Steroidal epoxides as anticancer agents in lung, prostate and breast cancers: The case of 1,2-epoxysteroids.

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of cancer.

Influence of Zinc on Histoplasma capsulatum Planktonic and Biofilm Cells.

Histoplasma capsulatum causes a fungal respiratory disease. Some studies suggest that the fungus requires zinc to consolidate the infection. This study aimed to investigate the influence of zinc and the metal chelator TPEN on the growth of Histoplasma in planktonic and biofilm forms. The results showed that zinc increased the metabolic activity, cell density, and cell viability of planktonic growth. Similarly, there was an increase in biofilm metabolic activity but no increase in biomass or extracellular matrix production. N'-N,N,N,N-tetrakis-2-pyridylmethylethane-1,2 diamine (TPEN) dramatically reduced the same parameters in the planktonic form and resulted in a decrease in metabolic activity, biomass, and extracellular matrix production for the biofilm form. Therefore, the unprecedented observations in this study highlight the importance of zinc ions for the growth, development, and proliferation of H. capsulatum cells and provide new insights into the role of metal ions for biofilm formation in the dimorphic fungus Histoplasma, which could be a potential therapeutic strategy.

Contextual inequalities in specialized dental public health care in Brazil.

The present study aimed to investigate the contextual inequalities of specialized public dental care (SPDC) in Brazil. The outcome was the trajectory of dental specialized production in municipalities with SPDC (from 2015 to 2017) obtained by group-based trajectory modeling. A Poisson regression model was used to analyze the factors associated with the high trajectory of SPDC production. The inequality indicators for SPDC production were the slope index and the concentration index according to contextual factors. The study included 954 SPDC units distributed across 893 municipalities. Among the municipalities evaluated, 62.9% had a low trajectory of SPDC. Large-sized municipalities had the highest production (IRR = 2.84, 95%CI: 1.94-4.14) and the southern region had the lowest production (IRR = 0.73, 95%CI: 0.58-0.92). Municipalities presenting a very high human development index (HDI) showed the greatest SPDC production (IRR = 3.34, 95%CI: 1.09-10.24), as well as municipalities with the highest tertile of schooling rate (IRR = 1.23, 95%CI: 1.00-1.50). The absolute inequality was 52.1 percentage points for the average monthly wage (p < 0.001), 61.0 percentage points for the HDI (p < 0.001), -22.1 for infant mortality rate (p <0.001), and 14.8 for the schooling rate (p = 0.012). Thus, there are contextual inequalities in the Brazilian SPDC. Higher scores for social indicators were associated with better SPDC performance.

Batimastat Induces Cytotoxic and Cytostatic Effects in In Vitro Models of Hematological Tumors.

The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat's therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.

When the solution becomes the problem: a review on antimicrobial resistance in dairy cattle.

Antibiotics' action, once a 'magic bullet', is now hindered by widespread microbial resistance, creating a global antimicrobial resistance (AMR) crisis. A primary driver of AMR is the selective pressure from antimicrobial use. Between 2000 and 2015, antibiotic consumption increased by 65%, reaching 34.8 billion tons, 73% of which was used in animals. In the dairy cattle sector, antibiotics are crucial for treating diseases like mastitis, posing risks to humans, animals and potentially leading to environmental contamination. To address AMR, strategies like selective dry cow therapy, alternative treatments (nanoparticles, phages) and waste management innovations are emerging. However, most solutions are in development, emphasizing the urgent need for further research to tackle AMR in dairy farms.

Antibiotics are becoming less effective at fighting infections because of antimicrobial resistance (AMR). This phenomenon is mainly caused by the abuse and misuse of antibiotics in both human and veterinary medicine. In the dairy cow industry, the use of antibiotics to treat diseases is a big concern. Ways to tackle this include the promotion of the responsible use of antibiotics, the development of alternative treatments and the discovery of better methods to deal with animal waste. However, much of these are still in development.

Targeting of G-quadruplex DNA with 99mTc(I)/Re(I) Tricarbonyl Complexes Carrying Pyridostatin Derivatives.

The main goal of this work was to elucidate the potential relevance of (radio)metal chelates of 99mTc and Re targeting G-quadruplex structures for the design of new tools for cancer theranostics. 99mTc provides the complexes with the ability to perform single-photon-emission computed tomography imaging studies, while the Re complexes should act as anticancer agents upon interaction with specific G4 DNA or RNA structures present in tumor tissues. Towards this goal, we have developed isostructural 99mTc(I) and Re(I) tricarbonyl complexes anchored by a pyrazolyl-diamine (Pz) chelator carrying a pendant pyridostatin (PDS) fragment as the G4-binding motif. The interaction of the PDF-Pz-Re (8) complex with different G4-forming oligonucleotides was studied by circular dichroism, fluorescence spectroscopy and FRET-melting assays. The results showed that the Re complex retained the ability to bind and stabilize G4-structures from different DNA or RNA sequences, namely those present on the SRC proto-oncogene and telomeric RNA (TERRA sequence). PDF-Pz-Re (8) showed low to moderate cytotoxicity in PC3 and MCF-7 cancer cell lines, as typically observed for G4-binders. Biodistribution studies of the congener PDF-Pz-99mTc (12) in normal mice showed that the complex undergoes a fast blood clearance with a predominant hepatobiliary excretion, pointing also for a high in vitro stability.

Featuring long-lifetime deep-red emitting iridiumIII complexes with high colour purity: insights into the excited state dynamics from spectroscopic and theoretical perspectives.

The significant attention drawn to IrIII-complexes in recent years has boosted the development of new compounds with advantageous photophysical features. However, obtaining IrIII deep-red-emitting complexes with long lived excited state, high colour purity and high quantum yield (Φ) remains a challenging task. To address this issue, this study reports the synthesis and photophysical investigation of three novel zwitterionic complexes, [Ir(C^N)2bqdc] (C^N = ppy, phq, and bzq), with ppy = 2-phenylpyridine (Ir-pb), phq = 2-phenylquinoline (Ir-qb), bzq = benzo[h]quinoline (Ir-bb), and bqdc = potassium 2,2'-biquinoline-4,4'-dicarboxylate. These complexes exhibit high quantum yields and long emission lifetimes with high colour purity in the deep-red region. The structural characterisation carried out by usual spectroscopic measurements supports the proposed structures, while the photophysical study unveiled the high contribution of the 3MLCT state to the hybrid emitter state, as endorsed by theoretical investigations. The desired correspondence between the calculations and the experimental data set affirmed the accuracy of the theoretical analysis, which enabled us to establish a relationship between the ground-to-excited-state geometry distortion and the lifetime through the nonradiative decay (knr). Furthermore, these newly synthesized complexes exhibit quenching in the presence of molecular oxygen. In deoxygenated DMSO solution the knr values halve, increasing the quantum yields (34.0, 10.6, and 26.6%) and the lifetimes (1.13, 1.11, and 1.72 µs), while leading to quite pure deep-red emission - CIE coordinates: (0.67, 0.33), (0.60, 0.40;), (0.65, 0.35) for Ir-pb, Ir-qb, and Ir-bb, respectively. These complexes display considerable potential for a wide range of applications, such as photodynamic therapy, due to their attractive photophysical properties, and are among the deep-red-emitting complexes reported in the literature with longer lifetimes and higher Φ.

Host-Guest Chemosensor Ensembles based on Water-Soluble Sulfonated Calix[n]arenes and a Pyranoflavylium Dye for the Optical Detection of Biogenic Amines.

Biogenic amines (BAs) are biologically active nitrogen-containing compounds formed during the food spoilage process and are often related as key markers of food quality, safety, and freshness. Because their presence in foods at high levels can cause significant health problems, researchers have been focused on developing novel strategies and methods for early detection and capture of these analytes. Herein, water-soluble sulfonated calix[n]arene macrocycles (SC4, SC6, and SC8) and a pH-sensitive dye (4'-hydroxy-10-methylpyranoflavylium) were investigated as host-guest systems for BA sensing. The hosts were able to bind the flavylium cation of the dye with association constants of 103 to 104 M-1. The dye complexation also allowed tuning its pKa from 6.72 (free) toward high values: 7.68 (SC4), 7.79 (SC6), and 8.45 (SC8). These data were crucial to optimize the host-guest complexes as optical sensing systems for putrescine/tyramine (pH 7.2-7.6), yielding a colorimetric redshift from yellow to red. The BA sensing was also demonstrated by fluorescence quenching for the calix[n]arene/dye complexes and fluorescence recovery after the addition of BAs. 1H NMR spectroscopy was used to demonstrate the interaction mode, confirming an encapsulation-driven mechanism. Overall, these host-guest systems demonstrated great potential for the detection of BAs, one of the main key markers of food spoilage.

Clinical Relevance of Lepidoglyphus destructor Sensitisation in Allergic Rhinitis: Nasal Provocation Test as in vivo Assessment.

BACKGROUND: Dust mites are the leading cause of respiratory allergic diseases worldwide. Allergy to storage mites (SMs) has mostly been related to occupational exposures. However, recent studies have shown that sensitisation to SM, such as Lepidoglyphus destructor (Lep d), is of considerable importance also in urban populations, with high prevalence in dust samples of domestic environments. Co-sensitisation between house dust mites (HDMs) and SM is now regarded as very frequent in some regions, and cross-reactivity between them seems to be narrow. Therefore, SM allergenic capacity is increasingly a subject of study. The nasal provocation test (NPT), as an in vivo technique, could be considered the gold standard for the clinical relevance assessment of an allergen, in polysensitised rhinitis patients. OBJECTIVE: The objective of this study was to analyse the clinical relevance of the SM Lep d, by assessing the relationship between in vivo sensitisation and expression of allergic respiratory disease in an urban setting. PATIENTS AND METHODS: In our study, we enrolled a total of 32 allergic patients with rhinitis (with or without asthma) with proven sensitisation by skin prick test (SPT) and specific IgE (sIgE) to HDMs and/or SM. Patients underwent NPT with Lep d using subjective (Lebel Symptom Score Scale) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal response. RESULTS: Most of the patients with positive SPT and sIgE to Lep d had a positive NPT (24/27; 89%). True Lep d allergy, assessed by a positive NPT, could be predicted by a SPT wheal size >9.7 mm and a sIgE >0.42 kUA/L, with 100%/95.7% sensitivity and 75.0%/83.3% specificity, respectively. Co-sensitisation between Lep d and Der p was high, 75.0%. Asthma was more frequent in the positive Lep d NPT group (54 vs. 12%, p < 0.05). Significantly more patients from this group reported physical exercise, nonspecific irritants, and respiratory infections as relevant triggers of respiratory symptoms (p < 0.01-p < 0.05). CONCLUSIONS: To our knowledge, this is the first study to show that sensitisation to Lep d may have clinical relevance in a non-occupational setting. In this group, there seems to be a relationship between allergy to Lep d and severity of respiratory disease, with more bronchial inflammation, when comparing with mite-allergic patients sensitised only to HDM. Therefore, the authors consider that sensitisation to Lep d should be considered when assessing and treating allergic respiratory disease in urban environments.

Farmers' Perceptions on Implementing Automatic Milking Systems in Large USA Dairies: Decision-Making Process, Management Practices, Labor, and Herd Performance.

Automatic Milking System (AMS) installations are increasing in the USA despite the higher investment cost than conventional systems. Surveys on AMSs conducted outside the USA focused on small-medium herds, specific regions, or aspects of AMS milking. This study described farmers' perceptions about the decision-making process of adopting an AMS in the USA's large dairies (≥7 AMS boxes) regarding changes in technology, housing, management practices, labor, herd performance, and health. After being contacted, 27 of 55 farmers from large AMS herds completed the survey. The main reasons for adopting an AMS were labor costs, cows' welfare, and herd performance. Most farms constructed new barns, used a free-flow traffic system, and changed their feed management. Increases in water and energy use were perceived by 42% and 62% of farmers, respectively. Farmers estimated decreases in labor costs of over 21%, and AMS employees worked 40-60 h/week. Milk production increases were reported by 58%, with 32% observing higher milk fat and protein content. Easier sick cow detection, better mastitis management, and improvements in pregnancy rates were reported. Thus, farmers transitioning to AMSs perceived altered resource utilization, labor cost savings, and improvements in employee quality of life, animal welfare, and farm management. While 54% of respondents would recommend an AMS to other farms, 38% suggested considering additional aspects prior to adoption.

Os impactos da revisão de patologia em pacientes com diagnóstico de câncer de mama / The results of pathology review in patients diagnosed with breast cancer

A carga global de câncer deverá ser de 28,4 milhões de casos em 2040. Estima-se que os países em desenvolvimento serão responsáveis por ⅔ dos casos de câncer diagnosticados no mundo até 2035. A mortalidade por câncer de mama é significativamente maior nos países em desenvolvimento. Logo, a otimização da capacidade de prevenção e de tratamento do câncer nos países em desenvolvimento é fundamental para o controle global do câncer. A agilidade e a acurácia do diagnóstico histopatológico são críticas ao cuidado de alta qualidade dos pacientes com câncer de mama, no entanto, a obtenção de uma revisão histopatológica com eficiência ainda constitui um desafio a esses países devido à escassez de recursos. A prática institucional do Instituto Nacional de Câncer exige a revisão do material histopatológico no laboratório central, um protocolo que preza pela segurança e qualidade do cuidado oferecido, mas que certamente contribui para prolongar o tempo até o início do tratamento. A literatura demonstra que o atraso no tempo para início de cirurgia, quimioterapia e radioterapia tem impactos negativos nos desfechos oncológicos. Estudos anteriores divergem quanto à necessidade de revisão rotineira de patologia em pacientes com câncer de mama. Neste estudo, foi realizada uma comparação entre os resultados histopatológicos de pacientes que se submeteram a biópsias mamárias em um laboratório externo e as revisões patológicas feitas no Instituto Nacional do Câncer. Descrevemos a taxa de discordância e estimamos a alteração na conduta terapêutica baseada nesses resultados. A análise minuciosa dos dados sugere uma taxa de discordância muito baixa e a possibilidade de dispensar a revisão histopatológica, o que pode reduzir o tempo até o início do tratamento na instituição e, por consequência, melhorar o prognóstico dos pacientes.

The global burden of cancer is expected to be 28.4 million cases in 2040. It is estimated that developing countries will account for ⅔ of the cancer cases detected in the world by 2035. Mortality from breast cancer is significantly higher in developing countries. Therefore, optimizing cancer prevention and treatment capacity in developing countries is essential for global cancer control. The agility and accuracy of histopathological diagnosis are critical to the high-quality care of patients with breast cancer, however, obtaining an efficient histopathological review remains a challenge in these countries due to the scarcity of resources. The institutional practice of the Brazilian National Cancer Institute requires a review of the histopathological material in the central laboratory, a protocol that values the safety and quality of the care offered, but which certainly contributes to prolonging the time until treatment begins. The literature demonstrates that delays in starting surgery, chemotherapy and radiotherapy have negative impacts on oncological outcomes. Previous studies disagree regarding the need for routine pathology review in patients with breast cancer. In this study, we performed a comparison between the histopathological results of patients who underwent breast biopsies in an external laboratory and pathological reviews carried out at the Brazilian National Cancer Institute. We described the discordance rate and estimated the change in therapeutic management based on these results. A thorough analysis of the data suggests a very low discordance rate and the possibility of waiving a histopathological review, which can reduce the time until treatment begins at the institution and, consequently, improve the patients' prognosis

Effective Postoperative Pain Management in Thoracic Outlet Syndrome Surgery: The Role of the Erector Spinae Plane Block.

Thoracic outlet syndrome (TOS) often necessitates surgical intervention to alleviate neurovascular bundle compression, which can result in severe postoperative pain. The myriad of surgical techniques available for TOS treatment, the intricate involvement of diverse sensory pathways, and the limited literature on effective analgesic methods for these specific cases underscore the need for successful approaches. This report introduces an efficacious multimodal analgesic strategy that incorporates the erector spinae plane (ESP) block to enhance postoperative pain management after a supraclavicular surgical approach. By combining this fascial block with a comprehensive rationale for its implementation, this case offers valuable insights into improving the postoperative care of TOS patients, ultimately aiming to enhance their comfort and recovery.

Risk of Second Tumors in Retinoblastoma Survivors after Ionizing Radiation: A Review.

Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Effectively, RB patients present a higher risk of SMN incidence compared to other oncology patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. Over the decades, some studies have been performed to better understand this subject, evaluating the risk of the development of SMNs in RB patients. Furthermore, this risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB. This review aims to clarify the effect of ionizing radiation in RB patients and to understand the association between the risk of SMN incidence in patients that underwent radiation therapy, especially in hereditary RB individuals.

Acrocomia aculeata associated with doxorubicin: cardioprotection and anticancer activity.

Doxorubicin (Dox) is a chemotherapeutic agent widely used in the clinic, whose side effects include cardiotoxicity, associated with decreased antioxidant defenses and increased oxidative stress. The association of Dox with natural antioxidants can extend its use if not interfering with its pharmacological potential. In this study, we aimed to understand the effects and mechanisms of the aqueous extract of Acrocomia aculeata leaves (EA-Aa) in cancer cells and the co-treatment with Dox, in in vitro and in vivo models. It was found that EA-Aa showed a relevant decrease in the viability of cancer cells (K562 and MCF-7) and increased apoptosis and death. The Dox cytotoxic effect in co-treatment with EA-Aa was increased in cancer cells. The therapeutic association also promoted a change in cell death, leading to a higher rate of apoptosis compared to the Dox group, which induced necrosis. In addition, in non-cancer cells, EA-Aa enhanced red blood cell (RBC) redox state with lower hemolysis and malondialdehyde (MDA) content and had no in vitro nor in vivo toxicity. Furthermore, EA-Aa showed antioxidant protection against Dox-induced cytotoxicity in H9c2 cells (cardiomyoblast), partially mediated by the NRF2 pathway. In vivo, EA-Aa treatment showed a relevant decrease in MDA levels in the heart, kidney, and brain, evaluated in C57Bl/6 mice induced to cardiotoxicity by Dox. Together, our results proved the effectiveness of EA-Aa in potentiating Dox anticancer effects, with antioxidant and cardioprotective activity, suggesting EA-Aa as a potential Dox pharmacological adjuvant.

Repair of Aortic Regurgitation in Young Adults: Sooner Rather Than Later.

Background Establishing surgical criteria for aortic valve replacement (AVR) in severe aortic regurgitation in young adults is challenging due to the lack of evidence-based recommendations. We studied indications for AVR in young adults with severe aortic regurgitation and their outcomes, as well as the relationship between presurgical echocardiographic parameters and postoperative left ventricular (LV) size, function, clinical events, and valve-related complications. Methods and Results Data were collected retrospectively on 172 consecutive adult patients who underwent AVR or repair for severe aortic regurgitation between 2005 and 2019 in a tertiary cardiac center (age at surgery 29 [22-41] years, 81% male). One-third underwent surgery before meeting guideline indications. Postsurgery, 65% achieved LV size and function normalization. LV ejection fraction showed no significant change from baseline. A higher presurgical LV end-systolic diameter correlated with a lack of LV normalization (odds ratio per 1-cm increase 2.81, P<0.01). The baseline LV end-systolic diameter cut-off for predicting lack of LV normalization was 43 mm. Pre- and postoperative LV dimensions and postoperative LV ejection fraction predicted clinical events during follow-up. Prosthetic valve-related complications occurred in 20.3% during an average 5.6-year follow-up. Freedom from aortic reintervention was 98%, 96.5%, and 85.4% at 1, 5, and 10 years, respectively. Conclusions Young adult patients with increased baseline LV end-systolic diameter or prior cardiac surgery are less likely to achieve LV normalization after AVR. Clinicians should carefully balance the long-term benefits of AVR against procedural risks and future interventions, especially in younger patients. Evidence-based criteria for AVR in severe aortic regurgitation in young adults are crucial to improve outcomes.

Alternative Non-Mammalian Animal and Cellular Methods for the Study of Host-Fungal Interactions.

In the study of fungal pathogenesis, alternative methods have gained prominence due to recent global legislation restricting the use of mammalian animals in research. The principle of the 3 Rs (replacement, reduction, and refinement) is integrated into regulations and guidelines governing animal experimentation in nearly all countries. This principle advocates substituting vertebrate animals with other invertebrate organisms, embryos, microorganisms, or cell cultures. This review addresses host-fungus interactions by employing three-dimensional (3D) cultures, which offer more faithful replication of the in vivo environment, and by utilizing alternative animal models to replace traditional mammals. Among these alternative models, species like Caenorhabditis elegans and Danio rerio share approximately 75% of their genes with humans. Furthermore, models such as Galleria mellonella and Tenebrio molitor demonstrate similarities in their innate immune systems as well as anatomical and physiological barriers, resembling those found in mammalian organisms.

Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture.

BACKGROUND: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 × data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function. RESULTS: We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection. CONCLUSIONS: We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.

Iron age genomic data from Althiburos - Tunisia renew the debate on the origins of African taurine cattle.

The Maghreb is a key region for understanding the dynamics of cattle dispersal and admixture with local aurochs following their earliest domestication in the Fertile Crescent more than 10,000 years ago. Here, we present data on autosomal genomes and mitogenomes obtained for four archaeological specimens of Iron Age (∼2,800 cal BP-2,000 cal BP) domestic cattle from the Eastern Maghreb, i.e. Althiburos (El Kef, Tunisia). D-loop sequences were obtained for an additional eight cattle specimens from this site. Maternal lineages were assigned to the elusive R and ubiquitous African-T1 haplogroups found in two and ten Althiburos specimens, respectively. Our results can be explained by post-domestication hybridization of Althiburos cattle with local aurochs. However, we cannot rule out an independent domestication in North Africa considering the shared ancestry of Althiburos cattle with the pre-domestic Moroccan aurochs and present-day African taurine cattle.

Exploring Prokaryotic Communities in the Guts and Mucus of Nudibranchs, and Their Similarity to Sediment and Seawater Microbiomes.

In the present study, we compared mucus and gut-associated prokaryotic communities from seven nudibranch species with sediment and seawater from Thai coral reefs using high-throughput 16S rRNA gene sequencing. The nudibranch species were identified as Doriprismatica atromarginata (family Chromodorididae), Jorunna funebris (family Discodorididae), Phyllidiella nigra, Phyllidiella pustulosa, Phyllidia carlsonhoffi, Phyllidia elegans, and Phyllidia picta (all family Phyllidiidae). The most abundant bacterial phyla in the dataset were Proteobacteria, Tenericutes, Chloroflexi, Thaumarchaeota, and Cyanobacteria. Mucus and gut-associated communities differed from one another and from sediment and seawater communities. Host phylogeny was, furthermore, a significant predictor of differences in mucus and gut-associated prokaryotic community composition. With respect to higher taxon abundance, the order Rhizobiales (Proteobacteria) was more abundant in Phyllidia species (mucus and gut), whereas the order Mycoplasmatales (Tenericutes) was more abundant in D. atromarginata and J. funebris. Mucus samples were, furthermore, associated with greater abundances of certain phyla including Chloroflexi, Poribacteria, and Gemmatimonadetes, taxa considered to be indicators for high microbial abundance (HMA) sponge species. Overall, our results indicated that nudibranch microbiomes consisted of a number of abundant prokaryotic members with high sequence similarities to organisms previously detected in sponges.