Enhanced recruitment of Th2 and CLA-negative lymphocytes by the S128R polymorphism of E-selectin

E-selectin is a cytokine-inducible endothelial cell adhesion molecule that binds a restricted population of T lymphocytes consisting of Th1 memory cells bearing the cutaneous lymphocyte Ag (CLA). A serine to arginine (S128R) polymorphism in E-selectin has been reported at increased frequency in patients with systemic lupus erythematosus and atherosclerosis. Here we tested the hypothesis that the S128R substitution may contribute to increased vascular disease by altering the number and/or phenotype of lymphocytes interacting with E-selectin under shear flow. We observed that CHO cell monolayers transfected with S128R recruited significantly greater numbers of unfractionated lymphocytes than monolayers expressing an equivalent density of wild-type (WT) E-selectin. Depletion of the CLA(+) subpopulation or generation of CLA(-) lymphoblasts abolished rolling and arrest on WT E-selectin, but left a residual population that interacted with S128R. Generation of Th subsets revealed preferential interaction of Th0 and Th2, but not Th1, cells with S128R compared with WT. However, only T cells of a memory phenotype interacted with S128R, since neither monolayer supported rolling of CD45RA(+) cells. Our results demonstrate that the S128R polymorphism extends the range of lymphocytes recruited by E-selectin, which may provide a mechanistic link between this polymorphism and vascular inflammatory disease.     

Optimal thermal conditions for corals extend poleward with oceanic warming

Aim

The capacity for poleward range expansions beyond the tropics in corals hinges on ecophysiological constraints and resulting responses to climatic variability. We aimed to determine how future warming will affect coral habitat suitability at the poleward range edges of these foundational species in the Northwest Pacific.

Location

Northwest Pacific.

Methods

We generated models integrating thermal physiological constraints of corals adapted to extreme seasonality in Hong Kong, specifically the minimum annual temperature and the proportion of time annually spent at seasonal extremes. With these models, we projected habitat suitability for five coral species under current and future climatic conditions across the Northwest Pacific.

Results

Climate model projections reveal an easing of thermal constraints on the leading-edge of coral ecophysiological limits with an expansion of thermally suitable habitat poleward by 2°–7° in latitude depending on the coral species and model considered. We also highlight a potential divergence of present and future thermal regimes that may lead to a mismatch in suitability for corals currently inhabiting high latitude reefs.

Main Conclusions

Understanding the thermal constraints on coral distributions and defining the potential range of corals under climate change is critical for adaptive management that focuses on coral conservation and ensuring ecosystem function of existing subtropical and temperate ecosystems.     

Microbotanical signatures of kreb: differentiating inflorescence phytoliths from northern African wild grasses

Vegetation History and Archaeobotany - Throughout northern Africa, evidence for an intensification of wild grass gathering is reflected in Holocene archaeological contexts. However, both the...     

Serum concentrations of vitamin D-binding protein (Group-specific component) in cystic fibrosis

Summary Vitamin D-binding protein (DBP) concentrations were determined in the sera of 90 cystic fibrosis homozygotes, 57 obligate heterozygotes, and 46 normal controls. Very significantly lower mean concentrations were found in the sera of CF homozygotes compared with both heterozygotes and controls (P<0.01, Wilcoxon Rank Sums Test). Subdivision of the samples by Gc phenotype showed that this relationship held true both in the Gc1 and Gc2-1 phenotypes. The small sample size of the Gc2 genotype makes the significance levels of limited usefulness, but the pattern of variation of DBP levels among CF homozygotes, heterozygotes, and controls was consistent with that observed for the Gc1 and Gc2-1 classes. Haptoglobin levels showed high coefficients of variation when compared among CF homozygotes, obligate heterozygotes, and controls, presumably because of nonspecific elevation in the acute-phase response. Alpha₂-macroglobulin levels were, if anything, slightly elevated in CF homozygotes compared with controls, while albumin levels showed no significant mean differences between these groups. Since the DBP concentration does not vary with age nor with levels of vitamin D and its metabolites, we interpret our results to mean that DBP levels are specifically decreased in cystic fibrosis, perhaps as the result of impaired glycosylation of the protein.A preliminary report of this work appeared in the Proceedings of the 8th International Congress on Cystic Fibrosis.     

Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study

BackgroundThere is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS.Methods and findingsWe conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin.Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor.ConclusionsThese multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation.Trial registrationClinicalTrials.gov - {"type":"clinical-trial","attrs":{"text":"NCT03507309","term_id":"NCT03507309"}}NCT03507309

Amit Kaura and colleagues investigate whether mildly elevated high sensitivity C-reactive protein is associated with mortality risk in patients with suspected acute coronary syndromes.     

Early plant domestications in southern India: some preliminary archaeobotanical results

Analysis of flotation samples from twelve sites in Karnataka and Andhra Pradesh (south India) provides clear evidence for the predominant subsistence plants of the Neolithic period (2,800–1,200 cal b.c.). This evidence indicates that the likely staples were two pulses (Vigna radiata and Macrotyloma uniflorum) and two millet-grasses (Brachiaria ramosa and Setaria verticillata) which were indigenous to the Indian peninsula. At some sites there is evidence for limited cultivation of wheats (Triticum diococcum, Triticum durum/aestivum) and barley (Hordeum vulgare), and a few crops that originated in Africa, including hyacinth bean (Lablab purpureus), pearl millet (Pennisetum glaucum) and finger millet (Eleusine coracana). In addition there is evidence for cotton (Gossypium sp.), and linseed (Linum sp.), as well as gathered fruits of Ziziphus and two Cucurbitaceae. This evidence suggests that the earliest agriculture in south India, dating to the third millennium b.c., was based on plants domesticated in the region, and that subsequently from the late 3^rd millennium b.c. through the 2^nd millennium additional crops from other regions were adopted into the subsistence system.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00334-004-0036-9     

Effects of shear stress on endothelial cell haptotaxis on micropatterned surfaces

Endothelial cell (EC) migration plays a critical role in vascular remodeling. Here we investigated the interactions between haptotaxis (induced by extracellular matrix gradient) and mechanotaxis (induced by mechanical forces) during EC migration. A micropatterning technique was used to generate step changes of collagen surface density. Due to haptotaxis, ECs developed focal adhesions and migrated into the area with higher surface density of collagen. Different levels of fluid shear stress were applied on ECs in the direction perpendicular to collagen strips. Shear stress at 2 dyn/cm2 did not affect haptotaxis, while shear stress at 3 dyn/cm2 or higher was sufficient to drive the migration of most ECs in the flow direction and against haptotaxis. Immunostaining revealed the increase of focal adhesions and lamellipodial protrusion in the direction of flow. These results suggest that shear stress beyond a certain threshold can be a predominant factor to determine the direction of EC migration.     

A lower Cambrian protoconodont apparatus from the Placentian of southeastern Newfoundland

A cluster of three pyritized, naturally arranged, conoidal sclerites has been found on a bedding surface in the lower Cambrian Chapel Island Formation in southeastern Newfoundland. The elements are about 4 mm in length and are morphologically similar to protoconodonts but neither their original chemical composition nor internal structure is preserved. Arrangement of the elements suggests that they belonged to an apparatus that performed a grasping function. The specimen is described here as ProtohertzinaEfficacynadia n.sp. This is the oldest hitherto described protoconodont apparatus, apart from clusters of Mongolodus described from the lower Cambrian of the Lesser Himalaya. This paper adds to the scant knowledge of early protoconodonts that we consider to be the earliest biomineralized predators.     

Cystic fibrosis allele frequency,sex ratio anomalies and fertility: a new theory for the dissemination of mutant alleles

Summary The observation that mothers of cystic fibrosis patients come from sibships that are larger than those of the fathers is explained by a decrease in sex ratio with increasing size of parental sibships. This feature also provides the basis for a new theory for the dissemination of the major mutant allele, deduced to have arisen 2700–5000 years ago, in accordance with an overall heterozygote advantage of around 3%. In heterozygous women with heterozygous partners, sex-related selection probably occurs after fertilization.     

Behaviorally measured tactile sensitivity in the common bottlenose dolphin,Tursiops truncatus

Little research has been conducted on the somatosensory system of toothed whales and it remains uncertain how tactile sensitivity varies about their bodies. In this study, tactile sensitivity to high-frequency (250-Hz) displacement of the skin was quantified in three trained adult common bottlenose dolphins (Tursiops truncatus) using a vibratory device (tactor). The magnitude of skin displacement was controlled by varying the voltage to the tactor held against the skin surface with a constant force. Tactile thresholds were determined using an adaptive method of limits in which dolphins reported perception of the tactile stimulus by producing a whistle. Displacement thresholds ranged from 2.4 to 40 μm, with the greatest sensitivity found along the rostrum, melon, and blowhole. Sensitivity decreased caudally along the body, with the dorsal fin and tip of the fluke being the least sensitive locations tested. The results support hypotheses that the follicles on the dolphin rostrum are particularly important for perception. The reduction in tactile sensitivity at the appendages is consistent with their primary role in stabilization and locomotion compared to exploration or environmental sensing.