The etiology of Down syndrome: Maternal MCM9 polymorphisms increase risk of reduced recombination and nondisjunction of chromosome 21 during meiosis I within oocyte.

Altered patterns of recombination on 21q have long been associated with the nondisjunction chromosome 21 within oocytes and the increased risk of having a child with Down syndrome. Unfortunately the genetic etiology of these altered patterns of recombination have yet to be elucidated. We for the first time genotyped the gene MCM9, a candidate gene for recombination regulation and DNA repair in mothers with or without children with Down syndrome. In our approach, we identified the location of recombination on the maternal chromosome 21 using short tandem repeat markers, then stratified our population by the origin of meiotic error and age at conception. We observed that twenty-five out of forty-one single nucleotide polymorphic sites within MCM9 exhibited an association with meiosis I error (N = 700), but not with meiosis II error (N = 125). This association was maternal age-independent. Several variants exhibited aprotective association with MI error, some were neutral. Maternal age stratified characterization of cases revealed that MCM9 risk variants were associated with an increased chance of reduced recombination on 21q within oocytes. The spatial distribution of single observed recombination events revealed no significant change in the location of recombination among women harbouring MCM9 risk, protective, or neutral variant. Additionally, we identified a total of six novel polymorphic variants and two novel alleles that were either risk imparting or protective against meiosis I nondisjunction. In silico analyses using five different programs suggest the risk variants either cause a change in protein function or may alter the splicing pattern of transcripts and disrupt the proportion of different isoforms of MCM9 products within oocytes. These observations bring us a significant step closer to understanding the molecular basis of recombination errors in chromosome 21 nondisjunction within oocytes that leads to birth of child with Down syndrome.

Down Syndrome Biobank Consortium: A perspective.

Individuals with Down syndrome (DS) have a partial or complete trisomy of chromosome 21, resulting in an increased risk for early-onset Alzheimer's disease (AD)-type dementia by early midlife. Despite ongoing clinical trials to treat late-onset AD, individuals with DS are often excluded. Furthermore, timely diagnosis or management is often not available. Of the genetic causes of AD, people with DS represent the largest cohort. Currently, there is a knowledge gap regarding the underlying neurobiological mechanisms of DS-related AD (DS-AD), partly due to limited access to well-characterized brain tissue and biomaterials for research. To address this challenge, we created an international consortium of brain banks focused on collecting and disseminating brain tissue from persons with DS throughout their lifespan, named the Down Syndrome Biobank Consortium (DSBC) consisting of 11 biobanking sites located in Europe, India, and the USA. This perspective describes the DSBC harmonized protocols and tissue dissemination goals.

Genetic aetiology of Down syndrome birth: novel variants of maternal DNMT3B and RFC1 genes increase risk of meiosis II nondisjunction in the oocyte.

The aim of the present work was to explore the intriguing association of maternal folate regulator gene polymorphisms and mutations with the incidence of chromosome 21 nondisjunction and Down syndrome birth. We tested polymorphisms/mutations of DNMT3B and RFC1 genes for their association with meiotic errors in oocyte among the 1215 Down syndrome child-bearing women and 900 controls. We observed that 23 out of 31 variants of DNMT3B and RFC1 exhibited an association with meiosis II nondisjunction in maternal age-independent manner. Additionally, we have reported 17 novel mutations and 1 novel polymorphic variant that are unique to the Indian Bengali speaking cohort and increased odds in favour of meiosis II nondisjunction. We hypothesize that the risk variants and mutations of DNMT3B and RFC1 genes may cause reduction in two or more recombination events and also cause peri-centromeric single exchange that increases the risk of nondisjunction at any age of women. In silico analyses predicted the probable damages of the transcripts or proteins from the respective genes owing to the said polymorphisms. These findings from the largest population sample tested ever revealed that mutations/polymorphisms of the genes DNMT3B and RFC1 impair recombination that leads to chromosome 21 nondisjunction in the oocyte at meiosis II stage and bring us a significant step closer towards understanding the aetiology of chromosome 21 nondisjunction and birth of a child with Down syndrome to women at any age.

Effects of plant growth retardant daminozide (Alar) on neuromuscular co-ordination behavior in Drosophila melanogaster.

Daminozide (alar), a plant growth retardant, is used in different fruit orchard to make fruits attractive and reduce pre-harvest losses. Previously data demonstrated that acute daminozide exposure affected reproductive fitness and produced neurodegeneration in Drosophila melanogaster. The goal of this study was to determine whether continuous exposure to daminozide affects neuromuscular co-ordination in D. melanogaster as manifested in various behavioral responses. Fruit flies were exposed to 200 or 400 mg/L concentration of daminozide for two successive generations. Treated D. melanogaster were examined for the behaviors indicative of neuromuscular coordination and cognitive abilities, that include climbing, social interaction, adult grooming, migration, flight, male aggression, and adult courtship. Aberrant behavioral responses were noted among treated D. melanogaster of both sexes as evidenced by the following parameters: reduction in flight duration, abnormal social interaction, altered copulatory acts, and over-aggressiveness. Data suggest that daminozide produces impairment in neuromuscular coordination and cognitive ability in Drosophila, which was reflected as altered behavioral patterns. As Drosophila is considered as a reliable in vivo model utilized in toxicity testing, our findings may help us to anticipate and monitor potential daminozide-induced toxicity in animals and humans.

Novel variations in spermatogenic transcription regulators RFX2 and TAF7 increase risk of azoospermia.

PURPOSE: Genetic etiology of idiopathic male infertility is enigmatic owing to involvement of multiple gene regulatory networks in spermatogenesis process. Any change in optimal function of the transcription factors involved in this process owing to polymorphisms/mutations may increase the risk of infertility. We investigated polymorphisms/mutations of spermatogenic transcription regulators TAF7 and RFX2 and analysed their association with incidence of azoospermia among the men from West Bengal, India. METHODS: Genotyping was carried by Sanger's dideoxy sequencing of 130 azoospermic men who were detected negative in Y chromosome microdeletion screening and 140 healthy controls. Association study was done by suitable statistical methods. In silico analysis was performed to infer the intuitive damaging effects of detected variants at transcripts and protein level. RESULTS: We found significant association of TAF7 C16T (MW827584 G > A), RFX2 562delT (MZ560629delA), rs11547633 A > C, rs17606721 A > G, MW827583 C > T, and MZ379836 C > T variants with the incidence of azoospermia. In silico analysis predicted that the variants either alter the natural splice junctions of the transcript or cause probable damage in the structure of proteins of respective genes. CONCLUSION: Polymorphisms/mutations of TAF7 and RFX2 genes increase risk of male infertility in Bengali population. The novel variants may be used as markers for male infertility screening in ART practise.

Risk of Down syndrome birth: Consanguineous marriage is associated with maternal meiosis-II nondisjunction at younger age and without any detectable recombination error.

Consanguineous marriage was examined as a risk factor for Down syndrome birth. We genotyped Down syndrome family trios using short tandem repeat markers on 21q-to interpret the parental and meiotic stage of origin of errors as well as to record recombination profile along long arm of chromosome 21. We then compared nonconsanguineous (N = 811) group with-the consanguineous (N =157) marriages. We report for the first time that consanguineous marriage is associated with an increased risk for nondisjunction of chromosome 21 in oocytes-during the second meiotic division. We observed the absence of recombination more frequently in younger mothers in nonconsanguineous meiosis I cases. This was in contrast to an equal distribution of nonrecombinant cases across the age categories in the meiosis I consanguineous group. Moreover, the non-consanguineous group exhibited preferential telomeric recombination in meiosis I error among younger women and centromeric recombination in meiosis II errors in older women. In contrast, the consanguineous group exhibited medially placed recombination events in both meiosis I and meiosis II nondisjunction errors. Additionally, we recorded reduced maternal age at conception in the-consanguineous group. These findings suggest novel risk factors associated that increase the risk of chromosome 21 nondisjunction in the families with consanguinity.

Combined association of Presenilin-1 and Apolipoprotein E polymorphisms with maternal meiosis II error in Down syndrome births.

Alzheimer's disease and Down syndrome often exhibit close association and predictively share common genetic risk-factors. Presenilin-1 (PSEN-1) and Apolipoprotein E (APOE) genes are associated with early and late onset of Alzheimer's disease, respectively. Presenilin -1 is involved in faithful chromosomal segregation. A higher frequency of the APOE ε4 allele has been reported among young mothers giving birth to Down syndrome children. In this study, 170 Down syndrome patients, grouped according to maternal meiotic stage of nondisjunction and maternal age at conception, and their parents were genotyped for PSEN-1 intron-8 and APOE polymorphisms. The control group consisted of 186 mothers of karyotypically normal children. The frequencies of the PSEN-1 T allele and TT genotype, in the presence of the APOE ε4 allele, were significantly higher among young mothers (< 35 years) with meiosis II nondisjunction than in young control mothers (96.43% vs. 65.91% P = 0.0002 and 92.86% vs. 45.45% P < 0.0001 respectively) but not among mothers with meiosis I nondisjunction. We infer that the co-occurrence of the PSEN-1 T allele and the APOE ε4 allele associatively increases the risk of meiotic segregation error II among young women.

Novel Mutations Reduce Expression of Meiotic Regulators SYCE1 and BOLL in Testis of Azoospermic Men from West Bengal, India.

We investigated the polymorphisms/mutations in synaptonemal complex central element protein 1 (SYCE1) and CDC25A mRNA-binding protein (BOLL) to test whether they increase the risk of azoospermia among Bengali-speaking men from West Bengal, India. Sanger's dideoxy sequencing was used to genotype 140 azoospermic individuals who tested negative for Y chromosome microdeletion and 120 healthy controls. In both cases and controls, qRT-PCR was used to determine the expression summary of SYCE1 and BOLL. The perceived harmful consequences of identified mutations were inferred using in silico analysis. Suitable statistical approaches were used to conduct the association study. We found SYCE1 177insT (ON245141), 10650T > G (ON257012), 10093insT (ON257013), 10653insG (ON292504), rs10857748A > G, rs10857749G > A, and rs10857750T > A and BOLL 7708T > A (ON245141insT), rs72918816T > C, and rs700655C > T variants with the prevalence of azoospermia. Data from qRT-PCR and in silico studies projected that the variations would either disrupt the transcript's natural splice junctions or cause probable damage to the structure of the genes' proteins. SYCE1 gene variants [177insT (ON245141), 10650T > G (ON257012), 10093insT (ON257013), 10653insG (ON292504), rs10857748A > G, rs10857749G > A, rs10857750T > A] and BOLL gene variants [7708T > A (ON245141insT), rs72918816T > C, rs700655C > T] reduce the expression of respective gene in testicular tissue among azoospermic male as revealed from qRT-PCR result. These genetic variations could be utilized as screening tools for male infertility to determine the best course of treatment in routine ART practise.

Fruit ripening retardant Daminozide induces cognitive impairment, cell specific neurotoxicity, and genotoxicity in Drosophila melanogaster.

BACKGROUND: We explored neurotoxic and genotoxic effects of Daminozide, a fruit ripening retardant, on the brain of Drosophila melanogaster, based on our previous finding of DNA fragmentation in larval brain cell in the flies experimentally exposed to this chemicals. METHODS: Adult flies were subjected to two distinct concentrations of daminozide (200 mg/L and 400 mg/L) mixed in culture medium, followed by an examination of specific behaviors such as courtship conditioning and aversive phototaxis, which serve as indicators of cognitive functions. We investigated brain histology and histochemistry to assess the overall toxicity of daminozide, focusing on neuron type-specific effects. Additionally, we conducted studies on gene expression specific to neuronal function. Statistical comparisons were then made between the exposed and control flies across all tested attributes. RESULTS: The outcome of behavioral assays suggested deleterious effects of Daminozide on learning, short term and long term memory function. Histological examination of brain sections revealed cellular degeneration, within Kenyon cell neuropiles in Daminozide-exposed flies. Neurone specific Immuno-histochemistry study revealed significant reduction of dopaminergic and glutaminergic neurones with discernible reduction in cellular counts, alteration in cell and nuclear morphology among daminozide exposed flies. Gene expression analyses demonstrated upregulation of rutabaga (rut), hb9 and down regulation of PKa- C1, CrebB, Ace and nAchRbeta-1 in exposed flies which suggest dysregulation of gene functions involved in motor neuron activity, learning, and memory. CONCLUSION: Taken together, our findings suggests that Daminozide induces multifaceted harmful impacts on the neural terrain of Drosophila melanogaster, posing a threat to its cognitive abilities.

Tuning the solution phase photophysics of two de novo designed hydrogen bond sensitive 9-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one derivatives.

Two new fluorophores, 6,7-dimethoxy-9-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (DMTCO) and 5-methyl-8,9-dihydro-5H-[1,3]dioxolo[4,5-b]carbazol-6(7H)-one (MDDCO), first of their kind, have been synthesized from the corresponding methoxy and methylenedioxy derivatives of 2,3,4,9-tetrahydro-1H-carbazol-1-one respectively. Comprehensive photophysical characterization of these compounds has been carried out in sixteen different homogeneous solvents and binary solvent mixtures. Both of these compounds are sensitive to solvent polarity, but the sensitivity is much higher in electronic excited state observed by steady-state and time-resolved fluorescence experiments than in ground state studied by UV-vis absorption spectroscopy. The fluorescence spectral shifts are linearly correlated with the empirical parameters of the protic solvents and also the quantitative influence of the empirical solvent parameters on the emission maxima of the compounds has been calculated. The change in dipole moment of the compounds in their excited state has been calculated from the shifts in corresponding emission maxima in pure solvents. A higher dipole moment change of both DMTCO and MDDCO in protic solvents is due to intermolecular hydrogen bonding which is further confirmed by the comparison of their behaviour in toluene-acetonitrile and toluene-methanol solvent mixtures. From structural features, MDDCO is more planar compared to DMTCO, which is reflected better in fluorescence quenching of the former with organic bases, N,N-dimethylaniline and N,N-diethylaniline. Laser flash photolysis experiments prove that the quenching interaction originates from photoinduced electron transfer from the bases to the compounds.

Novel Mutations of TSPY1 Gene Associate Spermatogenic Failure Among Men.

Etiology of male infertility is intriguing owing to complex genetic regulation of human spermatogenesis and ethnic variations in genetic architecture of human populations. The present study characterizes the role of Y chromosome specific spermatogenic regulator testis-specific protein Y-encoded 1 (TSPY1) gene mutation in spermatogenic failure. This case-control study includes 163 cases of spermatogenic failure and 175 age-matched fertile men as controls. We found five novel base substitutions, namely, MT162695, MN879413, MN889982, MN889983, MN719943, two deletions MN734578 and MN734579, three novel insertions MN719941, MN719942 and MN719944 through Sanger's dideoxy sequencing of TSPY1 gene reading frame. All these mutations exhibited strong association with male infertility. In silico analyses suggest prospective disruption in splice sites and alteration in different isoforms of TSPY1 transcripts and amino acid sequence in TSPY1 protein. The study provides novel evidence in favour of implication of TSPY1 gene in male fertility. The outcome sheds light to get insight into the issue of idiopathic male infertility in Bengali population.

Evaluation of potency of the selected bioactive molecules from Indian medicinal plants with MPro of SARS-CoV-2 through in silico analysis.

BACKGROUND: The recent outbreak of the novel SARS-CoV-2 across the globe and the absence of specific drug against this virus lead the scientific community to look into some alternative indigenous treatments. India as a hub of Ayurvedic and medicinal plants can shed light on its treatment using specific active bio-molecules from these plants. OBJECTIVES: Keeping our herbal resources in mind, we were interested to inquire whether some phytochemicals from Indian spices and medicinal plants can be used as alternative therapeutic agents in contrast to synthetic drugs. MATERIALS AND METHODS: We used in silico molecular docking approach to test whether bioactive molecules of herbal origin such as hyperoside, nimbaflavone, ursolic acid, 6-gingerol, 6-shogaol and 6-paradol, curcumin, catechins and epigallocatechin, α-Hederin, piperine could bind and potentially block the Mproenzyme of the SARS-CoV-2 virus. RESULTS: Ursolic acid showed the highest docking score (-8.7 kcal/mol) followed by hyperoside (-8.6 kcal/mol), α-Hederin (-8.5 kcal/mol) and nimbaflavone (-8.0 kcal/mol). epigallocatechin, catechins, and curcumin also exhibited high binding affinity (Docking score -7.3, -7.1 and -7.1 kcal/mol) with the Mpro. The remaining tested phytochemicals exhibited moderate binding and inhibitory effects. CONCLUSION: This finding provides a basis for biochemical assay of tested bioactive molecules on SARS-CoV-2 virus.

Anti-biofilm efficacy of green-synthesized ZnO nanoparticles on oral biofilm: In vitro and in silico study.

The development of biofilm on the biotic and abiotic surfaces is the greatest challenge for health care sectors. At present times, oral infection is a common concern among people with an unhealthy lifestyle and most of these biofilms-associated infections are resistant to antibiotics. This has increased a search for the development of alternate therapeutics for eradicating biofilm-associated infection. Nanobiotechnology being an effective way to combat such oral infections may encourage the use of herbal compounds, such as bio-reducing and capping agents. Green-synthesis of ZnO nanoparticles (ZnO NP) by the use of the floral extract of Clitoria ternatea, a traditionally used medicinal plant, showed stability for a longer period of time. The NPs as depicted by the TEM image with a size of 10 nm showed excitation spectra at 360 nm and were found to remain stable for a considerable period of time. It was observed that the NPs were effective in the eradication of the oral biofilm formed by the major tooth attacking bacterial strains namely Porphyromonsas gingivalis and Alcaligenes faecalis, by bringing a considerable reduction in the extracellular polymeric substances (EPS). It was observed that the viability of the Porphyromonsas gingivalis and Alcaligenes faecalis was reduced by NP treatment to 87.89 ± 0.25% in comparison to that of amoxicillin. The results went in agreement with the findings of modeling performed by the use of response surface methodology (RSM) and artificial neural network (ANN). The microscopic studies and FT-IR analysis revealed that there was a considerable reduction in the biofilm after NP treatment. The in silico studies further confirmed that the ZnO NPs showed considerable interactions with the biofilm-forming proteins. Hence, this study showed that ZnO NPs derived from Clitoria ternatea can be used as an effective alternative therapeutic for the treatment of biofilm associated oral infection.

Differences in clinical presentation, severity, and treatment of COVID-19 among individuals with Down syndrome from India and high-income countries: Data from the Trisomy 21 Research Society survey.

Background: People with Down syndrome (DS) are one of the highest risk groups for mortality associated with COVID-19, but outcomes may differ across countries due to different co-morbidity profiles, exposures, and societal practices, which could have implications for disease management. This study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and several high-income countries (HICs). Methods: We used data from an international survey to examine the differences in disease manifestation and management for COVID-19 patients with DS from India vs HIC. De-identified survey data collected from April 2020 to August 2021 were analysed. Results: COVID-19 patients with DS from India were on average nine years younger than those from HICs. Comorbidities associated with a higher risk for severe COVID-19 were more frequent among the patients from India than from HICs. Hospitalizations were more frequent among patients from India as were COVID-19-related medical complications. Treatment strategies differed between India and HICs, with more frequent use of antibiotics in India. The average severity score of 3.31 was recorded for Indian DS in contrast to 2.3 for European and 2.04 for US cases. Conclusions: Presentation and outcomes of COVID-19 among individuals with DS were more severe for patients from India than for those from HIC. Global efforts should especially target vaccination campaigns and other risk-reducing interventions for individuals with DS from low-income countries.

COVID-19 Vaccination of Individuals with Down Syndrome-Data from the Trisomy 21 Research Society Survey on Safety, Efficacy, and Factors Associated with the Decision to Be Vaccinated.

Individuals with Down syndrome (DS) are among the groups with the highest risk for severe COVID-19. Better understanding of the efficacy and risks of COVID-19 vaccines for individuals with DS may help improve uptake of vaccination. The T21RS COVID-19 Initiative launched an international survey to obtain information on safety and efficacy of COVID-19 vaccines for individuals with DS. De-identified survey data collected between March and December 2021 were analyzed. Of 2172 individuals with DS, 1973 (91%) had received at least one vaccine dose (57% BNT162b2), 107 (5%) were unvaccinated by choice, and 92 (4%) were unvaccinated for other reasons. Most participants had either no side effects (54%) or mild ones such as pain at the injection site (29%), fatigue (12%), and fever (7%). Severe side effects occurred in <0.5% of participants. About 1% of the vaccinated individuals with DS contracted COVID-19 after vaccination, and all recovered. Individuals with DS who were unvaccinated by choice were more likely to be younger, previously recovered from COVID-19, and also unvaccinated against other recommended vaccines. COVID-19 vaccines have been shown to be safe for individuals with DS and effective in terms of resulting in minimal breakthrough infections and milder disease outcomes among fully vaccinated individuals with DS.

Understanding etiology of chromosome 21 nondisjunction from gene × environment models.

Maternal risk factors and their interactions with each other that associate chromosome 21 nondisjunction are intriguing and need incisive study to be resolved. We determined recombination profile of nondisjoined chromosome 21 and maternal genotypes for four selected polymorphic variants from the folate regulators genes stratifying the women according to the origin of segregation error and age at conception. We conducted association study for genotype and maternal addiction to smokeless chewing tobacco, usually chopped tobacco leaves or paste of tobacco leaves with the incidence of Down syndrome birth. Additionally, we designed various logistic regression models to explore the effects of maternal genotype, maternal habit of smokeless chewing tobacco, maternal age at conception and all possible interactions among them on chromosome 21 nondisjunction. We found folate regulator gene mutations are associated with maternal meiosis II error. Regression models revealed smokeless chewing tobacco and folate polymorphic/mutant risk genotype interact with each other to increase the risk of reduced and single peri-centromeric recombination events on chromosome 21 that nondisjoined at meiosis II in the oocytes and the effect is maternal age independent. We inferred maternal folate polymorphic/mutant risk genotypes and habit of smokeless chewing tobacco interact with each other and increase the risk of meiosis II error in oocytes in maternal age-independent manner.

Genes regulating development and behavior exhibited altered expression in Drosophila melanogaster exposed to bisphenol A: use of real-time quantitative PCR (qRT-PCR) and droplet digital PCR (ddPCR) in genotoxicity study.

Toxicity of bisphenol A on morphological and life-history traits of model insect Drosophila melanogaster was reported in our previous work. In the present study, we have analyzed the adversity of bisphenol A on the reproductive behavior of adult and on the expression of selected genes in the larva and adult stage of fruit fly exposed to bisphenol A (0.007 g/2 ml. or 3.5 mg/ml), in addition to determination of LC50 value of bisphenol A in larva and pupal stage. We employed both the quantitative reverse transcriptase PCR and droplet digital PCR for analyzing the expression profile of seven genes namely, decapentaplegic, vestigial, wingless, foraging, insulin-like receptor, doublesex, and fruitless. We found bisphenol A has more adverse effects on male sexual behavior than females. Moreover, we observed significant downregulation of all the selected genes in treated larvae except, fruitless in male where it showed significant upregulation. On contrary among the treated adult flies, significant downregulation of all target genes in both sexes is evident, except, doublesex and fruitless in males which showed significant upregulation. We did not observe any deviation of male: female sex ratio from 1:1 under bisphenol A exposure. All these results suggest bisphenol A adversely affects the optimum functioning of genes which are involved in the regulation of metabolic pathways, behavioral pattern, stress response, endocrine homeostasis, neural functioning, and the development of the specific organ in Drosophila melanogaster. Our result not only provides a foundation to study further the bisphenol A toxicity on different pivotal genes in Drosophila but also suggests the use of the droplet digital PCR technology in toxicity measurement at the molecular level in eukaryotic model systems.

Microbial Fabrication of Nanomaterial and Its Role in Disintegration of Exopolymeric Matrices of Biofilm.

Bacterial biofilms are responsible for the development of various chronic wound-related and implant-mediated infections and confer protection to the pathogenic bacteria against antimicrobial drugs and host immune responses. Hence, biofilm-mediated chronic infections have created a tremendous burden upon healthcare systems worldwide. The development of biofilms upon the surface of medical implants has resulted in the failure of various implant-based surgeries and therapies. Although different conventional chemical and physical agents are used as antimicrobials, they fail to kill the sessile forms of bacterial pathogens due to the resistance exerted by the exopolysaccharide (EPS) matrices of the biofilm. One of the major techniques used in addressing such a problem is to directly check the biofilm formation by the use of novel antibiofilm materials, local drug delivery, and device-associated surface modifications, but the success of these techniques is still limited. The immense expansion in the field of nanoscience and nanotechnology has resulted in the development of novel nanomaterials as biocidal agents that can be either easily integrated within biomaterials to prevent the colonization of microbial cells or directly approach the pathogen overcoming the biofilm matrix. The antibiofilm efficacies of these nanomaterials are accomplished by the generation of oxidative stresses and through alterations of the genetic expressions. Microorganism-assisted synthesis of nanomaterials paved the path to success in such therapeutic approaches and is found to be more acceptable for its "greener" approach. Metallic nanoparticles functionalized with microbial enzymes, silver-platinum nanohybrids (AgPtNHs), bacterial nanowires, superparamagnetic iron oxide (Fe3O4), and nanoparticles synthesized by both magnetotactic and non-magnetotactic bacteria showed are some of the examples of such agents used to attack the EPS.

Prevalence of Y chromosome microdeletion in azoospermia factor subregions among infertile men from West Bengal, India.

BACKGROUND: Etiology of male infertility is intriguing and Y chromosome microdeletion within azoospermia factor (AZF) sub-regions is considered major cause. We conducted a screening for Y chromosome microdeletion in an infertile male cohort from West Bengal, India to characterize Y chromosome microdeletion among infertile men. METHODS: We recruited case subjects that were categorized on the basis of sperm count as azoospermia (N = 63), severe oligozoospermia (N = 38), and oligozoospermia (N = 17) and compared them with age, demography, and ethnicity matched healthy proven fertile control males (N = 84). Sequence Tagged Site makers and polymerase chain reaction based profiling of Y chromosome was done for AZF region and SRY for cases and controls. RESULTS: We scored 16.1% of cases (19 out of 118) that bear one or more microdeletions in the studied loci and none among the controls. The aberrations were more frequent among azoospermic males (17 of 19) than in severe oligozoospermic subjects (2 of 19). CONCLUSION: Our study provides the results of screening of the largest Bengali infertile men sample genotyped with the maximum number of STS markers spanning the entire length of Y chromosome long arm. Y chromosome microdeletion is a significant genetic etiology of infertility among Bengali men.

Functionalized Chitosan Nanomaterials: A Jammer for Quorum Sensing.

The biggest challenge in the present-day healthcare scenario is the rapid emergence and spread of antimicrobial resistance due to the rampant use of antibiotics in daily therapeutics. Such drug resistance is associated with the enhancement of microbial virulence and the acquisition of the ability to evade the host's immune response under the shelter of a biofilm. Quorum sensing (QS) is the mechanism by which the microbial colonies in a biofilm modulate and intercept communication without direct interaction. Hence, the eradication of biofilms through hindering this communication will lead to the successful management of drug resistance and may be a novel target for antimicrobial chemotherapy. Chitosan shows microbicidal activities by acting electrostatically with its positively charged amino groups, which interact with anionic moieties on microbial species, causing enhanced membrane permeability and eventual cell death. Therefore, nanoparticles (NPs) prepared with chitosan possess a positive surface charge and mucoadhesive properties that can adhere to microbial mucus membranes and release their drug load in a constant release manner. As the success in therapeutics depends on the targeted delivery of drugs, chitosan nanomaterial, which displays low toxicity, can be safely used for eradicating a biofilm through attenuating the quorum sensing (QS). Since the anti-biofilm potential of chitosan and its nano-derivatives are reported for various microorganisms, these can be used as attractive tools for combating chronic infections and for the preparation of functionalized nanomaterials for different medical devices, such as orthodontic appliances. This mini-review focuses on the mechanism of the downregulation of quorum sensing using functionalized chitosan nanomaterials and the future prospects of its applications.