Nuclear factor I genes regulate neuronal migration

Neuronal migration plays a central role in the formation of the brain, and deficits in this process can lead to aberrant brain function and subsequent disease. Neuronal migration is a complex process that involves the interaction of the neuron with the surrounding environmental milieu, and as such involves both cell-intrinsic and cell-extrinsic mechanisms. Studies performed in rodent models to investigate the formation of brain structures have provided key insights into how neuronal migration is coordinated during development. Within the cerebral cortex, glutamatergic neurons derived from the cortical ventricular zone migrate radially into the cortical plate, whereas interneurons derived within the ventrally located ganglionic eminences migrate tangentially into the cortex. Within the embryonic cerebellum, cerebellar granule neuron progenitors migrate from the rhombic lip over the surface of the cerebellar anlage, before differentiating and migrating radially into the internal granule layer of the cerebellum perinatally. In this review, we focus on one family of proteins, the nuclear factor I transcription factors, and review our understanding of how these molecules contribute to the formation of the hippocampus and the cerebellum via the regulation of neuronal migration

Spring plankton dynamics in the Eastern Bering Sea, 1971-2050 : mechanisms of interannual variability diagnosed with a numerical model

A new planktonic ecosystem model was constructed for the Eastern Bering Sea based on observations from the 2007-2010 BEST/BSIERP (Bering Ecosystem Study/Bering Sea Integrated Ecosystem Research Program) field program. When run with forcing from a data-assimilative ice-ocean hindcast of 1971-2012, the model performs well against observations of spring bloom time evolution (phytoplankton and microzooplankton biomass, growth and grazing rates, and ratios among new, regenerated, and export production). On the southern middle shelf (57°N, station M2), the model replicates the generally inverse relationship between ice-retreat timing and spring bloom timing known from observations, and the simpler direct relationship between the two that has been observed on the northern middle shelf (62°N, station M8). The relationship between simulated mean primary production and mean temperature in spring (15 February to 15 July) is generally positive, although this was found to be an indirect relationship which does not continue to apply across a future projection of temperature and ice cover in the 2040s. At M2, the leading direct controls on total spring primary production are found to be advective and turbulent nutrient supply, suggesting that mesoscale, wind-driven processes - A dvective transport and storminess - may be crucial to long-term trends in spring primary production in the southeastern Bering Sea, with temperature and ice cover playing only indirect roles. Sensitivity experiments suggest that direct dependence of planktonic growth and metabolic rates on temperature is less significant overall than the other drivers correlated with temperature described above

Uptake and utilization of 'colloidal DOM' by heterotrophic flagellates in seawater

A variety of macromolecules labeled with FITC (fluorescein isothiocyanate), including carbohydrates (dextran) and proteins (ferritin, casein, albumin, concavalin A), spanning a range of molecular weights from 55 to 2000 kD, were actively ingested by marine heterotrophic flagellates at substrate concentrations of 1 to 10 mg/L. The uptake capacity for the macromolecules was positively correlated to clearance rate for bacterial-sized prey Ingested FITC appeared In the food vacuoles of the cells The biomass of a cultured bacterivorous flagellate species Increased in cultures amended with 10 mg of 2000 kD dextran/L to an extent that could not be explained by bacterivory However. 40 kD devtran did not stimulate flagellate growth On the basis of these results, we suggest that protists have the capacity to ingest colloids of widely different sizes, spanning the size range of bacteria and larger organisms to macromolecules possibly including the recently discovered abundant non-living submicrometer colloids in sea water

The Human Skin Microbiome Associates with the Outcome of and Is Influenced by Bacterial Infection

The influence of the skin microbiota on host susceptibility to infectious agents is largely unexplored. The skin harbors diverse bacterial species that may promote or antagonize the growth of an invading pathogen. We developed a human infection model for Haemophilus ducreyi in which human volunteers are inoculated on the upper arm. After inoculation, papules form and either spontaneously resolve or progress to pustules. To examine the role of the skin microbiota in the outcome of H. ducreyi infection, we analyzed the microbiomes of four dose-matched pairs of “resolvers” and “pustule formers” whose inoculation sites were swabbed at multiple time points. Bacteria present on the skin were identified by amplification and pyrosequencing of 16S rRNA genes. Nonmetric multidimensional scaling (NMDS) using Bray-Curtis dissimilarity between the preinfection microbiomes of infected sites showed that sites from the same volunteer clustered together and that pustule formers segregated from resolvers (P = 0.001, permutational multivariate analysis of variance [PERMANOVA]), suggesting that the preinfection microbiomes were associated with outcome. NMDS using Bray-Curtis dissimilarity of the endpoint samples showed that the pustule sites clustered together and were significantly different than the resolved sites (P = 0.001, PERMANOVA), suggesting that the microbiomes at the endpoint differed between the two groups. In addition to H. ducreyi, pustule-forming sites had a greater abundance of Proteobacteria, Bacteroidetes, Micrococcus, Corynebacterium, Paracoccus, and Staphylococcus species, whereas resolved sites had higher levels of Actinobacteria and Propionibacterium species. These results suggest that at baseline, resolvers and pustule formers have distinct skin bacterial communities which change in response to infection and the resultant immune response

Climate variability, oceanography, bowhead whale distribution, and Iñupiat subsistence whaling near Barrow, Alaska

Author Posting. © Arctic Institute of North America, 2010. This article is posted here by permission of Arctic Institute of North America for personal use, not for redistribution. The definitive version was published in Arctic 63 (2010): 179-194.The annual migration of bowhead whales (Balaena mysticetus) past Barrow, Alaska, has provided subsistence hunting to Iñupiat for centuries. Bowheads recurrently feed on aggregations of zooplankton prey near Barrow in autumn. The mechanisms that form these aggregations, and the associations between whales and oceanography, were investigated using field sampling, retrospective analysis, and traditional knowledge interviews. Oceanographic and aerial surveys were conducted near Barrow during August and September in 2005 and 2006. Multiple water masses were observed, and close coupling between water mass type and biological characteristics was noted. Short-term variability in hydrography was associated with changes in wind speed and direction that profoundly affected plankton taxonomic composition. Aggregations of ca. 50–100 bowhead whales were observed in early September of both years at locations consistent with traditional knowledge. Retrospective analyses of records for 1984–2004 also showed that annual aggregations of whales near Barrow were associated with wind speed and direction. Euphausiids and copepods appear to be upwelled onto the Beaufort Sea shelf during Eor SEwinds. A favorable feeding environment is produced when these plankton are retained and concentrated on the shelf by the prevailing westward Beaufort Sea shelf currents that converge with the Alaska Coastal Current flowing to the northeast along the eastern edge of Barrow Canyon.This work was supported by NSF Grants OPPPP-0436131 to C. Ashjian (S. Braund Subcontract), OPPPP-0436110 to R. Campbell, OPPPP-0436127 to W. Maslowski, OPPPP-0436009 to C. Nicolson and J. Kruse, OPPPP-043166 to S. Okkonen, and OPPPP-0435956 to Y. Spitz, E. Sherr, and B. Sherr

Spring plankton dynamics in the Eastern Bering Sea, 1971-2050: Mechanisms of interannual variability diagnosed with a numerical model

A new planktonic ecosystem model was constructed for the Eastern Bering Sea based on observations from the 2007–2010 BEST/BSIERP (Bering Ecosystem Study/Bering Sea Integrated Ecosystem Research Program) field program. When run with forcing from a data-assimilative ice-ocean hindcast of 1971–2012, the model performs well against observations of spring bloom time evolution (phytoplankton and microzooplankton biomass, growth and grazing rates, and ratios among new, regenerated, and export production). On the southern middle shelf (57°N, station M2), the model replicates the generally inverse relationship between ice-retreat timing and spring bloom timing known from observations, and the simpler direct relationship between the two that has been observed on the northern middle shelf (62°N, station M8). The relationship between simulated mean primary production and mean temperature in spring (15 February to 15 July) is generally positive, although this was found to be an indirect relationship which does not continue to apply across a future projection of temperature and ice cover in the 2040s. At M2, the leading direct controls on total spring primary production are found to be advective and turbulent nutrient supply, suggesting that mesoscale, wind-driven processes—advective transport and storminess—may be crucial to long-term trends in spring primary production in the southeastern Bering Sea, with temperature and ice cover playing only indirect roles. Sensitivity experiments suggest that direct dependence of planktonic growth and metabolic rates on temperature is less significant overall than the other drivers correlated with temperature described above.This is the publisher’s final pdf. The article is copyrighted by American Geophysical Union and published by John Wiley & Sons, Inc. It can be found at: http://agupubs.onlinelibrary.wiley.com/agu/jgr/journal/10.1002/%28ISSN%292169-9291/Keywords: microzooplankton, phenology, phytoplankton bloom, climate change, ecosystem model, Bering Se

Aetiology and prevalence of mixed-infections and mono-infections in non-gonococcal urethritis in men: a case-control study

Objectives: Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) cause the majority of non-gonococcal urethritis (NGU). The role of Ureaplasma urealyticum (UU) in NGU is unclear. Prior case-control studies that examined the association of UU and NGU may have been confounded by mixed infections and less stringent criteria for controls. The objective of this case-control study was to determine the prevalence and aetiology of mixed infections in men and assess if UU monoinfection is associated with NGU. Methods: We identified 155 men with NGU and 103 controls. Behavioural and clinical information was obtained and men were tested for Neisseria gonorrhoeae and CT, MG, UU and Trichomonas vaginalis (TV). Men who were five-pathogen negative were classified as idiopathic urethritis (IU). Results: Twelve per cent of NGU cases in which a pathogen was identified had mixed infections, mostly UU coinfections with MG or CT; 27% had IU. In monoinfected NGU cases, 34% had CT, 17% had MG, 11% had UU and 2% had TV. In controls, pathogens were rarely identified, except for UU, which was present in 20%. Comparing cases and controls, NGU was associated with CT and MG monoinfections and mixed infections. UU monoinfection was not associated with NGU and was almost twice as prevalent in controls. Men in both the case and control groups who were younger and who reported no prior NGU diagnosis were more likely to have UU (OR 0.97 per year of age, 95% CI 0.94 to 0.998 and OR 6.3, 95% CI 1.4 to 28.5, respectively). Conclusions: Mixed infections are common in men with NGU and most of these are UU coinfections with other pathogens that are well-established causes of NGU. UU monoinfections are not associated with NGU and are common in younger men and men who have never previously had NGU. Almost half of NGU cases are idiopathic

Sounding Situated Knowledges - Echo in Archaeoacoustics

This article proposes that feminist epistemologies via Donna Haraway's “Situated Knowledges” can be productively brought to bear upon theories of sonic knowledge production, as “sounding situated knowledges.” Sounding situated knowledges re-reads debates around the “nature of sound” with a Harawayan notion of the “natureculture of sound.” This aims to disrupt a traditional subject-object relation which I argue has perpetuated a pervasive “sonic naturalism” in sound studies. The emerging field of archaeoacoustics (acoustic archaeology), which examines the role of sound in human behaviour in archaeology, is theorized as an opening with potentially profound consequences for sonic knowledge production which are not currently being realized. The echo is conceived as a material-semiotic articulation, which akin to Haraway's infamous cyborg, serves as a feminist figuration which enables this renegotiation. Archaeoacoustics research, read following Haraway both reflectively and diffractively, is understood as a critical juncture for sound studies which exposes the necessity of both embodiedness and situatedness for sonic knowledge production. Given the potential opened up by archaeoacoustics through the figure of echo, a critical renegotiation of the subject-object relation in sound studies is suggested as central in further developing theories of sonic knowledge production

Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein

The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which contains a docking site for substrates called the PIF pocket. Here, we used a chemical biology approach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities. The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket was accessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates. The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1

Bacterial Communities of the Coronal Sulcus and Distal Urethra of Adolescent Males

Lactobacillus-dominated vaginal microbiotas are associated with reproductive health and STI resistance in women, whereas altered microbiotas are associated with bacterial vaginosis (BV), STI risk and poor reproductive outcomes. Putative vaginal taxa have been observed in male first-catch urine, urethral swab and coronal sulcus (CS) specimens but the significance of these observations is unclear. We used 16 S rRNA sequencing to characterize the microbiota of the CS and urine collected from 18 adolescent men over three consecutive months. CS microbiotas of most participants were more stable than their urine microbiotas and the composition of CS microbiotas were strongly influenced by circumcision. BV-associated taxa, including Atopobium, Megasphaera, Mobiluncus, Prevotella and Gemella, were detected in CS specimens from sexually experienced and inexperienced participants. In contrast, urine primarily contained taxa that were not abundant in CS specimens. Lactobacilllus and Streptococcus were major urine taxa but their abundance was inversely correlated. In contrast, Sneathia, Mycoplasma and Ureaplasma were only found in urine from sexually active participants. Thus, the CS and urine support stable and distinct bacterial communities. Finally, our results suggest that the penis and the urethra can be colonized by a variety of BV-associated taxa and that some of these colonizations result from partnered sexual activity