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Abstract Accurate short-term predictions of COVID-19 cases with empirical models allow Health Officials to prepare for hospital contingencies in a two–three week window given the delay between case reporting and the admission of patients in a hospital. We investigate the ability of Gompertz-type empiric models to provide accurate prediction up to two and three weeks to give a large window of preparation in case of a surge in virus transmission. We investigate the stability of the prediction and its accuracy using bi-weekly predictions during the last trimester of 2020 and 2021. Using data from 2020, we show that understanding and correcting for the daily reporting structure of cases in the different countries is key to accomplish accurate predictions. Furthermore, we found that filtering out predictions that are highly unstable to changes in the parameters of the model, which are roughly 20%, reduces strongly the number of predictions that are way-off. The method is then tested for robustness with data from 2021. We found that, for this data, only 1–2% of the one-week predictions were off by more than 50%. This increased to 3% for two-week predictions, and only for three-week predictions it reached 10%.

Abstract The public health emergency caused by the Covid-19 outbreak in March 2020 encouraged worldwide initiatives to monitor the genetic diversity and features of the SARS-CoV-2 circulating variants, mainly based on the genomic surveillance. However, due to the impossibility to carry out extensive sequencing in resource-limited hospitals, other PCR-based strategies could be applied to efficiently monitor the circulating variants without the need to greatly expand the sequencing capacity. In our case, overpassing the technical limitations inherent to a second level hospital, we were able to characterize the weekly distribution of SARS-CoV-2 by the RT-qPCR amplification patterns visualization, single nucleotide polymorphism genotyping, and sequencing of randomly selected samples. All these molecular approaches allowed us to trace the epidemiology of SARS-CoV-2 viruses circulating in Ibiza and Formentera (Balearic Islands, Spain) during the third to the sixth pandemic waves (January 2021–July 2022), in which three major lineages that were considered as VOCs (Alpha, Delta, and Omicron), and many other non-VOC variants were detected and tracked.

Abstract Iberian pigs and its crosses are produced to obtain high-quality meat products. The objective of this work was to evaluate a wide panel of DNA markers, selected by biological and functional criteria, for association with traits related to muscle growth, fatness, meat quality and metabolism. We used 18 crossbred Iberian pigs with divergent postnatal growth patterns for whole genome sequencing and SNP discovery, with over 13 million variants being detected. We selected 1023 missense SNPs located on annotated genes and showing different allele frequencies between pigs with makerdly different growth patterns. We complemented this panel with 192 candidate SNPs obtained from literature mining and from muscle RNAseq data. The selected markers were genotyped in 480 Iberian × Duroc pigs from a commercial population, in which phenotypes were obtained, and an association study was performed for the 1005 successfully genotyped SNPs showing segregation. The results confirmed the effects of several known SNPs in candidate genes (such as LEPR, ACACA, FTO, LIPE or SCD on fatness, growth and fatty acid composition) and also disclosed interesting effects of new SNPs in less known genes such as LRIG3, DENND1B, SOWAHB, EPHX1 or NFE2L2 affecting body weight, average daily gain and adiposity at different ages, or KRT10, NLE1, KCNH2 or AHNAK affecting fatness and FA composition. The results provide a valuable basis for future implementation of marker-assisted selection strategies in swine and contribute to a better understanding of the genetic architecture of relevant traits.

Abstract Plasma treatment is recognized as a suitable technology to improve germination efficiency of numerous seeds. In this work Quinoa seeds have been subjected to air plasma treatments both at atmospheric and low pressure and improvements found in germination rate and percentage of success. Seed water uptake by exposure to water vapor, although slightly greater for plasma treated seeds, did not justify the observed germination improvement. To identify other possible factors contributing to germination, the chemical changes experienced by outer parts of the seed upon plasma exposure have been investigated by X-ray photoemission spectroscopy (XPS) and scanning electron microscopy (SEM-EDX). XPS revealed that the outer layers of the Quinoa plasma treated seeds were highly oxidized and appeared enriched in potassium ions and adsorbed nitrate species. Simultaneously, SEM-EDX showed that the enrichment in potassium and other mineral elements extended to the seed pericarp and closer zones. The disappearance from the surface of both potassium ions and nitrate species upon exposure of the plasma treated seeds to water vapor is proposed as a factor favoring germination. The use of XPS to study chemical changes at seed surfaces induced by plasma treatments is deemed very important to unravel the mechanisms contributing to germination improvement.

Abstract Retention is a key element in HIV prevention programs. In Sub-Saharan Africa most data on retention come from HIV clinical trials or people living with HIV attending HIV treatment and control programs. Data from observational cohorts are less frequent. Retention at 6-/12-month follow-up and its predictors were analyzed in OKAPI prospective cohort. From April 2016 to April 2018, 797 participants aged 15–59 years attending HIV Voluntary Counseling and Testing in Kinshasa were interviewed about HIV-related knowledge and behaviors at baseline and at 6- and 12-month follow-ups. Retention rates were 57% and 27% at 6- and 12-month follow up; 22% of participants attended both visits. Retention at 6-month was significantly associated with 12-month retention. Retention was associated with low economic status, being studying, daily/weekly Internet access, previous HIV tests and aiming to share HIV test with partner. Contrarily, perceiving a good health, living far from an antiretroviral center, daily/weekly alcohol consumption and perceiving frequent HIV information were inversely associated with retention. In conclusion, a high attrition was found among people attending HIV testing participating in a prospective cohort in Kinshasa. Considering the low retention rates and the predictors found in this study, more HIV cohort studies in Kinshasa need to be evaluated to identify local factors and strategies that could improve retention if needed.

Abstract The eyelid motor system has been used for years as an experimental model for studying the neuronal mechanisms underlying motor and cognitive learning, mainly with classical conditioning procedures. Nonetheless, it is not known yet which brain structures, or neuronal mechanisms, are responsible for the acquisition, storage, and expression of these motor responses. Here, we studied the temporal correlation between unitary activities of identified eyelid and vibrissae motor cortex neurons and the electromyographic activity of the orbicularis oculi and vibrissae muscles and magnetically recorded eyelid positions during classical conditioning of eyelid and vibrissae responses, using both delay and trace conditioning paradigms in behaving mice. We also studied the involvement of motor cortex neurons in reflexively evoked eyelid responses and the kinematics and oscillatory properties of eyelid movements evoked by motor cortex microstimulation. Results show the involvement of the motor cortex in the performance of conditioned responses elicited during the classical conditioning task. However, a timing correlation analysis showed that both electromyographic activities preceded the firing of motor cortex neurons, which must therefore be related more with the reinforcement and/or proper performance of the conditioned responses than with their acquisition and storage.

Abstract Classical eyeblink conditioning is an experimental model widely used for the study of the neuronal mechanisms underlying the acquisition of new motor and cognitive skills. There are two principal interpretations of the role of the cerebellum in the learning of eyelid conditioned responses (CRs). One considers that the cerebellum is the place where this learning is acquired and stored, while the second suggests that the cerebellum is mostly involved in the proper performance of acquired CRs, implying that there must be other brain areas involved in the learning process. We checked the timing of cerebellar interpositus nucleus (IPN) neurons’ firing rate with eyelid CRs in both wild-type (WT) and Lurcher (a model of cerebellar cortex degeneration) mice. We used delay and trace conditioning paradigms. WT mice presented a better execution for delay vs. trace conditioning and also for these two paradigms than did Lurcher mice. IPN neurons were activated during CRs following the activation of the orbicularis oculi muscle. Firing patterns of IPN neurons were altered in Lurcher mice. In conclusion, the cerebellum seems to be mostly related with the performance of conditioned responses, rather than with their acquisition.

While epidemiological evidence has long linked obesity with an increased risk of breast cancer, the intricate interactions between adipocytes and cancer cells within the tumor microenvironment remain largely uncharted territory. The use of organotypic three-dimensional (3D) cell cultures that more accurately mimic the spatial architecture of tumors represents an innovative approach to this complex issue. In the present study, we investigated the effects of adipocytes on the proteome of Hs578t breast cancer cells cultured in a 3D microenvironment. Using different treatments, we rigorously optimized the experimental conditions to induce the optimal differentiation of 3T3-L1 fibroblasts into mature adipocytes. Then, we grow the Hs578t cells in a simulated microenvironment using an on-top model for organotypic 3D cultures. Our data showed that cancer cells formed 3D stellate-like architectures when grown over an extracellular matrix proteins-enriched scaffold for 48 h. Proteomic profiling using LC-MS/MS mass spectrometry of Hs578t cells grown in 3D conditions with or without the adipocyte-enriched culture discovered 916 unique proteins. Of these, 605 showed no significant changes in abundance, whereas 87 proteins were significantly upregulated and 224 downregulated after interaction with fat cells (p < 0.05, FC > 2.0). Bioinformatic analysis of upregulated proteins indicated that the most enriched GO terms and molecular functions were related to lipids transport, cell differentiation, hypoxia response, and cell junctions. In addition, several modulated proteins have been previously associated with breast cancer progression. Interestingly, lipid transport proteins, including PITPNM2, ATP2C1, ABCA12, HDLBP, and APOB, showed perturbations in their expression, which were also associated with low overall survival in breast cancer patients. Functional studies showed that the knockdown of apolipoprotein B (APOB) expression in Hs578t cells reduced the size of 3D cellular structures. Moreover, APOB-knocked cells cocultured with adipocytes for 48 h exhibited a significant decrease of intracellular lipids, whereas an increase in the adipocytes was found. Our results indicate that the 3D microenvironment and the adipocytes crosstalk reprogram the proteome of breast cancer cells. These data help us understand the environmental effects in gene expression and contribute to discovering novel tumor proteins with potential intervention in breast cancer therapy., (© 2024. The Author(s).)

The demersal fish orange roughy (Hoplostethus atlanticus) can live for up to 250 years, twenty times more than its congener silver roughy (Hoplostethus mediterraneus). Studies of Hoplostethus have focused mainly on its ecology and conservation due to its vulnerability to commercial fishing. In this work, we present the de novo genomes of orange and silver roughies and explore the genomic mechanisms that could contribute to such differential longevities. Using comparative genomics on a list of more than 400 genes, we identified gene candidates with differential residue changes in Hoplostethus that are related to genomic instability, disabled macroautophagy and intercellular communication. We hypothesized that these mechanisms could have been selected as adaptations to the deep environment and, as an epiphenomenon of these mechanisms, may have contributed to an extension of the lifespan of H. atlanticus., (© 2024. The Author(s).)

While brain size in primates and their relatives within Euarchontoglires is well-studied, less research has examined brain shape, or the allometric trajectories that underlie the relationship between size and shape. Defining these patterns is key to understanding evolutionary trends. 3D geometric morphometric analyses of endocranial shape were performed on 140 species of extant euarchontoglirans using digital cranial endocasts. Principal component analyses on Procrustes shape variables show a clear phylogenetic pattern in endocranial shape, supported by an ANOVA which identified significant differences in shape among several groups (e.g., Platyrrhini, Strepsirrhini, Scandentia, Rodentia, and Lagomorpha). ANOVAs of shape and size also indicate that allometry has a small but significant impact on endocranial shape across Euarchontoglires, with homogeneity of slopes tests finding significant differences in the scaling relationship between shape and size among these same groups. While most of these clades possess a distinct endocranial morphotype, the highly derived platyrrhines display the strongest relationship between size and shape. Rodents show the most diversity in endocranial shape, potentially attributed to their comparatively weak relationship between shape and size. These results suggest fundamental differences in how shape and size covary among Euarchontoglires, which may have facilitated the adaptive radiations that characterize members of this group., (© 2024. The Author(s).)

Accurate short-term predictions of COVID-19 cases with empirical models allow Health Officials to prepare for hospital contingencies in a two-three week window given the delay between case reporting and the admission of patients in a hospital. We investigate the ability of Gompertz-type empiric models to provide accurate prediction up to two and three weeks to give a large window of preparation in case of a surge in virus transmission. We investigate the stability of the prediction and its accuracy using bi-weekly predictions during the last trimester of 2020 and 2021. Using data from 2020, we show that understanding and correcting for the daily reporting structure of cases in the different countries is key to accomplish accurate predictions. Furthermore, we found that filtering out predictions that are highly unstable to changes in the parameters of the model, which are roughly 20%, reduces strongly the number of predictions that are way-off. The method is then tested for robustness with data from 2021. We found that, for this data, only 1-2% of the one-week predictions were off by more than 50%. This increased to 3% for two-week predictions, and only for three-week predictions it reached 10%., (© 2024. The Author(s).)

Here we present an improved, rapid method for filling quasi-nulls in symmetrical radiation patterns synthesized by equispaced linear arrays, leading to the generation of multiple solutions. Considering the polynomial representation of the pattern, this null-filling is achieved by displacing the roots radially off the unit circle, keeping a constant displacement. This allows analyzing how the potential solutions vary with the quasi-uniform filling and the associated directivity loss. This method is based on the Cardano-Vieta relations, which link the coefficients of a complex Schelkunoff polynomial with its roots. As examples of application, we have considered a 20/100 element Dolph-Chebyshev pattern, with a spacing between the elements [Formula: see text], side lobe level of - 20/- 28 dB and three inner sidelobes at - 40/- 50 dB., (© 2024. The Author(s).)

At the molecular level, triple-negative breast cancer (TNBC) is frequently categorized as PAM50 basal-like subtype, but despite the advances in molecular analyses, the clinical outcome for these subtypes is uncertain. Long non-coding RNAs (lncRNAs) are master regulators of genes involved in hallmarks of cancer, which makes them suitable biomarkers for breast cancer (BRCA) diagnosis and prognosis. Here, we evaluated the regulatory role of lncRNA SOX9-AS1 in these subtypes. Using the BRCA-TCGA cohort, we observed that SOX9-AS1 was significantly overexpressed in basal-like and TNBC in comparison with other BRCA subtypes. Survival analyzes showed that SOX9-AS1 overexpression was associated with a favorable prognosis in TNBC and basal-like patients. To study the functions of SOX9-AS1, we determined the expression levels in a panel of nine BRCA cell lines finding increased levels in MDA-MB-468 and HCC1187 TNBC. Using subcellular fractionation in these cell lines, we ascertained that SOX9-AS1 was located in the cytoplasmic compartment. In addition, we performed SOX9-AS1 gene silencing using two short-harping constructs, which were transfected in both cell models and performed a genome-wide RNA-seq analysis. Data showed that 351 lncRNAs and 740 mRNAs were differentially expressed in MDA-MB-468 while 56 lncRNAs and 100 mRNAs were modulated in HCC1187 cells (Log2FC < - 1.5 and > 1.5, p.adj value < 0.05). Pathway analysis revealed that the protein-encoding genes potentially regulate lipid metabolic reprogramming, and epithelial-mesenchymal transition (EMT). Expression of lipid metabolic-related genes LIPE, REEP6, GABRE, FBP1, SCD1, UGT2B11, APOC1 was confirmed by RT-qPCR. Functional analysis demonstrated that the knockdown of SOX9-AS1 increases the triglyceride synthesis, cell migration and invasion in both two TNBC cell lines. In conclusion, high SOX9-AS1 expression predicts an improved clinical course in patients, while the loss of SOX9-AS1 expression enhances the aggressiveness of TNBC cells., (© 2024. The Author(s).)

The public health emergency caused by the Covid-19 outbreak in March 2020 encouraged worldwide initiatives to monitor the genetic diversity and features of the SARS-CoV-2 circulating variants, mainly based on the genomic surveillance. However, due to the impossibility to carry out extensive sequencing in resource-limited hospitals, other PCR-based strategies could be applied to efficiently monitor the circulating variants without the need to greatly expand the sequencing capacity. In our case, overpassing the technical limitations inherent to a second level hospital, we were able to characterize the weekly distribution of SARS-CoV-2 by the RT-qPCR amplification patterns visualization, single nucleotide polymorphism genotyping, and sequencing of randomly selected samples. All these molecular approaches allowed us to trace the epidemiology of SARS-CoV-2 viruses circulating in Ibiza and Formentera (Balearic Islands, Spain) during the third to the sixth pandemic waves (January 2021-July 2022), in which three major lineages that were considered as VOCs (Alpha, Delta, and Omicron), and many other non-VOC variants were detected and tracked., (© 2023. Springer Nature Limited.)

MALAT1 long non-coding RNA has oncogenic roles but has been poorly studied in indolent B-cell neoplasms. Here, MALAT1 expression was analyzed using RNA-seq, microarrays or qRT-PCR in primary samples from clinico-biological subtypes of chronic lymphocytic leukemia (CLL, n = 266), paired Richter transformation (RT, n = 6) and follicular lymphoma (FL, n = 61). In peripheral blood (PB) CLL samples, high MALAT1 expression was associated with a significantly shorter time to treatment independently from other known prognostic factors. Coding genes expressed in association with MALAT1 in CLL were predominantly related to oncogenic pathways stimulated in the lymph node (LN) microenvironment. In RT paired samples, MALAT1 levels were lower, concordant with their acquired increased independency of external signals. Moreover, MALAT1 levels in paired PB/LN CLLs were similar, suggesting that the prognostic value of MALAT1 expression in PB is mirroring expression differences already present in LN. Similarly, high MALAT1 expression in FL predicted for a shorter progression-free survival, in association with expression pathways promoting FL pathogenesis. In summary, MALAT1 expression is related to pathophysiology and more aggressive clinical behavior of indolent B-cell neoplasms. Particularly in CLL, its levels could be a surrogate marker of the microenvironment stimulation and may contribute to refine the clinical management of these patients., (© 2023. Springer Nature Limited.)

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by RT-qPCR in an independent set of FFPE tissues with a reviewed diagnosis of CIN2+ (n = 105) and ≤ CIN1 (n = 105). The Ingenuity Pathway Analysis (IPA) was conducted to identify mRNAs inversely correlated with the top 25 differentially expressed miRNAs. Inverse correlations with 401 unique mRNA targets were identified for fourteen of the top 25 differentially expressed miRNAs. Eleven of these miRNAs targeted 26 proteins of pathways deregulated by HPV E6 and E7 oncoproteins and two of them, miR-143-5p and miR-29a-3p, predicted CIN2+ and CIN3+ in the independent validation by RT-qPCR of FFPE tissues from hrHPV-positive women., (© 2023. The Author(s).)

Dermatological conditions are a relevant health problem. Machine learning (ML) models are increasingly being applied to dermatology as a diagnostic decision support tool using image analysis, especially for skin cancer detection and disease classification. The objective of this study was to perform a prospective validation of an image analysis ML model, which is capable of screening 44 skin diseases, comparing its diagnostic accuracy with that of General Practitioners (GPs) and teledermatology (TD) dermatologists in a real-life setting. Prospective, diagnostic accuracy study including 100 consecutive patients with a skin problem who visited a participating GP in central Catalonia, Spain, between June 2021 and October 2021. The skin issue was first assessed by the GPs. Then an anonymised skin disease picture was taken and uploaded to the ML application, which returned a list with the Top-5 possible diagnosis in order of probability. The same image was then sent to a dermatologist via TD for diagnosis, as per clinical practice. The GPs Top-3, ML model's Top-5 and dermatologist's Top-3 assessments were compared to calculate the accuracy, sensitivity, specificity and diagnostic accuracy of the ML models. The overall Top-1 accuracy of the ML model (39%) was lower than that of GPs (64%) and dermatologists (72%). When the analysis was limited to the diagnoses on which the algorithm had been explicitly trained (n = 82), the balanced Top-1 accuracy of the ML model increased (48%) and in the Top-3 (75%) was comparable to the GPs Top-3 accuracy (76%). The Top-5 accuracy of the ML model (89%) was comparable to the dermatologist Top-3 accuracy (90%). For the different diseases, the sensitivity of the model (Top-3 87% and Top-5 96%) is higher than that of the clinicians (Top-3 GPs 76% and Top-3 dermatologists 84%) only in the benign tumour pathology group, being on the other hand the most prevalent category (n = 53). About the satisfaction of professionals, 92% of the GPs considered it as a useful diagnostic support tool (DST) for the differential diagnosis and in 60% of the cases as an aid in the final diagnosis of the skin lesion. The overall diagnostic accuracy of the model in this study, under real-life conditions, is lower than that of both GPs and dermatologists. This result aligns with the findings of few existing prospective studies conducted under real-life conditions. The outcomes emphasize the significance of involving clinicians in the training of the model and the capability of ML models to assist GPs, particularly in differential diagnosis. Nevertheless, external testing in real-life conditions is crucial for data validation and regulation of these AI diagnostic models before they can be used in primary care., (© 2023. The Author(s).)

The purpose of this study is to compare axial rotation range of motion for the upper cervical spine during three movements: axial rotation, rotation + flexion + ipsilateral lateral bending and rotation + extension + contralateral lateral bending before and after occiput-atlas (C0-C1) stabilization. Ten cryopreserved C0-C2 specimens (mean age 74 years, range 63-85 years) were manually mobilized in 1. axial rotation, 2. rotation + flexion + ipsilateral lateral bending and 3. rotation + extension + contralateral lateral bending without and with a screw stabilization of C0-C1. Upper cervical range of motion and the force used to generate the motion were measured using an optical motion system and a load cell respectively. The range of motion (ROM) without C0-C1 stabilization was 9.8° ± 3.9° in right rotation + flexion + ipsilateral lateral bending and 15.5° ± 5.9° in left rotation + flexion + ipsilateral lateral bending. With stabilization, the ROM was 6.7° ± 4.3° and 13.6° ± 5.3°, respectively. The ROM without C0-C1 stabilization was 35.1° ± 6.0° in right rotation + extension + contralateral lateral bending and 29.0° ± 6.5° in left rotation + extension + contralateral lateral bending. With stabilization, the ROM was 25.7° ± 6.4° (p = 0.007) and 25.3° ± 7.1°, respectively. Neither rotation + flexion + ipsilateral lateral bending (left or right) or left rotation + extension + contralateral lateral bending reached statistical significance. ROM without C0-C1 stabilization was 33.9° ± 6.7° in right rotation and 28.0° ± 6.9° in left rotation. With stabilization, the ROM was 28.5° ± 7.0° (p = 0.005) and 23.7° ± 8.5° (p = 0.013) respectively. The stabilization of C0-C1 reduced the upper cervical axial rotation in right rotation + extension + contralateral lateral bending and right and left axial rotations; however, this reduction was not present in left rotation + extension + contralateral lateral bending or both combinations of rotation + flexion + ipsilateral lateral bending., (© 2023. The Author(s).)

Escherichia coli glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) are key enzymes of the pentose phosphate pathway, responsible for the NADPH production in cells. We investigated modification of both enzymes mediated by peroxyl radicals (ROO · ) to determine their respective susceptibilities to and mechanisms of oxidation. G6PDH and 6PGDH were incubated with AAPH (2,2'-azobis(2-methylpropionamidine)dihydrochloride), which was employed as ROO · source. The enzymatic activities of both enzymes were determined by NADPH release, with oxidative modifications examined by electrophoresis and liquid chromatography (LC) with fluorescence and mass (MS) detection. The activity of G6PDH decreased up to 62.0 ± 15.0% after 180 min incubation with 100 mM AAPH, whilst almost total inactivation of 6PGDH was determined under the same conditions. Although both proteins contain abundant Tyr (particularly 6PGDH), these residues were minimally affected by ROO · , with Trp and Met being major targets. LC-MS and in silico analysis showed that the modification sites of G6PDH are distant to the active site, consistent with a dispersed distribution of modifications, and inactivation resulting from oxidation of multiple Trp and Met residues. In contrast, the sites of oxidation detected on 6PGDH are located close to its catalytic site indicating a more localized oxidation, and a consequent high susceptibility to ROO · -mediated inactivation., (© 2022. The Author(s).)

Iberian pigs and its crosses are produced to obtain high-quality meat products. The objective of this work was to evaluate a wide panel of DNA markers, selected by biological and functional criteria, for association with traits related to muscle growth, fatness, meat quality and metabolism. We used 18 crossbred Iberian pigs with divergent postnatal growth patterns for whole genome sequencing and SNP discovery, with over 13 million variants being detected. We selected 1023 missense SNPs located on annotated genes and showing different allele frequencies between pigs with makerdly different growth patterns. We complemented this panel with 192 candidate SNPs obtained from literature mining and from muscle RNAseq data. The selected markers were genotyped in 480 Iberian × Duroc pigs from a commercial population, in which phenotypes were obtained, and an association study was performed for the 1005 successfully genotyped SNPs showing segregation. The results confirmed the effects of several known SNPs in candidate genes (such as LEPR, ACACA, FTO, LIPE or SCD on fatness, growth and fatty acid composition) and also disclosed interesting effects of new SNPs in less known genes such as LRIG3, DENND1B, SOWAHB, EPHX1 or NFE2L2 affecting body weight, average daily gain and adiposity at different ages, or KRT10, NLE1, KCNH2 or AHNAK affecting fatness and FA composition. The results provide a valuable basis for future implementation of marker-assisted selection strategies in swine and contribute to a better understanding of the genetic architecture of relevant traits., (© 2022. The Author(s).)

Capacitive-resistive energy transfer therapy (CRet) is used to improve the rehabilitation of different injuries. This study aimed to evaluate and compare the changes in temperature and current flow during different CRet applications on upper and lower molars and incisors, with and without implants, on ten cryopreserved corpses. Temperatures were taken on molars and incisors with invasive devices and skin temperature was taken with a digital thermometer at the beginning and after treatments. Four interventions: 15 VA capacitive hypothermic (CAPH), 8 watts resistive (RES8), 20 watts resistive (RES20) and 75 VA capacitive (CAP75) were performed for 5 min each. All treatments in this study generated current flow (more than 0.00005 A/m 2 ) and did not generate a significant temperature increase (p > 0.05). However, RES20 application slightly increased surface temperature on incisors without implants (p = 0.010), and molar with (p = 0.001) and without implant (p = 0.008). Also, CAP75 application increased surface temperature on molars with implant (p = 0.002) and upper incisor with implant (p = 0.001). In conclusion, RES8 and CAPH applications seem to be the best options to achieve current flow without an increase in temperature on molars and incisors with and without implants., (© 2022. The Author(s).)

The glucagon-like peptide-1 receptor agonist family together with the renal sodium/glucose cotransporter-2 inhibitors have garnered interest as potential therapeutic agents for subjects with type 2 diabetes and obesity. In these patients, bariatric surgery is indicated based in a BMI ≥ 35 kg/m 2 . A 24-week non-blinded, randomized pilot study to assess the efficacy of subcutaneous exenatide 2.0 mg once weekly plus oral dapagliflozin 10 mg once daily (Group A) compared to a control group (Group B) in 56 patients with type 2 diabetes awaiting bariatric surgery was conducted (EudraCTid.: 2017-001,454-33). Both groups received an energy-deficit low-fat diet. The primary endpoint was the proportion of patients running off the criteria for bariatric surgery at the end of the follow-up period (BMI ≤ 35.0 kg/m 2 or a BMI ≤ 40.0 kg/m 2 plus an HbA1c ≤ 6.0%). Changes in the BMI were also of interest. The proportion of patients who ran off the criteria for bariatric surgery was larger in Group A than in the control group (45.8% vs. 12.0%, p = 0.010). Participants in Group A exhibited an absolute decrease in body weight and BMI of 8.1 kg (95%IC: - 11.0 to - 5.2) and 3.3 kg/m 2 (95%IC: - 4.5 to - 2.2), respectively (p < 0.001 for both in comparison with Group B). A higher percentage of participants in Group A reached a BMI < 35 kg/m 2 (45.8 vs 12.0%) and lost > 10% of their initial body weight (20.8 vs 0%) compared to Group B. The combination of exenatide plus dapagliflozin appears as a strategic option to reduce the waiting list for bariatric surgery, especially in those patients with type 2 diabetes., (© 2022. The Author(s).)

Subspecies are widely included as conservation units because of their potential to become new species. However, their practical recognition includes variable criteria, such as morphological, genetic, geographic and other differences. Centaurea aspera ssp. scorpiurifolia is a threatened taxon endemic to Andalusia (Spain), which coexists in most of its distribution area with similar taxa. Because of the difficulty to identify it using morphology alone, we aimed to sample all the populations cited as ssp. scorpiurifolia as exhaustively as possible, morphologically characterise them, and analyse their genetic structuring using microsatellites, to better understand difficulties when conserving subspecies. Three different Centaurea species were found which were easily identified. Within C. aspera, two genetic populations and some admixed individuals were observed, one including ssp. scorpiurifolia individuals and the other including individuals identified as subspecies aspera, stenophylla, and scorpiurifolia. A morphological continuum between these two genetic populations and a wide overlapping of their biogeographic distribution were also found. This continuum can affect the conservation of ssp. scorpiurifolia because of potential misidentifications and harmful effects of subspecific hybridization. Misidentifications could be partly overcome by using as many different traits as possible, and conservation priority should be given to populations representative of the ends of this continuum., (© 2022. The Author(s).)

The aims of the study were (1) to compare the cure risk of intramammary treatment of pure platelet rich plasma (P-PRP) or cefquinome sulfate (CS) in cows with subclinical mastitis (SCM) caused by Gram-positive bacteria, evaluated via somatic cell count (SCC) and the microbiological analysis of milk; (2) to compare the inflammatory/anti-inflammatory response of mammary gland to both treatments through the analyses of interleukins (IL), interferon gamma (IFN-γ), and tumour necrosis factor alpha (TNF-α) in milk. A non-inferiority randomized clinical trial was conducted. The null hypothesis was that cure risk in the experimental group (P-PRP) was inferior to the reference group (CS). A total of 103 cows were selected according to SCC and presence of Gram-positive bacteria, 49 cows were treated with CS and 54 cows were treated with P-PRP after determination of its cellular and molecular quality control. Cure was assessed by milk analyses at day 21 and 22 after treatment. Cows that remained with SCM were retreated at day 26, and cure assessed at day 47 and 48. Overall, bacteriological cure was observed in 16 cows (30%) of the P-PRP group, and 35 cows (71%) in CS group. Staphylococcus aureus cure risk was higher in CS group, but inconclusive for Streptococcus spp. The mean SCC increased in relation to time only in the P-PRP group. A direct relation between time and treatment for IL-1, IL-2, and IL-6 was observed, while no differences were observed for IL-4. Furthermore, IL-1 and IL-2 increased in cows treated twice in both groups. IL-8, IFN-γ, and TNF-α showed a significant interaction between time and treatment. IFN-γ concentration was lower in the P-PRP group compared to the CS on days 0 and 22. Leukocyte counts were lower in P-PRP when compared to whole blood. TGF-β1 and PF4 concentrations were higher in platelet lysates in comparison to P-PRGS and plasma. Moreover, PDGF-BB concentration was significantly higher in platelet lysates in comparison to plasma. Results obtained in this study demonstrate that SCM treated with PRP showed a lower rate of bacteriologic cure when compared to animals treated with CS., (© 2021. The Author(s).)

Ceftolozane/tazobactam (C/T) has emerged as a potential agent for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. As it is a time-dependent antimicrobial, prolonged infusion may help achieve pharmacokinetic/pharmacodynamic (PK/PD) targets. To compare alternative steady-state concentrations (Css) of C/T in continuous infusion (CI) against three XDR P. aeruginosa ST175 isolates with C/T minimum inhibitory concentration (MIC) values of 2 to 16 mg/L in a hollow-fiber infection model (HFIM). Duplicate 10-day HFIM assays were performed to evaluate Css of C/T in CI: one compared 20 and 45 mg/L against the C/T-susceptible isolate while the other compared 45 and 80 mg/L against the two C/T-non-susceptible isolates. C/T resistance emerged when C/T-susceptible isolate was treated with C/T in CI at a Css of 20 mg/L; which showed a deletion in the gene encoding AmpC β-lactamase. The higher dosing regimen (80 mg/L) showed a slight advantage in effectiveness. The higher dosing regimen has the greatest bactericidal effect, regardless of C/T MIC. Exposure to the suboptimal Css of 20 mg/L led to the emergence of C/T resistance in the susceptible isolate. Antimicrobial regimens should be optimized through C/T levels monitoring and dose adjustments to improve clinical management., (© 2021. The Author(s).)

Malaria is a highly prevalent parasitic disease in regions with tropical and subtropical climates worldwide. Among the species of Plasmodium causing human malaria, P. vivax is the second most prevalent and the most geographically widespread species. A major target of a pre-erythrocytic vaccine is the P. vivax circumsporozoite protein (PvCSP). In previous studies, we fused two recombinant proteins representing three allelic variants of PvCSP (VK210, VK247 and P. vivax-like) to the mumps virus nucleocapsid protein to enhance immune responses against PvCSP. The objective of the present study was to evaluate the protective efficacy of these recombinants in mice challenged with transgenic P. berghei parasites expressing PvCSP allelic variants. Formulations containing Poly (I:C) or Montanide ISA720 as adjuvants elicited high and long-lasting IgG antibody titers specific to each PvCSP allelic variant. Immunized mice were challenged with two existing chimeric P. berghei parasite lines expressing PvCSP-VK210 and PvCSP-VK247. We also developed a novel chimeric line expressing the third allelic variant, PvCSP-P. vivax-like, as a new murine immunization-challenge model. Our formulations conferred partial protection (significant delay in the time to reach 1% parasitemia) against challenge with the three chimeric parasites. Our results provide insights into the development of a vaccine targeting multiple strains of P. vivax., (© 2021. The Author(s).)

This study compares upper cervical spine range of motion (ROM) in the three cardinal planes before and after occiput-atlas (C0-C1) stabilization. After the dissection of the superficial structures to the alar ligament and the fixation of C2, ten cryopreserved upper cervical columns were manually mobilized in the three cardinal planes of movement without and with a screw stabilization of C0-C1. Upper cervical ROM and mobilization force were measured using the Vicon motion capture system and a load cell respectively. The ROM without C0-C1 stabilization was 19.8° ± 5.2° in flexion and 14.3° ± 7.7° in extension. With stabilization, the ROM was 11.5° ± 4.3° and 6.6° ± 3.5°, respectively. The ROM without C0-C1 stabilization was 4.7° ± 2.3° in right lateral flexion and 5.6° ± 3.2° in left lateral flexion. With stabilization, the ROM was 2.3° ± 1.4° and 2.3° ± 1.2°, respectively. The ROM without C0-C1 stabilization was 33.9° ± 6.7° in right rotation and 28.0° ± 6.9° in left rotation. With stabilization, the ROM was 28.5° ± 7.0° and 23.7° ± 8.5° respectively. Stabilization of C0-C1 reduced the upper cervical ROM by 46.9% in the sagittal plane, 55.3% in the frontal plane, and 15.6% in the transverse plane. Also, the resistance to movement during upper cervical mobilization increased following C0-C1 stabilization.

We study the effect that disturbances in the ecological landscape exert on the spatial distribution of a population that evolves according to the nonlocal FKPP equation. Using both numerical and analytical techniques, we characterize, as a function of the interaction kernel, the three types of stationary profiles that can develop near abrupt spatial variations in the environmental conditions vital for population growth: sustained oscillations, decaying oscillations and exponential relaxation towards a flat profile. Through the mapping between the features of the induced wrinkles and the shape of the interaction kernel, we discuss how heterogeneities can reveal information that would be hidden in a flat landscape.

Capacitive-resistive electric transfer therapy is used in physical rehabilitation and sports medicine to treat muscle, bone, ligament and tendon injuries. The purpose is to analyze the temperature change and transmission of electric current in superficial and deep knee tissues when applying different protocols of capacitive-resistive electric transfer therapy. Five fresh frozen cadavers (10 legs) were included in this study. Four interventions (high/low power) were performed for 5 min by a physiotherapist with experience. Dynamic movements were performed to the posterior region of the knee. Capsular, intra-articular and superficial temperature were recorded at 1-min intervals and 5 min after the treatment, using thermocouples placed with ultrasound guidance. The low-power protocols had only slight capsular and intra-capsular thermal effects, but electric current flow was observed. The high-power protocols achieved a greater increase in capsular and intra-articular temperature and a greater current flow than the low-power protocols. The information obtained in this in vitro study could serve as basic science data to hypothesize capsular and intra-articular knee recovery in living subjects. The current flow without increasing the temperature in inflammatory processes and increasing the temperature of the tissues in chronic processes with capacitive-resistive electric transfer therapy could be useful for real patients.

The dynamic knee valgus (DKV) during different sport maneuvers has been widely described as risk factor to develop an anterior cruciate ligament injury. Hip and knee muscles seem to have a crucial role to prevent the dynamic knee valgus. This study aimed to give normative and correlational data about DKV and hip and knee neuromuscular response (NMR) among healthy active males. The hypothesis is that DKV could be correlated with hip NMR. A cross-sectional correlational study. Research Anatomy Laboratory. The study was carried out among 50 active, non-injured males. Dynamic Knee-Valgus angle and lower limb posterior chain muscles Neuromuscular Response. DKV was measured using Kinovea software during a Single-Legged Drop Jump test and NMR was measured using tensiomyography and myotonometry for gluteus maximum, biceps femoris, semitendinosus, lateral and medial gastrocnemius. Right and left limbs were both performed and analyzed independently. No significant correlation was observed between DKV and hip and knee muscles NMR. This study shows normative and correlational data about dynamic knee valgus, tensiomyography and myotonometry for healthy and active males. The DKV control seems to be non-correlated with isolated hip and knee muscles NMR so this suggests it is more about Central Nervous System activity than about isolated muscles NMR.

Circumsporozoite protein (CSP) variants of P. vivax, besides having variations in the protein repetitive portion, can differ from each other in aspects such as geographical distribution, intensity of transmission, vectorial competence and immune response. Such aspects must be considered to P. vivax vaccine development. Therefore, we evaluated the immunogenicity of novel recombinant proteins corresponding to each of the three P. vivax allelic variants (VK210, VK247 and P. vivax-like) and of the C-terminal region (shared by all PvCSP variants) in naturally malaria-exposed populations of Brazilian Amazon. Our results demonstrated that PvCSP-VK210 was the major target of humoral immune response in studied population, presenting higher frequency and magnitude of IgG response. The IgG subclass profile showed a prevalence of cytophilic antibodies (IgG1 and IgG3), that seem to have an essential role in protective immune response. Differently of PvCSP allelic variants, antibodies elicited against C-terminal region of protein did not correlate with epidemiological parameters, bringing additional evidence that humoral response against this protein region is not essential to protective immunity. Taken together, these findings increase the knowledge on serological response to distinct PvCSP allelic variants and may contribute to the development of a global and effective P. vivax vaccine.

Oxidative stress and inflammatory cytokines affect the human brain, increasing the risk for mood and cognitive disorders. Such risk might be selective to brain-specific regions. Here, we determined whether BXD recombinant inbred (RI) mice strains are more suitable than C57BL/6J mice for the understanding of the relationship between antioxidant response and inflammatory responses. We hypothesized that inflammatory responses could be independent of antioxidant response and be inherent to brain-specific regions. This hypothesis will be addressed by the analyses of mRNA expression. We explored, at 7-months-of-age, the innate activation of proinflammatory cytokines (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), as well as Kelch-like ECH-associating protein 1 (Keap1), nuclear factor erythroid 2 related factor 2 (Nrf2) and glutathione peroxidase 1 (Gpx1) mRNA in both male and female BXD84/RwwJ RI, BXD21/TyJ RI and control strain (C57BL/6J mice). We report that: (1) The cerebellum is more sensitive to antioxidant response in the BXD21/TyJ RI strain; (2) The cerebellum, hippocampus and striatum show increased levels of cytokines in the BXD21/TyJ RI strain; (3) The BXD RI strain has lower brain weight relative to control strain (C57BL/6 mice). In conclusion, our novel data show the utility of the BXD21/TyJ RI strain mice in offering mechanistic insight into Nrf2's role in the inflammatory system.

Chemotherapy activates a novel cytoplasmic DNA damage response resulting in Golgi apparatus fragmentation and cancer cell survival. This mechanism is regulated by Golgi phosphoprotein-3 (GOLPH3)/Myo18A/F-actin axis. Analyzing the functions of miR-3135b, a small non-coding RNA with unknown functions, we found that its forced overexpression attenuates the Golgi apparatus fragmentation induced by chemotherapeutic drugs in colorectal cancer (CRC) cells. First, we found that miR-3135b is downregulated in CRC cell lines and clinical tumors. Bioinformatic predictions showed that miR-3135b could be regulating protein-encoding genes involved in cell survival, resistance to chemotherapy, and Golgi dynamics. In agreement, ectopic transfection of miR-3135b in HCT-15 cancer cells significantly inhibited cell proliferation, sensitized cells to 5-fluoruracil (5-FU), and promoted late apoptosis and necrosis. Also, miR-3135b overexpression impaired the cell cycle progression in HCT-15 and SW-480 cancer cells. Because GOLPH3, a gene involved in maintenance of Golgi structure, was predicted as a potential target of miR-3135b, we studied their functional relationships in response to DNA damage induced by chemotherapy. Immunofluorescence and cellular ultrastructure experiments using antibodies against TGN38 protein, a trans-Golgi network marker, showed that 5-FU and doxorubicin treatments result in an apoptosis-independent stacks dispersal of the Golgi ribbon structure in both HCT-15 and SW-480 cells. Remarkably, these cellular effects were dramatically hindered by transfection of miR-3135b mimics. In addition, our functional studies confirmed that miR-3135b binds to the 3'-UTR of GOLPH3 proto-oncogene, and also reduces the levels of p-AKT1 (Ser473) and p-mTOR (Ser2448) signaling transducers, which are key in cell survival and autophagy activation. Moreover, we found that after treatment with 5-FU, TGN38 factor coimmunolocalizes with beclin-1 autophagic protein in discrete structures associated with the fragmented Golgi, suggesting that the activation of pro-survival autophagy is linked to loss of Golgi integrity. These cellular effects in autophagy and Golgi dispersal were reversed by miR-3135b. In summary, we provided experimental evidence suggesting for the first time a novel role for miR-3135b in the protection of chemotherapy-induced Golgi fragmentation via GOLPH3/AKT1/mTOR axis and protective autophagy in colorectal cancer cells.

Two paroxysmal explosions occurred at Stromboli volcano in the Summer 2019, the first of which, on July 3, caused one fatality and some injuries. Within the 56 days between the two paroxysmal explosions, effusive activity from vents located in the summit area of the volcano occurred. No significant changes in routinely monitored parameters were detected before the paroxysmal explosions. However, we have calculated the polarization and the fractal dimension time series of the seismic signals from November 15, 2018 to September 15, 2019 and we have recognized variations that preceded the paroxysmal activity. In addition, we have defined a new parameter, based on RSAM estimation, related to the Very Long Period events, called VLP size, by means of which we have noticed significant variations through the whole month preceding the paroxysm of July 3. In the short term, we have analyzed the signals of a borehole strainmeter installed on the island, obtaining automatic triggers 10 minutes and 7.5 minutes before the July 3 and the August 28 paroxysms, respectively. The results of this study highlight mid-term seismic precursors of paroxysmal activity and provide valuable evidence for the development of an early warning system for paroxysmal explosions based on strainmeter measurements.

Autophagy is an evolutionarily conserved process that plays a key role in the maintenance of overall cellular health. While it has been suggested that autophagy may elicit cardioprotective and pro-survival modulating functions, excessive activation of autophagy can also be detrimental. In this regard, the zebrafish is considered a hallmark model for vertebrate regeneration, since contrary to adult mammals, it is able to faithfully regenerate cardiac tissue. Interestingly, the role that autophagy may play in zebrafish heart regeneration has not been studied yet. In the present work, we hypothesize that, in the context of a well-established injury model of ventricular apex resection, autophagy plays a critical role during cardiac regeneration and its regulation can directly affect the zebrafish regenerative potential. We studied the autophagy events occurring upon injury using electron microscopy, in vivo tracking of autophagy markers, and protein analysis. Additionally, using pharmacological tools, we investigated how rapamycin, an inducer of autophagy, affects regeneration relevant processes. Our results show that a tightly regulated autophagic response is triggered upon injury and during the early stages of the regeneration process. Furthermore, treatment with rapamycin caused an impairment in the cardiac regeneration outcome. These findings are reminiscent of the pathophysiological description of an injured human heart and hence put forward the zebrafish as a model to study the poorly understood double-sword effect that autophagy has in cardiac homeostasis.

Gestational Diabetes Mellitus (GDM) is characterised by insulin resistance accompanied by reduced beta-cell compensation to increased insulin demand, typically observed in the second and third trimester and associated with adverse pregnancy outcomes. There is a need for a biomarker that can accurately monitor status and predict outcome in GDM, reducing foetal-maternal morbidity and mortality risks. To this end, circulating microRNAs (miRNAs) present themselves as promising candidates, stably expressed in serum and known to play crucial roles in regulation of glucose metabolism. We analysed circulating miRNA profiles in a cohort of GDM patients (n = 31) and nondiabetic controls (n = 29) during the third trimester for miRNA associated with insulin-secretory defects and glucose homeostasis. We identified miR-330-3p as being significantly upregulated in lean women with GDM compared to nondiabetic controls. Furthermore, increased levels of miR-330-3p were associated with better response to treatment (diet vs. insulin), with lower levels associated with exogenous insulin requirement. We observed miR-330-3p to be significantly related to the percentage of caesarean deliveries, with miR-330-3p expression significantly higher in spontaneously delivered GDM patients. We report this strong novel association of circulating miR-330-3p with risk of primary caesarean delivery as a pregnancy outcome linked with poor maternal glycaemic control, strengthening the growing body of evidence for roles of diabetes-associated miRNAs in glucose homeostasis and adaptation to the complex changes related to pregnancy.

Eco-evolutionary frameworks can explain certain features of communities in which ecological and evolutionary processes occur over comparable timescales. Here, we investigate whether an evolutionary dynamics may interact with the spatial structure of a prey-predator community in which both species show limited mobility and predator perceptual ranges are subject to natural selection. In these conditions, our results unveil an eco-evolutionary feedback between species spatial mixing and predators perceptual range: different levels of mixing select for different perceptual ranges, which in turn reshape the spatial distribution of prey and its interaction with predators. This emergent pattern of interspecific interactions feeds back to the efficiency of the various perceptual ranges, thus selecting for new ones. Finally, since prey-predator mixing is the key factor that regulates the intensity of predation, we explore the community-level implications of such feedback and show that it controls both coexistence times and species extinction probabilities.

To evaluate the effectiveness of the different insulin therapies on obstetrics-fetal outcomes in women with pregestational diabetes mellitus. We enrolled 147 pregnant women with pre-existing type 1 or 2 diabetes mellitus. Clinical and biochemical parameters were analysed in relation to obstetric and fetal outcomes. 14.2% received treatment with Neutral Protamine Hagedorn insulin and short-acting insulin analogues; 19% with premixed human insulin; 40.1% with insulin glargine and lispro, 6.2% with detemir and aspart and 20% with continuous subcutaneous insulin infusion. All 5 types of treatment achieved a reduction of the mean HbA1c during pregnancy (p = 0.01). Pre-pregnancy care was carried out for 48% of patients. We found no statistically significant differences between the different insulin therapies and the obstetric-fetal outcomes. In conclusión, the different insulin therapies used in patients with pregestational diabetes mellitus does not seem to affect obstetric-fetal outcomes.

CRISPR/Cas9 system has been widely applied in many plant species to induce mutations in the genome for studying gene function and improving crops. However, to our knowledge, there is no report of CRISPR/Cas9-mediated genome editing in melon (Cucumis melo). In our study, phytoene desaturase gene of melon (CmPDS) was selected as target for the CRISPR/Cas9 system with two designed gRNAs, targeting exons 1 and 2. A construct (pHSE-CmPDS) carrying both gRNAs and the Cas9 protein was delivered by PEG-mediated transformation in protoplasts. Mutations were detected in protoplasts for both gRNAs. Subsequently, Agrobacterium-mediated transformation of cotyledonary explants was carried out, and fully albino and chimeric albino plants were successfully regenerated. A regeneration efficiency of 71% of transformed plants was achieved from cotyledonary explants, a 39% of genetic transformed plants were successful gene edited, and finally, a 42-45% of mutation rate was detected by Sanger analysis. In melon protoplasts and plants most mutations were substitutions (91%), followed by insertions (7%) and deletions (2%). We set up a CRISPR/Cas9-mediated genome editing protocol which is efficient and feasible in melon, generating multi-allelic mutations in both genomic target sites of the CmPDS gene showing an albino phenotype easily detectable after only few weeks after Agrobacterium-mediated transformation.

We study a system of active particles with soft repulsive interactions that lead to an active cluster-crystal phase in two dimensions. We use two different modelizations of the active force - Active Brownian particles (ABP) and Ornstein-Uhlenbeck particles (AOUP) - and focus on analogies and differences between them. We study the different phases appearing in the system, in particular, the formation of ordered patterns drifting in space without being altered. We develop an effective description which captures some properties of the stable clusters for both ABP and AOUP. As an additional point, we confine such a system in a large channel, in order to study the interplay between the cluster crystal phase and the well-known accumulation near the walls, a phenomenology typical of active particles. For small activities, we find clusters attached to the walls and deformed, while for large values of the active force they collapse in stripes parallel to the walls.

Tardigrades, also known as water bears, are small aquatic animals that inhabit marine, fresh water or limno-terrestrial environments. While all tardigrades require surrounding water to grow and reproduce, species living in limno-terrestrial environments (e.g. Ramazzottius varieornatus) are able to undergo almost complete dehydration by entering an arrested state known as anhydrobiosis, which allows them to tolerate ionic radiation, extreme temperatures and intense pressure. Previous studies based on comparison of the genomes of R. varieornatus and Hypsibius dujardini - a less tolerant tardigrade - have pointed to potential mechanisms that may partially contribute to their remarkable ability to resist extreme physical conditions. In this work, we have further annotated the genomes of both tardigrades using a guided approach in search for novel mechanisms underlying the extremotolerance of R. varieornatus. We have found specific amplifications of several genes, including MRE11 and XPC, and numerous missense variants exclusive of R. varieornatus in CHEK1, POLK, UNG and TERT, all of them involved in important pathways for DNA repair and telomere maintenance. Taken collectively, these results point to genomic features that may contribute to the enhanced ability to resist extreme environmental conditions shown by R. varieornatus.

Porcine circovirus type 2 (PCV2) is the aetiological agent of PCV2-Systemic Disease (PCV2-SD) and PCV2-Subclinical Infection (PCV2-SI). PCV2 is highly resistant to environmental conditions, being able to remain in the farm environment and thus represent a risk for infection maintenance. The aim of this study was to identify, under field conditions, the possible critical points in the environment of non-vaccinated farrow-to-weaning swine farms where PCV2 could accumulate and persist. For that, environmental samples from five swine farms with PCV2-SD or PCV2-SI were taken and analysed by qPCR, including different farm areas, farm personnel and management implements. PCV2 DNA was detected in the environment of all farms (42.9% of positive samples). Overall, the PCV2-SD herd seemed to present more positive samples and higher viral loads than the PCV2-SI herds. At individual farm level, weaning areas appeared to be the most contaminated facilities. In addition, PCV2 was found at high levels in most samples from farm workers, especially work boots, suggesting that they may play a role in within-farm transmission. In addition, PCV2 was detected in areas without animals the like warehouses, offices and farm perimeter. Therefore, this study is helpful to improve measures to reduce within-farm PCV2 dissemination.

Migratory birds usually respond to climate change by modifying breeding and/or wintering areas, as well as by reproducing earlier. In addition, changes in winter habitat use or breeding phenology could have important carry-over effects on subsequent breeding success. Here, we studied age- and sex-dependent carry-over effects from wintering to the breeding stage of a small aerial insectivorous long-distance migratory bird, the barn swallows (Hirundo rustica) breeding in Denmark during 1984-2013. First, we used stable isotope analyses combined with ringing recoveries to identify wintering areas. Second, we found that environmental conditions as inferred by Normalized Differential Vegetation Index (NDVI) have deteriorated at the wintering grounds. Third, we used confirmatory path analysis to quantify the indirect effect of winter conditions on subsequent breeding success. Females advanced onset of breeding, laid more eggs and raised more fledglings in the first brood when ecological conditions during the previous winter improved. This response was age dependent, since yearlings did not respond to this environmental cue but the response was increasingly stronger as females aged. Males showed a similar response to winter conditions, although not statistically significant. These results highlight the importance of studying carry-over effects within the context of climate change, especially in relation to age of individuals.

In untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4 + T cell counts. HIV-1 envelope glycoprotein complex (Env) is a major cytopathic determinant in viral replication; therefore, we have deeply characterized Env function in this rare clinical phenotype. Full-length Env clones isolated from individuals with Viral Load (VL) > 10,000 copies/mL classified as VNPs (n = 15) or rapid progressors (RPs, n = 17) were geno- and phenotypically analyzed by determining diversity, expression, CD4 binding/signaling, fusogenicity, infectivity and autophagy induction. Selected Env clones from VNPs and RPs (n = 32) showed similar expression, fusion and infection abilities. Env clones from both groups showed similar affinity for CD4 during cell-to-cell transmission and consistently induced similar levels of CD4 signaling, measured by α-tubulin acetylation. Moreover, we demonstrate for the first time that primary Env clones from VNP and RP induce autophagy in uninfected cells and that this feature correlated with fusogenic capacity but was unrelated to disease progression. In conclusion, our data suggest that Env clones from VNP individuals are fully functional. Therefore, the paradoxical CD4 + T cell count stability coexisting with high levels of viral replication is unrelated to Env function.