Evidence for Sodium-Coupled Acid-Base Transport Across the Basolateral Membrane of the Reabsorptive Duct of the Human Eccrine Sweat Gland

Intracellular pH was measured in isolated nonperfused ducts of human eccrine sweat glands in vitro to investigate basolateral acid-base transport mechanisms. Bath sodium removal led to a bicarbonate-independent, 4-acetamido-4′-isothiocyanatostilbene-2,2′-disulfonic acid insensitive acidification. The recovery of this acidification was ethylisopropyl amiloride sensitive, suggestive of basolateral sodium:hydrogen exchange. Whereas bath chloride removal led to a small acidification this was not 4-acetamido-4′-isothiocyanatostilbene-2,2′-disulfonic acid sensitive and its causes remain unclear. Elevation of bath potassium to depolarize the basolateral membrane led to a small alkalinization but this was not mimicked by addition of barium or chloride removal. As chloride removal and barium addition would be expected to cause larger depolarizations than potassium elevation these observations do not support a major role for electrogenic acid-base transport. In conclusion, although this study does not support a major role for electrogenic acid-base transport, it has demonstrated the basolateral presence of sodium-coupled acid-base transport in the reabsorptive duct of the human eccrine sweat gland, which most likely represents a sodium:hydrogen exchanger involved in regulation of intracellular pH

Saving the sagebrush sea: An ecosystem conservation plan for big sagebrush plant communities

Vegetation change and anthropogenic development are altering ecosystems and decreasing biodiversity. Successful management of ecosystems threatened by multiple stressors requires development of ecosystem conservation plans rather than single species plans. We selected the big sagebrush (Artemisia tridentata Nutt.) ecosystem to demonstrate this approach. The area occupied by the sagebrush ecosystem is declining and becoming increasingly fragmented at an alarming rate because of conifer encroachment, exotic annual grass invasion, and anthropogenic development. This is causing rangewide declines and localized extirpations of sagebrush associated fauna and flora. To develop an ecosystem conservation plan, a synthesis of existing knowledge is needed to prioritize and direct management and research. Based on the synthesis, we concluded that efforts to restore higher elevation conifer-encroached, sagebrush communities were frequently successful, while restoration of exotic annual grass-invaded, lower elevation, sagebrush communities often failed. Overcoming exotic annual grass invasion is challenging and needs additional research to improve the probability of restoration and identify areas where success would be more probable. Management of fire regimes will be paramount to conserving sagebrush communities, as infrequent fires facilitate conifer encroachment and too frequent fires promote exotic annual grasses. Anthropogenic development needs to be mitigated and reduced to protect sagebrush communities and this probably includes more conservation easements and other incentives to landowners to not develop their properties. Threats to the sustainability of sagebrush ecosystem are daunting, but a coordinated ecosystem conservation plan that focuses on applying successful practices and research to overcome limitations to conservation is most likely to yield success

Laser Microdissection of Narrow Sheath Mutant Maize Uncovers Novel Gene Expression in the Shoot Apical Meristem

Microarrays enable comparative analyses of gene expression on a genomic scale, however these experiments frequently identify an abundance of differentially expressed genes such that it may be difficult to identify discrete functional networks that are hidden within large microarray datasets. Microarray analyses in which mutant organisms are compared to nonmutant siblings can be especially problematic when the gene of interest is expressed in relatively few cells. Here, we describe the use of laser microdissection microarray to perform transcriptional profiling of the maize shoot apical meristem (SAM), a ~100-μm pillar of organogenic cells that is required for leaf initiation. Microarray analyses compared differential gene expression within the SAM and incipient leaf primordium of nonmutant and narrow sheath mutant plants, which harbored mutations in the duplicate genes narrow sheath1 (ns1) and narrow sheath2 (ns2). Expressed in eight to ten cells within the SAM, ns1 and ns2 encode paralogous WUSCHEL1-like homeobox (WOX) transcription factors required for recruitment of leaf initials that give rise to a large lateral domain within maize leaves. The data illustrate the utility of laser microdissection-microarray analyses to identify a relatively small number of genes that are differentially expressed within the SAM. Moreover, these analyses reveal potentially conserved WOX gene functions and implicate specific hormonal and signaling pathways during early events in maize leaf development

Quantification of Cell Signaling Networks Using Kinase Activity Chemosensors

The ability to directly determine endogenous kinase activity in tissue homogenates provides valuable insights into signaling aberrations that underlie disease phenotypes. When activity data is collected across a panel of kinases, a unique “signaling fingerprint” is generated that allows for discrimination between diseased and normal tissue. Here we describe the use of peptide-based kinase activity sensors to fingerprint the signaling changes associated with disease states. This approach leverages the phosphorylation-sensitive sulfonamido-oxine (Sox) fluorophore to provide a direct readout of kinase enzymatic activity in unfractionated tissue homogenates from animal models or clinical samples. To demonstrate the application of this technology, we focus on a rat model of nonalcoholic fatty liver disease (NAFLD). Sox-based activity probes allow for the rapid and straightforward analysis of changes in kinase enzymatic activity associated with disease states, providing leads for further investigation using traditional biochemical approaches

Deconstructing HD 28867

The 3" pair of B9 stars, HD 28867, is one of the brightest X-ray sources in the Taurus-Auriga star forming region. In this multi-wavelength study, we attempt to deduce the source of the X-ray emission. We show that the East component is the X-ray source. The East component has a near-IR excess and displays narrow absorption lines in the optical, both of which are consistent with a cool stellar companion. This companion is one of the brightest low mass pre-main sequence stars in Tau-Aur; at 2 microns it and the B9 star are equally bright. We see evidence for radial velocity variability in the cool component of >34 km/s. It is not visible in K band speckle imaging, which constrains the companion to lie within 14 AU of the B star. We also report on a possible fourth member of the group, an M1 star 18" south of HD 28867.Comment: accepted by the Astronomical Journa

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer's disease: a case series.

BACKGROUND: The causes of phenotypic heterogeneity in familial Alzheimer's disease with autosomal dominant inheritance are not well understood. We aimed to characterise clinical phenotypes and genetic associations with APP and PSEN1 mutations in symptomatic autosomal dominant familial Alzheimer's disease (ADAD). METHODS: We retrospectively analysed genotypic and phenotypic data (age at symptom onset, initial cognitive or behavioural symptoms, and presence of myoclonus, seizures, pyramidal signs, extrapyramidal signs, and cerebellar signs) from all individuals with ADAD due to APP or PSEN1 mutations seen at the Dementia Research Centre in London, UK. We examined the frequency of presenting symptoms and additional neurological features, investigated associations with age at symptom onset, APOE genotype, and mutation position, and explored phenotypic differences between APP and PSEN1 mutation carriers. The proportion of individuals presenting with various symptoms was analysed with descriptive statistics, stratified by mutation type. FINDINGS: Between July 1, 1987, and Oct 31, 2015, age at onset was recorded for 213 patients (168 with PSEN1 mutations and 45 with APP mutations), with detailed history and neurological examination findings available for 121 (85 with PSEN1 mutations and 36 with APP mutations). We identified 38 different PSEN1 mutations (four novel) and six APP mutations (one novel). Age at onset differed by mutation, with a younger onset for individuals with PSEN1 mutations than for those with APP mutations (mean age 43·6 years [SD 7·2] vs 50·4 years [SD 5·2], respectively, p<0·0001); within the PSEN1 group, 72% of age at onset variance was explained by the specific mutation. A cluster of five mutations with particularly early onset (mean age at onset <40 years) involving PSEN1's first hydrophilic loop suggests critical functional importance of this region. 71 (84%) individuals with PSEN1 mutations and 35 (97%) with APP mutations presented with amnestic symptoms, making atypical cognitive presentations significantly more common in PSEN1 mutation carriers (n=14; p=0·037). Myoclonus and seizures were the most common additional neurological features; individuals with myoclonus (40 [47%] with PSEN1 mutations and 12 [33%] with APP mutations) were significantly more likely to develop seizures (p=0·001 for PSEN1; p=0·036 for APP), which affected around a quarter of the patients in each group (20 [24%] and nine [25%], respectively). A number of patients with PSEN1 mutations had pyramidal (21 [25%]), extrapyramidal (12 [14%]), or cerebellar (three [4%]) signs. INTERPRETATION: ADAD phenotypes are heterogeneous, with both age at onset and clinical features being influenced by mutation position as well as causative gene. This highlights the importance of considering genetic testing in young patients with dementia and additional neurological features in order to appropriately diagnose and treat their symptoms, and of examining different mutation types separately in future research. FUNDING: Medical Research Council and National Institute for Health Research

The APOKASC Catalog: An Asteroseismic and Spectroscopic Joint Survey of Targets in the Kepler Fields

We present the first APOKASC catalog of spectroscopic and asteroseismic properties of 1916 red giants observed in the Kepler fields. The spectroscopic parameters provided from the Apache Point Observatory Galactic Evolution Experiment project are complemented with asteroseismic surface gravities, masses, radii, and mean densities determined by members of the Kepler Asteroseismology Science Consortium. We assess both random and systematic sources of error and include a discussion of sample selection for giants in the Kepler fields. Total uncertainties in the main catalog properties are of order 80 K in Teff , 0.06 dex in [M/H], 0.014 dex in log g, and 12% and 5% in mass and radius, respectively; these reflect a combination of systematic and random errors. Asteroseismic surface gravities are substantially more precise and accurate than spectroscopic ones, and we find good agreement between their mean values and the calibrated spectroscopic surface gravities. There are, however, systematic underlying trends with Teff and log g. Our effective temperature scale is between 0-200 K cooler than that expected from the Infrared Flux Method, depending on the adopted extinction map, which provides evidence for a lower value on average than that inferred for the Kepler Input Catalog (KIC). We find a reasonable correspondence between the photometric KIC and spectroscopic APOKASC metallicity scales, with increased dispersion in KIC metallicities as the absolute metal abundance decreases, and offsets in Teff and log g consistent with those derived in the literature. We present mean fitting relations between APOKASC and KIC observables and discuss future prospects, strengths, and limitations of the catalog data.Comment: 49 pages. ApJSupp, in press. Full machine-readable ascii files available under ancillary data. Categories: Kepler targets, asteroseismology, large spectroscopic survey

Sports tribes and academic identity: teaching the sociology of sport in a changing disciplinary landscape

Using data from 15 semi-structured interviews with UK-based early/mid-career academics, this paper offers an empirically informed assessment of how lecturers teaching/researching the sociology of sport are managing their careers in a changing higher education landscape. Those interviewed were involved in the delivery of sociological content to a range of sports-themed courses with the interviews focusing on the changing fashions in studying sport (including a rapid increase in enrolment on certain sports-themed courses), and on the nature of the relationships with colleagues working in the same area (i.e. sport), but who teach/research it from a different discipline. The paper draws upon the processes of individualisation which lay at the root of reflexive modernisation to better understand the lived experiences of those interviewed. Using the metaphors of tribes, doors and boundaries, I assess the extent to which those interviewed felt there were opportunities for an interdisciplinary pedagogic approach to ‘sport’. The paper explores the relationship between the sociology of sport and its parent discipline (i.e. sociology) and where it might feature in a future (post-disciplinary?) landscape