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Communication between cells in metazoan organisms is mediated by a remarkably small number of highly conserved signaling pathways. Given this small number of signaling pathways, the existence of multiple related ligands for many of these pathways represents a key evolutionary innovation for encoding complexity into cell–cell signaling. Relatedly, crosstalk between pathways is another critical feature, which allows a modest number of pathways to ultimately generate an enormously diverse range of outcomes. It would thus be useful to have genetic tools to identify and manipulate not only those cells that express a given signaling ligand but also those cells that specifically coexpress pairs of signaling ligands. We present a collection of split-Gal4 knock-in lines targeting many of the ligands for highly conserved signaling pathways in Drosophila (Notch, Hedgehog, fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor β (TGF β), Janus kinase/signal transducer and activator of transcription (JAK/STAT), Jun kinase (JNK), and platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF)-related receptor (PVR). We demonstrate that these lines faithfully recapitulate the endogenous expression pattern of their targets and that they can be used to identify cells and tissues that coexpress pairs of ligands. As a proof of principle, we demonstrate that the 4th chromosome TGF β ligands myoglianin and maverick are broadly coexpressed in muscles and other tissues of both larva and adults and that the JAK/STAT ligands upd2 and upd3 are partially coexpressed from cells of the midgut following gut damage. Together with our previously collection of split-Gal4 lines targeting the 7 Wnt ligands, this resource allows Drosophila researchers to identify and genetically manipulate cells that specifically express pairs of conserved ligands from nearly all the major intercellular signaling pathways. [ABSTRACT FROM AUTHOR]

Sugarcane is a high-impact crop used in the majority of global sugar production, with India being the second largest global producer. Understanding the timing and length of sugarcane growth stages is critical to improving the sustainability of sugarcane management. Earth observation (EO) data have been shown to be sensitive to the variation in sugarcane growth, but questions remain as to how to reliably extract sugarcane phenology over wide areas so that this information can be used for effective management. This study develops an automated approach to derive sugarcane growth stages using EO data from Landsat-8 and Sentinel-2 satellite data in the Indian state of Andhra Pradesh. The developed method is then evaluated in the State of Telangana. Normalised difference vegetation index (NDVI) EO data from Landsat-8 and Sentinel-2 were pre-processed to filter out clouds and to harmonise sensor response. Pixel-based cloud filtering was selected over filtering by scene in order to increase the temporal frequency of observations. Harmonising data from two different sensors further increased temporal resolution to 3–6 days (70% of sampled fields). To automate seasonal decomposition, harmonised signals were resampled at 14 days, and low-frequency components, related to seasonal growth, were extracted using a fast Fourier transform. The start and end of each season were extracted from the time series using difference of Gaussian and were compared to assessments based on visual observation for both Unit 1 (R2 = 0.72–0.84) and Unit 2 (R2 = 0.78–0.82). A trapezoidal growth model was then used to derive crop growth stages from satellite-measured phenology for better crop management information. Automated assessments of the start and the end of mid-season growth stages were compared to visual observations in Unit 1 (R2 = 0.56–0.72) and Unit 2 (R2 = 0.36–0.79). Outliers were found to result from cloud cover that was not removed by the initial screening as well as multiple crops or harvesting dates within a single field. These results demonstrate that EO time series can be used to automatically determine the growth stages of sugarcane in India over large areas, without the need for prior knowledge of planting and harvest dates, as a tool for improving sustainable production. [ABSTRACT FROM AUTHOR]

Perceptual segregation of complex sounds such as speech and music simultaneously emanating from multiple sources is a remarkable ability that is common in humans and other animals alike. Unlike animal physiological experiments with simplified sounds or human investigations with spatially broad imaging techniques, this study combines insights from animal single-unit recordings with segregation of speech-like sound mixtures. Ferrets are trained to attend to a female voice and detect a target word, both in presence and absence of a concurrent equally salient male voice. Recordings are made in primary and secondary auditory cortical fields, and in frontal cortex. During task performance, representation of the female words becomes enhanced relative to the male in all, but especially in higher cortical regions. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings underscore the role of the principle of temporal coherence whereby attention to a target voice binds together all neural responses coherently modulated with the target, thus ultimately forming and extracting a common auditory stream. Ferrets learned to attend and react to words of a female voice embedded in a speech mixture with a male. Recordings in auditory cortex reveal rapidly enhanced responses to the attended female voice and a simultaneous suppression of the male distractor. [ABSTRACT FROM AUTHOR]

The application of phyto-nanotechnology in horticulture is a sustainable tool for agriculture due to its cost-effectiveness and eco-friendly properties. Essential micro-elements have been used as nano-fertilizer to enhance crop production. Fine-tuning of the nanoparticle dose is also recognized as the critical factor determining their impact on plant growth. Therefore, this study aimed to investigate the effects of iron (Fe) and manganese (Mn) oxide nanoparticles (NPs) on potato plants physiological and biochemical changes under the hydroponic conditions. Observations revealed that the plant growing in the adapted hydroponics media (supplemented with 4.0 mg L− 1 Fe3O4 NPs and 1.0 mg L− 1 MnO2 NPs instead of original Fe and Mn salt respectively) improved various physiological and biochemical parameters, total biomass, and tuber yield compared to the untreated control. The growth-promoting impact of metal oxide NPs (hereafter refers as MONPs) simultaneously induced the activity of various antioxidant enzymes (SOD, CAT, POD) and contributed to the adequate reduction in malondialdehyde (MDA) and hydrogen peroxide (H2O2) content relative to the untreated control plants. This indicated that the application of MONPs could improve the potato yield per plant via modulating the plant antioxidant machinery. In addition, the application of MONPs as nano-nutrient appreciably improved the photosynthetic efficiency of plants via modulating the photosynthetic pigment content like Chl a, Chl b, total Chl, ratio Chl a/b, carotenoids as well as soluble sugar. The SEM-EDX elemental mapping also showed a slightly higher content of metals ions (Fe, Mn, and Ca) in the root and shoot tissues, however, the TEM analysis also confirmed absorption as well as transportation of MONPs in the root tissues growing in the presence of MONPs. This study opened the opportunity of utilizing MONPs as nano-nutrient in a hydroponic condition for development of pathogen-free potato tuber. [ABSTRACT FROM AUTHOR]

Cyanobacterial harmful algal blooms release toxins and form thick blanket layers on the water surface causing widespread problems, including serious threats to human health, water ecosystem, economics, and recreation. To identify the potential drivers for the bloom, there is a need for extensive observations of the water sources with bloom occurrences. However, the traditional methods for monitoring water sources, such as collection of point ground samples, have proven limited due to spatial and temporal variability of water resources, and the cost associated with collecting samples that accurately represent this variability. These limitations can be addressed through the use of high-frequency satellite data. In this study, we explored the use of Random Forest (RF), which is one of the widely used machine learning architectures, to evaluate the performance of Sentinel-3 OLCI (Ocean and Land Color Imager) images in predicting bloom proxies in the western region of Lake Erie. The sixteen available bands of Sentinel-3 images were used as the predictor variables, while four proxies of the cyanobacterial masses, including Chlorophyll-a, Microcystin, Phycocyanin, and Secchi-depth, were considered as response variables in the RF models, with one RF model per proxy. Each of the proxies comes with a unique set of traits that can help with bloom detection. Among four RF models, the model for Chlorophyll-a performed the best with R2 = 0.55 and RMSE = 20.84 µg/L, while R2 performance for the rest of the other proxies was less than 0.5. This is because Chlorophyll-a is the most dominant and optically active pigment in water, while Phycocyanin, which is a strong indicator of harmful bloom, is present in low concentrations. Additionally, Microcystin, responsible for bloom toxicity, has limited spectral sensitivity, and Secchi-depth could be influenced by various factors besides blooms, such as colored dissolved organic and inorganic matter. On further examining the relationship between the proxies, Microcystin and Secchi-depth were significantly correlated with Chlorophyll-a, which enhances the usefulness of Chlorophyll-a in accurately identifying the presence of algal blooms. [ABSTRACT FROM AUTHOR]

Zero forcing is a combinatorial game played on a graph with the ultimate goal of changing the colour of all the vertices at minimal cost. Originally this game was conceived as a one player game, but later a two-player version was devised in-conjunction with studies on the inertia of a graph, and has become known as the q -analogue of zero forcing. In this paper, we study and compute the q -analogue zero forcing number for various families of graphs. We begin with by considering a concept of contraction associated with trees. We then significantly generalize an equation between this q -analogue of zero forcing and a corresponding nullity parameter for all threshold graphs. We close by studying the q -analogue of zero forcing for certain Kneser graphs, and a variety of cartesian products of structured graphs. [ABSTRACT FROM AUTHOR]

Serum or plasma is frequently utilized in biomedical research; however, its application is impeded by the requirement for invasive sample collection. The non-invasive nature of urine collection makes it an attractive alternative for disease characterization and biomarker discovery. Mass spectrometry-based protein profiling of urine has led to the discovery of several disease-associated biomarkers. Proteomic analysis of urine has not only been applied to disorders of the kidney and urinary bladder but also to conditions affecting distant organs because proteins excreted in the urine originate from multiple organs. This review provides a progress update on urinary proteomics carried out over the past decade. Studies summarized in this review have expanded the catalog of proteins detected in the urine in a variety of clinical conditions. The wide range of applications of urine analysis—from characterizing diseases to discovering predictive, diagnostic and prognostic markers—continues to drive investigations of the urinary proteome. [ABSTRACT FROM AUTHOR]

The body's homeostasis depends on the vascular endothelium, which controls angiogenesis, vascular tone, inflammation, cell trafficking, hemostasis, and the movement of nutrients and waste out of the body. Endothelial cells (ECs) are the primary gatekeepers of many of these vessel wall functions, despite only having a single cell's thickness. Normally quiescent ECs in the context of cancer are activated by anti-cancer therapies, the tumor microenvironment, and factors secreted by the tumor. Crucially, this dysfunctional endothelium actively participates in tumor metastasis and progression rather than just acting as a passive bystander. Compared to the healthy vasculature, ECs in the tumor vasculature are heterogeneous and have a different gene expression profile. Tumor-associated ECs, in particular, exhibit increased pro-angiogenic characteristics and upregulated expression of adhesion molecules and proinflammatory cytokines, facilitating the intra- and extravasation of spreading tumor cells. Furthermore, the downregulation of important anticoagulant molecules and increased endothelial secretion of prothrombotic molecules can directly encourage cancerassociated thrombosis. Many anti-cancer therapies are also less effective in their delivery and function when there is dysfunction in the tumor endothelium. The review highlights some of the most recent research showing how tumor-associated ECs influence angiogenesis, inflammation, coagulation, and metastasis to contribute to the progression of tumors. Undoubtedly, a better understanding of how the tumor microenvironment subverts quiescent ECs and how phenotypic alterations in the vessel wall support the survival and spread of tumor cells will aid in the identification of new therapeutic targets to slow the advancement of cancer. [ABSTRACT FROM AUTHOR]

Although tandem mass tag (TMT)-based isobaric labeling has become a powerful approach for multiplexed protein quantitation, automating the workflow for this technique has not been easy to achieve for widespread adoption. This is because preparation of TMT-labeled peptide samples involves multiple steps ranging from protein extraction, denaturation, reduction, and alkylation to tryptic digestion, desalting, labeling, and cleanup, all of which require a high level of proficiency. The variability resulting from multiple processing steps is inherently problematic, especially with large-scale clinical studies that involve hundreds of samples where reproducibility is critical for quantitation. Here, we sought to compare the performance of a recently introduced platform, AccelerOme, for an automated proteomic workflow employing TMT labeling with the manual processing of samples. Cell pellets were prepared and subjected to a 16-plex experiment using an automated platform and a conventional manual protocol. Single-shot liquid chromatography with tandem mass spectrometry analysis revealed a higher number of proteins and peptides identified using the automated platform. Efficiency of tryptic digestion, alkylation, and TMT labeling were similar in both manual and automated processes. In addition, comparison of quantitation accuracy and precision showed similar performance in an automated workflow compared to manual sample preparation by an expert. Overall, we demonstrated that the automated platform performs at a level similar to a manual process performed by an expert for TMT-based proteomics. We anticipate that this automated workflow will increasingly replace manual pipelines and has the potential to be applied to large-scale TMT-based studies, providing robust results and high sample throughput. [ABSTRACT FROM AUTHOR]

For precision in clinical oncology practice, detection of tumor-derived peptides and proteins in urine offers an attractive and noninvasive alternative for diagnostic or screening purposes. In this study, we report comparative quantitative proteomic profiling of urine samples from patients with gastric cancer and healthy controls using tandem mass tags-based multiplexed mass spectrometry approach. We identified 1504 proteins, of which 246 were differentially expressed in gastric cancer cases. Notably, ephrin A1 (EFNA1), pepsinogen A3 (PGA3), sortilin 1 (SORT1), and vitronectin (VTN) were among the upregulated proteins, which are known to play crucial roles in the progression of gastric cancer. We also found other overexpressed proteins, including shisa family member 5 (SHISA5), mucin like 1 (MUCL1), and leukocyte cell derived chemotaxin 2 (LECT2), which had not previously been linked to gastric cancer. Using a novel approach for targeted proteomics, SureQuant, we validated changes in abundance of a subset of proteins discovered in this study. We confirmed the overexpression of vitronectin and sortilin 1 in an independent set of urine samples. Altogether, this study provides molecular candidates for biomarker development in gastric cancer, and the findings also support the promise of urinary proteomics for noninvasive diagnostics and personalized/precision medicine in the oncology clinic. [ABSTRACT FROM AUTHOR]

The current research aimed to explore the attitude of randomly selected 220youths of Uttarakhand(110 males and 110 females), having different socio-demographic backgrounds, towards the old. This quantitative study employed a cross-sectional questionnaire. A selfstructured socio-demographic questionnaire andFarboni Scale of Ageism (FSA) developed by Fraboni, et al., (1990) were employed to measure ageism. The result revealed that the majority of youth respondents had high ageism. A significant gender difference in mean scores of ageism levels was reported with higher ageist attitudes among females. Further ageism was found to be significantly higher among respondents having no exposure to living with the elderly or having financially dependent elderly as compared to their counterparts. The study validates the results of other studies that report higher ageism among the young population globally. A programme focusing on youth education regarding ageing and related changes need to be developed by stakeholders to promote and sustain a positive ageist attitude towards the elderly population. [ABSTRACT FROM AUTHOR]

In this paper we show that for any fusion B of an association scheme A , the generalized Hamming scheme H (n , B) is a nontrivial fusion of H (n , A) . We analyze the case where A is the association scheme on a strongly-regular graph, and determine the parameters of all strongly-regular graphs for which the generalized Hamming scheme, H (2 , A) , has extra fusions, in addition to the one arising from the trivial fusion of A . [ABSTRACT FROM AUTHOR]

Chronic abdominal symptoms, especially in conjunction with risk factors such as iron deficiency anaemia, necessitate consideration of pica. Bowel wall thickening, either on ultrasound or computed tomography, may be a sign of a retained foreign body. An abdominal ultrasound shows abdominal ascites with dilated bowel loops and wall thickening. [Extracted from the article]

Loss of the desmosomal plaque protein plakophilin3 (PKP3) leads to increased tumor progression and metastasis. As metastatic tumors are often resistant to therapy, we wished to determine whether PKP3 loss led to increased radioresistance. PKP3 knockdown cells showed increased resistance to radiation in vitro and in vivo. The increase in resistance was accompanied by an increased ability to clear reactive oxygen species (ROS) and increased autophagy. The increase in autophagy was required for radioresistance and ROS clearance as inhibiting autophagy using either chloroquine or knocking down ATG3 re-sensitized the PKP3 knockdown clones to radiotherapy. These experiments suggest that autophagy inhibitors could target therapy-resistant PKP3 deficient tumors. [Display omitted] • Loss of Plakophilin3 leads to radio-resistance. • p38β activation is required for the induction of radio-resistance. • The induction of autophagy is required for increased radio-resistance observed upon plakophilin3 loss. [ABSTRACT FROM AUTHOR]

Hijras are the transgender community and have been socio-economically marginalized and hence their mental healthcare needs to be addressed. This was a descriptive, qualitative study, conducted in Mysore, India to examine the mental health status of 33 transgender women (TGW) and their response to the "Meditation on Twin Hearts (MTH)" intervention. Assessment of anxiety, depression and suicidality was carried out before the meditative session followed by a single session of MTH. Their feedback on meditation experience was collected, coded, and transformed into quantitative data. Among total participants, 39.4% of TGW exhibited severe anxiety, 21.2% has severe depression and 75.8% of them were at suicidal risk. Depression was positively correlated with anxiety and suicidal behavior. Most participants reported MTH was useful with signs of improvements in mental state. Thus, a single session of MTH has shown good signs of improvement in mental state among TGW. [ABSTRACT FROM AUTHOR]

Active surface deformation, displacement pattern, and erosional variability is estimated using the geomorphologically sensitive morphometry along with the Persistent Scatterer Interferometric Synthetic Aperture Radar (PSInSAR) technique using the Sentinel-1Adata (119 images) acquired between 07- 02-2017 and 10-02-2021. The average velocities for this dataset are estimated to be between ±11 mm/y. The Raunthi River catchment from where the flood was triggered is undergoing ~8 mm/y subsidence and ~10 mm/y uplift. Compared to this the basin wide deformation (Rishi Ganga basin) is estimated to be around ±10 mm/y with commulative ground displacement of around ±45 mm. The times series analysis suggests an increase in the ground displacement by around 5 mm/y and seems to be responsible for the expansion of pre-existing cracks in the vicinity of the Vaikrita Thrust (VT) and subsequent failure of the northern face of Nandi Peak on 7th February 2021. The Global Positioning System (GPS) derived strain distribution pattern indicate a relatively higher accumulation of strain (>0.35µ strain/y). The normalized steepness index (k sn) variation along the longitudinal section of Rishi Ganga and Raunthi River sub-basin in Central Himalayan region shows anomalous increase at the glacio-fluvial transitional processes. Moreover, the χ profiles as well as planform plots shows anomalously lower values within the Raunthi River sub-basin when compared with the Rishi Ganga basin. Based on the lower values of χ it is observed that Raunthi River sub-basin is undergoing high erosion which can be caused by the presence of sheared lithology and incision of the relict glacial and paraglacial sediments. We negate the suggestion that abrupt rise in the temperature was the major triggering mechanism for the recent disaster, instead it is the sheared lithology and pre-existing fissure developed because of differential uplift and subsidence in Raunthi River that led to the wedge failure and subsequent flash flood. Had the climate was the major driver of the recent tragedy ?, it should have impacted multiple hanging glaciers in the Rishi Ganga valley. Therefore, the study calls for detailed geomorphological, structural and glaciological investigation in regions dominated by glacial and paraglacial processes in the strategic regions of the Himalaya. Towards this, the state of art PSInSAR technique seems to provide fast and reliable detection of terrain instability/stability along with identification of potential areas of slope failures in near future in the glacial and preglacial zones. [ABSTRACT FROM AUTHOR]

Joshi, N., Arya, P.C., and Saulnier-Talbot, É., 2024. Benthic foraminifera are useful bioindicators of heavy metal and organic enrichment in northern temperate coastal zones: An executive summary review. In: Phillips, M.R.; Al-Naemi, S., and Duarte, C.M. (eds.), Coastlines under Global Change: Proceedings from the International Coastal Symposium (ICS) 2024 (Doha, Qatar). Journal of Coastal Research, Special Issue No. 113, pp. 926-930. Charlotte (North Carolina), ISSN 0749-0208. Benthic foraminifera are known to respond to naturally occurring and anthropogenically induced stresses. A considerable body of literature exists describing the effects that contamination by heavy metal and organic enrichment have on these organisms in coastal environments. Our analysis of the literature since 1980 shows that metal enrichment leads to deformations and altered foraminiferal test chemistry, whereas organic enrichment tends to mostly affect foraminiferal abundance and community structure, with little evidence for morphological effects. This review highlights the usefulness of the ecological response of foraminifera in assessing the current and long-term state of ecosystems of temperate benthic coastal environments, especially in the context of increased heavy metal and organic contamination by anthropogenic activities. [ABSTRACT FROM AUTHOR]

Cortical processing of arithmetic and of language rely on both shared and task-specific neural mechanisms, which should also be dissociable from the particular sensory modality used to probe them. Here, spoken arithmetical and non-mathematical statements were employed to investigate neural processing of arithmetic, compared with general language processing, in an attention-modulated cocktail party paradigm. Magnetoencephalography (MEG) data were recorded from 22 human subjects listening to audio mixtures of spoken sentences and arithmetic equations while selectively attending to one of the two speech streams. Short sentences and simple equations were presented diotically at fixed and distinct word/symbol and sentence/equation rates. Critically, this allowed neural responses to acoustics, words, and symbols to be dissociated from responses to sentences and equations. Indeed, the simultaneous neural processing of the acoustics of words and symbols was observed in auditory cortex for both streams. Neural responses to sentences and equations, however, were predominantly to the attended stream, originating primarily from left temporal, and parietal areas, respectively. Additionally, these neural responses were correlated with behavioral performance in a deviant detection task. Source-localized temporal response functions (TRFs) revealed distinct cortical dynamics of responses to sentences in left temporal areas and equations in bilateral temporal, parietal, and motor areas. Finally, the target of attention could be decoded from MEG responses, especially in left superior parietal areas. In short, the neural responses to arithmetic and language are especially well segregated during the cocktail party paradigm, and the correlation with behavior suggests that they may be linked to successful comprehension or calculation. [ABSTRACT FROM AUTHOR]

Peroxisomes are versatile cell organelles that exhibit a repertoire of organism and cell-type dependent functions. The presence of oxidases and antioxidant enzymes is a characteristic feature of these organelles. The role of peroxisomes in various cell types in human health and disease is under investigation. Defects in the biogenesis of the organelle and its function lead to severe debilitating disorders. In this manuscript, we discuss the distribution and functions of peroxisomes in the nervous system and especially in the brain cells. The important peroxisomal functions in these cells and their role in the pathology of associated disorders such as neurodegeneration are highlighted in recent studies. Although the cause of the pathogenesis of these disorders is still not clearly understood, emerging evidence supports a crucial role of peroxisomes. In this review, we discuss research highlighting the role of peroxisomes in brain development and its function. We also provide an overview of the major findings in recent years that highlight the role of peroxisome dysfunction in various associated diseases. [ABSTRACT FROM AUTHOR]

In the northwest Himalayan region, the ongoing out-of-sequence deformation caused emergence of Back Thrust (BT) around 43ka, which attributed the growth of anticlines parallel to the strike of major thrusts. This spatial and temporal geomorphic deformation is accompanied by coexisting river incision in the axial zone of anticlines and base-level fall along with upstream migration of knickpoints in the longitudinal river course. We used the Stream Power Incision model (SPIM) which relates the normalized steepness index (k sn), and concavity index (θ ref) with the slope (S) of longitudinal river profile as a power-law function of upstream area (A). and estimated these parameters for Beas, Soan, and Sutlej rivers to decipher the spatial distribution of deformation pattern. Using SRTM DEM and based on strike parallel variations of the k sn we identified segmented nature of the NW Himalayan thrusts. Further, the dynamics of river basins and transience along the tributaries and main stem rivers has been analyzed by Chi analysis (χ), which is attributed to geometric disequilibrium of the rivers. The results of k sn and χ analysis together suggests that the crustal shortening of NW Himalaya is caused by segmental reactivation of the thrusts. Further, investigating the change in steepness along longitudinal course aids in understanding the differential uplifts patterns in actively deforming segments of major NW Himalayan thrusts. [ABSTRACT FROM AUTHOR]

We consider the problem of estimating the best subgroup and testing for treatment effect in a clinical trial. We define the best subgroup as the subgroup that maximizes a utility function that reflects the trade-off between the subgroup size and the treatment effect. For moderate effect sizes and sample sizes, simpler methods for subgroup estimation worked better than more complex tree-based regression approaches. We propose a three-stage design with a weighted inverse normal combination test to test the hypothesis of no treatment effect across the three stages. [ABSTRACT FROM AUTHOR]

SRD5A3-CDG is a congenital disorder of glycosylation (CDG) resulting from pathogenic variants in SRD5A3 and follows an autosomal recessive inheritance pattern. The enzyme encoded by SRD5A3 , polyprenal reductase, plays a crucial role in synthesizing lipid precursors essential for N-linked glycosylation. Despite insights from functional studies into its enzymatic function, there remains a gap in understanding global changes in patient cells. We sought to identify N-glycoproteomic and proteomic signatures specific to SRD5A3-CDG, potentially aiding in biomarker discovery and advancing our understanding of disease mechanisms. Using tandem mass tag (TMT)-based relative quantitation, we analyzed fibroblasts derived from five patients along with control fibroblasts. N-glycoproteomics analysis by liquid chromatography–tandem mass spectrometry (LC–MS/MS) identified 3,047 glycopeptides with 544 unique N-glycosylation sites from 276 glycoproteins. Of these, 418 glycopeptides showed statistically significant changes with 379 glycopeptides decreased (P  < 0.05) in SRD5A3-CDG patient-derived samples. These included high mannose, complex and hybrid glycan-bearing glycopeptides. High mannose glycopeptides from protocadherin Fat 4 and integrin alpha-11 and complex glycopeptides from CD55 were among the most significantly decreased glycopeptides. Proteomics analysis led to the identification of 5,933 proteins, of which 873 proteins showed statistically significant changes. Decreased proteins included cell surface glycoproteins, various mitochondrial protein populations and proteins involved in the N-glycosylation pathway. Lysosomal proteins such as N-acetylglucosamine-6-sulfatase and procathepsin-L also showed reduced levels of phosphorylated mannose-containing glycopeptides. Our findings point to disruptions in glycosylation pathways as well as energy metabolism and lysosomal functions in SRD5A3-CDG, providing clues to improved understanding and management of patients with this disorder. [ABSTRACT FROM AUTHOR]

Organelles are dynamic structures of a eukaryotic cell that compartmentalize various essential functions and regulate optimum functioning. On the other hand, ageing is an inevitable phenomenon that leads to irreversible cellular damage and affects optimum functioning of cells. Recent research shows compelling evidence that connects organelle dysfunction to ageing-related diseases/disorders. Studies in several model systems including yeast have led to seminal contributions to the field of ageing in uncovering novel pathways, proteins and their functions, identification of pro- and anti-ageing factors and so on. In this review, we present a comprehensive overview of findings that highlight the role of organelles in ageing and ageing-associated functions/pathways in yeast. [ABSTRACT FROM AUTHOR]

Developmental readiness plays an important role in early childhood period and it sets the basis for future development. It is multi-faceted concept comprised of physical, cognitive, socio-emotional and self-help skills of children. Thus developmental readiness of children assures smooth and successful transition to formal schooling. The purpose of the present study was to assess the developmental readiness of private school children. The total sample of the study comprised of 200 children (i.e., 100 rural & 100 urban) of class- I randomly selected from private schools of rural and urban area. Self-structured Developmental readiness checklist was used to assess its different components. The results revealed that most of the rural and urban children had high level of skills across all domains. Locale differences showed that both rural children showed significantly better skills across various domains of developmental readiness than urban children except in cognitive skills and fine motor skills. Implications of research for practice are also discussed in the present study. [ABSTRACT FROM AUTHOR]

We consider the problem of estimating a biomarker-based subgroup and testing for treatment effect in the overall population and in the subgroup after the trial. We define the best subgroup as the subgroup that maximizes the power for comparing the experimental treatment with the control. In the case of continuous outcome and a single biomarker, both a non-parametric method of estimating the subgroup and a method based on fitting a linear model with treatment by biomarker interaction to the data perform well. Several procedures for testing for treatment effect in all and in the subgroup are discussed. Cross-validation with two cohorts is used to estimate the biomarker cut-off to determine the best subgroup and to test for treatment effect. An approach that combines the tests in all patients and in the subgroup using Hochberg's method is recommended. This test performs well in the case when there is a subgroup with sizable treatment effect and in the case when the treatment is beneficial to everyone. [ABSTRACT FROM AUTHOR]

The rapid evolution of mass spectrometry-based single-cell proteomics now enables the cataloging of several thousand proteins from single cells. We investigated whether we could discover cellular heterogeneity beyond proteome, encompassing post-translational modifications (PTM), protein-protein interaction, and variants. By optimizing the mass spectrometry data interpretation strategy to enable the detection of PTMs and variants, we have generated a high-definition dataset of single-cell and nuclear proteomic-states. The data demonstrate the heterogeneity of cell-states and signaling dependencies at the single-cell level and reveal epigenetic drug-induced changes in single nuclei. This approach enables the exploration of previously uncharted single-cell and organellar proteomes revealing molecular characteristics that are inaccessible through RNA profiling. This study explored single cells and single organelles to reveal unique molecular characteristics such as mutant peptides and modulation of diverse post-translational modifications that are inaccessible through DNA/RNA profiling. [ABSTRACT FROM AUTHOR]

The article comments on a study which evaluated outcomes of hospital admission location for low acuity infants at 35 weeks of gestational age across 13 Kaiser Permanente hospitals in North California. Study results presented indicate length of hospital stay of infants in a neonatal intensive care unit, breast feeding rates and readmission rates to admission location. Emphasis is given on the need for clinicians to ensure infant safety and identify infant characteristics to prevent readmission.

The morphotectonic elements of the Baijnath Klippe (BK) have been examined to understand the kinematics of the Inner Kumaun Lesser Himalaya from Tertiary to Late Quaternary. The BK is bounded by two thrusts: the Askot Thrust (AT), to the north and the Baijnath Thrust (BjT), to the south. The older (20 Ma) hanging wall rocks (mylonites and phyllites) are underlain and surrounded by quartzites (equivalent to Nagthat Formation of Outer Lesser Himalaya). The kinematics study and strain analysis along Dewal–Narayanbagarh transect provides the varied intensity of deformation (D1, D2, and D3) within the zone of BK. The D1 event is characterized by isoclinal tight folds in phyllite and mylonite; the D2 phase is characterized by open folding in mylonite. However, the youngest event D3 phase is observed as a regional synclinal folding of BK and associated rocks. The presence of 1–3-km-thick mylonite zone parallel to the thrust planes is related to the compressional event of Miocene age. The geomorphic pattern and chronologically constraints (OSL ages) with spatial variability in the incision/uplift rate suggests that the terrain is undergoing differential crustal deformation during Late Quaternary. Kinematic indicators such as streaky foliations, S–C foliation, mantled porphyroclasts, micro-shears with bookshelf gliding, and mica fish found in mylonites (macroscopic as well as microscopic) indicate ductile deformation in the area. We used Flinn plot (Rf/ϕ) and Fry (Tectonophysics 60:89–105, 1979) analysis to delineate the finite strain pattern in 21 oriented samples collected across the BK bound thrusts (BjT and AT). The strain analysis revealed an increasing trend of strained quartz grains, which presents triaxialoblate strain geometry (flattening i.e., 0 < k < 1) towards the structural discontinuity. The textural (chessboard, myrmekite, undulose extinction and fracturing in quartz and feldspar) and mineralogical properties (non-flaky) of quartz and feldspar indicate the temperature of deformation and mylonitization ranging 300–500 °C. [ABSTRACT FROM AUTHOR]

The consequence of strain accumulation along various Himalayan thrusts is manifested in shaping the topography and present day lanscape features of the Himalaya. Consequently, the strain accomodation is attributed to the occurrence of various devastating earthquakes in the Himalayan domain including 1905 Kangra earthquake (Mw 7.8) which occurred along the Kangra valley fault. In the present study, we analyzed and estimatedsss fault related parameters, gradient-length anomaly (GLA) analysis together with Interferometric Synthetic Aperture Radar (In-SAR) measurements to understand the landscape evolution and deformation pattern within the Soan dun (piggy back basin) in the northwest Himalayan front. We combined the results of geodetic, geological, geomorphology and InSAR to constrain the uplift and subsidence between Himalayan Frontal Thrust (HFT) and Main Boundary Thrust (MBT) zones. The estimated results of fault parameters reveal that the horizontal shortening of northwest Himalaya is higher than the vertical uplift. The computed values of GLA magnitude analysis for the uplifted region vary from −9.21 to −0.77, whereas these range from 5.48 to 26.60 for the subsided region. The depicted range of vertical deformation observed from the InSAR measurements ranges from −3.13 to +3.14 mm/y, where the positive and negative value of phases are correlated with the ground uplift and subsidence. The rate of deformation observed from Persistent Scatterer Interferometry (PSI) phase velocity and GLA magnitude is positively supported by the chronologically constrained uplift rates as 3.4 ± 0.3 mm/y. The geomorphic evidences such as folded, tilted and truncated alluvial fan surfaces, offsetting of channels, fault scarps and displaced sedimentary sequences indicate active nature of the Soan dun. The study would be eventually useful for seismic hazard assessment and future infrastructure development in the seismotectonically active regions like Soan dun of NW Himalayan front. [ABSTRACT FROM AUTHOR]

BACKGROUND: The risk of early-onset sepsis is low in well-appearing late-preterm and term infants even in the setting of chorioamnionitis. The empirical antibiotic strategies for chorioamnionitis-exposed infants that are recommended by national guidelines result in antibiotic exposure for numerous well-appearing, uninfected infants. We aimed to reduce unnecessary antibiotic use in chorioamnionitis-exposed infants through the implementation of a treatment approach that focused on clinical presentation to determine the need for antibiotics. METHODS: Within a quality-improvement framework, a new treatment approach was implemented in March 2015. Well-appearing late-preterm and term infants who were exposed to chorioamnionitis were clinically monitored for at least 24 hours in a level II nursery; those who remained well appearing received no laboratory testing or antibiotics and were transferred to the level I nursery or discharged from the hospital. Newborns who became symptomatic were further evaluated and/or treated with antibiotics. Antibiotic use, laboratory testing, culture results, and clinical outcomes were collected. RESULTS: Among 277 well-appearing, chorioamnionitis-exposed infants, 32 (11.6%) received antibiotics during the first 15 months of the quality-improvement initiative. No cases of culture result-positive early-onset sepsis occurred. No infant required intubation or inotropic support. Only 48 of 277 (17%) patients had sepsis laboratory testing. The implementation of the new approach was associated with a 55% reduction (95% confidence interval 40%-65%) in antibiotic exposure across all infants >34 weeks' gestation born at our hospital. CONCLUSIONS: A management approach using clinical presentation to determine the need for antibiotics in chorioamnionitis-exposed infants was successful in reducing antibiotic exposure and was not associated with any clinically relevant delays in care or adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: Ketamine is increasingly used for treatment‐resistant depression (TRD) while its mechanism of action is still being investigated. In this systematic review, we appraise the current evidence of metabolomic biomarkers for racemic ketamine and esketamine in patients with TRD and healthy controls (HCs). Methods: A comprehensive search of several databases (Ovid MEDLINE®, Embase, and Epub Ahead of Print) was performed from each database's inception to June 29, 2022, in any language, was conducted. We included studies wherein the metabolomic biomarkers for racemic ketamine or esketamine were investigated in TRD or HCs. Our main outcomes were to examine changes in metabolites among patients treated with ketamine/esketamine and explore the association with response to ketamine/esketamine. Results: A total of 1859 abstracts were screened of which 11 were included for full‐text review. Of these, a total of five articles were included (N = 147), including three RCTs (n = 129) and two open‐label trials (n = 18). All studies used racemic ketamine; one study additionally used esketamine. The included studies evaluated patients with treatment‐resistant bipolar depression (n = 22), unipolar depression (n = 91), and HCs (n = 34). The included studies reported alteration in several metabolites including acylcarnitines, lipids, kynurenine (KYN), and arginine with ketamine in TRD. Studies suggest the involvement of energy metabolism, KYN, and arginine pathways. In HCs, acetylcarnitine decreased post‐infusion, whereas inconsistent findings were observed after the ketamine infusion in TRD patients. Conclusions: This systematic review provides preliminary evidence that ketamine may cause changes in several important pathways involved in energy metabolism and inflammation. Larger and more rigorous studies are needed. [ABSTRACT FROM AUTHOR]

Objective: To investigate scalp hair as biomarker for chronic fluoride exposure among fluoride endemic and low fluoride areas. Methodology: Two areas were identified in Vadodara district, Ajod, as a low fluoride area (Fluoride content of drinking water = 0.11 ppm) and Karsan, a high fluoride area (fluoride content in drinking water = 3.43 ppm). The study was performed on a total of 36 participants from the two villages, 18 from Ajod and 18 from Karsan. Thylstrup Fejerskov Index (TFI) was recorded for each of the participants and sample of hair was collected from the occipital region. Analysis of hair samples was done for assessing the fluoride content. Results: The study consisted of total 36 participants, ranging from the age of 34–60 years and a mean age of 46.53 years. The mean TFI score for the participants in Karsan was 3.39 (±0.979) and in Ajod was 0.83 (±0.786). The difference in this mean score between the two groups was found to be statistically significant. Furthermore, the average fluoride content in hair of the participants in Karsan was 3.40(±1.043) and that in Ajod was 0.35 (±0.063). This difference was statistically significant between the two groups. The TFI scores were found to be positively correlated with the fluoride content in hair. Conclusion: Hair can be used as a useful biomaterial for fluoride exposure monitoring. Having certain advantages over other biomaterials such as easy to collect, store, and transport, hair also serves as a biomarker of chronic fluoride exposure. Hair analysis should thus play a greater role in routinely measuring the chronic exposure to fluorides. [ABSTRACT FROM AUTHOR]

Guar ( Cyamopsis tetragonaloba (L.) Taub) is an annual legume plant and an important source of guar gum, which has great industrial and medicinal value due to phenolic compounds. Thus the consumption of guar and its products has been associated with a reduction in the risk of contracting some types of cancer and other chronic diseases. Phenolic compounds or polyphenols act as antioxidants with mechanisms involving both free radical scavenging and metal chelation. Thus, fifteen different cultivars of the cluster bean leaves i.e. Cyamopsis tetragonaloba (L.) Taub were evaluated for their content of phenolic acids and flavonoids using optimized high performance liquid chromatography (HPLC) with UV detection. These cultivars were also analyzed for antioxidant property using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) activity. Rajasthan guar cultivar-1031 (RGC-1031) showed higher phenolic contents along with better antioxidant property. These results were also confirmed with HPLC where ten phenolic/flavonoid compounds were detected and quantified at varying levels in leaves of different cultivars of guar. Polyphenols such as sinapic acid, cholorogenic acid, caffeic acid, gallic acids and ferulic acid were detected with binary mode of pumps within 10 min with a flow rate of 1.0 mL/min where as flavanoids like kaempferol and myricetin were also identified showing variations among all cultivars. The total phenolic contents and total flavonoid contents in all cultivar were in the range 60.03 to 204.67 mg GAE/g and 4.26 to 12.43 mg QE/g, respectively. In particular, the cultivar RGC-1031 showed the highest content while Local-Selection showed the least content of the total polyphenols. Kaempferol was found to be major constituent in the studied guar cultivars than other phenolics. The extensive variability was observed in polyphenols among fifteen cultivars of guar. The Principal component analysis (PCA) showed that Local-Selection contained higher kaempferol and myricetin, while Pusa Selection-1 recorded higher cholorogenic acid and kaempferol. [ABSTRACT FROM AUTHOR]

With the rising demand of the new users about technological assistance, the libraries need to change their traditional way of functioning. The present generation is very much attracted towards social networking sites (SNS). It is obvious for the libraries and information centres to tap the opportunity and provide services to the users by using SNS. Since these sites provide quick and free access, the libraries can make good use of it. The present study attempts to find out the awareness of the librarians of management institutions towards SNS and explores how much they are using it. The study highlights that the librarians are much aware of SNS and are using them for their personal and professional purpose, but on the same hand fails to use the SNS in their libraries. [ABSTRACT FROM AUTHOR]

The wealth of complementary data available from remote sensing missions can hugely aid efforts towards accurately determining land use and quantifying subtle changes in land use management or intensity. This study reviewed 112 studies on fusing optical and radar data, which offer unique spectral and structural information, for land cover and use assessments. Contrary to our expectations, only 50 studies specifically addressed land use, and five assessed land use changes, while the majority addressed land cover. The advantages of fusion for land use analysis were assessed in 32 studies, and a large majority (28 studies) concluded that fusion improved results compared to using single data sources. Study sites were small, frequently 300-3000 km² or individual plots, with a lack of comparison of results and accuracies across sites. Although a variety of fusion techniques were used, pre-classification fusion followed by pixel-level inputs in traditional classification algorithms (e.g., Gaussian maximum likelihood classification) was common, but often without a concrete rationale on the applicability of the method to the land use theme being studied. Progress in this field of research requires the development of robust techniques of fusion to map the intricacies of land uses and changes therein and systematic procedures to assess the benefits of fusion over larger spatial scales. [ABSTRACT FROM AUTHOR]

A highly efficient Polyvinylpyrrolidone (PVP) coated copper–iron oxide magnetic nanoparticles as catalyst has been developed for the Huisgen 1,3-dipolar cycloaddition reactions between organic azides and terminal alkynes which is known to be the best example in click chemistry. The in situ generated Cu(I) species is the catalytically active species for click reaction. Wide ranges of 1,2,3 triazoles have been synthesized in good yields by use of the catalyst at room temperature. This nanocatalyst can be recovered by applying an external magnetic field which results in easy separation of the catalyst without filtration and can be reused three times without loss of its significant activity. This catalyst was characterized by FT-IR, XRD, XPS, FESEM, and TEM. [ABSTRACT FROM AUTHOR]

Mapping forest aboveground biomass (AGB) using satellite data is an important task, particularly for reporting of carbon stocks and changes under climate change legislation. It is known that AGB can be mapped using synthetic aperture radar (SAR), but relationships between AGB and radar backscatter may be confounded by variations in biophysical forest structure (density, height or cover fraction) and differences in the resolution of satellite and ground data. Here, we attempt to quantify the effect of these factors by relating L-band ALOS PALSAR HV backscatter and unique country-wide LiDAR-derived maps of vegetation penetrability, height and AGB over Denmark at different spatial scales (50 m to 500 m). Trends in the relations indicate that, first, AGB retrieval accuracy from SAR improves most in mapping at 100-m scale instead of 50 m, and improvements are negligible beyond 250 m. Relative errors (bias and root mean squared error) decrease particularly for high AGB values (>110 Mg ha-1) at coarse scales, and hence, coarse-scale mapping (⩾150 m) may be most suited for areas with high AGB. Second, SAR backscatter and a LiDAR-derived measure of fractional forest cover were found to have a strong linear relation (R2 = 0.79 at 250-m scale). In areas of high fractional forest cover, there is a slight decline in backscatter as AGB increases, indicating signal attenuation. The two results demonstrate that accounting for spatial scale and variations in forest structure, such as cover fraction, will greatly benefit establishing adequate plot-sizes for SAR calibration and the accuracy of derived AGB maps. [ABSTRACT FROM AUTHOR]

Background: Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by acantholysis of keratinocytes due to pathogenic desmoglein-3 autoantibodies. Role of vitamin D has been recently implicated in various autoimmune conditions due to its immunomodulatory effects on innate and adaptive immune responses. One of the key mechanisms of the immune regulation by vitamin D is through its anti-inflammatory effects by suppression of Th17 functions. Thus, vitamin D may be involved in pathogenesis of PV. In this study, the serum vitamin D, IL-17 and TGF-β levels in PV patients as well as healthy controls were estimated in order to understand the underlying immune mechanism involved in disease pathogenesis. Results: This retrospective study included 30 biopsy proven PV patients’ sera. Ten age matched volunteers without any cutaneous or autoimmune conditions were recruited as healthy control (HC). Serum Vitamin D levels were measured using chemiluminescence, whereas IL-17 and TGF-β levels were determined using ELISA. All patients showed deficient vitamin D levels (11.1 ± 5.8 ng/ml). Moreover, all the PV patients had elevated serum IL-17 levels (210.7 ± 105.3), whereas it was not detectable in any (n = 10) of the healthy controls sera (ELISA sensitivity ≥ 8 pg/ml). The mean serum TGF-β concentration was also lower in patient sera as compared to healthy control, and the TGF-β/IL-17 ratio was drastically reduced in patients (30.30 ± 28), as compared to healthy controls (1363.34 ± 559.52). Conclusions: Hypovitaminosis is common in North India, as ascertained by deficient levels in healthy controls, and was also consistently observed in PV patient. These low levels were not related to age or gender. The increased serum IL-17 and dramatic reduction in TGF-β/IL-17 ratio in diseased patients further indicate that dysregulation of the Treg/Th-17 axis of T effector cells may be of significance in pathogenesis of PV. Thus, the study indicates that vitamin D insufficiency may be a predisposing factor in PV, contributing through its role in any of the various adaptive immune mechanisms that regulate T cell functions in vivo. Thus, there is a need to further evaluate the Treg/Th-17 axis, as it may have an important role in disease progression. [ABSTRACT FROM AUTHOR]

Deforestation of mangroves is of global concern given their importance for carbon storage, biogeochemical cycling and the provision of other ecosystem services, but the links between rates of loss and potential drivers or risk factors are rarely evaluated. Here, we identified key drivers of mangrove loss in Kenya and compared two different approaches to predicting risk. Risk factors tested included various possible predictors of anthropogenic deforestation, related to population, suitability for land use change and accessibility. Two approaches were taken to modelling risk; a quantitative statistical approach and a qualitative categorical ranking approach. A quantitative model linking rates of loss to risk factors was constructed based on generalized least squares regression and using mangrove loss data from 1992 to 2000. Population density, soil type and proximity to roads were the most important predictors. In order to validate this model it was used to generate a map of losses of Kenyan mangroves predicted to have occurred between 2000 and 2010. The qualitative categorical model was constructed using data from the same selection of variables, with the coincidence of different risk factors in particular mangrove areas used in an additive manner to create a relative risk index which was then mapped. Quantitative predictions of loss were significantly correlated with the actual loss of mangroves between 2000 and 2010 and the categorical risk index values were also highly correlated with the quantitative predictions. Hence, in this case the relatively simple categorical modelling approach was of similar predictive value to the more complex quantitative model of mangrove deforestation. The advantages and disadvantages of each approach are discussed, and the implications for mangroves are outlined. [ABSTRACT FROM AUTHOR]

Roots of the susceptible “JG-62” and resistant “WR-315” chickpeas (Cicer arietinum L.) were inoculated with a conidial suspension of Fusarium oxysporum f. sp. ciceris. Anatomical and biochemical studies were carried out in a time-course manner to elucidate the infection process and plant defence reactions. Scanning electron microscope images revealed fungal colonisation in the root hair region. Early occurrence of fungal biofilms associated with the infected “JG-62” root epidermis was also visualised. After 96 h of inoculation, a gradual accumulation of polysaccharide positive deposits was observed in the xylem vessels of the infected “JG-62” roots. Fungal mycelium was observed in the vessel lumen of infected “JG-62” after 22 days of inoculation. Due to fungal invasion during this period, some of the vessels also appeared collapsed in “JG-62”, whereas vessels in “WR-315” remained intact. The host plant defence responses specifically linked to the susceptible interactions were the induction of ascorbate peroxidase, guaiacol peroxidase and superoxide dismutase in roots and shoots. [ABSTRACT FROM PUBLISHER]

Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential. [ABSTRACT FROM AUTHOR]

Cystic lymphangiomas are uncommon congenital benign tumours of vascular origin with a lymphatic differentiation originating across various anatomical locations. Large intrabdominal cysts may mimic ascites. We report the case of a one-and-a-half-year-old male child with a giant cystic lymphangioma originating in the greater omentum presenting as tubercular ascites. This report aims to highlight the limitations of biochemical investigations such as ascitic adenosine deaminase (ADA) in differentiating the epidemiologically prevalent tubercular ascites from an intrabdominal cyst, especially in a resource-poor nation as ours, where invasive diagnostic procedures pose an economic burden. [ABSTRACT FROM AUTHOR]

ADAM33 has been linked to airway structural changes in patients with asthma, leading to airway hyperresponsiveness, narrowing, and ultimately poor treatment responsiveness. This study aimed to evaluate the genetic association of ADAM33 SNPs with asthma, disease severity, and treatment responsiveness to ICS+LABA in the South Indian population. In this case–control study (486 controls and 503 cases), we performed genotyping using MassArray for six SNPs of ADAM33, namely rs2280091, rs2787094, rs3918396, rs67044, rs2853209, and rs3918392. We studied the association with asthma and treatment responsiveness to ICS+LABA, using genotype, allele frequency distribution, and haplotype analysis. A significant clinical finding of the study was that certain patients in the disease severity group (moderate and mild) showed poor or no improvement after a three-month follow-up of regular ICS+LABA therapy. Of the studied ADAM33 SNPs, rs2853209 showed an association with asthma. The further analysis of asthma patients according to disease severity suggested an association between moderate disease and the minor allele "T" for rs2853209. The homozygous minor allele of SNP rs2787094 was found to be associated with poorer lung function and the least lung-function improvement after three months of ICS+LABA therapy. The haplotype analysis of six SNPs showed a significant association between the rs2853209 and rs3918396 blocks and asthma. ADAM33 gene polymorphism has clinical relevance in terms of disease association and response to treatment. SNP rs2853209 seemed most relevant to asthma, and SNP rs2787094 could be a genetic marker for predicting response to ICS+LABA therapy in the study population. [ABSTRACT FROM AUTHOR]

Congenital leukemia (CL) is an extremely rare disorder in the newborn, significant proportion of which is of myeloid origin, primarily of M4 or M5 morphology. As compared to pediatric leukemia, CL is a more aggressive disease. Acute myeloid leukemia (AML-M7) or acute megakaryocytic leukemia is a rare type of AML with an incidence of 0.5 per million per year. Median age of presentation is 6 years, and children may present with a broad variety of symptoms including low-grade fever, diarrhea, easy bruising, failure to gain weight and life-threatening conditions. [ABSTRACT FROM AUTHOR]

Transcription factor HAND2 has a significant role in vascularization, angiogenesis, and cardiac neural crest development. It is one of the key cardiac factors crucial for the enhanced derivation of functional and mature myocytes from non-myocyte cells. Here, we report the generation of the recombinant human HAND2 fusion protein from the heterologous system. First, we cloned the full-length human HAND2 gene (only protein-coding sequence) after codon optimization along with the fusion tags (for cell penetration, nuclear translocation, and affinity purification) into the expression vector. We then transformed and expressed it in Escherichia coli strain, BL21(DE3). Next, the effect (in terms of expression) of tagging fusion tags with this recombinant protein at two different terminals was also investigated. Using affinity chromatography, we established the one-step homogeneous purification of recombinant human HAND2 fusion protein; and through circular dichroism spectroscopy, we established that this purified protein had retained its secondary structure. We then showed that this purified human protein could transduce the human cells and translocate to its nucleus. The generated recombinant HAND2 fusion protein showed angiogenic potential in the ex vivo chicken embryo model. Following transduction in MEF2C overexpressing cardiomyoblast cells, this purified recombinant protein synergistically activated the α-MHC promoter and induced GFP expression in the α-MHC-eGFP reporter assay. Prospectively, the purified bioactive recombinant HAND2 protein can potentially be a safe and effective molecular tool in the direct cardiac reprogramming process and other biological applications. [ABSTRACT FROM AUTHOR]

Hurler–Scheie syndrome (MPS IH/S), also known as mucopolysaccharidosis type I-H/S (MPS IH/S), is a lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase (IDUA) leading to the accumulation of glycosaminoglycans (GAGs) in various tissues, resulting in a wide range of symptoms affecting different organ systems. Postgenomic omics technologies offer the promise to understand the changes in proteome, phosphoproteome, and phosphorylation-based signaling in MPS IH/S. Accordingly, we report here a large dataset and the proteomic and phosphoproteomic analyses of fibroblasts derived from patients with MPS IH/S (n = 8) and healthy individuals (n = 8). We found that protein levels of key lysosomal enzymes such as cathepsin D, prosaposin, arylsulfatases (arylsulfatase A and arylsulfatase B), and IDUA were downregulated. We identified 16,693 unique phosphopeptides, corresponding to 4,605 proteins, in patients with MPS IH/S. We found that proteins related to the cell cycle, mitotic spindle assembly, apoptosis, and cytoskeletal organization were differentially phosphorylated in MPS IH/S. We identified 12 kinases that were differentially phosphorylated, including hyperphosphorylation of cyclin-dependent kinases 1 and 2, hypophosphorylation of myosin light chain kinase, and calcium/calmodulin-dependent protein kinases. Taken together, the findings of the present study indicate significant alterations in proteins involved in cytoskeletal changes, cellular dysfunction, and apoptosis. These new observations significantly contribute to the current understanding of the pathophysiology of MPS IH/S specifically, and the molecular mechanisms involved in the storage of GAGs in MPS more generally. Further translational clinical omics studies are called for to pave the way for diagnostics and therapeutics innovation for patients with MPS IH/S. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and incomplete differentiation of epidermis, and accumulation of neutrophils and proinflammatory T cells in epidermis and dermis. Chemokines are believed to be the main players mediating the chemotaxis of leucocytes to the lesional site. Previous studies have established the role of various chemokine ligands and receptors at the lesional site in psoriasis.Aims: In this study, we have compared the serum levels of various chemokines, namely, inducible protein-10 (IP-10) (CXCL10), MCP-1 (CCL-2), monokine induced by gamma interferon (MIG) (CXCL-9), RANTES (CCL5), interleukin (IL)-8, and eotaxin in patients with chronic plaque psoriasis with that of healthy controls. We also studied whether the chemokine levels varied within different patient groups based on various clinical and demographic parameters, and if any of these chemokines correlated with disease activity.Methods: We studied 40 patients with chronic plaque psoriasis from a single center. Their clinical and demographic details were recorded in predesigned prforma. Patients with unstable forms of psoriasis like guttate, erythrodermic, or pustular psoriasis were excluded. The serum chemokine levels were measured by flow cytometry-based bead array set system. The serum levels of the patients were compared with that of 25 healthy controls. A subgroup analysis was also done to study the correlation of chemokine levels with age, sex, duration, and severity of disease.Results: We observed a significant decrease in serum level of all these chemokines in patients, when compared with that of healthy controls. We also found that MIG levels showed a positive correlation with disease severity based on Psoriasis Area and Severity Index.Limitations: The major limitation of the study is lack of data on the lesional chemokine levels compared to serum chemokines.Conclusion: The inflammatory process in psoriasis is orchestrated through chemokines. MIG is a potential serum biomarker for assessing disease severity. [ABSTRACT FROM AUTHOR]

Neurogenin 3 (NGN3) transcription factor is vital for the development of endocrine cells of the intestine and pancreas. NGN3 is also critical for the neural precursor cell determination in the neuroectoderm. Additionally, it is one of the vital transcription factors for deriving human β-cells from specialized somatic cells. In the current study, the production and purification of the human NGN3 protein from Escherichia coli (E. coli) is reported. First, the 642 bp protein-coding nucleotide sequence of the NGN3 gene was codon-optimized to enable enhanced protein expression in E. coli strain BL21(DE3). The codon-optimized NGN3 sequence was fused in-frame to three different fusion tags to enable cell penetration, nuclear translocation, and affinity purification. The gene insert with the fusion tags was subsequently cloned into an expression vector (pET28a(+)) for heterologous expression in BL21(DE3) cells. A suitable genetic construct and the ideal expression conditions were subsequently identified that produced a soluble form of the recombinant NGN3 fusion protein. This NGN3 fusion protein was purified to homogeneity (purity > 90%) under native conditions, and its secondary structure was retained post-purification. This purified protein, when applied to human cells, did not induce cytotoxicity. Further, the cellular uptake and nuclear translocation of the NGN3 fusion protein was demonstrated followed by its biological activity in PANC-1 cells. Prospectively, this recombinant protein can be utilized for various biological applications to investigate its functionality in cell reprogramming, biological processes, and diseases. [ABSTRACT FROM AUTHOR]

The shoreline of Gujarat in western coast of India has remained exposed to tsunamis and storm surges in past from distant to regional sources and processes. The catalogue of past tsunami and storm events whose geological signatures have been archived in the coastal records, often hints at frequency, magnitude and recurrence. In present work, we compile all possible signatures of palaeo-extreme wave events and attempt to assess the vulnerability to this rapidly developing shoreline. We report a total of six major extreme wave events, out of which atleast two have been identified to be associated with palaeotsunami deposits, whereas three are storm surge deposits and one is designated as a washover deposit. Archeological findings like the presence of thick walls around Dholavira (an ancient Harappan coastal trading centre) is also supportive of Harappan learning from the wrath of marine waves they would have faced. This study reports the wider time gap between the events, attributed to lack of preservation, difficulty in recognition, higher reworking or lack of detailed investigation ~ making the task of estimating recurrence a mammoth effort. The study shows that the shoreline of Gujarat has remained vulnerable to extreme wave events atleast during the last 6000 years, and have affected ancient settlers as well as modern anthropological activities. [ABSTRACT FROM AUTHOR]

This study presents a comparative account on synthesis and characterization of ZnO/CuO (ZC) nanostructures by exploiting the capping, stabilizing and reducing characteristics of the biogenic green surfactants (rhamnolipid and surfactin) vis-à-vis chemical surfactant (sodium dodecyl sulfate). The ZC material is characterized by various sophisticated analytical tools such as X-ray diffraction (XRD), spectroscopic, and microscopic methods. The optical studies reveal the bandgap energy of the pristine ZC to be 3.77 eV, which varies marginally for SDS@ZnO/CuO (3.65 eV), rhamnolipd@ZnO/CuO (3.69 eV) and surfactin@ZnO/CuO (3.75 eV). In addition, antibacterial activities of the prepared samples against two pathogenic bacteria, Micrococcus luteus (ATCC 4698) and Escherichia coli DH5α (CP026085) are investigated and the mode of action is demonstrated through the destabilization and disruption of the bacterial membranes and subsequent killing. [Display omitted] [ABSTRACT FROM AUTHOR]