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31142666

Introduction and Dispersal of Sindbis Virus from Central Africa to Europe.

Bird-hosted viruses have the potential to be transported over large areas of the world and to be transmitted in distant geographical regions. Sindbis virus (SINV) is a mosquito-borne alphavirus that is locally amplified in a bird-mosquito enzootic cycle and distributed all over the Old World and Australia/Oceania. Sindbis virus genotype I (SINV-I) is the cause of disease outbreaks in humans in South Africa as well as in northern Europe. To trace the evolutionary history and potential strain-disease association of SINV-I, we sequenced plete genomes isolated from field material in Europe, as well as in Africa and the Middle East, collected over 58 years. These were analyzed together with 30 additional published whole SINV-I genomes using Bayesian analysis. Our results suggested that SINV-I was introduced only once to northern Europe from central Africa, in the 1920s. After its first introduction to Sweden, it spread east and southward on two separate occasions in the 1960s and 1970s. Another introduction from central Africa to southern/central Europe seems to have occurred, and where these two introductions meet, one bination event was detected in central Europe. In addition, another binant strain was found in central Africa, where the most divergent SINV-I strains also originated.

31142668

Herpes Simplex Virus 1 Can Enter Dynamin 1 and 2 Double-Knockout Fibroblasts.

Dynamin GTPases, best known for their role in membrane fission of endocytic vesicles, provide a target for viruses to be exploited during endocytic uptake. Recently, we found that entry of herpes simplex virus 1 (HSV-1) into skin cells depends on dynamin, although our results supported that viral internalization occurs via both direct fusion with the plasma membrane and via endocytic pathways. To further explore the role of dynamin for efficient HSV-1 entry, we utilized conditional dynamin 1 and dynamin 2 double-knockout (DKO) fibroblasts as an experimental tool. Strikingly, HSV-1 entered control and DKO fibroblasts parable efficiencies. parison, we infected DKO cells with Semliki Forest virus, which is known to adopt clathrin-mediated endocytosis as its internalization pathway, and observed efficient virus entry. These results support the notion that the DKO cells provide alternative pathways for viral uptake. Treatment of cells with the dynamin inhibitor dynasore confirmed that HSV-1 entry depended on dynamin in the control fibroblasts. As expected, dynasore did not interfere with viral entry into DKO cells. Electron microscopy of HSV-1-infected cells suggests viral entry after fusion with the plasma membrane and by endocytosis in both dynamin-expressing and dynamin-deficient cells. Infection at low temperatures where endocytosis is blocked still resulted in HSV-1 entry, although at a reduced level, which suggests that nonendocytic pathways contribute to successful entry. Overall, our results strengthen the impact of dynamin for HSV-1 entry, as only cells that adapt to the lack of dynamin allow dynamin-independent entry.

31142669

Structural Basis for Cooperative Binding of EBNA1 to the Epstein-Barr Virus Dyad Symmetry Minimal Origin of Replication.

Epstein-Barr virus is associated with several human malignancies, including nasopharyngeal carcinoma, gastric cancer, and lymphoma. Latently infected cells carry a circularized EBV episome where the origin of replication (

31142670

Kaposi Sarcoma-Associated Herpesvirus Glycoprotein H Is Indispensable for Infection of Epithelial, Endothelial, and Fibroblast Cell Types.

Kaposi a-associated herpesvirus (KSHV) is an emerging pathogen and is the causative infectious agent of Kaposi a and two malignancies of B cell origin. To date, there is no licensed KSHV vaccine. Development of an effective vaccine against KSHV continues to be limited by a poor understanding of how the virus initiates acute primary infection

31142672

The Absence of Lymphotoxin-α, a Herpesvirus Entry Mediator (HVEM) Ligand, Affects Herpes Simplex Virus 1 Infection

Previously, we reported that the absence of herpesvirus entry mediator (HVEM) decreases latency but not primary infection in ocularly infected mice. Recently, we reported that similar to the absence of HVEM, the absence of HVEM ligands (i.e., LIGHT, CD160, and B and T lymphocyte attenuator [BTLA]) also decreased latency but not primary infection. Similar to LIGHT, CD160, and BTLA, another member of tumor necrosis factor (TNF) superfamily, lymphotoxin-α (LTα), also interacts with HVEM. To determine whether LTα decreases latency in infected mice, we ocularly infected LTα

31142671

Cytomegalovirus Evades TRAIL-Mediated Innate Lymphoid Cell 1 Defenses.

Cytomegalovirus (CMV) establishes a lifelong infection facilitated, in part, by circumventing immune defenses mediated by tumor necrosis factor (TNF)-family cytokines. An example of this is the mouse CMV (MCMV) m166 protein, which restricts expression of the TNF-related apoptosis-inducing ligand (TRAIL) death receptors, promoting early-phase replication. We show here that replication of an MCMV mutant lacking m166 is also severely attenuated during viral persistence in the salivary glands (SG). Depleting group I innate lymphoid cells (ILCs) or infecting

31142673

Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G

BK polyomavirus (BKPyV) is a small DNA virus that establishes a life-long persistent infection in the urinary tract of most people. BKPyV is known to cause severe morbidity in renal transplant recipients and can lead to graft rejection. The simple 5.2-kbp double-stranded DNA (dsDNA) genome expresses just seven known proteins; thus, it relies heavily on the host machinery to replicate. How the host proteome changes over the course of infection is key to understanding this host-virus interplay. Here, for the first time quantitative temporal viromics has been used to quantify global changes in >9,000 host proteins in two types of primary human epithelial cells throughout 72 h of BKPyV infection. These data demonstrate the importance of cell cycle progression and pseudo-G

31142675

Sustained correction of associative learning deficits after brief, early treatment in a rat model of Fragile X Syndrome.

Fragile X Syndrome (FXS) is one of the mon monogenic forms of autism and intellectual disability. Preclinical studies in animal models have highlighted the potential of pharmaceutical intervention strategies for alleviating the symptoms of FXS. However, whether treatment strategies can be tailored to developmental time windows that define the emergence of particular phenotypes is unknown. Similarly, whether a brief, early intervention can have long-lasting beneficial effects, even after treatment cessation, is also unknown. To address these questions, we first examined the developmental profile for the acquisition of associative learning in a rat model of FXS. Associative memory was tested using a range of behavioral paradigms that rely on an animal's innate tendency to explore novelty.

31142674

A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication.

Viral proteins must intimately interact with the host cell machinery during virus replication. Here, we used the yeast

31142676

Depicting brighter possibilities for treating blindness.

Advances in preclinical research are now being translated into innovative clinical solutions for blindness.

31142677

Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using magnetic resonance imaging.

Myocardial oxygenation-the ability of blood vessels to supply the heart muscle (myocardium) with oxygen-is a critical determinant of cardiac function. Impairment of myocardial oxygenation is a defining feature of ischemic heart disease (IHD), which is caused by pathological conditions that affect the blood vessels supplying oxygen to the heart muscle. Detecting altered myocardial oxygenation can help guide interventions and prevent acute life-threatening events such as heart attacks (myocardial infarction); however, current diagnosis of IHD relies on surrogate metrics and exogenous contrast agents for which many patients are contraindicated. An oxygenation-sensitive cardiac magnetic resonance imaging (CMR) approach used previously to demonstrate that CMR signals can be sensitized to changes in myocardial oxygenation showed limited ability to detect small changes in signals in the heart because of physiologic and imaging noise during data acquisition. Here, we demonstrate a CMR-based approach termed cfMRI [cardiac functional magnetic resonance imaging (MRI)] that detects myocardial oxygenation. cfMRI uses carbon dioxide for repeat interrogation of the functional capacity of the heart's blood vessels via a fast MRI approach suitable for clinical adoption without limitations of key confounders (cardiac/respiratory motion and heart rate changes). This method integrates multiple whole-heart images within putational framework to reduce noise, producing confidence maps of alterations in myocardial oxygenation. cfMRI permits noninvasive monitoring of myocardial oxygenation without requiring ionizing radiation, contrast agents, or needles. This has the potential to broaden our ability to noninvasively identify IHD and a diverse spectrum of heart diseases related to myocardial ischemia.

31142678

Safe targeting of T cell acute lymphoblastic leukemia by pathology-specific NOTCH inhibition.

Given the high frequency of activating

31142679

Reprogrammed marrow adipocytes contribute to myeloma-induced bone disease.

Osteolytic lesions in multiple myeloma are caused by osteoclast-mediated bone resorption and reduced bone formation. A unique feature of myeloma is a failure of bone healing after successful treatment. We observed adipocytes on trabecular bone near the resorbed area in successfully treated patients. Normal marrow adipocytes, when cocultured with myeloma cells, were reprogrammed and produced adipokines that activate osteoclastogenesis and suppress osteoblastogenesis. These adipocytes have reduced expression of peroxisome proliferator-activated receptor γ (PPARγ) mediated by recruitment of b plex 2 (PRC2), which modifies

31142680

Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge.

Nipah virus is an emerging pathogen in the

31142681

Effects of feeding management on disease incidence and blood metabolites in dairy herds in Iwate Prefecture, Japan.

The objective of the present study was to identify the effect of feeding management on disease incidence and blood metabolite levels in dairy herds in Iwate Prefecture, Japan. A generalized linear model approach was used to identify the risk factors for ketosis and displaced abomasum (DA) in dairy herds (n=30), and metabolic profile test (MPT) results pared to verify the involvement of the factors. Consequently, the proportion of corn silage (CS) with ≥30% of dry matter (DM) fed to cows during the lactation period was confirmed as the most reliable risk factor for ketosis, while no risk factor was identified for DA. Meanwhile, the incidence rates of ketosis and DA were significantly (P<0.05) higher in the herds that were fed CS (n=20) than in those fed a non-CS diet (n=10). When the MPT results of the herds fed with CS containing ≥30% of DM (HCS group, n=4; 76 cows), with CS containing <30% of DM (LCS group, n=14; 285 cows), and a non-CS diet (NCS group, n=12; 236 cows) pared, the HCS group showed higher beta-hydroxybutyric and lower blood urea nitrogen concentrations for until 49 days after parturition. Overall, feeding cows with CS diets containing over 30% of DM might increase their risk of developing negative energy and protein balances, thereby resulting in increasing incidences of ketosis in the Iwate Prefecture.

31142682

Detection of human epidermal growth factor receptor 2 overexpression in canine anal sac gland carcinoma.

Canine anal sac gland carcinoma (ASGC) frequently occurs in the apocrine glands of the canine anal sac and shows aggressive biological behavior. The expression of human epidermal growth factor receptor 2 (HER2) has been reported in various human and canine tumors. HER2 is a promising therapeutic target of these tumors, and HER2-targeted drugs, such as trastuzumab and lapatinib, have improved the e of these patients. In this study, HER2 expression in ASGC was evaluated to investigate its potential as a therapeutic target for canine ASGC. HER2 mRNA expression in surgically resected ASGC tissues was significantly higher than that in normal anal sac tissue. To evaluate the expression of HER2 protein, paraffin-embedded ASGC tissues were immunohistochemically evaluated. Strong and broad staining of HER2 was detected in ASGC tissues, while HER2 was weakly to moderately stained in normal anal sac apocrine glands and squamous epithelia. The degree of HER2 expression in ASGC tissues was scored based on its intensity and positivity (score: 0-3+). Scoring of HER2 expression revealed 6 samples (24%) scored 3+, 14 (56%) scored 2+, and 5 (20%) scored 1+, with no samples scoring 0. In all, 80% of canine ASGC tissues were positive for HER2 (scored ≥2+). Furthermore, putative HER2-overexpressed cells in ASGC were detected with trastuzumab by flow cytometry. These preliminary data may lead to further evaluation of the role of HER2 in canine ASGC as a mechanism of malignancy and as a therapeutic target for HER2-targeted therapy.

31142683

Wall thickness and mucous cell distribution in the rabbit large intestine.

To achieve a better understanding of rabbit large intestinal functions, such as production of hard and soft feces and cecal fermentation, knowledge of the intestinal wall structure is essential. However, such knowledge is far plete. Therefore, the aims of this study were to measure the thickness of the wall and its constituent layers and describe distribution of mucous cells in each segment of the large intestine in New Zealand White rabbits. Results showed that the cecum had the thinnest entire wall throughout the large intestine, and the fusus coli and rectum had a thicker entire wall parison to the cecum, the first segment of the proximal colon, the second segment of the proximal colon, and the distal colon. Moreover, the thickness of the mucosa in the fusus coli and that of the inner and outer layers of the tunica muscularis in the rectum were greater than that of the other segments. Mucous cells in the mucosa were the fewest in the cecum and most numerous in the fusus coli. This study provides detailed knowledge of the wall thickness and distribution of mucous cells in the large intestine of the rabbit. These findings are important for improving our understanding of rabbit intestinal physiology and pathology.

31142684

Slc:Hartley guinea pigs frequently possess duplication of the caudal vena cava.

The formation of the caudal vena cava is plex process involving development, regression, and anastomosis. In mammals, the normal caudal vena cava runs to the right side of the abdominal aorta, while duplication of the caudal vena cava has been identified as a congenital abnormality in panion animals and humans. The present study demonstrates that Slc:Hartley guinea pigs frequently possess asymptomatic duplicated caudal vena cava. The prevalence was 30% and 24% for males and females, respectively, with no sex-related differences. In accordance with Saad et al. (2012)'s criteria, duplicated caudal vena cava were classified into two distinct variations. The dominant variation was plete duplication without iliac anastomosis where the left caudal vena cava continued from the mon iliac vein and joined the left renal vein; the left renal vein ran to the right to join the right caudal vena cava. The alternative variation was an plete duplication where the left caudal vena cava joined the right infrarenal caudal vena cava at a more cranial point than in normal cases; the renal segment was unchanged. Iliac anastomosis was not found in any cases. Duplicated caudal vena cava neither affected the body weight nor the kidney weight. In conclusion, Slc:Hartley guinea pigs frequently possess asymptomatic duplicated caudal vena cava in the absence of iliac anastomosis and appear to be a novel and useful animal model for duplicated caudal vena cava in animals and humans.

31142685

Sex Differences in Clinical Characteristics and Outcomes of Patients With Venous Thromboembolism　- From the COMMAND VTE Registry.

It remains controversial whether sex category is a risk for recurrent venous thromboembolism (VTE) and major bleeding among VTE patients.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive acute symptomatic VTE patients from 29 centers in Japan between January 2010 and August 2014. pared the clinical characteristics and es of men and women. Men accounted for 1,169 (39%) and women 1,858 (61%). Compared with women, men were younger (64.9±14.7 vs. 68.6±15.6 years old, P<0.001), more often had prior VTE (7.2% vs. 5.1%, P=0.02), and less often had transient risk factors for VTE (30% vs. 40%, P<0.001). The proportions of active cancer and pulmonary embolism parable between men and women (24% vs. 22%, P=0.26; 56% vs. 57%, P=0.48, respectively). The cumulative 3-year incidences of recurrent VTE, major bleeding, and all-cause death were not significantly different between men and women (7.0% vs. 8.6%, P=0.47; 10.6% vs. 9.2%, P=0.25; 25.2% vs. 23.4%, P=0.35, respectively). The adjusted risks of men relative to women for recurrent VTE and for major bleeding remained insignificant (HR 0.83, 95% CI 0.63-1.09, P=0.17; HR 1.15, 95% CI 0.90-1.47, P=0.25, respectively).

31142689

Usefulness of relative fat mass in estimating body adiposity in Korean adult population.

Various indicators have been suggested as replacements of body mass index (BMI) for estimating body fat percentage, including the recently introduced relative fat mass (RFM). However, RFM has not been assessed in different ethnicities; therefore, we evaluated whether RFM can be used to estimate body fat percentage in Korean adults and whether RFM is a useful indicator of obesity. Based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011, we analyzed a total of 18,706 individuals (7,970 men, 10,643 women) aged ≥20 years who underwent dual-energy X-ray absorptiometry. pared obesity (body fat ≥25% for men, 35% for women) misclassification rate of RFM (≥25 for men, 35 for women) and BMI (≥25 kg/m

31142688

Basal glucagon hypersecretion and response to oral glucose load in prediabetes and mild type 2 diabetes.

Dysregulation of glucagon secretion plays an important role in the pathogenesis of type 2 diabetes (T2DM). However it hasn't been elucidated involvement of glucagon dysregulation in pathophysiology of T2DM. Recently a new glucagon sandwich enzyme-linked immunosorbent assay (ELISA) became available that can measure plasma glucagon level with higher accuracy and simpler procedure than the conventional RIA method. We performed OGTT for adult subjects aged 20-69 years to define normal glucose tolerance (NGT, n = 25), borderline glucose intolerance (defined as pre-diabetes mellitus: preDM, n = 15), or diabetes mellitus (DM, n = 13), and we measured glucagon levels with this new ELISA method at fasting and during OGTT. Plasma glucose, insulin, glucagon and active GLP-1 were also measured. This study took place in diabetes outpatient clinic in Kitasato University Hospital and an affiliated outpatient clinic. PreDM and DM exhibited higher fasting plasma glucagon levels than NGT (34.4 ± 4.6 and 44.1 ± 5.0 vs. 20.6 ± 3.6 pg/mL), and statistical significance was observed between NGT and DM (p < 0.05). There was significant correlation between fasting glucagon level and indexes of insulin sensitivity. During OGTT, glucagon levels were less suppressed in DM and preDM than in NGT, whereas no apparent relationship was observed between glucagon and GLP-1 secretion. Significant positive correlation was observed between glucagon levels during OGTT and fasting TG. In conclusion, subjects with mild T2DM exhibited fasting hyperglucagonemia and insufficient suppression to oral glucose pared to NGT subjects.

31142691

Combined Treatment with Triptolide and Tyrosine Kinase Inhibitors Synergistically Enhances Apoptosis in Non-small Cell Lung Cancer H1975 Cells but Not H1299 Cells through EGFR/Akt Pathway.

Lung cancer is one of the mon malignant cancers in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a second- or third-line therapy for mutated non-small cell lung cancer (NSCLC). It usually es drug resistance after a period of treatment. Triptolide (TPL) is an epoxy diterpenoid pound extracted from Tripterygium wilfordii HOOK. F. and many studies demonstrated that TPL has a synergistic effect bined with chemotherapy drugs. In this research, we plan to evaluate bined effect of TPL and EGFR-TKIs (Gefitinib, Erlotinib, and Icotinib) and investigate the possible mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to detect the cell bined effect was evaluated by Combination Index. Molecular docking study was used to predict the binding ability of TPL. The expression of proteins was detected by Western blot. MTT results showed TPL had synergistic effect with three EGFR-TKIs at different concentrations on H1975 cells but not on H1299 cells. Molecular docking study demonstrated that TPL with T790M/L858R EGFR can form a more pound than that with wild type EGFR. Western blot results showed TPL inhibited the EGFR/Akt pathway and increased the expression of Bax and the ratio of Bax and Bcl-2 in H1975 cells. In conclusion, TPL had synergistic effect with three EGFR-TKIs on H1975 cells but not on H1299 cells, which may be due to the binding ability of TPL and different-type EGFR. The synergistic effect of TPL on H1975 cells may be partly related to the inhibition of the EGFR/Akt pathway.

31142690

DNA Methylation Analysis Identifies Differentially Methylated Sites Associated with Early-Onset Intracranial Atherosclerotic Stenosis.

Studies have suggested that genetic and environmental factors do not account for all risks and mechanisms of intracranial atherosclerotic stenosis (ICAS). DNA methylation may play a role in the progression of ICAS.

31142693

Intrahepatic Cholestasis of Pregnancy as a Clinical Manifestation of Sodium-Taurocholate Cotransporting Polypeptide Deficiency.

Intrahepatic cholestasis of pregnancy (ICP) is the mon pregnancy-related liver disorder. Although the etiology of ICP is not fully understood thus far, some genetic factors might contribute to the development of this condition. Sodium-taurocholate cotransporting polypeptide (NTCP), the protein encoded by the gene Solute Carrier Family 10, Member 1 (SLC10A1), is the primary transporter expressed in the basolateral membrane of the hepatocyte to uptake conjugated bile salts from the plasma. NTCP deficiency arises from biallelic SLC10A1 mutations which impair the NTCP function and cause intractably elevated levels of total bile acids (TBA) in the plasma (hypercholanemia). In this study, all the SLC10A1 exons and their flanking sequences were analyzed by Sanger sequencing to investigate the etiology for hypercholanemia in two male infants aged 2 and 20 months, respectively, from two unrelated families. As a result, both patients are homozygous for the reported pathogenic variant c.800C>T (p.Ser267Phe) that could impair the NTCP function to uptake bile acids, and the diagnosis of NTCP deficiency was thus made. Their mothers are also homozygotes of the same variant and both had been diagnosed to have ICP in the third trimester, with one of them undergoing cesarean section. The father of the first patient in this paper has the same SLC10A1 genotype c.800C>T/c.800C>T, also exhibiting slight hypercholanemia with a plasma TBA level of 21.5 μmol/L. In conclusion, we suggest that with hypercholanemia being mon laboratory change, NTCP deficiency may be a genetic factor leading to ICP and even cesarean section in clinical practice.

31142692

Lenvatinib-induced thyroid abnormalities in unresectable hepatocellular carcinoma.

Lenvatinib has anti-tumor activity against advanced hepatocellular carcinoma (HCC). Hypothyroidism is also a plication in patients treated with lenvatinib. However, studies on lenvatinib-induced thyroid toxicity and destructive thyroiditis are limited. Therefore, this study aimed to clarify the frequency and timing of thyroid abnormalities in lenvatinib for unresectable HCC. This retrospective study enrolled 50 patients with advanced HCC treated with lenvatinib. Patients were classified to have euthyroid, subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis. The timing of thyroid dysfunction was assessed, and risk factors for incident hypothyroidism or thyrotoxicosis were evaluated using multivariate models. Subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis occurred in 7 (14.0%), 26 (52.0%), and 5 (10.0%) patients, respectively. In the 33 patients with hypothyroidism, 27 (84.4%) developed the condition within 2 weeks of starting lenvatinib treatment. Of the 5 patients with thyrotoxicosis, 3 developed the condition within 8 weeks of starting lenvatinib administration. One patient developed thyrotoxicosis in only 1 week of the initiation of treatment. No correlation between the presence of antibodies and the incidence and severity of thyroid dysfunction due to the autoimmune mechanism was observed. The progression-free survival was significantly better in the hypothyroidism group. Lenvatinib treatment for unresectable HCC not only causes hypothyroidism, but also thyrotoxicosis. Moreover, these thyroid conditions develop within the early period of treatment at a higher prevalence. Patients with thyroid dysfunction had better prognosis. Based on these results, in patients administered with lenvatinib, there is need for careful assessment for the possibility of thyroid dysfunction from the onset of treatment.

31142694

Identification of feline Kiss1 and distribution of immunoreactive kisspeptin in the hypothalamus of the domestic cat.

In recent years, the Kiss1 gene has been reported in a number of vertebrate species, and a substantial dataset has been acquired to demonstrate the critical role of kisspeptins in the reproductive system; yet limited information is available for carnivores. In the present study, we identified and characterized feline Kiss1 by isolating and cloning its full-length cDNA in the domestic cat hypothalamus and caracal testis, using the method of rapid amplification of cDNA ends. Additionally, we isolated and cloned the 3' end of Kiss1 cDNA, containing kisspeptin-10 (Kp10), from the ovaries of a clouded leopard and Siberian tiger. Nucleotide sequencing revealed that domestic cat Kiss1 cDNA is of 711 base pairs and caracal Kiss1 cDNA is of 792 base pairs, both having an open reading frame of 450 base pairs, encoding a precursor protein Kiss1 of 149 amino acids. The core sequence of the feline kisspeptin Kp10 was found to be identical in all species analyzed here and is highly conserved in other vertebrate species. Using an anti-Kp10 antibody, we found the immunoreactive kisspeptin to be localized in the periventricular and infundibular nuclei of the cat hypothalamus. The results show that kisspeptin is highly conserved among different feline families, and its immunoreactive distribution in the hypothalamus may indicate its physiological function in the domestic cat.

31142701

Qiliqiangxin Attenuates Oxidative Stress-Induced Mitochondrion-Dependent Apoptosis in Cardiomyocytes via PI3K/AKT/GSK3β Signaling Pathway.

Qiliqiangxin capsule (QLQX) is a well-known traditional Chinese medicine that exhibits cardioprotective effects in heart failure patients. However, it remains unclear whether and by which mechanism QLQX attenuates oxidative stress-induced mitochondria-dependent myocardial apoptosis. In vivo, Sprague Dawley (SD) rats received left anterior descending coronary artery ligation for 4 weeks to establish a model of heart failure after acute myocardial infarction, and then were treated with QLQX for another 4 weeks. We evaluated cardiac function, oxidative stress injury, as well as the expressions of mitochondria-dependent apoptosis and its signaling factors. The results indicated that QLQX protected cardiac function and attenuated oxidative stress-induced myocardial apoptosis. Meanwhile, QLQX elevated the Bcl-2 expression, declined the expressions of Bax, cytochrome c, apoptotic protease activating factor-1 (Apaf-1), cleaved-caspase 9 and cleaved-caspase 3, and up-regulated the ratios of phospho-AKT/AKT and phospho-glycogen synthase kinase-3β (GSK3β)/GSK3β. In vitro, H9c2 cardiomyocytes were pretreated with QLQX, then exposed to H

31142702

Conserved amino acids around the DIII-DI linker region of the Newcastle disease virus fusion protein are critical for protein folding and fusion activity.

Newcastle disease virus (NDV), an avian paramyxovirus, causes Newcastle disease (ND) which is a highly contagious and fatal viral disease affecting poultry and most species of birds. The fusion (F) protein of NDV mediates membrane fusion, which is essential to the processes of viral entry, replication, and dissemination. Although several domains of NDV F are known to have important effects on regulating the membrane fusion activity, the role of the region around domain III (DIII) and domain I (DI) still remains ill-defined. Site-directed mutagenesis was utilized to change the conserved amino acids at 269, 274, 277, 286, 287, 290, 295, and 297 to alanine in order to investigate the effects of these conserved amino acids around the DIII and DI linker region of the NDV F protein on fusion activity. It was found that five of these substitutions almost abolished fusion activity except for mutants I269A, Q286A, and N297A, which showed 57.1%, 161.1%, and 97.7% of the wt F level, respectively. Four (I274A, D277A, V287A, and P290A) of these five mutants likely result in interfering with folding or transporting of the molecule since these proteins were minimally expressed at the cell surface, formed aggregates, or not proteolytically cleaved. However, mutant L295A almost abolished fusion activity even with a similar level of cell surface expression. These data indicated that conserved amino acids around the DIII-DI linker region are critical for the folding of the F protein and have an important influence on fusion activity.

31142703

Comparison of Silent Navigator Waveform Generation Methods.

The silent navigator technique utilizes a non-selective excitation and an appropriate respiratory waveform generation method is necessary for an accurate motion detection. pared three methods for silent navigator waveform generation. The profile generation method with coil selection (prof-selection) resulted in a high cross correlation with bellows signals and a large respiration amplitude. The prof-selection method should be used for silent navigator waveform generation.

31142704

Combination of Peak Exercise Systolic Blood Pressure and Left Atrial Diameter as a Novel Non-Spirometry Prognostic Predictor Comparable to Peak Oxygen Uptake for Heart Failure With Reduced Ejection Fraction.

Although peak oxygen uptake (pV̇O

31142706

[Recurrent ataxia and respiratory failure with probable paraneoplastic syndrome responsive to plasma exchange therapy].

An 80-year-old male with prostatic adenocarcinoma who was treated with orchiectomy presented dysarthria and difficulty in walking. His symptoms subacutely progressed. Seven days later, he was non-ambulatory and was admitted to our hospital. He had poor vision and cerebellar ataxia of the lower extremities; however, his muscle strength, tendon reflexes, and sensory functions were preserved. Paraneoplastic retinopathy was diagnosed based on electroretinographic and visual field defect. Further, brain and spinal MRI, cerebral spinal fluid, and nerve conduction assessments were normal. These symptoms were followed by consciousness disturbance and respiratory failure; consequently, he required non-invasive positive pressure ventilation (NPPV) and tube feeding. Steroid pulse therapy and plasma exchange (PE) were performed. In response to the therapy, all these symptoms were relieved, and NPPV and tube feeding were withdrawn. However, the same symptoms occurred additional three times throughout the course of approximately 1 year. Each time, PE was the most effective treatment. Although paraneoplastic neurological syndrome associated with prostatic cancer is rare, immunotherapy could be a therapeutic choice to relive symptoms.

31142708

[Current status and future prospect of enzyme replacement therapy for Fabry disease].

Fabry disease is characterized by deficient activity of α-galactosidase A, which results in accumulation of glycolipids, such as globotriaosylceremide, in various tissue. Clinical symptoms are varied. In childhood, pain in extremities, hypohidrosis, and angiokeratoma are main symptoms, In adulthood, renal, cardiac and cerebrovascular symptoms are occurred In past, only symptomatic treatments were available. In early 2000th, enzyme replacement therapy was developed after positive results of clinical trials. Ten years after approval, the data of long term safety and efficacy of enzyme replacement.

31142709

[Acute sensory neuropathy associated with Hodgkin's lymphoma: a case study].

The case of a 17-year-old man with Hodgkin's lymphoma who presented with paraneoplastic sensory neuropathy is presented. The patient visited our hospital because of acute progression of dysesthesiae in the bilateral face and extremities. He also developed an ataxic gait due to decreased deep sensation. Post-contrast T

31142707

[A case of Miller Fisher syndrome with a false-positive edrophonium test].

A 69-year-old woman presented with acute bilateral ptosis, ophthalmoplegia, ataxia, and hyporeflexia in the extremities following an antecedent upper respiratory infection. We suspected that she had Miller Fisher syndrome (MFS) and performed an edrophonium test (ET) to rule out myasthenia gravis (MG). Edrophonium chloride improved the patient's bilateral ptosis, but not her ophthalmoplegia. Given the absence of the waning phenomenon on electrophysiological examination, the anti-acetylcholine receptor antibody, and a diurnal variation of symptoms, we concluded that the ET result was a false-positive. A diagnosis of MFS was confirmed by the presence of a positive anti-GQ1b antibody. To our knowledge, this is the first case report of MFS with a false-positive ET.

31142710

[A case of angioedema with dysarthria mimicking transient ischemic attack].

An 85-year-old woman was transported to our emergency room by ambulance with plaint of slurred speech. Neurological examination revealed dysarthria only. We considered that lingual edema identified on physical examination might have influenced dysarthria. However, we were unable to perform sufficient evaluation, since she could not open her mouth widely or push the tongue out beyond the lips. We considered the incidence of acute cerebrovascular disease because of the acute onset, and performed emergency brain MRI. Imaging revealed that although no abnormality was present in the brain parenchyma, edema of the tongue and soft palate was evident on T

31142711

[An autopsy case of nivolumab-induced myasthenia gravis and myositis].

An 84-year-old woman developed blepharoptosis, diplopia, weakness of extremities, and dysphagia with elevation of serum CK levels after treatment with nivolumab against renal cell carcinoma. 3 Hz repetitive stimulation showed waning in the trapezius muscle, leading to the diagnosis of myasthenia gravis. Laboratory examination showed that anti-acetylcholine receptor antibody was negative. We performed IVIg and steroid therapy. However, her symptoms did not improve, and she died of respiratory failure, although serum CK levels ameliorated to the normal range. The results of autopsy showed atrophy of muscle fibers and massive infiltration of inflammatory cells in the endomysium of the iliopsoas muscle and diaphragm, indicating occurrence of myositis. Immunohistochemical analysis showed that CD8-positive T cells mainly infiltrates in the endomysium with a small number of CD4-potive T cells. Here, we report an autopsy case of nivolumab-induced myasthenia gravis and myositis.

31142712

[A case of secondary central nervous system lymphoma presenting marked hypoglycorrhachia].

A 67-year-old male was transferred to our hospital with diplopia, decreased deep tendon reflex and ataxia. He had been suspected Fisher syndrome because of previous upper respiratory tract infection. A cerebrospinal fluid examination showed marked hypoglycorrhachia, pleocytosis and elevated protein, and cytological examination suggested malignant lymphoma. puted tomography revealed a left adrenal mass. A biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. He was treated with bination of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin and prednisolone) and intrathecal administration of methotrexate, cytarabine and prednisolone. Neurological symptoms were gradually improved. Malignancy should be considered in addition to bacterial, fungal or tuberculous meningitis in a case with marked hypoglycorrhachia.