Species richness and functional attributes of fish assemblages across a large-scale salinity gradient in shallow coastal areas

Coastal ecosystems are biologically productive, and their diversity underlies various ecosystem services to humans. However, large-scale species richness (SR) and its regulating factors remain uncertain for many organism groups, owing not least to the fact that observed SR (SRobs) depends on sample size and inventory completeness (IC). We estimated changes in SR across a natural geographical gradient using statistical rarefaction and extrapolation methods, based on a large fish species incidence dataset compiled for shallow coastal areas (<30 m depth) from Swedish fish survey databases. The data covered a ca. 1300 km north-south distance and a 12-fold salinity gradient along sub-basins of the Baltic Sea plus the Skagerrak and, depending on the sub-basin, 4 to 47 years of samplings during 1975-2021. Total fish SRobs was 144, and the observed fish species were of 74 % marine and 26 % freshwater origin. In the 10 sub-basins with sufficient data for further analysis, IC ranged from 77 % to 98 %, implying that ca. 2 %-23 % of likely existing fish species had remained undetected. Sample coverage exceeded 98.5 %, suggesting that undetected species represented <1.5 % of incidences across the sub-basins, i.e. highly rare species. To compare sub-basins, we calculated standardized SR (SRstd) and estimated SR (SRest). Sub-basin-specific SRest varied between 35 +/- 7 (SE) and 109 +/- 6 fish species, being ca. 3 times higher in the most saline (salinity 29-32) compared to the least saline sub-basins (salinity < 3). Analysis of functional attributes showed that differences with decreasing salinity particularly reflected a decreasing SR of benthic and demersal fish, of piscivores and invertivores, and of marine migratory species. We conclude that, if climate change continues causing an upper-layer freshening of the Baltic Sea, this may influence the SR, community composition and functional characteristics of fish, which in turn may affect ecosystem processes such as benthic-pelagic coupling and connectivity between coastal and open-sea areas

Functioning and disability in multiple sclerosis from the patient perspective

Multiple sclerosis (MS) has a great impact on functioning and disability. The perspective of those who experience the health problem has to be taken into account to obtain an in-depth understanding of functioning and disability. The objective was to describe the areas of functioning and disability and relevant contextual factors in MS from the patient perspective. A qualitative study using focus group methodology was performed. The sample size was determined by saturation. The focus groups were digitally recorded and transcribed verbatim. The meaning condensation procedure was used for data analysis. Identified concepts were linked to International Classification of Functioning, Disability and Health (ICF) categories according to established linking rules. Six focus groups with a total of 27 participants were performed. In total, 1327 concepts were identified and linked to 106 ICF categories of the ICF components Body Functions, Activities and Participation and Environmental Factors. This qualitative study reports on the impact of MS on functioning and disability from the patient perspective. The participants in this study provided information about all physical aspects and areas of daily life affected by the disease, as well as the environmental factors influencing their lives

Kunskapsunderlag för ekosystembaserad havsförvaltning i Bottenhavet

Ekosystembaserad havsförvaltning anges som ett viktigt verktyg för att nå Sveriges miljömål. Denna rapport tar ett första steg i riktning mot ett vetenskapligt underlag för att stödja ekosystembaserad havsförvaltning i ett pilotområde i södra Bottenhavet. Ekosystemkomponenter (dvs. arter och livsmiljöer) som är viktiga för modellering av ekosystemet identifieras och deras status samt faktorer som påverkar dem redovisas. Även kunskapsluckor kopplade till påverkansfaktorer diskuteras, samt hur dessa påverkansfaktorer integreras med ekosystemkomponenterna, liksom vilka ekosystemtjänster som ekosystemkomponenterna bidrar till. Många av ekosystemkomponenterna har inte god miljöstatus, särskilt grunda bottnar som har ett högt exploateringstryck. Oroväckande nog saknas det övervakning av både grunda kustnära mjukbottnar och utsjöbankar, fastän dessa områden är av intresse för exploatering samtidigt som de har hög biodiversitet och är kopplade till många ekosystemtjänster. Dock finns det en del data tillgängligt i området som kan användas vid modellering för att ta fram kartor över ekosystemkomponenter och även ekosystemtjänster, som kan vara viktiga underlag för ekosystembaserad förvaltning i södra Bottenhavet. I flera fall är kunskapen om belastningar i södra Bottenhavet och hur de kopplar till statusen av ekosystemkomponenter relativt god, men det saknas information om kumulativa effekter av påverkansfaktorer. Många av de marina arter som finns längst in i Östersjön lever här vid sin nordliga utbredningsgräns, vilket kan innebära att de är extra känsliga för mänskliga belastningar och klimatförändring. Storskaligt fiske efter strömming i utsjön och dess effekter på strömmingsbestånden kan påverka ekosystemets funktion. Strömmingen är talrik och spelar en stor roll i södra Bottenhavets ekosystem. Eftersom strömming vandrar mellan utsjön och kusten kan den koppla samman näringsvävar i kust och utsjö. I Bottenhavets område kan man se tydliga intressekonflikter gällande resursförvaltning. Traditionella lokala näringar baserar sig mycket på fiske av strömming och laxfisk, men vikande fångster av den mer storvuxna strömming som fiskas för humankonsumtion, liksom av laxfisk, skapar problem för det kustnära yrkesfisket. Här finns en uppenbar konkurrenssituation både med det storskaliga pelagiska fisket i utsjön och med naturliga predatorer. Dessa konflikter är svåra att lösa med de förvaltningsmetoder som används idag. Södra Bottenhavets ekosystem skulle sannolikt gynnas av en mer helhetsbaserad förvaltning av fiskbestånden och livsmiljöer, utifrån samtliga faktorer som påverkar dem. I kustområdet gäller detta även, inte minst, de områden där gösens och sikens status är mycket svag, liksom viktiga områden för rekrytering av gädda. En sådan mer helhetsbaserad förvaltning innefattar en samplanering av fiskeregleringar, skyddade områden och åtgärder för att restaurera och skydda diverse livsmiljöer. Förbättring av livsmiljöer för fisk förväntas även gynna andra delar av den biologiska mångfalden och ekosystemtjänster, inklusive olika arters motståndskraft och förmåga att anpassa sig till pågående klimatförändringar

Insights on the Evolution of Mycoparasitism from the Genome of Clonostachys rosea

Peer reviewe

Alopecia in a Viable Phospholipase C Delta 1 and Phospholipase C Delta 3 Double Mutant

BACKGROUND: Inositol 1,4,5trisphosphate (IP(3)) and diacylglycerol (DAG) are important intracellular signalling molecules in various tissues. They are generated by the phospholipase C family of enzymes, of which phospholipase C delta (PLCD) forms one class. Studies with functional inactivation of Plcd isozyme encoding genes in mice have revealed that loss of both Plcd1 and Plcd3 causes early embryonic death. Inactivation of Plcd1 alone causes loss of hair (alopecia), whereas inactivation of Plcd3 alone has no apparent phenotypic effect. To investigate a possible synergy of Plcd1 and Plcd3 in postnatal mice, novel mutations of these genes compatible with life after birth need to be found. METHODOLOGY/PRINCIPAL FINDINGS: We characterise a novel mouse mutant with a spontaneously arisen mutation in Plcd3 (Plcd3(mNab)) that resulted from the insertion of an intracisternal A particle (IAP) into intron 2 of the Plcd3 gene. This mutation leads to the predominant expression of a truncated PLCD3 protein lacking the N-terminal PH domain. C3H mice that carry one or two mutant Plcd3(mNab) alleles are phenotypically normal. However, the presence of one Plcd3(mNab) allele exacerbates the alopecia caused by the loss of functional Plcd1 in Del(9)olt1Pas mutant mice with respect to the number of hair follicles affected and the body region involved. Mice double homozygous for both the Del(9)olt1Pas and the Plcd3(mNab) mutations survive for several weeks and exhibit total alopecia associated with fragile hair shafts showing altered expression of some structural genes and shortened phases of proliferation in hair follicle matrix cells. CONCLUSIONS/SIGNIFICANCE: The Plcd3(mNab) mutation is a novel hypomorphic mutation of Plcd3. Our investigations suggest that Plcd1 and Plcd3 have synergistic effects on the murine hair follicle in specific regions of the body surface

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570