How the Impact of Median Neuropathy on Sensorimotor Control Capability of Hands for Diabetes: An Achievable Assessment from Functional Perspectives

To comprehend the sensorimotor control ability in diabetic hands, this study investigated the sensation, motor function and precision pinch performances derived from a pinch-holding-up activity (PHUA) test of the hands of diabetic patients and healthy subjects. The precision, sensitivity and specificity of the PHUA test in the measurements of diabetic patients were also analyzed. We hypothesized that the diabetic hands would have impacts on the sensorimotor functions of the hand performances under functionally quantitative measurements. One hundred and fifty-nine patients with clinically defined diabetes mellitus (DM) and 95 age- and gender-matched healthy controls were included. Semmes-Weinstein monofilament (SWM), static and moving two-point discrimination (S2PD and M2PD), maximal pinch strength and precision pinch performance tests were conducted to evaluate the sensation, motor and sensorimotor status of the recruited hands. The results showed that there were significant differences (all p<0.05) in SWM, S2PD, M2PD and maximum pinch strength between the DM and control groups. A higher force ratio in the DM patients than in the controls (p<0.001) revealed a poor ability of pinch force adjustment in the DM patients. The percentage of maximal pinch strength was also significantly different (p<0.001) between the DM and control groups. The sensitivity, specificity and area under the receiver operating characteristic curve were 0.85, 0.51, and 0.724, respectively, for the PHUA test. Statistically significant degradations in sensory and motor functions and sensorimotor control ability were observed in the hands of the diabetic patients. The PHUA test could be feasibly used as a clinical tool to determine the sensorimotor function of the hands of diabetic patients from a functional perspective.     

Viral pathogen discovery

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Wavelet-based Gaussian-mixture hidden Markov model for the detection of multistage seizure dynamics: A proof-of-concept study

Background  

Epilepsy is a common neurological disorder characterized by recurrent electrophysiological activities, known as seizures. Without the appropriate detection strategies, these seizure episodes can dramatically affect the quality of life for those afflicted. The rationale of this study is to develop an unsupervised algorithm for the detection of seizure states so that it may be implemented along with potential intervention strategies.     

Structural analysis of papain-like NlpC/P60 superfamily enzymes with a circularly permuted topology reveals potential lipid binding sites

NlpC/P60 superfamily papain-like enzymes play important roles in all kingdoms of life. Two members of this superfamily, LRAT-like and YaeF/YiiX-like families, were predicted to contain a catalytic domain that is circularly permuted such that the catalytic cysteine is located near the C-terminus, instead of at the N-terminus. These permuted enzymes are widespread in virus, pathogenic bacteria, and eukaryotes. We determined the crystal structure of a member of the YaeF/YiiX-like family from Bacillus cereus in complex with lysine. The structure, which adopts a ligand-induced, "closed" conformation, confirms the circular permutation of catalytic residues. A comparative analysis of other related protein structures within the NlpC/P60 superfamily is presented. Permutated NlpC/P60 enzymes contain a similar conserved core and arrangement of catalytic residues, including a Cys/His-containing triad and an additional conserved tyrosine. More surprisingly, permuted enzymes have a hydrophobic S1 binding pocket that is distinct from previously characterized enzymes in the family, indicative of novel substrate specificity. Further analysis of a structural homolog, YiiX (PDB 2if6) identified a fatty acid in the conserved hydrophobic pocket, thus providing additional insights into possible function of these novel enzymes.     

Rac-1 Superactivation Triggers Insulin-independent Glucose Transporter 4 (GLUT4) Translocation That Bypasses Signaling Defects Exerted by c-Jun N-terminal kinase (JNK)- and Ceramide-induced Insulin Resistance

Insulin activates a cascade of signaling molecules, including Rac-1, Akt, and AS160, to promote the net gain of glucose transporter 4 (GLUT4) at the plasma membrane of muscle cells. Interestingly, constitutively active Rac-1 expression results in a hormone-independent increase in surface GLUT4; however, the molecular mechanism and significance behind this effect remain unresolved. Using L6 myoblasts stably expressing myc-tagged GLUT4, we found that overexpression of constitutively active but not wild-type Rac-1 sufficed to drive GLUT4 translocation to the membrane of comparable magnitude with that elicited by insulin. Stimulation of endogenous Rac-1 by Tiam1 overexpression elicited a similar hormone-independent gain in surface GLUT4. This effect on GLUT4 traffic could also be reproduced by acutely activating a Rac-1 construct via rapamycin-mediated heterodimerization. Strategies triggering Rac-1 “superactivation” (i.e. to levels above those attained by insulin alone) produced a modest gain in plasma membrane phosphatidylinositol 3,4,5-trisphosphate, moderate Akt activation, and substantial AS160 phosphorylation, which translated into GLUT4 translocation and negated the requirement for IRS-1. This unique signaling capacity exerted by Rac-1 superactivation bypassed the defects imposed by JNK- and ceramide-induced insulin resistance and allowed full and partial restoration of the GLUT4 translocation response, respectively. We propose that potent elevation of Rac-1 activation alone suffices to drive insulin-independent GLUT4 translocation in muscle cells, and such a strategy might be exploited to bypass signaling defects during insulin resistance.     

Responses of protocerebral neurons in Manduca sexta to sex-pheromone mixtures

Male Manduca sexta moths are attracted to a mixture of two components of the female’s sex pheromone at the natural concentration ratio. Deviation from this ratio results in reduced attraction. Projection neurons innervating prominent male-specific glomeruli in the male’s antennal lobe produce maximal synchronized spiking activity in response to synthetic mixtures of the two components centering around the natural ratio, suggesting that behaviorally effective mixture ratios are encoded by synchronous neuronal activity. We investigated the physiological activity and morphology of downstream protocerebral neurons that responded to antennal stimulation with single pheromone components and their mixtures at various concentration ratios. Among the tested neurons, only a few gave stronger responses to the mixture at the natural ratio whereas most did not distinguish among the mixtures that were tested. We also found that the population response distinguished among the two pheromone components and their mixtures, prior to the peak population response. This observation is consistent with our previous finding that synchronous firing of antennal-lobe projection neurons reaches its maximum before the firing rate reaches its peak. Moreover, the response patterns of protocerebral neurons are diverse, suggesting that the representation of olfactory stimuli at the level of protocerebrum is complex.     

Calculations of the φ -ψ Conformational Contour Maps for N-Acetyl Alanine N'-Methyl Amide and of the Characteristic Ratios of Poly-L-alanine Using Various Molecular Mechanics Forcefields

Abstract

We generated φ -ψ conformational energy contour maps for the of N-acetyl alanine N'-methyl amide using the molecular mechanics forcefields AMBER, AMBER3, BI085, CFF91, CVFF, MM2, MM3, MM+, and SYBYL. With MM2, MM3, and MM+, we used a dielectric constant of ? = 1.5, the default effective value for these forcefields. With the other forcefields we used ? = 1 and 4, except with SYBYL, which, in Spartan 3.1, has no electrostatic term. All forcefields yielded the C^eq ₇ conformation as a low-energy minimum or the global minimum. Most of the forcefields also yielded a minimum-energy conformation in the C₅,α_R, and α_t. regions of the φ -ψ contour map. Fewer of the forcefields yielded a minimum in the C^ax ₇ region; however, adiabatic relaxation frequently lowered the relative energy of this region. Based on the appearance of the φ -ψ maps, the following pairs of forcefields were broadly similar (but not identical) to each other but dissimilar to the other pairs: AMBER3 and AMBER, BI085 and CHARMM, MM+ and MM2, SYBYL and ECEPP, and CFF91 and MM3. We used the data from the φ -ψ contour maps to compute the characteristic ratio of poly-L-alanine. Most of the computed values deviated significantly from the experimental value. Only the computed characteristic ratio of CFF91 without adiabatic relaxation at ? = 4 and MM3 without adiabatic relaxation at ? = 1.5 agreed with the experimental value.