Association between the MTHFR (rs1801133) gene variation and serum trace elements levels (Copper and Zinc) in individuals diagnosed with neural tube defects.

BACKGROUND AND AIMS: Neural tube defects (NTDs) occur when the neural tube fails to close within 28 days of human embryonic development. This results in central nervous system disorders like anencephaly, spina bifida, and encephalocele. Early diagnosis and treatment are crucial to minimize their impact on an individual's health and well-being. The present study aims to define the association between prenatal exposure to trace elements (Cu and Zn) and the single nucleotide polymorphism (SNP) of the MTHFR gene involved in folate metabolism pathways in neural tube defects in children and their mothers. MATERIAL AND METHODS: A cross-sectional study involving 331 participants (90 NTD cases, 88 healthy mothers, 85 NTD children, and 68 healthy children) from antenatal check-ups in Obstetrics and Gynaecology and Pediatric Surgery for Neural Tube Defects in the Outpatient Department (OPD) and Inpatient Department (IPD). Assessed Cu and Zn concentrations and their associations. Genomic DNA was extracted, and real-time PCR was used to determine genotypes. Atomic absorption spectrophotometry measured trace elements. Statistical analyses included Chi-Square tests, odds ratios, and Mann-Whitney U tests. RESULTS: Significant associations were found between MTHFR C677T genotypes and NTD risk in mothers (p = 0.0491) and children (p = 0.0297). Allelic frequency analysis indicated a T allele association with NTD risk in children (p = 0.0107). Recessive models showed significant associations in mothers (p = 0.0169) and children (p = 0.1678). Cu levels differed significantly between NTD cases and controls (p < 0.0001), with MTHFR genotypes influencing Cu levels. Zinc levels also varied significantly (p < 0.0001). CONCLUSION: This study reveals complex associations between MTHFR C677T genotypes, trace element concentrations, and NTD risk in mothers and children. This targeted approach allows healthcare providers to identify at-risk pregnancies early, enabling personalised interventions like folic acid supplementation and counselling to moderate neural tube defect (NTD) risk in a future pregnancy.

BCR-ABL kinase domain mutations in CML patients, experience from a tertiary care center in North India.

Background: Chronic Myeloid Leukemia is characterized by the presence of the Philadelphia Chromosome (Ph) which contains the BCR::ABL1 fusion gene that occurs due to a reciprocal translocation between chromosomes 9 and 22. This accounts for up to 15 % of all adult leukemias [1]. Most patients treated with first line tyrosine kinase inhibitor (TKI) imatinib achieve durable response but may undergo relapse at some stage [2]. The most important mechanism that may confer imatinib resistance is point mutation within BCR::ABL kinase domain. Other generation ABL tyrosine kinase inhibitors such as dasatinib, nilotinib, bosutinib and ponatinib help to overcome imatinib resistance [3]. Sensitivity of the patient to each of the above TKIs depends upon the individual candidate mutation present. Thus, it is important to perform mutation analysis for effective therapeutic management of CML patients once they show imatinib resistance. We used direct sequencing to identify the different types of mutations responsible for resistance of imatinib treatment from north India. Methods: In this study, the patient resistance for the imatinib were analyzed for BCR::ABL kinase domain mutation by direct sequencing and the detected mutations along with their percentage prevalence were reported. Results: 329 patients with CML-CP were analyzed for BCR::ABL kinase domain mutation. Total 66 (20.06 %) patients out of 329 had mutation in at least one of the domains of BCR::ABL conferring resistance to different generations of TKI. Mutations in BCR::ABL kinase domain was observed in different domain of BCR::ABL. ATP binding P-Loop (42.42 %), Direct binding site (36.36 %), C-Loop (10.60 %), A-Loop (6.06 %), SH2 contact (3.03 %), SH3 contact (1.51 %). Conclusion: Total 20.06 % patients (66/329) show mutation in at least one of the structural motifs of BCR-ABL kinase domain, which further confer the resistance to a particular generation of TKI.

The Rapid Evaluation of Down Syndrome With Quantitative Fluorescence Polymerase Chain Reaction (QF-PCR): A Pilot Study Among the Population in Eastern Uttar Pradesh, India.

Background and objective Down syndrome (DS) is characterized by the presence of an additional chromosome; it is a typical chromosomal disorder causing intellectual disability in individuals. The diagnostic process for DS often involves conventional karyotyping, which can be time-consuming. Trisomy 21 and other chromosomal abnormalities may now be quickly and accurately diagnosed using quantitative fluorescence polymerase chain reaction (QF-PCR). In light of this, this study aimed to investigate chromosomal abnormalities in DS using conventional karyotyping and QF-PCR among the population in eastern Uttar Pradesh, India. Methods Blood samples from 40 individuals with clinically diagnosed DS were collected. Conventional karyotyping involved standard cytogenetic techniques, while QF-PCR utilized DNA extraction and analysis with chromosome-specific short tandem repeat (STR) markers. Results Various distinct physical characteristics were observed in the DS individuals, such as mongoloid slant and low-set ears. Karyotyping and QF-PCR analyses revealed different chromosomal configurations associated with DS trisomy 21, with additional chromosomal abnormalities found in some individuals, including partial monosomy 18 and mosaic trisomy 21. However, in a few cases, neither karyotyping nor QF-PCR revealed any abnormalities. Conclusions The study demonstrated that QF-PCR is a reliable and rapid method for diagnosing DS, providing results within 24 hours. This approach allows for the simultaneous diagnosis of a large number of samples and reduces the time required to obtain results. In the diagnostic procedure for DS, we believe QF-PCR will prove to be a useful tool. Furthermore, therapeutic interventions based on their clinical traits and molecular karyotyping can enhance the quality of life of people with DS.

Enhancement of the Rate of Surface Reactions by the Elastocapillary Effect.

We examined the effect of deformability of a solid substrate on the kinetics of a surface reaction that occurs between chemical species present in it and a liquid dispensed on it. In particular, we have dispensed aqueous solutions of gold and silver salt as sessile drops or as a liquid pool on a cross-linked film of poly(dimethylsiloxane) (PDMS). The PDMS surface contains organosilane (SiH), which reduces the salt, producing metallic nanoparticles at the solid-liquid interface. These experiments reveal that, for a sufficiently soft solid, the reaction proceeds about three times faster in the drop mode than in the pool mode. The reaction conditions in both cases remain exactly identical except that, for the drop, the vertical component of the liquid surface tension deforms the solid substrate at the three-phase contact line. We have estimated the solid-liquid and solid-air interfacial energy, which along with the surface energy of the liquid gives an estimate of excess free energy. This energy is found to be different for the drop and pool modes. By considering that this excess free energy decreases the activation energy barrier for the reaction, we have shown that the reaction rate constant in the drop mode should indeed exceed that in the pool mode by about three times.

Correction: SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection.

[This corrects the article DOI: 10.7759/cureus.29544.].

Studying kinetics of a surface reaction using elastocapillary effect.

HYPOTHESIS: When a liquid is inserted inside a microfluidic channel, embedded within a soft elastomeric layer, e.g. poly(dimethylsiloxane) (PDMS), the thin wall of the channel deforms, due to change in solid-liquid interfacial energy. This phenomenon is known as Elastocapillary effect. The evolution of a new species at this interface too alters the interfacial energy and consequently the extent of deformation. Hence, it should be possible to monitor dynamics of physical and chemical events occurring near to the solid-liquid interface by measuring this deformation by a suitable method, e.g., optical profilometer. EXPERIMENTS: Aqueous solution of a metal salt inserted into these channels reacts with Silicon-hydride present in PDMS, yielding metallic nanoparticles at the channel surface. The kinetics of this reaction was captured in real time, by measuring the wall deformation. Similarly, physical adsorption of a protein: Bovine Serum Albumin, on PDMS surface too was monitored. FINDING: The rate of change in deformation can be related to rate of these processes to extract the respective reaction rate constant. These results show that Elastocapillary effect can be a viable analytical tool for in-situ monitoring of many physical and chemical processes for which, the reaction site is inaccessible to conventional analytical methods.

Platform-Based Internationalization of Smaller Firms: The Role of Government Policy.

Governments are recognizing anticompetitive concerns and market distortions associated with the rise of e-commerce platforms. Thus, policies are being crafted to level the playing field between large platform operators and small platform sellers. In addition, policies mitigating barriers to internationalization associated with using e-commerce platforms are also being developed. This study aims to explore these policy actions impacting the platform-based internationalization of small and micro enterprises (SMEs). The case study method is adopted to provide rich insights into the Indian Government policy actions impacting the e-commerce platform-based internationalization of Indian SMEs. More specifically, this investigation analyzes the extent to which the Indian Government policy actions have mitigated the home market and industry-level barriers to export for SMEs leveraging e-commerce platforms for their internationalization efforts. Study findings provide rich policy implications and fodder for future empirical testing of key qualitative insights uncovered in this study. Supplementary Information: The online version contains supplementary material available at 10.1007/s11575-022-00492-z.

SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection.

BACKGROUND AND OBJECTIVES: India had faced a devastating second outbreak of COVID-19 infection, in which a majority of the viral sequences were found to be of the B.1.617.2 lineage (Delta-variant). While India and the world focused on vaccination, reports of vaccine-immunity evasion by the virus, termed "breakthrough cases", emerged worldwide. Our study was focused on the primary objective to identify the mutations associated with breakthrough infections SARS-CoV-2. METHODS: In our study, we extracted the SARS-CoV-2 RNA (ribonucleic acid) from reverse transcription-polymerase chain reaction (RT-PCR) positive COVID-19 patients, and 150 random samples were sent for sequencing to the Centre for Cellular & Molecular Biology, Hyderabad. Whole genome sequences of 150 SARS-CoV-2 viral samples were analyzed thoroughly. We mostly found B.1.617 and its sub-lineages in the genomic sequencing results. RESULTS AND INTERPRETATION: On further analysis of patient data, it was seen that nine patients had been vaccinated against the SARS-CoV-2 previously. These nine patients had B.1.617/B.1 or A strains, and all of them had similar genomic variations in spike proteins as well as non-structural proteins (NSPs). The mutations seen in these sequences in the Spike (S), NSPs, and open reading frame (ORF) regions would have produced amino acid changes known to improve viral replication, confer drug resistance, influence host-cell interaction, and lead to antigenic drift. CONCLUSIONS: Increased virulence culminating in vaccine immunity evasion may be inferred from these specific mutations. Our study adds to the growing body of evidence linking rapidly emerging mutations in the S (Spike) and ORF genes of the SARS-CoV-2 genome to immune evasion.

Liquid Spreading Induced by In Situ Generation of Metallic Nanoparticles.

Spreading or pinning of a liquid drop on a solid substrate is determined by the surface energy of solid and liquid, topography of substrate surface, and different external forces like electric field, magnetic field, and vibration. Here we present a novel mechanism of depinning, driven by in situ generation of a species following reaction between a constituent of the droplet and one in the substrate. In particular, fluoro-carbon (FC) functionalized agarose and pHEMA gels are used as the substrates; the substrate is soaked with chloroauric acid. A drop of poly(dimethylsiloxane) (PDMS) mixed with the cross-linking agent is dispensed on it. The drop does not spread in absence of the salt, but as the salt concentration increases, the spreading diameter increases with decrease in the contact angle. The Si-H group, present as a constituent in the cross-linking agent, reduces the salt, leading to in situ generation of gold nanoparticles, that mitigates the pinning effect of the drop and the drop spreads.

Confinement-Induced Alteration of Morphologies of Oil-Water Emulsions.

Reversible alteration between different emulsion morphologies like core-shell and Janus is conventionally triggered by altering the interfacial energy between different phases. In contrast, here, we show that the morphology of dispersed droplets can be changed also when the emulsion is sufficiently confined between two parallel plates. In particular, we use three immiscible phases: silicone oil, paraffin oil, and aqueous solution of surface-active agents like agarose, sodium dodecylsulfate, dioctyl sodium sulfosuccinate, and cetyl trimethylammonium bromide to generate oil-in-water emulsions consisting of complex morphologies of the dispersed droplets. In the unconfined state, the core-shell drops appear with paraffin oil at the core and silicone oil at the shell. However, the morphology of oil droplets changes to Janus when the emulsion is confined between two parallel plates. We have shown that the meniscus of the continuous phase that forms between the parallel plates alters the pressure field in the emulsion and the total energy of the system, which trigger such morphological transition.

Genome-Wide Assessment of Polygalacturonases-Like (PGL) Genes of Medicago truncatula, Sorghum bicolor, Vitis vinifera and Oryza sativa Using Comparative Genomics Approach.

The polygalacturonases (PG) is one of the important members of pectin-degrading glycoside hydrolases of the family GH28. In plants, PG represents multigene families associated with diverse processes. In the present study, an attempt has been made to investigate the diversity of PG genes among monocots and dicots with respect to phylogeny, gene duplication and subcellular localization to get an insight into the evolutionary and functional attributes. The genome-wide assessment of Medicago truncatula, Vitis vinifera Sorghum bicolor, and Oryza sativa L. ssp. japonica genomes revealed 53, 49, 38 and 35 PG-like (PGL) genes, respectively. The predominance of glyco_hydro_28 domain, hydrophilic nature and genes with multiple introns were uniformly observed. The subcellular localization showed the presence of signal sequences targeting the secretory pathways. The phylogenetic tree constructed marked uniformity with three distinct clusters for each plant irrespective of the variability in the genome sizes. The site-specific selection pressure analysis based on K a/K s values showed predominance of purifying selection pressures among different groups identified in these plants. The functional divergence analysis revealed significant site-specific selective constraints. Results of site-specific selective pressure analysis throw light on the functional diversity of PGs in various plant processes and hence its constitutive nature. These findings are further strengthened by functional divergence analysis which reveals functionally diverse groups in all the four species representing monocots and dicots. The outcome of the present work could be utilized for deciphering the novel functions of PGs in plants.