Miracle-dz/UniFAR-FTUs huggingface dataset:
Hydrogen Sulfide Increases Production of NADPH Oxidase-Dependent Hydrogen Peroxide and Phospholipase D-Derived Phosphatidic Acid in Guard Cell Signaling1

Hydrogen sulfide (H2S) is an important gaseous signaling molecule in plants that participates in stress responses and development. l-Cys desulfhydrase 1, one of the enzymatic sources of H2S in plants, participates in abscisic acid-induced stomatal closure. We combined pharmacological and genetic approaches to elucidate the involvement of H2S in stomatal closure and the interplay between H2S and other second messengers of the guard cell signaling network, such as hydrogen peroxide (H2O2) and phospholipase D (PLD)-derived phosphatidic acid in Arabidopsis (Arabidopsis thaliana). Both NADPH oxidase isoforms, respiratory burst oxidase homolog (RBOH)D and RBOHF, were required for H2S-induced stomatal closure. In vivo imaging using the cytosolic ratiometric fluorescent biosensor roGFP2-Orp1 revealed that H2S stimulates H2O2 production in Arabidopsis guard cells. Additionally, we observed an interplay between H2S and PLD activity in the regulation of reactive oxygen species production and stomatal movement. The PLDα1 and PLDδ isoforms were required for H2S-induced stomatal closure, and most of the H2S-dependent H2O2 production required the activity of PLDα1. Finally, we showed that H2S induced increases in the PLDδ-derived phosphatidic acid levels in guard cells. Our results revealed the involvement of H2S in the signaling network that controls stomatal closure, and suggest that H2S regulates NADPH oxidase and PLD activity in guard cells.
Ladder-Style DenseNets for Semantic Segmentation of Large Natural Images

Recent progress of deep image classification models provides a large potential to improve state-of-the-art performance in related computer vision tasks. However, the transition to semantic segmentation is hampered by strict memory limitations of contemporary GPUS. The extent of feature map caching required by convolutional backprop poses significant challenges even for moderately sized PASCAL images, while requiring careful architectural considerations when the source resolution is in the megapixel range. To address these concerns, we propose a DenseNet-based ladder-style architecture which is able to deliver high modelling power with very lean representations at the original resolution. The resulting fully convolutional models have few parameters, allow training at megapixel resolution on commodity hardware and display fair semantic segmentation performance even without ImageNet pre-training. We present experiments on Cityscapes and Pascal VOC 2012 datasets and report competitive results.
Measurement of cochlear length using the ‘A' value for cochlea basal diameter: A feasibility study†

Objectives: To determine whether the cochlea basal diameter (A value) measurement can be consistently and precisely obtained from high-resolution temporal bone imaging for use in cochlear length estimation. Methods: A feasibility study at a tertiary referral center was performed using the temporal bone CTs of 40 consecutive patients. The distance from the round window to the lateral wall was measured for each cochlea by two independent reviewers, a neuroradiologist and an otolaryngologist. The interrater reliability was calculated using the intraclass correlation coefficient (ICC) and the Bland–Altman plot. Results: Forty patients (19 males, 21 females) for a total of 80 cochleae were included. Interrater reliability on the same ear had a high level of agreement by both the ICC and the Bland–Altman plot. ICCs were 0.90 (95% CI: 0.82, 0.94) for the left ear and 0.96 (95% CI: 0.92, 0.98) for the right ear. Bland–Altman plot confirmed interrater reliability with all 96% of measurements falling within the 95% limits of agreement. Conclusions: Measurement between the round window and lateral cochlear wall can be consistently and reliably obtained from high-resolution temporal bone CT scans. Thus, it is feasible to utilize this method to estimate the cochlear length of patients undergoing cochlear implantation.
Serum transforming growth factor-beta 1 levels in normoalbuminuric and normotensive patients with type 2 diabetes. Effect of metformin and rosiglitazone

OBJECTIVE: a)To determine serum Transforming Growth Factor-beta 1 (TGF-β1) levels in patients with type 2 diabetes who do not have diabetes related complications and in healthy controls, b) to evaluate the effects of metformin and rosiglitazone on TGF-β1 levels. DESIGN: In the washout period, 61 patients with Fasting Plasma Glucose levels (FPG) higher than 140 mg/dl, Postprandial Glucose (PPG) levels higher than 180 mg/dl and A1c levels exceeding 6.5% were treated with glimperide. After 4 weeks, 39 of these patients were randomised to receive either metformin or rosiglitazone for 12 weeks. Thirty healthy controls were also studied. RESULTS: There were no significant differences with regard to age, gender, body weight and BMI between patients and healthy controls. Type 2 diabetics had higher waist circumference, FPG, total cholesterol, LDL-cholesterol and triglyceride levels. Baseline TGF-β1 levels in diabetics were higher than in controls (29.84±7.04 ng/ml vs 11.37±4.06 ng/ml, p<0.001). Metformin or rosiglitazone did not significantly modify the TGF-β1 levels. In a multiple regression analysis FPG was the only variable that was significantly associated with plasma TGF-β1 levels. CONCLUSION: The elevated levels of TGF-β1 in subjects with type 2 diabetes possibly indicate a tendency for renal and endothelial damage in such patients. The association of TGF-β1 with FPG possibly links poor diabetic control to vascular damage, leading to diabetic complications. Lack of changes in the levels of TGF-β1 after therapy may reflect inadequate therapy duration.
Identification and characterisation of a cryptic Golgi complex in Naegleria gruberi

ABSTRACT Although the Golgi complex has a conserved morphology of flattened stacked cisternae in most eukaryotes, it has lost the stacked organisation in several lineages, raising the question of what range of morphologies is possible for the Golgi. In order to understand this diversity, it is necessary to characterise the Golgi in many different lineages. Here, we identify the Golgi complex in Naegleria, one of the first descriptions of an unstacked Golgi organelle in a non-parasitic eukaryote, other than fungi. We provide a comprehensive list of Golgi-associated membrane trafficking genes encoded in two species of Naegleria and show that nearly all are expressed in mouse-passaged N. fowleri cells. We then study distribution of the Golgi marker (Ng)CopB by fluorescence in Naegleria gruberi, identifying membranous structures that are disrupted by Brefeldin A treatment, consistent with Golgi localisation. Confocal and immunoelectron microscopy reveals that NgCOPB localises to tubular membranous structures. Our data identify the Golgi organelle for the first time in this major eukaryotic lineage, and provide the rare example of a tubular morphology, representing an important sampling point for the comparative understanding of Golgi organellar diversity. This article has an associated First Person interview with the first author of the paper. Highlighted Article: The first micrographic evidence of a cryptic Golgi organelle in the amoeba Naegleria gruberi is presented, revealing the Golgi in this species has a rare tubular morphology.
Calsequestrin depolymerizes when calcium is depleted in the sarcoplasmic reticulum of working muscle

Significance We show that calsequestrin, the main Ca2+ storing protein of muscle, is polymerized inside the sarcoplasmic reticulum (SR) and its mobility increases greatly upon SR depletion, indicating depolymerization. Deep depletion causes massive calsequestrin migration and radical SR remodeling, often accompanied by a surge in intra-SR free Ca2+. The changes in calsequestrin polymerization observed in aqueous solutions therefore also occur in vivo. These changes help explain some uniquely advantageous properties of the SR as a source of calcium for contractile activation. The results support untested hypotheses about additional calsequestrin roles in the control of channel gating and facilitation of calcium flux. They also provide insights on the consequences of calsequestrin mutations for functional competence and structural stability of skeletal and cardiac muscle. Calsequestrin, the only known protein with cyclical storage and supply of calcium as main role, is proposed to have other functions, which remain unproven. Voluntary movement and the heart beat require this calcium flow to be massive and fast. How does calsequestrin do it? To bind large amounts of calcium in vitro, calsequestrin must polymerize and then depolymerize to release it. Does this rule apply inside the sarcoplasmic reticulum (SR) of a working cell? We answered using fluorescently tagged calsequestrin expressed in muscles of mice. By FRAP and imaging we monitored mobility of calsequestrin as [Ca2+] in the SR--measured with a calsequestrin-fused biosensor--was lowered. We found that calsequestrin is polymerized within the SR at rest and that it depolymerized as [Ca2+] went down: fully when calcium depletion was maximal (a condition achieved with an SR calcium channel opening drug) and partially when depletion was limited (a condition imposed by fatiguing stimulation, long-lasting depolarization, or low drug concentrations). With fluorescence and electron microscopic imaging we demonstrated massive movements of calsequestrin accompanied by drastic morphological SR changes in fully depleted cells. When cells were partially depleted no remodeling was found. The present results support the proposed role of calsequestrin in termination of calcium release by conformationally inducing closure of SR channels. A channel closing switch operated by calsequestrin depolymerization will limit depletion, thereby preventing full disassembly of the polymeric calsequestrin network and catastrophic structural changes in the SR.
Temperature and parasite life-history are important modulators of the outcome of Trypanosoma rangeli–Rhodnius prolixus interactions

SUMMARY Trypanosoma rangeli is a protozoan parasite, which does not cause disease in humans, although it can produce different levels of pathogenicity to triatomines, their invertebrate hosts. We tested whether infection imposed a temperature-dependent cost on triatomine fitness using T. rangeli with different life histories. Parasites cultured only in liver infusion tryptose medium (cultured) and parasites exposed to cyclical passages through mice and triatomines (passaged) were used. We held infected insects at four temperatures between 21 and 30 °C and measured T. rangeli growth in vitro at the same temperatures in parallel. Overall, T. rangeli infection induced negative effects on insect fitness. In the case of cultured infection, parasite effects were temperature-dependent. Intermoult period, mortality rates and ecdysis success were affected in those insects exposed to lower temperatures (21 and 24 °C). For passaged-infected insects, the effects were independent of temperature, intermoult period being prolonged in all infected groups. Trypanosoma rangeli seem to be less tolerant to higher temperatures since cultured-infected insects showed a reduction in the infection rates and passaged-infected insects decreased the salivary gland infection rates in those insects submitted to 30 °C. In vitro growth of T. rangeli was consistent with these results.
Why do we think we know what we know? A metaknowledge analysis of the salt controversy.

BACKGROUND Although several public health organizations have recommended population-wide reduction in salt intake, the evidence on the population benefits remains unclear. We conducted a metaknowledge analysis of the literature on salt intake and health outcomes. METHODS We identified reports--primary studies, systematic reviews, guidelines and comments, letters or reviews--addressing the effect of sodium intake on cerebro-cardiovascular disease or mortality. We classified reports as supportive or contradictory of the hypothesis that salt reduction leads to population benefits, and constructed a network of citations connecting these reports. We tested for citation bias using an exponential random graph model. We also assessed the inclusion of primary studies in systematic reviews on the topic. RESULTS We identified 269 reports (25% primary studies, 5% systematic reviews, 4% guidelines and 66% comments, letters, or reviews) from between 1978 and 2014. Of these, 54% were supportive of the hypothesis, 33% were contradictory and 13% were inconclusive. Reports were 1.51 [95% confidence interval (CI) 1.38 to 1.65] times more likely to cite reports that drew a similar conclusion, than to cite reports drawing a different conclusion. In all, 48 primary studies were selected for inclusion across 10 systematic reviews. If any given primary study was selected by a review, the probability that a further review would also have selected it was 27.0% (95% CI 20.3% to 33.7%). CONCLUSIONS We documented a strong polarization of scientific reports on the link between sodium intake and health outcomes, and a pattern of uncertainty in systematic reviews about what should count as evidence.
Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei

The predominant secretory cargo of bloodstream form Trypanosoma brucei is variant surface glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre‐cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post‐mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of endoplasmic reticulum exit sites (ERES) in post‐mitotic cells dropped from 3.9 ± 0.6 to 2.7 ± 0.1 eight hours after blocking VSG synthesis. The secretory pathway was still functional in these stalled cells, as monitored using Cathepsin L. Rates of phospholipid and glycosylphosphatidylinositol‐anchor biosynthesis remained relatively unaffected, except for the level of sphingomyelin which increased. However, both endoplasmic reticulum and Golgi morphology became distorted, with the Golgi cisternae becoming significantly dilated, particularly at the trans‐face. Membrane accumulation in these structures is possibly caused by reduced budding of nascent vesicles due to the drastic reduction in the total amount of secretory cargo, that is, VSG. These data argue that the total flux of secretory cargo impacts upon the biogenesis and maintenance of secretory structures and organelles in T. brucei, including the ERES and Golgi.
Prevalence of NS5A resistance associated substitutions in patients with hepatitis C virus genotypes 1a and 3: Impact on current therapeutic strategies

The presence of resistance‐associated substitutions (RASs) at NS5A region might compromise the efficacy of Direct Acting Antiviral agents (DAAs). HCV resistance at NS5A region is mainly focused on patients with hepatitis C virus (HCV) genotypes 1a (G1a) and 3 (G3) with other factors of poor treatment response (ie cirrhosis, prior treatment‐exposure, or HCV‐RNA >800 000 IU/mL). Herein, we evaluated in a cohort of HCV G1a and G3 infected patients the prevalence of RASs at domain I NS5A using population‐based sequencing and the impact of RASs on the optimization of current therapeutic strategies. The RASs considered as clinically relevant were: M28A/G/T, Q30D/E/H/G/K/L/R, L31M/V/F, H58D, and Y93C/H/N/S for G1a and Y93H for G3. A total of 232 patients naïve to NS5A inhibitors were included (166 G1a, 66 G3). The overall prevalence of NS5A RASs for G1a and G3 patients was low (5.5%) or null, respectively. A high proportion of patients harbored, at least, one factor of poor response (78.9% for G1a, and 75.8% for G3). Overall, the rates of patients harboring NS5A RASs in combination with any of the other factors were low and the vast majority of patients (G1a> 94% and G3 100%) could be treated with standard treatments of 12 weeks without ribavirin. In conclusion, testing NS5A RASs in specific HCV‐infected populations (ie G1a & G3, cirrhosis, prior treatment experienced, HCV‐RNA >800 000 IU/mL) might be useful to optimize current NS5A‐based therapies avoiding ribavirin‐related toxicities, and shortening treatment duration in the majority of patients.
Management and outcomes of cochlear implantation in patients with congenital cytomegalovirus (cCMV)-related deafness

Objective: Congenital Cytomegalovirus (cCMV) is a well-defined cause for neonatal mortality and morbidity, particularly sensorineural hearing loss and other neurodevelopmental disruption. We present a retrospective study which provides an overview of the assessment and preoperative work-up for patients diagnosed with cCMV and their cochlear implant (CI) outcomes. Method: This was a retrospective case series study of all children with a confirmed diagnosis of cCMV who underwent cochlear implantation at St Thomas’ Hospital from 2003 to 2015. Data were collected on the preoperative audiology, imaging findings, and neurological assessment. CI outcomes were measured using the Speech Intelligibility Rating (SIR), Category of Auditory Performance (CAP), and Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS). Results: Eleven patients underwent cochlear implantation, 45% had severe-to-profound hearing loss, and 55% had bilateral profound hearing loss. The mean age at initial assessment was 2.1 years (median 1.7, range 0.6–7.5) and the mean age of implantation was 4.0 years (median 2.5, range 0.9–11.8). The mean length of follow-up was 4.8 years (median 2.3, range 1.5–14). Six patients had bilateral simultaneous implantation (55%), four bilateral sequential (36%), and one unilateral (9%). Nine patients had white matter changes on magnetic resonance imaging, largely in the periventricular and cortical regions. Of the 11 patients, 4 (36%) had associated neurological comorbidities and 3 (27%) had additional neurocognitive developmental delay of varying severity. The majority of patients showed improvement in auditory outcomes. No statistically significant correlation was found between age of implantation, neurocognitive, and neurological comorbidities or length of follow-up and hearing outcomes. Conclusion: While the overall outcomes were mixed, most children in our cohort were found to benefit from cochlear implantation. Our data also highlight the significant neurodevelopmental comorbidities associated with cCMV and their negative impact on CI outcomes. With the recent advances in medical treatment, this underlines the importance of multidisciplinary management of these patients.
NDR1 protein kinase promotes IL‐17‐ and TNF‐α‐mediated inflammation by competitively binding TRAF3

Interleukin 17 (IL‐17) is an important inducer of tissue inflammation and is involved in numerous autoimmune diseases. However, how its signal transduction is regulated is not well understood. Here, we report that nuclear Dbf2‐related kinase 1 (NDR1) functions as a positive regulator of IL‐17 signal transduction and IL‐17‐induced inflammation. NDR1 deficiency or knockdown inhibits the IL‐17‐induced phosphorylation of p38, ERK1/2, and p65 and the expression of chemokines and cytokines, whereas the overexpression of NDR1 promotes IL‐17‐induced signaling independent of its kinase activity. Mechanistically, NDR1 interacts with TRAF3 and prevents its binding to IL‐17R, which promotes the formation of an IL‐17R‐Act1‐TRAF6 complex and downstream signaling. Consistent with this, IL‐17‐induced inflammation is significantly reduced in NDR1‐deficient mice, and NDR1 deficiency significantly protects mice from MOG‐induced experimental autoimmune encephalomyelitis (EAE) and 2,4,6‐trinitrobenzenesulfonic acid (TNBS)‐induced colitis likely by its inhibition of IL‐17‐mediated signaling pathway. NDR1 expression is increased in the colons of ulcerative colitis (UC) patients. Taken together, these findings suggest that NDR1 is involved in the development of autoimmune diseases.
A new morphinandienone alkaloid from the stems of Fissistigma tungfangense

Abstract A new morphinandienone alkaloid, fissistigmine A (1), together with three known alkaloids (2−4), were isolated and identified from the stems of Fissistigma tungfangense. Among them, fissistigmine A (1) represents the first example of a novel naturally occurring morphinandienone alkaloid with a unique cleavage of the C-9−N-17 bond. All isolated compounds were evaluated for their anti-rheumatoid arthritis activities via examining their anti-proliferative effects on synoviocytes in vitro. Compound 1 exhibited inhibitory effect on the proliferation of synoviocytes with an IC50 value of 114.6 ± 2.2 μM.
Finite Element Modeling of Reinforced Concrete Beams Strengthened with FRP Laminates

In this paper an analysis model is presented for reinforced concrete beams externally reinforced with fiber reinforced polymer (FRP) laminates using finite elements method adopted by ANSYS. The finite element models are developed using a smeared cracking approach for concrete and three dimensional layered elements for the FRP composites. The results obtained from the ANSYS finite element analysis are compared with the experimental data for six beams with different conditions from researches (all beams are deficient shear reinforcement). The comparisons are made for load-deflection curves at mid-span; and failure load. The results from finite element analysis were calculated at the same location as the experimental test of the beams. The accuracy of the finite element models is assessed by comparison with the experimental results, which are to be in good agreement. The load-deflection curves from the finite element analysis agree well with the experimental results in the linear range, but the finite elements results are slightly stiffer than that from the experimental results. The maximum difference in ultimate loads for all cases is 7.8%.