Amino acid restriction, aging, and longevity: an update.

Various so-called dietary restriction paradigms have shown promise for extending health and life. All such paradigms rely on ad libitum (hereafter ad lib) feeding, something virtually never employed in animals whose long-term health we value, either as a control or, except for food restriction itself, for both control and treatment arms of the experiment. Even though the mechanism(s) remain only vaguely understood, compared to ad lib-fed animals a host of dietary manipulations, including calorie restriction, low protein, methionine, branched-chain amino acids, and even low isoleucine have demonstrable health benefits in laboratory species in a standard laboratory environment. The remaining challenge is to determine whether these health benefits remain in more realistic environments and how they interact with other health enhancing treatments such as exercise or emerging geroprotective drugs. Here we review the current state of the field of amino acid restriction on longevity of animal models and evaluate its translational potential.

Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

Multi-omics for studying and understanding polar life.

Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss 'omics' approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.

Search for a Dark-Matter-Induced Cosmic Axion Background with ADMX.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

Initial evaluation of USP apparatus 4 for measuring dissolution profile of man-made vitreous fibers.

We report the successful evaluation of a US Pharmacopeia Apparatus 4 (USP-4) system in measuring the dissolution profiles of man-made vitreous fibers (MMVF)1. Glass and stone wool fibers with different (high- and low-) solubility profiles were tested in closed-loop configuration using a sodium/potassium phosphate buffer solution or an acetate buffer, respectively. Results confirm a need to operate in diluted conditions to avoid silicon saturation in the simulant solution and suppression of fiber dissolution. A clear fiber-to-fiber differentiation with good cell-to-cell reproducibility was achieved. These findings support the continued development of a USP-4 protocol for MMVF in vitro acellular testing.

Soil water dynamics and biomass production of young rooibos (Aspalathus linearis) plants.

Rooibos (Aspalathus linearis) is endemic to certain regions of the Western- and Northern Cape of South Africa, where it is also commercially grown. Being low-rainfall regions, information on the soil water balance of rooibos is essential, but such data is limited. Consequently, the effect of inorganic fertilisation and soil depth on soil water dynamics in a young rooibos plantation at Nardouwsberg, Western Cape were studied. Soil water content of plots planted to unfertilised and fertilised plants as well as that of bare soil were determined over the duration of the 2016/17 season. All treatments were replicated on shallow and deep soils sites and plant growth was determined at the end of the season. At the end of the study, the profile soil water content and evapotranspiration of the bare and planted plots were similar which prove that fallowing (water harvesting) is not an option in the sandy soils of this region. With the exception of the 20-30 cm root zone of the planted plots at the deep site, the water content decreased to levels below the permanent wilting point in the soil profile during summer. It was concluded that rooibos plants could survive through an adapted root system. A further survival method was proposed, involving moisture moved through evaporation from the deeper soil layers into the drying-front in the ~ 10-30 cm soil layer where a condensation-evaporation cycle enables rooibos to harvest small amounts of water. The highest shoot biomass with the longest taproot resulted from the unfertilised treatment on the deep soil thanks to higher soil water content, whereas the shoot and root biomass of the fertilised treatment at both sites were low due to high P soil concentration. This study revealed that unfertilised plants on deeper soils result in higher rooibos production under drought conditions.

The social formation of fitness: lifetime consequences of prenatal nutrition and postnatal care in a wild mammal population.

Research in medicine and evolutionary biology suggests that the sequencing of parental investment has a crucial impact on offspring life history and health. Here, we take advantage of the synchronous birth system of wild banded mongooses to test experimentally the lifetime consequences to offspring of receiving extra investment prenatally versus postnatally. We provided extra food to half of the breeding females in each group during pregnancy, leaving the other half as matched controls. This manipulation resulted in two categories of experimental offspring in synchronously born litters: (i) 'prenatal boost' offspring whose mothers had been fed during pregnancy, and (ii) 'postnatal boost' offspring whose mothers were not fed during pregnancy but who received extra alloparental care in the postnatal period. Prenatal boost offspring lived substantially longer as adults, but postnatal boost offspring had higher lifetime reproductive success (LRS) and higher glucocorticoid levels across the lifespan. Both types of experimental offspring had higher LRS than offspring from unmanipulated litters. We found no difference between the two experimental categories of offspring in adult weight, age at first reproduction, oxidative stress or telomere lengths. These findings are rare experimental evidence that prenatal and postnatal investments have distinct effects in moulding individual life history and fitness in wild mammals. This article is part of the theme issue 'Evolutionary ecology of inequality'.

Contrasting continental patterns of adaptive population divergence in the holarctic ectomycorrhizal fungus Boletus edulis.

In the hyperdiverse fungi, the process of speciation is virtually unknown, including for the > 20 000 species of ectomycorrhizal mutualists. To understand this process, we investigated patterns of genome-wide differentiation in the ectomycorrhizal porcini mushroom, Boletus edulis, a globally distributed species complex with broad ecological amplitude. By whole-genome sequencing 160 individuals from across the Northern Hemisphere, we genotyped 792 923 single nucleotide polymorphisms to characterize patterns of genome-wide differentiation and to identify the adaptive processes shaping global population structure. We show that B. edulis exhibits contrasting patterns of genomic divergence between continents, with multiple lineages present across North America, while a single lineage dominates Europe. These geographical lineages are inferred to have diverged 1.62-2.66 million years ago, during a period of climatic upheaval and the onset of glaciation in the Pliocene-Pleistocene boundary. High levels of genomic differentiation were observed among lineages despite evidence of substantial and ongoing introgression. Genome scans, demographic inference, and ecological niche models suggest that genomic differentiation is maintained by environmental adaptation, not physical isolation. Our study uncovers striking patterns of genome-wide differentiation on a global scale and emphasizes the importance of local adaptation and ecologically mediated divergence, rather than prezygotic barriers such as allopatry or genomic incompatibility, in fungal population differentiation.

The effect of supraphysiological dose of nandrolone decanoate administration on the inflammatory, neurotrophin and behavioral response in adult and old male mice.

This study examined the effect of 6 weeks of supraphysiological nandrolone decanoate (ND) administration in adult mice (7 months) on cognitive function and neuroinflammation during aging. Male C57BL/6 mice were randomized into ND (10 mg·kg-1·wk-1) or control (CTL) groups. Half of the mice were tested at a young (Y) age (ND-Y and CTL-Y), 1 week following final ND administration, while the remaining mice were tested at 16 months (O) (ND-O and CTL-O). Learning and memory were better in young mice compared to older mice, regardless of treatment. ND-O displayed decreased anxiety as compared to all other groups. TNFα and IL1ß expression were higher in older mice, regardless of treatment. ND administration in young mice appeared to attenuate the neuroinflammatory response in aging mice as evidenced by decreased COX2, IL-4 and increased IL-10 expression in ND-O compared to CTL-O. BDNF AR and ER expression increased in ND-O compared to CTL-O. Results of the study indicated that supraphysiological ND administration had no negative effect on learning and memory but may attenuate anxiety in older mice. In addition, ND administration in young adult mice may attenuate the inflammatory response during aging, which may be related to elevations in both AR and ER expression.

The effects of electronic nicotine vapor on voluntary alcohol consumption in female and male C57BL/6 J mice.

SIGNIFICANCE: Alcohol drinking and nicotine vaping often co-occur and dependence on both substances is common. However, the impact of nicotine vaping on alcohol consumption is not fully understood. METHODS: We examined the effects of nicotine vaping on ethanol drinking in female and male C57BL/6 J mice using an electronic nicotine delivery system and intermittent access two-bottle choice (IA-2BC) drinking. Mice were exposed to electronic nicotine vapor (3%) or propylene glycol/vegetable glycerol (PG/VG) control for 3 h sessions daily for 4 weeks and voluntary alcohol consumption was monitored. Nicotine vapor exposure was stopped and voluntary alcohol drinking was measured for a 2 week abstinence period. We also examined the effects of alcohol and nicotine on locomotion, temperature, and nicotine metabolism. RESULTS: Following acute nicotine vapor exposure, alcohol drinking was increased in males but not in females. Thermoregulation was disrupted following nicotine vapor exposure and voluntary drinking. Male and female mice displayed increased locomotor activity immediately following chronic nicotine vapor exposure, and an anxiolytic effect was seen in males. In nicotine vapor abstinence, female mice displayed increased alcohol consumption. Locomotor activity and anxiolytic effects remained elevated in male but not female mice. Female mice displayed higher levels of serum nicotine and hydroxycotinine, suggesting impaired metabolism following chronic drinking and nicotine vapor exposure. CONCLUSION: Collectively, these results suggest that while both male and female ethanol-drinking mice experience the stimulatory effects of nicotine vapor, only in males is there a parallel increase in ethanol drinking and only females display impairments in nicotine metabolism after drinking.

In situ recording of Mars soundscape.

Before the Perseverance rover landing, the acoustic environment of Mars was unknown. Models predicted that: (1) atmospheric turbulence changes at centimetre scales or smaller at the point where molecular viscosity converts kinetic energy into heat1, (2) the speed of sound varies at the surface with frequency2,3 and (3) high-frequency waves are strongly attenuated with distance in CO2 (refs. 2-4). However, theoretical models were uncertain because of a lack of experimental data at low pressure and the difficulty to characterize turbulence or attenuation in a closed environment. Here, using Perseverance microphone recordings, we present the first characterization of the acoustic environment on Mars and pressure fluctuations in the audible range and beyond, from 20 Hz to 50 kHz. We find that atmospheric sounds extend measurements of pressure variations down to 1,000 times smaller scales than ever observed before, showing a dissipative regime extending over five orders of magnitude in energy. Using point sources of sound (Ingenuity rotorcraft, laser-induced sparks), we highlight two distinct values for the speed of sound that are about 10 m s-1 apart below and above 240 Hz, a unique characteristic of low-pressure CO2-dominated atmosphere. We also provide the acoustic attenuation with distance above 2 kHz, allowing us to explain the large contribution of the CO2 vibrational relaxation in the audible range. These results establish a ground truth for the modelling of acoustic processes, which is critical for studies in atmospheres such as those of Mars and Venus.

A Process-Oriented Model of Decision-Making toward Landscape-Scale Prescribed Fire Implementation in the Southern Great Plains, USA.

In this investigation, we developed a model of the psychological drivers of landowners' decisions to implement prescribed fire on their properties. The Southern Great Plains in the USA evolved with fire and prescribed fire is an important management tool aimed at maintaining and enhancing ecological and economic resilience in the region. The conceptualized model is reflective of a decision-making paradigm that considers decision making to be a process inclusive of a variety of factors and their inter-relationships to arrive at judgments on whether or not to utilize prescribed fire. The approach considered a spectrum of inputs, obstacles, and their associations to capture the complexity of decision making that is often lost when modeling single factors in dynamic social-ecological settings. Further, we considered the decision to use prescribed fire as a multifactor process that incorporates not only individual barriers to fire implementation but inter-barrier associations and other inputs (e.g., sociodemographic variables). Path analysis revealed five statistically significant relationships within the hypothesized model. For prescribed fire decision making, women tended to be more analytical whereas men were more inclined to rely on heuristics. Additionally, those who indicated owning their property for non-consumptive recreation-related reasons were also more inclined to rely upon heuristics. Texans reported more experience with prescribed fire as did respondents who indicated owning property for livestock product. Alternately, those owning their property for an investment and non-consumptive recreation opportunities reported less experience with prescribed fire. Last, ownership for crop and livestock production was positively associated with past wildfire experience. Findings have implications for three issue areas: (1) the provision of an evolved conceptualization through which prescribed fire implementation decisions can be examined, (2) enhancing the approach of prescribed fire outreach to a changing landowner population, and (3) improving the content and delivery of prescribed fire education efforts.

A veil of ignorance can promote fairness in a mammal society.

Rawls argued that fairness in human societies can be achieved if decisions about the distribution of societal rewards are made from behind a veil of ignorance, which obscures the personal gains that result. Whether ignorance promotes fairness in animal societies, that is, the distribution of resources to reduce inequality, is unknown. Here we show experimentally that cooperatively breeding banded mongooses, acting from behind a veil of ignorance over kinship, allocate postnatal care in a way that reduces inequality among offspring, in the manner predicted by a Rawlsian model of cooperation. In this society synchronized reproduction leaves adults in a group ignorant of the individual parentage of their communal young. We provisioned half of the mothers in each mongoose group during pregnancy, leaving the other half as matched controls, thus increasing inequality among mothers and increasing the amount of variation in offspring birth weight in communal litters. After birth, fed mothers provided extra care to the offspring of unfed mothers, not their own young, which levelled up initial size inequalities among the offspring and equalized their survival to adulthood. Our findings suggest that a classic idea of moral philosophy also applies to the evolution of cooperation in biological systems.

Exercise-induced muscle damage: mechanism, assessment and nutritional factors to accelerate recovery.

There have been a multitude of reviews written on exercise-induced muscle damage (EIMD) and recovery. EIMD is a complex area of study as there are a host of factors such as sex, age, nutrition, fitness level, genetics and familiarity with exercise task, which influence the magnitude of performance decrement and the time course of recovery following EIMD. In addition, many reviews on recovery from exercise have ranged from the impact of nutritional strategies and recovery modalities, to complex mechanistic examination of various immune and endocrine signaling molecules. No one review can adequately address this broad array of study. Thus, in this present review, we aim to examine EIMD emanating from both endurance exercise and resistance exercise training in recreational and competitive athletes and shed light on nutritional strategies that can enhance and accelerate recovery following EIMD. In addition, the evaluation of EIMD and recovery from exercise is often complicated and conclusions often depend of the specific mode of assessment. As such, the focus of this review is also directed at the available techniques used to assess EIMD.

Search for Invisible Axion Dark Matter in the 3.3-4.2 µeV Mass Range.

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 µeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.

Trophic transfer efficiency in the Lake Superior food web: assessing the impacts of non-native species.

Ecosystem-based management relies on understanding how perturbations influence ecosystem structure and function (e.g., invasive species, exploitation, abiotic changes). However, data on unimpacted systems are scarce, therefore, we often rely on impacted systems to make inferences about 'natural states.' Among the Laurentian Great Lakes, Lake Superior provides a unique case study to address non-native species impacts because the food web is dominated by native species. Additionally, Lake Superior is both vertically (benthic versus pelagic) and horizontally (nearshore versus offshore) structured by depth, providing an opportunity to compare the function of these sub-food webs. We developed an updated Lake Superior EcoPath model using data from the 2005/2006 lake-wide multi-agency surveys covering multiple trophic levels. We then compared trophic transfer efficiency (TTE) to previously published EcoPath models. Finally, we compared ecosystem function of the 2005/2006 ecosystem to that with non-native linkages removed and compared native versus non-native species-specific approximations of TTE and trophic flow. Lake Superior was relatively efficient (TTE = 0.14) compared to systems reported in a global review (average TTE = 0.09) and the microbial loop was highly efficient (TTE > 0.20). Non-native species represented a very small proportion (<0.01%) of total biomass and were generally more efficient and had higher trophic flow compared to native species. Our results provide valuable insight into the importance of the microbial loop and represent a baseline estimate of non-native species impacts on Lake Superior. Finally, this work is a starting point for further model development to predict future changes in the Lake Superior ecosystem.

Genetic analysis of Boletus edulis suggests that intra-specific competition may reduce local genetic diversity as a woodland ages.

Ectomycorrhizal fungi are key players in terrestrial ecosystems yet their mating systems and population dynamics remain poorly understood. We investigated the fine-scale relatedness structure and genetic diversity of Boletus edulis, one of the world's most commercially important wild mushrooms. Microsatellite genotyping of fruiting bodies from 14 different sites around Bielefeld in Germany revealed little in the way of population structure over a geographic scale of several kilometres. However, on a more local scale we found evidence for elevated relatedness as well as inbreeding. We also observed a significant negative association between the genetic diversity of fruit and the age of the trees under which they were sampled. Taken together, our results suggest that as genets mature, they compete and potentially create conditions under which further spores struggle to become established. By implication, even though this species is widely picked, propagules remain common enough to create strong competition when new habitats become available.

False negative diagnoses of critical congenital heart disease with screening neonatal pulse oximetry.

BACKGROUND: False negative pulse oximeter results occur in new born infants with critical congenital heart disease who have an oximeter saturation ≥95%. Some of these infants have abnormal physical findings but others do not. OBJECTIVES: To determine the causes of false negative results. METHODS: Mathematical analysis of determinants of arterial oxygen saturation and discussion of oximeter bias. RESULTS: False negative oximeter results are not rare; the sensitivity of pulse oximetry screening for critical congenital heart disease is about 80%. The high saturation may be due to a very small right-to-left shunt at the time of study, a relatively high cardiac output and mixed venous saturation, or to positive bias in oximeter readings. It may also be due to some critical congenital heart lesions that do not show desaturation at the time of testing. CONCLUSIONS: A diagnosis of a normal heart based on a negative oximeter test is presumptive, and requires careful follow-up for 1-2 weeks after birth.

Neuropsychological, Psychiatric, and Functional Correlates of Clinical Trial Enrollment.

Screen failure rates in Alzheimer's disease (AD) clinical trial research are unsustainable, with participant recruitment being a top barrier to AD research progress. The purpose of this project was to understand the neuropsychological, psychiatric, and functional features of individuals who failed screening measures for AD trials. Previously collected clinical data from 38 patients (aged 50-83) screened for a specific industry-sponsored clinical trial of MCI/early AD (Biogen 221AD302, [EMERGE]) were analyzed to identify predictors of AD trial screen pass/fail status. Worse performance on non-memory cognitive domains like crystalized knowledge, executive functioning, and attention, and higher self-reported anxiety, was associated with failing the screening visit for the EMERGE AD clinical trial, whereas we were not able to detect a relationship between screening status and memory performance, self-reported depression, or self-reported daily functioning. By identifying predictors of AD trial screen passing/failure, this research may influence decision-making about which patients are most likely to successfully enroll in a trial, thereby potentially lowering participant burden, maximizing study resources, and reducing costs.