Lysosomal acid lipase regulates VLDL synthesis and insulin sensitivity in mice

AIMS/HYPOTHESIS: Lysosomal acid lipase (LAL) hydrolyses cholesteryl esters and triacylglycerols (TG) within lysosomes to mobilise NEFA and cholesterol. Since LAL-deficient (Lal (-/-) ) mice suffer from progressive loss of adipose tissue and severe accumulation of lipids in hepatic lysosomes, we hypothesised that LAL deficiency triggers alternative energy pathway(s). METHODS: We studied metabolic adaptations in Lal (-/-) mice. RESULTS: Despite loss of adipose tissue, Lal (-/-) mice show enhanced glucose clearance during insulin and glucose tolerance tests and have increased uptake of [(3)H]2-deoxy-D-glucose into skeletal muscle compared with wild-type mice. In agreement, fasted Lal (-/-) mice exhibit reduced glucose and glycogen levels in skeletal muscle. We observed 84% decreased plasma leptin levels and significantly reduced hepatic ATP, glucose, glycogen and glutamine concentrations in fed Lal (-/-) mice. Markedly reduced hepatic acyl-CoA concentrations decrease the expression of peroxisome proliferator-activated receptor α (PPARα) target genes. However, treatment of Lal (-/-) mice with the PPARα agonist fenofibrate further decreased plasma TG (and hepatic glucose and glycogen) concentrations in Lal (-/-) mice. Depletion of hepatic nuclear factor 4α and forkhead box protein a2 in fasted Lal (-/-) mice might be responsible for reduced expression of microsomal TG transfer protein, defective VLDL synthesis and drastically reduced plasma TG levels. CONCLUSIONS/INTERPRETATION: Our findings indicate that neither activation nor inactivation of PPARα per se but rather the availability of hepatic acyl-CoA concentrations regulates VLDL synthesis and subsequent metabolic adaptations in Lal (-/-) mice. We conclude that decreased plasma VLDL production enhances glucose uptake into skeletal muscle to compensate for the lack of energy supply

Genetic Differentiation of the Western Capercaillie Highlights the Importance of South-Eastern Europe for Understanding the Species Phylogeography

The Western Capercaillie (Tetrao urogallus L.) is a grouse species of open boreal or high altitude forests of Eurasia. It is endangered throughout most mountain range habitat areas in Europe. Two major genetically identifiable lineages of Western Capercaillie have been described to date: the southern lineage at the species' southernmost range of distribution in Europe, and the boreal lineage. We address the question of genetic differentiation of capercaillie populations from the Rhodope and Rila Mountains in Bulgaria, across the Dinaric Mountains to the Slovenian Alps. The two lineages' contact zone and resulting conservation strategies in this so-far understudied area of distribution have not been previously determined. The results of analysis of mitochondrial DNA control region sequences of 319 samples from the studied populations show that Alpine populations were composed exclusively of boreal lineage; Dinaric populations of both, but predominantly (96%) of boreal lineage; and Rhodope-Rila populations predominantly (>90%) of southern lineage individuals. The Bulgarian mountains were identified as the core area of the southern lineage, and the Dinaric Mountains as the western contact zone between both lineages in the Balkans. Bulgarian populations appeared genetically distinct from Alpine and Dinaric populations and exhibited characteristics of a long-term stationary population, suggesting that they should be considered as a glacial relict and probably a distinct subspecies. Although all of the studied populations suffered a decline in the past, the significantly lower level of genetic diversity when compared with the neighbouring Alpine and Bulgarian populations suggests that the isolated Dinaric capercaillie is particularly vulnerable to continuing population decline. The results are discussed in the context of conservation of the species in the Balkans, its principal threats and legal protection status. Potential conservation strategies should consider the existence of the two lineages and their vulnerable Dinaric contact zone and support the specificities of the populations

Propranolol in the preoperative treatment of Kasabach–Merritt syndrome: a case report

Abstract Background Kasabach–Merritt syndrome represents the association of hemangioma with thrombocytopenia and consumptive coagulopathy. We present a case of Kasabach–Merritt syndrome treatment with orally administered propranolol. Case presentation A 4.5-month-old caucasian female infant with congenital giant hemangioma in the posterior region of her neck presented to our Institute for Childhood Diseases where she underwent clinical, laboratory, and radiological investigations. A low blood platelet count indicated the use of corticosteroids and blood components as first-line therapy. The lack of therapeutic response induced the introduction of orally administered propranolol as additive therapy. A 3-week treatment led to a reduction in the size of hemangioma and a rise in platelet count which enabled surgical treatment and definite healing. Conclusion Orally administered propranolol as monotherapy or in combination with other therapeutic modalities may play a key role in the treatment of Kasabach–Merritt syndrome

Axial torsion and gangrene of Meckel’s diverticulum: Case report

Introduction. Meckel’s diverticulum (MD) is the most prevalent congenital anomaly of small intestine. It develops due to the incomplete obliteration of omphalomesenterict duct which normally undergoes obliteration during the seventh week of gestation. In the majority of cases MD is asymptomatic but it may cause various complications, such as bleeding, intestinal obstruction and inflammation. Cases of umbilical sinuses, fistulas and neoplasms related with MD have been reported, but extremely rare gangrene due to its axial torsion, especially in children, as is the case of our patients. Case Outline. An 11-year-old boy admitted to hospital due to 24 hours epigastric pain, vomiting and malaise. After a complete physical examination, and appropriate pre-surgical laboratory and radiographic tests, surgical exploration was performed with a midline abdominal incision. On 60th cm proximal to the ileocecal valve we found a long and in a narrow based ganrenous MD with axial torsion and fibrotic cord extending from the tip of MD to the ileal mesentery. Surrounding ileum had normal appearance. A demarcation and subsequent resection of MD and the surrounding ileum was performed with endto- end ileal anastomosis. Postoperative recovery was successful and the patient was discharged after six days. Conclusion. Axial torsion of MD is presented with non-specific abdominal symptoms and difficult preoperative diagnosis. The choice of diagnosis and therapy is surgical exploration and resection of MD

On possible proxies of AGN light-curves cadence selection in future time domain surveys

Motivated by upcoming photometric and spectroscopic surveys [Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST), Manuakea Spectroscopic Explorer], we design the statistical proxies to measure the cadence effects on active galactic nuclei (AGNs) variability-observables [time-lags, periodicity, and structure-function (SF)]. We constructed a multiple-regression model to statistically identify the cadence-formal error pattern knowing AGN time-lags and periodicity from different surveys. We defined the simple metric for the SF’s properties, accounting for the ‘observed’ SF’s deviation relative to those obtained from the homogenously sampled light curves. We tested the regression models on different observing strategies: the optical data set of long light curves of eight AGN with peculiarities and the artificial data sets based on several idealized and LSST-like cadences. The SFs metric is assessed on synthetic data sets. The regression models (for both data types) predict similar cadences for time-lags and oscillation detection, whereas for light curves with low variability (-10 per cent), cadences for oscillation detection differ. For higher variability (-20 per cent), predicted cadences are larger than for Fvar - 10 per cent. The predicted cadences are decreasing with redshift. SFs with dense and homogenous cadences are more likely to behave similarly. SFs with oscillatory signals are sensitive to the cadences, possibly impacting LSST-like operation strategy. The proposed proxies can help to select spectroscopic and photometric-surveys cadence strategies, and they will be tested further in larger samples of objects