Miracle-dz/UniFAR-FTUs huggingface dataset:
The Arabidopsis Chloroplast Division Protein DYNAMIN-RELATED PROTEIN5B Also Mediates Peroxisome Division[W]

Peroxisomes are highly dynamic organelles. This work shows that the plant-specific dynamin-related protein DRP5B, which was previously identified as a chloroplast division protein, is also involved in peroxisome division. DRP5B interacts with several other components of the peroxisome division machinery, suggesting that it acts cooperatively with these factors. Peroxisomes are highly dynamic organelles involved in various metabolic pathways. The division of peroxisomes is regulated by factors such as the PEROXIN11 (PEX11) proteins that promote peroxisome elongation and the dynamin-related proteins (DRPs) and FISSION1 (FIS1) proteins that function together to mediate organelle fission. In Arabidopsis thaliana, DRP3A/DRP3B and FIS1A (BIGYIN)/FIS1B are two pairs of homologous proteins known to function in both peroxisomal and mitochondrial division. Here, we report that DRP5B, a DRP distantly related to the DRP3s and originally identified as a chloroplast division protein, also contributes to peroxisome division. DRP5B localizes to both peroxisomes and chloroplasts. Mutations in the DRP5B gene lead to peroxisome division defects and compromised peroxisome functions. Using coimmunoprecipitation and bimolecular fluorescence complementation assays, we further demonstrate that DRP5B can interact or form a complex with itself and with DRP3A, DRP3B, FIS1A, and most of the Arabidopsis PEX11 isoforms. Our data suggest that, in contrast with DRP3A and DRP3B, whose orthologs exist across plant, fungal, and animal kingdoms, DRP5B is a plant/algal invention to facilitate the division of their organelles (i.e., chloroplasts and peroxisomes). In addition, our results support the notion that proteins involved in the early (elongation) and late (fission) stages of peroxisome division may act cooperatively.
Exceptional Case Touch not the cat bot a glove*: ANCA-positive pauci-immune necrotizing glomerulonephritis secondary to Bartonella henselae

A 36-year-old male presented with a secondary, but anti-neutrophil cytoplasmic antibody (ANCA) (proteinase-3) positive, vasculitis with renal insufficiency due to a pauci-immune necrotizing glomerulonephritis. An infective process was initially excluded by blood cultures and an echocardiogram prior to immunosuppression. The patient’s condition failed to improve and re-evaluation confirmed infective endocarditis requiring valve replacement. Subsequent tissue cultures identified Bartonella henselae. Antibiotic treatment led to full resolution of physical, biochemical and immunological markers. This is the first case of B. henselae endocarditis-associated ANCA positivity with a pauci-immune glomerulonephritis. It demonstrates the importance of revisiting standard investigations in patients not improving expectantly on conventional therapy.
Dual HER 2 / PIK 3 CA Targeting Overcomes Single-Agent Acquired Resistance in HER 2-Ampli fi ed Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo

HER2/neu gene amplification andPIK3CAdrivermutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu–amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplificationwith orwithout oncogenic PIK3CAmutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0–G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent–treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor–resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option forUSCpatients harboring tumorswithHER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy. Mol Cancer Ther; 14(11); 2519–26. 2015 AACR.
Intracranial Steno-Occlusive Arterial Disease and its Associations in Egyptian Ischemic Stroke Patients

Background and Purpose— Intracranial arterial steno-occlusive disease is prevalent among non-white populations. We explored whether a similar pattern exists in Egyptians and assessed its clinical-radiological associations. Methods— Consecutive acute ischemic stroke patients were recruited for 6 months and had magnetic resonance imaging/magnetic resonance angiography of brain within 2 days of the event. Magnetic resonance angiography was analyzed for significant stenosis (>50%), flow gaps, and complete occlusions in the major intracranial arteries. Results— A total of 143 patients completed the study (62.4±12.6 years, 58.7% males). Magnetic resonance angiography showed symptomatic arterial stenosis in 27.3%, asymptomatic stenosis in 16.1%, and occlusions in 23.7% patients. Carotid duplex showed stenosis >70% in only 7.7% patients. Patients with intracranial arterial steno-occlusive disease had higher National Institutes of Health Stroke Score at admission (10.9±7 versus 8±5.6; P=0.01). Conclusion— Symptomatic and asymptomatic intracranial arterial steno-occlusive disease was prevalent in this Egyptian acute stroke sample. This might have important implications on stroke management in this population.
Enhancement of Visual Field Predictions with Pointwise Exponential Regression (PER) and Pointwise Linear Regression (PLR)

Purpose The study was conducted to evaluate threshold smoothing algorithms to enhance prediction of the rates of visual field (VF) worsening in glaucoma. Methods We studied 798 patients with primary open-angle glaucoma and 6 or more years of follow-up who underwent 8 or more VF examinations. Thresholds at each VF location for the first 4 years or first half of the follow-up time (whichever was greater) were smoothed with clusters defined by the nearest neighbor (NN), Garway-Heath, Glaucoma Hemifield Test (GHT), and weighting by the correlation of rates at all other VF locations. Thresholds were regressed with a pointwise exponential regression (PER) model and a pointwise linear regression (PLR) model. Smaller root mean square error (RMSE) values of the differences between the observed and the predicted thresholds at last two follow-ups indicated better model predictions. Results The mean (SD) follow-up times for the smoothing and prediction phase were 5.3 (1.5) and 10.5 (3.9) years. The mean RMSE values for the PER and PLR models were unsmoothed data, 6.09 and 6.55; NN, 3.40 and 3.42; Garway-Heath, 3.47 and 3.48; GHT, 3.57 and 3.74; and correlation of rates, 3.59 and 3.64. Conclusions Smoothed VF data predicted better than unsmoothed data. Nearest neighbor provided the best predictions; PER also predicted consistently more accurately than PLR. Smoothing algorithms should be used when forecasting VF results with PER or PLR. Translational Relevance The application of smoothing algorithms on VF data can improve forecasting in VF points to assist in treatment decisions.
Increases in Land Surface Temperature in Response to Fire in Siberian Boreal Forests and Their Attribution to Biophysical Processes

Wildfire is the most prevalent natural disturbance in boreal forests and impacts climate through biogeochemical (e.g., greenhouse gas emission from biomass burning) and biophysical (e.g., albedo [α], evapotranspiration [ET], and roughness) processes. We used satellite observations to investigate the immediate (i.e., 1 year after fire) biophysical effects of fire in Siberian boreal forests. We found that boreal forest fires have a net annual warming effect (0.0728 to 0.325 K) due to strong summer warming and weak winter cooling. Fires also increased the diurnal temperature range and seasonal amplitude. These effects are strongest in summer and significantly higher in evergreen than in deciduous coniferous forests. Decreases in ET contributed to warming effects in summer, and increases in α contributed to cooling in winter. Our results suggest that the increase in observed land surface temperature immediately following fires in boreal ecosystems is most likely due to reduced ET leading to a strong positive feedback on the surface radiative budget.
Discover Patterns and Mobility of Twitter Users - A Study of Four US College Cities

Geo-tagged tweets provide useful implications for studies in human geography, urban science, location-based services, targeted advertising, and social network. This research aims to discover the patterns and mobility of Twitter users by analyzing the spatial and temporal dynamics in their tweets. Geo-tagged tweets are collected over a period of six months for four US Midwestern college cities: (1) West Lafayette, IN; (2) Bloomington, IN; (3) Ann Arbor, MI; (4) Columbus, OH. Various analytical and statistical methods are used to reveal the spatial and temporal patterns of tweets, and the tweeting behaviors of Twitter users. It is discovered that Twitter users are most active between 9:00 pm and 11:00 pm. In smaller cities, tweets aggregate at campuses and apartment complexes, while tweets in residential areas of bigger cities make up the majority of tweets. We also found that most Twitter users have two to four places of frequent visits. The mean mobility range of frequent Twitter users is linearly correlated to the size of the city, specifically, about 40% of the city radius. The research therefore confirms the feasibility and promising future for using geo-tagged microblogging services such as Twitter to understand human behavior patterns and carry out other geo-social related studies.
Dust properties inside molecular clouds from coreshine modeling and observations

Context. Using observations to deduce dust properties, grain-size distribution, and physical conditions in molecular clouds is a highly degenerate problem.Aims. The coreshine phenomenon, a scattering process at 3.6 and 4.5 μm that dominates absorption, has revealed its ability to explore the densest parts of clouds. We use this effect to constrain the dust parameters. The goal is to investigate to what extent grain growth (at constant dust mass) inside molecular clouds is able to explain the coreshine observations. We aim to find dust models that can explain a sample of Spitzer coreshine data. We also examine the consistency with near-infrared data we obtained for a few clouds.Methods. We selected four regions with a very high occurrence of coreshine cases: Taurus-Perseus, Cepheus, Chameleon, and L183/L134. We built a grid of dust models and investigated the key parameters to reproduce the general trend of surface brightnesses and intensity ratios of both coreshine and near-infrared observations with the help of a 3D Monte Carlo radiative transfer code. The grid parameters allowed us to investigate the effect of coagulation upon spherical grains up to 5 μm in size derived from the DustEm diffuse interstellar medium grains. Fluffiness (porosity or fractal degree), ices, and a handful of classical grain-size distributions were also tested. We used the near- and mostly mid-infrared intensity ratios as strong discriminants between dust models.Results. The determination of the background-field intensity at each wavelength is a key issue. In particular, an especially strong background field explains why we do not see coreshine in the Galactic plane at 3.6 and 4.5 μm. For starless cores, where detected, the observed 4.5 μm/3.6 μm coreshine intensity ratio is always lower than ~0.5, which is also what we find in the models for the Taurus-Perseus and L183 directions. Embedded sources can lead to higher fluxes (up to four times higher than the strongest starless core fluxes) and higher coreshine ratios (from 0.5 to 1.1 in our selected sample). Normal interstellar radiation-field conditions are sufficient to find suitable grain models at all wavelengths for starless cores. The standard interstellar grains are not able to reproduce observations and, because of the multiwavelength approach, only a few grain types meet the criteria set by the data. Porosity does not affect the flux ratios, while the fractal dimension helps to explain coreshine ratios, but does not seem able to reproduce near-infrared observations without a mix of other grain types.Conclusions. Combined near- and mid-infrared wavelengths confirm the potential of revealing the nature and size distribution of dust grains. Careful assessment of the environmental parameters (interstellar and background fields, embedded or nearby reddened sources) is required to validate this new diagnostic.
Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice Published, JLR Papers in Press, October 24, 2007.

A combination of the interrelated metabolic risk factors obesity, insulin resistance, dyslipidemia, and hypertension, often described as the “metabolic syndrome,” is known to increase the risk of developing cardiovascular disease and diabetes. Stearoyl-coenzyme A desaturase (SCD) activity has been implicated in the metabolic syndrome, but detailed studies of the beneficial metabolic effects of SCD deficiency have been limited. Here, we show that absence of the Scd1 gene product reduces plasma triglycerides and reduces weight gain in severely hyperlipidemic low density lipoprotein receptor (LDLR)-deficient mice challenged with a Western diet. Absence of SCD1 also increases insulin sensitivity, as measured by intraperitoneal glucose and insulin tolerance testing. SCD1 deficiency dramatically reduces hepatic lipid accumulation while causing more modest reductions in plasma apolipoproteins, suggesting that in conditions of sustained hyperlipidemia, SCD1 functions primarily to mediate lipid stores. In addition, absence of SCD1 partially ameliorates the undesirable hypertriglyceridemic effect of antiatherogenic liver X receptor agonists. Our results demonstrate that constitutive reduction of SCD activity improves the metabolic phenotype of LDLR-deficient mice on a Western diet.
Children Born Preterm at the Turn of the Millennium Had Better Lung Function Than Children Born Similarly Preterm in the Early 1990s

Objective Compare respiratory health in children born extremely preterm (EP) or with extremely low birthweight (ELBW) nearly one decade apart, hypothesizing that better perinatal management has led to better outcome. Design Fifty-seven (93%) of 61 eligible 11-year old children born in Western Norway in 1999–2000 with gestational age (GA) <28 weeks or birthweight <1000 gram (EP1999–2000) and matched term-controls were assessed with comprehensive lung function tests and standardized questionnaires. Outcome was compared with data obtained at 10 years of age from all (n = 35) subjects born at GA <29 weeks or birthweight <1001 gram within a part of the same region in 1991–92 (EP1991–1992) and their matched term-controls. Results EP1999–2000 had significantly reduced forced expiratory flow in 1 second (FEV1), FEV1 to forced vital capacity (FEV1/FVC) and forced expiratory flow between 25–75% of FVC (FEF25–75), with z-scores respectively -0.34, -0.50 and -0.61 below those of the term-control group, and more bronchial hyperresponsiveness to methacholine (dose-response-slope 13.2 vs. 3.5; p<0.001), whereas other outcomes did not differ. Low birthweight z-scores, but not neonatal bronchopulmonary dysplasia (BPD) or low GA, predicted poor outcome. For children with neonatal BPD, important lung-function variables were better in EP1999–2000 compared to EP1991–1992. In regression models, improvements were related to more use of antenatal corticosteroids and surfactant treatment in the EP1999–2000. Conclusions Small airway obstruction and bronchial hyperresponsiveness were still present in children born preterm in 1999–2000, but outcome was better than for children born similarly preterm in 1991–92, particularly after neonatal BPD. The findings suggest that better neonatal management not only improves survival, but also long-term pulmonary outcome.
Natural and Anthropogenic Controls on Wood Loads in River Corridors of the Rocky, Cascade, and Olympic Mountains, USA

Wood in rivers creates habitat, shapes the morphology of valley bottoms, and acts as a pool of organic carbon (OC). Effective riverine wood management depends on a robust understanding of the spatial distribution of wood throughout river networks. This motivates the analysis of wood load in relation to both reach‐ and basin‐scale processes. We present wood load data coupled with precipitation, forest stand characteristic, land use, and geomorphic data across four basins in the Rocky, Cascade, and Olympic Mountains of the western U.S. We compare basins with differing land use within the same climatic region and basins in differing climates and statistically model intrabasin wood load variability. Wood load is a function of metrics that generally describe river corridor spatial heterogeneity, metrics that describe wood storage patterns, and, at a broader scale, metrics that relate to wood supply. From this, we generate a conceptual model to describe controls on wood load across spatial scales. We use this model to propose that spatial heterogeneity and wood storage pattern together determine reach‐scale wood trapping efficiency. Trapping efficiency in turn regulates how wood supply to valley bottoms determines wood load. We also find that wood in an undisturbed basin stores significant amounts of OC and that wood load restoration has the potential to restore significant amounts of OC to valley bottoms. This conceptual model of wood load controls may serve as a framework to guide wood load modeling and restoration at multiple scales.
Predictors of survival in sepsis: what is the best inflammatory marker to measure?

Purpose of review Sepsis is relevant due to its high morbidity and mortality. For both sepsis diagnosis and outcome prediction many biomarkers have been described in the literature. Most of these markers are objects of scientific interest rather than being introduced into daily clinical practice. However, due to their unspecific character and their insufficient predictive value for the individual person, research focus is still on new aspects in sepsis-related biomarkers. Recent findings Beyond the widely used acute-phase proteins C-reactive protein (CRP) and procalcitonin (PCT), many new molecules have been studied deriving from different organs or cells affected, due to the systemic nature of sepsis. Cytokines, coagulation factors/characteristics, vasoactive hormones, and several others have been recently proved to be relevant in sepsis syndrome and probably useful for outcome prediction. However, single time point measurements may be less predictive than consideration of the time-dependent course of parameters. Clinical decision just based on a biomarker is still not feasible because of the huge inter-individual differences in the inflammatory response. Summary Many biomarkers display relevant correlation with the clinical outcome of patients with severe sepsis and septic shock. Consideration of their time courses may be more reliable than absolute levels. Clinical decision should not be based only on biomarkers but organ dysfunctions, for example, should also be taken into account.
Oxygen Uptake of the Nonworking Left Ventricle

Comparisons have been made in the open chest dog of the oxygen usage of the left ventricle whose external work has been reduced to zero by 4 different procedures. The average oxygen usage of the left myocardium/100 Gm. /min. is about 2.0 cc. in complete arrest with vagal stimulation or with intracoronary potassium injection; 3.8 cc. in fibrillation; and 3.4 cc. in the empty but beating heart. The oxygen value in the arrested heart approximates 27 per cent of that in the control state and the uptake during vagal stoppage varies directly with the control metabolic level. In the fibrillating ventricle the higher values are related to the intensity of fibrillatory movements, and in the empty beating heart to the control metabolic rate and to the frequency of the heart beat. The experiments with vagal arrest also permit estimation of the oxygen debt of the myocardium.
Verifying the stroke-free phenotype by structured telephone interview.

BACKGROUND AND PURPOSE Case-control, cohort, and twin studies support a genetic contribution to ischemic stroke risk. Sibling pair linkage methods require identification of concordant or discordant siblings or both. We designed and tested a structured telephone interview to verify the stroke-free phenotype. METHODS A coordinator unaware of medical record data used an 8-item questionnaire to conduct a structured telephone interview of 70 outpatients aged >60 years. The questionnaire inquired about the sudden onset of deficits in strength, sensation, vision, and language. A subject was defined as stroke free by interview if responses to all items on the questionnaire were negative. Results of the telephone interview were compared with data obtained from a systematic medical record review (benchmark). RESULTS Interview time was 5 minutes or less for all subjects. All subjects who began the interview completed it. Records were reviewed in all subjects. Medical record review detected ischemic stroke or transient ischemic attack (TIA), or both, in 5 patients (7%). There were no significant differences in sex distribution or risk factor rates in patients who were designated stroke free or not stroke free by interview. Having 1 or more positive items on the questionnaire was significantly associated with finding stroke (P<0.001), TIA (P<0.001), or either stroke or TIA (P<0.001), on medical record review. The telephone interview had a sensitivity of 1.0 (95% CI 0.48 to 1.0), specificity of 0.86 (95% CI 0.75 to 0.93), positive predictive value of 0.36 (95% CI 0.13 to 0.65), and negative predictive value of 1.0 (95% CI 0.94 to 1.0). CONCLUSIONS Our instrument can identify the stroke-free individual with a high degree of confidence in a very efficient manner. It may be particularly suited for centralized verification of stroke discordancy in multicentered sib-pair genetic studies.
Proceedings From the American College of Rheumatology Reproductive Health Summit: The Management of Fertility, Pregnancy, and Lactation in Women With Autoimmune and Systemic Inflammatory Diseases

Most autoimmune and systemic inflammatory diseases are more common in women than in men, including women of child-bearing age. Therefore, for many of our patients, family planning is an important clinical issue. The management of pregnancy in autoimmune diseases is complex, benefitting optimally from a multidisciplinary approach that takes into consideration: prepregnancy counseling; treatments received prior to, during, and after pregnancy; early recognition of both obstetric complications and medical complications relating to the underlying disease; prenatal fetal development; and postnatal management of the