S_T-Current-Affair__1_

Endosymbiotic Theory

  • Darwin > Neo-Darwin > Lynn Margulis
  • Challenged consensus of evolution.
  • Theory of Symbiogenesis.
    • Origin of eukaryotic cells from prokaryotic organisms.
    • Mitochondria, plastids, and other organelles descended from free-living prokaryotes.
  • Gyanobacterium evolved into new organelle named Nikoplast.

Criteria for Organelles

  1. Functionally and structurally integrated into the host cell.
  2. Depend on the host cell for protein import.
  3. Synchronize its growth with the host cell.
  4. Be inherited during host cell division.
  • Nutcoplast meets all these criteria; recent evolutionary development (~100 mya).

Applications

  • Revolutionizing agriculture: sustainable alternative for ammonia production.
  • Engineering Host Cells: enable nitrogen fixation.
  • Genetic Transformation.
  • KP.2 and KP.11: descendents of JN.1 variant; symptoms similar to Omnicron variants; FLiRT due to key amino acid changes.
  • Discovery: Candida Aalbicans (marine algae) is host for UCYN-D (nitrogen fixation).
  • Callies vaccination can still prevent severe COVID-19 from newer variants.

Xenotransplantation

  • Etymology: Xeno (foreign) + Transplantation (moving something to another place).
  • Process:
    • Remove pig genes that trigger immune response using CRISPR-Cas9 genetic editing.
    • Add human genes.

Genetic Reconstruction

  • Process of retrieving, sequencing, and assembling the genome of an organism.

Genome Sequencing

  • Used to identify genetic markers for disease resistance and drought tolerance in crop plants.
  • Helps reduce the time required to develop new varieties of crop plants.
  • Can be used to decipher host-pathogen relationships in crops.

Pigs in Xenotransplantation

  • Health values are used to replace human health values; similar anatomy + physiology.

Challenges

  • Need of Immunosuppressants.
  • Transplanted organs may carry infectious agents.
  • Xenotransplant definition:
    • Live cells, tissues from non-human source.
    • Human body fluids, tissues, organs that have had ex-vivo contact with live non-human cells (e.g., pig liver for temporary perfusion).

X-Chromosome

  • Encodes ~800 protein-encoding genes; both males & females have an X-chromosome.
  • X Chromosome Inactivation (XCI):
    • XX in females > Twice amount of X-linked proteins.
    • To balance this, one chromosome in each cell is randomly inactivated.
    • Biological functions and sex-specific susceptibility.
    • Through epigenetics > genes are influenced by the environment where they operate [ex: Methylation]. DND L RND regulation methylation Histone Modification.

Diseases linked to X-chromosome

  1. X-linked genetic diseases, e.g Red-Green Colour Blindness.
  2. X-Chromosome Aneuploidy, e.g. Klinefelter Syndrome (XXY), Turner Syndrome (X instead of XX).
    • Use of 2 non-protein riding RNA--xist and tsix , -Rumaidathritis, So,a Duchene muscular dystorphy.
  • Possible applications: New Medicines for Alzheimers's and other diseases.

H5N1 Outbreak

  • Avian A influenza (H5N1).
  • Texas Cattle herd (expanded to 36 herds across US).
  • Reverse spillover: cattle to poultry.
  • Mode of transmission: unclear.
  • Possible routes: Contaminated feed, milking equipment, airborne transmission.
  • Pasteurization of Milk helps prevent this disease, kills live virus.
  • Indian Outbreaks limited to poultry.

Dengue

  • Latin America's dengue spike: Jan - April 2024 → 6 million cases; 1/3rd increase.
  • Aedes aegypti mosquito.
  • Four viral strains: DENV 1-4; vaccines protect against all four strains.

Why These Outbreaks?

  1. 2°C warming /decade in Latin America → Mosquito breeding habitats earlier than usual.
  2. El Nino (2023) ↑ temp in Pacific Ocean.
  3. Rapid urbanization + Poor Waste Management.

Vaccines Available

  • Qdenga (Japan-made vaccine).
  • Dengvaxia (Sanofi Pasteur, France) - can only be given to previously affected people - uses live weakened form of all four strains.
  • NIH Single-Shot Vaccine (U.S.).

Japanese Encephalitis

  • Common symptoms include: High fever, Headache Neck stiffness Disorientation Stupor & coma Tremors & convulsions Muscle weakness Paralysis
  • 80% of infected individuals show no symptoms. Symptoms are similar to Japanese encephalitis.
  • Dengue Vaccine Trials in India ↳ I death + 8 cases.
  • Mode of Transmission: Culex species of Mosquitoes. No vaccines available.
  • Widal Test-- rapid blood test diagnosing Typhoid fever - gold standard--culture - problem-time consuming -(enteric fever).

Typhoid Fever

  • Cause: Salmonella typhi and other related bacteria.
  • Transmission: Through contaminated food and water.
  • Symptoms: High fever, stomach pain, and weakness, nausea, vomiting, diarrhea or constipation, and skin rash.
  • Some individuals remain asymptomatic but continue to spread the bacteria (carriers).

Widal Test

Salmonella immune system Antigen producing antigen infection ↳ S O(somatic) H(flagella).

  • Widal Test detects prepares antibodies IgG.

Issues

  1. False +ves & false-ves.
  2. Comparison needed to 2 blood sBinding,clumping samples (7-14 days apart) (agglutination).
  3. ross-reactivity with other unjections v of wital antigen measured Vaccinationfalse the.
  • Anti-biotics reduces detectable antibody levels false positive -- use of SAM ⑪ Old technique (1800) already discontinued in mayis.

Microcephaly

  • Condition where baby's head is smaller than normal.
  • SASS6 gene in Microcephaly; required to form centrioles adjunction impaire reduces cell division brain growth; neurons are high sensitive to centride defects.
    • Risk 4 in consanguineous marriage (marriage byw closely related individuals).
    • Centrioles -spindle formation and all division. SDSSOgune- :le 62thr (isoleucine replaced by therionine).

Sickle Cell Anaemia

  • Highest prevalence in S. Asia + India (
  • 20 million cases.
  • Issues: Drug-Hydronyusea Phama companies only market 500 mg and 200 mg of Hydronywea Pediatric. close lesser inaccurate administration doses are broken mannually ICMR has invited Expression of Interest for developing pediatric oral formulations of hydronyurea for SCD. efficacy.I side-effects.
  • Galabia -10 mg/kg also helps in thalassemia.
  • National Mission to eliminate Sickle Cell Anemia by 2047.

Tuberculosis (TB)

  • Bacterial infection spread through air caused by Mycobacterium tuberculosis.
  • Types of TB:
    • Pulmonary TB: infects lungs.
    • Extrapulmonary TB: infects other body parts (Brain, spine, lymph nodes, Skeletal TB &bones, TB Meningitis Brain, Ocular TB) aka Koch's disease.

Issues

  • Can't be detected in standard tests > Organ failure undiagnosed long-term disability immune privilege -persisteven after Bigis.
  • Lack of awareness.
  • Lack of standardized diagnostic and treatment protocols - no formal guidelines for most organs. India: INDEX-TB Guidelines (2014) -clinical protocols for to organ system; aims, to eliminate TB by 2025; TB deaths in India -4.8 latche / year ↓ ml TB cases undiagnosed.
  • ICMR working > Early detection to revie treatment protocol -Better intervention disease markers post infection also needed to use advanced tools like RNA sequencing single all.

Vaccines for TB

  • MTBVA) -- live-attenuated star of tuberculosis' designed and constructed by Prof. Carlos Martin (Univ - ofZaragoza, Spain first vaccine to be Institute pasteus derived from tuberculosis.
  • BCG used live-attenuated M. Louis derived from bovine TB Stain Phase I Post-Marketing Trial -
  • Assessment of adverse events following immunization (AEFI) + Advese events of Special Interest CAESI).

Regulatory Bodies

Regulatory Body
Central Drugs Standard Control Organization (CDSCO)
State Licensing Authority (SLA)
Central Licensing Approval Authority (CLAA)
Vaccine Subject Expert Committee (SEC)
Technical Committee
Review Committee on Genetic Manipulation (RCGM)
Function
National Regulatory Authority (NRA) responsible for granting permission to manufacture or import vaccines for testing, regulating clinical trials, granting marketing approval, handling post-approval changes, lot release, inspecting manufacturing facilities, and pharmacovigilance.
Responsible for inspecting manufacturing facilities, generating manufacturing licenses for CLAA approval, export certification, and quality monitoring through market sampling.
SLA forwards the manufacturing license in a prescribed format to the CLAA for approval, and CLAA accords approval if the applicant meets the requirements.
Advises the Drugs Controller General (India) on clinical trial proposals, marketing approvals, post-approval changes, safety, and immunogenicity aspects. It comprises experts from various fields, and its recommendations are advisory.
An applicant who is not satisfied with the recommendations of the SEC can appeal to the Technical Committee, which is headed by the Director General of Health Services (DGHS).
Under the Department of Biotechnology, oversees the development and preclinical evaluation of recombinant DNA-derived products. Authorizes research and development activities, exchange of genetically engineered cell banks for research purposes, and reviews data up to preclinical evaluation.

Diseases Saved by Vaccination

The impact of 50 years of vaccination on children worldwide chart shows the number of lives saved by various vaccinations across the worldMeasles 27.95MTetanus 13.17MTuberculosis 10.87MHib disease 2.85MPolio 1.57MYellow fever 0.55MHepatitis B 0.46MRotavirus 0.4MDiphtheria 0.36MRubella 0.29M

GAVI Objectives

  • Increase vaccine coverage in low-income countries.
  • Ensure affordability of vaccines by negotiating lower prices.
  • Strengthen healthcare systems for sustainable immunization programs.
  • Introduce new and underused vaccines into developing countries.
  • Prevent outbreaks of vaccine-preventable diseases.

Historical Evolution of Vaccination

  • 1974: Intervention of WHO
  • 2000s: Intervention of GAVI
  • Expansion
  • GAVI: set up as "Global Health Partnership" to create equal access to new and underused vaccines WHO + UNICEF + WB + Vaccine Manufactures. Bill and Melinda f gates foundation Most life-saving vaccine Measles.

Key Notes

  • worker bus, spiders, munkats. genes explain this altruism. green beard gines individuals bearing them reguise and preferential zate. behave harmfully to those who have adifferent copy Amoeba Dictyostelium discoideum single-celled organism that can form multicellular structures.

Reverse Transcriptase

  • Discovered in 1970 by Howard Temin and David Baltimore.
  • The enzyme converts RNA to DNA, which contradicted the earlier belief that genetic information flows only from DNA → RNA → Protein (Central Dogma).

Revolutionized research in molecular biology, enabling researchers to

  • Convert RNA into DNA for cloning and gene studies.
  • Detect RNA viruses like HIV, Hepatitis B, and SARS-CoV-2.
  • Develop diagnostic tools and antiviral drugs.
  • when infected by Bacteriophage prevents visies use reverse transcriptase protein halts bacterial replich c spreading New within Bacterial reverse Transcriptase host bacteria and evolution: Bacterial reverse <precursors of those Transcripte found in eukaryotes, play rote in Genetic adaptation & anti-Humans, a telomerase, val defence mechanism etc .

Applications

  1. Solutions to AMR.
  2. Retrocements in Human genome.
  3. Gene editing tools for Biotech Not all junk.
  4. Treatment to wial ana infections.

Gene Therapy

  • Medical technique that involves modifying or manipulating genes to treat or prevent diseases.
  • Aims to correct genetic disorders at their root by introducing, removing, or altering genetic material within a person’s cells.

Promising Treatments

How is Gene Therapy done? Four approaches 1) Gene Augmentation addJunn gene 11) Gene Inhibition silencing of defective gene . (11) Gene Editing I use of CRISPR , TALEN IV) Cell-based Gene Therapy> Ex-vo modefic of patientscell Types : Somatic Gene therapy Gamline Gene therapy Delivery Methods of Gene Therapy Viral vectors Adeno associated Urus, Lentiviruses, Retroviruses. Non-Vural Methods ElectropolationCRISPR-based Liposomes Technologies gat based electric nanoparticle pulses to introduce DNA into cells AAV-why is it commonly used ! 1) Non-Pathogenic a safe . 11) Long-Term Gene Expression stable reduces risk of unwanted expressions (11) Minimal Immune response IV) Has FDA approval.

Gene Desert

  • A gene desert is a large region of DNA that lacks protein-coding genes. These regions make up a significant portion of the human genome but do not directly encode proteins.

Inflammatory Bowel Disease

  • Autoimmune disease; 5% of global population affected.

Research Findings

  • ETS2 gene associated with IBD. ETS2 cientests found anenhances gene in gene desat region expression of ETS2 gene

Cancer

  • Breakthrough in oncology.
  • Diagnosis: Traditional Methods Biopsus Surgeries; diagnostics New advancements in Cancer genetics NGS liquid biopsies. Traditional vs NGS
  • Mutation in DNA can alter all growth 2 function

H5N2

  • Is a subtype of the species Influenzavirus A (avian influenza virus or bird flu virus).
  • The subtype infects a wide variety of birds, including chickens, ducks, turkeys, falcons, and ostriches.
  • Affected birds usually do not appear ill, and the disease is often mild.
  • Big Data in Cancer Diagnosis: processing genetic data in real time. in Mexico Scripps Research Institute t. nanoparticlesa MIT N332! GT5 eOD-G78 Vaccine Challenge for HIV. Dr. Michael Gottileb -- Just cases of discovery of HIV AIDS (1981).

HIV

  • Extremely high rate of mutation. HIV variants sall influenza variants in a year. difficult for immune system to catch up. bn Abs Broadly-Neutralizing Anti-bodies found in small sub-set of patients. can neutralize multiple HIV stains Germline-targeting N332-GTS Higgea Identify precusor B-alls that can produce response eOD-G78 (mice 2 S monkey Boost these cells to their pope. mRNA vaccines demonstrated Trigger them to start easy to develop, producing bnAbs rapidly

Masld

*Alcoholic Fatty Liver Diseasenow,It is calledMetabolic dysfunction-associated steatotic Liver disease (MASLD) Insulin Resistance and Fatty LiverHigh glucose levels insulin product Constant Carb insulin Normal metabolismintakeresistance disturbedHow-ultrasoundLiveExcess Converte,fatty Glucose AcidEarly Detection Casymptomatic at early stage Diagnosis, lateFederation of Obstetric Comprehensive Immunisation ScheduleGynaecological Societies of India orgh list of vaccines and recommended frequency practioners of Obs2Gynal

World Health Assembly

  • The World Health Assembly(WHA) is the decision-making body of the World Health Organization (WHO). Held annually in Geneva, Switzerland at the WHO headquartersTruenat Platformrapid molecular testpulmonary, extra pulmonary, and rifampicin-resistance TB. Developed by Goa-based Molbio (molecular diagnostic company real-time quantitative micro-PCR portable battery operated can test to diseasesbeyond TUB Results in less then 1 Hour

Pathogen related test

  • Urine Dipstick Test: Most common test. 50-60% accuracy, leading to misdiagnosis and inappropriate antibiotic use. Determines the presence of infection but not the specific bacteria causing it. Laboratory Urine Culture: Gold standard for testing but takes 2-3 days for results. Delays in prescribing effective antibiotics, increasing AMR risk. PA-100 AST System by System Synergy Astrego phenotypic test - identifies bacteria causing infection. t antibiotic susceptibility delivers result in 45 minutes rational use of anti-biotic other tests Wine dipstick test (point of care test) Laboratory Wine Culture Longitude Price givenfor infection management, efforts to stop AMR

Research Insights

  • This research helps in understanding: Origins of the bubonic plague pandemic. Evolution of malarial parasites. Spread of the mpox virus. Historical occurrence of Down’s syndrome. scientists have analyzed ancient and modern genomes > Trace origins of medieval epidemic, Study dietary adaptations and genetic mutations Evidence of Genetic resistance the select to certain disease in specific in some popl immune genes Scientists have used saccharogenetics to study ancient burial sites archaeogenetic study of ancient DNA extracted from archaeological and historical remainsto understand human evolution, migrations, disease patterm

Kerala's Proactive Measures

  • Implemented ‘Rebuild Kerala’ project for H5N1 surveillance.
  • Launched ‘One Health’ approach in four districts: Alappuzha Pathanamthitta Kottayam Idukki Community surveillance: 2.5 lakh volunteers engaged in early detection. Village-level health units monitor and report sick animals/birds.
  • Alerts help in preventing further transmission.
  • Kerala, water bodies, migratory birds, owls, and integrated farms form part of the ecosystem. have reported HpN, outbreaks.

Gene Therapy Research

  • MoTA + AllMS /CRISPR-Cas9 based Gene Therapy The method has been approved by Current Research & Testing U.S FDA for a cell-based gene therapy conducted by CSIR Jos Sickle Cell Disease. and Institute of Genomics and Integrated Biology.
  • If successful <Clinical Trial Stage CRISPR expensive gout has prioritized this under Sickle All Disease Eradication Mission (2023-47) key areas of improvement Stanthening healthcare infla increasing access to screeningPolicy reform.

Genes and Counselling

ThreepillarsHealth Promotion-Awareness genes + pre-marital genetic counsellingPillars PreventionHolistic Management (screening & Early detect

Genomics Revolution in India

  • 99 ethnic groups. Genome Jan, 2024 DBT. sequencing of 10, 000 genomes Sequencing under Genome India' project. 2020 CSIR sequencing of 1,008 individuals - Multi-omics approach integrat of multi-omics data types to get a comprehensive understanding of biological processes, diseases and treatment response Genomics Transcriptomic-RNA molecula Multi- Proteomic proteins & Jun Omics > Metabolomia I small molecules involved in metabolism Epigenomic studies chemical modific on DNA that regulates gene activity 1 Genetics in TB treatment TB Bacteria mutations leading to AMR CSIR Whole Genome Sequencing of TB stains

PaReGD

  • Rare Genetic Disorders Paediatr Rare mission launched to Genetic Disorders map genetic disorders (PaRe GD) 2 facilitate early diagnosis funded by DBT, MoST, Gol Cancers Genome-based Cancer Treatment Indian Cancer Genome Consortium (ICGC-India focuses on genome sequencing to detect cancer-causing mutat Antimicrobial Resistance -understand AMR profile without growing in lab

Challenges in Zika Visu Surveillance

  • ⑪ CDSCO, no approved diagnostic tests Jos Zika in India diagnosis clinical suspicion/ classical symptomsNational Institute of Virology handles most sample but struggles due to high load
    4 Bharat Biotech's