When can embryos learn? A test of the timing of learning in embryonic amphibians

Learning is crucial to the survival of organisms across their life span, including during embryonic development. We set out to determine when learning becomes possible in amphibian development by exposing spotted salamander (Ambystoma maculatum) embryos to chemical stimuli from a predator (Ambystoma opacum), nonpredator (Lithobates clamitans), or control at developmental stages 16–21 or 36–38 (Harrison 1969 ). Once exposures were completed and embryos hatched, we recorded the number of movements and time spent moving of individuals in both groups and all treatments. There was no significant difference in number of movements or time spent moving among any of the treatments. The groups that were exposed to predator stimuli and a blank control at stages 36–38 were also tested to determine whether there was a difference in refuge preference or difference in survivorship when exposed to a predator (marbled salamander). There was no difference in survival or refuge preference between individuals; however, all individuals preferred vegetated over open areas regardless of treatment type. We discuss hypotheses for the absence of embryonic learning in this species and suggest it may be the result of the intensity of the predator–prey interaction between the predator, large marbled salamander larvae, and the prey, spotted salamander larvae.     

Associations between Cognition,Gender and Monocyte Activation among HIV Infected Individuals in Nigeria

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes.     

Culture-Independent Identification of Nontuberculous Mycobacteria in Cystic Fibrosis Respiratory Samples

Respiratory tract infections with nontuberculous mycobacteria (NTM) are increasing in prevalence and are a significant cause of lung function decline in individuals with cystic fibrosis (CF). NTM have been detected in culture-independent analyses of CF airway microbiota at lower rates than would be expected based on published prevalence data, likely due to poor lysing of the NTM cell wall during DNA extraction. We compared a standard bacterial lysis protocol with a modified method by measuring NTM DNA extraction by qPCR and NTM detection with bacterial 16S rRNA gene sequencing. The modified method improved NTM DNA recovery from spiked CF sputum samples by a mean of 0.53 log₁₀ copies/mL for M. abscessus complex and by a mean of 0.43 log₁₀ copies/mL for M. avium complex as measured by qPCR targeting the atpE gene. The modified method also improved DNA sequence based NTM detection in NTM culture-positive CF sputum and bronchoalveolar lavage samples; however, both qPCR and 16S rRNA gene sequencing remained less sensitive than culture for NTM detection. We highlight the limitations of culture-independent identification of NTM from CF respiratory samples, and illustrate how alterations in the bacterial lysis and DNA extraction process can be employed to improve NTM detection with both qPCR and 16S rRNA gene sequencing.     

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

The Qatari law, as in many other countries, uses brain death as the main criteria for organ donation and cessation of medical support. By contrast, most of the public in Qatar do not agree with the limitation or withdrawal of medical care until the time of cardiac death. The current study aims to examine the duration of somatic survival after brain death, organ donation rate in brain-dead patients as well as review the underlying etiologies and level of support provided in the state of Qatar. This is a retrospective study of all patients diagnosed with brain death over a 10-year period conducted at the largest tertiary center in Qatar (Hamad General Hospital). Among the 53 patients who were diagnosed with brain death during the study period, the median and mean somatic survivals of brain-dead patients in the current study were 3 and 4.5 days respectively. The most common etiology was intracranial hemorrhage (45.3%) followed by ischemic stroke (17%). Ischemic stroke patients had a median survival of 11 days. Organ donation was accepted by only two families (6.6%) of the 30 brain dead patients deemed suitable for organ donation. The average somatic survival of brain-dead patients is less than one week irrespective of supportive measures provided. Organ donation rate was extremely low among brain-dead patients in Qatar. Improved public education may lead to significant improvement in resource utilization as well as organ transplant donors and should be a major target area of future health care policies.     

Potent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines

Development of a class of bicyclic inhibitors of the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against a related parasite PKG orthologue, is reported. Examination of key sub-structural elements led to new compounds with good levels of inhibitory activity against the recombinant kinase and in vitro activity against the parasite. Key examples were shown to possess encouraging in vitro ADME properties, and computational analysis provided valuable insight into the origins of the observed activity profiles.     

Social contact and hormonal changes predict post-conflict cooperation between friends

Long-term cooperation between individuals necessitates repairing damage arising from inevitable competing interests. How two members of a valuable relationship switch from competing to cooperating constitutes an important problem for any social species. Observations of non-human animals suggest that affiliative contact immediately following a contest facilitates continued cooperation. Behavioral studies further indicate that winners and losers frequently differ in hormonal changes following a competition. We tested the hypothesis that immediate contact with increases in cortisol (and testosterone for men) for winners following competition would facilitate subsequent cooperation between adult same-sex friends. Results show that contact (versus no contact) immediately following competition enhanced subsequent cooperation between female friends. During contact, increases in winner's cortisol for both sexes, and in testosterone for men, predicted future cooperation. Our results suggest two mechanisms that maintain social bonds following competition between established allies.     

Protein kinase A phosphorylation of human phosphodiesterase 3B promotes 14-3-3 protein binding and inhibits phosphatase-catalyzed inactivation

Recent studies confirm that intracellular cAMP concentrations are nonuniform and that localized subcellular cAMP hydrolysis by cyclic nucleotide phosphodiesterases (PDEs) is important in maintaining these cAMP compartments. Human phosphodiesterase 3B (HSPDE3B), a member of the PDE3 family of PDEs, represents the dominant particulate cAMP-PDE activity in many cell types, including adipocytes and cells of hematopoietic lineage. Although several previous reports have shown that phosphorylation of HSPDE3B by either protein kinase A (PKA) or protein kinase B (PKB) activates this enzyme, the mechanisms that allow cells to distinguish these two activated forms of HSPDE3B are unknown. Here we report that PKA phosphorylates HSPDE3B at several distinct sites (Ser-73, Ser-296, and Ser-318), and we show that phosphorylation of HSPDE3B at Ser-318 activates this PDE and stimulates its interaction with 14-3-3 proteins. In contrast, although PKB-catalyzed phosphorylation of HSPDE3B activates this enzyme, it does not promote 14-3-3 protein binding. Interestingly, we report that the PKA-phosphorylated, 14-3-3 protein-bound, form of HSPDE3B is protected from phosphatase-dependent dephosphorylation and inactivation. In contrast, PKA-phosphorylated HSPDE3B that is not bound to 14-3-3 proteins is readily dephosphorylated and inactivated. Our data are presented in the context that a selective interaction between PKA-activated HSPDE3B and 14-3-3 proteins represents a mechanism by which cells can protect this enzyme from deactivation. Moreover, we propose that this mechanism may allow cells to distinguish between PKA- and PKB-activated HSPDE3B.