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The honey bee, Apis mellifera L., is one of the main pollinators worldwide. In a temperate climate, seasonality affects the life span, behavior, physiology, and immunity of honey bees. In consequence, it impacts their interaction with pathogens and parasites. In this study, we used Bayesian statistics and modeling to examine the immune response dynamics of summer and winter honey bee workers after injection with the heat-killed bacteria Serratia marcescens, an opportunistic honey bee pathogen. We investigated the humoral and cellular immune response at the transcriptional and functional levels using qPCR of selected immune genes, antimicrobial activity assay, and flow cytometric analysis of hemocyte concentration. Our data demonstrate increased antimicrobial activity at transcriptional and functional levels in summer and winter workers after injection, with a stronger immune response in winter bees. On the other hand, an increase in hemocyte concentration was observed only in the summer bee population. Our results indicate that the summer population mounts a cellular response when challenged with heat-killed S. marcescens, while winter honey bees predominantly rely on humoral immune reactions. We created a model describing the honey bee immune response dynamics to bacteria-derived components by applying Bayesian statistics to our data. This model can be employed in further research and facilitate the investigating of the honey bee immune system and its response to pathogens. [ABSTRACT FROM AUTHOR]

Advancements in veterinary medicine have resulted in increased life spans for dogs, necessitating a better understanding of quality of life for older dogs. This study aimed to evaluate quality of life (QoL) progression and its potential association with mortality in senior and geriatric dogs. The Canine Owner-Reported Quality of Life Questionnaire (CORQ), consisting of 17 questions across four domains (vitality, companionship, pain, and mobility) was employed. Higher scores indicated better quality of life, with 7 as the highest potential score for each question. In a cross-sectional analysis including 92 dogs, we found an inverse correlation between overall CORQ (and all domain scores) and fractional lifespan. The domain of vitality demonstrated the lowest scores, while companionship exhibited the highest. A longitudinal analysis, including 34 dogs, revealed that when dogs reach the geriatric stage (100% of their calculated lifespan), their expected overall CORQ is 5.95 out of 7, and dogs are expected to have a monthly decline of 0.05 units in the score. Cox proportional hazard analysis demonstrated a significant association between overall CORQ scores and mortality, with dogs scoring below 5.35 being at a higher risk of mortality. This study underscores the association between aging, declining quality of life, and increased mortality risk in aging dogs. [ABSTRACT FROM AUTHOR]

For management efforts to succeed in Caribbean fisheries, local fishers must support and be willing to comply with fishing regulations. This is more likely when fishers are included in a stock assessment process that utilizes robust scientific evidence, collected in collaboration with fishers, to evaluate the health of fish stocks. Caribbean parrotfishes are important contributors to coral reef ecosystem health while also contributing to local fisheries. Scientifically robust stock assessments require regional species-specific information on age-based key life history parameters, derived from fish age estimates. Evaluation of the accuracy of age estimation methods for fish species is a critical initial step in managing species for long-term sustainable harvest. The current study resulted from a collaborative research program between fish biologists and local fishers investigating age, growth, and reproductive biology of the seven parrotfish species landed in U.S. Caribbean fisheries; specifically, we validated age estimation for stoplight parrotfish Sparisoma viride and queen parrotfish Scarus vetula. This is the first study to directly validate age estimation for any parrotfish species through analysis of Δ14C from eye lens cores. Our age estimation validation results show that enumeration of opaque zones from thin sections of sagittal otoliths for a Sparisoma and a Scarus species provides accurate age estimates. The oldest stoplight parrotfish and queen parrotfish in the Δ14C age estimation validation series were 14 y and 16 y; while the oldest stoplight parrotfish and queen parrotfish we aged to-date using the Δ14C validated age estimation method were 20 y and 21 y, respectively. Fish longevity (maximum age attained/life span) is a key life history parameter used for estimation of natural mortality, survivorship, and lifetime reproductive output. Past reviews on parrotfishes from the Pacific and Atlantic concluded that most Caribbean/western Atlantic parrotfish species are relatively short-lived with estimated maximum ages ranging from 3–9 y. However, information from our collaborative research in the U.S. Caribbean combined with recently published age estimates for Brazilian parrotfish species indicate that many western Atlantic parrotfishes are relatively long-lived with several species attaining maximum ages in excess of 20 y. [ABSTRACT FROM AUTHOR]

Mating and receipt of male Sex Peptide hormone cause increased egg laying, increased midgut size and decreased life span in female Drosophila. Feeding mated females with the synthetic steroid mifepristone decreases egg production, reduces midgut size, and increases life span. Here, several gene mutations were assayed to investigate possible mechanisms for mifepristone action. Drosophila Dhr96 is a hormone receptor, and a key positive regulator of midgut lipid uptake and metabolism. Dhr96[1] null mutation increased female life span, and reduced the effects of mifepristone on life span, suggesting that Dhr96[1] mutation and mifepristone may act in part through the same mechanism. Consistent with this idea, lipidomics analysis revealed that mating increases whole-body levels of triglycerides and fatty-acids in triglycerides, and these changes are reversed by mifepristone. Maternal tudor[1] mutation results in females that lack the germ-line and produce no eggs. Maternal tudor[1] mutation increased mated female life span, and reduced but did not eliminate the effects of mating and mifepristone on life span. This indicates that decreased egg production may be related to the life span benefits of mifepristone, but is not essential. Mifepristone increases life span in w[1118] mutant mated females, but did not increase life span in w[1118] mutant virgin females. Mifepristone decreased egg production in w[1118] mutant virgin females, indicating that decreased egg production is not sufficient for mifepristone to increase life span. Mifepristone increases life span in virgin females of some, but not all, white[+] and mini-white[+] strains. Backcrossing of mini-white[+] transgenes into the w[1118] background was not sufficient to confer a life span response to mifepristone in virgin females. Taken together, the data support the hypothesis that mechanisms for mifepristone life span increase involve reduced lipid uptake and/or metabolism, and suggest that mifepristone may increase life span in mated females and virgin females through partly different mechanisms. [ABSTRACT FROM AUTHOR]

FAM3C/ILEI is an important factor in epithelial-to-mesenchymal transition (EMT) induction, tumor progression and metastasis. Overexpressed in many cancers, elevated ILEI levels and secretion correlate with poor patient survival. Although ILEI's causative role in invasive tumor growth and metastasis has been demonstrated in several cellular tumor models, there are no available transgenic mice to study these effects in the context of a complex organism. Here, we describe the generation and initial characterization of a Tet-ON inducible Fam3c/ILEI transgenic mouse strain. We find that ubiquitous induction of ILEI overexpression (R26-ILEIind) at weaning age leads to a shortened lifespan, reduced body weight and microcytic hypochromic anemia. The anemia was reversible at a young age within a week upon withdrawal of ILEI induction. Vav1-driven overexpression of the ILEIind transgene in all hematopoietic cells (Vav-ILEIind) did not render mice anemic or lower overall fitness, demonstrating that no intrinsic mechanisms of erythroid development were dysregulated by ILEI and that hematopoietic ILEI hyperfunction did not contribute to death. Reduced serum iron levels of R26-ILEIind mice were indicative for a malfunction in iron uptake or homeostasis. Accordingly, the liver, the main organ of iron metabolism, was severely affected in moribund ILEI overexpressing mice: increased alanine transaminase and aspartate aminotransferase levels indicated liver dysfunction, the liver was reduced in size, showed increased apoptosis, reduced cellular iron content, and had a fibrotic phenotype. These data indicate that high ILEI expression in the liver might reduce hepatoprotection and induce liver fibrosis, which leads to liver dysfunction, disturbed iron metabolism and eventually to death. Overall, we show here that the novel Tet-ON inducible Fam3c/ILEI transgenic mouse strain allows tissue specific timely controlled overexpression of ILEI and thus, will serve as a versatile tool to model the effect of elevated ILEI expression in diverse tissue entities and disease conditions, including cancer. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA), sport, and exercise levels generally tend to fluctuate or decline from childhood to adulthood. Life events and transitions may have a positive or negative impact on these behaviors. However, most research in this regard is quantitatively framed and we know little about why and how life events and transitions affect PA-related behaviors. Objectives: The aim of this study is to understand when, why, and how individuals change their daily PA, sport, and exercise behaviors and related attitudes in the context of life events and transitions and what underlying dynamics promote these changes from a subjective perspective. Methods: Forty-six young inactive adults (33 women) aged between 20 and 40 years from the iReAct study participated in a mixed-method biographical mapping, which combines a semi-structured interview with a drawing activity to explore subjective experiences of life events, transitions, and PA-related behaviors across the life span. To analyze data, we conducted a reflexive thematic analysis. Results: We developed three overarching themes that reflect the underlying dynamics which are associated with the occurrence of critical life events and transitions and lead to subsequent changes in daily PA and sport and exercise behavior: (1) The finitude of temporal resources; (2) The plasticity of priorities and motives; and (3) The (in)conveniences of context. Conclusion: Our results illustrate that there is not a straight causal link between life events and behavior. Rather, critical life events and transitions can have a tremendous impact on temporal resources, individual priorities and motives, and contextual factors, such as the physical and infrastructural environment and social settings and relationships. Consequently, more or less extensive changes in those circumstances can lead to individual adaptations in daily PA or sport and exercise and related attitudes, as they require individuals to re-balance behavioral patterns. [ABSTRACT FROM AUTHOR]

RNAi targeting the electron transport chain has been proven to prolong life span in many different species, and experiments specifically with Drosophila melanogaster and Caenorhabditis elegans have shown a distinct role for neurons. To determine which subset of neurons is implicated in this life span extension, we used the GAL4/UAS system to activate RNAi against genes of Complex I and Complex V. We found life span extension of 18–24% with two glutamate neuron (D42 and VGlut) GAL4 lines. We used the GAL80 system to determine if the overlapping set of glutamate neurons in these two GAL4 lines imparts the life span extension. Limiting GAL4 activity to non-VGlut glutamate neurons in the D42 background failed to extend life span, suggesting that glutamate neurons have an important role in aging. Interestingly, RNAi of the electron transport chain in D42 glutamate neurons also caused an increase in daytime and nighttime sleep and a decrease in nighttime locomotor activity. Changes to sleep patterns and prolonged life span were not accompanied by any changes in female fertility or response to starvation. Our findings demonstrate that a small subset of neurons can control life span, and further studies can look into the contributions made by glutamate neurons. [ABSTRACT FROM AUTHOR]

Alien invasive species are posing conservation challenges worldwide. Pet trade, one of the many ways, is worsening the situation. Especially, pet turtles have been released into nature due to their longer life span and peoples' religious and traditional beliefs. In addition, unwanted and undesired pets are also released. While information on the successful local establishment and subsequent dispersal into new habitats is required to designate an invasive and ecosystem-disturbing species, alien freshwater turtle nests have always been hard to find and identify in nature. Because one should identify nests by the eggs, which do not always guide properly, as adults abandon the sites quickly. We thought the recent advancement in DNA technology may help improve the situation. We studied Pseudemys peninsularis, one of the most traded freshwater turtle pet species, which has already been reported from a wide range of wild areas in South Korea. Yet, it is not designated as ecosystem-disturbing species due to a lack of adequate information on their local reproduction and establishment. We conducted surveys and found two nests in Jeonpyeongje Neighborhood Park, Maewol-dong, Seo-gu, Gwangju. We developed the methodology for extracting DNA from the eggshells and successfully identified the nests by phylogenetic analysis and verified through egg characteristics and morphological features of artificially hatched juveniles. This was the first successful initiative to extract DNA from freshwater turtle eggshells. We believe it will help future researchers identify the alien invasive turtle nests and develop their control and management policies. In addition, our study also included comparative descriptions and schematic diagrams of the eggs of eight freshwater turtles, including a native and three ecosystem-disturbing species, from South Korea. We urged an immediate designation of P. peninsularis as an ecosystem-disturbing species considering its local establishment, distribution range, and potential negative impact on native ecosystems. [ABSTRACT FROM AUTHOR]

Limb Girdle Muscular Dystrophy 2I (LGMDR9) is one of the most common LGMD characterized by defects in glycosylation of α-dystroglycan (matriglycan) resulting from mutations of Fukutin-related protein (FKRP). There is no effective therapy currently available. We recently demonstrated that ribitol supplement increases levels of matriglycan in cells in vitro and in FKRP-P448L (P448L) mutant mouse model through drinking water administration. To be clinically relevant, we have now conducted a dose-escalating efficacy study by gavage in P448L mutant mice. Six months of ribitol treatment daily significantly rescued functions of skeletal, respiratory, and cardiac muscles dose-dependently. This was associated with a dose dependent increase in matriglycan and improvement in muscle pathology with reductions in muscle degeneration, inflammatory infiltration and fibrosis. Importantly, ribitol significantly increased life span and muscle functions of the female animals receiving treatment from 10 months of age. The only observed side effect was gastrointestinal tract bloating with loose stool and this effect is also dose dependent. The results validate the mechanism that ribitol as a pre-substrate of glycosyltransferase is able to compensate for the decreased function of mutant FKRP with restoration of matriglycan expression and provide a guidance for future clinical trial design. [ABSTRACT FROM AUTHOR]

Understanding shark mating dynamics and mating site use may be vital to species management. The Dry Tortugas courtship and mating ground (DTCMG) has been known as a mating site for nurse sharks, Ginglymostoma cirratum, since 1895. In a 30-yr (1992–2021) study we have documented long-term site fidelity to this area with data from 137 adult sharks (89 female, 48 male) tagged with PIT, fin, and acoustic tags. Of 118 sharks tagged from 1993 to 2014, at least 80 (68%) returned to the DTCMG in subsequent years during the June-July mating season. Known individuals returned in up to 16 different mating seasons and over periods of up 28 years, indicating that life span extends well into the forties for this species. Of all returning sharks, 59% (N = 47) have been monitored for over 10 years and 13% (N = 10) have been monitored for over 20 years. Males arrived annually in May and June and departed in July, whereas females arrived biennially or triennially in June, with a secondary peak in site use in September and August, likely associated with thermoregulation during gestation. During the mating season, males made more frequent visits of shorter duration (median = 34 visits for 1 h per visit) to the DTCMG, whereas females made fewer visits but remained on site for longer periods (median = 12.5 visits for 4.4 h per visit). Females typically mated biennially but showed a triennial cycle in 32% of cases, with many females switching cycles at least once. This pattern would reduce the potential reproductive lifetime output of a female by 11% compared to what would be projected from a strict biennial cycle. The long-term mating site fidelity of this shark population reveals the importance of identifying and protecting mating sites for this and other elasmobranch species. [ABSTRACT FROM AUTHOR]

Cancer has become a leading cause of death and aroused the cancer scare. Breast and cervical cancer are two main health threats for women. In order to reduce mortality through early detection and early treatment, cancer screening has been widely recommended and applied for breast and cervical cancer detection and prevention. However, the benefit of cancer screening has been a controversial issue for the recent decades. The Chinese government has launched a free screening program on breast and cervical cancer for women since 2009. There is lack of strong data and sufficient information, however, to examine the effect of breast and cervical cancer screening. A Difference-in-Difference model estimated by Cox proportional hazard estimation was applied to evaluate the effects of breast and cervical cancer screening using data from Nown County Cancer Registry between the year 2009 and 2013. Based on the case study in a county of central China, this study found that the screening program reduced the risk of death, but found the lion's share for the benefit has been mainly due to the cervical cancer screening rather breast cancer screening, which may be related to the difference between early detection screening and preventive screening. Our results suggest sufficient funding and better education of related cancer knowledge will be meaningful measures for the prevention and treatment of breast and cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Social status gradients are powerful health determinants for individuals living in poverty. We tested whether winning an Academy award (Oscar) for acting was associated with long-term survival. Methods: We conducted a longitudinal cohort analysis of all actors and actresses nominated for an Academy award in a leading or a supporting role. For each, a control was identified based on age, sex, and co-staring in the same film. Results: Overall, 2,111 individuals were analyzed with 1,122 total deaths occurring during a median follow-up of 68.8 years. Comparisons of winners to controls yielded a 4.8% relative difference average life-span (95% confidence interval: 1.6 to 7.9, p = 0.004), a 5.1 year absolute increase in life expectancy (95% confidence interval: 3.0 to 7.2, p < 0.001), and a 41% improvement in mortality hazard (95% confidence interval: 19 to 68, p < 0.001). The increased survival tended to be greater in recent years, for individuals winning at a younger age, and among those with multiple wins. The increased survival replicated in secondary analyses comparing winners to nominees and was not observed in analyses comparing nominees to controls. Conclusions: Academy award winning actors and actresses show a positive association between success and survival, suggesting the importance of behavioral, psychological, or other modifiable health factors unrelated to poverty. [ABSTRACT FROM AUTHOR]

A Polymer Electrolytic Membrane Fuel Cell (PEMFC) is an efficient power device for automobiles, but its efficiency and life span depend upon its air delivery system. To ensure improved performance of PEMFC, the air delivery system must ensure proper regulation of Oxygen Excess Ratio (OER). This paper proposes two nonlinear control strategies, namely Integral Sliding Mode Control (ISMC) and Fast Terminal ISMC (FTISMC). Both the controllers are designed to control the OER at a constant level under load disturbances while avoiding oxygen starvation. The derived controllers are implemented in MATLAB/ Simulink. The corresponding simulation results depict that FTISMC has faster tracking performance and lesser fluctuations due to load disturbances in output net power, stack voltage/power, error tracking, OER, and compressor motor voltage. Lesser fluctuations in these parameters ensure increased efficiency and thus extended life of a PEMFC. The results are also compared with super twisting algorithm STA to show the effectiveness of the proposed techniques. ISMC and FTISMC yield 7% and 20% improved performance as compared to STA. The proposed research finds potential applications in hydrogen-powered fuel cell electric vehicles. [ABSTRACT FROM AUTHOR]

Recent work has unearthed many empirical regularities in mortality trends, including the inverse correlation between life expectancy and life span inequality, and the compression of mortality into older age ranges. These regularities have furnished important insights into the dynamics of mortality by describing, in demographic terms, how different attributes of the life table deaths distribution interrelate and change over time. However, though empirical evidence suggests that the demographically-meaningful metrics these regularities involve (e.g., life span disparity and life table entropy) are correlated to the moments of the deaths distribution (e.g., variance), the broader theoretical connections between life span inequality and the moments of the deaths distribution have yet to be elucidated. In this article we establish such connections and leverage them to furnish new insights into mortality dynamics. We prove theoretical results linking life span disparity and life table entropy to the central moments of the deaths distribution, and use these results to empirically link statistical measures of variation of the deaths distribution (e.g., variance, index of dispersion) to life span disparity and life table entropy. We validate these results via empirical analyses using data from the Human Mortality Database and extract from them several new insights into mortality shifting and compression in human populations. [ABSTRACT FROM AUTHOR]

Begomoviruses are transmitted by whitefly (Bemisia tabaci Gennadius, Hemiptera: Aleyrodidae) in a persistent-circulative way. Once B. tabaci becomes viruliferous, it remains so throughout its life span. Not much is known about the copies of begomoviruses ingested and/or released by B. tabaci during the process of feeding. The present study reports the absolute quantification of two different begomoviruses viz. tomato leaf curl New Delhi virus (ToLCNDV, bipartite) and chilli leaf curl virus (ChiLCV, monopartite) at different exposure of active acquisition and inoculation feeding using a detached leaf assay. A million copies of both the begomoviruses were acquired by a single B. tabaci with only 5 min of active feeding and virus copy number increased in a logarithmic model with feeding exposure. Whereas, a single B. tabaci could inoculate 8.21E+09 and 4.19E+11 copies of ToLCNDV and ChiLCV, respectively in detached leaves by 5 min of active feeding. Virus copies in inoculated leaves increased with an increase in feeding duration. Comparative dynamics of these two begomoviruses indicated that B. tabaci adult acquired around 14-fold higher copies of ChiLCV than ToLCNDV 24 hrs post feeding. Whereas, the rate of inoculation of ToLCNDV by individual B. tabaci was significantly higher than ChiLCV. The study provides a better understanding of begomovirus acquisition and inoculation dynamics by individual B. tabaci and would facilitate research on virus-vector epidemiology and screening host resistance. [ABSTRACT FROM AUTHOR]

Objective: To evaluate how self-reported leisure-time physical activity (PA) changes during the adult life span, and to study how PA is related to cardiovascular risk factors using longitudinal studies. Methods: Several Swedish population-based longitudinal studies were used in the present study (PIVUS, ULSAM, SHE, and SHM, ranging from hundreds to 30,000 participants) to represent information across the adult life span in both sexes. Also, two cross-sectional studies were used as comparison (EpiHealth, LifeGene). PA was assessed by questionnaires on a four or five-level scale. Results: Taking results from several samples into account, an increase in PA from middle-age up to 70 years was found in males, but not in females. Following age 70, a decline in PA was seen. Young adults reported both a higher proportion of sedentary behavior and a higher proportion high PA than the elderly. Females generally reported a lower PA at all ages. PA was mainly associated with serum triglycerides and HDL-cholesterol, but also weaker relationships with fasting glucose, blood pressure and BMI were found. These relationships were generally less strong in elderly subjects. Conclusion: Using data from multiple longitudinal samples the development of PA over the adult life span could be described in detail and the relationships between PA and cardiovascular risk factors were portrayed. In general, a higher or increased physical activity over time was associated with a more beneficial cardiovascular risk factor profile, especially lipid levels. [ABSTRACT FROM AUTHOR]

Background: Applicability of totally implantable venous access port (TIVAP) and peripherally inserted central venous catheter (PICC) in non-hematological malignancies patients remains controversial. Methods: A systematic studies search in the public databases PubMed, EMBASE, Wan Fang, CNKI (China National Knowledge Infrastructure), the Cochrane Library and Google Scholar (updated to May 1, 2020) was performed to identify eligible researches. All statistical tests in this meta-analysis were performed using Stata 12.0 software (Stata Corp, College Station, TX). A P value less than 0.05 was considered statistically significant. Results: Thirteen studies were included in this final meta-analysis. The pooled data showed that compared with PICC, TIVAP was associated with a higher first-puncture success rate (OR:2.028, 95%CI:1.25–3.289, P<0.05), a lower accidental removal rate (OR:0.447, 95%CI:0.225–0.889, P<0.05) and lower complication rates, including infection (OR:0.570, 95%CI: 0.383–0.850, P<0.05), occlusion (OR:0.172, 95%CI:0.092–0.324, P<0.05), malposition (OR:0.279, 95%CI:0.128–0.608, P<0.05), thrombosis (OR:0.191, 95%CI, 0.111–0.329, P<0.05), phlebitis (OR:0.102, 95%CI, 0.038–0.273, P<0.05), allergy (OR:0.155, 95%CI:0.035–0.696, P<0.05). However, no difference was found in catheter life span (P>0.05) and extravasation (P>0.05). Moreover, TIVAP is more expensive compared with PICC in six-month use (weighted mean difference:3.132, 95%CI:2.434–3.83, P<0.05), but is much similar in 12 months use (P>0.05). Conclusion: For the patients with non-hematological malignancies, TIVAP was superior to PICC in the data related to placement and the incidence of complications. Meanwhile, TIVAP is more expensive compared with PICC in six-month use, but it is much similar in twelve-month use. [ABSTRACT FROM AUTHOR]

Background: Lung Cancer (LC) is one of the most common malign diseases worldwide. So far, it is unclear if the development of LC incidence and mortality leads to morbidity compression or expansion and whether these developments differ by socioeconomic characteristics. This study analyses time trends in social and gender inequalities in life years with and without LC in Germany. Methods: The study is based on data of a large German statutory health insurance provider (N = 2,511,790). Incidence and mortality risks were estimated from multistate survival models. Trends in life years with and without LC were analysed using multistate life table analyses. All analyses were performed separately for gender, time period (2006–2009 and 2014–2017), and income group (<60% and ≥60% of the German average income). Results: Among men, declining LC incidence rates resulted in gains of life years free of LC and declining LC- affected life years and led to a relative compression, which was strongest in men with higher incomes. Among women, a clear increase in life years with LC led to an expansion of the lifespan affected by LC. This expansion was mainly driven by increasing incidence rates in women with low incomes. Overall, income inequalities in LC increased in both genders. Conclusions: Our analyses reveal that developments in the length of life affected by LC differed substantially by gender and income and led to widening health inequalities over time. Public health efforts should mainly focus on vulnerable groups to reduce the persisting social inequalities in LC. [ABSTRACT FROM AUTHOR]

Dietary restriction (DR) increases life span and improves health in most model systems tested, including non-human primates. In C. elegans, as in other models, DR leads to reprogramming of metabolism, improvements in mitochondrial health, large changes in expression of cytoprotective genes and better proteostasis. Understandably, multiple global transcriptional regulators like transcription factors FOXO/DAF-16, FOXA/PHA-4, HSF1/HSF-1 and NRF2/SKN-1 are important for DR longevity. Considering the wide-ranging effects of p53 on organismal biology, we asked whether the C. elegans ortholog, CEP-1 is required for DR-mediated longevity assurance. We employed the widely-used TJ1 strain of cep-1(gk138). We show that cep-1(gk138) suppresses the life span extension of two genetic paradigms of DR, but two non-genetic modes of DR remain unaffected in this strain. We find that two aspects of DR, increased autophagy and up-regulation of the expression of cytoprotective xenobiotic detoxification program (cXDP) genes, are dampened in cep-1(gk138). Importantly, we find that background mutation(s) in the strain may be the actual cause for the phenotypic differences that we observed and cep-1 may not be directly involved in genetic DR-mediated longevity assurance in worms. Identifying these mutation(s) may reveal a novel regulator of longevity required specifically by genetic modes of DR. [ABSTRACT FROM AUTHOR]

Sepsis is the leading cause of death in hospitalized patients and beyond the hospital stay and these long-term sequelae are due in part to unresolved inflammation. Metabolic shift from oxidative phosphorylation to aerobic glycolysis links metabolism to inflammation and such a shift is commonly observed in sepsis under normoxic conditions. By shifting the metabolic state from aerobic glycolysis to oxidative phosphorylation, we hypothesized it would reverse unresolved inflammation and subsequently improve outcome. We propose a shift from aerobic glycolysis to oxidative phosphorylation as a sepsis therapy by targeting the pathways involved in the conversion of pyruvate into acetyl-CoA via pyruvate dehydrogenase (PDH). Chemical manipulation of PDH using dichloroacetic acid (DCA) will promote oxidative phosphorylation over glycolysis and decrease inflammation. We tested our hypothesis in a Drosophila melanogaster model of surviving sepsis infected with Staphylococcus aureus. Drosophila were divided into 3 groups: unmanipulated, sham and sepsis survivors, all treated with linezolid; each group was either treated or not with DCA for one week following sepsis. We followed lifespan, measured gene expression of Toll, defensin, cecropin A, and drosomycin, and levels of lactate, pyruvate, acetyl-CoA as well as TCA metabolites. In our model, metabolic effects of sepsis are modified by DCA with normalized lactate, TCA metabolites, and was associated with improved lifespan of sepsis survivors, yet had no lifespan effects on unmanipulated and sham flies. While Drosomycin and cecropin A expression increased in sepsis survivors, DCA treatment decreased both and selectively increased defensin. [ABSTRACT FROM AUTHOR]

Male and female mosquito larvae compete for different subsets of the yeast food resource in laboratory microcosms. Males compete more intensely with males, and females with females. The amount and timing of food inputs alters both growth and competition, but the effects are different between sexes. Increased density increases competition among males. Among females, density operates primarily by changing the food/larva or total food; this affects competition in some interactions and growth in others. Food added earlier in the life span contributes more to mass than the same quantity added later. After a period of starvation larvae appear to use some of the subsequent food input to rebuild physiological reserves in addition to building mass. The timing of pupation is affected by the independent factors and competition, but not in the same way for the two sexes, and not in the same way as mass at pupation for the two sexes. There is an effect of density on the timing of pupation for females independent of competition or changes in food/larva or total food. Male and female larvae have different larval life history strategies. Males grow quickly to a minimum size, then pupate, depending on the amount of food available. Males that do not grow quickly enough may delay pupation further to grow larger, resulting in a bimodal distribution of sizes and ages. Males appear to have a maximum size determined by the early food level. Females grow faster than males and grow larger than males on the same food inputs. Females affect the growth and competition among males by manipulating the number of particles in the microcosm through changes in feeding behavior. Mosquito larvae appear to have evolved to survive periods of starvation and take advantage of intermittent inputs of food into containers. [ABSTRACT FROM AUTHOR]

Some bacteria species found in the mosquito midgut have demonstrated their role in interrupting the development of Plasmodium within the midgut of the Anopheles mosquito and have been identified as potential candidates for novel bacteria-mediated disease control. However, to use these bacteria successfully in biocontrol mechanisms their effect on the fitness of the vector into which they have been introduced has to be evaluated. This study investigated the effect of two such bacteria candidates, Enterobacter cloacae and Serratia marcescens, on Anopheles gambiae s.l. fitness. Pupae and larvae of Anopheles gambiae s.l. mosquitoes were collected by dipping method and reared to adults. The effect of these bacteria on mosquito fitness was assessed by reintroducing isolates of each bacteria separately into antibiotic-treated female adult mosquitoes through sugar meal. Wild type (non-antibiotic-treated) mosquitoes and those antibiotic-treated with no bacteria reintroduction were used as controls. The mosquitoes were monitored on longevity/survival, fecundity, hatch rate, and larval survival. The antibiotic-treated adult mosquitoes had reduced life span with median survival of 14 days while the bacteria-reintroduced groups and the wild type survived to day 22 (p< 0.0001). Treatment with Enterobacter and Serratia did not affect the average egg deposition (p>0.05) but they affected hatch rates positively (p = 0.008). There was, however, some evidence that suggests Enterobacter could have a positive effect on larval development (p < 0.0001). With no observed negative effect on survival/longevity of Anopheles gambiae, introducing E. cloacae and S. marcescens in future bacteria-associated control strategies is unlikely to result in mosquitoes that will be outlived by the wild population. This, however, requires evaluations under field conditions. [ABSTRACT FROM AUTHOR]

Objective: There are controversial opinions on anticoagulation for continuous venovenous hemofiltration (CVVH) in patients with liver failure (LF) and increased bleeding risk. Therefore, we conducted a retrospective study to evaluate the efficacy and safety of regional citrate anticoagulation (RCA) versus no-anticoagulation for CVVH in these patients. Methods: The included patients were divided into RCA and no-anticoagulation group according to the CVVH anticoagulation strategy they accepted for CVVH. Filter lifespan, bleeding, citrate accumulation, catheter occlusion, and totCa/ionCa ratio were evaluated as outcomes. Results: In the original cohort, the filter lifespan of the RCA group (41 patients, 79 filters) was significantly longer than the no-anticoagulation group (62 patients, 162 filters) (> 72 hours vs 39.5 hours (IQR 31.2–47.8), P = 0.002). The adjusted results demonstrated that RCA could significantly reduce the risk of filter failure (HR = 0.459, 95%CI 0.26–0.82, P = 0.008). Four episodes of totCa/ionCa > 2.5 were observed in the RCA group and continuously accepted RCA-CVVH after the reduction of citrate dose and blood flow. No obvious citrate accumulation was observed in these patients. In the matched cohort, the filter lifespan of the RCA group was significantly longer than the no-anticoagulation group (P = 0.013) as well. No significant difference in the episodes of totCa/ionCa > 2.5 was observed between the two matched groups (P = 0.074). Both in the original cohort and the matched cohort, the bleeding, acidosis, alkalosis, and catheter occlusion incidences were not significantly different between the two groups. Conclusions: In LF patients with increased bleeding risk who underwent CVVH, RCA could prolong the filter lifespan and be safely used with careful blood gas monitoring and citrate dose adjusting. Further prospective, randomized, control studies are warranted to obtain robust evidences. [ABSTRACT FROM AUTHOR]

The black soldier fly Hermetia illucens is gaining growing interest as a tool for the valorisation of bio-waste in a circular economy perspective. Although a wide variety of studies are available for larvae rearing, the indoor breeding of adults still presents a great challenge for industrial purposes. This study was designed to assess the simultaneous influence of 3 different light sources (the Mix of LED UV:blue:green 1:1:3, White LED, Neon light) and 3 types of nutrition (sugar and water, only water, no sugar no water) on adult performances, obtaining different egg production parameters that included the number and weight of the egg masses and single eggs laid by the females, the duration of pre-oviposition and oviposition period, the adult life span, the hatchability of the eggs. Our results showed that production parameters are influenced mainly by nutrition rather than light factor, although light plays an important secondary role. Moreover, the presence of sugar positively affects the egg production (12,93–27,10 mg eggs/female) and increases oviposition period (18,2–31,8 days) and adult lifespan (20,79–27,11 days). Light sources also affect egg production parameters, with the exposure to the Mix of LEDs resulting in the best performance of flies. Results obtained from this study are very useful for the design and management of an efficient industrial black soldier fly mass rearing process. [ABSTRACT FROM AUTHOR]

Sirt1, a member of the sirtuin gene family, encodes the most conserved mammalian NAD+-dependent deacetylase enzyme responsible for removing acetyl groups from many proteins. The Sirt1 gene is known as a longevity gene whose knockout in mice leads to decreased lifespan relative to the wild type. This study aimed to explore phenotypic changes in zebrafish Sirt1-knockouts and to investigate the function of the Sirt1 gene. Targeted knockout of Sirt1 in zebrafish (Danio rerio) was achieved using the CRISPR-Cas9 genome editing system. We created a 4-bp insertion-homozygote Sirt1-knockout zebrafish. Although there was no evident difference in appearance in the early stages of development, a significant increase in reactive oxygen species and in the extent of apoptosis in Sirt1-knockout zebrafish was observed. Sirt1 knockout caused inflammatory genes, including IL-1b, IL-6 and TNF-α to be highly expressed. Additionally, the lack of Sirt1 caused chronic inflammation and intestinal atrophy, thereby increasing pro-apoptotic events, which ultimately reduced the lifespan of transgenic zebrafish. Overall, our data demonstrate that lack of Sirt1 caused a significantly increased generation of reactive oxygen species that resulted in chronic inflammation and regeneration. Continuous repetition of these events played an important role in accelerating aging, thereby decreasing lifespan. Our findings using the knockout zebrafish model confirmed the association of the Sirt1 gene to aging processes and lifespan. Furthermore, the Sirt1-knockout mutant zebrafish developed in our study will surely be a valuable model to explore the mechanism of chronic inflammation. [ABSTRACT FROM AUTHOR]

Integrating elements from life tables into population models within a matrix framework has been an underutilized method of describing host–parasitoid population dynamics. This type of modeling is useful in describing demographically-structured populations and in identifying points in the host developmental timeline susceptible to parasitic attack. We apply this approach to investigate the effect of parasitism by the Asian parasitoid Aphelinus certus on its host, the soybean aphid (Aphis glycines). We present a matrix population model with coupled equations that are analogous to a Nicholson–Bailey model. To parameterize the model, we conducted several bioassays outlining host and parasitoid life history and supplemented these studies with data obtained from the literature. Analysis of the model suggests that, at a parasitism rate of 0.21 d−1, A. certus is capable of maintaining aphid densities below economically damaging levels in 31.0% of simulations. Several parameters—parasitoid lifespan, colonization timeline, host developmental stage, and mean daily temperature—were also shown to markedly influence the overall dynamics of the system. These results suggest that A. certus might provide a valuable service in agroecosystems by suppressing soybean aphid populations at relatively low levels of parasitism. Our results also support the use of A. certus within a dynamic action threshold framework in order to maximize the value of biological control in pest management programs. [ABSTRACT FROM AUTHOR]

In this paper we investigate the changes in the functional connectivity intensity, and some related properties, in healthy people, across the life span and at resting state. For the explicit computation of the functional connectivity we exploit a recently proposed model, that bases not only on the correlations data provided by the acquisition equipment, but also on different parameters, such as the anatomical distances between nodes and their degrees. The leading purpose of the paper is to show that the proposed approach is able to recover the main aspects of resting state condition known from the available literature, as well as to suggest new insights, perspectives and speculations from a neurobiological point of view. Our study involves 133 subjects, both males and females of different ages, with no evidence of neurological diseases or systemic disorders. First, we show how the model applies to the sample, where the subjects are grouped into 28 different groups (14 of males and 14 of females), according to their age. This leads to the construction of two graphs (one for males and one for females), that can be realistically interpreted as representative of the neural network during the resting state. Second, following the idea that the brain network is better understood by focusing on specific nodes having a kind of centrality, we refine the two output graphs by introducing a new metric that favours the selection of nodes having higher degrees. As a third step, we extensively comment and discuss the obtained results. In particular, it is remarkable that, despite a great overlapping exists between the outcomes concerning males and females, some intriguing differences appear. This motivates a deeper local investigation, which represents the fourth part of the paper, carried out through a thorough statistical analysis. As a result, we are enabled to support that, for two special age groups, a few links contribute in differentiating the behaviour of males and females. In addition, we performed an average-based comparison between the proposed model and the traditional statistical correlation-based approach, then discussing and commenting the main outlined discrepancies. [ABSTRACT FROM AUTHOR]

Currently, separate measures are used to estimate the impact of animal diseases on mortality and animal welfare. This article introduces a novel metric, the Welfare-Adjusted Life Year (WALY), to estimate disease impact by combining welfare compromise and premature death components. Adapting the Disability-Adjusted Life Year approach used in human health audits, we propose WALY as the sum of a) the years lived with impaired welfare due to a particular cause and b) the years of life lost due to the premature death from the same cause. The years lived with impaired welfare are the product of the average duration of each welfare impediment, reflecting the actual condition that compromises animal welfare, the probability of an incident case developing and impaired welfare weights, representing the degree of impaired welfare. The years of life lost are calculated using the standard expected lifespan at the time of premature death. To demonstrate the concept, we estimated WALYs for 10 common canine diseases, namely mitral valve disease, dilated cardiomyopathy, chronic kidney disease, diabetes mellitus, atopic dermatitis, splenic haemangiosarcoma, appendicular osteosarcoma, cranial cruciate ligament disease, thoracolumbar intervertebral disc disease and cervical spondylomyelopathy. A survey of veterinarians (n = 61) was conducted to elicit impaired welfare weights for 35 welfare impediments. Paired comparison was the primary method to elicit weights, whereas visual analogue scale and time trade-off approaches rescaled these weights onto the desired scale, from 0 (the optimal welfare imaginable) to 1 (the worst welfare imaginable). WALYs for the 10 diseases were then estimated using the impaired welfare weights and published epidemiological data on disease impacts. Welfare impediment “amputation: one limb” and “respiratory distress” had the lowest and highest impaired welfare weights at 0.134 and 0.796, rescaled with a visual analogue scale, and 0.117 and 0.857, rescaled with time trade-off. Among the 10 diseases, thoracolumbar intervertebral disc disease and atopic dermatitis had the smallest and greatest adverse impact on dogs with WALYs at 2.83 (95% UI: 1.54–3.94) and 9.73 (95% uncertainty interval [UI]: 7.17–11.8), respectively. This study developed the WALY metric and demonstrated that it summarises welfare compromise as perceived by humans and total impact of diseases in individual animals. The WALY can potentially be used for prioritisation of disease eradication and control programs, quantification of population welfare and longitudinal surveillance of animal welfare in companion animals and may possibly be extended to production animals. [ABSTRACT FROM AUTHOR]

Introduction: Animal models have been vital for scientific discovery but have limitations, especially in infectious disease research. It is essential to develop a means to study these diseases in human models. We hypothesized that altruistic people would willingly participate in research near the end-of-life (EOL), for the benefit of science and to provide one last gift to society. Methodology: Two surveys were administered to 377 self-reported HIV-negative and 96 HIV-positive individuals. Hypothetical questions assessed their willingness to participate in altruistic research in the last 6 months of life, which might result in a shortened lifespan or physical discomforts. The self-reported HIV-negative group was also asked about willingness to be exposed to infectious pathogens for the sake of research. Results: Almost all responders expressed willingness to participate in research at the EOL, regardless of HIV-status. The majority of participants were willing to endure physical discomfort for the sake of research. ‘Blood draws’ was identified as the most tolerable physical discomfort (>70% in both groups). In both groups, >60% were willing to shorten their lifespans for the sake of research. A third of the self-reported HIV-negative group expressed willingness to be exposed to at least one infectious agent to participate in EOL research. Conclusions: Our exploratory study demonstrates that people would welcome the opportunity to participate in altruistic research near the EOL. Such research could greatly impact the way infectious disease research is conducted. This study is limited however by its hypothetical nature. Further research is necessary to confirm this interest in those with terminal illness before any further clinical research effort at the EOL can be performed. [ABSTRACT FROM AUTHOR]

Isogenic wild type yeast cells raised in controlled environments display a significant range of lifespan variation. Recent microfluidic studies suggest that differential growth or gene expression patterns may explain some of the heterogeneity of aging assays. Herein, we sought to complement this work by similarly examining a large set of replicative lifespan data from traditional plate assays. In so doing, we reproduced the finding that short-lived cells tend to arrest at senescence with a budded morphology. Further, we found that wild type cells born unusually small did not have an extended lifespan. However, large birth size and/or high inter-generational growth rates significantly correlated with a reduced lifespan. Finally, we found that SIR2 expression levels correlated with lifespan and intergenerational growth. SIR2 expression was significantly reduced in large cells and increased in small wild type cells. A moderate increase in SIR2 expression correlated with reduced growth, decreased proliferation and increased lifespan in plate aging assays. We conclude that cellular growth rates and SIR2 expression levels may contribute to lifespan variation in individual cells. [ABSTRACT FROM AUTHOR]

Over the past decade, veno-venous extracorporeal membrane oxygenation (vvECMO) has been increasingly utilized in respiratory failure in patients. This study presents our institution´s experience focusing on the life span of ECMO systems reflecting the performance of a particular system. A retrospective review of our ECMO database identified 461 adult patients undergoing vvECMO (2010–2017). Patients that required more than one system and survived the first exchange >24 hours (n = 139) were included. Life span until the first exchange and exchange criteria were analyzed for all systems (PLS, Cardiohelp HLS-set, both Maquet Cardiopulmonary, Rastatt, Germany; Deltastream/Hilite7000LT, iLA-activve, Xenios/NovaLung, Heilbronn, Germany; ECC.O5, LivaNova, Mirandola, Italy). At our ECMO center, the frequency of a system exchange was 30%. The median (IQR) life span was 9 (6–12) days. There was no difference regarding the different systems (p = 0.145 and p = 0.108, respectively). However, the Deltastream systems were exchanged more frequently due to elective technical complications (e. g. worsened gas transfer, development of coagulation disorder, increased bleedings complications) compared to the other exchanged systems (p = 0.013). In summary, the used ECMO systems are safe and effective for acute respiratory failure. There is no evidence for the usage of a specific system. Only the increased predictability of an imminent exchange preferred the usage of a Deltastream system. However, the decision to use a particular system should not depend solely on the possible criteria for an exchange. [ABSTRACT FROM AUTHOR]

Few researchers have investigated how contact across the lifespan influences racial bias and whether diversity of contact is beneficial regardless of the race of the perceiver. This research aims to address these gaps in the literature with a focus on how diversity in childhood and current contact shapes implicit racial bias across perceivers’ racial group. In two investigations, participants completed an Implicit Association Test and a self-report measure of the racial diversity of their current and childhood contact. In both studies, increased contact with Black compared with White individuals, both in childhood (Study 2) and currently (Studies 1 and 2), was associated with reduced implicit pro-White racial bias. For Black individuals (Study 2) more contact with Black compared with White individuals also was associated with reduced implicit pro-White racial bias. These findings suggest that diversity in contact across the lifespan may be related to reductions in implicit racial biases and that this relationship may generalize across racial groups. [ABSTRACT FROM AUTHOR]

Objective: Leisure-time physical activity (LTPA) has considerable benefits for cardiovascular health and longevity, while occupational physical activity (OPA) is associated with an elevated cardiovascular risk. This “health paradox” may be explained by different effects on the autonomic nervous system from OPA and LTPA. Thus, we aimed to investigate whether objectively measured OPA and LTPA are differentially associated with autonomic regulation among workers. Methods: The study comprised 514 blue-collar workers from the Danish cohort DPHACTO. Physical activity (i.e. walking, climbing stairs, running and cycling) was assessed objectively using accelerometers worn on the thigh, hip and trunk over multiple working days. During this period, a heart rate monitor was used to sample heart period intervals from the ECG signal. Heart rate and heart rate variability (HRV) indices were analyzed during nocturnal sleep as markers of autonomic regulation. Multiple regression analysis was used to determine the main effects of OPA and LTPA and their interaction on heart rate and HRV, adjusting for multiple confounders. Results: Statistically significant interaction was found between OPA and LTPA on heart rate (adjusted p<0.0001) and HRV indices in time (rMSSD, adjusted p = 0.004) and frequency-domains (HF, adjusted p = 0.022; LF, adjusted p = 0.033). The beneficial effect of LTPA on nocturnal heart rate and HRV clearly diminished with higher levels of OPA, and high levels of both OPA and LTPA had a detrimental effect. Conclusion: We found contrasting associations for objectively measured OPA and LTPA with heart rate and HRV during sleep. Differential effects of OPA and LTPA on autonomic regulation may contribute to the physical activity health paradox. [ABSTRACT FROM AUTHOR]

Standard evolutionary theories of aging and mortality, implicitly based on assumptions of spatial averaging, hold that natural selection cannot favor shorter lifespan without direct compensating benefit to individual reproductive success. However, a number of empirical observations appear as exceptions to or are difficult to reconcile with this view, suggesting explicit lifespan control or programmed death mechanisms inconsistent with the classic understanding. Moreover, evolutionary models that take into account the spatial distributions of populations have been shown to exhibit a variety of self-limiting behaviors, maintained through environmental feedback. Here we extend recent work on spatial modeling of lifespan evolution, showing that both theory and phenomenology are consistent with programmed death. Spatial models show that self-limited lifespan robustly results in long-term benefit to a lineage; longer-lived variants may have a reproductive advantage for many generations, but shorter lifespan ultimately confers long-term reproductive advantage through environmental feedback acting on much longer time scales. Numerous model variations produce the same qualitative result, demonstrating insensitivity to detailed assumptions; the key conditions under which self-limited lifespan is favored are spatial extent and locally exhaustible resources. Factors including lower resource availability, higher consumption, and lower dispersal range are associated with evolution of shorter lifespan. A variety of empirical observations can parsimoniously be explained in terms of long-term selective advantage for intrinsic mortality. Classically anomalous empirical data on natural lifespans and intrinsic mortality, including observations of longer lifespan associated with increased predation, and evidence of programmed death in both unicellular and multicellular organisms, are consistent with specific model predictions. The generic nature of the spatial model conditions under which intrinsic mortality is favored suggests a firm theoretical basis for the idea that evolution can quite generally select for shorter lifespan directly. [ABSTRACT FROM AUTHOR]

Strong seasonality in abiotic harshness and pollinator availability shape the reproductive success of plants. Plant species can avoid or can tolerate harsh abiotic conditions and can attract different pollinators, but it remains unknown (i) which of these capacities is most important for flowering phenology, (ii) whether tolerance/avoidance of abiotic harshness reinforces or relaxes the phenological differentiation of species attracting different pollinators. We assembled possibly the first functional trait database for a North African steppe covering 104 species. We inferred avoidance of harshness (drought) from dormancy, i.e. annual life-span and seed size. We inferred tolerance or resistance to harshness from small specific leaf area, small stature, deep roots and high dry matter content. We inferred the type of pollinators attracted from floral colour, shape and depth. We found that avoidance traits did not affect flowering phenology, and among tolerance traits only deep roots had an effect by delaying flowering. Flower colour (red or purple), and occasionally flower depth, delayed flowering. Dish, gullet and flag shape accelerated flowering. Interactive effects however were at least as important, inversing the mentioned relationship between floral characters and flowering phenology. Specifically, among drought-tolerant deep-rooted species, flowering phenologies converged among floral types attracting different pollinators, without becoming less variable overall. Direct and interactive effects of root depth and floral traits explained at least 45% of the variance in flowering phenology. Also, conclusions on interactive effects were highly consistent with and without including information on family identity or outliers. Overall, roots and floral syndromes strongly control flowering phenology, while many other traits do not. Surprisingly, floral syndromes and the related pollinators appear to constrain phenology mainly in shallow-rooted, abiotically little tolerant species. Lack of abiotic tolerance might hence constrain accessible resources and thereby impose a stronger synchronization with biotic partners such as pollinators. [ABSTRACT FROM AUTHOR]

There is a large variability in lifespans of individuals even if they are genetically identical and raised under the same environmental conditions. Our recent system wide study of replicative aging in baker’s yeast predicts that protein biogenesis is a driver of aging. Here, we address how the natural variation in replicative lifespan within wild-type populations of yeast cells correlates to three biogenesis-related parameters, namely cell size, ribosomal protein Rpl13A-GFP levels, and division times. Imaging wild type yeast cells in microfluidic devices we observe that in all cells and at all ages, the division times as well as the increase in cell size that single yeast undergo while aging negatively correlate to their lifespan. In the longer-lived cells Rpl13A-GFP levels also negatively correlate to lifespan. Interestingly however, at young ages in the population, ribosome concentration was lowest in the cells that increased the most in size and had shorter lifespans. The correlations between these molecular and cellular properties related to biogenesis and lifespan explain a small portion of the variation in lifespans of individual cells, consistent with the highly individual and multifactorial nature of aging. [ABSTRACT FROM AUTHOR]

Multisensory interactions are well established to convey an array of perceptual and behavioral benefits. One of the key features of multisensory interactions is the temporal structure of the stimuli combined. In an effort to better characterize how temporal factors influence multisensory interactions across the lifespan, we examined audiovisual simultaneity judgment and the degree of rapid recalibration to paired audiovisual stimuli (Flash-Beep and Speech) in a sample of 220 participants ranging from 7 to 86 years of age. Results demonstrate a surprisingly protracted developmental time-course for both audiovisual simultaneity judgment and rapid recalibration, with neither reaching maturity until well into adolescence. Interestingly, correlational analyses revealed that audiovisual simultaneity judgments (i.e., the size of the audiovisual temporal window of simultaneity) and rapid recalibration significantly co-varied as a function of age. Together, our results represent the most complete description of age-related changes in audiovisual simultaneity judgments to date, as well as being the first to describe changes in the degree of rapid recalibration as a function of age. We propose that the developmental time-course of rapid recalibration scaffolds the maturation of more durable audiovisual temporal representations. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is often chronic and disabling across the lifespan. The gold standard treatment for adolescent PTSD is Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT), though treatment response is variable and mediating neural mechanisms are not well understood. Here, we test whether PTSD symptom reduction during TF-CBT is associated with individual differences in large-scale brain network organization during emotion processing. Twenty adolescent girls, aged 11–16, with PTSD related to assaultive violence completed a 12-session protocol of TF-CBT. Participants completed an emotion processing task, in which neutral and fearful facial expressions were presented either overtly or covertly during 3T fMRI, before and after treatment. Analyses focused on characterizing network properties of modularity, assortativity, and global efficiency within an 824 region-of-interest brain parcellation separately during each of the task blocks using weighted functional connectivity matrices. We similarly analyzed an existing dataset of healthy adolescent girls undergoing an identical emotion processing task to characterize normative network organization. Pre-treatment individual differences in modularity, assortativity, and global efficiency during covert fear vs neutral blocks predicted PTSD symptom reduction. Patients who responded better to treatment had greater network modularity and assortativity but lesser efficiency, a pattern that closely resembled the control participants. At a group level, greater symptom reduction was associated with greater pre-to-post-treatment increases in network assortativity and modularity, but this was more pronounced among participants with less symptom improvement. The results support the hypothesis that modularized and resilient brain organization during emotion processing operate as mechanisms enabling symptom reduction during TF-CBT. [ABSTRACT FROM AUTHOR]

Background: Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated. Objective: To investigate the survival and lethal bleeding frequency in two strains of E-16 hemophilia A mice. Methods: We prospectively studied factor VIII deficient hemizygous affected males (n = 83) and homozygous affected females (n = 55) for survival and bleeding frequency. Animals were evaluated for presence and location of bleeds as potential cause of death. Results and Conclusions: Hemophilia A mice had a median survival of 254 days, which is significantly shortened compared to wild type controls (p < 0.0001). In addition, the hemophilia A mice experienced hemorrhage in several tissues. This previously-underappreciated shortened survival in the hemophilia A murine model provides new outcomes for investigation of therapeutics and also reflects the shortened lifespan of patients if left untreated. [ABSTRACT FROM AUTHOR]

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. [ABSTRACT FROM AUTHOR]

Addressing the lack of population-based data the purpose of this representative study was to assess procrastination and its associations with distress and life satisfaction across the life span. A representative German community sample (1,350 women; 1,177 men) between the ages of 14 and 95 years was examined by the short form of the General Procrastination Scale (GPS-K; 1) and standardized scales of perceived stress, depression, anxiety, fatigue and life satisfaction. As hypothesized, procrastination was highest in the youngest cohort (14–29 years). Only in the youngest and most procrastinating cohort (aged 14 to 29 years), men procrastinated more than women. As we had further hypothesized, procrastination was consistently associated with higher stress, more depression, anxiety, fatigue and reduced satisfaction across life domains, especially regarding work and income. Associations were also found with lack of a partnership and unemployment. Findings are discussed with regard to potential developmental and cohort effects. While procrastination appears to be a pervasive indicator for maladjustment, longitudinal analyses in high-risk samples (e.g. late adolescence, unemployment) are needed to identify means and mechanisms of procrastinating. [ABSTRACT FROM AUTHOR]

Transferring Saccharomyces cerevisiae cells to water is known to extend their lifespan. However, it is unclear whether this lifespan extension is due to slowing the aging process or merely keeping old yeast alive. Here we show that in water-transferred yeast, the toxicity of polyQ proteins is decreased and the aging biomarker 47Q aggregates at a reduced rate and to a lesser extent. These beneficial effects of water-transfer could not be reproduced by diluting the growth medium and depended on de novo protein synthesis and proteasomes levels. Interestingly, we found that upon water-transfer 27 proteins are downregulated, 4 proteins are upregulated and 81 proteins change their intracellular localization, hinting at an active genetic program enabling the lifespan extension. Furthermore, the aging-related deterioration of the heat shock response (HSR), the unfolded protein response (UPR) and the endoplasmic reticulum-associated protein degradation (ERAD), was largely prevented in water-transferred yeast, as the activities of these proteostatic network pathways remained nearly as robust as in young yeast. The characteristics of young yeast that are actively maintained upon water-transfer indicate that the extended lifespan is the outcome of slowing the rate of the aging process. [ABSTRACT FROM AUTHOR]

An increase in the exposure and predisposition of civilian populations to disasters has been recorded in the last decades. In major disasters, as demonstrated recently in Nepal (2015) and previously in Haiti (2010), external aid is vital, yet in the first hours after a disaster, communities must usually cope alone with the challenge of providing emergent lifesaving care. Communities therefore need to be prepared to handle emergency situations. Mapping the needs of the populations within their purview is a trying task for decision makers and community leaders. In this context, the elderly are traditionally treated as a susceptible population with special needs. The current study aimed to explore variations in the level of community resilience along the lifespan. The study was conducted in nine small to mid-size towns in Israel between August and November 2011 (N = 885). The Conjoint Community Resiliency Assessment Measure (CCRAM), a validated instrument for community resilience assessment, was used to examine the association between age and community resilience score. Statistical analysis included spline and logistic regression models that explored community resiliency over the lifespan in a way that allowed flexible modeling of the curve without prior constraints. This innovative statistical approach facilitated identification of the ages at which trend changes occurred. The study found a significant rise in community resiliency scores in the age groups of 61–75 years as compared with younger age bands, suggesting that older people in good health may contribute positively to building community resiliency for crisis. Rather than focusing on the growing medical needs and years of dependency associated with increased life expectancy and the resulting climb in the proportion of elders in the population, this paper proposes that active "young at heart" older people can be a valuable resource for their community. [ABSTRACT FROM AUTHOR]

Gene-diet interactions play a crucial but poorly understood role in susceptibility to obesity. Accordingly, the development of genetically tractable model systems to study the influence of diets in obesity-prone genetic backgrounds is a focus of current research. Here I present a modified synthetic Drosophila diet optimized for timely larval development, a stage dedicated to energy storage. Specifically increasing the levels of individual macronutrients–carbohydrate, lipid, or protein–resulted in markedly different organismal effects. A high-carbohydrate diet adversely affected the timing of development, size, early lifespan and body fat. Strikingly, quadrupling the amount of dietary lipids had none of these effects. Diets rich in protein appeared to be the most beneficial, as larvae developed faster, with no change in size, into long-lived adults. I believe this synthetic diet will significantly facilitate the study of gene-diet interactions in organismal energy balance. [ABSTRACT FROM AUTHOR]

αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT) ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR) including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI) in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin) abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR. [ABSTRACT FROM AUTHOR]

One expression of executive control involves proactive preparation for future events, and this contrasts with stimulus driven reactive control exerted in response to events. Here we describe findings from a response inhibition task, delivered using a smartphone-based platform, that allowed us to index proactive and reactive inhibitory self-control in a large community sample (n = 12,496). Change in stop-signal reaction time (SSRT) when participants are provided with advance information about an upcoming trial, compared to when they are not, provides a measure of proactive control while SSRT in the absence of advance information provides a measure of reactive control. Both forms of control rely on overlapping frontostriatal pathways known to deteriorate in healthy aging, an age-related decline that occurs at an accelerated rate in men compared to women. Here we ask whether these patterns of age-related decline are reflected in similar changes in proactive and reactive inhibitory control across the lifespan. As predicted, we observed a decline in reactive control with natural aging, with a greater rate of decline in men compared to women (~10 ms versus ~8 ms per decade of adult life). Surprisingly, the benefit of preparation, i.e. proactive control, did not change over the lifespan and women showed superior proactive control at all ages compared to men. Our results suggest that reactive and proactive inhibitory control partially rely on distinct neural substrates that are differentially sensitive to age-related change. [ABSTRACT FROM AUTHOR]

Two distinct forms of atypical bovine spongiform encephalopathies (H-BSE and L-BSE) can be distinguished from classical (C-) BSE found in cattle based on biochemical signatures of disease-associated prion protein (PrPSc). H-BSE is transmissible to wild-type mice—with infected mice showing a long survival period that is close to their normal lifespan—but not to hamsters. Therefore, rodent-adapted H-BSE with a short survival period would be useful for analyzing H-BSE characteristics. In this study, we investigated the transmissibility of H-BSE to hamster prion protein transgenic (TgHaNSE) mice with long survival periods. Although none of the TgHaNSE mice manifested the disease during their lifespan, PrPSc accumulation was observed in some areas of the brain after the first passage. With subsequent passages, TgHaNSE mice developed the disease with a mean survival period of 220 days. The molecular characteristics of proteinase K-resistant PrPSc (PrPres) in the brain were identical to those observed in first-passage mice. The distribution of immunolabeled PrPSc in the brains of TgHaNSE mice differed between those infected with H-BSE as compared to C-BSE or L-BSE, and the molecular properties of PrPres in TgHaNSE mice infected with H-BSE differed from those of the original isolate. The strain-specific electromobility, glycoform profiles, and proteolytic cleavage sites of H-BSE in TgHaNSE mice were indistinguishable from those of C-BSE, in which the diglycosylated form was predominant. These findings indicate that strain-specific pathogenic characteristics and molecular features of PrPres in the brain are altered during cross-species transmission. Typical H-BSE features were restored after back passage from TgHaNSE to bovinized transgenic mice, indicating that the H-BSE strain was propagated in TgHaNSE mice. This could result from the overexpression of the hamster prion protein. [ABSTRACT FROM AUTHOR]

Face recognition in young human adults preferentially relies on the processing of horizontally-oriented visual information. We addressed whether the horizontal tuning of face perception is modulated by the extensive experience humans acquire with faces over the lifespan, or whether it reflects an invariable processing bias for this visual category. We tested 296 subjects aged from 6 to 74 years in a face matching task. Stimuli were upright and inverted faces filtered to preserve information in the horizontal or vertical orientation, or both (HV) ranges. The reliance on face-specific processing was inferred based on the face inversion effect (FIE). FIE size increased linearly until young adulthood in the horizontal but not the vertical orientation range of face information. These findings indicate that the protracted specialization of the face processing system relies on the extensive experience humans acquire at encoding the horizontal information conveyed by upright faces. [ABSTRACT FROM AUTHOR]

The question on how individuals allocate resources into maintenance and reproduction is one of the central questions in life history theory. Yet, resource allocation into maintenance on the organismic level can only be measured indirectly. This is different in a social insect colony, a “superorganism” where workers represent the soma and the queen the germ line of the colony. Here, we investigate whether trade-offs exist between maintenance and reproduction on two levels of biological organization, queens and colonies, by following single-queen colonies of the ant Cardiocondyla obscurior throughout the entire lifespan of the queen. Our results show that maintenance and reproduction are positively correlated on the colony level, and we confirm results of an earlier study that found no trade-off on the individual (queen) level. We attribute this unexpected outcome to the existence of a positive feedback loop where investment into maintenance (workers) increases the rate of resource acquisition under laboratory conditions. Even though food was provided ad libitum, variation in productivity among the colonies suggests that resources can only be utilized and invested into additional maintenance and reproduction by the colony if enough workers are available. The resulting relationship between per-capita and colony productivity in our study fits well with other studies conducted in the field, where decreasing per-capita productivity and the leveling off of colony productivity have been linked to density dependent effects due to competition among colonies. This suggests that the absence of trade-offs in our laboratory study might also be prevalent under natural conditions, leading to a positive association of maintenance, (= growth) and reproduction. In this respect, insect colonies resemble indeterminate growing organisms. [ABSTRACT FROM AUTHOR]

Introduction: Obsessive-compulsive disorder (OCD) is a common and chronic condition that can have disabling effects throughout the patient's lifespan. Frequent symptoms among OCD patients include fear of contamination and washing compulsions. Several studies have shown a link between contamination fears, disgust over-reactivity, and insula activation in OCD. In concordance with the role of insula in disgust processing, new neural models based on neuroimaging studies suggest that abnormally high activations of insula could be implicated in OCD psychopathology, at least in the subgroup of patients with contamination fears and washing compulsions. Methods: In the current study, we used a Brain Computer Interface (BCI) based on real-time functional magnetic resonance imaging (rtfMRI) to aid OCD patients to achieve down-regulation of the Blood Oxygenation Level Dependent (BOLD) signal in anterior insula. Our first aim was to investigate whether patients with contamination obsessions and washing compulsions can learn to volitionally decrease (down-regulate) activity in the insula in the presence of disgust/anxiety provoking stimuli. Our second aim was to evaluate the effect of down-regulation on clinical, behavioural and physiological changes pertaining to OCD symptoms. Hence, several pre- and post-training measures were performed, i.e., confronting the patient with a disgust/anxiety inducing real-world object (Ecological Disgust Test), and subjective rating and physiological responses (heart rate, skin conductance level) of disgust towards provoking pictures. Results: Results of this pilot study, performed in 3 patients (2 females), show that OCD patients can gain self-control of the BOLD activity of insula, albeit to different degrees. In two patients positive changes in behaviour in the EDT were observed following the rtfMRI trainings. Behavioural changes were also confirmed by reductions in the negative valence and in the subjective perception of disgust towards symptom provoking images. Conclusion: Although preliminary, results of this study confirmed that insula down-regulation is possible in patients suffering from OCD, and that volitional decreases of insula activation could be used for symptom alleviation in this disorder. [ABSTRACT FROM AUTHOR]