Contribution of Food from Market Purchases and Home Production to Child Nutrient Intake: Evidence from the EFFECTS Study Baseline Data.

BACKGROUND: Child undernutrition is prevalent in Tanzania, and households rely primarily on local markets and home production as food sources. However, little is known about the contribution of food market purchases to nutrient intakes among children consuming complementary foods. OBJECTIVES: To quantify the relationships between diversity of foods purchased and produced by households and adequate child nutrient intake in Mara, Tanzania. METHODS: Cross-sectional baseline dietary and household food source data from the Engaging Fathers for Effective Child Nutrition and Development in Tanzania study were collected from mothers of 586 children aged 9-23 mo clustered in 80 villages in Mara, Tanzania. We conducted mixed effects linear regressions to quantify the association between the diversity of foods consumed at home, from market purchases and home production, and nutrient intake adequacy (based on 24-h food recalls). RESULTS: Children had inadequate diets, with fewer than half of children consuming adequate amounts of vitamin A, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B9 (folate), calcium, iron, and zinc. Breastfeeding was associated with higher overall mean adequacy (b = 0.15-0.19 across models, P < 0.001). Diversity of foods purchased was positively associated with the intake of vitamin B12 and calcium (both P < 0.001); this effect was attenuated among breastfed children. Among nonbreastfed children, production diversity was positively associated with vitamin A intake (b=0.04; P < .05) but not with intake of other nutrients. CONCLUSIONS: Both household food purchase and food production diversities were positively associated with children's nutrient intake in rural Mara, Tanzania. Nutrition programming should consider the role of food markets in addition to home food production to improve child diets. This trial was registered at clinicaltrials.gov as NCT03759821, https://clinicaltrials.gov/study/NCT03759821.

Quantitative assessment of machine learning reliability and resilience.

Advances in machine learning (ML) have led to applications in safety-critical domains, including security, defense, and healthcare. These ML models are confronted with dynamically changing and actively hostile conditions characteristic of real-world applications, requiring systems incorporating ML to be reliable and resilient. Many studies propose techniques to improve the robustness of ML algorithms. However, fewer consider quantitative techniques to assess changes in the reliability and resilience of these systems over time. To address this gap, this study demonstrates how to collect relevant data during the training and testing of ML suitable for the application of software reliability, with and without covariates, and resilience models and the subsequent interpretation of these analyses. The proposed approach promotes quantitative risk assessment of ML technologies, providing the ability to track and predict degradation and improvement in the ML model performance and assisting ML and system engineers with an objective approach to compare the relative effectiveness of alternative training and testing methods. The approach is illustrated in the context of an image recognition model, which is subjected to two generative adversarial attacks and then iteratively retrained to improve the system's performance. Our results indicate that software reliability models incorporating covariates characterized the misclassification discovery process more accurately than models without covariates. Moreover, the resilience model based on multiple linear regression incorporating interactions between covariates tracks and predicts degradation and recovery of performance best. Thus, software reliability and resilience models offer rigorous quantitative assurance methods for ML-enabled systems and processes.

Anthropogenic impacts on urban blue space and its reciprocal effect on human and socio-ecological health.

Quantifying anthropogenic impacts on blue space (BS) and its effect on human and socio-ecological health was least explored. The present study aimed to do this in reference to the urban BS transformation scenario of Eastern India. To measure BS transformation, Landsat image-based water indices were run from 1990 to 2021. Anthropogenic impact score (AIS) and 7 components scores of 78 selected BS on 70 parameters related data driven from the field. Total 345 respondents were taken for human and socio-ecological health assessment. For this, depression (DEP), anxiety (ANX), stress (STR), physical activities (PA), social capital (SC), therapeutic landscape (TL) and environment building (EB) parameters were taken. The result exhibited that BS was reduced. About 50% of urban core BS was reported highly impacted. Human and socio-ecological health was identified as good in proximity to BS, but it was observed better in the cases of larger peripheral BS. AIS on BS was found to be positively associated with mental health (0.47-0.63) and negatively associated with PA, SC, TL and EB (-0.50 to -0.90). Standard residual in ordinary least square was reported low (-1.5 to 1.5) in 95% BS. Therefore, BS health restoration and management is crucial for sustaining the living environment.

How hydrological components of urban blue space influence the thermal milieu?

Present study examines the possible improvement of thermal discomfort mitigation. Unlike prior researches, which focused primarily on cooling effects of urban blue space, this study, instead of physical presence of blue space considers its hydrological components. The aim of the study is to better understand the role hydrological components like water consistency depth etc. In temperature regulation. The work uses field surveys and modeling to demonstrate how these hydrological factors influence the cooling effect of blue space, providing insights on urban thermal management. To fulfill the purpose, spatial association of hydrological components blue space with its thermal environment and cooling effects was assessed. The control of hydrological components on the surrounding air temperature was examined by conducting case studies. RESULTS: reveals greater hydro-duration, deeper water, and higher Water Presence Frequency (WPF) produce greater cooling effects. The study demonstrates a favorable correlation between hydrological richness and temperature reduction. The study also analyzes how land use and wetland size affect temperature, emphasizing the significance of hydrological conservation and restoration for successful temperature mitigation. Due to their hydrology, larger wetlands are able to moderate temperature to some extent, whereas smaller, fragmented wetlands being hydrologically poor are not so influential in this regard. With these results, the present study reaches beyond to the general understanding regarding the cooling effects of the urban blue spaces. While the previous studies primarily focused on estimating the cooling effect of urban blue space, the current one shows its synchronization with the hydrological characteristics. Novelty also entrusts here, through the modeling and field survey current study demonstrates deeper and consistent water coverage in the urban blue space for maximum period of a year pronounces the cooling effect. In addition, in this cooling effect, the role of land use which is a strong determinant of many aspects of the urban environment is also highlighted. Since all these findings define specific hydrological feature, the study has several practical implications. Mare restoration of urban blue space is not enough to mitigate the thermal discomfort. In order to optimize the cooling effect, the conservation of the hydrological richness is essential. The hydrological richness of the smaller wetlands and the edge of the larger wetlands is to be improved. The connection of these wetlands with the adjacent mighty may strengthen the hydrology. The vegetation was found to promote the cooling effect whereas shorter building helped in spreading the cooling effect. Such finding drives to incorporate the blue space with the green infrastructure along with restricting the building height atleast at the edge of the blue space.

Riboflavin salvage by Borrelia burgdorferi supports carbon metabolism and is essential for survival in the tick vector.

The Lyme disease agent, Borrelia burgdorferi, harbors a significantly reduced genome and relies on the scavenging of critical nutrients from its tick and mammalian hosts for survival. Riboflavin salvage has been shown to be important for B. burgdorferi infection of mice, yet the contributions of riboflavin to B. burgdorferi metabolism and survival in the tick remain unknown. Using a targeted mass spectrometry approach, we confirmed the importance of bb0318, the putative ATPase component of an ABC-type riboflavin transporter, for riboflavin salvage and the production of FMN and FAD. This analysis further revealed that Δbb0318 B. burgdorferi displayed increased levels of glycerol 3-phosphate compared to the wild-type. The glycerol 3-phosphate dehydrogenase activity of GlpD was found to be FAD-dependent and the transcription and translation of glpD were significantly decreased in Δbb0318 B. burgdorferi. Finally, gene bb0318 was found to be important for maximal spirochete burden in unfed larvae and essential for survival in feeding ticks. Together, these data demonstrate the importance of riboflavin salvage for B. burgdorferi carbon metabolism and survival in ticks.

Factors influencing and changes in childhood vaccination coverage over time in Bangladesh: a multilevel mixed-effects analysis.

INTRODUCTION: This study aimed to investigate the associated factors and changes in childhood vaccination coverage over time in Bangladesh. METHODS: Bangladesh's Demographic and Health Surveys from 2011, 2014, and 2017-18 provided data for this study on vaccination coverage among children aged 12 to 35 months. For three survey periods, multilevel binary logistic regression models were employed. RESULTS: The overall prevalence (weighted) of full vaccination among children aged 12-35 months were 86.17% in 2011, 85.13% in 2014, and 89.23% in 2017-18. Children from families with high wealth index, mothers with higher education, and over the age of 24 and who sought at least four ANC visits, as well as children from urban areas were more likely to receive full vaccination. Rangpur division had the highest change rate of vaccination coverage from 2011 to 2014 (2.26%), whereas Sylhet division had the highest change rate from 2014 to 2017-18 (34.34%). CONCLUSION: To improve immunization coverage for Bangladeshi children, policymakers must integrate vaccine programs, paying special attention to mothers without at least a high school education and families with low wealth index. Increased antenatal care visits may also aid in increasing the immunization coverage of their children.

Nature's palette: An emerging frontier for coloring dairy products.

Consumers all across the world are looking for the most delectable and appealing foods, while also demanding products that are safer, more nutritious, and healthier. Substitution of synthetic colorants with natural colorants has piqued consumer and market interest in recent years. Due to increasing demand, extensive research has been conducted to find natural and safe food additives, such as natural pigments, that may have health benefits. Natural colorants are made up of a variety of pigments, many of which have significant biological potential. Because of the promising health advantages, natural colorants are gaining immense interest in the dairy industry. This review goes over the use of various natural colorants in dairy products which can provide desirable color as well as positive health impacts. The purpose of this review is to provide an in-depth look into the field of food (natural or synthetic) colorants applied in dairy products as well as their potential health benefits, safety, general trends, and future prospects in food science and technology. In this paper, we listed a plethora of applications of natural colorants in various milk-based products.

Deciphering the Interregional and Interhemisphere Proteome of the Human Brain in the Context of the Human Proteome Project.

This study, which performs an extensive mass spectrometry-based analysis of 19 brain regions from both left and right hemispheres, presents the first draft of the human brain interhemispheric proteome. This high-resolution proteomics data provides comprehensive coverage of 3300 experimentally measured (nonhypothetical) proteins across multiple regions, allowing the characterization of protein-centric interhemispheric differences and synapse biology, and portrays the regional mapping of specific regions for brain disorder biomarkers. In the context of the Human Proteome Project (HPP), the interhemispheric proteome data reveal specific markers like chimerin 2 (CHN2) in the cerebellar vermis, olfactory marker protein (OMP) in the olfactory bulb, and ankyrin repeat domain 63 (ANKRD63) in basal ganglia, in line with regional brain transcriptomes mapped in the Human Protein Atlas (HPA). In addition, an in silico analysis pipeline was used to predict the structure and function of the uncharacterized uPE1 protein ANKRD63, and parallel reaction monitoring (PRM) was applied to validate its region-specific expression. Finally, we have built the Interhemispheric Brain Proteome Map (IBPM) Portal (www.brainprot.org) to stimulate the scientific community's interest in the brain molecular landscape and accelerate and support research in neuroproteomics. Data are available via ProteomeXchange with identifier PXD019936.

Fluorescence-Reported Allelic Exchange Mutagenesis-Mediated Gene Deletion Indicates a Requirement for Chlamydia trachomatis Tarp during In Vivo Infectivity and Reveals a Specific Role for the C Terminus during Cellular Invasion.

The translocated actin recruiting phosphoprotein (Tarp) is a multidomain type III secreted effector used by Chlamydia trachomatis In aggregate, existing data suggest a role of this effector in initiating new infections. As new genetic tools began to emerge to study chlamydial genes in vivo, we speculated as to what degree Tarp function contributes to Chlamydia's ability to parasitize mammalian host cells. To address this question, we generated a complete tarP deletion mutant using the fluorescence-reported allelic exchange mutagenesis (FRAEM) technique and complemented the mutant in trans with wild-type tarP or mutant tarP alleles engineered to harbor in-frame domain deletions. We provide evidence for the significant role of Tarp in C. trachomatis invasion of host cells. Complementation studies indicate that the C-terminal filamentous actin (F-actin)-binding domains are responsible for Tarp-mediated invasion efficiency. Wild-type C. trachomatis entry into HeLa cells resulted in host cell shape changes, whereas the tarP mutant did not. Finally, using a novel cis complementation approach, C. trachomatis lacking tarP demonstrated significant attenuation in a murine genital tract infection model. Together, these data provide definitive genetic evidence for the critical role of the Tarp F-actin-binding domains in host cell invasion and for the Tarp effector as a bona fide C. trachomatis virulence factor.

Aggregation dynamics of charged peptides in water: Effect of salt concentration.

Extensive molecular dynamics simulations have been employed to probe the effects of salts on the kinetics and dynamics of early-stage aggregated structures of steric zipper peptides in water. The simulations reveal that the chemical identity and valency of cation in the salt play a crucial role in aggregate dynamics and morphology of the peptides. Sodium ions induce the most aggregated structures, but this is not replicated equivalently by potassium ions which are also monovalent. Divalent magnesium ions induce aggregation but to a lesser extent than that of sodium, and their interactions with the charged peptides are also significantly different. The aggregate morphology in the presence of monovalent sodium ions is a compact structure with interpenetrating peptides, which differs from the more loosely connected peptides in the presence of either potassium or magnesium ions. The different ways in which the cations effectively renormalize the charges of peptides are suggested to be the cause of the differential effects of different salts studied here. These simulations underscore the importance of understanding both the valency and nature of salts in biologically relevant aggregated structures.

Biophysical characterization of actin bundles generated by the Chlamydia trachomatis Tarp effector.

Chlamydia trachomatis entry into host cells is mediated by pathogen-directed remodeling of the actin cytoskeleton. The chlamydial type III secreted effector, translocated actin recruiting phosphoprotein (Tarp), has been implicated in the recruitment of actin to the site of internalization. Tarp harbors G-actin binding and proline rich domains required for Tarp-mediated actin nucleation as well as unique F-actin binding domains implicated in the formation of actin bundles. Little is known about the mechanical properties of actin bundles generated by Tarp or the mechanism by which Tarp mediates actin bundle formation. In order to characterize the actin bundles and elucidate the role of different Tarp domains in the bundling process, purified Tarp effectors and Tarp truncation mutants were analyzed using Total Internal Reflection Fluorescence (TIRF) microscopy. Our data indicate that Tarp mediated actin bundling is independent of actin nucleation and the F-actin binding domains are sufficient to bundle actin filaments. Additionally, Tarp-mediated actin bundles demonstrate distinct bending stiffness compared to those crosslinked by the well characterized actin bundling proteins fascin and alpha-actinin, suggesting Tarp may employ a novel actin bundling strategy. The capacity of the Tarp effector to generate novel actin bundles likely contributes to chlamydia's efficient mechanism of entry into human cells.

A new class of enhanced kinetic sampling methods for building Markov state models.

Markov state models (MSMs) and other related kinetic network models are frequently used to study the long-timescale dynamical behavior of biomolecular and materials systems. MSMs are often constructed bottom-up using brute-force molecular dynamics (MD) simulations when the model contains a large number of states and kinetic pathways that are not known a priori. However, the resulting network generally encompasses only parts of the configurational space, and regardless of any additional MD performed, several states and pathways will still remain missing. This implies that the duration for which the MSM can faithfully capture the true dynamics, which we term as the validity time for the MSM, is always finite and unfortunately much shorter than the MD time invested to construct the model. A general framework that relates the kinetic uncertainty in the model to the validity time, missing states and pathways, network topology, and statistical sampling is presented. Performing additional calculations for frequently-sampled states/pathways may not alter the MSM validity time. A new class of enhanced kinetic sampling techniques is introduced that aims at targeting rare states/pathways that contribute most to the uncertainty so that the validity time is boosted in an effective manner. Examples including straightforward 1D energy landscapes, lattice models, and biomolecular systems are provided to illustrate the application of the method. Developments presented here will be of interest to the kinetic Monte Carlo community as well.

Decreased Frequency and Secretion of CD26 Promotes Disease Progression in Indian Post Kala-azar Dermal Leishmaniasis.

PURPOSE: Leishmania, the causative organisms for leishmaniasis, reside in host macrophages and survive by modulating the microbicidal pathways via attenuation of the oxidative burst and/or suppression of cell-mediated immunity. As post kala-azar dermal leishmaniasis (PKDL), the dermal sequela of visceral leishmaniasis, has no animal model, the underlying mechanism(s) that nullify the microbicidal effector mechanisms remain poorly understood. This study was aimed at assessing the status of dipeptidyl peptidase CD26, a co-stimulatory molecule that is essential for T-cell signal activation. METHODS: The frequency/expression of CD26 and CD45RO/RA was evaluated by flow cytometry, while levels of soluble CD26 (sCD26), CXCL-10, RANTES, IL-10 and TGF-ß along with adenosine deaminase (ADA) activity were measured using ELISA. RESULTS: In patients with PKDL vis-à-vis healthy individuals, there was a significant decrease in the frequency and expression of CD26 on CD3(+)CD8(+) T-cells, which was accompanied by a significant lowering of plasma levels of sCD26. Furthermore, these patients showed a significant decrease in the frequency of CD45RO(+)/CD8(+) T-cells, concomitant with a significant increase in the proportion of CD45RA(+)/CD8(+) T-cells. This could collectively translate into reduced formation of the immunological synapse of CD26, CD45RO, and ADA, and lead to an attenuation of the Th1 responses. The decreased levels of CD26 and sCD26 correlated negatively with raised levels of Th2 cytokines, IL-10, and TGF-ß along with the lesional parasite load, indicating disease specificity. CONCLUSIONS: Taken together, the decreased expression and secretion of CD26 in patients with PKDL resulted in impairment of the CD26-ADA interaction, and thereby possibly contributed to T-cell unresponsiveness, emphasizing the need to develop immunomodulatory therapies against PKDL and by extension, the leishmaniases.

Antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom in experimental animal models.

Pain and inflammation are intimately associated with rheumatoid arthritis, a growing bone-joint related problem of the modern society. Though several therapeutic managements are available for arthritis, their side effects not only limit their use, but also advocate the quest for natural therapies. In this study, we explored the antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom (BFV) in experimental animal models. Rheumatoid arthritis was induced by Freund's complete adjuvant (FCA) in male Wistar albino rats. Lyophilized BFV was diluted in 0.9% NaCl. Antiarthritic activity showed that BFV significantly reduced the paw and ankle diameters; urinary hydroxyproline, glucosamine levels and serum ACP/ALP/TNF-α/IL-1ß/IL-17/Cathepsin-K/MMP-1 levels. These parameters were significantly increased in FCA induced arthritic animals. Joint histopathology study indicated the partial restoration of joint structure. Treatment with BFV significantly reduced the mean latency time of tail flick response, acetic acid induced writhing response and formalin induced licking response in male albino mice. BFV treatment also significantly reduced carrageenan induced paw edema and xylene induced ear edema in male albino mice. The results indicated that BFV possess antinociceptive, anti-inflammatory and antiarthritic properties and further studies are warranted to find the active constituents present in BFV.

A Defective Oxidative Burst and Impaired Antigen Presentation are Hallmarks of Human Visceral Leishmaniasis.

PURPOSE: Survival of the Leishmania parasite within monocytes hinges on its ability to effectively nullify their microbicidal effector mechanisms. Accordingly, this study aimed to delineate this biological niche in patients with visceral leishmaniasis (VL). METHODS: In monocytes, the redox status, antigen presenting capacity, expression of Toll-like receptors (TLRs), co-stimulatory molecules (CD80/86) and generation of intracellular cytokines (IL-8, IL-1ß, IL-10 and LAP-TGF-ß1) was measured by flow cytometry, levels of circulating cytokines (IL-1ß, IL-6, TNF-α, IL-8, IL-4, IL-13, IL-10 and GM-CSF) by ELISA and arginase activity by spectrophotometry. RESULTS: Within monocytes, generation of an oxidative burst was markedly attenuated as evident by decreased generation of nitric oxide and reactive oxygen species, concomitant with raised levels of thiols. This was accompanied by lowered frequency of TLR4(+) monocytes, but the arginase activity remained unaltered. Pathogen persistence was enhanced by the predominance of anti-inflammatory cytokines within monocytes, notably IL-10. Alongside, development of adaptive immunity was severely attenuated as manifested by a pronounced impairment of antigen presentation and co-stimulation evident by down regulation of CD54, HLA-DR and CD86. Treatment corrected the redox imbalance and reversed the impaired antigen presentation. CONCLUSIONS: In VL, monocyte functions were severely impaired facilitating parasite persistence; anti-leishmanial chemotherapy mediated parasite elimination through modulation of the macrophage microenvironment by restoring its redox status and antigen presenting capacity.

Prostate adenocarcinomas aberrantly expressing p63 are molecularly distinct from usual-type prostatic adenocarcinomas.

We have described a rare group of prostate adenocarcinomas that show aberrant expression of p63, a protein strongly expressed in prostatic basal cells and absent from usual-type acinar prostate cancers. The partial basal-like immunophenotype of these tumors is intriguing in light of the persistent debate surrounding the cell-of-origin for prostate cancer; however, their molecular phenotype is unknown. We collected 37 of these tumors on radical prostatectomy and biopsy and assessed subsets for a diverse panel of molecular markers. The majority of p63-expressing tumors were positive for the ΔNp63 isoform (6/7) by immunofluorescence and p63 mRNA (7/8) by chromogenic in situ hybridization. Despite p63 positivity, these tumors uniformly expressed luminal-type cytokeratin proteins such as CK18 (13/13), CK8 (8/8), and markers of androgen axis signaling commonly seen in luminal cells, including androgen receptor (10/11), NKX3.1 (8/8), and prostein (12/13). Conversely, basal cytokeratins such as CK14 and CK15 were negative in all cases (0/8) and CK5/6 was weakly and focally positive in 36% (4/11) of cases. Pluripotency markers including ß-catenin, Oct4, and c-kit were negative in p63-expressing tumors (0/11). Despite nearly universal expression of androgen receptor and downstream androgen signaling targets, p63-expressing tumors lacked ERG rearrangements by fluorescence in situ hybridization (0/14) and ERG protein expression (0/37). No tumors expressed SPINK1 or showed PTEN protein loss (0/19). Surprisingly, 74% (14/19) of p63-expressing tumors expressed GSTP1 protein at least focally, and 33% (2/6) entirely lacked GSTP1 CpG island hypermethylation by bisulfite sequencing. In contrast to usual prostatic adenocarcinomas, prostate tumors with p63 expression show a mixed luminal/basal immunophenotype, uniformly lack ERG gene rearrangement, and frequently express GSTP1. These data strongly suggest that p63-expressing prostate tumors represent a molecularly distinct subclass and further study of this rare tumor type may yield important insights into the role of p63 in prostatic biology and the prostate cancer cell-of-origin.

A parameter free relative density based biclustering method for identifying non-linear feature relations.

The existing biclustering algorithms often depend on assumptions like monotonicity or linearity of feature relations for finding biclusters. Though a few algorithms overcome this problem using density-based methods, they tend to miss out many biclusters because they use global criteria for identifying dense regions. The proposed method, PF-RelDenBi, uses local variations in marginal and joint densities for each pair of features to find the subset of observations, forming the basis of the relation between them. It then finds the set of features connected by a common set of observations using a non-linear feature relation index, resulting in a bicluster. This approach allows us to find biclusters based on feature relations, even if the relations are non-linear or non-monotonous. Additionally, the proposed method does not require the user to provide any parameters, allowing its application to datasets from different domains. To study the behaviour of PF-RelDenBi on datasets with different properties, experiments were carried out on sixteen simulated datasets and the performance has been compared with eleven state-of-the-art algorithms. The proposed method is seen to produce better results for most of the simulated datasets. Experiments were conducted with five benchmark datasets and biclusters were detected using PF-RelDenBi. For the first two datasets, the detected biclusters were used to generate additional features that improved classification performance. For the other three datasets, the performance of PF-RelDenBi was compared with the eleven state-of-the-art methods in terms of accuracy, NMI and ARI. The proposed method is seen to detect biclusters with greater accuracy. The proposed technique has also been applied to the COVID-19 dataset to identify some demographic features that are likely to affect the spread of COVID-19.

Effect of channel morphological changes on wetland transformation.

Keeping aside the traditional approaches to investigating floodplain wetland transformation, the current study investigated various aspects of it through changes in river channel morphology and drainage pattern. The study analyzed wetland transformation using satellite image-based machine learning and intensive fieldwork. Ordinary Least Square (OLS) regression was applied to identify dominant influencing factors among 24 contributing factors under six clusters to eight dependent phenomena of transformation. The result showed that 57 % of wetland area lost since 1991, and existing wetland has also experiencing hydrological scarcity. From 1991 to 2021, the area under low water depth (<1 m.) inflated from 18.55 % to 50.54 %, the hydro-period narrowed down, and the appearance of water become inconsistent. The OLS result showed that changes in channel morphology (bottle neck channel, embankment-driven carrying capacity enhancement, etc.), interruptions in river and wetland connecting channels (source closure, breaching the continuity, conversion in to agricultural land, etc.), and changes in flood ambience (regulated by dam construction, erection of embankments, etc.) majorly contributed to wetland transformation. Very high explainability was found in the cases of rate of wetland loss, decreasing water depth under greater depth, narrowing hydro-period (R2 > 0.9). The findings of this work would be a good policy document for floodplain wetland management.

Impact of sunitinib resistance on clear cell renal cell carcinoma therapeutic sensitivity in vitro.

Sunitinib resistance creates a major clinical challenge for the treatment of advanced clear cell renal cell carcinoma (ccRCC) and functional and metabolic changes linked to sunitinib resistance are not fully understood. We sought to characterize the molecular and metabolic changes induced by the development of sunitinib resistance in ccRCC by developing and characterizing two human ccRCC cell lines resistant to sunitinib. Consistent with the literature, sunitinib-resistant ccRCC cell lines presented an aberrant overexpression of Axl and PD-L1, as well as a metabolic rewiring characterized by enhanced OXPHOS and glutamine metabolism. Therapeutic challenges of sunitinib-resistant ccRCC cell lines in vitro using small molecule inhibitors targeting Axl, AMPK and p38, as well as using PD-L1 blocking therapeutic antibodies, showed limited CTL-mediated cytotoxicity in a co-culture model. However, the AMPK activator metformin appears to sensitize the effect of PD-L1 blocking therapeutic antibodies and to enhance CTLs' cytotoxic effects on ccRCC cells. These effects were not broadly observed with the Axl and the p38 inhibitors. Taken together, these data suggest that targeting certain pathways aberrantly activated by sunitinib resistance such as the AMPK/PDL1 axis might sensitize ccRCC to immunotherapies as a second-line therapeutic approach.

Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion.

Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer's patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3-10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients.