Long-Evans and Sprague-Dawley rats exhibit divergent responses to refeeding after caloric restriction

Mature male Sprague-Dawley (SD) and Long-Evans (LE) rats were instrumented with telemetry transmitters for measurement of heart rate (HR) and housed in room calorimeters for assessment of food intake and oxygen consumption (Vo(2)) at standard laboratory temperatures (23 degrees C) to examine physiological responses to caloric restriction (CR; 60% of baseline ad libitum calories for 2 wk) and refeeding. Ad libitum controls had stable food intake (84-88 kcal/day) and gained weight at rates of 3-4 g/day. Groups from both strains assigned to CR exhibited similar patterns of weight loss and reductions in Vo(2) and HR. Upon refeeding, SD rats exhibited a mild, transient hyperphagic response (1 day) accompanied by sustained suppression of Vo(2) and HR that remained evident 8 days after refeeding. In contrast, LE rats exhibited sustained daily hyperphagia that persisted 8 days after refeeding and was accompanied by a complete restoration of HR and Vo(2). The lower HR and Vo(2) observed during refeeding in SD rats were not due to reduced locomotor activity. The results reveal a strain-dependent divergent response to recovery from CR. We conclude that during recovery from CR, homeostatic stimulation of appetite or suppression of energy expenditure may occur selectively to restore body weight.     

Voltage-dependent anion-selective channel 1 (VDAC1)--a mitochondrial protein, rediscovered as a novel enzyme in the plasma membrane

The eukaryotic porin or voltage-dependent anion-selective channel (VDAC1) is a pore-forming protein discovered twenty five years ago in the mitochondrial outer membrane. Its gene in eukaryotes is known, but its tertiary structure has never been solved. Structure predictions highlight the presence of several amphipathic beta-strands possibly organised in a beta-barrel. VDAC1 has recently been described as being a NADH:ferricyanide reductase in the plasma membrane. There it affects the regulation of cell growth and death. Physiological cell death (apoptosis) has become a major research focus of biomedical research. Regulation of the enzyme will have impacts on cancer and autoimmune diseases (insufficient apoptosis) as well as neurodegenerative diseases (excessive apoptosis). VDAC1 in the plasma membrane establishes a novel level of apoptosis regulation putatively via its redox activity.     

Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented.     

Characterization of the human porin isoform 1 (HVDAC1) gene by amplification on the whole human genome: A tool for porin deficiency analysis

The deficiency of porin isoform 1 (HVDAC1) in human skeletal muscle has been associated with a pathological phenotype related to defects in the bioenergetic metabolism. In the best studied case, porin deficiency was not apparent in cultured fibroblasts: this observation raised the conclusion that no molecular defect was in the cDNA sequence coding for the protein. To get more insight in the pathogenetic mechanism that is involved in porin isoform 1 deficiency, we have determined the whole structure of the corresponding human gene. On the basis of the corresponding mouse gene structure and the human cDNA sequence, we designed long extension PCR amplifications using the whole genomic DNA as a template. Exonic/intronic regions were isolated and the exons and surrounding introns sequenced. The 5' and 3' extremities of the gene were determined by genome walking. The porin isoform 1 human gene is made up of 9 exons and spans about 33 kbp. A whole panel of PCR parameters was set and is now ready to be used for specific amplification upon patients' genomic DNA. The analysis of the putative promoter sequence was performed. It revealed the presence of a sterol Repressor element (SRE), an SRY, the testis-determining factor, and a nuclear respiratory factor 2 (NRF-2) binding site. These sites, according to results from literature, could be involved in the functional modulation of the gene expression.     

Lesion Load May Predict Long-Term Cognitive Dysfunction in Multiple Sclerosis Patients

Background

Magnetic Resonance Imaging (MRI) techniques provided evidences into the understanding of cognitive impairment (CIm) in Multiple Sclerosis (MS).

Objectives

To investigate the role of white matter (WM) and gray matter (GM) in predicting long-term CIm in a cohort of MS patients.

Methods

303 out of 597 patients participating in a previous multicenter clinical-MRI study were enrolled (49.4% were lost at follow-up). The following MRI parameters, expressed as fraction (f) of intracranial volume, were evaluated: cerebrospinal fluid (CSF-f), WM-f, GM-f and abnormal WM (AWM-f), a measure of lesion load. Nine years later, cognitive status was assessed in 241 patients using the Symbol Digit Modalities Test (SDMT), the Semantically Related Word List Test (SRWL), the Modified Card Sorting Test (MCST), and the Paced Auditory Serial Addition Test (PASAT). In particular, being SRWL a memory test, both immediate recall and delayed recall were evaluated. MCST scoring was calculated based on the number of categories, number of perseverative and non-perseverative errors.

Results

AWM-f was predictive of an impaired performance 9 years ahead in SDMT (OR 1.49, CI 1.12–1.97 p = 0.006), PASAT (OR 1.43, CI 1.14–1.80 p = 0.002), SRWL-immediate recall (OR 1.72 CI 1.35–2.20 p<0.001), SRWL-delayed recall (OR 1.61 CI 1.28–2.03 p<0.001), MCST-category (OR 1.52, CI 1.2–1.9 p<0.001), MCST-perseverative error(OR 1.51 CI 1.2–1.9 p = 0.001), MCST-non perseverative error (OR 1.26 CI 1.02–1.55 p = 0.032).

Conclusion

In our large MS cohort, focal WM damage appeared to be the most relevant predictor of the long-term cognitive outcome.     

Geographically widespread swordfish barcode stock identification: a case study of its application

Background

The swordfish (Xiphias gladius) is a cosmopolitan large pelagic fish inhabiting tempered and tropical waters and it is a target species for fisheries all around the world. The present study investigated the ability of COI barcoding to reliably identify swordfish and particularly specific stocks of this commercially important species.

Methodology

We applied the classical DNA barcoding technology, upon a 682 bp segment of COI, and compared swordfish sequences from different geographical sources (Atlantic, Indian Oceans and Mediterranean Sea). The sequences of the 5′ hyper-variable fragment of the control region (5′dloop), were also used to validate the efficacy of COI as a stock-specific marker.

Case Report

This information was successfully applied to the discrimination of unknown samples from the market, detecting in some cases mislabeled seafood products.

Conclusions

The NJ distance-based phenogram (K2P model) obtained with COI sequences allowed us to correlate the swordfish haplotypes to the different geographical stocks. Similar results were obtained with 5′dloop. Our preliminary data in swordfish Xiphias gladius confirm that Cytochrome Oxidase I can be proposed as an efficient species-specific marker that has also the potential to assign geographical provenance. This information might speed the samples analysis in commercial application of barcoding.     

Population vulnerability and disability in Kenya's tsetse fly habitats

Background

Human African Trypanosomiasis (HAT), also referred to as sleeping sickness, and African Animal Trypanosomaisis (AAT), known as nagana, are highly prevalent parasitic vector-borne diseases in sub-Saharan Africa. Humans acquire trypanosomiasis following the bite of a tsetse fly infected with the protozoa Trypanosoma brucei (T.b.) spp. –i.e., T.b. gambiense in West and Central Africa and T.b. rhodesiense in East and Southern Africa. Over the last decade HAT diagnostic capacity to estimate HAT prevalence has improved in active case-finding areas but enhanced passive surveillance programs are still lacking in much of rural sub-Saharan Africa.

Methodology/Principal Findings

This retrospective-cross-sectional study examined the use of national census data (1999) to estimate population vulnerability and disability in Kenya''s 7 tsetse belts to assess the potential of HAT-acquired infection in those areas. A multilevel study design estimated the likelihood of disability in individuals, nested within households, nested within tsetse fly habitats of varying levels of poverty. Residents and recent migrants of working age were studied. Tsetse fly''s impact on disability was conceptualised via two exposure pathways: directly from the bite of a pathogenic tsetse fly resulting in HAT infection or indirectly, as the potential for AAT takes land out of agricultural production and diseased livestock leads to livestock morbidity and mortality, contributing to nutritional deficiencies and poverty. Tsetse belts that were significantly associated with increased disability prevalence were identified and the direct and indirect exposure pathways were evaluated.

Conclusions/Significance

Incorporating reports on disability from the national census is a promising surveillance tool that may enhance future HAT surveillance programs in sub-Saharan Africa. The combined burdens of HAT and AAT and the opportunity costs of agricultural production in AAT areas are likely contributors to disability within tsetse-infested areas. Future research will assess changes in the spatial relationships between high tsetse infestation and human disability following the release of the Kenya 2009 census at the local level.