Choatecox2717

The painted urchin Lytechinus pictus is a sea urchin in the family Toxopneustidae and one of several sea urchin species that are routinely used as an experimental research organism. Recently, L. read more pictus has emerged as a tractable model system for establishing transgenic sea urchin lines due to its amenability to long term laboratory culture. We present the first published genome of L. pictus. This chromosomal-level assembly was generated using Illumina sequencing in conjunction with Oxford Nanopore Technologies long read sequencing and HiC chromatin conformation capture sequencing. The 998.9-Mb assembly exhibits high contiguity and has a scaffold length N50 of 46.0 Mb with 97% of the sequence assembled into 19 chromosomal-length scaffolds. These 19 scaffolds exhibit a high degree of synteny compared with the 19 chromosomes of a related species Lytechinus variegatus. Ab initio and transcript evidence gene modeling, combined with sequence homology, identified 28,631 gene models that capture 92% of BUSCO orthologs. This annotation strategy was validated by manual curation of gene models for the ABC transporter superfamily, which confirmed the completeness and accuracy of the annotations. Thus, this genome assembly, in conjunction with recent high contiguity assemblies of related species, positions L. pictus as an exceptional model system for comparative functional genomics and it will be a key resource for the developmental, toxicological, and ecological biology scientific communities.Anastrepha fraterculus (Wiedemann), Ceratitis capitata (Wiedemann), and Drosophila suzukii (Matsumura) are the main fruit pests in Brazil. Here, we evaluated the susceptibility of Brazilian populations of A. fraterculus, C. capitata, and D. suzukii to selected insecticides. In ingestion bioassays, adults from a laboratory susceptible population of each species were exposed to five different modes of action of insecticide. Then, field populations of each species were exposed to the diagnostic concentrations to evaluate possible changes in susceptibility. Our findings indicate that lambda-cyhalothrin, malathion, and spinosad had similar levels of toxicity against a susceptible laboratory population of A. fraterculus, with LC50 values of 6.34, 6.54, and 8.76 µg a.i./ml, respectively. Ceratitis capitata had similar susceptibilities to spinosad (1.30 µg a.i./ml), spinetoram (2.76 µg a.i./ml), and malathion (7.10 µg a.i./ml), but a lower susceptibility to lambda-cyhalothrin (76.55 µg a.i./ml). For D. suzukii, the LC50 values of deltamethrin (0.67 µg a.i./ml), malathion (3.30 µg a.i./mL), spinosad (4.16 µg a.i./ml), and spinetoram (4.75 µg a.i./ml) were lower than for abamectin (15.02 µg a.i./ml), acetamiprid (39.38 a.i./ml), and thiamethoxam (70.15 µg a.i./ml). The diagnostic concentrations, based on LC99 values of the insecticides, caused more than 99% mortality for most field populations of each species. For lambda-cyhalothrin the populations RS-1 (A. fraterculus) and SC (C. capitata) showed approximately 10% of live insects. These differences represent the natural variation in population susceptibility and not due to insecticide selection pressure. The diagnostic concentrations defined here should be used in future resistance monitoring programs in Brazil.

To explore Bayesian networks (BNs) in understanding the relationships between musculoskeletal symptoms and the development of PsA in people with psoriasis.

Incident cases of psoriasis were identified between 1998 and 2015 from the UK Clinical Research Practice Datalink. Musculoskeletal symptoms identified by medcodes were concatenated into primary groups, each made up of several sub-groups. Baseline demographics for gender, age, body mass index (BMI), psoriasis severity, alcohol use and smoking status were also extracted. Several BN structures were composed using a combination of expert knowledge and data-oriented modelling using 1) primary musculoskeletal symptom groups, 2) musculoskeletal symptom sub-groups and 3) demographic variables. Predictive ability of the networks using the receiver operating characteristic curve (AUC) was calculated.

Over one million musculoskeletal symptoms were extracted for the 90,189 incident cases of psoriasis identified, of which 1409 developed PsA. The BN analysis yielded direct relationships between gender, BMI, arthralgia, finger pain, fatigue, hand pain, hip pain, knee pain, swelling, back pain, myalgia and PsA. The best BN, achieved by using the more site-specific musculoskeletal symptom sub-groups, was 76% accurate in predicting the development of PsA in a test set and had an AUC of 0.73 (95% confidence interval (CI) 0.70-0.75).

The presented BN model may be a useful method to identify clusters of symptoms that predict the development of PsA with reasonable accuracy. Using a BN approach, we have shown that there are several symptoms which are predecessors of PsA, including fatigue, specific types of pain, and swelling.

The presented BN model may be a useful method to identify clusters of symptoms that predict the development of PsA with reasonable accuracy. link2 Using a BN approach, we have shown that there are several symptoms which are predecessors of PsA, including fatigue, specific types of pain, and swelling.

Taxane based conventional chemotherapy serves as the standard treatment regimen for triple-negative breast cancer (TNBC). However, the efficacy is plateaued due to toxicities, chemoresistance and metastasis. Hence, the development of new therapies that provide long-term cover is needed. Brusatol, a natural quassinoid, has been implicated to inhibit the migration and proliferation of metastatic cells in lung and liver carcinoma, but its efficacy in TNBC has not been explored.

The growth inhibitory activity on TNBC cells was measured using MTT assay and flow cytometry. Epithelial to mesenchymal transition (EMT) and apoptotic markers were quantified using western blotting. The caspases using Calorimetric assay.

Brusatol along with paclitaxel showed an enhanced growth inhibitory activity and a combined synergistic effect. In addition, brusatol was also observed to inhibit the invasion, migratory potential of TNBC cells. Mechanistically, brusatol and its combination were observed to decrease the matrix metalloproteinase (MMP) and a modest increase in the reactive oxygen species (ROS) production. Furthermore, brusatol treatment activated both intrinsic and extrinsic pathways with morphological changes of apoptosis in TNBC cells.

This is the first in vitro report demonstrating antineoplastic, anti-EMT and synergistic activity of brusatol and in combination with paclitaxel in TNBC cell. Further in-vivo studies are needed to substantiate the above findings.

This is the first in vitro report demonstrating antineoplastic, anti-EMT and synergistic activity of brusatol and in combination with paclitaxel in TNBC cell. Further in-vivo studies are needed to substantiate the above findings.Small heterodimer partner (SHP) is a crucial regulator of bile acid (BA) transport and synthesis; however, its intestine-specific role is not fully understood. Here, we report that male Intestine-specific Shp Knockout (IShpKO) mice exhibit higher intestinal BA but not hepatic or serum BA levels compared to the f/f Shp animals when challenged with an acute (5-day) 1% cholic acid (CA) diet. We also find that BA synthetic genes Cyp7A1 and Cyp8b1 are not repressed to the same extent in IShpKO compared to control mice post-CA challenge. link3 Loss of intestinal SHP did not alter Fxrα mRNA but increased Asbt (BA ileal uptake transporter) and Ostα (BA ileal efflux transporter) expression even under chow-fed conditions. Surprisingly, the acute CA diet in IShpKO did not elicit the expected induction of Fgf15 but was able to maintain the suppression of Asbt, and Ostα/β mRNA levels. At the protein level, ASBT was downregulated, while OSTα/β expression was induced and maintained regardless of diet. Examination of ileal histology in IShpKO mice challenged with acute CA diet revealed reduced villi length and goblet cell numbers. However, no difference in villi length, and the expression of BA regulator and transporter genes was seen between f/f Shp and IShpKO animals after chronic (14-day) CA diet suggesting a potential adaptive response. We found the upregulation of the Pparα-Ugt axis after 14-days of CA diet may reduce the BA burden and compensate for the ileal SHP function. Thus, our study reveals that ileal SHP expression contributes to both overall intestinal structure and BA homeostasis.

Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB.

We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends.

A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) -1.5%, P < 0.001] and a -8.170 (-16.064 to -0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC -3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC -0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae.

In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.

In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.The natural ends of linear chromosomes resemble those of accidental double-strand breaks (DSBs). DSBs induce a multifaceted cellular response that promotes the repair of lesions and slows down cell cycle progression. This response is not elicited at chromosome ends, which are organized in nucleoprotein structures called telomeres. Besides counteracting DSB response through specialized telomere-binding proteins, telomeres also prevent chromosome shortening. Despite of the different fate of telomeres and DSBs, many proteins involved in the DSB response also localize at telomeres and participate in telomere homeostasis. In particular, the DSB master regulators Tel1/ATM and Mec1/ATR contribute to telomere length maintenance and arrest cell cycle progression when chromosome ends shorten, thus promoting a tumor-suppressive process known as replicative senescence. During senescence, the actions of both these apical kinases and telomere-binding proteins allow checkpoint activation while bulk DNA repair activities at telomeres are still inhibited.