Insertion of the CXC chemokine ligand 9 (CXCL9) into the mouse hepatitis virus genome results in protection from viral-induced encephalitis and hepatitis.

The role of the CXC chemokine ligand 9 (CXCL9) in host defense following infection with mouse hepatitis virus (MHV) was determined. Inoculation of the central nervous system (CNS) of CXCL9-/- mice with MHV resulted in accelerated and increased mortality compared to wild type mice supporting an important role for CXCL9 in anti-viral defense. In addition, infection of RAG1-/- or CXCL9-/- mice with a recombinant MHV expressing CXCL9 (MHV-CXCL9) resulted in protection from disease that correlated with reduced viral titers within the brain and NK cell-mediated protection in the liver. Survival in MHV-CXCL9-infected CXCL9-/- mice was associated with reduced viral burden within the brain that coincided with increased T cell infiltration. Similarly, viral clearance from the livers of MHV-CXCL9-infected mice was accelerated but independent of increased T cell or NK cell infiltration. These observations indicate that CXCL9 promotes protection from coronavirus-induced neurological and liver disease

Clinical findings and genetic screening for copy number variation mutations in a cohort of South African patients with Parkinson’s disease

Background. Parkinson’s disease (PD), with a prevalence of up to 4% in Western countries, appears to be less common in Africa, possibly in part because of genetic factors. African studies investigating the genetic causation of PD are limited.Objective. To describe the clinical and genetic findings in a group of black South African patients with PD.Methods. All black African patients with PD from a tertiary hospital neurology clinic were examined. Symptoms were scored according to the Unified Parkinson’s Disease Rating Scale (UPDRS), and patients were classified according to motor features. Genomic DNA was extracted and multiplex ligation-dependent probe amplification was used for detection of copy number variation (CNV) mutations in the known PD-causing genes.Results. Sixteen patients were identified (ages 56 - 82 years). Three had a family history of PD. Classification into motor subtypes showed 44% mixed, 31% akinetic-rigid, and 25% tremor-dominant subtypes. UPDRS scores ranged from 7 to 88, with dementia in 20%. No patient had G2019S LRRK2 and A30P SNCA mutations, and all except one had no CNV mutations in the known PD-causing genes. A female patient (age of onset 50 years, no family history) had a parkin gene heterozygous deletion of exon 4. She had hyperreflexia, bilateral Hoffmann’s reflexes, normal plantar responses and no dystonia.Conclusion. This group of black African patients showed similar characteristics to patients in Western studies, possibly with a higher proportion having tremor dominant disease. Genetic analysis showed one parkin gene mutation. The limited knowledge on PD-causing genes and mutations in black populations warrants further studies involving next-generation sequencing approaches

The Limits of Anthropocene Narratives

The rapidly growing transdisciplinary enthusiasm about developing new kinds of Anthropocene stories is based on the shared assumption that the Anthropocene predicament is best made sense of by narrative means. Against this assumption, this article argues that the challenge we are facing today does not merely lie in telling either scientific, socio-political, or entangled Anthropocene narratives to come to terms with our current condition. Instead, the challenge lies in coming to grips with how the stories we can tell in the Anthropocene relate to the radical novelty of the Anthropocene condition about which no stories can be told. What we need to find are meaningful ways to reconcile an inherited commitment to narrativization and the collapse of storytelling as a vehicle of understanding the Anthropocene as our current predicament

Laser cooling of a diatomic molecule

It has been roughly three decades since laser cooling techniques produced ultracold atoms, leading to rapid advances in a vast array of fields. Unfortunately laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for many applications. For example, heteronuclear molecules possess permanent electric dipole moments which lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures make ultracold molecules attractive candidates for use in quantum simulation of condensed matter systems and quantum computation. Also ultracold molecules may provide unique opportunities for studying chemical dynamics and for tests of fundamental symmetries. Here we experimentally demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using an optical cycling scheme requiring only three lasers, we have observed both Sisyphus and Doppler cooling forces which have substantially reduced the transverse temperature of a SrF molecular beam. Currently the only technique for producing ultracold molecules is by binding together ultracold alkali atoms through Feshbach resonance or photoassociation. By contrast, different proposed applications for ultracold molecules require a variety of molecular energy-level structures. Our method provides a new route to ultracold temperatures for molecules. In particular it bridges the gap between ultracold temperatures and the ~1 K temperatures attainable with directly cooled molecules (e.g. cryogenic buffer gas cooling or decelerated supersonic beams). Ultimately our technique should enable the production of large samples of molecules at ultracold temperatures for species that are chemically distinct from bialkalis.Comment: 10 pages, 7 figure

Predictors of Limb Fat Gain in HIV Positive Patients Following a Change to Tenofovir-Emtricitabine or Abacavir-Lamivudine

Background Antiretroviral treatment (cART) in HIV causes lipoatrophy. We examined predictors of anthropometric outcomes over 96 weeks in HIV-infected, lipoatrophic adults receiving stable cART randomised to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) fixed dose combinations. Methodology/Principal Findings The STEAL study was a prospective trial of virologically suppressed participants randomised to either TDF-FTC (n = 178) or ABC-3TC (n = 179). Anthropometric assessment was conducted at baseline, weeks 48 and 96. The analysis population included those with baseline and week 96 data remaining on randomised therapy. Distribution of limb fat change was divided into four categories (≤0%, \u3e0-10%, \u3e10-20%, \u3e20%). Baseline characteristics [demographics, medical history, metabolic and cardiovascular biomarkers] were assessed as potential predictors of change in percent subcutaneous limb fat using linear regression. 303 participants (85% of STEAL population) were included. Baseline characteristics were: mean (±SD) age 45 (±8) years; thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI) duration 4 (±3) years; limb fat 5.4 (±3.0)kg; body mass index 24.7 (±3.5) kg/m2. Mean (SD) limb fat gain to week 48 and 96 was 7.6% (±22.4) and 13.2% (±27.3), respectively, with no significant difference between groups. 51.5% of all participants had \u3e10% gain in limb fat. Predictors of greater limb fat gain at week 96 were baseline tNRTI (10.3, p = 0.001), glucose \u3e6 mmol/L (16.1, p = 0.04), higher interleukin 6 (IL-6) (2.8, p = 0.004) and lower baseline limb fat (3.8-6.4 kg - 11.2; \u3e6.4 kg - 15.7, p trend\u3c0.001). Conclusions/Significance Modest peripheral fat gain occurred with both TDF-FTC and ABC-3TC. Baseline factors associated with more severe lipodystrophy (lipoatrophy, baseline tNRTI, raised IL6, and glucose) predicted greater limb fat recovery at 96 weeks

During the summer 2009 outbreak of "swine flu" in Scotland what respiratory pathogens were diagnosed as H1N1/2009?

<p>Abstract</p> <p>Background</p> <p>During the April-July 2009 outbreak of H1N1/2009 in scotland the West of Scotland Specialist Virology Centre (WoSSVC) in Glasgow tested > 16 000 clinical samples for H1N1/2009. Most were from patients clinically diagnosed with H1N1/2009. Out of these, 9% were positive. This study sought to determine what respiratory pathogens were misdiagnosed as cases of H1N1/2009 during this time.</p> <p>Methods</p> <p>We examined the results from 3247 samples which were sent to the laboratory during April-July 2009. All were from patients clinically diagnosed as having H1N1/2009 (based on accepted criteria) and all were given a full respiratory screen using real time reverse transcriptase polymerase chain reaction (rtRT-PCR) assays.</p> <p>Results</p> <p>In total, respiratory pathogens were detected in 27.9% (95% confidence interval, 26.3-29.5%) of the samples submitted. Numerous pathogens were detected, the most common of which were rhinovirus (8.9% (95% confidence interval, 7.9-9.9%)), parainfluenza 1 (1.9% (95% confidence interval, 1.4-2.4%)) and 3 (4.1% (95% confidence interval, 3.3-4.9%)), and adenovirus ((3.5% (95% confidence interval, 2.9-4.2%)).</p> <p>Conclusions</p> <p>This study highlights the problems of using a clinical algorithm to detect H1N1/2009. Clinicians frequently misdiagnosed common respiratory pathogens as H1N1/2009 during the spring/summer outbreak in Scotland. Many undesirable consequences would have resulted, relating to treatment, infection control, and public health surveillance.</p

Polymorphism in NEDD4L Is Associated with Increased Salt Sensitivity, Reduced Levels of P-renin and Increased Levels of Nt-proANP

OBJECTIVE: Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L) is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC), thus a candidate gene for salt sensitivity. Carriers of an intact NEDD4L C2-domain, encoded by the NEDD4L rs4149601 (G/A) GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T) polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4L is associated with increased salt sensitivity. METHODS: 39 normotensive subjects were studied. The difference in 24-hour systolic blood pressure after four weeks on 150 mmol/day NaCl intake and four weeks on 50 mmol/day NaCl was defined as salt sensitivity. The rs4149601 and rs2288774 polymorphisms were genotyped using PCR-based techniques. RESULTS: Carriers of the rs4149601 GG-genotype together with the rs2288774 CC-genotype had significantly higher salt sensitivity (median, IQR) (18.0, 7.5–20.0 mmHg vs 6.0, 0.0–10.0 mmHg, P = 0.007) and lower plasma renin concentration (P-renin) (6.0, 2.0–9.5 mU/L vs 15.0, 9.0–24.0 mU/L, P = 0.005) as compared to non-carriers of these genotypes. In carriers of the rs4149601 GG-genotype together with the rs2288774 CC- or CT-genotype, as compared to non-carriers, salt sensitivity was (8.0, 6.0–18.0 mmHg vs 5.0, 0.0–10.0 mmHg, P = 0.07) and P-renin (9.0, 6.0–16.0 mU/L vs 15.0, 9.0–28.0 mU/L, P = 0.03). CONCLUSION: Genetic NEDD4L variation seems to affect salt sensitivity and P-renin in normotensive subjects, suggesting that genotyping of NEDD4L may be clinically useful in order to identify subjects who benefit from dietary salt restriction in the prevention of hypertension

Very Cold Gas and Dark Matter

We have recently proposed a new candidate for baryonic dark matter: very cold molecular gas, in near-isothermal equilibrium with the cosmic background radiation at 2.73 K. The cold gas, of quasi-primordial abundances, is condensed in a fractal structure, resembling the hierarchical structure of the detected interstellar medium. We present some perspectives of detecting this very cold gas, either directly or indirectly. The H$_2$ molecule has an "ultrafine" structure, due to the interaction between the rotation-induced magnetic moment and the nuclear spins. But the lines fall in the km domain, and are very weak. The best opportunity might be the UV absorption of H$_2$ in front of quasars. The unexpected cold dust component, revealed by the COBE/FIRAS submillimetric results, could also be due to this very cold H$_2$ gas, through collision-induced radiation, or solid H$_2$ grains or snowflakes. The $\gamma$-ray distribution, much more radially extended than the supernovae at the origin of cosmic rays acceleration, also points towards and extended gas distribution.Comment: 16 pages, Latex pages, crckapb macro, 3 postscript figures, uuencoded compressed tar file. To be published in the proceeedings of the "Dust-Morphology" conference, Johannesburg, 22-26 January, 1996, D. Block (ed.), (Kluwer Dordrecht

Dissecting the Relation between a Nuclear Receptor and GATA: Binding Affinity Studies of Thyroid Hormone Receptor and GATA2 on TSHβ Promoter

Background: Much is known about how genes regulated by nuclear receptors (NRs) are switched on in the presence of a ligand. However, the molecular mechanism for gene down-regulation by liganded NRs remains a conundrum. The interaction between two zinc-finger transcription factors, Nuclear Receptor and GATA, was described almost a decade ago as a strategy adopted by the cell to up-or down-regulate gene expression. More recently, cell-based assays have shown that the Zn-finger region of GATA2 (GATA2-Zf) has an important role in down-regulation of the thyrotropin gene (TSH beta) by liganded thyroid hormone receptor (TR). Methodology/Principal Findings: In an effort to better understand the mechanism that drives TSH beta down-regulation by a liganded TR and GATA2, we have carried out equilibrium binding assays using fluorescence anisotropy to study the interaction of recombinant TR and GATA2-Zf with regulatory elements present in the TSH beta promoter. Surprisingly, we observed that ligand (T3) weakens TR binding to a negative regulatory element (NRE) present in the TSH beta promoter. We also show that TR may interact with GATA2-Zf in the absence of ligand, but T3 is crucial for increasing the affinity of this complex for different GATA response elements (GATA-REs). Importantly, these results indicate that TR complex formation enhances DNA binding of the TR-GATA2 in a ligand-dependent manner. Conclusions: Our findings extend previous results obtained in vivo, further improving our understanding of how liganded nuclear receptors down-regulate gene transcription, with the cooperative binding of transcription factors to DNA forming the core of this process.Medical Research Council (MRC), UKConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazi