Why Are Male Social Relationships Complex in the Doubtful Sound Bottlenose Dolphin Population?

Copyright 2008 Elsevier B.V., All rights reserved.Peer reviewedPublisher PD

Complementarity of Spike- and Rate-Based Dynamics of Neural Systems

Relationships between spiking-neuron and rate-based approaches to the dynamics of neural assemblies are explored by analyzing a model system that can be treated by both methods, with the rate-based method further averaged over multiple neurons to give a neural-field approach. The system consists of a chain of neurons, each with simple spiking dynamics that has a known rate-based equivalent. The neurons are linked by propagating activity that is described in terms of a spatial interaction strength with temporal delays that reflect distances between neurons; feedback via a separate delay loop is also included because such loops also exist in real brains. These interactions are described using a spatiotemporal coupling function that can carry either spikes or rates to provide coupling between neurons. Numerical simulation of corresponding spike- and rate-based methods with these compatible couplings then allows direct comparison between the dynamics arising from these approaches. The rate-based dynamics can reproduce two different forms of oscillation that are present in the spike-based model: spiking rates of individual neurons and network-induced modulations of spiking rate that occur if network interactions are sufficiently strong. Depending on conditions either mode of oscillation can dominate the spike-based dynamics and in some situations, particularly when the ratio of the frequencies of these two modes is integer or half-integer, the two can both be present and interact with each other

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD

Dietary zinc supplementation of 3xTg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction

The overall effect of brain zinc (Zn2+) in the progression and development of Alzheimer's disease (AD) is still not completely understood. Although an excess of Zn2+ can exacerbate the pathological features of AD, a deficit of Zn2+ intake has also been shown to increase the volume of amyloid plaques in AD transgenic mice. In this study, we investigated the effect of dietary Zn2+ supplementation (30 p.p.m.) in a transgenic mouse model of AD, the 3xTg-AD, that expresses both β amyloid (Aβ)- and tau-dependent pathology. We found that Zn2+ supplementation greatly delays hippocampal-dependent memory deficits and strongly reduces both Aβ and tau pathology in the hippocampus. We also evaluated signs of mitochondrial dysfunction and found that Zn2+ supplementation prevents the age-dependent respiratory deficits we observed in untreated 3xTg-AD mice. Finally, we found that Zn2+ supplementation greatly increases the levels of brain-derived neurotrophic factor (BDNF) of treated 3xTg-AD mice. In summary, our data support the idea that controlling the brain Zn2+ homeostasis may be beneficial in the treatment of AD

Mapping post-glacial expansions: The peopling of Southwest Asia

Archaeological, palaeontological and geological evidence shows that post-glacial warming released human populations from their various climate-bound refugia. Yet specific connections between these refugia and the timing and routes of post-glacial migrations that ultimately established modern patterns of genetic variation remain elusive. Here, we use Y-chromosome markers combined with autosomal data to reconstruct population expansions from regional refugia in Southwest Asia. Populations from three regions in particular possess distinctive autosomal genetic signatures indicative of likely refugia: one, in the north, centered around the eastern coast of the Black Sea, the second, with a more Levantine focus, and the third in the southern Arabian Peninsula. Modern populations from these three regions carry the widest diversity and may indeed represent the most likely descendants of the populations responsible for the Neolithic cultures of Southwest Asia. We reveal the distinct and datable expansion routes of populations from these three refugia throughout Southwest Asia and into Europe and North Africa and discuss the possible correlations of these migrations to various cultural and climatic events evident in the archaeological record of the past 15,000 years

Rhabdovirus Matrix Protein Structures Reveal a Novel Mode of Self-Association

The matrix (M) proteins of rhabdoviruses are multifunctional proteins essential for virus maturation and budding that also regulate the expression of viral and host proteins. We have solved the structures of M from the vesicular stomatitis virus serotype New Jersey (genus: Vesiculovirus) and from Lagos bat virus (genus: Lyssavirus), revealing that both share a common fold despite sharing no identifiable sequence homology. Strikingly, in both structures a stretch of residues from the otherwise-disordered N terminus of a crystallographically adjacent molecule is observed binding to a hydrophobic cavity on the surface of the protein, thereby forming non-covalent linear polymers of M in the crystals. While the overall topology of the interaction is conserved between the two structures, the molecular details of the interactions are completely different. The observed interactions provide a compelling model for the flexible self-assembly of the matrix protein during virion morphogenesis and may also modulate interactions with host proteins

N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells

IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models

Offspring of Mothers Fed a High Fat Diet Display Hepatic Cell Cycle Inhibition and Associated Changes in Gene Expression and DNA Methylation

The association between an adverse early life environment and increased susceptibility to later-life metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease is described by the developmental origins of health and disease hypothesis. Employing a rat model of maternal high fat (MHF) nutrition, we recently reported that offspring born to MHF mothers are small at birth and develop a postnatal phenotype that closely resembles that of the human metabolic syndrome. Livers of offspring born to MHF mothers also display a fatty phenotype reflecting hepatic steatosis and characteristics of non-alcoholic fatty liver disease. In the present study we hypothesised that a MHF diet leads to altered regulation of liver development in offspring; a derangement that may be detectable during early postnatal life. Livers were collected at postnatal days 2 (P2) and 27 (P27) from male offspring of control and MHF mothers (n = 8 per group). Cell cycle dynamics, measured by flow cytometry, revealed significant G0/G1 arrest in the livers of P2 offspring born to MHF mothers, associated with an increased expression of the hepatic cell cycle inhibitor Cdkn1a. In P2 livers, Cdkn1a was hypomethylated at specific CpG dinucleotides and first exon in offspring of MHF mothers and was shown to correlate with a demonstrable increase in mRNA expression levels. These modifications at P2 preceded observable reductions in liver weight and liver∶brain weight ratio at P27, but there were no persistent changes in cell cycle dynamics or DNA methylation in MHF offspring at this time. Since Cdkn1a up-regulation has been associated with hepatocyte growth in pathologic states, our data may be suggestive of early hepatic dysfunction in neonates born to high fat fed mothers. It is likely that these offspring are predisposed to long-term hepatic dysfunction

Childhood solid tumours in relation to infections in the community in Cumbria during pregnancy and around thetime of birth

In a retrospective cohort study of all 99 976 live births in Cumbria, 1975–1992, we investigated whether higher levels of community infections during the mother's pregnancy and in early life were risk factors for solid tumours (brain/spinal and other tumours), diagnosed 1975–1993 under age 15 years. Logistic regression was used to relate risk to incidence of community infections in three prenatal and two postnatal quarters. There was an increased risk of brain/spinal tumours among children exposed around or soon after birth to higher levels of community infections, in particular measles (OR for trend=2.1, 95%CI : 1.3–3.6, P=0.008) and influenza (OR for exposure=3.3, 95%CI : 1.5–7.4, P=0.005). There was some evidence of an association between exposure to infections around and soon after birth and risk of other tumours, but this may have been a chance finding. The findings are consistent with other recent epidemiological studies suggesting brain tumours may be associated with perinatal exposure to infections

Incidence and Outcome of Acute Phosphate Nephropathy in Iceland

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Oral sodium phosphate solutions (OSPS) are widely used for bowel cleansing prior to colonoscopy and other procedures. Cases of renal failure due to acute phosphate nephropathy following OSPS ingestion have been documented in recent years, questioning the safety of OSPS. However, the magnitude of the problem remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population based, retrospective analysis of medical records and biopsies of all cases of acute phosphate nephropathy that were diagnosed in our country in the period from January 2005 to October 2008. Utilizing the complete official sales figures of OSPS, we calculated the incidence of acute phosphate nephropathy in our country. Fifteen cases of acute phosphate nephropathy were diagnosed per 17,651 sold doses of OSPS (0.085%). Nine (60%) were women and mean age 69 years (range 56-75 years). Thirteen patients had a history of hypertension (87%) all of whom were treated with either ACE-I or ARB and/or diuretics. One patient had underlying DM type I and an active colitis and one patient had no risk factor for the development of acute phosphate nephropathy. Average baseline creatinine was 81.7 µmol/L and 180.1 at the discovery of acute renal failure, mean 4.2 months after OSPS ingestion. No patient had a full recovery of renal function, and at the end of follow-up, 26.6 months after the OSPS ingestion, the average creatinine was 184.2 µmol/L. The average eGFR declined from 73.5 ml/min/1.73 m(2) at baseline to 37.3 ml/min/1.73 m(2) at the end of follow-up. One patient reached end-stage renal disease and one patient died with progressive renal failure. CONCLUSION/SIGNIFICANCE: Acute phosphate nephropathy developed in almost one out of thousand sold doses of OSPS. The consequences for kidney function were detrimental. This information can be used in other populations to estimate the impact of OSPS. Our data suggest that acute phosphate nephropathy may be greatly underreported worldwide