The effects of water flow and sedimentation on interactions between massive Porites and algal turf

Interactions between scleractinian corals and benthic algae can be an important process structuring reef communities, yet interaction dynamics are not fixed and may be influenced by abiotic factors such as sedimentation, a process often underlying reef degradation. However, rates of sedimentation and the effects of trapped sediments may be influenced by water flow. The first goal of this study was to quantify gradients in sedimentation and flow along fringing and back reefs of the north shore of Moorea, French Polynesia, and determine whether such gradients correlate with changes in the frequency and outcomes of massive Porites–algal turf interactions. On the back reef, the frequency of Porites–algal turf interactions and the competitive success of algal turfs increased significantly with decreasing flow. Sedimentation, however, was not a significant driver of the observed patterns. Along fringing reefs, in the absence of a flow gradient, it was the gradient in sedimentation that best explained spatial variation in Porites–algal turf interaction frequencies and the competitive success of algal turfs. The second goal was to quantify the separate and combined effects of flow and sedimentation on Porites–algal turf interactions in a laboratory setting. The combined effects of low flow and sedimentation significantly increased the area of Porites tissue damaged when in contact with algal turf, while high flow attenuated the negative effects of sedimentation. Together, these results implicate flow and sedimentation as important drivers of biological interactions between massive Porites and algal turf.     

Dietary l-glutamine supplementation modulates microbial community and activates innate immunity in the mouse intestine

This study was conducted to determine effects of dietary supplementation with 1 % l-glutamine for 14 days on the abundance of intestinal bacteria and the activation of intestinal innate immunity in mice. The measured variables included (1) the abundance of Bacteroidetes, Firmicutes, Lactobacillus, Streptococcus and Bifidobacterium in the lumen of the small intestine; (2) the expression of toll-like receptors (TLRs), pro-inflammatory cytokines, and antibacterial substances secreted by Paneth cells and goblet cells in the jejunum, ileum and colon; and (3) the activation of TLR4-nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), and phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt) signaling pathways in the jejunum and ileum. In the jejunum, glutamine supplementation decreased the abundance of Firmicutes, while increased mRNA levels for antibacterial substances in association with the activation of NF-κB and PI3K-Akt pathways. In the ileum, glutamine supplementation induced a shift in the Firmicutes:Bacteroidetes ratio in favor of Bacteroidetes, and enhanced mRNA levels for Tlr4, pro-inflammatory cytokines, and antibacterial substances participating in NF-κB and JNK signaling pathways. These results indicate that the effects of glutamine on the intestine vary with its segments and compartments. Collectively, dietary glutamine supplementation of mice beneficially alters intestinal bacterial community and activates the innate immunity in the small intestine through NF-κB, MAPK and PI3K-Akt signaling pathways.     

Deep-sea water inhibits metastatic potential in HT-29 human colorectal adenocarcinomas via MAPK/NF-κB signaling pathway

A previous investigation showed that deep-sea water (DSW) can affect the expression of genes that regulate metastasis, including cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), urokinase plasminogen activator (uPA) and uPA receptor (uPAR), in HT-29 human colorectal adenocarcinomas. In the present study, we investigated the effects of DSW on inducible nitric oxide synthase (iNOS) expression and cell migration and also explored the mechanism of DSW-induced anti-metastatic potential in HT-29 human colorectal adenocarcinomas. Cytokine-induced expression of iNOS, which is highly expressed in colon cancer and enhances cancer growth and metastasis, was decreased in a hardness-dependent manner by DSW. Also, the wound healing assay revealed that DSW inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration in a hardness-dependent manner. DSW also decreased the phosphorylation of various MAPKs, including p38, ERK and JNK, and suppressed the nuclear translocation of NF-κB but not c-Jun. The results suggest that DSW may inhibit cancer cell growth related to iNOS overexpression and PKC-mediated cell migration in HT-29 human colorectal adenocarcinomas and the antimetastatic potential of DSW may be regulated by prevention of NF-κB nuclear translocation via inhibition of p38, ERK and JNK phosphorylation. In conclusion, the present investigation demonstrates that DSW inhibits cancer growth and metastasis via down-regulation of iNOS expression and the MAPK/NF-κB signaling pathway.     

Basic amino acids and dimethylarginines targeted metabolomics discriminates primary hepatocarcinoma from hepatic colorectal metastases

Hepatocellular carcinoma (HCC) is a very aggressive neoplasia requiring early and accurate diagnosis to improve patient outcomes with timely treatment. The liver is also very frequently colonized by metastases, and the most frequent differential diagnosis is HCC against intrahepatic cholangiocarcinoma or metastatic adenocarcinoma. Metabolomics is a powerful tool for identification of altered biomarkers in cancer, and to evaluate the efficacy of drug treatments. Here we analyzed by HILIC-MS/MS methylated arginines, basic amino acids (Arg, Cit, Orn), and their ratios in the extracts of primary HCC tissues, liver metastases from colorectal carcinoma (MET), cirrhotic related hepatitis-C-virus (CIR), and non-cirrhotic normal liver (NT) adjacent tissues. We found high levels of Arg (p < 0.0001) and Arg/Orn (p < 0.01) in MET compared to other tissues. In MET, compared to NT and CIR, Arg concentration was fivefold higher, while in HCC it was twofold higher. ADMA increased twofold compared to NT and CIR, while in HCC it was 50 % higher. Arg/Cit and ADMA/SDMA ratios were significantly higher in MET compared to NT and CIR (p < 0.005). Arg/Orn, Arg/Cit, and ADMA/SDMA ratios increased progressively from NT, CIR, HCC, to MET tissues. Arg/Cit correlated significantly with Arg/Orn ratios (r = 0.77; p < 0.0001), and discriminates tumor from non-tumor samples. In addition, the discriminant lactate/glucose ratio we previously found by NMR, also correlated significantly with the Arg levels (r = 0.64; p < 0.0001), and discriminated MET from all other tissues. The results indicated that Arg in MET is higher than other tissue classes, suggesting that, together with the lactate/glucose ratio, it can be considered a further biomarker for HCC-metastases differentiation.     

Expression status of let-7a and miR-335 among breast tumors in patients with and without germ-line BRCA mutations

The genetic factors of cancer predisposition remain elusive in the majority of familial and/or early-onset cases of breast cancer (BC). This type of BC is promoted by germ-line mutations that inactivate BRCA1 or BRCA2. On the other hand, recent studies have indicated that alterations in the levels of miRNA expression are linked to this disease. Although BRCA1 and BRCA2 gene mutations have been reported to commonly lead to alterations in genes that encode cancer-related proteins, little is known regarding the putative impact of these mutations on noncoding miRNAs. In the present study, we aimed to determine whether miRNA dysregulation is involved in the pathogenesis of BRCA-mutated BC. An expression analysis of 14 human miRNAs previously shown to be related to BC diagnosis, prognosis, and drug resistance was conducted using tissues from 60 familial and/or early-onset patients whose peripheral blood samples had been screened for BRCA1 and BRCA2 mutations through sequence analysis. Let-7a and miR-335 expression levels were significantly downregulated in the tumors of patients with a BRCA mutation compared with those of patients without a BRCA mutation (P = 0.04 and P = 0.02, respectively). Our results defined the associations between the expression status of let-7a and miR-335 and BRCA mutations. The expression analysis of these miRNAs might be used as biomarkers of the BRCA mutation status of early-onset and/or familial BC.     

Increased Expression of Angiogenic Factors in Cultured Human Brain Arteriovenous Malformation Endothelial Cells

To compare the mRNA level of angiogenic factor vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2, and MMP-9 in cultured human brain arteriovenous malformation (AVM) endothelial cells (ECs) and normal brain endothelial cells (BECs). Tissue explants both from deformed vessels of AVM and normal microvessel were put into culture for endothelial cells. After the monolayer adherent ECs reached confluence, they were tested with endothelial specific marker CD34 and von Willebrand factor (vWF) by immunochemical assay. mRNA levels of VEGF-A, MMP-2, and MMP-9 in AVM endothelial cells (AVMECs) and BECs were measured by PCR. Immunostaining confirmed that more than 95 % of the cultured cells were CD34 (Fig. 1b) and/or vWF positive. Expression levels of VEGF-A and MMP-2 mRNAs were significantly higher in AVMECs than in BECs. The MMP-9 level was also increased in AVMECs, but the difference was not statistically significant. Vascular tissue explants adherent method is a better approach for isolation and culture of AVMECs. Cultured AVMECs expressed higher angiogenic factors (VEGF, MMP-2) than the controlled BECs, implicating angiogenesis plays an important role in the pathogenesis of AVM.     

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells

Cystic fibrosis transmembrane conductance regulator (CFTR) acts as a cAMP-dependent chloride channel, has been studied in various types of cells. CFTR is abundantly expressed in vascular smooth muscle cells and closely linked to vascular tone regulation. However, the functional significance of CFTR in basilar vascular smooth muscle cells (BASMCs) remains elusive. Accumulating evidence has shown the direct role of CFTR in cell apoptosis that contributes to several main pathological events in CF, such as inflammation, lung injury and pancreatic insufficiency. We therefore investigated the role of CFTR in BASMC apoptotic process induced by hydrogen peroxide (H₂O₂). We found that H₂O₂-induced cell apoptosis was parallel to a significant decrease in endogenous CFTR protein expression. Silencing CFTR with adenovirus-mediated CFTR specific siRNA further enhanced H₂O₂-induced BASMC injury, mitochondrial cytochrome c release into cytoplasm, cleaved caspase-3 and -9 protein expression and oxidized glutathione levels; while decreased cell viability, the Bcl-2/Bax ratio, mitochondrial membrane potential, total glutathione levels, activities of superoxide dismutase and catalase. The pharmacological activation of CFTR with forskolin produced the opposite effects. These results strongly suggest that CFTR may modulate oxidative stress-related BASMC apoptosis through the cAMP- and mitochondria-dependent pathway and regulating endogenous antioxidant defense system.     

Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts

Interleukin-13 (IL-13) is associated with the production of collagen in airway remodelling of asthma. Yet, the molecular mechanisms underlying IL-13 induction of collagen remain unclear; the aim of this study is to address this issue. IL-13 dose- and time-dependently-induced collagen I production in primary cultured airway fibroblasts; this was accompanied with the STAT6 phosphorylation, and pre-treatment of cells with JAK inhibitor suppressed IL-13-induced collagen I production. Further study indicated that IL-13 stimulated JAK/STAT6-dependent PDGF production and subsequent ERK1/2 MAPK activation in airway fibroblasts, and the presence of either PDGF receptor blocker or MEK inhibitor partially suppressed IL-13-induced collagen I production. Taken together, our study suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I production in airway fibroblasts.     

Inhibition of MMP-2 but not MMP-9 Influences Inner Ear Spiral Ganglion Neurons In Vitro

Matrix metalloproteinases (MMPs) play an important role in modeling of the extracellular matrix. There is increasing evidence that these proteases are important in neurite elongation and axonal guidance during development in the central nervous system and retina. Moreover, they are also expressed after acute injury and can be the key mediators of pathogenesis. However, the role of MMPs in the inner ear is largely unknown. Our group recently demonstrated that general inhibition of MMPs resulted in auditory hair cell loss in vitro. In the present study, we investigated the role of MMPs in inner ear spiral ganglion neuron (SGN) survival, neuritogenesis and neurite extension by blocking MMPs known to be involved in axonal guidance, neurite elongation, and apoptosis in other neuronal systems. Spiral ganglion (SG) explants from 5-day-old Wistar rats were treated with different concentrations of the general MMP inhibitor GM6001, a specific MMP-2 inhibitor, and a specific MMP-9 inhibitor, in vitro. The general inhibitor of MMPs and the specific inhibition of MMP-2 significantly reduced both the number of neurites that extended from SG explants, as well as the length of individual neurites. However, neither the general inhibitor of MMPs nor the specific inhibition of MMP-2 influenced SGN survival. Inhibition of MMP-9 had no influence on SGNs. The data suggest that MMPs, and more specifically MMP-2, influence the growth of developing afferent neurites in the mammalian inner ear in vivo.     

Molecular evidence to reconcile taxonomic instability in mahseer species (Pisces: Cyprinidae) of India

The mahseers are an important group of fishes endemic to Asia with most species considered threatened. Conservation plans to save declining wild populations are hindered by unstable taxonomy, and detailed systematic review could form a solid platform for future management and conservation. D-loop and cytochrome c oxidase I (COI) mtDNA sequences were examined in nine mahseer species of Tor, Neolissochilus, and Naziritor. Pseudogenes amplified in a portion of the species limited the utility of the D-loop region. ABGD analysis, NJ, ML, and MP methods and genetic distance (TrN?+?I?+?G) using COI data revealed concordant species delimiting patterns. The three genera were monophyletic, separated as distinct clades (TrN?+?I?+?G 0.064 to 0.106), and Naziritor was flagged as a separate genus, distinct from Puntius (TrN?+?I?+?G 0.196). Out of seven nominal species known for Tor cogeners from India, only five were recovered with mtDNA data (TrN?+?I?+?G 0.000 to 0.037) and two species could not be distinguished with the molecular data set employed. Tor mosal, synonymized as Tor putitora, was rediscovered as a distinct species (TrN?+?I?+?G 0.031) based on its type locality. Tor mussulah was confirmed as a separate species (TrN?+?I?+?G 0.019 to 0.026). Two valid species, Tor macrolepis and T. mosal mahanadicus, were not distinct from T. putitora (TrN?+?I?+?G 0.00). The high divergence with mtDNA data failed to validate T. mosal mahanadicus as a subspecies of T. mosal (TrN?+?I?+?G 0.031). Morphological outliers discovered within the distribution range of Tor tor (TrN?+?I?+?G 0.022 to 0.025) shared the same lineage with T. putitora (TrN?+?I?+?G 0.002 to 0.005), indicating a new extended distribution of the Himalayan mahseer T. putitora in the rivers of the Indian central plateau. The findings indicate the need for integrating molecular and morphological tools for taxonomic revision of the Tor and Naziritor genera, so that taxa are precisely defined for accurate in situ and ex situ conservation decisions.     

Gene expression profiling of endometrium versus bone marrow-derived mesenchymal stem cells: upregulation of cytokine genes

Postulated Stem/progenitor cells involved in endometrium regeneration are epithelial, mesenchymal, and endothelial. Bone marrow (BM) has been implicated in endometrial stem cells. We aimed at studying gene expression profiling of endometrial mesenchymal stem cells compared to BM MSCS to better understand their nature and functional phenotype. Endometrial tissues were obtained from premenopausal hysterectomies (n = 3), minced and enzymatically digested as well as Normal BM aspirates (n=3). Immunophenotyping, differentiation to mesoderm, and proliferation were studied. The expression profile of 84 genes relevant to mesenchymal stem cells was performed. Fold change calculations were determined with SA Biosciences data analysis software. VEGF, G-CSF, and GM-CSF in cultures supernatants of MSCs were assayed by Luminex immunoassay. Endo MSCs possess properties similar to BM MSCs. Cumulative population doubling was significantly higher in Endo MSCs compared to BM MSCs (p < 0.001). 52 core genes were shared between both generated MSCs including stemness, self-renewal, members of the Notch, TGFB, FGF, and WNT.16 downregulated genes (VCAM, IGF1)and 16 upregulated in Endo MSCs compared to BM (p < 0.05 → fourfolds). They included mostly cytokine and growth factor genes G-CSF, GM-CSF, VWF, IL1b, GDF15, and KDR. VEGF and G-CSF levels were higher in Endo MSCs supernatants (p < 0.0001). Cells sharing MSC and endothelial cell characteristics could be isolated from the human endometrium. Endo MSCs share a core genetic profile with BM MSCs including stemness. They show upregulation of genes involved in vasculogenesis, angiogenesis, cell adhesion, growth proliferation, migration, and differentiation of endothelial cells, all contributing to endometrial function.     

Prioritizing non-marine invertebrate taxa for Red Listing

The IUCN Red List of threatened species is biased towards vertebrate animals, a major limitation on its utility for overall biodiversity assessment. There is a need to increase the representation of invertebrates (currently 21 % of species assessed on the List; <1 % of all invertebrates). A prioritisation system of terrestrial and freshwater groups is presented here, categorising taxa by species richness, assessment practicality, value for human land use and bioindication, and potential to act as conservation flagships. 25 major taxonomic groupings were identified as priorities, including the Annelida, Arthropoda, Mollusca, and Onycophora. Of these, the high-level taxa that emerge as highest priorities are Odonata (dragonflies and damselflies), Araneae (spiders), Mantophasmatodea (heelwalkers), Plecoptera (stoneflies), non-marine Mollusca (Bivalvia and Gastropoda), Trichoptera (caddisflies), Coleoptera (beetles), Lepidoptera (moths and butterflies), Oligochaetes (earthworms), Orthoptera (grasshoppers and crickets), Decapoda (crayfish, crabs, shrimps) and Diptera (flies). Of these Red Listing is well advanced for Decapoda, freshwater Mollusca and Odonata. This leaves eight higher taxa with currently a minimum or patchy Red List assessment coverage. We recommend that Red List assessments in future focus on these groups, as well as completion of assessments for terrestrial Molluscs and Odonata. However, we also recommend realism, and as some of groups are very large, it will be necessary to focus on subsets such as certain functionally important or charismatic taxa or on a sampled subset which is representative of a larger taxon.     

The stimulatory effects of alpha1-adrenergic receptors on TGF-beta1, IGF-1 and hyaluronan production in human skin fibroblasts

Skin fibroblasts modulate tissue repair, wound healing and immunological responses. Adrenergic receptors (ARs) mediate important physiological functions, such as endocrine, metabolic and neuronal activity. In this study, the expression α1A-ARs in human skin fibroblasts is examined and verified. Regulatory effects of α1-agonist cirazoline on cell migration and the production of transforming growth factor β1 (TGF-β1), insulin-like growth factor 1 (IGF-1), hyaluronan (HA), fibronectin and procollagen type I carboxy-terminal peptide (PIP) by human skin fibroblasts are assessed and validated. α1A-AR mRNA and protein were found in human skin fibroblasts WS1. Exposure of cirazoline doubled skin fibroblast migration and the increase in cell migration was attenuated by α1-antagonist prazosin. TGF-β1 mRNA and production were enhanced after exposure to cirazoline and IGF-1 production was also increased after treatment with cirazoline. Exposure to cirazoline also enhanced HA and PIP production. The increases in TGF-β1, IGF-1, HA and PIP production were partially abolished in fibroblasts transfected with α1A-AR short interfering RNAs, indicating that α1A-ARs are involved in the cirazoline-induced increases in TGF-β1, IGF-1, HA and PIP production. Thus, α1A-ARs are stably expressed and stimulate cell migration and TGF-β1, IGF-1, HA and PIP production in human skin fibroblasts. Moreover, TGF-β1, IGF-1, HA and PIP production and the cell migration of human skin fibroblasts are possibly modulated by natural catecholamines produced by the endocrine system or sympathetic innervation, which could directly or indirectly participate in cytokine secretion, fibroblast migration and matrix production of wound healing in the skin.     

Age-related changes in the distribution of transient receptor potential vanilloid 4 channel (TRPV4) in the central nervous system of rats

Transient receptor potential vanilloid type 4 (TRPV4) channels are expressed in the central nervous system, but their role in regulating the aging process under physiological and pathological conditions is still largely unknown. To identify age-related changes in the TRPV4 channel that contribute to the central nervous system, we investigated the distribution of TRPV4 in the brain and spinal cord regions of adult and aged rats. The expression of TRPV4 in the brain and spinal cord of adult and aged Sprague–Dawley rats was compared using immunohistochemistry performed with antibodies recognizing TRPV4 on free floating sections and western blotting analysis. TRPV4 immunoreactivity was significantly increased in the cerebral cortex, hippocampal formation, thalamus, basal nuclei, cerebellum and spinal cord of aged rats compared with adult control rats. In the cerebral cortex, TRPV4 immunoreactivity was significantly increased in pyramidal cells of aged rats. In addition, TRPV4 immunoreactivity was increased in the spinal cord, hippocampal formation, thalamus, basal nuclei and cerebellum of aged rats. This first demonstration of age-related increases in TRPV4 expression in the brain and spinal cord may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases. The exact regulatory mechanism and its functional significance require further elucidation.     

Sons and daughters beyond your control: episodes in the prehistory of the attention deficit/hyperactivity syndrome

Hyperactive and inattentive children have been discussed in both the pedagogic and medical literature since the nineteenth century, and many controversies associated with attention deficit and hyperactivity disorder (ADHD) have been repeatedly analyzed in different contexts. The ‘prehistory’ of the ADHD concept—that is, up to the definition of ADHD in DSM-III and of the corresponding ‘hyperkinetic disorder’ in ICD-9—is outlined, with an emphasis on the literature not previously discussed in English language reviews of the subject.     

Tunable Extraordinary THz Transmission Using Liquid Metal-Based Devices

In this paper, we report novel designs of tunable THz plasmonic devices based on liquid metals. The designed devices will be able to dynamically control and change the spectrum responses of extraordinary THz wave transmissions. Different THz device configurations are investigated, and numerical simulations have been conducted to theoretically verify the performance of the proposed structures. Moreover, an equivalent circuit model has been developed to describe the operating principle of the proposed THz devices. Good agreement has been achieved between the theoretical models and the numerical results. These new THz devices are expected to be applied in various areas of sensing, communication, and imaging.     

Size class homogeneity of repeat lengths and evolutionary divergence of ribosomal RNA genes in fishes as studied by restriction fragment length analysis

Fish ribosomal RNA genes (rDNA) have been compared by restriction endonuclease digestion followed by Southern hybridization using rRNA or cloned rRNA genes as labelled probes. In several species belonging to the orders Cypriniformes and Perciformes, the simple restriction patterns revealed a high degree of size class homogeneity among the rDNA repeats and similar restriction map within a species. Different species have different restriction patterns and fragment lengths arising mostly out of different length of the nontranscribed spacer. Polymorphic restriction sites are present in some species. The species-specific differences in fragment lengths produced in rDNA by some restriction enzymes can thus be used to study interspecific fish hybrids.