Spatial and temporal variability in early successional patterns of an invertebrate assemblage at an offshore oil platform

The effects of selected physical and biological factors on the early development of a subtidal invertebrate assemblage were examined at an offshore oil platform in the Santa Barbara Channel (California, USA). The effects of date, year, length, and depth of submersion were investigated by replacing sets of ceramic tiles with new tiles at frequencies of 2, 4, 6, 12, and 24 months at three depths (6, 12, and 18 m) over a period of 24 months. The effects of existing colonists and depth were explored in a second experiment by removing selected early colonists from ceramic tiles deployed at the same three depths over a period of 12 months. More than 40 invertebrate taxa from seven phyla colonized the tiles. Colonial tunicates and encrusting bryozoans appeared early in the successional sequence (∼2 months), in cover ranging from <5% to 80% and from <5% to 55%, respectively. Tubiculous amphipods, barnacles, and sponges could also appear early, but in low cover (<20%). Composition of the assemblage changed over time with barnacles, sponges, and mussels becoming the principal space holders on tiles submerged for 24 months. When potential competitors were removed monthly, variation in the cover of dominant taxa (i.e., bryozoans, amphipods, barnacles) was maintained to 12 months, suggesting that other factors, such as larval availability or post-settlement mortality, were responsible for these patterns. Development of this assemblage appeared to fit a pattern of early succession that was largely predictable in terms of the composition and sequence of occurrence of dominant taxa, but variable in rate of development, depending on date of submersion, year, and depth.     

Inhibitory effects of particulate materials in growing cultures of Thiobacillus ferrooxidans

Particulate materials (flowers of sulfur, fluorapatite, glass beads, and pyrite) inhibited the growth of Thiobacillus ferrooxidans on ferrous iron at pH 1.5. The degree of inhabitation varied with the type of the particulate and culture conditions. The inhibition caused by pyrite involved a soluble toxic component. The inhibition caused by sulfur particles and glass beads was alleviated by incubation under static culture conditions (i.e., no shaking) but oxidation rates declined because of lack of aeration an increase in the pH above 2 also relieved the inhibition. The nature of inhibition. The nature of inhibition by different particles varied from declined iron oxidation rates to prolonged lag periods depending on the concentration of the test material. Thus, the results indicate that the bacterial activity at the liquid-solid interface is different from that in the bulk liquid phase and is influenced by the proton concentration and by the physiochemical properties of the solids.     

VU6005806/AZN-00016130, an advanced M4 positive allosteric modulator (PAM) profiled as a potential preclinical development candidate

This letter describes progress towards an M₄ PAM preclinical candidate that resulted in the discovery of VU6005806/AZN-00016130. While the thieno[2,3-c]pyridazine core has been a consistent feature of key M₄ PAMs, no work had previously been reported with respect to alternate functionality at the C3 position of the pyridazine ring. Here, we detail new chemistry and analogs that explored this region, and quickly led to VU6005806/AZN-00016130, which was profiled as a putative candidate. While, the β-amino carboxamide moiety engendered solubility limited absorption in higher species precluding advancement (or requiring extensive pharmaceutical sciences formulation), VU6005806/AZN-00016130 represents a new, high quality preclinical in vivo probe.     

Utility of the lateral meniscal notch in distinguishing hominin taxa

In humans, a notch marking the posterior attachment of the lateral meniscus is often visible on the posterior, lateral plateau of the tibia, adjacent to the intercondylar eminence. In theory, the presence or absence of this notch in dry bone can be used to differentiate the fossil remains of Australopithecus from those of the genus Homo. In a small-scale study, however, we found examples of modern human tibiae that appear not to have such a notch. In other cases, the morphology of the surrounding bone made it difficult to determine whether or not the notch was present. Although based on a small sample, this study questions: 1) the theoretical postulate that the lateral meniscal notch can be used to differentiate between hominin taxa, and 2) the practical reliability of determining the absence or presence of the notch in fossil remains.     

IL-6 Mediated Degeneration of Forebrain GABAergic Interneurons and Cognitive Impairment in Aged Mice through Activation of Neuronal NADPH Oxidase

Background

Multiple studies have shown that plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) are elevated in patients with important and prevalent adverse health conditions, including atherosclerosis, diabetes, obesity, obstructive sleep apnea, hypertension, and frailty. Higher plasma levels of IL-6, in turn, increase the risk of many conditions associated with aging including age-related cognitive decline. However, the mechanisms underlying this association between IL-6 and cognitive vulnerability remain unclear.

Methods and Findings

We investigated the role of IL-6 in brain aging in young (4 mo) and aged (24 mo) wild-type C57BL6 and genetically-matched IL-6^−/− mice, and determined that IL-6 was necessary and sufficient for increased neuronal expression of the superoxide-producing immune enzyme, NADPH-oxidase, and this was mediated by non-canonical NFκB signaling. Furthermore, superoxide production by NADPH-oxidase was directly responsible for age-related loss of parvalbumin (PV)-expressing GABAergic interneurons, neurons essential for normal information processing, encoding, and retrieval in hippocampus and cortex. Targeted deletion of IL-6 or elimination of superoxide by chronic treatment with a superoxide-dismutase mimetic prevented age-related loss of PV-interneurons and reversed age-related cognitive deficits on three standard tests of spatial learning and recall.

Conclusions

Present results indicate that IL-6 mediates age-related loss of critical PV-expressing GABAergic interneurons through increased neuronal NADPH-oxidase-derived superoxide production, and that rescue of these interneurons preserves cognitive performance in aging mice, suggesting that elevated peripheral IL-6 levels may be directly and mechanistically linked to long-lasting cognitive deficits in even normal older individuals. Further, because PV-interneurons are also selectively affected by commonly used anesthetic agents and drugs, our findings imply that IL-6 levels may predict adverse CNS effects in older patients exposed to these compounds through specific derangements in inhibitory interneurons, and that therapies directed at lowering IL-6 may have cognitive benefits clinically.     

Testosterone and Visceral Fat in Midlife Women: The Study of Women's Health Across the Nation (SWAN) Fat Patterning Study

Visceral fat (VF) increases with the menopause and is an independent predictor of the metabolic syndrome, diabetes, and cardiovascular disease (CVD) in women. Little is known about how hormonal changes during the menopausal transition are related to the increase in VF. We aimed to determine the relationship between bioavailable testosterone and VF in middle‐aged women at various stages of the menopausal transition and whether this relationship is independent of age and other CVD risk factors. The Study of Women's Health Across the Nation (SWAN) is a longitudinal, community‐based study. This report uses baseline data from a population‐based longitudinal ancillary study at the Chicago site to examine the cross‐sectional relationship between testosterone and computed tomography (CT)–assessed VF in women at different stages of the menopausal transition. Included are 359 women (47.2% black), aged 42–60 years, who were randomly selected from a complete community census in which a 72% participation rate was achieved. In multivariate models, bioavailable testosterone was associated with VF independent of age, race, percent total body fat, and other cardiovascular risk factors. Bioavailable testosterone was a stronger predictor than estradiol and was interchangeable in its strength of association with sex hormone–binding globulin (SHBG). As bioavailable testosterone was associated with VF even after adjusting for insulin resistance, this suggests that it plays an important role in regional fat distribution. Our findings may have direct implications in explaining the effect of menopause‐related testosterone predominance on VF accumulation and subsequent cardiovascular risk.     

Characterization and partial purification of CD34+ progenitor cell ecto-phosphatidic acid phosphohydrolase

Phosphatidic acid and its hydrolysis product, diacylglycerol, play potentially vital roles as extracellular messengers in numerous cellular systems and may play a key role in regulating hematopoiesis. In this study, we describe an ecto-phosphatidic acid phosphohydrolase that potentially regulates cellular responses to phosphatidic acid on bone marrow derived human hematopoietic progenitors. We partially purified hematopoietic progenitor ecto-PAPase using a novel in-gel phosphatase assay and then characterized the enzyme on phenotypically defined subpopulations of hematopoietic CD34+ progenitors isolated by flow cytometry. The most pronounced PAPase activity was confined to uncommitted CD34+/CD38+ hematopoietic progenitors, which lacked the expression of other lineage-associated antigens. We conclude that hematopoietic progenitor cells at various stages of maturation possess a potent ecto-PAPase, an enzyme well positioned to regulate progenitor cell growth and differentiation induced by phosphatidic acid and related lipids.