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Despite decades of research and handling of semen for use in artificial insemination (AI) and other assisted reproductive technologies, 5-10% of selected boar sires are still considered sub-fertile, escaping current assessment methods for sperm quality and resilience to preservation. As end-product, the ejaculate (emitted spermatozoa sequentially exposed to the composite seminal plasma, the SP) ought to define the homeostasis of the testes, the epididymis, and the accessory sexual glands. Yet, linking findings in the ejaculate to sperm production biology and fertility is suboptimal. The present essay critically reviews how the ejaculate of a fertile boar can help us to diagnose both reproductive health and resilience to semen handling, focusing on methods -available and under development- to identify suitable biomarkers for cryotolerance and fertility. Bulk SP, semen proteins and microRNAs (miRNAs) have, albeit linked to sperm function and fertility after AI, failed to enhance reproductive outcomes at commercial level, perhaps for just being components of a complex functional pathway. Hence, focus is now on the interaction sperm-SP, comparing in vivo with ex vivo, and regarding nano-sized lipid bilayer seminal extracellular vesicles (sEVs) as priority. sEVs transport fragile molecules (lipids, proteins, nucleic acids) which, shielded from degradation, mediate cell-to-cell communication with spermatozoa and the female internal genital tract. Such interaction modulates essential reproductive processes, from sperm homeostasis to immunological female tolerance. sEVs can be harvested, characterized, stored, and manipulated, e.g. can be used for andrological diagnosis, selection of breeders, and alternatively be used as additives to improve cryosurvival and fertility.

microRNAs play pivotal roles during mammalian reproduction, including the cross-talk between gametes, embryos and the maternal genital tract. Mating induces changes in the expression of mRNA transcripts in the female, but whether miRNAs are involved remains to be elucidated. In the current study, we mapped 181 miRNAs in the porcine peri-ovulatory female reproductive tract: Cervix (Cvx), distal and proximal uterus (Dist-Ut, Prox-Ut), Utero-tubal-junction (UTJ), isthmus (Isth), ampulla (Amp), and infundibulum (Inf) when exposed to semen (natural mating (NM) or artificial insemination (AI-P1)) or to infusions of sperm-free seminal plasma (SP): the first 10 mL of the sperm rich fraction (SP-P1) or the entire ejaculate (SP-E). Among the most interesting findings, NM decreased mir-671, implicated in uterine development and pregnancy loss prior to embryo implantation, in Cvx, Dist-UT, Prox-UT, Isth, and Inf, while it increased in Amp. NM and SP-E induced the downregulation of miR-let7A-1 (Dist-UT, Prox-UT), a regulator of immunity during pregnancy. miR-34C-1, a regulator of endometrial receptivity gene expression, was increased in Dist-UT, UTJ and Amp (NM), in Prox-UT (AI-P1), and in Amp (SP-P1). miR-296, a modulator of the inflammatory response and apoptosis, was upregulated in the UTJ (all treatments). NM elicited the highest miRNA activity in the sperm reservoir (UTJ), suggesting that key-regulators such as miR-34c or miR-296 may modulate the metabolic processes linked to the adequate preparation for gamete encounter in the oviduct. Our results suggest that SP should be maintained in AI to warrant miRNA regulation within the female genital tract for reproductive success.

Aims: Lymph node metastases (LNM) are one of the most important prognostic indicators in solid tumours and a major component of cancer staging. Neoadjuvant therapy might influence nodal status by induction of regression. Our aim is to determine the prevalence and role of regression of LNM on outcomes in patients with rectal cancer. Methods and results: Four independent study populations of rectal cancer patients treated with similar regimens of chemoradiotherapy were pooled together to obtain a total cohort of 469 patients. Post-treatment nodal status (ypN) and signs of tumour regression (Reg) were incorporated to form three-tiered (ypN− Reg+, ypN− Reg− and ypN+) and four-tiered (ypN− Reg+, ypN− Reg−, ypN+ Reg+ and ypN+ Reg−) classifications. In our cohort, 31% of patients presented with ypN+ rectal cancer. As expected, we found significantly worse overall survival (OS) in ypN+ patients compared to ypN− patients (P = 0.002). The percentage of ypN− patients with lymph nodes with complete regression was 20% in our cohort. While node-negative patients with and without regression had similar OS (P = 0.09), disease-free survival (DFS) was significantly better in node-negative patients with regression (P = 0.009). Conclusions: Regression in lymph nodes is frequent, and node-negative patients with evidence of lymph node regression have better DFS compared to node-negative patients without such evidence.

BackgroundAmblyopia is the most common developmental vision disorder in children. The initial treatment consists of refractive correction. When insufficient, occlusion therapy may further improve visual acuity. However, the challenges and compliance issues associated with occlusion therapy may result in treatment failure and residual amblyopia. Virtual reality (VR) games developed to improve visual function have shown positive preliminary results. The aim of this study is to determine the efficacy of these games to improve vision, attention, and motor skills in patients with residual amblyopia and identify brain-related changes. We hypothesize that a VR-based training with the suggested ingredients (3D cues and rich feedback), combined with increasing the difficulty level and the use of various games in a home-based environment is crucial for treatment efficacy of vision recovery, and may be particularly effective in children.MethodsThe AMBER study is a randomized, cross-over, controlled trial designed to assess the effect of binocular stimulation (VR-based stereoptic serious games) in individuals with residual amblyopia (n = 30, 6-35 years of age), compared to refractive correction on vision, selective attention and motor control skills. Additionally, they will be compared to a control group of age-matched healthy individuals (n = 30) to account for the unique benefit of VR-based serious games. All participants will play serious games 30 min per day, 5 days per week, for 8 weeks. The games are delivered with the Vivid Vision Home software. The amblyopic cohort will receive both treatments in a randomized order according to the type of amblyopia, while the control group will only receive the VR-based stereoscopic serious games. The primary outcome is visual acuity in the amblyopic eye. Secondary outcomes include stereoacuity, functional vision, cortical visual responses, selective attention, and motor control. The outcomes will be measured before

The combination of estrus synchronization and superovulation (SS) treatments causes alterations in ovarian and endometrial gene expression patterns, resulting in abnormal follicle and oocyte growth, fertilization, and embryo development. However, the impact of combined SS treatments on the transcriptome of the surviving embryos remains unidentified. In this study, we examined gene expression changes in day 6 blastocysts that survived a brief regimen of synchronization treatment combined with superovulation. The sows were included in one of three groups: SS7 group (n = 6), sows were administered Altrenogest (ALT) 7 days from the day of weaning and superovulated with eCG 24 h after the end of ALT treatment and hCG at the onset of estrus; SO group (n = 6), ALT nontreated sows were superovulated with eCG 24 h postweaning and hCG at the onset of estrus; control group (n = 6), weaned sows displaying natural estrus. Six days after insemination, the sows underwent a surgical intervention for embryo collection. Transcriptome analysis was performed on blastocyst-stage embryos with good morphology. Differentially expressed genes (DEGs) between groups were detected using one-way ANOVA with an un-adjusted p-value < 0.05 and a fold change 1.5. The effect of SO treatment on the number of altered pathways and DEGs within each pathway was minimal. Only four pathways were disrupted comprising only a total of four altered transcripts, which were not related to reproductive functions or embryonic development. On the other hand, the surviving blastocysts subjected to SS7 treatments exhibited moderate gene expression changes in terms of DEGs and fold changes, with seven pathways disrupted containing a total of 10 transcripts affected. In this case, the up-regulation of certain pathways, such as the metabolic pathway, with two up-regulated genes associated with reproductive functions, namely RDH10 and SPTLC2, may suggest suboptimal embryo quality, while the down-regulation of others

Mammalian follicles are constituted of a complex structure composed of several layers of granulosa cells surrounding the oocyte and of theca cells that reside beneath its basement membrane. During folliculogenesis, granulosa cells separate into two anatomically and functionally distinct sub-types; the mural cells lining the follicle wall and the oocyte-surrounding cumulus cells, i.e. those in intimate metabolic contact with the oocyte. The cumulus cells connecting with the oocyte have trans-zonal cytoplasmic projections which, penetrating the zona pellucida, form the cumulus-oocyte complex. The connections through gap junctions allow the transfer of small molecules between oocyte and cumulus cells, such as ions, metabolites, and amino acids necessary for oocyte growth, as well as small regulatory molecules that control oocyte development. The bi-directional communication between the oocyte and cumulus cells is crucial for the development and functions of both cell types. Our current knowledge of the relationship between the oocyte and its surrounding cumulus cells continues to change as we gain a greater understanding of factors regulating oocyte development and folliculogenesis. This review will mainly focus on the reciprocal interaction between oocytes and cumulus cells during the latter stages of follicle development i.e. through antral development to periovulatory events including oocyte maturation, expansion, and degradation of the cumulus matrix.

The future health of the offspring can be influenced by longstanding maternal anxiety and depression disorders during pregnancy. The present study aimed to explore the effect of psychiatric disorders during pregnancy on placental epigenetics.

The most commonly used technique to vitrify pig embryos is the super open pulled straw (SOPS), where a maximum of 6 embryos can be vitrified simultaneously per device without compromising the minimum volume necessary for optimal preservation. Since optimal embryo transfer (ET) demands a transfer of 20-40 embryos per recipient, the customary use of SOPS complicates embryo warming and ET in field conditions. Such complications could be avoided when using the Cryotop® (OC) system, which has been proven to be an effective option for vitrifying at least 20 porcine embryos simultaneously. This study aimed to investigate the changes in the transcriptome of blastocysts caused by vitrification using both systems. In vivo-derived blastocysts were OC- (n = 60; 20 embryos/device) and SOPS- (n = 60; 4-6 embryos/device) vitrified and cultured for 24 h after warming. Nonvitrified blastocysts (n = 60) cultured for 24 h postcollection acted as controls. At the end of culture, 48 viable embryos from each group (6 pools of 8 embryos) were selected for microarray (GeneChip® Porcine Genome Array, P/N 900624, Affymetrix) analysis of differentially expressed genes (DEGs). The survival rate of embryos vitrified with the OC and SOPS systems (>97%) was similar to that of the control embryos (100%). Microarray analysis of each vitrification system compared to the control group showed 245 DEGs (89 downregulated and 156 upregulated) for the OC system and 210 (44 downregulated and 166 upregulated) for the SOPS system. Two pathways were enriched for the DEGs specifically altered in each vitrification system compared to the control (glycolysis/gluconeogenesis and carbon metabolism pathways for the OC system and amino sugar and nucleotide sugar metabolism and lysosome pathways in the SOPS group). The OC group showed 31 downregulated and 24 upregulated genes and two enriched pathways (mineral absorption and amino sugar and nucleotide sugar metabolism pathways) when compared to the SOPS group. In sum

Artificial insemination (AI) for pigs relies on liquid storage of extended semen at 17°C, which preserves sperm quality and ensures its fertilizing capacity. Routine quality controls include the evaluation of sperm motility, viability and capacitation status. The physiological functions of all these features depend on transmembrane aquaporins (AQPs), proteins playing key roles in osmoadaptation. In this study, we made a relative quantification, using RT-qPCR, of the mRNA of several sperm AQPs in AI-liquid semen doses before and after a 48-hr incubation period, aiming to determine possible quantitative compromising expression changes during the process that could serve as a diagnostic tool. Our results showed a decrease in classical sperm motility variables (total and progressive motility and velocity) and sperm viability after 48-hr storage, whereas capacitation status increased overtime. mRNA expression increased in the orthodox AQP4 and AQP6 after 48-hr incubation, relative to control (0 hr) and 24-hr time-points. Moreover, mRNA expression of aquaglyceroporins AQP3, AQP7 and AQP10 was higher after 48-hr incubation, confirmed by AQP7-protein validation using Western blot. Our results indicate that expression levels of AQPs-mRNA can change in ejaculated pig spermatozoa under conditions of ex-vivo incubation that could modify sperm homeostasis, suggesting it could eventually become a relevant molecular biomarker to assess the efficiency of liquid storage of pig semen.

The most commonly used technique to vitrify pig embryos is the super open pulled straw (SOPS), where a maximum of 6 embryos can be vitrified simultaneously per device without compromising the mini-mum volume necessary for optimal preservation. Since optimal embryo transfer (ET) demands a transfer of 20-40 embryos per recipient, the customary use of SOPS complicates embryo warming and ET in field conditions. Such complications could be avoided when using the Cryotop (R) (OC) system, which has been proven to be an effective option for vitrifying at least 20 porcine embryos simultaneously. This study aimed to investigate the changes in the transcriptome of blastocysts caused by vitrification using both systems. In vivo-derived blastocysts were OC-(n 1/4 60; 20 embryos/device) and SOPS-(n 1/4 60; 4-6 embryos/device) vitrified and cultured for 24 h after warming. Nonvitrified blastocysts (n 1/4 60) cultured for 24 h postcollection acted as controls. At the end of culture, 48 viable embryos from each group (6 pools of 8 embryos) were selected for microarray (GeneChip (R) Porcine Genome Array, P/N 900624, Affymetrix) analysis of differentially expressed genes (DEGs). The survival rate of embryos vitrified with the OC and SOPS systems (>97%) was similar to that of the control embryos (10 0%). Microarray analysis of each vitrification system compared to the control group showed 245 DEGs (89 downregulated and 156 upregulated) for the OC system and 210 (44 downregulated and 166 upregulated) for the SOPS system. Two pathways were enriched for the DEGs specifically altered in each vitrification system compared to the control (glycolysis/gluconeogenesis and carbon metabolism pathways for the OC system and amino sugar and nucleotide sugar metabolism and lysosome pathways in the SOPS group). The OC group showed 31 downregulated and 24 upregulated genes and two enriched pathways (mineral absorption and amino sugar and nucleotide sugar metabolism pathways) when compared to the, Funding Agencies|Spanish Ministry of Science and Innovation; ERDF "A way of making Europe", Madrid, Spain; Fundacion Seneca, Murcia, Spain; Research Council FORMAS, Stockholm, Sweden [19892/GERM/15]; [2019-00288]; [PRE2019-090508]; [RTI2018-093525-B-I00]

The combination of estrus synchronization and superovulation (SS) treatments causes alterations in ovarian and endometrial gene expression patterns, resulting in abnormal follicle and oocyte growth, fertilization, and embryo development. However, the impact of combined SS treatments on the transcriptome of the surviving embryos remains unidentified. In this study, we examined gene expression changes in day 6 blastocysts that survived a brief regimen of synchronization treatment combined with superovulation. The sows were included in one of three groups: SS7 group (n = 6), sows were administered Altrenogest (ALT) 7 days from the day of weaning and superovulated with eCG 24 h after the end of ALT treatment and hCG at the onset of estrus; SO group (n = 6), ALT nontreated sows were superovulated with eCG 24 h postweaning and hCG at the onset of estrus; control group (n = 6), weaned sows displaying natural estrus. Six days after insemination, the sows underwent a surgical intervention for embryo collection. Transcriptome analysis was performed on blastocyst-stage embryos with good morphology. Differentially expressed genes (DEGs) between groups were detected using one-way ANOVA with an un-adjusted p-value < 0.05 and a fold change 1.5. The effect of SO treatment on the number of altered pathways and DEGs within each pathway was minimal. Only four pathways were disrupted comprising only a total of four altered transcripts, which were not related to reproductive functions or embryonic development. On the other hand, the surviving blastocysts subjected to SS7 treatments exhibited moderate gene expression changes in terms of DEGs and fold changes, with seven pathways disrupted containing a total of 10 transcripts affected. In this case, the up-regulation of certain pathways, such as the metabolic pathway, with two up-regulated genes associated with reproductive functions, namely RDH10 and SPTLC2, may suggest suboptimal embryo quality, while the down-r, Funding Agencies|MCIN/AEI/ERDF a way of making Europe, Madrid, Spain [RTI2018-093525-B-I00]; Fundacion Seneca, Murcia, Spain [19892/GERM/15]; Swedish Research Council FORMAS, Stockholm, Sweden [2019-00288]

La búsqueda del primer empleo puede resultar una tarea compleja para muchos jóvenes universitarios, porque hay muchas dudas de cómo empezar y qué hacer para conseguirlo lo antes posible. Por otro lado, es vital la formación en empleabilidad, dado que ésto les puede ayudar y facilitar su inserción laboral lo antes posible. Las Redes Sociales profesionales pueden servir como un instrumento útil para aquellos que quieran encontrar su primer empleo, porque profesionales en recursos humanos les pueden orientar para conseguirlo. Este Trabajo de Fin de Grado pretende analizar dos expertas en orientación para la empleabilidad que conectan con los jóvenes a través de Instagram, entre otros medios. Ellas son: Eva Porto (no pertenece a la Universidad de Valladolid) e Inés Moya (de la Universidad de Valladolid)., Grado en Administración y Dirección de Empresas

Introduction The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab. Methods This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Results Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (− 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints—the visuospatial/executive domain + 0.04 (p = 0.651), naming domain − 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain − 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain − 0.05 (p = 0.224)—but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level—0–54 mg/dL, 55–69 mg/dL and ≥ 70 mg/dL; p = 0.454—or between alirocumab and evolocumab arms. Conclusion We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab. Registration ClinicalTtrials.gov Identifier numb

Introduction: The future health of the offspring can be influenced by longstanding maternal anxiety and depression disorders during pregnancy. The present study aimed to explore the effect of psychiatric disorders during pregnancy on placental epigenetics. Methods: We measured DNA methylation patterns in term-placentas of women either suffering longstanding anxiety and depression symptoms (Index group, with overt symptoms), or a healthy population (Control, none/ only mild symptoms). Whole genome DNA methylation profiling was performed using the TruSeq (R) Methyl Capture EPIC Library Prep Kit (Illumina, San Diego, CA, USA) for library preparation and NGS technology for genomic DNA sequencing.Results: The results of high-throughput DNA methylation analysis revealed that the Index group had differential DNA methylation at epigenome-wide significance (p < 0.05) in 226 genes in the placenta. Targeted enrichment analyses identified hypermethylation of genes associated with psychiatric disorders (BRINP1, PUM1), and ion homeostasis (COMMD1), among others. The ECM (extracellular matrix)-receptor interaction pathway was significantly dysregulated in the Index group compared to the Control. In addition, DNA methylation/mRNA integration analyses revealed that four genes with key roles in neurodevelopment and other important processes (EPB41L4B, BMPR2, KLHL18, and UBAP2) were dysregulated at both, DNA methylation and transcriptome levels in the Index group compared to Control.Discussion: The presented results increase our understanding of how maternal psychiatric disorders may affect the newborn through placental differential epigenome, suggesting DNA methylation status as a biomarker when aiming to design new preventive techniques and interventions.

Aims:Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome. Methods and results:The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19–3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23–5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS. Conclusions: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response

Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology., Funding Agencies|Fondo Europeo de Desarrollo Regional (FEDER) [CP18/00116, PI19/01643, PI17/01443, PI15/00301, PI17/0190, CPII16/00031, CIBEREHD CB06/04/0021]; Fondo de Investigacion Sanitaria [CP18/00116, PI19/01643, PI17/01443, PI15/00301, PI17/0190, CPII16/00031, CIBEREHD CB06/04/0021]; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdireccion General de Investigacion Sanitaria, Ministerio de Economia y Competitividad [CP18/00116, PI19/01643, PI17/01443, PI15/00301, PI17/0190, CPII16/00031, CIBEREHD CB06/04/0021]; Ministerio de Educacion, Direccion General de Investigacion [SAF 2016-76648-R]; Agencia de Gestio dAjuts Universitaris i de Recerca, de la Generalitat de Catalunya [2014 SGR 1285]; Vall dHebron Institut de Recerca, Programa de becas predoctorales Amics de Vall dHebron [PRED-VHIR-2016-34, PRED-VHIR-2014-018]; Swedish Research Council [2019-00653]; European Unions Horizon research and innovation programme 2020 [848228]

Contains fulltext : 284096.pdf (Publisher’s version ) (Open Access)

Not only do soils provide 98.7% of the calories consumed by humans, they also provide numerous other functions upon which planetary survivability closely depends. However, our continuously increasing focus on soils for biomass provision (food, fiber, and energy) through intensive agriculture is rapidly degrading soils and diminishing their capacity to deliver other vital functions. These tradeoffs in soil functionality - the increased provision of one function at the expense of other critical planetary functions - are the focus of this review. We examine how land-use change for biomass provision has decreased the ability of soils to regulate the carbon pool and thereby contribute profoundly to climate change, to cycle the nutrients that sustain plant growth and ecosystem health, to protect the soil biodiversity upon which many other functions depend, and to cycle the Earth's freshwater supplies. We also examine how this decreasing ability of soil to provide these other functions can be halted and reversed. Despite the complexity and the interconnectedness of soil functions, we show that soil organic carbon plays a central role and is a master indicator for soil functioning and that we require a better understanding of the factors controlling the behavior and persistence of C in soils. Given the threats facing humanity and their economies, it is imperative that we recognize that Soil Security is itself an existential challenge and that we need to increase our focus on the multiple functions of soils for long-term human welfare and survivability of the planet.

During pregnancy, the immune system is modified to allow developmental tolerance of the semi-allogeneic fetus and placenta to term. Pregnant women suffering from stress, anxiety, and depression show dysfunctions of their immune system that may be responsible for fetal and/or newborn disorders, provided that placental gene regulation is compromised. The present study explored the effects of maternal chronic self-perceived stress, anxiety, and depression during pregnancy on the expression of immune-related genes and pathways in term placenta. Pregnancies were clinically monitored with the Beck Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 divided patients into two groups: Index group (>10, n = 11) and a Control group (<10, n = 11), whose placentae were sampled at delivery. The placental samples were subjected to RNA-Sequencing, demonstrating that stress, anxiety, and depression during pregnancy induced a major downregulation of placental transcripts related to immune processes such as T-cell regulation, interleukin and cytokine signaling, or innate immune responses. Expression differences of main immune-related genes, such as CD46, CD15, CD8 alpha & beta ILR7 alpha, and CCR4 among others, were found in the Index group (P < 0.05). Moreover, the key immune-like pathway involved in humoral and cellular immunity named "Primary immunodeficiency" was significantly downregulated in the Index group compared with Controls. Our results show that mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perceived depressive symptoms and anxiety during pregnancy. These findings may help unveil mechanisms ruling the impact of maternal psychiatric symptoms and lead to new prevention/intervention strategies in complicated pregnancies. Summary Sentence Mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perce

Enhanced efficiency nitrogen fertilisers (EENFs) attempt to improve nitrogen use efficiency (NUE) by synchronizing nitrogen (N) supply with crop demand to improve crop productivity/profitability and minimize environmental impacts. This study evaluated the impact of ten EENFs (at 125 and 250 kg N ha−1) compared to urea-N (at 0, 62.5, 125, 175, 250 and 300 kg N ha−1) subsurface banded in a no-till maize (Zea mays L.) production system. Crop growth was examined in both the year of application and in the following year (without fertiliser N) to assess residual impacts. Nitrous oxide emissions from a subset of EENFs applied at 150 kg N ha−1 in an adjacent experiment were monitored in year 1. Grain yield increased with increasing rates of applied urea-N in year 1, with a maximum potential yield of 11.2 t ha−1 achieved at ≥ 175 kg N ha−1. However, grain and biomass yield, agronomic NUE, and N transfer efficiency did not increase with EENFs compared to urea-N, and some controlled release fertilisers (CRFs) decreased yield by 9–16%. Nitrification inhibitors decreased cumulative N2O emissions by 67%, while CRFs had no significant effect. Residual fertiliser N remaining in the soil at the end of the first season was strongly correlated with grain yield in the subsequent cropping year, but EENFs did not have a greater residual impact on crop growth than urea-N. The inability of EENFs to deliver increased crop N uptake or grain yield does not provide a clear case for their use as an alternative to conventional urea.

n/a, Funding Agencies|European UnionEuropean Commission [H2020- MSCA-IF-2019-891663, H2020- MSCA-IF-2019-891382]

Nanoparticulate double-heterojunction photocatalysts comprising TiO2(Anatase)/WO3/TiO2(Rutile) were produced by a sol–gel method. The resulting photocatalysts exhibit clear synergistic effects when tested toward the degradation of methyl orange under both UV and visible light. Kinetic studies indicate that the degradation rate on the best double-heterojunction photocatalyst (10 wt % WO3-TiO2) depends mainly on the amount of dye concentration, contrary to pure oxides in which the degradation rate is limited by diffusion-controlled processes. The synergistic effects were confirmed through systematic and careful studies including holes and OH radical formation, X-ray diffraction, electron microscopy, elemental analysis, UV–vis diffuse reflectance spectroscopy, and surface area analysis. Our results indicate that the successful formation of a double heterojunction in the TiO2(Anatase)/WO3/TiO2(Rutile) system leads to enhanced photoactivity when compared to individual oxides and commercial TiO2 P25.

Noncommunicable diseases (NCDs), including cancer, are responsible for almost 70% of all deaths worldwide. Tobacco use is a risk factor common to most NCDs. This article discusses tobacco control policies and highlights major achievements and open challenges to reduce smoking prevalence and attributable morbidity and mortality in the 21st century. The introduction of the WHO Framework Convention on Tobacco Control in 2005 has been a key achievement in the field and has already facilitated a drop in both smoking prevalence and exposure to secondhand smoke. Indicatively, the size of the worldwide population benefiting from at least one cost-effective tobacco control policy has quadrupled since 2007. In addition, plain cigarette packaging has been successfully introduced as a tobacco control policy, surmounting efforts of the tobacco industry to challenge this based on trade and investment law. Nevertheless, tobacco control still faces major challenges. Smoking prevalence needs to be further reduced in a rather expedited manner. Smoke-free environments should be extended, and the use of plain tobacco packaging with large pictorial health warnings for all tobacco products should be further promoted in some parts of the world. Some of these measures will require prompt determination and diligence. For example, bold political decisions are needed to significantly increase real prices of tobacco products through excise taxes, ban added ingredients that are currently used to increase the attractiveness of tobacco products and ban the tobacco industrys corporate social responsibility initiatives. Finally, the debate on harm reduction strategies for tobacco control still needs to be resolved.

info:eu-repo/semantics/published

The ability of plants to sense and integrate daily and seasonal changes in light and temperature and to adjust their growth and development accordingly, is critical to withstand severe weather oscillations in a year. While molecular mechanisms controlling light responses are relatively well established, those involved in the perception and response to temperature are just beginning to be understood. Phytochromes emerged as major temperature sensors; due to warmer temperatures accelerate the dark reversal reaction to the Pr inactive state. Downstream of phytochromes, the bHLH Phytochrome Interacting Factors, and in particular PIF4, act as central signaling hubs to growth coordination in response to light and temperature cues, and to the gibberellin and brassinosteroid pathways. Here we discuss recent findings showing that phytochromes control PIFs activity not only by signaling their destruction in the light, but by modulating transcriptional repression of these factors by the circadian clock. Together with this repression, phytochromes inactivate the COP1/SPA ubiquitin ligase, which negatively regulates light signaling through degradation of a large set of nuclear photomorphogenesis-promoting factors that suppress PIFs activity.

Semen changes the gene expression in endometrial and oviductal tissues modulating important processes for reproduction. We tested the hypothesis that mating and/or sperm-free seminal plasma deposition in the reproductive tract affect the expression of genes associated with sperm-lining epithelium interactions, ovulation, and pre-implantation effects (nerve growth factor, NGF; α/β hydrolase domain-containing protein 2, ABHD2; C-terminal tensin-like protein, CTEN or TNS4; and versican, VCAN) in the period 10-72 h post-mating. In Experiment 1, does (n = 9) were treated with gonadotropin-releasing hormone (GnRH) (control), GnRH-stimulated, and vaginally infused with sperm-free seminal plasma (SP-AI), or GnRH-stimulated and naturally mated (NM). In Experiment 2, does (n = 15) were GnRH-stimulated and naturally mated. Samples were retrieved from the internal reproductive tracts (cervix-to-infundibulum) 20 h post-treatment (Experiment 1) or sequentially collected at 10, 24, 36, 68, or 72 h post-mating (Experiment 2, 3 does/period). All samples were processed for gene expression analysis by quantitative PCR. Data showed an upregulation of endometrial CTEN and NGF by NM, but not by SP-AI. The findings suggest that the NGF gene affects the reproductive tract of the doe during ovulation and beyond, influencing the maternal environment during early embryonic development., Funding agencies: Research Council FORMAS, Stockholm [2017-00946, 2019-00288]; Swedish Research Council (Vetenskapsradet, VR)Swedish Research Council [2015-05919]; Juan de la Cierva Incorporacion Postdoctoral Research Program (MICINN) [IJDC-2015-24380]; [2018 FI_B 00236]

Pig embryo transfer (ET) is burdened by high embryo mortality, with cytokines playing a significant role in recruitment of immune cells during embryo attachment and placentation. We hereby tested if their levels in endometrium and placenta from sows carrying hemi-allogeneic (artificially inseminated sows; C+ positive control) or allogeneic embryos (sows subjected to ET; ET) during peri-implantation (D18) or post-implantation (D24) are suitable mirrors of embryo rejection or tolerance after ET. Non-pregnant sows (C-) were used as negative controls. A set of cytokines was assayed in the tissues through multiplexed microsphere-based flow cytometry (Luminex xMAP, Millipore. USA). Fewer (58.7%. p < 0.003) conceptuses were recovered at D24 after ET compared to C+ (80.9%); with more than 20% of the ET conceptuses being developmentally delayed. Cytokine levels shifted during implantation. Anti-inflammatory IL-10 levels were significantly (p < 0.05) lower in ET sows compared to C+ at D24 of pregnancy. The C+ controls (carrying hemi-allogeneic embryos) consistently showed higher levels of pro-inflammatory TNF-α, IFN-γ, and IL-2 cytokines at D18 and IL-1α at D24, compared to the ET group. This clear dysregulation of pro- and anti-inflammatory cytokine levels in sows subjected to ET could be associated with an impaired maternal immune tolerance, explaining the high embryonic mortality of ET programs., Funding agencies: European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grantEuropean Union (EU) [891663]; Seneca Foundation Murcia (Spain)Fundacion Seneca [20780/PD/18]; Grupo AGROPOR I+D+I. AIE. org. Murcia, Spain [IKE-2019-00133

The RNA-binding proteins (RBPs), some of them induced by transient receptor potential (TRP) ion channels, are crucial regulators of RNA function that can contribute to reproductive pathogenesis, including inflammation and immune dysfunction. This study aimed to reveal the influence of spermatozoa, seminal plasma, or natural mating on mRNA expression of RBPs and TRP ion channels in different segments of the internal genital tract of oestrous, preovulatory sows. Particularly, we focused on mRNA expression changes of the cold-inducible proteins (CIPs) and related TRP channels. Pre-ovulatory sows were naturally mated (NM) or cervically infused with semen (Semen-AI) or sperm-free seminal plasma either from the entire ejaculate (SP-TOTAL) or the sperm-rich fraction (SP-AI). Samples (cervix to infundibulum) were collected by laparotomy under general anaesthesia for transcriptomic analysis (GeneChip(R)Porcine Gene 1.0 ST Array) 24 h after treatments. The NM treatment induced most of the mRNA expression changes, compared to Semen-AI, SP-AI, and SP-TOTAL treatments including unique significative changes inCIRBP,RBM11,RBM15B,RBMS1,TRPC1,TRPC4,TRPC7, andTRPM8. The findings on the differential mRNA expression on RBPs and TRP ion channels, especially to CIPs and related TRP ion channels, suggest that spermatozoa and seminal plasma differentially modulated both protein families during the preovulatory phase, probably related to a still unknown early signalling mechanism in the sow reproductive tract., Funding Agencies|Research Council FORMAS, Stockholm [2017-00946, 2019-00288]; Swedish Research Council (Vetenskapsradet, VR)Swedish Research Council [2015-05919]; Government of Catalonia-AGAURAgencia de Gestio DAjuts Universitaris de Recerca Agaur (AGAUR)Generalitat de Catalunya; European Social FundEuropean Social Fund (ESF) [2018 FI_B 00236]; Government of Spain-Ministry of Education, Culture and Sports [FPU15/06029]; Seneca Foundation, Murcia (Spain)Fundacion Seneca [20780/PD/18]

Semen-through its specific sperm and seminal plasma (SP) constituents-induces changes of gene expression in the internal genital tract of pigs, particularly in the functional sperm reservoir at the utero-tubal junction (UTJ). Although seminal effects are similarly elicited by artificial insemination (AI), major changes in gene expression are registered after natural mating, a fact suggesting the act of copulation induces per se changes in genes that AI does not affect. The present study explored which pathways were solely influenced by copulation, affecting the differential expression of genes (DEGs) of the pre/peri-ovulatory genital tract (cervix, distal uterus, proximal uterus and UTJ) of estrus sows, 24 h after various procedures were performed to compare natural mating with AI of semen (control 1), sperm-free SP harvested from the sperm-peak fraction (control 2), sperm-free SP harvested from the whole ejaculate (control 3) or saline-extender BTS (control 4), using a microarray chip (GeneChip(R)porcine gene 1.0 st array). Genes related to neuroendocrine responses (ADRA1,ADRA2,GABRB2,CACNB2), smooth muscle contractility (WNT7A), angiogenesis and vascular remodeling (poFUT1,NTN4) were, among others, overrepresented with distal and proximal uterine segments exhibiting the highest number of DEGs. The findings provide novel evidence that relevant transcriptomic changes in the porcine female reproductive tract occur in direct response to the specific act of copulation, being semen-independent., Funding Agencies|Research Council FORMAS, Stockholm [2017-00946, 2019-00288]; Swedish Research Council (Vetenskapsradet, VR)Swedish Research Council [2015-05919]; Seneca Foundation Murcia (Spain)Fundacion Seneca [20,780/PD/18]

Semen modifies the expression of genes related to immune function along the porcine female internal genital tract. Whether other pathways are induced by the deposition of spermatozoa and/or seminal plasma (SP), is yet undocumented. Here, to determine their relative impact on the uterine and tubal transcriptomes, microarray analyses were performed on the endocervix, endometrium and endosalpinx collected from pre-ovulatory sows 24 h after either mating or artificial insemination (AI) with specific ejaculate fractions containing spermatozoa or sperm-free SP. After enrichment analysis, we found an overrepresentation of genes and pathways associated with sperm transport and binding, oxidative stress and cell-to-cell recognition, such as PI3K-Akt, FoxO signaling, glycosaminoglycan biosynthesis and cAMP-related transcripts, among others. Although semen (either after mating or AI) seemed to have the highest impact along the entire genital tract, our results demonstrate that the SP itself also modifies the transcriptome. The detected modifications of the molecular profiles of the pre/peri-ovulatory endometrium and endosalpinx suggest an interplay for the survival, transport and binding of spermatozoa through, for instance the up-regulation of the Estrogen signaling pathway associated with attachment and release from the oviductal reservoir., Funding agency: Linköping University

The infusion of boar seminal plasma (SP) before artificial insemination (AI) positively alters the expression of endometrial genes and pathways involved in embryo development. This study aimed to determine which transcriptome changes occur in preimplantation embryos in response to SP infusions during estrus. Postweaning estrus sows received 40-mL intrauterine infusions of either SP (N = 6) or BTS extender (control group; N = 6) 30 min before each of two post-cervical AIs. On Day 6, embryos were surgically collected and analyzed for differential gene expression. Microarray analysis of embryos revealed 210 annotated genes, differentially expressed (p-value < 0.05 and fold change 2) in SP-blastocysts, compared to controls. Most of these genes were associated with biological, cellular, metabolic and developmental processes. The pathways enriched among the upregulated genes related to signal transduction, cellular processes and the endocrine system. Among altered genes involved in these pathways, the SP-group showed a conspicuous overexpression of ApoA-I, CDK1, MAPK1, SMAD2, PRKAA1 and RICTOR, with reported key roles in embryo development, implantation, or progression of pregnancy. In conclusion, the results demonstrate that SP infusions prior to AI upregulates the expression of embryo development related genes in Day 6 pig embryos., Funding agencies: the MINECO-FEDER (AGL2015-69735-R), Madrid, Spain; the FundacionSeneca (19892/GERM/15), Murcia, Spain; the MICIU/FEDER (RTI2018-093525-B-I00), Madrid, Spain; the European Union’s Horizon 2020 research and innovation program under the MSCA (grant agreement No 891663); and the Swedish Research Council FORMAS (Projects 2017-00946 and 2019-00288), Stockholm, Sweden.

Glucocorticoids are steroid hormones modulating different functions in mammals, including reproduction, that act through the glucocorticoid receptor, encoded by the gene called NR3C1. Here, we describe how the expression levels of the glucocorticoid receptor change along the different compartments of the female rabbit internal reproductive tract 20 h after insemination with sperm-free seminal plasma or natural mating (whole semen) (Experiment 1) and how these levels change at 10, 24, 36, 68, and 72 h post-mating, during specific stages over time, i.e., ovulation, fertilization and the interval of early embryo development to the morula stage occurs (Experiment 2). NR3C1 -upregulation was found in the infundibulum at 20 h after all treatments, especially after sperm-free seminal plasma infusion compared to mating (Experiment 1). In Experiment 2, the receptor gene expression levels increased in a spatio-temporal sequence, corresponding to the assumed location of the rabbit embryos (particularly morulae) in the oviductal various segments and timepoints (particularly 72 h), compared to down-expression at uterine regions. We conclude that NR3C1 may play a relevant role in the rabbit female reproductive tract. Rabbits are interesting as research animal models for reproduction, due to their condition of species of induced ovulation, with the release of endogenous gonadotropin-releasing hormone (GnRH) due to coitus. Glucocorticoid (GC) signaling, crucial for physiological homeostasis, is mediated through a yet unclear mechanism, by the GC receptor (NR3C1/GR). After mating, the female reproductive tract undergoes dynamic modifications, triggered by gene transcription, a pre-amble for fertilization and pregnancy. This study tested the hypothesis that when ovulation is induced, the expression of NR3C1 is influenced by sperm-free seminal plasma (SP), similarly to after mating (whole semen), along the different segments of the internal reproductive tract of female rabbits. Semen

Anxiety, chronical stress, and depression during pregnancy are considered to affect the offspring, presumably through placental dysregulation. We have studied the term placentae of pregnancies clinically monitored with the Beck's Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 classed patients into an Index group (>10,n= 23) and a Control group (<10,n= 23). Cortisol concentrations in hair (HCC) were periodically monitored throughout pregnancy and delivery. Expression differences of main glucocorticoid pathway genes, i.e., corticotropin-releasing hormone (CRH), 11 beta-hydroxysteroid dehydrogenase (HSD11B2), glucocorticoid receptor (NR3C1), as well as other key stress biomarkers (Arginine Vasopressin, AVP and O-GlcNAc transferase, OGT) were explored in medial placentae using real-time qPCR and Western blotting. Moreover, gene expression changes were considered for their association with HCC, offspring, gender, and birthweight. A significant dysregulation of gene expression for CRH, AVP, and HSD11B2 genes was seen in the Index group, compared to controls, while OGT and NR3C1 expression remained similar between groups. Placental gene expression of the stress-modulating enzyme 11 beta-hydroxysteroid dehydrogenase (HSD11B2) was related to both hair cortisol levels (Rho = 0.54;p< 0.01) and the sex of the newborn in pregnancies perceived as stressful (Index,p< 0.05). Gene expression of CRH correlated with both AVP (Rho = 0.79;p< 0.001) and HSD11B2 (Rho = 0.45;p< 0.03), and also between AVP with both HSD11B2 (Rho = 0.6;p< 0.005) and NR3C1 (Rho = 0.56;p< 0.03) in the Control group but not in the Index group; suggesting a possible loss of interaction in the mechanisms of action of these genes under stress circumstances during pregnancy.

Vitrification is the ideal method for long-lasting storage of porcine embryos. However, both strict airline regulations for transport of liquid nitrogen dewars and the technical problems experienced when vitrified embryos are transferred using non-surgical procedures have led to the introduction of alternative storage methods, such as preserving embryos in liquid state. This study evaluated whether a pH-stable medium containing high concentrations of either foetal calf serum (FCS; 50%) or BSA (4%) combined with storage at temperatures of 17 degrees C or 20 degrees C maintained in vivo-derived morulae and blastocysts alive and unhatched (a sanitary requirement for embryo transportation) during 72 h of storage. Neither FCS nor BSA supplements were able to counteract the negative effect of low temperatures (17 degrees C) on embryonic survival after storage. At 20 degrees C, the protective effect of FCS or BSA depended on embryo stage. While FCS successfully arrested embryo development of only blastocysts, BSA arrested the development of both morulae and blastocysts. Over 80% of BSA arrested embryos restarted development by conventional culture and progressed to further embryonic stages, including hatching. In conclusion, porcine morulae and blastocysts can survive and remain unhatched during at least 72 h when stored at 20 degrees C in a BSA-containing medium., Funding Agencies|Ministry of Economy and Competitiveness (Madrid, Spain)/the European Regional Development Fund [AGL2015-69735-R]; Seneca Foundation, Murcia, Spain [19892/GERM/15]; Research Council FORMAS, Stockholm [2017-00946]; Ministry of Economy and Competitiveness (Madrid, Spain) [BES2013-064087, BES-2013-064069, BES-2016-077869]

Background: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. Methods: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, post-bronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. Main outcomes: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. Findings: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. Conclusions: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Background: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. Methods: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, post-bronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. Main outcomes: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. Findings: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. Conclusions: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

L’ère du sur-mesure est arrivée : les robots sont partout et permettent de perfectionner des produits et de les rendre uniques. Depuis leur création, les robots sont développés dans l’optique d’assister les humains, comme une extension de leurs propriétés. Toutefois, la place de l’Homme devient une importante réflexion, car l’intégration des robots dans la société est inévitable. Dans cette industrie 4.0, la disruption qu’elle engendre bouleverse les modèles organisationnels existants et la systémie des entreprises, les poussant à se transformer et à se digitaliser. Les robots apportent aux entreprises des performances accrues, tout en octroyant aux collaborateurs des tâches plus épanouissantes. Néanmoins, un robot ne possédera jamais une intelligence identique à celle d’un humain, car il leur manque une chose : la créativité. C’est pourquoi, une entreprise doit opter pour une mixité dans ses équipes, où robots et humains seront en totale synergie. Selon certaines entreprises à Genève, une collaboration est totalement envisageable puisqu’elle n’est pas dans une optique de remplacement des collaborateurs, mais de soutien dans ses différentes activités. Les entreprises commencent à s’intéresser aux robots collaboratifs, car les collaborateurs possèdent des capacités uniques, ce qui les rendront irremplaçables au sein des industries. Au contraire, leur place est encore plus importante aujourd’hui, contribuant de ce fait à ce que beaucoup d’entreprises aient des outils comme le Lean Management et aient modifié leur stratégie pour une approche sociologique, redonnant une place importante aux collaborateurs dans un système participatif. Dans les recommandations, j’explique que le marché de la robotique industrielle va énormément progresser et que les robots vont continuer à s’installer dans la plupart des métiers. En effet, ils continueront leur évolution au niveau de leur technique. La robotique collaborative amènera de nouvelles possibilités pour un humain d’évoluer et

This study aimed (1) to evaluate the in vitro post-warming survival of porcine embryos after re vitrification and (2) to assess the efficacy of transport of embryos in dry shipper (DS) in maintaining the viability and quality of vitrified embryos for a 3-day period. Embryos at the compacted or cavitating morula (CCM) and unhatched blastocyst (UBL) stages were surgically obtained from weaned, crossbred sows. In the first experiment, more than 85% of the embryos survived an initial vitrification and warming and achieved comparable survival rates to those of their fresh counterparts. In contrast, those embryos subjected to a second vitrification and warming had clearly lower survival rates (60% and 64% for re vitrified embryos from the CCM and UBL groups, respectively) compared to the survival rates of the initial vitrification and fresh control groups (P amp;lt; 0.01). Hatching rates were similar in re-vitrified blastocysts derived from vitrified CCMs and fresh control groups (50.8% and 55.3%, respectively). However, differences (P amp;lt; 0.01) in hatching rates were recorded in re-vitrified blastocysts derived from vitrified UBLs and fresh control blastocysts (14.7% and 90.0%, respectively). In the second experiment, vitrified embryos were stored in a liquid nitrogen tank for one month. Then, the straws containing the embryos were transferred to a DS (DS group) or to another liquid nitrogen tank (control group) for an additional three days. Embryos from the DS and control groups had similar survival and hatching rates, regardless of the embryonic stage considered. The DS storage of CCMs and UBLs did not affect their development after culturing, including total cell numbers, compared to the control, although their apoptotic index was slightly higher (P amp;lt; 0.05), regardless of the developmental stage. In conclusion, although re-vitrification negatively affects embryo survival, this study demonstrated that amp;gt;60% of vitrified embryos could be successfully re-v, Funding Agencies|Ministry of Economy and Competitiveness (Madrid, Spain)/the European Regional Development Fund [AGL2015-69735-R]; Seneca Foundation, Murcia, Spain [19892/GERM/15]

The oil overlay micro-drop system is widely used for cultures of mammalian gametes and embryos. We evaluated hereby the effects of two unaltered commercial oils-Sigma mineral oil (S-MO) and Nidoil paraffin oil (N-PO)-on in vitro embryo production (IVP) outcomes using a pig model. The results showed that while either oil apparently did not affect oocyte maturation and fertilization rates, S-MO negatively affected embryo cleavage rates, blastocyst formation rates, and, consequently, total blastocyst efficiency of the system. No differences in the oxidation state were found between the oils or culture media incubated under S-MO or N-PO. Although both oils slightly differed in elemental composition, there were no differences in the concentrations of elements between fresh media and media incubated under oils. By contrast, we demonstrated clear oil-type differences in both the composition of volatile organic compounds (VOC) and the transfer of some of these VOCs (straight-chain alkanes and pentanal and 1,3-diethyl benzene) to the culture medium, which could have influenced embryonic development., Funding Agencies|MINECO-FEDER, Madrid, Spain [AGL2015-69735-R]; Fundacion Seneca, Murcia, Spain [19892/GERM/15]; MINECO [BES-2013-064087, BES-2013-064069]

Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene HTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms HTR4b/i and putatively impairs HTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. In vitro assays confirmed expression regulation via three 3'UTR binding sites. The novel isoform HTR4b_2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that HTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that HTR4 might be involved in the development of IBS-D.

The Aichi 15 goal of the Convention on Biological Diversity, the Bonn Challenge, and the Initiative 20x20 are initiatives aimed at fostering restoration in Latin America; however, they are efforts that do not specify restoration processes. In this study, the countries having a restoration plan in Latin America were identified to analyze later the scope of the plans. The countries with restoration plans were Brazil, Colombia, Ecuador and Guatemala. The analysis showed that their objectives and restoration approaches coincide. It is outlined the consideration of setting objectives for recovering ecosystemic services in a sustainable way, as well as the adoption of long term and landscape-scale restauration approaches. The assistance of ecological succession is considered as a cost-effective way for restoration. Social participation is important for the construction and operation of initiatives, and a legal framework associated with the plans already exists. However, it is necessary for the philosophical framework of the plans to be strengthened, for socio-economic criteria and those of success to be included to the prioritization of areas, and for the ascending approaches to be developed in the restoration processes that benefit their financing. Protocols for monitoring biophysical and socioeconomic aspects of restoration should be included in the plans. The plans under consideration are a major step to comply with international commitments. However, the challenge will not only be to consolidate such instruments, but also ensure that the elements of these instruments allow the large scale recovery of systems., La meta Aichi 15 del Convenio sobre la Diversidad Biológica, el Reto de Bonn y la Iniciativa 20x20 son iniciativas orientadas a impulsar la restauración en Latinoamérica, sin embargo, son esfuerzos que no especifican los procesos de restauración.En este estudio se buscaron los países que cuentan con un plan de restauración en Latinoamérica para, posteriormente, analizar los alcances de estos. Los países con un plan de restauración fueron Brasil, Colombia, Ecuador y Guatemala. El análisis mostró que sus objetivos y enfoques de restauración coinciden. Destaca la consideración del establecimiento de objetivos hacia la recuperación de servicios ecosistémicos de manera sostenible, la adopción de enfoques de restauración a escala del paisaje y de largo plazo. La asistencia de la sucesión ecológica es considerada una vía costo-efectiva para la restauración. La participación social es importante para la construcción y operación de las iniciativas y existe un marco legal asociado a los planes. No obstante, falta fortalecer en los planes el marco filosófico, incluir criterios socioeconómicos y de éxito de la restauración en la priorización de áreas, desarrollar enfoques ascendentes en los procesos de restauración que beneficien su financiamiento. En los planes también deberán incluirse protocolos para el monitoreo de aspectos biofísicos y socioeconómicos de la restauración. Los planes examinados constituyen un gran paso para cumplir con los compromisos internacionales, sin embargo, el desafío no solo radicará en consolidar talesinstrumentos, sino en que los elementos que los compongan permitan la recuperación a gran escala de los ecosistemas.

Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.

PURPOSE: To evaluate visual outcomes, spectacle independence, and quality of life among nonastigmatic and astigmatic patients who received AcrySof IQ ReSTOR toric or nontoric multifocal intraocular lenses (IOLs) (Alcon Laboratories, Fort Worth, TX) compared with those who received commercially available nontoric monofocal IOLs after bilateral cataract removal. METHODS: This randomized, patient- and observer-technician-masked study was conducted at 20 sites in Europe. Patients were randomized to receive monofocal (nontoric only) or multifocal (nontoric or toric, as needed) IOLs. Primary efficacy endpoints included percentage of patients achieving binocular uncorrected distance and near acuity of 0.1 logMAR or better (20/25 Snellen), spectacle independence, and scores on the National Eye Institute Refractive Error and Quality of Life questionnaire domains. Safety endpoints included adverse events and refractive error within 0.5 and 1.0 diopters. RESULTS: In the multifocal group (n = 108) versus the monofocal group (n = 100), significantly more patients achieved uncorrected distance and near acuity of 0.1 logMAR or better (45.7% vs 2.1%; P < .0001) and spectacle independence (73.3% vs 25.3%; P < .0001) at 6 months. The percentage of patients who achieved uncorrected distance visual acuity of 20/40 or better at 6 months was 92% in the multifocal group and 97% in the monofocal group. National Eye Institute Refractive Error and Quality of Life scores were significantly better for dependence on correction in the multifocal group (P < .0001) and for glare in the monofocal group (P = .0157); other domain scores were similar between groups. No significant trends in study device-related adverse events were observed. CONCLUSIONS: Monofocal and multifocal IOLs provided good clinical outcomes. More patients receiving multifocal IOLs attained better uncorrected visual acuity at a range of distances and spectacle independence compared with patients who received monofocal IOLs. Mono

Background and aims Altered intestinal barrier is associated with immune activation and clinical symptoms in diarrhoea-predominant IBS (IBS-D). Increased mucosal antigen load may induce specific responses; however, local antibody production and its contribution to IBS aetiopathogenesis remain undefined. This study evaluated the role of humoral activity in IBS-D. Methods A single mucosal jejunal biopsy, luminal content and blood were obtained from healthy volunteers (H; n = 30) and IBS-D (n = 49; Rome III criteria) participants. Intraepithelial lymphocytes, mast cells, B lymphocytes and plasma cells were studied by imaging techniques. Differential gene expression and pathway analysis were assessed by microarray and PCR techniques. Blood and luminal immunoglobulins (Igs) were quantified. Gastrointestinal symptoms, respiratory atopy and stress and depression were also recorded. Results Patients with IBS-D showed a higher number and activation of mucosal B lymphocytes and plasma cells (p less than 0.05). Mast cell density was increased in patients with IBS-D (non-atopic) and in close proximity to plasma cells (p less than 0.05). Microarray profiling identified differential humoral activity in IBS-D, involving proliferation and activation of B lymphocytes and Igs production (p less than 0.001). Mucosal humoral activity was higher in IBS-D, with upregulation of germline transcripts and Ig genes (1.3-fold-1.7-fold increase; p less than 0.05), and increased IgG(+) cells and luminal IgG compared with H (p less than 0.05), with no differences in blood. Biological markers of humoral activity correlated positively with bowel movements, stool form and depression. Conclusions Enhanced small bowel humoral immunity is a distinctive feature of IBS-D. Mucosal Ig production contributes to local inflammation and clinical manifestations in IBS-D., Funding Agencies|Fondo de Investigacion Sanitaria; CIBERehd, Instituto de Salud Carlos III, Subdireccion General de Investigacion Sanitaria, Ministerio de Economia y Competitividad [CP10/00502, PI13/00935, CM08/00229, CM10/00155, FI12/00254, PI12/00314, EII2011-0035, PI11/00716]; Ministerio de Educacion, Direccion General de Investigacion [SAF 2009-07416]; Agencia de Gestio dAjuts Universitaris i de Recerca, de la Generalitat de Catalunya [2009 SGR 219, 2011 BP/A00099]; Rome Foundation; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas [CB06/04/0021]

Increasing human demands on soil-derived ecosystemservices requires reliable data on global soil resources for sustainable development. The soil organic carbon (SOC) pool is a key indicator of soil quality as it affects essential biological, chemical and physical soil functions such as nutrient cycling, pesticide and water retention, and soil structure maintenance. However, information on the SOC pool, and its temporal and spatial dynamics is unbalanced. Even in well-studied regions with a pronounced interest in environmental issues information on soil carbon (C) is inconsistent. Several activities for the compilation of global soil C data are underway. However, different approaches for soil sampling and chemical analysesmake even regional comparisons highly uncertain. Often, the procedures used so far have not allowed the reliable estimation of the total SOC pool, partly because the available knowledge is focused on not clearly defined upper soil horizons and the contribution of subsoil to SOC stocks has been less considered. Evenmore difficult is quantifying SOC pool changes over time. SOC consists of variable amounts of labile and recalcitrant molecules of plant, and microbial and animal origin that are often operationally defined. A comprehensively active soil expert community needs to agree on protocols of soil surveying and lab procedures towards reliable SOC pool estimates. Already established long-term ecological research sites,where SOC changes are quantified and the underlying mechanisms are investigated, are potentially the backbones for regional, national, and international SOC monitoring programs.

Objective Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD. Design Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry. Results Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found. Conclusions These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.