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This article presents a methodology for automatic fault detection in photovoltaic arrays. Due to the great importance in the construction of increasingly robust photovoltaic plants, automatic fault detection has become a necessary tool to extend the useful life of these plants, avoid system shutdowns and reduce serious safety problems. In the present study, nine possible faults are detected, caused by malfunction in the bypass and blocking diodes. The solution consists of training two models based on artificial neural networks, the first model is a binary classifier that detects whether or not a fault occurs, the second is a multiclass classifier that detects the fault type. The obtained models were trained from simulation data, in an architecture of 9 photovoltaic panels interconnected in three rows by three columns matrix (extendable to larger systems). The evaluation shows that the prediction system has a total accuracy of 92.95%. Finally, this methodology is intended to be implemented in Colombia, in zones with difficult access and not interconnected to the electricity grid, seeking to reduce corrective maintenance.

This study seeks to analyze different energy solutions for the Kanalitojo Indigenous Community that is located 25 kilometers from the municipal seat of the municipality of Puerto Carreño, in the State of Vichada, eastern Colombia. For the development of this study, a technical performance analysis has been applied to each proposed solution considering the amount of electricity generation and demand. The first solution refers to a hydrokinetic turbine connected to a distribution network. The second solution combines the use of solar panels, hydrokinetic turbine, and portable batteries with which it is possible to transport the generated energy to the places where the community needs it. The third proposed energy solution refers to the use of micro-cogeneration units and portable batteries. With the use of the capabilities of the TRNSYS v17 energy simulation software, the comparative technical analysis between each solution for the same load demand is carried out. This analysis has shown a great advantage in the use of solar panels, hydrokinetic turbine, and portable batteries with an electricity surplus of 103.8%. However, technically the first solution based on a hydrokinetic turbine is more suitable for the community challenges due to it meets the electricity demand of the community by an excess of 12.4% and the capital and operating expenditure are less.

The industrial and economic development of the industrialized countries, from the nineteenth century, has gone hand in hand with the development of electricity, the internal combustion engine, computers, the Internet, data use, and the intensive use of knowledge focused on science and the technology. Most conventional energy sources have proven to be finite and exhaustible. In turn, the different production activities of goods and services using fossil fuels and conventional energy have significantly increased the pollution of the environment, and with it, contributed to global warming. The objective of this work was to carry out a theoretical approach to data analytics and business intelligence technologies applied to smart electrical-system networks with renewable energies. For this paper, a bibliometric and bibliographic review about Big Data Analytics, ICT tools of industry 4.0 and Business intelligence was carried out in different databases available in the public domain. The results of the analysis indicate the importance of the use of data analytics and business intelligence in the management of energy companies. The paper concludes by pointing out how business intelligence and data analytics are being applied in specific examples of energy companies and their growing importance in strategic and operational decision-making.

This work aims to evaluate the provision of energy services in non-interconnected zones (NIZ) between 2018 and 2019 using open data from the Colombian government and business intelligence methodology. The analysis is approached from the ETL (Extract, Transform, Load). It focuses on the variables obtained from the National Monitoring Centre (CNM) for monitoring the operation of these zones, where there is a Telemetry System that provides monthly information on location variables, energy variables, such as active and reactive energy maximum power, maximum power per day, and hours of service delivery. We concluded that in the years, 2018–2019 energy consumption in NIZ has remained stable with a variation of 0.19%. On the other hand, the NIZ include 56% of Colombia’s states, and the energy consumption is concentrated in 6 of the 93 municipalities with 80% of national consumption. The challenges in these areas are associated not only with the quality and provision of energy services but also with the environmental challenges that mean that most of these areas obtain their energy supply from fossil fuels, being protected areas such as ecological reserves, the biosphere, or the jungle.

The off-grid communities in Colombia are characterised by the diversity of their geography, socio-cultural contexts, and structures of the system. Despite their potential, the opportunities for access to energy and therefore other conditions to develop education, productivity, health, technological projects, and recreation are highly limited. Under those conditions, the implementation of projects with water and/or energy solutions based on renewable sources would bridge the gaps of isolation and social marginalisation that have detained the future of these communities for years. Projects around water and/or energy require the input of external stakeholders to communities, despite of the willingness to change their realities towards a better lifestyle. To achieve a common point of interests among stakeholders, the dialogues, the understanding of the community cosmovision and the ethical perspectives regarding the use of natural resources are needed. Furthermore, it is necessary to identify perceptions of confidence and risk of renewable energy projects within the community. To design water and/or energy solutions based on the abovementioned in a sustainable manner, the framework “Community, wAter-Renewable Energies, Diversity” CARED is being developed, for which the first phase in its implementation is presented. The process has been carried out in the Wayuu indigenous community “La Paz” located nearby Manaure in La Guajira state in the northeast of Colombia.

Hemodynamically unstable pelvic fractures are challenging high-energy traumas. In many cases, these severely injured patients have additional traumatic injuries that also require a trauma surgeon's attention. However, these patients are often in extremis and require a multidisciplinary approach that needs to be set up in minutes. This calls for an evidence-based treatment algorithm. We think that the treatment of hemodynamically unstable pelvic fractures should primarily involve thorough resuscitation, mechanical stabilization, and preperitoneal pelvic packing. Angioembolization should be considered in patients that remain hemodynamically unstable. However, it should be used as an adjunct, rather than a primary means to achieve hemodynamic stability as most of the exsanguinating bleeding sources in pelvic trauma are of venous origin. Time is of the essence in these patients and should therefore be used appropriately. Hence, the hemodynamic status and physiology should be the driving force behind each decision-making step within the algorithm.

Relative to conventional two-dimensional (2-D) culture, three-dimensional (3-D) suspension culture of epithelial cells more closely mimics the in vivo cell microenvironment regarding cell architecture, cell to matrix interaction, and osmosis exchange. However, primary normal human keratinocytes (NHKc) rapidly undergo terminal differentiation and detachment-induced cell death (anoikis) upon disconnection from the basement membrane, thus greatly constraining their use in 3-D suspension culture models. Here, we examined the 3-D anchorage-free growth potential of NHKc isolated from neonatal skin explants of 59 different individuals. We found that 40% of all isolates naturally self-assembled into multicellular spheroids within 24 h in anchorage-free culture, while 60% did not. Placing a single spheroid back into 2-D monolayer culture yielded proliferating cells that expressed elevated levels of nuclear P63 and basal cytokeratin 14. These cells also displayed prolonged keratinocyte renewal and a gene expression profile corresponding to cellular heterogeneity, quiescence, and de-differentiation. Notably, spheroid-derived (SD) NHKc were enriched for a P63/K14 double-positive population that formed holoclonal colonies and reassembled into multicellular spheroids during 3-D suspension subculture. This study reveals marked phenotypic differences in neonatal keratinocyte suspension cultures isolated from different individuals and present a model system that can be readily employed to study epithelial cell behavior, along with a variety of dermatological diseases.

Renewable energy projects are being developed and implemented in different geographical areas of several continents. In each of them, many communities develop their lives that have cultural, social and environmental potentials; as well as perceptions, beliefs and criteria for the acceptance of renewable energy projects in their territories. Through the methodology of mapping SCOPUS articles published worldwide, this work examines the perceptions, beliefs and criteria of community acceptability against renewable energy projects that are based on the use of natural resources such as sun, water, wind, earth, and biomass. These perceptions and beliefs can come from ancestral traditions that mark the relationship of communities with beings of nature and not with natural resources, which is the modern vision. Other perceptions, beliefs and criteria of acceptability in non-ancestral communities may be related to risk perception, low levels of trust and credibility between stakeholders, confusion regarding the operation of renewable energy systems, among others. Whatever their origin, the experience in implementing these projects has taught about the relevance of involving communities during the stages of their development, the need to know the different places from where their worlds are explained and thus improving the levels of relevance, acceptance, and sustainability of renewable energy systems.

There is evidence to suggest that the Coronavirus Disease 2019 (COVID-19) pandemic may hamper our achievement of the Sustainable Development Goals (SDGs). Here, we use non-human primates as a case study to examine the impacts of COVID-19 on the ability to achieve biodiversity conservation and management sustainability targets. We collected data through a survey of members of the IUCN SSC Primate Specialist Group from January to March 2022. Of the 93 experts that responded to our survey, we found that 39% had not been able to visit any of their field sites since March 2020, 54% said they had less funding available for their primate-related work, and only one out of ten said they had managed to achieve at least 76–100% of their planned primate-related work since March 2020. Six out of ten respondents (61%) felt that primate conservation efforts in protected areas were worse than before the onset of the COVID-19 pandemic and one-third (33%) felt hunting was happening more frequently than before. This study provides evidence of the impacts of COVID-19 on progress towards achieving the SDGs, and provides practical lessons learned for biodiversity conservation efforts moving forward.

Targeting cancer hallmarks is a cardinal strategy to improve antineoplastic treatment. However, cross-talk between signaling pathways and key oncogenic processes frequently convey resistance to targeted therapies. The p53 and Wnt pathway play vital roles for the biology of many tumors, as they are critically involved in cancer onset and progression. Over recent decades, a high level of interaction between the two pathways has been revealed. Here, we provide a comprehensive overview of molecular interactions between the p53 and Wnt pathway discovered in cancer, including complex feedback loops and reciprocal transactivation. The mutational landscape of genes associated with p53 and Wnt signaling is described, including mutual exclusive and co-occurring genetic alterations. Finally, we summarize the functional consequences of this cross-talk for cancer phenotypes, such as invasiveness, metastasis or drug resistance, and discuss potential strategies to pharmacologically target the p53-Wnt interaction.

Tight junctions play an important role in maintaining barrier integrity of intestinal epithelia. Activation of AMP-activated protein kinase (AMPK) promotes tight junction assembly in intestinal epithelial cells (IEC). Fructo-oligosaccharides (FOS), well-known prebiotics, have previously been shown to alleviate inflammation-associated intestinal epithelial disruption although the mechanisms were unclear. This study aimed to investigate any effect of FOS on AMPK activity and tight junction assembly under non-inflammatory and inflammatory conditions using T84 cells as an IEC model. As analyzed by western blot, FOS induced AMPK activation through a calcium sensing receptor (CaSR)-phospholipase C (PLC)- Ca2+/calmodulin-dependent protein kinase kinase-β (CaMKKβ) pathway. Calcium switch assays and immunofluorescence staining of zonula occludens-1 (ZO-1) revealed that FOS induced tight junction assembly via an CaMKKβ-AMPK-dependent mechanism in IEC. Interestingly, FOS reversed the suppressive effect of lipopolysaccharide (LPS) on AMPK activity and tight junction assembly via a CaMKKβ pathway. Taken together, these findings uncover a prebiotic-independent effect of FOS in promoting intestinal epithelial tight junction assembly through AMPK activation, which may have implications for the treatment of diseases whose pathogenesis involves impaired intestinal barrier function.

Mentha is a strongly scented herb of the Lamiaceae (formerly Labiatae) and includes about 30 species and hybrid species that are distributed or introduced throughout the globe. These fragrant plants have been selected throughout millennia for use by humans as herbs, spices, and pharmaceutical needs. The distilling of essential oils from mint began in Japan and England but has become a significant industrial product for the US, China, India, and other countries. The US Department of Agriculture (USDA), Agricultural Research Service, National Clonal Germplasm Repository (NCGR) maintains a mint genebank in Corvallis, Oregon. This facility preserves and distributes about 450 clones representing 34 taxa, hybrid species, advanced breeder selections, and F1 hybrids. Mint crop wild relatives are included in this unique resource. The majority of mint accessions and hybrids in this collection were initially donated in the 1970s by the A.M. Todd Company, located in Kalamazoo, Michigan. Other representatives of diverse mint taxa and crop wild relatives have since been obtained from collaborators in Australia, New Zealand, Europe, and Vietnam. These mints have been evaluated for cytology, oil components, verticillium wilt resistance, and key morphological characters. Pressed voucher specimens have been prepared for morphological identity verification. An initial set of microsatellite markers has been developed to determine clonal identity and assess genetic diversity. Plant breeders at private and public institutions are using molecular analysis to determine identity and diversity of the USDA mint collection. Evaluation and characterization includes essential oil content, disease resistance, male sterility, and other traits for potential breeding use. These accessions can be a source for parental genes for enhancement efforts to produce hybrids, or for breeding new cultivars for agricultural production. Propagules of Mentha are available for distribution to international researchers as stem cuttings, rhizome cuttings, or seed, which can be requested through the GRIN-Global database of the US National Plant Germplasm System, subject to international treaty and quarantine regulations.

Abstract Epidermal growth factor receptor tyrosine kinase inhibitors (EGFr TKIs) are first‐line therapies for various cancers, and cause dose‐limiting severe diarrhea in many patients. We hypothesized that diarrhea caused by EGFr TKIs might reflect actions on epithelial transport, barrier function, or both, which we tested using cell cultures including murine and human enteroid‐derived monolayers (EDMs), analyzed using electrophysiological and other relevant methods. EGFr TKIs (such as afatinib, erlotinib, and osimertinib) reversed the acute inhibitory effect of EGF on chloride secretion induced by carbachol (CCh) across T84 human colonic epithelial cells, which correlated with the diarrhea‐inducing effect of each agent clinically. EGFr TKIs also reduced transepithelial electrical resistance (TEER), whereas co‐treatment with CCh delayed the decrease in TEER compared with that of cells co‐treated with EGF. Furthermore, afatinib and erlotinib prevented EGF‐ or CCh‐induced EGFr phosphorylation. EGFr TKIs also suppressed phosphorylation of extracellular signal‐regulated kinase (Erk)1/2 in response to EGF, whereas they had weaker effects on CCh‐induced Erk1/2 phosphorylation. In human EDMs, EGF potentiated ion transport induced by CCh, whereas afatinib reversed this effect. The ability of EGFr TKIs to reverse the effects of EGF on calcium‐dependent chloride secretion could contribute to the diarrheal side effects of these agents, and their disruption of epithelial barrier dysfunction is likely also pathophysiologically significant. CCh‐activated Erk1/2 phosphorylation was relatively insensitive to EGFr TKIs and delayed the deleterious effects of EGFr TKIs on barrier function. These findings confirm and extend those of other authors, and may be relevant to designing strategies to overcome the diarrheal side effects of EGFr TKIs.

Summary: Liver X receptors (LXRs) and their ligands are potent regulators of midbrain dopaminergic (mDA) neurogenesis and differentiation. However, the molecular mechanisms by which LXRs control these functions remain to be elucidated. Here, we perform a combined transcriptome and chromatin immunoprecipitation sequencing (ChIP-seq) analysis of midbrain cells after LXR activation, followed by bioinformatic analysis to elucidate the transcriptional networks controlling mDA neurogenesis. Our results identify the basic helix-loop-helix transcription factor sterol regulatory element binding protein 1 (SREBP1) as part of a cluster of proneural transcription factors in radial glia and as a regulator of transcription factors controlling mDA neurogenesis, such as Foxa2. Moreover, loss- and gain-of-function experiments in vitro and in vivo demonstrate that Srebf1 is both required and sufficient for mDA neurogenesis. Our data, thus, identify Srebf1 as a central player in mDA neurogenesis.

We present neuropsychological and functional outcome data in a teenager undergoing stereotactic laser amygdalohippocampotomy (SLAH) who had drug-resistant mesial temporal lobe epilepsy due to left hippocampal sclerosis. Given strong baseline cognitive performance, there was concern for post-operative declines in language and verbal memory were this patient to undergo open resection. She was evaluated pre- and post-ablation with clinical and experimental neuropsychological measures including semantic memory, category-specific object/face recognition and naming, spatial learning, and socio-emotional processing. The patient became seizure-free following SLAH and experienced significant improvements in school performance and social engagement. She experienced improvement in recognition and naming of multiple object categories, memory functions, and verbal fluency. In contrast, the patient declined significantly in her ability to recognize emotional tone from facial expressions, a socio-emotional process that had been normal prior to surgery. We believe this decline was related to surgical disruption of the limbic system, an area highly involved in emotional processing, and suspect such deficits are an under-assessed and unrecognized risk for all surgeries involving the amygdalohippocampal complex and broader limbic system regions. We hope this positive SLAH outcome will serve as impetus for group level research to establish its safety and efficacy in the pediatric setting.

Different efforts have been carried out in the last years in order to find some alternatives for fossil fuels. Biofuels have been considered as one of the possible substitutes for fossil fuels because the majority of vehicles and co-generation systems can use them without any modification and produce fewer emissions. Additionally, some developing countries are presented as a good location for biofuels production due to their weather, economic and social conditions. The methodology used in this study is as follows: firstly, the current drivers and barriers that affect the production of biofuels in Colombia were identified in the available literature. The results showed Colombia presents some special conditions for the production of biofuels that allow it to generate a competitive advantage compared to other countries. However, some barriers can affect the adoption and production of biofuels in the country. Secondly, a survey was realised to biofuel producers, suppliers and researchers in order to validate their motivations and perceptions. Some similitudes and differences with regard to the literature were found in the surveys. Hence, this information allowed the authors to understand the reality of biofuels in Colombia from the views of the stakeholders. Additionally, a set of policies were analysed. The authors believe that this set of policies will help stakeholders to have a better production of biofuels in Colombia.

Maju Mathews,1 Isaac Nuamah,1 Adam J Savitz,1 David W Hough,1 Dean Najarian,2 Edward Kim,2 Srihari Gopal1 1Janssen Research and Development, LLC, Titusville, NJ, USA; 2Janssen Scientific Affairs, Titusville, LLC, NJ, USA Objective: The aim of this study was to evaluate the safety of 3-monthly paliperidone palmitate (PP3M) vs once-monthly paliperidone palmitate (PP1M) treatment with regard to extrapyramidal symptom (EPS)-related treatment-emergent adverse events (TEAEs) in patients with schizophrenia, previously stabilized on PP1M treatment. Patients and methods: Data on overall incidence, time to onset (TTO), and time to resolution (TTR) of EPS-related TEAEs (overall, subclasses such as dyskinesia, dystonia, hyperkinesia, parkinsonism, and tremor) from a randomized double-blind (DB) non-inferiority study were compared between PP3M and PP1M. Subgroup analysis was performed by age (18–25, 26–50, and 50+ years) and final open-label (OL) dose (50/75, 100, and 150 mg eq.). Results: Overall incidence of spontaneously reported EPS-related TEAEs decreased from 12.6% (PP1M) in OL phase to 8.3% (PP3M) and 7.4% (PP1M) in the DB phase; overall median TTO and TTR values were comparable between both groups. Among patients with reported EPS-related TEAEs, the median TTO for all EPS-related TEAEs was 17 days (PP1M) in OL phase and 115 days (PP3M) and 98.5 days (PP1M) in DB phase; median TTR was 36.5 days (PP1M) in OL phase and 91 days (PP3M) and 85.5 days (PP1M) in DB phase. No clear dose- or age-related differences in TTO and TTR of EPS-related TEAEs were noted. Conclusion: Despite differences in apparent half-life and pharmacokinetic profiles (peak plasma exposure of PP3M formulation is 70% higher than that of PP1M formulation), both PP3M and PP1M formulations exhibited comparable incidence of EPS-related TEAEs, TTO, and TTR in patients with schizophrenia. Keywords: extrapyramidal symptoms, once-monthly paliperidone palmitate, 3-monthly paliperidone palmitate, time to onset, time to resolution

Bo-Ram Lee,1,* Jung-Hee Kim,1,* Eun-Sook Choi,1,2 Jung-Hoon Cho,3 Eunjoo Kim1,2 1Companion Diagnostics and Medical Technology Research Group, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea; 2Global Center for Bio-Convergence Spin System (BicSPINS), Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea; 3School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37666, Republic of Korea *These authors contributed equally to this work Introduction: Exosomes, nano-sized extracellular vesicles, are known to circulate through the blood stream to transfer molecular signals from tissue to tissue. Methods: To determine whether exosomes affect aging in animals, we primarily identified the changes in exosomal miRNA contents during the aging process. In exosomes from 12-month-old mice, mmu-miR-126-5p and mmu-miR-466c-5p levels were decreased and mmu-miR-184-3p and mmu-miR-200b-5p levels were increased significantly compared with those of 3-month-old mice. Their levels in exosomes were partially correlated with those in tissues: levels of only mmu-miR-126-5p and mmu-miR-466c-5p in lungs and/or liver were decreased, but those of mmu-miR-184-3p and mmu-miR-200b-5p in tissues did not coincide with those of exosomes. Results and discussion: In the aged tissues injected with young exosomes isolated from serum, mmu-miR-126b-5p levels were reversed in the lungs and liver. Expression changes in aging-associated molecules in young exosome-injected mice were obvious: p16Ink4A, MTOR, and IGF1R were significantly downregulated in the lungs and/or liver of old mice. In addition, telomerase-related genes such as Men1, Mre11a, Tep1, Terf2, Tert, and Tnks were significantly upregulated in the liver of old mice after injection of young exosomes. Conclusion: These results indicate that exosomes from young mice could reverse the expression pattern of aging-associated molecules in aged mice. Eventually, exosomes may be used as a novel approach for the treatment and diagnosis of aging animals. Keywords: exosome, injection, reverse aging, telomerase, biomarker, molecular therapy

Interactions between proteins underlie all aspects of complex biological mechanisms. Therefore, methodologies based on complex network analyses can facilitate identification of promising candidate genes involved in phenotypes of interest and put this information into appropriate contexts. To facilitate discovery and gain additional insights into globally important pathogenic fungi, we have reconstructed computationally inferred interactomes using an interolog and domain-based approach for 15 diverse Ascomycete fungal species, across nine orders, specifically Aspergillus fumigatus, Bipolaris sorokiniana, Blumeria graminis f. sp. hordei, Botrytis cinerea, Colletotrichum gloeosporioides, Colletotrichum graminicola, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Fusarium verticillioides, Leptosphaeria maculans, Magnaporthe oryzae, Saccharomyces cerevisiae, Sclerotinia sclerotiorum, Verticillium dahliae, and Zymoseptoria tritici. Network cartography analysis was associated with functional patterns of annotated genes linked to the disease-causing ability of each pathogen. In addition, for the best annotated organism, namely F. graminearum, the distribution of annotated genes with respect to network structure was profiled using a random walk with restart algorithm, which suggested possible co-location of virulence-related genes in the protein–protein interaction network. In a second ‘use case’ study involving two networks, namely B. cinerea and F. graminearum, previously identified small silencing plant RNAs were mapped to their targets. The F. graminearum phenotypic network analysis implicates eight B. cinerea targets and 35 F. graminearum predicted interacting proteins as prime candidate virulence genes for further testing. All 15 networks have been made accessible for download at www.phi-base.org providing a rich resource for major crop plant pathogens.

Rubus (Rosaceae) comprises more than 500 species with additional commercially cultivated raspberries and blackberries. The most recent (> 100 years old) global taxonomic treatment of the genus defined 12 subgenera; two subgenera were subsequently described and some species were rearranged. Intra- and interspecific ploidy levels and hybridization make phylogenetic estimation of Rubus challenging. Our objectives were to estimate the phylogeny of 94 taxonomically and geographically diverse species and three cultivars using chloroplast DNA sequences and target capture of approximately 1,000 low copy nuclear genes; estimate divergence times between major Rubus clades; and examine the historical biogeography of species diversification. Target capture sequencing identified eight major groups within Rubus. Subgenus Orobatus and Subg. Anoplobatus were monophyletic, while other recognized subgenera were para- or polyphyletic. Multiple hybridization events likely occurred across the phylogeny at subgeneric levels, e.g., Subg. Rubus (blackberries) × Subg. Idaeobatus (raspberries) and Subg. Idaeobatus × Subg. Cylactis (Arctic berries) hybrids. The raspberry heritage within known cultivated blackberry hybrids was confirmed. The most recent common ancestor of the genus was most likely distributed in North America. Multiple distribution events occurred during the Miocene (about 20 Ma) from North America into Asia and Europe across the Bering land bridge and southward crossing the Panamanian Isthmus. Rubus species diversified greatly in Asia during the Miocene. Rubus taxonomy does not reflect phylogenetic relationships and subgeneric revision is warranted. The most recent common ancestor migrated from North America towards Asia, Europe, and Central and South America early in the Miocene then diversified. Ancestors of the genus Rubus may have migrated to Oceania by long distance bird dispersal. This phylogeny presents a roadmap for further Rubus systematics research. In conclusion, the target capture dataset provides high resolution between species though it also gave evidence of gene tree/species tree and cytonuclear discordance. Discordance may be due to hybridization or incomplete lineage sorting, rather than a lack of phylogenetic signal. This study illustrates the importance of using multiple phylogenetic methods when examining complex groups and the utility of software programs that estimate signal conflict within datasets.

Abstract Background Parentage assignment is usually based on a limited number of unlinked, independent genomic markers (microsatellites, low-density single nucleotide polymorphisms (SNPs), etc.). Classical methods for parentage assignment are exclusion-based (i.e. based on loci that violate Mendelian inheritance) or likelihood-based, assuming independent inheritance of loci. For true parent–offspring relations, genotyping errors cause apparent violations of Mendelian inheritance. Thus, the maximum proportion of such violations must be determined, which is complicated by variable call- and genotype error rates among loci and individuals. Recently, genotyping using high-density SNP chips has become available at lower cost and is increasingly used in genetics research and breeding programs. However, dense SNPs are not independently inherited, violating the assumptions of the likelihood-based methods. Hence, parentage assignment usually assumes a maximum proportion of exclusions, or applies likelihood-based methods on a smaller subset of independent markers. Our aim was to develop a fast and accurate trio parentage assignment method for dense SNP data without prior genotyping error- or call rate knowledge among loci and individuals. This genomic relationship likelihood (GRL) method infers parentage by using genomic relationships, which are typically used in genomic prediction models. Results Using 50 simulated datasets with 53,427 to 55,517 SNPs, genotyping error rates of 1–3% and call rates of ~ 80 to 98%, GRL was found to be fast and highly (~ 99%) accurate for parentage assignment. An iterative approach was developed for training using the evaluation data, giving similar accuracy. For comparison, we used the Colony2 software that assigns parentage and sibship simultaneously to increase the power of the likelihood-based method and found that it has considerably lower accuracy than GRL. We also compared GRL with an exclusion-based method in which one of the parameters was estimated using GRL assignments.This method was slightly more accurate than GRL. Conclusions We show that GRL is a fast and accurate method of parentage assignment that can use dense, non-independent SNPs, with variable call rates and unknown genotyping error rates. By offering an alternative way of assigning parents, GRL is also suitable for estimating the expected proportion of inconsistent parent–offspring genotypes for exclusion-based models.

Abstract Background The soil dwelling saprotrophic non-pathogenic fungus Fusarium venenatum, routinely used in the commercial fermentation industry, is phylogenetically closely related to the globally important cereal and non-cereal infecting pathogen F. graminearum. This study aimed to sequence, assemble and annotate the F. venenatum (strain A3/5) genome, and compare this genome with F. graminearum. Results Using shotgun sequencing, a 38,660,329 bp F. venenatum genome was assembled into four chromosomes, and a 78,618 bp mitochondrial genome. In comparison to F. graminearum, the predicted gene count of 13,946 was slightly lower. The F. venenatum centromeres were found to be 25% smaller compared to F. graminearum. Chromosome length was 2.8% greater in F. venenatum, primarily due to an increased abundance of repetitive elements and transposons, but not transposon diversity. On chromosome 3 a major sequence rearrangement was found, but its overall gene content was relatively unchanged. Unlike homothallic F. graminearum, heterothallic F. venenatum possessed the MAT1–1 type locus, but lacked the MAT1–2 locus. The F. venenatum genome has the type A trichothecene mycotoxin TRI5 cluster, whereas F. graminearum has type B. From the F. venenatum gene set, 786 predicted proteins were species-specific versus NCBI. The annotated F. venenatum genome was predicted to possess more genes coding for hydrolytic enzymes and species-specific genes involved in the breakdown of polysaccharides than F. graminearum. Comparison of the two genomes reduced the previously defined F. graminearum-specific gene set from 741 to 692 genes. A comparison of the F. graminearum versus F. venenatum proteomes identified 15 putative secondary metabolite gene clusters (SMC), 109 secreted proteins and 38 candidate effectors not found in F. venenatum. Five of the 15 F. graminearum-specific SMCs that were either absent or highly divergent in the F. venenatum genome showed increased in planta expression. In addition, two predicted F. graminearum transcription factors previously shown to be required for fungal virulence on wheat plants were absent or exhibited high sequence divergence. Conclusions This study identifies differences between the F. venenatum and F. graminearum genomes that may contribute to contrasting lifestyles, and highlights the repertoire of F. graminearum-specific candidate genes and SMCs potentially required for pathogenesis.

Abstract Background Sexual initiation occurs early in Sierra Leone. This study aims to analyze the determinants of condom and/or contraceptive use among a representative sample of young persons (10 to 24 years) in Sierra Leone. Methods This is a secondary analysis of data from a study conducted to monitor the implementation of a UNFPA package of interventions directed to improve SRH in young people of Sierra Leone. This assessment was conducted in 2016 at the end of the Ebola outbreak. In consequence, determinants linked to healthy lifestyle behaviors and UNFPA interventions were explored in addition to the usual determinants: socio demographic and sexual lifestyle. This study is a household quantitative survey with open ended questions used to illustrate and complete the analysis. Results A total of 1409 young people were interviewed: of these, 216 boys and 381 girls were sexually active. Those who were pregnant or wished for pregnancy were excluded, leaving 194 boys and 268 girls for the analysis of determinants. The proportion of young people using neither condom nor other contraception at their last sexual intercourse in the whole sample was 40.5% and there was no statistically significant difference between boys and girls (42.3 vs 39.2; P = 0.504). Determinants were assessed and, after multivariable analysis, results differed between boys and girls and showed the importance of behavioral aspects. Four determinants were common to boys and girls: literacy, distance, negotiation capacity and hand washing. However, the distance factor for girls was to the health facility and for boys it was to school. Three more determinants remained in the boy’s model: sleeping under a bednet, number of sexual partners and knowledge of contraceptive methods. Opinions about condoms and contraception revealed important barriers; opposition to contraceptive use was the main reason for non-use for both boys and girls, while lack of access was an important reason for boys. Conclusion There is a need to reach out to the 40% of young people who are sexually active and neither pregnant nor with pregnancy desire, and are not using condom or contraception.

Summary: Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. : Maffioletti et al. generate human 3D artificial skeletal muscles from healthy donors and patient-specific pluripotent stem cells. These human artificial muscles accurately model severe genetic muscle diseases. They can be engineered to include other cell types present in skeletal muscle, such as vascular cells and motor neurons. Keywords: skeletal muscle, pluripotent stem cells, iPS cells, myogenic differentiation, tissue engineering, disease modeling, muscular dystrophy, organoids

Several recent reports have described associations between gestational diabetes (GDM) and changes to the epigenomic landscape where the DNA samples were derived from either cord or placental sources. We employed genome-wide 450K array analysis to determine changes to the epigenome in a unique cohort of maternal blood DNA from 11 pregnant women prior to GDM development relative to matched controls. Hierarchical clustering segregated the samples into 2 distinct clusters comprising GDM and healthy pregnancies. Screening identified 100 CpGs with a mean β-value difference of ≥0.2 between cases and controls. Using stringent criteria, 5 CpGs (within COPS8, PIK3R5, HAAO, CCDC124, and C5orf34 genes) demonstrated potentials to be clinical biomarkers as revealed by differential methylation in 8 of 11 women who developed GDM relative to matched controls. We identified, for the first time, maternal methylation changes prior to the onset of GDM that may prove useful as biomarkers for early therapeutic intervention.

Sung In Jeong,1,* Seong-Cheol Park,2,* Sun-Jeong Park,2,* Eun-Ji Kim,2 Hun Heo,2 Jong-Seok Park,1 Hui-Jeong Gwon,1 Youn-Mook Lim,1 Mi-Kyeong Jang2 1Research Division for Industry and Environment, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, 2Department of Polymer Science and Engineering, College of Engineering, Sunchon National University, Suncheon, Korea *These authors contributed equally to this work Introduction: Although numerous studies have been conducted with the aim of developing drug-delivery systems, chemically synthesized gene carriers have shown limited applications in the biomedical fields due to several problems, such as low-grafting yields, undesirable reactions, difficulties in controlling the reactions, and high-cost production owing to multi-step manufacturing processes. Materials and methods: We developed a 1-step synthesis process to produce 2-aminoethyl methacrylate-grafted water-soluble chitosan (AEMA-g-WSC) as a gene carrier, using gamma irradiation for simultaneous synthesis and sterilization, but no catalysts or photoinitiators. We analyzed the AEMA graft site on WSC using 2-dimensional nuclear magnetic resonance spectroscopy (2D NMR; 1H and 13C NMR), and assayed gene transfection effects in vitro and in vivo. Results: We revealed selective grafting of AEMA onto C6-OH groups of WSC. AEMA-g-WSC effectively condensed plasmid DNA to form polyplexes in the size range of 170 to 282 nm. AEMA-g-WSC polyplexes in combination with psi-hBCL2 (a vector expressing short hairpin RNA against BCL2 mRNA) inhibited tumor cell proliferation and tumor growth in vitro and in vivo, respectively, by inducing apoptosis. Conclusion: The simple grafting process mediated via gamma irradiation is a promising method for synthesizing gene carriers. Keywords: water-soluble chitosan, 2-aminoethyl methacrylate, gamma irradiation, gene delivery

Every year, enteric infections and associated diarrhea kill millions of people. The situation is compounded by increases in the number of enteric pathogens that are acquiring resistance to antibiotics, as well as (hitherto) a relative paucity of information on host molecular targets that may contribute to diarrhea. Many forms of diarrheal disease depend on the dysregulation of intestinal ion transporters, and an associated imbalance between secretory and absorptive functions of the intestinal epithelium. A number of major transporters have been implicated in the pathogenesis of diarrheal diseases and thus an understanding of their expression, localization, and regulation after infection with various bacteria, viruses, and protozoa likely will prove critical in designing new therapies. This article surveys our understanding of transporters that are modulated by specific pathogens and the mechanism(s) involved, thereby illuminating targets that might be exploited for new therapeutic approaches.

Community college presidents must understand the phenomenon of campus safety. For this mixed-methods study, community college presidents in one state were surveyed, and three presidents from the same community college system participated in in-depth interviews. Descriptive statistics measured the levels community college presidents' knowledge and perceptions on campus safety. The in-depth interviews provided a deeper understanding of the connections between community college presidents and campus safety. Overall, the results show that campus safety is important to community college presidents, who believe that, overall, their institutions are safe. We found that community college presidents believe they should be proactive and reinforce values that promote and prioritize campus safety, follow regulations, and provide sufficient resources to ensure campus safety measures. However, inadequate funding also plays a role in what can be allocated, and community college presidents voiced that they were concerned about promoting safety in the face of declining budgets and resources.

Myelodysplastic syndromes (MDS) are uncommon in children and have poor prognosis. Here, the authors interrogate the genomic landscape of MDS, confirming adult and paediatric MDS are separate diseases with disparate mechanisms, and highlighting that SAMD9/SAMD9L mutations represent a new class of MDS predisposition.

Consumer behavior is a complex phenomenon encompassing internal, external, and situational factors. This study examined perceptions of market consumers about fruits and vegetables in Trinidad and Tobago in terms of produce origin, growing method, and willingness to pay. A stratified purposive sample of consumers at 14 unique market locations was surveyed to measure the three constructs and demographics. Descriptive statistics, correlational analysis, a ttest, and one-way analysis of variance were used to analyze the data. Findings revealed consumers have positive perceptions of locally grown produce and produce grown without chemicals. Findings also revealed a slight willingness to pay more for such characteristics. There were small to moderate correlations among the three constructs. Male and female perceptions of locally grown produce were significantly different, but no differences were found based on age. Extension educators working with producers who sell directly to consumers can utilize results from this study in working with clientele to tailor marketing and production strategies. Further research into social norms and perceived behavior control is recommended to better understand consumer behavior and help Extension better prepare stakeholders for success in the market places.

Abstract Background Overweight and obesity is a major public health concern that includes associations with the development of cardiovascular disease (CVD) risk factors during childhood and adolescence as well as premature mortality in adults. Despite the high prevalence of childhood and adolescent obesity as well as adult CVD, individual studies as well as previous systematic reviews examining the relationship between childhood obesity and adult CVD have yielded conflicting results. The purpose of this study was to use the aggregate data meta-analytic approach to address this gap. Methods Studies were included if they met the following criteria: (1) longitudinal and cohort studies (including case-cohort), (2) childhood exposure and adult outcomes collected on the same individual over time, (3) childhood obesity, as defined by the original study authors, (4) English-language articles, (5) studies published up to June, 2015, (6) one or more of the following CVD risk factors [systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), non-high-density lipoprotein cholesterol (non-HDL), and triglycerides (TG)], (7) outcome(s) not self-reported, and (8) exposure measurements (child’s adiposity) assessed by health professionals, trained investigators, or self-reported. Studies were retrieved by searching three electronic databases as well as citation tracking. Fisher’s r to z score was calculated for each study for each outcome. Pooled effect sizes were calculated using random-effects models while risk of bias was assessed using the STROBE instrument. In order to try and identify sources of heterogeneity, random-effects meta-regression was also performed. Results Of the 4840 citations reviewed, a total of 23 studies were included in the systematic review and 21 in the meta-analysis. The findings suggested that childhood obesity is significantly and positively associated with adult SBP (Zr = 0.11; 95% CI: 0.07, 0.14), DBP (Zr = 0.11; 95% CI: 0.07, 0.14), and TG (Zr =0.08; 95% CI: 0.03, 0.13), and significantly and inversely associated with adult HDL (Zr = −0.06; 95% CI: -0.10, −0.02). For those studies that adjusted for adult body mass index (BMI), associations were reversed, suggesting that adult BMI may be a potential mediator. Nine studies had more than 33% of items that placed them at an increased risk for bias. Conclusions The results of this study suggest that childhood obesity may be a risk factor for selected adult CVD risk factors. However, a need exists for additional, higher-quality studies that include, but are not limited to, both unadjusted and adjusted measures such as BMI before any definitive conclusions can be reached. Systematic review and meta-analysis PROSPERO 2015: CRD42015019763 .

In this study, p-type Bi0.5Sb1.5Te3 based nanocomposites with addition of different weight percentages of Ga2O3 nanoparticles are fabricated by mechanical milling and spark plasma sintering. The fracture surfaces of all Bi0.5Sb1.5Te3 nanocomposites exhibited similar grain distribution on the entire fracture surface. The Vickers hardness is improved for the Bi0.5Sb1.5Te3 nanocomposites with 6 wt% added Ga2O3 due to exhibiting fine microstructure, and dispersion strengthening mechanism. The Seebeck coefficient of Bi0.5Sb1.5Te3 nanocomposites are significantly improved owing to the decrease in carrier concentration. The electrical conductivity is decreased rapidly upon the addition of Ga2O3 nanoparticle due to increasing carrier scattering at newly formed interfaces. The peak power factor of 3.24 W/mK2 is achieved for the base Bi0.5Sb1.5Te3 sintered bulk. The Bi0.5Sb1.5Te3 nanocomposites show low power factor than base sample due to low electrical conductivity.

Abstract Following several years enrolling disease-specific and otherwise healthy cohorts into the Coriell Personalized Medicine Collaborative, a prospective study aimed at evaluating the clinical utility of personal genomic information for common complex disease and pharmacogenomics, the Coriell Personalized Medicine Collaborative expanded to create a military cohort, specifically, the United States Air Force. Initial recruitment focused on Air Force Medical Service personnel and later expanded to include all Active Duty Air Force members and beneficiaries. Now in its 6th year, the study has produced a wide variety of insights, including optimal study design for military-sponsored genomic research, and discussion on genetic information sharing between and amongst Air Force study participants, civilian and military researchers, and the United States Department of Defense. Over the longer term, analyses will further contribute to the development of policies and processes relevant to clinical decision support and data sharing within the US military, and on-going work with the Air Force Medical Service sub-cohort will generate critical insights into how best to deploy useful genomic information in clinical care. Here we discuss challenges faced and critical success factors for military-civilian collaborations around genomic research.

Recently described scientific literature has identified the airborne presence of 2,3-butanedione (diacetyl) and 2,3-pentanedione at concentrations approaching or potentially exceeding the current American Conference of Industrial Hygienistsâ (ACGIH) Threshold Limit Values (TLVs) at commercial coffee roasting and production facilities. Newly established National Institutes of Occupational Safety and Health (NIOSH) Recommended Exposure Limits for diacetyl and 2,3-pentanedione are even more conservative. Chronic exposure to these alpha-diketones at elevated airborne concentrations has been associated with lung damage, specifically bronchiolitis obliterans, most notably in industrial food processing facilities.Workers at a large commercial coffee roaster were monitored for both eight-hour and task-based, short-term, 15-min sample durations for airborne concentrations of these alpha-diketones during specific work processes, including the coffee bean roasting, blending and grinding processes, during two separate 8-h work periods. Additionally, the authors performed real-time Fourier transform infrared spectroscopy (FTIR) analysis of the workersâ breathing zone as well as the area workplace air for the presence of organic compounds to determine the sources, as well as quantitate and identify various organic compounds proximal to the roasting and grinding processes. Real-time FTIR measurements provided both the identification and quantitation of diacetyl and 2,3-pentanedione, as well as other organic compounds generated during coffee bean roasting and grinding operations.Airborne concentrations of diacetyl in the workersâ breathing zone, as eight-hour time-weighted averages were less than the ACGIH TLVs for diacetyl, while concentrations of 2,3-pentanedione were below the limit of detection in all samples. Short-term breathing zone samples revealed airborne concentrations for diacetyl that exceeded the ACGIH short-term exposure limit of 0.02 parts per million (ppm) in two samples collected on a grinder operator. FTIR analysis of air samples collected from both the workersâ breathing zone and area air samples revealed low concentrations of various organics with diacetyl and 2,3-pentanedione at concentrations less than the limit of detection for the FTIR methods. Neither the breathing zone nor area air samples measured using the FTIR reflected airborne concentrations of organic compounds that, when detected, approached the ACGIH TLVs or regulatory standards, when available. FTIR analysis of headspace of ground coffee beans revealed ppm concentrations of expected alpha diketones, carbon monoxide and other volatile organic compounds (VOCs).Coffee roasting and grinding, with adequate building ventilation and typical roasted bean handling and grinding, appears to generate very low, if any, concentrations of diacetyl and 2,3-pentanedione in the workersâ breathing zones. This study also confirmed via FTIR that roasted coffee beans naturally generate alpha-diketones and other organic compounds as naturally occurring compounds resultant of the roasting and then released during the grinding process. Keywords: Diacetyl, 2,3-Butanedione, 2,3-Pentanedione, Alpha-diketones, Coffee roasting, Coffee grinding, Exposure assessment, Fourier transform infrared spectroscopy (FTIR)

Seong Soo An,1,* Sun Ah Park,2,* Eva Bagyinszky,1 Sun Oh Bae,1 Yoon-Jeong Kim,2 Ji Young Im,2 Kyung Won Park,3 Kee Hyung Park,4 Eun-Joo Kim,5 Jee Hyang Jeong,6 Jong Hun Kim,7 Hyun Jeong Han,8 Seong Hye Choi,9 SangYun Kim10 1Department of Bionano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Dong-A University College of Medicine and Institute of Convergence Bio-Health, Busan, 4Department of Neurology, Gachon University Gil Medical Center, Incheon, 5Department of Neurology, Pusan National University Hospital, Busan, 6Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul, 7Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, 8Department of Neurology, Myongii Hospital, Goyang, 9Department of Neurology, Inha University School of Medicine, Incheon, 10Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: Early-onset Alzheimer’s disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16-17), PSEN1 (exons 3-12), and PSEN2 (exons 3-12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We suggest early AD onset and not carrying APOE ε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population. Keywords: Alzheimer’s disease, mutation, presenilin, apolipoprotein-E, sequencing, early onset Alzheimer’s disease, genetics

Cross-kingdom small RNA (sRNA) silencing has recently emerged as a mechanism facilitating fungal colonization and disease development. Here we characterized RNAi pathways in Zymoseptoria tritici, a major fungal pathogen of wheat, and assessed their contribution to pathogenesis. Computational analysis of fungal sRNA and host mRNA sequencing datasets was used to define the global sRNA populations in Z. tritici and predict their mRNA targets in wheat. 389 in planta-induced sRNA loci were identified. sRNAs generated from some of these loci were predicted to target wheat mRNAs including those potentially involved in pathogen defense. However, molecular approaches failed to validate targeting of selected wheat mRNAs by fungal sRNAs. Mutant strains of Z. tritici carrying deletions of genes encoding key components of RNAi such as Dicer-like (DCL) and Argonaute (AGO) proteins were generated, and virulence bioassays suggested that these are dispensable for full infection of wheat. Nonetheless, our results did suggest the existence of non-canonical DCL-independent pathway(s) for sRNA biogenesis in Z. tritici. dsRNA targeting essential fungal genes applied in vitro or generated from an RNA virus vector in planta in a procedure known as HIGS (Host-Induced Gene Silencing) was ineffective in preventing Z. tritici growth or disease. We also demonstrated that Z. tritici is incapable of dsRNA uptake. Collectively, our data suggest that RNAi approaches for gene function analyses in this fungal species and potentially also as a control measure may not be as effective as has been demonstrated for some other plant pathogenic fungi.

Objective: The aim of this study was to study growth patterns of children born after suspected fetal growth restriction (FGR) at term and to compare the effect of induction of labor (IoL) and expectant management (EM), also in relation to neurodevelopmental and behavioral outcome at age 2.Methods: We performed a 2 years' follow-up of growth of children included in the Disproportionate Intrauterine Growth Restriction Trial at Term (DIGITAT) study, a Randomized Controlled Trial (RCT) comparing IoL with EM in pregnancies with suspected FGR at term. We collected data on child growth until the age of 2 years. Standard deviation scores (SDSs) for height and weight were calculated at different ages. We assessed the effects of IoL compared with EM and the effects of a birth weight below or above the 3rd or 10th centile on catch-up growth. Target height SDSs were calculated using the height of both parents.Results: We found a significant increase in SDS in the first 2 years. Children born after EM showed more catch-up growth in the first month [height: mean difference −0.7 (95% CI: 0.2; 1.3)] and weight [mean difference −0.5 (95% CI: 0.3; 0.7)]. Children born with a birth weight below the 3rd and 10th centiles showed more catch-up growth after 1 year [mean difference −0.8 SDS (95% CI: −1.1; −0.5)] and after 2 years [mean difference −0.7 SDS (95% CI: −1.2; −0.2)] as compared to children with a birth weight above the 3rd and 10th centiles. SDS at birth had the strongest effect on adverse neurodevelopmental outcome at 2 years of age.Conclusion: After FGR at term, postnatal catch-up growth is generally present and associated with the degree of FGR. Obstetric management in FGR influences postnatal growth. Longer-term follow-up is therefore needed and should be directed at growth and physical health.Clinical Trial Registration:www.ClinicalTrials.gov, identifier SRCTN10363217.

Fusarium Head Blight (FHB) is the number one floral disease of cereals and poses a serious health hazard by contaminating grain with the harmful mycotoxin deoxynivalenol (DON). Fungi adapt to fluctuations in their environment, coordinating development and metabolism accordingly. G-protein coupled receptors (GPCRs) communicate changes in the environment to intracellular G-proteins that direct the appropriate biological response, suggesting that fungal GPCR signalling may be key to virulence. Here we describe the expansion of non-classical GPCRs in the FHB causing pathogen, Fusarium graminearum, and show that class X receptors are highly expressed during wheat infection. We identify class X receptors that are required for FHB disease on wheat, and show that the absence of a GPCR can cause an enhanced host response that restricts the progression of infection. Specific receptor sub-domains are required for virulence. These non-classical receptors physically interact with intracellular G-proteins and are therefore bona fide GPCRs. Disrupting a class X receptor is shown to dysregulate the transcriptional coordination of virulence traits during infection. This amounts to enhanced wheat defensive responses, including chitinase and plant cell wall biosynthesis, resulting in apoplastic and vascular occlusions that impede infection. Our results show that GPCR signalling is important to FHB disease establishment.

Synonymous with secondary hemophagocytic lymphohistiocytosis, macrophage activation syndrome (MAS) is a term used by rheumatologists to describe a potentially life-threatening complication of systemic inflammatory disorders, most commonly systemic juvenile idiopathic arthritis (sJIA) and systemic lupus erythematosus (SLE). Clinical and laboratory features of MAS include sustained fever, hyperferritinemia, pancytopenia, fibrinolytic coagulopathy, and liver dysfunction. Soluble interleukin-2 receptor alpha chain (sCD25) and sCD163 may be elevated, and histopathology often reveals characteristic increased hemophagocytic activity in the bone marrow (and other tissues), with positive CD163 (histiocyte) staining. A common hypothesis as to the pathophysiology of many cases of MAS proposes a defect in lymphocyte cytolytic activity. Specific heterozygous gene mutations in familial HLH-associated cytolytic pathway genes (e.g., PRF1, UNC13D) have been linked to a substantial subset of MAS patients. In addition, the pro-inflammatory cytokine environment, particularly IL-6, has been shown to decrease NK cell cytolytic function. The inability of NK cells and cytolytic CD8 T cells to lyse infected and otherwise activated antigen presenting cells results in prolonged cell-to-cell (innate and adaptive immune cells) interactions and amplification of a pro-inflammatory cytokine cascade. The cytokine storm results in activation of macrophages, causing hemophagocytosis, as well as contributing to multi-organ dysfunction. In addition to macrophages, dendritic cells likely play a critical role in antigen presentation to cytolytic lymphocytes, as well as contributing to cytokine expression. Several cytokines, including tumor necrosis factor, interferon-gamma, and numerous interleukins (i.e., IL-1, IL-6, IL-18, IL-33), have been implicated in the cytokine cascade. In addition to broadly immunosuppressive therapies, novel cytokine targeted treatments are being explored to dampen the overly active immune response that is responsible for much of the pathology seen in MAS.

Primates are extracted from the wild for the pet trade across the world. In Madagascar, lemurs are kept as illegal pets and an understanding of lemur pet ownership at the national level is lacking. In 2013 and 2016, we undertook a national survey in 11 of Madagascar's 22 administrative regions (n = 28 towns) with 1,709 households. To our knowledge, this is the first national survey of the household ownership of pet primates in a country where they are endemic. In the 1.5 years prior to being surveyed, 8% ± 4% (towns as replicates) of respondents had seen a captive lemur while a further 0.7% ± 0.5% of respondents had owned one personally. We estimate that 33,428 ± 24,846 lemurs were kept in Malagasy households in the six months prior to our survey efforts, with 18,462 ± 12,963 of these pet lemurs estimated in urban household alone. Rates of lemur ownership did not differ by province but increased with the human population of a town and with the popularity of the town on Flickr (a proxy indicator for tourism). We found that the visibility of pet lemur ownership did not differ across the country, but it did increase with the size of the town and popularity with tourists. Areas with visible pet lemurs were not always the areas with the highest rates of pet lemur ownership, highlighting that many pet lemurs are hidden from the general public. Our study highlights the need for conservation programs to consider both the proportion of inhabitants that own pet lemurs and the total number of lemurs that are potentially being kept as pets in those towns. We close by noting that for some species, even just a small amount of localized live extraction for pet ownership could be enough to cause localized population extinctions over time. Moreover, an urgent response is needed to combat a recent and alarming rise in illegal exploitation of biodiversity across Madagascar.

Content shared on social media platforms can impact public perceptions of wildlife. These perceptions, which are in part shaped by context (e.g. non-naturalistic setting, presence of a human), can influence people's desires to interact with or acquire wild animals as pets. However, few studies have examined whether this holds true for wild animals featured in viral videos. This study reports on opportunistic data collected on Twitter before, during, and after a video that featured a habituated ring-tailed lemur (Lemur catta), called "Sefo", in southern Madagascar went 'viral' (i.e. circulated rapidly on the internet). Our dataset of 13,953 tweets (from an 18.5-week time period in early 2016) referencing lemurs was collected using targeted keywords on the Twitonomy Service. We identified 613 individual tweets about people wanting a lemur as a pet. In addition, 744 tweets that were captured in our dataset linked to the Sefo viral video. We found that as the number of tweets about the viral video increased, so did the number of tweets where an individual wanted to have a lemur as a pet. Most tweets (91%) did not make reference to a specific species of lemur, but when they did, they often (82%) referenced ring-tailed lemurs (L. catta), ruffed lemurs (Varecia spp.), and mouse lemurs (Microcebus spp.). This study serves as a case study to consider how viral content can impact how wild animals are perceived. We close by noting that social media sites like Twitter, which are increasingly providing their users with news and information, should carefully consider how information about wild animals is shared on their platforms, as it may impact animal welfare.

This qualitative intersectional narrative inquiry examined how Multiracial college students find sense of belongingin student organizations by negotiating multiple racial identities and locations in traditionally monoracial spaces.Multiracial students sought membership in organizations because they felt invisible at their institutions. To findbelonging within student communities, they engaged in a difficult process of placemaking in which they experiencedmonoracism and other racialized microaggressions within student organizations. In time, they developed a sense ofbelonging by curating a small cohort of friends connected through their organizational involvement. These findingsreveal implications that further inform approaches for student involvement professionals and others who work withMultiracial students to increase their support and engagement across involvement contexts.

No abstract available.