Comparative transcriptomics in Yersinia pestis: a global view of environmental modulation of gene expression

<p>Abstract</p> <p>Background</p> <p>Environmental modulation of gene expression in <it>Yersinia pestis </it>is critical for its life style and pathogenesis. Using cDNA microarray technology, we have analyzed the global gene expression of this deadly pathogen when grown under different stress conditions <it>in vitro</it>.</p> <p>Results</p> <p>To provide us with a comprehensive view of environmental modulation of global gene expression in <it>Y. pestis</it>, we have analyzed the gene expression profiles of 25 different stress conditions. Almost all known virulence genes of <it>Y. pestis </it>were differentially regulated under multiple environmental perturbations. Clustering enabled us to functionally classify co-expressed genes, including some uncharacterized genes. Collections of operons were predicted from the microarray data, and some of these were confirmed by reverse-transcription polymerase chain reaction (RT-PCR). Several regulatory DNA motifs, probably recognized by the regulatory protein Fur, PurR, or Fnr, were predicted from the clustered genes, and a Fur binding site in the corresponding promoter regions was verified by electrophoretic mobility shift assay (EMSA).</p> <p>Conclusion</p> <p>The comparative transcriptomics analysis we present here not only benefits our understanding of the molecular determinants of pathogenesis and cellular regulatory circuits in <it>Y. pestis</it>, it also serves as a basis for integrating increasing volumes of microarray data using existing methods.</p

SPHINX: The Joint Mixing of Weights, Tasks, and Visual Embeddings for Multi-modal Large Language Models

We present SPHINX, a versatile multi-modal large language model (MLLM) with a joint mixing of model weights, tuning tasks, and visual embeddings. First, for stronger vision-language alignment, we unfreeze the large language model (LLM) during pre-training, and introduce a weight mix strategy between LLMs trained by real-world and synthetic data. By directly integrating the weights from two domains, the mixed LLM can efficiently incorporate diverse semantics with favorable robustness. Then, to enable multi-purpose capabilities, we mix a variety of tasks for joint visual instruction tuning, and design task-specific instructions to avoid inter-task conflict. In addition to the basic visual question answering, we include more challenging tasks such as region-level understanding, caption grounding, document layout detection, and human pose estimation, contributing to mutual enhancement over different scenarios. Additionally, we propose to extract comprehensive visual embeddings from various network architectures, pre-training paradigms, and information granularity, providing language models with more robust image representations. Based on our proposed joint mixing, SPHINX exhibits superior multi-modal understanding capabilities on a wide range of applications. On top of this, we further propose an efficient strategy aiming to better capture fine-grained appearances of high-resolution images. With a mixing of different scales and high-resolution sub-images, SPHINX attains exceptional visual parsing and reasoning performance on existing evaluation benchmarks. We hope our work may cast a light on the exploration of joint mixing in future MLLM research. Code is released at https://github.com/Alpha-VLLM/LLaMA2-Accessory.Comment: Work in progress. Code and demos are released at https://github.com/Alpha-VLLM/LLaMA2-Accessor

Characterization of Zur-dependent genes and direct Zur targets in Yersinia pestis

<p>Abstract</p> <p>Background</p> <p>The zinc uptake regulator Zur is a Zn²⁺-sensing metalloregulatory protein involved in the maintenance of bacterial zinc homeostasis. Up to now, regulation of zinc homeostasis by Zur is poorly understood in <it>Y. pestis</it>.</p> <p>Results</p> <p>We constructed a <it>zur </it>null mutant of <it>Y. pestis </it>biovar <it>microtus </it>strain 201. Microarray expression analysis disclosed a set of 154 Zur-dependent genes of <it>Y. pestis </it>upon exposure to zinc rich condition. Real-time reverse transcription (RT)-PCR was subsequently used to validate the microarray data. Based on the 154 Zur-dependent genes, predicted regulatory Zur motifs were used to screen for potential direct Zur targets including three putative operons <it>znuA, znuCB </it>and <it>ykgM</it>-<it>RpmJ2</it>. The LacZ reporter fusion analysis verified that Zur greatly repressed the promoter activity of the above three operons. The subsequent electrophoretic mobility shift assay (EMSA) demonstrated that a purified Zur protein was able to bind to the promoter regions of the above three operons. The DNase I footprinting was used to identify the Zur binding sites for the above three operons, verifying the Zur box sequence as predicted previously in γ-Proteobacteria. The primer extension assay was further used to determine the transcription start sites for the above three operons and to localize the -10 and -35 elements. Zur binding sites overlapped the -10 sequence of its target promoters, which was consistent with the previous observation that Zur binding would block the entry of the RNA polymerase to repress the transcription of its target genes.</p> <p>Conclusion</p> <p>Zur as a repressor directly controls the transcription of <it>znuA, znuCB </it>and <it>ykgM</it>-<it>RpmJ2 </it>in <it>Y. pestis </it>by employing a conserved mechanism of Zur-promoter DNA association as observed in γ-Proteobacteria. Zur contributes to zinc homeostasis in <it>Y. pestis </it>likely through transcriptional repression of the high-affinity zinc uptake system ZnuACB and two alternative ribosomal proteins YkgM and RpmJ2.</p

Outcomes of two types of iodine-125 seed delivery with metal stents in treating malignant biliary obstruction: a systematic review and meta-analysis

PURPOSETo conduct a meta-analysis comparing the efficacy and safety of two types of iodine-125 (I-125) seed delivery with metal stents (the study group) versus conventional metal stents (the control group) in patients with malignant biliary obstruction (MBO).METHODSOur team systematically searched the PubMed, Embase, and Cochrane Library databases for relevant studies published from January 2012 up to July 2021. Survival time and stent dysfunction were the primary measured outcomes. Subgroup analyses were conducted according to the type of I-125 seed delivery.RESULTSEleven studies, including 1057 patients in total, were pooled for stent dysfunction. The study group showed a lower risk of stent dysfunction than the control group [odds ratio (OR): 0.61, 95% confidence interval (CI) 0.46–0.81, P = 0.001]. The pooled results of six studies reporting overall survival (OS) showed that the study group had a better survival outcome than the control group [hazard ratio (HR): 0.34, 95% CI: 0.28–0.42, P 0.05). The study group was significantly superior to the control group, with better survival and decreased stent dysfunction. Meanwhile, the delivery of I-125 seeds did not increase adverse events.CONCLUSIONThe delivery of I-125 with metal stents may be considered a preferable technique for MBO

Screening and Degradation Characteristics of a Fumonisin B1-Degrading Fungal Strain

A fungal strain capable of degrading fumonisin B1 (FB1) from ground maize samples heavily contaminated with fumonisin was obtained by enrichment culture method. The strain was named as FDS-2, and was characterized for its growth and degradation characteristics, and the initial degradation pathway of FB1 by FDS-2 was investigated. The strain was identified as Exophiala spinifera according to its culture characteristics, microscopic characteristics and phylogenetic tree based on RNA-internal transcribed spacer (ITS) sequence characteristics. The optimum growth and degradation conditions were 30 ℃ and pH 5.0. Under these conditions, the strain could completely degrade 250 μg of FB1 within 48 h. Intracellular FB1-degrading enzymes were discovered in this strain. Using liquid chromatography-mass spectrometry (LC-MS) to analyze the degradation products, it was determined that the primary degradation pathway began with the degradation of FB1 into hydrolyzed FB1. This study provides a strain resource and a theoretical basis for the biodegradation of fumonisin in grain and feed

Reciprocal facilitation between annual plants and burrowing crabs:Implications for the restoration of degraded saltmarshes

Increasing evidence shows that facilitative interactions between species play an essential role in coastal wetland ecosystems. However, there is a lack of understanding of how such interactions can be used for restoration purposes in saltmarsh ecosystems. We therefore studied the mechanisms of reciprocal facilitative interactions between native annual plants, Suaeda salsa, and burrowing crabs, Helice tientsinensis, in a middle-elevation saltmarsh (with generally high plant density and moderate tides) in the Yellow River Delta of China. We investigated the relationship between the densities of the plants and crab burrows in different seasons. Then, we tested whether and how saltmarsh plants and crabs indeed facilitate each other in a series of field and laboratory experiments. Finally, we applied the results by creating a field-scale artificial approach for microtopographic modification to restore a degraded saltmarsh. We found that the density of plant seedlings in spring was positively correlated with the density of crab burrows in the previous autumn; moreover, the density of crab burrows was correlated with the density of plants in summer. The concave-convex surface microtopography created by crabs promoted seed retention and seedling establishment of saltmarsh plants in winter and spring. These plants in turn facilitated crabs by inhibiting predators, providing food and reducing physical stresses for crabs in summer and autumn. The experimental removal of saltmarsh plants decreased crab burrow density, while both transplanting and simulating plants in bare patches promoted crabs. The microtopographic modification, inspired by our new understanding of the interactions between saltmarsh plants and crabs, showed that these degraded saltmarsh ecosystems can be restored by a single ploughing intervention. Synthesis. Our results suggest a reciprocal facilitation between annual plants and burrowing crabs in a middle-elevation saltmarsh ecosystem. This knowledge yielded new restoration options for degraded coastal saltmarshes through the one-time ploughing initiation of microtopographic variation, which could promote the re-establishment of ecosystem engineers and lead to the efficient recovery of pioneer coastal vegetation and associated fauna

Manipulating Steady Heat Conduction by Sensu-shaped Thermal Metamaterials

10.1038/srep10242Scientific Reports

Involvement of Glutamate Transporter-1 in Neuroprotection against Global Brain Ischemia-Reperfusion Injury Induced by Postconditioning in Rats

Ischemic postconditioning refers to several transient reperfusion and ischemia cycles after an ischemic event and before a long duration of reperfusion. The procedure produces neuroprotective effects. The mechanisms underlying these neuroprotective effects are poorly understood. In this study, we found that most neurons in the CA1 region died after 10 minutes of ischemia and is followed by 72 hours of reperfusion. However, brain ischemic postconditioning (six cycles of 10 s/10 s reperfusion/re-occlusion) significantly reduced neuronal death. Significant up-regulation of Glutamate transporter-1 was found after 3, 6, 24, 72 hours of reperfusion. The present study showed that ischemic postconditioning decreases cell death and that upregulation of GLT-1 expression may play an important role on this effect