Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood Pressure, Renal Function, and Proteinuria in Children with Unilateral Renal Agenesis

Background/Aim: Unilateral renal agenesis (URA) is a model for a reduced nephron number that is believed to be a risk factor for blood pressure (BP) elevation and reduced renal function. The aim of the study was to investigate BP and renal function in children with URA. Methods: Data on children with URA from two pediatric nephrology centers were firstly retrospectively reviewed (renal ultrasound and scintigraphy, clinical BP, creatinine clearance, urinalysis). Children with normal renal ultrasound and scintigraphy were thereafter investigated using ambulatory BP monitoring. Results: Twenty-nine children with URA were investigated – 14 children with an abnormal kidney (mostly scarring) and 15 children with healthy kidneys. Hypertension was diagnosed on the basis of clinical BP in 57% of the children with abnormal kidneys and on the basis of ambulatory BP monitoring in 1 child (7%) with healthy kidneys. The mean ambulatory BP in children with normal kidneys was not significantly different from that in controls. Forty-three percent of the children with abnormal kidneys had a reduced renal function, but none of children with normal kidneys. Conclusions: Children with abnormalities of a solitary kidney have often hypertension, proteinuria, or a reduced renal function. In contrast, children with healthy solitary kidneys have BP and renal function similar to those of healthy children.
Molecular Pathways Molecular Pathways : In fl ammation-Associated Nitric-Oxide Production as a Cancer-Supporting RedoxMechanism and a Potential Therapeutic Target

It is widely accepted that many cancers express features of inflammation, driven by both microenvironmental cells and factors, and the intrinsic production of inflammation-associated mediators from malignant cells themselves. Inflammation results in intracellular oxidative stress with the ultimate biochemical oxidants composed of reactive nitrogens and oxygens. Although the role of inflammation in carcinogensis is well accepted, we now present data showing that inflammatory processes are also active in the maintenance phase of many aggressive forms of cancer. The oxidative stress of inflammation is proposed to drive a continuous process of DNA adducts and crosslinks, as well as posttranslational modifications to lipids and proteins that we argue support growth and survival. In this perspective, we introduce data on the emerging science of inflammation-driven posttranslational modifications on proteins responsible for driving growth, angiogenesis, immunosuppression, and inhibition of apoptosis. Examples include data from human melanoma, breast, head and neck, lung, and colon cancers. Fortunately, numerous antioxidant agents are clinically available, and we further propose that the pharmacologic attenuation of these inflammatory processes, particularly the reactive nitrogen species, will restore the cancer cells to an apoptosis-permissive and growth-inhibitory state. Our mouse model data using an arginine antagonist that prevents enzymatic production of nitric oxide directly supports this view. We contend that selected antioxidants be considered as part of the cancer treatment approach, as they are likely to provide a novel and mechanistically justified addition for therapeutic benefit. Clin Cancer Res; 19(20); 5557–63. 2013 AACR.
Apical constriction initiates new bud formation during monopodial branching of the embryonic chicken lung

Branching morphogenesis sculpts the airway epithelium of the lung into a tree-like structure to conduct air and promote gas exchange after birth. In the avian lung, a series of buds emerges from the dorsal surface of the primary bronchus via monopodial branching to form the conducting airways; anatomically, these buds are similar to those formed by domain branching in the mammalian lung. Here, we show that monopodial branching is initiated by apical constriction of the airway epithelium, and not by differential cell proliferation, using computational modeling and quantitative imaging of embryonic chicken lung explants. Both filamentous actin and phosphorylated myosin light chain were enriched at the apical surface of the airway epithelium during monopodial branching. Consistently, inhibiting actomyosin contractility prevented apical constriction and blocked branch initiation. Although cell proliferation was enhanced along the dorsal and ventral aspects of the primary bronchus, especially before branch formation, inhibiting proliferation had no effect on the initiation of branches. To test whether the physical forces from apical constriction alone are sufficient to drive the formation of new buds, we constructed a nonlinear, three-dimensional finite element model of the airway epithelium and used it to simulate apical constriction and proliferation in the primary bronchus. Our results suggest that, consistent with the experimental results, apical constriction is sufficient to drive the early stages of monopodial branching whereas cell proliferation is dispensable. We propose that initial folding of the airway epithelium is driven primarily by apical constriction during monopodial branching of the avian lung.
Unaltered Secretion of β-Amyloid Precursor Protein in Gelatinase A (Matrix Metalloproteinase 2)-deficient Mice*

The β-amyloid peptide, which forms extracellular cerebral deposits in Alzheimer’s disease, is derived from a large membrane-spanning glycoprotein referred to as the β-amyloid precursor protein (APP). The APP is normally cleaved within the β-amyloid region by a putative proteinase (α-secretase) to generate large soluble amino-terminal derivatives of APP, and this event prevents the β-amyloid peptide formation. It has been suggested that the gelatinase A (matrix metalloproteinase 2, a 72-kDa type IV collagenase) may act either as α-secretase or as β-secretase. Mice devoid of gelatinase A generated by gene targeting develop normally, except for a subtle delay in their growth, thus providing a useful system to examine the role of gelatinase A in the cleavage and secretion of APP in vivo. We show here that APP is cleaved within the β-amyloid region and secreted into the extracellular milieu of brain and cultured fibroblasts without gelatinase A activity. The data suggest that gelatinase A does not play an essential role in the generation and release of soluble derivatives of APP at physiological conditions.
A Kinase-Independent Activity of Cdk9 Modulates Glucocorticoid Receptor-Mediated Gene Induction

A gene induction competition assay has recently uncovered new inhibitory activities of two transcriptional cofactors, NELF-A and NELF-B, in glucocorticoid-regulated transactivation. NELF-A and -B are also components of the NELF complex, which participates in RNA polymerase II pausing shortly after the initiation of gene transcription. We therefore asked if cofactors (Cdk9 and ELL) best known to affect paused polymerase could reverse the effects of NELF-A and -B. Unexpectedly, Cdk9 and ELL augmented, rather than prevented, the effects of NELF-A and -B. Furthermore, Cdk9 actions are not blocked either by Ckd9 inhibitors (DRB or flavopiridol) or by two Cdk9 mutants defective in kinase activity. The mode and site of action of NELF-A and -B mutants with an altered NELF domain are similarly affected by wild-type and kinase-dead Cdk9. We conclude that Cdk9 is a new modulator of GR action, that Ckd9 and ELL have novel activities in GR-regulated gene expression, that NELF-A and -B can act separately from the NELF complex, and that Cdk9 possesses activities that are independent of Cdk9 kinase activity. Finally, the competition assay has succeeded in ordering the site of action of several cofactors of GR transactivation. Extension of this methodology should be helpful in determining the site and mode of action of numerous additional cofactors and in reducing unwanted side effects.
Genetic Characterization of Pseudomonas syringae pv. syringae Strains from Stone Fruits in California

ABSTRACT Strains of Pseudomonas syringae pv. syringae were isolated from healthy and diseased stone fruit tissues sampled from 43 orchard sites in California in 1995 and 1996. These strains, together with P. syringae strains from other hosts and pathovars, were tested for pathogenicity and the presence of the syrBand syrC genes and were genetically characterized by using enterobacterial repetitive intergenic consensus (ERIC) primers and PCR. All 89 strains of P. syringae pv. syringae tested were moderately to highly pathogenic on Lovell peach seedlings regardless of the host of origin, while strains of other pathovars exhibited low or no pathogenicity. The 19 strains of P. syringae pv. syringae examined by restriction fragment length polymorphism analysis contained the syrB and syrC genes, whereas no hybridization occurred with 4 strains of other P. syringaepathovars. The P. syringae pv. syringae strains from stone fruit, except for a strain from New Zealand, generated ERIC genomic fingerprints which shared four fragments of similar mobility. Of the P. syringae pv. syringae strains tested from other hosts, only strains from rose, kiwi, and pear generated genomic fingerprints that had the same four fragments as the stone fruit strains. Analysis of the ERIC fingerprints from P. syringaepv. syringae strains showed that the strains isolated from stone fruits formed a distinct cluster separate from most of the strains isolated from other hosts. These results provide evidence of host specialization within the diverse pathovar P. syringae pv. syringae.
Feedforward Compensation Mediated by the Central and Peripheral Actions of a Single Neuropeptide Discovered Using Representational Difference Analysis

Compensatory mechanisms are often used to achieve stability by reducing variance, which can be accomplished via negative feedback during homeostatic regulation. In principle, compensation can also be implemented through feedforward mechanisms where a regulator acts to offset the anticipated output variation; however, few such neural mechanisms have been demonstrated. We provide evidence that an Aplysia neuropeptide, identified using an enhanced representational difference analysis procedure, implements feedforward compensation within the feeding network. We named the novel peptide “allatotropin-related peptide” (ATRP) because of its similarity to insect allatotropin. Mass spectrometry confirmed the peptide's identity, and in situ hybridization and immunostaining mapped its distribution in the Aplysia CNS. ATRP is present in the higher-order cerebral-buccal interneuron (CBI) CBI-4, but not in CBI-2. Previous work showed that CBI-4-elicited motor programs have a shorter protraction duration than those elicited by CBI-2. Here we show that ATRP shortens protraction duration of CBI-2-elicited ingestive programs, suggesting a contribution of ATRP to the parametric differences between CBI-4-evoked and CBI-2-evoked programs. Importantly, because Aplysia muscle contractions are a graded function of motoneuronal activity, one consequence of the shortening of protraction is that it can weaken protraction movements. However, this potential weakening is offset by feedforward compensatory actions exerted by ATRP. Centrally, ATRP increases the activity of protraction motoneurons. Moreover, ATRP is present in peripheral varicosities of protraction motoneurons and enhances peripheral motoneuron-elicited protraction muscle contractions. Therefore, feedforward compensatory mechanisms mediated by ATRP make it possible to generate a faster movement with an amplitude that is not greatly reduced, thereby producing stability.
Effect of continuous positive airway pressure on blood pressure : a placebo trial.

This study examined the effect of continuous positive airway pressure (CPAP) treatment on blood pressure in patients with obstructive sleep apnea. Thirty-nine patients with sleep apnea were studied. Ambulatory blood pressure monitoring was obtained before and after patients were randomized to receive either 1 week of CPAP or placebo CPAP (CPAP administered at ineffective pressure). Blood pressure was examined over daytime hours (6 AM to 10 PM) and during nighttime hours (10 PM to 6 AM). Daytime mean arterial blood pressure decreased significantly but equally in both the active treatment group and the placebo treatment group (P=0.001). Nighttime mean arterial pressure levels decreased to a much greater extent over time in the patients who received active CPAP treatment (P=0. 032). CPAP does appear to decrease nighttime blood pressure. However, the decrease in daytime blood pressure may reflect a nonspecific response (ie, placebo), since both the active treatment group and the placebo treatment group developed comparable decreases in blood pressure.
The impact of iconic gestures on foreign language word learning and its neural substrate

Vocabulary acquisition represents a major challenge in foreign language learning. Research has demonstrated that gestures accompanying speech have an impact on memory for verbal information in the speakers' mother tongue and, as recently shown, also in foreign language learning. However, the neural basis of this effect remains unclear. In a within‐subjects design, we compared learning of novel words coupled with iconic and meaningless gestures. Iconic gestures helped learners to significantly better retain the verbal material over time. After the training, participants' brain activity was registered by means of fMRI while performing a word recognition task. Brain activations to words learned with iconic and with meaningless gestures were contrasted. We found activity in the premotor cortices for words encoded with iconic gestures. In contrast, words encoded with meaningless gestures elicited a network associated with cognitive control. These findings suggest that memory performance for newly learned words is not driven by the motor component as such, but by the motor image that matches an underlying representation of the word's semantics. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.
Molecular Coupling between Voltage Sensor and Pore Opening in the Arabidopsis Inward Rectifier K+ Channel KAT1

Animal and plant voltage-gated ion channels share a common architecture. They are made up of four subunits and the positive charges on helical S4 segments of the protein in animal K+ channels are the main voltage-sensing elements. The KAT1 channel cloned from Arabidopsis thaliana, despite its structural similarity to animal outward rectifier K+ channels is, however, an inward rectifier. Here we detected KAT1-gating currents due to the existence of an intrinsic voltage sensor in this channel. The measured gating currents evoked in response to hyperpolarizing voltage steps consist of a very fast (τ = 318 ± 34 μs at −180 mV) and a slower component (4.5 ± 0.5 ms at −180 mV) representing charge moved when most channels are closed. The observed gating currents precede in time the ionic currents and they are measurable at voltages (less than or equal to −60) at which the channel open probability is negligible (≈10−4). These two observations, together with the fact that there is a delay in the onset of the ionic currents, indicate that gating charge transits between several closed states before the KAT1 channel opens. To gain insight into the molecular mechanisms that give rise to the gating currents and lead to channel opening, we probed external accessibility of S4 domain residues to methanethiosulfonate-ethyltrimethylammonium (MTSET) in both closed and open cysteine-substituted KAT1 channels. The results demonstrate that the putative voltage–sensing charges of S4 move inward when the KAT1 channels open.
On the detection of several obstacles in 2D Stokes flow: Topological sensitivity and combination with shape derivatives

We consider the inverse problem of detecting the location and the shape of several obstacles immersed in a fluid flowing in a larger bounded domain Ω from partial boundary measurements in the two dimensional case. The fluid flow is governed by the steady-state Stokes equations. We use a topological sensitivity analysis for the Kohn-Vogelius functional in order to find the number and the qualitative location of the objects. Then we explore the numerical possibilities of this approach and also present a numerical method which combines the topological gradient algorithm with the classical geometric shape gradient algorithm; this blending method allows to find the number of objects, their relative location and their approximate shape.
Trends in Phenological Parameters and Relationship Between Land Surface Phenology and Climate Data in the Hyrcanian Forests of Iran

Vegetation activity may be changed in response to climate variability by affecting seasonality and phenological events. Monitoring of land surface phenological changes play a key role in understanding feedback of ecosystem dynamics. This study focuses on the analysis of trends in land surface phenology derived parameters using normalized difference vegetation index time series based on Global Inventory Monitoring and Mapping Studies data in the Hyrcanian forests of Iran covering the period 1981–2012. First, we applied interpolation for data reconstruction in order to remove outliers and cloud contamination in time series. Phenological parameters were retrieved by using the midpoint approach, whereas trends were estimated using the Theil–Sen approach. Correlation coefficients were evaluated from multiple linear regression between phenological parameters against temperature and precipitation time series. Significant Mann–Kendall test analysis indicate average start of season (SOS) and end of season (EOS) increased by −0.16 and +0.14 days per year, respectively. Results of significant trend analysis showed that later EOS was associated with increasing temperature trends and we found strongest relationships between temperature and phenological parameters in the west of the Hyrcanian forests, where precipitation was abundant. Moreover, SOS correlated strongly with total precipitation and mean temperature. This study allows us to better estimate the drivers affecting the vegetation dynamics in the Hyrcanian forests of Iran.
Sympathoinhibitory effects of telmisartan through the reduction of oxidative stress in the rostral ventrolateral medulla of obesity-induced hypertensive rats

Objectives: Sympathetic nervous system (SNS) activity is critically involved in the development and progression of obesity-induced hypertension. Angiotensin II type 1 receptor (AT1R)-induced oxidative stress in the rostral ventrolateral medulla (RVLM), a vasomotor center in the brainstem, activates the SNS in hypertensive rats. The aim of the present study was to determine whether oral administration of an AT1R blocker (ARB) inhibits SNS activity via antioxidative effects in the RVLM of rats with dietary-induced obesity. Methods and results: Obesity-prone rats fed a high-fat diet were divided into groups treated with either telmisartan obesity-prone (TLM-OP), or losartan obesity-prone (LOS-OP), or vehicle obesity-prone (VEH-OP). SBP, SNS activity, and oxidative stress in the RVLM were significantly higher in obesity-prone rats than in obesity-resistant rats. Body weight, visceral fat, blood glucose, serum insulin, and plasma adiponectin concentrations were significantly lower in TLM-OP and LOS-OP than in VEH-OP, and plasma adiponectin concentrations were significantly higher in TLM-OP than in LOS-OP. Although SBP was reduced to similar levels both in TLM-OP and LOS-OP, both oxidative stress in the RVLM and SNS activity were significantly lower in TLM-OP than in LOS-OP or VEH-OP. Conclusion: Orally administered telmisartan inhibited SNS activity through antioxidative effects via AT1R blockade in the RVLM of obesity-prone rats. AT1R and oxidative stress in the RVLM might be novel treatment targets for obesity-induced hypertension through sympathoinhibition, and telmisartan might be preferable for obesity-induced hypertension.
The distribution and impact of viral lineages in domains of life

Living organisms can be conveniently classified into three domains, Archaea, Bacteria, and Eukarya (Woese et al., 1990). The three domains are united by several features that support the common origin of life including the presence of ribosomes, double-stranded DNA genomes, a nearly universal genetic code, physical compartments (i.e., membranes), and the ability to carry out metabolism and oxidation-reduction reactions. In comparison, other types of genetic material and particles (e.g., viruses, plasmids, and other selfish genetic elements) are often excluded from the definition of “life” (for opposing views see Raoult and Forterre, 2008; Forterre, 2011, 2012a). However, they can still influence the evolution of cellular organisms, and in conjunction, establish complex life cycles.
A mutation causing pseudohypoaldosteronism type 1 identifies a conserved glycine that is involved in the gating of the epithelial sodium channel

Pseudohypoaldosteronism type 1 (PHA‐1) is an inherited disease characterized by severe neonatal salt‐wasting and caused by mutations in subunits of the amiloride‐sensitive epithelial sodium channel (ENaC). A missense mutation (G37S) of the human ENaC β subunit that causes loss of ENaC function and PHA‐1 replaces a glycine that is conserved in the N‐terminus of all members of the ENaC gene family. We now report an investigation of the mechanism of channel inactivation by this mutation. Homologous mutations, introduced into α, β or γ subunits, all significantly reduce macroscopic sodium channel currents recorded in Xenopus laevis oocytes. Quantitative determination of the number of channel molecules present at the cell surface showed no significant differences in surface expression of mutant compared with wild‐type channels. Single channel conductances and ion selectivities of the mutant channels were identical to that of wild‐type. These results suggest that the decrease in macroscopic Na currents is due to a decrease in channel open probability (Po), suggesting that mutations of a conserved glycine in the N‐terminus of ENaC subunits change ENaC channel gating, which would explain the disease pathophysiology. Single channel recordings of channels containing the mutant α subunit (αG95S) directly demonstrate a striking reduction in Po. We propose that this mutation favors a gating mode characterized by short‐open and long‐closed times. We suggest that determination of the gating mode of ENaC is a key regulator of channel activity.
Modeling Large-Strain, High-Rate Deformation in Metals

The large strain deformation response of 6061-T6 and Ti-6Al-4V has been evaluated over a range in strain rates from 10{sup -4} s{sup -1} to over 10{sup 4} s{sup -1}. The results have been used to critically evaluate the strength and damage components of the Johnson-Cook (JC) material model. A new model that addresses the shortcomings of the JC model was then developed and evaluated. The model is derived from the rate equations that represent deformation mechanisms active during moderate and high rate loading. Another model that accounts for the influence of void formation on yield and flow behavior of a ductile metal (the Gurson model) was also evaluated. The characteristics and predictive capabilities of these models are reviewed.