Genomic regions, candidate genes, and pleiotropic variants associated with physiological and anatomical indicators of heat stress response in lactating sows.

BACKGROUND: Heat stress (HS) poses significant threats to the sustainability of livestock production. Genetically improving heat tolerance could enhance animal welfare and minimize production losses during HS events. Measuring phenotypic indicators of HS response and understanding their genetic background are crucial steps to optimize breeding schemes for improved climatic resilience. The identification of genomic regions and candidate genes influencing the traits of interest, including variants with pleiotropic effects, enables the refinement of genotyping panels used to perform genomic prediction of breeding values and contributes to unraveling the biological mechanisms influencing heat stress response. Therefore, the main objectives of this study were to identify genomic regions, candidate genes, and potential pleiotropic variants significantly associated with indicators of HS response in lactating sows using imputed whole-genome sequence (WGS) data. Phenotypic records for 18 traits and genomic information from 1,645 lactating sows were available for the study. The genotypes from the PorcineSNP50K panel containing 50,703 single nucleotide polymorphisms (SNPs) were imputed to WGS and after quality control, 1,622 animals and 7,065,922 SNPs were included in the analyses. RESULTS: A total of 1,388 unique SNPs located on sixteen chromosomes were found to be associated with 11 traits. Twenty gene ontology terms and 11 biological pathways were shown to be associated with variability in ear skin temperature, shoulder skin temperature, rump skin temperature, tail skin temperature, respiration rate, panting score, vaginal temperature automatically measured every 10 min, vaginal temperature measured at 0800 h, hair density score, body condition score, and ear area. Seven, five, six, two, seven, 15, and 14 genes with potential pleiotropic effects were identified for indicators of skin temperature, vaginal temperature, animal temperature, respiration rate, thermoregulatory traits, anatomical traits, and all traits, respectively. CONCLUSIONS: Physiological and anatomical indicators of HS response in lactating sows are heritable but highly polygenic. The candidate genes found are associated with important gene ontology terms and biological pathways related to heat shock protein activities, immune response, and cellular oxidative stress. Many of the candidate genes with pleiotropic effects are involved in catalytic activities to reduce cell damage from oxidative stress and cellular mechanisms related to immune response.

Machine learning applied to fMRI patterns of brain activation in response to mutilation pictures predicts PTSD symptoms.

BACKGROUND: The present study aimed to apply multivariate pattern recognition methods to predict posttraumatic stress symptoms from whole-brain activation patterns during two contexts where the aversiveness of unpleasant pictures was manipulated by the presence or absence of safety cues. METHODS: Trauma-exposed participants were presented with neutral and mutilation pictures during functional magnetic resonance imaging (fMRI) collection. Before the presentation of pictures, a text informed the subjects that the pictures were fictitious ("safe context") or real-life scenes ("real context"). We trained machine learning regression models (Gaussian process regression (GPR)) to predict PTSD symptoms in real and safe contexts. RESULTS: The GPR model could predict PTSD symptoms from brain responses to mutilation pictures in the real context but not in the safe context. The brain regions with the highest contribution to the model were the occipito-parietal regions, including the superior parietal gyrus, inferior parietal gyrus, and supramarginal gyrus. Additional analysis showed that GPR regression models accurately predicted clusters of PTSD symptoms, nominal intrusion, avoidance, and alterations in cognition. As expected, we obtained very similar results as those obtained in a model predicting PTSD total symptoms. CONCLUSION: This study is the first to show that machine learning applied to fMRI data collected in an aversive context can predict not only PTSD total symptoms but also clusters of PTSD symptoms in a more aversive context. Furthermore, this approach was able to identify potential biomarkers for PTSD, especially in occipitoparietal regions.

Epidemiology of tongue squamous cell carcinoma: A retrospective cohort study.

OBJECTIVE: To analyze the epidemiological profile and the specific survival of patients diagnosed with tongue squamous cell carcinoma at the National Cancer Institute (INCA). MATERIALS AND METHODS: Hospital Cancer Registry System Data and Mortality Information from 2007 to 2009 were retrieved in a retrospective cohort study of patients diagnosed with tongue squamous cell carcinoma. Specific survival was estimated using the Kaplan-Meier method. The association between independent variables and the risk of death was explored in a Cox proportional hazards regression model. RESULTS: A total of 346 patients were eligible, mostly male (77.5%), smokers (87.6%), with alcohol consumption (80.9%), with low education (65.6%), advanced staging at the time of diagnosis (71.1%), and presenting a high mortality rate (72.5%). In total, 44.5% of patients underwent a surgical approach alone or associated with another treatment modality, of which 85.1% of patients underwent neck dissection and 90.1% had free surgical margins. Specific survival was 40.6% in two years and 31.2% in five years. CONCLUSION: The 5-year specific survival was considered worse in individuals over 60 years, and who did not undergo surgical treatment or had surgery associated with another treatment, compared to patients undergoing isolated surgery.

Historical perspective of vaginal hysterectomy: the resilience of art and evidence-based medicine in the age of technology.

OBJECTIVE: The aim of this study was to describe, from a historical perspective, the relevance, resilience and outcomes of vaginal hysterectomy (VH) in gynecology in the age of technological scenario. METHODS: The authors searched records from January 2011 to January 2021 on the following databases: Medline, EMBASE, and CENTRAL (The Cochrane Library) for combinations of the terms "vaginal hysterectomy," "outcomes" AND "history"; and before that period, if the search had historical relevance. INCLUSION CRITERIA: randomized clinical trials; hysterectomy performed for benign gynecological conditions; and VH outcomes compared with Abdominal Hysterectomy (AH), Laparoscopic Hysterectomy (LH) or Robotic Hysterectomy (RH). RESULTS: The VH combines sequences of reproducible techniques which have been developed over the years to safely and effectively overcome the limitations of difficult cases of vaginal extirpation from the uterus. CONCLUSION: The authors support endoscopic surgical approaches in complex surgery for benign indications, urogynecology, and gynecologic oncology when appropriate. However, what makes the gynecological surgeon different from the general surgeon is the vaginal access. It is essential to continue to train residents in vaginal surgical skills and provide safe and cost-effective patient care. The art of technology is the resilience of keeping only the patient at the center of innovation.

First detection of Psittacid alphaherpesvirus 5 and coinfection with beak and feather disease virus in naturally infected captive ringneck parakeets (Psittacula krameri) in Brazil.

This study describes a case report in captive rose-ringed parakeets (Psittacula krameri) that developed clinical signs and eventually died after introducing new birds without quarantine. Bronchopneumonia and airsacculitis with syncytial cells associated with intranuclear inclusion bodies were found. Herpesvirus was detected in lungs and liver by PCR, and a nearly complete genome sequence of a Psittacid alphaherpesvirus 5 was obtained from the lung of a bird. Metagenomic analysis also identified beak and feather disease virus in the same samples. The study also highlights the importance of quarantine for avoiding the introduction of new diseases in captive aviaries.

The top-100 cited articles on post-traumatic stress disorder: a historical bibliometric analysis.

This is a bibliometric analysis of the most-cited articles on post-traumatic stress disorder (PTSD) with the objective of identifying citation patterns for researchers, journals, centers, periods, topics, and nations. A search was conducted in Thomson Reuters' WoS Core Collection employing the expression TI = (posttraumatic stress disorder OR post-traumatic stress disorder OR PTSD). The 100 most-cited articles were downloaded, and the relevant data were extracted and analyzed. These studies had a total of 69,649 citations, ranging from a minimum of 360 to a maximum of 6029 citations, with an average of 696.49, a standard deviation of 720.92, mode of 369, and a median of 512. Eighty-eight percent of the most-cited articles on PTSD originated from the USA, with just six cities accounting for 52% of the publications and the Boston area alone responsible for almost one-fifth of the total output. The universities of Yale and Harvard headed the ranking of institutions with larger numbers of highly-cited articles. Female researchers represented 42.3% of all authors, 51% of the first authors, and 48% of the corresponding authors. The proportion of M.D. authors decreased significantly between the 1980-1999 (42%) and the 2000-2019 (27.2%) periods while that of Ph.D. authors increased from 44% to 57.4%. The most studied population was military veterans (28%). Female victims of sexual or physical violence, traumatized children, and adult survivors of childhood abuse were assessed in only 6-7% of the most-cited publications. Ten clinical trials evaluated psychological interventions but only three investigated pharmacotherapy. We concluded that influential research on PTSD remains centralized in the USA. A balanced gender representation in publications was found. There was a heavy reliance on combat veterans as the study population. Few highly-cited studies on the pharmacotherapy for PTSD were identified. Focused efforts are needed to address these challenges.

Hematological and histopathological evaluation of meat-type quails fed Madagascar cockroach meal.

Aiming at the sustainability of meat production, insects can replace traditional ingredients in the diet of poultry. Studies evaluating performance in birds have emerged to ensure this ability, but few address the health parameters of animals. This study was carried out to evaluate the effects of the inclusion of Madagascar cockroach meal in traditional diets on hematological and histopathological traits of meat-type quails. The inclusion of Madagascar cockroach meal in the diet was evaluated in four levels: 0%, 6%, 12%, and 18%. Observations for hematological and histopathological traits from 6 repetitions on each group were recorded for both sexes at 35 days of age. Hematological parameters were not influenced by Madagascar cockroach inclusion on diet and quail's sex. Red and white blood cells count were within the normal range for poultry. No significant findings were observed during the histopathological evaluation of the pancreas, duodenum, jejunum, and ileum. Liver fatty degeneration was visualized in all treatments in the same intensity. Quail's diets containing up to 18% insect meal during the growth period did not affect the studied health parameters, so the Madagascar cockroach meal could be considered as an alternative to a protein ingredient for poultry production.

Estimation of genetic parameters and inbreeding depression in Piau pig breed.

This study is aimed at estimating genetic parameters, effective population size, inbreeding, and inbreeding depression for birth weight, weaning weight, and average pre-weaning daily weight gain (ADG) in Piau pigs. We used information from 3841 Piau pigs, and four linear models were fitted in single-trait analyses, including or excluding maternal genetic effect, common litter effect, or a combination. The adjustments of the models were compared using the likelihood ratio test, in which the model that presented the best fit for each trait was used to estimate the (co)variance components. The inbreeding depression effect was evaluated using a linear model that included the fixed effects of sex, parity order, contemporary group, and inbreeding coefficient as a fixed covariate. The weights at birth and weaning showed low direct heritabilities (0.08 and 0.05, respectively), while the ADG showed moderate heritability (0.20). The weight at birth showed high genetic correlations with the weight at weaning (0.90) and the ADG (0.82). The weight at weaning and the ADG also showed a high genetic correlation (0.99). There was an inbreeding increase over the generations and a reduction in the effective population size. In the last generation evaluated, all the animals were inbred, the average inbreeding coefficient was 0.07, and the effective population size was 20.8. A significant inbreeding effect on ADG was observed, where an increase of 1% in the inbreeding coefficient resulted in a decrease of 0.005 g in the ADG. Thus, increasing effective population size is mandatory for controlling inbreeding and reducing the loss of variability in this Piau pig population.

The invisible scars of emotional abuse: a common and highly harmful form of childhood maltreatment.

BACKGROUND: Childhood maltreatment (CM) is unfortunately widespread globally and has been linked with an increased risk of a variety of psychiatric disorders in adults, including posttraumatic stress disorder (PTSD). These associations are well established in the literature for some maltreatment forms, such as sexual and physical abuse. However, the effects of emotional maltreatment are much less explored, even though this type figures among the most common forms of childhood maltreatment. Thus, the present study aims to investigate the impact of each type of childhood maltreatment, both individually and conjointly, on revictimization and PTSD symptom severity using a nonclinical college student sample. METHODS: Five hundred and two graduate and undergraduate students participated in the study by completing questionnaires assessing lifetime traumatic experiences in general, maltreatment during childhood and PTSD symptoms. Bivariate and multivariate negative binomial regressions were applied to examine the associations among childhood maltreatment, revictimization, and PTSD symptom severity. RESULTS: Our results showed that using bivariate models, all types of CM were significantly associated with revictimization and PTSD symptom severity. Multivariate models showed that emotional abuse was the type of maltreatment associated with the highest incidence rates of revictimization and PTSD symptom severity. CONCLUSIONS: These data provide additional evidence of the harmful effects of childhood maltreatment and its long-term consequences for individuals' mental health. Notably, the findings highlight the importance of studying the impacts of emotional abuse, which seems to be a highly prevalent, understudied, and chronic form of maltreatment that is as toxic as other maltreatment forms.

Runting and Stunting Syndrome in Broiler Chickens: Histopathology and Association With a Novel Picornavirus.

Runting stunting syndrome (RSS) in commercial chickens has been reported worldwide, and although several studies have attempted to clarify the cause and describe the lesions, there are gaps in knowledge of the epidemiology, pathogenesis, and etiology. The study objective was to use commercial chicks naturally affected by RSS to describe the histologic changes of RSS in all segments of the small intestine in chicks of different ages and to identify viral gene sequences in affected chicks and their association with histologic lesions. Chicks lacking clinical signs but from the same houses and from unaffected houses were used as controls. The average weight of affected chicks was significantly lower than expected for their flocks. Macroscopically, the small intestines had paler serosa, with watery, mucoid, or foamy contents and poorly digested food. Histologic lesions were characterized by necrotic crypts, crypt dilation, and flattening of the crypt epithelium. Histomorphometry of the intestines revealed villous atrophy especially in the jejunum and ileum. Histologic changes in other organs were not observed. Random next-generation sequencing of total RNA extracted from formalin-fixed paraffin-embedded tissues detected avian nephritis virus, avian rotavirus, and picornavirus in jejunal segments from 7-day-old chicks. No viruses were detected in the jejunum of 1-day-old chicks. Detection of picornaviral reads was significantly associated (P < .05) with histologic lesions of RSS. Sequence analysis of the picornavirus revealed genetic similarity with the genus Gallivirus. Using in situ hybridization for galliviral nucleic acid sequences, the signal was associated with crypt lesion severity, although signal was detected both in chicks with and without RSS.

Effects of bovine somatotropin on productive performance and Minas Padrão cheese.

We aimed to evaluate the effects of two brands of bST (bovine somatoropin) on productive performance and on Minas Padrão cheese yield. Fifteen Girolando cows with more than 60 days of lactation were used. The animals were distributed in a randomized block design, according to days in milk, with three treatments (somatotropin A, somatotropin B, and control). The animals received a balanced diet with commercial concentrate and corn silage as roughage. It was measured milk yield and composition, dry matter intake, body condition score (BCS), and feeding behavior; it was compared by Tukey at 5.0% of significance level. Physical-chemical composition of Minas Padrão cheese was obtained from the different treatments, was also measured, being evaluated in a completely randomized design, and compared by Tukey at 1.0% of significance level. The dry matter intake per body weight lower in control treatment (p < 0.05) was equal to 2.85, somatotropin A was equal to 3.17, and somatotropin B was equal to 3.17. Animals that received bST showed higher milk production (p < 0.05), with control being 17.56 kg/day, somatotropin A 21.12 kg/day, and somatotropin B 20.69 kg/day. The physical-chemical composition of milk showed significant differences (p < 0.05) for the fat, protein, and dry extract contents. The somatotropin applications also influenced the BCS (p < 0.05) and the feeding behavior in time for total intake, time spent with rumination, and idleness. The application of bST increased milk yield and technical and economic yields of Minas Padrão cheese did not show significant differences between treatments.

Effects of load and emotional state on EEG alpha-band power and inter-site synchrony during a visual working memory task.

Motivationally/emotionally engaging stimuli are strong competitors for the limited capacity of sensory and cognitive systems. Thus, they often act as distractors, interfering with performance in concurrent primary tasks. Keeping task-relevant information in focus while suppressing the impact of distracting stimuli is one of the functions of working memory (WM). Macroscopic brain oscillations in the alpha band (8-13 Hz) have recently been identified as a neural correlate of WM processing. Using electroencephalography, we examined the extent to which changes in alpha power and inter-site connectivity during a typical WM task are sensitive to load and emotional distraction. Participants performed a lateralized change-detection task with two levels of load (four vs. two items), which was preceded by naturalistic scenes rated either as unpleasant or neutral, acting as distractors. The results showed the expected parieto-occipital alpha reduction in the hemisphere contralateral to the WM task array, compared to the ipsilateral hemisphere, during the retention interval. Selectively heightened oscillatory coupling between frontal and occipital sensors was observed (1) during the retention interval as a function of load, and (2) upon the onset of the memory array, after viewing neutral compared to unpleasant distractors. At the end of the retention interval, we observed greater coupling during the unpleasant compared to the neutral condition. These findings are consistent with the notions that (1) representing more items in WM requires greater interconnectivity across cortical areas, and (2) unpleasant emotional distractors interfere with subsequent WM processing by disrupting processing during the encoding stage.

Monitoring cellulose oxidation for protein immobilization in paper-based low-cost biosensors.

The oxidation of paper by periodate was investigated and systematically characterized by Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy, X-ray diffraction, goniometry, and dynamic mechanical analysis. For the first time, in situ FTIR microscopy analysis was performed, yielding chemical images of carbonyl groups on the cellulose fibers. The enhancement of protein immobilization on oxidized paper was quantified by a colorimetric assay with Ponceau dye, demonstrating that 0.5-h oxidation suffices to functionalize the paper-based devices. The oxidized paper was applied as a sensor for protein quantification in urine, a test able to detect levels of proteinuria and even microalbuminuria. The quantification was based on the capture of proteins through covalent bonds formed with the carbonyl groups on the oxidized paper followed by the staining of the region with Ponceau dye. There is a linear dependency between human serum albumin (HSA) concentration and the length of the stained blot from 0.1 to 3 mg mL-1. This method correlated linearly with a reference method showing a higher sensitivity (0.866 cm mL mg-1) than the latter. The limit of quantification was 0.1 mg mL-1, three times lower than that of the commercial strip. Graphical abstract Paper oxidation with periodate and extensive characterization, including microspectroscopy. The conversion of cellulose hydroxyl groups to aldehyde enhances covalent immobilization of protein on paper for application as analytical device. The oxidized paper determined protein in urine, suitable for proteinuria diagnosis.

Breakthrough candidemia after the introduction of broad spectrum antifungal agents: A 5-year retrospective study.

Candidemia is the main invasive fungal disease among hospitalized patients. Several breakthrough candidemia (BrC) cases have been reported, but few studies evaluate the epidemiology, risk factors, molecular characterization, antifungal susceptibility profile and outcome of those patients, especially in developing countries and including patients using broad spectrum antifungals. We conducted a retrospective study from 2011 to 2016, including patients aged 12 years or older with candidemia. Epidemiological characteristics and risk factors for candidemia were evaluated and compared with patients with BrC using univariate and multivariate analysis. Sequential Candida isolates from BrC were identified by internal transcribed spacer sequencing, genotyped with amplified fragment length polymorphism fingerprinting (AFLP), and tested for antifungal susceptibility. From 148 candidemia episodes, 27 breakthrough episodes (18%) were identified, with neutropenia and mucositis being independent risk factors for BrC. Candida non-albicans was more frequent in the BrC group (P < .001). AFLP showed high correlation with conventional methods of identification among breakthrough isolates and a high genetic similarity among isolates from the same patient was observed. C. albicans was the most susceptible species with low MIC values for all antifungal agents tested. In contrast, we found isolates of C. glabrata, C. parapsilosis and C. tropicalis resistant to triazoles and echinocandins. In conclusion, BrC occurred mainly in severely immunosuppressed patients, with neutropenia and mucositis. Mortality did not differ between the groups. Candida non-albicans species were more recovered from BrC, with C. albicans being the most susceptible to antifungals.

COELOMIC TERATOMA IN A BLUE-AND-YELLOW MACAW (ARA ARARAUNA).

A 2-mo-old, female blue-and-yellow macaw (Ara ararauna) presented with severe abdominal distension, pain, and respiratory distress. Ultrasonographic examination detected a heterogeneous mass with multiple anechoic areas, compatible with a multilocular cyst, occupying most of the coelomic cavity. Postmortem examination revealed a mass of 12.0 × 8.5 × 5.0 cm, which had an irregular surface and was connected by a pedicle to the ileum. This mass compressed and displaced the liver, proventriculus, gizzard, and intestines cranially to the left. The cut surface was lobulated, gray-white, mildly firm or soft, and was interspersed with multiple cysts filled with viscous and opaque liquid. Microscopically, it was composed of well- differentiated embryonic tissues from the endoderm, mesoderm, and ectoderm; therefore, it was diagnosed as a mature teratoma, which was theorized to have originated from Meckel's diverticulum. This study is the first, to the authors' knowledge to report a case of a teratoma in a blue-and-yellow macaw.

Low-level laser therapy stimulates tissue repair and reduces the extracellular matrix degradation in rats with induced arthritis in the temporomandibular joint.

The objective of this study was to characterize morphological and biochemistry action of low-level laser therapy (LLLT) on induced arthritis in the temporomandibular joint (TMJ) of rats. Twenty-four male Wistar rats were randomly divided into groups with 12 animals each: (AG) group with arthritis induced in the left TMJ and (LG) group with arthritis induced in the left TMJ and treated with LLLT (830 nm, 30 mW, 3 J/cm(2)). Right TMJs in the AG group were used as noninjected control group (CG). Arthritis was induced by intra-articular injection of 50 µl Complete Freund's Adjuvant (CFA) and LLLT began 1 week after arthritis induction. Histopathological analysis was performed using sections stained with hematoxylin-eosin, Toluidine Blue, and picrosirius. Biochemical analysis was determined by the total concentration of sulfated glycosaminoglycans (GAGs) and evaluation of matrix metalloproteinases (MMP-2 and MMP-9). Statistical analysis was performed using paired and unpaired t tests, with p < 0.05. Compared to AG, LG had minor histopathological changes in the TMJ, smaller thickness of the articular disc in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001), high birefringence of collagen fibers in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001) on the articular disc, and statistically lower activity of MMP-2 latent (p < 0.0001), MMP-2 active (P = 0.02), MMP-9 latent (p < 0.0001), and MMP-9 active (p < 0.0001). These results suggest that LLLT can increase the remodeling and enhancing tissue repair in TMJ with induced arthritis.

(+)-Catechin attenuates activation of hepatic stellate cells.

(+)-Catechin is a type of catechin present in large amounts in açaí fruits and cocoa seeds. Besides its antioxidant and anti-inflammatory activities, little is known about its effects in the liver, especially during hepatic fibrosis. We report here the effects of (+)-catechin on hepatic stellate cells. (+)-Catechin induced quiescent phenotype in GRX cells, along with an increase in lipid droplets. Proliferator-activated receptor γ mRNA expression was upregulated, whereas type I collagen mRNA expression was downregulated. Pro-inflammatory cytokines were not influenced by (+)-catechin, whereas the levels of interleukin 10 were significantly increased. The data provide evidence that (+)-catechin can reduce hepatic stellate cell activation.

Exploring the potential of ruthenium(II)-phosphine-mercapto complexes as new anticancer agents.

The search for new metal-based anticancer drug candidates is a fundamental task in medicinal inorganic chemistry. In this work, we assessed the potential of two new Ru(II)-phosphine-mercapto complexes as potential anticancer agents. The complexes, with the formula [Ru(bipy)(dppen)(Lx)]PF6 [(1), HL1 = 2-mercapto-pyridine and (2), HL2 = 2-mercapto-pyrimidine, bipy = 2,2'-bipyridine, dppen = cis-1,2-bis(diphenylphosphino)-ethylene] were synthesized and characterized by nuclear magnetic resonance (NMR) [1H, 31P(1H), and 13C], high resolution mass spectrometry (HR-MS), cyclic voltammetry, infrared and UV-Vis spectroscopies. Complex 2 was obtained as a mixture of two isomers, 2a and 2b, respectively. The composition of these metal complexes was confirmed by elemental analysis and liquid chromatography-mass spectrometry (LC-MS). To obtain insights into their lipophilicity, their distribution coefficients between n-octanol/PBS were determined. Both complexes showed affinity mainly for the organic phase, presenting positive log P values. Also, their stability was confirmed over 48 h in different media (i.e., DMSO, PBS and cell culture medium) via HPLC, UV-Vis and 31P{1H} NMR spectroscopies. Since enzymes from the P-450 system play a crucial role in cellular detoxification and metabolism, the microsomal stability of 1, which was found to be the most interesting compound of this study, was investigated using human microsomes to verify its potential oxidation in the liver. The analyses by LC-MS and ESI-MS reveal three main metabolites, obtained by oxidation in the dppen and bipy moieties. Moreover, 1 was able to interact with human serum albumin (HSA). The cytotoxicity of the metal complexes was tested in different cancerous and non-cancerous cell lines. Complex 1 was found to be more selective than cisplatin against MDA-MB-231 breast cancer cells when compared to MCF-10A non-cancerous cells. In addition, complex 1 affects cell morphology and migration, and inhibits colony formation in MDA-MB-231 cells, making it a promising cytotoxic agent against breast cancer.

Detection and characterization of copy number variation in three differentially-selected Nellore cattle populations.

Introduction: Nellore cattle (Bos taurus indicus) is the main beef cattle breed raised in Brazil. This breed is well adapted to tropical conditions and, more recently, has experienced intensive genetic selection for multiple performance traits. Over the past 43 years, an experimental breeding program has been developed in the Institute of Animal Science (IZ, Sertaozinho, SP, Brazil), which resulted in three differentially-selected lines known as Nellore Control (NeC), Nellore Selection (NeS), and Nellore Traditional (NeT). The primary goal of this selection experiment was to determine the response to selection for yearling weight (YW) and residual feed intake (RFI) on Nellore cattle. The main objectives of this study were to: 1) identify copy number variation (CNVs) in Nellore cattle from three selection lines; 2) identify and characterize CNV regions (CNVR) on these three lines; and 3) perform functional enrichment analyses of the CNVR identified. Results: A total of 14,914 unique CNVs and 1,884 CNVRs were identified when considering all lines as a single population. The CNVRs were non-uniformly distributed across the chromosomes of the three selection lines included in the study. The NeT line had the highest number of CNVRs (n = 1,493), followed by the NeS (n = 823) and NeC (n = 482) lines. The CNVRs covered 23,449,890 bp (0.94%), 40,175,556 bp (1.61%), and 63,212,273 bp (2.54%) of the genome of the NeC, NeS, and NeT lines, respectively. Two CNVRs were commonly identified between the three lines, and six, two, and four exclusive regions were identified for NeC, NeS, and NeT, respectively. All the exclusive regions overlap with important genes, such as SMARCD3, SLC15A1, and MAPK1. Key biological processes associated with the candidate genes were identified, including pathways related to growth and metabolism. Conclusion: This study revealed large variability in CNVs and CNVRs across three Nellore lines differentially selected for YW and RFI. Gene annotation and gene ontology analyses of the exclusive CNVRs to each line revealed specific genes and biological processes involved in the expression of growth and feed efficiency traits. These findings contribute to the understanding of the genetic mechanisms underlying the phenotypic differences among the three Nellore selection lines.