susceptibility to cannabis-induced psychotic symptoms, with youth cannabis use potentially advancing the onset of schizophrenia in genetically vulnerable individuals.

Policy Considerations

• Global Trends: The global trend toward legalizing medical and recreational cannabis underscores the need for informed policymaking to mitigate risks, particularly for vulnerable populations such as children and individuals with mental illnesses.
• Decriminalization Debate: Broader debates on decriminalization necessitate measures to prevent commercialization and ensure safeguards against misuse, emphasizing protection for vulnerable segments of society.

Conclusion

• Navigating the complexities of cannabis necessitates a balanced approach, leveraging its therapeutic potential while addressing associated risks through evidence-based policymaking and clinical interventions.

Back2Basics: Narcotic Drugs and Psychotropic Substances Act, 1985

• The NDPS Act is a comprehensive law that consolidates and amends the existing laws relating to narcotic drugs and psychotropic substances in India.
• The Act prohibits the manufacture, cultivation, possession, sale, purchase, transport, storage, or consumption of drugs without permission from appropriate authorities.
• Violations are punishable with rigorous imprisonment for a minimum of 10 years and a fine.
• Lesser punishments are mandated for illegal possession in small quantities for personal consumption.
• The Act also provides for the forfeiture of property derived from, or used in, illicit traffic in narcotic drugs and psychotropic substances.
• Drugs covered include:

1. Narcotic Drugs: Coca leaf, cannabis (hemp), opium, poppy straw, and their manufactured goods.
2. Psychotropic Substances: Any substance that modifies the mind, including amphetamine, methaqualone, diazepam, alprazolam, ketamine, etc.
3. Other substances: Cocaine, morphine, diacetylmorphine, or any other narcotic drug or any psychotropic substance as may be specified on this behalf by the Central Government.

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In the news

• Recently identified by scientists at Stanford University, obelisks represent a distinct class of virus-like entities residing within the human body.

What are Obelisks?

• Novel Discoveries: Recently identified, obelisks represent a distinct class of virus-like entities residing within the human body.
• Genetic Diversity: Comprising diverse RNA molecules, obelisks have pervaded both human and global microbiomes, yet remained unnoticed until now.
• Distinctive Characteristics:

• 1. Structural Symmetry: Named after the rod-like, highly symmetrical structures formed by their twisted RNA strands.
  2. Genetic Makeup: Obelisks boast compact genetic sequences of approximately 1,000 nucleotides, devoid of known similarities to other biological agents.
  3. Size Disparity: Significantly larger than conventional genetic molecules like plasmids, which are primarily composed of DNA.

• Taxonomic Position: Positioned between viruses and viroids, obelisks constitute a unique class of organisms with intriguing properties.
• Host Interaction: While the hosts of certain obelisks remain unidentified, bacterial associations are speculated, hinting at a broader ecological significance.
• Spatial Distribution: Various types of obelisks inhabit diverse regions within the human body, highlighting their pervasive presence and potential physiological roles.

Understanding Viroids: Nature’s Tiny RNA Loops

• Genetic Cousins: Viroids are compact loops of RNA, closely related to DNA, primarily infecting plant organisms.
• Discovery: In 1971, Theodor Diener identified viroids during research on potato spindle tuber disease, revealing naked RNA entities devoid of protein coats or lipid layers.
• Unique Features:
  1. Lack of Encapsulation: Unlike larger RNA viruses, viroids lack protective shells, relying solely on their RNA structure for stability.
  2. Genetic Composition: Viroid RNA does not encode protein-building instructions, contrasting with viruses that carry genetic blueprints for their replication machinery.
• Host Interactions: Viroids exploit host enzymes for replication, highlighting their parasitic nature within plant cells.

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Introduction

• Approximately 20 years ago, biologist Caroline Gargett embarked on a quest to uncover remarkable cells within hysterectomy tissue.
• Dr. Gargett discovered two types of cells in the endometrium through rigorous microscopy examination, suspected to be adult stem cells due to their regenerative capabilities.
• The discovery of these cells, known as endometrial stromal mesenchymal stem cells, opened new avenues for research in tissue repair and disease treatment.

What are Endometrial Stem Cells?

• Potential for Regeneration: Endometrial stem cells possess the ability to differentiate into various cell types, including neurons, cartilage, fat, bone, heart, liver, and skin cells.
• Collection Methods: These stem cells can be obtained through a biopsy procedure or harvested from menstrual blood, offering a less invasive and more accessible means of procurement.

Application in Women’s Health

• Understanding Endometriosis: Endometrial stem cells have been linked to endometriosis, a condition affecting millions of women worldwide, providing insights into its etiology and potential therapeutic targets.
• Diagnostic and Therapeutic Potential: Differences in menstrual stem cells between healthy individuals and those with endometriosis offer promising avenues for diagnostic tests and targeted treatments.
• Treatment Innovations: Clinical trials exploring the transplantation of menstrual stem cells have shown potential for treating pelvic organ prolapse and other gynecological conditions.

Beyond Gynecological Diseases

• Wider Therapeutic Applications: Research indicates the potential of menstrual stem cells in treating diseases beyond gynecological disorders, including diabetes and wound healing.
• Clinical Trials and Future Prospects: Small-scale trials have demonstrated the safety and efficacy of stem cell transplantation in humans, paving the way for further exploration and application in diverse medical fields.

Challenges and Biases

• Underrepresentation in Research: Despite their therapeutic potential, menstrual stem cells constitute a minuscule fraction of stem cell research, attributed to cultural taboos and biases surrounding menstruation.
• Funding and Investment: Limited funding and gender bias in research funding pose significant challenges to advancing research on menstrual stem cells, necessitating greater advocacy and support.

Way Forward

• Addressing Bias: Tackling sex and gender bias in research funding is crucial for fostering equitable investments in women’s health research.
• Recognition and Validation: By overcoming cultural taboos and biases, menstrual stem cells can be recognized as a valuable resource in regenerative medicine, transforming perceptions of menstruation from inconvenience to scientific opportunity.

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Introduction

• The year 1944 witnessed the simultaneous emergence of artificial neural networks, laying the foundation for deep learning, and the discovery of streptomycin, the first aminoglycoside antibiotic.
• This historical synchrony ultimately connects deep learning and antibiotics.

Why in news?

• In December 2023, scientists introduced a groundbreaking alliance between deep learning and antibiotics by leveraging deep learning techniques to discover a new class of antibiotics, addressing a multi-decade gap in antibiotic development.

Deep Learning in Antibiotic Discovery

• Different Approach: Unlike previous applications of deep learning in drug discovery, this study focused on identifying chemical motifs or substructures used by the deep learning model to evaluate compounds for antibiotic potential, rendering the model “explainable”.
• Proven Efficacy: The research successfully demonstrated the effectiveness of two compounds from the newfound antibiotic class against methicillin-resistant Staphylococcus aureus (MRSA) infections, a major cause of human fatalities in 2019.
• Recognition and Expansion: Experts praised the study for its contributions to antibiotic research and its potential to enhance drug development strategies.

Understanding Deep Learning and Explainability

• Neural Networks: Deep learning relies on artificial neural networks, comprising layers of artificial “neurons” that process inputs and yield outputs through training and testing phases.
• Training and Testing: Deep learning networks are trained on large datasets with annotated inputs to learn specific tasks. During testing, they classify novel inputs based on their learned knowledge.
• The Black Box Issue: Most deep learning models lack transparency in explaining how they arrive at their conclusions, remaining “black boxes.”
• Explainable Deep Learning: In contrast, the study’s model was designed to be explainable, allowing it to not only predict antibiotic potential but also elucidate the substructures contributing to this property.

Journey to Novel Antibiotics

• Experimental Screening: The research began by screening over 39,000 compounds to inhibit S. aureus growth, shortlisting 512 active compounds.
• Graph Neural Network (GNN): A GNN was trained on the dataset, representing atoms as nodes and bonds as edges on a mathematical graph.
• Selecting Non-Toxic Compounds: To ensure safety, 306 compounds were identified that didn’t harm human cells, and other GNNs were trained to identify cytotoxic compounds.
• Identifying Potential Antibiotics: The GNNs evaluated a database of over 1.2 crore compounds, identifying 3,646 potential antibiotics based on substructures.
• Substructure Rationales: The study introduced “rationales” to explain the substructures that conferred antibiotic properties to molecules.
• Efficacy Against MRSA and VRE: Certain compounds, including N-[2-(2-chlorophenoxy)ethyl]aniline, exhibited inhibition of MRSA and vancomycin-resistant enterococci (VRE).
• Mouse Models: One compound effectively reduced MRSA-related skin and thigh infections in mouse models.

Significance and Ongoing Challenges

• Transparency in Drug Discovery: The study’s significance lies in rendering deep learning approaches to drug discovery more transparent and reproducible across drug categories.
• Future Exploration: Researchers are applying substructure rationales to design new antibiotics and explore applications in drugs targeting age-related disorders.
• Addressing a Lacuna: An identified shortcoming is that explainability analysis occurred after predicting antibiotic properties. Implicitly incorporating explainability in deep learning models is proposed as a more robust approach.

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Introduction

• To combat the menace of growing antibiotic resistance, scientists at CSIR-Indian Institute of Integrative Medicine (IIIM), Jammu, have made a groundbreaking discovery.
• They found that phytocannabinoids, compounds found in the cannabis plant, possess previously untapped antibiotic properties.

Understanding India’s AMR Challenge

• Escalating AMR Threat: AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to antibiotics, leading to increased disease risk and treatment complications.
• Alarming Statistics: In 2019, India reported 2.97 lakh deaths attributed to AMR and 10.42 lakh linked to AMR-related factors.
• Contributing Factors: Overuse of antibiotics, misuse in animal husbandry, and inadequate waste disposal practices are exacerbating AMR, potentially making India the “AMR capital of the world.”

Cannabis Unveils Antibiotic Potential

• Phytocannabinoid Research: IIIM researchers explored the antibiotic properties of tetrahydrocannabidiol (THCBD), a semisynthetic phytocannabinoid derived from cannabis.
• Fighting MRSA: THCBD exhibited remarkable efficacy against Methicillin-resistant Staphylococcus aureus (MRSA), a highly resistant strain of bacteria responsible for numerous deaths worldwide.
• Synergy with Existing Antibiotics: THCBD complemented or showed indifference to common antibiotics like mupirocin, penicillin G, and ciprofloxacin, suggesting potential combinatory treatments.

Overcoming Cannabis Research Challenges

• Legal Constraints: Cannabis research faces legal constraints due to its intoxicating properties, making collaboration with other institutes challenging.
• Policy Advocacy: The research project aims to advocate for a unified national policy for cannabis research, highlighting its antibacterial potential and transforming it into a valuable resource.

Future Prospects for THCBD

• Collaborative Efforts: IIIM researchers seek collaborations to expedite their progress in developing THCBD as a potential drug.
• Addressing Solubility Challenge: Ensuring THCBD’s solubility is a critical step. The molecule leans slightly towards lipophilicity, requiring optimization for proper absorption in biological systems.
• Healthcare Impact: This research not only promises significant contributions to the healthcare system but also offers economic benefits by establishing related industries and creating sustainable job opportunities.

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Introduction

• The human microbiome, consisting of trillions of microorganisms residing primarily in the digestive tract, plays a crucial role in regulating health and disease.
• This intricate microbial community impacts various facets of human well-being, encompassing digestion, nutrient absorption, metabolite processing, immune function, and mental health.

What are Human Microbiomes?

• The human microbiome refers to the vast and diverse community of microorganisms, including bacteria, viruses, fungi, and other microbes, that inhabit various parts of the human body, such as the skin, mouth, gut, and reproductive organs.
• These microorganisms play a crucial role in maintaining health by aiding digestion, supporting the immune system, and influencing metabolic processes.
• Imbalances in the microbiome have been linked to various health conditions, including digestive disorders and autoimmune diseases.
• Research on the human microbiome has grown significantly in recent years, leading to a better understanding of its impact on overall well-being.

Genomic Advancements in Microbiome Research

• Challenges in Study: Many microbiome microorganisms defy conventional laboratory culturing, necessitating innovative approaches.
• The Human Microbiome Project: Launched in 2012, this international consortium initiated genomic exploration of the human microbiome through DNA sequencing.
• Technological Progress: Advancements in genomic technology over the last decade have empowered scientists to achieve greater revelations.

Impact on Human Health

• Vital Physiological Functions: The human gut microbiome significantly contributes to essential processes like digestion, nutrient absorption, and the production of necessary enzymes.
• Health Conditions: Imbalances in microbial populations can lead to various health conditions, emphasizing the importance of a balanced microbiome.
• Response to Antibiotics: The gut microbiome can undergo significant changes when individuals take antibiotics, eventually reverting to its original state.

Manipulating Microbiome for Clinical Outcomes

• Microbiota Transplants: Researchers have employed treatments like fecal microbiota transplants to manage infections and metabolic syndromes, demonstrating the potential to artificially alter the human microbiome.

From Genetics to Gut Microbes

• Genetic Influence on Microbes: Recent studies suggest that genetic variations in individuals may affect the diversity and abundance of gut microbes.
• A Link to ABO Blood Group: Researchers identified a link between genetic variants in the ABO blood group and microbial genes involved in metabolizing N-acetylgalactosamine, revealing potential links to cardiometabolic traits and even COVID-19 susceptibility.

Implications for Cancer and Neurons

• Cancer Link: Gut microbes have been associated with the development of colorectal cancer, offering new prospects for cancer therapy.
• Neuronal Signaling: Microbiome-produced vitamin B12 may influence neuronal signaling through its impact on choline availability.

Role in Urobilinogen Metabolism

• Yellow Urine Pigment: Researchers uncovered the role of the human microbiome in metabolizing urobilinogen, impacting bilirubin levels and jaundice.
• Personalized Healthcare: These genetic insights are shaping future healthcare by enabling personalized interventions.

Conclusion

• The study of the human microbiome, guided by genomic research, continues to unravel its profound impact on human health and well-being.
• From its vital role in physiological functions to potential links with diseases and even neurological processes, the microbiome is an essential component of our overall health.
• Understanding the genetic intricacies of this microbial community holds great promise for personalized healthcare and innovative therapies.

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Introduction

• New Antibiotic Class: Researchers have identified zosurabalpin, a new class of antibiotics showing potential against the drug-resistant bacterium Acinetobacter baumannii.
• Effective against CRAB: Zosurabalpin has been found effective against carbapenem-resistant Acinetobacter baumannii (CRAB)-induced pneumonia and sepsis in mouse models.

About Zosurabalpin

• Development Process: The antibiotic originated from a tethered macrocyclic peptide (MCP) selectively targeting A. baumannii and was optimized for efficacy and tolerability.
• Novel Mode of Action: Zosurabalpin operates through a previously unknown mechanism, inhibiting the transport of lipopolysaccharide (LPS) in bacteria.
• Inhibition of LPS Transport: By blocking a protein complex essential for LPS transport to the bacterial surface, zosurabalpin disrupts the outer membrane structure of Gram-negative bacteria, leading to bacterial death.

Effectiveness and Clinical Trials

• Laboratory and Animal Studies: Zosurabalpin demonstrated effectiveness against over 100 CRAB clinical samples in the lab and significantly reduced bacterial levels in mice with CRAB-induced pneumonia and sepsis.
• Phase I Clinical Trials: The antibiotic has undergone evaluation in two phase I clinical trials, marking the initial steps towards potential human use.

Implications and Future Prospects

• Addressing Antibiotic Resistance: The discovery of zosurabalpin offers hope in the fight against antibiotic-resistant bacteria, a growing global health concern.
• Potential Clinical Application: If further trials are successful, zosurabalpin could become a vital tool in treating infections caused by drug-resistant Acinetobacter baumannii.
• Continued Research: Ongoing and future studies will be crucial to fully understand the antibiotic’s safety, efficacy, and potential resistance mechanisms.

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Central Idea

• The Nizam’s Institute of Medical Sciences in Hyderabad reports three to four cases of Huntington’s disease monthly, with each case impacting entire families.

Understanding Huntington’s Disease  

Role of the HTT Gene and Glutamine Repeats

• Genetic Mutation: Huntington’s disease is caused by a mutation in the HTT gene, leading to abnormal huntingtin (Htt) proteins that damage neurons.
• Polyglutamine Tracts: The severity of the disease correlates with the length of glutamine repeats in the Htt protein; longer repeats result in earlier and more severe symptoms.
• Inheritance Pattern: The disease manifests even if only one copy of the HTT gene is mutated, demonstrating its dominant nature.
• Similar Proteins and Diseases: Other proteins with polyglutamine tracts, when mutated, can also cause neuronal degeneration, leading to disorders like spinocerebellar ataxia.

Fruit Fly Study: A Model for Understanding Huntington’s

• Genetic Engineering in Flies: Researchers engineered fruit flies to express the human HTT gene with extended polyglutamine tracts in their neurons.
• Gal4/UAS System: Utilizing the Gal4 gene from baker’s yeast, the study induced expression of mutated HTT in fly neurons.
• Symptoms in Flies: Flies with longer glutamine tracts exhibited symptoms similar to Huntington’s disease, unlike those with shorter, normal tracts.

Yod1 Gene Discovery

• Gene Expression Experiment: The study explored the effects of altering the expression of 32 genes on disease-like symptoms in fruit flies.
• Yod1’s Protective Role: Overexpression of the Yod1 gene eliminated neurodegeneration and other disease-like effects in flies with longer glutamine tracts.

Broader Implications and Future Research

• Potential in Human Treatment: If overexpression of the human version of Yod1 shows similar benefits in fruit flies, it could be a promising avenue for treating Huntington’s in humans.
• Value of Model Organisms: Studies in fruit flies and yeasts are pivotal for understanding molecular mechanisms of diseases like Huntington’s.

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Central Idea

• Revolutionary Development: The medical world is witnessing a significant breakthrough with the approval of CRISPR-based therapies for sickle-cell disease and β-thalassemia in the U.K. and the U.S.
• Global Impact: These advancements hold the potential to transform the lives of millions suffering from these inherited blood disorders.

CRISPR Technology: From Discovery to Application

• Origins of CRISPR: Discovered in archaea in 1993, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) elements were later found to form an antiviral defense system in bacteria with Cas (CRISPR-associated) proteins.
• Nobel Prize-Winning Innovation: Emmanuelle Charpentier and Jennifer Doudna’s work on CRISPR-Cas9 as a ‘molecular scissor’ earned them the 2020 Nobel Prize in chemistry.
• Eukaryotic Genome Editing: Subsequent research demonstrated CRISPR-Cas9’s ability to edit eukaryotic genomes, paving the way for various applications in genetic therapies and agriculture.

CRISPR in Medicine: Recent Approvals and Applications

• CRISPR-Based Treatment for Blood Disorders: The MHRA in the U.K. and the FDA in the U.S. approved ‘Casgevy’ for treating sickle-cell disease and transfusion-dependent β-thalassemia.
• Treatment Mechanism: Casgevy involves modifying a patient’s blood stem cells to correct the genetic defect causing sickling, then regrafting them to produce normal red blood cells.
• Historical Context: This approval marks a full circle from Linus Carl Pauling’s description of sickle-cell disease as a molecular disorder 74 years ago.

Emerging CRISPR Technologies and Approaches

• Base-Editing: This technique allows genome editing at the single nucleotide level.
• Prime Editing: A newer method that uses a search-and-replace strategy for precise genome modifications.
• Epigenetic Modifications: CRISPR systems are also being developed to target epigenetic effects.

Challenges and Future Prospects

• Safety and Accuracy Concerns: Issues like off-target events, where CRISPR-Cas9 edits unintended parts of the genome, pose significant challenges.
• Balancing Risks and Benefits: While the potential of these technologies is enormous, their risks must be weighed against both short- and long-term benefits.
• Ongoing Research and Surveillance: Continuous scrutiny is essential to uncover potential side effects that are currently unknown.

Conclusion

• Celebrating Advances: The approval of therapies like Casgevy heralds a new era for millions suffering from genetic diseases.
• Optimistic Outlook: The advancements in CRISPR technology signal a promising future in the field of genetic medicine and disease treatment.

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Central Idea

• The UK recently completed sequencing half a million whole genomes, nearly 0.7% of its population, under ‘deCODE’ Initiative.
• Various countries have launched large-scale genome projects, with some focusing on specific populations like African ancestry.

About ‘deCODE’ Initiative

• Inception: Launched in Iceland in 1996, deCODE genomics enrolled most of the Icelandic population for genetic studies.
• Contributions: The initiative enhanced disease genetics understanding and set standards for handling genomic data, integrating medical records with genealogies.

Merit of Large-Scale Sequencing

• Disease Research and Understanding: Large-scale genome sequencing allows researchers to identify genetic variations associated with various diseases. This information is crucial for understanding the genetic basis of diseases, including rare genetic disorders and complex conditions like cancer.
• Personalized Therapies: With a better understanding of an individual’s genetic makeup, it becomes possible to develop personalized and targeted therapies. 
• Genetic Counseling: Large-scale genome sequencing provides valuable information for genetic counseling, helping individuals and families understand their risk for certain genetic conditions.
• Identification of Rare Variants: Large-scale sequencing efforts contribute to the identification of rare genetic variants that might be responsible for certain diseases. These discoveries are essential for expanding our knowledge of the genetic landscape and improving diagnostic capabilities.
• Population Genetics and Evolution: Genome sequencing on a large scale allows researchers to study the genetic diversity within populations. This information is valuable for understanding human evolution, migration patterns, and population-specific genetic traits.

Ethical and Regulatory Challenges

• Privacy Concerns: Genome sequencing generates highly sensitive and personal information. There is a risk that genetic data could be misused or lead to privacy breaches.
• Informed Consent: Obtaining informed consent for genome sequencing is complex due to the vast amount of information generated and the potential for incidental findings.
• Data Ownership and Control: Balancing individual rights with the need for research and medical advancements requires careful consideration of data sharing, ownership, and access policies.
• Genetic Discrimination: Concerns about genetic discrimination in areas such as employment, insurance, and education may discourage individuals from undergoing genome sequencing. L
• Access to Genetic Services: Disparities in access to genetic services and genomic technologies may exacerbate existing healthcare inequalities.
• Ethical Use of Genetic Data in Research: Researchers must adhere to ethical standards when using genetic data in research. This includes obtaining proper consent, ensuring data security, and transparently communicating the purpose and potential risks of the research.

Long-Term Impact and Future Prospects

• Beyond Individual Health: Population-scale genomics will enhance our understanding of human evolution, migration, and adaptation.
• Personalized Medicine: It paves the way for personalized healthcare based on individual genetic profiles.
• Billion Genome Project: The possibility of sequencing a billion genomes in a single project is on the horizon, alongside individuals’ rights to access and understand their own genomic data.

Conclusion

• Population-scale genomics is at the forefront of a genomic revolution, with the potential to transform healthcare, deepen our understanding of human biology, and shape our approach to medicine and biology.
• This evolving field promises to bring personalized, precise treatments and a richer comprehension of our genetic heritage.

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Central Idea

• Recent breakthroughs in genetic research have shed light on the complexities of early embryonic development, particularly focusing on the inner cell mass, a key component in forming the human body.

Embryonic Development Explained

• Life’s Commencement: Life begins with the fusion of sperm and egg, creating a zygote, the first cell of a new individual.
• Cellular Multiplication: The zygote undergoes rapid cell division, marking the onset of embryonic development.
• Diverse Cell Differentiation: As the embryo develops, cells differentiate into various types, leading to the formation of organs and tissues.
• Journey to Birth: This intricate process culminates in the birth of a newborn after nine months of gestation.

Early Stages of Development

• Inner Cell Mass Formation: Early embryonic cells cluster around the inner cell mass, vital for the embryo’s development.
• Pluripotency of Cells: These cells are pluripotent, meaning they can develop into any cell type in the body.
• Scientific Focus: The inner cell mass is a primary subject of study due to its critical role in human development.

Gene Expression in Embryonic Cells

• Analyzing Gene Activity: Researchers study the proteins produced by genes to understand cell-specific gene expression.
• Deciphering Cell Development: This research provides insights into the active genes in each cell, revealing the mechanisms of cell development.

Discoveries in the Inner Cell Mass

• 2016 Research Insights: Manvendra Singh’s reanalysis of gene expression data identified a new group of non-committed cells in the inner cell mass.
• Enigma of Cell Death: These cells, unlike others, do not progress to later developmental stages and are eliminated early on.

HERVH Gene and Cell Survival

• HERVH’s Crucial Function: A 2014 study revealed that HERVH, a gene with virus-like properties, is essential for maintaining pluripotency in embryonic stem cells.
• Gene Expression Variations: Singh’s research showed that while most inner cell mass cells express HERVH, the non-committed cells that eventually die do not.
• Independent Confirmation: This discovery was corroborated by researchers at the University of Spain in lab-fertilized embryos.

Understanding ‘Jumping Genes’

• Transposons in Non-Committed Cells: The non-committed cells express transposons, or ‘jumping genes’, which can cause DNA damage and lead to cell death.
• HERVH’s Protective Role: HERVH protects most cells from the harmful effects of transposons, but cells lacking HERVH expression are vulnerable.
• Natural Selection in Embryos: The early human embryo acts as a selection ground, favoring cells with HERVH expression.
• HERVH’s Unique Nature: Interestingly, HERVH itself is a transposon but functions protectively rather than destructively.

Implications for Placenta and Beyond

• Placental Development: Cells that form the placenta also exhibit transposon activity but manage to survive without HERVH expression.
• Impact on Regenerative Medicine: Understanding HERVH’s role in cell pluripotency has profound implications for regenerative medicine and could influence embryo viability in fertility treatments.Top of Form

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