Food restriction during pregnancy alters brain’s antioxidant network in dams and their offspring

Dietary restriction increases life span and protects distinct organisms against a series of diseases, among which, those related to oxidative stress, like neurodegenerative diseases. Interferences in the maternal environment are known to reprogram the offspring metabolism response, impacting in the risk of chronic diseases development in adulthood. We aimed to assess the effects of 40% food restriction on reactive species levels, enzymatic and non-enzymatic antioxidant defenses, and oxidative damage parameters in the cerebellum and total cerebral cortex of pregnant rats and their offspring. Dams and pups showed oxidative modulation caused by food restriction in both structures. Dichlorofluorescein oxidation, reflecting reactive species levels, was reduced in the cerebellum of dams and offspring, while the cerebral cortex was not affected. Decreased mitochondrial superoxide levels were found in the cerebellum and cerebral cortex of pups, while nitric oxide was increased in the cortex. We also measured the activities of important antioxidant enzymes responsible by reactive oxygen species elimination. Superoxide dismutase activity was increased in the cerebellum of dams and in both structures of pups, while it was decreased in dams’ cerebral cortex. Both brain structures were affected concerning to catalase, glutathione peroxidase, and glutaredoxin activities, which were reduced in pups and dams. Non-enzymatic defenses were decreased in pups, while dams showed an adaptive pattern in the cerebellum and no alteration in the cerebral cortex. Even though the results suggest increased oxidative status, lipids and proteins were not oxidatively affected. Our data suggest that intrauterine food restriction may disrupt oxidative status, impairing the antioxidant network.     

Maltotriose transport and utilization in Baker’s and Brewer’s yeast

Maltotriose is metabolized by baker’s and brewer’s yeast only oxidatively, with a respiratory quotient of 1.0, the being, depending on the strain used, 0–11, as compared with of 6–42μL CO₂ per h per mg dry substance. The transport appeared to proceed by facilitated diffusion (no effects of NaF, iodoacetamide and 3-chlorophenylhydrazonomalononitrile) with a K_T of more than 50mm and was inhibited by maltose > maltotriose > methyl-α-D-glucoside > maltotetraose >D-fruetose >D-glucose. The transport was present constitutively in bothSaccharomyces cerevisiae (baker’s yeast) and inS. uvarum (brewer’s yeast) and it was not significantly stimulated by preincubation with glucose or maltose. The pH optimum was 4.5–5.5, the temperature dependence yielded an activation energy of 26 kJ/mol.     

Chasing genes in Alzheimer’s and Parkinson’s disease

Alzheimers disease (AD), the most common type of dementia, and Parkinsons disease (PD), the most common movement disorder, are both neurodegenerative adult-onset diseases characterized by the progressive loss of specific neuronal populations and the accumulation of intraneuronal inclusions. The search for genetic and environmental factors that determine the fate of neurons during the ageing process has been a widespread approach in the battle against neurodegenerative disorders. Genetic studies of AD and PD initially focused on the search for genes involved in the aetiological mechanisms of monogenic forms of these diseases. They later expanded to study hundreds of patients, affected relative-pairs and population-based studies, sometimes performed on special isolated populations. A growing number of genes (and pathogenic mutations) is being identified that cause or increase susceptibility to AD and PD. This review discusses the way in which strategies of gene hunting have evolved during the last few years and the significance of finding genes such as the presenilins, -synuclein, parkin and DJ-1. In addition, we discuss possible links between these two neurodegenerative disorders. The clinical, pathological and genetic presentation of AD and PD suggests the involvement of a few overlapping interrelated pathways. Their imbricate features point to a spectrum of neurodegeneration (tauopathies, synucleinopathies, amyloidopathies) that need further intense investigation to find the missing links.     

Is Food Worth Fighting for? ESS’s in Mixed Populations of Kleptoparasites and Foragers

We extend the game theoretic model of kleptoparasitism discussed in Broom et al. (2004), by considering a population of foragers consisting of two groups with different behaviours—those who forage and steal from other feeders, and those who only forage. We a sume that those who do not steal have a better foraging rate than those who are also looking out for opportunities to steal. We also allow either type to resist an attack or not resist. We look for Evolutionary Stable States, of either a mixture of the two behaviours, or where the whole population has just one of these behaviours. We find nine such ESS’s, dependent on the environmental parameters, although in fact only five of these are distinguishable. In general, we find that if the overall population density is low, food-stealing becomes less viable, and there is an ESS consisting of only foragers. Conversely, when there are many animals looking for, and finding, food, there is an ESS consisting of just kleptoparasites (which are also foraging). In between, an ESS will contain both pure-foragers and stealers. There is some empirical evidence of such behaviours. We find that when there is a mixture of the two types, they must both have the same resistive behaviour. We can thus have some individuals challenging for food but not resisting challenges, and others not challenging and not resisting. This shows how aggressive behaviour may be context-dependent, as seen in practice.     

Phosphorus in sediments — speciation and analysis

Characterization of sediment phosphorus is commonly based on sequential chemical extractions, in which phosphorus is supposed to be selectively removed from different compounds in the sediments. The first extraction schemes were designed to quantify discrete chemical or mineralogical compounds. As extraction schemes have been tested on different sediments, several systematic errors have been detected and the schemes have been modified and simplified accordingly. Other chemical extractions or treatments have attempted to determine phosphorus bound to particles with a certain strength or binding energy, the purpose being to determine the labile, loosely bound, exchangeable, mobile or algal-available fraction of sediment phosphorus. All extraction procedures yield operationally defined fractions and cannot be used for identification of discrete phosphorus compounds. The many methodological modifications make it necessary to be cautious when comparing results from the literature in this field.     

Catecholamine metabolism in children with Asperger’s and Kanner’s syndromes

In a stable state children with Asperger’s and Kanner’s syndromes demonstrate a similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine, and by an increase in dopamine and homovanillic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanillic acid, epinephrine and 3-methoxy-4-hydroxyphenylglycol (MHPG). In the aggravated state children with Kanner’s syndrome were characterized by increased plasma MHPG, decreased excretion of tyrosine and increased expression of normetanephrine. The observed imbalance in dopamine and epinephrine/norepinephrine systems suggests importance of combined analysis of changes in catecholamines and their metabolites as the most informative approach in the study of the effect of autistic disorders.     

What Explains Differences in Men’s and Women’s Production?

Researchers commonly use long-term average production inequalities to characterize cross-cultural patterns in foraging divisions of labor, but little is known about how the strategies of individuals shape such inequalities. Here, we explore the factors that lead to daily variation in how much men produce relative to women among Martu, contemporary foragers of the Western Desert of Australia. We analyze variation in foraging decisions on temporary foraging camps and find that the percentage of total camp production provided by each gender varies primarily as a function of men’s average bout successes with large, mobile prey. When men target large prey, either their success leads to a large proportional contribution to the daily harvest, or their failure results in no contribution. When both men and women target small reliable prey, production inequalities by gender are minimized. These results suggest that production inequalities among Martu emerge from stochastic variation in men’s foraging success on large prey measured against the backdrop of women’s consistent production of small, low-variance resources.

Peyer’s Patches and Mesenteric Lymph Nodes Cooperatively Promote Enteropathy in a Mouse Model of Food Allergy

Background and Objective

To improve the efficacy and safety of tolerance induction for food allergies, identifying the tissues responsible for inducing intestinal inflammation and subsequent oral tolerance is important. We used OVA23-3 mice, which express an ovalbumin-specific T-cell receptor, to elucidate the roles of local and systemic immune tissues in intestinal inflammation.

Methods and Results

OVA23-3 mice developed marked enteropathy after consuming a diet containing egg white (EW diet) for 10 days but overcame the enteropathy (despite continued moderate inflammation) after receiving EW diet for a total of 28 days. Injecting mice with anti-IL-4 antibody or cyclosporine A confirmed the involvement of Th2 cells in the development of the enteropathy. To assess the individual contributions of Peyer’s patches (PPs), mesenteric lymph nodes (MLNs), and the spleen to the generation of effector CD4⁺ T-cells, we analyzed the IL-4 production, proliferation in response to ovalbumin, and CD4⁺ T-cell numbers of these tissues. EW feeding for 10 days induced significant IL-4 production in PPs, the infiltration of numerous CD4⁺ T-cells into MLNs, and a decrease in CD4⁺ T-cell numbers in spleen. On day 28, CD4⁺ T-cells from all tissues had attenuated responses to ovalbumin, suggesting tolerance acquisition, although MLN CD4⁺ T-cells still maintained IL-4 production with proliferation. In addition, removal of MLNs but not the spleen decreased the severity of enteropathy and PP-disrupted mice showed delayed onset of EW-induced inflammatory responses. Disruption of peripheral lymphoid tissues or of both PPs and MLNs almost completely prevented the enteropathy.

Conclusions

PPs and MLNs coordinately promote enteropathy by generating effector T-cells during the initial and exacerbated phases, respectively; the spleen is dispensable for enteropathy and shows tolerogenic responses throughout EW-feeding. The regulation of PPs may suppress the initiation of intestinal inflammation, subsequently restricting MLNs and inhibiting the progression of food-allergic enteropathy.     

Metalloproteinase’s Activity and Oxidative Stress in Mild Cognitive Impairment and Alzheimer’s Disease

Matrix metalloproteinases (MMPs) and oxidative stress have been implicated in neurological diseases such as Alzheimer’s disease (AD). Plasma MMP-2 and MMP-9 activities were assessed in Mild Cognitive Impairment (MCI) and AD subjects compared with aged-matched controls, and subsequently analysed in relation to oxidative stress markers. Both MMP-2 and MMP-9 showed no significant changes versus control subjects. Plasma glutathione peroxidase Se-dependent (GPx-Se) activity and malondialdehyde (MDA) levels were higher in AD than in controls (P < 0.05), suggesting a role for GPx-Se in controlling oxidative stress in AD. Negative correlations were observed between MMPs and MDA in AD and MCI patients (P < 0.05). In conclusion, oxidative stress events did not include activation of MMPs and this similar pattern in AD and MCI suggests that both are biochemically equivalent.     

Systems biology approach to Wilson’s disease

Wilson’s disease (WD) is a severe disorder of copper misbalance, which manifests with a wide spectrum of liver pathology and/or neurologic and psychiatric symptoms. WD is caused by mutations in a gene encoding a copper-transporting ATPase ATP7B and is accompanied by accumulation of copper in tissues, especially in the liver. Copper-chelation therapy is available for treatment of WD symptoms and is often successful, however, significant challenges remain with respect to timely diagnostics and treatment of the disease. The lack of genotype-phenotype correlation remains unexplained, the causes of fulminant liver failure are not known, and the treatment of neurologic symptoms is only partially successful, underscoring the need for better understanding of WD mechanisms and factors that influence disease manifestations. Recent gene and protein profiling studies in animal models of WD began to uncover cellular processes that are primarily affected by copper accumulation in the liver. The results of such studies, summarized in this review, revealed new molecular players and pathways (cell cycle and cholesterol metabolism, mRNA splicing and nuclear receptor signaling) linked to copper misbalance. A systems biology approach promises to generate a comprehensive view of WD onset and progression, thus helping with a more fine-tune treatment and monitoring of the disorder.     

Rural and Urban Students’ Perceptions of and Attitudes toward Brown Bears in Turkey

Many studies have examined adults’ perceptions of and attitudes toward large carnivores to assess human–wildlife conflict and inform conservation strategies, but there have been few studies concerning children. I studied secondary school students’ perceptions of and attitudes toward brown bears (Ursus arctos) and other large mammals in Turkey via a questionnaire survey. The questionnaire, consisting of 18 questions, was completed by 215 rural and 98 urban secondary school students. Both sets of students liked bears; they were also afraid of them and unsure about living with them in the future. While there were no gender differences in attitudes and perceptions, there were marked differences between urban and rural students. Urban students had less contact with nature, gained more of their knowledge about bears from documentaries, and had less positive attitudes toward bears. They were also more likely to be afraid of species not present in Turkey, for example, anaconda, while rural students were most afraid of wild boars. Factor analysis identified three important themes: familiarity with bears, conservation of bears, and experiencing conflict with bears, which explained 49.8% of the variance in attitudes toward bears. The most important factor for the development of negative attitudes toward bears was personal experience of human–bear conflict, suggesting that measures to reduce human–bear conflict in rural areas may help to sustain students’ positive attitudes toward the conservation of bears.     

Natural Antioxidants Protect Neurons in Alzheimer’s Disease and Parkinson’s Disease

“Modern” medicine and pharmacology require an effective medical drug with a single compound for a specific disease. This seams very scientific but usually has unavoidable side effects. For example, the chemical therapy to cancer can totally damage the immunological ability of the patient leading to death early than non-treatment. On the other hand, natural antioxidant drugs not only can cure the disease but also can enhance the immunological ability of the patient leading to healthier though they usually have several compounds or a mixture. For the degenerative disease such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), natural antioxidant drugs are suitable drugs, because the pathogenesis of these diseases is complex with many targets and pathways. These effects are more evidence when the clinic trial is for long term treatment. The author reviews the studies on the protecting effects of natural antioxidants on neurons in neurodegenerative diseases, especially summarized the results about protective effect of green tea polyphenols on neurons against apoptosis of cellular and animal PD models, and of genestine and nicotine on neurons against Aβ—induced apoptosis of hippocampal neuronal and transgenic mouse AD models. Special issue in honor of Dr. Akitane Mori.     

Food Insecurity and Children’s Mental Health: A Prospective Birth Cohort Study

Food insecurity (which can be defined as inadequate access to sufficient, safe, and nutritious food that meets individuals’ dietary needs) is concurrently associated with children’s psychological difficulties. However, the predictive role of food insecurity with regard to specific types of children’s mental health symptoms has not previously been studied. We used data from the Longitudinal Study of Child Development in Québec, LSCDQ, a representative birth cohort study of children born in the Québec region, in Canada, in 1997–1998 (n = 2120). Family food insecurity was ascertained when children were 1½ and 4½ years old. Children’s mental health symptoms were assessed longitudinally using validated measures of behaviour at ages 4½, 5, 6 and 8 years. Symptom trajectory groups were estimated to identify children with persistently high levels of depression/anxiety (21.0%), aggression (26.2%), and hyperactivity/inattention (6.0%). The prevalence of food insecurity in the study was 5.9%. In sex-adjusted analyses, children from food-insecure families were disproportionately likely to experience persistent symptoms of depression/anxiety (OR: 1.79, 95% CI 1.15–2.79) and hyperactivity/inattention (OR: 3.06, 95% CI 1.68–5.55). After controlling for immigrant status, family structure, maternal age at child’s birth, family income, maternal and paternal education, prenatal tobacco exposure, maternal and paternal depression and negative parenting, only persistent hyperactivity/inattention remained associated with food insecurity (fully adjusted OR: 2.65, 95% CI 1.16–6.06). Family food insecurity predicts high levels of children’s mental health symptoms, particularly hyperactivity/inattention. Addressing food insecurity and associated problems in families could help reduce the burden of mental health problems in children and reduce social inequalities in development.     

Addison’s Disease Symptoms – A Cross Sectional Study in Urban South Africa

Background

Addison’s disease is a potentially life-threatening disorder, and prompt diagnosis, and introduction of steroid replacement has resulted in near normal life-expectancy. There are limited data describing the clinical presentation of Addison’s disease in South Africa. It is hypothesised that patients may present in advanced state of ill-health, compared to Western countries.

Patients

A national database of patients was compiled from primary care, referral centres and private practices. 148 patients were enrolled (97 white, 34 mixed ancestry, 5 Asian and 12 black).

Methods

Demographic and clinical data were elicited using questionnaires. Biochemical data were obtained from folder reviews and laboratory archived results.

Results

The majority of the cohort was women (62%). The median and inter-quartile age range (IQR) of patients at enrolment was 46.0 (32.0–61.0) years, with a wide range from 2.8–88.0 years. The median and IQR age at initial diagnosis was 34.0 (20.0–45.0) years (range 0.02–77.0) years, indicating that at the time of enrolment, the patients, on average, were diagnosed with Addison’s disease 12 years previously. Hyperpigmentation was observed in 76%, nausea and vomiting occurred in more than 40%, and weight loss was noted in 25%. Loss of consciousness as a presenting feature was recorded in 20%. with a 95% confidence interval [CI] of (14–28%) and shock occurred in 5% CI (1.5–8.5%). Case-finding was recorded at 3.1 per million.

Conclusions

The usual constellation of hyperpigmentation, nausea, vomiting and weight loss suggests Addison’s disease, but a significant proportion present with an advanced state of ill-health and Addisonian crises. A lower prevalence rate, compared to Western countries is suggested.     

The Limitations of Kim’s Reductive Physicalism in Accounting for Living Systems and an Alternative Nonreductionist Ontology

Jaegwon Kim's exclusion argument is a general ontological argument, applicable to any properties deemed supervenient on a microproperty basis, including biological properties. It implies that the causal power of any higher-level property must be reducible to the subset of the causal powers of its lower-level properties. Moreover, as Kim's recent version of the argument indicates, a higher-level property can be causally efficient only to the extent of the efficiency of its micro-basis. In response, I argue that the ontology that aims to capture experimentally based explanations of metabolic control systems and morphogenetic systems must involve causally relevant contextual properties. Such an ontology challenges the exclusiveness of micro-based causal efficiency that grounds Kim's reductionism, since configurations themselves are inherently causally efficient constituents. I anticipate and respond to the reductionist's objection that the nonreductionist ontology's account of causes and inter-level causal relations is incoherent. I also argue that such an ontology is not open to Kim's overdetermination objection.     

Metabolomics and mitochondrial dysfunction in Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by cognitive impairment, progressive neurodegeneration, and Aβ accumulation. Aβ oligomers can lead to synaptic damage via alterations in glutamate receptors and excitotoxicity, as well as mitochondrial dysfunction. AD is associated with various biological indicators, including (1) predisposing factors such as genetic risk factors, (2) laboratory markers such as Aβ and tau protein, and (3) diagnostic markers such as MRI and PET findings. However, these markers are not confirmed, invasive, or expensive. In the present study, we employed nuclear magnetic resonance (NMR) methods that are inexpensive, time-efficient, and can be performed using samples obtained from various easily accessible sources such as cerebrospinal fluid, plasma, and peripheral tissue, thus highlighting the clinical utility of this approach. NMR analyses of blood metabolites showed that glutamine, glutamate, leucine, oxaloacetate, aspartate, isoleucine, and 3-hydroxyisovalerate are increased in patients with AD compared with control individuals. These metabolites seem to be related to mitochondrial dysfunction. Our data indicated that 3-hydroxyisovalerate, which is linked to known pathologic processes associated with mitochondrial dysfunction and accelerated neurodegeneration, was increased in the blood samples of patients with AD.     

Oxidative and Inflammatory Pathways in Parkinson’s Disease

Parkinson’s disease (PD) is the second most prevalent age-related neurodegenerative disease with physiological manifestations including tremors, bradykinesia, abnormal postural reflexes, rigidity and akinesia and pathological landmarks showing losses of dopaminergic neurons in the substantia nigra. Although the etiology of PD has been intensively pursued for several decades, biochemical mechanisms and genetic and epigenetic factors leading to initiation and progression of the disease remain elusive. Environmental toxins including (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) MPTP, paraquat and rotenone have been shown to increase the risk of PD in humans. Oxidative stress remains the leading theory for explaining progression of PD. Studies with cell and animal models reveal oxidative and inflammatory properties of these toxins and their ability to activate glial cells which subsequently destroy neighboring dopaminergic neurons. This review describes pathological effects of neurotoxins on cells and signaling pathways for production of reactive oxygen species (ROS) that underline the pathophysiology of PD. Special issue article in honor of Dr. George DeVries.     

Periodontitis and Cognitive Decline in Alzheimer’s Disease

Periodontitis is common in the elderly and may become more common in Alzheimer’s disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer’s disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer’s disease. We aimed to determine if periodontitis in Alzheimer’s disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer’s Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer’s Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.     

Blood–brain-barriers in aging and in Alzheimer’s disease

The aging process correlates with a progressive failure in the normal cellular and organ functioning; these alterations are aggravated in Alzheimer’s disease (AD). In both aging and AD there is a general decrease in the capacity of the body to eliminate toxic compounds and, simultaneously, to supply the brain with relevant growth and nutritional factors. The barriers of the brain are targets of this age related dysfunction; both the endothelial cells of the blood–brain barrier and the choroid plexus epithelial cells of the blood-cerebrospinal fluid barrier decrease their secretory capacity towards the brain and their ability to remove toxic compounds from the brain. Additionally, during normal aging and in AD, the permeability of the brain barriers increase. As such, a greater contact of the brain parenchyma with the blood content alters the highly controlled neural environment, which impacts on neural function. Of interest, the brain barriers are more than mere obstacles to the passage of molecules and cells, and therefore active players in brain homeostasis, which is still to be further recognized and investigated in the context of health and disease. Herein, we provide a review on how the brain barriers change during aging and in AD and how these processes impact on brain function.