Sanderabbott0242

The speech-evoked auditory brainstem response (sABR) provides a measure of encoding complex stimuli in the brainstem, and this study employed the sABR to better understand the role of neural temporal jitter in the response patterns from older adults. In experiment 1, sABR recordings were used to investigate age-related differences in periodicity encoding of the temporal envelope and fine structure components of the response to a /da/speech token. A group of younger and a group of older adults (n = 22 per group) participated. The results demonstrated reduced amplitude of the fundamental frequency and harmonic components in the spectral domain of the recorded response of the older listeners. In experiment 2, a model of neural temporal jitter was employed to simulate in a group of young adults (n = 22) the response patterns measured from older adults. A small group of older adults (n = 7) were also tested under the jitter simulation conditions. In the young adults, the results showed a systematic reduction in the response amplitude of the most robust response components as the degree of applied jitter increased. In contrast, the older adults did not demonstrate significant response reduction when tested under jitter conditions. The overall pattern of results suggests that older adults have reduced neural synchrony for encoding periodic, complex signals at the level of the brainstem, and that this reduced synchrony can be modeled by simulating neural jitter via disruption of the temporal waveform of the stimulus.The association between idiopathic sudden sensorineural hearing loss (ISSNHL) and the radiologic characteristics of the vertebrobasilar artery is unclear. We hypothesized that the degree and direction of vertebrobasilar artery curvature in the posterior circulation contribute to the occurrence of ISSNHL. We consecutively enrolled patients diagnosed with unilateral ISSNHL in two tertiary hospitals. Magnetic resonance images were performed in all patients to exclude specific causes of ISSNHL, such as vestibular schwannoma, chronic mastoiditis, and anterior inferior cerebellar artery infarct. We measured the following parameters of posterior circulation vertebral and basilar artery diameter, the degree of basilar artery curvature (modified smoker criteria), and vertebral artery dominance. Pure tone audiometries were performed at admission and again 1 week and 3 months later. A total of 121 ISSNHL patients (mean age, 46.0 ± 17.3 years; 48.8% male) were included in these analyses. The proportion of patients with the left side hearing loss was larger than the proportion with the right side hearing loss (left, 57.9%; right, 42.1%). The majority of patients were characterized by a left dominant vertebral artery and right-sided basilar artery curvature. The direction of the basilar artery curvature was significantly associated with hearing loss lateralization (p = 0.036). Age and sex matched multivariable analyses revealed the absence of diabetes and right-sided basilar artery curvature as significant predictors for left sided hearing loss. There was no statistical difference between atherosclerotic cardiovascular risk score (high versus low) and hearing outcomes at 3 months. In ISSNHL, the laterality of hearing loss was inversely associated with the direction of basilar artery curvature. Our results, therefore, indicate the importance of vascular assessment when evaluating ISSNHL.We examined the effect of boundary conditions in imitation ski jumping on movement dynamics and coordination. We compared imitation ski jumps with--and without--the possibility to generate shear propulsion forces. Six elite ski jumpers performed imitation jumps by jumping from a fixed surface and from a rolling platform. The ground reaction force vector, kinematics of body segments, and EMG of eight lower limb muscles were recorded. Net joint dynamics were calculated using inverse dynamics. The two imitation jumps differed considerably from each other with regard to the dynamics (moments, forces), whereas the kinematics were very similar. Knee power was higher and hip power was lower on the rolling platform than on the fixed surface. Mean EMG levels were very similar for both conditions, but differences in the development of muscle activity were indicated for seven of eight muscles. These differences are reflected in a subtle difference of the alignment of ground reaction force with centre of mass the ground reaction force runs continuously close to but behind the centre of mass on the rolling platform and fluctuates around it on the fixed surface. This likely reflects a different strategy for controlling angular momentum.Acute limb ischemia is a common cause of morbidity and mortality following trauma both in civilian centers and in combat related injuries. buy Entinostat Rapid determination of tissue viability and surgical restoration of blood flow are desirable, but not always possible. We sought to characterize the response to increasing periods of hind limb ischemia in a porcine model such that we could define a period of critical ischemia (the point after which irreversible neuromuscular injury occurs), evaluate non-invasive methods for characterizing that ischemia, and establish a model by which we could predict whether or not the animal's locomotion would return to baselines levels post-operatively. Ischemia was induced by either application of a pneumatic tourniquet or vessel occlusion (performed by clamping the proximal iliac artery and vein at the level of the inguinal ligament). The limb was monitored for the duration of the procedure with both 3-charge coupled device (3CCD) and infrared (IR) imaging for tissue oxygenation and peefore critical ischemia.In this study, levels and estimated daily intake (EDI) of two toxic elements, Cd and Pb, and eight essential elements Ca, P, Zn, Mn, Co, Cu, Se and Mo, were determined in Nigerian rice samples. The mean levels of Cd, Pb and Co were 5.43±0.88, 38.66±5.42, 25.8±3.18 ng/g. The mean levels of Ca, P, Zn, Mn, Cu, Se and Mo were 71.5±7.31, 951±52.0, 10.2±0.63, 8.5±0.47, 3.07±0.18, 40.1±9.2 and 0.39±0.05 µg/g, respectively. The percentage contribution to the reference values for each element was 0.54, 7.71, 0.38, 9.51, 8.97, 31.3, 30.7, 5.1 and 60.7% for Cd, Pb, Ca, P, Zn, Mn, Cu, Se and Mo, respectively. The elemental nutrient levels in Nigerian rice samples are comparable to those obtained from other regions and their consumption does not pose any serious health risk to consumers.The Fe(II)- and 2-oxoglutarate (2-OG)-dependent dioxygenases comprise a large and diverse enzyme superfamily the members of which have multiple physiological roles. Despite this diversity, these enzymes share a common chemical mechanism and a core structural fold, a double-stranded β-helix (DSBH), as well as conserved active site residues. The prolyl hydroxylases are members of this large superfamily. Prolyl hydroxylases are involved in collagen biosynthesis and oxygen sensing in mammalian cells. Structural-mechanistic studies with prolyl hydroxylases have broader implications for understanding mechanisms in the Fe(II)- and 2-OG-dependent dioxygenase superfamily. Here, we describe crystal structures of an N-terminally truncated viral collagen prolyl hydroxylase (vCPH). The crystal structure shows that vCPH contains the conserved DSBH motif and iron binding active site residues of 2-OG oxygenases. Molecular dynamics simulations are used to delineate structural changes in vCPH upon binding its substrate. Kinetic investigations are used to report on reaction cycle intermediates and compare them to the closest homologues of vCPH. The study highlights the utility of vCPH as a model enzyme for broader mechanistic analysis of Fe(II)- and 2-OG-dependent dioxygenases, including those of biomedical interest.Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.We investigated whether ethnic differences in handgrip strength, a marker of poor muscle strength and quality, is a potential cause of ethnic disparities in type 2 diabetes mellitus. We included 2086 Dutch, 2216 South Asian Surinamese, 2084 African Surinamese, 1786 Ghanaian, 2223 Turkish and 2199 Moroccan origin participants from the HELIUS study. We analyzed ethnic differences in handgrip strength, and its association with type 2 diabetes mellitus using logistic regression analyses adjusted for socio-demographic factors, body composition and lifestyle factors. Additionally, we investigated whether handgrip strength explained the ethnic differences in type 2 diabetes mellitus. We found that handgrip strength differed significantly across ethnic groups. After full adjustment, we found an inverse association with type 2 diabetes mellitus (OR 0.95; 95% CI 0.92-0.97) that did not differ substantially between ethnic groups, men and among women, and lean and overweight individuals. The association was not affected by the measure used to define type 2 diabetes mellitus, but was attenuated by exclusion of people with known diabetes. The ethnic differences in type 2 diabetes mellitus were not explained by handgrip strength (e.g. the OR for the South Asian Surinamese vs. Dutch changed from 5.03; 3.69-6.68 to 4.87; 3.57-6.65). In conclusion, we found large ethnic differences in handgrip strength and a consistent association of low handgrip strength with prevalent type 2 diabetes mellitus. This suggests that handgrip strength may be investigated as a target for intervention or a marker to identify people at risk of type 2 diabetes mellitus.