Maternal health status correlates with nest success of leatherback sea turtles (Dermochelys coriacea) from Florida

Of the seven sea turtle species, the critically endangered leatherback sea turtle (Dermochelys coriacea) exhibits the lowest and most variable nest success (i.e., hatching success and emergence success) for reasons that remain largely unknown. In an attempt to identify or rule out causes of low reproductive success in this species, we established the largest sample size (n = 60–70 for most values) of baseline blood parameters (protein electrophoresis, hematology, plasma biochemistry) for this species to date. Hematologic, protein electrophoretic and biochemical values are important tools that can provide information regarding the physiological condition of an individual and population health as a whole. It has been proposed that the health of nesting individuals affects their reproductive output. In order to establish correlations with low reproductive success in leatherback sea turtles from Florida, we compared maternal health indices to hatching success and emergence success of their nests. As expected, hatching success (median = 57.4%) and emergence success (median = 49.1%) in Floridian leatherbacks were low during the study period (2007–2008 nesting seasons), a trend common in most nesting leatherback populations (average global hatching success = ∼50%). One protein electrophoretic value (gamma globulin protein) and one hematologic value (red blood cell count) significantly correlated with hatching success and emergence success. Several maternal biochemical parameters correlated with hatching success and/or emergence success including alkaline phosphatase activity, blood urea nitrogen, calcium, calcium∶phosphorus ratio, carbon dioxide, cholesterol, creatinine, and phosphorus. Our results suggest that in leatherbacks, physiological parameters correlate with hatching success and emergence success of their nests. We conclude that long-term and comparative studies are needed to determine if certain individuals produce nests with lower hatching success and emergence success than others, and if those individuals with evidence of chronic suboptimal health have lower reproductive success.     

Desulfohalophilus alkaliarsenatis gen. nov., sp. nov., an extremely halophilic sulfate- and arsenate-respiring bacterium from Searles Lake, California

A haloalkaliphilic sulfate-respiring bacterium, strain SLSR-1, was isolated from a lactate-fed stable enrichment culture originally obtained from the extreme environment of Searles Lake, California. The isolate proved capable of growth via sulfate-reduction over a broad range of salinities (125-330?g/L), although growth was slowest at salt-saturation. Strain SLSR-1 was also capable of growth via dissimilatory arsenate-reduction and displayed an even broader range of salinity tolerance (50-330?g/L) when grown under these conditions. Strain SLSR-1 could also grow via dissimilatory nitrate reduction to ammonia. Growth experiments in the presence of high borate concentrations indicated a greater sensitivity of sulfate-reduction than arsenate-respiration to this naturally abundant anion in Searles Lake. Strain SLSR-1 contained genes involved in both sulfate-reduction (dsrAB) and arsenate respiration (arrA). Amplicons of 16S rRNA gene sequences obtained from DNA extracted from Searles Lake sediment revealed the presence of close relatives of strain SLSR-1 as part of the flora of this ecosystem despite the fact that sulfate-reduction activity could not be detected in situ. We conclude that strain SLSR-1 can only achieve growth via arsenate-reduction under the current chemical conditions prevalent at Searles Lake. Strain SLSR-1 is a deltaproteobacterium in the family Desulfohalobiacea of anaerobic, haloalkaliphilic bacteria, for which we propose the name Desulfohalophilus alkaliarsenatis gen. nov., sp. nov.     

Laboratory evaluation of large-scale decontamination approaches

Aims: To evaluate the effectiveness of two spray‐based decontamination methods for surface contamination reduction and to determine the potential for contamination spread by these methods. Methods and Results: Material coupons (treated plywood and concrete) were contaminated with c. 1 × 10⁷ spores of Bacillus atrophaeus by aerosol deposition. Decontaminants (pH‐adjusted bleach or Spor‐Klenz^® RTU) were applied to coupons by either backpack sprayer or gas‐powered sprayer. Contact time, reapplication frequency and rinse method were also varied. In addition to surface removal efficacy, partitioning of contamination between the rinsate and aerosol fractions was determined. Results indicated that pH‐adjusted bleach was effective (≥6 logs reduction) when two applications and a 30 min contact time were administered, regardless of the decontaminant application method or material. Spor‐Klenz^® RTU was effective on wood, but achieved ≤3 logs reduction on concrete. A shortened application procedure with pH‐adjusted bleach resulted in lower efficacy on wood, and a greater apparent potential for contamination spread. Conclusions: Consideration of material surface type is important when selecting a decontaminant. Also, achieving conditions that effectively inactivate surface biological contamination are critical to preventing the spread of contamination. Significance and Impact of the Study: Results presented here are intended to help development of remediation plans following a biological contamination incident.     

First report of molecular diagnosis of Tunisian hemophiliacs A: identification of 8 novel causative mutations

ABSTRACT: INTRODUCTION: Hemophilia A is an X linked recessive hemorrhagic disorder caused by mutations in the F8 gene that lead to qualitative and/or quantitative deficiencies of coagulation factor VIII (FVIII). Molecular diagnosis of hemophilia A is challenging because of the high number of different causative mutations that are distributed throughout the large F8 gene. Molecular studies of these mutations are essential in order to reinforce our understanding of their pathogenic effect responsible for the disorder. Aim In this study we have performed molecular analysis of 28 Tunisian hemophilia A patients and analyzed the F8 mutation spectrum. METHODS: We screened the presence of intron 22 and intron 1 inversion in severe hemophilia A patients by southern blotting and polymerase chain reaction (PCR). Detection of point mutations was performed by dHPLC/sequencing of the coding F8 gene region. We predict the potential functional consequences of novel missense mutations with bioinformatics approaches and mapping of their spatial positions on the available FVIII 3D structure. RESULTS: We identified 23 different mutations in 28 Tunisian hemophilia A patients belonging to 22 unrelated families. The identified mutations included 5 intron 22 inversions, 7 insertions, 4 deletions and 7 substitutions. In total 18 point mutations were identified, of which 9 are located in exon 14, the most mutated exonic sequence in the F8 gene. Among the 23 mutations, 8 are novel and not deposited in the HAMSTeRS database nor described in recently published articles. CONCLUSION: The mutation spectrum of Tunisian hemophilia A patients is heterogeneous with the presence of some characteristic features. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1693269827490715.     

Nitric Oxide Has Differential Effects on Currents in Different Subsets of Manduca sexta Antennal Lobe Neurons

Nitric oxide has been shown to regulate many biological systems including olfaction. In the moth olfactory system nitric oxide is produced in the antennal lobe in response to odor stimulation and has complex effects on the activity of both projection neurons and local interneurons. To examine the cell autonomous effects of nitric oxide on these cells, we used patch-clamp recording in conjunction with pharmacological manipulation of nitric oxide to test the hypothesis that nitric oxide differentially regulates the channel properties of these different antennal lobe neuron subsets. We found that nitric oxide caused increasing inward currents in a subset of projection neurons while the effects on local neurons were variable but consistent within identifiable morphological subtypes.     

Synthesis and SAR study of 4-arylpiperidines and 4-aryl-1,2,3,6-tetrahydropyridines as 5-HT₂C agonists

A series of substituted 4-arylpiperidines and a smaller family of 4-aryl-1,2,3,6-tetrahydropyridines were synthesized and their biological activity at the 5-HT(2C) receptor studied to determine whether either series showed noteworthy agonist activity. Structure-activity relationships were developed from the performed receptor binding assays and functional studies, and the results of the analysis are presented herein.     

White matter differences between healthy young ApoE4 carriers and non-carriers identified with tractography and support vector machines

The apolipoprotein E4 (ApoE4) is an established risk factor for Alzheimer's disease (AD). Previous work has shown that this allele is associated with functional (fMRI) changes as well structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess the diffusion characteristics and the white matter (WM) tracts of healthy young (20-38 years) ApoE4 carriers and non-carriers. No significant differences in diffusion indices were found between young carriers (ApoE4+) and non-carriers (ApoE4-). There were also no significant differences between the groups in terms of normalised GM or WM volume. A feature selection algorithm (ReliefF) was used to select the most salient voxels from the diffusion data for subsequent classification with support vector machines (SVMs). SVMs were capable of classifying ApoE4 carrier and non-carrier groups with an extremely high level of accuracy. The top 500 voxels selected by ReliefF were then used as seeds for tractography which identified a WM network that included regions of the parietal lobe, the cingulum bundle and the dorsolateral frontal lobe. There was a non-significant decrease in volume of this WM network in the ApoE4 carrier group. Our results indicate that there are subtle WM differences between healthy young ApoE4 carriers and non-carriers and that the WM network identified may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age.     

The matricellular protein thrombospondin-1 globally regulates cardiovascular function and responses to stress via CD47

Matricellular proteins play diverse roles in modulating cell behavior by engaging specific cell surface receptors and interacting with extracellular matrix proteins, secreted enzymes, and growth factors. Studies of such interactions involving thrombospondin-1 have revealed several physiological functions and roles in the pathogenesis of injury responses and cancer, but the relatively mild phenotypes of mice lacking thrombospondin-1 suggested that thrombospondin-1 would not be a central player that could be exploited therapeutically. Recent research focusing on signaling through its receptor CD47, however, has uncovered more critical roles for thrombospondin-1 in acute regulation of cardiovascular dynamics, hemostasis, immunity, and mitochondrial homeostasis. Several of these functions are mediated by potent and redundant inhibition of the canonical nitric oxide pathway. Conversely, elevated tissue thrombospondin-1 levels in major chronic diseases of aging may account for the deficient nitric oxide signaling that characterizes these diseases, and experimental therapeutics targeting CD47 show promise for treating such chronic diseases as well as acute stress conditions that are associated with elevated thrombospondin-1 expression.     

Survival patterns in white-tailed and mule deer after oral inoculation with a standardized, conspecific prion dose

We orally inoculated white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) with a standardized, conspecific prion dose and collected biologic samples throughout the disease course. Mule deer (PRNP genotype 225SS) and PRNP genotype 96GG white-tailed deer succumbed along similar trajectories, but 96GS- and 96SS-genotype individuals tended to survive longer.     

iTRAQ-based proteomic profiling of breast cancer cell response to doxorubicin and TRAIL

Breast cancer is a molecularly heterogeneous disease, and predicting response to chemotherapy remains a major clinical challenge. To minimize adverse side-effects or cumulative toxicity in patients unlikely to benefit from treatment, biomarkers indicating treatment efficacy are critically needed. iTRAQ labeling coupled with multidimensional LC-MS/MS of the enriched mitochondria and endoplasmic reticulum fraction, key organelles regulating apoptosis, has led to the discovery of several differentially abundant proteins in breast cancer cells treated with the chemotherapeutic agent doxorubicin followed by the death receptor ligand, TRAIL, among 571 and 801 unique proteins identified in ZR-75-1 and MDA-MB-231 breast cancer cell lines, respectively. The differentially abundant proteins represent diverse biological processes associated with cellular assembly and organization, molecular transport, oxidative stress, cell motility, cell death, and cancer. Despite many differences in molecular phenotype between the two breast cancer cell lines, a comparison of their subproteomes following drug treatment revealed three proteins displaying common regulation: PPIB, AHNAK, and SLC1A5. Changes in these proteins, detected by iTRAQ, were confirmed by immunofluorescence, visualized by confocal microscopy. These novel potential biomarkers may have clinical utility for assessing response to cancer treatment and may provide insight into new therapeutic targets for breast cancer.