Miracle-dz/UniFAR-FTUs huggingface dataset:
Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome.

BACKGROUND Mutations that map to the KvLQT1 gene on human chromosome 11 account for more than 50% of inherited long QT syndrome (LQTS). It has been discovered recently that the KvLQT1 and minK proteins functionally interact to generate a current with biophysical properties similar to I(Ks), the slowly activating delayed-rectifier cardiac potassium current. Since I(Ks) modulates the repolarization of cardiac action potentials it is reasonable to hypothesize that mutations in KvLQT1 reduce I(Ks), resulting in the prolongation of cardiac action potential duration. METHODS AND RESULTS We expressed LQTS-associated KvLQT1 mutants in Xenopus oocytes either individually or in combination with wild-type KvLQT1 or in combination with both wild-type KvLQT1 and minK. Substitutions of alanine with proline in the S2-S3 cytoplasmic loop (A177P) or threonine with isoleucine in the highly conserved signature sequence of the pore (T311I) yield inactive channels when expressed individually, whereas substitution of leucine with phenylalanine in the S5 transmembrane domain (L272F) yields a functional channel with reduced macroscopic conductance. However, all these mutants inhibit wild-type KvLQT1 currents in a dominant-negative fashion. CONCLUSIONS In LQTS-affected individuals these mutations would be predicted to result in a diminution of the cardiac I(Ks) current, subsequent prolongation of cardiac repolarization, and an increased risk of arrhythmias.
Age-Related Changes in Postural Control in Physically Inactive Older Women

Background and Purpose: The maintenance of postural control is influenced by the complexity of a given task. Tasks that require greater attention and cognitive involvement increase the risk of falls among older adults. The aim of the present study was to evaluate the adaptation of the postural control system to different levels of task complexity in physically inactive young and older women. Methods: A cross-sectional study was conducted with adult women classified as physically inactive based on the results of the International Physical Activity Questionnaire. The participants were 27 young (20-30 years of age) and 27 older (60-80 years of age) women. Sway velocity of the center of pressure in the anterior-posterior and medial-lateral directions was calculated using a force plate under 6 conditions: standing directly on the force plate or on a foam placed over the force plate, eyes open or closed, and dual-task complexity with and without the foam. Results and Discussion: A 2-way analysis of variance revealed that sway velocity increased in both groups when the task conditions were altered. The older women exhibited significantly greater sway velocity compared with the young women on all tasks. However, the patterns of postural control adaptation to the different levels of complexity were similar among all participants. Conclusions: In this study, the adaption of the postural control system to different levels of task complexity did not differ between physically inactive young and physically inactive older women. However, the physically inactive older women exhibited greater sway velocity compared with the young women.
Increased risk for recurrent major depression in DYT1 dystonia mutation carriers

Background: Prior studies suggest that dystonia is comorbid with affective disorders. This comorbidity could be a reaction to a chronic debilitating disorder or expression of a predisposing gene. The authors took advantage of the identification of a gene for dystonia, DYT1, to test these alternative explanations. Methods: The authors administered a standardized psychiatric interview to members of families with an identified DYT1 mutation. The authors classified family members into three groups: mutation carriers with dystonia (manifesting carriers; n = 96), mutation carriers without dystonia (non-manifesting carriers; n = 60), and noncarriers (n = 65). Results: The risk for recurrent major depressive disorder was increased in both non-manifesting carriers (RR = 4.95, CI = 1.72 to 14.29) and manifesting carriers (RR = 3.62, CI = 1.00 to 10.53) compared with noncarriers. Mutation carriers also had earlier age at onset of recurrent major depressive disorder than noncarriers. The severity of motor signs was not associated with the likelihood of recurrent depression. Mutation carriers did not have an increased risk for other affective disorders, such as single major depression or bipolar disorder. Conclusions: Early-onset recurrent major depression is associated with the DYT1 GAG mutation and this association is independent of motor manifestations of dystonia. These findings suggest that early-onset recurrent depression is a clinical expression of the DYT1 gene mutation.
The Core of Chloroplast Nucleoids Contains Architectural SWIB Domain Proteins[W][OA]

The transcriptionally active chromosome from spinach chloroplasts was analyzed by two-dimensional gel electrophoresis and mass spectrometry to identify proteins involved in structuring of the nucleoid core. SWI/SNF complex B domain–containing proteins were identified that might be functional equivalents of the bacterial nucleoid-associated proteins involved in shaping of nucleoid architecture. A highly enriched fraction of the transcriptionally active chromosome from chloroplasts of spinach (Spinacia oleracea) was analyzed by two-dimensional gel electrophoresis and mass spectrometry to identify proteins involved in structuring of the nucleoid core. Among such plastid nucleoid-associated candidate proteins a 12-kD SWIB (SWI/SNF complex B) domain–containing protein was identified. It belongs to a subgroup of low molecular mass SWIB domain proteins, which in Arabidopsis thaliana has six members (SWIB-1 to SWIB-6) with predictions for localization in the two DNA-containing organelles. Green/red fluorescent protein fusions of four of them were shown to be targeted to chloroplasts, where they colocalize with each other as well as with the plastid envelope DNA binding protein in structures corresponding to plastid nucleoids. For SWIB-6 and SWIB-4, a second localization in mitochondria and nucleus, respectively, could be observed. SWIB-4 has a histone H1 motif next to the SWIB domain and was shown to bind to DNA. Moreover, the recombinant SWIB-4 protein was shown to induce compaction and condensation of nucleoids and to functionally complement a mutant of Escherichia coli lacking the histone-like nucleoid structuring protein H-NS.
Supporting Online Material Materials and Methods Figs. S1 to S8 Tables S1 to S10 References a Genome-wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants

Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10. T ype 2 diabetes (T2D) is a disease characterized by insulin resistance and impaired pancreatic beta-cell function that affects >170 million people worldwide (1). With first-degree relatives having ~3.5 times as much risk as compared to individuals in the general middle-aged population (2), hereditary factors, together with lifestyle and behavioral factors, play an important role in determining T2D risk (3). To date, intense efforts to identify genetic risk factors in T2D have met with only limited success. This study, reports from our collaborators (4–6), and the recently published work of Sladek et al. (7) describe results of genome-wide association (GWA) studies that further define the genetic architecture of T2D and identify biological pathways involved in T2D pathogenesis. had ≥10 copies of the less common allele [minor allele frequency (MAF) > 0.002] and passed quality-control criteria (8). We tested these 315,635 SNPs for association with T2D using a model that is additive on the log-odds scale (Table 1 and tables S3 and S4) (8). We observed a modest excess (41 observed versus 31.6 expected; P = 0.19) of SNPs with P values < 10 −4 (fig. S1). These results argue against the existence of multiple common SNPs with a large impact on T2D disease risk but are consistent with the presence of multiple common SNPs that each confer modest risk. The results also suggest that the matching of cases and controls by birth province, sex, and age (8) has been successful; in …
Evolving Social Weighted Networks: Nonlocal Dynamics of Open Source Communities

Complex networks emerge under different conditions through simple rules of growth and evolution. Such rules are typically local when dealing with biological systems and most social webs. An important deviation from such scenario is provided by communities of agents engaged in technology development, such as open source (OS) communities. Here we analyze their network structure, showing that it defines a complex weighted network with scaling laws at different levels, as measured by looking at e-mail exchanges. We also present a simple model of network growth involving non-local rules based on betweenness centrality. The model outcomes fit very well the observed scaling laws, suggesting that the overall goals of the community and the underlying hierarchical organization play a key role is shaping its dynamics.
High-Density Lipoproteins Inhibit Vascular Endothelial Inflammation by Increasing 3&bgr;-Hydroxysteroid-&Dgr;24 Reductase Expression and Inducing Heme Oxygenase-1

Rationale: Lipid-free apolipoprotein (apo) A-I and discoidal reconstituted high-density lipoproteins (rHDL) containing apoA-I, (A-I)rHDL, inhibit vascular inflammation by increasing 3&bgr;-hydroxysteroid-&Dgr;24 reductase (DHCR24) expression. Objective: To determine whether the lipid-free apoA-I–mediated and (A-I)rHDL-mediated increase in DHCR24 expression induces the cytoprotective and potentially cardioprotective enzyme, heme oxygenase-1 (HO-1). Methods and Results: In vivo: A single intravenous infusion of lipid-free apoA-I (8 mg/kg) administered 24 hours before inserting a nonocclusive periarterial carotid collar into New Zealand White rabbits decreased collar-induced endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression, reduced intima/media neutrophil infiltration, and increased DHCR24 and HO-1 mRNA levels. Knockdown of vascular DHCR24 and HO-1 and systemic administration of tin-protoporphyrin-IX, an HO inhibitor, abolished these anti-inflammatory effects. In vitro: Preincubation of human coronary artery endothelial cells with (A-I)rHDL before activation with tumor necrosis factor-&agr; increased DHCR24 and HO-1 mRNA levels and inhibited cytokine-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression. Transfection of the cells with DHCR24 and HO-1 small interfering RNA and tin-protoporphyrin-IX treatment abolished these effects. The (A-I)rHDL-mediated induction of HO-1 was reduced in human coronary artery endothelial cells transfected with DHCR24 small interfering RNA. Transfection of human coronary artery endothelial cells with HO-1 small interfering RNA and tin-protoporphyrin-IX treatment did not inhibit the (A-I)rHDL-mediated increase in DHCR24 expression. Inhibition of phosphatidylinositol 3-kinase/Akt reduced the (A-I)rHDL-mediated increase in HO-1, but not DHCR24 expression. The activation of phosphatidylinositol 3-kinase/Akt by (A-I)rHDL was decreased in human coronary artery endothelial cells that were transfected with DHCR24 small interfering RNA. Conclusions: Lipid-free apoA-I and (A-I)rHDL inhibit inflammation by increasing DHCR24 expression, which, in turn, activates phosphatidylinositol 3-kinase/Akt and induces HO-1.
Shortening the induction delivery interval with prostaglandins: a randomized controlled trial of solo or in combination.

OBJECTIVE To compare the efficacy and safety of misoprostol alone with dinoprostone followed by misoprostol, all inserted intravaginally in induction of labor at term and the obstetrical outcome. MATERIAL AND METHODS A pilot study comprising 111 primigravidae, >37 gestational weeks with singleton pregnancy in cephalic presentation having an unfavorable Bishop score admitted for labor induction, were considered and randomly allocated into two groups. In group I (n=55) with intravaginal 25mcg misoprostol 4 hourly (six doses at the most) and and group II (n=56), with dinoprostone 0.5mg followed eight hours later by 25mcg misoprostol induction to vaginal delivery time was found to be significantly different, being 14.8 h in group-I and shorter in group-II with a mean of 11.6 h. Vaginal delivery rates within 12 h (groups-I and -II: 47.2%, as compared to 60.7%, respectively) were found to be higher with dinoprostone-misoprostol induction, as well as vaginal delivery rates in 24 h, 80.0% and 91.1%. The need for oxytocin augmentation was more frequent in the misoprostol than in the dinoprostone-misoprostol group, (61.8%, and 39.3%), and all these observations were statistically significant. Abnormal foetal heart rate pattern occurred more frequently (18.2%) in group-I in contrast to 5.3% in group-II, as was the incidence rate of (18.2%) who had passage of meconium in group-I, this rate being significantly different from group-II having meconium passage in 3 cases, a rate of 5.3%. CONCLUSION Using dinoprostone followed by vaginal misoprostol is safe and effective for induction of labor with less need for oxytocin augmentation and shorter induction delivery interval.
FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women.

OBJECTIVE FSH, via its receptor (FSHR), influences bone remodeling and osteoclast proliferation and activity. The aim of this study was to evaluate the influence of two single nucleotide polymorphisms (SNPs) of the FSHR gene on bone mineral density (BMD) and bone turnover markers (bone alkaline phosphatase and type I collagen C-telopeptides) in postmenopausal women. METHODS Two hundred and eighty-nine unrelated postmenopausal women were genotyped for the SNPs rs1394205 and rs6166. BMD was estimated using dual-energy X-ray absorptiometry and quantitative ultrasound (QUS) methodologies. RESULTS AA rs6166 women showed a lower BMD (femoral neck and total body), lower stiffness index (calcaneal QUS), and higher serum levels of bone turnover markers compared to GG rs6166 women. The prevalence of osteoporosis was significantly higher in AA rs6166 women compared with GG rs6166 women. These results were not influenced by circulating levels of FSH and estrogens. CONCLUSION The SNP rs6166 of the FSHR gene significantly influences BMD in postmenopausal women. In particular, AA rs6166 women are at increased risk of postmenopausal osteoporosis compared with GG rs6166 women, independently of circulating levels of FSH and estrogens. Previous studies have demonstrated that this SNP influences cell and tissue response to hyperstimulation of FSHR in vivo and in vitro. Our study results appear in agreement with these experimental data and with known biological actions of FSH/FSHR system in bone homeostasis.
ISO 9241-9 evaluation of video game controllers

Fifteen participants completed a study comparing video game controllers for point-select tasks. We used a Fitts' law task, as per ISO 9241-9, using the Nintendo Wii Remote for infrared pointing, the Nintendo Classic Controller for analogue stick pointing, and a standard mouse as a baseline condition. The mouse had the highest throughput at 3.78 bps. Both game controllers performed poorly by comparison. The Wii Remote throughput was 31.5% lower, at 2.59 bps, and the Classic Controller 60.8% lower at 1.48 bps. Comparing just the video game controllers, the Wii Remote presents a 75% increase in throughput over the Classic Controller. Error rates for the mouse, Classic Controller, and the Wii Remote were 3.53%, 6.58%, and 10.2%, respectively. Fourteen of 15 participants expressed a preference for the Wii Remote over the Classic Controller for pointing tasks in a home entertainment environment.
Context-Related Acoustic Variation in Male Fallow Deer (Dama dama) Groans

While social and behavioural contexts are known to affect the acoustic structure of vocal signals in several mammal species, few studies have investigated context-related acoustic variation during inter-sexual advertisement and/or intra-sexual competition. Here we recorded male fallow deer groans during the breeding season and investigated how key acoustic parameters (fundamental frequency and formant frequencies) vary as a function of the social context in which they are produced. We found that in the presence of females, male fallow deer produced groans with higher mean fundamental frequency when vocal males were also present than they did when no vocal males were in close vicinity. We attribute this to the increased arousal state typically associated with this context. In addition, groan minimum formant frequency spacing was slightly, but significantly lower (indicating marginally more extended vocal tracts) when males were alone than when potential mates and/or competitors were nearby. This indicates that, contrary to our predictions, male fallow deer do not exaggerate the acoustic impression of their body size by further lowering their formant frequencies in the presence of potential mating partners and competitors. Furthermore, since the magnitude of the variation in groan minimum formant frequency spacing remains small compared to documented inter-individual differences, our findings are consistent with the hypothesis that formants are reliable static cues to body size during intra- and inter-sexual advertisement that do not concurrently encode dynamic motivation-related information.
Learning from induced changes in opponent (re)actions in multi-agent games

Multi-agent learning is a growing area of research. An important topic is to formulate how an agent can learn a good policy in the face of adaptive, competitive opponents. Most research has focused on extensions of single agent learning techniques originally designed for agents in more static environments. These techniques however fail to incorporate a notion of the effect of own previous actions on the development of the policy of the other agents in the system. We argue that incorporation of this property is beneficial in competitive settings. In this paper, we present a novel algorithm to capture this notion, and present experimental results to validate our claims.
Evaluating water table response to rainfall events in a shallow aquifer and canal system

Shallow aquifers typically have greater hydrologic connectivity and response to recharge and changes in surface water management practices than deeper aquifers and are therefore often managed to reduce the risk of flooding. Quantification of the water table elevation response under different management scenarios provides valuable information in shallow aquifer systems to assess indirect influences of such modifications. The episodic master recession method was applied to the 15‐min water table elevation and NEXRAD rainfall data for 6 wells to identify water table response and individual rainfall events. The objectives of this study were to evaluate the effects of rainfall, water table elevation, canal stage, site‐specific characteristics, and canal structure modification/water management practice on the fluctuations in water table elevations using multiple/stepwise multiple linear regression techniques. With the modification of canal structure and operation adjustment, significant difference existed in water table response in the southern wells due to its relative downstream position regarding the general groundwater flow direction and the structural modification locations. On average, water table response height and flood risk were lower after than before the structure modification to canals. The effect of rainfall event size on the height of water table response was greater than the effect of antecedent water table elevation and canal stage on the height of water table response. Other factors including leakance of the canal bed sediment, specific yield, and rainfall on i − 1 day had significant effects on the height of water table response as well. Antecedent water table elevation and canal stage had greater and more linear effects on the height of water table response after the management changes to canals. Variation in water table response height/rainfall event size ratio was attributed to difference in Sy, antecedent soil water content, hydraulic gradient, rainfall size, and run‐off ratio. After the structure modification, water table response height/rainfall event size ratio demonstrated more linear and proportional relationship with antecedent water table elevation and canal stage.
Within-wingbeat damping: dynamics of continuous free-flight yaw turns in Manduca sexta

Free-flight body dynamics and wing kinematics were collected from recordings of continuous, low-speed, multi-wingbeat yaw turns in hawkmoths (Manduca sexta) using stereo videography. These data were used to examine the effects of rotational damping arising from interactions between the body rotation and flapping motion (flapping counter-torque, FCT) on continuous turning. The moths were found to accelerate during downstroke, then decelerate during upstroke by an amount consistent with FCT damping. Wing kinematics related to turning were then analysed in a simulation of hawkmoth flight; results were consistent with the observed acceleration–deceleration pattern. However, an alternative wing kinematic which produced more continuous and less damped accelerations was found in the simulation. These findings demonstrate that (i) FCT damping is detectable in the dynamics of continuously turning animals and (ii) FCT-reducing kinematics do exist but were not employed by turning moths, possibly because within-wingbeat damping simplifies control of turning by allowing control systems to target angular velocity rather than acceleration.