Reduction of circulating cholesterol and apolipoprotein levels during sepsis

Sepsis with multiple organ failure is frequently associated with a substantial decrease of cholesterol levels. This decrease of cholesterol is strongly associated with mortality suggesting a direct relation between inflammatory conditions and altered cholesterol homeostasis. The host response during sepsis is mediated by cytokines and growth factors, which are capable of influencing lipid metabolism. Conversely lipoproteins are also capable of modulating cytokine production during the inflammatory response. Therefore the decrease in circulating cholesterol levels seems to play a crucial role in the pathophysiology of sepsis. In this review the interaction between cytokines and lipid metabolism and its clinical consequences will be discussed

Primordial Black Holes: sirens of the early Universe

Primordial Black Holes (PBHs) are, typically light, black holes which can form in the early Universe. There are a number of formation mechanisms, including the collapse of large density perturbations, cosmic string loops and bubble collisions. The number of PBHs formed is tightly constrained by the consequences of their evaporation and their lensing and dynamical effects. Therefore PBHs are a powerful probe of the physics of the early Universe, in particular models of inflation. They are also a potential cold dark matter candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

SREBP Coordinates Iron and Ergosterol Homeostasis to Mediate Triazole Drug and Hypoxia Responses in the Human Fungal Pathogen Aspergillus fumigatus

Sterol regulatory element binding proteins (SREBPs) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. Adding to the recognized importance of SREBPs in human health, SREBPs in the human fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus are required for fungal virulence and susceptibility to triazole antifungal drugs. To date, the exact mechanism(s) behind the role of SREBP in these observed phenotypes is not clear. Here, we report that A. fumigatus SREBP, SrbA, mediates regulation of iron acquisition in response to hypoxia and low iron conditions. To further define SrbA's role in iron acquisition in relation to previously studied fungal regulators of iron metabolism, SreA and HapX, a series of mutants were generated in the ΔsrbA background. These data suggest that SrbA is activated independently of SreA and HapX in response to iron limitation, but that HapX mRNA induction is partially dependent on SrbA. Intriguingly, exogenous addition of high iron or genetic deletion of sreA in the ΔsrbA background was able to partially rescue the hypoxia growth, triazole drug susceptibility, and decrease in ergosterol content phenotypes of ΔsrbA. Thus, we conclude that the fungal SREBP, SrbA, is critical for coordinating genes involved in iron acquisition and ergosterol biosynthesis under hypoxia and low iron conditions found at sites of human fungal infections. These results support a role for SREBP–mediated iron regulation in fungal virulence, and they lay a foundation for further exploration of SREBP's role in iron homeostasis in other eukaryotes

Advantages of the single delay model for the assessment of insulin sensitivity from the intravenous glucose tolerance test

The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative

Multiple Episodes of Convergence in Genes of the Dim Light Vision Pathway in Bats

The molecular basis of the evolution of phenotypic characters is very complex and is poorly understood with few examples documenting the roles of multiple genes. Considering that a single gene cannot fully explain the convergence of phenotypic characters, we choose to study the convergent evolution of rod vision in two divergent bats from a network perspective. The Old World fruit bats (Pteropodidae) are non-echolocating and have binocular vision, whereas the sheath-tailed bats (Emballonuridae) are echolocating and have monocular vision; however, they both have relatively large eyes and rely more on rod vision to find food and navigate in the night. We found that the genes CRX, which plays an essential role in the differentiation of photoreceptor cells, SAG, which is involved in the desensitization of the photoactivated transduction cascade, and the photoreceptor gene RH, which is directly responsible for the perception of dim light, have undergone parallel sequence evolution in two divergent lineages of bats with larger eyes (Pteropodidae and Emballonuroidea). The multiple convergent events in the network of genes essential for rod vision is a rare phenomenon that illustrates the importance of investigating pathways and networks in the evolution of the molecular basis of phenotypic convergence

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Androgen deprivation modulates the inflammatory response induced by irradiation

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine whether radiation (RT)-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies.</p> <p>Methods</p> <p>The mRNA and tissue sections obtained from the lungs, intestines and livers of irradiated mice with or without androgen deprivation were analyzed by real-time PCR and histological analysis. Activation of NF-kappa B was examined by measuring nuclear protein levels in the intestine and lung 24 h after irradiation. We also examined the levels of cyclooxygenase-2 (COX-2), TGF-β1 and p-AKT to elucidate the related pathway responsible to irradiation (RT) -induced fibrosis.</p> <p>Results</p> <p>We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-κB activation and COX-2 expression. However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine. These different responses were probably due to the increase of RT-induced NF-κB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-β1 and the induced epithelial-mesenchymal transition (EMT) via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis.</p> <p>Conclusion</p> <p>When irradiation was given to patients with total androgen deprivation, the augmenting effects on the RT-induced inflammation and fibrosis should take into consideration for complications associated with radiotherapy.</p

Complete Mitochondrial Genome Sequence of Three Tetrahymena Species Reveals Mutation Hot Spots and Accelerated Nonsynonymous Substitutions in Ymf Genes

The ciliate Tetrahymena, a model organism, contains divergent mitochondrial (Mt) genome with unusual properties, where half of its 44 genes still remain without a definitive function. These genes could be categorized into two major groups of KPC (known protein coding) and Ymf (genes without an identified function). To gain insights into the mechanisms underlying gene divergence and molecular evolution of Tetrahymena (T.) Mt genomes, we sequenced three Mt genomes of T.paravorax, T.pigmentosa, and T.malaccensis. These genomes were aligned and the analyses were carried out using several programs that calculate distance, nucleotide substitution (dn/ds), and their rate ratios (ω) on individual codon sites and via a sliding window approach. Comparative genomic analysis indicated a conserved putative transcription control sequence, a GC box, in a region where presumably transcription and replication initiate. We also found distinct features in Mt genome of T.paravorax despite similar genome organization among these ∼47 kb long linear genomes. Another significant finding was the presence of at least one or more highly variable regions in Ymf genes where majority of substitutions were concentrated. These regions were mutation hotspots where elevated distances and the dn/ds ratios were primarily due to an increase in the number of nonsynonymous substitutions, suggesting relaxed selective constraint. However, in a few Ymf genes, accelerated rates of nonsynonymous substitutions may be due to positive selection. Similarly, on protein level the majority of amino acid replacements occurred in these regions. Ymf genes comprise half of the genes in Tetrahymena Mt genomes, so understanding why they have not been assigned definitive functions is an important aspect of molecular evolution. Importantly, nucleotide substitution types and rates suggest possible reasons for not being able to find homologues for Ymf genes. Additionally, comparative genomic analysis of complete Mt genomes is essential in identifying biologically significant motifs such as control regions

Risk of chronic kidney disease after cancer nephrectomy.

The incidence of early stage renal cell carcinoma (RCC) is increasing and observational studies have shown equivalent oncological outcomes of partial versus radical nephrectomy for stage I tumours. Population studies suggest that compared with radical nephrectomy, partial nephrectomy is associated with decreased mortality and a lower rate of postoperative decline in kidney function. However, rates of chronic kidney disease (CKD) in patients who have undergone nephrectomy might be higher than in the general population. The risks of new-onset or accelerated CKD and worsened survival after nephrectomy might be linked, as kidney insufficiency is a risk factor for cardiovascular disease and mortality. Nephron-sparing approaches have, therefore, been proposed as the standard of care for patients with type 1a tumours and as a viable option for those with type 1b tumours. However, prospective data on the incidence of de novo and accelerated CKD after cancer nephrectomy is lacking, and the only randomized trial to date was closed prematurely. Intrinsic abnormalities in non-neoplastic kidney parenchyma and comorbid conditions (including diabetes mellitus and hypertension) might increase the risks of CKD and RCC. More research is needed to better understand the risk of CKD post-nephrectomy, to develop and validate predictive scores for risk-stratification, and to optimize patient management

Clinical management of borderline tumours of the ovary: results of a multicentre survey of 323 clinics in Germany

The aim of this survey was to analyse the standard of care in diagnostic, surgery, chemotherapy and aftercare management for patients with borderline tumours of the ovary (BOTs) in Germany. A structured questionnaire comprising different dimensions was sent to all 1114 gynaecological departments. The questionnaire could be returned anonymously. The overall response rate was 29.0% (323 departments). Most departments were on secondary care (71.8%), tertiary care (23.2%) or university hospital (5.0%) level. Most clinicians performed not more than five BOT operations (89.2%) per year. Most departments (93.2%) used in addition to classical bimanual examination and vaginal ultrasound, tumour marker CA-125 detection, CT scan, MRI or PET-CT techniques. Departments in university and tertiary care hospitals performed more often a fresh frozen section (87 vs 64%). In young women, clinicians performed much seldom unilateral salpingo-oophorectomy (92%) and only in 53% biopsies of the contralateral ovary. Generally, biopsies of the contralateral ovary were performed in 4–53% of the patients. Chemotherapy was mostly favoured in ‘high-risk' patients with tumour residual, microinvasion or invasive implants. Thus, a high grade of insecurity in diagnostic and therapy of BOT exists in some gynaecological departments and underlines the need for more educational and study activities