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The human intestinal tract is colonized by a large number of diverse microorganisms that play various important physiologic functions. In inflammatory gut diseases including celiac disease (CeD), a dysbiotic state of microbiome has been observed. Interestingly, this perturbed microbiome is normalized towards eubiosis in patients showing recovery after treatment. The treatment has been observed to increase the abundance of beneficial microbes in comparison to non-treated patients. In this study, we investigated the effect of Prevotella histicola or Prevotella melaninogenica, isolated from the duodenum of a treated CeD patient, on the induction and maintenance of oral tolerance to gliadin, a CeD associated subgroup of gluten proteins, in NOD.DQ8.ABo transgenic mice. Conventionally raised mice on a gluten free diet were orally gavaged with bacteria before and after injection with pepsin trypsin digested gliadin (PTD-gliadin). P. histicola suppressed the cellular response to gliadin, whereas P. melaninogenica failed to suppress an immune response against gliadin. Interestingly, tolerance to gliadin in NOD.DQ8.ABo mice may be associated with gut microbiota as mice gavaged with P melaninogenica harbored a different microbial diversity as compared to P. histicola treated mice. This study provides experimental evidence that gut microbes like P. histicola from treated patients can suppress the immune response against gliadin epitopes., Competing Interests: Declaration of competing interest The authors declare the following conflicts of interest: Dr. Joseph Murray, Dr. Veena Taneja, and Dr. Eric Marietta are co-inventors on patent #9005603 “PREVOTELLA HISTICOLA PREPARATIONS AND THE TREATMENT OF AUTOIMMUNE CONDITIONS.”, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ataxin-2 (Atx2) is a translational control molecule mutated in spinocerebellar ataxia type II and amyotrophic lateral sclerosis. While intrinsically disordered domains (IDRs) of Atx2 facilitate mRNP condensation into granules, how IDRs work with structured domains to enable positive and negative regulation of target mRNAs remains unclear. Using the Targets of RNA-Binding Proteins Identified by Editing technology, we identified an extensive data set of Atx2-target mRNAs in the Drosophila brain and S2 cells. Atx2 interactions with AU-rich elements in 3'UTRs appear to modulate stability/turnover of a large fraction of these target mRNAs. Further genomic and cell biological analyses of Atx2 domain deletions demonstrate that Atx2 (1) interacts closely with target mRNAs within mRNP granules, (2) contains distinct protein domains that drive or oppose RNP-granule assembly, and (3) has additional essential roles outside of mRNP granules. These findings increase the understanding of neuronal translational control mechanisms and inform strategies for Atx2-based interventions under development for neurodegenerative disease., Competing Interests: AS, JH, AK, SP, JH, AP, KA, KR, DT, DJ, BB No competing interests declared, KV Senior editor, eLife, MR Reviewing editor, eLife, (© 2021, Singh et al.)

The tassel of the maize plant is responsible for the production and dispersal of pollen for subsequent capture by the silk (stigma) and fertilization of the ovules. Both the amount and timing of pollen shed are physiological traits that impact the production of a hybrid seed. This study describes an automated end-to-end pipeline that combines deep learning and image processing approaches to extract tassel flowering patterns from time-lapse camera images of plants grown under field conditions. Inbred lines from the SAM and NAM diversity panels were grown at the Curtiss farm at Iowa State University, Ames, IA, during the summer of 2016. Using a set of around 500 pole-mounted cameras installed in the field, images of plants were captured every 10 minutes of daylight hours over a three-week period. Extracting data from imaging performed under field conditions is challenging due to variabilities in weather, illumination, and the morphological diversity of tassels. To address these issues, deep learning algorithms were used for tassel detection, classification, and segmentation. Image processing approaches were then used to crop the main spike of the tassel to track reproductive development. The results demonstrated that deep learning with well-labeled data is a powerful tool for detecting, classifying, and segmenting tassels. Our sequential workflow exhibited the following metrics: mAP for tassel detection was 0.91, F1 score obtained for tassel classification was 0.93, and accuracy of semantic segmentation in creating a binary image from the RGB tassel images was 0.95. This workflow was used to determine spatiotemporal variations in the thickness of the main spike-which serves as a proxy for anthesis progression., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Seyed Vahid Mirnezami et al.)

The problem of the efficient design of material microstructures exhibiting desired properties spans a variety of engineering and science applications. The ability to rapidly generate microstructures that exhibit user-specified property distributions can transform the iterative process of traditional microstructure-sensitive design. We reformulate the microstructure design process using a constrained generative adversarial network (GAN) model. This approach explicitly encodes invariance constraints within GANs to generate two-phase morphologies for photovoltaic applications obeying design specifications: specifically, user-defined short-circuit current density and fill factor combinations. Such invariance constraints can be represented by differentiable, deep learning-based surrogates of full physics models mapping microstructures to photovoltaic properties. Furthermore, we propose a multi-fidelity surrogate that reduces expensive label requirements by a factor of five. Our framework enables the incorporation of expensive or non-differentiable constraints for the fast generation of microstructures (in 190 ms) with user-defined properties. Such proposed physics-aware data-driven methods for inverse design problems can be used to considerably accelerate the field of microstructure-sensitive design., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aim of the Study: Hepatitis C virus (HCV) can cause a chronic liver infection which could then develop into fibrosis, cirrhosis, and hepatocellular carcinoma. Today the diagnosis of liver fibrosis also includes the use of biomarkers. The purpose of our study was to determine the ability of the fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-to-platelet ratio (APRI) to predict the severity of liver fibrosis or cirrhosis., Material and Methods: Medical records of 106 patients with HCV-related liver fibrosis were analyzed. All patients underwent clinical examination, blood tests (complete blood count, total bilirubin, etc.) and transient elastography. FIB-4 and APRI were calculated for each patient., Results: Twenty-six patients (24.52%) had F4 fibrosis, 80 patients (75.48%) had non-F4 fibrosis (F0-F3). There was a statistically significant difference ( p < 0.05) between non-F4 fibrosis patients and F4 fibrosis patients in many parameters, including APRI (F4 fibrosis patients had higher values: 2.06 ±3.22 compared to 0.68 ±0.76 of the non-F4 group; p = 0.044) and FIB-4 (F4 fibrosis patients had higher values: 4.84 ±4.14 compared to 2.29 ±2.90 of the non-F4 group; p = 0.006). Receiver operating characteristic (ROC) curve analysis for APRI and FIB-4 revealed that the area under the curve (AUC) of FIB-4 was 0.855 (CI: 0.813-0.936), while the APRI score had an AUC of 0.767 (CI: 0.79-0.932)., Conclusions: In this study, patients with severe fibrosis or cirrhosis were found to have a higher FIB-4 value than APRI in the context of chronic hepatitis C., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Clinical and Experimental Hepatology.)

Ever since the flavonoids and other antioxidants in rice were demonstrated with immense health benefits, much interest has been diverted to study the native indigenous rice landraces. In the present investigation, three pigmented rare Indian rice landraces and two non-pigmented rice varieties were analyzed for their phytoconstituents like total phenolic content (TPC), total flavonoid content (TFC), total anthocyanin content and antioxidant potential using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. The phytochemical profile was compared between seed, seedling, stem, leaf and root tissues of the different varieties. Pigmented rice cultivars demonstrated higher levels of bioactive compounds as compared to the non-pigmented cultivars exhibiting a strong correlation between the antioxidant activity of the grain and their phenolic and flavonoid content. Among the five different rice studied, black navara was found to be superior in terms of its phytochemical composition. Further, the expression levels of flavonoid genes among pigmented and non-pigmented rice was studied. Higher gene expression profiles were observed in the 8 flavonoid genes studied in pigmented rice varieties as compared to non-pigmented varieties. The colorlessness of non-pigmented rice and its lower levels of phytoconstituents correlated with the low transcript levels of flavonoid genes recorded in them. This study provides a basis for understanding the health-promoting properties of pigmented rice over non-pigmented rice at the biochemical and molecular levels., (© Association of Food Scientists & Technologists (India) 2020.)

Sugammadex, given its high affinity for amino-steroid neuromuscular blockers, offers rapid and reliable neuromuscular blockade reversal, making it a popular reversal agent. This characteristic can be very useful in pregnant women, where incomplete reversal can have poor maternal and fetal outcomes. However, its use antenatally in pregnancy is controversial given concerns for progesterone binding, a hormone that is crucial for maintenance of pregnancy. This case series presents obstetric and fetal outcomes in 25 pregnant women who received sugammadex during the antenatal period, thus highlighting the need for further research into the safety of sugammadex during pregnancy., Competing Interests: Conflicts of Interest: None., (Copyright © 2021 International Anesthesia Research Society.)

Chikungunya (CHIKV) and Dengue (DENV) viruses cause an acute febrile illness which is hard to clinically differentiate and treat since both exhibit similar symptoms. Hence, this study was aimed at identifying the expression profiles of cytokines on co-infected samples and compare with CHIKV and DENV mono-infected samples. Serum samples of 292 suspected patients during 2009-2011 were analyzed. The presence of primary (IgM)/secondary (IgG) antibodies and early NS1 Dengue antigens were confirmed by capture ELISA. Molecular diagnosis and serotypes were discriminated by RT-PCR, confirmed by sequencing. All the plasma samples were assayed for cytokine expression by BDTM cytometry bead array (CBA) and compared with independent mono-infection viral load. Among the tested samples, 82 were confirmed as Dengue positive; 52 through IgM (17.8%), and 30 through IgG (10.2%). Additionally, 186 samples were confirmed as Chikungunya, 96 through IgM (32.6%) and 92 through IgG (31.5%) ELISA, respectively. Interestingly, 19 patients were co-infection positive in which, only 6 were confirmed for CHIKV and 7 for DENV by RT-PCR. Among 8 cytokines, IL-2, IL-8, IFNα, IFN γ, and IL-12 were found to be significantly different between co-infected and CHIKV mono-infected patients and correlated with viral load. DENV viral load was correlated with cytokine expression and a significant difference in IL-2 and IL-12 was observed between DENV mono-infected and DENV and CHIKV co-infected patients. Results indicated that apart from serological and molecular confirmation, cytokines could be used as a specific biomarker for the diagnosis of DENV and CHIKV. In the future, the role of independent cytokines can be determined to understand the pathogenesis and etiology of these dreadful diseases.

β-Casomorphin-7 (BCM-7) is a heptapeptide dietary molecule derived from the digestion of the β-casein of dairy and dairy products. In this review, we have covered the extensive details about BCM and its derived peptides out of the gastrointestinal and enzymatic digestion of milk and milk products, its structure and properties, and its immunological aspects related to human health among infants and adults of both genders. We have left judgment about BCM's pros and cons to the reader by describing the details in a cyclopedic perspective. In addition, a section on the possible ways to detect BCMs from their sources using proteomics, genome-based techniques, such as PCR and aptamers, and other analytical techniques equip the reader to get an idea about the details of the diagnostics available and possible applications in future. Overall, this review will provide information to the end-users of milk and milk products to enable them to make their own decisions about BCMs., 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 Ltd. All rights reserved.)

Organopesticides (OPs) are a group of various synthetic chemicals prevalently used in agriculture and homestead plantations. OPs were originally developed to remove insects, weeds, and other pests from agricultural fields for improving crop yields. Modern pesticides including organochlorine pesticides, organophosphorus pesticides, and amido-formyl ester are closely related to our lives. Many people are exposed to various OPs during farming practice. OPs can cause adverse effects and provoke serious impacts on normal reproductive functions of humans, resulting in loss of fertility. The effects of OPs in the reproductive system include association with fluctuation in the levels of sex hormones, delayed menstrual cycle, ovarian dysfunction, alteration in ovary weight, changes of follicle growth, altered oocyte feasibility, and changed the quality of spermatogenesis. Current literature clearly states that exposure to various OPs can impair the fertility of women and cause a high risk of reproductive potential. However, investigations on OPs exposure to woman fertility remain scarce. This review highlights effects of exposure to OPs on the fertility of occupational women and mechanisms of action involved in such effects on the reproductive function of women along with their related impacts.

Protein arginine methyltransferase 3 (PRMT3) regulates protein functions by introducing asymmetric dimethylation marks at the arginine residues in proteins. However, very little is known about the interaction partners of PRMT3 and their functional outcomes. Using yeast-two hybrid screening, we identified Retinal dehydrogenase 1 (ALDH1A1) as a potential interaction partner of PRMT3 and confirmed this interaction using different methods. ALDH1A1 regulates variety of cellular processes by catalyzing the conversion of retinaldehyde to retinoic acid. By molecular docking and site-directed mutagenesis, we identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner. Our findings show that in addition to regulating protein functions by introducing methylation modifications, PRMT3 could also regulate global gene expression through protein-protein interactions.

Diabetes mellitus (DM) is a risk factor for cancer. The role of DM-induced hyperglycemic (HG) stress in blood cancer is poorly understood. Epidemiologic studies show that individuals with DM are more likely to have a higher rate of mutations in genes found in pre-leukemic hematopoietic stem and progenitor cells (pre-LHSPCs) including TET2. TET2-mutant pre-LHSPCs require additional hits to evolve into full-blown leukemia and/or an aggressive myeloproliferative neoplasm (MPN). Intrinsic mutations have been shown to cooperate with Tet2 to promote leukemic transformation. However, the extrinsic factors are poorly understood. Using a mouse model carrying Tet2 haploinsufficiency to mimic the human pre-LHSPC condition and HG stress, in the form of an Ins2Akita/+ mutation, which induces hyperglycemia and type 1 DM, we show that the compound mutant mice developed a lethal form of MPN and/or acute myeloid leukemia (AML). RNA-Seq revealed that this was due in part to upregulation of proinflammatory pathways, thereby generating a feed-forward loop, including expression of the antiapoptotic, long noncoding RNA (lncRNA) Morrbid. Loss of Morrbid in the compound mutants rescued the lethality and mitigated MPN/AML. We describe a mouse model for age-dependent MPN/AML and suggest that hyperglycemia acts as an environmental driver for myeloid neoplasms, which could be prevented by reducing expression levels of the inflammation-related lncRNA Morrbid.

Plant stress phenotyping is essential to select stress-resistant varieties and develop better stress-management strategies. Standardization of visual assessments and deployment of imaging techniques have improved the accuracy and reliability of stress assessment in comparison with unaided visual measurement. The growing capabilities of machine learning (ML) methods in conjunction with image-based phenotyping can extract new insights from curated, annotated, and high-dimensional datasets across varied crops and stresses. We propose an overarching strategy for utilizing ML techniques that methodically enables the application of plant stress phenotyping at multiple scales across different types of stresses, program goals, and environments., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Biological membranes can achieve remarkably high permeabilities, while maintaining ideal selectivities, by relying on well-defined internal nanoscale structures in the form of membrane proteins. Here, we apply such design strategies to desalination membranes. A series of polyamide desalination membranes-which were synthesized in an industrial-scale manufacturing line and varied in processing conditions but retained similar chemical compositions-show increasing water permeability and active layer thickness with constant sodium chloride selectivity. Transmission electron microscopy measurements enabled us to determine nanoscale three-dimensional polyamide density maps and predict water permeability with zero adjustable parameters. Density fluctuations are detrimental to water transport, which makes systematic control over nanoscale polyamide inhomogeneity a key route to maximizing water permeability without sacrificing salt selectivity in desalination membranes., (Copyright © 2021, American Association for the Advancement of Science.)

Sarcopenia is a commonly prevalent geriatric condition mainly characterized by progressive loss of the skeletal muscle mass that results in noticeably reduced muscle strength and quality. Most of the geriatric population above 60 years of age are overweight, leading to the accumulation of fat in the muscles resulting in abated muscle function. The increased loss of muscle mass is associated with high rates of disability, poor motility, frailty and mortality. The excessive degeneration of muscles is now also being observed in middle-aged people. Therefore, geriatrics has recently started shifting towards the identification of early stages of the disability in order to expand the life span of the patient and reduce physical dependence. Recent findings have indicated that patients with increased physical activity are also affected by sarcopenia, therefore indicating the role of nutritional supplements to enhance muscle health which in turn helps to counteract sarcopenia. Various interventions with physical training have not provided substantial improvements to this disorder, thereby highlighting the crucial role of nutritional supplementation in enhancing muscle mass and strength. Nutritional supplementation has not only been shown to enhance the positive effects of physical interventions but also have a profound impact on the gut microbiome that has come forward as a key regulator of muscle mass and function. This brief review throws light upon the efficiency of nutrients and nutraceutical supplementation by highlighting their ancillary effects in physical interventions as well as improving the gut microbiome status in sarcopenic adults, thereby giving rise to a multimodal intervention for the treatment of sarcopenia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Obesity is a growing worldwide problem that generally starts in the early years of life and affects minorities more often than Whites. Thus, there is an urgency to determine factors that can be used as targets as indicators of obesity. In this study, we attempt to generate a profile of gut and oral microbial clades predictive of disease status in African American (AA) and European American (EA) children. 16S rDNA sequencing of the gut and saliva microbial profiles were correlated with salivary amylase, socioeconomic factors (e.g., education and family income), and obesity in both ethnic populations. Gut and oral microbial diversity between AA and EA children showed significant differences in alpha-, beta-, and taxa-level diversity. While gut microbial diversity between obese and non-obese was not evident in EA children, the abundance of gut Klebsiella and Magasphaera was associated with obesity in AA children. In contrast, an abundance of oral Aggregatibacter and Eikenella in obese EA children was observed. These observations suggest an ethnicity-specific association with gut and oral microbial profiles. Socioeconomic factors influenced microbiota in obesity, which were ethnicity dependent, suggesting that specific approaches to confront obesity are required for both populations.

Protein arginine methyltransferase 5 (PRMT5) symmetrically dimethylates arginine residues in various proteins affecting diverse cellular processes such as transcriptional regulation, splicing, DNA repair, differentiation, and cell cycle. Elevated levels of PRMT5 are observed in several types of cancers and are associated with poor clinical outcomes, making PRMT5 an important diagnostic marker and/or therapeutic target for cancers. Here, using yeast two-hybrid screening, followed by immunoprecipitation and pull-down assays, we identify a previously uncharacterized protein, FAM47E, as an interaction partner of PRMT5. We report that FAM47E regulates steady-state levels of PRMT5 by affecting its stability through inhibition of its proteasomal degradation. Importantly, FAM47E enhances the chromatin association and histone methylation activity of PRMT5. The PRMT5-FAM47E interaction affects the regulation of PRMT5 target genes expression and colony-forming capacity of the cells. Taken together, we identify FAM47E as a protein regulator of PRMT5, which promotes the functions of this versatile enzyme. These findings imply that disruption of PRMT5-FAM47E interaction by small molecules might be an alternative strategy to attenuate the oncogenic function(s) of PRMT5., (© 2020 Chakrapani et al.)

Dual-focus lenses that impose simultaneous competing myopic defocus over the entire visual field produce axial hyperopic shifts in refractive error. The purpose of this study was to characterize the effects of eccentricity on the ability of myopic defocus signals to influence central refractive development in infant monkeys. From 24 to 152 days of age, rhesus monkeys were reared with binocular, dual-focus lenses that had central, zero-powered zones surrounded by alternating concentric annular power zones of +3D and zero power. Between subject groups the diameter of the central, zero-powered zone was varied from 2 mm to 8 mm in 2 mm steps (+3D/pl 2 mm, n = 6; +3D/pl 4 mm, n = 6; +3D/pl 6 mm, n = 8, or + 3D/pl 8 mm, n = 6). For the treatment lens with 2, 4, 6 and 8 mm central zones, objects at eccentricities beyond 11°, 16°, 19° and 23°, respectively, were imaged exclusively through the dual-power peripheral zones. Refractive status (retinoscopy), corneal power (keratometry) and axial dimensions (ultrasonography) were measured at two-week intervals. Comparison data were obtained from monkeys reared with binocular, single-vision +3D full-field lenses (+3D FF, n = 6) and 41 normal control monkeys reared with unrestricted vision. At the end of the rearing period, with the exception of the +3D/pl 8 mm group (median = +3.64 D), the ametropias for the other lens-reared groups (medians: FF = +4.39 D, 2 mm = +5.19 D, 4 mm = +5.59 D, 6 mm = +3.50 D) were significantly more hyperopic than that for the normal monkeys (+2.50 D). These hyperopic errors were associated with shallower vitreous chambers. The key finding was that the extent and consistency of these hyperopic ametropias varied with the eccentricity of the dual-focus zones. The results confirm that myopic defocus in the near periphery can slow axial growth, but that imposed defocus beyond about 20° from the fovea does not consistently alter central refractive development., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Seventeen chalcone analogues were synthesized from 7-methoxy-3,4-dihydronaphthalen1(2H)-one and various aromatic aldehydes under basic conditions and their therapeutic properties were studied in mouse hippocampal cell line HT-22 against neuronal cell death induced by glutamate. From this study, we selected an analogue C01 as a active compound which showed significantly high neuroprotection. This compound inhibited Ca 2+ influx and reactive oxygen species (ROS) accumulation inside cells. The glutamate-induced cell death was analyzed by flow cytometry and it showed that C01 significantly reduced apoptotic or dead cell induced by 5 mM glutamate. Western blot analysis indicates that glutamate-mediated activation of MAPKs were inhibited by compound C01 treatment. In addition, the C01enhanced Bcl-2 and decreased Bax, the anti and pro apoptotic proteins respectively. Further analysis showed that, C01 prevented the nuclear translocation of AIF (apoptosis inducing factor) and inhibited neuronal cell death. Taken together, compound C01 treatment resulted in decreased neurotoxicity induced by 5 mM of glutamate. Our finding confirmed that compound C01 has neuro-therapeutic potential against glutamate-mediated neurotoxicity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Studies in chickens suggest low intensity ambient lighting causes myopia. The purpose of this experiment was to examine the effects of low intensity ambient lighting (dim light) on normal refractive development in macaque monkeys. Seven infant rhesus monkeys were reared under dim light (room illumination level: ~55 lx) from 24 to ~310 days of age with otherwise unrestricted vision. Refractive error, corneal power, ocular axial dimensions, and choroidal thickness were measured in anesthetized animals at the onset of the experiment and periodically throughout the dim-light-rearing period, and were compared with those of normal-light-reared monkeys. We found that dim light did not produce myopia; instead, dim-light monkeys were hyperopic relative to normal-light monkeys (median refractive errors at ~155 days, OD: +3.13 D vs. +2.31 D; OS: +3.31D vs. +2.44 D; at ~310 days, OD: +2.75D vs. +1.78D, OS: +3.00D vs. +1.75D). In addition, dim-light rearing caused sustained thickening in the choroid, but it did not alter corneal power development, nor did it change the axial nature of the refractive errors. These results showed that, for rhesus monkeys and possibly other primates, low ambient lighting by itself is not necessarily myopiagenic, but might compromise the efficiency of emmetropization., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is an endocrine metabolic disorder, occurring worldwide due to aging, advancement in lifestyle by modernization. T2DM is characterized by higher levels of glucose in the blood due to unresponsive secretion of pancreatic insulin and insulin activity or altogether. T2DM is regarded as a powerful genetic susceptible disease that leads to high risk with insulin resistance and β-cell dysfunction. To manage and overcome type 2 diabetes, physical activity, diet strategies, and other therapeutic medications along with usage of antiglycemic agents are developed and attempted appropriately. In the present review, attention has been focused on the understanding of T2DM outcomes, complications with possible management strategies, and pathophysiology of T2DM. Further, a detailed note on antiglycemic agents in use and other possible drugs of choice was discussed in the light of current preventive strategies are presented in this review., (© 2019 International Union of Biochemistry and Molecular Biology, Inc.)

Background: Mucormycosis is a serious and often fatal mycotic infection caused by members of class Mucormycetes in populations with immunologic or metabolic disorders. Though several clinical manifestations are associated with mucormycetes, gastrointestinal involvement is quite rare., Case Description: We described a rare case of invasive fungal infection due to Syncephalastrum racemosum associated with gastric adenocarcinoma in a 48-year-old male patient with type II Diabetes mellitus. He presented with complaints of abdominal pain, nausea, vomiting, dyspepsia, dysphagia, loss of appetite, and weight. Histopathological examination showed broad and aseptate hyphae and culture of endoscopic biopsy tissue from pylorus and antrum yielded the fungal pathogen S. racemosum. The species was confirmed by molecular sequencing of D1/D2 region of the ribosomal DNA. The in vitro susceptibility of S. racemosum was tested by broth microdilution assay as per CLSI guidelines. The MICs suggest that the isolate was susceptible to Amphotericin B (0.25 µg/ml), Itraconazole (0.25 µg/ml) and Posaconazole (0.06 µg/ml) and showed resistance to Micafungin (>16 µg/ml). The patient was successfully treated with radical subtotal gastrectomy with lymphadenectomy and Amphotericin B antifungal therapy. There was a dilemma in concluding the pathogenicity of the isolate since; the symptoms noted were common for both gastric adenocarcinoma and mucormycosis. A review of previously reported cases on Syncephalastrum was presented in the paper with their clinical manifestations, treatment, and outcome., Conclusion: To the best of our knowledge, this is the first report from India on the gastrointestinal involvement of S. racemosum. Patients with immunocompromised status are more prone to mucormycotic infections, and any typical presentations should be carefully examined for their etiological agent, and appropriate species directed therapy would help in a better outcome.

Maize (corn) is the dominant grain grown in the world. Total maize production in 2018 equaled 1.12 billion tons. Maize is used primarily as an animal feed in the production of eggs, dairy, pork and chicken. The US produces 32% of the world's maize followed by China at 22% and Brazil at 9% ( https://apps.fas.usda.gov/psdonline/app/index.html#/app/home ). Accurate national-scale corn yield prediction critically impacts mercantile markets through providing essential information about expected production prior to harvest. Publicly available high-quality corn yield prediction can help address emergent information asymmetry problems and in doing so improve price efficiency in futures markets. We build a deep learning model to predict corn yields, specifically focusing on county-level prediction across 10 states of the Corn-Belt in the United States, and pre-harvest prediction with monthly updates from August. The results show promising predictive power relative to existing survey-based methods and set the foundation for a publicly available county yield prediction effort that complements existing public forecasts.

Premise: Maize yields have significantly increased over the past half-century owing to advances in breeding and agronomic practices. Plants have been grown in increasingly higher densities due to changes in plant architecture resulting in plants with more upright leaves, which allows more efficient light interception for photosynthesis. Natural variation for leaf angle has been identified in maize and sorghum using multiple mapping populations. However, conventional phenotyping techniques for leaf angle are low throughput and labor intensive, and therefore hinder a mechanistic understanding of how the leaf angle of individual leaves changes over time in response to the environment., Methods: High-throughput time series image data from water-deprived maize ( Zea mays subsp. mays ) and sorghum ( Sorghum bicolor ) were obtained using battery-powered time-lapse cameras. A MATLAB-based image processing framework, Leaf Angle eXtractor (LAX), was developed to extract and quantify leaf angles from images of maize and sorghum plants under drought conditions., Results: Leaf angle measurements showed differences in leaf responses to drought in maize and sorghum. Tracking leaf angle changes at intervals as short as one minute enabled distinguishing leaves that showed signs of wilting under water deprivation from other leaves on the same plant that did not show wilting during the same time period., Discussion: Automating leaf angle measurements using LAX makes it feasible to perform large-scale experiments to evaluate, understand, and exploit the spatial and temporal variations in plant response to water limitations., (© 2020 Kenchanmane Raju et al. Applications in Plant Sciences published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Gallium nitride (GaN) was epitaxially grown on nitrogen doped single layer graphene (N-SLG) substrates using chemical vapour deposition (CVD) technique. The results obtained using x-ray diffractometer (XRD) revealed the hexagonal crystal structure of GaN. Photoluminescence (PL) spectroscopy, energy dispersive x-ray (EDX) spectroscopy and x-ray photoelectron (XPS) spectroscopy revealed traces of oxygen, carbon and nitrogen occurring either as contamination or as an effect of doping during the GaN growth process. In addition, PL revealed a weak yellow luminescence peak in all the samples due to the presence of N-SLG. From the obtained results it was evident that, presence of N-SLG underneath GaN helped in improving the material properties. It was seen from the current-voltage (I-V) response that the barrier height estimated is in good agreement with the Schottky-Mott model, while the ideality factor is close to unity, emphasizing that there are no surface and interface related inhomogeneity in the samples. The photodetector fabricated with this material exhibit high device performances in terms of carrier mobility, sensitivity, responsivity and detectivity. The hall measurement values clearly portray that, the GaN thus grown possess high electron contents which was beneficial in attaining extraordinary device performance.

Staphylococcus aureus (Sa) is a serious concern due to increasing resistance to antibiotics. The bacterial dihydrofolate reductase enzyme is effectively inhibited by trimethoprim, a compound with antibacterial activity. Previously, we reported a trimethoprim derivative containing an acryloyl linker and a dihydophthalazine moiety demonstrating increased potency against S. aureus. We have expanded this series and assessed in vitro enzyme inhibition (K i ) and whole cell growth inhibition properties (MIC). Modifications were focused at a chiral carbon within the phthalazine heterocycle, as well as simultaneous modification at positions on the dihydrophthalazine. MIC values increased from 0.0626-0.5 μg/mL into the 0.5-1 μg/mL range when the edge positions were modified with either methyl or methoxy groups. Changes at the chiral carbon affected K i measurements but with little impact on MIC values. Our structural data revealed accommodation of predominantly the S-enantiomer of the inhibitors within the folate-binding pocket. Longer modifications at the chiral carbon, such as p-methylbenzyl, protrude from the pocket into solvent and result in poorer K i values, as do modifications with greater torsional freedom, such as 1-ethylpropyl. The most efficacious K i was 0.7 ± 0.3 nM, obtained with a cyclopropyl derivative containing dimethoxy modifications at the dihydrophthalazine edge. The co-crystal structure revealed an alternative placement of the phthalazine moiety into a shallow surface at the edge of the site that can accommodate either enantiomer of the inhibitor. The current design, therefore, highlights how to engineer specific placement of the inhibitor within this alternative pocket, which in turn maximizes the enzyme inhibitory properties of racemic mixtures., 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 Masson SAS. All rights reserved.)

Valvular heart disease has recently become an increasing public health concern due to the high prevalence of valve degeneration in aging populations. For patients with severely impacted aortic valves that require replacement, catheter-based bioprosthetic valve deployment offers a minimally invasive treatment option that eliminates many of the risks associated with surgical valve replacement. Although recent percutaneous device advancements have incorporated thinner, more flexible biological tissues to streamline safer deployment through catheters, the impact of such tissues in the complex, mechanically demanding, and highly dynamic valvular system remains poorly understood. The present work utilized a validated computational fluid-structure interaction approach to isolate the behavior of thinner, more compliant aortic valve tissues in a physiologically realistic system. This computational study identified and quantified significant leaflet flutter induced by the use of thinner tissues that initiated blood flow disturbances and oscillatory leaflet strains. The aortic flow and valvular dynamics associated with these thinner valvular tissues have not been previously identified and provide essential information that can significantly advance fundamental knowledge about the cardiac system and support future medical device innovation. Considering the risks associated with such observed flutter phenomena, including blood damage and accelerated leaflet deterioration, this study demonstrates the potentially serious impact of introducing thinner, more flexible tissues into the cardiac system., Competing Interests: The authors declare no competing interest.

Mastitis is a major inflammatory response of the mammary gland due to various pathogenic invasions and is a serious disease that affects the production yield and health status of cows. Astaxanthin (AST), a xanthophyll carotenoid, is a secondary metabolite synthesized by microalgae and yeasts that has been reported to suppress various inflammatory responses. However, the protective effect of AST on lipopolysaccharide (LPS)-induced mammary epithelial cells has not yet been reported. The present study results indicated that AST treatment markedly attenuated the oxidative stress markers and nitric oxide (NO) while improving the anti-oxidant enzymes in LPS exposed cells. On the other hand, LPS-exposed cells showed nuclear translocation of nuclear factor-κB (NF-κB) with the activation of inflammatory cytokines such as monocyte chemoattractant protein-1, tumor necrosis factor-α, interferon-γ, and interleukin-6 (IL-6). In addition, mRNA expression analysis revealed that the histone deacetylase (HDAC) -1, -2, -3, -6, -7 and pentraxin 3 (PTX3) expressions were increased in the LPS group. Furthermore, the activity of HDAC was increased to 2-fold with a significant reduction in the histone acetyltransferase activity in cells exposed to LPS. However, AST was able to inhibit the nuclear translocation of NF-κB with attenuated HDAC activity. Intriguingly, HDAC inhibition studies demonstrated that the cytokines such as IL-4, IL-8, granulocyte-mcrophage colony stimulating factor, C-reactive protein, IL-17A, and IL-22 were significantly suppressed which were upregulated in LPS treatment; while AST was found acting by improving the anti-inflammatory cytokine IL-10, and thioredoxin reductase levels. Collectively, these findings provide novel insights into the role of HDACs in regulating cellular processes involved in the pathogenesis of LPS-induced mastitis as well as the potential use of AST as a therapeutic in treatment for controlling disease progression., (© 2020 Wiley Periodicals, Inc.)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Premise: Trichomes are hair-like appendages extending from the plant epidermis. They serve many important biotic roles, including interference with herbivore movement. Characterizing the number, density, and distribution of trichomes can provide valuable insights on plant response to insect infestation and define the extent of plant defense capability. Automated trichome counting would speed up this research but poses several challenges, primarily because of the variability in coloration and the high occlusion of the trichomes., Methods and Results: We developed a simplified method for image processing for automated and semi-automated trichome counting. We illustrate this process using 30 leaves from 10 genotypes of soybean ( Glycine max ) differing in trichome abundance. We explored various heuristic image-processing methods including thresholding and graph-based algorithms to facilitate trichome counting. Of the two automated and two semi-automated methods for trichome counting tested and with the help of regression analysis, the semi-automated manually annotated trichome intersection curve method performed best, with an accuracy of close to 90% compared with the manually counted data., Conclusions: We address trichome counting challenges including occlusion by combining image processing with human intervention to propose a semi-automated method for trichome quantification. This provides new opportunities for the rapid and automated identification and quantification of trichomes, which has applications in a wide variety of disciplines., (© 2020 Mirnezami et al. Applications in Plant Sciences is published by Wiley Periodicals LLC on behalf of the Botanical Society of America.)

Studies of patients with acute myeloid leukemia (AML) have led to the identification of mutations that affect different cellular pathways. Some of these have been classified as preleukemic, and a stepwise evolution program whereby cells acquire additional mutations has been proposed in the development of AML. How the timing of acquisition of these mutations and their impact on transformation and the bone marrow (BM) microenvironment occurs has only recently begun to be investigated. We show that constitutive and early loss of the epigenetic regulator, TET2, when combined with constitutive activation of FLT3, results in transformation of chronic myelomonocytic leukemia-like or myeloproliferative neoplasm-like phenotype to AML, which is more pronounced in double-mutant mice relative to mice carrying mutations in single genes. Furthermore, we show that in preleukemic and leukemic mice there are alterations in the BM niche and secreted cytokines, which creates a permissive environment for the growth of mutation-bearing cells relative to normal cells., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Inhibition of anti-apoptotic proteins BCL-2 and MCL-1 to release pro-apoptotic protein BIM and reactivate cell death could potentially be an efficient strategy for the treatment of leukemia. Here, we show that a lncRNA, MORRBID, a selective transcriptional repressor of BIM, is overexpressed in human acute myeloid leukemia (AML), which is associated with poor overall survival. In both human and animal models, MORRBID hyperactivation correlates with two recurrent AML drivers, TET2 and FLT3 ITD . Mice with individual mutations of Tet2 or Flt3 ITD develop features of chronic myelomonocytic leukemia (CMML) and myeloproliferative neoplasm (MPN), respectively, and combined presence results in AML. We observe increased levels of Morrbid in murine models of CMML, MPN, and AML. Functionally, loss of Morrbid in these models induces increased expression of Bim and cell death in immature and mature myeloid cells, which results in reduced infiltration of leukemic cells in tissues and prolongs the survival of AML mice., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

We report a root system architecture (RSA) traits examination of a larger scale soybean accession set to study trait genetic diversity. Suffering from the limitation of scale, scope, and susceptibility to measurement variation, RSA traits are tedious to phenotype. Combining 35,448 SNPs with an imaging phenotyping platform, 292 accessions (replications = 14) were studied for RSA traits to decipher the genetic diversity. Based on literature search for root shape and morphology parameters, we used an ideotype-based approach to develop informative root (iRoot) categories using root traits. The RSA traits displayed genetic variability for root shape, length, number, mass, and angle. Soybean accessions clustered into eight genotype- and phenotype-based clusters and displayed similarity. Genotype-based clusters correlated with geographical origins. SNP profiles indicated that much of US origin genotypes lack genetic diversity for RSA traits, while diverse accession could infuse useful genetic variation for these traits. Shape-based clusters were created by integrating convolution neural net and Fourier transformation methods, enabling trait cataloging for breeding and research applications. The combination of genetic and phenotypic analyses in conjunction with machine learning and mathematical models provides opportunities for targeted root trait breeding efforts to maximize the beneficial genetic diversity for future genetic gains., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article. The USDA is an equal opportunity provider and employer., (Copyright © 2020 Kevin G. Falk et al.)

Background: Liver fibrosis is a frequent complication of chronic hepatitis C virus (HCV) infection. Its evaluation is very important for the prognosis of these patients. The aim of this study was to evaluate the possibility of exploiting the platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio as non-invasive predictive markers of liver fibrosis., Methods: We recruited 120 patients with chronic HCV infection. They were subjected to various clinical investigations to assess the severity of fibrosis. Transient elastography and some serological tests were performed, and the platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio were estimated., Results: Sixty-four patients had F4 fibrosis (defined by elastography) and their platelet to lymphocyte ratio (69.92 ± 26.47) was lower than in patients with non-F4 fibrosis (95.19 ± 48.15) (p = 0.001). The neutrophil to lymphocyte ratio was also estimated, but the difference between the 2 groups of patients was not significant statistically (p = 0.07)., Conclusion: The platelet to lymphocyte ratio can be used as a predictive biomarker of liver fibrosis, unlike the neutrophil to lymphocyte ratio which is not predictive of this HCV-related chronic hepatitis complication. More studies are needed to validate this hypothesis.

Glutamate-induced neurotoxicity is characterized by cellular Ca 2+ uptake, which is upstream of reactive oxygen species (ROS)-induced apoptosis signaling and MAPKs activation. In the present study, we synthesized isoliquiritigenin analogs with electron-donating and electron-withdrawing functional groups. These analogs were evaluated for neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells. Among these analogs, compound BS11 was selected as a potent neuroprotective agent. Cellular Ca 2+ concentration, ROS level, MAPKs activation and AIF translocation to the nucleus were increased upon treatment with 5 mM glutamate. In contrast, we identified that compound BS11 reduced the cellular Ca 2+ concentration and ROS level upon glutamate exposure. Western blot analysis showed that MAPK activation was decreased by treatment with compound BS11. We further identified that cotreatment of compound BS11 and glutamate inhibited translocation of AIF to the nucleus., 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 Ltd. All rights reserved.)

Competing Interests: Competing interests: None declared.

We consider inertial focusing of particles in channels with triangular cross sections. The number and the location of inertial focusing positions in isosceles triangular channels can change with varying blockage ratios ( a / H ) and Reynolds numbers ( Re ). In triangular channels, asymmetric velocity gradient induced by the sloped sidewalls leads to changes in the direction and the strength of the inertial lift forces. Therefore, varying the configuration (specifically, angle) of the triangular cross section is expected to lead to a better understanding of the nature of the inertial lift forces. We fabricated triangular microchannels with various apex angles using channel molds that were shaped by a planing process, which provides precise apex angles and sharp corners. The focusing position shift was found to be affected by the channel cross section, as expected. It was determined that the direction of the focusing position shift can be reversed depending on whether the vertex is acute or obtuse. More interestingly, corner focusing modes and splitting of the corner focusing were observed with increasing Re , which could explain the origin of the inertial focusing position changes in triangular channels. We conducted fluid dynamic simulations to create force maps under various conditions. These force maps were analyzed to identify the basins of attraction of various attractors and pinpoint focusing locations using linear stability analysis. Calculating the relative sizes of the basins of attractions and exhaustively identifying the focusing positions, which are very difficult to investigate experimentally, provided us a better understanding of trends in the focusing mechanism., (Copyright © 2020 Author(s).)

Iron-based polyanionic materials can be exploited to realize low cost, durable, and safe cathodes for both bulk and thin film sodium-ion batteries. Herein, we report pulsed laser deposited mixed phosphate Na 4 Fe 3 (PO 4 ) 2 P 2 O 7 as a positive electrode for thin film sodium-ion microbatteries. The bulk material and thin films of Na 4 Fe 3 (PO 4 ) 2 P 2 O 7 are employed by solution combustion synthesis (SCS) and the pulsed laser deposition (PLD) technique, respectively. Phase purity and the nature of the crystallinity of the thin films were confirmed by grazing incidence X-ray diffraction and transmission electron microscopy. Identification of surface roughness and morphology was obtained from atomic force microscopy and scanning electron microscopy, respectively. Emerging electrochemical properties were observed from charge-discharge profiles of the thin films, which are well comparable to bulk material properties. The Na 4 Fe 3 (PO 4 ) 2 P 2 O 7 thin film electrodes delivered a highly reversible Na + storage capacity of ∼120 mAh g -1 with an excellent stability of over 500 cycles. Electrochemical analysis results revealed that the thickness of the film affects the storage capacity., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

As new generations of thin-film semiconductors are moving toward solution-based processing, the development of printing formulations will require information pertaining to the free energies of mixing of complex mixtures. From the standpoint of in silico material design, this move necessitates the development of methods that can accurately and quickly evaluate these formulations in order to maximize processing speed and reproducibility. Here, we make use of molecular dynamics (MD) simulations, in combination with the two-phase thermodynamic (2PT) model, to explore the free energy of mixing surfaces for a series of halogenated solvents and high-boiling point solvent additives used in the development of thin-film organic semiconductors. Although the combined methods generally show good agreement with available experimental data, the computational cost to traverse the free-energy landscape is considerable. Hence, we demonstrate how a Bayesian optimization scheme, coupled with the MD and 2PT approaches, can drastically reduce the number of simulations required, in turn shrinking both the computational cost and time.

Drug resistance and damage caused to the normal cells are the drawbacks which have limited the use of the existing effective anticancer drugs. Attainment of a steady and extended release by encapsulating dual drugs into biocompatible and biodegradable vehicles is the key to enable the use of these drugs for effective inhibition of cancer. In this study, carboxymethyl chitosan (CMCS), a proficient water-soluble derivative of chitosan has been synthesized using chemical route and used for the delivery of 5-Fluorouracil and doxorubicin individually as well as in combination. Carboxymethylation occuring at -NH 2 and OH sites of chitosan, has been confirmed using FTIR. EDX and Fluorescence studies elucidate the encapsulation of 5-Fluorouracil and doxorubicin into CMCS. The capability of CMCS to release the drugs in a more sustained and prolonged manner is evident from the obtained release profiles. About 14.9 µg/ml is enough to cause 50% cell death by creating oxidative stress and effectuating DNA fragmentation. Amidst the existing reports, the uniqueness of this work lies in using this rare coalition of drugs for the suppression of breast cancer and in reducing the side effects of drugs by encapsulating them into CMCS, which is evidenced by the high hemocompatibilty of the samples.

In the present study, a novel up-converting phosphor technology-based lateral flow (UPT-LF) assay was developed as a point of care testing method for the rapid and quantitative detection of β-Hydroxybutyrate (BHB) in milk and serum samples. BHB is one of the most important serum molecular markers not only in ketosis but also for other metabolic disorders in bovines. The developed UPT-LF assay has high sensitivity compared with existing kits in the market for BHB quantification. The detection limit of UPT-BHB- LF assay, with a coefficient of variation (CV) < 10% was 0.01 mM, which is lower than the clinical diagnosis cutoff value of serum BHB (1 mM); while 0.1 mM is the standard level of BHB in milk samples. The relatively good stability and reproducibility of UPT-LF assay with CV<10% results for both serum and milk samples at various storage temperatures demonstrates the superiority of this method and therefore it could be used as a point of care method for the quantitative detection of BHB in the biological samples for veterinary applications. The claimed performance of this assay along with a shorter detection time makes it a viable point-of-care method for the quantitative detection of BHB in the biological samples of veterinary applications., Competing Interests: Declaration of competing interest The authors declare that they have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Droplet-based techniques have had a profound impact in chemistry, owing to their ability to perform rapid and massively parallel reactions in minute fluid volumes. In many applications, concentration enrichment is required to increase the speed of reactions or the sensitivity of assays; but in-droplet concentration enrichment remains challenging. Here, we interface electrokinetic concentration polarization with droplet microfluidics to accomplish in-droplet demixing. This result is significant because the concentration of any charged species in the droplet can be enriched and the approach can be readily integrated into existing droplet workflows. Further, we show that such electrokinetic enrichment is rapid, on the order of seconds, and is robust, occurring over a wide parametric space. We further demonstrate electrokinetic separation of two anionic fluorophores within the droplet. Such a capability potentiates the droplet-templated synthesis of particles with gradient composition and the development of mobility-shift assays, which rely on discrimination of multiple species tagged with a single color fluorophore. Finally, by using a calcium-binding dye as an indicator, we demonstrate in-droplet cation exchange. This demonstration of cation exchange in droplets is significant because of its broad applicability to strategies for synthesis and bioassays. These results lay the foundation for new advanced droplet techniques with transformative applications.

Objective: To determine whether the sacral anatomical interspace landmark (SAIL) technique is more accurate than the classic intercristal line (ICL) technique in pregnant patients and to assess the percentage of clinical determinations above the third lumbar vertebra., Methods: In this prospective, randomized, open-label trial, there were 110 singleton pregnant patients with gestational age greater than 37 weeks included. Selection procedure was a convenience sample of pregnant patients who presented for office visits or vaginal or cesarean delivery between March 15 and July 31, 2018, at a single-center obstetric tertiary care university hospital. Both techniques were evaluated by 2 physicians independently assessing each method. Before data collection, we hypothesized that the SAIL technique would be more accurate than the ICL technique in determining the L4-L5 interspace, and that the SAIL technique would produce more estimations below the third lumbar vertebra than the ICL technique. Therefore, the primary outcome was accuracy in identifying the L4-L5 lumbar interspace with SAIL vs ICL. The secondary outcome was difference in clinical assessments above the third lumbar vertebra. Both outcomes were measured via ultrasonography., Results: Patients were 31 ± 5 years of age (mean ± SD) and had body mass index of 31.8 ± 5.7 kg/m 2 and gestational age of 38.8 ± 1.1 weeks. A total of 110 patients were analyzed. SAIL correctly identified the L4-L5 interspace 49% of the time vs 8% using ICL ( p < 0.0001). Estimations above L3 were 1% for SAIL vs 31% for ICL ( p < 0.0001)., Conclusions: Our study shows improved accuracy in identifying intervertebral space using the SAIL technique; this may prevent direct mechanical trauma to the conus medullaris when lumbar punctures are performed in pregnancy., Clinicaltrialsgov Identifier: NCT03433612., (© 2019 American Academy of Neurology.)

The aim of the present study was to develop a linear regression model aiding to a quick scan of the most important sites for mutation of an anticancer biologic trastuzumab. The important sites identified on trastuzumab can be used to carry out site-directed mutagenesis to improve the binding affinity of the drug towards its antigen, human epidermal growth factor receptor 2 (HER2). This will lead to low dosage requirement of the drug for treating cancer patients, which in turn help to cut the cost and combat development of resistance. A quantitative structure-activity relationship (QSAR) model was built by multiple linear regressions using genetic algorithm-based feature selection (GA-MLR) method using 48 dependent variables (dissociation constant K d ) and 226 independent variables (theoretical descriptors generated using a proteometrics approach). The final QSAR model selected in the study was more on the basis of ability to predict accurately independent test data and generalization ability of the model rather than mere statistical significance of the model. With combined analysis of descriptors presented in final QSAR model and most frequent descriptors pooled from all solution models, it was demonstrated that the modeling procedure was able to bring on the factors important for antigen-antibody interactions with an example of HER2-trastuzumab interaction reported in previous experimental studies. This paper will allow the prediction of the most preferable site to mutate for improving the binding affinity of trastuzumab with HER2 and also will be helpful in selecting most preferable amino acids to substitute in the selected site for mutations. This is the novel report on proteometrics approach with autocorrelation formalism for antibody engineering, which can be extended to other antibody-antigen pairs., (© 2019 John Wiley & Sons, Ltd.)

Determining the genetic control of root system architecture (RSA) in plants via large-scale genome-wide association study (GWAS) requires high-throughput pipelines for root phenotyping. We developed Core Root Excavation using Compressed-air (CREAMD), a high-throughput pipeline for the cleaning of field-grown roots, and Core Root Feature Extraction (COFE), a semiautomated pipeline for the extraction of RSA traits from images. CREAMD-COFE was applied to diversity panels of maize ( Zea mays ) and sorghum ( Sorghum bicolor ), which consisted of 369 and 294 genotypes, respectively. Six RSA-traits were extracted from images collected from >3,300 maize roots and >1,470 sorghum roots. Single nucleotide polymorphism (SNP)-based GWAS identified 87 TAS (trait-associated SNPs) in maize, representing 77 genes and 115 TAS in sorghum. An additional 62 RSA-associated maize genes were identified via expression read depth GWAS. Among the 139 maize RSA-associated genes (or their homologs), 22 (16%) are known to affect RSA in maize or other species. In addition, 26 RSA-associated genes are coregulated with genes previously shown to affect RSA and 51 (37% of RSA-associated genes) are themselves transe-quantitative trait locus for another RSA-associated gene. Finally, the finding that RSA-associated genes from maize and sorghum included seven pairs of syntenic genes demonstrates the conservation of regulation of morphology across taxa., (© 2020 American Society of Plant Biologists. All Rights Reserved.)

Background: Root system architecture (RSA) traits are of interest for breeding selection; however, measurement of these traits is difficult, resource intensive, and results in large variability. The advent of computer vision and machine learning (ML) enabled trait extraction and measurement has renewed interest in utilizing RSA traits for genetic enhancement to develop more robust and resilient crop cultivars. We developed a mobile, low-cost, and high-resolution root phenotyping system composed of an imaging platform with computer vision and ML based segmentation approach to establish a seamless end-to-end pipeline - from obtaining large quantities of root samples through image based trait processing and analysis., Results: This high throughput phenotyping system, which has the capacity to handle hundreds to thousands of plants, integrates time series image capture coupled with automated image processing that uses optical character recognition (OCR) to identify seedlings via barcode, followed by robust segmentation integrating convolutional auto-encoder (CAE) method prior to feature extraction. The pipeline includes an updated and customized version of the Automatic Root Imaging Analysis (ARIA) root phenotyping software. Using this system, we studied diverse soybean accessions from a wide geographical distribution and report genetic variability for RSA traits, including root shape, length, number, mass, and angle., Conclusions: This system provides a high-throughput, cost effective, non-destructive methodology that delivers biologically relevant time-series data on root growth and development for phenomics, genomics, and plant breeding applications. This phenotyping platform is designed to quantify root traits and rank genotypes in a common environment thereby serving as a selection tool for use in plant breeding. Root phenotyping platforms and image based phenotyping are essential to mirror the current focus on shoot phenotyping in breeding efforts., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Bovine metabolic diseases are silent clinical conditions caused by a disturbance in normal cellular metabolic processes majorly due to the demand for nutrients, physiological stress and inflammation in lactating animals. Even though these are non-devastating diseases, conditions like mastitis and ketosis highly influence cow's lactation and fertility performance that leads to economic losses. Hence, in the present study, a combined detection including a sensitive paper-based colorimetric device for the rapid determination of somatic cells (SCC) and electrochemical detection of β-hydroxybutyrate (BHB) in the milk samples has been developed. The working range was 1 × 10 5 to 2 × 10 6 for SCC and 0.05 to 2.5 mM BHB in which the normal and extreme cases of mastitis and ketosis values exist. The detection method is based on reaction using substrate 5-Bromo-indoxyl acetate (5BIA) and enzyme (BHB dehydrogenase) for the enzymes (esterase) and substrate (BHB) present in the milk samples during mastitis and ketosis respectively. An increase in blue color development was associated with an increase in the number of SCC; likewise, the increased voltage denoted the increase concentration of BHB in the samples. The repeatability was evaluated, and the % relative standard deviation (RSD) value <8.0 (n = 12). The limit of detection (LOD) was close to that achieved by a desktop spectrophotometer. The applicability of the developed kit demonstrated good sensitivity that can be deployed for other biological samples of interest. The proposed method provides a rapid, sensitive and promising tool for the regular monitoring of cows as a point of care tests (POC) at the field level., (Copyright © 2019. Published by Elsevier B.V.)

Exosomes are endosomal-derived vesicles that play a critical role in cell-to-cell communication and are secreted in several biological fluids including serum, saliva, urine, ascites, and cerebro-spinal fluid amongst others. Exosomes are small (30-150 nm diameter) with a distinctive bilipid protein structure. They can carry and exchange various cargos between cells and are used as a non-invasive biomarker for several diseases. Exosomes are considered the best biomarkers for cancer diagnosis, owing to their unique characteristics. Here, we provide a review of the up-to-date applications of exosomes, derived from various sources, in the prognosis and diagnosis of several diseases including cancer, cardiovascular and regenerative diseases as well as, arthritis, neurological diseases, and diabetes mellitus. The role of exosomes and their applications in biomedical research and preclinical trials have also been briefly discussed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. Here we discover that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Furthermore, genetic and pharmacological inhibition of EZH2 decreases the repopulating potential of p53 mutant HSPCs. Thus, we uncover an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations.