The Importance of <em>Sceletium tortuosum</em> (L.) N.E. Brown and Its Viability as a Traditional African Medicinal Plant

Sceletium tortuosum is a succulent plant that belongs to the family Mesembryanthemaceae (Aizoaceae). It is indigenous to South Africa, where it is well known by the indigenous people, especially in Namaqualand where the plant is utilized regularly for its medicinal and psycho-active properties. The main alkaloids responsible for these properties are mesembrine, mesembrenine (mesembrenone), and mesembrenol. The potential of the plant to be an alternative supplement in the promotion of health and treating a variety of psychological and psychiatric disorders such as depression and anxiety has stimulated interest in its pharmacological property and possibility of its commercialization. The economic value of indigenous medicinal plants in South Africa is approximately US$60 000 000 or R4 000 000 000 annually. Thus, interest in the knowledge and use of Traditional African Medicinal Plants (TAMP) as well as meeting pharmacological and economic needs of ever-increasing human population has led to the commercialization of traditional African medicines at a fast rate. It was found that S. tortuosum has clear pharmaceutical and economical importance and is one of the only known plants to contain the alkaloids mesembrenone and mesembrine which can be utilized for the promotion of health and/or treating a variety of psychological disorders such as anxiety and depression

Understanding the Astrophysics of Galaxy Evolution: the role of spectroscopic surveys in the next decade

Over the last decade optical spectroscopic surveys have characterized the low redshift galaxy population and uncovered populations of star-forming galaxies back to z ~ 7. This work has shown that the primary epoch of galaxy building and black hole growth occurs at redshifts of 2 to 3. The establishment of the concordance LCDM cosmology shifted the focus of galaxy population studies from constraining cosmological parameters to characterizing the processes which regulate the formation and evolution of galaxies.In the next decade, high redshift observers will attempt to formulate a coherent evolutionary picture connecting galaxies in the high redshift Universe to galaxies today. In order to link galaxy populations at different redshifts, we must not only characterize their evolution in a systematic way, we must establish which physical processes are responsible for it. Considerable progress has already been made in understanding how galaxies evolved from z ~ 1 to the present day. Large spectroscopic surveys in the near infrared are required to push these studies back towards the main epoch of galaxy building. Only then will we understand the full story of the formation of L* galaxies like our own Milky Way. A large near-IR spectroscopic survey will also provide the calibration needed to avoid systematics in the large photometric programs proposed to study the nature of dark matter and dark energy. We provide an outline design for a multi-object 0.4 to 1.8 micron spectrograph, which could be placed on an existing telescope, and which would allow a full characterization of the galaxy population out to z ~ 2. We strongly recommend a serious further study to design a real instrument, which will be required for galaxy formation studies to advance to the next frontier.Comment: White paper, primary author J.E. Gunn, submitted to Astro2010 Decadal Survey, see http://www7.nationalacademies.org/bpa/Astro2010_SWP_byTitle.htm

Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. Results: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. Conclusion: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project

The Numerical INJection Analysis (NINJA) project is a collaborative effort between members of the numerical relativity and gravitational-wave data analysis communities. The purpose of NINJA is to study the sensitivity of existing gravitational-wave search algorithms using numerically generated waveforms and to foster closer collaboration between the numerical relativity and data analysis communities. We describe the results of the first NINJA analysis which focused on gravitational waveforms from binary black hole coalescence. Ten numerical relativity groups contributed numerical data which were used to generate a set of gravitational-wave signals. These signals were injected into a simulated data set, designed to mimic the response of the Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this data using search and parameter-estimation pipelines. Matched filter algorithms, un-modelled-burst searches and Bayesian parameter-estimation and model-selection algorithms were applied to the data. We report the efficiency of these search methods in detecting the numerical waveforms and measuring their parameters. We describe preliminary comparisons between the different search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ

Survival and Passage of Juvenile Chinook Salmon and Steelhead Passing through Bonneville Dam, 2010

Pacific Northwest National Laboratory (PNNL) and subcontractors conducted an acoustic-telemetry study of juvenile salmonid fish passage and survival at Bonneville Dam in 2010. The study was conducted to assess the readiness of the monitoring system for official compliance studies under the 2008 Biological Opinion and Fish Accords and to assess performance measures including route-specific fish passage proportions, travel times, and survival based upon a single-release model. This also was the last year of evaluation of effects of a behavioral guidance device installed in the Powerhouse 2 forebay. The study relied on releases of live Juvenile Salmon Acoustic Telemetry System tagged smolts in the Columbia River and used acoustic telemetry to evaluate the approach, passage, and survival of passing juvenile salmon. This study supports the U.S. Army Corps of Engineers continual effort to improve conditions for juvenile anadromous fish passing through Columbia River dams

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development