Ge and Si Isotope Behavior During Intense Tropical Weathering and Ecosystem Cycling

Chemical weathering of volcanic rocks in warm and humid climates contributes disproportionately to global solute fluxes. Geochemical signatures of solutes and solids formed during this process can help quantify and reconstruct weathering intensity in the past. Here, we measured silicon (Si) and germanium (Ge) isotope ratios of the soils, clays, and fluids from a tropical lowland rainforest in Costa Rica. The bulk topsoil is intensely weathered and isotopically light (mean ± 1σ: δ³⁰Si = −2.1 ± 0.3‰, δ⁷⁴Ge = −0.13 ± 0.12‰) compared to the parent rock (δ³⁰Si = −0.11 ± 0.05‰, δ⁷⁴Ge = 0.59 ± 0.07‰). Neoforming clays have even lower values (δ³⁰Si = −2.5 ± 0.2‰, δ⁷⁴Ge = −0.16 ± 0.09‰), demonstrating a whole‐system isotopic shift in extremely weathered systems. The lowland streams represent mixing of dilute local fluids (δ³⁰Si = 0.2 − 0.6‰, δ⁷⁴Ge = 2.2 − 2.6‰) with solute‐rich interbasin groundwater (δ³⁰Si = 1.0 ± 0.2‰, δ⁷⁴Ge = 4.0‰). Using a Ge‐Si isotope mass balance model, we calculate that 91 ± 9% of Ge released via weathering of lowland soils is sequestered by neoforming clays, 9 ± 9% by vegetation, and only 0.2 ± 0.2% remains dissolved. Vegetation plays an important role in the Si cycle, directly sequestering 39 ± 14% of released Si and enhancing clay neoformation in surface soils via the addition of amorphous phytolith silica. Globally, volcanic soil δ⁷⁴Ge closely tracks the depletion of Ge by chemical weathering (τGe), whereas δ³⁰Si and Ge/Si both reflect the loss of Si (τ_{Si}). Because of the different chemical mobilities of Ge and Si, a δ⁷⁴Ge‐δ³⁰Si multiproxy system is sensitive to a wider range of weathering intensities than each isotopic system in isolation

Ge/Si and Ge Isotope Fractionation During Glacial and Non-glacial Weathering: Field and Experimental Data From West Greenland

Glacial environments offer the opportunity to study the incipient stages of chemical weathering due to the high availability of finely ground sediments, low water temperatures, and typically short rock-water interaction times. In this study we focused on the geochemical behavior of germanium (Ge) in west Greenland, both during subglacial weathering by investigating glacier-fed streams, as well as during a batch reactor experiment by allowing water-sediment interaction for up to 2 years in the laboratory. Sampled in late August 2014, glacial stream Ge and Si concentrations were low, ranging between 12–55 pmol/L and 7–33 µmol/L, respectively (Ge/Si = 0.9–2.2 µmol/mol, similar to parent rock). As reported previously, the dissolved stable Ge isotope ratio (δ74Ge) of the Watson River was 0.86 ± 0.24‰, the lowest among global rivers and streams measured to date. This value was only slightly heavier than the suspended load (0.48 ± 0.23‰), which is likely representative of the bulk parent rock composition. Despite limited Ge/Si and δ74GeGe fractionation, both Ge and Si appear depleted relative to Na during subglacial weathering, which we interpret as the relatively congruent uptake of both phases by amorphous silica (aSi). Continued sediment-water interaction over 470–785 days in the lab produced a large increase in dissolved Si concentrations (up to 130–230 µmol/L), a much smaller increase in dissolved Ge (up to ∼70 pmol/L), resulting in a Ge/Si decrease (to 0.4–0.5 µmol/mol) and a significant increase in δ74Ge (to 1.9–2.2‰). We argue that during the experiment, both Si and Ge are released by the dissolution of previously subglacially formed aSi, and Ge is then incorporated into secondary phases (likely adsorbed to Fe oxyhydroxides), with an associated Δ74Gesecondary−dissolved fractionation factor of −2.15 ± 0.46‰. In summary, we directly demonstrate Ge isotope fractionation during the dissolution-precipitation weathering reactions of natural sediments in the absence of biological Ge and Si uptake, and highlight the significant differences in Ge behavior during subglacial and non-glacial weathering.</jats:p

Enhanced Avidity Maturation of Antibody to Human Immunodeficiency Virus Envelope: DNA Vaccination with gp120-C3d Fusion Proteins

DNA vaccination can elicit both humoral and cellular immune responses and can confer protection against several pathogens. However, DNA vaccines expressing the envelope (Env) protein of human immunodeficiency virus (HIV) have been relatively ineffective at generating high titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, we report that fusion of Env and the complement component, C3d, in a DNA vaccine, enhances the titers of antibody to Env. Plasmids were generated that expressed a secreted form of Env (sgp120) from three isolates of HIV and these same forms fused to three tandem copies of the murine homologue of C3d (sgp120-3C3d). Analyses of titers and avidity maturation of the raised antibody indicated that immunizations with each of the sgp120-3C3d-expressing DNAs accelerated both the onset and the avidity maturation of antibody to Env. Originally published AIDS Research and Human Retroviruses, Vol. 17, No. 9, June 200

Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator

Zuranolone (SAGE-217) is a novel, synthetic, clinical stage neuroactive steroid GABAA receptor positive allosteric modulator designed with the pharmacokinetic properties to support oral daily dosing. In vitro, zuranolone enhanced GABAA receptor current at nine unique human recombinant receptor subtypes, including representative receptors for both synaptic (γ subunit-containing) and extrasynaptic (δ subunit-containing) configurations. At a representative synaptic subunit configuration, α1β2γ2, zuranolone potentiated GABA currents synergistically with the benzodiazepine diazepam, consistent with the non-competitive activity and distinct binding sites of the two classes of compounds at synaptic receptors. In a brain slice preparation, zuranolone produced a sustained increase in GABA currents consistent with metabotropic trafficking of GABAA receptors to the cell surface. In vivo, zuranolone exhibited potent activity, indicating its ability to modulate GABAA receptors in the central nervous system after oral dosing by protecting against chemo-convulsant seizures in a mouse model and enhancing electroencephalogram β-frequency power in rats. Together, these data establish zuranolone as a potent and efficacious neuroactive steroid GABAA receptor positive allosteric modulator with drug-like properties and CNS exposure in preclinical models. Recent clinical data support the therapeutic promise of neuroactive steroid GABAA receptor positive modulators for treating mood disorders; brexanolone is the first therapeutic approved specifically for the treatment of postpartum depression. Zuranolone is currently under clinical investigation for the treatment of major depressive episodes in major depressive disorder, postpartum depression, and bipolar depression

Smokers' reactions to FDA regulation of tobacco products: Findings from the 2009 ITC United States survey

<p>Abstract</p> <p>Background</p> <p>On June 22, 2009, the US FDA was granted the authority to regulate tobacco products through the Family Smoking Prevention and Tobacco Control Act (FSPTCA). The intent is to improve public health through regulations on tobacco product marketing and tobacco products themselves. This manuscript reports baseline data on smokers' attitudes and beliefs on specific issues relevant to the FSPTCA.</p> <p>Method</p> <p>Between November 2009 and January 2010, a telephone survey among a nationally representative sample of n = 678 smokers in the US was performed as part of the International Tobacco Control (ITC) United States Survey. Participants answered a battery of questions on their attitudes and beliefs about aspects of the FSPTCA.</p> <p>Results</p> <p>Most smokers were unaware of the new FDA tobacco regulations. Smokers indicated support for banning cigarette promotion and nearly a quarter supported requiring tobacco companies to sell cigarettes in plain packaging. Seventy two percent of smokers supported reducing nicotine levels to make cigarettes less addictive if nicotine was made easily available in non-cigarette form.</p> <p>Conclusion</p> <p>Most smokers were limited in their understanding of efforts to regulate tobacco products in general. Smokers were supportive of efforts to better inform the public about health risks, restrict advertising, and make tobacco products less addictive.</p

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review

Background Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses. To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. Methods We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. Results Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. Conclusion There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect

Modeling recursive RNA interference.

An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments

Opportunities to Learn Mathematics Pedagogy and Connect Classroom Learning to Practice: A Study of Future Teachers in the United States and Singapore

In this study, we conducted secondary analyses using the TEDS-M database to explore future mathematics specialists teachers’ opportunities to learn (OTL) how to teach mathematics. We applied latent class analysis techniques to differentiate among groups of prospective mathematics specialists with potentially different OTL mathematics pedagogy within the United States and Singapore. Within the United States, three subgroups were identified: (a) Comprehensive OTL, (b) Limited OTL, and (c) OTL Mathematics Pedagogy. Within Singapore, four subgroups were identified: (a) Comprehensive OTL, (b) Limited Opportunities to Connect Classroom Learning with Practice, (c) OTL Mathematics Pedagogy, and (d) Basic OTL. Understanding the opportunities different prospective teachers had to learn from and their experiences with different components of instructional practice in university and practicum settings has implications for teacher preparation programs

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Acquisition of uropygial gland microbiome by hoopoe nestlings

Mutualistic symbioses between animals and bacteria depend on acquisition of appropriate symbionts while avoiding exploitation by non-beneficial microbes. The mode of acquisition of symbionts would determine, not only the probability of encountering but also evolutionary outcomes of mutualistic counterparts. The microbiome inhabiting the uropygial gland of the European hoopoe (Upupa epops) includes a variety of bacterial strains, some of them providing antimicrobial benefits. Here, the mode of acquisition and stability of this microbiome is analyzed by means of Automated rRNA Intergenic Spacer Analysis and two different experiments. The first experiment impeded mothers’ access to their glands, thus avoiding direct transmission of microorganisms from female to offspring secretions. The second experiment explored the stability of the microbiomes by inoculating glands with secretions from alien nests. The first experiment provoked a reduction in similarity of microbiomes of mother and nestlings. Interestingly, some bacterial strains were more often detected when females had not access to their glands, suggesting antagonistic effects among bacteria from different sources. The second experiment caused an increase in richness of the microbiome of receivers in terms of prevalence of Operational Taxonomic Units (OTUs) that reduced differences in microbiomes of donors and receivers. That occurred because OTUs that were present in donors but not in receivers incorporated to the microbiome of the latter, which provoked that cross-inoculated nestlings got similar final microbiomes that included the most prevalent OTUs. The results are therefore consistent with a central role of vertical transmission in bacterial acquisition by nestling hoopoes and support the idea that the typical composition of the hoopoe gland microbiome is reached by the incorporation of some bacteria during the nestling period. This scenario suggests the existence of a coevolved core microbiome composed by a mix of specialized vertically transmitted strains and facultative symbionts able to coexist with them. The implications of this mixed mode of transmission for the evolution of the mutualism are discussedMinisterio de Ciencia e Innovación (España)Junta de Andalucí