Calbindin-D28k gene expression in the developing mouse kidney

Calbindin-D28k gene expression in the developing mouse kidney. Calbindin-D28k appears in the metanephric kidney during embryogenesis. We studied the temporal appearance and spatial distribution of calbindin-D28k mRNA in the developing kidneys of 12-day fetal through 21-day postnatal mice by in situ hybridization. 35S-UTP-labeled antisense (cRNA) probe to calbindin-D28k mRNA hybridized to the ureteric buds of 12-day embryos, whereas adjacent metanephrogenic tissue was unlabeled. By embryonic day 13, Y-shaped bodies of “advancing” ureteric buds were labeled intensely. In 16-day embryos, ampullae of ureteric buds were located immediately beneath the renal capsule and labeled strongly, in contrast to metanephric tubules and S-shaped bodies. The former were unlabeled and the latter were labeled only at points of contact with the ampullae. Subsequently, the ampullae of the metanephric ureteric buds hybridized with the cRNA probe, and from the 18th embryonic to the 21st postnatal day, this labeling was intense. The cRNA probe did not hybridize with the renal vesicles, proximal tubules, or tubular segments of Henle's loop derived from nephrogenic blastema, but it did label distal nephron segments. By the 21st postnatal day, collecting ducts and ureter no longer were labeled. In conclusion, calbindin-D28k mRNA is present in the developing mouse kidney, and its distribution during nephrogenesis is identical to that of calbindin-D28k per se. Collectively, these findings show that the calbindin-D28k gene is transcribed and its message is translated by the cells of the ureteric bud during the initial stage of renal morphogenesis

Learning the Relation between Similarity Loss and Clustering Loss in Self-Supervised Learning

Self-supervised learning enables networks to learn discriminative features from massive data itself. Most state-of-the-art methods maximize the similarity between two augmentations of one image based on contrastive learning. By utilizing the consistency of two augmentations, the burden of manual annotations can be freed. Contrastive learning exploits instance-level information to learn robust features. However, the learned information is probably confined to different views of the same instance. In this paper, we attempt to leverage the similarity between two distinct images to boost representation in self-supervised learning. In contrast to instance-level information, the similarity between two distinct images may provide more useful information. Besides, we analyze the relation between similarity loss and feature-level cross-entropy loss. These two losses are essential for most deep learning methods. However, the relation between these two losses is not clear. Similarity loss helps obtain instance-level representation, while feature-level cross-entropy loss helps mine the similarity between two distinct images. We provide theoretical analyses and experiments to show that a suitable combination of these two losses can get state-of-the-art results. Code is available at https://github.com/guijiejie/ICCL.Comment: This paper is accepted by IEEE Transactions on Image Processin

Signet-ring cell lymphoma: clinicopathologic, immunohistochemical, and fluorescence in situ hybridization studies of 7 cases

Context Signet-ring cell lymphoma (SRCL) is a rare morphologic variant of non–Hodgkin lymphoma. Although it was initially reported as a rare morphologic variant of follicular lymphoma (FL), SRCL has to date been described in most types of non–Hodgkin lymphoma, mostly as single-case reports. Objective To study SRCL systematically by immunohistochemical stains and fluorescent in situ hybridization analyses. Design Seven SRCL cases were stained for CD3, CD5, CD20, PAX-5, CD10, CD21, CD23, cyclin D1, BCL2, BCL6, Ki-67, and MUM-1, and were analyzed by fluorescent in situ hybridization for BCL2, BCL6, MYC, and MALT1 rearrangements. Clinical information and patient outcome were reviewed in all patients. Results The patients were 3 women and 3 men, ranging in age from 31 to 75 years (average 60.3 years). The lesions involved lymph nodes, tonsil, parotid gland, soft tissue, and breast. There were 4 FLs, 1 diffuse large B-cell lymphoma (DLBCL), 1 DLBCL with FL, and 1 DLBCL with marginal zone lymphoma. All cases had typical signet-ring cell morphology. They were positive for CD20 and BCL-2, and had low-to-intermediate Ki-67 proliferation index (10%-40%) except in the parotid DLBCL with FL (70%). BCL-6 was detected in all but 1 FL (6/7). Fluorescent in situ hybridization detected IGH/BCL2 translocation in 1 FL, increased BCL6 copy number in another FL, BCL6 rearrangement, and increased copy number of MYC and MALT1 in the DLBCL with marginal zone lymphoma. Conclusions The FL with signet-ring cell morphology (1/5) tends to lack IGH/BCL2 translocation, and an extended immunohistochemical study is recommended for correct diagnosis and classification of SRCL

Forage Grasses and Legumes with Broad Adaptation for Southeast Asia

A wide range of forages is currently being evaluated by farmers and researchers in seven countries in Southeast Asia. Broadly-adapted species have been identified for fodder banks, grazed systems, tree cropping, erosion control and improved fallows. The most promising accessions to date are Stylosanthes guianensis CIAT 184, Brachiaria decumbens cv Basilisk, Brachiaria humidicola cv Tully and CIAT 6133, CIAT 6780, Centrosema pubescens CIAT 15160 and Andropogon gayanus cv Kent and CIAT 621. Other forages that show promise are Paspalum atratum, Arachis pintoi, and Macroptilium gracile cv. Maldonado. Local seed supply and distribution systems are needed to ensure that these species reach their potential on farms

Identification and Characterization of Three New Cytochrome P450 Genes and the Use of RNA Interference to Evaluate Their Roles in Antioxidant Defense in Apis cerana cerana Fabricius

Cytochrome P450s play critical roles in maintaining redox homeostasis and protecting organisms from the accumulation of toxic reactive oxygen species (ROS). The biochemical functions of the P450 family have essentially been associated with the metabolism of xenobiotics. Here, we sequenced and characterized three P450 genes, AccCYP314A1, AccCYP4AZ1, and AccCYP6AS5, from Apis cerana cerana Fabricius; these genes play a critical role in maintaining biodiversity. Quantitative PCR (qPCR) analysis indicated that the three genes were all predominantly expressed in the epidermis (EP), followed by the brain (BR) and midgut (MG). In addition, the highest expression levels were detected in the dark-eyed pupae and adult stages. The three genes were induced by temperature (4°C and 44°C), heavy metals (CdCl2 and HgCl2), pesticides (DDV, deltamethrin, and paraquat) and UV treatments. Furthermore, Western blot analysis indicated that the protein expression levels could be induced by some abiotic stressors, a result that complements the qPCR results. We analyzed the silencing of these three genes and found that silencing these genes enhanced the enzymatic activities of peroxidase (POD) and catalase (CAT). Additionally, we investigated the expression of other antioxidant genes and found that some were upregulated, while others were downregulated, suggesting that the upregulated genes may be involved in compensating for the silencing of AccCYP314A1, AccCYP4AZ1, and AccCYP6AS5. Our findings suggest that AccCYP314A1, AccCYP4AZ1, and AccCYP6AS5 may play very significant roles in the antioxidant defense against damage caused by ROS

Measuring multipartite entanglement via dynamic susceptibilities

Entanglement plays a central role in our understanding of quantum many body physics, and is fundamental in characterising quantum phases and quantum phase transitions. Developing protocols to detect and quantify entanglement of many-particle quantum states is thus a key challenge for present experiments. Here, we show that the quantum Fisher information, representing a witness for genuinely multipartite entanglement, becomes measurable for thermal ensembles via the dynamic susceptibility, i.e., with resources readily available in present cold atomic gas and condensed-matter experiments. This moreover establishes a fundamental connection between multipartite entanglement and many-body correlations contained in response functions, with profound implications close to quantum phase transitions. There, the quantum Fisher information becomes universal, allowing us to identify strongly entangled phase transitions with a divergent multipartiteness of entanglement. We illustrate our framework using paradigmatic quantum Ising models, and point out potential signatures in optical-lattice experiments.Comment: 5+5 pages, 3+2 figure

LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma

Multiple myeloma (MM) remains an incurable hematological malignancy. Despite tremendous advances in the treatment, about 10% of patients still have very poor outcomes with median overall survival less than 24 months. Our study aimed to underscore the critical mechanisms pertaining to the rapid disease progression and provide novel therapeutic selection for these ultra-high-risk patients. We utilized single-cell transcriptomic sequencing to dissect the characteristic bone marrow niche of patients with survival of less than two years (EM24). Notably, an enrichment of LILRB4high pre-matured plasma-cell cluster was observed in the patients in EM24 compared to patients with durable remission. This cluster exhibited aggressive proliferation and drug-resistance phenotype. High-level LILRB4 promoted MM clonogenicity and progression. Clinically, high expression of LILRB4 was correlated with poor prognosis in both newly diagnosed MM patients and relapsed/refractory MM patients. The ATAC-seq analysis identified that high chromosomal accessibility caused the elevation of LILRB4 on MM cells. CRISPR-Cas9 deletion of LILRB4 alleviated the growth of MM cells, inhibited the immunosuppressive function of MDSCs, and further rescued T cell dysfunction in MM microenvironment. The more infiltration of myeloid-derived suppressive cells (MDSCs) was observed in EM24 patients as well. Therefore, we innovatively generated a TCR-based chimeric antigen receptor (CAR) T cell, LILRB4-STAR-T. Cytotoxicity experiment demonstrated that LILRB4-STAR-T cells efficaciously eliminated tumor cells and impeded MDSCs function. In conclusion, our study elucidates that LILRB4 is an ideal biomarker and promising immunotherapy target for high-risk MM. LILRB4-STAR-T cell immunotherapy is promising against tumor cells and immunosuppressive tumor microenvironment in MM

A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss

BackgroundHearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the genetic causes are largely unknown, which is in contrast to childhood-onset hearing loss.MethodsFamily and cohort studies included exome sequencing and characterisation of the hearing phenotype. Ex vivo protein expression addressed the functional effect of a DNA variant.ResultsAn in-frame deletion of 12 nucleotides in RIPOR2 was identified as a highly penetrant cause of adult-onset progressive hearing loss that segregated as an autosomal dominant trait in 12 families from the Netherlands. Hearing loss associated with the deletion in 63 subjects displayed variable audiometric characteristics and an average (SD) age of onset of 30.6 (14.9) years (range 0-70 years). A functional effect of the RIPOR2 variant was demonstrated by aberrant localisation of the mutant RIPOR2 in the stereocilia of cochlear hair cells and failure to rescue morphological defects in RIPOR2-deficient hair cells, in contrast to the wild-type protein. Strikingly, the RIPOR2 variant is present in 18 of 22 952 individuals not selected for hearing loss in the Southeast Netherlands.ConclusionCollectively, the presented data demonstrate that an inherited form of adult-onset hearing loss is relatively common, with potentially thousands of individuals at risk in the Netherlands and beyond, which makes it an attractive target for developing a (genetic) therapy.Otorhinolaryngolog

The natural history and genotype–phenotype correlations of TMPRSS3 hearing loss:an international, multi-center, cohort analysis

TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype–phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.</p