Tilapia aquaculture, emerging diseases, and the roles of the skin microbiomes in health and disease

This is the finale version. Available on open access from Springer via the DOI in this recordAquaculture is playing an increasingly important role in global food security, especially for low-income and food-deficit countries. The majority of aquaculture production occurs in freshwater earthen ponds and tilapia has quickly become one of the most widely adopted culture species in these systems. Tilapia are now farmed in over 140 countries facilitated by their ease of production, adaptability to a wide range of environmental conditions, fast growth, and high nutritional value. Typically, tilapia have been considered a hardy, disease resilient species; however, the disease is increasing with subsequent threats to the industry as their production is intensified. In this review, we discuss tilapia production, with a focus on Bangladesh as one of the top producing countries, and highlight the problems associated with disease and treatment approaches for them, including the misuse of antimicrobials. We address a key missing component in understanding health and disease processes for sustainable production in aquaculture, specifically the role played by the microbiome. Here we examine the importance of the microbiome in supporting health, focused on the symbiotic microbial community of the fish skin mucosal surface, the abiotic and biotic factors that influence the microbiome, and the shifts that are associated with diseased states. We also identify conserved taxa of skin microbiomes that may be used as indicators of health status for tilapia offering new opportunities to mitigate and manage the disease and optimize environmental growing conditions and farming practices.University of ExeterWorldFishCefasBiotechnology and Biological Sciences Research Council (BBSRC)CGIAR Research Program on Fish Agri-Food Systems (FISH

Road Damage Detection Acquisition System based on Deep Neural Networks for Physical Asset Management

Research on damage detection of road surfaces has been an active area of re-search, but most studies have focused so far on the detection of the presence of damages. However, in real-world scenarios, road managers need to clearly understand the type of damage and its extent in order to take effective action in advance or to allocate the necessary resources. Moreover, currently there are few uniform and openly available road damage datasets, leading to a lack of a common benchmark for road damage detection. Such dataset could be used in a great variety of applications; herein, it is intended to serve as the acquisition component of a physical asset management tool which can aid governments agencies for planning purposes, or by infrastructure mainte-nance companies. In this paper, we make two contributions to address these issues. First, we present a large-scale road damage dataset, which includes a more balanced and representative set of damages. This dataset is composed of 18,034 road damage images captured with a smartphone, with 45,435 in-stances road surface damages. Second, we trained different types of object detection methods, both traditional (an LBP-cascaded classifier) and deep learning-based, specifically, MobileNet and RetinaNet, which are amenable for embedded and mobile and implementations with an acceptable perfor-mance for many applications. We compare the accuracy and inference time of all these models with others in the state of the art

An extragalactic supernebula confined by gravity

Little is known about the origins of the giant star clusters known as globular clusters. How can hundreds of thousands of stars form simultaneously in a volume only a few light years across the distance of the sun to its nearest neighbor? Radiation pressure and winds from luminous young stars should disperse the star-forming gas and disrupt the formation of the cluster. Globular clusters in our Galaxy cannot provide answers; they are billions of years old. Here we report the measurement of infrared hydrogen recombination lines from a young, forming super star cluster in the dwarf galaxy, NGC 5253. The lines arise in gas heated by a cluster of an estimated million stars, so young that it is still enshrouded in gas and dust, hidden from optical view. We verify that the cluster contains 4000-6000 massive, hot "O" stars. Our discovery that the gases within the cluster are bound by gravity may explain why these windy and luminous O stars have not yet blown away the gases to allow the cluster to emerge from its birth cocoon. Young clusters in "starbursting" galaxies in the local and distant universe may be similarly gravitationally confined and cloaked from view.Comment: Letter to Natur

Patients' Costs and Cost-Effectiveness of Tuberculosis Treatment in DOTS and Non-DOTS Facilities in Rio de Janeiro, Brazil

Costs of tuberculosis diagnosis and treatment may represent a significant burden for the poor and for the health system in resource-poor countries.The aim of this study was to analyze patients' costs of tuberculosis care and to estimate the incremental cost-effectiveness ratio (ICER) of the directly observed treatment (DOT) strategy per completed treatment in Rio de Janeiro, Brazil.We interviewed 218 adult patients with bacteriologically confirmed pulmonary tuberculosis. Information on direct (out-of-pocket expenses) and indirect (hours lost) costs, loss in income and costs with extra help were gathered through a questionnaire. Healthcare system additional costs due to supervision of pill-intake were calculated considering staff salaries. Effectiveness was measured by treatment completion rate. The ICER of DOT compared to self-administered therapy (SAT) was calculated.DOT increased costs during the treatment phase, while SAT increased costs in the pre-diagnostic phase, for both the patient and the health system. Treatment completion rates were 71% in SAT facilities and 79% in DOT facilities. Costs per completed treatment were US$194 for patients and U$ 189 for the health system in SAT facilities, compared to US$336 and US$ 726 in DOT facilities. The ICER was US$ 6,616 per completed DOT treatment compared to SAT.Costs incurred by TB patients are high in Rio de Janeiro, especially for those under DOT. The DOT strategy doubles patients' costs and increases by fourfold the health system costs per completed treatment. The additional costs for DOT may be one of the contributing factors to the completion rates below the targeted 85% recommended by WHO

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

Cost of Dry Eye Treatment in an Asian Clinic Setting

10.1371/journal.pone.0037711PLoS ONE76

Metabolic control and bone health in adolescents with type 1 diabetes

<p>Abstract</p> <p>Background</p> <p>Adults with type 1 diabetes (T1D) have decreased bone mineral density (BMD) and increased fracture risk, yet the etiologies remain elusive. Early detection of derangements in bone biomarkers during adolescence could lead to timely recognition. In adolescents with T1D, we evaluated the relationships between metabolic control, BMD, and bone anabolic and turnover markers.</p> <p>Methods</p> <p>Cross-sectional study of 57 adolescent subjects with T1D who had HbA1c consistently ≥ 9% (Poor Control, PC n = 27) or < 9% (Favorable Control, FC n = 30) for two years prior to enrollment. Subjects had T1DM for at least three years and were without diabetes complications, known celiac disease, or other chronic diseases.</p> <p>Results</p> <p>There were no differences between HbA1c groups in BMD, components of the IGF system, or 25-hydroxyvitamin D status. The prevalence of 25-hydroxyvitamin D abnormalities was similar to that seen in the general adolescent population. Few patients met the recommended dietary allowance (RDA) for vitamin D or calcium.</p> <p>Conclusions</p> <p>These data provide no evidence of association between degree of metabolic control and BMD in adolescents with T1D. Adolescents with T1D have a high prevalence of serum 25-hydroxyvitamin D abnormalities. Longitudinal studies are needed to evaluate the predictive value of vitamin D abnormalities on fracture risk.</p

Metabolic Disturbances Associated with Systemic Lupus Erythematosus

The metabolic disturbances that underlie systemic lupus erythematosus are currently unknown. A metabolomic study was executed, comparing the sera of 20 SLE patients against that of healthy controls, using LC/MS and GC/MS platforms. Validation of key differences was performed using an independent cohort of 38 SLE patients and orthogonal assays. SLE sera showed evidence of profoundly dampened glycolysis, Krebs cycle, fatty acid β oxidation and amino acid metabolism, alluding to reduced energy biogenesis from all sources. Whereas long-chain fatty acids, including the n3 and n6 essential fatty acids, were significantly reduced, medium chain fatty acids and serum free fatty acids were elevated. The SLE metabolome exhibited profound lipid peroxidation, reflective of oxidative damage. Deficiencies were noted in the cellular anti-oxidant, glutathione, and all methyl group donors, including cysteine, methionine, and choline, as well as phosphocholines. The best discriminators of SLE included elevated lipid peroxidation products, MDA, gamma-glutamyl peptides, GGT, leukotriene B4 and 5-HETE. Importantly, similar elevations were not observed in another chronic inflammatory autoimmune disease, rheumatoid arthritis. To sum, comprehensive profiling of the SLE metabolome reveals evidence of heightened oxidative stress, inflammation, reduced energy generation, altered lipid profiles and a pro-thrombotic state. Resetting the SLE metabolome, either by targeting selected molecules or by supplementing the diet with essential fatty acids, vitamins and methyl group donors offers novel opportunities for disease modulation in this disabling systemic autoimmune ailment

KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer

<p>Abstract</p> <p>Background</p> <p>KAI1 was initially identified as a metastasis-suppressor gene in prostate cancer. It is a member of the tetraspan transmembrane superfamily (TM4SF) of membrane glycoproteins. As part of a tetraspanin-enriched microdomain (TEM), KAI1 inhibits tumor metastasis by negative regulation of Src. However, the underlying regulatory mechanism has not yet been fully elucidated. CUB-domain-containing protein 1 (CDCP1), which was previously known as tetraspanin-interacting protein in TEM, promoted metastasis via enhancement of Src activity. To better understand how KAI1 is involved in the negative regulation of Src, we here examined the function of KAI1 in CDCP1-mediated Src kinase activation and the consequences of this process, focusing on HIF-1 α and VEGF expression.</p> <p>Methods</p> <p>We used the human prostate cancer cell line PC3 which was devoid of KAI1 expression. Vector-transfected cells (PC3-GFP clone #8) and KAI1-expressing PC3 clones (PC3-KAI1 clone #5 and #6) were picked after stable transfection with KAI1 cDNA and selection in 800 <it>μ</it>g/ml G418. Protein levels were assessed by immunoblotting and VEGF reporter gene activity was measured by assaying luciferase activitiy. We followed tumor growth <it>in vivo </it>and immunohistochemistry was performed for detection of HIF-1, CDCP1, and VHL protein level.</p> <p>Results</p> <p>We demonstrated that Hypoxia-inducible factor 1α (HIF-1α) and VEGF expression were significantly inhibited by restoration of KAI1 in PC3 cells. In response to KAI1 expression, CDCP1-enhanced Src activation was down-regulated and the level of von Hippel-Lindau (VHL) protein was significantly increased. In an <it>in vivo </it>xenograft model, KAI1 inhibited the expression of CDCP1 and HIF-1α.</p> <p>Conclusions</p> <p>These novel observations may indicate that KAI1 exerts profound metastasis-suppressor activity in the tumor malignancy process via inhibition of CDCP1-mediated Src activation, followed by VHL-induced HIF-1α degradation and, ultimately, decreased VEGF expression.</p