A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities

To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K(+)) channels and resultant K(+) efflux. Sperm-specific SLO3 K(+) channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K(+) conductance is both Ca(2+)- and pH i -sensitive. It has been debated whether Ca(2+)-sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca(2+) sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca(2+) and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca(2+), the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca(2+) sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established.info:eu-repo/semantics/publishe

3D-printed facsimiles as classroom primary sources: a comparative review

3D prints have been promised as a saviour of material truth, a path to universal primary source accessibility. By replicating a Babylonian tablet using several 3D print technologies, we show that 3D scanning and printing are as fraught as any other representational technology. The scans and prints alike feature technological infidelities, some of which can be readily mistaken for the real thing. 3D prints might still have their use if approached appropriately. The methods of traditional textual scholarship might be just the framework that we need

BK channels of five different subunit combinations underlie the de novo KCNMA1 G375R channelopathy

The molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the tetrameric BK channel is unknown. Here, we address this question by recording from single BK channels expressed to mimic a G375R mutation heterozygous with a WT allele. Five different types of functional BK channels were expressed: 3% were consistent with WT, 12% with homotetrameric mutant, and 85% with three different types of hybrid (heterotetrameric) channels assembled from both mutant and WT subunits. All channel types except WT showed a marked gain-of-function in voltage activation and a smaller decrease-of-function in single-channel conductance, with both changes in function becoming more pronounced as the number of mutant subunits per tetrameric channel increased. The net cellular response from the five different types of channels comprising the molecular phenotype was a shift of -120 mV in the voltage required to activate half of the maximal current through BK channels, giving a net gain-of-function. The WT and homotetrameric mutant channels in the molecular phenotype were consistent with genetic codominance as each displayed properties of a channel arising from only one of the two alleles. The three types of hybrid channels in the molecular phenotype were consistent with partial dominance as their properties were intermediate between those of mutant and WT channels. A model in which BK channels randomly assemble from mutant and WT subunits, with each subunit contributing increments of activation and conductance, approximated the molecular phenotype of the heterozygous G375R mutation

Nineteenth-Century Popular Science Magazines, Narrative, and the Problem of Historical Materiality

In his Some Reminiscences of a Lecturer, Andrew Wilson emphasizes the importance of narrative to popular science lecturing. Although Wilson promotes the teaching of science as useful knowledge in its own right, he also recognizes that the way science is taught can encourage audiences to take the subject up and read further on their own. Form, according to Wilson, should not be divorced from scientific content and lecturers should ensure that not only is their science accurate, but that it is presented in a way that will provoke curiosity and stimulate interest. This paper discusses the influence of narrative in structuring scientific objects and phenomena, and considers the consequences of such presentations for historical research. As scientific journalism necessarily weaves both its intended audience and the objects under discussion into its accounts, these texts demand that we recognize their nature as social relationships inscribed in historical objects

Magnetic moments of the 3/2 resonances and their quark spin structure

We discuss magnetic moments of the $J=3/2$ baryons based on an earlier model for the baryon magnetic moments, allowing for flavor symmetry breaking in the quark magnetic moments as well as a general quark spin structure. From our earlier analysis of the nucleon-hyperon magnetic moments and the measured values of the magnetic moments of $\Delta^{++}$ and $\Omega^{-}$ we predict the other magnetic moments and deduce the spin structure of the resonance particles. We find from experiment that the total spin polarization of the decuplet baryons, $\Delta\Sigma(3/2)$, is considerably smaller than the non-relativistic quark model value of 3, although the data is still not good enough to give a precise determination.Comment: 13 pages, REVTeX, 2 figures, minor clarifying change

Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors

We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata

Can a “state of the art” chemistry transport model simulate Amazonian tropospheric chemistry?

We present an evaluation of a nested high-resolution Goddard Earth Observing System (GEOS)-Chem chemistry transport model simulation of tropospheric chemistry over tropical South America. The model has been constrained with two isoprene emission inventories: (1) the canopy-scale Model of Emissions of Gases and Aerosols from Nature (MEGAN) and (2) a leaf-scale algorithm coupled to the Lund-Potsdam-Jena General Ecosystem Simulator (LPJ-GUESS) dynamic vegetation model, and the model has been run using two different chemical mechanisms that contain alternative treatments of isoprene photo-oxidation. Large differences of up to 100 Tg C yr^(−1) exist between the isoprene emissions predicted by each inventory, with MEGAN emissions generally higher. Based on our simulations we estimate that tropical South America (30–85°W, 14°N–25°S) contributes about 15–35% of total global isoprene emissions. We have quantified the model sensitivity to changes in isoprene emissions, chemistry, boundary layer mixing, and soil NO_x emissions using ground-based and airborne observations. We find GEOS-Chem has difficulty reproducing several observed chemical species; typically hydroxyl concentrations are underestimated, whilst mixing ratios of isoprene and its oxidation products are overestimated. The magnitude of model formaldehyde (HCHO) columns are most sensitive to the choice of chemical mechanism and isoprene emission inventory. We find GEOS-Chem exhibits a significant positive bias (10–100%) when compared with HCHO columns from the Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY) and Ozone Monitoring Instrument (OMI) for the study year 2006. Simulations that use the more detailed chemical mechanism and/or lowest isoprene emissions provide the best agreement to the satellite data, since they result in lower-HCHO columns

Enhanced cell deconvolution of peripheral blood using DNA methylation for high-resolution immune profiling

DNA methylation microarrays can be employed to interrogate cell-type composition in complex tissues. Here, we expand reference-based deconvolution of blood DNA methylation to include 12 leukocyte subtypes (neutrophils, eosinophils, basophils, monocytes, naïve and memory B cells, naïve and memory CD4 + and CD8 + T cells, natural killer, and T regulatory cells). Including derived variables, our method provides 56 immune profile variables. The IDOL (IDentifying Optimal Libraries) algorithm was used to identify libraries for deconvolution of DNA methylation data for current and previous platforms. The accuracy of deconvolution estimates obtained using our enhanced libraries was validated using artificial mixtures and whole-blood DNA methylation with known cellular composition from flow cytometry. We applied our libraries to deconvolve cancer, aging, and autoimmune disease datasets. In conclusion, these libraries enable a detailed representation of immune-cell profiles in blood using only DNA and facilitate a standardized, thorough investigation of immune profiles in human health and disease

Temporal and spatial variability of dissolved organic and inorganic phosphorus, and metrics of phosphorus bioavailability in an upwelling-dominated coastal system

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 110 (2005): C10S13, doi:10.1029/2004JC002837.High-frequency temporal and spatial shifts in the various dissolved P pools (total, inorganic, and organic) are linked to upwelling/relaxation events and to phytoplankton bloom dynamics in the upwelling-dominated Oregon coastal system. The presence and regulation of alkaline phosphatase activity (APA) is apparent in the bulk phytoplankton population and in studies of cell-specific APA using Enzyme Labeled Fluorescence (ELF®). Spatial and temporal variability are also evident in phytoplankton community composition and in APA. The spatial pattern of dissolved phosphorus and APA variability can be explained by bottom-controlled patterns of upwelling, and flushing times of different regions within the study area. The presence of APA in eukaryotic taxa indicates that dissolved organic phosphorus (DOP) may contribute to phytoplankton P nutrition in this system, highlighting the need for a more complete understanding of P cycling and bioavailability in the coastal ocean.KCR acknowledges WHOI for rapid-response funding that made possible participation on this first COAST cruise, and NSF-OCE grant 0119134 for support of subsequent work on these and other COAST samples