Metformin induces S‐adenosylmethionine restriction to extend the Caenorhabditis elegans healthspan through H3K4me3 modifiers

Metformin, a widely prescribed first‐line drug for the treatment of type II diabetes mellitus, has been shown to extend lifespan and delay the onset of age‐related diseases. The precisely mechanisms by which these effects are realized remain elusive. We find that metformin exposure is restricted to adults, which is sufficient to extend lifespan. However, limiting metformin exposure to the larvae has no significant effect on Caenorhabditis elegans longevity. Here, we show that after metformin treatment, the level of S‐adenosylmethionine (SAM) is reduced in adults but not in the larvae. Potential mechanisms by which reduced SAM might increase lifespan include altering the histone methylation. However, the molecular connections between metformin, SAM limitation, methyltransferases, and healthspan‐associated phenotypes are unclear. Through genetic screening of C. elegans, we find that metformin promotes the healthspan through an H3K4 methyltransferase/demethylase complex to downregulate the targets, including mTOR and S6 kinase. Thus, our studies provide molecular links between meformin, SAM limitation, histone methylation, and healthspan and elucidate the mode action of metformin‐regulated healthspan extension will boost its therapeutic application in the treatment of human aging and age‐related diseases.     

Genetic diversity and sex‐biased dispersal in the brown spotted pitviper (Protobothrops mucrosquamatus): Evidence from microsatellite markers

Dispersal plays a vital role in the geographical distribution, population genetic structure, quantity dynamics, and evolution of a species. Sex‐biased dispersal is common among vertebrates and many studies have documented a tendency toward male‐biased dispersal in mammals and female‐biased dispersal in birds. However, dispersal patterns in reptiles remain poorly understood. In this study, we explored the genetic diversity and dispersal patterns of the widely distributed Asian pitviper Protobothrops mucrosquamatus. In total, 16 polymorphic microsatellite loci were screened in 150 snakes (48 males, 44 females, 58 samples without sex information) covering most of their distribution. Microsatellite analysis revealed high genetic diversity in P. mucrosquamatus. Bayesian clustering of population assignment identified two major clusters for all populations, somewhat inconsistent with the mitochondrial DNA phylogeny of P. mucrosquamatus reported in previous research. Analyses based on 92 sex‐determined and 37 samples of P. mucrosquamatus from three small sites in Sichuan, China (Mingshan, Yibin, and Zizhong) consistently suggested female‐biased dispersal in P. mucrosquamatus, which is the first example of this pattern in snakes. The female‐biased dispersal patterns in P. mucrosquamatus may be explained by local resource competition.     

Detectability and impact of repetitive surveys on threatened West African crocodylians

West African crocodylians are among the most threatened and least studied crocodylian species globally. Assessing population status and establishing a basis for population monitoring is the highest priority action for this region. Monitoring of crocodiles is influenced by many factors that affect detectability, including environmental variables and individual‐ or population‐level wariness. We investigated how these factors affect detectability and counts of the critically endangered Mecistops cataphractus and the newly recognized Crocodylus suchus. We implemented 195 repetitive surveys at 38 sites across Côte d’Ivoire between 2014 and 2019. We used an occupancy‐based approach and a count‐based GLMM analysis to determine the effect of environmental and anthropogenic variables on detection and modeled crocodile wariness over repetitive surveys. Despite their rarity and level of threat, detection probability of both species was relatively high (0.75 for M. cataphractus and 0.81 for C. suchus), but a minimum of two surveys were required to infer absence of either species with 90% confidence. We found that detection of M. cataphractus was significantly negatively influenced by fishing net encounter rate, while high temperature for the previous 48 h of the day of the survey increased C. suchus detection. Precipitation and aquatic vegetation had significant negative and positive influence, respectively, on M. cataphractus counts and showed the opposite effect for C. suchus counts. We also found that fishing encounter rate had a significant negative effect on C. suchus counts. Interestingly, survey repetition did not generally affect wariness for either species, though there was some indication that at least M. cataphractus was more wary by the fourth replicate. These results are informative for designing future survey and monitoring protocols for these threatened crocodylians in West Africa and for other endangered crocodylians globally.     

3,6'‐disinapoyl sucrose attenuates Aβ1‐42‐ induced neurotoxicity in Caenorhabditis elegans by enhancing antioxidation and regulating autophagy

The aggregation of β‐amyloid (Aβ) has the neurotoxicity, which is thought to play critical role in the pathogenesis of Alzheimer''s disease (AD). Inhibiting Aβ deposition and neurotoxicity has been considered as an important strategy for AD treatment. 3,6''‐Disinapoyl sucrose (DISS), one of the oligosaccharide esters derived from traditional Chinese medicine Polygalae Radix, possesses antioxidative activity, neuroprotective effect and anti‐depressive activity. This study was to explore whether DISS could attenuate the pathological changes of Aβ_1‐42 transgenic Caenorhabditis elegans (C. elegans). The results showed that DISS (5 and 50 μM) treatment significantly prolonged the life span, increased the number of egg‐laying, reduced paralysis rate, decreased the levels of lipofuscin and ROS and attenuated Aβ deposition in Aβ_1‐42 transgenic C. elegans. Gene analysis showed that DISS could up‐regulate the mRNA expression of sod‐3, gst‐4, daf‐16, bec‐1 and lgg‐1, while down‐regulate the mRNA expression of daf‐2 and daf‐15 in Aβ_1‐42 transgenic C. elegans. These results suggested that DISS has the protective effect against Aβ_1‐42‐induced pathological damages and prolongs the life span of C. elegans, which may be related to the reduction of Aβ deposition and neurotoxicity by regulating expression of genes related to antioxidation and autophagy.     

Intelligent high‐throughput intervention testing platform in Daphnia

We present a novel platform for testing the effects of interventions on the life‐ and healthspan of a short‐lived freshwater organism with complex behavior and physiology—the planktonic crustacean Daphnia magna. Within this platform, dozens of complex behavioral features of both routine motion and response to stimuli are continuously quantified over large synchronized cohorts via an automated phenotyping pipeline. We build predictive machine‐learning models calibrated using chronological age and extrapolate onto phenotypic age. We further apply the model to estimate the phenotypic age under pharmacological perturbation. Our platform provides a scalable framework for drug screening and characterization in both life‐long and instant assays as illustrated using a long‐term dose‐response profile of metformin and a short‐term assay of well‐studied substances such as caffeine and alcohol.     

Molecular approaches reveal weak sibship aggregation and a high dispersal propensity in a non‐native fish parasite

Inferring parameters related to the aggregation pattern of parasites and to their dispersal propensity are important for predicting their ecological consequences and evolutionary potential. Nonetheless, it is notoriously difficult to infer these parameters from wildlife parasites given the difficulty in tracking these organisms. Molecular‐based inferences constitute a promising approach that has yet rarely been applied in the wild. Here, we combined several population genetic analyses including sibship reconstruction to document the genetic structure, patterns of sibship aggregation, and the dispersal dynamics of a non‐native parasite of fish, the freshwater copepod ectoparasite Tracheliastes polycolpus. We collected parasites according to a hierarchical sampling design, with the sampling of all parasites from all host individuals captured in eight sites spread along an upstream–downstream river gradient. Individual multilocus genotypes were obtained from 14 microsatellite markers, and used to assign parasites to full‐sib families and to investigate the genetic structure of T. polycolpus among both hosts and sampling sites. The distribution of full‐sibs obtained among the sampling sites was used to estimate individual dispersal distances within families. Our results showed that T. polycolpus sibs tend to be aggregated within sites but not within host individuals. We detected important upstream‐to‐downstream dispersal events of T. polycolpus between sites (modal distance: 25.4 km; 95% CI [22.9, 27.7]), becoming scarcer as the geographic distance from their family core location increases. Such a dispersal pattern likely contributes to the strong isolation‐by‐distance observed at the river scale. We also detected some downstream‐to‐upstream dispersal events (modal distance: 2.6 km; 95% CI [2.2–23.3]) that likely result from movements of infected hosts. Within each site, the dispersal of free‐living infective larvae among hosts likely contributes to increasing genetic diversity on hosts, possibly fostering the evolutionary potential of T. polycolpus.     

Novel hosts can incur fitness costs to a frugivorous insect pest

In phytophagous insects, adult attraction and oviposition preference for a host plant are often positively correlated with their immature fitness; however, little is known how this preference–performance relationship changes within insect populations utilizing different host plants. Here, we investigated differences in the preference and performance of two populations of a native North American frugivorous insect pest, the plum curculio (Conotrachelus nenuphar)—one that utilizes peaches and another that utilizes blueberries as hosts—in the Mid‐Atlantic United States. We collected C. nenuphar adult populations from peach and blueberry farms and found that they exhibited a clear preference for the odors of, as well as an ovipositional preference for, the hosts they were collected from, laying 67%–83% of their eggs in their respective collected hosts. To measure C. nenuphar larval performance, a fitness index was calculated using data on larval weights, development, and survival rate from egg to 4th instars when reared on the parent''s collected and novel hosts. Larvae of C. nenuphar adults collected from peach had high fitness on peach but low fitness when reared on blueberry. In contrast, larvae from C. nenuphar adults collected in blueberry had high fitness regardless of the host on which they were reared. In this study, we show that utilizing a novel host such as blueberry incurs a fitness cost for C. nenuphar from peaches, but this cost was not observed for C. nenuphar from blueberries, indicating that the preference–performance relationship is present in the case of insects reared on peach, but insects reared on blueberry were more flexible and able to utilize either host, despite preferring blueberry.     

Morphological and Molecular Characterization of Pomegranate Fruit Rot Pathogen, <Emphasis Type="Italic">Chaetomella raphigera</Emphasis>, and its Virulence Factors

A new fungal pathogen was isolated from rotten pomegranates collected from the orchards of different parts of Maharashtra. The pathogen was morphologically identified as Chaetomella raphigera followed by sequencing of ITS and D1/D2 hypervariable region of LSU (28S) of rRNA gene. The pathogen produced pectinase, cellulase, xylanase and protease in liquid medium at a concentration of 71, 13.8, 54.3 and 7 U/ml respectively. Enzyme activity was also determined during pathogenesis in the tissues artificially infected by C. raphigera. Xylanase activity was maximum (25.1 U/g) followed by pectinase (19.2 U/g) and cellulase (1.5 U/g), whereas, protease activity was unnoticed. There was significant correlation (P < 0.05) between disease rating scale and pectinase, xylanase and cellulase activity in infected tissues. This indicates the simultaneous production of hydrolytic enzymes that aids in necrosis of fruit tissues. The elevated levels of these enzymes in infected tissues as compared with control suggest their possible role in pathogenesis. Thus, pectinase, cellulase and xylanase produced by C. raphigera acts as major virulence factors in the development of fruit rot in pomegranates. This is a first report of fungal fruit rot caused by C. raphigera in pomegranate.     

Long‐term changes in occurrence,relative abundance,and reproductive fitness of bat species in relation to arrival of White‐nose Syndrome in West Virginia,USA

White‐nose syndrome (WNS) is a disease caused by the fungus Pseudogymnoascus destructans which has resulted in the deaths of millions of bats across eastern North America. To date, hibernacula counts have been the predominant means of tracking the spread and impact of this disease on bat populations. However, an understanding of the impacts of WNS on demographic parameters outside the winter season is critical to conservation and recovery of bat populations impacted by this disease. We used long‐term monitoring data to examine WNS‐related impacts to summer populations in West Virginia, where WNS has been documented since 2009. Using capture data from 290 mist‐net sites surveyed from 2003 to 2019 on the Monongahela National Forest, we estimated temporal patterns in presence and relative abundance for each bat species. For species that exhibited a population‐level response to WNS, we investigated post‐WNS changes in adult female reproductive state and body mass. Myotis lucifugus (little brown bat), M. septentrionalis (northern long‐eared bat), and Perimyotis subflavus (tri‐colored bat) all showed significant decreases in presence and relative abundance during and following the introduction of WNS, while Eptesicus fuscus (big brown bat) and Lasiurus borealis (eastern red bat) responded positively during the WNS invasion. Probability of being reproductively active was not significantly different for any species, though a shift to earlier reproduction was estimated for E. fuscus and M. septentrionalis. For some species, body mass appeared to be influenced by the WNS invasion, but the response differed by species and reproductive state. Results suggest that continued long‐term monitoring studies, additional research into impacts of this disease on the fitness of WNS survivors, and a focus on providing optimal nonwintering habitat may be valuable strategies for assessing and promoting recovery of WNS‐affected bat populations.     

Assessment of medium and large‐sized mammals and their behavioral response toward anthropogenic activities in Jorgo‐Wato Protected Forest,Western Ethiopia

Medium and large‐sized mammals of Jorgo‐Wato Protected Forest have not yet been documented though the forest established before four decades. Hence, this study aims to document medium and large mammals and the behavioral responses of selected mammals toward anthropogenic activities in the study area. The study was conducted from February 2015 to June 2016, encompassing the wet and dry seasons. Data were collected mainly through camera traps, indirect and direct evidence. The study revealed about 23 medium and large‐sized mammals that belong to seven orders namely Bovidae, Carnivora, Primates, Rodentia, Tubulidentata, Lagomorpha, and Hyracoidea. Papio anubis, C. guereza, and C. aethiops were the most abundant large mammals in JWPF. Because of high anthropogenic activities, African buffalo shifted its activity period from diurnal into crepuscular and nocturnal. African buffalo traveled longer distances during the wet season (mean = 14.33 km, SD = 1.25 km) than during the dry season (mean = 9.00 km, SD = 2.16 km). This could be due to the fact that the local people were less likely to go to the forest for resource exploitation during the wet season as they are fully engaged in agricultural activities. However, low agricultural activities during the dry season allow the local people to extract resources and involve in bushmeat hunting which could limit the movement of mammals to their refugia. African buffalo preferred to rest on and adjacent to a gravel road (22.1%) in the forest, followed by on open rocky hilltops (14.7%) at night time, but rest in the bottomland thicket vegetation during the dry daytime. Regardless of high human pressure in the area, this study has revealed a good number of medium and large‐sized mammals that could be used as baseline information to design a sound conservation and management action plan of large mammals and their habitat in Jorgo‐Wato Protected Forest.     

Mitochondrial aconitase 1 regulates age‐related memory impairment via autophagy/mitophagy‐mediated neural plasticity in middle‐aged flies

Age‐related memory impairment (AMI) occurs in many species, including humans. The underlying mechanisms are not fully understood. In wild‐type Drosophila (w¹¹¹⁸ ), AMI appears in the form of a decrease in learning (3‐min memory) from middle age (30 days after eclosion [DAE]). We performed in vivo, DNA microarray, and behavioral screen studies to identify genes controlling both lifespan and AMI and selected mitochondrial Acon1 (mAcon1). mAcon1 expression in the head of w¹¹¹⁸ decreased with age. Neuronal overexpression of mAcon1 extended its lifespan and improved AMI. Neuronal or mushroom body expression of mAcon1 regulated the learning of young (10 DAE) and middle‐aged flies. Interestingly, acetyl‐CoA and citrate levels increased in the heads of middle‐aged and neuronal mAcon1 knockdown flies. Acetyl‐CoA, as a cellular energy sensor, is related to autophagy. Autophagy activity and efficacy determined by the positive and negative changes in the expression levels of Atg8a‐II and p62 were proportional to the expression level of mAcon1. Levels of the presynaptic active zone scaffold protein Bruchpilot were inversely proportional to neuronal mAcon1 levels in the whole brain. Furthermore, mAcon1 overexpression in Kenyon cells induced mitophagy labeled with mt‐Keima and improved learning ability. Both processes were blocked by pink1 knockdown. Taken together, our results imply that the regulation of learning and AMI by mAcon1 occurs via autophagy/mitophagy‐mediated neural plasticity.