Top 10 Biorxiv Papers Today
Tyler B Johnson,
Jon J Brudvig,
Kimmo K Lehtimäki,
Jacob T Cain,
Katherine A White,
Jukka T Puoliväli,
Jill M Weimer
While research has accelerated the development of new treatments for pediatric neurodegenerative disorders, the ability to demonstrate the long-term efficacy of these therapies has been hindered by the lack of convincing, noninvasive methods for tracking disease progression both in animal models and in human clinical trials. Here, we unveil a new translational platform for tracking disease progression in an animal model of a pediatric neurodegenerative disorder, CLN6-Batten disease. Instead of looking at a handful of parameters or a single 'needle in a haystack', we embrace the idea that disease progression, in mice and patients alike, is a diverse phenomenon best characterized by a combination of relevant biomarkers. Thus, we employed a multi-modal quantitative approach where 144 parameters were longitudinally monitored to allow for individual variability. We use a range of noninvasive neuroimaging modalities and kinematic gait analysis, all methods that parallel those commonly used in the clinic, followed by a powerful...
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Objective: To determine hippocampal morphometric parameters, including granule cell dispersion and features of malrotation, as potential biomarkers for SUDEP from an archival post-mortem series. Methods: In a retrospective study of 187 archival post-mortems from three groups, SUDEP (68; 14 with hippocampal sclerosis (HS)), non-SUDEP epilepsy controls (EP-C =66; 25 with HS) and non-epilepsy controls (NEC= 53), Nissl/H&E stained sections from left and right hippocampus from five coronal levels were digitised. Image analysis was carried out for granule cell layer (GCL) thickness and measurements of hippocampal dimensions (HD) for shape [width (HD1), height (HD2)] and medial hippocampal positioning in relation to the parahippocampal gyrus (PHG) length (HD3). A qualitative evaluation of hippocampal malrotational (HMAL) features, dentate gyrus invaginations (DGI) and subicular/CA1 folds (SCF) was also made. Results: GCL thickness was increased in HS more than those without (p<0.001). In non-HS cases increased GCL thickness was noted in...
Hippocampal morphometry in sudden and unexpected death in epilepsy (SUDEP) https://t.co/JU8JHjzAic #bioRxiv
: [66, 3, 68, 25, 132, 132, 135, 70, 70, 119, 68, 119, 68, 125, 69, 125, 69]
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Potato late blight, caused by Phytophthora infestans , is one of the major threats affecting the quality and output of potato all over the world. Reactive oxygen species (ROS) acted as a signal molecule to transmit signals in plants at the early stage of disease infection, and it could induce disease resistance of the plant, including potato late blight. Anionic peroxidases in many plants were reported to be involved in defense to disease. However, limited information about anionic peroxidase genes is available for the potato. Here, we reported that the expression of the StPOPA , a gene encoding a suberization-associated anionic peroxidase, was associated with resistance in potato against P. infestans. The StPOPA gene was induced by P. infestans infection, mechanical damage, jasmonic acid and ethylene treatment. Overexpression of the StPOPA gene in potato enhanced the resistance against P. infestans via promoting the accumulation of callose in the cell wall and ROS in the cytoplasm, which restricted the infection and spreading of...
StPOPA, encoding an anionic peroxidase in Solanum tuberosum, enhances resistance against Phytophthora infestans https://t.co/aKUHAEH5Kn #bioRxiv
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Chris Zhiyi Zhang,
Hepatocarcinogenesis is attributed to the reprogramming of cellular metabolism as consequence of the alteration in metabolite-related gene regulation. Identifying the mechanism of aberrant metabolism is of great potential to provide novel targets for the treatment of hepatocellular carcinoma (HCC). Here, we demonstrated that glycogen synthase 2 (GYS2) restricted tumor growth in HBV-related HCC via a negative feedback loop with p53. Expression of GYS2 was significantly downregulated in HCC and correlated with decreased glycogen content and unfavorable patient outcomes. GYS2 overexpression suppressed, whereas GYS2 knockdown facilitated cell proliferation in vitro and tumor growth in vivo via modulating p53 expression. GYS2 competitively bound to MDM2 to prevent p53 from MDM2-mediated ubiquitination and degradation. Furthermore, GYS2 enhanced the p300-induced acetylation of p53 at K373/382, which in turn inhibited the transcription of GYS2 in the support of HBx/HDAC1 complex. In summary, our findings suggest that GYS2 serves as a...
A GYS2/p53 negative feedback loop restricts tumor growth in HBV-related hepatocellular carcinoma https://t.co/YUay8hgrlZ #bioRxiv
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Elevated uric acid (UA) is a key factor for disorders, including gout or kidney stones and result from abrogated expression of Urate Oxidase (Uro) and diet. To understand the genetic pathways influencing UA metabolism we established a Drosophila melanogaster model with elevated UA using Uro knockdown. Reduced Uro expression resulted in the accumulation of UA concretions and diet-dependent shortening of lifespan. Inhibition of insulin-like signaling (ILS) pathway genes reduced UA and the concretion load. In humans, SNPs in the ILS genes AKT2 and FOXO3 were associated with UA levels or gout, supporting a conserved role for ILS in modulating UA metabolism. Downstream of the ILS pathway UA pathogenicity was mediated partly by NADPH Oxidase, whose inhibition attenuated the reduced lifespan and concretion accumulation. Thus, genes in the ILS pathway represent potential therapeutic targets for treating UA associated pathologies, including gout and kidney stones.
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Monika S Mellem,
Atul R Mahableshwarkar,
William J Martin,
The Diagnostic and Statistical Manual of Mental Disorders (DSM) has been the standard for diagnosing psychiatric disorders in the United States. Yet, evidence has suggested that symptoms in psychiatric disorders are not restricted to the boundaries between DSM categories, implicating an underlying latent transdiagnostic structure of psychopathology. Here, we applied an importance-guided machine learning technique for model selection to item-level data from self-reported instruments contained within the Consortium for Neuropsychiatric Phenomics dataset. From 578 questionnaire items, we identified a set of phenotypic features which consisted of 85 items that were shared across diagnoses of schizophrenia (SCZ), bipolar disorder (BD), and attention deficit/hyperactivity disorder (ADHD). A transdiagnostic classifier trained on the shared phenotypic features reliably distinguished the patient group as a whole from healthy controls (classification AUC = 0.95) and only 10 items were needed to attain the performance level of AUC being...
Highly Predictive Transdiagnostic Features Shared across Schizophrenia, Bipolar Disorder, and ADHD Identified Using a Machine Learning Based Approach https://t.co/TcpETFeQX2 #bioRxiv
@NBDT_journal I like this one: https://t.co/ytIWB04AXi
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Christian P Rivera,
Oluwasanmi V Ariyo,
Victor O Omojola,
Manu O Platt
Children with sickle cell anemia have elevated stroke risks as well as other arterial complications, but morphological changes to large arteries are not well defined, and the focus has been on the microcirculation where deoxygenation promotes sickling of red blood cells. The goal of this study was to define morphological changes in carotid and cerebral arteries in the Townes transgenic sickle cell mouse model, and to specifically determine anatomical measurement differences in mice homozygous for β-globin S mutation (SS) compared to heterozygous (AS) littermate controls. We used a combination of live imaging with ultrasound and microcomputed tomography (micro-CT) imaging of corrosion casted vessels to quantify arterial dimensions and changes in mice 4, 12, and 24 weeks of age with or without sickle cell anemia. 12 week SS mice had significantly larger common carotid artery diameters than AS mice, and significantly larger diameters in the extracranial and intracranial portions of the internal carotid artery (ICA), determined by...
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[Background] McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop arthritis in the ankle, leading finally to ankylosis. There is no published data that drug treatment has been trialed on these mice. [Objectives] This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16-1, for the treatment of ankylosis in McH-lpr/lpr-RA1 mice. [Methods] Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16-1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines. [Results] Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the...
The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed ankylosing arthritis https://t.co/vXeb6Ixtho #bioRxiv
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Chentao Yao, Falin He, Xiao Sun, Shiang Sun, Haili Tan, Xiangdong Li, Jiwang Zhang, Xingyin Jiang
In recent years, banded leaf sheath blight in corn has become an important disease in corn that seriously affects quality and yield. This paper aims to evaluate the sensitivity of Rhizoctonia solani to thifluzamide in corn, to clarify the effect of seed coating using a thifluzamide suspension agent on safety and physiological indicators and to determine banded leaf sheath blight in corn control effectiveness in the field, thereby providing a basis for the application of thifluzamide suspension agent as a seed coating. In this study, the thifluzamide sensitivity of 102 strains of R. solani in corn in different regions of Shandong was determined using the mycelial growth rate method, and the average half-maximal effective concentration value (EC50) was 0.086±0.004 μg/mL. The sensitivity was consistent with a continuous and skewed normal distribution, and the sensitivity distribution frequency exhibited a continuous, unimodal curve, indicating that thifluzamide had strong inhibitory activity on the mycelial growth of R. solani in...
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Zika virus (ZIKV) continuous spread has affected more than 80 countries and no licenced vaccine is currently available. The Asian-lineage is the causative agent of major outbreaks across the globe and most of the current ZIKV vaccine candidates aim to provide homologous efficacy in ZIKV pre-clinical challenge models. In contrast, the African-lineage of ZIKV is mainly restricted to sylvatic transmission but not much is known about the ability of this virus to emerge from a sylvatic to human transmission. Efficacy of ZIKV vaccine in mice or macaques relies on the quantification of viraemia by RT-PCR. However, questions remain as to whether current ZIKV vaccine candidates offer lineage-transcending protection and viral clearance in key organs, such as the brain and reproductive tract. Here, we show the cross-protective capabilities of our previously reported simian adenoviral-vectored zika vaccines (ChAdOx1 ZIKV) against a heterologous African-ZIKV challenge model, in which A129 mice display a high susceptibility to ZIKV infection....
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