Notes

Erratum: Ciliary extracellular vesicles are dissimilar to the actual cytosolic extracellular vesicles.
Differentiation of Crohn's disease (CD) from intestinal tuberculosis (ITB) is a big challenge to gastroenterologists because of their indistinguishable features and insensitive diagnostic tools. A non-invasive biomarker is urgently required to distinguish ITB/CD patients particularly in India, a TB endemic region, where CD frequency is increasing rapidly due to urbanization. Among the three differentially expressed miRNAs obtained from small RNA transcriptomic profiling of ileocaecal/terminal ileal tissue of ITB/CD patients (n = 3), only two down-regulated miRNAs, miR-31-5p, and miR-215-5p showed comparable data in qRT-PCR. Out of which, only miR-215-5p was detectable in the patient's plasma, but there was no significant difference in expression between ITB/CD. On the other hand, miR-375-3p, the pulmonary TB specific marker was found in higher amount in the plasma of ITB patients than CD while reverse expression was observed in the ileocaecal/terminal ileal tissues of the same patients. Next, using Bioplex pro-human cytokine 48-plex screening panel, only three chemokines, Eotaxin-1/CCL11, SDF-1α/CXCL12, and G-CSF have noted significantly different levels in the serum of ITB/CD patients. ROC analysis has revealed that compared to a single molecule, a combination of miR-375-3p + Eotaxin-1/CCL11 + SDF-1α /CXCL12 + G-CSF showed a better AUC of 0.83, 95% CI (0.69-0.96) with 100% specificity and positive predictive value while sensitivity, negative predictive value, and accuracy were 56%, 69%, and 78% respectively in distinguishing ITB from CD. This study suggests that a combination of plasma markers shows better potential in differentiating ITB from CD than a single marker and this panel of markers may be used for clinical management of ITB/CD patients.Despite the widespread use of anilines, synthetic challenges to these targets still exist. Selectivity is often an issue, when using the traditional nitration-reduction sequence or more modern approaches, including arene C-H aminations catalyzed by transition metals, photosensitizers, or electrodes. Accordingly, there is still a need for general methods to rapidly, directly access specific isomers of substituted anilines. Here, we report a simple route towards the synthesis of such motifs starting from benzyl alcohols, which are converted to anilines by the use of arylsulfonyl hydroxylamines, via an aza-Hock rearrangement. Good to excellent yields are observed. The method is applicable to various benzyl alcohol surrogates (such as ethers, esters, and halides) as well as simple alkylarenes. Functionalizations of pharmaceutically relevant structures are feasible under the reaction conditions. Over ten amination reagents can be used, which facilitates the rapid assembly of a vast set of compounds.Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Yet, the transcriptional and epigenetic regulation of YS hematopoiesis remains poorly characterized. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta-gonad-mesonephros (AGM) blood development. Loss of EZH2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMPs), while the generation of primitive erythroid cells is not affected. EZH2 activity is critical for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but subsequently dispensable. We identify a lack of Wnt signaling downregulation as the primary reason for the production of non-functional EMPs. Together, our findings demonstrate a critical and stage-specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.RNA editing is a feature of RNA maturation resulting in the formation of transcripts whose sequence differs from the genome template. Brain RNA editing may be altered in Alzheimer's disease (AD). Here, we analyzed data from 1,865 brain samples covering 9 brain regions from 1,074 unrelated subjects on a transcriptome-wide scale to identify inter-regional differences in RNA editing. We expand the list of known brain editing events by identifying 58,761 previously unreported events. We note that only a small proportion of these editing events are found at the protein level in our proteome-wide validation effort. We also identified the occurrence of editing events associated with AD dementia, neuropathological measures and longitudinal cognitive decline in SYT11, MCUR1, SOD2, ORAI2, HSDL2, PFKP, and GPRC5B. Thus, we present an extended reference set of brain RNA editing events, identify a subset that are found to be expressed at the protein level, and extend the narrative of transcriptomic perturbation in AD to RNA editing.Breast cancer analysis implies that radiologists inspect mammograms to detect suspicious breast lesions and identify mass tumors. Artificial intelligence techniques offer automatic systems for breast mass segmentation to assist radiologists in their diagnosis. With the rapid development of deep learning and its application to medical imaging challenges, UNet and its variations is one of the state-of-the-art models for medical image segmentation that showed promising performance on mammography. In this paper, we propose an architecture, called Connected-UNets, which connects two UNets using additional modified skip connections. We integrate Atrous Spatial Pyramid Pooling (ASPP) in the two standard UNets to emphasize the contextual information within the encoder-decoder network architecture. We also apply the proposed architecture on the Attention UNet (AUNet) and the Residual UNet (ResUNet). We evaluated the proposed architectures on two publically available datasets, the Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM) and INbreast, and additionally on a private dataset. Experiments were also conducted using additional synthetic data using the cycle-consistent Generative Adversarial Network (CycleGAN) model between two unpaired datasets to augment and enhance the images. Qualitative and quantitative results show that the proposed architecture can achieve better automatic mass segmentation with a high Dice score of 89.52%, 95.28%, and 95.88% and Intersection over Union (IoU) score of 80.02%, 91.03%, and 92.27%, respectively, on CBIS-DDSM, INbreast, and the private dataset.The pathway to receiving specialty care for first episode psychosis (FEP) among Black youth in the US has received little attention despite documented challenges that negatively impact engagement in care and clinical outcomes. We conducted a systematic review of US-based research, reporting findings related to the pathway experiences of Black individuals with FEP and their family members. AZD0095 molecular weight A systematic search of PubMed, PsycInfo, and Embase/Medline was performed with no date restrictions up to April 2021. Included studies had samples with at least 75% Black individuals and/or their family members or explicitly examined racial differences. Of the 80 abstracts screened, 28 peer-reviewed articles met the inclusion criteria. Studies were categorized into three categories premordid and prodromal phase, help-seeking experiences, and the duration of untreated psychosis (DUP). Compounding factors such as trauma, substance use, and structural barriers that occur during the premorbid and prodromal contribute to delays in treatment initiation and highlight the limited use of services for traumatic childhood experiences (e.g., sexual abuse). Studies focused on help-seeking experiences demonstrated the limited use of mental health services and the potentially traumatic entry to services (e.g., law enforcement), which is associated with a longer DUP. Although the majority of studies focused on help-seeking experiences and predictors of DUP, findings suggests that for Black populations, there is a link between trauma and substance use in the pathway to care that impacts the severity of symptoms, initiation of treatment, and DUP. The present review also identifies the need for more representative studies of Black individuals with FEP.Intestinal surface changes in size and function, but what propels these alterations and what are their metabolic consequences is unknown. Here we report that the food amount is a positive determinant of the gut surface area contributing to an increased absorptive function, reversible by reducing daily food. While several upregulated intestinal energetic pathways are dispensable, the intestinal PPARα is instead necessary for the genetic and environment overeating-induced increase of the gut absorptive capacity. In presence of dietary lipids, intestinal PPARα knock-out or its pharmacological antagonism suppress intestinal crypt expansion and shorten villi in mice and in human intestinal biopsies, diminishing the postprandial triglyceride transport and nutrient uptake. Intestinal PPARα ablation limits systemic lipid absorption and restricts lipid droplet expansion and PLIN2 levels, critical for droplet formation. This improves the lipid metabolism, and reduces body adiposity and liver steatosis, suggesting an alternative target for treating obesity.Organic semiconducting polymers have opened a new paradigm for soft electronics due to their intrinsic flexibility and solution processibility. However, the contradiction between the mechanical stretchability and electronic performances restricts the implementation of high-mobility polymers with rigid molecular backbone in deformable devices. Here, we report the realization of high mobility and stretchability on curvilinear polymer microstructures fabricated by capillary-gradient assembly method. Curvilinear polymer microstructure arrays are fabricated with highly ordered molecular packing, controllable pattern, and wafer-scale homogeneity, leading to hole mobilities of 4.3 and 2.6 cm2 V-1 s-1 under zero and 100% strain, respectively. Fully stretchable field-effect transistors and logic circuits can be integrated in solution process. Long-range homogeneity is demonstrated with the narrow distribution of height, width, mobility, on-off ratio and threshold voltage across a four-inch wafer. This solution-assembly method provides a platform for wafer-scale and reproducible integration of high-performance soft electronic devices and circuits based on organic semiconductors.Steviol glycosides are the intensely sweet components of extracts from Stevia rebaudiana. These molecules comprise an invariant steviol aglycone decorated with variable glycans and could widely serve as a low-calorie sweetener. However, the most desirable steviol glycosides Reb D and Reb M, devoid of unpleasant aftertaste, are naturally produced only in trace amounts due to low levels of specific β (1-2) glucosylation in Stevia. Here, we report the biochemical and structural characterization of OsUGT91C1, a glycosyltransferase from Oryza sativa, which is efficient at catalyzing β (1-2) glucosylation. The enzyme's ability to bind steviol glycoside substrate in three modes underlies its flexibility to catalyze β (1-2) glucosylation in two distinct orientations as well as β (1-6) glucosylation. Guided by the structural insights, we engineer this enzyme to enhance the desirable β (1-2) glucosylation, eliminate β (1-6) glucosylation, and obtain a promising catalyst for the industrial production of naturally rare but palatable steviol glycosides.
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