The occurrence of the second moult of Ascaris lumbricoides and Ascaris suum

Maung M. 1978. The occurrence of the second moult of Ascaris lumbricoides and Ascaris suum. International Journal for Parasitology 8: 371–378. Eggs of Ascaris lumbricoides and A. suum were cultured at 28°C and observed daily. Larvae were released by pressure, by artificial hatching with CO₂, and by natural hatching after infection of laboratory mice. The early stages of development in the egg were observed to comprise two moults, one occurring immediately after the other. Both moults were initiated within the egg, but the time of completion of the second moult varied considerably, and in some instances was not completed until the larvae reached the liver of experimentally infected animals.     

Folding up and Moving on—Nascent Protein Folding on the Ribosome

All cellular proteins are synthesized by the ribosome, an intricate molecular machine that translates the information of protein coding genes into the amino acid alphabet. The linear polypeptides synthesized by the ribosome must generally fold into specific three-dimensional structures to become biologically active. Folding has long been recognized to begin before synthesis is complete. Recently, biochemical and biophysical studies have shed light onto how the ribosome shapes the folding pathways of nascent proteins. Here, we discuss recent progress that is beginning to define the role of the ribosome in the folding of newly synthesized polypeptides.     

Battling for Ribosomes: Translational Control at the Forefront of the Antiviral Response

In the early stages of infection, gaining control of the cellular protein synthesis machinery including its ribosomes is the ultimate combat objective for a virus. To successfully replicate, viruses unequivocally need to usurp and redeploy this machinery for translation of their own mRNA. In response, the host triggers global shutdown of translation while paradoxically allowing swift synthesis of antiviral proteins as a strategy to limit collateral damage. This fundamental conflict at the level of translational control defines the outcome of infection. As part of this special issue on molecular mechanisms of early virus–host cell interactions, we review the current state of knowledge regarding translational control during viral infection with specific emphasis on protein kinase RNA-activated and mammalian target of rapamycin-mediated mechanisms. We also describe recent technological advances that will allow unprecedented insight into how viruses and host cells battle for ribosomes.     

Design,synthesis and molecular docking of thiazolidinedione based benzene sulphonamide derivatives containing pyrazole core as potential anti-diabetic agents

We herein report the design, synthesis and molecular docking studies of 2,4-thiazolidinedione derivatives containing benzene sulphonyl group which are docked against the Peroxisome Proliferator Activated Receptor (PPARγ) target. Compound 7p was most effective in lowering the blood glucose level as compared to standard drugs pioglitazone and rosiglitazone. Compound 7p exhibited potent PPAR-γ transactivation of 61.2% with 1.9 folds increase in gene expression. In molecular docking studies 7p showed excellent interactions with amino acids TYR 473, SER 289, HIE 449, TYR 327, ARG 288, MET 329 and LEU 228. Compound 7p did not cause any damage to the liver without any noteworthy weight gain and may be considered as promising candidates for the development of new antidiabetic agents.     

Setting “Spanish legacies” into further context: some findings and thoughts from CILS4EU

This contribution compares some major findings of “Spanish Legacies” to findings from the CILS4EU study that has been conducted in four other European countries. Despite the differences in the immigration history and the composition of the immigrant youth, basic results of psychosocial adaptation are surprisingly similar for England, Germany, the Netherlands, and Sweden. This confirms the mostly optimistic picture of the future of the second generation in Europe as drawn for Spain. In a sense, the similarities suggest that the role of the receiving context might be less important than is expected in overarching theoretical frameworks such as “segmented assimilation”. Some aspects of integration that are not covered in “Spanish Legacies” could raise more doubts on the smoothness of the adaptation processes for some immigrants groups.     

H2O2 mediates nitrate‐induced iron chlorosis by regulating iron homeostasis in rice

The uptake of nitrate by plant roots causes a pH increment in rhizosphere and leads to iron (Fe) deficiency in rice. However, little is known about the mechanism how the nitrate uptake‐induced high rhizosphere pH causes Fe deficiency. Here, we found that rice showed severe leaf chlorosis and large amounts of Fe plaque were aggregated on the root surface and intercellular space outside the exodermis in a form of ferrihydrite under alkaline conditions. In this case, there was significantly decreased Fe concentration in shoots, and the Fe deficiency responsive genes were strongly induced in the roots. The high rhizosphere pH induced excess hydrogen peroxide (H₂O₂) production in the epidermis due to the increasing expression of NADPH‐oxidase respiratory burst oxidase homolog 1, which enhanced root oxidation ability and improved the Fe plaque formation in rhizosphere. Further, the concentrated H₂O₂ regulated the phenylpropanoid metabolism with increased lignin biosynthesis and decreased phenolics secretion, which blocked apoplast Fe mobilization efficiency. These factors coordinately repressed the Fe utilization in rhizosphere and led to Fe deficiency in rice under high pH. In conclusion, our results demonstrate that nitrate uptake‐induced rhizosphere alkalization led to Fe deficiency in rice, through H₂O₂‐dependent manners of root oxidation ability and phenylpropanoid metabolism.     

Tardive dyskinesia risk with first‐ and second‐generation antipsychotics in comparative randomized controlled trials: a meta‐analysis

Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2 receptor partial agonists (second‐generation antipsychotics, SGAs) is considered significantly lower than with D2 antagonists (first‐generation antipsychotics, FGAs). As some reports questioned this notion, we meta‐analyzed randomized controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we calculated raw and annualized pooled TD rates for each antipsychotic. Data from 57 head‐to‐head RCTs, including 32 FGA and 86 SGA arms, were meta‐analyzed, yielding 32 FGA‐SGA pairs and 35 SGA‐SGA pairs. The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3‐7.8%) vs. 2.6% (95% CI: 2.0‐3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39‐0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28‐0.45, p<0.0001, number‐needed‐to‐treat, NNT=20). Meta‐regression showed no FGA dose effect on FGA‐SGA comparisons (Z=?1.03, p=0.30). FGA‐SGA TD RaRs differed by SGA comparator (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and aripiprazole over other non‐clozapine SGAs in exploratory pairwise comparisons. SGA‐SGA comparisons confirmed the olanzapine advantage vs. non‐clozapine SGAs (RaR=0.66, 95% CI: 0.49‐0.88, p=0.006, k=17, NNT=100). This meta‐analysis confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not driven by high dose FGA comparators, and documents significant differences with respect to this risk between individual SGAs.     

Lifetime inbreeding depression in a leaf beetle

Ongoing habitat loss and fragmentation result in rapid population size reductions, which can increase the levels of inbreeding. Consequently, many species are threatened by inbreeding depression, a loss of individual fitness following the mating of close relatives. Here, we investigated inbreeding effects on fitness‐related traits throughout the lifetime of the mustard leaf beetle (Phaedon cochleariae) and mechanisms for the avoidance of inbreeding. Previously, we found that these beetles have family‐specific cuticular hydrocarbon profiles, which are likely not used as recognition cue for precopulatory inbreeding avoidance. Thus, we examined whether adult beetles show postcopulatory inbreeding avoidance instead. For this purpose, we determined the larval hatching rate of eggs laid by females mated sequentially with two nonsiblings, two siblings, a nonsibling, and a sibling or vice versa. The beetles suffered from inbreeding depression throughout their entire ontogeny, as evinced by a prolonged larval development, a decreased larval and adult survival and a decreased reproductive output of inbred compared to outbred individuals. The highest larval hatching rates were detected when females were mated with two nonsiblings or first with a sibling and second with a nonsibling. Significantly lower hatching rates were measured in the treatments with a sibling as second male. Thus, the results do not support the existence of postcopulatory inbreeding avoidance in P. cochleariae, but revealed evidence for second male sperm precedence. Consequently, an alternative strategy to avoid inbreeding costs might exist in this beetle, such as a polyandrous mating system, potentially coupled with a specific dispersal behavior.     

Landscape‐scale lidar analysis of aboveground biomass distribution in secondary Brazilian Atlantic Forest

Secondary forests account for more than half of tropical forests and represent a growing carbon sink, but rates of biomass accumulation vary by a factor of two or more even among plots in the same landscape. To better understand the drivers of this variability, we used airborne lidar to measure forest canopy height and estimate biomass over 4529 ha at Serra do Conduru Park in Southern Bahia, Brazil. We measured trees in 30 georeferenced field plots (0.25‐ha each) to estimate biomass using allometry. Then we estimated aboveground biomass density (ABD) across the lidar study area using a statistical model developed from our field plots. This model related the 95th percentile of the distribution of lidar return heights to ABD. We overlaid this map of ABD on a Landsat‐derived forest age map to determine rates of biomass accumulation. We found rapid initial biomass regeneration (~6 Mg/ha yr), which slowed as forests aged. We also observed high variability in both height and biomass across the landscape within forests of similar age. Nevertheless, a regression model that accounted for spatial autocorrelation and included forest age, slope, and distance to roads or open areas explained 62 and 77 percent of the landscape variation in ABD and canopy height, respectively. Thus, while there is high spatial heterogeneity in forest recovery, and the drivers of this heterogeneity warrant further investigation, we suggest that a relatively simple set of predictor variables is sufficient to explain the majority of variance in both height and ABD in this landscape.     

Structural Basis of Cyclic Nucleotide Selectivity in cGMP-dependent Protein Kinase II

Membrane-bound cGMP-dependent protein kinase (PKG) II is a key regulator of bone growth, renin secretion, and memory formation. Despite its crucial physiological roles, little is known about its cyclic nucleotide selectivity mechanism due to a lack of structural information. Here, we find that the C-terminal cyclic nucleotide binding (CNB-B) domain of PKG II binds cGMP with higher affinity and selectivity when compared with its N-terminal CNB (CNB-A) domain. To understand the structural basis of cGMP selectivity, we solved co-crystal structures of the CNB domains with cyclic nucleotides. Our structures combined with mutagenesis demonstrate that the guanine-specific contacts at Asp-412 and Arg-415 of the αC-helix of CNB-B are crucial for cGMP selectivity and activation of PKG II. Structural comparison with the cGMP selective CNB domains of human PKG I and Plasmodium falciparum PKG (PfPKG) shows different contacts with the guanine moiety, revealing a unique cGMP selectivity mechanism for PKG II.