Sterigmatocystin limits plasmodium falciparum proliferation and transmission

As part of our drug discovery program against malaria, the Penicillium janthinellum ex-tract was discovered to inhibit P. falciparum proliferation in blood and transmission to mosquitoes. Bioactivity-guided fractionation of P. janthinellum extraction was carried out using chromatographic techniques. We determined the activities of fractions against Plasmodium falciparum asexual stage parasite proliferation in culture and sexual stage parasite transmission to mosquitoes using standard membrane feeding assays (SMFA). One active compound was isolated. Based on mass spectrom-etry and nuclear magnetic resonance profiles, the compound was structurally determined to be sterigmatocystin. Sterigmatocystin inhibited P. falciparum proliferation in the blood with an IC50 of 34 µM and limited the sexual parasites to infect mosquitoes with an IC50 of 48 µM. Meanwhile, sterigmatocystin did not show any acute toxicity to human kidney cells at a concentration of 64 µM or lower. Sterigmatocystin can be used as a drug lead for malaria control and as a probe to understand molecular mechanisms of malaria transmission

Identifying crystal accumulation in granitoids through amphibole composition and in situ zircon O isotopes in North Qilian Orogen

Granitoids are the main constituents of the continental crust, and an understanding of their petrogenesis is key to the origin and evolution of continents. Whether crystal fractionation is the dominant way to generate evolved magmas has long been debated, mostly because such processes would produce large volumes of complementary cumulates, which remains elusive. Mafic magmatic enclaves (MMEs) are ubiquitous in granitoids and their presence was initially recognized as cumulates. However, because many MMEs lack obvious evidence of accumulation, such as the classic cumulate textures and modal layering, the cumulate origin of MMEs has been abandoned and the model of magma mixing between mafic and felsic magmas has become popular. In this study, we conduct a combined study of amphibole composition and in situ O isotopes in zircons on three suites of orogenic granitoids with MMEs from the North Qilian Orogenic Belt (NQOB). We find that the MMEs and their host granodiorites show overlapping zircon δ18O values, affirming that they share the same parental magmas. The amphibole compositions indicate that amphiboles from the MMEs are not in equilibrium with a melt whose composition was that of the bulk-rock. These new data, together with the published bulk-rock data, suggest that the MMEs in our study have clear cumulate signatures and are thus of cumulate origin. Our study provides evidence for crystal accumulation in granitoids in the NQOB. This new understanding calls for re-examination on the petrogenesis of some intermediate magmatic rocks (granitoid/andesite) in discussing models of continental crustal growth

A diverse global fungal library for drug discovery

Background: Secondary fungal metabolites are important sources for new drugs against infectious diseases and cancers. Methods: To obtain a library with enough diversity, we collected about 2,395 soil samples and 2,324 plant samples from 36 regions in Africa, Asia, and North America. The collection areas covered various climate zones in the world. We examined the usability of the global fungal extract library (GFEL) against parasitic malaria transmission, Gram-positive and negative bacterial pathogens, and leukemia cells. Results: Nearly ten thousand fungal strains were isolated. Sequences of nuclear ribosomal internal transcribed spacer (ITS) from 40 randomly selected strains showed that over 80% were unique. Screening GFEL, we found that the fungal extract from was able to block transmission to , and the fungal extract from was able to kill myelogenous leukemia cell line K562. We also identified a set of candidate fungal extracts against bacterial pathogens

Low-degree melt metasomatic origin of heavy Fe isotope enrichment in the MORB mantle

Studies of mid-ocean ridge basalts (MORB) show a variable Fe isotope composition of the oceanic upper mantle. To test a recent hypothesis that heavy Fe isotope enrichment in the MORB mantle results from the same process of incompatible element enrichment, we conduct an Fe isotope study of well-characterized MORB samples from a magmatically robust segment (OH-1) of the Mid-Atlantic Ridge (MAR) at ∼ 35°N. The data show large Fe isotope variation (Fe = +0.03 to +0.18‰) that correlates well with the abundances and ratios of more-to-less incompatible elements and with Sr-Nd-Hf isotopes. Our findings in support of the hypothesis can be detailed as follows: (1) the oceanic upper mantle has a heterogeneous Fe isotope composition on varying small spatial scales with isotopically heavy Fe (high-Fe) preferentially associated with pyroxenite lithologies; (2) such lithologies, which are also enriched in the progressively more incompatible elements, are of low-degree (low-F) melt metasomatic origin; (3) with all the conceivable processes considered, the low-F melt metasomatism takes place at the lithosphere-asthenosphere boundary (LAB) beneath ocean basins through crystallization of incipient (Low-F) melt in the seismic low velocity zone (LVZ) at the base of the growing oceanic lithosphere (i.e., LAB) over the Earth's history since the onset of plate tectonics, forming composite lithologies with geochemically enriched pyroxenite veins dispersed in the depleted peridotite matrix; (4) such mantle of composite lithology when transported to beneath the present-day ocean ridges will undergo decompression melting and produce MORB melts with geochemical trends of “melting-induced mixing” as observed at the MAR and global MORB; (5) we predict all this to be a globally common process and widespread

Iron isotope fractionation during skarn Cu-Fe mineralization

Fe isotopes have been applied to the petrogenesis of ore deposits. However, the behavior of iron isotopes in the mineralization of porphyry-skarn deposits is still poorly understood. In this study, we report the Fe isotopes of ore mineral separations (magnetite, pyrite, chalcopyrite and pyrrhotite ) from two different skarn deposits, i.e., the Tonglvshan Cu-Fe skarn deposit developed in an oxidized hydrothermal system and the Anqing Cu skarn deposit developed in a reduced hydro-thermal system. In both deposits, the Fe isotopes of calculated equilibrium fluids are lighter than those of the intrusions responsible for the skarn and porphyry mineralization, corroborating the “light-Fe fluid” hypothesis. Interestingly, chalcopyrite in the oxidized-Tonglvshan skarn deposit has lighter Fe than chalcopyrite in the reduced-Anqing skarn deposit, which is best understood as the result of the prior precipitation of magnetite (heavy Fe) from the ore fluid in the oxidized-Tonglvshan systems and the prior precipitation of pyrrhotite (light Fe) from the ore fluid in the reduced-Anqing system. The δ 56Fe for pyrite shows an inverse correlation with δ 56Fe of magnetite in the Tonglvshan. In both deposits, the Fe isotope fractionation between chalcopyrite and pyrite is offset from equilibrium line at 350℃ and lies between the FeS-chalcopyrite equilibrium line and pyrite-chalcopyrite equilibrium line at 350℃. These observations are consistent with the FeS pathway towards pyrite formation. That is, Fe isotopes fractionation during pyrite formation depends on a path, from the initial FeS-fluid equilibrium towards the pyrite-fluid equilibrium due to the increasing extent of Fe isotopic exchange with fluids. This finding, together with the data from other deposits, allows us to propose that the pathway effect of pyrite formation in the Porphyry-skarn deposit mineralization is the dominant mechanism that controls Fe isotope characteristics

Integrating the Local Property and Topological Structure in the Minimum Spanning Tree Brain Functional Network for Classification of Early Mild Cognitive Impairment

Abnormalities in the brain connectivity in patients with neurodegenerative diseases, such as early mild cognitive impairment (EMCI), have been widely reported. Current research shows that the combination of multiple features of the threshold connectivity network can improve the classification accuracy of diseases. However, in the construction of the threshold connectivity network, the selection of the threshold is very important, and an unreasonable setting can seriously affect the final classification results. Recent neuroscience research suggests that the minimum spanning tree (MST) brain functional network is helpful, as it avoids the methodological biases while comparing networks. In this paper, by employing the multikernel method, we propose a framework to integrate the multiple properties of the MST brain functional network for improving the classification performance. Initially, the Kruskal algorithm was used to construct an unbiased MST brain functional network. Subsequently, the vector kernel and graph kernel were used to quantify the two different complementary properties of the network, such as the local connectivity property and the topological property. Finally, the multikernel support vector machine (SVM) was adopted to combine the two different kernels for EMCI classification. We tested the performance of our proposed method for Alzheimer's Disease Neuroimaging Initiative (ANDI) datasets. The results showed that our method achieved a significant performance improvement, with the classification accuracy of 85%. The abnormal brain regions included the right hippocampus, left parahippocampal gyrus, left posterior cingulate gyrus, middle temporal gyrus, and other regions that are known to be important in the EMCI. Our results suggested that, combining the multiple features of the MST brain functional connectivity offered a better classification performance in the EMCI

MSIsensor-ct: Microsatellite instability detection using cfDNA sequencing data

MOTIVATION: Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach. RESULTS: We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various levels of circulating tumor DNA (ctDNA) and sequencing depth showed 100% accuracy within the limit of detection (LOD) of 0.05% ctDNA content. MSIsensor-ct requires only BAM files as input, rendering it user-friendly and readily integrated into next generation sequencing (NGS) analysis pipelines. AVAILABILITY: MSIsensor-ct is freely available at https://github.com/niu-lab/MSIsensor-ct. SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online

Proteome changes of lungs artificially infected with H-PRRSV and N-PRRSV by two-dimensional fluorescence difference gel electrophoresis

<p>Abstract</p> <p>Background</p> <p>Porcine reproductive and respiratory syndrome with PRRS virus (PRRSV) infection, which causes significant economic losses annually, is one of the most economically important diseases affecting swine industry worldwide. In 2006 and 2007, a large-scale outbreak of highly pathogenic porcine reproductive and respiratory syndrome (PRRS) happened in China and Vietnam. However little data is available on global host response to PRRSV infection at the protein level, and similar approaches looking at mRNA is problematic since mRNA levels do not necessarily predict protein levels. In order to improve the knowledge of host response and viral pathogenesis of highly virulent Chinese-type PRRSV (H-PRRSV) and Non-high-pathogenic North American-type PRRSV strains (N-PRRSV), we analyzed the protein expression changes of H-PRRSV and N-PRRSV infected lungs compared with those of uninfected negative control, and identified a series of proteins related to host response and viral pathogenesis.</p> <p>Results</p> <p>According to differential proteomes of porcine lungs infected with H-PRRSV, N-PRRSV and uninfected negative control at different time points using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mass spectrometry identification, 45 differentially expressed proteins (DEPs) were identified. These proteins were mostly related to cytoskeleton, stress response and oxidation reduction or metabolism. In the protein interaction network constructed based on DEPs from lungs infected with H-PRRSV, HSPA8, ARHGAP29 and NDUFS1 belonged to the most central proteins, whereas DDAH2, HSPB1 and FLNA corresponded to the most central proteins in those of N-PRRSV infected.</p> <p>Conclusions</p> <p>Our study is the first attempt to provide the complex picture of pulmonary protein expression during H-PRRSV and N-PRRSV infection under the in vivo environment using 2D-DIGE technology and bioinformatics tools, provides large scale valuable information for better understanding host proteins-virus interactions of these two PRRSV strains.</p