RIPK1 regulates starvation resistance by modulating aspartate catabolism.

RIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal period without a clear mechanism. Metabolism regulation and autophagy are critical to neonatal survival from severe starvation at birth. However, the mechanism by which RIPK1 regulates starvation resistance and survival remains unclear. Here, we address this question by discovering the metabolic regulatory role of RIPK1. First, metabolomics analysis reveals that Ripk1 deficiency specifically increases aspartate levels in both mouse neonates and mammalian cells under starvation conditions. Increased aspartate in Ripk1-/- cells enhances the TCA  flux and ATP production. The energy imbalance causes defective autophagy induction by inhibiting the AMPK/ULK1 pathway. Transcriptional analyses demonstrate that Ripk1-/- deficiency downregulates gene expression in aspartate catabolism by inactivating SP1. To summarize, this study reveals that RIPK1 serves as a metabolic regulator responsible for starvation resistance.

Causes of mortality in northern elephant seal pups on San Miguel Island, California.

In February 2015, we conducted a field study of causes of mortality of northern elephant seal (Mirounga angustirostris) pups on San Miguel Island, California. Autopsies were performed on 18 freshly dead pups. Ages of pups ranged from stillborn to 6-8 wk. Gross and histologic lesions included trauma (9 of 18 pups), multifocal necrotizing myopathy (8 of 18), starvation with emaciation (7 of 18), congenital anomalies (3 of 18), bacterial infections (3 of 18), and perinatal mortality (stillbirths and neonates; 2 of 18). Trauma and emaciation or starvation were the most significant contributors to death. Bacterial infections included hemolytic Escherichia coli isolated from the lungs of 2 pups with pneumonia. Additionally, non-hemolytic Streptococcus sp. and hemolytic E. coli were isolated from the liver of an emaciated pup that had mild multifocal suppurative hepatitis. Other lesions, including a previously described necrotizing myopathy, congenital anomalies, and bacterial infections, were detected concurrently in cases with starvation and/or emaciation or trauma.

Anammox bacteria exhibit capacity to withstand long-term starvation stress: A proteomic-based investigation of survival mechanisms.

Although anammox bacteria are commonly exposed to long-term starvation during transportation and preservation process, physiological changes in these organisms during long-term starvation are not well understood, nor are the molecular bases of their starvation survival strategies. To reveal survival mechanisms during long-term anaerobic and anoxic starvation (60 days at 20 ±â€¯1 °C), metaproteomic technology was utilized to identify differentially expressed proteins in Candidatus Kuenenia stuttgartiensis. Our results showed that Candidatus Kuenenia stuttgartiensis exhibits a capacity to withstand long-term starvation stress. Although activity decay rates of 0.0129 d-1 and 0.0049 d-1 were observed for anammox sludge in anoxic and anaerobic starvation, the relative abundance of Candidatus Kuenenia stuttgartiensis, the shape of anammox granules, and the fraction of viable cells remained constant under both anaerobic and anoxic starvation conditions. Metaproteomics results illustrated that Candidatus Kuenenia stuttgartiensis maintained stable levels of most intracellular proteins, especially enzymes involved in principal metabolic pathways after 60-d of anaerobic or anoxic starvation, thereby allowing cells to regain metabolic activities once substrates became available. Induction of starvation proteins could be a survival strategy employed by Candidatus Kuenenia stuttgartiensis to resist long-term starvation stresses. During anaerobic starvation, 34 proteins were upregulated, five of which were associated with carbohydrate catabolism and oxidation of organic compounds, thereby increasing potential for utilization of endogenous carbon sources to produce energy. During anoxic starvation, only two proteins were upregulated, which may be attributed to insufficient energy for the synthesis of starvation-induced proteins.

Women live longer than men even during severe famines and epidemics.

Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors.

Frailty and famine: Patterns of mortality and physiological stress among victims of famine in medieval London.

OBJECTIVES: Famine can be defined as a shortage of foodstuffs that instigates widespread excess mortality due to starvation, infectious disease, and social disruption. Like other causes of catastrophic mortality, famine has the potential to be selective. This study examines how famines in medieval London were selective with respect to previous stress, age, and sex. METHODS: This study compares famine burials to nonfamine (attritional) burials from the St Mary Spital cemetery, London (c. 1120-1540 AD). We evaluate the associations between age, sex, and skeletal stress indicators [cribra orbitalia, linear enamel hypoplasia (LEH), and periosteal lesions] using hierarchical log-linear analysis. Additionally, sex is modeled as a covariate affecting the Gompertz hazard of mortality. RESULTS: Significant associations exist between famine burials and LEH and between attritional burials and periosteal lesions, independent of age or sex. Sex did not significantly affect risk of mortality in the 12th-13th centuries. However, males interred in attritional burials c. 1400-1539 AD faced a lower risk of mortality compared to females. DISCUSSION: The LEH results suggest that early exposure to stressors increased frailty in the context of famine. The periosteal lesion results suggest that individuals were more likely to survive stressors and thus form these lesions under nonfamine conditions. Hazard analysis suggests that a cultural or biological transformation during this period affected sex differences in mortality. Possible causes include the selective mortality during the Black Death, which might have influenced risks of mortality among survivors, or unequal distribution of improvements in standards of living after the epidemic. Am J Phys Anthropol 160:272-283, 2016. © 2016 Wiley Periodicals, Inc.

[Organization of medical support for troops, defending Leningrad and the people of the blockaded city].

The data on the composition of forces of medical services and organization of medical-evacuation support for troops defending the blockaded Leningrad are presented. The information about the health losses among the population of Leningrad as a result of bombing, shelling and disease is given. Extremely high rates of morbidity and mortality in residents were associated with hunger, hypothermia and emotional stress. The clinical picture of some diseases has different peculiarities because of alimentary dystrophy background. The city health service suffered huge losses: 482 medical institutions were destroyed, only about 300 people from 1.5 thousand of medical personnel in 1942 saved working capability. The health care service of the local air defense played an essential role in delivery of medical aid. The contribution of civil and military health workers in saving residents lives in the blockaded Leningrad was appreciated.

The protozoan parasite Trichomonas gallinae causes adult and nestling mortality in a declining population of European Turtle Doves, Streptopelia turtur.

Studies incorporating the ecology of clinical and sub-clinical disease in wild populations of conservation concern are rare. Here we examine sub-clinical infection by Trichomonas gallinae in a declining population of free-living European Turtle Doves and suggest caseous lesions cause mortality in adults and nestlings through subsequent starvation and/or suffocation. We found a 100% infection rate by T. gallinae in adult and nestling Turtle Doves (n = 25) and observed clinical signs in three adults and four nestlings (28%). Adults with clinical signs displayed no differences in any skeletal measures of size but had a mean 3.7% reduction in wing length, with no overlap compared to those without clinical signs. We also identified T. gallinae as the suggested cause of mortality in one Red-legged Partridge although disease presentation was different. A minimum of four strains of T. gallinae, characterized at the ITS/5.8S/ITS2 ribosomal region, were isolated from Turtle Doves. However, all birds with clinical signs (Turtle Doves and the Red-legged Partridge) carried a single strain of T. gallinae, suggesting that parasite spill over between Columbidae and Galliformes is a possibility that should be further investigated. Overall, we highlight the importance of monitoring populations for sub-clinical infection rather than just clinical disease.

Long-term health and socioeconomic consequences of early-life exposure to the 1959-1961 Chinese Famine.

This research investigates long-term consequences of early-life malnutrition by examining effects of the 1959-1961 Chinese Famine. Taking into account temporal and geographic variations in famine severity, we construct a difference-in-differences estimator to identify effects of early-life exposure to famine on perceived health and socioeconomic outcomes in midlife. Using a sample of 1716 adults born in 1955-1966 in rural China from a nationally representative survey-the 2005 Chinese General Social Survey-we find that the famine had adverse effects on mid-life health for males born into families where at least one parent was a Communist Party member and females regardless of parental party membership. Being born during the famine had no effects on years of education or income for either gender. Quantile regressions suggest intense mortality selection among males who had no party-affiliated parents. Our study highlights the importance of timing and contexts of life experiences in shaping health.

Long-run effects of gestation during the Dutch Hunger Winter famine on labor market and hospitalization outcomes.

The Dutch Hunger Winter (1944/45) is the most-studied famine in the literature on long-run effects of malnutrition in utero. Its temporal and spatial demarcations are clear, it was severe, it was not anticipated, and nutritional conditions in society were favorable and stable before and after the famine. This is the first study to analyze effects of in utero exposure on labor market outcomes and hospitalization late in life, and the first to use register data covering the full Dutch population to examine long-run effects of this famine. We provide results of famine exposure by sub-interval of gestation. We find a significantly negative effect of exposure during the first trimester of gestation on employment outcomes 53 or more years after birth. Hospitalization rates in the years before retirement are higher after middle or late gestational exposure.

Impacts of extreme climatic events on the energetics of long-lived vertebrates: the case of the greater flamingo facing cold spells in the Camargue.

Most studies analyzing the effects of global warming on wild populations focus on gradual temperature changes, yet it is also important to understand the impact of extreme climatic events. Here we studied the effect of two cold spells (January 1985 and February 2012) on the energetics of greater flamingos (Phoenicopterus roseus) in the Camargue (southern France). To understand the cause of observed flamingo mass mortalities, we first assessed the energy stores of flamingos found dead in February 2012, and compared them with those found in other bird species exposed to cold spells and/or fasting. Second, we evaluated the monthly energy requirements of flamingos across 1980-2012 using the mechanistic model Niche Mapper. Our results show that the body lipids of flamingos found dead in 2012 corresponded to 2.6±0.3% of total body mass, which is close to results found in woodcocks (Scolopax rusticola) that died from starvation during a cold spell (1.7±0.1%), and much lower than in woodcocks which were fed throughout this same cold spell (13.0±2%). Further, Niche Mapper predicted that flamingo energy requirements were highest (+6-7%) during the 1985 and 2012 cold spells compared with 'normal' winters. This increase was primarily driven by cold air temperatures. Overall, our findings strongly suggest that flamingos starved to death during both cold spells. This study demonstrates the relevance of using mechanistic energetics modelling and body condition analyses to understand and predict the impact of extreme climatic events on animal energy balance and winter survival probabilities.

The starvation-predation trade-off shapes the strategic use of protein for energy during fasting.

The primary function of lipid storage by animals is as an energy source for surviving periods without food. However, muscle and organ protein can be metabolised for energy, and empirical studies have shown that the onset of protein metabolism begins before the exhaustion of lipid reserves. Since protein tissues are important for reasons other than resisting starvation, the adaptive basis for this early onset is unclear. Here, we report the results of a model of the optimal proportion of energy to obtain from protein catabolism during a period without food of unpredictable duration. We assume either that the animal aims only to maximise the duration of survival or that it also has to take account of its future reproductive success given its state when the food supply recommences. In the latter case we find impressive quantitative agreement with observations on lean and obese penguins and rats. Analysis shows that this agreement breaks down if predation risk is insignificant, protein in the form of muscle is ineffective against predation, or there is no benefit to conserving lipid (e.g. for reproduction). This result implies that animals have not evolved to maximise their starvation resistance because doing so would leave them vulnerable when an interruption ends. Our model allows us to make several specific predictions concerning the relationship between the ecological pressures on animals and their starvation survival strategies.

Livestock mortality in pastoralist herds in Ethiopia and implications for drought response.

Participatory epidemiology methods were employed retrospectively in three pastoralist regions of Ethiopia to estimate the specific causes of excess livestock mortality during drought. The results showed that starvation/dehydration accounted for between 61.5 and 100 per cent of excess livestock mortality during drought, whereas disease-related mortality accounted for between 0 and 28.1 per cent of excess mortality. Field observations indicate that, in livestock, disease risks and mortality increase in the immediate post-drought period, during rain. The design of livelihoods-based drought response programmes should include protection of core livestock assets, and it should take account of the specific causes of excess livestock mortality during drought and immediately afterwards. This study shows that, when comparing livestock feed supplementation and veterinary support, relatively more aid should be directed at the former if the objective is to protect core livestock during drought. Veterinary support should consider disease-related mortality in the immediate post-drought period, and tailor inputs accordingly.

Hydrodynamic starvation in first-feeding larval fishes.

Larval fishes suffer prodigious mortality rates, eliminating 99% of the brood within a few days after first feeding. Hjort (1914) famously attributed this "critical period" of low survival to the larvae's inability to obtain sufficient food [Hjort (1914) Rapp P-v Réun Cons Int Explor Mer 20:1-228]. However, the cause of this poor feeding success remains to be identified. Here, we show that hydrodynamic constraints on the ubiquitous suction mechanism in first-feeding larvae limit their ability to capture prey, thereby reducing their feeding rates. Dynamic-scaling experiments revealed that larval size is the primary determinant of feeding rate, independent of other ontogenetic effects. We conclude that first-feeding larvae experience "hydrodynamic starvation," in which low Reynolds numbers mechanistically limit their feeding performance even under high prey densities. Our results provide a hydrodynamic perspective on feeding of larval fishes that focuses on the physical properties of the larvae and prey, rather than on prey concentration and the rate of encounters.

Starvation of children in Syria--sanctions and the politics of revenge.

As Syria completes two years of western sanctions (2011-13), their dramatic effects on health are being highlighted with first reports of starvation deaths among children in the suburbs of Damascus. Although heavy fighting has taken place in this area, experts had predicted for some time the unworkability of sanctions for regime change, arguing that only civilians would pay the price in a country (Syria in this case) which was once well on the way to meeting the Millennium Development Goals 4 targets on reducing child mortality. In this, as in the case of other "sanctioned" countries, it is not just "civilians" but the most vulnerable among them--children, who are experiencing the tragic consequences of sanctions.

Identifying the intergenerational effects of the 1959-1961 Chinese Great Leap Forward Famine on infant mortality.

Using the 1959-1961 Chinese Great Leap Forward Famine as a natural experiment, this study examines the relationship between mothers' prenatal exposure to acute malnutrition and their children's infant mortality risk. According to the results, the effect of mothers' prenatal famine exposure status on children's infant mortality risk depends on the level of famine severity. In regions of low famine severity, mothers' prenatal famine exposure significantly reduces children's infant mortality, whereas in regions of high famine severity, such prenatal exposure increases children's infant mortality although the effect is not statistically significant. Such a curvilinear relationship between mothers' prenatal malnutrition status and their children's infant mortality risk is more complicated than the linear relationship predicted by the original fetal origins hypothesis but is consistent with the more recent developmental origins of health and disease theory.

Genetic aspects of scurvy and the European famine of 1845-1848.

The view of scurvy being exclusively a nutritional disorder needs to be updated. Genetic polymorphisms of HFE and haptoglobin (Hp) may explain the geographic variability of mortality caused by the European famine of the mid-19th century. In this period, potatoes had fallen victim to the potato blight and Ireland was more severely hit than continental Europe. Hereditary hemochromatosis is a genetic disorder with mutations in the HFE gene, characterized by iron overload (with a reduced vitamin C stability) and with a predominance of affected men. The Irish have the world's highest frequency of the C282Y mutation and the particular iron metabolism of the Irish helps to understand the size of the catastrophe and the observed overrepresentation of male skeletons showing scurvy. Hp is a plasma α2-glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin and vitamin C. The relative number of scurvy victims corresponds with the Hp 2-2 frequency, which is associated with iron conservation and has an impact on vitamin C stability. As iron is more abundant in males, males are overrepresented in the group of skeletons showing scurvy signs.

Anthropometric predictors of mortality in undernourished adults in the Ajiep Feeding Programme in Southern Sudan.

BACKGROUND: Various nutritional assessment tools are available to assess adult undernutrition, but few are practical in poorly served areas of low-income countries. OBJECTIVE: The objective was to assess the relation between midupper arm circumference (MUAC), weight, body mass index (BMI), and clinical assessment for edema in predicting mortality in adults with severe acute undernutrition. DESIGN: Demographic and anthropometric data that were collected in an observational study of 197 adults were analyzed. Participants were aged 18-59 y and were admitted to a therapeutic feeding center in Ajiep, Southern Sudan, during the height of the 1998 famine. Receiver operating curves were calculated and compared. RESULTS: The mean (±SD) age of the participants was 40.1 ±10.8 y, and the mean (±SD) MUAC, weight, and BMI (in kg/m(2)) were 16.4 ± 1.3 cm, 35.1 ± 5.2 kg, and 12.6 ± 1.5, respectively. The area under the receiver operating curve for MUAC (0.71) was higher (P = 0.01) than those of BMI (0.57) and weight (0.51). Mean age, weight, and BMI on admission did not differ between survivors and nonsurvivors (P > 0.17). MUAC and edema were independently associated with mortality. For every 1-cm increase in admission MUAC, the odds of subsequent mortality decreased by 58% (adjusted OR: 0.42; 95% CI: 0.28, 0.63; P < 0.001). CONCLUSIONS: In this study, which was conducted at the height of a major famine among adults with extremely severe grades of undernutrition, MUAC and edema were better indicators of short-term prognosis than was BMI. Further studies are needed to define a critical MUAC threshold for the diagnosis of acute adult undernutrition.

Sex- and age-related mortality profiles during famine: testing the 'body fat' hypothesis.

During famines females generally have a mortality advantage relative to males, and the highest levels of mortality occur in the very young and the elderly. One popular hypothesis is that the sex differential in mortality may reflect the greater body fatness combined with lower metabolism of females, which may also underpin the age-related patterns of mortality among adults. This study evaluated the 'body fat' hypothesis using a previously published and validated mathematical model of survival during total starvation. The model shows that at a given body weight females would indeed be expected to survive considerably longer than males in the absence of food. At a mass of 70 kg for example a female aged 30 would survive for 144 days compared with life expectancy of only 95 days for a male of the same age and weight. This effect is contributed to by both the higher body fatness and lower metabolism of the females at a given body weight. However, females are generally smaller than males and in addition to a sex effect there was also a major effect of body size - heavier individuals survive longer. When this body size effect was removed by considering survival in relation to BMI the sex effect was much reduced, and could be offset by a relatively small difference in pre-famine BMI between the sexes. Nevertheless, combining these predictions with observed mean BMIs of males and females across 48 countries at the low end of the obesity spectrum suggests that in the complete absence of food females would survive on average about 40% longer (range 6 to 64.5%) than males. The energy balance model also predicted that older adult individuals should survive much longer than younger adult individuals, by virtue of their lower resting metabolic rates and lower activity levels. Observations of the female survival advantage in multiple famines span a much wider range than the model prediction (5% to 210%). This suggests in some famines body fatness may be a significant factor influencing the mortality differential between the sexes, but in other famines other factors are likely to be more important. Moreover, the pattern of mortality in relation to age is completely opposite that predicted. These data emphasize the complex nature of famine mortality and suggest that a simple model of energy utilization alone is inadequate to explain the major aspects of this phenomenon.