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BackgroundAlcohol abuse is a risk factor for bone damage and fracture‐related complications. Through precise β‐catenin signaling, canonical Wnt signaling plays a key role in fracture repair by promoting the differentiation of new bone and cartilage cells. In this study, we examined the effects of alcohol on the Wnt pathway in injured bone using a murine model of alcohol‐induced impaired fracture healing.MethodsMale C57Bl/6 or T cell factor (TCF)‐transgenic mice were administered 3 daily intraperitoneal doses of alcohol or saline. One hour following the final injection, mice were subjected to a stabilized, mid‐shaft tibial fracture. Injured and contralateral tibias were harvested at 6, 9, or 14 days post‐fracture for the analysis of biomechanical strength, callus tissue composition, and Wnt/β‐catenin signaling.ResultsAcute alcohol treatment was associated with a significant decrease in fracture callus volume, diameter, and biomechanical strength at day 14 post‐fracture. Histology revealed an alcohol‐related reduction in cartilage and bone formation at the fracture site, and that alcohol inhibited normal cartilage maturation. Acute alcohol exposure caused a significant 2.3‐fold increase in total β‐catenin protein at day 6 and a significant decrease of 53 and 56% at days 9 and 14, respectively. lacZ staining in β‐galactosidase‐expressing TCF‐transgenic mice revealed spatial and quantitative differences in Wnt‐specific transcriptional activation at day 6 in the alcohol group. Days 9 and 14 post‐fracture showed that acute alcohol exposure decreased Wnt transcriptional activation, which correlates with the modulation of total β‐catenin protein levels observed at these time points.ConclusionsAcute alcohol exposure resulted in significant impairment of fracture callus tissue formation, perturbation of the key Wnt pathway protein β‐catenin, and disruption of normal Wnt‐mediated transcription. These data suggest that the canonical Wnt pathway is a target for alcohol in bone and may partially explain why impaired fracture healing is observed in alcohol‐abusing individuals.

AbstractObjectiveTo assess the epidemiological evidence on the joint effects of climate variability and socioecological factors on dengue transmission.MethodsFollowing PRISMA guidelines, a detailed literature search was conducted in PubMed, Web of Science and Scopus. Peer‐reviewed, freely available and full‐text articles, considering both climate and socioecological factors in relation to dengue, published in English from January 1993 to October 2015 were included in this review.ResultsTwenty studies have met the inclusion criteria and assessed the impact of both climatic and socioecological factors on dengue dynamics. Among those, four studies have further investigated the relative importance of climate variability and socioecological factors on dengue transmission. A few studies also developed predictive models including both climatic and socioecological factors.ConclusionsDue to insufficient data, methodological issues and contextual variability of the studies, it is hard to draw conclusion on the joint effects of climate variability and socioecological factors on dengue transmission. Future research should take into account socioecological factors in combination with climate variables for a better understanding of the complex nature of dengue transmission as well as for improving the predictive capability of dengue forecasting models, to develop effective and reliable early warning systems.

La production industrielle d'huile de palme génère simultanément une quantité substantielle de fibres de grappe de fruits vides (EFB) qui pourraient être utilisées comme matière première dans une bioraffinerie à base de lignocellulose. Les sous-produits de la lignine générés par ce processus peuvent offrir des possibilités d'isolation des produits à valeur ajoutée, tels que le p-hydroxybenzoate (pBz), pour aider à compenser les coûts d'exploitation. L'analyse de la lignine EFB par spectroscopie de résonance magnétique nucléaire (RMN) a clairement révélé la présence d'acétate lié et de pBz, la saponification révélant que 1,1 % en poids de l'EFB était du pBz ; avec une teneur en lignine de 22,7 %, 4,8 % de la lignine est du pBz qui peut être obtenu comme composant pur pour être utilisé comme charge chimique. L'analyse de la lignine EFB par RMN et dérivatisation suivie d'un clivage réducteur (DFRC) a montré que le pBz acylate sélectivement le groupe γ-hydroxyle des unités S. Cette sélectivité suggère que le pBz, de manière analogue à l'acétate dans le kénaf, le p-coumarate dans les graminées et le ferrate dans un peuplier transgénique augmenté d'une féruloyl-CoA monolignol transférase (FMT), est incorporé dans la chaîne de lignine en croissance via son conjugué monolignol γ-p-hydroxybenzoylé. L'implication de tels conjugués dans la lignification des palmiers est prouvée par l'observation de nouvelles unités couplées au β-β non résinol p-hydroxybenzoylé dans les lignines. Ensemble, les données impliquent l'existence de p-hydroxybenzoyl-CoA :monolignol transférases qui sont impliquées dans la lignification chez les différents saules (Salix spp.), peupliers et peupliers faux-trembles (Populus spp., famille des Salicacées) et palmiers (famille des Arecacées) qui ont des lignines p-hydroxybenzoylées. Même sans augmenter les niveaux par la sélection ou le génie génétique, les « déchets » actuels de l'EFB d'huile de palme devraient être en mesure de générer un flux important d'acide p-hydroxybenzoïque qui offre des opportunités pour le développement de produits à valeur ajoutée dérivés de l'industrie du palmier à huile. La producción industrial de aceite de palma genera simultáneamente una cantidad sustancial de fibras de racimo de frutas vacías (EFB) que podrían utilizarse como materia prima en una biorrefinería a base de lignocelulosa. Los subproductos de lignina generados por este proceso pueden ofrecer oportunidades para el aislamiento de productos de valor agregado, como el p-hidroxibenzoato (pBz), para ayudar a compensar los costos operativos. El análisis de la lignina EFB por espectroscopía de resonancia magnética nuclear (RMN) reveló claramente la presencia de acetato unido y pBz, y la saponificación reveló que el 1,1% en peso del EFB era pBz; con un contenido de lignina del 22,7 %, el 4,8 % de la lignina es pBz que se puede obtener como un componente puro para su uso como materia prima química. El análisis de la lignina EFB por RMN y la derivatización seguida de escisión reductora (DFRC) mostró que pBz acila selectivamente el grupo γ-hidroxilo de las unidades S. Esta selectividad sugiere que pBz, análogamente con acetato en kenaf, p-cumarato en gramíneas y ferular en un álamo transgénico aumentado con una feruloil-CoA monolignol transferasa (FMT), se incorpora a la cadena de lignina en crecimiento a través de su conjugado de monolignol γ-p-hidroxibenzoilado. La participación de dichos conjugados en la lignificación de la palma se demuestra al observar nuevas unidades no acopladas a β-β-resinol p-hidroxibenzoiladas en las ligninas. Juntos, los datos implican la existencia de p-hidroxibenzoil-CoA:monolignol transferasas que participan en la lignificación en los diversos sauces (Salix spp.), álamos y álamo temblón (Populus spp., familia Salicaceae) y palmeras (familia Arecaceae) que tienen ligninas p-hidroxibenzoiladas. Incluso sin mejorar los niveles mediante mejoramiento o ingeniería genética, los 'desechos' actuales de aceite de palma EFB deberían ser capaces de generar una corriente considerable de ácido p-hidroxibenzoico que ofrezca oportunidades para el desarrollo de productos de valor agregado derivados de la industria de la palma aceitera. The industrial production of palm oil concurrently generates a substantial amount of empty fruit bunch (EFB) fibers that could be used as a feedstock in a lignocellulose-based biorefinery. Lignin byproducts generated by this process may offer opportunities for the isolation of value-added products, such as p-hydroxybenzoate (pBz), to help offset operating costs. Analysis of the EFB lignin by nuclear magnetic resonance (NMR) spectroscopy clearly revealed the presence of bound acetate and pBz, with saponification revealing that 1.1 wt% of the EFB was pBz; with a lignin content of 22.7 %, 4.8 % of the lignin is pBz that can be obtained as a pure component for use as a chemical feedstock. Analysis of EFB lignin by NMR and derivatization followed by reductive cleavage (DFRC) showed that pBz selectively acylates the γ-hydroxyl group of S units. This selectivity suggests that pBz, analogously with acetate in kenaf, p-coumarate in grasses, and ferulate in a transgenic poplar augmented with a feruloyl-CoA monolignol transferase (FMT), is incorporated into the growing lignin chain via its γ-p-hydroxybenzoylated monolignol conjugate. Involvement of such conjugates in palm lignification is proven by the observation of novel p-hydroxybenzoylated non-resinol β–β-coupled units in the lignins. Together, the data implicate the existence of p-hydroxybenzoyl-CoA:monolignol transferases that are involved in lignification in the various willows (Salix spp.), poplars and aspen (Populus spp., family Salicaceae), and palms (family Arecaceae) that have p-hydroxybenzoylated lignins. Even without enhancing the levels by breeding or genetic engineering, current palm oil EFB 'wastes' should be able to generate a sizeable stream of p-hydroxybenzoic acid that offers opportunities for the development of value-added products derived from the oil palm industry. ينتج الإنتاج الصناعي لزيت النخيل في الوقت نفسه كمية كبيرة من ألياف مجموعة الفاكهة الفارغة (EFB) التي يمكن استخدامها كمادة وسيطة في مصفاة حيوية تعتمد على اللجينوسليلوز. قد توفر المنتجات الثانوية لليجنين الناتجة عن هذه العملية فرصًا لعزل المنتجات ذات القيمة المضافة، مثل p - hydroxybenzoate (pBz)، للمساعدة في تعويض تكاليف التشغيل. كشف تحليل اللجنين EFB بواسطة مطياف الرنين المغناطيسي النووي (NMR) بوضوح عن وجود أسيتات مرتبطة و pBz، مع كشف التصبن أن 1.1 ٪ بالوزن من EFB كان pBz ؛ مع محتوى اللجنين بنسبة 22.7 ٪، 4.8 ٪ من اللجنين عبارة عن pBz يمكن الحصول عليه كمكون نقي للاستخدام كمادة وسيطة كيميائية. أظهر تحليل اللجنين EFB بواسطة NMR والاشتقاق متبوعًا بالانقسام الاختزالي (DFRC) أن pBz يعمل بشكل انتقائي على أسيتيل مجموعة γ - hydroxyl من وحدات S. تشير هذه الانتقائية إلى أن pBz، بالتناظر مع الأسيتات في الكناف، و p - comarate في الأعشاب، و ferulate في حور معدّل وراثيًا معززًا بـ feruloyl - CoA monolignol transferase (FMT)، يتم دمجه في سلسلة اللجنين المتنامية عبر γ - p - hydroxybenzoylated monolignol conjugate. ثبت تورط مثل هذه المترافقات في ترصيع النخيل من خلال ملاحظة وحدات p - hydroxybenzoylated غير الراتينول β - β المقترنة في اللجنين. معا، تشير البيانات إلى وجود p - hydroxybenzoyl - CoA: monolignol transferases التي تشارك في تبييض في الصفصاف المختلفة (Salix spp.)، الحور والحور (Populus spp.، عائلة Salicaceae)، والنخيل (عائلة Arecaceae) التي تحتوي على p - hydroxybenzoylated lignins. حتى من دون تعزيز المستويات عن طريق التكاثر أو الهندسة الوراثية، يجب أن تكون "نفايات" زيت النخيل الحالية قادرة على توليد تيار كبير من حمض p - hydroxybenzoic الذي يوفر فرصًا لتطوير منتجات ذات قيمة مضافة مشتقة من صناعة نخيل الزيت.

Recurrent cycles of climatic change during the Quaternary period have dramatically affected the population genetic structure of many species. We reconstruct the recent demographic history of the coyote ( Canis latrans ) through the use of Bayesian techniques to examine the effects of Late Quaternary climatic perturbations on the genetic structure of a highly mobile generalist species. Our analysis reveals a lack of phylogeographic structure throughout the range but past population size changes correlated with climatic changes. We conclude that even generalist carnivorous species are very susceptible to environmental changes associated with climatic perturbations. This effect may be enhanced in coyotes by interspecific competition with larger carnivores.

Heatwaves have potential health and safety implications for many workers, and heatwaves are predicted to increase in frequency and intensity with climate change. There is currently a lack of comparative evidence for the effects of heatwaves on workers' health and safety in different climates (sub-tropical and temperate). This study examined the relationship between heatwave severity (as defined by the Excess Heat Factor) and workers' compensation claims, to define impacts and identify workers at higher risk.Workers' compensation claims data from Australian cities with temperate (Melbourne and Perth) and subtropical (Brisbane) climates for the years 2006-2016 were analysed in relation to heatwave severity categories (low and moderate/high severity) using time-stratified case-crossover models.Consistent impacts of heatwaves were observed in each city with either a protective or null effect during heatwaves of low-intensity while claims increased during moderate/high-severity heatwaves compared with non-heatwave days. The highest effect during moderate/high-severity heatwaves was in Brisbane (RR 1.45, 95% CI: 1.42-1.48). Vulnerable worker subgroups identified across the three cities included: males, workers aged under 34 years, apprentice/trainee workers, labour hire workers, those employed in medium and heavy strength occupations, and workers from outdoor and indoor industrial sectors.These findings show that work-related injuries and illnesses increase during moderate/high-severity heatwaves in both sub-tropical and temperate climates. Heatwave forecasts should signal the need for heightened heat awareness and preventive measures to minimise the risks to workers.

The aim of the present study was to investigate the effects of ethanol in vitro on the phospholipid biosynthetic pathways in hepatocytes isolated from the rat. We have used [methyl‐14C]‐choline, [1‐3H]‐ethanolamine and L‐[3‐3H]‐serine as exogenous precursors of the corresponding phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). Incubation of hepatocytes in the presence of ethanol significantly alters the incorporation of radiolabel from [14C]‐choline and [3H]‐ethanolamine into the metabolic intermediates and the final products of the CDP‐choline and CDP‐ethanolamine pathways. Radioactivity in the metabolic intermediates of both pathways was significantly decreased and the amount of label in PE was reduced whilst that of PC was not modified. In the presence of 4‐methylpyrazole, an inhibitor of alcohol dehydrogenase (ADH) activity, ethanol produces a reduction in the label of choline phosphate, ethanolamine phosphate and a significant decrease in the amount of PC and PE radiolabel. On the other hand, ethanol increases the incorporation of serine into phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine, although this effect is observed only in the absence of 4‐methylpyrazole, indicating that this alteration is produced by some metabolite generated as a consequence of hepatic alcohol metabolism. Ethanol also interferes with the methylation of phosphatidylethanolamine produced via the CDP‐ethanolamine pathway but it does not alter phosphatidylethanolamine methylation when this phospholipid is produced by mitochondrial phosphatidylserine decarboxylation, suggesting the existence of different intramembrane pools of phosphatidylethanolamine, which may exhibit different sensitivity to alcohol. Our results indicate that ethanol exerts two different effects on phospholipid metabolism in hepatocytes: a stimulatory effect on the incorporation of exogenous substrates into different phospholipids probably related to an alteration in the availability of lipogenic substrates as a consequence of ethanol metabolism, and another inhibitory effect produced by ethanol per se, which can be observed only when ethanol metabolism is inhibited by the presence of a specific inhibitor of alcohol dehydrogenase activity.

Little is known about the validity of repeated 24-h dietary recalls (24-HDR) as a measure of total energy intake (EI) in young children. This study aimed to evaluate the validity of proxy-reported EI by comparison with total energy expenditure (TEE) measured by the doubly labeled water (DLW) technique.The agreement between EI and TEE was investigated in 36 (47.2% boys) children aged 4-10 years from Belgium and Spain using subgroup analyses and Bland-Altman plots. Low-energy-reporters (LER), adequate-energy-reporters (AER) and high-energy-reporters (HER) were defined from the ratio of EI over TEE by application of age- and sex-specific cut-off values.There was good agreement between means of EI (1500 kcal/day) and TEE (1523 kcal/day) at group level though in single children, i.e. at the individual level, large differences were observed. Almost perfect agreement between EI and TEE was observed in thin/normal weight children (EI: 1511 kcal/day; TEE: 1513 kcal/day). Even in overweight/obese children the mean difference between EI and TEE was only -86 kcal/day. Among the participants, 28 (78%) were classified as AER, five (14%) as HER and three (8%) as LER.Two proxy-reported 24-HDRs were found to be a valid instrument to assess EI on group level but not on the individual level.