Environmental niche modelling is an acclaimed method for estimating species' present or future distributions. However, in marine environments the assembly of representative data from reliable and unbiased occurrences is challenging. Here, we aimed to model the environmental niche and distribution of marine, parasitic nematodes from the Pseudoterranova decipiens complex using the software Maxent. The distribution of these potentially zoonotic species is of interest, because they infect the muscle tissue of host species targeted by fisheries. To achieve the best possible model, we used two different approaches. The land distance (LD) model was based on abiotic data, whereas the definitive host distance (DHD) model included species-specific biotic data. To assess whether DHD is a suitable descriptor for Pseudoterranova spp., the niches of the parasites and their respective definitive hosts were analysed using ecospat. The performance of LD and DHD was compared based on the variables' contribution to the model. The DHD-model clearly outperformed the LD-model. While the LD-model gave an estimate of the parasites' niches, it only showed the potential distribution. The DHD-model produced an estimate of the species' realised distribution and indicated that biotic variables can help to improve the modelling of data-poor, marine species.

Since the first reports on foam sclerotherapy, multiple studies have been conducted to determine the physical properties and behavior of foams, but relatively little is known about their biological effects on the endothelial cells lining the vessel wall. Moreover, a systematic comparison of the biological performance of foams produced with different methods has not been carried out yet. Herein, a 2D in vitro method was developed to compare efficacy of commercially available polidocanol injectable foam (PEM, Varithena) and physician-compounded foams (PCFs). Endothelial cell attachment upon treatment with foam was quantified as an indicator of therapeutic efficacy, and was correlated with foam physical characteristics and administration conditions. An ex vivo method was also developed to establish the disruption and permeabilisation of the endothelium caused by sclerosing agents. It relied on the quantitation of extravasated bovine serum albumin conjugated to Evans Blue, as an indicator of endothelial permeability. In our series of comparisons, PEM presented a greater overall efficacy compared to PCFs, across the different biological models, which was attributed to its drainage dynamics and gas formulation. This is consistent with earlier studies that indicated superior physical cohesiveness of PEM compared to PCFs.

How the stressosome, the epicenter of the stress response in bacteria, transmits stress signals from the environment has remained elusive. The stressosome consists of multiple copies of three proteins RsbR, RsbS and RsbT, a kinase that is important for its activation. Using cryo-electron microscopy, we determined the atomic organization of the Listeria monocytogenes stressosome at 3.38 Å resolution. RsbR and RsbS are organized in a 60-protomers truncated icosahedron. A key phosphorylation site on RsbR (T209) is partially hidden by an RsbR flexible loop, whose "open" or "closed" position could modulate stressosome activity. Interaction between three glutamic acids in the N-terminal domain of RsbR and the membrane-bound mini-protein Prli42 is essential for Listeria survival to stress. Together, our data provide the atomic model of the stressosome core and highlight a loop important for stressosome activation, paving the way towards elucidating the mechanism of signal transduction by the stressosome in bacteria.

Development of bio-microactuators combining microdevices and cellular mechanical functions has been an active research field owing to their desirable properties including high mechanical integrity and biocompatibility. Although various types of devices were reported, the use of as-is natural muscle tissue should be more effective. An earthworm muscle-driven valve has been created. Long-time (more than 2 min) and repeatable displacement was observed by chemical (acetylcholine) stimulation. The generated force of the muscle (1 cm × 3 cm) was 1.57 mN on average for 2 min by the acetylcholine solution (100 mM) stimulation. We demonstrated an on-chip valve that stopped the constant pressure flow by the muscle contraction. For electrical control, short pulse stimulation was used for the continuous and repeatable muscle contraction. The response time was 3 s, and the pressure resistance was 3.0 kPa. Chemical stimulation was then used for continuous muscle contraction. The response time was 42 s, and the pressure resistance was 1.5 kPa. The ON (closed) state was kept for at least 2 min. An on-chip valve was demonstrated that stopped the constant pressure flow by the muscle contraction. This is the first demonstration of the muscle-based valve that is 100% chemically actuated and controlled.

Accumulation of amino acid (AA) insertions/substitutions are observed in the Gag-protein of HIV-1 variants resistant to HIV-1 protease inhibitors. Here, we found that HIV-1 carrying AA insertions in capsid protein (CA) undergoes aberrant CA degradation. When we generated recombinant HIV-1s (rHIV-1s) containing 19-AAs in Gag, such insertions caused significant CA degradation, which initiated in CA's C-terminal. Such rHIV-1s had remarkable morphological abnormality, decreased infectivity, and no replicative ability, which correlated with levels of CA degradation. The CA degradation observed was energy-independent and had no association with cellular/viral proteolytic mechanisms, suggesting that the CA degradation occurs due to conformational/structural incompatibility caused by the 19-AA insertions. The incorporation of degradation-prone CA into the wild-type CA resulted in significant disruption of replication competence in "chimeric" virions. The data should allow better understanding of the dynamics and mechanisms of CA decomposition/degradation and retroviral uncoating, which may lead to new approach for antiretroviral modalities.

Biological target (commonly genes or proteins) identification is still largely a manual process, where experts manually try to collect and combine information from hundreds of data sources, ranging from scientific publications to omics databases. Targeting the wrong gene or protein will lead to failure of the drug development process, as well as incur delays and costs. To improve this process, different software platforms are being developed. These platforms rely strongly on efficacy estimates based on target-disease association scores created by computational methods for drug target prioritization. Here novel computational methods are presented to more accurately evaluate the efficacy and safety of potential drug targets. The proposed efficacy scores utilize existing gene expression data and tissue/disease specific networks to improve the inference of target-disease associations. Conversely, safety scores enable the identification of genes that are essential, potentially susceptible to adverse effects or carcinogenic. Benchmark results demonstrate that our transcriptome-based methods for drug target prioritization can increase the true positive rate of target-disease associations. Additionally, the proposed safety evaluation system enables accurate predictions of targets of withdrawn drugs and targets of drug trials prematurely discontinued.

Autophagy is a self-degradation system wherein cellular materials are recycled. Although autophagy has been extensively studied in yeast and mammalian systems, integrated stress responses in microalgae remain poorly understood. Accordingly, we carried out a comparative study on the oxidative stress responses of Chlamydomonas reinhardtii wild-type and a starchless (sta6) mutant previously shown to accumulate high lipid content under adverse conditions. To our surprise, the sta6 mutant exhibited significantly higher levels of lipid peroxidation in the same growth conditions compared to controls. The sta6 mutant was more sensitive to oxidative stress induced by H2O2, whereas the wild-type was relatively more resistant. In addition, significantly up-regulated autophagy-related factors including ATG1, ATG101, and ATG8 were maintained in the sta6 mutant regardless of nitrogen availability. Also, the sta6 mutant exhibited relatively higher ATG8 protein level compared to wild-type under non-stress condition, and quickly reached a saturation point of autophagy when H2O2 was applied. Our results indicate that, in addition to the impact of carbon allocation, the increased lipid phenotype of the sta6 mutant may result from alterations in the cellular oxidative state, which in turn activates autophagy to clean up oxidatively damaged components and fuel lipid production.

The gas-detecting ability of nanostructured ZnO has led to significant attention being paid to the development of a unique and effective approach to its synthesis. However, its poor sensitivity, cross-sensitivity to humidity, long response/recovery times and poor selectivity hinder its practical use in environmental and health monitoring. In this context, the addition of noble metals, as dopants or catalysts to modify the ZnO surface has been examined to enhance its sensing performance. Herein, we report preparation of Pd-loaded ZnO nanoparticles via a chemical precipitation approach. Various Pd loadings were employed to produce surface-modified ZnO nanostructure sensors, and their resulting NH3 sensing capabilities both in dry and humid environments were investigated. Through a comparative gas sensing study between the pure and Pd-loaded ZnO sensors upon exposure to NH3 at an optimal operating temperature of 350 °C, the Pd-loaded ZnO sensors were found to exhibit enhanced sensor responses and fast response/recovery times. The influence of Pd loading and its successful incorporation into ZnO nanostructure was examined by X-ray diffraction, high resolution-transmission electron microscopy, and X-ray photoelectron spectroscopy. XPS studies demonstrated that in all samples, Pd existed in two chemical states, namely Pd° and Pd2+. The possible sensing mechanism related to NH3 gas is also discussed in detail.

This study investigated the repair effects of three Astragalus polysaccharides (APSs) with different molecular weights (Mws) on injured human renal proximal tubular epithelial (HK-2) cells to reveal the effect of Mw of polysaccharide on cell repair. A damage model was established by injuring HK-2 cells with 2.6 mM oxalate, and APS0, APS1, and APS2 with Mw of 11.03, 4.72, and 2.61 KDa were used to repair the damaged cells. After repair by APSs, the morphology of damaged HK-2 cells gradually returned to normal, the destruction of intercellular junctions recovered, intracellular reactive oxygen species production amount decreased, and their mitochondrial membrane potential increased. In addition, the cell cycle progression gradually normalized, lysosome integrity increased, and cell apoptotic rates obviously declined in the repaired cells. All three APSs could promote the expression of Keap1, Nrf2, SOD1, and CAT. In addition, the expression levels of inflammation markers containing MCP-1 and IL-6 decreased after APS repair. We deduced that APSs exert their repair function by activating the Nrf2-Keap1 signaling pathway and inhibiting inflammation. Among the APSs, APS1 with a moderate Mw provided the strongest repair effect. APSs may have a preventive effect on kidney stones.

Surfactants during routine washing have a tremendous effect on lipid loss from hair. This study aims to understand the loss of lipids from hair upon contact with surfactants and develop a way to prevent the lipid loss. The change in lipid levels depends on the relative hydrophobicity of the lipid. We herein propose that the change in lipid levels can be protected by two modifications. In the case of fatty acids and cholesterol (group A), the concentration difference between virgin hair versus surface modified hair with highly charged polymer was 22 to 32% higher after washing with surfactants while the loss of squalene and wax esters (group B) in response to surfactants still occurred even after the surface modification. In the hair treated by internal modification with the carbodiimide reaction, 52.0 to 81.3% more lipids in group B were prevented than in the untreated hair. Finally, different types of lipids were successfully protected by surface and internal modifications from the surfactant treatment. This study will be the basis for understanding the mechanisms by which surfactants damage the lipid barrier of tissues including hair and for establishing strategies to defend the barrier.

Calcium/calmodulin-dependent protein kinase type II delta (CaMKIIδ), the predominant CaMKII isoform expressed in the heart, has been implicated in the progression of myocardial infarction- and pressure overload-induced pathological remodeling. However, the role of CaMKIIδ in volume overload (VO) has not been explored. We have previously reported an activation of CaMKII during transition to HF in long-term VO. Here, we address whether CaMKIIδ is critically involved in the mortality, myocardial remodeling, and heart failure (HF) progression in response to VO. CaMKIIδ knockout (δ-KO) and wild-type (WT) littermates were exposed to aortocaval shunt-induced VO, and the progression of adverse myocardial remodeling was assessed by serial echocardiography, histological and molecular analyses. The mortality rates during 10 weeks of VO were similar in δ-KO and WT mice. Both genotypes displayed comparable eccentric myocardial hypertrophy, altered left ventricle geometry, perturbed systolic and diastolic functions after shunt. Additionally, cardiomyocytes hypertrophy, augmented myocyte apoptosis, and up-regulation of hypertrophic genes were also not significantly different in δ-KO versus WT hearts after shunt. Therefore, CaMKIIδ signaling seems to be dispensable for the progression of VO-induced maladaptive cardiac remodeling. Accordingly, we hypothesize that CaMKIIδ-inhibition as a therapeutic approach might not be helpful in the context of VO-triggered HF.

The zoonotic Plasmodium knowlesi parasite is the most common cause of human malaria in Malaysia. Genetic analysis has shown that the parasites are divided into three subpopulations according to their geographic origin (Peninsular or Borneo) and, in Borneo, their macaque host (Macaca fascicularis or M. nemestrina). Whilst evidence suggests that genetic exchange events have occurred between the two Borneo subpopulations, the picture is unclear in less studied Peninsular strains. One difficulty is that P. knowlesi infected individuals tend to present with low parasitaemia leading to samples with insufficient DNA for whole genome sequencing. Here, using a parasite selective whole genome amplification approach on unprocessed blood samples, we were able to analyse recent genomes sourced from both Peninsular Malaysia and Borneo. The analysis provides evidence that recombination events are present in the Peninsular Malaysia parasite subpopulation, which have acquired fragments of the M. nemestrina associated subpopulation genotype, including the DBPβ and NBPXa erythrocyte invasion genes. The NBPXb invasion gene has also been exchanged within the macaque host-associated subpopulations of Malaysian Borneo. Our work provides strong evidence that exchange events are far more ubiquitous than expected and should be taken into consideration when studying the highly complex P. knowlesi population structure.

Three different types of feedstocks and their biochars were used to remove Cr(III), Cd(II), Cu(II) and Pb(II) ions from a mixture of multiple heavy metals. The effect of the initial concentration of heavy metals in solution has been analysed, and kinetics modelling and a comparison of the adsorption capacity of such materials have been performed to elucidate the possible adsorption mechanisms. The results show that the adsorption capacity is dependent on the type of feedstock and on the pyrolysis conditions. The adsorption capacity of the biomass types is ranked as follows: FO (from sewage sludge)>> LO > ZO (both from agriculture biomass waste)>> CO (from wood biomass waste). Biochars, which are the product of the pyrolysis of feedstocks, clearly improve the adsorption efficiency in the case of those derived from wood and agricultural biomasses. Complexation and cation exchange have been found to be the two main adsorption mechanisms in systems containing multiple heavy metals, with cation exchange being the most significant. The pore structure of biomass/biochar cannot be neglected when investigating the adsorption mechanism of each material. All the disposal biomasses presented here are good alternatives for heavy metal removal from wastewaters.

Citrus fruit ripening is a complex process involving biochemical, physiological and molecular events that differ between the flesh and the peel of the fruit. We characterized sweet orange peel maturation by means of a comparative transcriptomic analysis between Navelate orange (Citrus sinensis L. Osbeck) and its mutant fruit Pinalate, which presents a severe blockage at early steps of the carotenoid biosynthetic pathway and consequently reduced ABA levels. Peel ripening involved the decrease of the photosynthetic activity and the transmembrane transport processes, as well as the buildup of starch and cuticular waxes and the cell wall modification. In addition, a number of biotic and abiotic stress responses, including the defense response, and the response to blue light, water deprivation and abscisic acid stimulus were modulated in a ripening-stage specific manner. The regulation of energy-related processes and secondary metabolism pathways was attenuated in Pinalate, while the molecular mechanisms underlying stress responses displayed dependency on ABA levels. These results indicate that ABA is a key signal inducing stress responses along orange peel ripening, which might determine the fruit postharvest performance.

Gut microbiota are important for various aspects of host physiology, and its composition is generally influenced by both intrinsic and extrinsic contexts of the host. Social bee gut microbiota composition is simple and highly stable hypothesized to be due to their unique food habit and social interactions. Here, we focused on hornets, the largest of the eusocial wasps - Vespa mandarinia and V. simillima. Unlike the well-studied honey bees, adult hornets are generally herbivorous but also hunt insects for broods, a unique behavior which could influence their gut microbiota. Analysis of the gut microbiome using 16S rRNA gene sequencing revealed that the two species have simple gut microbiota, composed of seven or eight consistently maintained 'core' operational taxonomic units (OTUs). While the two Vespa species shared some OTUs, the structures of their gut communities differed. Phylogenetic analysis indicated association of core OTUs with host diet. Intriguingly, prey honey bee gut microbes were detected in the V. simillima gut (and to a lesser extent in V. mandarinia), suggesting migration of microorganisms from the prey gut. This is the first report uncovering gut microbiome in hornets, giving additional insight into how food habit affects gut microbiota of social insects.

Caveolin-1 (Cav1), the coat protein for caveolae, also forms non-caveolar Cav1 scaffolds. Single molecule Cav1 super-resolution microscopy analysis previously identified caveolae and three distinct scaffold domains: smaller S1A and S2B scaffolds and larger hemispherical S2 scaffolds. Application here of network modularity analysis of SMLM data for endogenous Cav1 labeling in HeLa cells shows that small scaffolds combine to form larger scaffolds and caveolae. We find modules within Cav1 blobs by maximizing the intra-connectivity between Cav1 molecules within a module and minimizing the inter-connectivity between Cav1 molecules across modules, which is achieved via spectral decomposition of the localizations adjacency matrix. Features of modules are then matched with intact blobs to find the similarity between the module-blob pairs of group centers. Our results show that smaller S1A and S1B scaffolds are made up of small polygons, that S1B scaffolds correspond to S1A scaffold dimers and that caveolae and hemispherical S2 scaffolds are complex, modular structures formed from S1B and S1A scaffolds, respectively. Polyhedral interactions of Cav1 oligomers, therefore, leads progressively to the formation of larger and more complex scaffold domains and the biogenesis of caveolae.

Tissue amino acid profiles depend on the cell types and extracellular components that constitute the tissue, and their functions and activities. We aimed to characterize the tissue amino acid profiles in several types of pancreatic tumors and lesions. We examined tissue amino acid profiles in 311 patients with pancreatic tumors or lesions. We used newly developed LC-MS/MS methods to obtain the profiles, which were compared with clinicopathological data. Each tumor or lesion presented a characteristic tissue amino acid profile. Certain amino acids were markedly altered during the multistep pancreatic carcinogenesis and pancreatic ductal adenocarcinoma (PDAC) progression. A tissue amino acid index (TAAI) was developed based on the amino acids that were notably changed during both carcinogenesis and cancer progression. Univariate and multivariate survival analyses revealed that PDAC patients with a high TAAI exhibited a significantly shorter survival rate, and these findings were validated using a second cohort. We suggest that tissue amino acid profiles are characteristic for normal tissue type, tumor histological type, and pathological lesion, and are representative of the cancer grade or progression stage in multistep carcinogenesis and of malignant characteristics. The TAAI could serve as an independent prognosticator for patients with PDAC.

Neuroblastoma is the most common extra-cranial pediatric solid tumor, responsible for 13-15% of pediatric cancer death. Its intrinsic heterogeneity makes it difficult to target for successful therapy. The adaptor protein p140Cap/SRCIN1 negatively regulates tumor cell features and limits breast cancer progression. This study wish to assess if p140Cap is a key biological determinant of neuroblastoma outcome. RNAseq profiles of a large cohort of neuroblastoma patients show that SRCIN1 mRNA levels are an independent risk factor inversely correlated to disease aggressiveness. In high-risk patients, CGH+SNP microarray analysis of primary neuroblastoma identifies SRCIN1 as frequently altered by hemizygous deletion, copy-neutral loss of heterozygosity, or disruption. Functional experiments show that p140Cap negatively regulates Src and STAT3 signaling, affects anchorage-independent growth and migration, in vivo tumor growth and spontaneous lung metastasis formation. p140Cap also increases sensitivity of neuroblastoma cells to doxorubicin and etoposide treatment, as well as to a combined treatment with chemotherapy drugs and Src inhibitors. Our functional findings point to a causal role of p140Cap in curbing the aggressiveness of neuroblastoma, due to its ability to impinge on specific molecular pathways, and to sensitize cells to therapeutic treatment. This study provides the first evidence that the SRCIN1/p140Cap adaptor protein is a key player in neuroblastoma as a new independent prognostic marker for patient outcome and treatment. Altogether, these data highlight the potential clinical impact of SRCIN1/p140Cap expression in neuroblastoma tumors, in terms of reducing cytotoxic effects of chemotherapy, one of the main issues for pediatric tumor treatment.

Nuclear degradation is a major event during programmed cell death (PCD). The breakdown of nuclear components has been well characterized during apoptosis, one form of PCD. Many nonapoptotic forms of PCD have been identified, but our understanding of nuclear degradation during those events is limited. Here, we take advantage of Drosophila oogenesis to investigate nuclear degeneration during stress-induced apoptotic and developmental nonapoptotic cell death in the same cell type in vivo. We find that nuclear Lamin, a caspase substrate, dissociates from the nucleus as an early event during apoptosis, but remains associated with nuclei during nonapoptotic cell death. Lamin reveals a series of changes in nuclear architecture during nonapoptotic death, including nuclear crenellations and involutions. Stretch follicle cells contribute to these architecture changes, and phagocytic and lysosome-associated machinery in stretch follicle cells promote Lamin degradation. More specifically, we find that the lysosomal cathepsin CP1 facilitates Lamin degradation.

The cytoskeletal interacting protein Septin 9 (SEPT9), a member of the septin gene family, has been proposed to have oncogenic functions. It is a known hot spot of retroviral tagging insertion and a fusion partner of both de novo and therapy-induced mixed lineage leukemia (MLL). Of all septins, SEPT9 holds the strongest link to cancer, especially breast cancer. Murine models of breast cancer frequently exhibit SEPT9 amplification in the form of double minute chromosomes, and about 20% of human breast cancer display genomic amplification and protein over expression at the SEPT9 locus. Yet, a clear mechanism by which SEPT9 elicits tumor-promoting functions is lacking. To obtain unbiased insights on molecular signatures of SEPT9 upregulation in breast tumors, we overexpressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supports a role of SEPT9 in invasion. Functional studies reveal that SEPT9 upregulation is sufficient to increase degradation of the extracellular matrix, while SEPT9 downregulation inhibits this process. The degradation pattern is peripheral and associated with focal adhesions (FAs), where it is coupled with increased expression of matrix metalloproteinases (MMPs). SEPT9 overexpression induces MMP upregulation in human tumors and in culture models and promotes MMP3 secretion to the media at FAs. Downregulation of SEPT9 or chemical inhibition of septin filament assembly impairs recruitment of MMP3 to FAs. Our results indicate that SEPT9 promotes upregulation and both trafficking and secretion of MMPs near FAs, thus enhancing migration and invasion of breast cancer cells.