Caveolar disruption causes contraction of rat femoral arteries via reduced basal NO release and subsequent closure of BKCa channels
Background and Purpose. Caveolae act as signalling hubs in endothelial and smooth muscle cells. Caveolar disruption by the membrane cholesterol depleting agent methyl-β-cyclodextrin (M-β-CD) has various functional effects on arteries including (i) impairment of endothelium-dependent relaxation, and (ii) alteration of smooth muscle cell (SMC) contraction independently of the endothelium. The aim of this study was to explore the effects of M-β-CD on rat femoral arteries. Methods. Isometric force was measured in rat femoral arteries stimulated to contract with a solution containing 20 mM K+ and 200 nM Bay K 8644 (20 K/Bay K) or with one containing 80 mM K+(80 K). Results. Incubation of arteries with M-β-CD (5 mM, 60 min) increased force in response to 20 K/Bay K but not that induced by 80 K. Application of cholesterol saturated M-β-CD (Ch-MCD, 5 mM, 50 min) reversed the effects of M-β-CD. After mechanical removal of endothelial cells M-β-CD caused only a small enhancement of contractions to 20 K/Bay K. This result suggests M-β-CD acts via altering release of an endothelial-derived vasodilator or vasoconstrictor. When nitric oxide synthase was blocked by pre-incubation of arteries with L-NAME (250 µM) the contraction of arteries to 20 K/Bay K was enhanced, and this effect was abolished by pre-treatment with M-β-CD. This suggests M-β-CD is inhibiting endothelial NO release. Inhibition of large conductance voltage- and Ca2+-activated (BKCa) channels with 2 mM TEA+ or 100 nM Iberiotoxin (IbTX) enhanced 20 K/Bay K contractions. L-NAME attenuated the contractile effect of IbTX, as did endothelial removal. Conclusions. Our results suggest caveolar disruption results in decreased release of endothelial-derived nitric oxide in rat femoral artery, resulting in a reduced contribution of BKCa channels to the smooth muscle cell membrane potential, causing depolarisation and contraction.
Al-Brakati et al. (2015) Caveolar disruption causes contraction of rat femoral arteries via reduced basal NO release and subsequent closure of BKCa channels. PeerJ 3:e966 https://doi.org/10.7717/peerj.966
Trans-species polymorphism at antimicrobial innate immunity cathelicidin genes of Atlantic cod and related species
Natural selection, the most important force in evolution, comes in three forms. Negative purifying selection removes deleterious variation and maintains adaptations. Positive directional selection fixes beneficial variants, producing new adaptations. Balancing selection maintains variation in a population. Important mechanisms of balancing selection include heterozygote advantage, frequency-dependent advantage of rarity, and local and fluctuating episodic selection. A rare pathogen gains an advantage because host defenses are predominantly effective against prevalent types. Similarly, a rare immune variant gives its host an advantage because the prevalent pathogens cannot escape the host’s apostatic defense. Due to the stochastic nature of evolution, neutral variation may accumulate on genealogical branches, but trans-species polymorphisms are rare under neutrality and are strong evidence for balancing selection. Balanced polymorphism maintains diversity at the major histocompatibility complex (MHC) in vertebrates. The Atlantic cod is missing genes for both MHC-II and CD4, vital parts of the adaptive immune system. Nevertheless, cod are healthy in their ecological niche, maintaining large populations that support major commercial fisheries. Innate immunity is of interest from an evolutionary perspective, particularly in taxa lacking adaptive immunity. Here, we analyze extensive amino acid and nucleotide polymorphisms of the cathelicidin gene family in Atlantic cod and closely related taxa. There are three major clusters, Cath1, Cath2, and Cath3, that we consider to be paralogous genes. There is extensive nucleotide and amino acid allelic variation between and within clusters. The major feature of the results is that the variation clusters by alleles and not by species in phylogenetic trees and discriminant analysis of principal components. Variation within the three groups shows trans-species polymorphism that is older than speciation and that is suggestive of balancing selection maintaining the variation. Using Bayesian and likelihood methods positive and negative selection is evident at sites in the conserved part of the genes and, to a larger extent, in the active part which also shows episodic diversifying selection, further supporting the argument for balancing selection.
Halldórsdóttir et al. (2015) Trans-species polymorphism at antimicrobial innate immunity cathelicidin genes of Atlantic cod and related species. PeerJ 3:e976 https://doi.org/10.7717/peerj.976
Causes of mortality across different immigrant groups in Northeastern Italy
Background. Despite massive immigration towards Southern Europe in the last two decades, data on mortality by cause among immigrants in Italy are scarce. The aim of this study was to investigate mortality from all and from specific causes of death among immigrants residing in the Veneto Region (Northeastern Italy). Methods. Mortality records for the period 2008–2013 were extracted from the regional archive of causes of death, whereas population data were obtained from the 2011 Italian census. Immigrants were grouped by area of provenience based on the information on country of citizenship available both in mortality and census data. Standardized Mortality Ratios (SMR) with 95% Confidence Intervals (CI) were computed for the period 2008–2013 in subjects aged 20–59 years, with rates of Italian citizens as a reference. Results. Overall mortality was reduced both in male (SMR 0.86, CI [0.80–0.92]) and female immigrants (SMR 0.72, CI [0.65–0.78]), although an increased risk was observed for subjects from Sub-Saharan Africa. Significantly raised SMR for circulatory diseases were found among Sub-Saharan Africans and Southern Asians in both genders. Sub-Saharan Africans experienced a higher risk of death, especially from cerebrovascular diseases: SMR 4.78 (CI [2.67–7.89]) and SMR 6.09 (CI [1.96–14.2]) in males and females, respectively. Among Southern Asians, the increase in mortality from ischemic heart diseases reached statistical significance in males (SMR 2.53, CI [1.42–4.18]). In spite of a lower risk of death for all neoplasms combined, mortality from cancer of cervix uteri was increased among immigrants (SMR 2.61, CI [1.35–4.56]), as well as for other cancer sites in selected immigrant groups. A raised mortality was found for infectious diseases in Sub-Saharan Africans (both genders), and for transport accidents among females from Eastern Europe. Conclusion. Our study showed great variations in mortality by cause and area of provenience among immigrants resident in the Veneto Region and highlighted specific health issues that should be addressed through tailored efforts in chronic diseases prevention.
Fedeli et al. (2015) Causes of mortality across different immigrant groups in Northeastern Italy. PeerJ 3:e975 https://doi.org/10.7717/peerj.975
Research on human sociality rarely includes kinship, social structure, sex, and familiarity, even though these variables influence sociality in non-human primates. However, cross-cultural ethnographic and observational studies with humans indicate that, beginning after age 5 years, males and females form differing social structures with unrelated individuals in a community. Specifically, compared with females, human males exhibit greater tolerance for and form larger, interconnected groups of peers which we term “gregariousness.” To examine sex differences in gregariousness early in life when children first interact with peers without adult supervision, 3- to 6-year-old children were given the choice to enter one of three play areas: an empty one, one with an adult, or one with a familiar, same-sex peer. More males than females initially chose the play area with the same-sex peer, especially after age 5 years. Sex differences in gregariousness with same-sex peers likely constitute one facet of human sociality.
Benenson et al. (2015) Sex differences in human gregariousness. PeerJ 3:e974 https://doi.org/10.7717/peerj.974
Identification of miR-194-5p as a potential biomarker for postmenopausal osteoporosis
The incidence of osteoporosis is high in postmenopausal women due to altered estrogen levels and continuous calcium loss that occurs with aging. Recent studies have shown that microRNAs (miRNAs) are involved in the development of osteoporosis. These miRNAs may be used as potential biomarkers to identify women at a high risk for developing the disease. In this study, whole blood samples were collected from 48 postmenopausal Chinese women with osteopenia or osteoporosis and pooled into six groups according to individual T-scores. A miRNA microarray analysis was performed on pooled blood samples to identify potential miRNA biomarkers for postmenopausal osteoporosis. Five miRNAs (miR-130b-3p, -151a-3p, -151b, -194-5p, and -590-5p) were identified in the microarray analysis. These dysregulated miRNAs were subjected to a pathway analysis investigating whether they were involved in regulating osteoporosis-related pathways. Among them, only miR-194-5p was enriched in multiple osteoporosis-related pathways. Enhanced miR-194-5p expression in women with osteoporosis was confirmed by quantitative reverse transcription–polymerase chain reaction analysis. For external validation, a significant correlation between the expression of miR-194-5p and T-scores was found in an independent patient collection comprised of 24 postmenopausal women with normal bone mineral density, 30 postmenopausal women with osteopenia, and 32 postmenopausal women with osteoporosis (p < 0.05). Taken together, the present findings suggest that miR-194-5p may be a viable miRNA biomarker for postmenopausal osteoporosis.
Meng et al. (2015) Identification of miR-194-5p as a potential biomarker for postmenopausal osteoporosis. PeerJ 3:e971 https://doi.org/10.7717/peerj.971
Rapid cessation of acute diarrhea using a novel solution of bioactive polyphenols: a randomized trial in Nicaraguan children
Goal. We assessed the effectiveness of bioactive polyphenols contained in solution (LX) to restore normal bowel function in pediatric patients with acute diarrhea. Background. While providing oral rehydration solution (ORS) is standard treatment for diarrhea in developing countries, plant-derived products have been shown to positively affect intestinal function. If a supplement to ORS resolves diarrhea more rapidly than ORS alone, it is an improvement to current care. Study. In a randomized, double-blind, placebo-controlled cross-over study, 61 pediatric patients with uncontrolled diarrhea were randomized to receive either ORS + LX on day 1 and then ORS + water on day 2 (study arm) or ORS + water on day 1 and then ORS + LX on day 2 (control arm). Time to resolution and number of bowel movements were recorded. Results. On day 1, the mean time to diarrhea resolution was 3.1 h (study arm) versus 9.2 h (control arm) (p = 0.002). In the study arm, 60% of patients had normal stool at their first bowel movement after consumption of the phenolic redoxigen solution (LX). On day 2, patients in the study arm continued to have normal stool while patients in the control arm achieved normal stool within 24 h after consuming the test solution. Patients in the control arm experienced a reduction in the mean number of bowel movements from day 1 to day 2 after consuming the test solution (p = 0.0001). No adverse events were observed. Conclusions. Significant decreases in bowel movement frequency and rapid normalization of stool consistency were observed with consumption of this novel solution.
Dover et al. (2015) Rapid cessation of acute diarrhea using a novel solution of bioactive polyphenols: a randomized trial in Nicaraguan children. PeerJ 3:e969 https://doi.org/10.7717/peerj.969
Back from the dead; the curious tale of the predatory cyanobacterium Vampirovibrio chlorellavorus
An uncultured non-photosynthetic basal lineage of the Cyanobacteria, the Melainabacteria, was recently characterised by metagenomic analyses of aphotic environmental samples. However, a predatory bacterium, Vampirovibrio chlorellavorus, originally described in 1972 appears to be the first cultured representative of the Melainabacteria based on a 16S rRNA sequence recovered from a lyophilised co-culture of the organism. Here, we sequenced the genome of V. chlorellavorus directly from 36 year-old lyophilised material that could not be resuscitated confirming its identity as a member of the Melainabacteria. We identified attributes in the genome that likely allow V. chlorellavorus to function as an obligate predator of the microalga Chlorella vulgaris, and predict that it is the first described predator to use an Agrobacterium tumefaciens-like conjugative type IV secretion system to invade its host. V. chlorellavorus is the first cyanobacterium recognised to have a predatory lifestyle and further supports the assertion that Melainabacteria are non-photosynthetic.
Soo et al. (2015) Back from the dead; the curious tale of the predatory cyanobacterium Vampirovibrio chlorellavorus. PeerJ 3:e968 https://doi.org/10.7717/peerj.968
Accuracy of the interferon-gamma release assay for the diagnosis of tuberculous pleurisy: an updated meta-analysis
Background and Objectives. The best method for diagnosing tuberculous pleurisy (TP) remains controversial. Since a growing number of publications focus on the interferon-gamma release assay (IGRA), we meta-analyzed the available evidence on the overall diagnostic performance of IGRA applied to pleural fluid and peripheral blood. Materials and Methods. PubMed and Embase were searched for relevant English papers up to October 31, 2014. Statistical analyses were performed using Stata and Meta-DiSc. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV) and diagnostic odds ratio (DOR) were count. Summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize the overall diagnostic performance. Results. Fifteen publications met our inclusion criteria and were included in the meta analysis. The following pooled estimates for diagnostic parameters of pleural IGRA were obtained: sensitivity, 0.82 (95% CI [0.79–0.85]); specificity, 0.87 (95% CI [0.84–0.90]); PLR, 4.94 (95% CI [2.60–9.39]); NLR, 0.22 (95% CI [0.13–0.38]); PPV, 0.91 (95% CI [0.85–0.96]); NPV, 0.79 (95% CI [0.71–0.85]); DOR, 28.37 (95% CI [10.53–76.40]); and AUC, 0.91. The corresponding estimates for blood IGRA were as follows: sensitivity, 0.80 (95% CI [0.76–0.83]); specificity, 0.70 (95% CI [0.65–0.75]); PLR, 2.48 (95% CI [1.95–3.17]); NLR, 0.30 (95% CI [0.24–0.37]); PPV, 0.79 (95% CI [0.60–0.87]); NPV, 0.75 (95% CI [0.62–0.83]); DOR, 9.96 (95% CI [6.02–16.48]); and AUC, 0.89. Conclusions. This meta analysis suggested that pleural IGRA has potential for serving as a complementary method for diagnosing TP; however, its cost, high turn around time, and sub-optimal performance make it unsuitable as a stand-alone diagnostic tool. Better tests for the diagnosis of TP are required.
Pang et al. (2015) Accuracy of the interferon-gamma release assay for the diagnosis of tuberculous pleurisy: an updated meta-analysis. PeerJ 3:e951 https://doi.org/10.7717/peerj.951
Can parasites halt the invader? Mermithid nematodes parasitizing the yellow-legged Asian hornet in France
Since its introduction in France 10 years ago, the yellow-legged Asian bee-hawking hornet Vespa velutina has rapidly spread to neighboring countries (Spain, Portugal, Belgium, Italy, and Germany), becoming a new threat to beekeeping activities. While introduced species often leave behind natural enemies from their original home, which benefits them in their new environment, they can also suffer local recruitment of natural enemies. Three mermithid parasitic subadults were obtained from V. velutina adults in 2012, from two French localities. However, these were the only parasitic nematodes reported up to now in Europe, in spite of the huge numbers of nests destroyed each year and the recent examination of 33,000 adult hornets. This suggests that the infection of V. velutina by these nematodes is exceptional. Morphological criteria assigned the specimens to the genus Pheromermis and molecular data (18S sequences) to the Mermithidae, due to the lack of Pheromermis spp. sequences in GenBank. The species is probably Pheromermis vesparum, a parasite of social wasps in Europe. This nematode is the second native enemy of Vespa velutina recorded in France, after a conopid fly whose larvae develop as internal parasitoids of adult wasps and bumblebees. In this paper, we provide arguments for the local origin of the nematode parasite and its limited impact on hornet colony survival. We also clarify why these parasites (mermithids and conopids) most likely could not hamper the hornet invasion nor be used in biological control programs against this invasive species.
Villemant et al. (2015) Can parasites halt the invader? Mermithid nematodes parasitizing the yellow-legged Asian hornet in France. PeerJ 3:e947 https://doi.org/10.7717/peerj.947
Bird biodiversity assessments in temperate forest: the value of point count versus acoustic monitoring protocols
Effective monitoring programs for biodiversity are needed to assess trends in biodiversity and evaluate the consequences of management. This is particularly true for birds and faunas that occupy interior forest and other areas of low human population density, as these are frequently under-sampled compared to other habitats. For birds, Autonomous Recording Units (ARUs) have been proposed as a supplement or alternative to point counts made by human observers to enhance monitoring efforts. We employed two strategies (i.e., simultaneous-collection and same-season) to compare point count and ARU methods for quantifying species richness and composition of birds in temperate interior forests. The simultaneous-collection strategy compares surveys by ARUs and point counts, with methods matched in time, location, and survey duration such that the person and machine simultaneously collect data. The same-season strategy compares surveys from ARUs and point counts conducted at the same locations throughout the breeding season, but methods differ in the number, duration, and frequency of surveys. This second strategy more closely follows the ways in which monitoring programs are likely to be implemented. Site-specific estimates of richness (but not species composition) differed between methods; however, the nature of the relationship was dependent on the assessment strategy. Estimates of richness from point counts were greater than estimates from ARUs in the simultaneous-collection strategy. Woodpeckers in particular, were less frequently identified from ARUs than point counts with this strategy. Conversely, estimates of richness were lower from point counts than ARUs in the same-season strategy. Moreover, in the same-season strategy, ARUs detected the occurrence of passerines at a higher frequency than did point counts. Differences between ARU and point count methods were only detected in site-level comparisons. Importantly, both methods provide similar estimates of species richness and composition for the region. Consequently, if single visits to sites or short-term monitoring are the goal, point counts will likely perform better than ARUs, especially if species are rare or vocalize infrequently. However, if seasonal or annual monitoring of sites is the goal, ARUs offer a viable alternative to standard point-count methods, especially in the context of large-scale or long-term monitoring of temperate forest birds.
Klingbeil et al. (2015) Bird biodiversity assessments in temperate forest: the value of point count versus acoustic monitoring protocols. PeerJ 3:e973 https://doi.org/10.7717/peerj.973