A novel mutation (c. 341A>G) in the SRY gene in a 46,XY female patient with gonadal dysgenesis

SRY (sex-determining region Y) gene, MIM 480000, NM_005634) is crucial for sex differentiation which encodes the protein responsible for initiating testis differentiation. SRY mutations are associated with the presence of XY gonadal dysgenesis symptoms.     

Overweight People Have Low Levels of Implicit Weight Bias,but Overweight Nations Have High Levels of Implicit Weight Bias

Although a greater degree of personal obesity is associated with weaker negativity toward overweight people on both explicit (i.e., self-report) and implicit (i.e., indirect behavioral) measures, overweight people still prefer thin people on average. We investigated whether the national and cultural context – particularly the national prevalence of obesity – predicts attitudes toward overweight people independent of personal identity and weight status. Data were collected from a total sample of 338,121 citizens from 71 nations in 22 different languages on the Project Implicit website (https://implicit.harvard.edu/) between May 2006 and October 2010. We investigated the relationship of the explicit and implicit weight bias with the obesity both at the individual (i.e., across individuals) and national (i.e., across nations) level. Explicit weight bias was assessed with self-reported preference between overweight and thin people; implicit weight bias was measured with the Implicit Association Test (IAT). The national estimates of explicit and implicit weight bias were obtained by averaging the individual scores for each nation. Obesity at the individual level was defined as Body Mass Index (BMI) scores, whereas obesity at the national level was defined as three national weight indicators (national BMI, national percentage of overweight and underweight people) obtained from publicly available databases. Across individuals, greater degree of obesity was associated with weaker implicit negativity toward overweight people compared to thin people. Across nations, in contrast, a greater degree of national obesity was associated with stronger implicit negativity toward overweight people compared to thin people. This result indicates a different relationship between obesity and implicit weight bias at the individual and national levels.     

Perception of Human-Derived Risk Influences Choice at Top of the Food Chain

On human-used landscapes, animal behavior is a trade-off between maximizing fitness and minimizing human-derived risk. Understanding risk perception in wildlife can allow mitigation of anthropogenic risk, with benefits to long-term animal fitness. Areas where animals choose to rest should minimize risk from predators, which for large carnivores typically equate to humans. We hypothesize that high human activity leads to selection for habitat security, whereas low activity enables trading security for forage. We investigated selection of resting (bedding) sites by GPS radiocollared adult grizzly bears (n = 10) in a low density population on a multiple-use landscape in Canada. We compared security and foods at resting and random locations while accounting for land use, season, and time of day. On reclaimed mines with low human access, bears selected high horizontal cover far from trails, but did not avoid open (herbaceous) areas, resting primarily at night. In protected areas bears also bedded at night, in areas with berry shrubs and Hedysarum spp., with horizontal cover selected in the summer, during high human access. On public lands with substantial human recreation, bears bedded at day, selected resting sites with high horizontal cover in the summer and habitat edges, with bedding associated with herbaceous foods. These spatial and temporal patterns of selection suggest that bears perceive human-related risk differentially in relation to human activity level, season and time of day, and employ a security-food trade-off strategy. Although grizzly bears are presently not hunted in Alberta, their perceived risks associated with humans influence resting-site selection.     

ICA Extracts Epileptic Sources from fMRI in EEG-Negative Patients: A Retrospective Validation Study

Simultaneous EEG-fMRI has proven to be useful in localizing interictal epileptic activity. However, the applicability of traditional GLM-based analysis is limited as interictal spikes are often not seen on the EEG inside the scanner. Therefore, we aim at extracting epileptic activity purely from the fMRI time series using independent component analysis (ICA). To our knowledge, we show for the first time that ICA can find sources related to epileptic activity in patients where no interictal spikes were recorded in the EEG. The epileptic components were identified retrospectively based on the known localization of the ictal onset zone (IOZ). We demonstrate that the selected components truly correspond to epileptic activity, as sources extracted from patients resemble significantly better the IOZ than sources found in healthy controls. Furthermore, we show that the epileptic components in patients with and without spikes recorded inside the scanner resemble the IOZ in the same degree. We conclude that ICA of fMRI has the potential to extend the applicability of EEG-fMRI for presurgical evaluation in epilepsy.     

Discerning Apical and Basolateral Properties of HT-29/B6 and IPEC-J2 Cell Layers by Impedance Spectroscopy,Mathematical Modeling and Machine Learning

Quantifying changes in partial resistances of epithelial barriers in vitro is a challenging and time-consuming task in physiology and pathophysiology. Here, we demonstrate that electrical properties of epithelial barriers can be estimated reliably by combining impedance spectroscopy measurements, mathematical modeling and machine learning algorithms. Conventional impedance spectroscopy is often used to estimate epithelial capacitance as well as epithelial and subepithelial resistance. Based on this, the more refined two-path impedance spectroscopy makes it possible to further distinguish transcellular and paracellular resistances. In a next step, transcellular properties may be further divided into their apical and basolateral components. The accuracy of these derived values, however, strongly depends on the accuracy of the initial estimates. To obtain adequate accuracy in estimating subepithelial and epithelial resistance, artificial neural networks were trained to estimate these parameters from model impedance spectra. Spectra that reflect behavior of either HT-29/B6 or IPEC-J2 cells as well as the data scatter intrinsic to the used experimental setup were created computationally. To prove the proposed approach, reliability of the estimations was assessed with both modeled and measured impedance spectra. Transcellular and paracellular resistances obtained by such neural network-enhanced two-path impedance spectroscopy are shown to be sufficiently reliable to derive the underlying apical and basolateral resistances and capacitances. As an exemplary perturbation of pathophysiological importance, the effect of forskolin on the apical resistance of HT-29/B6 cells was quantified.     

The Phr1 Ubiquitin Ligase Promotes Injury-Induced Axon Self-Destruction

1. Download : Download full-size image

     

Rates of unfolding, rather than refolding, determine thermal stabilities of thermophilic, mesophilic, and psychrotrophic 3-isopropylmalate dehydrogenases

The relationship between the thermal stability of proteins and rates of unfolding and refolding is still an open issue. The data are very scarce, especially for proteins with complex structure. Here, time-dependent denaturation-renaturation experiments on Thermus thermophilus, Escherichia coli, and Vibrio sp. I5 3-isopropylmalate dehydrogenases (IPMDHs) of different heat stabilities are presented. Unfolding, as monitored by several methods, occurs in a single first-order step with half-times of approximately 1 h, several minutes, and few seconds for the thermophilic, mesophilic, and psychrotrophic enzymes, respectively. The binding of Mn*IPM (the manganese complex of 3-isopropylmalate) markedly reduces the rates of unfolding; this effect is more prominent for the less stable enzyme variants. Refolding is a two-step or multistep first-order process involving an inactive intermediate(s). The restoration of the native structure and reactivation take place with a half-time of a few minutes for all three IPMDHs. Thus, the comparative experimental unfolding-refolding studies of the three IPMDHs with different thermostabilities have revealed a close relationship between thermostability and unfolding rate. Structural analysis has shown that the differences in the molecular contacts between selected nonconserved residues are responsible for the different rates of unfolding. On the other hand, the folding rates might be correlated with the absolute contact order, which does not significantly vary between IPMDHs with different thermostabilities. On the basis of our observations, folding rates appear to be dictated by global structural characteristics (such as native topology, i.e., contact order) rather than by thermodynamic stability.     

Insulinoma--diagnosis and treatment

Insulinomas are the most common functioning endocrine tumors of pancreas. Approximately 10% are multiple, less than 10% can be malignant and 5-10% associated with the MEN-1 syndrome. Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. The aim of this lecture is to present the up-to-date information concerning the prevalence, diagnosis and treatment of insulinoma.     

Octreotide suppression test in diagnosing and predicting the outcome of therapy in patients with neuroendocrine tumors. Preliminary report

INTRODUCTION: Chromogranin A (CgA) is a non-specific marker of neuroendocrine tumors (NET) and is important in monitoring the disease course and NET treatment. AIM OF THE STUDY: Usefulness of suppression test of CgA secretion with octreotide in diagnosis and predicting the therapy outcome in NET patients. MATERIAL AND METHODS: The study included 32 patients with NET of gastrointestinal tract, lung and of unknown origin. CgA level in blood plasma on fasting, before and 30, 60, 90 and 120 minutes after subcutaneous administration of 100 mug octreotide, was determined in all patients. The subjects were divided into two subgroups with relation to CgA level and to the results of somatostatin receptor scintigraphy (SRS). RESULTS: Statistically significant CgA decrease after octreotide administration in all study time points and positive results of SRS were found in the patients with the elevated CgA level. No statistically significant decrease of CgA level after octreotide was found in the group with normal CgA levels. In this group, 13 patients had a negative result of SRS, and somatostatin receptors expression was found in one patient. Tolerance of somatostatin analogs (SSA) therapy was very good. CONCLUSIONS: Octreotide suppression test with CgA level assessment in NET patients is a simple, straightforward examination, providing information on the predicted response to the applied SSA and the data on initial clinical tolerance of those agents. This examination can also be a screening test useful in planning the treatment with SSA in patients with NET.