Comparative analysis of commercially available kits for optimal DNA extraction from bovine fecal samples.

In the field of metagenomic research, the choice of DNA extraction methods plays a pivotal yet often underestimated role in shaping the reliability and interpretability of microbial community data. This study delves into the impact of five commercially available DNA extraction kits on the analysis of bovine fecal microbiota. Recognizing the importance of accurate DNA extraction in elucidating microbial community dynamics, we systematically assessed DNA yield, quality, and microbial composition across these kits using 16S rRNA gene sequencing. Notably, the FastDNA spin soil kit yielded the highest DNA concentration, while significant variations in quality were observed across kits. Furthermore, differential abundance analysis revealed kit-specific biases that impacted taxa representation. Microbial richness and diversity were significantly influenced by the choice of extraction kit, with QIAamp DNA stool minikit, QIAamp Power Pro, and DNeasy PowerSoil outperforming the Stool DNA Kit. Principal-coordinate analysis revealed distinct clustering based on DNA isolation procedures, particularly highlighting the unique microbial community composition derived from the Stool DNA Kit. This study also addressed practical implications, demonstrating how kit selection influences the concentration of Gram-positive and Gram-negative bacterial taxa in samples. This research highlights the need for consideration of DNA extraction kits in metagenomic studies, offering valuable insights for researchers striving to advance the precision and depth of microbiota analyses in ruminants.

Multifaceted Applications of DNA-Capped Silver Nanoparticles in Photonics, Photocatalysis, Antibacterial Activity, Cytotoxicity, and Bioimaging.

Deoxyribonucleic acid (DNA) capped silver nanoparticles are exceptional nanomaterials, featuring precise size and shape control enabled by DNA as a capping agent. DNA stabilizes these nanoparticles' role leading to uniform structures for diverse applications. These nanoparticles are excellent in photonics and medical applications, enhancing fluorescence and medical imaging. In this study, we explore the multifaceted applications of DNA-capped silver nanoparticles, delving into their optical, photocatalytic, antibacterial, cytotoxic, and bioimaging properties. Employing UV-visible absorption spectroscopy and scanning electron microscopy, we provide an analysis of confirmation of silver nanoparticles. The investigation demonstrates substantial photocatalytic efficacy, photodegradation of methylene blue is higher than rhodamine 6G. The presence of silver nanoparticles enhances the fluorescence of rhodamine 6G doped sol-gel glasses. Furthermore, our findings illustrate significant antibacterial effects, encompassing both Gram-positive and Gram-negative bacteria, with DNA-capped silver nanoparticles exhibiting antibacterial activity. Cytotoxicity assessments on HeLa cells reveal concentration-dependent effects, with an LC50 value of 47 µL. Additionally, the in vitro experiments with HeLa cells suggest the promising utility of DNA-capped silver nanoparticles for bioimaging applications. This comprehensive analysis highlights the multifunctionality and potential of DNA-capped silver nanoparticles, offering promising avenues for further exploration and innovation within various scientific domains, particularly in the realm of nanomaterial research.

Photocatalytic, Antibacterial, Cytotoxic and Bioimaging Applications of Fluorescent CdS Nanoparticles Prepared in DNA Biotemplate.

Synthesizing nanoparticles in biotemplates has been cited as one of the most promising way to obtain monodispersed inorganic nanoparticles. In this method, uniform voids in porous materials serve as hosts to confine the synthesized nanoparticles. DNA template can be described as a smart glue for assembling nanoscale building blocks. Here we investigate the photocatalytic, antibacterial, cytotoxic, and bioimaging applications of DNA capped CdS. XRD, SEM, TEM, UV-visible absorption, and photoluminescence spectra were used to study structural, morphological, and optical properties of CdS nanoparticles. Prepared CdS nanoparticles exhibit visible fluorescence. The photocatalytic activity of CdS towards Rhodamine 6G and Methylene blue are 64% and 91% respectively. A disc-diffusion method is used to demonstrate antibacterial screening. It was shown that CdS nanoparticles inhibit Gram-positive bacteria and Gram-negative bacteria effectively. DNA capped CdS shows higher activity than uncapped CdS nanoparticles. MTT cell viability assays were carried out in HeLa cells to investigate the cytotoxicity for 24 h. At a concentration 2.5 µg/ml, it shows 84% cell viability and 43% viability at 12.5 µg/ml. The calculated LC50 value is equal to 8 µg/ml. These DNA capped CdS nanoparticles were taken for an in-vitro experiment with HeLa cells to exhibit the possibility of bioimaging applications. The present study suggests that the synthesized CdS nanoparticles could be a potential photocatalyst, antibacterial agent, and biocompatible nanoparticle for bioimaging applications.

Co-existence of halo-tolerant Pseudomonas fluorescens and Enterococcus hirae with multifunctional growth promoting traits to ameliorate salinity stress in Vigna radiata.

Soil salinization has become a prominent obstacle in diverse arid and semi-arid region damaging agricultural productivity globally. From this perspective, present investigation was aimed to compare the potential compatible consortium of bio-inoculants for improving Plant Growth Promoting (PGP) attributes, anti-oxidative enzymes, grain yield and profitability of Vigna radiata in saline soil conditions. A total of 101 rhizobacterium isolated from salt affected regions of Punjab, India were screened for their ability to induce salt tolerance, multifunctional PGP traits and antagonistic activities. The 16S rRNA sequencing identified the strains LSMR-29 and LSMRS-7 as Pseudomonas flourescens and Enterococcus hirae, respectively. In-vitro compatible halo-tolerant dual inoculant (LSMR-29 + LSMRS-7) as bio-inoculants mitigated salt stress in Vigna radiata (spring mungbean) seedling with improved seed germination, biomass and salt tolerance index together with the presence of nifH, acds, pqq and ipdc gene under salinity stress as compared to single inoculants. Further, the potential of single and dual bio-inoculants were also exploited for PGP attributes in pot and field experiments. Results indicated that a significant improvement in chlorophyll content (2.03 fold), nodulation (1.24 fold), nodule biomass (1.23 fold) and leghemoglobin content (1.13 fold) with dual inoculant of LSMR-29 + LSMRS-7 over the LSMR-29 alone. The concentrations of macro & micronutrients, proline, soil enzyme activities i.e. soil dehydrogenase, acid & alkaline phosphatases and antioxidant enzymes such as superoxide dismutase, catalase and peroxidase also found to be high for LSMR-29 + LSMRS-7 as compared to un-inoculated control. The high grain yield thereby leading to Benefit: Cost (B: C) ratio at field scale was indicative of the commercial use bio-inoculants under salt affected Vigna radiata (spring mungbean) to improvement of productivity and soil health. The current finding reveals a co-inoculation of halo-tolerating Pseudomonas fluorescens and Enterococcus hirae containing ACC deaminase could prove to be novel approach for inducing salt tolerance and improving productivity of Vigna radiata (spring mungbean).

A rapid realist review of clinical neuropsychology rehabilitation programmes to improve psychological wellbeing and quality of life for people with acquired brain injuries.

Approximately 20% of acquired brain injury (ABI) survivors experience reduced psychological wellbeing (PWB). Neuropsychological rehabilitation (NPR) is one approach supporting people with ABI to participate meaningfully in activities despite challenges. Although literature supports NPR effectiveness, little is known about change mechanisms. This systematic realist review identifies what NPR programmes have been designed, delivered, and evaluated for people with ABI to improve PWB and/or quality of life (QOL), as well as providing a context-relevant understanding of what NPR includes and how NPR might lead to positive outcomes. A rapid realist review was conducted in three phases: (1) structured retrieval and evidence extraction; (2) stakeholder consultation; (3) analysis and synthesis. Searches were completed, and findings from 35 publications and one stakeholder consultation were synthesized into a refined logic model. Six context-mechanism-outcome chains (CMOCs) were identified. Participants' relationships to internal experiences, and feelings of self-worth, mastery, and connection appeared to be mechanisms that led to improved PWB and QOL. Adaptation and individualized programmes were also key mechanisms to explain successful NPR. Embedding CMOCs into NPR could improve PWB and/or QOL for people with ABI. The logic model will inform ongoing development of a new online, group-based, NPR programme.

Proton and molecular permeation through the basal plane of monolayer graphene oxide.

Two-dimensional (2D) materials offer a prospect of membranes that combine negligible gas permeability with high proton conductivity and could outperform the existing proton exchange membranes used in various applications including fuel cells. Graphene oxide (GO), a well-known 2D material, facilitates rapid proton transport along its basal plane but proton conductivity across it remains unknown. It is also often presumed that individual GO monolayers contain a large density of nanoscale pinholes that lead to considerable gas leakage across the GO basal plane. Here we show that relatively large, micrometer-scale areas of monolayer GO are impermeable to gases, including helium, while exhibiting proton conductivity through the basal plane which is nearly two orders of magnitude higher than that of graphene. These findings provide insights into the key properties of GO and demonstrate that chemical functionalization of 2D crystals can be utilized to enhance their proton transparency without compromising gas impermeability.

Understanding who benefits most from cognitive rehabilitation for multiple sclerosis: A secondary data analysis.

BACKGROUND: Up to 70% of people with multiple sclerosis (MS) experience cognitive difficulties. Cognitive rehabilitation is a type of therapy that helps manage cognitive problems. OBJECTIVE: The Cognitive Rehabilitation for Attention and Memory in MS (CRAMMS) trial showed some evidence of effectiveness of cognitive rehabilitation in improving cognitive function, with some participants benefitting more than others. We therefore conducted a secondary analysis of the CRAMMS data to understand who benefits most. METHODS: We grouped baseline data into four categories of possible predictors. We used regression models to identify specific factors/characteristics that could predict the likelihood that an individual will benefit from cognitive rehabilitation. RESULTS: The models predicted whether a participant improved or did not improve in neuropsychological function following cognitive rehabilitation in up to 86% of participants. Results suggest that younger participants with medium to high education, diagnosed with relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS) who have not experienced any recent relapses, with mild to moderate cognitive difficulties were most likely to benefit from cognitive rehabilitation. CONCLUSION: We can predict which participants are most likely to demonstrate significant improvements in neuropsychological function following group-based cognitive rehabilitation. Clinically, this allows us to optimise limited neuropsychology resources by offering such cognitive rehabilitation to those most likely to benefit.

LP30K protein manifested in hemocytes of Bombyx mori larva on Nosema bombycis infection and showed functional evolution based on glucose- binding domain.

Infection by microsporidian Nosema bombycis induced appearance of exclusive protein conjugate of 190 kDa in hemocytes of silkworm Bombyx mori L (Lepidoptera: Bombycidae). Mass spectrometry of the band showed peptides of low molecular weight 30 kDa lipoprotein (LP30K). Six accessions of LP30K identified from the hemocytes comprised 30 K lipoprotein 1, 30 K protein 1, 2, 6, 7 and 11. Two uncharacterised proteins (UCP) identified from the hemocytes showed 100% similarity with LP30K sequence, altogether showed abundance after the infection. The LP30K accessions H9J4F6 (Q00802), E5EVW2 and the UCP accessions D4QGC0 and D4QGB9 showed presence of glucose binding protein I domain "ADSDVPNDILEEQLYNSIVVADYDSAVEK" that binds with fungal glucans to inhibit infection. However glucose binding protein II domain "TLAPRTDDVLAEQLYMSVVIGEYETAIAK" is absent in LP30K accessions from hemocytes showed loss of DNA sequences encoding the domain. The accessions H9J4F5, H9B440, A7LIK7 and H9B444 showed 92% identity with B. mori LP30K protein (NP_001095198.2) however the glucose binding domain I is absent in these accessions suggesting isoform- specific restricted fungal defense activity. Phylogeny tree of the LP30K homologues showed four groups including microvitellogenin and 30 kDa proteins showing functional diversity endorsed with evolutionary diversity. LP30K accessions with glucose binding domain diverged from that without glucose binding domain exemplify co-evolution for domain- dependent functional roles like storage and immune reactions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03685-x.

Whole-cell synthesis of 2,5-furandicarboxylic acid from pineapple waste under various fermentation strategies.

2,5-Furandicarboxylic acid (FDCA) is one of the platform chemicals and monomers used in plastic industries, currently synthesized by carcinogenic and toxic chemical processes with high pressure and temperature. The aim of this study was to develop a bioprocess for the production of FDCA. 5-(Hydroxymethyl)furfural (HMF) was synthesized (22.67 ± 1.36 g/l/h) from pineapple peel using chromium(III) chloride (CrCl3) at 100 °C. After optimization, approximately 3 mg/l/h FDCA was produced by Aspergillus flavus APLS-1 from HMF in a 2.5 L fermenter in a batch strategy. Parallel and immobilized packed bad bioreactors showed less production of FDCA. A fed-batch strategy produced 3.5 ± 0.3 mg/l/h of FDCA in shake flasks. Also, approximately 0.55 mg/l/h of FDCA was produced from pineapple waste derived HMF. However, these bioprocesses may be improved to increase the yield of renewable FDCA, in the future. This is the first report on FDCA production from pineapple waste.

Correction: Blood brain barrier permeable gold nanocluster for targeted brain imaging and therapy: an in vitro and in vivo study.

Correction for 'Blood brain barrier permeable gold nanocluster for targeted brain imaging and therapy: an in vitro and in vivo study' by L. V. Nair et al., J. Mater. Chem. B, 2017, 5, 8314-8321, https://doi.org/10.1039/C7TB02247F.

pH-dependent water permeability switching and its memory in MoS2 membranes.

Intelligent transport of molecular species across different barriers is critical for various biological functions and is achieved through the unique properties of biological membranes1-4. Two essential features of intelligent transport are the ability to (1) adapt to different external and internal conditions and (2) memorize the previous state5. In biological systems, the most common form of such intelligence is expressed as hysteresis6. Despite numerous advances made over previous decades on smart membranes, it remains a challenge to create a synthetic membrane with stable hysteretic behaviour for molecular transport7-11. Here we demonstrate the memory effects and stimuli-regulated transport of molecules through an intelligent, phase-changing MoS2 membrane in response to external pH. We show that water and ion permeation through 1T' MoS2 membranes follows a pH-dependent hysteresis with a permeation rate that switches by a few orders of magnitude. We establish that this phenomenon is unique to the 1T' phase of MoS2, due to the presence of surface charge and exchangeable ions on the surface. We further demonstrate the potential application of this phenomenon in autonomous wound infection monitoring and pH-dependent nanofiltration. Our work deepens understanding of the mechanism of water transport at the nanoscale and opens an avenue for the development of intelligent membranes.

Prospective Evaluation of Response to Treatment, Survival Functions, Recurrence Pattern and Toxicity Profile in Indian Patients with Oligo-Brain Metastasis Treated with Only SRS.

Background: Prospective analysis of oligo-brain metastasis in Indian patients treated with SRS-only treatment. Methods: Between January 2017 and May 2022, 235 patients were screened and 138 histologically proven and radiologically confirmed. One to five brain metastasis patients aged more than 18 years with good Karnofsky performance status (KPS >70) accrued in ethical and scientific committee-approved prospective observational study protocol for treatment with only radiosurgery (SRS) with robotic radiosurgery (CyberKnife, CK) [AIMS IRB: 2020-071; CTRI No: REF/2022/01/050237]. Immobilization was performed with a thermoplastic mask, contrast CT simulation was performed with 0.625 mm slices, fused with T1 contrast/T2 FLAIR MRI images for contouring. Planning target volume (PTV) margin of 2-3 mm and a dose of 20-30 Gy in 1-5 fractions. Response to treatment, new brain lesions free survival, overall survival, and toxicity profile after CK were evaluated. Results: In total,: 138 patients with 251 lesions were accrued (median age 59 years (interquartile range [IQR] 49-67 years; female 51%; headache in 34%, motor deficit in 7%, KPS >90 in 56%; lung primary in 44%, breast in 30%; oligo-recurrence in 45%; synchronous oligo-metastases in 33%; adenocarcinoma primary in 83%). One hundred seven patients (77%) received upfront Stereotactic radiotherapy (SRS), 15 (11%) received postoperative SRS, 12 (9%) received whole brain radiotherapy (WBRT) before SRS, and 3 (2%) received WBRT plus SRS boost. The majority had solitary (56%) brain metastasis, 28% had two to three lesions, and 16% had four to five brain lesions. Frontal (39%) was the most common site. Median PTV was 15.5 mL (IQR - 8.1-28.5 mL). Seventy-one (52%) patients were treated with single fractions, 14% with three, and 33% with five fractions. Fraction schedules were 20-2 4 Gy/1fr; 27 Gy/3fr, and 25 Gy/5 fractions (mean BED 74.6 Gy [SD ± 48.1; mean MU 16608], mean treatment time was 49 min (range 17-118 min]. Twelve Gy normal brain volume was 40.8 mL (3.2%) (range 19.3-73.7 mL). At a mean follow-up of 15 months (SD 11.9 months; max 56 months), the mean actuarial OS after SRS-only treatment was 23.7 months (95% confidence interval [CI] 20-28). Further 124 (90%) patients had >3 months, 108 (78%) had >6 months, 65 (47%) had >12 months, and 26 (19%) had >24 months follow-up. Intracranial disease and extracranial disease were controlled in 72 (52.2%) and 60 (43.5%), respectively. "In-field" recurrence, "out-of-field," and "both in and out-of-field" recurrences were in 11%, 42%, and 46%, respectively. At the last follow-up, 55 patients (40%) were alive, 75 (54%) died due to disease progression, and the status of 8 (6%) patients was not known. Among 75 patients who died, 46 (61%) had extracranial disease progression, 12 (16%) had only intracranial progression, and 8 (11%) had unrelated causes. Also, 12/117 (9%) had radiological confirmation of radiation necrosis. Prognostication based on western patients (primary tumor type, number of lesions extracranial disease) showed similar outcomes. Conclusions: SRS alone in brain metastasis is feasible in the Indian subcontinent with similar survival outcomes, recurrence patterns, and toxicity as published in the western literature. Patient selection, dose schedule, and planning need to be standardized to have similar outcomes. WBRT can be safely omitted in Indian patients with oligo-brain metastasis. Western prognostication nomogram is applicable in the Indian patient population.

Photocatalytic and Enhanced Biological Activities of Schiff Base Capped Fluorescent CdS Nanoparticles.

In the present work, biocompatible CdS nanoparticles were synthesized using Schiff base ligand, 3-((2-(-(1-(2hydroxyphenyl)ethylidene)amino)ethyl)imino)-2-pentone, by a simple ultrasonic irradiation method. The structural, morphological, and optical properties were studied using XRD, SEM, TEM, UV-visible absorption, and photoluminescence (PL) spectra. The quantum confinement effect of the Schiff base capped CdS nanoparticles was confirmed by using UV-visible and PL spectrum analysis. This CdS nanoparticles were an effective photocatalyst for degrading rhodamine 6G and methylene blue with a 70% and 98% degradation capacity, respectively. Furthermore, the disc-diffusion method demonstrated that CdS nanoparticles inhibit G-positive bacteria and G-negative bacteria more effectively. These Schiff base capped CdS nanoparticles were taken for an in-vitro experiment with HeLa cells to exhibit the possibility of providing optical probes in biological applications and observed under a fluorescence microscope. In addition, MTT cell viability assays were carried out to investigate the cytotoxicity for 24 h. As a result of this study, 2.5 µg/ml doses of CdS nanoparticles are suitable for imaging and are effective in destroying HeLa cells. The present study suggests that the synthesized Schiff base capped CdS nanoparticles could be a potential photocatalyst, antibacterial agent, and biocompatible nanoparticle for bioimaging applications.

OPERATIONALIZING ORAL HEALTH OUTCOME MEASURES TO IMPROVE THE ORAL HEALTH OF PERSONS WITH INTELLECTUAL DISABILITIES.

Individuals with intellectual disability (ID) face significant challenges in preventing oral diseases. They also lack access to high-quality oral health care in professional settings. To understand the effects of oral conditions on their lives and health, it is necessary to assess their oral health outcome measures. For those with mild ID, who possess adequate linguistic and cognitive abilities, accessibility features should be incorporated in the dental patient reported outcome (dPRO) measures. But many other individuals often lack the linguistic and cognitive ability to self-report through dPRO measures. While self-reported measures are preferable, requiring dPROs in this population would result in a high amount of missing data and the inability to assess interventions for improving their dental health. Thus, there is a need to use proxy-reported outcome (ProxRO) measures, observer reported outcome (ObsRO) measures, and clinician reported outcome (ClinRO) measures among those with ID. This is also a common approach taken by other specialties that work closely with those with ID, where the measures for activities of daily living and adaptive behavior measures use reporting by caregivers. ProxRO measures in dentistry that were created for infants and young children provide a structure for appropriate adaptations and the creation of relevant outcome measures. Including input from the intensely multidisciplinary teams that provide supports for those with ID is key to creating high-quality measures and oral health interventions for those with ID.

Psychological impact of lung cancer screening using a novel antibody blood test followed by imaging: the ECLS randomized controlled trial.

BACKGROUND: The Early CDT®-Lung antibody blood test plus serial computed tomography scans for test-positives (TPGs) reduces late-stage lung cancer presentation. This study assessed the psychological outcomes of this approach. METHODS: Randomized controlled trial (n = 12 208) comparing psychological outcomes 1-12 months post-recruitment in a subsample (n = 1032) of TPG, test-negative (TNG) and control groups (CG). RESULTS: Compared to TNG, TPG had lower positive affect (difference between means (DBM), 3 months (3m: -1.49 (-2.65, - 0.33)), greater impact of worries (DBM 1m: 0.26 (0.05, 0.47); 3m: 0.28 (0.07, 0.50)), screening distress (DBM 1m: 3.59 (2.28, 4.90); 3m: 2.29 (0.97, 3.61); 6m: 1.94 (0.61, 3.27)), worry about tests (odds ratio (OR) 1m: 5.79 (2.66, 12.63) and more frequent lung cancer worry (OR 1m: 2.52 (1.31, 4.83); 3m: 2.43 (1.26, 4.68); 6m: 2.87 (1.48, 5.60)). Compared to CG, TPG had greater worry about tests (OR 1m: 3.40 (1.69, 6.84)). TNG had lower negative affect (log-transformed DBM 3m: -0.08 (-0.13, -0.02)), higher positive affect (DBM 1m: 1.52 (0.43, 2.61); 3m: 1.43 (0.33, 2.53); 6m: 1.27 (0.17, 2.37)), less impact of worries (DBM 3m: -0.27 (-0.48, -0.07)) and less-frequent lung cancer worry (OR 3m: 0.49 (0.26, 0.92)). CONCLUSIONS: Negative psychological effects in TPG and positive effects in TNG were short-lived and most differences were small.

Dipteran endoparasitoid Exorista bombycis utilizes antihemocyte components against host defense of silkworm Bombyx mori.

Dipteran endoparasitoids avoid host immune response; however, antidefense components from the Dipterans are unknown. Infestation of commercial silkworm Bombyx mori Linnaeus (Lepidoptera: Bombycidae) by endoparasitoid Exorista bombycis Louis (Diptera: Tachinidae) induced immune reactions, cytotoxicity, granulation, degranulation, and augmented release of cytotoxic marker enzyme lactate dehydrogenase (LDH), and degranulation-mediator enzyme ß-hexosaminidase in hemocytes. In this study, by reverse phase high-performance liquid chromatography, fractions of E. bombycis larval tissue protein with antihemocytic activity are separated. From the fraction, peptides of hemocyte aggregation inhibitor protein (HAIP) and pyridoxamine phosphate oxidase (PNPO) are identified by mass spectrometry. Interacting partners of HAIP and PNPO are retrieved that further enhance the virulence of the parasitoid. PNPO and HAIP genes showed a four- to seven fold increase in expression in the integument of the parasitoid larva. Together, the dipteran endoparasitoid E. bombycis exploit antihemocyte activity to inhibit host defense reactions in addition to defense evasion contemplated.

Significant regional inequalities in the prevalence of intellectual disability and trends from 1990 to 2019: a systematic analysis of GBD 2019.

AIMS: Policymakers and researchers have little evidence on prevalence rates of intellectual disability (ID) or their changes over time to tailor healthcare interventions. Prevalence rates and trends of ID are especially lacking in regions with lower socio-demographic development. Additionally, the assessment of inequalities in the prevalence of ID across regions with varying socio-demographic development is understudied. This study assessed variations in prevalence rates of ID from 1990 to 2019 and the related inequalities between low and high socio-demographic index (SDI) regions. METHODS: This study used global data from 1990 to 2019 for individuals with ID from the 2019 Global Burden of Diseases study. Data analyses were performed from September 2021 to January 2022. Prevalence for individuals with ID was extracted by sex, age groups and SDI regions. Annual percentage change (APC) was estimated for each demographic group within SDI regions to assess their prevalence trends over 30 years. Relative and absolute inequalities were calculated between low and high SDI regions for the various age groups. RESULTS: In 2019, there were 107.62 million (1.74%) individuals with ID, with an APC of -0.80 (-0.88 to -0.72). There was a slightly higher prevalence among males (1.42%) than females (1.37%). The highest prevalence rates were found in the low-middle SDI regions (2.42%) and the lowest prevalence rates were in the high SDI regions (0.33%). There was a large reduction in the prevalence rate between the youngest age group v. the oldest age group in all the SDI regions and at all time points. The relative inequalities between low and high SDI regions increased over three decades. CONCLUSIONS: While an overall decrease in global prevalence rate for ID was found, relative inequalities continue to increase with lower SDI regions needing more comprehensive support services. The demographic trends indicate a significantly higher mortality rate among those with ID v. the rest of the population. Our study highlights the necessity for policies and interventions targeting lower SDI regions to mobilise resources that better support individuals with ID and achieve sustainable development goals proposed by the United Nations.

17ß-Estradiol Concentration and Direct ß2-Adrenoceptor Inhibition Determine Estrogen-Mediated Reversal of Adrenergic Immunosuppression.

Background: Sympathetic innervation of lymphoid organs, and the presence of 17ß-estradiol (estrogen or E2) and adrenergic receptors (ARs) on lymphocytes, suggests that sympathetic stimulation and hormonal activation may influence immune functions. Purpose: Modeling and simulating these pathways may help to understand the dynamics of neuroendocrine-immune modulation at the cellular and molecular levels. Methods: Dose- and receptor-dependent effects of E2 and AR subtype-specific agonists were established in vitro on lymphocytes from young male Sprague-Dawley rats and were modeled in silico using the MATLAB Simbiology toolbox. Kinetic principles were assigned to define receptor-ligand dynamics, and concentration/time plots were obtained using Ode15s solvers at different time intervals for key regulatory molecules. Comparisons were drawn between in silico and in vitro data for validating the constructed model with sensitivity analysis of key regulatory molecules to assess their individual impacts on the dynamics of the system. Finally, docking studies were conducted with key ligands E2 and norepinephrine (NE) to understand the mechanistic principles underlying their interactions. Results: Adrenergic activation triggered proapoptotic signals, while E2 enhanced survival signals, showing opposing effects as observed in vitro. Treatment of lymphocytes with E2 shows a 10-fold increase in survival signals in a dose-dependent manner. Cyclic adenosine monophosphate (cAMP) activation is crucial for the activation of survival signals through extracellular signal-regulated kinase (p-ERK) and cAMP responsive element binding (p-CREB) protein. Docking studies showed the direct inhibition of ERK by NE and ß2-AR by E2 explaining how estrogen signaling overrides NE-mediated immunosuppression in vitro. Conclusion: The cross-talk between E2 and adrenergic signaling pathways determines lymphocyte functions in a receptor subtype and coactivation-dependent manner in health and disease.

Anti-microbial and cytotoxic activity of ZzAMP, a serine protease inhibitor (SPI) with nutraceutical potential from rhizomes of medicinal plant, Zingiber zerumbet.

Serine protease Inhibitors (SPIs) abundantly reported in plant storage organs constitute important candidate molecules for antimicrobial and anticancer therapeutics. Our earlier studies had identified antimicrobial protein/or peptides (AMP) from Zingiber zerumbet rhizomes designated ZzAMP inhibiting serine protease (SP) of necrotrophic phytopathogen, Pythium myriotylum. Considering the high ethno-medicinal applications of Z. zerumbet rhizomes, present study evaluated the anti-bacterial, anti-oxidant and cytotoxic properties of ZzAMP. Though ZzAMP displayed low radical scavenging activity (IC50 1000 µg/ml), it exhibited considerable anti-bacterial activity towards the nosocomial pathogen Klebsiella pneumonia (93%), which produced maximal extracellular protease (30.6 ± 1.47 U/ml) amongst the pathogens screened. Evaluation of cytotoxic activity of ZzAMP revealed decrease in viability of cancer cell line, HeLa (IC50 115.09 µg/ml) compared to normal cells, L929 (IC50 299.95 µg/ml). Present experiments showing antimicrobial and cytotoxic activities of ZzAMP with minimal damage to normal cells are indicative of its potential as a promising nutraceutical protein.

Mutational landscape and in silico structure models of SARS-CoV-2 spike receptor binding domain reveal key molecular determinants for virus-host interaction.

BACKGROUND: SARS-CoV-2, the causative agent of COVID-19 pandemic is a RNA virus prone to mutations. Formation of a stable binding interface between the Receptor Binding Domain (RBD) of SARS-CoV-2 Spike (S) protein and Angiotensin-Converting Enzyme 2 (ACE2) of host is pivotal for viral entry. RBD has been shown to mutate frequently during pandemic. Although, a few mutations in RBD exhibit enhanced transmission rates leading to rise of new variants of concern, most RBD mutations show sustained ACE2 binding and virus infectivity. Yet, how all these mutations make the binding interface constantly favourable for virus remain enigmatic. This study aims to delineate molecular rearrangements in the binding interface of SARS-CoV-2 RBD mutants. RESULTS: Here, we have generated a mutational and structural landscape of SARS-CoV-2 RBD in first six months of the pandemic. We analyzed 31,403 SARS-CoV-2 genomes randomly across the globe, and identified 444 non-synonymous mutations in RBD that cause 49 distinct amino acid substitutions in contact and non-contact amino acid residues. Molecular phylogenetic analysis suggested independent emergence of RBD mutants. Structural mapping of these mutations on the SARS-CoV-2 Wuhan reference strain RBD and structural comparison with RBDs from bat-CoV, SARS-CoV, and pangolin-CoV, all bound to human or mouse ACE2, revealed several changes in the interfacial interactions in all three binding clusters. Interestingly, interactions mediated via N487 residue in cluster-I and Y449, G496, T500, G502 residues in cluster-III remained largely unchanged in all RBD mutants. Further analysis showed that these interactions are evolutionarily conserved in sarbecoviruses which use ACE2 for entry. Importantly, despite extensive changes in the interface, RBD-ACE2 stability and binding affinities were maintained in all the analyzed mutants. Taken together, these findings reveal how SARS-CoV-2 uses its RBD residues to constantly remodel the binding interface. CONCLUSION: Our study broadly signifies understanding virus-host binding interfaces and their alterations during pandemic. Our findings propose a possible interface remodelling mechanism used by SARS-CoV-2 to escape deleterious mutations. Future investigations will focus on functional validation of in-silico findings and on investigating interface remodelling mechanisms across sarbecoviruses. Thus, in long run, this study may provide novel clues to therapeutically target RBD-ACE2 interface for pan-sarbecovirus infections.