Indices of adrenal cortical activity in men exposed to cold

Thesis (M.A.)--Boston UniversityEvidence of physiological acclimatization of man to cold is scanty and not clear-cut. Certainly no adaptations have been described comparable to the dramatic changes which occur when men are acclimatized to heat. This study is an attempt to demonstrate acclimatization to cold in man, not in terms of indices specific for cold stress, but rather by measurement of the systemic strain placed on the body. Experiments were designed to answer two questions: (a) Does cold exposure result in a systemic strain on the body? and (b) Does continued cold exposure give rise to (unknown) specific physiologic a aptations with a consequent reduced strain? Since stimulation of tne pituitary-adrenal cortical axis seems to be a common denominator in all known stress situations, adrenal cortical activity was used as a measure of the degree of distortion to the homeostasis. The following experimental design was used: Twelve young soldiers previously brought into good physical condition by mild exercise were exposed to the following successive sets of conditions: four weeks of no cold exposure (baseline period) during which control measurements were made; twelve consecutive days of continuous cold exposure at 60°F.; nine days of no cold exposure; five days of re-exposure to cold (60°F.); five days of no cold exposure. Adrenal cortical activity was assessed by means of circulating eosinophil counts and urinary uric acid: creatinine ratios. During cold exposure periods the men remained continuously in the cold room, leaving it only for meals, bathing and control procedures (a total of 4 1/4 hours daily). They reclined nude except for cotton shorts on army beds from 8:00 A.M. till noon and from 1:15 P.M. till 4:30 P.M. In order to obtain comparable conditions throughout all experimental periods for the assessment of basal levels of adrenal cortical activity, the men lay quietly from 7:00- 8:00A.M. in a constant temperature room maintained at 85°F. +/- 1°F.; at the end of this hour, urine was collected and blood drawn. These samples also served as controls for the measurement of acute responses after four hours in the cold. Sixty degrees Fahrenheit was selected as the cold temperature because it eliminated the danger of cold injury, making it unnecessary to rewarm the men periodically or to clothe them. It was deemed an adequate stimulus because men exhibit the usual cold responses at this temperature - shivering, diuresis, hemoconcentration and peripheral vasoconstriction - within 45 minutes to two hours after the start of exposure. Furthermore preliminary experiments showed this temperature to produce marked discomfort which, however, was tolerable for prolonged periods. The following results were obtained: 1. There was a significant depression of basal eosinophil counts on the fourth and eighth days of the first cold period, with a return to approximately control levels on the eleventh day. 2. A "rebound" of basal eosinophil counts to levels significantly above controls was observed in the nine-day period between cold exposures. 3. Eosinophil counts taken on the fourth day of re-exposure were not significantly different from controls, but were significantly below "rebound" values. 4. No marked differences from normal diurnal variation were observed in the eosinophil counts after four hours of cold exposure at 60°F. 5. No trends were observed in basal uric acid: creatinine ratios. 6. During acute four-hour exposure, uric acid: creatinine ratios were significantly higher than controls. Although no correlation existed between eosinophil and (U-A)/C changes, there was a significant correlation between rate of urine flow and (U-A)/C. Although both eosinophil counts and uric acid: creatinine ratios are preserved to measure activity related to 11-oxygenated corticosteroids, the results show a qualitative difference between the two indices. The eosinophil data indicate changes in basal activity but no marked response to acute exposure, whereas the (U-A)/C data suggest acute responses but no change in basal levels. This confirms the findings of previous workers of a lack of parallelism between these indices in conditions of mild stress. The changes in basal eosinophil counts suggest positive findings of acclimatization to cold. The significant decreases on the fourth and eighth days of exposure indicate increased adrenal cortical activity; the return toward pre-exposure levels on the eleventh day suggest a return of activity toward normal. These results are consistent with, but do not prove, the thesis that cold exposure under the conditions described results in a systemic strain on the body, and that the strain is lessened on extended exposure. This suggests that physiological acclimatization to cold occurs. These conclusions are based on assumptions that (a) changes in circulating eosinophil counts reflect changes in adrenal cortical activity and (b) changes in such activity are a measure of the severity of strain placed on the body

Optical Properties of Epitaxial Single-Crystal Chemical-Vapor-Deposited Diamond

Epitaxial single-crystal chemical-vapor-deposited diamond was obtained from Element Six Ltd. (Ascot, UK) and from Apollo Diamond (Boston, MA). Both companies provided 5 x 5 mm squares with thicknesses ranging from 0.5 to 1.5 mm. In addition, Element Six provided 10-mm-diameter disks with a thickness of 1.0 mm. The absorptance of all specimens at 1064 nm was measured by laser calorimetry, with good agreement between independent measurements at the University of Central Florida and at QinetiQ (Malvern, UK). Depolarization at 1064 nm and ultraviolet absorption properties are also reported

Association Between Cytokines and Liver Histology in Children with Nonalcoholic Fatty Liver Disease.

BackgroundReliable non-invasive markers to characterize inflammation, hepatocellular ballooning, and fibrosis in nonalcoholic fatty liver disease (NAFLD) are lacking. We investigated the relationship between plasma cytokine levels and features of NAFLD histology to gain insight into cellular pathways driving NASH and to identify potential non-invasive discriminators of NAFLD severity and pattern.MethodsCytokines were measured from plasma obtained at enrollment in pediatric participants in NASH Clinical Research Network studies with liver biopsy-proven NAFLD. Cytokines were chosen a priori as possible discriminators of NASH and its components. Minimization of Akaike Information Criterion (AIC) was used to determine cytokines retained in multivariable models.ResultsOf 235 subjects, 31% had "Definite NASH" on liver histology, 43% had "Borderline NASH", and 25% had NAFLD but not NASH. Total plasminogen activator inhibitor 1 (PAI1) and activated PAI1 levels were higher in pediatric participants with Definite NASH and with lobular inflammation. Interleukin-8 (IL-8) was higher in those with stage 3-4 fibrosis and lobular inflammation. sIL-2rα was higher in children with stage 3-4 fibrosis and portal inflammation. In multivariable analysis, PAI1 variables were discriminators of Borderline/Definite NASH, definite NASH, lobular inflammation and ballooning. IL-8 increased with steatosis and fibrosis severity; sIL-2rα increased with fibrosis severity and portal inflammation. IL-7 decreased with portal inflammation and fibrosis severity.ConclusionsPlasma cytokines associated with histology varied considerably among NASH features, suggesting promising avenues for investigation. Future, more targeted analysis is needed to identify the role of these markers in NAFLD and to evaluate their potential as non-invasive discriminators of disease severity

Pgc-1α Overexpression Downregulates Pitx3 and Increases Susceptibility to MPTP Toxicity Associated with Decreased Bdnf

Multiple mechanisms likely contribute to neuronal death in Parkinson’s disease (PD), including mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1α) positively regulates the expression of genes required for mitochondrial biogenesis and the cell’s antioxidant responses. Also, expression of PGC-1α-regulated genes is low in substantia nigra (SN) neurons in early PD. Thus upregulation of PGC-1α is a candidate neuroprotective strategy in PD. Here, an adeno-associated virus (AAV) was used to induce unilateral overexpression of Pgc-1α, or a control gene, in the SN of wild-type C57BL/6CR mice. Three weeks after AAV administration, mice were treated with saline or MPTP. Overexpression of Pgc-1α in the SN induced expression of target genes, but unexpectedly it also greatly reduced the expression of tyrosine hydroxylase (Th) and other markers of the dopaminergic phenotype with resultant severe loss of striatal dopamine. Reduced Th expression was associated with loss of Pitx3, a transcription factor that is critical for the development and maintenance of dopaminergic cells. Expression of the neurotrophic factor Bdnf, which also is regulated by Pitx3, similarly was reduced. Overexpression of Pgc-1α also led to increased sensitivity to MPTP-induced death of Th+ neurons. Pgc-1α overexpression alone, in the absence of MPTP treatment, did not lead to cell loss in the SN or to loss of dopaminergic terminals. These data demonstrate that overexpression of Pgc-1α results in dopamine depletion associated with lower levels of Pitx3 and enhances susceptibility to MPTP. These data may have ramifications for neuroprotective strategies targeting overexpression of PGC-1α in PD

Surface properties of Mars' polar layered deposits and polar landing sites

On December 3, 1999, the Mars Polar Lander and Mars Microprobes will land on the planet's south polar layered deposits near (76°S, 195°W) and conduct the first in situ studies of the planet's polar regions. The scientific goals of these missions address several poorly understood and globally significant issues, such as polar meteorology, the composition and volatile content of the layered deposits, the erosional state and mass balance of their surface, their possible relationship to climate cycles, and the nature of bright and dark aeolian material. Derived thermal inertias of the southern layered deposits are very low (50–100 J m^(−2) s^(−1/2) K^(−1)), suggesting that the surface down to a depth of a few centimeters is generally fine grained or porous and free of an appreciable amount of rock or ice. The landing site region is smoother than typical cratered terrain on ∼1 km pixel^(−1) Viking Orbiter images but contains low-relief texture on ∼5 to 100 m pixel^(−1) Mariner 9 and Mars Global Surveyor images. The surface of the southern deposits is older than that of the northern deposits and appears to be modified by aeolian erosion or ablation of ground ice

Novel virus discovery and genome reconstruction from field RNA samples reveals highly divergent viruses in dipteran hosts.

We investigated whether small RNA (sRNA) sequenced from field-collected mosquitoes and chironomids (Diptera) can be used as a proxy signature of viral prevalence within a range of species and viral groups, using sRNAs sequenced from wild-caught specimens, to inform total RNA deep sequencing of samples of particular interest. Using this strategy, we sequenced from adult Anopheles maculipennis s.l. mosquitoes the apparently nearly complete genome of one previously undescribed virus related to chronic bee paralysis virus, and, from a pool of Ochlerotatus caspius and Oc. detritus mosquitoes, a nearly complete entomobirnavirus genome. We also reconstructed long sequences (1503-6557 nt) related to at least nine other viruses. Crucially, several of the sequences detected were reconstructed from host organisms highly divergent from those in which related viruses have been previously isolated or discovered. It is clear that viral transmission and maintenance cycles in nature are likely to be significantly more complex and taxonomically diverse than previously expected

Dissipative Chaos in Semiconductor Superlattices

We consider the motion of ballistic electrons in a miniband of a semiconductor superlattice (SSL) under the influence of an external, time-periodic electric field. We use the semi-classical balance-equation approach which incorporates elastic and inelastic scattering (as dissipation) and the self-consistent field generated by the electron motion. The coupling of electrons in the miniband to the self-consistent field produces a cooperative nonlinear oscillatory mode which, when interacting with the oscillatory external field and the intrinsic Bloch-type oscillatory mode, can lead to complicated dynamics, including dissipative chaos. For a range of values of the dissipation parameters we determine the regions in the amplitude-frequency plane of the external field in which chaos can occur. Our results suggest that for terahertz external fields of the amplitudes achieved by present-day free electron lasers, chaos may be observable in SSLs. We clarify the nature of this novel nonlinear dynamics in the superlattice-external field system by exploring analogies to the Dicke model of an ensemble of two-level atoms coupled with a resonant cavity field and to Josephson junctions.Comment: 33 pages, 8 figure

Human Gene-Centered Transcription Factor Networks for Enhancers and Disease Variants

SummaryGene regulatory networks (GRNs) comprising interactions between transcription factors (TFs) and regulatory loci control development and physiology. Numerous disease-associated mutations have been identified, the vast majority residing in non-coding regions of the genome. As current GRN mapping methods test one TF at a time and require the use of cells harboring the mutation(s) of interest, they are not suitable to identify TFs that bind to wild-type and mutant loci. Here, we use gene-centered yeast one-hybrid (eY1H) assays to interrogate binding of 1,086 human TFs to 246 enhancers, as well as to 109 non-coding disease mutations. We detect both loss and gain of TF interactions with mutant loci that are concordant with target gene expression changes. This work establishes eY1H assays as a powerful addition to the toolkit of mapping human GRNs and for the high-throughput characterization of genomic variants that are rapidly being identified by genome-wide association studies

Insecticide resistance and the future of malaria control in Zambia.

BACKGROUND: In line with the Global trend to improve malaria control efforts a major campaign of insecticide treated net distribution was initiated in 1999 and indoor residual spraying with DDT or pyrethroids was reintroduced in 2000 in Zambia. In 2006, these efforts were strengthened by the President's Malaria Initiative. This manuscript reports on the monitoring and evaluation of these activities and the potential impact of emerging insecticide resistance on disease transmission. METHODS: Mosquitoes were captured daily through a series of 108 window exit traps located at 18 sentinel sites. Specimens were identified to species and analyzed for sporozoites. Adult Anopheles mosquitoes were collected resting indoors and larva collected in breeding sites were reared to F1 and F0 generations in the lab and tested for insecticide resistance following the standard WHO susceptibility assay protocol. Annual cross sectional household parasite surveys were carried out to monitor the impact of the control programme on prevalence of Plasmodium falciparum in children aged 1 to 14 years. RESULTS: A total of 619 Anopheles gambiae s.l. and 228 Anopheles funestus s.l. were captured from window exit traps throughout the period, of which 203 were An. gambiae malaria vectors and 14 An. funestus s.s.. In 2010 resistance to DDT and the pyrethroids deltamethrin, lambda-cyhalothrin and permethrin was detected in both An. gambiae s.s. and An. funestus s.s.. No sporozoites were detected in either species. Prevalence of P. falciparum in the sentinel sites remained below 10% throughout the study period. CONCLUSION: Both An. gambiae s.s. and An. funestus s.s. were controlled effectively with the ITN and IRS programme in Zambia, maintaining a reduced disease transmission and burden. However, the discovery of DDT and pyrethroid resistance in the country threatens the sustainability of the vector control programme