Network Theory Analysis of Antibody-Antigen Reactivity Data: The Immune Trees at Birth and Adulthood

Motivation: New antigen microarray technology enables parallel recording of antibody reactivities with hundreds of antigens. Such data affords system level analysis of the immune system’s organization using methods and approaches from network theory. Here we measured the reactivity of 290 antigens (for both the IgG and IgM isotypes) of 10 healthy mothers and their term newborns. We constructed antigen correlation networks (or immune networks) whose nodes are the antigens and the edges are the antigen-antigen reactivity correlations, and we also computed their corresponding minimum spanning trees (MST) – maximal information reduced sub-graphs. We quantify the network organization (topology) in terms of the network theory divergence rate measure and rank the antigen importance in the full antigen correlation networks by the eigen-value centrality measure. This analysis makes possible the characterization and comparison of the IgG and IgM immune networks at birth (newborns) and adulthood (mothers) in terms of topology and node importance. Results: Comparison of the immune network topology at birth and adulthood revealed partial conservation of the IgG immune network topology, and significant reorganization of the IgM immune networks. Inspection of the antigen importance revealed some dominant (in terms of high centrality) antigens in the IgG and IgM networks at birth, which retain their importance at adulthood

Culturing Pancreatic Islets in Microfluidic Flow Enhances Morphology of the Associated Endothelial Cells

Pancreatic islets are heavily vascularized in vivo with each insulin secreting beta-cell associated with at least one endothelial cell (EC). This structure is maintained immediately post-isolation; however, in culture the ECs slowly deteriorate, losing density and branched morphology. We postulate that this deterioration occurs in the absence of blood flow due to limited diffusion of media inside the tissue. To improve exchange of media inside the tissue, we created a microfluidic device to culture islets in a range of flow-rates. Culturing the islets from C57BL6 mice in this device with media flowing between 1 and 7 ml/24 hr resulted in twice the EC-density and -connected length compared to classically cultured islets. Media containing fluorescent dextran reached the center of islets in the device in a flow-rate-dependant manner consistent with improved penetration. We also observed deterioration of EC morphology using serum free media that was rescued by addition of bovine serum albumin, a known anti-apoptotic signal with limited diffusion in tissue. We further examined the effect of flow on beta-cells showing dampened glucose-stimulated Ca2+-response from cells at the periphery of the islet where fluid shear-stress is greatest. However, we observed normal two-photon NAD(P)H response and insulin secretion from the remainder of the islet. These data reveal the deterioration of islet EC-morphology is in part due to restricted diffusion of serum albumin within the tissue. These data further reveal microfluidic devices as unique platforms to optimize islet culture by introducing intercellular flow to overcome the restricted diffusion of media components

Type IIB supergravity solutions with AdS5 from Abelian and non-Abelian T dualities

We present a large class of new backgrounds that are solutions of type IIB supergravity with a warped AdS${}_5$ factor, non-trivial axion-dilaton, $B$-field and three-form Ramond-Ramond flux but yet have no five-form flux. We obtain these solutions and many of their variations by judiciously applying non-Abelian and Abelian T-dualities, as well as coordinate shifts to AdS${}_5\times X_5$ IIB supergravity solutions with $X_5=S^5, T^{1,1}, Y^{p,q}$. We address a number of issues pertaining to charge quantization in the context of non-Abelian T-duality. We comment on some properties of the expected dual super conformal field theories by studying their CFT central charge holographically. We also use the structure of the supergravity Page charges, central charges and some probe branes to infer aspects of the dual super conformal field theories.Comment: 71 pages, one table. v2: References added, some normalizations corrected, results unchange

Self-Reported Serious Illnesses in Rural Cambodia: A Cross-Sectional Survey

BACKGROUND: There is substantial evidence that ill-health is a major cause of impoverishment in developing countries. Major illnesses can have a serious economic impact on poor households through treatment costs and income loss. However, available methods for measuring the impact of ill-health on household welfare display several shortcomings and new methods are thus needed. To understand the potential complex impact of major illnesses on household livelihoods, a study on poverty and illness was conducted in rural Cambodia, as part of an international comparative research project. A cross-sectional survey was performed to identify households affected by major illness for further in-depth interviews. METHODOLOGY AND PRINCIPAL FINDINGS: 5,975 households in three rural health districts were randomly selected through a two-stage cluster sampling and interviewed. 27% of the households reported at least one member with a serious illness in the year preceding the survey and 15% of the household members reported suffering from at least one serious illness. The most reported conditions include common tropical infectious diseases, chronic diseases (notably hypertension and heart diseases) and road traffic accidents. Such conditions were particularly concentrated among the poor, children under five, women, and the elderly. Poor women often reported complications related to pregnancy and delivery as serious illnesses. CONCLUSIONS AND SIGNIFICANCE: Despite some methodological limitations, this study provides new information on the frequency of self-reported serious illnesses among the rural Cambodia's population, which serves as a basis for further in-depth investigation on 'major illnesses' and their economic consequences on poor households. This can in turn help policy makers to formulate appropriate interventions to protect the poor from the financial burden associated with ill-health. Our findings suggest that every year a considerable proportion of rural population in Cambodia, especially the poor and vulnerable, are affected by serious illnesses, both communicable and non-communicable diseases

I Undervalue You but I Need You: The Dissociation of Attitude and Memory Toward In-Group Members

In the present study, the in-group bias or in-group derogation among mainland Chinese was investigated through a rating task and a recognition test. In two experiments,participants from two universities with similar ranks rated novel faces or names and then had a recognition test. Half of the faces or names were labeled as participants' own university and the other half were labeled as their counterpart. Results showed that, for either faces or names, rating scores for out-group members were consistently higher than those for in-group members, whereas the recognition accuracy showed just the opposite. These results indicated that the attitude and memory for group-relevant information might be dissociated among Mainland Chinese

Mitochondrial function as a determinant of life span

Average human life expectancy has progressively increased over many decades largely due to improvements in nutrition, vaccination, antimicrobial agents, and effective treatment/prevention of cardiovascular disease, cancer, etc. Maximal life span, in contrast, has changed very little. Caloric restriction (CR) increases maximal life span in many species, in concert with improvements in mitochondrial function. These effects have yet to be demonstrated in humans, and the duration and level of CR required to extend life span in animals is not realistic in humans. Physical activity (voluntary exercise) continues to hold much promise for increasing healthy life expectancy in humans, but remains to show any impact to increase maximal life span. However, longevity in Caenorhabditis elegans is related to activity levels, possibly through maintenance of mitochondrial function throughout the life span. In humans, we reported a progressive decline in muscle mitochondrial DNA abundance and protein synthesis with age. Other investigators also noted age-related declines in muscle mitochondrial function, which are related to peak oxygen uptake. Long-term aerobic exercise largely prevented age-related declines in mitochondrial DNA abundance and function in humans and may increase spontaneous activity levels in mice. Notwithstanding, the impact of aerobic exercise and activity levels on maximal life span is uncertain. It is proposed that age-related declines in mitochondrial content and function not only affect physical function, but also play a major role in regulation of life span. Regular aerobic exercise and prevention of adiposity by healthy diet may increase healthy life expectancy and prolong life span through beneficial effects at the level of the mitochondrion

Step by step: reconstruction of terrestrial animal movement paths by dead-reckoning

Background: Research on wild animal ecology is increasingly employing GPS telemetry in order to determine animal movement. However, GPS systems record position intermittently, providing no information on latent position or track tortuosity. High frequency GPS have high power requirements, which necessitates large batteries (often effectively precluding their use on small animals) or reduced deployment duration. Dead-reckoning is an alternative approach which has the potential to ‘fill in the gaps’ between less resolute forms of telemetry without incurring the power costs. However, although this method has been used in aquatic environments, no explicit demonstration of terrestrial dead-reckoning has been presented.Results: We perform a simple validation experiment to assess the rate of error accumulation in terrestrial dead-reckoning. In addition, examples of successful implementation of dead-reckoning are given using data from the domestic dog Canus lupus, horse Equus ferus, cow Bos taurus and wild badger Meles meles.Conclusions: This study documents how terrestrial dead-reckoning can be undertaken, describing derivation of heading from tri-axial accelerometer and tri-axial magnetometer data, correction for hard and soft iron distortions on the magnetometer output, and presenting a novel correction procedure to marry dead-reckoned paths to ground-truthed positions. This study is the first explicit demonstration of terrestrial dead-reckoning, which provides a workable method of deriving the paths of animals on a step-by-step scale. The wider implications of this method for the understanding of animal movement ecology are discussed

Dynamic GABAergic afferent modulation of AgRP neurons

Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues prior to ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the pre-consummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor (LepR)-expressing GABAergic DMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, DMHLepR neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior