Hypoxia induces no change in cutaneous thresholds for warmth and cold sensation

Hypoxia can affect perception of temperature stimuli by impeding thermoregulation at a neural level. Whether this impact on the thermoregulatory response is solely due to affected thermoregulation is not clear, since reaction time may also be affected by hypoxia. Therefore, we studied the effect of hypoxia on thermal perception thresholds for warmth and cold. Thermal perception thresholds were determined in 11 healthy overweight adult males using two methods for small nerve fibre functioning: a reaction-time inclusive method of limits (MLI) and a reaction time exclusive method of levels (MLE). The subjects were measured under normoxic and hypoxic conditions using a cross-over design. Before the thermal threshold tests under hypoxic conditions were conducted, the subjects were acclimatized by staying 14 days overnight (8 h) in a hypoxic tent system (Colorado Altitude Training: 4,000 m). For normoxic measurements the same subjects were not acclimatized, but were used to sleep in the same tent system. Measurements were performed in the early morning in the tent. Normoxic MLI cold sensation threshold decreased significantly from 30.3 ± 0.4 (mean ± SD) to 29.9 ± 0.7°C when exposed to hypoxia (P < 0.05). Similarly, mean normoxic MLI warm sensation threshold increased from 34.0 ± 0.9 to 34.5 ± 1.1°C (P < 0.05). MLE measured threshold for cutaneous cold sensation was 31.4 ± 0.4 and 31.2 ± 0.9°C under respectively normoxic and hypoxic conditions (P > 0.05). Neither was there a significant change in MLE warm threshold comparing normoxic (32.8 ± 0.9°C) with hypoxic condition (32.9 ± 1.0°C) (P > 0.05). Exposure to normobaric hypoxia induces slowing of neural activity in the sensor-to-effector pathway and does not affect cutaneous sensation threshold for either warmth or cold detection

Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men

AIMS/HYPOTHESIS: Obesity is characterised by increased triacylglycerol storage in adipose tissue. There is in vitro evidence for a blunted beta-adrenergically mediated lipolytic response in abdominal subcutaneous adipose tissue (SAT) of obese individuals and evidence for this at the whole-body level in vivo. We hypothesised that the beta-adrenergically mediated effect on lipolysis in abdominal SAT is also impaired in vivo in obese humans. METHODS: We investigated whole-body and abdominal SAT glycerol metabolism in vivo during 3 h and 6 h [2H5]glycerol infusions. Arterio-venous concentration differences were measured in 13 lean and ten obese men after an overnight fast and during intravenous infusion of the non-selective beta-adrenergic agonist isoprenaline [20 ng (kg fat free mass)(-1) min(-1)]. RESULTS: Lean and obese participants showed comparable fasting glycerol uptake by SAT (9.7+/-3.4 vs 9.3+/-2.5% of total release, p=0.92). Furthermore, obese participants showed an increased whole-body beta-adrenergically mediated lipolytic response versus lean participants. However, their fasting lipolysis was blunted [glycerol rate of appearance: 7.3+/-0.6 vs 13.1+/-0.9 micromol (kg fat mass)(-1) min(-1), p<0.01], as was the beta-adrenergically mediated lipolytic response per unit SAT [Delta total glycerol release: 140+/-71 vs 394+/-112 nmol (100 g tissue)(-1) min(-1), p<0.05] compared with lean participants. Net triacylglycerol flux tended to increase in obese compared with lean participants during beta-adrenergic stimulation [Delta net triacylglycerol flux: 75+/-32 vs 16+/-11 nmol (100 g tissue)(-1) min(-1), p=0.06]. CONCLUSIONS/INTERPRETATION: We demonstrated in vivo that beta-adrenergically mediated lipolytic response is impaired systematically and in abdominal SAT of obese versus lean men. This may be important in the development or maintenance of increased triacylglycerol stores and obesity

Default Mode Network Connectivity and Social Dysfunction in Major Depressive Disorder

Though social functioning is often hampered in Major Depressive Disorder (MDD), we lack a complete and integrated understanding of the underlying neurobiology. Connectional disturbances in the brain’s Default Mode Network (DMN) might be an associated factor, as they could relate to suboptimal social processing. DMN connectional integrity, however, has not been explicitly studied in relation to social dysfunctioning in MDD patients. Applying Independent Component Analysis and Dual Regression on resting-state fMRI data, we explored DMN intrinsic functional connectivity in relation to social dysfunctioning (i.e. composite of loneliness, social disability, small social network) among 74 MDD patients (66.2% female, Mean age = 36.9, SD = 11.9). Categorical analyses examined whether DMN connectivity differs between high and low social dysfunctioning MDD groups, dimensional analyses studied linear associations between social dysfunction and DMN connectivity across MDD patients. Threshold-free cluster enhancement (TFCE) with family-wise error (FWE) correction was used for statistical thresholding and multiple comparisons correction (P < 0.05). The analyses cautiously linked greater social dysfunctioning among MDD patients to diminished DMN connectivity, specifically within the rostromedial prefrontal cortex and posterior superior frontal gyrus. These preliminary findings pinpoint DMN connectional alterations as potentially germane to social dysfunction in MDD, and may as such improve our understanding of the underlying neurobiology

Anti‐cN‐1A autoantibodies are absent in juvenile dermatomyositis

Objectives: To assess anti‐cytosolic 5′‐nucleotidase 1A (cN‐1A/NTC51A) autoantibodies in children with juvenile dermatomyositis (JDM) and healthy controls, using three different methods of antibody detection, as well as verification of the results in an independent cohort. / Methods: Anti‐cN‐1A reactivity was assessed in 34 Dutch JDM patients and 20 healthy juvenile controls by a commercially available full‐length cN‐1A ELISA, a synthetic peptide ELISA and by immunoblotting using a lysate from cN‐1A expressing HEK‐293 cells. Sera from JDM patients with active disease and in remission were analysed. An independent British cohort of 110 JDM patients and 43 healthy juvenile controls was assessed by an in‐house full‐length cN‐1A ELISA. / Results: Anti‐cN‐1A reactivity was not present in JDM patients’ sera or in healthy controls when tested with the commercially available full‐length cN‐1A ELISA or by immunoblotting, both in active disease and in remission. Also, in the British JDM cohort anti‐cN‐1A reactivity was not detected. Three Dutch JDM patients tested weakly positive for one of the three synthetic cN‐1A peptides measured by ELISA. / Conclusion: JDM patients and young healthy individuals do not show anti‐cN‐1A reactivity as assessed by different antibody detection techniques

Prorenin anno 2008

For many years, prorenin has been considered to be nothing more than the inactive precursor of renin. Yet, its elevated levels in diabetic subjects with microvascular complications and its extrarenal production at various sites in the body suggest otherwise. This review discusses the origin, regulation, and enzymatic activity of prorenin, its role during renin inhibition, and the angiotensin-dependent and angiotensin-independent consequences of its binding to the recently discovered (pro)renin receptor. The review ends with the concept that prorenin rather than renin determines tissue angiotensin generation

Systematic Control of the Orientation of Organic Phosphorescent Pt Complexes in Thin Films for Increased Optical Outcoupling

Orienting light‐emitting molecules relative to the substrate is an effective method to enhance the optical outcoupling of organic light‐emitting devices. Platinum(II) phosphorescent complexes enable facile control of the molecular alignment due to their planar structures. Here, the orientation of Pt(II) complexes during the growth of emissive layers is controlled by two different methods: modifying the molecular structure and using structural templating. Molecules whose structures are modified by adjusting the diketonate ligand of the Pt complex, dibenzo‐(f,h)quinoxaline Pt dipivaloylmethane, (dbx)Pt(dpm), show an ≈20% increased fraction of horizontally aligned transition dipole moments compared to (dbx)Pt(dpm) doped into a 4,4′‐bis(N‐carbazolyl)‐1,1′‐biphenyl, CBP, host. Alternatively, a template composed of highly ordered 3,4,9,10‐perylenetetracarboxylic dianhydride monolayers is predeposited to drive the alignment of a subsequently deposited emissive layer comprising (2,3,7,8,12,13,17,18‐octaethyl)‐21H,23H‐porphyrinplatinum(II) doped into triindolotriazine. This results in a 60% increase in horizontally aligned transition dipole moments compared to the film deposited in the absence of the template. The findings provide a systematic route for controlling molecular alignment during layer growth, and ultimately to increase the optical outcoupling in organic light‐emitting diodes.Pt(II) complex orientation is controlled by modifying the molecular structure and structural templating. Molecules with modified structures show ≈20% increased fraction of horizontally aligned transition dipole moments (TDMs) when doped into a host. Alternatively, a highly ordered molecular template drives the alignment of a subsequently deposited polycrystalline emissive layer, showing a 60% increase in horizontally aligned TDMs versus without template.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151333/1/adma201900921.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151333/2/adma201900921_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151333/3/adma201900921-sup-0001-S1.pd

Endocrine responses during overnight recovery from exercise:Impact of nutrition and relationships with muscle protein synthesis

Nocturnal endocrine responses to exercise performed in the evening and the potential role of nutrition are poorly understood. To gain novel insight, 10 healthy men ingested carbohydrate with (C+P) and without (C) protein in a randomized order and double-blind manner during 2 hr of interval cycling followed by resistancetype exercise and into early postexercise recovery. Blood samples were obtained hourly throughout 9 hr of postexercise overnight recovery for analysis of key hormones. Muscle samples were taken from the vastus lateralis before and after exercise and then again the next morning (7 a.m.) to calculate mixed-muscle protein fractional synthetic rate (FSR). Overnight plasma hormone concentrations were converted into overall responses (expressed as area under the concentration curve) and did not differ between treatments for either growth hormone (1,464 ± 257 vs. 1,432 ± 164 pg/ml · 540 min) or total testosterone (18.3 ± 1.2 vs. 17.9 ± 1.2 nmol/L · 540 min, C and C+P, respectively). In contrast, the overnight cortisol response was higher with C+P (102 ± 11 nmol/L · 540 min) than with C (81 ± 8 nmol/L · 540 min; p = .02). Mixed-muscle FSR did not differ between C and C+P during overnight recovery (0.062% ± 0.006% and 0.062% ± 0.009%/hr, respectively) and correlated significantly with the plasma total testosterone response (r = .7, p < .01). No correlations with FSR were apparent for the response of growth hormone (r = –.2, p = .4), cortisol (r = .1, p = .6), or the ratio of testosterone to cortisol (r = .2, p = .5). In conclusion, protein ingestion during and shortly afte

Structural study of GaSb/AlSb strained-layer superlattice

Owing to the lattice mismatch between GaSb and AlSb, a superlattice consisting of alternating layers of these materials will be strained. We have carried out ion-channeling measurements by backscattering of 1.76-MeV He ions, and present an experimental procedure and a data-analysis technique to measure the difference in strain between the two individual layers of the superlattice. The data analysis is based on computer simulations of channeling, the accuracy of which is supported by the many fine details of the experiments reproduced in the simulations. X-ray rocking-curve analysis yielded detailed profiles of strains in directions perpendicular and parallel to the surface. The x-ray value for the strain present at an unirradiated spot on the crystal is in excellent agreement with the value calculated by elasticity theory. In the bombarded region, the values of strain are less than the value calculated by elasticity theory. It appears that bombardment by the He ions reduced the strain by 50% and created lateral inhomogeneities in the crystal structure