Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Evidence for rangewide panmixia despite multiple barriers to dispersal in a marine mussel

Oceanographic features shape the distributional and genetic patterns of marine species by interrupting or promoting connections among populations. Although general patterns commonly arise, distributional ranges and genetic structure are species-specific and do not always comply with the expected trends. By applying a multimarker genetic approach combined with Lagrangian particle simulations (LPS) we tested the hypothesis that oceanographic features along northeastern Atlantic and Mediterranean shores influence dispersal potential and genetic structure of the intertidal mussel Perna perna. Additionally, by performing environmental niche modelling we assessed the potential and realized niche of P. perna along its entire native distributional range and the environmental factors that best explain its realized distribution. Perna perna showed evidence of panmixia across > 4,000 km despite several oceanographic breaking points detected by LPS. This is probably the result of a combination of life history traits, continuous habitat availability and stepping-stone dynamics. Moreover, the niche modelling framework depicted minimum sea surface temperatures (SST) as the major factor shaping P. perna distributional range limits along its native areas. Forthcoming warming SST is expected to further change these limits and allow the species to expand its range polewards though this may be accompanied by retreat from warmer areas.Fundacao para a Ciencia e Tecnologia (FCT-MEC, Portugal) [UID/Multi/04326/2013, IF/01413/2014/CP1217/CT0004]; South African Research Chairs Initiative (SARChI) of the Department of Science and Technology; National Research Foundation; South African National Research Foundation (NRF); Portuguese Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BPD/85040/2012, SFRH/BPD/111003/2015]info:eu-repo/semantics/publishedVersio

Population genomics of marine zooplankton

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Bucklin, Ann et al. "Population Genomics of Marine Zooplankton." Population Genomics: Marine Organisms. Ed. Om P. Rajora and Marjorie Oleksiak. Springer, 2018. doi:10.1007/13836_2017_9.The exceptionally large population size and cosmopolitan biogeographic distribution that distinguish many – but not all – marine zooplankton species generate similarly exceptional patterns of population genetic and genomic diversity and structure. The phylogenetic diversity of zooplankton has slowed the application of population genomic approaches, due to lack of genomic resources for closelyrelated species and diversity of genomic architecture, including highly-replicated genomes of many crustaceans. Use of numerous genomic markers, especially single nucleotide polymorphisms (SNPs), is transforming our ability to analyze population genetics and connectivity of marine zooplankton, and providing new understanding and different answers than earlier analyses, which typically used mitochondrial DNA and microsatellite markers. Population genomic approaches have confirmed that, despite high dispersal potential, many zooplankton species exhibit genetic structuring among geographic populations, especially at large ocean-basin scales, and have revealed patterns and pathways of population connectivity that do not always track ocean circulation. Genomic and transcriptomic resources are critically needed to allow further examination of micro-evolution and local adaptation, including identification of genes that show evidence of selection. These new tools will also enable further examination of the significance of small-scale genetic heterogeneity of marine zooplankton, to discriminate genetic “noise” in large and patchy populations from local adaptation to environmental conditions and change.Support was provided by the US National Science Foundation to AB and RJO (PLR-1044982) and to RJO (MCB-1613856); support to IS and MC was provided by Nord University (Norway)

Understanding the global dynamics of the equatorial ionosphere in Africa for space weather capabilities: A science case for AfrequaMARN

The equatorial region of the Earth's ionosphere is one of the most complex ionospheric regions due to its interactions, instabilities, and several unresolved questions regarding its dynamics, electrodynamics, and physical processes. The equatorial ionosphere overall spans three continents with the longest region being that over the African continent. Satellite observations have demonstrated that very large differences exist in the formation of ionospheric irregularities over the African sector compared with other longitudinal sectors. This may be a consequence of the symmetric shape of the magnetic equator over the continent and the lack of variability in latitude. In this paper, we propose a science campaign to equip the African sector of the magnetic equator with ground-based instruments, specifically magnetometers and radars. The network of radars proposed is similar in style and technique to the high-latitude SuperDARN radar network, while the magnetometers will form an array along the equatorial belt. These two proposed space physics instruments will be used to study this region of the equatorial ionosphere over a long interval of time, at least one solar cycle. The deployment of an array of magnetometers (AfrequaMA) and a radar network (AfrequaRN) in the African sector of the magnetic equator is jointly called the Africa Equatorial Magnetometer Array and Radar Network (AfrequaMARN), which will provide simultaneous observations of both electric and magnetic variations over the African sector. We also examine the possible science questions such a magnetometer array and radar network would be able to address, both individually and in conjunction with other space-based and ground-based instrumentation. The proposed projects will clearly improve our understanding of the dynamics of the equatorial ionosphere and our understanding of its role in balancing the large-scale ionospheric current system, and will contribute to our ability to adequately model ionospheric and plasmaspheric densities. It will also enhance our understanding of global ionospheric processes, which will improve the space weather capabilities of the African and international space science communities

Invasion genetics of a freshwater mussel (Dreissena rostriformis bugensis) in eastern Europe: High gene flow and multiple introductions

In recent years, the quagga mussel, Dreissena rostriformis bugensis, native to the Dnieper and Bug Limans of the northern Black Sea, has been dispersed by human activities across the basin, throughout much of the Volga River system, and to the Laurentian Great Lakes. We used six published microsatellite markers to survey populations throughout its native and introduced range to identify relationships among potential source populations and introduced ones. Mussels from 12 sites in Eurasia, including the central Caspian Sea and one in North America (Lake Erie), were sampled. Field surveys in the Volga River basin suggested that the species first colonized the middle reach of the river near Kubyshev Reservoir, and thereafter spread both upstream and downstream. Evidence of considerable gene flow among populations was observed and genetic diversity was consistent with a larger, metapopulation that has not experienced bottlenecks or founder effects. We propose that high gene flow, possibly due to multiple invasions, has facilitated establishment of quagga mussel populations in the Volga River system. The Caspian Sea population (D. rostriformis rostriformis (= distincta)) was genetically more distinct than other populations, a finding that may be related to habitat differences. The geographical pattern of genetic divergence is not characteristic of isolation-by-distance but, rather, of long-distance dispersal, most likely mediated by commercial ships\u27 ballast water transfer. © 2005 Nature Publishing Group All rights reserved