Identification of Candidate Genes and Pathways Linked to the Temperament Trait in Sheep.

Temperament can be defined as the emotional variability among animals of the same species in response to the same stimulus, grouping animals by their reactivity as nervous, intermediate, or calm. Our goal was to identify genomic regions with the temperament phenotype measured by the Isolation Box Test (IBT) by single-step genome-wide association studies (ssGWAS). The database consisted of 4317 animals with temperament records, and 1697 genotyped animals with 38,268 effective Single Nucleotide Polymorphism (SNP) after quality control. We identified three genomic regions that explained the greatest percentage of the genetic variance, resulting in 25 SNP associated with candidate genes on chromosomes 6, 10, and 21. A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY, linked to the energetic activity of the organism, synaptic transmission, meat tenderness, and calcium associated activities. This is the first study to identify these genetic variants associated with temperament in sheep, which could be used as molecular markers in future behavioral research.

Genomic Regions Associated with Wool, Growth and Reproduction Traits in Uruguayan Merino Sheep.

The aim of this study was to identify genomic regions and genes associated with the fiber diameter (FD), clean fleece weight (CFW), live weight (LW), body condition score (BCS), pregnancy rate (PR) and lambing potential (LP) of Uruguayan Merino sheep. Phenotypic records of approximately 2000 mixed-age ewes were obtained from a Merino nucleus flock. Genome-wide association studies were performed utilizing single-step Bayesian analysis. For wool traits, a total of 35 genomic windows surpassed the significance threshold (PVE ≥ 0.25%). The proportion of the total additive genetic variance explained by those windows was 4.85 and 9.06% for FD and CFW, respectively. There were 42 windows significantly associated with LWM, which collectively explained 43.2% of the additive genetic variance. For BCS, 22 relevant windows accounted for more than 40% of the additive genetic variance, whereas for the reproduction traits, 53 genomic windows (24 and 29 for PR and LP, respectively) reached the suggestive threshold of 0.25% of the PVE. Within the top 10 windows for each trait, we identified several genes showing potential associations with the wool (e.g., IGF-1, TGFB2R, PRKCA), live weight (e.g., CAST, LAP3, MED28, HERC6), body condition score (e.g., CDH10, TMC2, SIRPA, CPXM1) or reproduction traits (e.g., ADCY1, LEPR, GHR, LPAR2) of the mixed-age ewes.

Genome-Wide Association Study of Parasite Resistance to Gastrointestinal Nematodes in Corriedale Sheep.

Selection of genetically resistant animals is one alternative to reduce the negative impact of gastrointestinal nematodes (GIN) on sheep production. The aim of this study was to identify genomic regions associated with GIN resistance in Corriedale sheep by single-step genome-wide association studies (ssGWAS) using 170, 507 and 50K single nucleotide polymorphisms (SNPs). Analysis included 19,547 lambs with faecal egg counts (FEC) records, a pedigree file of 40,056 animals and 454, 711 and 383 genotypes from 170, 507 and 50K SNPs, respectively. Genomic estimated breeding values (GEBV) were obtained with single-step genomic BLUP methodology (ssGBLUP), using a univariate animal model, which included contemporary group, type of birth and age of dam as class fixed effects and age at FEC recording as covariate. The SNP effects as wells as p-values were estimated with POSTGSF90 program. Significance level was defined by a chromosome-wise False Discovery Rate of 5%. Significant genomic regions were identified in chromosomes 1, 3, 12 and 19 with the 170 SNP set, in chromosomes 7, 12 and 24 using the 507 SNP chip and only in chromosome 7 with the 50K SNP chip. Candidate genes located in these regions, using Oar_v4.0 as reference genome, were TIMP3, TLR5, LEPR and TLR9 (170 SNPs), SYNDIG1L and MGRN1 (507 SNP chip) and INO80, TLN2, TSHR and EIF2AK4 (50K SNP chip). These results validate genomic regions associated with FEC previously identified in Corriedale and other breeds and report new candidate regions for further investigation.

New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi.

Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy-quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy-quinone core were considered for developing new anti-T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 µM) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 µM); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure-activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the Epc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy-quinones with higher potency against the protozoan parasite T. cruzi.

Histerectomía total laparoscópica por miomatosis uterina. Diferencias entre la cirugía abierta vs laparoscópica. A propósito de un caso / Laparoscopic total hysterectomy due to uterine myomatosis. Differences between open versus laparoscopic surgery. About a case

Resumen Introducción: Los primeros reportes de histerectomía se remontan al año 120 a. C. con Sorano de Efeso; sin embargo, fue hasta 1988 que H. Reich realizó la primera histerectomía laparoscópica. Las indicaciones para esta cirugía son: endometriosis, hemorragia uterina anormal, masas anexiales benignas, dolor pélvico crónico en relación con adherencias, secundarias a enfermedad inflamatoria pélvica o cirugía previa, cáncer de endometrio, de ovario y de cérvix estadio l. Caso clínico: Paciente de 44 años de edad, que 4 meses antes de la intervención quirúrgica inició su padecimiento con sangrado intermitente abundante con uso de 6 toallas sanitarias al día con ciclo menstrual de 15 × 15, acompañado de dolor tipo cólico, que remitía con tratamiento hormonal inyectable y antiinflamatorios no esteroideos. Se le realizó ultrasonido pélvico con reporte de miomatosis uterina. Pasó a quirófano y se encontró: útero de 10 × 7 × 7 cm con miomatosis de grandes elementos subserosos, el mayor de 7 × 7 × 7 cm en la pared posterior del útero. Egresó al tercer día de estancia hospitalaria sin datos de sangrado activo, tolerando la vía oral, canalizando gases. Justificación: La histerectomía por vía laparoscópica permite una mejor visualización gracias a la magnificación de la anatomía y la patología existente, mejor acceso al fondo del saco de Douglas y las fosas ováricas, mejor control hemostático, así como disminución del dolor de la incisión abdominal. Conclusión: Con esta técnica se ha demostrado una disminución de la estancia intrahospitalaria, un más rápido retorno a las actividades normales, así como reducción en el riesgo de infección en el sitio de la herida quirúrgica.

Abstract Introduction: The first reports of hysterectomy were in the year 120 BC. The first indications for surgery were: Endometriosis, Abnormal uterine bleeding, Benign adnexal masses, Chronic pelvic pain in relation to adhesions, secondary to inflammatory disease, but it was not until 1988 that the first laparoscopic hysterectomy was performed by H. Reich. Pelvic or prior surgery; Cancer of the endometrium, ovary and cervix stage l. Clinical case: a 44-year-old female patient who started her illness four months prior to surgery with intermittent heavy bleeding with the use of 6 sanitary towels per day with a 15 x 15 menstrual cycle accompanied by colic type pain, which referred with hormonal Injectable and non-steroidal anti-inflammatory drugs, pelvic ultrasound was performed with a report of uterine myomatosis, passed to the operating room where it was found as uterus of 10x7x7cm with myomatosis of large subserosal elements, the largest of 7x7x7cm in the posterior wall of the uterus, being graduated To the third day of hospital stay without data of active bleeding, tolerating the oral route, channeling gases. Justification: A laparoscopic hysterectomy allows better visualization by magnifying anatomy and existing pathology, better access to Douglas fundus and ovarian fossae, better hemostatic control as well as diminishing abdominal incision pain. Conclusion: decreased hospital stay, greater return to activities, shorter hospital stay, reduced infection at the surgical wound site.

Trypanothione Reductase: A Target for the Development of Anti- Trypanosoma cruzi Drugs.

BACKGROUND & OBJECTIVE: Chagas disease or American trypanosomiasis is a major parasitic disease in Latin America with restricted available treatment: nifurtimox and benznidazole. These two drugs are ineffective in the chronic phase of the disease; therefore, there is a need for the development of new, efficient and safe drugs for the treatment of this pathology. With this goal, one of the promising targets is trypanothione reductase (TR), a key enzyme in the metabolism of Trypanosoma cruzi. CONCLUSION: In this review, we analyse the importance of TR as a drug target, as well as the well-known and new inhibitors reported in the last decade as potential therapeutic agents for Chagas disease.

Structural analysis and molecular docking of trypanocidal aryloxy-quinones in trypanothione and glutathione reductases: a comparison with biochemical data.

A set of aryloxy-quinones, previously synthesized and evaluated against Trypanosoma cruzi epimastigotes cultures, were found more potent and selective than nifurtimox. One of the possible mechanisms of the trypanocidal activity of these quinones could be inhibition of trypanothione reductase (TR). Considering that glutathione reductase (GR) is the equivalent of TR in humans, biochemical, kinetic, and molecular docking studies in TR and GR were envisaged and compared with the trypanocidal and cytotoxic data of a set of aryloxy-quinones. Biochemical assays indicated that three naphthoquinones (Nq-h, Nq-g, and Nq-d) selectively inhibit TR and the TR kinetic analyses indicated that Nq-h inhibit TR in a noncompetitive mechanism. Molecular dockings were performed in TR and GR in the following three putative binding sites: the catalytic site, the dimer interface, and the nicotinamide adenine dinucleotide phosphate-binding site. In TR and GR, the aryloxy-quinones were found to exhibit high affinity for a site near it cognate-binding site in a place in which the noncompetitive kinetics could be justified. Taking as examples the three compounds with TR specificity (TRS) (Nq-h, Nq-g, and Nq-d), the presence of a network of contacts with the quinonic ring sustained by the triad of Lys62, Met400', Ser464' residues, seems to contribute hardly to the TRS. Compound Nq-b, a naphthoquinone with nitrophenoxy substituent, proved to be the best scaffold for the design of trypanocidal compounds with low toxicity. However, the compound displayed only a poor and non-selective effect toward TR indicating that TR inhibition is not the main reason for the antiparasitic activity of the aryloxy-quinones.