Coupling of hydraulic and electrical transport properties in sandstones

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Mutant huntingtin causes defective actin remodeling during stress: defining a new role for transglutaminase 2 in neurodegenerative disease

Huntington's disease (HD) is caused by an expanded CAG tract in the Interesting transcript 15 (IT15) gene encoding the 350 kDa huntingtin protein. Cellular stresses can trigger the release of huntingtin from the endoplasmic reticulum, allowing huntingtin nuclear entry. Here, we show that endogenous, full-length huntingtin localizes to nuclear cofilin–actin rods during stress and is required for the proper stress response involving actin remodeling. Mutant huntingtin induces a dominant, persistent nuclear rod phenotype similar to that described in Alzheimer's disease for cytoplasmic cofilin–actin rods. Using live cell temporal studies, we show that this stress response is similarly impaired when mutant huntingtin is present, or when normal huntingtin levels are reduced. In clinical lymphocyte samples from HD patients, we have quantitatively detected cross-linked complexes of actin and cofilin with complex formation varying in correlation with disease progression. By live cell fluorescence lifetime imaging measurement–Förster resonant energy transfer studies and western blot assays, we quantitatively observed that stress-activated tissue transglutaminase 2 (TG2) is responsible for the actin–cofilin covalent cross-linking observed in HD. These data support a direct role for huntingtin in nuclear actin re-organization, and describe a new pathogenic mechanism for aberrant TG2 enzymatic hyperactivity in neurodegenerative diseases

Negative tracheal pressure during neonatal endotracheal suction

Endotracheal tube (ETT) suction is the most frequently performed invasive procedure in ventilated newborn infants and is associated with adverse effects related to negative tracheal pressure. We aimed to measure suction catheter gas flow and intratracheal pressure during ETT suction of a test lung and develop a mathematical model to predict tracheal pressure from catheter and ETT dimensions and applied pressure. Tracheal pressure and catheter flow were recorded during suction of ETT sizes 2.5-4.0 mm connected to a test lung with catheters 5-8 French Gauge and applied pressures of 80-200 mm Hg. The fraction of applied pressure transmitted to the trachea was calculated for each combination, and data fitted to three nonlinear models for analysis. Tracheal pressure was directly proportional to applied pressure (r2 = 0.82-0.99), and catheter flow fitted a turbulent flow model (R2 = 0.85-0.96). With each ETT, increasing catheter size resulted in greater catheter flow (p < 0.0001) and thus lower intratracheal pressure (p < 0.0001). The fraction of applied pressure transmitted to the trachea was accurately modeled using ETT and catheter dimensions (R2 = 0.98-0.99). Negative tracheal pressure during in vitro ETT suction is directly proportional to applied pressure. This relationship is determined by ETT and catheter dimensions

Granulocyte-Colony-Stimulating Factor Alters the Proteomic Landscape of the Ventral Tegmental Area

Cocaine addiction is characterized by aberrant plasticity of the mesolimbic dopamine circuit, leading to dysregulation of motivation to seek and take drug. Despite the significant toll that cocaine use disorder exacts on society, there are currently no available pharmacotherapies. We have recently identified granulocyte-colony stimulating factor (G-CSF) as a soluble cytokine that alters the behavioral response to cocaine and which increases dopamine release from the ventral tegmental area (VTA). Despite these known effects on behavior and neurophysiology, the molecular mechanisms by which G-CSF affects brain function are unclear. In this study mice were treated with repeated injections of G-CSF, cocaine or a combination and changes in protein expression in the VTA were examined using an unbiased proteomics approach. Repeated G-CSF treatment resulted in alterations in multiple signaling pathways related to synaptic plasticity and neuronal morphology. While the treatment groups had marked overlap in their effect, injections of cocaine and the combination of cocaine and G-CSF lead to distinct patterns of significantly regulated proteins. These experiments provide valuable information as to the molecular pathways that G-CSF activates in an important limbic brain region and will help to guide further characterization of G-CSF function and evaluation as a possible translational target

Does obesity affect outcomes of adult burn patients?

Obesity negatively affects outcomes after trauma and surgery; results after burns are more limited and controversial. The purpose of this study was to determine the effect of obesity on clinical and economic outcomes after thermal injury. The National Inpatient Sample was queried for adults from 2005-2009 with International Classification of Diseases-9 codes for burn injury. Demographics and clinical outcomes of obese and nonobese cohorts were compared. Univariate and multivariate analysis using logistic regression models were performed. Data are expressed as median (interquartile range) or mean ± standard deviation and compared at P < 0.05. In 14,602 patients, 3.3% were obese (body mass index ≥30 kg/m(2)). The rate of obesity increased significantly by year (P < 0.001). Univariate analysis revealed significant differences between obese and nonobese patients in incidence of wound infection (7.2% versus 5.0%), urinary tract infection (7.2% versus 4.6%), deep vein thrombosis in total body surface area (TBSA) ≥10% (3.1% versus 1.1%), pulmonary embolism in TBSA ≥10% (2.3% versus 0.6%), length of stay [6 d (8) versus 5 d (9)], and hospital costs ($10,122.12 [$18,074.72] versus $7892.07 [$17,191.96]) (all P < 0.05). Death occurred less frequently in the obese group (1.9% versus 4%, P = 0.021). Significant predictors of grouped adverse events (urinary tract infection, wound infection, deep vein thrombosis, and pulmonary embolism) on multivariate analysis include obesity, TBSA ≥20%, age, and black race (all P ≤ 0.05). Obesity is an independent predictor of adverse events after burn injury; however, obesity is associated with decreased mortality. Our findings highlight the potential clinical and economic impact of the obesity epidemic on burn patients nationwide