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Objective The aim of this observational cohort study was to assess the effectiveness and safety of the IL-6-receptor inhibitor tocilizumab (TCZ) in Behçet's syndrome (BS) with refractory arterial involvement. Methods Ten patients admitted to the Rheumatology and Immunology Department of Peking University People's Hospital between January 2014 and December 2019 were enrolled. The enrolled patients met the BS international criteria and exhibited severe arterial impairments. Refractory arterio-BS was diagnosed based on objective vascular symptoms unexplainable by other known illnesses, and resistance to traditional immunosuppressants and glucocorticoids after 12 weeks. Patients received 8 mg/kg TCZ infusions every 4 weeks for ≥24 weeks, with simultaneous continuation of immunosuppressants and glucocorticoids. Clinical and imaging data were assessed before and after TCZ treatment. Results The enrolled patients were men aged 44.3 (10.5) years; the median disease duration was 186.5 (45.7) months, and the average age of arterial impairment onset was 38.7 (12.9) years. The following trends were observed: improvement and maintenance of symptoms after the 26.8 (7.2)-month follow-up, n  = 9; complete remission, n  = 6; partial response, n  = 3; immunosuppressant dose reduction, n  = 4; radiologic improvement of arterial lesions, n  = 4; and TCZ discontinuation owing to enlarged abdominal aortic aneurysm relapse, n  = 1. The average daily glucocorticoid dose reduced from 54.5 (20.6) to 8.3 (3.6) mg/d (P  < 0.001), while the median ESR and CRP values reduced from 50 (2–82) mm/h and 32.9 (2.1–62.3) mg/dl to 4 (1–10) mm/h and 2.9 (0.2–12.1) mg/dl, respectively (P  < 0.001). No TCZ-associated side effects were noted. Conclusion TCZ proved to be safe and effective for refractory arterial lesions in BS, with a steroid- and immunosuppressant-sparing benefit. [ABSTRACT FROM AUTHOR]

Motivation Chromosomal patterning of gene expression in cancer can arise from aneuploidy, genome disorganization or abnormal DNA methylation. To map such patterns, we introduce a weighted univariate clustering algorithm to guarantee linear runtime, optimality and reproducibility. Results We present the chromosome clustering method, establish its optimality and runtime and evaluate its performance. It uses dynamic programming enhanced with an algorithm to reduce search-space in-place to decrease runtime overhead. Using the method, we delineated outstanding genomic zones in 17 human cancer types. We identified strong continuity in dysregulation polarity—dominance by either up- or downregulated genes in a zone—along chromosomes in all cancer types. Significantly polarized dysregulation zones specific to cancer types are found, offering potential diagnostic biomarkers. Unreported previously, a total of 109 loci with conserved dysregulation polarity across cancer types give insights into pan-cancer mechanisms. Efficient chromosomal clustering opens a window to characterize molecular patterns in cancer genome and beyond. Availability and implementation Weighted univariate clustering algorithms are implemented within the R package 'Ckmeans.1d.dp' (4.0.0 or above), freely available at https://cran.r-project.org/package=Ckmeans.1d.dp. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Over 17 million km² of land is affected by soil flooding every year, resulting in substantial yield losses and jeopardizing food security across the globe. A key step in resolving this problem and creating stress-tolerant cultivars is an understanding of the mechanisms by which plants sense low-oxygen stress. In this work, we review the current knowledge about the oxygen-sensing and signaling pathway in mammalian and plant systems and postulate the potential role of ion channels as putative oxygen sensors in plant roots. We first discuss the definition and requirements for the oxygen sensor and the difference between sensing and signaling. We then summarize the literature and identify several known candidates for oxygen sensing in the mammalian literature. This includes transient receptor potential (TRP) channels; K+-permeable channels (Kv, BK and TASK); Ca2+ channels (RyR and TPC); and various chemo- and reactive oxygen species (ROS)-dependent oxygen sensors. Identified key oxygen-sensing domains (PAS, GCS, GAF and PHD) in mammalian systems are used to predict the potential plant counterparts in Arabidopsis. Finally, the sequences of known mammalian ion channels with reported roles in oxygen sensing were employed to BLAST the Arabidopsis genome for the candidate genes. Several plasma membrane and tonoplast ion channels (such as TPC, AKT and KCO) and oxygen domain-containing proteins with predicted oxygen-sensing ability were identified and discussed. We propose a testable model for potential roles of ion channels in plant hypoxia sensing. [ABSTRACT FROM AUTHOR]

The next-generation sequencing data, called high-throughput sequencing data, are recorded as count data, which are generally far from normal distribution. Under the assumption that the count data follow the Poisson [ABSTRACT FROM AUTHOR]

Waterlogging is a major abiotic stress that limits the growth of plants. The crucial role of Ca2+ as a second messenger in response to abiotic and biotic stimuli has been widely recognized in plants. However, the physiological and molecular mechanisms of Ca2+ distribution within specific cell types in different root zones under hypoxia is poorly understood. In this work, whole-plant physiological and tissue-specific Ca2+ changes were studied using several ACA (Ca2+-ATPase) and CAX (Ca2+/proton exchanger) knock-out Arabidopsis mutants subjected to waterlogging treatment. In the wild-type (WT) plants, several days of hypoxia decreased the expression of ACA8, CAX4, and CAX11 by 33% and 50% compared with the control. The hypoxic treatment also resulted in an up to 11-fold tissue-dependent increase in Ca2+ accumulation in root tissues as revealed by confocal microscopy. The increase was much higher in stelar cells in the mature zone of Arabidopsis mutants with loss of function for ACA8, ACA11, CAX4, and CAX11. In addition, a significantly increased Ca2+ concentration was found in the cytosol of stelar cells in the mature zone after hypoxic treatment. Three weeks of waterlogging resulted in dramatic loss of shoot biomass in cax11 plants (67% loss in shoot dry weight), while in the WT and other transport mutants this decline was only 14-22%. These results were also consistent with a decline in leaf chlorophyll fluorescence (Fv/Fm). It is suggested that CAX11 plays a key role in maintaining cytosolic Ca2+ homeostasis and/or signalling in root cells under hypoxic conditions. [ABSTRACT FROM AUTHOR]

The discovery of the START family of abscisic acid (ABA) receptors places these proteins at the front of a protein kinase/phosphatase signal cascade that promotes stomatal closure. The connection of these receptors to Ca2+ signals evoked by ABA has proven more difficult to resolve, although it has been implicated by studies of the pyrbactin-insensitive pyr1/pyl1/pyl2/pyl4 quadruple mutant. One difficulty is that flux through plasma membrane Ca2+ channels and Ca2+ release from endomembrane stores coordinately elevate cytosolic free Ca2+ concentration ([Ca2+]i) in guard cells, and both processes are facilitated by ABA. Here, we describe a method for recording Ca2+ channels at the plasma membrane of intact guard cells of Arabidopsis (Arabidopsis thaliana). We have used this method to resolve the loss of ABA-evoked Ca2+ channel activity at the plasma membrane in the pyr1/pyl1/pyl2/pyl4 mutant and show the consequent suppression of [Ca2+]i increases in vivo. The basal activity of Ca2+ channels was not affected in the mutant; raising the concentration of Ca2+ outside was sufficient to promote Ca2+ entry, to inactivate current carried by inward-rectifying K+ channels and to activate current carried by the anion channels, both of which are sensitive to [Ca2+]i elevations. However, the ABA-dependent increase in reactive oxygen species (ROS) was impaired. Adding the ROS hydrogen peroxide was sufficient to activate the Ca2+ channels and trigger stomatal closure in the mutant. These results offer direct evidence of PYR/PYL/RCAR receptor coupling to the activation by ABA of plasma membrane Ca2+ channels through ROS, thus affecting [Ca2+]i and its regulation of stomatal closure. [ABSTRACT FROM AUTHOR]

The dynamics of stomatal movements and their consequences for photosynthesis and transpirational water loss have long been incorporated into mathematical models, but none have been developed from the bottom up that are widely applicable in predicting stomatal behavior at a cellular level. We previously established a systems dynamic model incorporating explicitly the wealth of biophysical and kinetic knowledge available for guard cell transport, signaling, and homeostasis. Here we describe the behavior of the model in response to experimentally documented changes in primary pump activities and malate (Mal) synthesis imposed over a diurnal cycle. We show that the model successfully recapitulates the cyclic variations in H+, K+, Cl-, and Mal concentrations in the cytosol and vacuole known for guard cells. It also yields a number of unexpected and counterintuitive outputs. Among these, we report a diurnal elevation in cytosolic-free Ca2+ concentration and an exchange of vacuolar Cl- with Mai, both of which find substantiation in the literature but had previously been suggested to require additional and complex levels of regulation. These findings highlight the true predictive power of the OnGuard model in providing a framework for systems analysis of stomatal guard cells, and they demonstrate the utility of the OnGuard software and HoTSig library in exploring fundamental problems in cellular physiology and homeostasis. [ABSTRACT FROM AUTHOR]

Stomatal guard cells play a key role in gas exchange for photosynthesis while minimizing transpirational water loss from plants by opening and closing the stomatal pore. Foliar gas exchange has long been incorporated into mathematical models, several of which are robust enough to recapitulate transpirational characteristics at the whole-plant and community levels. Few models of stomata have been developed from the bottom up, however, and none are sufficiently generalized to be widely applicable in predicting stomatal behavior at a cellular level. We describe here the construction of computational models for the guard cell, building on the wealth of biophysical and kinetic knowledge available for guard cell transport, signaling, and homeostasis. The OnGuard software was constructed with the HoTSig library to incorporate explicitly all of the fundamental properties for transporters at the plasma membrane and tonoplast, the salient features of osmolite metabolism, and the major controls of cytosolic-free Ca2+ concentration and pH. The library engenders a structured approach to tier and interrelate computational elements, and the OnGuard software allows ready access to parameters and equations 'on the fly' while enabling the network of components within each model to interact computationally. We show that an OnGuard model readily achieves stability in a set of physiologically sensible baseline or Reference States; we also show the robustness of these Reference States in adjusting to changes in environmental parameters and the activities of major groups of transporters both at the tonoplast and plasma membrane. The following article addresses the predictive power of the OnGuard model to generate unexpected and counterintuitive outputs. [ABSTRACT FROM AUTHOR]

Microalgal photo-biocatalysis is a green technique for asymmetric synthesis. Asymmetric reduction of nonnatural prochiral ketones to produce chiral alcohols by microalgal photo-biocatalysis was studied in this work. Acetophenone (ACP) and ethyl acetoacetate (EAA) were chosen as model substrates for aromatic ketones and β-ketoesters, respectively. Two prokaryotic cyanophyta and two eukaryotic chlorophyta were selected as photo-biocatalysts. The results proved that nonnatural prochiral ketones can be reduced by microalgal photo-biocatalysis with high enantioselectivity. Illumination is indispensable to the photo-biocatalysis. For aromatic ketone, cyanophyta are eligible biocatalysts. For ACP asymmetric reduction reaction, about 45% yield and 97% e.e. can be achieved by the photo-biocatalysis reaction with Spirulina platensis as biocatalyst. On the contrary, chlorophyta are efficient biocatalysts for β-ketoester asymmetric reduction reaction among the four tested algae. For EAA asymmetric reduction reaction, about 70% yield and 90% e.e. can be achieved with Scenedesmus obliquus as biocatalyst. The microalgae used in this study outperformed other characterized biocatalysts such as microbial and plant cells. [ABSTRACT FROM AUTHOR]

As an important organic compound, chiral alcohols are the key chiral building blocks to many single enantiomer pharmaceuticals. Asymmetric reduction of the corresponding prochiral ketones to produce the chiral alcohols by biocatalysis is one of the most promising routes. Asymmetric reduction of different kinds of non-natural prochiral ketones catalyzed by various plants tissue was studied in this work. Acetophenone, 4′-chloroacetophenone and ethyl 4-chloroacetoacetate were chosen as the model substrates for simple ketone, halogen-containing aromatic ketone and β-ketoesters, respectively. Apple ( Malus pumila), carrot ( Daucus carota), cucumber ( Cucumis sativus), onion ( Allium cepa), potato ( Soanum tuberosum), radish ( Raphanus sativus) and sweet potato ( Ipomoea batatas) were chosen as the biocatalysts. It was found that these kinds of prochiral ketoness could be reduced by these plants tissue with high enantioselectivity. Both R- and S-form configuration chiral alcohols could be obtained. The e.e. and chemical yield could reach about 98 and 80% respectively for acetophenone and 4′-chloroacetophenone reduction reaction with favorable plant tissue. And the e.e. and yield for ethyl 4-chloroacetoacetate reduction reaction was about 91 and 45% respectively. [ABSTRACT FROM AUTHOR]

We compared how stomatal morphology and physiology control intrinsic leaf water use efficiency (iWUE) in two C3 and six C4 grasses grown at ambient (400 µmol mol–1) or glacial CO2 (180 µmol mol–1) and high (1000 µmol m–2 s–1) or low light intensity (200 µmol m–2 s–1). C4 grasses tended to have higher iWUE and CO2 assimilation rates, and lower stomatal conductance (g s), operational stomatal aperture (a op), and guard cell K+ influx rate relative to C3 grasses, while stomatal size (SS) and stomatal density (SD) did not vary according to the photosynthetic type. Overall, iWUE and g s depended most on a op and density of open stomata. In turn, a op correlated with K+ influx, stomatal opening speed on transition to high light, and SS. Species with higher SD had smaller and faster-opening stomata. Although C4 grasses operated with lower g s and a op at ambient CO2, they showed a greater potential to open stomata relative to maximal stomatal conductance (g max), indicating heightened stomatal sensitivity and control. We uncovered promising links between a op, g s, iWUE, and K+ influx among C4 grasses, and differential K+ influx responses of C4 guard cells to low light, revealing molecular targets for improving iWUE in C4 crops. [ABSTRACT FROM AUTHOR]

Aluminum-activated malate transporters (ALMTs) and slow anion channels (SLACs) are important in various physiological processes in plants, including stomatal regulation, nutrient uptake, and in response to abiotic stress such as aluminum toxicity. To understand their evolutionary history and functional divergence, we conducted phylogenetic and expression analyses of ALMTs and SLACs in green plants. Our findings from phylogenetic studies indicate that ALMTs and SLACs may have originated from green algae and red algae, respectively. The ALMTs of early land plants and charophytes formed a monophyletic clade consisting of three subgroups. A single duplication event of ALMTs was identified in vascular plants and subsequent duplications into six clades occurred in angiosperms, including an identified clade, 1-1. The ALMTs experienced gene number losses in clades 1-1 and 2-1 and expansions in clades 1-2 and 2-2b. Interestingly, the expansion of clade 1-2 was also associated with higher expression levels compared to genes in clades that experienced apparent loss. SLACs first diversified in bryophytes, followed by duplication in vascular plants, giving rise to three distinct clades (I, II, and III), and clade II potentially associated with stomatal control in seed plants. SLACs show losses in clades II and III without substantial expansion in clade I. Additionally, ALMT clade 2-2 and SLAC clade III contain genes specifically expressed in reproductive organs and roots in angiosperms, lycophytes, and mosses, indicating neofunctionalization. In summary, our study demonstrates the evolutionary complexity of ALMTs and SLACs, highlighting their crucial role in the adaptation and diversification of vascular plants. Molecular and phylogenetic analysis reveal aluminum-activated malate transporter and slow anion channel families played crucial roles during plant adaptation. [ABSTRACT FROM AUTHOR]

Environmental stresses severely affect plant growth and crop productivity. Regulated by 14-3-3 proteins (14-3-3s), H+-ATPases (AHAs) are important proton pumps that can induce diverse secondary transport via channels and co-transporters for the abiotic stress response of plants. Many studies demonstrated the roles of 14-3-3s and AHAs in coordinating the processes of plant growth, phytohormone signaling, and stress responses. However, the molecular evolution of 14-3-3s and AHAs has not been summarized in parallel with evolutionary insights across multiple plant species. Here, we comprehensively review the roles of 14-3-3s and AHAs in cell signaling to enhance plant responses to diverse environmental stresses. We analyzed the molecular evolution of key proteins and functional domains that are associated with 14-3-3s and AHAs in plant growth and hormone signaling. The results revealed evolution, duplication, contraction, and expansion of 14-3-3s and AHAs in green plants. We also discussed the stress-specific expression of those 14-3-3 and AHA genes in a eudicotyledon (Arabidopsis thaliana), a monocotyledon (Hordeum vulgare), and a moss (Physcomitrium patens) under abiotic stresses. We propose that 14-3-3s and AHAs respond to abiotic stresses through many important targets and signaling components of phytohormones, which could be promising to improve plant tolerance to single or multiple environmental stresses. [ABSTRACT FROM AUTHOR]

In rice (Oryza sativa L.), vascular bundle phloem tissue in the panicle neck is vital for the transport of photosynthetic products from leaf to panicle and is positively associated with grain yield. However, genetic regulation of the single large vascular bundle phloem area (LVPA) in rice panicle neck tissue remains poorly understood. In this study, we carried out genome-wide association analysis of LVPA in the panicle neck using 386 rice accessions and isolated and characterized the gene LVPA4, which is allelic to NARROW LEAF1 (NAL1). Phenotypic analyses were carried out on the near-isogenic line (NIL) NIL-LVPA4LT in the high-yielding indica (xian) cultivar Teqing and on overexpression lines transformed with a vector carrying the Lemont alleles of LVPA4. Both NIL-LVPA4LT and LVPA4 overexpression lines exhibited significantly increased LVPA, enlarged flag leaf size, and improved panicle type. NIL-LVPA4LT had a 7.6%-9.6% yield increase, mainly due to the significantly higher filled grain number per panicle, larger vascular system for transporting photoassimilates to spikelets, and more sufficient source supply that could service the increased sink capacity. Moreover, NIL-LVPA4LT had improved grain quality compared with Teqing, which was mainly attributed to substantial improvement in grain filling, especially for inferior spikelets in NIL-LVPA4LT. The single-nucleotide variation in the third exon of LVPA4 was associated with LVPA, spikelet number, and leaf size throughout sequencing analysis in 386 panels. The results demonstrate that LVPA4 has synergistic effects on source capacity, sink size, and flow transport and plays crucial roles in rice productivity and grain quality, thus revealing the value of LVPA4 in rice breeding programs for improved varieties. [ABSTRACT FROM AUTHOR]

The sustainable production of crops faces increasing challenges from global climate change and human activities, which leads to increasing instances of many abiotic stressors to plants. Among the abiotic stressors, drought, salinity and excessive levels of toxic metals cause reductions in global agricultural productivity and serious health risks for humans. Cytokinins (CKs) are key phytohormones functioning in both normal development and stress responses in plants. Here, we summarize the molecular mechanisms on the biosynthesis, metabolism, transport and signaling transduction pathways of CKs. CKs act as negative regulators of both root system architecture plasticity and root sodium exclusion in response to salt stress. The functions of CKs in mineral-toxicity tolerance and their detoxification in plants are reviewed. Comparative genomic analyses were performed to trace the origin, evolution and diversification of the critical regulatory networks linking CK signaling and abiotic stress. We found that the production of CKs and their derivatives, pathways of signal transduction and drought-response root growth regulation are evolutionarily conserved in land plants. In addition, the mechanisms of CK-mediated sodium exclusion under salt stress are suggested for further investigations. In summary, we propose that the manipulation of CK levels and their signaling pathways is important for plant abiotic stress and is, therefore, a potential strategy for meeting the increasing demand for global food production under changing climatic conditions. [ABSTRACT FROM AUTHOR]

Drought significantly affects stomatal regulation, leading to the reduced growth and productivity of plants. Plant 14-3-3 proteins were reported to participate in drought response by regulating the activities of a wide array of target proteins. However, the molecular evolution, expression pattern and physiological functions of 14-3-3s under drought stress remain unclear. In this study, a comparative genomic analysis and the tissue-specific expression of 14-3-3s revealed the highly conserved and early evolution of 14-3-3s in green plants and duplication and expansion of the 14-3-3s family members in angiosperms. Using barley (Hordeum vulgare) for the functional characterization of 14-3-3 proteins, the transcripts of five members out of six Hv14-3-3s were highly induced by drought in the drought-tolerant line, XZ141. Suppression of the expression of Hv14-3-3A through barley stripe mosaic virus-virus induced gene silencing resulted in significantly increased drought sensitivity and stomatal density as well as significantly reduced net CO2 assimilation (A) and stomatal conductance (gs) in barley. Moreover, we showed the functional interactions between Hv14-3-3s and key proteins in drought and stomatal responses in plants—such as Open Stomata 1 (HvOST1), Slow Anion Channel 1 (HvSLAC1), three Heat Shock Proteins (HvHSP90-1/2/5) and Dehydration-Responsive Element-Binding 3 (HvDREB3). Taken together, we propose that 14-3-3s are highly evolutionarily conserved proteins and that Hv14-3-3s represent a group of the core regulatory components for the rapid stomatal response to drought in barley. This study will provide important evolutionary and molecular evidence for future applications of 14-3-3 proteins in breeding drought-tolerant crops in a changing global climate. [ABSTRACT FROM AUTHOR]

To investigate the expression and roles of TAM (Tyro3/Axl/Mer) receptor tyrosine kinases (TK) in synovial fluid and synovial tissue of patients with rheumatoid arthritis (RA). The expression of TAM TKs in the synovial fluid and synovial tissues of RA and osteoarthritis (OA) patients was measured by ELISA and immunohistochemistry. The relationships between soluble TAM TKs (sTAM TKs) levels and the clinical features, laboratory parameters and disease activity were analyzed in RA. The concentrations of sTAM TK in the synovial fluids of RA patients were increased in comparison to those of OA patients. Compared with OA patients, the expression of membrane Tyro3 TK (mTyro3 TK) and mMer TK in RA patient synovial tissue were significantly increased, which may partly explain the possible mechanism of elevated levels of sTAM TK in RA patient synovial fluid. sAxl TK levels were decreased in RA patients under sulfasalazine treatment and elevated in patients under Iguratimod treatment. Furthermore, sTyro3 TK levels were positively correlated with erythrocyte sedimentation rate (ESR) and negatively correlated with white blood cells (WBCs), red blood cells (RBCs), and hemoglobin (HB) in RA patients. The levels of sMer TK were positively associated with disease duration and rheumatoid factor (RF) and negatively correlated with HB, complement 3 (C3), and C4. Taken together, TAM TKs might be involved in RA synovial tissue inflammation. [ABSTRACT FROM AUTHOR]

Oryza coarctata is the only wild rice species with significant salinity tolerance. The present work examines the role of the substantial rhizomatous tissues of O. coarctata in conferring salinity tolerance. Transition to an erect phenotype (shoot emergence) from prostrate growth of rhizome tissues is characterized by marked lignification and suberization of supporting sclerenchymatous tissue, epidermis, and bundle sheath cells in aerial shoot-proximal nodes and internodes in O. coarctata. With salinity, however, aerial shoot-proximal internodal tissues show reductions in lignification and suberization, most probably related to re-direction of carbon flux towards synthesis of the osmporotectant proline. Concurrent with hypolignification and reduced suberization, the aerial rhizomatous biomass of O. coarctata appears to have evolved mechanisms to store Na+ in these specific tissues under salinity. This was confirmed by histochemical staining, quantitative real-time reverse transcription–PCR expression patterns of genes involved in lignification/suberization, Na+ and K+ contents of internodal tissues, as well as non-invasive microelectrode ion flux measurements of NaCl-induced net Na+, K+, and H+ flux profiles of aerial nodes were determined. In O. coarctata , aerial proximal internodes appear to act as 'traffic controllers', sending required amounts of Na+ and K+ into developing leaves for osmotic adjustment and turgor-driven growth, while more deeply positioned internodes assume a Na+ buffering/storage role. [ABSTRACT FROM AUTHOR]

Halophyte species implement a "salt-including" strategy, sequestering significant amounts of Na+ to cell vacuoles. This requires a reduction of passive Na+ leak from the vacuole. In this work, we used quinoa (Chenopodium quinoa) to investigate the ability of halophytes to regulate Na+-permeable slow-activating (SV) and fast-activating (FV) tonoplast channels, linking it with Na+ accumulation in mesophyll cells and salt bladders as well as leaf photosynthetic efficiency under salt stress. Our data indicate that young leaves rely on Na+ exclusion to salt bladders, whereas old ones, possessing far fewer salt bladders, depend almost exclusively on Na+ sequestration to mesophyll vacuoles. Moreover, although old leaves accumulate more Na+, this does not compromise their leaf photochemistry. FV and SV channels are slightly more permeable for K+ than for Na+, and vacuoles in young leaves express less FV current and with a density unchanged in plants subjected to high (400 HIM NaCl) salinity. In old leaves, with an intrinsically lower density of the FV current, FV channel density decreases about 2-fold in plants grown under high salinity. In contrast, intrinsic activity of SV channels in vacuoles from young leaves is unchanged under salt stress. In vacuoles of old leaves, however, it is 2- and 7-fold lower in older compared with young leaves in control- and salt-grown plants, respectively. We conclude that the negative control of SV and FV tonoplast channel activity in old leaves reduces Na+ leak, thus enabling efficient sequestration of Na+ to their vacuoles. This enables optimal photosynthetic performance, conferring salinity tolerance in quinoa species. [ABSTRACT FROM AUTHOR]

The continued interest in protein engineering has led to intense efforts in developing novel stable enzymes, which could not only give boost to industrial and biomedical applications, but also enhance our understanding of the structure–function relationships of proteins. We present here the generation of three hybrid proteins of cytochrome c (cyt c) and peroxidase via structure-based rational mutagenesis of cyt c. Several residues (positions 67, 70, 71 and 80) in the distal heme region of cyt c were mutated to the highly conserved amino acids in the heme pocket of peroxidases. The multiple mutants were found to exhibit high peroxidase activity and conserve the impressive stability of cyt c. We expect that this strategy could be extended to other cases of metalloprotein engineering, and lead to the development of stable and active biocatalysts for industrial uses. Besides, this study also provides insight into the structure–function relationships of hemoproteins. [ABSTRACT FROM PUBLISHER]

Optical films that alter light transmittance may reduce energy consumption in high-tech greenhouses, but their impact on crop physiology remains unclear. We compared the stomatal responses of Capsicum plants grown hydroponically under control glass (70% diffuse light) or the smart glass (SG) film ULR-80, which blocked >50% of short-wave radiation and ~9% of photosynthetically active radiation (PAR). SG had no significant effects on steady-state (g s) or maximal (g max) stomatal conductance. In contrast, SG reduced stomatal pore size and sensitivity to exogenous abscisic acid (ABA), thereby increasing rates of leaf water loss, guard cell K+ and Cl– efflux, and Ca2+ influx. SG induced faster stomatal closing and opening rates on transition between low (100 µmol m–2 s–1) and high PAR (1500 µmol m–2 s–1), which compromised water use efficiency relative to control plants. The fraction of blue light (0% or 10%) did not affect g s in either treatment. Increased expression of stomatal closure and photoreceptor genes in epidermal peels of SG plants is consistent with fast stomatal responses to light changes. In conclusion, stomatal responses of Capsicum to SG were more affected by changes in light intensity than spectral quality, and re-engineering of the SG should maximize PAR transmission, and hence CO2 assimilation. [ABSTRACT FROM AUTHOR]

The initial aim of environmental epidemiology is to estimate the causal effects of environmental exposures on health outcomes. However, due to lack of enough covariates in most environmental data sets, current methods without enough adjustments for confounders inevitably lead to residual confounding. We propose a negative-control exposure based on a time-series studies (NCE-TS) model to effectively eliminate unobserved confounders using an after-outcome exposure as a negative-control exposure. We show that the causal effect is identifiable and can be estimated by the NCE-TS for continuous and categorical outcomes. Simulation studies indicate unbiased estimation by the NCE-TS model. The potential of NCE-TS is illustrated by 2 challenging applications: We found that living in areas with higher levels of surrounding greenness over 6 months was associated with less risk of stroke-specific mortality, based on the Shandong Ecological Health Cohort during January 1, 2010, to December 31, 2018. In addition, we found that the widely established negative association between temperature and cancer risks was actually caused by numbers of unobserved confounders, according to the Global Open Database from 2003–2012. The proposed NCE-TS model is implemented in an R package (R Foundation for Statistical Computing, Vienna, Austria) called NCETS, freely available on GitHub. [ABSTRACT FROM AUTHOR]

A novel magnetic solid-phase extraction technique coupled to ultraperformance liquid chromatography has been developed for separation and preconcentration of four sulfonylurea herbicides (sulfosulfuron, bensulfuron-methyl, pyrazosulfuron-ethyl and halosulfuro-methyl) in aqueous samples. The key point of this method was the application of a novel magnetic nanomaterial that composed of a low eutectic solvent as a shell coated on the magnetic core modified by polydopamine. The extensive active sites outside the low eutectic solvent can effectively adsorb the target herbicide in the extraction process. The obtained magnetic adsorbent was characterized with fourier transform infrared spectrometry, scanning electron microscopy and vibrating sample magnetometer. The influence parameters relevant to this method were optimized. Under the optimum conditions, good linearities could be obtained within the range of 1.0–200 μg L−1 for all analytes, with correlation coefficients ≥0.9908. The limit of detections of the method was between 0.0074 and 0.0100 μg L−1 and the relative standard deviations were 1.1–3.6%. The enrichment factor is 66.6. In the final experiment, the proposed method was successfully applied to the analysis of sulfonylurea herbicides residue in environment and drinking-water samples, and the obtained recoveries were between 70.6% and 109.4%. [ABSTRACT FROM AUTHOR]

Potassium (K+) is the major cationic inorganic nutrient utilized for osmotic regulation, cell growth, and enzyme activation in plants. Inwardly rectifying K+ channel 1 (AKT1) is the primary channel for root K+ uptake in plants, but the function of HvAKT1 in barley plants under drought stress has not been fully elucidated. In this study, we conducted evolutionary bioinformatics, biotechnological, electrophysiological, and biochemical assays to explore molecular mechanisms of HvAKT1 in response to drought in barley. The expression of HvAKT1 was significantly up-regulated by drought stress in the roots of XZ5—a drought-tolerant wild barley genotype. We isolated and functionally characterized the plasma membrane-localized HvAKT1 using Agrobacterium -mediated plant transformation and Barley stripe mosaic virus -induced gene silencing of HvAKT1 in barley. Evolutionary bioinformatics indicated that the K+ selective filter in AKT1 originated from streptophyte algae and is evolutionarily conserved in land plants. Silencing of HvAKT1 resulted in significantly decreased biomass and suppressed K+ uptake in root epidermal cells under drought treatment. Disruption of HvAKT1 decreased root H+ efflux, H+-ATPase activity, and nitric oxide (NO) synthesis, but increased hydrogen peroxide (H2O2) production in the roots under drought stress. Furthermore, we observed that overexpression of HvAKT1 improves K+ uptake and increases drought resistance in barley. Our results highlight the importance of HvAKT1 for root K+ uptake and its pleiotropic effects on root H+-ATPase, and H2O2 and NO in response to drought stress, providing new insights into the genetic basis of drought tolerance and K+ nutrition in barley. [ABSTRACT FROM AUTHOR]

Aluminum (Al) toxicity is the primary limiting factor of crop production on acid soils. Tibetan wild barley germplasm is a valuable source of potential genes for breeding barley with acid and Al tolerance. We performed microRNA and RNA sequencing using wild (XZ16, Al-tolerant; XZ61, Al-sensitive) and cultivated (Dayton, Al-tolerant) barley. A novel homeobox-leucine zipper transcription factor, HvHOX9 , was identified as a target gene of miR166b and functionally characterized. HvHOX9 was up-regulated by Al stress in XZ16 (but unchanged in XZ61 and Dayton) and was significantly induced only in root tip. Phylogenetic analysis showed that HvHOX9 is most closely related to wheat TaHOX9 and orthologues of HvHOX9 are present in the closest algal relatives of Zygnematophyceae. Barley stripe mosaic virus-induced gene silencing of HvHOX9 in XZ16 led to significantly increased Al sensitivity but did not affect its sensitivity to other metals and low pH. Disruption of HvHOX9 did not change Al concentration in the root cell sap, but led to more Al accumulation in root cell wall after Al exposure. Silencing of HvHOX 9 decreased H+ influx after Al exposure. Our findings suggest that miR166b /HvHOX9 play a critical role in Al tolerance by decreasing root cell wall Al binding and increasing apoplastic pH for Al detoxification in the root. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) signaling modulates sodium (Na+) transport in plants; however, the role of the Ca2+ sensor calmodulin (CaM) in salt tolerance is elusive. We previously identified a salt-responsive calmodulin (HvCaM1) in a proteome study of barley (Hordeum vulgare) roots. Here, we employed bioinformatic, physiological, molecular, and biochemical approaches to determine the role of HvCaM1 in barley salt tolerance. CaM1s are highly conserved in green plants and probably originated from ancestors of green algae of the Chlamydomonadales order. HvCaM1 was mainly expressed in roots and was significantly up-regulated in response to long-term salt stress. Localization analyses revealed that HvCaM1 is an intracellular signaling protein that localizes to the root stele and vascular systems of barley. After treatment with 200 mm NaCl for 4 weeks, HvCaM1 knockdown (RNA interference) lines showed significantly larger biomass but lower Na+ concentration, xylem Na+ loading, and Na+ transportation rates in shoots compared with overexpression lines and wild-type plants. Thus, we propose that HvCaM1 is involved in regulating Na+ transport, probably via certain class I high-affinity potassium transporter (HvHKT1;5 and HvHKT1;1)-mediated Na+ translocation in roots. Moreover, we demonstrated that HvCaM1 interacted with a CaM-binding transcription activator (HvCAMTA4), which may be a critical factor in the regulation of HKT1s in barley. We conclude that HvCaM1 negatively regulates salt tolerance, probably via interaction with HvCAMTA4 to modulate the down-regulation of HvHKT1;5 and/or the up-regulation of HvHKT1;1 to reduce shoot Na+ accumulation under salt stress in barley. [ABSTRACT FROM AUTHOR]

Plant organ growth and development are determined by a subtle balance between growth stimulation and inhibition. Fruit size and shape are important quality traits influencing yield and market value; however, the underlying mechanism regulating the balance of fruit growth to achieve final size and shape is not well understood. Here, we report a mechanistic model that governs cucumber (Cucumis sativus) fruit elongation through fine-tuning of ethylene homeostasis. We identified a cucumber mutant that bears short fruits owing to repressed cell division. SF1 (Short Fruit 1) encodes a cucurbit-specific RING-type E3 ligase, and the mutation resulted in its enhanced self-ubiquitination and degradation, but accumulation of ACS2 (1-aminocyclopropane-1-carboxylate synthase 2), a rate-limiting enzyme for ethylene biosynthesis. The overproduction of ethylene contributes to the short-fruit phenotype of sf1. Dysfunction of ACS2 resulted in reduced ethylene production, but still repressed cell division and shorter fruit, suggesting that ethylene is still required for basal fruit elongation. SF1 ubiquitinates and degrades both itself and ACS2 to control ethylene synthesis for dose-dependent effect on cell division and fruit elongation. Our findings reveal the mechanism by which ethylene dosage is regulated for the control of cell division in developing fruit. [ABSTRACT FROM AUTHOR]

Under environmental stresses, Haematococcus pluvialis accumulates large amounts of carotenoids. Scale of carotenoid biosynthesis depends on availability of geranylgeranyl pyrophosphate (GGPP) precursor, which is supplied by GGPP synthase (GGPPS) through sequential 1′-4 condensation of three isopentenyl pyrophosphates (IPPs) into dimethylallyl pyrophosphate (DMAPP). Using IPP and DMAPP as substrates, a tri-functional HpGGPPS was identified in this study to promiscuously synthesize allylic prenyl pyrophosphates (PPPs), e.g. C10 geranyl pyrophosphate (GPP), C15 farnesyl pyrophosphate (FPP), and C20 GGPP. Intriguingly, HpGGPPS can utilize GPP or FPP as a single substrate to synthesize GGPP by hydrolyzing the allylic PPP substrate into C5 IPP. Transcription of HpGGPPS and key carotenogenesis genes, morphological transformation, and carotenoid biosynthesis were differentially induced by environmental stresses, while HpGGPPS's products were low in vivo, implying that most of PPP flux had been shunted into carotenoid biosynthesis. Hydrolyzing allylic PPP intermediates into C5 building blocks by promiscuous HpGGPPS may be a fail safe for carotenoid accumulation against environmental stress. [ABSTRACT FROM AUTHOR]

Study Question: What is the impact of glucocorticoid (GC) on female reproduction?Summary Answer: Corticosterone (CORT) exposure causes little damage to oocyte quality or developmental competence but has an adverse effect on the uterus, which causes decreased implantation, embryo death and subsequent infertility.What Is Known Already: Chronic treatment with high GC doses is effective in controlling most allergic diseases but may lead to metabolic disorders such as obesity that are closely related with reproductive function.Study Design, Size, Duration: Hypercortisolism was induced in a female mouse model by supplementing the drinking water with 100 μg/ml of CORT. Controls received vehicle (1% v/v ethanol) only. After 4 weeks treatment mice were either mated or killed in estrus for hormone and organ measurements. In the first experiment, treatment with CORT or control continued during pregnancy but in the second CORT treatment was stopped after mating. To identify the effects of GC exposure on the uterus, blastocysts were generated by IVF of oocytes from CORT and control mice and replaced into recipients receiving the opposite treatment.Participants/materials, Setting, Methods: The effects of hypercortisolism on female mice were first characterized by living body fat content, body weight, food intake, hormone and biochemical measurements, a glucose tolerance test and an insulin resistance test. Fertility was determined with or without CORT-treatment during pregnancy. Oocyte quality was assessed by oocyte maturation, mitochondrial distribution, reactive oxygen species production, mitochondrial DNA mutations and morphology of blastocysts produced in vivo or in vitro. Blastocyst cross-transfer was done to evaluate the causes of embryonic development failure. Fetus development and uterus morphology evaluation as well as culture of oocytes in vitro with gradient concentrations of CORT were also carried out.Main Results and the Role Of Chance: In the hypercortisolism female mouse model, body weight and food intake were much higher than in the control, and corticosterone, estradiol, cholesterol (CHO) and triglycerides (TG) in the plasma of CORT-treated mice was significantly increased. The hypercortisolism female mice were infertile when CORT-treatment was sustained during pregnancy but fertile if CORT-treatment was stopped after mating. The rate of successful implantation in hypercortisolism mice with sustained CORT-treatment during pregnancy was significantly lower than in the control, and the implanted embryos could not develop beyond 13.5 dpc. Blastocyst cross-transfer showed that blastocysts from CORT-treated mice could develop to term in the uterus of control mice, but blastocysts from control mice failed to develop to term when they were transferred into CORT-treated mice, providing evidence that the infertility was mainly caused by an altered uterine environment. CORT administration did not affect oocyte maturation, mitochondrial distribution, ROS production and blastocyst morphology, but increased mitochondrial DNA mutations. Culture of oocytes in vitro with gradient concentrations of CORT showed that only very high concentrations of CORT caused damage to oocyte developmental competence.Large Scale Data: NA.Limitations, Reasons For Caution: The mouse model has the advantages of a consistent genetic and physiological background and openness to experimental manipulation over clinical studies but may not represent the human situation.Wider Implications Of the Findings: Our findings show that special care should be taken when administering CORT during pregnancy, and provide important information concerning female reproduction when treating patients by subjecting them to chronic GC exposure.Study Funding/competing Interest(s): This study was supported by the National Key R&D Program of China (Nos. 2016YFA0100400 and 2017YFC1000600) and the National Natural Science Foundation of China (31472055). The authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Our previous studies showed that high salt tolerance in Tibetan wild barley accessions was associated with HvHKT1;1, a member of the high-affinity potassium transporter family. However, molecular mechanisms of HvHKT1;1 for salt tolerance and its roles in K+/Na+ homeostasis remain to be elucidated. Functional characterization of HvHKT1;1 was conducted in the present study. NaCl-induced transcripts of HvHKT1;1 were significantly higher in the roots of Tibetan wild barley XZ16 relative to other genotypes, being closely associated with its higher biomass and lower tissue Na+ content under salt stress. Heterologous expression of HvHKT1;1 in Saccharomyces cerevisiae (yeast) and Xenopus laevis oocytes showed that HvHKT1;1 had higher selectivity for Na+ over K+ and other monovalent cations. HvHKT1;1 was found to be localized at the cell plasma membrane of root stele and epidermis. Knock-down of HvHKT1;1 in barley led to higher Na+ accumulation in both roots and leaves, while overexpression of HvHKT1;1 in salt-sensitive Arabidopsis hkt1-4 and sos1-12 loss-of-function lines resulted in significantly less shoot and root Na+ accumulation. Additionally, microelectrode ion flux measurements and root elongation assay revealed that the transgenic Arabidopsis plants exhibited a remarkable capacity for regulation of Na+, K+, Ca2+ and H+ homeostasis under salt stress. These results indicate that HvHKT1;1 is critical in radial root Na+ transport, which eventually reduces shoot Na+ accumulation. Additionally, HvHKT1;1 may be indirectly involved in retention of K+ and Ca2+ in root cells, which also improves plant salt tolerance. [ABSTRACT FROM AUTHOR]

Abscisic acid (ABA)-driven stomatal regulation reportedly evolved after the divergence of ferns, during the early evolution of seed plants approximately 360 million years ago. This hypothesis is based on the observation that the stomata of certain fern species are unresponsive to ABA, but exhibit passive hydraulic control. However, ABA-induced stomatal closure was detected in some mosses and lycophytes. Here, we observed that a number of ABA signaling and membrane transporter protein families diversified over the evolutionary history of land plants. The aquatic ferns Azolla filiculoides and Salvinia cucullata have representatives of 23 families of proteins orthologous to those of Arabidopsis (Arabidopsis thaliana) and all other land plant species studied. Phylogenetic analysis of the key ABA signaling proteins indicates an evolutionarily conserved stomatal response to ABA. Moreover, comparative transcriptomic analysis has identified a suite of ABA-responsive genes that differentially expressed in a terrestrial fern species, Polystichum proliferum. These genes encode proteins associated with ABA biosynthesis, transport, reception, transcription, signaling, and ion and sugar transport, which fit the general ABA signaling pathway constructed from Arabidopsis and Hordeum vulgare. The retention of these key ABA-responsive genes could have had a profound effect on the adaptation of ferns to dry conditions. Furthermore, stomatal assays have shown the primary evidence for ABA-induced closure of stomata in two terrestrial fern species P. proliferum and Nephrolepis exaltata. In summary, we report, to our knowledge, new molecular and physiological evidence for the presence of active stomatal control in ferns. [ABSTRACT FROM AUTHOR]

Regulation of root cell K+ is essential for acclimation to low oxygen stress. The potential roles of GORK (depolarization- activated guard cell outward-rectifying potassium) channels and RBOHD (respiratory burst oxidase homologue D) in plant adaptive responses to hypoxia were investigated in the context of tissue specificity (epidermis versus stele; elongation versus mature zone) in roots of Arabidopsis. The expression of GORK and RBOHD was down-regulated by 2- to 3-fold within 1 h and 24 h of hypoxia treatment in Arabidopsis wild-type (WT) roots. Interestingly, a loss of the functional GORK channel resulted in a waterlogging-tolerant phenotype, while rbohD knockout was sensitive to waterlogging. To understand their functions under hypoxia stress, we studied K+, Ca2+, and reactive oxygen species (ROS) distribution in various root cell types. gork1-1 plants had better K+ retention ability in both the elongation and mature zone compared with the WT and rbohD under hypoxia. Hypoxia induced a Ca2+ increase in each cell type after 72 h, and the increase was much less pronounced in rbohD than in the WT. In most tissues except the elongation zone in rbohD, the H2O2 concentration had decreased after 1 h of hypoxia, but then increased significantly after 24 h of hypoxia in each zone and tissue, further suggesting that RBOHD may shape hypoxia-specific Ca2+ signatures via the modulation of apoplastic H2O2 production. Taken together, our data suggest that plants lacking functional GORK channels are more capable of retaining K+ for their better performance under hypoxia, and that RBOHD is crucial in hypoxia-induced Ca2+ signalling for stress sensing and acclimation mechanism. [ABSTRACT FROM AUTHOR]

In this article, we propose a new statistical method-MutRSeq-for detecting differentially expressed single nucleotide variants (SNVs) based on RNA-seq data. Specifically, we focus on nonsynonymous mutations and employ a hierarchical likelihood approach to jointly model observed mutation events as well as read count measurements from RNA-seq experiments. We then introduce a likelihood ratio-based test statistic, which detects changes not only in overall expression levels, but also in allele-specific expression patterns. In addition, this method can jointly test multiple mutations in one gene/pathway. The simulation studies suggest that the proposed method achieves better power than a few competitors under a range of different settings. In the end, we apply this method to a breast cancer data set and identify genes with nonsynonymous mutations differentially expressed between the triple negative breast cancer tumors and other subtypes of breast cancer tumors. [ABSTRACT FROM AUTHOR]

A thorough understanding of ionic detoxification and homeostasis is imperative for improvement of salt tolerance in crops. However, the homeostasis of elements and their relationship to metabolites under salt stress have not been fully elucidated in plants. In this study, Tibetan wild barley accessions, XZ16 and XZ169, differing in salt tolerance, and a salt-tolerant cultivar CM72 were used to investigate ionomic profile changes in tissues in response to 150 and 300 mM NaCl at the germination and seedling stages. At the germination stage, the contents of Ca and Fe significantly decreased in roots, while K and S contents increased, and Ca and Mg contents decreased in shoots, after 10 d of treatment. At the seedling stage, the contents of K, Mg, P and Mn in roots and of K, Ca, Mg and S in shoots decreased significantly after 21 d of treatment. Moreover, Na had a significant negative correlation with metabolites involved in glycolysis, α-ketoglutaric acid, maleic acid and alanine in roots, and metabolites associated with the tricarboxylic acid (TCA) cycle, sucrose, polyols and aspartate in leaves. The salt-tolerant genotypes XZ16 and CM72 showed a lower Na content in tissues, and less reduction in Zn and Cu in roots, of Ca, Mg and S in leaves, and shoot DW than the sensitive genotype XZ169, when exposed to a higher salt level. The results indicated that restriction of Na accumulation and rearrangement of nutrient elements and metabolites in barley tissues are possibly attributable to development of salt tolerance. [ABSTRACT FROM PUBLISHER]

Endothelial cells (ECs) are critical for angiogenesis, and microRNAs play important roles in this process. We investigated the regulatory role of microRNAs in ECs of hepatocellular carcinoma (HCC) by examining the microRNA expression profile of human umbilical vein endothelial cells (HUVECs) in the absence or presence of human HCC cells, and identified miR-146a as the most highly upregulated microRNA. Furthermore, we revealed that miR-146a promoted the expression of platelet-derived growth factor receptor α (PDGFRA) in HUVECs, and this process was mediated by BRCA1. Overexpression of PDGFRA in the ECs of HCC tissues was associated with microvascular invasion and predicted a poorer prognosis. These results suggest that miR-146a plays a key role in regulating the angiogenic activity of ECs in HCC through miR-146a–BRCA1–PDGFRA pathway. MiR-146a and PDGFRA may emerge as potential anti-angiogenic targets on ECs for HCC therapy. [ABSTRACT FROM AUTHOR]

Large-scale genome-wide association studies (GWAS) have identified over 40 genomic regions significantly associated with type 2 diabetes mellitus. However, GWAS results are not always straightforward to interpret, and linking these loci to meaningful disease etiology is often difficult without extensive follow-up studies. The authors expanded on previously reported type 2 diabetes mellitus GWAS from the nested case-control studies of 2 prospective US cohorts by incorporating expression single nucleotide polymorphism (SNP) information and applying SNP set enrichment analysis to identify sets of SNPs associated with genes that could provide further biologic insight to traditional genome-wide analysis. Using data collected between 1989 and 1994 in these previous studies to form a nested case-control study, the authors found that 3 of the most significantly associated SNPs to type 2 diabetes mellitus in their study are expression SNPs to the lymphocyte antigen 75 gene (LY75), the ubiquitin-specific peptidase 36 gene (USP36), and the phosphatidylinositol transfer protein, cytoplasmic 1 gene (PITPNC1). SNP set enrichment analysis of the GWAS results identified enrichment for expression SNPs to the macrophage-enriched module and the Gene Ontology (GO) biologic process fat cell differentiation human, which includes the transcription factor 7-like 2 gene (TCF7L2), as well as other type 2 diabetes mellitus-associated genes. Integrating genome-wide association, gene expression, and gene set analysis may provide valuable biologic support for potential type 2 diabetes mellitus susceptibility loci and may be useful in identifying new targets or pathways of interest for the treatment and prevention of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Rapid, reliable determination of the genetic relatedness of clinical isolates in a microbiologic laboratory is essential when investigating cases of nosocomial outbreak. Methods: Twenty-four Acinetobacter baumannii strains were collected in intensive care units (ICUs) from June 2008 to May 2010. The minimum inhibitory concentrations (MICs) of 18 antimicrobial agents were determined for each strain. Genotyping and dendrographic analysis of A. baumannii strains were performed using the DiversiLab System. Results: Twenty-four A. baumannii strains were classified into 4 groups: Group 1, composed of 16 strains divided into 4 patterns; Group 2, composed of 6 strains divided into 3 patterns; and Groups 3 and 4, composed of one strain each. The groups showed different patterns of drug resistance, and variable patterns of drug resistance were observed within each group. Conclusions: The DiversiLab System provides a simple, rapid method for evaluating the epidemiological status of nosocomial A. baumannii infections. [ABSTRACT FROM AUTHOR]

Plant microRNAs (miRNAs) play crucial regulatory roles in various developmental processes. In this study, we characterize the miRNA profile of the shoot apical meristem (SAM) of an important legume crop, soybean, by integrating high-throughput sequencing data with miRNA microarray analysis. A total of 8423 non-redundant sRNAs were obtained from two libraries derived from micro-dissected SAM or mature leaf tissue. Sequence analysis allowed the identification of 32 conserved miRNA families as well as 8 putative novel miRNAs. Subsequent miRNA profiling with microarrays verified the expression of the majority of these conserved and novel miRNAs. It is noteworthy that several miRNAs* were expressed at a level similar to or higher than their corresponding mature miRNAs in SAM or mature leaf, suggesting a possible biological function for the star species. In situ hybridization analysis revealed a distinct spatial localization pattern for a conserved miRNA, miR166, and its star speciessuggesting that they serve different roles in regulating leaf development. Furthermore, localization studies showed that a novel soybean miRNA, miR4422a, was nuclear-localized. This study also indicated a novel expression pattern of miR390 in soybean. Our approach identified potential key regulators and provided vital spatial information towards understanding the regulatory circuits in the SAM of soybean during shoot development. [ABSTRACT FROM PUBLISHER]

Introduction. Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks. Aim. To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat. Main Outcome Measures. Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined. Methods. Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 µg/kg (N = 10) and IGF-1 10 µg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3′,5′-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed. Results. After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 µg/kg and the IGF-1 10 µg/kg group compared with the vehicle-only group at 4 and 8 weeks ( P < 0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats. Conclusions. IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways. Pu, X-Y, Wang X-H, Gao W-C, Yang Z-H, and Li S-L. Insulin-like growth factor-1 restores erectile function in aged rats: Modulation the integrity of smooth muscle and nitric oxide-cyclic guanosine monophosphate signaling activity. J Sex Med 2008;5:1345–1354. [ABSTRACT FROM AUTHOR]

Background: Biliary complications continue to be an important determinant of the recipient's survival rate after orthotopic liver transplantation (OLT). The objective of this study was to evaluate the incidence of early biliary complications in OLT in the presence or absence of a 1-tube. Methods: This retrospective study, based on inpatient data, focused on the relationship between 1-tube placement and early biliary complications of 84 patients after OLI, from November 2002 to June 2005. Patients were divided into two groups based on whether or not a 1-tube was used following bile duct reconstruction: 1-tube group (group I, n = 33); non-I-tube group (group II, n = 51). Results: 45.2% of 011 recipients had a malignant neoplasm. There were no significant differences in the demographic characteristics or operation data between the two groups. Overall, early biliary tract complications developed in 19.0% (16/84) of patients. The rate of early biliary complications was 30.3% (10/33) and 11.8% (6/51) in groups III, respectively (p=0.035). Biliary complications which were directly caused by I-tube placement occurred in 12.1% (4/33) of patients in group I. Overall, the percentage of malignant neoplasms, chronic viral cirrhosis, fulminant liver failure and other primary disease recipients with early biliary complications were 6.2%, 37.5%, 43.8% and 12.5%, respectively. Conclusion: This study suggests that the use of a I-tube in Chinese patients undergoing OLT causes a higher incidence of early biliary complications. Most of the early biliary complications occurred in chronic viral cirrhosis and fulminant liver failure recipients. [ABSTRACT FROM AUTHOR]

To develop a fast and reliable method for selecting metal-poor galaxies (MPGs), especially in large surveys and huge data bases, a support vector machine (svm) supervized learning algorithms is applied to a sample of star-forming galaxies from the Sloan Digital Sky Survey data release 9 provided by the Max Planck Institute and the Johns Hopkins University (http://www.sdss3.org/dr9/spectro/spectroaccess.php). A two-step approach is adopted: (i) the svm must be trained with a subset of objects that are known to be either MPGs or metal-rich galaxies (MRGs), treating the strong emission line flux measurements as input feature vectors in n-dimensional space, where n is the number of strong emission line flux ratios. (ii) After training on a sample of star-forming galaxies, the remaining galaxies are classified in the automatic test analysis as either MPGs or MRGs using a 10-fold cross-validation technique. For target selection, we have achieved an acquisition accuracy for MPGs of ∼96 and ∼95 per cent for an MPG threshold of 12 + log(O/H) = 8.00 and 12 + log(O/H) = 8.39, respectively. Running the code takes minutes in most cases under the matlab 2013a software environment. The code in the Letter is available on the web (http://fshi5388.blog.163.com). The svm method can easily be extended to any MPGs target selection task and can be regarded as an efficient classification method particularly suitable for modern large surveys. [ABSTRACT FROM PUBLISHER]