Large Scale Structure traced by Molecular Gas at High Redshift

We present observations of redshifted CO(1-0) and CO(2-1) in a field containing an overdensity of Lyman break galaxies (LBGs) at z=5.12. Our Australia Telescope Compact Array observations were centered between two spectroscopically-confirmed z=5.12 galaxies. We place upper limits on the molecular gas masses in these two galaxies of M(H_2) <1.7 x 10^10 M_sun and <2.9 x 10^9 M_sun (2 sigma), comparable to their stellar masses. We detect an optically-faint line emitter situated between the two LBGs which we identify as warm molecular gas at z=5.1245 +/- 0.0001. This source, detected in the CO(2-1) transition but undetected in CO(1-0), has an integrated line flux of 0.106 +/- 0.012 Jy km/s, yielding an inferred gas mass M(H_2)=(1.9 +/- 0.2) x 10^10 M_sun. Molecular line emitters without detectable counterparts at optical and infrared wavelengths may be crucial tracers of structure and mass at high redshift.Comment: 4 pages, accepted for publication in ApJ Letter

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe

Functional or not functional; that's the question Can we predict the diagnosis functional movement disorder based on associated features?

Background and purpose Functional movement disorders (FMDs) pose a diagnostic challenge for clinicians. Over the years several associated features have been shown to be suggestive for FMDs. Which features mentioned in the literature are discriminative between FMDs and non-FMDs were examined in a large cohort. In addition, a preliminary prediction model distinguishing these disorders was developed based on differentiating features. Method Medical records of all consecutive patients who visited our hyperkinetic outpatient clinic from 2012 to 2019 were retrospectively reviewed and 12 associated features in FMDs versus non-FMDs were compared. An independentttest for age of onset and Pearson chi-squared analyses for all categorical variables were performed. Multivariate logistic regression analysis was performed to develop a preliminary predictive model for FMDs. Results A total of 874 patients were eligible for inclusion, of whom 320 had an FMD and 554 a non-FMD. Differentiating features between these groups were age of onset, sex, psychiatric history, family history, more than one motor phenotype, pain, fatigue, abrupt onset, waxing and waning over long term, and fluctuations during the day. Based on these a preliminary predictive model was computed with a discriminative value of 91%. Discussion Ten associated features are shown to be not only suggestive but also discriminative between hyperkinetic FMDs and non-FMDs. Clinicians can use these features to identify patients suspected for FMDs and can subsequently alert them to test for positive symptoms at examination. Although a first preliminary model has good predictive accuracy, further validation should be performed prospectively in a multi-center study

The diagnostic value of clinical neurophysiology in hyperkinetic movement disorders:A systematic review

Introduction: To guide the neurologist and neurophysiologist with interpretation and implementation of clinical neurophysiological examinations, we aim to provide a systematic review on evidence of electrophysiological features used to differentiate between hyperkinetic movement disorders. Methods: A PRISMA systematic search and QUADAS quality evaluation has been performed in PubMed to identify diagnostic test accuracy studies comparing electromyography and accelerometer features. We included papers focusing on tremor, dystonia, myoclonus, chorea, tics and ataxia and their functional variant. The features were grouped as 1) basic features (e.g., amplitude, frequency), 2) the influence of tasks on basic features (e.g., entrainment, distraction), 3) advanced analyses of multiple signals, 4) and diagnostic tools combining features. Results: Thirty-eight cross-sectional articles were included discussing tremor (n = 28), myoclonus (n = 5), dystonia (n = 5) and tics (n = 1). Fifteen were rated as ‘high quality’. In tremor, the basic and task-related features showed great overlap between clinical tremor syndromes, apart from rubral and enhanced physiological tremor. Advanced signal analyses were best suited for essential, parkinsonian and functional tremor, and cortical, non-cortical and functional jerks. Combinations of electrodiagnostic features could identify essential, enhanced physiological and functional tremor. Conclusion: Studies into the diagnostic accuracy of electrophysiological examinations to differentiate between hyperkinetic movement disorders have predominantly been focused on clinical tremor syndromes. No single feature can differentiate between them all; however, a combination of analyses might improve diagnostic accuracy

Cardiometabolic Plasticity in Response to a Short-Term Diet and Exercise Intervention in Young Hispanic and NonHispanic White Adults

BACKGROUND: Young adult Mexican Americans (MA) exhibit lower insulin sensitivity (Si) than nonHispanic whites (NHW), even when controlling for fitness and adiposity. It is unclear if MA are as responsive to the same lifestyle intervention as NHW. OBJECTIVE: We developed a model to examine cardiometabolic plasticity (i.e., changes in Si and plasma lipids) in MA compared to NHW adults in response to a diet-exercise intervention. DESIGN: Sedentary subjects (20 NHW: 11F, 9M, 23.0 y, 25.5 kg/m(2); 17 MA: 13F, 4M, 22.7 y, 25.4 kg/m(2)) consumed their habitual diets and remained sedentary for 7 days, after which fasting blood samples were obtained, and a 3-h intravenous glucose tolerance test (IVGTT) was performed with the insulin area under the curve (IAUC) used to estimate Si. Subjects then completed a 7-day diet/exercise intervention (diet: low saturated fat, low added sugar, high fiber; exercise: cycling, six total sessions lasting 40-45 min/session at 65% VO(2) max). Pre-intervention tests were repeated. RESULTS: Pre intervention IAUC was 28% higher (p<0.05) in MA (IAUC pre  =  2298 µU*180 min/mL) than in NHW (IAUC = 1795 µU*180 min/mL). Following the intervention, there was a significant reduction in IAUC in MA (29%) and NHW (32%), however, the IAUC remained higher (p<0.05) for MA (post  = 1635 µU*180 min/mL) than for NHW (post = 1211 µU*180 min/mL). Pre test plasma lipids were not different in MA compared to NHW. Plasma cholesterol and TG concentrations significantly improved in both groups, but concentrations of low density lipoprotein-cholesterol and small dense LDL particles significantly improved only in the NHW. CONCLUSION: With a short-term diet-exercise intervention, the magnitude of improvements in Si and serum cholesterol and TG in Hispanics are similar to those in NHW. However, because at the outset MA were less insulin sensitive compared to NHW, within the short timeframe studied the ethnic gap in insulin sensitivity remained

L-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study

<p>Abstract</p> <p>Background</p> <p>Accumulating evidence suggests that the brain's nitric oxide (NO) signalling system may be involved in the pathophysiology of schizophrenia and could thus constitute a novel treatment target. The study was designed to investigate the benefit of L-lysine, an amino acid that interferes with NO production, as an add-on treatment for schizophrenia.</p> <p>Methods</p> <p>L-lysine, 6 g/day, was administered to 10 patients with schizophrenia as an adjunctive to their conventional antipsychotic medication. The study was designed as a single-blinded, cross-over study where patients were randomly assigned to initial treatment with either L-lysine or placebo and screened at baseline, after four weeks when treatment was crossed over, and after eight weeks.</p> <p>Results</p> <p>L-lysine treatment caused a significant increase in blood concentration of L-lysine and was well tolerated. A significant decrease in positive symptom severity, measured by the Positive And Negative Syndrome Scale (PANSS), was detected. A certain decrease in score was also observed during placebo treatment and the effects on PANSS could not unequivocally be assigned to the L-lysine treatment. Furthermore, performance on the Wisconsin Card Sorting Test was significantly improved compared to baseline, an effect probably biased by training. Subjective reports from three of the patients indicated decreased symptom severity and enhanced cognitive functioning.</p> <p>Conclusions</p> <p>Four-week L-lysine treatment of 6 g/day caused a significant increase in blood concentration of L-lysine that was well tolerated. Patients showed a significant decrease in positive symptoms as assessed by PANSS in addition to self-reported symptom improvement by three patients. The NO-signalling pathway is an interesting, potentially new treatment target for schizophrenia; however, the effects of L-lysine need further evaluation to decide the amino acid's potentially beneficial effects on symptom severity in schizophrenia.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00996242">NCT00996242</a></p

[18F]FDG PET in conditions associated with hyperkinetic movement disorders and ataxia:a systematic review

PURPOSE: To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [18F]FDG PET, in conditions associated with hyperkinetic movement disorders and ataxia. In addition, correlations between glucose metabolism and clinical variables as well as the effect of treatment on glucose metabolism are discussed.METHODS: A systematic literature search was performed according to PRISMA guidelines. Studies concerning tremors, tics, dystonia, ataxia, chorea, myoclonus, functional movement disorders, or mixed movement disorders due to autoimmune or metabolic aetiologies were eligible for inclusion. A PubMed search was performed up to November 2021.RESULTS: Of 1240 studies retrieved in the original search, 104 articles were included. Most articles concerned patients with chorea (n = 27), followed by ataxia (n = 25), dystonia (n = 20), tremor (n = 8), metabolic disease (n = 7), myoclonus (n = 6), tics (n = 6), and autoimmune disorders (n = 5). No papers on functional movement disorders were included. Altered glucose metabolism was detected in various brain regions in all movement disorders, with dystonia-related hypermetabolism of the lentiform nuclei and both hyper- and hypometabolism of the cerebellum; pronounced cerebellar hypometabolism in ataxia; and striatal hypometabolism in chorea (dominated by Huntington disease). Correlations between clinical characteristics and glucose metabolism were often described. [18F]FDG PET-showed normalization of metabolic alterations after treatment in tremors, ataxia, and chorea.CONCLUSION: In all conditions with hyperkinetic movement disorders, hypo- or hypermetabolism was found in multiple, partly overlapping brain regions, and clinical characteristics often correlated with glucose metabolism. For some movement disorders, [18F]FDG PET metabolic changes reflected the effect of treatment.</p

Deep GMRT 150 MHz observations of the LBDS-Lynx region: Ultra-Steep Spectrum Radio Sources

It has been known for nearly three decades that high redshift radio galaxies exhibit steep radio spectra, and hence ultra-steep spectrum radio sources provide candidates for high-redshift radio galaxies. Nearly all radio galaxies with z > 3 have been found using this redshift-spectral index correlation. We have started a programme with GMRT to exploit this correlation at flux density levels about 10 to 100 times deeper than the known high-redshift radio galaxies which were identified primarily using the already available radio catalogues. In our programme, we have obtained deep, high resolution radio observations at 150 MHz with GMRT for several 'deep' fields which are well studied at higher radio frequencies and in other bands of the electromagnetic spectrum, with an aim to detect candidate high redshift radio galaxies. In this paper we present results from the deep 150 MHz observations of LBDS-Lynx field, which has been already imaged at 327, 610 and 1412 MHz with the WSRT and at 1400 and 4860 MHz with the VLA. The 150 MHz image made with GMRT has a rms noise of ~0.7 mJy/beam and a resolution of ~19" X 15". It is the deepest low frequency image of the LBDS-Lynx field. The source catalog of this field at 150 MHz has about 765 sources down to ~20% of the primary beam response, covering an area of about 15 degree$^2$. Spectral index was estimated by cross correlating each source detected at 150 MHz with the available observations at 327, 610, 1400 and 4860 MHz and also using available radio surveys such as WENSS at 327 MHz and NVSS and FIRST at 1400 MHz. We find about 150 radio sources with spectra steeper than 1. About two-third of these are not detected in SDSS, hence are strong candidate high-redshift radio galaxies, which need to be further explored with deep infra-red imaging and spectroscopy to estimate the redshift.Comment: Accepted for publication in MNRAS, 24 pages (including 12 pages online material), 9 Figures, 5 Table