Benzimidazole and aminoalcohol derivatives show in vitro anthelmintic activity against Trichuris muris and Heligmosomoides polygyrus

[EN]Background: Infections by gastrointestinal nematodes cause significant economic losses and disease in both humans and animals worldwide. The discovery of novel anthelmintic drugs is crucial for maintaining control of these parasitic infections. Methods: For this purpose, the aim of the present study was to evaluate the potential anthelmintic activity of three series of compounds against the gastrointestinal nematodes Trichuris muris and Heligmosomoides polygyrus in vitro. The compounds tested were derivatives of benzimidazole, lipidic aminoalcohols and diamines. A primary screening was performed to select those compounds with an ability to inhibit T. muris L1 motility by > 90% at a single concentration of 100 µM; then, their respective IC50 values were calculated. Those compounds with IC50 < 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10 µM. Results: Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC50 values < 10 µM on T. muris L1 assay, showing IC50 values of 3.30, 8.89 and 4.17 µM, respectively. However, only two of them displayed activity against the adult stage of the parasites: BZ12 killed 81% of adults of T. muris (IC50 of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC50 of 5.3 µM) but only 17% of T. muris. Conclusions: BZ6 and BZ12 could be considered as a starting point for the synthesis of further structurally related compounds.SIFinancial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and Junta de Castilla y León co-financed by FEDER, UE [LE020P17]. EVG was funded by FPU17/00627; VCGA and MAB are recipients of Junta de Castilla y Leon (JCyL) (LE082-18, LE051-18, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y competitividad; MMV, RYC-2015-18368

Cáncer de piel en pacientes entre 40 y 70 años de edad en el Hospital Universidad del Norte, en la ciudad de Barranquilla durante el periodo 2014-2018

El cáncer de piel es la proliferación celular maligna desarrollada en cualquiera de las capas de la piel; dermis o epidermis. Actualmente es un problema de índole pública debido al aumento de su tasa de incidencia en los últimos 50 años. En Colombia se incrementa dicha incidencia 2 veces a partir de los 40 años presentándose un pico de incidencia después de los 69 años de edad Este estudio de investigación buscó describir los factores sociodemográficos y fototipo de piel asociados al cáncer de piel en pacientes entre 40 y 70 años de edad, que consultan al Hospital Universidad del Norte, en la ciudad de Barranquilla en el periodo 2014 -2018. Así mismo se elaboró una caracterización dentro de la población estudiada que buscó determinar los fototipos de piel más prevalentes dentro de la misma, comparando las distintas variables sociodemográficas y la explosión a los rayos UV. La población de estudio se logró obtener por medio una base de datos diligénciala y obtenida por la institución prestadora de servicios Hospital Universidad Del Norte. La obtención de los datos del estudio se realizó por medio de una encuesta realizada por contacto telefónico y posterior recopilación en base de datos. Como resultado se obtuvieron la caracterización demográfica de la población y se encontró al sexo femenino como el mas prevalente y un promedio de edad en pacientes entrevistados fue de 56 años. Así mismo se observó que el fototipo de piel más frecuente tanto a nivel de la población como fotipo con la patología estudiada es el fototipo de piel 3. En la misma línea se encontró que el tipo de cáncer más frecuente fue el basocelular y que este se asocia tanto a la exposición constante como intermitente.PregradoMedic

Inspection of the grapevine BURP superfamily highlights an expansion of RD22 genes with distinctive expression features in berry development and ABA-mediated stress responses

The RESPONSIVE TO DEHYDRATION 22 (RD22) gene is a molecular link between abscisic acid (ABA) signalling and abiotic stress responses. Its expression has been used as a reliable ABA early response marker. In Arabidopsis, the single copy RD22 gene possesses a BURP domain also located at the C-terminus of USP embryonic proteins and the beta subunit of polygalacturonases. In grapevine, a RD22 gene has been identified but putative paralogs are also found in the grape genome, possibly forming a large RD22 family in this species. In this work, we searched for annotations containing BURP domains in the Vitis vinifera genome. Nineteen proteins were defined by a comparative analysis between the two genome predictions and RNA-Seq data. These sequences were compared to other plant BURPs identified in previous genome surveys allowing us to reconceive group classifications based on phylogenetic relationships and protein motif occurrence. We observed a lineage-specific evolution of the RD22 family, with the biggest expansion in grapevine and poplar. In contrast, rice, sorghum and maize presented highly expanded monocot-specific groups. The Vitis RD22 group may have expanded from segmental duplications as most of its members are confined to a region in chromosome 4. The inspection of transcriptomic data revealed variable expression of BURP genes in vegetative and reproductive organs. Many genes were induced in specific tissues or by abiotic and biotic stresses. Three RD22 genes were further studied showing that they responded oppositely to ABA and to stress conditions. Our results show that the inclusion of RNA-Seq data is essential while describing gene families and improving gene annotations. Robust phylogenetic analyses including all BURP members from other sequenced species helped us redefine previous relationships that were erroneously established. This work provides additional evidence for RD22 genes serving as marker genes for different organs or stresses in grapevine

Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus

[EN] The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminantsSIFinancial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and MICINN/AEI (PID2020- 119035RB-100). EVG was funded by FPU17/00627, FPU17/05346; VCGA, MAB, MCP and LGP are recipients of Junta de Castilla y León (JCyL) (LE082-18, LE051-18, LE135-19, LE096-20, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y competitividad; MMV, RYC-2015-18368

Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2 allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11

For 21 putative BRCA1 and BRCA2 splice site variants, the concordance between mRNA analysis and predictions by in silico programs was evaluated. Aberrant splicing was confirmed for 12 alterations. In silico prediction tools were helpful to determine for which variants cDNA analysis is warranted, however, predictions for variants in the Cartegni consensus region but outside the canonical sites, were less reliable. Learning algorithms like Adaboost and Random Forest outperformed the classical tools. Further validations are warranted prior to implementation of these novel tools in clinical settings. Additionally, we report here for the first time activated cryptic donor sites in the large exon 11 of BRCA2 by evaluating the effect at the cDNA level of a novel tandem duplication (5 breakpoint in intron 4; 3 breakpoint in exon 11) and of a variant disrupting the splice donor site of exon 11 (c.6841+1G>C). Additional sites were predicted, but not activated. These sites warrant further research to increase our knowledge on cis and trans acting factors involved in the conservation of correct transcription of this large exon. This may contribute to adequate design of ASOs (antisense oligonucleotides), an emerging therapy to render cancer cells sensitive to PARP inhibitor and platinum therapies

First Look at z > 1 Bars in the Rest-Frame Near-Infrared with JWST Early CEERS Imaging

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of {\it{JWST}} CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at $z>1$ based on rest-frame NIR F444W images of high resolution (~1.3 kpc at z ~ 1-3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at $z>1$ with spectroscopic redshifts, including the two highest redshift bars at ~2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at $z$ ~ 1.1-2.3 presented in our study have projected semi-major axes of ~2.9-4.3 kpc and projected ellipticities of ~0.41-0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ~ $1 \times 10^{10}$ to $2 \times 10^{11}$ $M_{\odot}$, star formation rates of ~ 21-295 $M_{\odot}$ yr$^{-1}$, and several have potential nearby companions. Our finding of bars at $z$ ~1.1-2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8-10 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ~ 0.Comment: 16 pages, 5 figures. Accepted for Publication in Astrophysical Journal Letter

CEERS Key Paper. VII. JWST/MIRI Reveals a Faint Population of Galaxies at Cosmic Noon Unseen by Spitzer

The Cosmic Evolution Early Release Science program observed the Extended Groth Strip (EGS) with the Mid-Infrared Instrument (MIRI) on the James Webb Space Telescope (JWST) in 2022. In this paper, we discuss the four MIRI pointings that observed with longer-wavelength filters, including F770W, F1000W, F1280W, F1500W, F1800W, and F2100W. We compare the MIRI galaxies with the Spitzer/MIPS 24 μm population in the EGS field. We find that MIRI can observe an order of magnitude deeper than MIPS in significantly shorter integration times, attributable to JWST's much larger aperture and MIRI’s improved sensitivity. MIRI is exceptionally good at finding faint (L IR &lt; 1010 L ⊙) galaxies at z ∼ 1-2. We find that a significant portion of MIRI galaxies are “mid-IR weak”—they have strong near-IR emission and relatively weaker mid-IR emission, and most of the star formation is unobscured. We present new IR templates that capture how the mid-to-near-IR emission changes with increasing infrared luminosity. We present two color-color diagrams to separate mid-IR weak galaxies and active galactic nuclei (AGN) from dusty star-forming galaxies and find that these color diagrams are most effective when used in conjunction with each other. We present the first number counts of 10 μm sources and find that there are ≲10 IR AGN per MIRI pointing, possibly due to the difficulty of distinguishing AGN from intrinsically mid-IR weak galaxies (due to low metallicities or dust content). We conclude that MIRI is most effective at observing moderate-luminosity (L IR = 109-1010 L ⊙) galaxies at z = 1-2, and that photometry alone is not effective at identifying AGN within this faint population.</p

ABORDAJE FISIOTERAPÉUTICO EN USUARIO DE LA CLÍNICA DE LA POLICÍA REGIONAL CARIBE CON PARÁLISIS DE LOS NERVIOS FACIAL Y MOTOR OCULAR. REPORTE DE CASO

Introducción: La parálisis facial es un trastorno neuromuscular relativamente frecuente generado por la lesión de las vías centrales o periféricas del nervio facial como consecuencia de una lesión, se presenta con asimetría, disfunción  y disminución en el desempeño de los músculos de la expresión facial. A nivel mundial se estima una incidencia anual de 23/100.000 habitantes afectando a ambos géneros por igual entre los 10 y los 45 años. Resumen del caso: El objetivo de este artículo es la presentación del caso clínico de un paciente que presentó este trastorno por secuela de fractura ósea del occipital y del peñasco a causa de traumatismo craneoencefálico, con un periodo de evolución de 9 meses. Discusión: Se justifica la importancia y pertinencia de las modalidades cinéticas en la recuperación de la funcionalidad del paciente con este tipo de trastorno. Conclusiones: La parálisis facial genera un impacto funcional y psicológico importante para la persona que la padece, por tanto la intervención fisioterapéutica debe enfocarse desde la rehabilitación integral tanto funcional como de integración social

CEERS Epoch 1 NIRCam Imaging: Reduction Methods and Simulations Enabling Early JWST Science Results

We present the data release and data reduction process for the Epoch 1 NIRCam observations for the Cosmic Evolution Early Release Science Survey (CEERS). These data consist of NIRCam imaging in six broadband filters (F115W, F150W, F200W, F277W, F356W and F444W) and one medium band filter (F410M) over four pointings, obtained in parallel with primary CEERS MIRI observations (Yang et al. in prep). We reduced the NIRCam imaging with the JWST Calibration Pipeline, with custom modifications and reduction steps designed to address additional features and challenges with the data. Here we provide a detailed description of each step in our reduction and a discussion of future expected improvements. Our reduction process includes corrections for known pre-launch issues such as 1/f noise, as well as in-flight issues including snowballs, wisps, and astrometric alignment. Many of our custom reduction processes were first developed with pre-launch simulated NIRCam imaging over the full 10 CEERS NIRCam pointings. We present a description of the creation and reduction of this simulated dataset in the Appendix. We provide mosaics of the real images in a public release, as well as our reduction scripts with detailed explanations to allow users to reproduce our final data products. These represent one of the first official public datasets released from the Directors Discretionary Early Release Science (DD-ERS) program.Comment: 27 pages, 14 figures, submitted to ApJ. Accompanying CEERS public Data Release 0.5 available at ceers.github.io/releases.htm

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts