Diapause affects cuticular hydrocarbon composition and mating behavior of both sexes in Drosophila montana

Envipnmental cues,mainly photoperiod and temperature,are known to control female adult reproductive diapause in several insect species.Diapause enhances female survival during adverse conditions and postpones progeny production to the favorable season.Male diapause(a reversible inability to inseminate receptive females)has been studied much less than female diapause.However,if the males maximized their chances to fertilize females while minimizing their energy expenditure,they would be expected to be in diapause at the same time as females.We investigated Drosophila montana male mating bchavior under short-day conditions that induce diapause in females and found the males to be reproductively inactive.We also found that males reared under long-day conditions(reproducing individuals)court reproducing postdiapause fermales,but not diapausing ones.The diapausing fies of both sexes had more long-chain and less short-chain hydrocarbons on their cuticle than the reproducing ones,which presumably increase their survival under stressful conditions,but at the same time decrease their attractiveness.Our study shows that the mating behavior of females and males is well coordinated during and afier overwintering and it also gives support to the dual role of insect cuticular hydrocarbons in adaptation and mate choice.     

Native tree regeneration in native tree plantations: understanding the contribution of Araucaria angustifolia to biodiversity conservation in the threatened Atlantic Forest in Argentina

Deforestation is a global process that has strongly affected the Atlantic Forest in South America, which has been recognised as a threatened biodiversity hotspot. An important proportion of deforested areas were converted to forest plantations. Araucaria angustifolia is a native tree to the Atlantic Forest, which has been largely exploited for wood production and is currently cultivated in commercial plantations. An important question is to what extent such native tree plantations can be managed to reduce biodiversity loss in a highly diverse and vulnerable forest region . We evaluated the effect of stand age, stand basal area, as a measure of stand density, and time since last logging on the density and richness of native tree regeneration in planted araucaria stands that were successively logged over 60 years, as well as the differences between successional groups in the response of plant density to stand variables. We also compared native tree species richness in planted araucaria stands to neighbouring native forest. Species richness was 71 in the planted stands (27 ha sampled) and 82 in native forest (18 ha sampled) which approximate the range of variation in species richness found in the native forests of the study area. The total abundance and species richness of native trees increased with stand age and time since last logging, but ecological groups differed in their response to such variables. Early secondary trees increased in abundance with stand age 3–8 times faster than climax or late secondary trees. Thus, the change in species composition is expected to continue for a long term. The difference in species richness between native forest and planted stands might be mainly explained by the difference in plant density. Therefore, species richness in plantations can contribute to local native tree diversity if practices that increase native tree density are implemented.     

Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis

Cochlear inner hair cells (IHCs) develop from pre‐sensory pacemaker to sound transducer. Here, we report that this involves changes in structure and function of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around hearing onset in mice. As synapses matured they changed from holding several small presynaptic active zones (AZs) and apposed postsynaptic densities (PSDs) to one large AZ/PSD complex per SGN bouton. After the onset of hearing (i) IHCs had fewer and larger ribbons; (ii) Ca_V1.3 channels formed stripe‐like clusters rather than the smaller and round clusters at immature AZs; (iii) extrasynaptic Ca_V1.3‐channels were selectively reduced, (iv) the intrinsic Ca²⁺ dependence of fast exocytosis probed by Ca²⁺ uncaging remained unchanged but (v) the apparent Ca²⁺ dependence of exocytosis linearized, when assessed by progressive dihydropyridine block of Ca²⁺ influx. Biophysical modeling of exocytosis at mature and immature AZ topographies suggests that Ca²⁺ influx through an individual channel dominates the [Ca²⁺] driving exocytosis at each mature release site. We conclude that IHC synapses undergo major developmental refinements, resulting in tighter spatial coupling between Ca²⁺ influx and exocytosis.     

Serum Autotaxin Is a Parameter for the Severity of Liver Cirrhosis and Overall Survival in Patients with Liver Cirrhosis – A Prospective Cohort Study

Background

Autotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients.

Methods

Patients with liver cirrhosis were prospectively enrolled and followed until death, liver transplantation or last contact. Blood samples drawn at the day of inclusion in the study were assessed for ATX content by an enzyme-linked immunosorbent assay. ATX levels were correlated with the stage as well as complications of cirrhosis. The prognostic value of ATX was investigated by uni- and multivariate Cox regression analyses. LPA concentration was determined by liquid chromatography-tandem mass spectrometry.

Results

270 patients were enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as compared to healthy subjects (0.814±0.42 mg/l vs. 0.258±0.40 mg/l, P<0.001). Serum ATX levels correlated with the Child-Pugh stage and the MELD (model of end stage liver disease) score and LPA levels (r = 0.493, P = 0.027). Patients with hepatic encephalopathy (P = 0.006), esophageal varices (P = 0.002) and portal hypertensive gastropathy (P = 0.008) had higher ATX levels than patients without these complications. Low ATX levels were a parameter independently associated with longer overall survival (hazard ratio 0.575, 95% confidence interval 0.365–0.905, P = 0.017).

Conclusion

Serum ATX is an indicator for the severity of liver disease and the prognosis of cirrhotic patients.     

Epigenetic and pharmacological control of pigmentation via Bromodomain Protein 9 (BRD9)

Lineage-specific differentiation programs are activated by epigenetic changes in chromatin structure. Melanin-producing melanocytes maintain a gene expression program ensuring appropriate enzymatic conversion of metabolites into the pigment, melanin, and transfer to surrounding cells. During neuroectodermal development, SMARCA4 (BRG1), the catalytic subunit of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes, is essential for lineage specification. SMARCA4 is also required for development of multipotent neural crest precursors into melanoblasts, which differentiate into pigment-producing melanocytes. In addition to the catalytic domain, SMARCA4 and several SWI/SNF subunits contain bromodomains which are amenable to pharmacological inhibition. We investigated the effects of pharmacological inhibitors of SWI/SNF bromodomains on melanocyte differentiation. Strikingly, treatment of murine melanoblasts and human neonatal epidermal melanocytes with selected bromodomain inhibitors abrogated melanin synthesis and visible pigmentation. Using functional genomics, iBRD9, a small molecule selective for the bromodomain of BRD9 was found to repress pigmentation-specific gene expression. Depletion of BRD9 confirmed a requirement for expression of pigmentation genes in the differentiation program from melanoblasts into pigmented melanocytes and in melanoma cells. Chromatin immunoprecipitation assays showed that iBRD9 disrupts the occupancy of BRD9 and the catalytic subunit SMARCA4 at melanocyte-specific loci. These data indicate that BRD9 promotes melanocyte pigmentation whereas pharmacological inhibition of BRD9 is repressive.     

Scale-up of stirring as foam disruption (SAFD) to industrial scale

Foam disruption by agitation—the stirring as foam disruption (SAFD) technique—was scaled up to pilot and production scale using Rushton turbines and an up-pumping hydrofoil impeller, the Scaba 3SHP1. The dominating mechanism behind SAFD—foam entrainment—was also demonstrated at production scale. The mechanistic model for SAFD defines a fictitious liquid velocity generated by the (upper) impeller near the dispersion surface, which is correlated with complete foam disruption. This model proved to be scalable, thus enabling the model to be used for the design of SAFD applications. Axial upward pumping impellers appeared to be more effective with respect to SAFD than Rushton turbines, as demonstrated by retrofitting a 12,000 l bioreactor, i.e. the triple Rushton configuration was compared with a mixed impeller configuration from Scaba with a 20% lower ungassed power draw. The retrofitted impeller configuration allowed 10% more broth without risking excessive foaming. In this way a substantial increase in the volumetric productivity of the bioreactor was achieved. Design recommendations for the application of SAFD are given in this paper. Using these recommendations for the design of a 30,000 l scale bioreactor, almost foamless Escherichia coli fermentations were realised. Electronic Publication     

A Non-classical Assembly Pathway of Escherichia coli Pore-forming Toxin Cytolysin A

Cytolysin A (ClyA) is an α-pore forming toxin from pathogenic Escherichia coli (E. coli) and Salmonella enterica. Here, we report that E. coli ClyA assembles into an oligomeric structure in solution in the absence of either bilayer membranes or detergents at physiological temperature. These oligomers can rearrange to create transmembrane pores when in contact with detergents or biological membranes. Intrinsic fluorescence measurements revealed that oligomers adopted an intermediate state found during the transition between monomer and transmembrane pore. These results indicate that the water-soluble oligomer represents a prepore intermediate state. Furthermore, we show that ClyA does not form transmembrane pores on E. coli lipid membranes. Because ClyA is delivered to the target host cell in an oligomeric conformation within outer membrane vesicles (OMVs), our findings suggest ClyA forms a prepore oligomeric structure independently of the lipid membrane within the OMV. The proposed model for ClyA represents a non-classical pathway to attack eukaryotic host cells.     

Canopy tree mortality depends on the proportion of crown exposed to sunlight,but this effect varies with species' wood density

Understanding what drives changes in tree mortality as well as the covariates influencing trees' response is a research priority to predict forest responses to global change. Here, we combined drone photogrammetry and ground-based data to assess the influence of crown exposure to light (relative to total crown area), growth deviations (relative to conspecifics), tree size, and species' wood density (as a surrogate for light-demanding and shade-tolerant life-history strategies) on the mortality of 984 canopy trees in an Amazon terra firme forest. Trees with lower wood density were less prone to die when their proportion of crown was more exposed to sunlight, but this relationship with relative crown exposure weakened and slightly reversed as wood density increased. Trees growing less than their species average had higher mortality, especially when the species' wood density decreased. The role of wood density in determining the survival of canopy trees under varying light conditions indicates differential responses of light-demanding versus shade-tolerant species. Our results highlight the importance of accounting for life-history strategies, via plant functional types, in vegetation dynamic models aiming to predict forest demography under a rapidly changing climate. Abstract in Spanish is available with online material.     

All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH,Detemir, and Glargine

Background

Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.

Objective

To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.

Methods

23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006–2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years).

Results

2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30–0.50) for detemir, and 0.55 (95% CI, 0.44–0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54–0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.

Conclusion

In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.