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Despite widespread variation in life span across species, three clear patterns exist: sex differences in life span are ubiquitous, life span is commonly traded against reproduction, and nutrition has a major influence on these traits and how they trade‐off. One process that potentially unites these patterns is intralocus sexual conflict over the optimal intake of nutrients for life span and reproduction. If nutrient intake has sex‐specific effects on life span and reproduction but nutrient choice is genetically linked across the sexes, intralocus sexual conflict will occur and may prevent one or both sexes from feeding to their nutritional optima.Here we determine the potential for this process to operate in the decorated cricket Gryllodes sigillatus. Using the Geometric Framework for Nutrition, we restrict male and female crickets to diets varying in the ratio of protein to carbohydrates and total nutrient content to quantify the effects on life span and daily reproductive effort in the sexes. We then use inbred lines to estimate the quantitative genetic basis of nutrient choice in males and females. We combine the nutrient effects and genetic estimates to predict the magnitude of evolutionary constraint for these traits in each sex. Finally, we present male and female crickets with a much broader range of diet pairs to determine how the sexes actively regulate their intake of nutrients.We show that protein and carbohydrate intake have contrasting effects on life span and reproduction in the sexes and that there are strong positive intersexual genetic correlations for the intake of these nutrients under dietary choice. This is predicted to accelerate the evolutionary response of nutrient intake in males but constrain it in females, suggesting they are losing the conflict. Supporting this view, males and females regulate nutrient intake to a common nutrient ratio that was not perfectly optimal for life span or reproduction in either sex, especially in females.Our findings show that intralocus sexual conflict over the optimal intake of nutrients is likely to be an important process generating sex differences in life span and reproduction and may help explain why females age faster and live shorter than males in G. sigillatus. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

Iridium‐based oxides, currently the state‐of‐the‐art oxygen evolution reaction (OER) electrocatalysts in acidic electrolytes, are cost‐intensive materials which undergo significant corrosion under long‐term OER operation. Thus, numerous researchers have devoted their efforts to mitigate iridium corrosion by decoration with corrosion‐resistant metal oxides and/or supports to maximize OER catalyst durability whilst retaining high activity. Herein a one‐step, facile electrochemical route to obtain improved IrOx thin film OER stability in acid by decorating with amorphous tungsten sulphide (WS3−x) upon electrochemical decomposition of a [WS4]2− aqueous precursor is proposed. The rationale behind applying such WS3−x decoration stems from the generation of a tungsten oxide phase, a well‐known corrosion‐resistant photoactive OER catalyst. The study demonstrates the viability of the proposed WS3−x decoration, allowing the tailoring of experimental parameters responsible for WS3−x nanoparticle size and surface coverage. OER stability tests coupled by ex situ SEM and XPS corroborate the beneficial effect of WS3−x decoration, yielding improved OER specific activity metrics along with minimized Ir surface roughening, a characteristic of electrodissolution. Iridium decoration with electrodeposited, corrosion‐resistant oxides is consequently shown to be a promising route to maximize OER stabilities. [ABSTRACT FROM AUTHOR]

Objective: To explore preferences for self‐management and support services in patients with inflammatory joint disease (IJD) and to investigate whether these preferences differ by age, sex, diagnosis, and disease duration. Methods: We used a nationwide cross‐sectional online survey for patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis. Descriptive statistics were applied to explore preferences and to test for differences according to the different subgroups of patients. Results: The questionnaire was completed by 664 patients. Younger patients indicated greater interest in 1‐to‐1 discussions with psychologists or another patient, educational sessions, events, and online services, and older patients indicated greater interest in talks by researchers. More women than men indicated interest in health professionals' 1‐to‐1 discussions, occupational therapists' question‐and‐answer (Q and A) sessions, physical activity, and informational websites. Patients with axial spondyloarthritis tended to indicate the most interest in the different services, and patients with rheumatoid arthritis the least interest, reaching statistical significance regarding discussion groups about IJD experiences, 1‐to‐1 discussions with psychologists or another patient, Q and A with another patient, stress/anger management, and online patient communication. More patients with short rather than long disease duration indicated interest in 1‐to‐1 discussions with rheumatologists or nurses, organized talks with experienced patients, and online services for patient communication and stories. Conclusion: Patients with IJD report various needs regarding self‐management and support services, including 1‐to‐1 services traditionally delivered as part of usual care, but also talks, physical activity, and educational and online services. Although preferences differed across age, sex, diagnosis, and disease duration, all subgroups indicated great need for support, with only small differences in their top preferences. [ABSTRACT FROM AUTHOR]

A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon‐13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C‐labeled NiII‐acyl complexes, formed from a 13CO insertion step with NiII‐alkyl intermediates, rapidly react in less than one minute with 2,2'‐dipyridyl disulfide to quantitatively form the corresponding 2‐pyridyl thioesters. Either the use of 13C‐SilaCOgen or 13C‐COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one‐pot acylation of a series of structurally diverse amines provides the desired 13C‐labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII‐acyl complexes and the disulfide providing a reactive NiIII‐acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon‐11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C‐labeled liraglutide and insulin degludec, representing two antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Objective: To explore the patients' views of the collection and use of patient-reported outcomes as part of routine care in patients with inflammatory arthritis.Methods: We conducted a qualitative focus group study based on interviews in each of the 5 geographical regions of Denmark. The analysis was based on content analysis. Four patient research partners were involved in the study.Results: In total, 32 adult patients (21 female) with rheumatoid arthritis (n = 21), psoriatic arthritis (n = 6), and axial spondyloarthritis (n = 5) participated. The mean age was 60 years (range 32-80 years). Five themes were derived from the analysis: 1) a need for information about why the data are collected, reflecting patients' uncertainty as to whether the collection of patient-reported outcomes primarily served to monitor their own disease, to save money, or to gather data for research purposes; 2) inclusion of patient-reported outcomes in the consultation, encompassing patients' expectations of active use of the patient-reported outcomes data during talks with rheumatologists or nurses; 3) reflections on how to respond to the patient-reported outcome measures (PROMs) to obtain high quality data, referring to patients' concerns about how to respond "correctly" and about issues that could affect their responses; 4) addressing patient-reported outcomes to the individual's challenges, reflecting the need for a more individualized approach; and 5) possibilities for improvement in the use of patient-reported outcomes, referring to patients' ideas for the future use of patient-reported outcomes.Conclusion: Information and dialogue regarding the purpose of patient-reported outcomes collection, how to respond to PROMs correctly, and inclusion of the patient-reported outcomes data in the consultation are of importance to patients with inflammatory arthritis who routinely complete patient-reported outcomes. [ABSTRACT FROM AUTHOR]

We studied the food quality of the aphid Rhopalosiphum padi to the pirate bug Orius majusculus using Ephestia eggs as high‐quality comparison prey. Several performance parameters were tested on individuals that had been reared and maintained on each of the two single‐prey diets or on a mixed diet. All fitness parameters were lower in individuals fed aphids only, indicating poor food quality of this prey. Compared with the pure Ephestia egg diet, the mixed diet enhanced teneral mass, while adult survival and female starvation tolerance were negatively affected and all other traits were unaffected. Body protein proportions were constant across diets, whereas lipid proportion was low in the aphid treatment. Preference for aphids was lower following a monotypic aphid diet than when reared on Ephestia eggs or a mixed diet. The results confirm that R. padi is low‐quality food for O. majusculus as it is for other generalist predators, even though O. majusculus may contribute significantly to population suppression of the aphid. [ABSTRACT FROM AUTHOR]

Habitats vary in food resources with carnivores often being prey limited, but it is unclear whether habitats facilitate a nutritionally balanced diet. Two paradigms in nutritional ecology, ecological stoichiometry and nutritional geometry, predict that carnivores are limited mainly by protein or lipid, respectively. Using the carabid beetle Anchomenus dorsalis and 10 other predatory beetles from agricultural fields, we developed and tested two simple procedures for quantifying macronutrient‐specific habitat conditions without requiring information about the natural prey. Both procedures assume that predators forage for nutrients rather than specific prey. Our results show that 10 of 11 species were food limited. Five species were lipid limited and one species was protein limited in the field. Co‐existing predator species showed considerable segregation of fundamental macronutritional niches. A linear relationship between specific nutrient limitation and the target lipid:protein (L:P) intake ratio indicates that species with high L:P target are more protein limited while species with low L:P target are more lipid limited. The study illustrates how species within a natural assemblage vary in nutritional niche and in specific nutrient limitation. [ABSTRACT FROM AUTHOR]

Context: Globally, primary health care is facing workforce shortages. Longer and higher‐quality placements in primary care increase the likelihood of medical students choosing this specialty. However, the recruitment and retention of community primary care teachers are challenging. Relevant research was predominantly carried out in the 1990s. We seek to understand contemporary facilitators and barriers to general practitioner (GP) engagement with undergraduate education. Communities of practice (CoP) theory offers a novel conceptualisation, which may be pertinent in other community‐based teaching settings. Methods: Semi‐structured interviews were undertaken with 24 GP teachers at four UK medical schools. We purposively sampled GPs new to teaching, established GP teachers and GPs who had recently stopped teaching. We undertook NVivo‐assisted deductive and inductive thematic analysis of transcripts. We used CoP theory to interpret data. Results: Communities of practice theory illustrated that teachers negotiate membership of three CoPs: (i) clinical practice; (ii) the medical school, and (iii) teaching. The delivery of clinical care and teaching may be integrated or exist in tension. This can depend upon the positioning of the teaching and teacher as central or peripheral to the clinical CoP. Remuneration, workload, space and the expansion of GP trainee numbers impact on this. Teachers did not identify strongly as members of the medical school or a teaching community. Perceptions of membership were affected by medical school communication and support. The findings demonstrate gaps in medical school recruitment. Conclusions: This research demonstrates the marginalisation of primary care‐based teaching and proposes a novel explanation rooted in CoP theory. Concepts including identity and membership may be pertinent to other community‐based teaching settings. We recommend that medical schools review and broaden recruitment methods. Teacher retention may be improved by optimising the interface between medical schools and teachers, fostering a teaching community, increasing professional rewards for teaching involvement and altering medical school expectations of learning in primary care. The authors demonstrate, through use of Communities of Practice theory, ways to improve retention and recruitment of community‐based clinical teachers. [ABSTRACT FROM AUTHOR]

Temperature influences biological processes of ectotherms including ecological interactions, but interaction strengths may depend on species‐specific traits. Furthermore, ectotherms acclimate to prevailing thermal conditions by adjusting physiological parameters, which often implies costs to other fitness‐related parameters. Both predators and prey may therefore pay thermal acclimation costs following exposure to suboptimal temperatures. However, these costs may be asymmetrical between predator and prey, and between the predator and different species of concurrent prey.We investigated whether thermal pre‐exposure affected subsequent kill rate and predator fitness when foraging on prey that differ in ease of capture, and whether changes were primarily caused by predator or by prey pre‐exposure effects. Specifically, we were interested in whether there were interactions between predator pre‐exposed temperature and specific prey.Using the mesostigmatid mite Gaeolaelaps aculeifer as a generalist predator and the collembolans Folsomia candida and Protaphorura fimata as prey, we measured the impact of present temperature, predator pre‐exposure temperature, prey pre‐exposure temperature (all 10 or 20°C), prey species, and all interactions on prey numbers killed, predator eggs produced, and exploitation of killed prey in a full factorial design.Mites killed P. fimata in equal numbers independent of the presence of F. candida, but killed F. candida when P. fimata was absent. Mite kill rate and reproduction were significantly affected by mite pre‐exposure temperature and test temperature, but not by prey pre‐exposure temperature. Significantly more of the slower prey was killed than of the quicker prey. Importantly, we found significant synergistic negative interaction effects between predator cold pre‐exposure and hunting prey of higher agility on predator kill rate and reproduction.Our findings show that the negative effects of cold and cold pre‐exposure on kill rate and reproduction may be more severe when predators forage on quick prey. The study implies that predator cold exposure has consequences for specific prey survival following cold due to altered predation pressures, which in nature should influence the specific prey population dynamics and apparent competition outcomes. The findings exemplify how not only current but also preceding conditions affect ecological interactions, and that effect strength depends on the species involved. This study shows that not only current temperature but also previously experienced temperature affects predator‐prey interaction strength, in a prey‐specific manner, and that the effect is much larger on the predator than on the prey. [ABSTRACT FROM AUTHOR]

1. The presence of predators is known to suppress prey populations not only by consumptive but also by non‐consumptive effects, as it stresses the prey inducing costly changes to behaviour and physiology. However, there is recent evidence that disturbance from non‐predacious, non‐competing commensals can also negatively affect herbivore performance. 2. Populations of cherry‐oat aphids (Rhopalosiphum padi L.) were initiated with adult aphids in mesocosms containing seedling wheat grass. Following aphid establishment, fruit flies (Drosophila melanogaster Meigen) were added at a relatively high density to half of the mesocosms and the aphids were left for another 5 days to reproduce. The experiment was performed over two blocks at 24 ± 4 °C. It was hypothesized that a relatively high density of commensals would stress the aphids and reduce their fitness, causing lower population growth and resulting in lower population sizes. 3. Aphid numbers were significantly lower in mesocosms with commensal flies after 5 days of fly presence across the two experimental blocks, documenting that fly disturbance suppresses aphid fitness and population growth. 4. The negative effect of fruit flies on aphid population growth must have come from the disturbance that flies imposed on the aphids in their search for food, indicating that the flies stressed the aphids. Thus, our study indicates that commensals may stress herbivores that do not distinguish between enemies and other active species in their environment, adding in the overall herbivore top‐down control through fitness costs. [ABSTRACT FROM AUTHOR]

Abstract: Alloys of platinum and gadolinium present significant activity enhancement over pure Pt for the oxygen reduction reaction (ORR), both in the form of extended electrode surfaces and nanoparticulate catalysts. The active phase consists of a compressed Pt overlayer formed on Pt5Gd electrodes upon exposure to the electrolyte by acid leaching. Here, we investigate the formation, strain and correlation lengths of the active Pt overlayer by using in situ synchrotron grazing incidence X‐ray diffraction on Gd/Pt(111) single‐crystalline electrodes. The overlayer forms upon exposure to electrolyte under open circuit conditions; the compressive strain relaxes slightly upon repeated electrochemical cycling in the potential range 0.6 to 1.0 V versus the reversible hydrogen electrode (RHE). In addition, the strain relaxes strongly when exposing the electrode to 1.2 V versus RHE, and the thickness of the crystalline portion of the overlayer increases with potential above 1.3 V versus RHE. [ABSTRACT FROM AUTHOR]

Abstract: The relationship between the binding of the reaction intermediates and oxygen reduction activity in alkaline media was experimentally explored. By introducing Cu into the 2nd surface layer of a Pt(111) single crystal, the surface reactivity was tuned. In both 0.1  m NaOH and 0.1  m KOH, the optimal catalyst should exhibit OH binding circa 0.1 eV weaker than Pt(111), via a Sabatier volcano; this observation suggests that the reaction is mediated via the same surface bound intermediates as in acid, in contrast to previous reports. In 0.1  m KOH, the alloy catalyst at the peak of the volcano exhibits a maximum activity of 101±8 mA cm−2 at 0.9 V vs. a reversible hydrogen electrode (RHE). This activity constitutes a circa 60‐fold increase over Pt(111) in 0.1  m HClO4. [ABSTRACT FROM AUTHOR]

Transgenic porcine cancer models bring novel possibilities for research. Their physical similarities with humans enable the use of surgical procedures and treatment approaches used for patients, which facilitates clinical translation. Here, we aimed to develop an inducible oncopig model of intestinal cancer. Transgenic (TG) minipigs were generated using somatic cell nuclear transfer by handmade cloning. The pigs encode two TG cassettes: (a) an Flp recombinase-inducible oncogene cassette containing KRAS-G12D, cMYC, SV40LT - which inhibits p53 - and pRB and (b) a 4-hydroxytamoxifen (4-OHT)-inducible Flp recombinase activator cassette controlled by the intestinal epithelium-specific villin promoter. Thirteen viable transgenic minipigs were born. The ability of 4-OHT to activate the oncogene cassette was confirmed in vitro in TG colonic organoids and ex vivo in tissue biopsies obtained by colonoscopy. In order to provide proof of principle that the oncogene cassette could also successfully be activated in vivo, three pigs were perorally treated with 400 mg tamoxifen for 2 × 5 days. After two months, one pig developed a duodenal neuroendocrine carcinoma with a lymph node metastasis. Molecular analysis of the carcinoma and metastasis confirmed activation of the oncogene cassette. No tumor formation was observed in untreated TG pigs or in the remaining two treated pigs. The latter indicates that tamoxifen delivery can probably be improved. In summary, we have generated a novel inducible oncopig model of intestinal cancer, which has the ability to form metastatic disease already two months after induction. The model may be helpful in bridging the gap between basic research and clinical usage. It opens new venues for longitudinal studies of tumor development and evolution, for preclinical assessment of new anticancer regimens, for pharmacology and toxicology assessments, as well as for studies into biological mechanisms of tumor formation and metastasis. [ABSTRACT FROM AUTHOR]

Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease. [ABSTRACT FROM AUTHOR]

The application of active filtering in large offshore wind power plants (WPPs) is presented in this study. The harmonic challenges such as sources of harmonic emission and resonances are identified and briefly explained. Also modern remedial harmonic mitigation methods as of active filtering are described and their application in real‐life WPP systems demonstrated. It is underlined that WPP components such as widespread medium‐voltage cable system and offshore grid transformers can introduce significant low‐frequency parallel resonances which can cause a significant harmonic voltage distortion at the point of common coupling. Active filtering in modern grid‐side converters used in wind turbines is applied simultaneously keeping sufficient harmonic/noise rejection. Extensive harmonic stability studies are also shown to prove the overall system robustness. [ABSTRACT FROM AUTHOR]

Purpose Monthly dosing with ranibizumab ( RBZ) is needed to achieve maximal visual gains in patients with neovascular ('wet') age-related macular degeneration ( wAMD). In Sweden, dosing is performed as needed ( RBZ PRN), resulting in suboptimal efficacy. Intravitreal aflibercept ( IVT- AFL) every 2 months after three initial monthly doses was clinically equivalent to RBZ monthly dosing ( RBZ q4) in wAMD clinical trials. We assessed the cost-effectiveness of IVT- AFL versus RBZ q4 and RBZ PRN in Sweden. Methods A Markov model compared IVT- AFL to RBZ q4 or RBZ PRN over 2 years. Health states were based on visual acuity in better-seeing eye; a proportion discontinued treatment monthly or upon visual acuity <20/400. Parameters were estimated from trial data, published literature or expert opinion. Analyses were performed from a societal perspective with a lifetime horizon. The model calculated costs, quality-adjusted life years ( QALYs) and incremental cost-effectiveness ratios ( ICERs), discounted 3% annually. Deterministic and probabilistic sensitivity analyses were performed. Results Lifetime cost of IVT- AFL was 578 400 SEK, compared with 565 700 SEK for RBZ PRN and 686 600 SEK for RBZ q4. Compared with RBZ PRN, the ICER of IVT- AFL was 27 000 SEK/ QALY gained. RBZ q4 cost 20.4 million SEK/ QALY gained versus IVT- AFL. Results were sensitive to IVT- AFL efficacy, but IVT- AFL had a 100% probability of being cost-effective versus both RBZ PRN and RBZ q4 at a willingness-to-pay threshold of 500 000 SEK. Conclusion Results suggest, in Sweden, at parity price level, IVT- AFL is less costly than RBZ q4, while demonstrating similar efficacy; IVT- AFL is cost-effective versus RBZ PRN. [ABSTRACT FROM AUTHOR]

Sexual selection may cause dietary requirements for reproduction to diverge across the sexes and promote the evolution of different foraging strategies in males and females. However, our understanding of how the sexes regulate their nutrition and the effects that this has on sex-specific fitness is limited. We quantified how protein (P) and carbohydrate (C) intakes affect reproductive traits in male (pheromone expression) and female (clutch size and gestation time) cockroaches ( Nauphoeta cinerea). We then determined how the sexes regulate their intake of nutrients when restricted to a single diet and when given dietary choice and how this affected expression of these important reproductive traits. Pheromone levels that improve male attractiveness, female clutch size and gestation time all peaked at a high daily intake of P:C in a 1:8 ratio. This is surprising because female insects typically require more P than males to maximize reproduction. The relatively low P requirement of females may reflect the action of cockroach endosymbionts that help recycle stored nitrogen for protein synthesis. When constrained to a single diet, both sexes prioritized regulating their daily intake of P over C, although this prioritization was stronger in females than males. When given the choice between diets, both sexes actively regulated their intake of nutrients at a 1:4.8 P:C ratio. The P:C ratio did not overlap exactly with the intake of nutrients that optimized reproductive trait expression. Despite this, cockroaches of both sexes that were given dietary choice generally improved the mean and reduced the variance in all reproductive traits we measured relative to animals fed a single diet from the diet choice pair. This pattern was not as strong when compared to the single best diet in our geometric array, suggesting that the relationship between nutrient balancing and reproduction is complex in this species. [ABSTRACT FROM AUTHOR]

Condition is defined as the pool of resources available to an individual that can be allocated to fitness-enhancing traits. Consequently, condition could influence developmental trade-offs if any occur. Although many studies have manipulated diet to demonstrate condition-dependent trait expression, few studies have determined the contribution of specific nutrients to condition or trade-offs., We used nutritional geometry to quantify the effects of dietary protein and carbohydrate content on larval performance and the development of adult morphology including body size as well as a primary and secondary sexually selected trait in male broad-horned beetles, Gnatocerus cornutus., We found that offspring survival, development rate and morphological traits were highly affected by dietary carbohydrate content and to a lesser extent by protein content and that all traits were maximized at a protein-to-carbohydrate ratio around 1:2. The absolute size of a secondary sexual character, the mandibles, had a heightened response to the increased availability and ratio of both macronutrients. Male genitalia, in contrast, were relatively insensitive to the increased availability of macronutrients., Overall, while nutrition influenced trait expression, the nutritional requirements of development rate and morphological traits were largely the same and resource acquisition seems to implement only weak trade-offs in this species., This finding contrasts with some resource constraint predictions, as beetles seem able to simultaneously meet the nutritional requirements of most traits. [ABSTRACT FROM AUTHOR]

Adaptations to hazardous environmental factors are essential for survival, although they may be maladaptive in conditions where the hazard is absent. In German cockroach ( Blattella germanica L.) populations, glucose aversion has evolved rapidly in response to glucose-containing insecticidal baits, but little is known about the consequences of this behaviour in the absence of bait. In the present study, glucose-averse ( GA) and wild-type ( WT) male German cockroaches are restricted to a range of nutritionally defined diets containing either glucose or fructose as the sole carbohydrate source, and time to first expression of courtship is measured by stimulating the male antennae daily with isolated antennae from receptive, 6-day-old females. Glucose-averse males that are restricted to glucose-containing diets mature their courtship responses significantly later than GA males restricted to fructose-containing diets, whereas there is no difference in maturation of courtship responses between GA males restricted to fructose-containing diets and WT males restricted to diets containing either sugar type. Glucose-averse males furthermore respond later to GA female antennae than to WT female antennae, all from 6-day-old females. This suggests that GA females are less sexually stimulating, and the results are also consistent with earlier findings showing that GA females contain less developed oocytes than WT females at this age. These findings demonstrate that an adaptive gustatory mutation conferring protection from a toxin may have comparatively detrimental effects under conditions where the toxin has vanished, both by delaying female sexual maturation and signalling and by delaying male sexual maturation and courtship under conditions where glucose is a major energy source. [ABSTRACT FROM AUTHOR]

Modest dietary restriction extends lifespan ( LS) in a diverse range of taxa and typically has a larger effect in females than males. Traditionally, this has been attributed to a stronger trade-off between LS and reproduction in females than in males that is mediated by the intake of calories. Recent studies, however, suggest that it is the intake of specific nutrients that extends LS and mediates this trade-off. Here, we used the geometric framework ( GF) to examine the sex-specific effects of protein (P) and carbohydrate (C) intake on LS and reproduction in Drosophila melanogaster. We found that LS was maximized at a high intake of C and a low intake of P in both sexes, whereas nutrient intake had divergent effects on reproduction. Male offspring production rate and LS were maximized at the same intake of nutrients, whereas female egg production rate was maximized at a high intake of diets with a P:C ratio of 1:2. This resulted in larger differences in nutrient-dependent optima for LS and reproduction in females than in males, as well as an optimal intake of nutrients for lifetime reproduction that differed between the sexes. Under dietary choice, the sexes followed similar feeding trajectories regulated around a P:C ratio of 1:4. Consequently, neither sex reached their nutritional optimum for lifetime reproduction, suggesting intralocus sexual conflict over nutrient optimization. Our study shows clear sex differences in the nutritional requirements of reproduction in D. melanogaster and joins the growing list of studies challenging the role of caloric restriction in extending LS. [ABSTRACT FROM AUTHOR]

In this communication, we report a straightforward synthesis of enantiomerically pure 2-alkyl azetidines. The protocol is based on a highly regioselective nickel-catalyzed cross-coupling of aliphatic organozinc reagents with an aziridine that features a tethered thiophenyl group. Activation by methylation transforms the sulfide into an excellent leaving group and triggers the formation of the 2-substituted azetidine core structure by cyclization. In addition, we have expanded this concept to the synthesis of enantiomerically pure, terminal alkyl aziridines. Coupling of a TMS-protected aziridine alcohol, followed by acidic work-up to remove the silyl group, provides 1,2-amino alcohol products that are readily cyclized to aziridines. Both of these sequences display excellent functional group tolerance and deliver the desired azetidine and aziridine products in good to excellent yields. [ABSTRACT FROM AUTHOR]

Background The majority of patients with ankylosing spondylitis (AS) are male, although potential gender differences have not been investigated in relation to disease management. Moreover, men's perceptions of experiencing AS have not been reported in the literature. Aims This study sought to develop an understanding of how men experience AS and the challenges related to living with AS as a chronic disease. Methods A purposive sample of 13 men diagnosed with AS, with a median age of 44 years (range 32-58) was recruited from a rheumatology outpatient clinic. The median duration of disease was 12 years (range 0.3-28 years), and the median time from the first symptom to final diagnosis was seven years (range 2-20 years). Semi-structured interviews were conducted using an interview guide, and the interviews were analysed using content analysis inspired by Graneheim qualitative methodology. Results The analysis revealed four categories: (1) 'Approaching a diagnosis'; (2) 'Ill in a social context'; (3) 'Challenged as a man'; and (4) 'The importance of remaining physically well'. Based on these categories, the overall category of 'An invisible companion for life' emerged, which captures the experience of living with an invisible, life-long disease. Conclusions These findings demonstrate that AS impacts men's perceptions of themselves as men, relationships as a partner and father, social lives, and masculine identity. Physical activity was highlighted as an important part of being a man, and not being able to exercise challenged the men's masculine identity. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The skin carries out specialist functions such as barrier formation and thermoregulation. The mode of cellular replenishment of the surface epithelium that forms the outermost layer during steady-state homeostasis is a subject of intensive investigations. A detailed analysis of the interfollicular epidermis reported in this issue of The EMBO Journal (Roy et al, ) reveals that hair follicles in their growth phase influence cellular behaviour of epithelial cells in their immediate proximity. [ABSTRACT FROM AUTHOR]

Mechanistic studies on the organocatalytic epoxidation of α,β-unsaturated aldehydes explore the autoinductive behavior of the reaction and establish that the hydrate/peroxyhydrate of the product is acting as a phase-transfer catalyst. Based on these studies, an improved methodology that provides high selectivities and decreased catalyst loading, through the addition of chloral hydrate, is developed. [ABSTRACT FROM AUTHOR]

A bibliography on the subject of stem cells is presented including "Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4," "Nanog is the gateway to the pluripotent ground state," and "The ground state of embryonic stem cell self-renewal."

Wind power plants (WPP) are for power system stability studies often represented with aggregated models where several wind turbines (WT) are aggregated into a single up‐scaled model. The advantage is a reduction in the model complexity and the computational time, and for a number of study types the accuracy of the results has been found acceptable. A large WPP is, however, both modular and distributed over a large geographical area, and feasibility of aggregating the WTs, thus, have to be reassessed when new applications are introduced for WPPs. Here, the power oscillation damping capabilities are investigated for a WPP, which includes the full layout of the collector grid and where the WTs are represented individually. With this approach, the influence of the WT control in terms of impact on oscillatory modes is assessed for the WTs individually. The initial results encourage that park level control is possible. Time domain simulations support that each WT contribute to a common WPP response. Park level active and reactive power‐based power oscillation damping controllers (POD) are designed and the positive damping contribution is demonstrated. Keeping the POD designs unchanged, the impact of WPP aggregation is investigated and it is shown that the level of WPP aggregation only has limited impact on the resulting modal damping. The study is based on a non‐linear, dynamic model of the 3.6 MW Siemens Wind Power WT. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor ( EGFR) pathway activation is a frequent event in human carcinomas. Mutations in EGFR itself are, however, rare, and the mechanisms regulating EGFR activation remain elusive. Leucine-rich immunoglobulin repeats-1 ( LRIG1), an inhibitor of EGFR activity, is one of four genes identified that predict patient survival across solid tumour types including breast, lung, melanoma, glioma, and bladder. We show that deletion of Lrig1 is sufficient to promote murine airway hyperplasia through loss of contact inhibition and that re-expression of LRIG1 in human lung cancer cells inhibits tumourigenesis. LRIG1 regulation of contact inhibition occurs via ternary complex formation with EGFR and E-cadherin with downstream modulation of EGFR activity. We find that LRIG1 LOH is frequent across cancers and its loss is an early event in the development of human squamous carcinomas. Our findings imply that the early stages of squamous carcinoma development are driven by a change in amplitude of EGFR signalling governed by the loss of contact inhibition. [ABSTRACT FROM AUTHOR]

Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic tumour tissue in vivo and that FoxO3A short-hairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13-23. Alternative influenza vaccines and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross-reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change in the vaccine formulations. In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Ferrets were immunised by particle-mediated epidermal delivery (gene gun) with DNA vaccines based on the haemagglutinin (HA) and neuraminidase (NA) and/or the matrix (M) and nucleoprotein genes of the 1918 H1N1 Spanish influenza pandemic virus or the 1968 H3N2 Hong Kong influenza pandemic virus. The animals were challenged with contemporary H1N1 or H3N2 viruses. We demonstrated that DNA vaccines encoding proteins of the original 1918 H1N1 pandemic virus induced protective cross-reactive immune responses in ferrets against infection with a 1947 H1N1 virus and a recent 1999 H1N1 virus. Similarly, a DNA vaccine, based on the HA and NA of the 1968 H3N2 pandemic virus, induced cross-reactive immune responses against a recent 2005 H3N2 virus challenge. DNA vaccines based on pandemic or recent seasonal influenza genes induced cross-reactive immunity against contemporary virus challenge as good as or superior to contemporary conventional trivalent protein vaccines. This suggests a unique ability of influenza DNA to induce cross-protective immunity against both contemporary and long-time drifted viruses. [ABSTRACT FROM AUTHOR]

Mammalian epidermis is maintained by self-renewal of stem cells and terminal differentiation of their progeny. New data reveal a diversity amongst stem cells that was previously unrecognized. Different stem cell populations have different locations and differ in whether they are quiescent or actively cycling. During normal epidermal homeostasis, each stem cell population feeds a restricted number of differentiated lineages. However, in response to injury or genetic manipulation the different pools of stem cells demonstrate multi-lineage differentiation ability. While it is well established that Wnt signalling promotes hair follicle (HF) differentiation, new observations suggest a role for EGF receptor signalling in promoting differentiation of interfollicular epidermis. NFATc1 maintains quiescence in the HF, while Lrig1 exerts the same function in the junctional zone. The stage is now set for exploring the relationship between the different epidermal stem cell populations and between quiescence and lineage selection. [ABSTRACT FROM AUTHOR]

The article focuses on the economic and agricultural impacts of ethanol and biodiesel expansion as well as project the U.S. agricultural sector. Study shows that the use of bioenergy feedstocks in producing transportation fuels could provide relevant environmental benefits and enliven rural economics other than lessening foreign oil reliance. Agriculture is considered as a feedstock source since fuels can be utilized with current engine technologies and are compatible with distribution infrastructure. It was found out that the economic gains are hoped to fall in the majority of the country's region due to the geographic decentralization of feedstock production. This suggests that its agricultural sector is in a position to play a significant role as an energy source.

Although DNA-based cancer vaccines have been successfully tested in mouse models, a major drawback of cancer vaccination still remains, namely that tumour antigens are weak and fail to generate a vigorous immune response in tumour-bearing patients. Genetic technology offers strategies for promoting immune pathways by adding immune-activating genes to the tumour antigen sequence. In this work, we converted a model non-immunogenic antigen into a vaccine by fusing it to domain I of the filamentous bacteriophage coat protein III gene. Vaccination with a DNA construct encoding the domain I fusion generated antigen-specific T helper 1-type cellular immune responses. These results demonstrate that the incorporation of protein III into a DNA vaccine formulation can modulate the gene-mediated immune response and may thus provide a strategy for improving its therapeutic effect. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify novel antibodies directed against cytosolic keratinocyte-specific antigens from a phage display antibody repertoire by using phage display subtraction. Phage display is a method of displaying foreign molecules on the surface of filamentous bacteriophage particles. It allows the interaction between two cognate molecules to be analysed through affinity selections. Recently, large repertoires of phage displayed human antibody fragments have been constructed. From such repertoires, antibodies can be obtained in vitro without the need for immunization or the hybridoma technology. A novel subtractive strategy for selecting antibodies from phage libraries was applied. Phage antibodies were selected against immobilized crude lysates of cultured human keratinocytes, the target antigens being unknown beforehand. A competing cell lysate was used to reduce retrieval of phage antibodies with specificities to commonly nondifferentially expressed antigens. A monoclonal single chain fragment variable (scFv) with specificity for crude lysates of cultured human keratinocytes was identified as demonstrated by ELISA assays and immunoblotting analysis. The cognate keratinocyte antigen was shown to be keratin 14 (K14) by using immunoblotting based on 2D PAGE and a corresponding 2D PAGE protein database. In accordance with the expected tissue localization of K14, the identified scFv stained the basal layer of human epidermis by indirect immunofluorescence analysis. Starting with crude cell lysates, phage display subtraction in combination with 2D PAGE and 2D PAGE protein databases can be used to identify antibody–antigen pairs that characterize a specific cell type. Abbreviations : Hanks, buffered saline solution; HRP, horseradish peroxidase; GST, glutathione S-transferase; IMAC, immobilized metal affinity chromatography; K14, Keratin 14; scFv, single chain fragment variable.. [ABSTRACT FROM AUTHOR]

Discusses a study that investigated how export assistance needs may vary across exporting status of agribusinesses in the United States. Assistance needs across export status; Model of export status; Measurement of the influence of firm characteristics on export status.

Uses a unique firm level data set to analyze differences in knowledge and use of many export assistance services provided by the United States government. Role of exports in the success of many agribusinesses; Knowledge of services by firm size; Knowledge of services by export experience.

Presents a study which assessed the efficiency of of 1993 legislation which required the United States Department of Agriculture to allocate funds for Market Promotion Programs (MPP) urgently. Reference to the Budget Reconciliation Act of 1993; Information on the MPP; Method used in the study; What the results indicated.