Physiological and behavioural effects of intermittent fasting vs daily caloric restriction in meat-type poultry.

Intermittent fasting (IF) is the practice of temporal food restriction to promote metabolic switching between a glucose- and a ketone-based metabolism, which has been reported to come with diverse health benefits. IF practices appear to confer many of the advantages of caloric restriction without restricting total energy intake, and studies in both rodents and humans suggest organism-wide improvements in neurological, cardiovascular and metabolic health. IF is also commonly employed in the commercial rearing of breeding meat-type poultry, i.e. broiler breeders, which require strict feed restriction throughout life to maintain physical health. While the scientific poultry literature holds vast amounts of data on such "skip-a-day" feeding schedules, it has been unclear to what extent avian and mammalian literature may be compared as broiler breeders are typically feed-restricted to around 30% of ad libitum intake even in IF schedules. In this study, we set out to disentangle the effects of IF and caloric restriction in meat-type poultry by employing both IF and daily feeding schedules at two different restriction levels. Our results suggest that the physiological response to IF in chickens is only marginally affected by the intensity of feed restriction, while behavioural parameters are more closely related to feeding level and are expected to better mirror animal welfare. Our results suggest that avian and mammalian literature on IF should be comparable. Meat-type chickens do show some peculiarities in response to IF, such as a reduced insulin sensitivity, but it is currently unclear whether this is true for all chickens or is an effect of the intense selection for rapid growth in meat-type chickens.

Enzymatically Polymerized Organic Conductors on Model Lipid Membranes.

Seamless integration between biological systems and electrical components is essential for enabling a twinned biochemical-electrical recording and therapy approach to understand and combat neurological disorders. Employing bioelectronic systems made up of conjugated polymers, which have an innate ability to transport both electronic and ionic charges, provides the possibility of such integration. In particular, translating enzymatically polymerized conductive wires, recently demonstrated in plants and simple organism systems, into mammalian models, is of particular interest for the development of next-generation devices that can monitor and modulate neural signals. As a first step toward achieving this goal, enzyme-mediated polymerization of two thiophene-based monomers is demonstrated on a synthetic lipid bilayer supported on a Au surface. Microgravimetric studies of conducting films polymerized in situ provide insights into their interactions with a lipid bilayer model that mimics the cell membrane. Moreover, the resulting electrical and viscoelastic properties of these self-organizing conducting polymers suggest their potential as materials to form the basis for novel approaches to in vivo neural therapeutics.

Metabolite-induced in vivo fabrication of substrate-free organic bioelectronics.

Interfacing electronics with neural tissue is crucial for understanding complex biological functions, but conventional bioelectronics consist of rigid electrodes fundamentally incompatible with living systems. The difference between static solid-state electronics and dynamic biological matter makes seamless integration of the two challenging. To address this incompatibility, we developed a method to dynamically create soft substrate-free conducting materials within the biological environment. We demonstrate in vivo electrode formation in zebrafish and leech models, using endogenous metabolites to trigger enzymatic polymerization of organic precursors within an injectable gel, thereby forming conducting polymer gels with long-range conductivity. This approach can be used to target specific biological substructures and is suitable for nerve stimulation, paving the way for fully integrated, in vivo-fabricated electronics within the nervous system.

Intermittent fasting induces chronic changes in the hepatic gene expression of Red Jungle Fowl (Gallus gallus).

BACKGROUND: Intermittent fasting (IF), the implementation of fasting periods of at least 12 consecutive hours on a daily to weekly basis, has received a lot of attention in recent years for imparting the life-prolonging and health-promoting effects of caloric restriction with no or only moderate actual restriction of caloric intake. IF is also widely practiced in the rearing of broiler breeders, the parent stock of meat-type chickens, who require strict feed restriction regimens to prevent the serious health problems associated with their intense appetites. Although intermittent fasting has been extensively used in this context to reduce feed competition and its resulting stress, the potential of IF in chickens as an alternative and complementary model to rodents has received less investigation. In both mammals and birds, the liver is a key component of the metabolic response to IF, responding to variations in energy balance. Here we use a microarray analysis to examine the liver transcriptomics of wild-type Red Jungle Fowl chickens fed either ad libitum, chronically restricted to around 70% of ad libitum daily or intermittently fasted (IF) on a 2:1 (2 days fed, 1 day fasted) schedule without actual caloric restriction. As red junglefowl are ancestral to domestic chicken breeds, these data serve as a baseline to which existing and future transcriptomic results from farmed birds such as broiler breeders can be compared. RESULTS: We find large effects of feeding regimen on liver transcriptomics, with most of the affected genes relating to energy metabolism. A cluster analysis shows that IF is associated with large and reciprocal changes in genes related to lipid and carbohydrate metabolism, but also chronic changes in genes related to amino acid metabolism (generally down-regulated) and cell cycle progression (generally up-regulated). The overall transcription pattern appears to be one of promoting high proliferative plasticity in response to fluctuations in available energy substrates. A small number of inflammation-related genes also show chronically changed expression profiles, as does one circadian rhythm gene. CONCLUSIONS: The increase in proliferative potential suggested by the gene expression changes reported here indicates that birds and mammals respond similarly to intermittent fasting practices. Our findings therefore suggest that the health benefits of periodic caloric restriction are ubiquitous and not restricted to mammals alone. Whether a common fundamental mechanism, for example involving leptin, underpins these benefits remains to be elucidated.

Point-of-care devices for physiological measurements in field conditions. A smorgasbord of instruments and validation procedures.

Point-of-care (POC) devices provide quick diagnostic results that increase the efficiency of patient care. Many POC devices are currently available to measure metabolites, blood gases, hormones, disease biomarkers or pathogens in samples as diverse as blood, urine, feces or exhaled breath. This diversity is potentially very useful for the comparative physiologist in field studies if proper validation studies are carried out to justify the accuracy of the devices in non-human species under different conditions. Our review presents an account of physiological parameters that can be monitored with POC devices and surveys the literature for suitable quantitative and statistical procedures for comparing POC measurements with reference "gold standard" procedures. We provide a set of quantitative tools and report on different correlation coefficients (Lin's Concordance Correlation Coefficient or the more widespread Pearson correlation coefficient), describe the graphical assessment of variation using Bland-Altman plots and discuss the difference between Model I and Model II regression procedures. We also report on three validation datasets for lactate, glucose and hemoglobin measurements in birds using the newly proposed procedures. We conclude the review with a haphazard account of future developments in the field, emphasizing the interest in lab-on-a-chip devices to carry out more complex experimental measurements than the ones currently available in POC devices.

The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene.

The most common pathology in frontotemporal dementia (FTD) is tau-negative, ubiquitin-immunoreactive (ub-ir) neuronal inclusions (FTLD-U). Recently, we identified mutations in the progranulin (PGRN) gene as the cause of autosomal dominant FTLD-U linked to chromosome 17. Here, we describe the neuropathology in 13 patients from 6 different families, each with FTD caused by a different PGRN mutation. The most consistent feature was the presence of ub-ir lentiform neuronal intranuclear inclusions (NII) in the neocortex and striatum. In addition, the neocortex showed moderate-to-severe superficial laminar spongiosis, chronic degenerative changes, ub-ir neurites and well-defined ub-ir neuronal cytoplasmic inclusions (NCI). In the striatum, there were numerous ub-ir neurites. NCI in the hippocampus usually had a granular appearance. In contrast, familial FTLD-U cases without PGRN mutations had no NII, less severe neocortical and striatal pathology and hippocampal NCI that were more often solid. Eight cases in which genetic analysis was not available also had NII and an overall pathology similar to those with proven mutations. None of our cases of FTLD-U without NII showed the same pattern of pathology as those with mutations. These findings suggest that FTD caused by PGRN mutations has a recognizable pathology with the most characteristic feature being ub-ir NII.

Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease.

BACKGROUND: Many cases of frontotemporal dementia (FTD) are familial, often with an autosomal dominant pattern of inheritance. Some are due to a mutation in the tau- encoding gene, on chromosome 17, and show an accumulation of abnormal tau in brain tissue (FTDP-17T). Most of the remaining familial cases do not exhibit tau pathology, but display neuropathology similar to patients with dementia and motor neuron disease, characterized by the presence of ubiquitin-immunoreactive (ub-ir), dystrophic neurites and neuronal cytoplasmic inclusions in the neocortex and hippocampus (FTLD-U). Recently, we described a subset of patients with familial FTD with autopsy-proven FTLD-U pathology and with the additional finding of ub-ir neuronal intranuclear inclusions (NII). NII are a characteristic feature of several other neurodegenerative conditions for which the genetic basis is abnormal expansion of a polyglutamine-encoding trinucleotide repeat region. The genetic basis of familial FTLD-U is currently not known, however the presence of NII suggests that a subset of cases may represent a polyglutamine expansion disease. METHODS: We studied DNA and post mortem brain tissue from 5 affected members of 4 different families with NII and one affected individual with familial FTLD-U without NII. Patient DNA was screened for CAA/CAG trinucleotide expansion in a set of candidate genes identified using a genome-wide computational approach. Genes containing CAA/CAG trinucleotide repeats encoding at least five glutamines were examined (n = 63), including the nine genes currently known to be associated with human disease. CAA/CAG tract sizes were compared with published normal values (where available) and with those of healthy controls (n = 94). High-resolution agarose gel electrophoresis was used to measure allele size (number of CAA/CAG repeats). For any alleles estimated to be equal to or larger than the maximum measured in the control population, the CAA/CAG tract length was confirmed by capillary electrophoresis. In addition, immunohistochemistry using a monoclonal antibody that recognizes proteins containing expanded polyglutamines (1C2) was performed on sections of post mortem brain tissue from subjects with NII. RESULTS: No significant polyglutamine-encoding repeat expansions were identified in the DNA from any of our FTLD-U patients. NII in the FTLD-U cases showed no 1C2 immunoreactivity. CONCLUSION: We find no evidence to suggest that autosomal dominant FTLD-U with NII is a polyglutamine expansion disease.

Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17.

Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia, consistent with a strong genetic component to the disease. In 1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17). The neuropathology of patients with defined MAPT mutations is characterized by cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the regulation of multiple processes including development, wound repair and inflammation. PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is increased in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival.

Endothelial function in post-menopausal former elite athletes.

OBJECTIVE: To characterize endothelial function in postmenopausal former elite athletes in comparison to sedentary controls and to study the influence of hormone replacement therapy (HRT) on endothelial function in these groups of women. DESIGN: Cross-sectional study. SETTING: Research unit at a university hospital. PARTICIPANTS: Twenty postmenopausal former elite but still active endurance female athletes and 19 age-matched sedentary controls. The group of athletes and control subjects were each subdivided into two groups on the basis of utilization or non-utilization of HRT involving estrogen and gestagen. METHODS: Flow-mediated vasodilatation (FMD) was employed as an indicator of endothelial function. Fasting blood samples were analyzed for lipids and body composition determined by dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURES: FMD, blood lipids and body composition. RESULTS: Former elite athletes not utilizing HRT demonstrated the highest FMD of all four subgroups, their values being significantly higher than those of control subjects not utilizing HRT (P < 0.05), whereas this difference was not seen between the subgroups of athletes and control subjects using HRT. Serum levels of cholesterol and low-density lipoprotein (LDL) and the percentage of fat mass were significantly lower in the former elite athletes than in the control group (P < 0.05 in all cases). However, these variables were not related to FMD. CONCLUSION: This investigation documents enhanced endothelial function in postmenopausal former elite endurance athletes not utilizing HRT, whereas the use of HRT equalizes FMD in former athletes and sedentary control subjects. Our findings suggest that long-term strenuous exercise has beneficial effects on endothelial function in postmenopausal women but that no further improvement can be obtained with HRT.

A family with tau-negative frontotemporal dementia and neuronal intranuclear inclusions linked to chromosome 17.

Over 30 different mutations have now been identified in MAPt that cause frontotemporal dementia (FTD). However, there are several families with FTD that show definite linkage to the region on chromosome 17 that contains MAPt, in which no mutation(s) has been identified. Although these families could have a complex mutation of the MAPt locus that has evaded detection it is also possible that another gene in this region is associated with FTD. This possibility is supported by neuropathological findings in these families, which consist of neuronal inclusions that are immunoreactive for ubiquitin (ub-ir) but not for tau. In addition to neuronal cytoplasmic inclusions, several chromosome 17-linked families are reported to have ub-ir neuronal intranuclear inclusions (NII); a finding which is uncommon in sporadic FTD. Here, we describe detailed clinical and neuropathological findings in a new large, multigenerational family with autosomal dominant FTD and autopsy proven tau-negative, ub-ir neuronal cytoplasmic and intranuclear inclusions. We have demonstrated that this family is linked to a 19.06 cM region of chromosome 17q21 with a maximum multipoint LOD score of 3.911 containing MAPt. By combining the results of our genetic analysis with those previously published for other families with similar pathology, we have further refined the minimal region to a 3.53 cM region of chromosome 17q21. We did not identify point mutations in MAPt by direct sequencing or any gross MAPt gene alterations using fluorescent in situ hybridization. In addition, tau protein extracted from members of this family was unremarkable in size and quantity as assessed by western blotting. Neuropathological characterization of the ub-ir NII in this family shows that they are positive for promyelocytic leukaemia protein (PML) and SUMO-1 that suggests that these inclusions form in the nuclear body and suggests a possible mechanism of neurodegeneration in tau-negative FTD linked to chromosome 17q21.

Athlete's heart in postmenopausal former elite endurance female athletes.

OBJECTIVE: To investigate cardiac structure and function and exercise capacity in senior former elite athlete women. DESIGN: Cross-sectional study. PARTICIPANTS: Twenty postmenopausal former elite endurance athletes and 19 age-matched sedentary controls. METHODS: All subjects underwent transthoracic Doppler echocardiography and maximal exercise test on a bicycle ergometer. MAIN OUTCOME MEASURES: Cardiac chamber dimensions, wall thickness, cardiac function, and exercise capacity. RESULTS: The athletes had a greater exercise capacity (183 +/- 26 vs. 144 +/- 36 W; P < 0.01) compared with controls. Three of 20 (15%) athletes and 9 of 19 (47%) controls exhibited ST depressions during exercise test (P < 0.05). Echocardiographic measurements demonstrated larger left ventricular diameter (2.9 +/- 0.3 vs. 2.6 +/- 0.2 cm/m; P < 0.01), left ventricular volume (64 +/- 14 vs. 54 +/- 8 mL/m; P < 0.05), right ventricular diameter (1.6 +/- 0.2 vs. 1.4 +/- 0.2 cm/m; P < 0.01), left atrial volume (20.8 +/- 6 vs. 16.6 +/- 3.6 mL/m; P < 0.05), and stroke volume (45 +/- 10 vs. 36 +/- 5 mL/m; P < 0.01) in athletes than controls, whereas interventricular septum (9.3 +/- 1.7 vs. 10.1 +/- 1.8 mm; P > 0.05) and posterior wall thickness (9.0 +/- 1.6 vs. 9.2 +/- 1.0 mm; P > 0.05) did not differ between the groups. CONCLUSIONS: This study demonstrates cardiac enlargement without increased wall thickness in postmenopausal former elite endurance athlete women. Our results also indicate that long-term training maintains a high level of cardiovascular fitness in the aging female athletes.

Pregnancy and neonatal outcomes in women with eating disorders.

OBJECTIVE: This study was initiated to examine pregnancy and neonatal outcomes in women with past or current eating disorders as compared with a control group. METHODS: Forty-nine nulliparous nonsmoking women previously diagnosed with eating disorders (24 anorexia nervosa, 20 bulimia nervosa, 5 eating disorders not otherwise specified) and 68 controls were recruited in early pregnancy. Data on antenatal complications, mode of delivery, and neonatal outcome variables were collected. For comparisons between groups 1-way analysis of variance or chi(2) test was used. RESULTS: Twenty-two percent of the patients had a verified relapse in eating disorders during pregnancy. Women with past or current eating disorders were at increased risk of hyperemesis (P < .01) and delivered infants with significantly lower birth weight (P < .01) and smaller head circumference (P < .001) as compared with controls. They were also at greater risk of delivering infants with microcephaly (P < .05) and small for gestational age infants (P < .05). CONCLUSION: Pregnant women with past or active eating disorders seem to be at greater risk for delivering infants with lower birth weight, smaller head circumference, microcephaly, and small for gestational age. LEVEL OF EVIDENCE: II-2.