Effect of acute exposure to high ambient temperature on the thermal, metabolic and hygric physiology of a small desert bird.

The intensity and frequency of extreme weather events, such as heat waves, are increasing as a consequence of global warming. Acute periods of extreme heat can be more problematic for wildlife than a chronic increase in mean temperature, to which animals can potentially acclimatise. Predicting effects of heat exposure requires a clear understanding of the capacity of individuals to respond to heat waves, so we examined the physiological response of a small desert bird, the zebra finch (Taeniopygia guttata), after acute previous exposure to high ambient temperature, simulating heatwave-like conditions. The standard physiology of the zebra finches was unaffected by prior exposure to heatwave-type conditions, suggesting that periodic exposure to heatwaves is unlikely to impact their longer-term day-to-day energy and water requirements. When finches were thermally challenged, prior experience of heatwave-like conditions did not impact overall body temperature and evaporative water loss, but birds previously experiencing high temperatures did reduce their metabolic heat production, and the variance in water loss and metabolism between individuals was significantly lower. This suggests that some individuals are more likely to become dehydrated if they have not had prior experience of high temperatures, and do not prioritise water conservation over thermoregulation. However, our observations overall suggest that acute periods of heat exposure do little to modify the general physiology of small birds, supporting the hypothesis that periodic extreme heat events may be more problematic for them than chronic warming.

Recurrence after hospitalization for acute coronary syndrome among HIV-infected and HIV-uninfected individuals.

OBJECTIVES: We evaluated the association of HIV infection and immunodeficiency with acute coronary syndrome (ACS) recurrence, and with all-cause mortality as a secondary outcome, after hospitalization for ACS among HIV-infected and HIV-uninfected individuals. METHODS: We conducted a retrospective cohort study within Kaiser Permanente Northern California of HIV-infected and HIV-uninfected adults discharged after ACS hospitalization [types: ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina] during 1996-2010. We compared the outcomes of ACS recurrence and all-cause mortality within 3 years, both overall by HIV status and stratified by recent CD4 count, with HIV-uninfected individuals as the reference group. Hazard ratios (HRs) were obtained from Cox regression models with adjustment for age, sex, race/ethnicity, year, ACS type, smoking, and cardiovascular risk factors. RESULTS: Among 226 HIV-infected and 86 321 HIV-uninfected individuals with ACS, HIV-infected individuals had a similar risk of ACS recurrence compared with HIV-uninfected individuals [HR 1.08; 95% confidence interval (CI) 0.76-1.54]. HIV infection was independently associated with all-cause mortality after ACS hospitalization overall (HR 2.52; 95% CI 1.81-3.52). In CD4-stratified models, post-ACS mortality was higher for HIV-infected individuals with CD4 counts of 201-499 cells/µL (HR 2.64; 95% CI 1.66-4.20) and < 200 cells/µL (HR 5.41; 95% CI 3.14-9.34), but not those with CD4 counts ≥ 500 cells/µL (HR 0.67; 95% CI 0.22-2.08), compared with HIV-uninfected individuals (P trend < 0.001). CONCLUSIONS: HIV infection and immunodeficiency were not associated with recurrence of ACS after hospitalization. All-cause mortality was higher among HIV-infected compared with HIV-uninfected individuals, but there was no excess mortality risk among HIV-infected individuals with high CD4 counts.

Higher temperatures during development reduce body size in the zebra finch in the laboratory and in the wild.

The most commonly documented morphological response across many taxa to climatic variation across their range follows Bergmann's rule, which predicts larger body size in colder climates. In observational data from wild zebra finches breeding across a range of temperatures in the spring and summer, we show that this relationship appears to be driven by the negative effect of high temperatures during development. This idea was then experimentally tested on zebra finches breeding in temperature-controlled climates in the laboratory. These experiments confirmed that those individualso produced in a hot environment (30 °C) were smaller than those produced in cool conditions (18 °C). Our results suggest a proximate causal link between temperature and body size and suggest that a hotter climate during breeding periods could drive significant changes in morphology within and between populations. This effect could account for much of the variation in body size that drives the well-observed patterns first described by Bergmann and that is still largely attributed to selection on adult body size during cold winters. The climate-dependent developmental plasticity that we have demonstrated is an important component in understanding how endotherms may be affected by climate change.

Functional and gene network analyses of transcriptional signatures characterizing pre-weaned bovine mammary parenchyma or fat pad uncovered novel inter-tissue signaling networks during development.

BACKGROUND: The neonatal bovine mammary fat pad (MFP) surrounding the mammary parenchyma (PAR) is thought to exert proliferative effects on the PAR through secretion of local modulators of growth induced by systemic hormones. We used bioinformatics to characterize transcriptomics differences between PAR and MFP from approximately 65 d old Holstein heifers. Data were mined to uncover potential crosstalk through the analyses of signaling molecules preferentially expressed in one tissue relative to the other. RESULTS: Over 9,000 differentially expressed genes (DEG; False discovery rate or=1.5-fold difference between PAR and MFP. Within the DEG highly-expressed in PAR vs. MFP (n = 736) we noted significant enrichment of functions related to cell cycle, structural organization, signaling, and DNA/RNA metabolism. Only actin cytoskeletal signaling was significant among canonical pathways. DEG more highly-expressed in MFP vs. PAR (n = 742) belong to lipid metabolism, signaling, cell movement, and immune-related functions. Canonical pathways associated with metabolism and signaling, particularly immune- and metabolism-related were significantly-enriched. Network analysis uncovered a central role of MYC, TP53, and CTNNB1 in controlling expression of DEG highly-expressed in PAR vs. MFP. Similar analysis suggested a central role for PPARG, KLF2, EGR2, and EPAS1 in regulating expression of more highly-expressed DEG in MFP vs. PAR. Gene network analyses revealed putative inter-tissue crosstalk between cytokines and growth factors preferentially expressed in one tissue (e.g., ANGPTL1, SPP1, IL1B in PAR vs. MFP; ADIPOQ, IL13, FGF2, LEP in MFP vs. PAR) with DEG preferentially expressed in the other tissue, particularly transcription factors or pathways (e.g., MYC, TP53, and actin cytoskeletal signaling in PAR vs. MFP; PPARG and LXR/RXR Signaling in MFP vs. PAR). CONCLUSIONS: Functional analyses underscored a reciprocal influence in determining the biological features of MFP and PAR during neonatal development. This was exemplified by the potential effect that the signaling molecules (cytokines, growth factors) released preferentially (i.e., more highly-expressed) by PAR or MFP could have on molecular functions or signaling pathways enriched in the MFP or PAR. These bidirectional interactions might be required to coordinate mammary tissue development under normal circumstances or in response to nutrition.

Teratogenic effects of a chelating agent and their prevention by zinc.

Ingestion of a chelating agent (ethylenediaminetetraacetic acid) by female rats during pregnancy impaired reproduction and resulted in congenitally malformed young. When ethylenediaminetetraacetic acid was fed from days 6 to 21 of gestation, all of the full-term young had gross congenital malformations. These effects were prevented by simultaneous supplementation with 1000 parts per million of dietary zinc.

Neurological defect: manganese in phenocopy and prevention of a genetic abnormality of inner ear.

A specific congenital ataxia may be caused by presence of mutant genes and by manganese deficiency during prenatal development in normal mice. Supplementation of the diet of mutant mice with manganese during prenatal development rectifies the aberrant development, resulting in normal behavior. The congential ataxa results from defective development of the the otoliths.

Zinc-deficient embryos: reduced thymidine incorporation.

The 12-day-old embryos of rats with a deficiency of zinc showed a reduced uptake of tritiated thymidine when compared with controls, as shown by liquid scintillation and autoradiography. The high incidence of gross congenital malformations resulting from zinc deficiency may thus be caused by DNA impaired DNA synthesis.

Copper supplementation in quaking mutant mice: reduced tremors and increased brain copper.

Mice homozygous for the mutant gene quaking (qk) with a high frequency of axial tremors had a low concentration of copper in the brain. Supplementation during pregnancy and lactation with a high level of dietary copper greatly reduced the frequency of tremors and brought brain copper level to normal in the off-spring. It is suggested that qk affects copper metabolism.

Gestational zinc deprivation in mice: persistence of immunodeficiency for three generations.

Pregnant Swiss Webster mice were fed a diet moderately deficient in zinc from day 7 of gestation until parturition. Offspring of these mice showed depressed immune function through 6 months of age. In addition, the second and third filial generations, all of which were fed only the normal control diet, continued to manifest reduced immunocompetence, although not to the same degree as in the first generation.

Liver mitochondria from manganese-deficient and pallid mice: function and ultrastructure.

Oxidative phosphorylation was studied in isolated liver mitochondria from manganese-deficient mice and in those from a mutant strain, pallid. In mitochondria from manganese-deficient mice, ratios of adenosine triphosphate formed to oxygen consumed were normal, but oxygen uptake was reduced. Electron microscopy of these mitochondria revealed ultrastructural abnormalities including elongation and reorientation of cristae. No biochemical or structural abnormalities were found in mitochondria from pallid mice.

Zinc binding: a difference between human and bovine milk.

Gel chromatography indicated that most of the zinc in cow's milk was associated with high-molecular-weight fractions, whereas zinc in human milk was associated with low-molecular-weight fractions. A species difference in zinc-binding ligands may explain why symptoms of the genetic disorder of zinc metabolism, acrodermatitis enteropathica, can be alleviated by feeding human but not cow's milk.

A mutation influencing the transportation of manganese, L-dopa, and L-tryptophan.

Transportation of manganese, L-dopa, and L-tryptophan was slower through the tissues, of intact pallid mice than through those of black C57Bl/6J mice, presumably because of the influence of the gene pallid.

Reaction of the antitumor antibiotic CC-1065 with DNA: structure of a DNA adduct with DNA sequence specificity.

Sequence-dependent variations in DNA revealed by x-ray crystallographic studies have suggested that certain DNA-reactive drugs may react preferentially with defined sequences in DNA. Drugs that wind around the helix and reside within one of the grooves of DNA have perhaps the greatest chance of recognizing sequence-dependent features of DNA. The antitumor antibiotic CC-1065 covalently binds through N-3 of adenine and resides within the minor groove of DNA. This drug overlaps with five base pairs for which a high sequence specificity exists.

Estrogen receptor alpha signaling pathways differentially regulate gonadotropin subunit gene expression and serum follicle-stimulating hormone in the female mouse.

Estrogen, acting via estrogen receptor (ER)alpha, regulates serum gonadotropin levels and pituitary gonadotropin subunit expression. However, the cellular pathways mediating this regulation are unknown. ERalpha signals through classical estrogen response element (ERE)-dependent genomic as well as nonclassical ERE-independent genomic and nongenomic pathways. Using targeted mutagenesis in mice to disrupt ERalpha DNA binding activity, we previously demonstrated that ERE-independent signaling is sufficient to suppress serum LH levels. In this study, we examined the relative roles of ERE-dependent and -independent estrogen signaling in estrogen regulation of LH, FSH, prolactin, and activin/inhibin subunit gene expression, pituitary LH and FSH protein content, and serum FSH levels. ERE-independent signaling was not sufficient for estrogen to induce pituitary prolactin mRNA or suppress pituitary LHbeta mRNA, LH content, or serum FSH in estrogen-treated ovariectomized mice. However, ERE-independent signaling was sufficient to reduce pituitary glycoprotein hormone alpha-subunit, FSHbeta, and activin-betaB mRNA expression. Together with previous serum LH results, these findings suggest ERE-independent ERalpha signaling suppresses serum LH via reduced secretion, not synthesis. Additionally, ERE-dependent and ERE-independent ERalpha pathways may distinctly regulate steps involved in the synthesis and secretion of FSH.

Investigating the management of diabetes in nursing homes using a mixed methods approach.

AIMS: As populations age there is an increased demand for nursing home (NH) care and a parallel increase in the prevalence of diabetes. Despite this, there is growing evidence that the management of diabetes in NHs is suboptimal. The reasons for this are complex and poorly understood. This study aimed to identify the current level of diabetes care in NHs using a mixed methods approach. METHODS: The nursing managers at all 44 NHs in County Galway in the West of Ireland were invited to participate. A mixed methods approach involved a postal survey, focus group and telephone interviews. RESULTS: The survey response rate was 75% (33/44) and 27% (9/33) of nursing managers participated in the qualitative research. The reported prevalence of diagnosed diabetes was 14% with 80% of NHs treating residents with insulin. Hypoglycaemia was reported as 'frequent' in 19% of NHs. A total of 36% of NHs have staff who have received diabetes education or training and 56% have access to diabetes care guidelines. Staff education was the most cited opportunity for improving diabetes care. Focus group and interview findings highlight variations in the level of support provided by GPs and access to dietetic, podiatry and retinal screening services. CONCLUSIONS: There is a need for national clinical guidelines and standards of care for diabetes management in nursing homes, improved access to quality diabetes education for NH staff, and greater integration between healthcare services and NHs to ensure equity, continuity and quality in diabetes care delivery.

A matter of focus: monoaminergic modulation of stimulus coding in mammalian sensory networks.

Although the presence of neuromodulators in mammalian sensory systems has been noted for some time, a groundswell of evidence has now begun to document the scope of these regulatory mechanisms in several sensory systems, highlighting the importance of neuromodulation in shaping feature extraction at all levels of neural processing. The emergence of more sophisticated models of sensory encoding and of the interaction between sensory and regulatory regions of the brain will challenge sensory neurobiologists to further incorporate a concept of sensory network function that is contingent on neuromodulatory and behavioral state.

Protection against anthramycin-induced toxicity in mice by coenzyme Q10.

Pretreatment of Swiss Webster mice with coenzyme Q10 (CoQ) markedly reduced the lethality of the antitumor antibiotic anthramycin as well as its ability to decrease ventricular weights. In tumor-bearing mice CoQ pretreatment did not produce any consistent alteration of radioactivity levels in blood, heart, tumor, lungs, kidneys, liver, muscles, brain, or spleen after [15-3H]anthramycin administration. Gross alterations in anthramycin distribution is probably not the mechanism by which CoQ alters the cardiotoxicity and lethality of anthramycin.

Mutagenic and recombinogenic effects of the antitumor antibiotic anthramycin.

Anthramycin, one of the pyrrolo(1,4)benzodiazepine antibiotics with potent antitumor activity, was tested for its effects on a number of genetic parameters. The results show that this antibiotic is nonmutagenic in the Ames strains of Salmonella typhimurium while mutagenic in only one and antimutagenic in the rest of the genes tested in the eukaryotic organism Saccharomyces cerevisiae. The antibiotic is, however, a potent recombinogen inasmuch as it induced mitotic crossing over, mitotic gene conversion, and possibly other chromosomal alterations in a diploid strain of S. cerevisiae. These studies emphasize the need for a battery of test systems including eukaryotic organisms to detect the genetic activity of certain antitumor drugs. The importance of considering data distinguishing between highly mutagenic and poorly mutagenic cancer chemotherapeutic agents is also discussed.

Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells.

A series of cationic porphyrins has been identified as G-quadruplex interactive agents (QIAs) that stabilize telomeric G-quadruplex DNA and thereby inhibit human telomerase; 50% inhibition of telomerase activity was achieved in HeLa cell-free extract at porphyrin concentrations in the range < or = 50 microM. Cytotoxicity of the porphyrins in vitro was assessed in normal human cells (fibroblast and breast) and human tumor cells representing models selected for high telomerase activity and short telomeres (breast carcinoma, prostate, and lymphoma). In general, the cytotoxicity (EC50, effective concentration for 50% inhibition of cell proliferation) against normal and tumor cells was > 50 microM. The porphyrins were readily absorbed into tumor cell nuclei in culture. Inhibition of telomerase activity in MCF7 cells by subcytotoxic concentrations of TMPyP4 showed time and concentration dependence at 1-100 microM TMPyP4 over 15 days in culture (10 population doubling times). The inhibition of telomerase activity was paralleled by a cell growth arrest in G2-M. These results suggest that relevant biological effects of porphyrins can be achieved at concentrations that do not have general cytotoxic effects on cells. Moreover, the data support the concept that a rational, structure-based approach is possible to design novel telomere-interactive agents with application to a selective and specific anticancer therapy.