Profiles of calreticulin and Ca2+ concentration under low temperature and salinity stress in the mud crab, Scylla paramamosain

Calreticulin (CRT) is an important molecular chaperon crucial to survival of organisms under adverse conditions. In this study, the potential roles of CRT in the mud crab, Scylla paramamosain, were investigated. Firstly, SpCRT gene expression was detected in various tissues of S. paramamosain with the highest expression found in the hepatopancreas. To evaluate potential role of SpCRT in cold adaption, sub-adult crabs were subjected to temperatures of 10, 15, 20 and 25 degrees C and the profiles of SpCRT gene were determined in the hepatopancreas, chela muscle and gills. The results showed that the expressions of SpCRT mRNA in these tissues were significantly higher for those crabs exposed to low temperatures of 10 and 15 degrees C as compared to those exposed to the higher temperatures, indicating SpCRT was involved in cold adaptation-probably through facilitating protein folding. When low temperature 10 degrees C or 15 degrees C was further combined with high and low salinity stress, the expression of SpCRT mRNA at low salinity (10 ppt) was in most cases significantly higher than that at high salinity (35 ppt), suggesting that under low temperatures, low salinity may represents a more stressful condition to the crab than high salinity. It was also shown that when crabs challenged by 10 degrees C, Ca2+ concentration increased rapidly in the hepatopancreas and an in vitro experiment further showed that the expression of SpCRT mRNA increased concurrently with added Ca2+ concentration; these results together imply that Ca2+ probably plays a major role in low temperature signaling, which induces expression of genes related to cold adaption, such as CRT

Cystic cavernous malformation of the cerebellopontine angle: Case report and literature review

<p>Abstract</p> <p>Background</p> <p>Cavernous malformations (CMs) in the cerebellopontine angle (CPA) are rare, and most of such CMs reported to date are solid and extend from the internal auditory canal into the CPA. In contrast, cystic CMs that arise in the CPA and do not involve the internal auditory canal and dura of the skull base are extremely rare.</p> <p>Case presentation</p> <p>A 50-year-old man presented with vertigo and progressive hearing loss in the right ear. MRI examination revealed a lesion in the CPA with solid and cystic components. Surgery was performed. Well-circumscribed adhesion to cranial nerves, the cerebellum, or the brain stem was noted during surgery. The lesion was totally resected. Pathological examination suggested the lesion to be a CM. At 1-year follow-up, the symptoms at presentation had resolved and no complications had occurred.</p> <p>Conclusion</p> <p>Although cystic CMs of the CPA have no established imaging features, a diagnosis of CMs may be suspected when a cystic lesion is present in the CPA and does not involve internal acoustic meatus or dura mater of the skull base. Skillful microsurgical techniques and monitoring of cranial nerves will secure good outcomes for patients with cystic CMs in the CPA.</p

Structure and Mechanism of Hormone Perception and Signal Transduction by Abscisic Acid Receptors

Ph.DDOCTOR OF PHILOSOPH

Using cell fate attractors to uncover transcriptional regulation of HL60 neutrophil differentiation

<p>Abstract</p> <p>Background</p> <p>The process of cellular differentiation is governed by complex dynamical biomolecular networks consisting of a multitude of genes and their products acting in concert to determine a particular cell fate. Thus, a systems level view is necessary for understanding how a cell coordinates this process and for developing effective therapeutic strategies to treat diseases, such as cancer, in which differentiation plays a significant role. Theoretical considerations and recent experimental evidence support the view that cell fates are high dimensional attractor states of the underlying molecular networks. The temporal behavior of the network states progressing toward different cell fate attractors has the potential to elucidate the underlying molecular mechanisms governing differentiation.</p> <p>Results</p> <p>Using the HL60 multipotent promyelocytic leukemia cell line, we performed experiments that ultimately led to two different cell fate attractors by two treatments of varying dosage and duration of the differentiation agent all-trans-retinoic acid (ATRA). The dosage and duration combinations of the two treatments were chosen by means of flow cytometric measurements of CD11b, a well-known early differentiation marker, such that they generated two intermediate populations that were poised at the apparently same stage of differentiation. However, the population of one treatment proceeded toward the terminally differentiated neutrophil attractor while that of the other treatment reverted back toward the undifferentiated promyelocytic attractor. We monitored the gene expression changes in the two populations after their respective treatments over a period of five days and identified a set of genes that diverged in their expression, a subset of which promotes neutrophil differentiation while the other represses cell cycle progression. By employing promoter based transcription factor binding site analysis, we found enrichment in the set of divergent genes, of transcription factors functionally linked to tumor progression, cell cycle, and development.</p> <p>Conclusion</p> <p>Since many of the transcription factors identified by this approach are also known to be implicated in hematopoietic differentiation and leukemia, this study points to the utility of incorporating a dynamical systems level view into a computational analysis framework for elucidating transcriptional mechanisms regulating differentiation.</p

Assessing and Enhancing Robustness of Deep Learning Models with Corruption Emulation in Digital Pathology

Deep learning in digital pathology brings intelligence and automation as substantial enhancements to pathological analysis, the gold standard of clinical diagnosis. However, multiple steps from tissue preparation to slide imaging introduce various image corruptions, making it difficult for deep neural network (DNN) models to achieve stable diagnostic results for clinical use. In order to assess and further enhance the robustness of the models, we analyze the physical causes of the full-stack corruptions throughout the pathological life-cycle and propose an Omni-Corruption Emulation (OmniCE) method to reproduce 21 types of corruptions quantified with 5-level severity. We then construct three OmniCE-corrupted benchmark datasets at both patch level and slide level and assess the robustness of popular DNNs in classification and segmentation tasks. Further, we explore to use the OmniCE-corrupted datasets as augmentation data for training and experiments to verify that the generalization ability of the models has been significantly enhanced

Neurotoxicological effects induced by up-regulation of miR-137 following triclosan exposure to zebrafish (Danio rerio).

Triclosan (TCS) is a prevalent anthropogenic contaminant in aquatic environments and its chronic exposure can lead to a series of neurotoxic effects in zebrafish. Both qRT-PCR and W-ISH identified that TCS exposure resulted in significant up-regulation of miR-137, but downregulation of its regulatory genes (bcl11aa, MAPK6 and Runx1). These target genes are mainly associated with neurodevelopment and the MAPK signaling pathway, and showed especially high expression in the brain. After overexpression or knockdown treatments by manual intervention of miR-137, a series of abnormalities were induced, such as ventricular abnormality, bent spine, yolk cyst, closure of swim sac and venous sinus hemorrhage. The most sensitive larval toxicological endpoint from intervened miR-137 expression was impairment of the central nervous system (CNS), ventricular abnormalities and notochord curvature. Microinjection of microRNA mimics or inhibitors of miR-137 both caused zebrafish malformations. The posterior lateral line neuromasts became obscured and decreased in number in intervened miR-137 groups and TCS-exposure groups. Up-regulation of miR-137 led to more severe neurotoxic effects than its down-regulation. Behavioral observations demonstrated that both TCS exposure and miR-137 over-expression led to inhibited hearing or vision sensitivity. HE staining indicated that hearing and vision abnormalities induced by long-term TCS exposure originated from CNS injury, such as reduced glial cells and loose and hollow fiber structures. The findings of this study enhance our mechanistic understanding of neurotoxicity in aquatic animals in response to TCS exposure. These observations provide theoretical guidance for development of early intervention treatments for nervous system diseases

Inulin ameliorates metabolic syndrome in high-fat diet-fed mice by regulating gut microbiota and bile acid excretion

Background: Inulin is a natural plant extract that improves metabolic syndrome by modulating the gut microbiota. Changes in the gut microbiota may affect intestinal bile acids. We suggest that inulin may improve metabolism by inducing bile acid excretion by gut microbes.Methods: Male C57/BL mice were fed either a high-fat diet (60% calories) or a regular diet for 16 weeks, with oral inulin (10% w/w). At the end of the experiment, the gene expression levels (FGF15, CD36, Srebp-1c, FASN, and ACC) in the liver and intestines, as well as the serum levels of triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, total cholesterol, and free fatty acids, were collected. The expression of FGF15 was examined using Western blot analysis. The fat distribution in the liver and groin was detected by oil red and hematoxylin and eosin staining. Simultaneously, the levels of serum inflammatory factors (alanine aminotransferase and aspartate aminotransferase) were detected to explore the side effects of inulin.Results: Inulin significantly improved glucose tolerance and insulin sensitivity, and decreased body weight and serum TG and LDL levels, in mice fed normal diet. Furthermore, inulin increased the α-diversity of the gut microbiota and increased the fecal bile acid and TG excretion in inulin-treated mice. In addition, inulin significantly reduced lipid accumulation in liver and inguinal fat, white fat weight, and hepatic steatosis. Western blot analysis showed that inulin reduced the expression of FGF15, a bile acid reabsorption protein.Conclusion: Inulin ameliorates the glucose and lipid metabolic phenotypes of mice fed a normal diet, including decreased intestinal lipid absorption, increased glucose tolerance, increased insulin sensitivity, and decreased body weight. These changes may be caused by an increase in bile acid excretion resulting from changes in the gut microbiota that affect intestinal lipid absorption

Novi VP2/VP3 rekombinantni senekavirus A izoliran u sjevernoj Kini

Senecavirus A (SVA), previously called the Seneca Valley virus, is the only member of the genus Senecavirus within the family Picornaviridae. This virus was discovered as a serendipitous finding in 2002 and named Seneca Valley virus 001 (SVV-001). SVA is an emerging pathogen that can cause vesicular lesions and epidemic transient neonatal a sharp decline in swine. In this study, an SVA strain was isolated from a pig herd in Shandong Province in China and identified as SVA-CH-SDFX-2022. The full-length genome was 7282 nucleotides (nt) in length and contained a single open reading frame (ORF), excluding the poly (A) tails of the SVA isolates. Phylogenetic analysis showed that the isolate shares its genomic organization, resembling and sharing high nucleotide identities of 90.5% to 99.6%, with other previously reported SVA isolates. The strain was proved by in vitro characterization and the results demonstrate that the virus has robust growth ability in vitro. The recombination event of the SVA-CH-SDFX-2022 isolate was found and occurred between nts 1836 and 2710, which included the region of the VP2 (partial), and VP3 (partial) genes. It shows the importance of faster vaccine development and a better understanding of virus infection and spread because of increased infection rates and huge economic losses. This novel incursion has substantial implications for the regional control of vesicular transboundary diseases, and will be available for further study of the epidemiology of porcine SVA. Our findings provide useful data for studying SVA in pigs.Senekavirus A (SVA), prije nazivan virusom doline Seneca Valley, jedini je pripadnik roda senekavirusa u porodici Picornaviridae. Virus je slučajno otkriven 2002. i nazvan virusom doline Seneca 001 (SVV-001). SVA je novi patogen koji može uzrokovati vezikularne lezije i prolaznu epidemiju novorođene prasadi s naglim gubicima u proizvodnji. U ovom je istraživanju soj SVA izoliran u populaciji svinja iz provincije Shandong u Kini i identificiran kao SVA-CHSDFX-2022. Kompletni genom izolata SVA imao je 7282 nukleotida (nt) u dužini i sadržavao je jedan otvoreni okvir za očitavanje (ORF), bez poli-A repova. Filogenetska je analiza pokazala da izolat u velikoj mjeri sadržava genomsku organizaciju i nukleotidne identitete, od 90,5 % do 99,6 %, s drugim poznatim SVA izolatima. Karakterizacija virusa je pokazala da ima veliku sposobnost rasta in vitro. Pronađena je rekombinacija izolata SVA-CH-SDFX-između nukleotida 1836 i 2710 što je uključilo regiju gena VP2 (parcijalno) i gena VP3 (parcijalno). Zbog visoke stope infektivnosti i golemih ekonomskih gubitaka važan je brži razvoj cjepiva i bolje razumijevanje zaraze. Rezultati ovog istraživanja pružaju korisne podatke za proučavanje SVA virusa, posebno s obzirom na njegovu epidemiologiju u svinja i regionalnu prekograničnu kontrolu vezikularnih bolesti