Inflammation as a Sex-Specific Mediator in the Relationship between Maternal and Offspring Obesity in C57Bl/6J Mice.

Maternal obesity is a well-established risk factor for offspring obesity development. The relationship between maternal and offspring obesity is mediated in part by developmental programming of offspring metabolic circuitry, including hypothalamic signaling. Dysregulated hypothalamic inflammation has also been linked to development of obesity. We utilized an established C57Bl/6J mouse model of high-fat, high-sugar diet induced maternal obesity to evaluate the effect of maternal obesity on systemic and hypothalamic TNF-α, IL-6, and IL-1ß levels in neonatal and adult offspring. The offspring of dams with obesity demonstrated increased adiposity and decreased activity compared to control offspring. Maternal obesity was associated with decreased plasma TNF-α, IL-6 and IL-1ß in adult female offspring and decreased plasma IL-6 in neonatal male offspring. Neonatal female offspring of obese dams had decreased TNF-α gene expression in the hypothalamus compared to control females, while neonatal and adult male offspring of obese dams had decreased IL-6 gene expression in the hypothalamus compared to control males. In summary, our results highlight important sex differences in the inflammatory phenotype of offspring exposed to maternal obesity. Sex-specific immunomodulatory mechanisms should be considered in future efforts to develop therapeutic interventions for obesity prevention and treatment.

Real-world persistence of multiple sclerosis disease-modifying therapies.

BACKGROUND AND PURPOSE: Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. METHODS: Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. RESULTS: In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. CONCLUSIONS: Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

Interconnecting global threats: climate change, biodiversity loss, and infectious diseases.

The concurrent pressures of rising global temperatures, rates and incidence of species decline, and emergence of infectious diseases represent an unprecedented planetary crisis. Intergovernmental reports have drawn focus to the escalating climate and biodiversity crises and the connections between them, but interactions among all three pressures have been largely overlooked. Non-linearities and dampening and reinforcing interactions among pressures make considering interconnections essential to anticipating planetary challenges. In this Review, we define and exemplify the causal pathways that link the three global pressures of climate change, biodiversity loss, and infectious disease. A literature assessment and case studies show that the mechanisms between certain pairs of pressures are better understood than others and that the full triad of interactions is rarely considered. Although challenges to evaluating these interactions-including a mismatch in scales, data availability, and methods-are substantial, current approaches would benefit from expanding scientific cultures to embrace interdisciplinarity and from integrating animal, human, and environmental perspectives. Considering the full suite of connections would be transformative for planetary health by identifying potential for co-benefits and mutually beneficial scenarios, and highlighting where a narrow focus on solutions to one pressure might aggravate another.

Impact of personalized diabetes care on distress and treatment satisfaction in people with breast cancer.

AIMS: In patients with breast cancer (BCa) and diabetes (DM), diabetes distress (DD) and treatment satisfaction (DTS) can influence BCa management and outcomes. We assessed the impact of implementing a personalized diabetes care model in patients with BCa. METHODS: Patients in active treatment or surveillance for BCa with an HbA1c > 53 mmol/mol (7%) or random blood glucose >11.1 mmol/L were included. Participants were offered continuous glucose monitoring (CGM), virtual care and a dedicated diabetes provider for 6 months. Primary outcomes included DD measured by the Diabetes Distress Survey (DDS) and DTS measured by the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Questionnaires were conducted at 0, 3 and 6 months. RESULTS: Thirty-one women were enrolled (median age 61, IQR 49.0-69.0). Compared to baseline, the mean DDS score was lower at both 3 months (2.2 vs. 1.8 [n = 27], p = 0.004, SD = 0.70) and 6 months (2.3 vs. 1.8 [n = 23], p = 0.002, SD = 0.70). The mean DTSQ score was higher at 3 months (baseline: 20.5 vs. 3 months: 28.7 [n = 28], p < 0.001, SD = 9.2) and 6 months (baseline: 20.4 vs. 6 months: 30.0 [n = 26], p < 0.001, SD = 9.7). CONCLUSIONS: Personalized diabetes care models that emphasize remote management and optimize access for those with BCa may lower DD and improve DTS.

Temperature Sensitivity of Fitness Components across Life Cycles Drives Insect Responses to Climate Change.

AbstractThermal performance curves (TPCs) are increasingly used as a convenient approach to predict climate change impacts on ectotherms that accounts for organismal thermal sensitivity; however, directly applying TPCs to temperature data to estimate fitness has yielded contrasting predictions depending on assumptions regarding climate variability. We compare direct application of TPCs to an approach integrating TPCs for different fitness components (e.g., per capita birth rate, adult life span) across ectotherm life cycles into a population dynamic model, which we independently validated with census data and applied to hemipteran insect populations across latitude. The population model predicted that climate change will reduce insect fitness more at higher latitudes due to its effects on survival but will reduce net reproductive rate more at lower latitudes due to its effects on fecundity. Directly applying TPCs underestimated climate change impacts on fitness relative to incorporating the TPCs into the population model due to simplifying survival dynamics across the life cycle. The population model predicted that climate change will reduce mean insect density and increase population variability at higher latitudes via reduced survival, despite faster development and a longer activity period. Our study highlights the importance of considering how multiple fitness components respond to climate variability across the life cycle to better understand and anticipate the ecological consequence of climate change.

The Evolving Landscape of Genetic Carrier Screening: Clinical Considerations and Challenges.

Importance: Genetic carrier screening is performed to identify carriers of rare genetic diseases. Identification of carriers allows patients to make informed reproductive health choices and can decrease the incidence of genetic disorders with serious medical implications. Objective: This review aims to provide an overview of the history of prenatal genetic screening and the various forms of carrier screening, a synopsis of recent changes in society recommendations and current practice guidelines, and discussion of clinical challenges associated with carrier screening. Evidence Acquisition: Published practice guidelines from relevant professional societies were reviewed and synthesized. PubMed search was performed for relevant history and clinical considerations of carrier screening. Results: Information and evidence summarized in this review include professional society practice guidelines, review articles, and peer-reviewed research articles. Conclusions and Relevance: Current practice guidelines differ between stakeholder professional organizations. Expanded carrier screening offers increased identification of rare disease carriers allowing for more informed reproductive choices. However, there are several barriers to the implementation of expanded carrier screening for all patients.

Fire-driven animal evolution in the Pyrocene.

Fire regimes are a major agent of evolution in terrestrial animals. Changing fire regimes and the capacity for rapid evolution in wild animal populations suggests the potential for rapid, fire-driven adaptive animal evolution in the Pyrocene. Fire drives multiple modes of evolutionary change, including stabilizing, directional, disruptive, and fluctuating selection, and can strongly influence gene flow and genetic drift. Ongoing and future research in fire-driven animal evolution will benefit from further development of generalizable hypotheses, studies conducted in highly responsive taxa, and linking fire-adapted phenotypes to their underlying genetic basis. A better understanding of evolutionary responses to fire has the potential to positively influence conservation strategies that embrace evolutionary resilience to fire in the Pyrocene.

Prenatal Genetic Screening in Twin Pregnancy.

Twin pregnancy presents unique considerations for aneuploidy screening. Pre-test counseling regarding benefits, alternatives, and options for aneuploidy screening should be provided to all patients carrying twin pregnancy. This article aims to review the options for aneuploidy screening in twin pregnancy including the potential benefits and limitations.

Standard-Dose Azithromycin in Class III Obese Patients Undergoing Unscheduled Cesarean Delivery.

OBJECTIVE: Perioperative antibiotic prophylaxis reduces cesarean wound complications. This study investigates whether integration of standard-dose (500 mg) azithromycin prophylaxis reduced wound complications in patients with class III obesity (body mass index [BMI] ≥ 40 kg/m2) undergoing unscheduled cesarean delivery. STUDY DESIGN: Retrospective cohort study of patients with class III obesity undergoing unscheduled cesarean delivery in single hospital system from January 1, 2017, to January 1, 2020. A standard dose (500 mg) of azithromycin was integrated into system order sets in 2018. Medical history and postoperative wound outcomes were compared in pre- and postintegration cohorts. Wound complication was defined as composite of wound seroma, hematoma, superficial or deep infection. RESULTS: A total of 1,273 patients met inclusion criteria, 303 patients in the preorder set group, and 970 patients in the postorder set group. Demographics were similar between the pre- and postintegration cohorts, including BMI (median: 44.4 kg/m2, p = 0.84) and weight at delivery (mean: 121.2 ± 17.8 kg, p = 0.57). Patients in the postintegration cohort had lower rates of composite postpartum wound complication (7.9 vs. 13.9%, p = 0.002), superficial infection or deep infection/abscess (6.7 vs. 10.2%, p = 0.042), and postpartum readmission or unscheduled visits (18.7 vs. 24.4%, p < 0.029). Rates of chorioamnionitis and endometritis were similar between the pre- and postintegration groups (8.6 vs. 6.9%, p = 0.33, and 1.7 vs. 1.9%, p = 0.81, respectively). Patients in the postintegration cohort had lower risk of postoperative composite wound complication (unadjusted odds ratio [OR]: 0.54, confidence interval [CI]: 0.36-0.80, p = 0.002) and lower rates of wound infection (unadjusted OR: 0.63, 95% CI: 0.40-0.99, p = 0.044). When comparing patients who received azithromycin at delivery and patients who did not, standard-dose azithromycin reduced risk of postoperative wound complication (unadjusted OR: 0.67, 95% CI: 0.46-0.99, p = 0.043). CONCLUSION: A standard dose of azithromycin provides adequate perioperative prophylaxis in class III obese patients, decreasing rates of postcesarean wound complications and unscheduled postpartum outpatient visits. KEY POINTS: · Class III obese patients undergoing unscheduled cesarean have high rates of wound complications.. · Standard-dose azithromycin reduces risk of postcesarean wound infection in class III obese patients.. · Standard-dose azithromycin reduces readmission, unscheduled visits in class III obese patients..

Mechanistic forecasts of species responses to climate change: The promise of biophysical ecology.

A core challenge in global change biology is to predict how species will respond to future environmental change and to manage these responses. To make such predictions and management actions robust to novel futures, we need to accurately characterize how organisms experience their environments and the biological mechanisms by which they respond. All organisms are thermodynamically connected to their environments through the exchange of heat and water at fine spatial and temporal scales and this exchange can be captured with biophysical models. Although mechanistic models based on biophysical ecology have a long history of development and application, their use in global change biology remains limited despite their enormous promise and increasingly accessible software. We contend that greater understanding and training in the theory and methods of biophysical ecology is vital to expand their application. Our review shows how biophysical models can be implemented to understand and predict climate change impacts on species' behavior, phenology, survival, distribution, and abundance. It also illustrates the types of outputs that can be generated, and the data inputs required for different implementations. Examples range from simple calculations of body temperature at a particular site and time, to more complex analyses of species' distribution limits based on projected energy and water balances, accounting for behavior and phenology. We outline challenges that currently limit the widespread application of biophysical models relating to data availability, training, and the lack of common software ecosystems. We also discuss progress and future developments that could allow these models to be applied to many species across large spatial extents and timeframes. Finally, we highlight how biophysical models are uniquely suited to solve global change biology problems that involve predicting and interpreting responses to environmental variability and extremes, multiple or shifting constraints, and novel abiotic or biotic environments.

Female and male C57BL/6J offspring exposed to maternal obesogenic diet develop altered hypothalamic energy metabolism in adulthood.

Maternal obesity is exceedingly common and strongly linked to offspring obesity and metabolic disease. Hypothalamic function is critical to obesity development. Hypothalamic mechanisms causing obesity following exposure to maternal obesity have not been elucidated. Therefore, we studied a cohort of C57BL/6J dams, treated with a control or high-fat-high-sugar diet, and their adult offspring to explore potential hypothalamic mechanisms to explain the link between maternal and offspring obesity. Dams treated with obesogenic diet were heavier with mild insulin resistance, which is reflective of the most common metabolic disease in pregnancy. Adult offspring exposed to maternal obesogenic diet had no change in body weight but significant increase in fat mass, decreased glucose tolerance, decreased insulin sensitivity, elevated plasma leptin, and elevated plasma thyroid-stimulating hormone. In addition, offspring exposed to maternal obesity had decreased energy intake and activity without change in basal metabolic rate. Hypothalamic neurochemical profile and transcriptome demonstrated decreased neuronal activity and inhibition of oxidative phosphorylation. Collectively, these results indicate that maternal obesity without diabetes is associated with adiposity and decreased hypothalamic energy production in offspring. We hypothesize that altered hypothalamic function significantly contributes to obesity development. Future studies focused on neuroprotective strategies aimed to improve hypothalamic function may decrease obesity development.NEW & NOTEWORTHY Offspring exposed to maternal diet-induced obesity demonstrate a phenotype consistent with energy excess. Contrary to previous studies, the observed energy phenotype was not associated with hyperphagia or decreased basal metabolic rate but rather decreased hypothalamic neuronal activity and energy production. This was supported by neurochemical changes in the hypothalamus as well as inhibition of hypothalamic oxidative phosphorylation pathway. These results highlight the potential for neuroprotective interventions in the prevention of obesity with fetal origins.

Impact of Respiratory Syncytial Virus on Child, Caregiver, and Family Quality of Life in the United States: Systematic Literature Review and Analysis.

BACKGROUND: Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection in US children, reduces quality of life (QOL) of children, their caregivers, and families. METHODS: We conducted a systematic literature review in PubMed, EconLit, and other databases in the United States of articles published since 2000, derived utility lost per RSV episode from cohort studies, and performed a systematic analysis. RESULTS: From 2262 unique citations, 35 received full-text review and 7 met the inclusion criteria (2 cohort studies, 4 modeling studies, and 1 synthesis). Pooled data from the 2 cohort studies (both containing only hospitalized premature infants) gave quality-adjusted life-year (QALY) losses per episode of 0.0173 at day 38. From the cohort study that also assessed caregivers' QOL, we calculated net QALYs lost directly attributable to RSV per nonfatal episode from onset to 60 days after onset for the child, caregiver, child-and-caregiver dyad of 0.0169 (167% over prematurity alone), 0.0031, and 0.0200, respectively. CONCLUSION: Published data on QOL of children in the United States with RSV are scarce and consider only premature hospitalized infants, whereas most RSV episodes occur in children who were born at term and were otherwise healthy. QOL studies are needed beyond hospitalized premature infants.

Cost of Respiratory Syncytial Virus Infections in US Infants: Systematic Literature Review and Analysis.

BACKGROUND: Limited data are available on the economic costs of respiratory syncytial virus (RSV) infections among infants and young children in the United States. METHODS: We performed a systematic literature review of 10 key databases to identify studies published between 1 January 2014 and 2 August 2021 that reported RSV-related costs in US children aged 0-59 months. Costs were extracted and a systematic analysis was performed. RESULTS: Seventeen studies were included. Although an RSV hospitalization (RSVH) of an extremely premature infant costs 5.6 times that of a full-term infant ($10 214), full-term infants accounted for 82% of RSVHs and 70% of RSVH costs. Medicaid-insured infants were 91% more likely than commercially insured infants to be hospitalized for RSV treatment in their first year of life. Medicaid financed 61% of infant RSVHs. Paying 32% less per hospitalization than commercial insurance, Medicaid paid 51% of infant RSVH costs. Infants' RSV treatment costs $709.6 million annually, representing $187 per overall birth and $227 per publicly funded birth. CONCLUSIONS: Public sources pay for more than half of infants' RSV medical costs, constituting the highest rate of RSVHs and the highest expenditure per birth. Full-term infants are the predominant source of infant RSVHs and costs.

Designing a Seasonal Acclimation Study Presents Challenges and Opportunities.

Organisms living in seasonal environments often adjust physiological capacities and sensitivities in response to (or in anticipation of) environment shifts. Such physiological and morphological adjustments ("acclimation" and related terms) inspire opportunities to explore the mechanistic bases underlying these adjustments, to detect cues inducing adjustments, and to elucidate their ecological and evolutionary consequences. Seasonal adjustments ("seasonal acclimation") can be detected either by measuring physiological capacities and sensitivities of organisms retrieved directly from nature (or outdoor enclosures) in different seasons or less directly by rearing and measuring organisms maintained in the laboratory under conditions that attempt to mimic or track natural ones. But mimicking natural conditions in the laboratory is challenging-doing so requires prior natural-history knowledge of ecologically relevant body temperature cycles, photoperiods, food rations, social environments, among other variables. We argue that traditional laboratory-based conditions usually fail to approximate natural seasonal conditions (temperature, photoperiod, food, "lockdown"). Consequently, whether the resulting acclimation shifts correctly approximate those in nature is uncertain, and sometimes is dubious. We argue that background natural history information provides opportunities to design acclimation protocols that are not only more ecologically relevant, but also serve as templates for testing the validity of traditional protocols. Finally, we suggest several best practices to help enhance ecological realism.

Les organismes vivant dans des environnements saisonniers ajustent souvent leurs capacités et leurs sensibilités physiologiques en réponse (ou en prévision de) aux changements environnementaux. De tels ajustements physiologiques et morphologiques (« acclimatation ¼ et termes apparentés) offrent l"opportunité d'explorer les mécanismes sous-jacents à ces ajustements, de détecter les indices qui les induisent et d'élucider leurs conséquences écologiques et évolutives. Les ajustements saisonniers ("acclimatation saisonnière") peuvent être détectés soit en mesurant les capacités physiologiques et les sensibilités d'organismes prélevés directement dans la nature (ou dans des enclos extérieurs) à différentes saisons, soit de manière moins directe en élevant et en mesurant des organismes maintenus en laboratoire dans des conditions qui tentent d"imiter ou de suivre les conditions naturelles. Mais il est difficile de reproduire les conditions naturelles en laboratoire car il faut pour cela connaître les cycles de température corporelle, la photopériode, le régime alimentaire, les environnements sociaux, entre autres variables pertinentes d'un point de vue écologique. Nous argumentons que les conditions traditionnellement utilisées en laboratoire ne parviennent généralement pas à se rapprocher des conditions saisonnières naturelles (température, photopériode, nourriture, « confinement ¼). Par conséquent, il n"est pas certain, et parfois douteux, que les écarts d"acclimatation qui en résultent se rapprochent correctement de ceux de la nature. Nous soutenons que les informations de base sur l"histoire naturelle offrent la possibilité de concevoir des protocoles d"acclimatation qui sont non seulement plus pertinents sur le plan écologique, mais servent également de modèles pour tester la validité des protocoles traditionnels. Enfin, nous suggérons plusieurs bonnes pratiques pour aider à améliorer le réalisme écologique.

Los organismos que viven en ambientes estacionales pueden ajustar sus capacidades y sensibilidades fisiológicas en respuesta (o en anticipación) a cambios ambientales. Estos ajustes fisiológicos y morfológicos ("aclimatación" y términos afines) dan la oportunidad para explorar el mecanismo que subyace a estos ajustes, también para detectar las señales que inducen tales ajustes y finalmente para dilucidar sus consecuencias ecológicas y evolutivas. Los ajustes estacionales ("aclimatación estacional") se pueden detectar midiendo las capacidades y sensibilidades fisiológicas de los organismos, ya sea en especímenes extraídos directamente de la naturaleza (o recintos al aire libre) en diferentes estaciones, como también, de una manera menos directa, en especímenes criados y mantenidos en el laboratorio bajo condiciones que simulan las condiciones naturales y sus cambios estacionales. Sin embargo, esta simulación en el laboratorio es un desafío; hacerlo requiere un conocimiento previo de la historia natural de los ciclos de temperatura corporal, los fotoperíodos, las raciones de alimentos, los entornos sociales, entre otras variables ecológicamente relevantes. Argumentamos que las condiciones tradicionales de laboratorio generalmente no se aproximan a las condiciones estacionales naturales (temperatura, fotoperíodo, comida, "bloqueo"). En consecuencia, es incierto y, a veces, dudoso si los cambios de aclimatación resultantes se aproximan correctamente a los de la naturaleza. Así también, la información de antecedentes de la historia natural brinda oportunidades para diseñar protocolos de aclimatación que no solo son más relevantes desde el punto de vista ecológico, sino que también sirven como plantillas para probar la validez de los protocolos tradicionales. Finalmente, sugerimos varias mejoras prácticas que pueden ayudar a lograr un realismo ecológico optimizado en las simulaciones de laboratorio.

The Effects of Diabetes and Glycemic Control on Cancer Outcomes in Individuals With Metastatic Breast Cancer.

BACKGROUND: It is unclear whether diabetes and glycemic control affects the outcomes of breast cancer, especially among those with metastatic disease. This study aims to determine the impact of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer (MBC). METHODS: Patients with a diagnosis of MBC between 2010 and 2021 were identified using the MBC database at 2 academic institutions. We evaluated the effects of diabetes and glycemic control on overall survival (OS) and time to next treatment (TTNT). RESULTS: We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes (matched for age, sex, ethnicity, and receptor subtype). OS at 5 years [diabetes: 54% (95% CI 47-62%) vs controls: 56% (95% CI 49-63%), P = 0.65] and TTNT at 1 year [diabetes: 43% (95% CI 36-50%) vs controls: 44% (95% CI 36-51%), P = 0.33] were similar between groups. A subgroup analysis comparing those with good glycemic control and those with poor glycemic control among patients with specific receptor subtype profiles showed no differences in OS at 5 years or TTNT at 1 year. In an 8-year landmark subgroup analysis, there was worse OS among individuals with diabetes compared to controls, and OS was found to be better among those with good glycemic control compared to those with poor control. CONCLUSIONS: Diabetes was not associated with increased mortality in individuals with MBC at 5 years. However, diabetes and hyperglycemia were associated with worse OS among a cohort of longer-term survivors. These findings suggest that individualized diabetes and glycemic goals should be considered in patients with MBC.

Temperature-sensitive development shapes insect phenological responses to climate change.

Phenological shifts vary within and among insect species and locations based on exposure and sensitivity to climate change. Shifts in environmental conditions and seasonal constraints along elevation and latitudinal gradients can select for differences in temperature sensitivity that generate differential phenological shifts. I examine the phenological implications of observed variation in developmental traits. Coupling physiological and ecological insight to link the environmental sensitivity of development to phenology and fitness offers promise in understanding variable phenological responses to climate change and their community and ecosystem implications. A key challenge in establishing these linkages is extrapolating controlled, laboratory experiments to temporally variable, natural environments. New lab and field experiments that incorporate realistic environmental variation are needed to test the extrapolations. Establishing the linkages can aid understanding and anticipating impacts of climate change on insects.

How Can We Fully Realize the Potential of Mathematical and Biological Models to Reintegrate Biology?

Both mathematical models and biological model systems stand as tractable representations of complex biological systems or behaviors. They facilitate research and provide insights, and they can describe general rules. Models that represent biological processes or formalize general hypotheses are essential to any broad understanding. Mathematical or biological models necessarily omit details of the natural systems and thus may ultimately be "incorrect" representations. A key challenge is that tractability requires relatively simple models but simplification can result in models that are incorrect in their qualitative, broad implications if the abstracted details matter. Our paper discusses this tension, and how we can improve our inferences from models. We advocate for further efforts dedicated to model development, improvement, and acceptance by the scientific community, all of which may necessitate a more explicit discussion of the purpose and power of models. We argue that models should play a central role in reintegrating biology as a way to test our integrated understanding of how molecules, cells, organs, organisms, populations, and ecosystems function.

High-Elevation Populations of Montane Grasshoppers Exhibit Greater Developmental Plasticity in Response to Seasonal Cues.

Populations of insects can differ in how sensitive their development, growth, and performance are to environmental conditions such as temperature and daylength. The environmental sensitivity of development can alter phenology (seasonal timing) and ecology. Warming accelerates development of most populations. However, high-elevation and season-limited populations can exhibit developmental plasticity to either advance or prolong development depending on conditions. We examine how diurnal temperature variation and daylength interact to shape growth, development, and performance of several populations of the montane grasshopper, Melanoplus boulderensis, along an elevation gradient. We then compare these experimental results to observed patterns of development in the field. Although populations exhibited similar thermal sensitivities of development under long-day conditions, development of high-elevation populations was more sensitive to temperature under short-day conditions. This developmental plasticity resulted in rapid development of high elevation populations in short-day conditions with high temperature variability, consistent with their observed capacity for rapid development in the field when conditions are permissive early in the season. Notably, accelerated development generally did not decrease body size or alter body shape. Developmental conditions did not strongly influence thermal tolerance but altered the temperature dependence of performance in difficult-to-predict ways. In sum, the high-elevation and season-limited populations exhibited developmental plasticity that enables advancing or prolonging development consistent with field phenology. Our results suggest these patterns are driven by the thermal sensitivity of development increasing when days are short early in the season compared to when days are long later in the season. Developmental plasticity will shape phenological responses to climate change with potential implications for community and ecosystem structure.

Grasshopper species' seasonal timing underlies shifts in phenological overlap in response to climate gradients, variability and change.

Species with different life histories and communities that vary in their seasonal constraints tend to shift their phenology (seasonal timing) differentially in response to climate warming. We investigate how these variable phenological shifts aggregate to influence phenological overlap within communities. Phenological advancements of later season species and extended durations of early season species may increase phenological overlap, with implications for species' interactions such as resource competition. We leverage extensive historic (1958-1960) and recent (2006-2015) weekly survey data for communities of grasshoppers along a montane elevation gradient to assess the impact of climate on shifts in the phenology and abundance distributions of species. We then examine how these responses are influenced by the seasonal timing of species and elevation, and how in aggregate they influence degrees of phenological overlap within communities. In warmer years, abundance distributions shift earlier in the season and become broader. Total abundance responds variably among species and we do not detect a significant response across species. Shifts in abundance distributions are not strongly shaped by species' seasonal timing or sites of variable elevations. The area of phenological overlap increases in warmer years due to shifts in the relative seasonal timing of compared species. Species that overwinter as nymphs increasingly overlap with later season species that advance their phenology. The days of phenological overlap also increase in warm years but the response varies across sites of variable elevation. Our phenological overlap metric based on comparing single events-the dates of peak abundance-does not shift significantly with warming. Phenological shifts are more complex than shifts in single dates such as first occurrence. As abundance distributions shift earlier and become broader in warm years, phenological overlap increases. Our analysis suggests that overall grasshopper abundance is relatively robust to climate and associated phenological shifts but we find that increased overlap can decrease abundance, potentially by strengthening species interactions such as resource competition.