A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the developed world. While treatment is effective for the neovascular or "wet" form of AMD, no therapy is successful for the non-neovascular or "dry" form. Here we discuss the current knowledge on dry AMD pathobiology and propose future research directions that would expedite the development of new treatments. In our view, these should emphasize system biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy

Social network analysis shows direct evidence for social transmission of tool use in wild chimpanzees

The authors are grateful to the Royal Zoological Society of Scotland for providing core funding for the Budongo Conservation Field Station. The fieldwork of CH was funded by the Leverhulme Trust, the Lucie Burgers Stichting, and the British Academy. TP was funded by the Canadian Research Chair in Continental Ecosystem Ecology, and received computational support from the Theoretical Ecosystem Ecology group at UQAR. The research leading to these results has received funding from the People Programme (Marie Curie Actions) and from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007–2013) REA grant agreement n°329197 awarded to TG, ERC grant agreement n° 283871 awarded to KZ. WH was funded by a BBSRC grant (BB/I007997/1).Social network analysis methods have made it possible to test whether novel behaviors in animals spread through individual or social learning. To date, however, social network analysis of wild populations has been limited to static models that cannot precisely reflect the dynamics of learning, for instance, the impact of multiple observations across time. Here, we present a novel dynamic version of network analysis that is capable of capturing temporal aspects of acquisition-that is, how successive observations by an individual influence its acquisition of the novel behavior. We apply this model to studying the spread of two novel tool-use variants, "moss-sponging'' and "leaf-sponge re-use,'' in the Sonso chimpanzee community of Budongo Forest, Uganda. Chimpanzees are widely considered the most "cultural'' of all animal species, with 39 behaviors suspected as socially acquired, most of them in the domain of tool-use. The cultural hypothesis is supported by experimental data from captive chimpanzees and a range of observational data. However, for wild groups, there is still no direct experimental evidence for social learning, nor has there been any direct observation of social diffusion of behavioral innovations. Here, we tested both a static and a dynamic network model and found strong evidence that diffusion patterns of moss-sponging, but not leaf-sponge re-use, were significantly better explained by social than individual learning. The most conservative estimate of social transmission accounted for 85% of observed events, with an estimated 15-fold increase in learning rate for each time a novice observed an informed individual moss-sponging. We conclude that group-specific behavioral variants in wild chimpanzees can be socially learned, adding to the evidence that this prerequisite for culture originated in a common ancestor of great apes and humans, long before the advent of modern humans.Publisher PDFPeer reviewe

Nutritional Asymmetries Are Related to Division of Labor in a Queenless Ant

Eusocial species exhibit pronounced division of labor, most notably between reproductive and non-reproductive castes, but also within non-reproductive castes via morphological specialization and temporal polyethism. For species with distinct worker and queen castes, age-related differences in behavior among workers (e.g. within-nest tasks versus foraging) appear to result from physiological changes such as decreased lipid content. However, we know little about how labor is divided among individuals in species that lack a distinct queen caste. In this study, we investigated how fat storage varied among individuals in a species of ant (Dinoponera australis) that lacks a distinct queen caste and in which all individuals are morphologically similar and capable of reproduction (totipotent at birth). We distinguish between two hypotheses, 1) all individuals are physiologically similar, consistent with the possibility that any non-reproductive may eventually become reproductive, and 2) non-reproductive individuals vary in stored fat, similar to highly eusocial species, where depletion is associated with foraging and non-reproductives have lower lipid stores than reproducing individuals. Our data support the latter hypothesis. Location in the nest, the probability of foraging, and foraging effort, were all associated with decreased fat storage

Trans-mitochondrial coordination of cristae at regulated membrane junctions

Reminiscent of bacterial quorum sensing, mammalian mitochondria participate in inter-organelle communication. However, physical structures that enhance or enable interactions between mitochondria have not been defined. Here we report that adjacent mitochondria exhibit coordination of inner mitochondrial membrane cristae at inter-mitochondrial junctions (IMJs). These electron-dense structures are conserved across species, resistant to genetic disruption of cristae organization, dynamically modulated by mitochondrial bioenergetics, independent of known inter-mitochondrial tethering proteins mitofusins and rapidly induced by the stable rapprochement of organelles via inducible synthetic linker technology. At the associated junctions, the cristae of adjacent mitochondria form parallel arrays perpendicular to the IMJ, consistent with a role in electrochemical coupling. These IMJs and associated cristae arrays may provide the structural basis to enhance the propagation of intracellular bioenergetic and apoptotic waves through mitochondrial networks within cells

Meaning in life in the Federal Republic of Germany: results of a representative survey with the Schedule for Meaning in Life Evaluation (SMiLE)

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Small bowel enteroclysis with magnetic resonance imaging and computed tomography in patients with failed and uncertain passage of a patency capsule

<p>Abstract</p> <p>Background</p> <p>Video capsule enteroscopy (VCE) has revolutionized small bowel imaging, enabling visual examination of the mucosa of the entire small bowel, while MR enteroclysis (MRE) and CT enteroclysis (CTE) have largely replaced conventional barium enteroclysis. A new indication for MRE and CTE is the clinical suspicion of small bowel strictures, as indicated by delayed or non-delivery of a test capsule given before a VCE examination, to exclude stenosis. The aim of this study was to determine the clinical value of subsequent MRE and CTE in patients in whom a test capsule did not present itself in due time.</p> <p>Methods</p> <p>Seventy-five consecutive patients were identified with a delayed or unnoticed delivery of the test capsule. Seventy patients consented to participate and underwent MRE (44) or CTE (26). The medical records and imaging studies were retrospectively reviewed and symptoms, laboratory results and imaging findings recorded.</p> <p>Results</p> <p>Lesions compatible with Crohns disease were shown by MRE in 5 patients, by CTE in one and by VCE in four, one of whom had lesions on MRE. In patients without alarm symptoms and findings (weight loss, haematochezia, anaemia, nocturnal diarrheoa, ileus, fistula, abscess and abnormal blood tests) imaging studies did not unveil any such lesion. VCE's were performed in only 20 patients, mainly younger than 50 years of age, although no stenotic lesion was shown by MRE and CTE. In the remaining 50 patients no VCE or other endoscopic intervention was performed indicating that the referring physician was content with the diagnostic information from MRE or CTE.</p> <p>Conclusion</p> <p>The diagnostic value of MRE and CTE is sufficient for clinical management of most patients with suspected small bowel disease, and thus VCE may be omitted or at least postponed for later usage.</p

Aging Predisposes Oocytes to Meiotic Nondisjunction When the Cohesin Subunit SMC1 Is Reduced

In humans, meiotic chromosome segregation errors increase dramatically as women age, but the molecular defects responsible are largely unknown. Cohesion along the arms of meiotic sister chromatids provides an evolutionarily conserved mechanism to keep recombinant chromosomes associated until anaphase I. One attractive hypothesis to explain age-dependent nondisjunction (NDJ) is that loss of cohesion over time causes recombinant homologues to dissociate prematurely and segregate randomly during the first meiotic division. Using Drosophila as a model system, we have tested this hypothesis and observe a significant increase in meiosis I NDJ in experimentally aged Drosophila oocytes when the cohesin protein SMC1 is reduced. Our finding that missegregation of recombinant homologues increases with age supports the model that chiasmata are destabilized by gradual loss of cohesion over time. Moreover, the stage at which Drosophila oocytes are most vulnerable to age-related defects is analogous to that at which human oocytes remain arrested for decades. Our data provide the first demonstration in any organism that, when meiotic cohesion begins intact, the aging process can weaken it sufficiently and cause missegregation of recombinant chromosomes. One major advantage of these studies is that we have reduced but not eliminated the SMC1 subunit. Therefore, we have been able to investigate how aging affects normal meiotic cohesion. Our findings that recombinant chromosomes are at highest risk for loss of chiasmata during diplotene argue that human oocytes are most vulnerable to age-induced loss of meiotic cohesion at the stage at which they remain arrested for several years

Retinal nerve fibre layer thickness profile in normal eyes using third-generation optical coherence tomography

Aims To establish four normal retinal nerve fibre layer (RNFL) thickness radial profiles based on third-generation optical coherence tomography (OCT) and to compare them with previously reported histologic measurements.Methods A total of 20 normal eyes were studied. A circular scan was adjusted to the size of the optic disc and three scans were performed with this radius and every 200 mu m thereafter, up to a distance of 1400 mu m. Four different radial sections (superotemporal, superonasal, inferonasal, and inferotemporal) were studied to establish RNFL thickness OCT profiles. Additionally, two radial scans orientated at 45 and 1351 crossing the optic disc centre were performed in six of 20 eyes, and RNFL thickness was measured at disc margin.Results Quadrant location and distance from disc margin interaction in RNFL thickness was statistically significant (P < 0.001). the RNFL thickness decreased (P < 0.001) as the distance from the disc margin increased for all sections. the measurements automatically generated by the OCT built-in software were thinner (P < 0.001) than histologic ones close to the disc margin.Conclusions Four normal OCT RNFL profiles were established and compared with histological data obtained from the same area. RNFL measurements assessed by OCT 3 were significantly thinner close to the optic disc margin.Hosp Olhos Araraquara, Glaucoma Sect, BR-14802530 Araraquara, SP, BrazilHosp Olhos Araraquara, Retina Diagnost & Treatment Div, BR-14802530 Araraquara, SP, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUSP, Inst Fis Sao Carlos, Sao Carlos, SP, BrazilUniv So Calif, Doheny Eye Inst, Dept Ophthalmol, Los Angeles, CA USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid–polyethylene glycol/gadolinium–diethylenetriamine-pentaacetic acid (PLA–PEG/Gd–DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA–PEG/Gd–DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA–PEG nanoparticles and the commercial contrast agent, Gd–DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA–PEG/Gd–DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was −12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA–PEG/Gd–DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed (r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd–DTPA. PLA–PEG/Gd–DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA–PEG/Gd–DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent