Miracle-dz/UniFAR-FTUs huggingface dataset:
The Subfamily-specific Assembly of Eag and Erg K+ Channels Is Determined by Both the Amino and the Carboxyl Recognition Domains*

Background: K+ channel subunits from different ether-à-go-go subfamilies cannot form heterotetramers. Results: Reversal of subfamily specificity was only possible when we exchanged both amino and carboxyl termini between two ether-à-go-go subunits. Conclusion: Both recognition domains are required for subfamily-specific assembly. Significance: This is the first evidence suggesting that the amino terminus of ether-à-go-go K+ channels governs subunit interaction specificity. A functional voltage-gated K+ (Kv) channel comprises four pore-forming α-subunits, and only members of the same Kv channel subfamily may co-assemble to form heterotetramers. The ether-à-go-go family of Kv channels (KCNH) encompasses three distinct subfamilies: Eag (Kv10), Erg (Kv11), and Elk (Kv12). Members of different ether-à-go-go subfamilies, such as Eag and Erg, fail to form heterotetramers. Although a short stretch of amino acid sequences in the distal C-terminal section has been implicated in subfamily-specific subunit assembly, it remains unclear whether this region serves as the sole and/or principal subfamily recognition domain for Eag and Erg. Here we aim to ascertain the structural basis underlying the subfamily specificity of ether-à-go-go channels by generating various chimeric constructs between rat Eag1 and human Erg subunits. Biochemical and electrophysiological characterizations of the subunit interaction properties of a series of different chimeric and truncation constructs over the C terminus suggested that the putative C-terminal recognition domain is dispensable for subfamily-specific assembly. Further chimeric analyses over the N terminus revealed that the N-terminal region may also harbor a subfamily recognition domain. Importantly, exchanging either the N-terminal or the C-terminal domain alone led to a virtual loss of the intersubfamily assembly boundary. By contrast, simultaneously swapping both recognition domains resulted in a reversal of subfamily specificity. Our observations are consistent with the notion that both the N-terminal and the C-terminal recognition domains are required to sustain the subfamily-specific assembly of rat Eag1 and human Erg.
Variability in clubhead presentation characteristics and ball impact location for golfers' drives

Abstract The purpose of the present study was to analyse the variability in clubhead presentation to the ball and the resulting ball impact location on the club face for a range of golfers of different ability. A total of 285 male and female participants hit multiple shots using one of four proprietary drivers. Self-reported handicap was used to quantify a participant's golfing ability. A bespoke motion capture system and user-written algorithms was used to track the clubhead just before and at impact, measuring clubhead speed, clubhead orientation, and impact location. A Doppler radar was used to measure golf ball speed. Generally, golfers of higher skill (lower handicap) generated increased clubhead speed and increased efficiency (ratio of ball speed to clubhead speed). Non-parametric statistical tests showed that low-handicap golfers exhibit significantly lower variability from shot to shot in clubhead speed, efficiency, impact location, attack angle, club path, and face angle compared with high-handicap golfers.
Comparison of Simulated and Observed Continental Tropical Anvil Clouds and Their Radiative Heating Profiles

AbstractVertically pointing millimeter-wavelength radar observations of anvil clouds extending from mesoscale convective systems (MCSs) that pass over an Atmospheric Radiation Measurement Program (ARM) field site in Niamey, Niger, are compared to anvil structures generated by the Weather Research and Forecasting (WRF) mesoscale model using six different microphysical schemes. The radar data provide the statistical distribution of the radar reflectivity values as a function of height and anvil thickness. These statistics are compared to the statistics of the modeled anvil cloud reflectivity at all altitudes. Requiring the model to be statistically accurate at all altitudes is a stringent test of the model performance. The typical vertical profile of radiative heating in the anvil clouds is computed from the radar observations. Variability of anvil structures from the different microphysical schemes provides an estimate of the inherent uncertainty in anvil radiative heating profiles. All schemes underestima.
Effects of dietary fiber supplementation on glycemic control in dogs with alloxan-induced diabetes mellitus.

The effect of a high insoluble-fiber (IF) diet containing 15% cellulose in dry matter, high soluble-fiber (SF) diet containing 15% pectin in dry matter, and low-fiber (LF) diet on glycemic control in 6 dogs with alloxan-induced insulin-dependent diabetes mellitus was evaluated. Each diet contained greater than 50% digestible carbohydrate in dry matter. A crossover study was used with each dog randomly assigned to a predetermined diet sequence. Each dog was fed each diet for 56 days. Caloric intake was adjusted weekly as needed to maintain each dog within 1.5 kg of its body weight measured prior to induction of diabetes mellitus. All dogs were given pork lente insulin and half of their daily caloric intake at 12-hour intervals. Mean (+/- SEM) daily caloric intake was significantly (P less than 0.05) less when dogs consumed the IF diet vs the SF and LF diets (66 +/- 3 kcal/kg, 81 +/- 5 kcal/kg, and 79 +/- 4 kcal/kg, respectively). Serum alkaline phosphatase activity was significantly (P less than 0.05) higher when dogs consumed the LF diet vs the IF and SF diets (182 +/- 37 IU/L, 131 +/- 24 IU/L, and 143 +/- 24 IU/L, respectively). Mean postprandial plasma glucose concentration measured every 2 hours for 24 hours, beginning at the time of the morning insulin injection, was significantly (P less than 0.05) lower at most blood sampling times in dogs fed IF and SF diets, compared with dogs fed the LF diet. (ABSTRACT TRUNCATED AT 250 WORDS)
Fluoride Inhibition of Polymorphonuclear Leukocytes

Significant inhibition of PMN metabolic activity by F- occurred at 0.1, 0.5 and 1.0 mM F- for O- 2 generation, 1-C14 CO 2 release labeled glucose and NBT-reduction respectively. This inhibition resulted primarily from F- suppression of non-oxidative glucose metabolism. As the concentration of F- in the O- 2 generating system increased beyond 10 mM, a rise in production of O- 2 anion occurred, peaking at 20 mM F-, followed by a rapid decline.
Current or past physical or sexual abuse as a risk marker for sexually transmitted disease in pregnant women.

CONTEXT Previous studies suggest that a history of physical or sexual violence is positively associated with a history of sexually transmitted disease (STD). It is important to determine whetherabuse is also a risk factor for current STD infection. METHODS Data were collected from 744 clients of an urban Midwestern prenatal clinic who gave birth in 1991-1996. Multiple logistic regression analyses were conducted to determine how the odds of having a history of STD or a current STD infection are affected by the experience of abuse. RESULTS Overall, 30% of the women had a history of STD, and 18% had a current STD infection. Results of multivariate analyses showed that compared with nonabused women, those who had experienced any type of abuse had nearly twice the odds of having a history of infection and of currently having an STD. In separate analyses by abuse type, women with a history of only sexual abuse had twice the odds and those with a history of both physical and sexual abuse had nearly three times the odds of having a current STD, compared with women who reported no abuse. CONCLUSIONS Abused women are at significantly increased risk of having a history of STD; abuse is also associated with an increased risk of current infection, especially among those with any history of sexual abuse. Future studies should be undertaken to better understand the role that abuse may play in relation to STD risk.
Inosine modulates gut barrier dysfunction and end organ damage in a model of ischemia-reperfusion injury.

INTRODUCTION Gut barrier failure is an important source of morbidity in critically ill patients, and patients undergoing aortic cross-clamp. Inosine, an endogenous purine nucleoside without known side effects, formed from the breakdown of adenosine by adenosine deaminase, has been shown to modify the effects of hypoxia on various tissues, including the heart and the brain. MATERIALS AND METHODS This study examined the effect of inosine on ischemia-reperfusion-induced gut barrier dysfunction and on the associated lung injury. Twenty-four male Sprague-Dawley rats were divided into three groups. Eight were subjected to 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Eight had 100 mg/kg inosine prior to ischemia-reperfusion and 8 had sham laparotomy with encircling but not occlusion of the superior mesenteric artery. RESULTS Rats treated with inosine had significantly less gut barrier dysfunction. Rats subjected to SMAO sustained a substantial lung injury and this was attenuated by inosine treatment. Serum cytokine levels were also significantly lower. CONCLUSIONS We conclude that inosine has a beneficial effect in modulating both gut barrier dysfunction and distant organ injury in response to gut ischemia-reperfusion.
Epidemiology of symptom-defined gastroesophageal reflux disease and reflux esophagitis: The systematic investigation of gastrointestinal diseases in China (SILC)

Abstract Objective. Gastroesophageal reflux disease (GERD) is thought to be less prevalent in China than in Western countries. However, essential population-based endoscopy data are lacking for this country. Material and methods. As part of a wider study, 3600 individuals selected randomly from the Shanghai region were asked to undergo endoscopy. Participants completed a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire. When sufficient numbers were available, associations were assessed using multiple logistic regression or the Wilcoxon rank-sum test. Results. Of 3153 (87.6%) individuals who completed the survey, 1030 (32.7%) agreed to endoscopy and 1029 endoscopies were suitable for analysis. Symptom-defined GERD was more prevalent in the endoscopy group (4.7%) than in the non-endoscopy group (1.7%). Prevalence estimates were 6.4% for reflux esophagitis, 1.8% for endoscopically suspected esophageal metaplasia and 0.7% for hiatus hernia. Reflux esophagitis was more prevalent in patients with symptom-defined GERD than in those without (12.5% [6/48] vs. 6.1% [60/981]), and was significantly associated with reflux symptoms of any frequency or severity (OR = 2.10, 95% CI 1.13–3.89) and with negative Helicobacter pylori infection (OR = 0.44, 95% CI 0.25–0.80). Only 28.8% of participants with reflux esophagitis had heartburn and/or regurgitation symptoms. Epigastric burning was significantly more severe and frequent in participants with reflux esophagitis than in those without (p = 0.05). Conclusions. Reflux esophagitis is less prevalent in China than reported in Western countries. Further work is needed to establish why reflux esophagitis appears less symptomatic in China than in Western countries.
Is routine electroencephalography (EEG) a useful biomarker for pharmacoresistant epilepsy?

People with seizure disorders who have been treated at the Kork Epilepsy Center over a prolonged time period and who thus provide data concerning the chronic course of epilepsy were investigated in order to address the potential role of electroencephalography (EEG) as a biomarker for pharmacoresistant epilepsy. Clinical course and the corresponding findings from their first recorded EEG, their first EEG following appropriate treatment, and their last EEG were compared. Furthermore, we investigated if interictal epileptiform discharges (IEDs) differ in amplitude and morphology if recorded in long‐term seizure‐free patients. The early cessation of IEDs was a relatively good marker for a good prognosis, especially in idiopathic generalized epilepsies. However, persistent IEDs had no major impact on the long‐term prognosis. We found no differences between IEDs in seizure‐free patients or patients with ongoing seizures. Therefore, in our hands, routine EEG was not an appropriate biomarker for the prediction of pharmacoresistant epilepsy. Additional factors such as etiology and pathophysiology also need to be considered.
A comprehensive knowledge base of synaptic electrophysiology in the rodent hippocampal formation

The cellular and synaptic architecture of the rodent hippocampus has been described in thousands of peer-reviewed publications. However, no human- or machine-readable public catalog of synaptic electrophysiology data exists for this or any other neural system. Harnessing state of the art information technology, we have developed a cloud-based toolset for identifying empirical evidence from the scientific literature pertaining to synaptic electrophysiology, for extracting the experimental data of interest, and for linking each entry to relevant text or figure excerpts. Mining more than 1,200 published journal articles, we have identified eight different signal modalities quantified by 68 different methods to measure synaptic amplitude, kinetics, and plasticity in hippocampal neurons. We have designed a data structure that both reflects these variabilities and maintains the existing relations among experimental modalities. Moreover, we mapped every annotated experiment to identified “synapse types,” i.e. specific pairs of presynaptic and postsynaptic neuron types. To this aim, we leveraged Hippocampome.org, an open-access knowledge base of morphologically, electrophysiologically, and molecularly characterized neuron types in the rodent hippocampal formation. Specifically, we have implemented a computational pipeline to systematically translate neuron type properties into formal queries in order to find all compatible synapse types. With this system, we have collected nearly 40,000 synaptic data entities covering 88% of the 3,120 potential connections in Hippocampome.org. Correcting membrane potentials with respect to liquid junction potentials significantly reduced the difference between theoretical and experimental reversal potentials, thereby enabling the accurate conversion of all synaptic amplitudes to conductance. This dataset allows for large-scale hypothesis testing of the general rules governing synaptic signals. To illustrate these applications, we confirmed several expected correlations between synaptic measurements and their covariates while suggesting previously unreported ones. We release all data open source at Hippocampome.org in order to further research across disciplines.
Volume Independent Stimulation of Renin Secretion by a Single Dose of Amiloride in Man

Summary The regulation of renin secretion is not understood in detail. There is evidence that amiloride (CAS 17440-83-4) has a stimulatory effect on the renin secretion but it is still in question whether this is volume and/or sodium independent. The purpose of this study was to investigate whether a single dose of amiloride has a direct stimulatory effect on the renin secretion in humans independent of its diuretic effect. Blood pressure, plasma renin activities and plasma aldosterone concentrations as well as serum electrolytes and serum creatinine were assessed in 11 healthy male humans over a period of 6 hours after a single dose of 20 mg of amiloride (Midamor ®), or placebo. Furthermore every hour urine was collected for analysis of urinary creatinine and electrolytes. To avoid a possible effect on the renin secretion via augmented diuresis induced by amiloride the urinary volume loss was replaced by 0.9 % NaCl solution. There was a decrease in plasma renin activities and plasma aldosterone concentrations after amiloride and placebo administration, but the plasma renin activity after amiloride was significantly higher compared with placebo. Also the plasma aldosterone concentration was higher after amiloride compared with placebo, but the difference did not reach statistical significance. Serum and urinary concentrations of sodium and potassium clearly confirmed the known potassium-saving and natriuretic effect of amiloride. Serum creatinine concentrations decreased and urinary sodium chloride concentrations increased due to the administered volume load using physiologic sodium chloride solution. The present study provides evidence that amiloride induces renin secretion by direct mechanisms in man, which might go along with augmented aldosterone secretion.
The role of image-guidance systems for head and neck surgery.

BACKGROUND Although image-guidance systems have gained widespread acceptance for neurosurgical procedures, their role for extracranial surgery of the head and neck is yet to be defined. OBJECTIVES To describe the authors' experience with image-guidance systems and to measure the effects of image-guided technology on the performance of minimally invasive otolaryngological procedures. DESIGN Prospective cohort study. METHODS Optical- and electromagnetic-based image-guidance systems were used during the performance of endoscopic surgery on patients with disease of the paranasal sinuses, orbit, skull base, and temporal bone (n = 79). Results were compared with those in control patients who underwent similar surgery without image guidance during the same period (n = 42). RESULTS Intraoperative anatomical localization was accurate to within 2 mm at the start of surgery in all cases. Accuracy degraded by 0.89 +/- 0.20 mm (mean +/- SE) during the operative procedure. The use of an image-guidance system increased operating room time by a mean of 17.4 minutes per case (image-guidance group, 137.3 +/- 6.0 minutes [mean +/- SE]; control group, 119.9 +/- 5.7 minutes; P=.006) and increased hospital charges by approximately $496 per case. Intraoperative blood loss (image-guidance group, 178.4 +/- 18.0 mL [mean +/- SE]; control group, 149.4 +/- 20.1 mL) and complication rates (image-guidance group, 2.7%; control group, 4.7%) did not differ significantly between groups. CONCLUSIONS Image-guidance systems can provide the head and neck surgeon with accurate information regarding anatomical localization in cases with poor surgical landmarks caused by extensive disease or prior surgery; however, the use of such systems is associated with increased operative time and expense.
Discrete mutations introduced in the predicted nucleotide-binding sites of the mdr1 gene abolish its ability to confer multidrug resistance

In cells stably transfected and overexpressing the mouse mdr1 gene, multidrug resistance is associated with an increased ATP-dependent drug efflux. Analysis of the predicted amino acid sequence of the MDR1 protein revealed the presence of two putative nucleotide-binding sites (NBS). To assess the functional importance of these NBS in the overall drug resistance phenotype conferred by mdr1, we introduced amino acid substitutions in the core consensus sequence for nucleotide binding, GXGKST. Mutants bearing the sequence GXAKST or GXGRST at either of the two NBS of mdr1 and a double mutant harboring the sequence GXGRST at both NBS were generated. The integrity of the two NBS was essential for the biological activity of mdr1, since all five mutants were unable to confer drug resistance to hamster drug-sensitive cells in transfection experiments. Conversely, a lysine-to-arginine substitution outside the core consensus sequence had no effect on the activity of mdr1. Failure to reduce intracellular accumulation of [3H]vinblastine paralleled the loss of activity in cell clones expressing mutant MDR1 proteins. However, the ability to bind the photoactivatable ATP analog 8-azido ATP was retained in the five inactive MDR1 mutants. This result implies that an essential step subsequent to ATP binding is impaired in these mutants, possibly ATP hydrolysis or secondary conformational changes induced by ATP-binding or hydrolysis. Our results suggest that the two NBS function in a cooperative fashion, since mutations in a single NBS completely abrogated the biological activity of mdr1.
Parental reflective functioning and the neural correlates of processing infant affective cues

ABSTRACT Parental reflective functioning refers to the capacity for a parent to understand their own and their infant’s mental states, and how these mental states relate to behavior. Higher levels of parental reflective functioning may be associated with greater sensitivity to infant emotional signals in fostering adaptive and responsive caregiving. We investigated this hypothesis by examining associations between parental reflective functioning and neural correlates of infant face and cry perception using event-related potentials (ERPs) in a sample of recent mothers. We found both early and late ERPs were associated with different components of reflective functioning. These findings suggest that parental reflective functioning may be associated with the neural correlates of infant cue perception and further support the value of enhancing reflective functioning as a mechanism in parenting intervention programs.
Early Detection of Alzheimer’s Disease with PET Imaging

Preclinical diagnosis of Alzheimer’s disease (AD) is one of the major challenges for the prevention of AD. AD biomarkers are needed not only to reveal preclinical pathologic changes, but also to monitor progression and therapeutics. PET neuroimaging can reliably assess aspects of the molecular biology and neuropathology of AD. The aim of this article is to review the use of FDG-PET and amyloid PET imaging in the early detection of AD.
Rectal carcinoma: MRI with histologic correlation before and after chemoradiation therapy.

OBJECTIVE The purpose of this study was to use MRI to compare the morphologic features of rectal cancer before and 6 weeks after chemotherapy and radiation treatment to correlate the posttreatment MRI appearances with the histologic findings in resected tumors. MATERIALS AND METHODS High-resolution T2-weighted MRI was performed before and immediately after a standardized 5-week course of chemoradiation therapy in the care of 30 patients with locally advanced adenocarcinoma of the rectum. Changes in morphologic features were evaluated with respect to primary tumor and nodal downstaging. The MRI findings after chemoradiation therapy were compared with the histologic findings in the resected specimens with respect to prediction of tumor stage and showing the relation between the tumor and the circumferential margin of resection. RESULTS Tumor shrinkage > 30% was found in 19 (63%; 95% CI, 46-81%) of 30 patients, but changes in MRI T stage occurred in only five (17%; 95% CI, 3-30%) of 30 patients. Tumor regression from the circumferential resection margin was found in five patients, all findings confirmed at histologic examination. Nodal downstaging was observed in 13 (68%; 95% CI, 48-89%) of 19 patients; 11 patients were node free on the basis of both MRI findings and subsequent histologic results. Overall prediction of distance between tumor and circumferential resection margin was good, with a mean difference of -0.2 mm and an interclass correlation coefficient of 0.74. MRI was not useful for gauging disease activity of persistent abnormalities in mucinous tumors that often represented inactive mucin lakes. CONCLUSION Decreases in tumor size and nodal downstaging can be seen on MRI after chemoradiation therapy in approximately two thirds of patients. The surgically more relevant parameter--distance between tumor and circumferential resection margin--can be accurately predicted. Errors were caused by the presence of considerable tumor, rectal wall fibrosis, and mucinous tumors.