A Mucormycosis Case in a Cirrhotic Patient Successfully Treated with Posaconazole and Review of Published Literature

Mucormycosis is an invasive fungal infection associated with a high mortality rate, especially in immunocompromised hosts. Mucormycosis rarely occurs in cirrhotic patients. Here, we report a case of mucormycosis with underlying liver cirrhosis and diabetes mellitus. The patient suffered from maxillary sinusitis and osteomyelitis, and the infection was successfully treated with antifungal agents, surgical debridement, and hyperbaric oxygen therapy. The antifungal treatments used were liposomal amphotericin B, itraconazole, and posaconazole. Although our patient had liver cirrhosis (Child-Pugh classification B), no hepatic decompensation was developed during the treatment course of posaconazole. This is the first report of the safe and effective use of posaconazole for the treatment of mucormycosis in a cirrhotic patient.     

Multimeric BLM is dissociated upon ATP hydrolysis and functions as monomers in resolving DNA structures

Bloom (BLM) syndrome is an autosomal recessive disorder characterized by an increased risk for many types of cancers. Previous studies have shown that BLM protein forms a hexameric ring structure, but its oligomeric form in DNA unwinding is still not well clarified. In this work, we have used dynamic light scattering and various stopped-flow assays to study the active form and kinetic mechanism of BLM in DNA unwinding. It was found that BLM multimers were dissociated upon ATP hydrolysis. Steady-state and single-turnover kinetic studies revealed that BLM helicase always unwound duplex DNA in the monomeric form under conditions of varying enzyme and ATP concentrations as well as 3′-ssDNA tail lengths, with no sign of oligomerization being discerned. Measurements of ATPase activity further indicated that BLM helicase might still function as monomers in resolving highly structured DNAs such as Holliday junctions and D-loops. These results shed new light on the underlying mechanism of BLM-mediated DNA unwinding and on the molecular and functional basis for the phenotype of heterozygous carriers of BLM syndrome.     

Effect of relative humidity on population growth of <Emphasis Type="Italic">Apolygus lucorum</Emphasis> (Heteroptera: Miridae)

Apolygus lucorum (Meyer-Dür) (Heteroptera: Miridae) is a significant insect pest of cotton, Chinese dates, grapes and many other crops in China, and its populations typically increase after heavy rains. However, the intrinsic mechanism of the rainfall-dependent outbreak is not yet fully understood. In our study, the effect of different relative humidity (RH), 40, 50, 60, 70, and 80% RH, on population growth of A. lucorum was evaluated in the laboratory. High humidity (e.g. 70 and 80% RH) was observed to significantly increase egg and nymph survival, prolong adult life longevity, and improve female fecundity. However, low humidity (e.g. 40 and 50% RH) led to unfavorable effects on survival and fecundity. As a result, the intrinsic capacity for increase (r _m), net production (R _o), and the finite rate of increase (λ) of A. lucorum population greatly increased with increasing relative humidity. Additionally, the relationships between r _m and R _o and relative humidity were good fits to the logistic models y = 36.82/(1 + Exp(10.76 − 0.19x)) (p < 0.001) and y = 0.10/(1 + Exp(9.26 − 0.19x)) (p = 0.003), respectively. This study provides insight into the phenology of A. lucorum, and may contribute to modeling of its population dynamics.     

Solution-Phase, parallel synthesis and pharmacological evaluation of acylguanidine derivatives as potential sodium channel blockers

Solution-phase synthesis of various acylguanidine derivatives and the evaluation of a small library of compounds as potential sodium channel blockers are described.     

Insertion of carrier proteins into hydrophilic loops of the Escherichia coli lactose permease

We describe the design and characterization of a set of fusion proteins of the Escherichia coli lactose (lac) permease in which a set of five different soluble “carrier” proteins (cytochrome_b562, flavodoxin, T4 lysozyme, β-lactamase and 70 kDa heat shock ATPase domain) were systematically inserted into selected loop positions of the transporter. The design goal was to increase the exposed hydrophilic surface area of the permease, while minimizing the internal flexibility of the resulting fusion proteins in order to improve the crystallization properties of the membrane protein. Fusion proteins with insertions into the central hydrophilic loop of the lac permease were active in transport lactose, although only the fusion proteins with E. coli cytochrome_b562, E. coli flavodoxin or T4 lysozyme were expressed at near wild-type lac permease levels. Eight other loop positions were tested with these three carriers, leading to the identification of additional fusion proteins that were active and well-expressed. By combining the results from the single carrier insertions, we have expressed functional “double fusion” proteins containing cytochrome_b562 domains inserted in two different loop positions.     

In-depth Profiling and Quantification of the Lysine Acetylome in Hepatocellular Carcinoma with a Trapped Ion Mobility Mass Spectrometer

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with limited therapeutic options. Comprehensive investigation of protein posttranslational modifications in HCC is still limited. Lysine acetylation is one of the most common types of posttranslational modification involved in many cellular processes and plays crucial roles in the regulation of cancer. In this study, we analyzed the proteome and K-acetylome in eight pairs of HCC tumors and normal adjacent tissues using a timsTOF Pro instrument. As a result, we identified 9219 K-acetylation sites in 2625 proteins, of which 1003 sites exhibited differential acetylation levels between tumors and normal adjacent tissues. Interestingly, many novel tumor-specific K-acetylation sites were characterized, for example, filamin A (K865), filamin B (K697), and cofilin (K19), suggesting altered activities of these cytoskeleton-modulating molecules, which may contribute to tumor metastasis. In addition, we observed an overall suppression of protein K-acetylation in HCC tumors, especially for enzymes from various metabolic pathways, for example, glycolysis, tricarboxylic acid cycle, and fatty acid metabolism. Moreover, the expression of deacetylase sirtuin 2 (SIRT2) was upregulated in HCC tumors, and its role of deacetylation in HCC cells was further explored by examining the impact of SIRT2 overexpression on the proteome and K-acetylome in Huh7 HCC cells. SIRT2 overexpression reduced K-acetylation of proteins involved in a wide range of cellular processes, including energy metabolism. Furthermore, cellular assays showed that overexpression of SIRT2 in HCC cells inhibited both glycolysis and oxidative phosphorylation. Taken together, our findings provide valuable information to better understand the roles of K-acetylation in HCC and to treat this disease by correcting the aberrant acetylation patterns.     

First record of symphoresy between nymphs of the stonefly Kempnyia tijucana,and chironomid larvae,Nanocladius (Plecopteracoluthus) sp., in the Neotropics

The symphoretic relationship between a species of Nanocladius (Plecopteracoluthus) (Diptera, Chironomidae) and Kempnyia tijucana (Plecoptera, Perlidae) is recorded and described for the first time from southeastern Brazil. About 31% of the collected perlids were hosts of the chironomid larvae. The entire larval cycle of N. (Plecopteracoluthus) sp. may be completed on a single instar of K. tijucana and the larval position on the host varied according to the stage of development of the chironomid, apparently being constant for young and old instars.     

Wildcat population density in NE Portugal: A regional stronghold for a nationally threatened felid

Population density data on depleted and endangered wildlife species are essential to assure their effective management and, ultimately, conservation. The European wildcat is an elusive and threatened species inhabiting the Iberian Peninsula, with fragmented populations and living in low densities. We fitted spatial capture–recapture models on camera-trap data, to provide the first estimate of wildcat density for Portugal and assess the most influential drivers determining it. The study was implemented in Montesinho Natural Park (NE Portugal), where we identified nine individuals, over a total effort of 3,477 trap-nights. The mean density estimate was 0.032 ± 0.012 wildcat/km², and density tended to increase with distance to humanized areas, often linked to lower human disturbance and domestic cat presence, with forest and herbaceous vegetation cover and with European rabbit abundance. Although, this density estimate is within the range of values estimated for protected areas elsewhere in the Iberian Peninsula, our estimates are low at the European level. When put in context, our results highlight that European wildcats may be living in low population densities across the Iberian Mediterranean biogeographic region. No phenotypic domestic or hybrid cats were detected, suggesting potentially low admixture rates between the two species, although genetic sampling would be required to corroborate this assertion. We provide evidence that Montesinho Natural Park may be a suitable area to host a healthy wildcat population, and thus be an important protected area in this species' conservation context.