Can hand dexterity predict the disability status of patients with multiple sclerosis?

Background: Multiple Sclerosis (MS) is the most common disabling neurological disease. Hand dysfunction is one of the main complaints of patients with MS. The present study aimed to compare hand dexterity of MS patients with low Expanded Disability Status Scale (EDSS) scores and healthy adults. It also sought to identify the predictors of disability status of patients with MS based on their manual dexterity and demographic characteristics. Methods: In this cross-sectional study, 60 (16 male/44 female) patients with MS and 60 (19 male/41 female) healthy people, who matched in terms of age and sex, were recruited. Their hand dexterity was evaluated by the Purdue Pegboard Test. The disability status of the MS group was determined by the Expanded Disability Status Scale. The data were analyzed using SPSS15. Results: The hand dexterity in MS group even with low EDSS score (1.5 ± 1.07) was weaker than control group. Moreover, the dexterity of dominant hand and alternating two hands coordination subtests of the PPT was a good discriminator between two groups (p<0.001). The results of linear regression analysis suggested dominant hand dexterity and disease duration as predictors of disability status that predict 60.5 per cent of the variation in EDSS scores in patients with MS (p<0.001). Conclusion: Reduced dominant hand dexterity in patients with MS is a disabling factor. Further research is recommended to determine if early hand rehabilitation can reduce the severity of disability in Patients with MS

Latent cytomegalovirus-driven recruitment of activated CD4+ T cells promotes virus reactivation

Human cytomegalovirus (HCMV) infection is not cleared by the initial immune response but persists for the lifetime of the host, in part due to its ability to establish a latent infection in cells of the myeloid lineage. HCMV has been shown to manipulate the secretion of cellular proteins during both lytic and latent infection; with changes caused by latent infection mainly investigated in CD34+ progenitor cells. Whilst CD34+ cells are generally bone marrow resident, their derivative CD14+ monocytes migrate to the periphery where they briefly circulate until extravasation into tissue sites. We have analyzed the effect of HCMV latent infection on the secretome of CD14+ monocytes, identifying an upregulation of both CCL8 and CXCL10 chemokines in the CD14+ latency-associated secretome. Unlike CD34+ cells, the CD14+ latency-associated secretome did not induce migration of resting immune cell subsets but did induce migration of activated NK and T cells expressing CXCR3 in a CXCL10 dependent manner. As reported in CD34+ latent infection, the CD14+ latency-associated secretome also suppressed the anti-viral activity of stimulated CD4+ T cells. Surprisingly, however, co-culture of activated autologous CD4+ T cells with latently infected monocytes resulted in reactivation of HCMV at levels comparable to those observed using M-CSF and IL-1β cytokines. We propose that these events represent a potential strategy to enable HCMV reactivation and local dissemination of the virus at peripheral tissue sites

Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease

IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as regulators of baseline and induced IL33 promoter activity. ATAC-Seq and ChIP-PCR identified chromatin accessibility and differential TF binding as additional control points for transcription from noncanonical promoters. In support of a role for these TFs in COPD pathogenesis, we found that AP-2 (TFAP2A, TFAP2C) and AP-1 (FOS and JUN) family members are upregulated in human COPD specimens. This study implicates integrative and pioneer TFs in regulating IL33 promoters and alternative splicing in human airway basal cells. Our work reveals a potentially novel approach for targeting IL-33 in development of therapeutics for COPD

Population-based identification of H a-excess sources in the Gaia DR2 and IPHAS catalogues

We present a catalogue of point-like H a-excess sources in the Northern Galactic Plane. Our catalogue is created using a new technique that leverages astrometric and photomeric information from Gaia to select H a-bright outliers in the INT Photometric H a Survey of the Northern Galactic Plane (IPHAS), across the colour-absolute magnitude diagram. To mitigate the selection biases due to stellar population mixing and to extinction, the investigated objects are first partitioned with respect to their positions in the Gaia colour-absolute magnitude space, and Galactic coordinates space, respectively. The selection is then performed on both partition types independently.MM acknowledges the support by the Spanish Ministry of Science, Innovation and University (MICIU/FEDER, UE) through grant RTI2018-095076-B-C21, and the Institute of Cosmos Sciences University of Barcelona (ICCUB, Unidad de Excelencia ‘Mar ́ıa de Maeztu’) through grant CEX2019- 000918-MPostprint (published version

Probing Grand Unified Theories with Cosmic Ray, Gamma-Ray and Neutrino Astrophysics

We explore scenarios where the highest energy cosmic rays are produced by new particle physics near the grand unification scale. Using detailed numerical simulations of extragalactic nucleon, gamma-ray, and neutrino propagation, we show the existence of an interesting parameter range for which such scenarios may explain part of the data and are consistent with all observational constraints. A combination of proposed observatories for ultra-high energy cosmic rays, neutrino telescopes of a few kilometer scale, and gamma-ray astrophysics instruments should be able to test these scenarios. In particular, for neutrino masses in the eV range, exclusive neutrino decay modes of superheavy particles can give rise to neutrino fluxes comparable to those predicted in models of active galactic nuclei.Comment: 15 latex pages, 5 postscript figures included, uses revtex.sty and psfig.sty. Submitted to Physical Review

Evolution of the new head by gradual acquisition of neural crest regulatory circuits

The neural crest, an embryonic stem-cell population, is a vertebrate innovation that has been proposed to be a key component of the ‘new head’, which imbued vertebrates with predatory behaviour. Here, to investigate how the evolution of neural crest cells affected the vertebrate body plan, we examined the molecular circuits that control neural crest development along the anteroposterior axis of a jawless vertebrate, the sea lamprey. Gene expression analysis showed that the cranial subpopulation of the neural crest of the lamprey lacks most components of a transcriptional circuit that is specific to the cranial neural crest in amniotes and confers the ability to form craniofacial cartilage onto non-cranial neural crest subpopulations3. Consistent with this, hierarchical clustering analysis revealed that the transcriptional profile of the lamprey cranial neural crest is more similar to the trunk neural crest of amniotes. Notably, analysis of the cranial neural crest in little skate and zebrafish embryos demonstrated that the transcriptional circuit that is specific to the cranial neural crest emerged via the gradual addition of network components to the neural crest of gnathostomes, which subsequently became restricted to the cephalic region. Our results indicate that the ancestral neural crest at the base of the vertebrate lineage possessed a trunk-like identity. We propose that the emergence of the cranial neural crest, by progressive assembly of an axial-specific regulatory circuit, allowed the elaboration of the new head during vertebrate evolution

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Limits to the muon flux from WIMP annihilation in the center of the Earth with the AMANDA detector

A search for nearly vertical up-going muon-neutrinos from neutralino annihilations in the center of the Earth has been performed with the AMANDA-B10 neutrino detector. The data sample collected in 130.1 days of live-time in 1997, ~10^9 events, has been analyzed for this search. No excess over the expected atmospheric neutrino background is oberved. An upper limit at 90% confidence level on the annihilation rate of neutralinos in the center of the Earth is obtained as a function of the neutralino mass in the range 100 GeV-5000 GeV, as well as the corresponding muon flux limit.Comment: 14 pages, 11 figures. Version accepted for publication in Physical Review