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.

A 22-pole radiofrequency ion trap setup for laboratory astrophysical studies.

The formation of large interstellar molecules starting from small reactants constitutes the bottom-up approach in astrochemistry. An experimental setup wherein the ionic reactant is prepared and allowed to react with neutral reactants within a confined interaction space is most desirable for this approach. Here, we present our efforts in constructing a 22-pole radio-frequency ion trap experimental setup that could act as a reaction chamber for the neutral reactant and trapped ions. A compact piezo-based pulsed supersonic expansion discharge source was developed to achieve efficient production of anions, particularly metal-bearing ions. In addition, two other ion sources, namely, the electron impact ion source and the plasma supersonic discharge ion source, were developed to cater to the production of specific ions. The geometry of this experimental setup facilitates photo excitation of trapped ions. The trapping efficiency was studied by trapping SF5+ and SF6- for a few seconds. The control exhibited by various parameters on the efficiency of the trapping is discussed in detail. Potential studies that could be performed with this new experimental setup are also discussed.

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.

Comparison of Antibacterial Activity of Various Additives to Glass Ionomer Restoration: An In Vitro Study.

Introduction: Glass-ionomer (GIC) cement was introduced in 1972 as a "new filling material of dentistry". It is bioactive and plays an important role in caries prevention due to its ability to release fluoride into the oral environment and remineralization of dental hard tissues. However, its properties such as moisture sensitivity, wear resistance, and bond strength are not sufficient to inflict the antimicrobial environment. This in vitro study aimed to evaluate the antibacterial property of four different GIC cements against S. mutans and L. acidophilus. Methodology: This study was conducted on 120 disk-shaped samples (30 for antibacterial activity), which were placed in Petri dishes holding Müeller Hinton agar. Bacterial strains were overhauled in the brain heart infusion culture medium, and by utilizing disposable straps on blood agar medium, 100 ml of the strain inoculum was plated out. Through the diffusion method on the solid medium, the antibacterial activity of GIC was determined. Results: The antibacterial activity was the highest for Riva silver and chemifill rock for 24 and 72 hours, respectively. For 48 hours, Equia forte and chemifill rock had the highest antibacterial activity, and there was a significant difference between the groups. Conclusion: Ketac™ molar easymix inhibited the growth of S. mutans and L. acidophilus but had the lowest antibacterial effect compared to other GICs.

Antibacterial Efficacy of Mineral Trioxide Aggregate, Bioactive Glass and Epoxy-Resin Based Sealer: An In-Vitro Interventional Study.

Aim: The aim and objective of this in vitro study was to evaluate the antibacterial efficacy of mineral trioxide aggregate, bioactive glass sealer, and epoxy-resin-based sealer. Materials and Methods: In the present study, 22 Mueller Hinton agar (MH agar) plates were employed and equally divided into two groups. Three holes were made by removal of agar at equidistant points and filled with root canal sealers. The strains of the bacteria used in this study were S. aureus (ATCC 6538) and C. albicans (ATCC 10231) and were divided into two groups and root canal sealers were divided into three subgroups: mineral trioxide aggregate (MTA) fillapex Sealer, Nishika Bioactive Glass sealer, and Syntex Epoxy Resin base sealer. For Staphylococcus aureus, peptone water was placed in a 2 mL test tube and bacteria were extracted from blood agar plates using a nichrome wire loop and poured into the peptone water-containing test tube and incubated for 2 hours and for C. albicans, fungi were grown at 37°C for 24 hours in MH Broth and seeded into MH agar to produce turbidity of 0.5 on the McFarland scale, which corresponds to a concentration of 108 CFU/mL. This MH broth was used as a second layer. The seeded agar was then added over the plates immediately after the insertion of sealer cement. After incubation, the diameters of zones of inhibition around the plates were measured. Results: The results of this study showed that the highest inhibition was recorded in Syntex sealer against Staphylococcus aureus followed by MTA fillapex sealer and Nishika sealer, whereas MTA fillapex showed the highest inhibition against C. albicans followed by Syntex sealer and Nishika sealer. Conclusion: Syntex sealer exhibits better antibacterial efficacy against Staphylococcus aureus and MTA fillapex exhibit better antibacterial efficacy against C. albicans.

Comparative Evaluation of Sealing Ability of Different Type of MTA as Root-End Filling Materials Using Dye Penetration Technique - An In Vitro Study.

Introduction: The main goal of the root-end filling material is to create a hermetic seal to protect against microbes and their by-products. Excellent biocompatibility and sealing ability are characteristics of MTA developed by Torabinejad et al. This study aimed to compare the sealing ability of different type MTA as root-end filling material using dye penetration technique. Material and Method: One-twenty (N = 120) extracted human maxillary anterior teeth were decontaminated, cleaned, and decoronated. Endodontic treatment and root-end resection were done. Then root-end cavity was prepared and filled with tested materials (N = 30). A calibrated stereomicroscope was used to evaluate linear measurement. All data were tabulated and statistically analyzed with a level of significance set at P < .05. Result: This order of increasing microleaks was observed: MTA Angelus < MTA Plus < PRO-Root MTA < Control group. There was a statistically significant difference in mean microleakage in MTA Angelus and MTA Plus groups (P = 0.040). MTA Angelus shows the least microleakage among all the bioceramic material groups. Conclusion: Although the sealing ability of MTA Angelus is superior to MTA Plus, PRO-Root MTA. MTA Plus, PRO-Root MTA could be considered an acceptable alternative to MTA Angelus in peri-radicular surgeries.

Morphological Variation of Mandibular Molars in Rohilkhand Population: An Original Research.

Introduction: In-depth knowledge of common and aberrant pulp morphology is essential for appropriate diagnosis and treatment planning before commencing root canal treatment. The radicular morphology of mandibular molars has been extensively studied. Considerable variation in the number of canals and roots found in these teeth has been reported. Aim: The purpose of this study is to investigate the root canal morphology of the mandibular molars among the Rohilkhand population using Dentascan. Materials and Methods: Dentascan images of mandibular molar were taken from 99 extracted teeth that were collected from the Department of Oral Surgery and Maxillofacial Surgery, Institute of Dental Sciences, Bareilly, and private clinics. The examination of root canal systems of the teeth was based on Vertucci's classification. Results: The mandibular molar (n = 99) were taken. Out of the 99 teeth examined, three canals were seen in 60 (60.6%) teeth, four canals in 39 (39.4%) teeth, 3% had extra distal roots, and 6% with C-shaped canals. Conclusion: Among mandibular first molars, only 3% had three roots. Mesial roots of the first molar typically present with two canals and two apical foramina with type IV or II canal configuration. Most distal roots of the first molar presented with a type I canal configuration. The remainder were distributed mainly between types II, IV, III, and V. Among 99 mandibular molars, 6% had single C-shaped roots.

Molecular growth of PANH via intermolecular Coulombic decay.

Nitrogen-bearing polycyclic aromatic hydrocarbons (PANHs) are ubiquitous in space. They are considered precursors to advanced biomolecules identified in meteorites. However, their chemical evolution into biomolecules in photodestructive astrophysical mediums remains a paradox. Here, we show that light can efficiently initiate the molecular mass growth of PANHs. Ultraviolet-photoexcited quinoline monomers, the smallest PANH, were observed to associate and intermolecular Coulombic decay between the associating monomers formed the cations of quinoline-dimer. Molecular rearrangements in the dimer cation lead to a dominant formation of cations heavier than quinoline. The enrichment of these heavier cations over all the other cations reveals the efficiency of this route for the mass growth of PANHs in space. This mechanism also leads to a highly reactive unsaturated PANH-ring via CH loss, a hitherto unknown channel in any photon-driven process. The occurrence of this efficient pathway toward complex molecules points to a rich chemistry in dense interstellar clouds.

Ambient-light-induced intermolecular Coulombic decay in unbound pyridine monomers.

Intermolecular Coulombic decay (ICD) is a process whereby photoexcited molecules relax by ionizing their neighbouring molecules. ICD is efficient when intermolecular interactions are active and consequently it is observed only in weakly bound systems, such as clusters and hydrogen-bonded systems. Here we report an efficient ICD between unbound molecules excited at ambient-light intensities. On the photoexcitation of gas-phase pyridine monomers, well below the ionization threshold and at low laser intensities, we detected the parent and heavier-than-parent cations. The isotropic emission of slow electrons revealed ICD as the underlying process. π-π* excitation in unbounded pyridine monomers triggered an associative interaction between them, which leads to an efficient three-centre ICD. The cation resulting from the molecular association of the three pyridine centres relaxed through fragmentation. This below-threshold ionization under ambient light has implications for the understanding of radiation damage and astrochemistry.

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.

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.

Highly porous Co(II)-salicylate metal-organic framework: synthesis, characterization and magnetic properties.

A new porous Co(II)-salicylate metal-organic framework material has been synthesized hydrothermally through the reaction of Co(II) chloride with sodium salicylate under mild alkaline pH conditions. To get an idea about the structural aspect of the material from the powder X-ray diffraction (PXRD) pattern, MAUD program has been successfully utilized and the assigned peaks match very well with a new tetragonal phase (space group, P4mm) having the unit cell parameters: a = b = 12.957 (0.042) Å; c = 12.738 (0.019) Å; α = ß = γ = 90°, V = 2138.73 Å(3). N(2) adsorption/desorption analyses suggested the material is highly porous in nature having high BET surface area and pore dimensions of 2.0-3.0 nm, which is within the range of small mesopores. Thermogravimetric analysis (TGA) revealed that the H(2)O molecules may be removed from the framework without collapsing the structure and the material is stable up to ca. 573 K. The material is characterized thoroughly by using different characterization tools such as TEM, SEM, UV-visible reflectance spectroscopy, FT IR spectroscopy and photoluminescence spectroscopy. X-Ray photoelectron spectroscopic (XPS) analysis was employed to understand the oxidation state of the cobalt atom and presence of other elements within the framework. The material shows interesting magnetic properties, where the magnetic moments monotonically increase with the decrease in temperature down to 9 K. Below 9 K there is a steep increase in magnetization on further lowering the temperature, thereby suggesting the onset of a long range ferromagnetic transition with ferromagnetic Curie temperature, T(C) = 8.5 K. Furthermore, the M-H curve at 2 K shows a clear hysteresis loop with a coercive field 150 Oe and remnant magnetization 0.8 µ(B)/f.u.