Telomeres are vital for cellular function. Oxidative stress is detrimental to telomere function as it causes telomere attrition. Increase in oxidative stress has a negative impact on sperm telomere and chromatin integrity and therefore, on sperm function and male fertility. TERRA, a long non-coding RNA is a fundamental component required for telomere length homeostasis. Aim: The present work aimed to study the effect of H2O2 induced oxidative stress on sperm TERRA expression and chromatin function. Methodology: 5 infertile and 5 fertile males were selected for the study. Baseline semen analysis was done as per WHO manual 2021. Sperm TERRA expression was assessed by real time qPCR. To assess chromatin function nuclear chromatin decondensation test was done. Results: Study showed that 500µM H2O2 increased TERRA expression as compared to untreated groups and the difference was found to be statistically significant. As compared to controls, cases showed more fold increase in TERRA expression. When treated samples of control and cases were compared, cases had more TERRA expression than controls however, the baseline TERRA expressions in untreated samples were less in cases as compared to controls. Both comparisons yielded statistically nonsignificant results. When nuclear chromatin decondensation was compared before and after H2O2 treatment, the percentage of sperm head decondensation decreased in both cases and controls. When treated and untreated samples of cases and controls were compared, the difference was statistically nonsignificant. Conclusion: Oxidative stress led to an increase in the expression of sperm TERRA and had a negative impact on nuclear chromatin decondensation. Similar studies with greater sample size can provide much more insight into TERRA mediated regulation of telomere function and chromatin integrity and how it is affected by oxidative stress.
Chromatin immunoprecipitation (ChIP) coupled to quantitative real-time PCR (ChIP-qPCR) or Next-Generation Sequencing (ChIP-seq) enables us to study the dynamics of chromatin recruitment of transcription factors (TFs). The popular model system Caenorhabditis elegans has provided us with fundamental understanding of the role of Insulin/IGF-1-like signaling (IIS) in metabolism and aging. The FOXO TF DAF-16 is the major output of the pathway that regulates most of the phenotypes associated with the IIS pathway. Here, we describe a ChIP protocol to study FOXO recruitment dynamics in whole C. elegans extracts. We discuss detailed practical procedures, including optimization, growth, harvesting, formaldehyde fixation, sonication of worms, TF immunoprecipitation for further downstream processing using qPCR as well as NGS for the analysis of FOXO-bound DNA.
Over the past two decades, the roles of stem cells have been studied in the contexts of developmental biology, tissue engineering, cancer therapy, neurodegenerative disorders and what not! Right since the discovery of prostate specific adult stem cells or stem-like cells in both stromal and epithelial compartments, their participation in prostate development and prostatic pathologies (like benign prostatic hyperplasia and prostate cancer) are being thoroughly investigated. The present mini-review summarizes the ins and outs of the histological organization of acinar prostate and prostate cancer, keeping the prostate-specific epithelial stem cells on the backdrop.
Insulin/IGF-1-like signalling (IIS) and dietary restriction (DR) are the two major modulatory pathways controlling longevity across species. Here, we show that both pathways license a common chromatin modifier, ZFP-1/AF10. The downstream transcription factors of the IIS and select DR pathways, DAF-16/FOXO or PHA-4/FOXA, respectively, both transcriptionally regulate the expression of zfp-1. ZFP-1, in turn, negatively regulates the expression of DAF-16/FOXO and PHA-4/FOXA target genes, apparently forming feed-forward loops that control the amplitude as well as the duration of gene expression. We show that ZFP-1 mediates this regulation by negatively influencing the recruitment of DAF-16/FOXO and PHA-4/FOXA to their target promoters. Consequently, zfp-1 is required for the enhanced longevity observed during DR and on knockdown of IIS. Our data reveal how two distinct sensor pathways control an overlapping set of genes, using different downstream transcription factors, integrating potentially diverse and temporally distinct nutritional situations.
Lowering insulin-IGF-1-like signalling (IIS) activates FOXO transcription factors (TF) to extend life span across species. To study the dynamics of FOXO chromatin occupancy under this condition in C. elegans, we report the first recruitment profile of endogenous DAF-16 and show that the response is conserved. DAF-16 predominantly acts as a transcriptional activator and binding within the 0.5 kb promoter-proximal region results in maximum induction of downstream targets that code for proteins involved in detoxification and longevity. Interestingly, genes that are activated under low IIS already have higher DAF-16 recruited to their promoters in WT. DAF-16 binds to variants of the FOXO consensus sequence in the promoter proximal regions of genes that are exclusively targeted during low IIS. We also define a set of 'core' direct targets, after comparing multiple studies, which tend to co-express and contribute robustly towards IIS-associated phenotypes. Additionally, we show that nuclear hormone receptor DAF-12 as well as zinc-finger TF EOR-1 may bind DNA in close proximity to DAF-16 and distinct TF classes that are direct targets of DAF-16 may be instrumental in regulating its indirect targets. Together, our study provides fundamental insights into the transcriptional biology of FOXO/DAF-16 and gene regulation downstream of the IIS pathway.
Dietary restriction (DR) increases life span and delays the onset of age-related diseases across species. However, the molecular mechanisms have remained relatively unexplored in terms of gene regulation. InC. elegans, a popular model for aging studies, the FOXA transcription factor PHA-4 is a robust genetic regulator of DR, although little is known about how it regulates gene expression. We profiled the transcriptome and miRNAome of an eat-2 mutant, a genetic surrogate of DR, by Next Generation sequencing and find that most of the miRNAs are upregulated in the young-adult worms, none significantly downregulated. Interestingly, PHA-4 can potentially regulate the expression of most of these miRNA genes. Remarkably, many of the PHA-4-regulated genes that are induced during DR are also targets of the PHA-4-upregulated miRNAs, forming a large feed-forward gene regulatory network. The genes targeted by the feed-forward loops (FFLs) are enriched for functions related to ubiquitin-mediated decay, lysosomal autophagy, cellular signalling, protein folding etc., processes that play critical roles in DR and longevity. Together our data provides a framework for understanding the complex and unique regulatory network employed during DR, suggesting that PHA-4 employs such FFLs to fine-tune gene expression and instil robustness in the system during energy crisis.
The five day symposium was attended by 187 delegates from various universities, academic institutions, and research and development organizations from all over the world.Distinguished scientists from 12 countries, including USA, Japan, Germany, France, Hungary, Romania, Taiwan, and Bangladesh also participated in the Symposium.128 research papers, including 17 invited talks covering almost all important aspects of Geo-Hazards research were presented in the Symposium.The five day symposium was divided into fourteen technical sessions comprising seventeen invited talks, thirty five oral presentations and ninety poster presentations, covering almost all aspects of Geo-Hazards research, namely: earthquakes, volcanoes, landslides, floods, radiation hazards, and related topics.This Topical Issue "Geo-Hazards" of Acta Geophysica consists of selected papers, presented during the symposium.All selected papers on various issues of Geo-Hazards research were peer reviewed before accepting for publication.It contains an interesting finding by Friedemann Freund on the change in charge carriers in the ionosphere before an impending earthquake, which can be used to develop a reliable earthquake warning system in near future.The paper by Bansal and Verma highlights the seismic hazard assessment and mitigation study in India.The work on seismotectonic studies in the Himalayan region of India is reported by Biswas et al., Hazarika et al., and Choudhury et al.The studies of various earthquake precursors are presented in the papers by A.
The 5th Congress of the Federation of Immunological Societies of Asia Oceania (FIMSA) was organized jointly with the 39th annual conference of the Indian Immunology Society (IIS) in New Delhi from March 14–17, 2012. Founded in 1992 as a non-profit scientific organization, the Federation currently has twelve immunology societies as its full members (Australia, New Zealand, Japan, Korea, Thailand, Hong Kong, Singapore, Taiwan, China, Sri Lanka, Iran, and India) and a few others as associate members. It is one of the four major Federations of the International Union of Immunological Societies (IUIS), the other three being the European Federation of Immunological Societies (EFIS), the Latin American Association of Immunology (ALAI: Asociación Latinoamericana de Inmunología), and the Federation of African Immunological Societies (FAIS). These Federations have played a key role in promoting collaboration and communication between immunologists through educational programs with the objective of advancing this science in Asia. The central theme of the FIMSA 2012 meeting was “Translational Immuno-logy in health and disease” with the focus of the main talks being applied research, broadly modeled on the bench-to-clinic theme. The Congress was followed by the FIMSA/IUIS/IIS Advanced Course on Basic and Translational Immunology (March 18–20, 2012) which was attended by 70 young scientists at the doctoral and post doctoral level. The Congress was attended by over 600 participants representing 31 countries with the bulk coming from the various states of India. A special effort was made to encourage the participation of young immunologists and post doctoral scientists by providing them bursary support and a platform for competitive presentation. The Congress was held in Hotel Le Meridien which provided an excellent scientific ambience. Situated in the heart of Delhi, very close to the historical monuments, and with the weather turning out to be brilliant, the week-long activity was a perfect blend of high science and social interaction. The Congress format was organized into 10 master lectures delivered by experienced researchers, nine theme-based symposia with 54 invited speakers and six parallel workshop sessions featuring 65 oral presentations selected from over 400 submitted abstracts. In addition, there were two dedicated poster review sessions. The program covered a wide range of important topics that included the immunological basis of autoimmune and infectious diseases including HIV and type 1 diabetes, cross talk between innate and adaptive immunity, immunodeficiencies, issues related to organ and bone marrow transplantation, immunological tolerance, tumor immunology, stem cells and regenerative medicine and new developments towards vaccine, immune diagnostics and cell therapy. The organizing committee introduced e-poster presentation at this Congress as an effective means of promoting peer networking and healthy discussion. Twelve computer stations were provided and these displayed the submitted posters in 3–4 screen pages each. The participants had the opportunity to view, at their convenience, the allotted posters of each day on big screens by clicking the poster number of interest; this also facilitated the discussion of the data with others and with the poster judges. Six best posters (2 for each day of the Congress) were awarded a cash prize and certificate during the valedictory ceremony. The awards were made available through a small grant from International Immunology (facilitated by the Editor-in-chief, Tadamitsu Kishimoto), which is published by Oxford University Press, on behalf of the Japanese Society for Immunology. An important highlight of the Congress was the session ‘Ten best oral presentations’, the participants of which were selected by a panel of international experts. Several awards were instituted to recognize the hard work put in by young researchers, with the ultimate goal being to promote excellence in research. Another important feature of the Congress was the ‘Round Table discussion’ session highlighting the issues related to ‘Gender equality and career development’. In addition to the scientific sessions, the meeting had a vibrant social program and an opportunity for the participants to experience traditional Indian hospitality and various facets of the diverse Indian culture. The registration fee of the Congress was kept affordably low, taking into consideration the difficult global economic situation and the cuts that have hit the research community in recent years. Fortunately, the meeting received crucial support from 7 government sponsor agencies and 18 private sponsors (http://www.fimsa2012.com). A pre-Congress press meeting was organized on the 14th March to which representatives of leading newspapers and electronic media were invited so that the general public could be briefed about the main features of the Congress. Narinder Mehra, the President of the Congress and his colleagues gave an overview of the meeting and the importance of immunology in health and disease. Stefan Kaufmann (President of IUIS) spoke about the importance of vaccines and immunotherapeutics in every day life and Nicholas King (FIMSA President) gave a perspective of the federation and of its various activities. The Congress was officially inaugurated by Sir Gustav Nossal (Australia), together with Stefan Kaufmann (President of IUIS, Germany), Nicholas King (FIMSA Presi-dent, Australia), GP Talwar (India), Jacob Natvig (Norway) and the organizers led by Congress President Narinder Mehra (Fig. 1 and 2). The inaugural and keynote address was delivered by Sir Gustav Nossal (Fig. 2A) who spoke on the development status of various vaccines and highlighted that immunology with its impact on human health could help prevent two-thirds of premature deaths, particularly those with an infectious cause. Interestingly while life expectancy at birth in the more developed world has improved from 70 years in the 1960s to >80 years in 2011, that in African countries (e.g. Zambia) has actually shown a decline from 45 to 39 years. Sir Gustav Nossal advocated the creation of a global fund for vaccine research for the three big diseases AIDS, TB and malaria. Further, he discussed the progress of the RV144 phase II trial of the prime boost vaccine ALVAL prime-AIDS; RTS,S from Glaxo Smith Kline for malaria; and three vaccines for TB currently in phase II trials namely, AERAS-402 crucell Ad35, MVA85 A/AERAS 485, GSKMT72, a recombinant fusion protein of Agtb 32 and tb 39. The first day of the conference started with a fantastic master lecture on peripheral regulatory T (Treg) cells by Abul Abbas (USA). He described how the immune system adapts to pathogenic inflammatory reactions by generating Foxp3+ve Treg cells in the periphery. A fraction of these cells survive as memory Treg cells and are able to limit subsequent inflammation in the tissue. He also showed that antigens and cytokines are the major stimuli that induce peripheral Treg cells and control their balance with effector cells. This was immediately followed by the second master lecture, which was given by James McCluskey (Australia) on the genetic control of immune response. James McCluskey talked about the extensive polymorphism in HLA molecules and the implication of this for determining immune response variables, and the risk of developing autoimmune disease, allergic reactions and HLA-linked drug induced hypersensitivity. The morning of the second day of the conference saw another wonderful series of master lectures, this time delivered by Rafi Ahmed (USA) and Stefan Kaufmann (Germany). Rafi Ahmed described the human B-cell response to influenza virus in people infected with the 2009 H1N1 pandemic strain and discussed the novel vaccination approaches for this virus which has been extensively discussed during the past decade. Stefan Kaufmann focused his lecture on host-pathogen interactions in tuberculosis. He described the novel vaccination strategies based on the improved rBCG strain which expresses listeriolysin but is devoid of urease. He showed that this candidate vaccine induces better protection and has proven to be safer than the wild type parental BCG. This vaccine has already successfully entered a phase II clinical trial. He highlighted the importance of biomarkers that could help to (i) discriminate latently infected individuals and patients with active TB, (ii) monitor clinical vaccine and drug trial, (iii) define mechanisms of disease pathogenesis, resistance and susceptibility and (iv) finally predict the risk of disease development. The close of the second day saw two more master lectures. One was given by Narinder Mehra (India) who highlighted the clinical relevance of antibodies in transplantation, the range of technologies for their detection and the importance of defining donor-specific and anti-HLA antibodies both in pre- as well as post-transplant stages. Narinder Mehra particularly stressed the potential role of antibodies to MICA, the molecule expressed primarily on endothelial cells, in transplantation. The other master lecture was given by Shigeo Koyasu (Japan) who presented studies on the type 2 innate immune response as predicted by natural helper (NH) cells. He described the role of these cells in lymphoid clusters in adipose tissues, termed fat associated lymphoid clusters (FACCs). The NH cells produce Th2 cytokines constitutively and support self renewal of B1 cells and IgA production by B cells. The concluding day of the Congress started with the master lectures by GP Talwar and Vijay Kuchroo. GP Talwar gave an overview of immunological approaches for the control of fertility through vaccination against human chorionic gonadotropin (hCG), which prevents unwanted pregnancy without impairment of ovulation and derangement of menstrual regularity. Recent studies by the Talwar group suggest that this vaccine is likely to have therapeutic applications in the treatment of hormone dependant cancers. Vijay Kuchroo (USA) highlighted T-cell subsets, particularly the IL-17-producing Th17 cells and their reciprocal relationship for the generation and induction of autoimmunity and FoxP3 Treg cells that inhibit autoimmune tissue injury. He discussed the specific nodal points in cellular differentiation that get activated during Th17-cell development. The last two master lectures of the Congress were delivered by Xuetao Cao (China) and Reinhold Schmidt (Germany). The former described the innate signaling pathways and their role in immune regulation. Xuetao Cao discussed TLRs and RLHs and the miRNA-mediated regulation of innate and adaptive immune response by IFN expression and signaling. Reinhold Schmidt described the role of autoantibodies in autoimmune diseases and defects in antibody receptor in immune response inflammatory syndrome (IRIS). Reinhold Schmidt showed that the function of FcγR III and IV are each essential to trigger FcγR linker for activation of T-cell-dependent signals that drives C5a production in the Arthus reaction. The master lectures of the morning each day were followed by three parallel sessions of theme-based symposia. Symposium one focused on immune regulatory networks and started with the talk of Yousuke Takahama (Japan), who provided an overview of T lymphocyte repertoire formation in the selective thymic microenvironment. Following this, Hannes Stockinger (Austria) presented the work of his group on a new ultrasensitive live cell-imaging technique for studying immune reactions, which made effective use of the visualization of lipid rafts in living cells for the first time. Another speaker Paola Castagnoli (Singapore) highlighted the role of NFAT signaling in myeloid hematopoiesis and DC activation. An Indian scientist Subhadha Chiplunkar presented novel findings on Notch and its role in regulating the anti-tumor effector functions of γδ T lymphocytes. Joshy Jacob (USA) showed that CD28 expressed on T cells plays an important part in the regulation of short- and long-lived plasma cells. The last talk of this symposium was delivered by Satyajit Rath (India) who described the role of apoptosis-inducing factor (Aif) in regulating death in the T-cell lineage. The second parallel symposium focused on host-pathogen interactions and started with the talk of Guna Karupiah (Australia), who showed that tumor necrosis factor (TNF) plays an anti-inflammatory role in the host response to Ectromelia virus (ECTV) infection. The lecture of Gennaro de Libero (Switzerland) discussed thelarge number of T cells that recognize non-peptide antigens presented by non-MHC molecules, and the involvement of these T-cell populations in infections and their functional capacities. Thereafter three Indian scientists Dipendra K Mitra, Javed Agrewal and Natrajan Krishnamurthy working in the field of immunology of tuberculosis presented the results of their most recent work. Dipendra Mitra provided an overview of the T-cell response in human tuberculosis, Javed Agrewala showed that the lipidated promiscuous peptide restrains the progression of Mycobacterium tuberculosis by activating innate and prolonging adaptive immunity. Natrajan Krishnamurthy introduced the audience to the importance of calcium homeostasis during mycobacterial infection and presented a potential new strategy regarding adjunct therapy for drug resistant TB using S-amlodipine which may be a new player in the fight against multi drug resistant tuberculosis. Surasakdi Wongratanacheewin (Thailand) showed how a helminth parasite, Opisthorchis Viverrini, uses its antigens to modulate the host immune response by stimulating regulatory cytokines leading to evasion of the host immune response by and survival of the parasite. The theme of the third symposium was Treg cells, cytokines and inflammation, which started with a lecture by Bhagirath Singh (Canada) who highlighted the properties of two populations of Th17 cells — one being pathogenic and the other protective. In addition, Bhagirath Singh stressed the controversial nature of Th17 cells in autoimmunity. Cindy Mah (Australia) introduced a relatively recently identified T-cell subset, i.e. T follicular helper (Tfh) cells, a subset of CD4+ T cells that localize to B-cell follicles where they are positioned so as to provide help to B cells. Nicholas King reported that timed interference of specific leukocyte subset migration can significantly increase survival without compromising sterilizing immunity in lethal neurotropic flavivirus infaction. Sudhir Gupta (USA) and Vineeta Bal (India) discussed the impact of ageing on various cell lineages, including T lymphocytes and DCs. The fourth theme focused on tumor and transplant immunology. It started with a lecture by Jonathan Sprent (Australia) who discussed the expansion of T-cell subsets using IL-2-/mab complexes and the implications of such expanded T-cell subsets for immunity and transplant tolerance. Rajiv Khanna (Australia) presented that his group, in collaboration with an Australian biotech company (Cellestis Inc.), has successfully developed a novel T-cell-based immune monitoring technology (QuantiFERON-CMV) that allows the identification of high risk transplant patients i.e. those who may develop virus-associated complications post-transplantation. Catherine Fridman (France) showed that in human primary non small cell lung cancers (NSCLCs), the tumor microenvironment may impair NK cells locally, making them less prone to kill tumors and hence contributing to cancer progression. Nina Bhardwaj (USA) presented an overview of the tumor microenvironment and showed that tumors secrete factors that modulate both innate and adaptive immunity. Koji Nomota (Japan) introduced the role of probiotics as efficient immunopotentiators, describing their translational role in cancer prevention. Symal Roy (India) presented that the poor stability of peptide-MHC complexes may determine defective cellular immunity in Leishmaniasis. The topic of the fifth symposium was adjuvants and vaccines. During her talk, Olivera Finn (USA) supported the feasibility of vaccinating individuals at high risk for developing cancer in order to prevent its recurrence or progression. Nilabh Shastri (USA) described an antigen ‘Toxo’ derived from Toxoplasm gondi which is to be used as a new vaccine target for this eukaryotic parasite. Gregory Tsay (Taiwan) suggested that RNA interference targeting IL-10 is an effective strategy to silence the IL-10 pathway and has therapeutic potential that could be useful in the management of SLE and possibly other immune-mediated disorders. Chetan Chitnis (India) and Nirbhay Kumar (USA) presented their research work which is moving towards the development of a vaccine against malaria. Sunil Arora (India) highlighted one of the reasons for the success of antiviral therapy in chronic hepatitis C infection which relates to the functional status of myeloid dendritic cells (mDCs) in these patients. The sixth symposium covered the broad theme of autoimmunity, featuring discussions on the genetic and functional aspects of autoimmune diseases. Chella David (USA) and Kamal Moudgil (USA) unraveled novel aspects of autoimmune pathogenesis. The role of complement in RA and SLE, with a main focus on B-cell functions, was highlighted by Anna Erdei (Hungary). Veena Taneja (USA) described the importance of the interaction between the HLA gene products and gut microbes in the development of rheumatoid arthritis. Moncef Zouali (France) and Rahul Pal (India) gave an overview of new pathways and new targets in autoimmune diseases. The theme-based symposium of the last day of the Congress featured talks on immune mechanisms underlying infectious diseases. In this session, Miles Davenport (Australia) explained that the CD8+ T-cell response to viral infection involves the recruitment of multiple different T-cell clonotypes, each bearing a unique T-cell receptor. Nageshwar Rao (India) discussed the mechanism leading to immune suppression during the progression of leprosy from tuberculoid to lepromatous, namely the overproduction of CD4+CD25+/FoxP3+ cells. Padmini Salgame (USA) showed that the T helper and regulatory response induced by helminths could modulate the host protective response against M. tuberculosis. Suresh Mahalingam (Australia) highlighted the link between viral infections and inflammatory disease focusing on the Chikungunia virus. Symposium 8 started with a theme focused on infections, immunodeficiencies and HIV. The first speaker of this symposium, Rose Ffrench (Australia), presented data on the production of interferon-lambda in chronic HCV infection. This was followed by Gurvinder Kaur (India) who discussed the genetic architecture of HIV infection particularly in relation to disease susceptibility, progression and transmission. Gurvinder Kaur's lecture focused on three sets of immuno-regulatory molecules and their genetic polymorphisms, namely HLA, chemokines and cytokine gene polymorphisms. Stanley Schwartz (USA) linked the application of nanotechnology to HIV infection and Madhu Vajpayee (India) discussed the abnormal behavior of T cells in HIV. Ashok Kumar (USA) and Nirupama Trehanpati (India) focused on the immunology of ocular infectious disease and HBV infection in newborns respectively. The theme of the last symposium covered cell therapy using DCs, stem cells and NKT cells. Jose Villadangos (Australia) acquainted the audience with the cell biology of pathogen detection, processing and presentation by DCs. Similarly, Ram Raj Singh (USA) discussed the mechanisms and role of Langerhans cells in auto-immune skin inflammation. Dominique Charron (France) highlighted the challenges faced during stem cell therapy including allogenicity and immunogenicity. The last lecture of this symposium was delivered by Stephen Minger (UK) on the therapeutic and research potential of human stem cells. The afternoon session of the first day included three parallel workshops on immune regulatory mechanisms, infection, immunity, autoimmunity and tolerance. The workshop sessions of the third day were devoted to the topics of tumor and transplant immunology, vaccines, adjuvants and diagnostics. These sessions included short oral presentations selected from the submitted abstracts on a competitive basis and consisted mostly of young scientists presenting their research work. Uma Kanga as joint organizing secretary of the Congress put in a lot of hard work in getting more than 400 submitted abstracts evaluated according to specified criteria by about 40 senior immunologists drawn from various countries in the region. Based on the evaluations the abstracts were grouped into posters or oral presentations and, of the latter, those ranked in the top ten were included in a separate session. One of the highlights of the FIMSA 2012 Congress was the ‘Ten best oral presentations’ session in which 10 participants, selected by a panel of experts on the basis of their submitted abstracts, presented their work in the spirit of healthy competition. A panel of judges then selected the best three for an award of US$ 500 each, kindly made available by the Annals of the New York Academy of Sciences (facilitated by the Editor-in-Chief, Douglas Braaten), which is published by Wiley on behalf of The New York Academy of Sciences. The awardees included Khalid Hussain Bhatt (India), Fatima Mami Chouaib (France) and Neeraj Kumar (India). The evening of the first day was occupied by a round table session on the very important topic of Gender Equality and Career Development and it was very keenly attended by a large gathering. The session was moderated by Olivera Finn (USA) and Narinder Mehra (India). Nirmal Ganguly (India) presented an overview of the global scenario with particular reference to the lack of opportunities to woman scientists, even in an economically advancing country like India. The panelists who took an active part in discussion included Paola Castagnoli (Singapore), Geetha Bansal (USA), Krishan Lal (President, Indian National Science Academy), Amarjeet Chandhiok (Additional Solicitor General, Govt of India), and Rose Ffrench (Australia). The list of all those who helped in making the FIMSA 2012 Congress a great success is too exhaustive; nevertheless the organizers take this opportunity to express their grateful thanks to all without naming individuals. It is highly satisfying that the Congress format of master lectures, theme-based symposia and oral workshop sessions were much appreciated. The meeting witnessed a full house attendance on all three days, thanks to the participation of a large number of young and enthusiastic scientists. The inclusion of (i) Ten Best Oral Presentations session, (ii) round table discussion on gender equality issues and (iii) the concept of ePoster viewing (Fig. 3) turned out to be the three major highlights of the meeting.
X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and adrenal cortex secondary to mutations in the ABCD1 gene that encode the peroxisomal membrane protein. We conducted a genomic and protein expression study of susceptibility gene with its clinical and biochemical analysis. To the best of our knowledge this is the first preliminary comprehensive study in Indian population that identified novel mutations and SNPs in a relatively large group. We screened 17 Indian indigenous X-linked adrenoleukodystrophy cases and 70 controls for mutations and SNPs in the exonic regions (including flanking regions) of ABCD1 gene by direct sequencing with ABI automated sequencer along with Western blot analysis of its endogenous protein, ALDP, levels in peripheral blood mononuclear cells. Single germ line mutation was identified in each index case in ABCD1 gene. We detected 4 novel mutations (2 missense and 2 deletion/insertion) and 3 novel single nucleotide polymorphisms. We observed a variable protein expression in different patients. These findings were further extended to biochemical and clinical observations as it occurs with great clinical expression variability. This is the first major study in this population that presents a different molecular genetic spectrum as compared to Caucasian population due to geographical distributions of ethnicity of patients. It enhances our knowledge of the causative mutations of X-ALD that grants holistic base to develop effective medicine against X-ALD.
A large number of ABCD1 gene mutations have been reported all over the world, but not previously in India. We report on the first known patient with childhood cerebral adrenoleukodystrophy and a de novo 3' splice-site mutation in this gene. Magnetic resonance imaging of the brain revealed large, confluent, hyperintense areas in the bilateral cerebral white matter, predominantly parieto-occipital, with extensions into posterior regions that led to breakdown of the blood-brain barrier. An increased level of very long chain fatty acids was also consistent with the biochemical defect for adrenoleukodystrophy. Sequencing of the ABCD1 gene of this patient identified a 3' splice-site mutation in the intervening sequence 4 (-2a > g). We did not find any mutation in the gene of the proband's mother, which confirms its de novo occurrence.