570 Biowissenschaften; Biologie
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Background/Aims:
The ET system might be involved in the pathogenesis of hypertensive disorders during pregnancy. The objective is to analyse the impact of ET-1 in hypertensive pregnant women by a strict meta-analysis of published human clinical studies.
Methods:
Based on the principle of Cochrane systematic reviews, Cohort studies in PubMed (Medline), Google Scholar and China Biological Medicine Database (CBM-disc) designed to identify the role of endothelin-1 (ET-1) in the pathophysiology of gestational hypertension and preeclampsia were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects model.
Results:
Sixteen published cohort studies including 1739 hypertensive cases and 409 controls were used in the meta-analysis. ET-1 plasma concentrations were higher in hypertensive pregnant women as compared to the controls (mean difference between groups: 19.02 [15.60~22.44], P < 0.00001,). These finding were driven by severity of hypertension and/or degree of proteinuria.
Conclusion:
Plasma ET-1 concentrations are elevated in hypertensive disorders during human pregnancy. In particular women with preeclampsia (hypertensive pregnant women with proteinuria) have substantially elevated plasma ET-1 concentration as compared to pregnant women with normal blood pressure.
Leukotriene B4 as an inflammatory mediator is an important biomarker for different respiratory diseases like asthma, chronic obstructive pulmonary disease or cystic lung fibrosis. Therefore the detection of LTB4 is helpful in the diagnosis of these pulmonary diseases. However, until now its determination in exhaled breath condensates suffers from problems of accuracy. Reasons for that could be improper sample collection and preparation methods of condensates and the lack of consistently assay specificity and reproducibility of the used immunoassay detection system. In this study we describe the development and the characterization of a specific monoclonal antibody (S27BC6) against LTB4, its use as molecular recognition element for the development of an enzyme-linked immunoassay to detect LTB4 and discuss possible future diagnostic applications.
Orthogonal systems for heterologous protein expression as well as for the engineering of synthetic gene regulatory circuits in hosts like Saccharomyces cerevisiae depend on synthetic transcription factors (synTFs) and corresponding cis-regulatory binding sites. We have constructed and characterized a set of synTFs based on either transcription activator-like effectors or CRISPR/Cas9, and corresponding small synthetic promoters (synPs) with minimal sequence identity to the host’s endogenous promoters. The resulting collection of functional synTF/synP pairs confers very low background expression under uninduced conditions, while expression output upon induction of the various synTFs covers a wide range and reaches induction factors of up to 400. The broad spectrum of expression strengths that is achieved will be useful for various experimental setups, e.g., the transcriptional balancing of expression levels within heterologous pathways or the construction of artificial regulatory networks. Furthermore, our analyses reveal simple rules that enable the tuning of synTF expression output, thereby allowing easy modification of a given synTF/synP pair. This will make it easier for researchers to construct tailored transcriptional control systems.
Genetic analyses of Australasian organisms have resulted in the identification of extensive cryptic diversity across the continent. The venomous elapid snakes are among the best-studied organismal groups in this region, but many knowledge gaps persist: for instance, despite their iconic status, the species-level diversity among Australo-Papuan blacksnakes (Pseudechis) has remained poorly understood due to the existence of a group of cryptic species within the P. australis species complex, collectively termed "pygmy mulga snakes". Using two mitochondrial and three nuclear loci we assess species boundaries within the genus using Bayesian species delimitation methods and reconstruct their phylogenetic history using multispecies coalescent approaches. Our analyses support the recognition of 10 species, including all of the currently described pygmy mulga snakes and one undescribed species from the Northern Territory of Australia. Phylogenetic relationships within the genus are broadly consistent with previous work, with the recognition of three major groups, the viviparous red-bellied black snake P. porphyriacus forming the sister species to two clades consisting of ovoviviparous species.
Background: The members of the genus Muntiacus are of particular interest to evolutionary biologists due to their extreme chromosomal rearrangements and the ongoing discussions about the number of living species. Red muntjacs have the largest distribution of all muntjacs and were formerly considered as one species. Karyotype differences led to the provisional split between the Southern Red Muntjac (Muntiacus muntjak) and the Northern Red Muntjac (M. vaginalis), but uncertainties remain as, so far, no phylogenetic study has been conducted. Here, we analysed whole mitochondrial genomes of 59 archival and 16 contemporaneous samples to resolve uncertainties about their taxonomy and used red muntjacs as model for understanding the evolutionary history of other species in Southeast Asia. Results: We found three distinct matrilineal groups of red muntjacs: Sri Lankan red muntjacs (including the Western Ghats) diverged first from other muntjacs about 1.5 Mya; later northern red muntjacs (including North India and Indochina) and southern red muntjacs (Sundaland) split around 1.12 Mya. The diversification of red muntjacs into these three main lineages was likely promoted by two Pleistocene barriers: one through the Indian subcontinent and one separating the Indochinese and Sundaic red muntjacs. Interestingly, we found a high level of gene flow within the populations of northern and southern red muntjacs, indicating gene flow between populations in Indochina and dispersal of red muntjacs over the exposed Sunda Shelf during the Last Glacial Maximum. Conclusions: Our results provide new insights into the evolution of species in South and Southeast Asia as we found clear genetic differentiation in a widespread and generalist species, corresponding to two known biogeographical barriers: The Isthmus of Kra and the central Indian dry zone. In addition, our molecular data support either the delineation of three monotypic species or three subspecies, but more importantly these data highlight the conservation importance of the Sri Lankan/South Indian red muntjac.
Diurnally-migrating Chaoborus spp. reach populations of up to 130,000 individuals m−2 in lakes up to 70 meters deep on all continents except Antarctica. Linked to eutrophication, migrating Chaoborus spp. dwell in the anoxic sediment during daytime and feed in the oxic surface layer at night. Our experiments show that by burrowing into the sediment, Chaoborus spp. utilize the high dissolved gas partial pressure of sediment methane to inflate their tracheal sacs. This mechanism provides a significant energetic advantage that allows the larvae to migrate via passive buoyancy rather than more energy-costly swimming. The Chaoborus spp. larvae, in addition to potentially releasing sediment methane bubbles twice a day by entering and leaving the sediment, also transport porewater methane within their gas vesicles into the water column, resulting in a flux of 0.01–2 mol m−2 yr−1 depending on population density and water depth. Chaoborus spp. emerging annually as flies also result in 0.1–6 mol m−2 yr−1 of carbon export from the system. Finding the tipping point in lake eutrophication enabling this methane-powered migration mechanism is crucial for ultimately reconstructing the geographical expansion of Chaoborus spp., and the corresponding shifts in the lake’s biogeochemistry, carbon cycling and food web structure.
Acid sphingomyelinase mediates murine acute lung injury following transfusion of aged platelets
(2017)
Pulmonary complications from stored blood products are the leading cause of mortality related to transfusion. Transfusion-related acute lung injury is mediated by antibodies or bioactive mediators, yet underlying mechanisms are incompletely understood. Sphingolipids such as ceramide regulate lung injury, and their composition changes as a function of time in stored blood. Here, we tested the hypothesis that aged platelets may induce lung injury via a sphingolipid-mediated mechanism. To assess this hypothesis, a two-hit mouse model was devised. Recipient mice were treated with 2 mg/kg intraperitoneal lipopolysaccharide (priming) 2 h before transfusion of 10 ml/kg stored (1-5 days) platelets treated with or without addition of acid sphingomyelinase inhibitor ARC39 or platelets from acid sphingomyelinase-deficient mice, which both reduce ceramide formation. Transfused mice were examined for signs of pulmonary neutrophil accumulation, endothelial barrier dysfunction, and histological evidence of lung injury. Sphingolipid profiles in stored platelets were analyzed by mass spectrophotometry. Transfusion of aged platelets into primed mice induced characteristic features of lung injury, which increased in severity as a function of storage time. Ceramide accumulated in platelets during storage, but this was attenuated by ARC39 or in acid sphingomyelinase-deficient platelets. Compared with wild-type platelets, transfusion of ARC39-treated or acid sphingomyelinase-deficient aged platelets alleviated lung injury. Aged platelets elicit lung injury in primed recipient mice, which can be alleviated by pharmacological inhibition or genetic deletion of acid sphingomyelinase. Interventions targeting sphingolipid formation represent a promising strategy to increase the safety and longevity of stored blood products.
The acentriolar Dictyostelium centrosome is a nucleus-associated body consisting of a core structure with three plaque-like layers, which are surrounded by a microtubule-nucleating corona. The core duplicates once per cell cycle at the G2/M transition, whereby its central layer disappears and the two outer layers form the mitotic spindle poles. Through proteomic analysis of isolated centrosomes, we have identified CP39 and CP75, two essential components of the core structure. Both proteins can be assigned to the central core layer as their centrosomal presence is correlated to the disappearance and reappearance of the central core layer in the course of centrosome duplication. Both proteins contain domains with centrosome-binding activity in their N- and C-terminal halves, whereby the respective N-terminal half is required for cell cycle-dependent regulation. CP39 is capable of self-interaction and GFP-CP39 overexpression elicited supernumerary microtubule-organizing centers and pre-centrosomal cytosolic clusters. Underexpression stopped cell growth and reversed the MTOC amplification phenotype. In contrast, in case of CP75 underexpression of the protein by RNAi treatment elicited supernumerary MTOCs. In addition, CP75RNAi affects correct chromosome segregation and causes co-depletion of CP39 and CP91, another central core layer component. CP39 and CP75 interact with each other directly in a yeast two-hybrid assay. Furthermore, CP39, CP75 and CP91 mutually interact in a proximity-dependent biotin identification (BioID) assay. Our data indicate that these three proteins are all required for proper centrosome biogenesis and make up the major structural components of core structure's central layer.
Biodiversity-multifunctionality relationships depend on identity and number of measured functions
(2017)
Biodiversity ensures ecosystem functioning and provisioning of ecosystem services, but it remains unclear how biodiversity-ecosystem multifunctionality relationships depend on the identity and number of functions considered. Here, we demonstrate that ecosystem multifunctionality, based on 82 indicator variables of ecosystem functions in a grassland biodiversity experiment, increases strongly with increasing biodiversity. Analysing subsets of functions showed that the effects of biodiversity on multifunctionality were stronger when more functions were included and that the strength of the biodiversity effects depended on the identity of the functions included. Limits to multifunctionality arose from negative correlations among functions and functions that were not correlated with biodiversity. Our findings underline that the management of ecosystems for the protection of biodiversity cannot be replaced by managing for particular ecosystem functions or services and emphasize the need for specific management to protect biodiversity. More plant species from the experimental pool of 60 species contributed to functioning when more functions were considered. An individual contribution to multifunctionality could be demonstrated for only a fraction of the species.
The performance of hybridization capture combined with next-generation sequencing (NGS) has seen limited investigation with samples from hot and arid regions until now. We applied hybridization capture and shotgun sequencing to recover DNA sequences from bone specimens of ancient-domestic dromedary (Camelus dromedarius) and its extinct ancestor, the wild dromedary from Jordan, Syria, Turkey and the Arabian Peninsula, respectively. Our results show that hybridization capture increased the percentage of mitochondrial DNA (mtDNA) recovery by an average 187-fold and in some cases yielded virtually complete mitochondrial (mt) genomes at multifold coverage in a single capture experiment. Furthermore, we tested the effect of hybridization temperature and time by using a touchdown approach on a limited number of samples. We observed no significant difference in the number of unique dromedary mtDNA reads retrieved with the standard capture compared to the touchdown method. In total, we obtained 14 partial mitochondrial genomes from ancient-domestic dromedaries with 17-95% length coverage and 1.27-47.1-fold read depths for the covered regions. Using whole-genome shotgun sequencing, we successfully recovered endogenous dromedary nuclear DNA (nuDNA) from domestic and wild dromedary specimens with 1-1.06-fold read depths for covered regions. Our results highlight that despite recent methodological advances, obtaining ancient DNA (aDNA) from specimens recovered from hot, arid environments is still problematic. Hybridization protocols require specific optimization, and samples at the limit of DNA preservation need multiple replications of DNA extraction and hybridization capture as has been shown previously for Middle Pleistocene specimens.
Background:
Physical growth of children and adolescents depends on the interaction of genetic and environmental factors e.g. diet and living conditions. Aim: We aim to discuss the influence of socioeconomic situation, using income inequality and GDP per capita as indicators, on body height, body weight and the variability of height and weight in infants and juveniles.
Material and methods:
We re-analyzed data from 439 growth studies on height and weight published during the last 35 years. We added year-and country-matched GDP per capita (in current US$) and the Gini coefficient for each study. The data were divided into two age groups: infants (age 2) and juveniles (age 7). We used Pearson correlation and principal component analysis to investigate the data.
Results:
Gini coefficient negatively correlated with body height and body weight in infants and juveniles. GDP per capita showed a positive correlation with height and weight in both age groups. In infants the standard deviation of height increases with increasing Gini coefficient. The opposite is true for juveniles. A correlation of weight variability and socioeconomic indicators is absent in infants. In juveniles the variability of weight increases with declining Gini coefficient and increasing logGDP per capita.
Discussion:
Poverty and income inequality are generally associated with poor growth in height and weight. The analysis of the within-population height and weight variations however, shows that the associations between wealth, income, and anthropometric parameters are very complex and cannot be explained by common wisdom. They point towards an independent regulation of height and weight.
Impact of normal weight obesity on fundamental motor skills in pre-school children aged 3 to 6 years
(2017)
Normal weight obesity is defined as having excessive body fat, but normal BMI. Even though previous research revealed that excessive body fat in children inhibited their physical activity and decreased motor performance, there has been only little evidence about motor performance of normal weight obese children. This study aims to establish whether normal weight obese pre-school children aged 3-6 years will have a significantly worse level of fundamental motor skills compared to normal weight non-obese counterparts. The research sample consisted of 152 pre-schoolers selected from a specific district of Prague, the Czech Republic. According to values from four skinfolds: triceps, subscapula, suprailiaca, calf, and BMI three categories of children aged 3-6 years were determined: A) normal weight obese n = 51; B) normal weight non-obese n = 52; C) overweight and obese n = 49. The Movement Assessment Battery for Children (MABC-2) was used for the assessment of fundamental motor skills. Normal weight obese children had significantly higher amount of adipose tissue p < 0.001 than normal weight non-obese children but the same average BMI. Moreover, normal weight obese children did not have significantly less amount of subcutaneous fat on triceps and calf compared to their overweight and obese peers. In majority of MABC-2 tests, normal weight obese pre-schoolers showed the poorest performance. Moreover, normal weight obese children had significantly worse total standard score = 38.82 compared to normal weight non-obese peers = 52.27; p < 0.05. In addition, normal weight obese children had a more than three times higher frequency OR = 3.69 CI95% (1.10; 12.35) of severe motor deficit performance <= 5th centile of the MABC-2 norm. These findings are strongly alarming since indices like BMI are not able to identify normal weight obese individual. We recommend verifying real portion of normal weight obese children as they are probably in higher risk of health and motor problems than overweight and obese population due to their low lean mass.
The transcriptional regulator MINIYO (IYO) is essential and rate-limiting for initiating cell differentiation in Arabidopsis thaliana. Moreover, IYO moves from the cytosol into the nucleus in cells at the meristem periphery, possibly triggering their differentiation. However, the genetic mechanisms controlling IYO nuclear accumulation were unknown, and the evidence that increased nuclear IYO levels trigger differentiation remained correlative. Searching for IYO interactors, we identified RPAP2 IYO Mate (RIMA), a homolog of yeast and human proteins linked to nuclear import of selective cargo. Knockdown of RIMA causes delayed onset of cell differentiation, phenocopying the effects of IYO knockdown at the transcriptomic and developmental levels. Moreover, differentiation is completely blocked when IYO and RIMA activities are simultaneously reduced and is synergistically accelerated when IYO and RIMA are concurrently overexpressed, confirming their functional interaction. Indeed, RIMA knockdown reduces the nuclear levels of IYO and prevents its prodifferentiation activity, supporting the conclusion that RIMA-dependent nuclear IYO accumulation triggers cell differentiation in Arabidopsis. Importantly, by analyzing the effect of the IYO/RIMA pathway on xylem pole pericycle cells, we provide compelling evidence reinforcing the view that the capacity for de novo organogenesis and regeneration from mature plant tissues can reside in stem cell reservoirs.
Core-specific sensorimotor exercises are proven to enhance neuromuscular activity of the trunk. However, the influence of high-intensity perturbations on training efficiency is unclear within this context. Sixteen participants (29 +/- 2 yrs; 175 +/- 8 cm; 69 +/- 13 kg) were prepared with a 12-lead bilateral trunk EMG. Warm-up on a dynamometer was followed by maximum voluntary isometric trunk (flex/ext) contraction (MVC). Next, participants performed four conditions for a one-legged stance with hip abduction on a stable surface (HA) repeated randomly on an unstable surface (HAP), on a stable surface with perturbation (HA + P), and on an unstable surface with perturbation (HAP + P). Afterwards, bird dog (BD) was performed under the same conditions (BD, BDP, BD + P, BDP + P). A foam pad under the foot (HA) or the knee (BD) was used as an unstable surface. Exercises were conducted on a moveable platform. Perturbations (ACC 50 m/sec(2);100 ms duration;10rep.) were randomly applied in the anterior-posterior direction. The root mean square (RMS) normalized to MVC (%) was calculated (whole movement cycle). Muscles were grouped into ventral right and left (VR;VL), and dorsal right and left (DR;DL). Ventral Dorsal and right-left ratios were calculated (two way repeated-measures ANOVA;alpha = 0,05). Amplitudes of all muscle groups in bird dog were higher compared to hip abduction (p <= 0.0001; Range: BD: 14 +/- 3% (BD;VR) to 53 +/- 4%; HA: 7 +/- 2% (HA;DR) to 16 +/- 4% (HA;DR)). EMG-RMS showed significant differences (p < 0.001) between conditions and muscle groups per exercise. Interaction effects were only significant for HA (p = 0.02). No significant differences were present in EMG ratios (p > 0.05). Additional high-intensity perturbations during core-specific sensorimotor exercises lead to increased neuromuscular activity and therefore higher exercise intensities. However, the beneficial effects on trunk function remain unclear. Nevertheless, BD is more suitable to address trunk muscles.
In mormyrid weakly electric fish, the electric organ discharge (EOD) is used for species recognition, orientation and prey localization. Produced in the muscle-derived adult electric organ, the EOD exhibits a wide diversity across species in both waveform and duration. While certain defining EOD characteristics can be linked to anatomical features of the electric organ, many factors underlying EOD differentiation are yet unknown. Here, we report the differential expression of 13 Kv1 voltage-gated potassium channel genes, two inwardly rectifying potassium channel genes, two previously studied sodium channel genes and an ATPase pump in two sympatric species of the genus Campylomormyrus in both the adult electric organ and skeletal muscle. Campylomormyrus compressirostris displays a basal EOD, largely unchanged during development, while C. tshokwe has an elongated, putatively derived discharge. We report an upregulation in all Kv1 genes in the electric organ of Campylomormyrus tshokwe when compared to both skeletal muscle and C. compressirostris electric organ. This pattern of upregulation in a species with a derived EOD form suggests that voltage-gated potassium channels are potentially involved in the diversification of the EOD signal among mormyrid weakly electric fish.
Polar nuclear migration is crucial during the development of diverse eukaryotes. In plants, root hair growth requires polar nuclear migration into the outgrowing hair. However, knowledge about the dynamics and the regulatory mechanisms underlying nuclear movements in root epidermal cells remains limited. Here, we show that both auxin and Rho-of-Plant (ROP) signaling modulate polar nuclear position at the inner epidermal plasma membrane domain oriented to the cortical cells during cell elongation as well as subsequent polar nuclear movement to the outer domain into the emerging hair bulge in Arabidopsis (Arabidopsis thaliana). Auxin signaling via the nuclear AUXIN RESPONSE FACTOR7 (ARF7)/ARF19 and INDOLE ACETIC ACID7 pathway ensures correct nuclear placement toward the inner membrane domain. Moreover, precise inner nuclear placement relies on SPIKE1 Rho-GEF, SUPERCENTIPEDE1 Rho-GDI, and ACTIN7 (ACT7) function and to a lesser extent on VTI11 vacuolar SNARE activity. Strikingly, the directionality and/or velocity of outer polar nuclear migration into the hair outgrowth along actin strands also are ACT7 dependent, auxin sensitive, and regulated by ROP signaling. Thus, our findings provide a founding framework revealing auxin and ROP signaling of inner polar nuclear position with some contribution by vacuolar morphology and of actin-dependent outer polar nuclear migration in root epidermal hair cells.
The heme-undecapeptide microperoxidase-11 (MP-11) was immobilized on mesoporous antimony-doped tin oxide (ATO) thin-film electrodes modified with the positively charged binding promotor polydiallyldimethylammonium chloride. Surface concentrations of MP-11 of 1.5 nmol cm(-2) were sufficiently high to enable spectroelectrochemical analyses. UV/Vis spectroscopy and resonance Raman spectroscopy revealed that immobilized MP-11 adopts a six-coordinated low-spin conformation, as in solution in the presence of a polycation. Cathodic reduction of hydrogen peroxide at potentials close to +500mV versus Ag/AgCl indicates that the reaction proceeds via a Compound I-type like intermediate, analogous to natural peroxidases, and confirms mesoporous ATO as a suitable host material for adsorbing the heme-peptide in its native state. A hydrogen peroxide sensor is proposed by using the bioelectrocatalytic properties of the MP-11-modified ATO.