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Hypoalbuminemia has been associated with poor outcome in critically ill population including sepsis and COVID-19. The observational study by Su et al showed a favorable albumin kinetics, with an initial downwards trend followed by recovery back to the predicted albumin levels, in survivors of COVID-19 and sepsis-induced acute respiratory distress syndrome (ARDS). However, nonsurvivors in COVID-19 group did not have an upwards recovery slope, while those in sepsis group did not follow any sort of albumin kinetics. Thus, authors concluded that the pattern of albumin kinetics may be predictive of outcome in COVID-19 and sepsis-induced ARDS. Here, we would like to highlight a few more points in this letter., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Utilization of biomolecules encapsulated nano particles is currently originating ample attention to generate unconventional nanomedicines in antiviral research. Zinc oxide nanoparticle has been extensively studied for antimicrobial, antifungal and antifouling properties due to high surface to volume ratios and distinctive chemical as well as physical properties. Nevertheless, still minute information is available on their response on viruses. Here, in situ nanostructured and polysaccharide encapsulated ZnO NPs are fabricated with having antiviral potency and low cytotoxicity (%viability ~ 90%) by simply controlling the formation within interspatial 3D networks of hydrogels through perfect locking mechanism. The two composites ChH@ZnO and ChB@ZnO shows exceedingly effective antiviral activity toward Human cytomegalovirus (HCMV) having cell viability 93.6% and 92.4% up to 400 μg mL -1 concentration. This study brings significant insights regarding the role of ZnO NPs surface coatings on their nanotoxicity and antiviral action and could potentially guide to the development of better antiviral drug., (Copyright © 2021. Published by Elsevier Ltd.)

Main Conclusion: Our transcriptomic analysis expanded the repertoire of nitrate-responsive genes/processes in rice and revealed their phenotypic association with root/shoot, stomata, tiller, panicle/flowering and yield, with agronomic implications for nitrogen use efficiency. Nitrogen use efficiency (NUE) is a multigenic quantitative trait, involving many N-responsive genes/processes that are yet to be fully characterized. Microarray analysis of early nitrate response in excised leaves of japonica rice revealed 6688 differentially expressed genes (DEGs), including 2640 hitherto unreported across multiple functional categories. They include transporters, enzymes involved in primary/secondary metabolism, transcription factors (TFs), EF-hand containing calcium binding proteins, hormone metabolism/signaling and methytransferases. Some DEGs belonged to hitherto unreported processes viz. alcohol, lipid and trehalose metabolism, mitochondrial membrane organization, protein targeting and stomatal opening. 1158 DEGs were associated with growth physiology and grain yield or phenotypic traits for NUE. We identified seven DEGs for shoot apical meristem, 66 for leaf/culm/root, 31 for tiller, 70 for heading date/inflorescence/spikelet/panicle, 144 for seed and 78 for yield. RT-qPCR validated nitrate regulation of 31 DEGs belonging to various important functional categories/traits. Physiological validation of N-dose responsive changes in plant development revealed that relative to 1.5 mM, 15 mM nitrate significantly increased stomatal density, stomatal conductance and transpiration rate. Further, root/shoot growth, number of tillers and grain yield declined and panicle emergence/heading date delayed, despite increased photosynthetic rate. We report the binding sites of diverse classes of TFs such as WRKY, MYB, HMG etc., in the 1 kb up-stream regions of 6676 nitrate-responsive DEGs indicating their role in regulating nitrate response/NUE. Together, these findings expand the repertoire of genes and processes involved in genomewide nitrate response in rice and reveal their physiological, phenotypic and agronomic implications for NUE., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The plant cytoskeleton persistently undergoes remodeling to achieve its roles in supporting cell division, differentiation, cell expansion and organelle transport. However, the links between cell metabolism and cytoskeletal networks, particularly how the proteinaceous components execute such processes remain poorly understood. We investigated the cytoskeletal proteome landscape of rice to gain better understanding of such events. Proteins were extracted from highly enriched cytoskeletal fraction of four-week-old rice seedlings, and the purity of the fraction was stringently monitored. A total of 2577 non-redundant proteins were identified using both gel-based and gel-free approaches, which constitutes the most comprehensive dataset, thus far, for plant cytoskeleton. The data set includes both microtubule and microfilament-associated proteins and their binding proteins comprising hypothetical as well as novel cytoskeletal proteins. Further, various in-silico analyses were performed, and the proteins were functionally classified on the basis of their gene ontology. The catalogued proteins were validated through their sequence analysis. Extensive comparative analysis of our dataset with the non-redundant set of cytoskeletal proteins across plant species affirms unique as well as overlapping candidates. Together, these findings unveil new insights of how cytoskeletons undergo dynamic remodeling in rice to drive seedling development processes in rapidly changing in planta environment., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The screening of a dehydration-responsive chloroplast proteome of chickpea led us to identify and investigate the functional importance of an uncharacterized protein, designated CaPDZ1. In all, we identified 14 CaPDZs, and phylogenetic analysis revealed that these belong to photosynthetic eukaryotes. Sequence analyses of CaPDZs indicated that CaPDZ1 is a unique member, which harbours a TPR domain besides a PDZ domain. The global expression analysis showed that CaPDZs are intimately associated with various stresses such as dehydration and oxidative stress along with certain phytohormone responses. The CaPDZ1-overexpressing chickpea seedlings exhibited distinct phenotypic and molecular responses, particularly increased photosystem (PS) efficiency, ETR and qP that validated its participation in PSII complex assembly and/or repair. The investigation of CaPDZ1 interacting proteins through Y2H library screening and co-IP analysis revealed the interacting partners to be PSII associated CP43, CP47, D1, D2 and STN8. These findings supported the earlier hypothesis regarding the role of direct or indirect involvement of PDZ proteins in PS assembly or repair. Moreover, the GUS-promoter analysis demonstrated the preferential expression of CaPDZ1 specifically in photosynthetic tissues. We classified CaPDZ1 as a dehydration-responsive chloroplast intrinsic protein with multi-fold abundance under dehydration stress, which may participate synergistically with other chloroplast proteins in the maintenance of the photosystem., (© 2021 Scandinavian Plant Physiology Society.)

Many frameworks exist to infer cause and effect relations in complex nonlinear systems, but a complete theory is lacking. A new framework is presented that is fully nonlinear, provides a complete information theoretic disentanglement of causal processes, allows for nonlinear interactions between causes, identifies the causal strength of missing or unknown processes, and can analyze systems that cannot be represented on directed acyclic graphs. The basic building blocks are information theoretic measures such as (conditional) mutual information and a new concept called certainty that monotonically increases with the information available about the target process. The framework is presented in detail and compared with other existing frameworks, and the treatment of confounders is discussed. While there are systems with structures that the framework cannot disentangle, it is argued that any causal framework that is based on integrated quantities will miss out potentially important information of the underlying probability density functions. The framework is tested on several highly simplified stochastic processes to demonstrate how blocking and gateways are handled and on the chaotic Lorentz 1963 system. We show that the framework provides information on the local dynamics but also reveals information on the larger scale structure of the underlying attractor. Furthermore, by applying it to real observations related to the El-Nino-Southern-Oscillation system, we demonstrate its power and advantage over other methodologies.

Fracture non-union is a significant orthopaedic problem affecting a substantial number of patients yearly. Treatment of nonunions is devastating to patients and costly to the healthcare system. Unfortunately, the diagnosis of non-union is typically made in a reactionary fashion by an orthopaedic surgeon based on clinical assessment and radiographic features several months into treatment. For this reason, investigators have been trying to develop prediction algorithms; however, these have relied on population-based approaches and lack the predictive capability necessary to make individual treatment decisions. There is also a growing body of literature focussed on identifying blood biomarkers that are associated with non-union. This review describes the research that has been done in this area. Further studies of patient-centered, precision medicine approaches will likely improve fracture non-union diagnostic/prognostic capabilities.

Objective: The aim of this study was to estimate the proportion of symptomatic and asymptomatic laboratory-confirmed coronavirus disease 2019 (COVID-19) cases among the population of Bangladesh. Methods: A cross-sectional survey was conducted in Dhaka City and other districts of Bangladesh between April 18 and October 12, 2020. A total of 32 districts outside Dhaka were randomly selected, and one village and one mahalla was selected from each district; 25 mahallas were selected from Dhaka City. From each village or mahalla, 120 households were enrolled through systematic random sampling. Results: A total of 44 865 individuals were interviewed from 10 907 households. The majority (70%, n  = 31 488) of the individuals were <40 years of age. Almost half of the individuals (49%, n  = 21 888) reported more than four members in their household. It was estimated that 12.6% ( n  = 160) of the households had one or more severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals, among whom 0.9% ( n  = 404) of individuals had at least one COVID-19-like symptom, at the national level. The prevalence of COVID-19 in the general population was 6.4%. Among the SARS-CoV-2-positive individuals, 87% were asymptomatic. Conclusions: The substantial high number of asymptomatic cases all over Bangladesh suggests that community-level containment and mitigation measures are required to combat COVID-19. Future studies to understand the transmission capability could help to define mitigation and control measures., (© 2021 The Authors.)

Ebola virus disease targets and destroys immune cells, including macrophages and dendritic cells, leading to impairment of host response. After infection, a combination of strategies including alteration and evasion of immune response culminating in a strong inflammatory response can lead to multi-organ failure and death in most infected patients. This review discusses immune response dynamics, mainly focusing on how Ebola manipulates innate and adaptive immune responses and strategizes to thwart host immune responses. We also discuss the challenges and prospects of developing therapeutics and vaccines against Ebola., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Understanding the normal-metal state transport in twisted bilayer graphene near magic angle is of fundamental importance as it provides insights into the mechanisms responsible for the observed strongly correlated insulating and superconducting phases. Here we provide a rigorous theory for phonon-dominated transport in twisted bilayer graphene describing its unusual signatures in the resistivity (including the variation with electron density, temperature, and twist angle) showing good quantitative agreement with recent experiments. We contrast this with the alternative Planckian dissipation mechanism that we show is incompatible with available experimental data. An accurate treatment of the electron-phonon scattering requires us to go well beyond the usual treatment, including both intraband and interband processes, considering the finite-temperature dynamical screening of the electron-phonon matrix element, and going beyond the linear Dirac dispersion. In addition to explaining the observations in currently available experimental data, we make concrete predictions that can be tested in ongoing experiments., (© 2021. The Author(s).)

A Pd(ii)/Cu(ii) catalysed domino synthesis of tricyanovinylindoles has been achieved using DMSO as a one-carbon synthon. The reaction proceeds via the construction of 2-aryl-3-formyl indole followed by sequential addition of malononitrile and a CN resulting in two C-C, one C[double bond, length as m-dash]C and one C-N bonds in the final product. Furthermore, post-synthetic modification results in the unprecedented formation of 4-cyano-3-indolylmaleimides. Photophysical studies of selected compounds show emission in the visible range.

Key Message: Foliar application of SA cross-talks and induce endogenous nitric oxide and reactive oxygen species to improve innate immunity and vigor of tomato plant against Fusarium oxysporum stress. The present investigation was aimed to demonstrate the efficacy of salicylic acid (SA), as a powerful elicitor or plant growth regulator (PGR) and its cross-talk with nitric oxide (NO) in tomato against the biotic stress caused by wilt pathogen, Fusarium oxysporum f. sp. lycopersici. Different defense-related enzymes and gene expression, phenol, flavonoid, and phenolic acid content along with NO generation and other physiological characters have been estimated after foliar application of SA. Total chlorophyll content was steadily maintained and the amount of death of cells was negligible after 72 h of SA treatment. Significant reduction of disease incidence was also recorded in SA treated sets. Simultaneously, NO generation was drastically improved at this stage, which has been justified by both spectrophotometrically and microscopically. A direct correlation between reactive oxygen species (ROS) generation and NO has been established. Production of defense enzymes, gene expressions, different phenolic acids was positively influenced by SA treatment. However, tomato plants treated with SA along with NO synthase (NOS) inhibitor or NO scavenger significantly reduce all those parameters tested. On the other hand, NO donor-treated plants showed the same inductive effect like SA. Furthermore, SA treated seeds of tomato also showed improved physiological parameters like higher seedling vigor index, shoot and root length, mean trichome density, etc. It is speculated that the cross-talk between SA and endogenous NO have tremendous ability to improve defense responses and growth of the tomato plant. It can be utilized in future sustainable agriculture for bimodal action., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Improving our fundamental understanding of multiphase turbulent flows will be beneficial for analyses of a wide range of industrial and geophysical processes. Herein, we investigate the topology of the local flow in vaporizing forced homogeneous isotropic turbulent two-phase flows. The invariants of the velocity-gradient, rate-of-strain, rate-of-rotation tensors, and scalar gradient were computed and conditioned for different distances from the liquid-gas surface. A Schur decomposition of the velocity gradient tensor into a normal and non-normal parts was undertaken to supplement the classical double decomposition into rotation and strain tensors. Using direct numerical simulations results, we show that the joint probability density functions of the second and third invariants have classical shapes in all carrier-gas regions but gradually change as they approach the carrier-liquid interface. Near the carrier-liquid interface, the distributions of the invariants are remarkably similar to those found in the viscous sublayer of turbulent wall-bounded flows. Furthermore, the alignment of both vorticity and scalar gradient with the strain-rate field changes spatially such that its universal behaviour occurs far from the liquid-gas interface. We found also that the non-normal effects of the velocity gradient tensor play a crucial role in explaining the preferred alignment., (© 2021. The Author(s).)

A new transmetallation approach is described for the synthesis of metal oxide nanocrystals (NCs). Typically, the synthesis of metal oxide NCs in oleyl alcohol is driven by metal-based esterification catalysis with oleic acid to produce oleyl oleate ester and M-OH monomers, which then condense to form MxOy solids. Here we show that the synthesis of Cu2O NCs by this method is limited by the catalytic ability of copper to drive esterification and thus produce Cu+-OH monomers. However, inclusion of 1-15 mol% of a group 13 cation (Al3+, Ga3+, or In3+) results in efficient synthesis of Cu2O NCs and exhibits size/morphology control based on the nature of M3+. Using a continuous-injection procedure where the copper precursor (Cu2+-oleate) and catalyst (M3+-oleate) are injected into oleyl alcohol at a controlled rate, we are able to monitor the reactivity of the precursor and M3+ catalyst using UV-visible and FTIR absorbance spectroscopies. These time-dependent measurements clearly show that M3+ catalysts drive esterification to produce M3+-OH species, which then undergo transmetallation of hydroxide ligands to generate Cu+-OH monomers required for Cu2O condensation. Ga3+ is found to be the "goldilocks" catalyst, producing NCs with the smallest size and a distinct cubic morphology not observed for any other group 13 metal. This is believed to be due to rapid transmetallation kinetics between Ga3+-OH and Cu+-oleate. These studies introduce a new mechanism for the synthesis of metal oxides where inherent catalysis by the parent metal (i.e. copper) can be circumvented with the use of a secondary catalyst to generate hydroxide ligands.

Background: Liver disease, a major cause of death worldwide, affects younger people compared with other major causes of death. Palliative and end-of-life care for these patients are often overlooked. Guidelines are emerging on what good end-of-life care in liver disease should look like, but there is a dearth of research into patients' perspectives even though they are most affected by these guidelines., Aim: To explore current knowledge and understanding of patients' lived experiences, perspectives and expectations in relation to palliative and end-of-life care in advanced liver disease., Design: Systematic review with thematic synthesis complying to the enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) statement., Setting and Participants: Database searches (Ovid Medline, 1946-2021 and Web of Science, 1970-2021) to identify qualitative studies exploring patients' perspectives of palliative and end-of-life care in advanced liver disease., Findings: Only eight articles met all criteria. Themes demonstrated repeated hospital admissions towards the end of life, lack of coordinated care in community and barriers in discussion about palliative care in end-stage liver disease due to lack of confidence among professionals and a negative view about palliative care among patients and carers. Emotional, financial and disability-related needs of patients and their carers are often neglected., Conclusion: There is a dearth of studies exploring patients' perspectives about care in advanced liver disease relating to palliative and end-of-life care. Lack of coordinated community support and honest conversations around palliative care leads to reduced quality of life. More primary research from diverse population is needed to improve palliative care and end-of-life care in end-stage liver disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

This article explores whether crowd-sourced human creativity within a gamified collaborative design framework can address the complexity of predictive environment design. This framework is predicated on gamifying crowd objectives and presenting environment design problems as puzzles. A usability study reveals that the framework is considered usable for the task. Participants were asked to configure an environment puzzle to reduce an important crowd metric, the total egress time. The design task was constructed to be straightforward and uses a simplified environment as a probe for understanding the utility of gamification and the performance of collaboration. Single-player and multiplayer designs outperformed both optimization and expert-sourced designs of the same environment and multiplayer designs further outperformed the single-player designs. Single-player and multiplayer iterations followed linear and exponential decrease trends in total egress time, respectively. Our experiments provide strong evidence toward an interesting novel approach of crowdsourcing collaborative environment design.

Background: Bangladesh is well advanced in the epidemiologic transition from communicable to noncommunicable diseases, which now account for two out of three deaths annually. This paper examines the latest nationally representative hypertension prevalence estimates, awareness, treatment, and control-to identify their association with potential correlates., Methods: The analyses are based on the recent Bangladesh Demographic and Health Survey 2017-18 data. Univariate analyses and bivariate analyses between the outcome variables and individual covariates were carried out. Then chi-square tests were done to see the proportional differences between them. To examine the demographic, socioeconomic and biological factors affecting hypertension, awareness, treatment and control, we used multivariate logistic regression models., Results: We found that prevalence of hypertension for females and males together aged 35 or more has risen by half between 2011 (25.7%) to 2017 (39.4%). With the broader age range used in 2017, the prevalence is now 27.5% in the population aged 18 years or more. The factors associated with hypertension included older age, being female, urban residence, higher wealth status, minimal education, higher body mass index and high blood glucose level. Following multivariate analyses, many of these characteristics were no longer significant, leaving only age, being female, nutritional status and elevated blood glucose level as important determinants. Over half (58%) of females and males who were found to be hypertensive were not aware they had the condition. Only one in eight (13%) had the condition under control., Conclusion: In the coming years, a rising trend in hypertension in Bangladeshi adults is expected due to demographic transition towards older age groups and increase in overweight and obesity among the population of Bangladesh. With more women being hypertensive than men, a targeted approach catering to high risk groups should be thoroughly implemented following the Multisectoral NCD Action Plan 2018-2025. Acting in close collaboration with other ministries/relevant sectors to bring an enabling environment for the citizens to adopt healthy lifestyle choices is a prerequisite for adequate prevention. While screening the adult population is essential, the public sector cannot possibly manage the ever-expanding numbers of hypertensives. The private sector and NGOs need to be drawn into the program to assist.

Hericium erinaceus (Bull.) Persoon, a popular medicinal edible mushroom, owns a long history of usage in traditional Chinese medicine and also in other oriental countries. Along with this, its several bioactive compounds have been evolved into food supplements. Meanwhile, this present investigation aimed at extracting bioactive components from fruiting bodies of H. erinaceus using two different solvents and evaluating its in vitro antioxidant, antimicrobial, and antiproliferative efficacy. Chemical analysis showed extracts were rich in phenol, flavonoids, and ascorbic acids while lesser amount of carotenoids were also detected in these extracts. Both extracts were able to scavenge 1,1-diphenyl-2-picrylhydrazyl (~76%) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) radicals (~81%) and also showed chelating activity (~73.05%). The ethanolic extract exhibited the highest antioxidant activity (total antioxidant capacity 2.17 µg ascorbic acid equivalent/mg of extract) whereas methanolic extract showed moderate capacity (total antioxidant capacity 1.42 µg ascorbic acid equivalent/mg of extract). All extracts displayed antibacterial activity against both Gram-positive and Gram-negative bacteria as well (minimum inhibition concentration 1,575-2,750 µg/ml) although methanolic extract showed some selectivity towards bacterial strains. Apart from these, ethanolic fraction has found to exhibit potent cytotoxicity (IC 50 403.12 µg/ml) towards lung adenocarcinoma cells. These studies thus provide the reference data that could support this mushroom as an easily accessible source of natural bioactive components. PRACTICAL APPLICATIONS: Mushroom extracts have long been traditionally used as miracle medicine to treat an extensive range of ailments. These findings indicate the potential benefits of the Hericium erinaceus (Bull.) Persoon extracts for the development of multi-target therapeutics as well as extraction with appropriate solvents also provide leads for the isolation of various principle compounds. The extracts thus could be used to treat oxidative stress-related disorders as they are found to contain antioxidant compounds like phenols and others and also they possessed good antimicrobial and anticancer activity., (© 2021 Wiley Periodicals LLC.)

Adverse effects of spaceflight on musculoskeletal health increase the risk of bone injury and impairment of fracture healing. Its yet elusive molecular comprehension warrants immediate attention, since space travel is becoming more frequent. Here we examined the effects of spaceflight on bone fracture healing using a 2 mm femoral segmental bone defect (SBD) model. Forty, 9-week-old, male C57BL/6J mice were randomized into 4 groups: 1) Sham surgery on Ground (G-Sham); 2) Sham surgery housed in Spaceflight (FLT-Sham); 3) SBD surgery on Ground (G-Surgery); and 4) SBD surgery housed in Spaceflight (FLT-Surgery). Surgery procedures occurred 4 days prior to launch; post-launch, the spaceflight mice were house in the rodent habitats on the International Space Station (ISS) for approximately 4 weeks before euthanasia. Mice remaining on the Earth were subjected to identical housing and experimental conditions. The right femur from half of the spaceflight and ground groups was investigated by micro-computed tomography (µCT). In the remaining mice, the callus regions from surgery groups and corresponding femoral segments in sham mice were probed by global transcriptomic and metabolomic assays. µCT confirmed escalated bone loss in FLT-Sham compared to G-Sham mice. Comparing to their respective on-ground counterparts, the morbidity gene-network signal was inhibited in sham spaceflight mice but activated in the spaceflight callus. µCT analyses of spaceflight callus revealed increased trabecular spacing and decreased trabecular connectivity. Activated apoptotic signals in spaceflight callus were synchronized with inhibited cell migration signals that potentially hindered the wound site to recruit growth factors. A major pro-apoptotic and anti-migration gene network, namely the RANK-NFκB axis, emerged as the central node in spaceflight callus. Concluding, spaceflight suppressed a unique biomolecular mechanism in callus tissue to facilitate a failed regeneration, which merits a customized intervention strategy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Tumor cell proliferation requires sufficient metabolic flux through the pentose phosphate pathway to meet the demand for biosynthetic precursors and to increase protection against oxidative stress which in turn requires an upregulation of substrate flow through glycolysis. This metabolic poise is often coupled with a shift in ATP production from mitochondrial OXPHOS to substrate-level phosphorylation. Despite major advances that were facilitated by using tumor-derived cell lines in research areas spanning from membrane to cytoskeletal biology, this distorted metabolic profile limits their impact as a model in physiology and toxicology. Substitution of glucose with galactose in the cell culture medium has been demonstrated to shift ATP production from substrate-level phosphorylation to mitochondrial OXPHOS. This increase in oxygen utilization is coupled to a global metabolic reorganization with potential impacts on macromolecule biosynthesis and cellular redox homeostasis, but a comprehensive analysis on the effects of sugar substitution in tumor-derived cells is still missing. To address this gap in knowledge we performed transcriptomic and metabolomic analyses on human hepatocellular carcinoma (HepG2) cells adapted to either glucose or galactose as the aldohexose source. We observed a shift toward oxidative metabolism in all primary metabolic pathways at both transcriptomic and metabolomic levels. We also observed a decrease in nicotinamide dinucleotide (NAD(P)) levels and subcellular NAD + -to-NADH ratios in cells cultured with galactose compared with glucose control cells. Our results suggest that galactose reduces both glycolytic and biosynthetic flux and restores a metabolic poise in HepG2 cells that closely reflects the metabolic state observed in primary hepatocytes.

Universal Health Coverage in Low- and Middle-Income Countries is increasingly expanding through incorporation of private clinics, pharmacies, and hospitals into an overall health system funded in whole or part through government-managed health insurance. This underscores the importance of policies on health provision which apply across the whole delivery system regardless of ownership status. To advance understanding of private-sector policies, and to facilitate sharing of lessons across countries with similar public-private distributions, we have analyzed data on the source of inpatient and outpatient care from 65 countries. While past studies have conducted similar analysis, ours advances the field in two ways. First, we limit our analysis to data sets from 2010 through 2019, making our study more up-to-date than past studies, while changing health seeking patterns for maternal health since 2010 means that our data set is more representative of overall inpatient care. Second, while past multi-country analysis of public-private ownership have been based on the Demographic Health Surveys, we have added to this data from the Multiple Indicator Cluster Surveys, significantly increasing the countries in our analysis. We have aggregated our analysis by WHO's regions. Outside of the EURO region, where the private sector delivers just 4% of all healthcare services, the private sector remains significant, and in many countries represents more than half of all care. The private sector provides nearly 40% of all healthcare in PAHO, AFRO, and WPRO regions, 57% in SEARO, and 62% in EMRO. While specific countries with two recent surveys show variation in the scale of both inpatient and outpatient private provision, we did not find regional or global trends toward or away from private care within LMICs. Private inpatient care is most important for the wealthy in many countries; public vs. private care varies less, by wealth, for outpatient services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Montagu and Chakraborty.)

Understanding the emergence of life from (primitive) abiotic components has arguably been one of the deepest and yet one of the most elusive scientific questions. Notwithstanding the lack of a clear definition for a living system, it is widely argued that heredity (involving self-reproduction) along with compartmentalization and metabolism are key features that contrast living systems from their non-living counterparts. A minimal living system may be viewed as "a self-sustaining chemical system capable of Darwinian evolution". It has been proposed that autocatalytic sets of chemical reactions (ACSs) could serve as a mechanism to establish chemical compositional identity, heritable self-reproduction, and evolution in a minimal chemical system. Following years of theoretical work, autocatalytic chemical systems have been constructed experimentally using a wide variety of substrates, and most studies, thus far, have focused on the demonstration of chemical self-reproduction under specific conditions. While several recent experimental studies have raised the possibility of carrying out some aspects of experimental evolution using autocatalytic reaction networks, there remain many open challenges. In this review, we start by evaluating theoretical studies of ACSs specifically with a view to establish the conditions required for such chemical systems to exhibit self-reproduction and Darwinian evolution. Then, we follow with an extensive overview of experimental ACS systems and use the theoretically established conditions to critically evaluate these empirical systems for their potential to exhibit Darwinian evolution. We identify various technical and conceptual challenges limiting experimental progress and, finally, conclude with some remarks about open questions.

With increased human presence in space, bone loss and fractures will occur. Thrombopoietin (TPO) is a recently patented bone healing agent. Here, we investigated the systemic effects of TPO on mice subjected to spaceflight and sustaining a bone fracture. Forty, 9-week-old, male, C57BL/6 J were divided into 4 groups: (1) Saline+Earth; (2) TPO + Earth; (3) Saline+Flight; and (4) TPO + Flight (n = 10/group). Saline- and TPO-treated mice underwent a femoral defect surgery, and 20 mice were housed in space ("Flight") and 20 mice on Earth for approximately 4 weeks. With the exception of the calvarium and incisor, positive changes were observed in TPO-treated, spaceflight bones, suggesting TPO may improve osteogenesis in the absence of mechanical loading. Thus, TPO, may serve as a new bone healing agent, and may also improve some skeletal properties of astronauts, which might be extrapolated for patients on Earth with restraint mobilization and/or are incapable of bearing weight on their bones.

Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9-2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.

The molecular mechanism of high-temperature stress (HTS) response, in plants, has so far been investigated using transcriptomics, while the dynamics of HTS-responsive proteome remain unexplored. We examined the adaptive responses of the resilient wheat cultivar 'Unnat Halna' and dissected the HTS-responsive proteome landscape. This led to the identification of 55 HTS-responsive proteins (HRPs), which are predominantly involved in metabolism and defense pathways. Interestingly, HRPs included a 2-cysteine peroxiredoxin (2CP), designated Ta2CP, presumably involved in stress perception and adaptation. Complementation of Ta2CP in yeast and heterologous expression in Arabidopsis demonstrated its role in thermotolerance. Both Ta2CP silencing and overexpression inferred the involvement of Ta2CP in plant growth and chlorophyll biosynthesis. We demonstrated that Ta2CP interacts with protochlorophyllide reductase b, TaPORB. Reduced TaPORB expression was found in Ta2cp-silenced plants, while upregulation was observed in Ta2CP-overexpressed plants. Furthermore, the downregulation of Ta2CP in Taporb-silenced plants and reduction of protochlorophyllide in Ta2cp-silenced plants suggested the key role of Ta2CP in chlorophyll metabolism. Additionally, the transcript levels of AGPase1 and starch were increased in Ta2cp-silenced plants. More significantly, HTS-treated Ta2cp-silenced plants showed adaptive responses despite increased reactive oxygen species and peroxide concentrations, which might help in rapid induction of high-temperature acclimation., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

The brain is the command center for the mammalian nervous system and an organ with enormous structural complexity. Protected within the skull, the brain consists of an outer covering of grey matter over the hemispheres known as the cerebral cortex. Underneath this layer reside many other specialized structures that are essential for multiple phenomenon important for existence. Acquiring samples of specific gross brain regions requires quick and precise dissection steps. It is understood that at the microscopic level, many sub-regions exist and likely cross the arbitrary regional boundaries that we impose for the purpose of this dissection. Mouse models are routinely used to study human brain functions and diseases. Changes in gene expression patterns may be confined to specific brain areas targeting a particular phenotype depending on the diseased state. Thus, it is of great importance to study regulation of transcription with respect to its well-defined structural organization. A complete understanding of the brain requires studying distinct brain regions, defining connections, and identifying key differences in the activities of each of these brain regions. A more comprehensive understanding of each of these distinct regions may pave the way for new and improved treatments in the field of neuroscience. Herein, we discuss a step-by-step methodology for dissecting the mouse brain into sixteen distinct regions. In this procedure, we have focused on male mouse C57Bl/6J (6-8 week old) brain removal and dissection into multiple regions using neuroanatomical landmarks to identify and sample discrete functionally-relevant and behaviorally-relevant brain regions. This work will help lay a strong foundation in the field of neuroscience, leading to more focused approaches in the deeper understanding of brain function.

The degree of brain injury is the governing factor for the magnitude of the patient's psycho- and physiological deficits post-injury, and the associated long-term consequences. The present scaling method used to segregate the patients among mild, moderate and severe phases of traumatic brain injury (TBI) has major limitations; however, a more continuous stratification of TBI is still elusive. With the anticipation that differentiating molecular markers could be the backbone of a robust method to triage TBI, we used a modified closed-head injury (CHI) Marmarou model with two impact heights (IH). By definition, IH directly correlates with the impact force causing TBI. In our modified CHI model, the rat skull was fitted with a helmet to permit a diffuse axonal injury. With the frontal cortex as the focal point of injury, the adjacent brain regions (hippocampus, HC and cerebellum, CB) were susceptible to diffuse secondary shock injury. At 8 days post injury (po.i.), rats impacted by 120 cm IH (IH 120 ) took a longer time to find an escape route in the Barnes maze as compared to those impacted by 100 cm IH (IH 100 ). Using a time-resolved interrogation of the transcriptomic landscape of HC and CB tissues, we mined those genes that altered their regulations in correlation with the variable IHs. At 14 days po.i., when all rats demonstrated nearly normal visuomotor performance, the bio-functional analysis suggested an advanced healing mechanism in the HC of IH 100 group. In contrast, the HC of IH 120 group displayed a delayed healing with evidence of active cell death networks. Combining whole genome rat microarrays with behavioral analysis provided the insight of neuroprotective signals that could be the foundation of the next generation triage for TBI patients., (Published by Elsevier Inc.)

Mushrooms have become the new superfood with their many bioactive metabolites and are potential candidates in the field of herbal medicine. Since not all mushrooms can be consumed whole, their active constituents and therapeutic benefits can be had in the form of beverages specially teas or coffees. In the present study, two forms of teas, infusion and decoction, were prepared from Hericium erinaceus (Bull.) Pers., a very popular mushroom in Chinese medicine. Both forms of tea were studied mycochemically and medicinally and a comparative view was presented on the basis of the findings. The tea preparations were rich in bioactive mycochemicals; interestingly, the infusion contained a higher amount of phenol (1.72 mg gallic acid equivalent/g of dry weight of mushrooms) than decoction (0.28 mg gallic acid equivalent/g of dry weight of mushrooms). Lycopene and β-carotene were found in very minute amounts. Both infusion and decoction exhibited good free radical scavenging potential, reducing power, and total antioxidant properties. However, the infusion fraction produced overall better results than the decoction fraction. Finally, the results suggest that H. erinaceus is a potent source of natural antioxidant and also can be consumed as a beverage.

The densities and speed of sound for liquid mixtures containing vitamin B 3 (niacin) at 0.01, 0.03, and 0.05 mol·kg -1 concentrations in aqueous propylene glycol and hexylene glycol at the variation of temperatures from 293.15 to 308.15 K have been measured using an Anton Paar DSA 5000 M. From volumetric experimental data, apparent molar volume ( V ϕ ), partial molar volume ( V ϕ 0 ), and partial molar volume of transfer (Δ V ϕ 0 ) are calculated along with the apparent molar isentropic compression ( K ϕ,  S ), partial molar isentropic compression ( K ϕ,  S 0 ), and partial molar isentropic compression of transfer (Δ K ϕ 0 ) using experimental acoustic data. The positive volumetric data (i.e., apparent molar volume and partial molar volume) indicates strong solute-solvent interactions inside the mixture. Along with these values, the empirical constants a , b , and c with the pair and triplet coefficients ( V AB , V ABB , K AB , K ABB ) are also calculated., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.

Key Message: A comparative proteomic study between WT and SAR-compromised rsi1/fld mutant reveals a set of proteins having possible roles in the SAR development. A partly infected plant shows enhanced resistance during subsequent infection through the development of systemic acquired resistance (SAR). Mobile signals generated at the site of primary infection travel across the plant for the activation of SAR. These mobile signals are likely to cause changes in the expression of a set of proteins in the distal tissue, which contributes to the SAR development. However, SAR-specific proteome is not revealed for any plant. The reduced systemic immunity 1 (rsi1)/(allelic to flowering locus D; fld) mutant of Arabidopsis is compromised for SAR but shows normal local resistance. Here we report the SAR-specific proteome of Arabidopsis by comparing differentially abundant proteins (DAPs) between WT and fld mutant. Plants were either mock-treated or SAR-induced by primary pathogen inoculation. For proteomic analysis, samples were collected from the systemic tissues before and after the secondary inoculation. Protein identification was carried out by using two-dimensional gel electrophoresis (2-DE) followed by tandem mass spectrometry. Our work identified a total of 94 DAPs between mock and pathogen treatment in WT and fld mutant. The DAPs were categorized into different functional groups along with their subcellular localization. The majority of DAPs are involved in metabolic processes and stress response. Among the subcellular compartments, plastids contained the highest number of DAPs, suggesting the importance of plastidic proteins in SAR activation. The findings of this study would provide resources to engineer efficient SAR activation traits in Arabidopsis and other plants.

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on both the physical and mental well-being of the global population. Relatively few studies have measured the impact of lockdown on utilisation of secondary mental health services in England., Aims: To describe secondary mental health service utilisation pre-lockdown and during lockdown within Leicestershire, UK, and the numbers of serious incidents during this time frame., Method: Data pertaining to mental health referral and hospital admissions to adult mental health, child and adolescent mental health, intellectual disability and mental health services for older people were collated retrospectively from electronic records for both 8 weeks pre-lockdown and the first 8 weeks of lockdown in England. Serious incidents during this time frame were also analysed., Results: Significantly (P < 0.05) reduced referrals to a diverse range of mental health services were observed during lockdown, including child and adolescent, adult, older people and intellectual disability services. Although admissions remained relatively stable before and during lockdown for several services, admissions to both acute adult and mental health services for older people were significantly (P < 0.05) reduced during lockdown. Numbers of serious incidents in the pre-lockdown and lockdown periods were similar, with 23 incidents pre-lockdown, compared with 20 incidents in lockdown., Conclusions: To the best of our knowledge, this is the first UK-based study reporting patterns of use of mental health services immediately prior to and during COVID-19 lockdown. Overall numbers of referrals and admissions reduced following commencement of COVID-19 lockdown. Potential reasons for these observations are discussed.

Prolonged residence of mice in spaceflight is a scientifically robust and ethically ratified model of muscle atrophy caused by continued unloading. Under the Rodent Research Program of the National Aeronautics and Space Administration (NASA), we assayed the large-scale mRNA and metabolomic perturbations in the quadriceps of C57BL/6j male mice that lived in spaceflight (FLT) or on the ground (control or CTR) for approximately 4 weeks. The wet weights of the quadriceps were significantly reduced in FLT mice. Next-generation sequencing and untargeted mass spectroscopic assays interrogated the gene-metabolite landscape of the quadriceps. A majority of top-ranked differentially suppressed genes in FLT encoded proteins from the myosin or troponin families, suggesting sarcomere alterations in space. Significantly enriched gene-metabolite networks were found linked to sarcomeric integrity, immune fitness, and oxidative stress response; all inhibited in space as per in silico prediction. A significant loss of mitochondrial DNA copy numbers in FLT mice underlined the energy deprivation associated with spaceflight-induced stress. This hypothesis was reinforced by the transcriptomic sequencing-metabolomics integrative analysis that showed inhibited networks related to protein, lipid, and carbohydrate metabolism, and adenosine triphosphate (ATP) synthesis and hydrolysis. Finally, we discovered important upstream regulators, which could be targeted for next-generation therapeutic intervention for chronic disuse of the musculoskeletal system. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research., (© 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.)

Human Cytomegalovirus has been implicated as a probable cause for the development of hepatic cholestasis among neonates. Our study tried to ascertain the exact demographic, biochemical and immunological markers to differentially diagnose patients with HCMV associated intrahepatic and extrahepatic cholestasis and also decipher the phylogenetic variability among the viral strains infecting the two groups. A total of 110 neonates collected over a span of 2 years were selected for the study classified into four different groups based on the presence of hepatic cholestasis and active HCMV infection. Our analysis predicted that total Cholesterol, GGT, ALP and TNFα were the only significant biological markers with exact cut-off scores, capable of distinguishing between HCMV associated intrahepatic and extrahepatic cholestasis. We confirmed that in patients belonging to both of these groups, the inflammasome is activated and the extent of this activation is more or less same except for the initial activators NLRP3 and AIM2 respectively. When we performed two separate phylogenetic analyses with HCMV gM and gN gene sequences, we found that in both cases the sequences from the IHC and EHC groups formed almost separate phylogenetic clusters. Our study has shown that the HCMV clinical strains infecting at intrahepatic and extrahepatic sites are phylogenetically segregated as distinct clusters. These two separate groups show different physiological as well as immunological modulations while infecting a similar host.

The statistical behaviours of the invariants of the velocity gradient tensor and flow topologies for Rayleigh-Bénard convection of Newtonian fluids in cubic enclosures have been analysed using Direct Numerical Simulations (DNS) for a range of different values of Rayleigh (i.e. [Formula: see text]) and Prandtl (i.e. [Formula: see text] and 320) numbers. The behaviours of second and third invariants of the velocity gradient tensor suggest that the bulk region of the flow at the core of the domain is vorticity-dominated whereas the regions in the vicinity of cold and hot walls, in particular in the boundary layers, are found to be strain rate-dominated and this behaviour has been found to be independent of the choice of Ra and Pr values within the range considered here. Accordingly, it has been found that the focal topologies S1 and S4 remain predominant in the bulk region of the flow and the volume fraction of nodal topologies increases in the vicinity of the active hot and cold walls for all cases considered here. However, remarkable differences in the behaviours of the joint probability density functions (PDFs) between second and third invariants of the velocity gradient tensor (i.e. Q and R) have been found in response to the variations of Pr. The classical teardrop shape of the joint PDF between Q and R has been observed away from active walls for all values of Pr, but this behavior changes close to the heated and cooled walls for high values of Pr (e.g. [Formula: see text]) where the joint PDF exhibits a shape mirrored at the vertical Q-axis. It has been demonstrated that the junctions at the edges of convection cells are responsible for this behaviour for [Formula: see text], which also increases the probability of finding S3 topologies with large negative magnitudes of Q and R. By contrast, this behaviour is not observed in the [Formula: see text] case and these differences between flow topology distributions in Rayleigh-Bénard convection in response to Pr suggest that the modelling strategy for turbulent natural convection of gaseous fluids may not be equally well suited for simulations of turbulent natural convection of liquids with high values of Pr.

We report the synthesis of novel silver-doped Prussian blue nanoscale coordination polymers (SPB NCPs), for dual modality photothermal ablation and oxidative toxicity in bacterial cells. The comparison of SPB NCPs (having Fe-CN-Ag bonds) with the conventionally used Prussian blue nanoscale coordination polymers (PB NCPs, having Fe-CN-Fe bonds) was investigated in terms of their physical and therapeutic properties. It was observed that both PB and SPB NCPs have similar physical dimensions, crystalline phase and optical properties. Both these NCPs showed robust photothermal effect by heat generation (hyperthermia) upon exposure to red laser light. However, among the two, only SPB NCP showed oxidase-like activity by generating H 2 O 2 in aqueous medium, presumably due to its silver content. In vitro antibacterial studies revealed that the SPB NCPs, but not PB NCPs, show inherent toxicity towards bacteria with an IC 50 value close to 2.5 μg/ml. It can be inferred that this toxicity is oxidative in nature, as a result of the oxidase-like behaviour shown by SPB NCPs. Furthermore, light activation resulted in substantial additional antibacterial effect (photothermal toxicity) in bacterial cells treated with SPB NCPs. In comparison, marginal additional photothermal toxicity was observed in PB NCP-treated bacteria. Thus, we conclude that the combination of dual modality oxidative and photothermal toxicities demonstrated by SPB NCPs, but not by control PB NCPs, makes the former promising antibacterial agents at low dosages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

At the heart of the phenome-to-genome approach is high throughput assays, which are liable to produce false results. This risk can be mitigated by minimizing the sample bias, specifically, recycling the same tissue specimen for both phenotypic and genotypic investigations. Therefore, our aim is to suggest a methodology of obtaining robust results from frozen specimens of compromised quality, particularly if the sample is produced in conditions with limited resources. For example, generating samples at the International Space Station (ISS) is challenging because the time and laboratory footprint allotted to a project can get expensive. In an effort to be economical with available resources, snap-frozen euthanized mice are the straightforward solution; however, this method increases the risk of temperature abuse during the thawing process at the beginning of the tissue collection. We found that prolonged immersion of snap frozen mouse carcass in 10% neutral buffered formalin at 4°C yielded minimal microscopic signs of ice crystallization and delivered tissues with histomorphology that is optimal for hematoxylin and eosin (H&E) staining and fixation on glass slides. We further optimized a method to sequester the tissue specimen from the H&E slides using an incubator shaker. Using this method, we were able to recover an optimal amount of RNA that could be used for downstream transcriptomics assays. Overall, we demonstrated a protocol that enables us to maximize scientific values from tissues collected in austere condition. Furthermore, our protocol can suggest an improvement in the spatial resolution of transcriptomic assays., (Copyright © 2020 Chakraborty, Schmitt, Honnold, Moyler, Butler, Nachabe, Gautam and Hammamieh.)

Pathogen-/microbe-associated molecular patterns (PAMPs/MAMPs) initiate complex defense responses by reorganizing the biomolecular dynamics of the host cellular machinery. The extracellular matrix (ECM) acts as a physical scaffold that prevents recognition and entry of phytopathogens, while guard cells perceive and integrate signals metabolically. Although chitosan is a known MAMP implicated in plant defense, the precise mechanism of chitosan-triggered immunity (CTI) remains unknown. Here, we show how chitosan imparts immunity against fungal disease. Morpho-histological examination revealed stomatal closure accompanied by reductions in stomatal conductance and transpiration rate as early responses in chitosan-treated seedlings upon vascular fusariosis. Electron microscopy and Raman spectroscopy showed ECM fortification leading to oligosaccharide signaling, as documented by increased galactose, pectin and associated secondary metabolites. Multiomics approach using quantitative ECM proteomics and metabolomics identified 325 chitosan-triggered immune-responsive proteins (CTIRPs), notably novel ECM structural proteins, LYM2 and receptor-like kinases, and 65 chitosan-triggered immune-responsive metabolites (CTIRMs), including sugars, sugar alcohols, fatty alcohols, organic and amino acids. Identified proteins and metabolites are linked to reactive oxygen species (ROS) production, stomatal movement, root nodule development and root architecture coupled with oligosaccharide signaling that leads to Fusarium resistance. The cumulative data demonstrate that ROS, NO and eATP govern CTI, in addition to induction of PR proteins, CAZymes and PAL activities, besides accumulation of phenolic compounds downstream of CTI. The immune-related correlation network identified functional hubs in the CTI pathway. Altogether, these shifts led to the discovery of chitosan-responsive networks that cause significant ECM and guard cell remodeling, and translate ECM cues into cell fate decisions during fusariosis., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Congenital nephrotic syndrome (CNS) is a rare but serious condition which affects neonates and is caused by monogenic defects of glomerular structural proteins or congenital viral infections. Several reports have established a causal relationship between human cytomegalovirus (HCMV) intrauterine infection and CNS, but thorough study assessing parameters has not yet been done., Methods: This study aimed to ascertain significant demographic, biochemical, serological, inflammatory and etiological parameters with 12 months follow-up to clinically identify and monitor neonates with HCMV-associated CNS and sought to decipher the phylogenetic nature of infecting strains. Differences between four patient groups (neonates < 4 weeks old) with or without CNS and HCMV infection were compared by unpaired t testing and one-way analysis of variance (ANOVA). Linear regression was performed to assess statistical significance among individual groups. Maximum-likelihood-based phylogenetic analysis was performed with HCMV gH gene sequences to compare clinically isolated and referenced NCBI strains. This was further supported by analysis of effective number of codons (ENc), codon adaptation index (CAI) and mRNA structural variation., Results: Patients with HCMV-associated CNS were found to have significant variations in many studied parameters compared with controls. The majority of clinical strains formed a separate phylogenetic cluster defining them as somewhat distinct from standard reference strains, which was supported by the other analyses., Conclusion: This study defined parameters for monitoring cases of HCMV-associated CNS, which suggest the possible existence of a selection force acting and rendering these HCMV strains able to infect selective host tissues and cause specific disease types.

This article was migrated. The article was marked as recommended. In March 2020, the United Kingdom declared a nationwide lockdown, a public health intervention in response to the COVID-19 pandemic. In addition, the increasing pressures on the country's publicly funded healthcare system, the National Health Service, required the early graduation of final year medical students so that they could join the workforce. Bristol Medical School responded to this health crisis by graduating 226 final year students. Since social distancing policies resulted in the prohibition of social gatherings, university graduation ceremonies were cancelled. The medical school felt it important to mark the students' qualification as these young doctors were to begin their careers amidst an unprecedented global health emergency. An online graduation ceremony was held on the video conferencing platform Zoom. This was attended by university staff and students from their homes across the UK and elsewhere in the world. Students commemorated their qualification by submitting photographs of themselves celebrating in homemade graduation robes and mortar boards which were included in the online event. The ceremony was a memorable occasion and created a sense of community in a time of social isolation. This novel situation gave rise to a unique celebration attracting media coverage and was reported on national TV and radio news bulletins along with newspapers. The structure for the online graduation ceremony outlined in this paper may be replicated for other graduation ceremonies or celebrations affected by the COVID-19 lockdown., (Copyright: © 2020 Blythe A et al.)

Nutrient dynamics in storage organs is a complex developmental process that requires coordinated interactions of environmental, biochemical, and genetic factors. Although sink organ developmental events have been identified, understanding of translational and post-translational regulation of reserve synthesis, accumulation, and utilization in legumes is limited. To understand nutrient dynamics during embryonic and cotyledonary photoheterotrophic transition to mature and germinating autotrophic seeds, an integrated proteomics and phosphoproteomics study in six sequential seed developmental stages in chickpea is performed. MS/MS analyses identify 109 unique nutrient-associated proteins (NAPs) involved in metabolism, storage and biogenesis, and protein turnover. Differences and similarities in 60 nutrient-associated phosphoproteins (NAPPs) containing 93 phosphosites are compared with NAPs. Data reveal accumulation of carbon-nitrogen metabolic and photosynthetic proteoforms during seed filling. Furthermore, enrichment of storage proteoforms and protease inhibitors is associated with cell expansion and seed maturation. Finally, combined proteoforms network analysis identifies three significant modules, centered around malate dehydrogenase, HSP70, triose phosphate isomerase, and vicilin. Novel clues suggest that ubiquitin-proteasome pathway regulates nutrient reallocation. Second, increased abundance of NAPs/NAPPs related to oxidative and serine/threonine signaling indicates direct interface between redox sensing and signaling during seed development. Taken together, nutrient signals act as metabolic and differentiation determinant governing storage organ reprogramming., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We investigate the superconducting critical current density ( J c ), transition temperature ( T c ), and flux pinning properties under hydrostatic pressure ( P ) for Cr 0.0009 NbSe 2 single crystal. The application of P enhances T c in both electrical resistivity (∼0.38 K GPa -1 : 0 ≤ P ≤ 2.5 GPa) and magnetization (∼0.98 K GPa -1 : 0 ≤ P ≤ 1 GPa) measurements, which leads to a monotonic increase in J c and flux pinning properties. The field-dependent J c at various temperatures under P is analyzed within the collecting pinning theory and it shows that δT c pinning is the crossover to δl pinning above the critical pressure ( P c ∼0.3 GPa). Our systematic analysis of the flux pinning mechanism indicates that both the density of pinning centers and pinning forces greatly increase with the application of P , which leads to an enhancement in the vortex state. Structural studies using synchrotron X-ray diffraction under pressure illustrate a stable hexagonal phase without any significant impurity phase and lattice parameter reduction with P shows highly anisotropic nature., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Lethal total body irradiation (TBI) triggers multifactorial health issues in a potentially short time frame. Hence, early signatures of TBI would be of great clinical value. Our study aimed to interrogate microRNA (miRNA) and metabolites, two biomolecules available in blood serum, in order to comprehend the immediate impacts of TBI. Mice were exposed to a lethal dose (9.75 Gy) of Cobalt-60 gamma radiation and euthanized at four time points, namely, days 1, 3, 7 and 9 post-TBI. Serum miRNA libraries were sequenced using the Illumina small RNA sequencing protocol, and metabolites were screened using a mass spectrometer. The degree of early impacts of irradiation was underscored by the large number of miRNAs and metabolites that became significantly expressed during the Early phase (day 0 and 1 post-TBI). Radiation-induced inflammatory markers for bone marrow aplasia and pro-sepsis markers showed early elevation with longitudinal increment. Functional analysis integrating miRNA-protein-metabolites revealed inflammation as the overarching host response to lethal TBI. Early activation of the network linked to the synthesis of reactive oxygen species was associated with the escalated regulation of the fatty acid metabolism network. In conclusion, we assembled a list of time-informed critical markers and mechanisms of significant translational potential in the context of a radiation exposure event.

Plants synthesize amino acids by collateral metabolic pathways using primary elements carbon and oxygen from air, hydrogen from water in soil and nitrogen from soil. Following synthesis, amino acids are immediately used for metabolism, transient storage or transported to the phloem. Different families of transporters have been identified for import of amino acids into plant cells. The first identified amino acid transporter, amino acid permease 1 (AAP1) in Arabidopsis belongs to a family of eight members and transports acidic, neutral, and basic amino acids. Legumes fix atmospheric nitrogen through a symbiotic relationship with root nodules bacteria. Following fixation, nitrogen is reduced to amino acids and is exported via different amino acid transporters. However, information is lacking about the structure of these important classes of amino acid transporter proteins in plant. We have amplified AAP from Phaseolus vulgaris, an economically important leguminous plant grown all over the world, and sequenced. The sequence has been characterized in silico and a three-dimensional structure of AAP has been predicted and validated. The information obtained not only enhances the knowledge about the structure of an amino acid permease gene in P. vulgaris, but will also help in designing protein-ligand studies using this protein as well.

Biosynthesis of copper oxide nanoparticles (CuONPs) in a cost-effective and eco-friendly way has gained its importance. CuONPs has been prepared from copper sulfate by using Adiantum lunulatum whole plant extract. CuONPs have been characterized by X-ray diffraction, Fourier transform infrared spectroscopic, transmission electron microscope, etc. Mono-disperse, spherical, pure, and highly stable CuONPs have formed with an average diameter of 6.5 ± 1.5 nm. Biosynthesized CuONPs at different concentrations were applied to seeds of Lens culinaris . Physiological characteristics were investigated in the germinated seeds. Roots obtained from the seeds treated with 0.025 mgmL -1 concentration of CuONPs showed highest activity of different defence enzymes and total phenolics. However, at higher concentration it becomes close to control. It showed gradual increase of antioxidative enzymes, in accordance with the increasing dose of CuONPs. Likewise, lipid peroxidation and proline content gradually increased with the increasing concentration. Reactive oxygen species and nitric oxide generation was also altered due to CuONPs treatment indicating stress signal transduction. Finally, this study provides a new approach of the production of valuable CuONPs, is a unique, economical, and handy tool for large scale saleable production which can also be used as a potent plant defence booster instead of other commercial uses.

Chloroplast, the photosynthetic machinery, converts photoenergy to ATP and NADPH, which powers the production of carbohydrates from atmospheric CO 2 and H 2 O. It also serves as a major production site of multivariate pro-defense molecules, and coordinate with other organelles for cell defense. Chloroplast harbors 30-50% of total cellular proteins, out of which 80% are membrane residents and are difficult to solubilize. While proteome profiling has illuminated vast areas of biological protein space, a great deal of effort must be invested to understand the proteomic landscape of the chloroplast, which plays central role in photosynthesis, energy metabolism and stress-adaptation. Therefore, characterization of chloroplast proteome would not only provide the foundation for future investigation of expression and function of chloroplast proteins, but would open up new avenues for modulation of plant productivity through synchronizing chloroplastic key components. In this review, we summarize the progress that has been made to build new understanding of the chloroplast proteome and implications of chloroplast dynamicsing generate metabolic energy and modulating stress adaptation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chloroplast, the energy organelle unique to photosynthetic eukaryotes, executes several crucial functions including photosynthesis. While chloroplast development and function are controlled by the nucleus, environmental stress modulated alterations perceived by the chloroplasts are communicated to the nucleus via retrograde signaling. Notably, coordination of chloroplast and nuclear gene expression is synchronized by anterograde and retrograde signaling. The chloroplast proteome holds significance for stress responses and adaptation. We unraveled dehydration-induced alterations in the chloroplast proteome of a grain legume, chickpea and identified an array of dehydration-responsive proteins (DRPs) primarily involved in photosynthesis, carbohydrate metabolism and stress response. Notably, 12 DRPs were encoded by chloroplast genome, while the rest were nuclear-encoded. We observed a coordinated expression of different multi-subunit protein complexes viz., RuBisCo, photosystem II and cytochrome b6f, encoded by both chloroplast and nuclear genome. Comparison with previously reported stress-responsive chloroplast proteomes showed unique and overlapping components. Transcript abundance of several previously reported markers of retrograde signaling revealed relay of dehydration-elicited signaling events between chloroplasts and nucleus. Additionally, dehydration-triggered metabolic adjustments demonstrated alterations in carbohydrate and amino acid metabolism. This study offers a panoramic catalogue of dehydration-responsive signatures of chloroplast proteome and associated retrograde signaling events, and cellular metabolic reprograming., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)