Dissociation of Immune Responses from Pathogen Colonization Supports Pattern Recognition in C. elegans

Caenorhabditis elegans has been used for over a decade to characterize signaling cascades controlling innate immune responses. However, what initiates these responses in the worm has remained elusive. To gain a better understanding of the initiating events we delineated genome-wide immune responses to the bacterial pathogen Pseudomonas aeruginosa in worms heavily-colonized by the pathogen versus worms visibly not colonized. We found that infection responses in both groups were identical, suggesting that immune responses were not correlated with colonization and its associated damage. Quantitative RT-PCR measurements further showed that pathogen secreted factors were not able to induce an immune response, but exposure to a non-pathogenic Pseudomonas species was. These findings raise the possibility that the C.elegans immune response is initiated by recognition of microbe-associated molecular patterns. In the absence of orthologs of known pattern recognition receptors, C. elegans may rely on novel mechanisms, thus holding the potential to advance our understanding of evolutionarily conserved strategies for pathogen recognition

TGFβ/BMP immune signaling affects abundance and function of C. elegans gut commensals.

The gut microbiota contributes to host health and fitness, and imbalances in its composition are associated with pathology. However, what shapes microbiota composition is not clear, in particular the role of genetic factors. Previous work in Caenorhabditis elegans defined a characteristic worm gut microbiota significantly influenced by host genetics. The current work explores the role of central regulators of host immunity and stress resistance, employing qPCR and CFU counts to measure abundance of core microbiota taxa in mutants raised on synthetic communities of previously-isolated worm gut commensals. This revealed a bloom, specifically of Enterobacter species, in immune-compromised TGFβ/BMP mutants. Imaging of fluorescently labeled Enterobacter showed that TGFβ/BMP-exerted control operated primarily in the anterior gut and depended on multi-tissue contributions. Enterobacter commensals are common in the worm gut, contributing to infection resistance. However, disruption of TGFβ/BMP signaling turned a normally beneficial Enterobacter commensal to pathogenic. These results demonstrate specificity in gene-microbe interactions underlying gut microbial homeostasis and highlight the pathogenic potential of their disruption

Not by Firkowicz's Fault: Daniel Chwolson's Comic Blunders in Research of Hebrew Epigraphy of the Crimea and Caucasus, and their Impact on Jewish Studies in Russia

Daniel Chwolson (1819-1911) made a huge impact upon the research of Hebrew epigraphy from the Crimea and Caucasus. Despite that, his role in the more-than-a-century-long controversy regarding Crimean Hebrew tomb inscriptions has not been well studied. Chwolson, at first, adopted Abraham Firkowicz's forgeries, and then quickly realized his mistake; however, he could not back up. The criticism by both Abraham Harkavy and German Hebraists questioned Chwolson's scholarly qualifications and integrity. Consequently, the interference of political pressure into the academic argument resulted in the prevailing of the scholarly flawed opinion. We revisit the interpretation of these findings by Russian, Jewish, Karaite and Georgian historians in the 19th and 20th centuries. During the Soviet period, Jewish Studies in the USSR were in neglect and nobody seriously studied the whole complex of the inscriptions from the South of Russia / the Soviet Union. The remnants of the scholarly community were hypnotized by Chwolson's authority, who was the teacher of their teachers' teachers. At the same time, Western scholars did not have access to these materials and/or lacked the understanding of the broader context, and thus a number of erroneous Chwolson's conclusion have entered academic literature for decades

Utilization of Murine Laparoscopy for Continuous In-Vivo Assessment of the Liver in Multiple Disease Models

BACKGROUND: Current strategies for follow up of murine models of liver disease are flawed by inability to continuously monitor disease progression in the tissue level, and necessitate sacrifice of animals for tissue sampling. AIMS: In this study we aimed at developing a safe repetitive tool for sampling livers in vivo, by utilization of a miniaturized endoscopy system for laparoscopic liver biopsies and for injection of tumor cells into livers. RESULTS: We report the development of a protocol for murine laparoscopy that allows repeated visualization of murine intra-abdominal organs. The system enables safe and repeated liver biopsies in mice and rats, yielding adequate tissue for histological staining and RNA extraction. In addition, injection of tumor cells into livers facilitates under-vision implantation of hepatic tumors in liver, followed by visualization of tumor growth. CONCLUSIONS: Murine laparoscopy may be employed as a novel imaging modality for continuous assessment and manipulation of chronic liver disease models

Isospectral domains with mixed boundary conditions

We construct a series of examples of planar isospectral domains with mixed Dirichlet-Neumann boundary conditions. This is a modification of a classical problem proposed by M. Kac.Comment: 9 figures. Statement of Theorem 5.1 correcte

Elevated resting heart rate is associated with the metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Increased resting heart rate (RHR) may be associated with increased cardiovascular morbidity. Our aim was to explore the possibility that increased RHR is associated with the prevalence of the metabolic syndrome (MetS) in a sample of apparently healthy individuals and those with cardiovascular risk factors.</p> <p>Methods</p> <p>We performed a cross-sectional analysis in a large sample of apparently healthy individuals who attended a general health screening program and agreed to participate in our survey. We analyzed a sample of 7706 individuals (5106 men and 2600 women) with 13.2% of men and 8.9% of the women fulfilling the criteria for the MetS. The participants were divided into quintiles of resting heart rate. Multiple adjusted odds ratio was calculated for having the MetS in each quintile compared to the first.</p> <p>Results</p> <p>The multi-adjusted odds for the presence of the MetS increased gradually from an arbitrarily defined figure of 1.0 in the lowest RHR quintile (<60 beats per minute (BPM) in men and <64 BPM in women) to 4.1 and 4.2 in men and women respectively in the highest one (≥80 BPM in men and ≥82 BPM in women).</p> <p>Conclusion</p> <p>Raised resting heart rate is significantly associated with the presence of MetS in a group of apparently healthy individuals and those with an atherothrombotic risk. The strength of this association supports the potential presence of one or more shared pathophysiological mechanisms for both RHR and the MetS.</p