Food insecurity and sarcopenia among community-dwelling older adults from southern Brazil.

Clocks slide rather than freeze during torpor in the mouse.

In organisms' natural environments, many events that function as motivating operations (MOs) operate concurrently and many reinforcers are available concurrently. Previous research has shown that (a) multiple MOs may interact to affect a single operant class of behavior reinforced by a single event, (b) a single MO may affect multiple operant classes of behavior reinforced by different events, and (c) consumption of/interaction with reinforcers can have motivating functions. This suggests that the effects of MOs and how these are described are contextual in that they depend on the circumstances under which they are assessed. The current study sought to extend understanding of context-specific effects of MOs on the overall and within-session patterns of operant responding of mice when sucrose pellets and water were concurrently available as reinforcers under four different MO conditions: food deprivation, food and water deprivation, water deprivation, and no deprivation. Results demonstrated interactions between MOs in terms of their effects on the overall and within-session patterns of behavior reinforced by sucrose pellets and water, differential effects of MOs on responding for different reinforcers, and individual differences in the effects of MOs. More contextually oriented basic research on MOs may contribute to our understanding of their effects in real-world circumstances.

The selection of the appropriate energy substrate under different physiological conditions is a key aspect of the energy metabolism homeostasis. We here show that Nos1 (nitric oxide synthase 1)-expressing cells in the paraventricular hypothalamic nucleus (PVH) serve as a pivotal node for controlling whole-body fat consumption in male mice. Nos1 neurons account for ~30% of PVH neurons that convey signals via polysynaptic pathways to individual peripheral tissues, including skeletal muscle and brown (BAT) and white (WAT) adipose tissues. Activation of these Nos1 neurons in the PVH area induces WAT lipolysis and fat oxidation in other peripheral tissues via the sympathetic nervous system, thereby increasing whole-body fat consumption. Inhibition of these neurons abolishes the increase in fat consumption during the light period, whereas long-term silencing lead to obesity independent of energy intake. These neurons are also necessary for cold-induced thermogenesis in BAT and the rapid increase in fat consumption elicited by food deprivation or other stressors. Nos1 neurons in the PVH area are therefore essential for controlling fat consumption and energy homeostasis.

Translation elongation and efficiency are modulated by the genetic code, with reduced translation efficiency and slow translation caused by 17 inhibitory codon pairs in the yeast Saccharomyces cerevisiae. Nine of these inhibitory pairs are functionally important as they are disproportionately strongly conserved within orthologous genes in Saccharomyces sensu stricto. For three pairs, including CGA-CGA, inhibition is triggered by ribosome collisions followed by known quality control responses, but the mechanisms by which nine other pairs cause inhibition are unknown. Here, our examination of the molecular basis of inhibition by one such pair, the highly conserved Leu-Pro CUC-CCG codon pair yielded four findings. First, inhibition is mediated by tRNALeu(UAG), which decodes CUC by an U●C wobble interaction and effectively competes with the nonessential Watson-Crick base pairing tRNALeu(GAG). Second, despite nearly universal conservation of U33 in tRNAs, the C33 alteration in tRNALeu(GAG) does not significantly impair its function. Third, inhibition likely is mediated by ribosome collisions, as many suppressors bear mutations known or predicted to reduce ribosome concentration, and as local reduction in ribosome concentration suppresses inhibition. Thus, differences between CUC-CCG and CGA-CGA inhibition likely occur downstream of ribosome collisions. Fourth, we find a link between the metabolic state and CUC-CCG inhibition, as we find six suppressor mutations in SCH9, a downstream effector of TORC1 that mediates ribosome production. As Sch9 is inactive during starvation, causing reduced ribosome concentration, one biological function of inhibitory pairs may be to mediate a change in relative expression during starvation conditions.

Role of the kidney in glucose homeostasis: the basis for pharmacotherapy and prevention of cardiorenal complications in diabetes.

The compartmentalization of metabolic enzymes into membraneless filaments termed cytoophidia represents a conserved regulatory mechanism, exemplified by cytidine triphosphate synthase (CTPS), which assembles into pH-sensitive cytoophidia in the cytosol. In Saccharomyces cerevisiae, nutritional deprivation both triggers CTPS cytoophidia assembly and disassembles the vacuolar H⁺-ATPase (V-ATPase) that acidifies vacuoles (lysosomes), yet whether these processes are functionally linked remains unknown. We demonstrate spatial proximity between the yeast CTPS homologs Ura7/Ura8, the V-ATPase, and the AP-3 adaptor complex that mediates vesicular transport to vacuoles. We show Ura7, the major CTPS isoform in yeast, localizes to vacuoles under both nutrient-rich and starvation conditions. Genetic disruption of AP-3 function altered Ura7 assembly dynamics in starved cells, reducing total structures yet dramatically enhancing Ura7 cytoophidia elongation (∼5-fold), suggesting a dual regulatory role for AP-3 that both promotes Ura7 assembly and restrains elongation. Moreover, combining nutritional and pharmacological V-ATPase inhibition triggered massive Ura7 cytoophidia formation. These findings reveal a previously unrecognized spatial coupling between metabolic enzyme compartmentalization, vacuolar trafficking, and the pH regulation machinery, suggesting a new organizational principle whereby CTPS assembly dynamics respond to vacuolar function.

Torture in custody is a widespread and underreported phenomenon. Victims often present patterned injuries and behaviors, making medico-legal evaluation crucial for documenting abuse and assessing consistency with the reported events. We report 4 cases of individuals who were victims of torture in custody. Injuries predominantly included blunt-force trauma, with additional methods such as suspension, suffocation, sexual humiliation, and deprivation of food and water, confirming a recurring typical pattern regarding the types of injuries, instruments used, and body areas involved. These cases reflect typical patterns of injuries and behaviors associated with custodial torture, highlighting the importance of identifying and documenting findings consistent with the victim's account and physical examination.

Three BODIPY-based fluorescent probes, AH+, BH+, and CH+, were synthesized for ratiometric pH sensing in living cells and fruit fly larvae. These probes were designed to target mitochondrial environments by functionalizing the BODIPY core with various substituent groups that tune their pH sensitivity. The probes exhibited strong ratiometric fluorescence changes with pKa values (AH+, 7.3; BH+, 7.5; CH+, 7.2) suitable for mitochondrial pH detection. Theoretical calculations supported these findings by establishing the geometries and electronic transitions and also resulted in the derivation of their pKa values. Confocal imaging confirmed mitochondrial accumulation of these probes in HeLa cells, facilitating a broad-range pH monitoring across a wide pH spectrum (3.5 to 9.1). These ratiometric pH sensors display good reversibility and response time under varying pH conditions. In application, the probe AH+ was utilized to monitor pH fluctuations under conditions of oxidative stress and starvation conditions. Dual-channel cell imaging revealed a pH-dependent fluorescence shift with precise transitions, demonstrating the feasibility of real-time monitoring of mitochondrial pH changes in living cells. Furthermore, the probe AH+ effectively visualized pH changes in Drosophila melanogaster larvae, further supporting its applicability across diverse biological systems. We demonstrate that a fluorescence ratiometric intensity graph for probe AH+ can be effectively employed to determine pH values within the mitochondria of HeLa cells.

Tau pathology is increasingly recognized as a driver of metabolic dysfunction in neurodegenerative diseases, extending beyond protein aggregation to include impairments in glucose metabolism and redox homeostasis. However, how metabolic cofactors affect tau-associated metabolic stress remains incompletely understood. In this study, we employed a fission yeast (Schizosaccharomyces pombe) model expressing human tau to investigate the effects of vitamin B6 on glucose metabolism and cellular redox balance under glucose-limited conditions in tau-expressing cells. Cells were treated with vitamin B6 and analyzed for tau expression and phosphorylation, glucose consumption, NAD⁺/NADH ratio, and the expression of selected glucose metabolism-related genes under glucose starvation conditions. Vitamin B6 treatment was associated with a reduction in tau protein expression and phosphorylation at specific residues (S262, S396, S404). In addition, vitamin B6 affected glucose metabolism-related gene expression and was accompanied by modest changes in glucose consumption and redox balance. These effects were observed in both control and tau-expressing cells, although the patterns of response differed between the two conditions. While vitamin B6 generally enhanced the expression of glucose utilization-related genes in control cells, its effects in tau-expressing cells were more variable, indicating altered metabolic regulation under tau-associated stress. These findings suggest that vitamin B6 may contribute to cellular metabolic adaptation under tau-induced stress. This study demonstrates the usefulness of fission yeast as a tractable model for examining metabolic aspects of tau pathology and provides insight into how metabolic cofactors influence tau-associated cellular stress.

Objective: To investigate the effects of fasting on anxiety-and depression-like behaviors in mice, and to elucidate the underlying neural mechanisms. Methods: Eight-week-old male C57BL/6J mice (n=44) and Fos-2A-iCreER transgenic mice (n=48) were randomly assigned using a random number table.The male C57BL/6J mice were divided into six groups (n=36): anxiety-like models were established by 2-hour acute restraint stress (ARS), depression-like models were induced by intraperitoneal injection of lipopolysaccharide, and control groups were also set up. Within each model, mice were further divided into a fasting group (24-hour food deprivation) and an ad libitum feeding group. Fasting efficacy was assessed by monitoring changes in body weight and food intake. Anxiety-like behaviors were evaluated using the open field test and elevated plus maze test, while depression-like behaviors were assessed using the tail suspension test and forced swimming test. Whole-brain neuronal activation in response to fasting was detected in both fasted and non-fasted C57BL/6J mice (n=8) was detected through c-Fos immunofluorescence staining. Subsequently, the Fos-2A-iCreER transgenic mice were selected. The targeted recombination into active promoters (TRAP) technique was employed to specifically label fasting-activated neurons, and chemogenetic techniques were employed to activate or inhibit fasting-related neuronal ensembles (n=24 per experiment). Anxiety-like and depression-like models were re-established separately, and mice in each model were divided into a fasting group (24-hour food deprivation) and an ad libitum feeding group, in order to investigate the effects of activating or inhibiting neurons related to fasting on anxiety-and depression-like behaviors. Results: The open field test and the elevated plus maze test provided evidence that anxiety-like models had been successfully established. In addition, the tail suspension test and the forced swimming test provided evidence that depression models had been successfully established. In comparison with the ad libitum feeding group, the mice fasted for 24 h showed lower body weight and higher food intake (all P<0.05). Fasted mice demonstrated increased distance travelled, prolonged duration, and elevated entries in the central area of the open field, as well as greater distance traveled, higher percentage of duration, and more entries in the open arms of the elevated plus maze. Additionally, fasted mice showed shorter immobility times in both the tail suspension test and the forced swimming test. All differences were statistically significant (all P<0.05). c-Fos staining revealed enhanced neuronal activation in the paraventricular thalamus (PVT) region after fasting (all P<0.05). Chemogenetic activation of fasting-related neuronal ensembles in the PVT mimicked the anti-anxiety and anti-depression effects observed following fasting: anxious mice showed greater distance traveled, longer duration, and more entries in the central area of the open field, as well as greater distance traveled, higher percentage of duration, and more entries in the open arms of the elevated plus maze; depressed mice showed shorter immobility times in both the tail suspension test and the forced swim test (all P<0.05).Conversely, chemogenetic inhibition of these neuronal ensembles reversed these effects (all P<0.05). Conclusion: Fasting activates PVT-related neuronal ensembles to elicit anti-anxiety and antidepression effects in mice.

This study explores whether sleep restriction (SR) and caffeine intake affect migraine susceptibility by testing if each condition, alone or in combination, precipitates migraine-like responses to subthreshold doses of calcitonin gene-related peptide (CGRP) or pituitary adenylate cyclase-activating polypeptide (PACAP) in male and female rats. Migraine is a debilitating neurological syndrome that affects approximately 15% of the global population, with a three-fold higher prevalence in females compared to males. Among the peripheral mechanisms underlying migraine, the release of vasoactive peptides by trigeminal ganglion (TG) neurons, such as CGRP and PACAP, plays a crucial role. Various environmental triggers-including sleep or food deprivation, caffeine intake or withdrawal, stress, and light exposure-have been associated with the onset of migraine attacks; however, the mechanisms by which these factors modulate nociceptive sensitization remain poorly understood. Male and female Wistar rats were subjected to SR for 6 h daily over 3 consecutive days using the gentle handling method, and the periorbital mechanical allodynia was assessed using von Frey filaments before and after each day of SR. Next, a subthreshold dose of CGRP (38 ng/10 μL) or PACAP (0.1 ng/10 μL) was administered into the TG on the third day of SR to evaluate whether sleep loss enhances susceptibility to migraine-like responses. Finally, two additional experiments were conducted to investigate the influence of caffeine (50 mg/kg, orally) exposure in combination of SR in CGRP and PACAP effects. In all experiments, on day 4 (i.e., 24 h after the last SR), the animals were exposed for 1 h to an aversive light for verification of latent sensitization. The results demonstrated that SR alone did not alter the periorbital mechanical threshold in either male or female rats. However, when SR was combined with the administration of CGRP or PACAP at subthreshold doses, a significant periorbital mechanical allodynia developed in female, but not in male rats. The exposure to light in the subsequent day caused a transitory reactivation of mechanical allodynia only in females. In well-rested animals, a 3-day caffeine regimen enabled behaviorally subthreshold doses of CGRP or PACAP to elicit migraine-like responses in females, but not in males. In sleep-restricted animals, combining caffeine with subthreshold doses of CGRP or PACAP rendered males susceptible to migraine-like responses and markedly exacerbated these responses in females, including 1 day later, after light exposure. These findings suggest that SR facilitates trigeminovascular sensitization, promoting migraine-like responses in a sex-specific manner and highlighting caffeine as an enhancer of this interaction. Beyond reinforcing the association between poor sleep and migraine, the data offer new insights into the involvement of the purinergic system and sex differences in migraine pathophysiology.

VviAHA10, a tonoplast P3A-type ATPase from Vitis vinifera, reveals a functional link between vacuolar flavonoid accumulation and abiotic stress responses.

Food‐related stimuli can promote feeding behaviors independent of metabolic need. Cue‐potentiated feeding (CPF) studies in rodents offer the potential to reveal the psychobiological mechanisms underlying learned overeating behaviors. We examined whether lateral hypothalamic area (LHA) cells expressing the feeding signal Melanin Concentrating Hormone (MCH) are sufficient and necessary for CPF. Tg(Pmch‐Cre) mice received bilateral infusion of the Cre‐dependent inhibitory DREADD (hM4Di), or optrode placement together with the excitatory opsin ChR2. Mice received food deprivation by restricting access to two daily meal pellets. Once weight reached ~90% from baseline, Pavlovian training commenced, in which a tone or noise conditioned stimulus (CS+) predicted the delivery of a sucrose solution, whereas a second CS− was unpaired with sucrose delivery. Following a minimum of 2 days of ad‐libitum pellet access, mice underwent CPF testing, where the amount of licking for sucrose in the presence of the CS+ and CS− cues was assessed. In both the chemogenetic and optogenetic studies, control mice displayed CPF as evidenced by increased lick rate during the CS+ compared to the CS−. hM4Di‐mediated inhibition of LHA MCH cells significantly impaired CPF through disrupting the capacity for the CS+ to increase the mean size of licking bursts, a measure thought to index the orosensory taste properties of sucrose. By contrast, optogenetic stimulation of LHA MCH cells enhanced CPF relative to eYFP‐treated controls. Our findings support a critical role for MCH‐expressing neurons in the LHA in learned overeating behavior.

Adolescent social isolation and food restriction impairs feeding in female mice.

Animals must continuously adapt their behavioral outputs in response to changes in internal state, including nutritional state. Here, we show that starvation induces a profound and progressive suppression of thermonociceptive behavior in Caenorhabditis elegans. During early food deprivation (1-hr off food), the thermoresponsive sensory neurons AWCs mediate robust heat-evoked reversals over a broad range of stimulus intensities via glutamate and FLP-6 neuropeptide signaling, each covering distinct heat intensity ranges. After six hours of food deprivation (prolonged starvation), heat-evoked reversal responses are nearly abolished, independently of any external food odor cues. Starvation triggers a shift in the distribution of AWC heat-evoked calcium response polarity, transitioning from mostly excitatory responses to a more heterogeneous pattern combining both excitatory and inhibitory activities. This switch relies on ASI neurons, proposed to work as internal state-sensing neurons. INS-32 and NLP-18 neuropeptide signals from ASI switch from a reversal-promoting to a reversal-inhibiting effect. In addition, reversal-promoting glutamatergic transmission by AWC is antagonized by glutamatergic transmission from non-AWC neurons that suppresses FLP-6-dependent reversals. Our findings define a circuit logic by which nociceptive responsiveness gating by internal nutritional state is linked to dynamic modulation of sensory neuron activity patterns and orchestrated by bidirectional glutamatergic and neuropeptidergic signals. More broadly, this study illustrates how sensory systems integrate metabolic information to prioritize behavioral outputs under changing physiological conditions, providing mechanistic insight into the plastic coupling between sensation, internal state, and action selection.

IntroductionRumination is usually considered to be a daily rhythmic process that is not dependent on food intake. Although this rhythm is described as circadian in the literature, to our knowledge, no experimental study has yet demonstrated its circadian origin. The objective of the present study was to explore the circadian control of the rumination rhythm in the goat (Capra hircus) and its possible entrainment by the timing of food availability.MethodsRumination was continuously recorded in bucks housed under constant darkness (DD) and constant ambient temperature (CTa). During Experiment 1 (n=6), food was provided once daily at 10h in Stage 1, four times a day (00h, 06h, 12h, and 18h) in Stage 2, ad libitum in Stage 3, and finally in Stage 4, bucks were food-deprived for four consecutive days. Experiment 2 was designed to investigate the effect of time-shifting of food distribution on the rumination rhythm under constant conditions. Food was given once a day, at 10h in stage 1, then shifted to 22h in stage 2 and returned to 10h in stage 3.ResultsIn Stage 1 and 2 of Experiment 1, rumination exhibited a clear rhythmic profile with a period not significant from 24.0 h. In Stage 3, the rhythm exhibited a progressive daily phase shift typical of a free-running state with a circadian period of 24.9 ± 0.1 h. During Stage 4, food deprivation did not abolish rumination or its rhythmicity, though it did alter the free-running period. Experiment 2 showed that the inversion time of the food distribution immediately induced a shift in rumination rhythm, the acrophases were delayed from 02h56 ± 28min (stage 1) to 14h55 ± 8min (stage 2). The return to amorning feeding in stage 3 has led to a phase advance in rumination rhythm, the acrophases being advanced from 14h55 ± 8min (stage 2) to 02h07 ± 13min (stage 3).DiscussionThis study provides the first evidence supporting a circadian origin of the rumination rhythm in goat. The results also clearly showed that feeding time was able to synchronize the rumination rhythm. Nevertheless, additional research is required in order to elucidate the complete neurobiological mechanisms underlying the circadian control of rumination in the goat.

Pancreatic ductal adenocarcinoma (PDAC), the most common histological subtype of pancreatic cancer, is an aggressive malignancy expected to become the second leading cause of cancer-related deaths by 2040. A hallmark of PDACs is the highly desmoplastic and hypovascularized nature of its microenvironment, which enables PDAC cells to adapt and survive under conditions of low oxygen and nutrient deprivation through various cellular mechanisms. Among these processes, autophagy has emerged as a key response mechanism to cope with these adverse conditions. Consequently, a deeper understanding of the molecular events driving autophagy could pave the way for the development of new and more effective treatments for PDAC. In this context, we provide evidence of novel pathway mediated by extracellular vesicles (EVs) that promotes autophagy in a paracrine manner in PDAC cells in response to starvation. Our findings indicate that, under starvation conditions, EVs-associated tetraspanins, namely CD9, CD63 and CD81, mobilize towards domains-like structures within the plasma membrane of PDAC cells. Correspondingly, a specific release of small EVs (sEVs) is observed in the starved cells. Notably, sEVs derived from starved cells, but not those from cells at basal conditions, strongly induce the autophagy pathway in PDAC cells cultured with optimal nutritional media. Interestingly, this ability to induce autophagy is specific to CD63/CD81 double-positive sEVs and is effective even in non-tumoral pancreatic cells. This sEVs-mediated autophagy is, at least partially, mediated by the activation of the FOXO3a pathway. It is worth noting that, although EVs release returns to basal level after 1h of recovery following starvation, these EVs retain a capacity to induce autophagy, suggesting a decupling between quantity and quality of secreted vesicles. Our results demonstrate that pancreatic cancer cells in nutrient-deprived environments release specific sEVs that, in turn, activate the FOXO3a pathway and autophagy flux in recipient cells.

BackgroundResource scarcity poses a real challenge to living organisms. The present study aimed to understand the implications of water and food lack on some biochemical markers. The study also aimed to investigate the expression of Hsp70 gene under the same stress conditions. The Hsp70 gene maintains cellular proteostasis. It is unique in its high sensitivity and rapid response to various stress factors compared to other Hsps.MethodsBrood frames of Carniolan hybrid bees were incubated at 30 °C and 70% RH. Emerged bees were placed in plastic cages (30 individuals per cage) and received daily diets of pollen-sugar pastes and sugar solutions. After nine days, bees were independently subjected to dehydration and starvation experiments for 24 h. One group was deprived of only sugar solutions (Dehydrated DH), another group was denied both sugar solutions and pollen pastes, receiving only tap water (Starved ST), while a third group continued without water or food deprivation (Control C). Bee samples were collected at 12-hour intervals in each experiment for subsequent investigations. Biochemical measurements were performed on total protein, total antioxidant capacity, peroxidase, catalase, glutathione S-transferase, and acid phosphatase. Gene expression of Hsp70 gene was under observation. Bee weights were also considered.ResultsBoth dehydrated and starved bees showed notable changes in their examined biomarkers. Starvation had a more pronounced and rapid biochemical effect. The decreases in Hsp70 mRNA levels following water or food deprivation were surprising to us and reflect the severity of these two stressors. Other differences were also recorded in the weights of dehydrated and starved bees.ConclusionsThis study reveals honeybees’ extreme sensitivity to nutritional stress and warns against depriving them of water or food for even a few hours.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40850-026-00265-3.

Fuel-dependent synthetic cells are compartments that require fuel to emerge and sustain. Without fuel, they decay, serving as a selection pressure in fueling-starvation experiments. Recently, we introduced fuel-dependent synthetic cells based on droplets as a route to synthetic life. These droplets grow, divide, and decay under starvation conditions. However, which parameters influence their lifetime and their ability to divide remain unknown. Moreover, previous designs of these synthetic cells suffer from the accumulation of waste products of their chemical reactions. In this work, we offer design rules for chemically fueled complex coacervate droplets with a focus on hexapeptides. We find that incorporating tryptophan into peptide designs increases the peptides' affinity for polyanions and thus their ability to form droplets. The resulting synthetic cells are longer-lived and more waste-resistant and can produce offspring when RNA is used as the polyanion. Placing the tryptophan close to the reactive C-terminus further extends the droplet lifetime by slowing deactivation. Together, these results lead to a new series of peptides to produce waste-resistant, RNA-compatible, fuel-dependent synthetic cells.