Abernethy malformation: beware in cases of unexplained hepatic encephalopathy in adults-case report and review of the relevant literature

The Abernethy malformation consists of a congenital extrahepatic portosystemic shunt and is believed to be extremely rare in humans. The potential implications of abnormal portovenous shunting and decreased hepatic portal flow are numerous and potentially serious. Although congenital extrahepatic portosystemic shunts are increasingly suspected and diagnosed in specialized centres, much of their clinical presentation and natural history is not fully understood. Symptoms of portosystemic shunt are mainly caused by increased levels of ammonia, which lead to signs of encephalopathy. Therapeutic options depend on the type of shunt and its clinical course, so the classification of the congenital portosystemic shunt is a key finding in these patients.info:eu-repo/semantics/publishedVersio

Postglacial recolonizations, watershed crossings and human translocations shape the distribution of chub lineages around the Swiss Alps

Background: Distributions of European fish species were shaped by glaciations and the geological history of river networks until human activities partially abrogated the restrictions of biogeographical regions. The nearby origins of the Rhine, Rhone, Danube and Po rivers in the Swiss Alps allow the examination of historical and human-influenced patterns in fish genetic structure over a small geographic scale. We investigated these patterns in the widespread European chub (Squalius cephalus) from the Rhone, Rhine and Danube catchments and its proposed southern sister species Italian chub (Squalius squalus) from the Po catchment. Results: A phylogenetic tree constructed from mitochondrial Cytochrome b and COI sequences was consistent with earlier work in that it showed a separation of European chub and Italian chub, which was also reflected in microsatellite allele frequencies, morphological traits and shape differences quantified by geometric morphometrics. A new finding was that the predominant mitochondrial haplotype of European chub from the Rhine and Rhone catchments was also discovered in some individuals from Swiss populations of the Italian chub, presumably as a result of human translocation. Consistent with postglacial recolonizations from multiple refugia along the major rivers, the nuclear genetic structure of the European chub largely reflected drainage structure, but it was modified by watershed crossings between Rhine and Rhone near Lake Geneva as well as between Danube and Rhine near Lake Constance. Conclusion: Our study adds new insights into the cyprinid colonization history of central Europe by showing that multiple processes shaped the distribution of different chub lineages around the Swiss Alps. Interestingly, we find evidence that cross-catchment migration has been mediated by unusual geological events such as drainage captures or watershed crossings facilitated by retreating glaciers, as well as evidence that human transport has interfered with the historical distribution of these fish (European chub haplotypes present in the Italian chub). The desirable preservation of evolutionarily distinct lineages will thus require the prevention of further translocations

Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic Therapy

Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies

The roles of static stability and tropical – extratropical interactions in the summer interannual variability of the North Atlantic sector

Summer seasonal forecast skill in the North Atlantic sector is lower than winter skill. To identify potential controls on predictability, the sensitivity of North Atlantic baroclinicity to atmospheric drivers is quantified. Using ERA-INTERIM reanalysis data, North Atlantic storm-track baroclinicity is shown to be less sensitive to meridional temperature-gradient variability in summer. Static stability shapes the sector’s interannual variability by modulating the sensitivity of baroclinicity to variations in meridional temperature gradients and tropopause height and by modifying the baroclinicity itself. High static stability anomalies at upper levels result in more zonal extratropical cyclone tracks and higher eddy kinetic energy over the British Isles in the summertime. These static stability anomalies are not strongly related to the summer NAO; but they are correlated with the suppression of convection over the tropical Atlantic and with a poleward-shifted subtropical jet. These results suggest a non-local driver of North Atlantic variability. Furthermore, they imply that improved representations of convection over the south-eastern part of North America and the tropical Atlantic might improve summer seasonal forecast skill

Yeast thioredoxin reductase Trr1p controls TORC1-regulated processes

The thioredoxin system plays a predominant role in the control of cellular redox status. Thioredoxin reductase fuels the system with reducing power in the form of NADPH. The TORC1 complex promotes growth and protein synthesis when nutrients, particularly amino acids, are abundant. It also represses catabolic processes, like autophagy, which are activated during starvation. We analyzed the impact of yeast cytosolic thioredoxin reductase TRR1 deletion under different environmental conditions. It shortens chronological life span and reduces growth in grape juice fermentation. TRR1 deletion has a global impact on metabolism during fermentation. As expected, it reduces oxidative stress tolerance, but a compensatory response is triggered, with catalase and glutathione increasing. Unexpectedly, TRR1 deletion causes sensitivity to the inhibitors of the TORC1 pathway, such as rapamycin. This correlates with low Tor2p kinase levels and indicates a direct role of Trr1p in its stability. Markers of TORC1 activity, however, suggest increased TORC1 activity. The autophagy caused by nitrogen starvation is reduced in the trr1Δ mutant. Ribosomal protein Rsp6p is dephosphorylated in the presence of rapamycin. This dephosphorylation diminishes in the TRR1 deletion strain. These results show a complex network of interactions between thioredoxin reductase Trr1p and the processes controlled by TOR

MSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease

Germline MLH1 and MSH2 mutations are scarce in young colorectal cancer patients with negative family history of the disease. To evaluate the contribution of germline MSH6 mutations to early-onset colorectal cancer, we have analysed peripheral blood of 38 patients diagnosed with this disease before 45 years of age and who presented no family history of hereditary nonpolyposis colorectal cancer-related cancers. Blood samples from 108 healthy volunteers were analysed for those genetic alterations suspected to affect the function of MSH6. Of the seven (18.4%) MSH6 alterations found, we have identified three novel germline mutations, one 8 bp deletion leading to a truncated protein and two missense mutations resulting in the substitution of amino acids belonging to different polarity groups. High-frequency microsatellite instability was found in the patient with the MSH6 deletion, but not in the other 27 carcinomas analysed. No MLH1 promoter methylation was detected in tumour tissue. Our findings suggest that germline MSH6 mutations contribute to a subset of early-onset colorectal cancer. Further studies are warranted to understand the genetic and environmental factors responsible for the variable penetration of MSH6 germline mutations, as well as to identify other causes of early-onset colorectal cancer