Miracle-dz/UniFAR-FTUs huggingface dataset:
A carbohydrate mimetic peptide modified size-shrinkable micelle nanocluster for anti-tumor targeting and penetrating drug delivery

Purpose To deliver the chemotherapeutics through the nanoparticles, the delivery system should accumulate at the tumor site first and then penetrate through the interstitium into the interior. The specific tumor-targeting pathway mediated via the receptor-ligand binding could achieve the desirable accumulation of nanoparticles, and the nanoparticles with smaller sizes were required for penetration. Methods and materials We constructed a size-shrinkable nanocluster modified with a tumor-targeting motif IF-7 (IF-7-MNC) based on a pH-sensitive framework which could be disintegrated in an acid environment to release the micelles aggregated inside. The micelles were constructed by amphiphilic block copolymers PEG−PLA to encapsulate paclitaxel (PTX), while the cross-linked framework consisting of TPGS-PEI was used as a net to gather and release micelles. This nanoplatform could specifically bind with the tumor receptor Annexin A1 through the ligand IF-7 and then shrunk into small micelles with a desirable size for penetration. Conclusion IF-7-MNC of 112.27±6.81 nm could shrink into micelles in PBS (0.01 M, pH 5.0) with sizes of 14.89±0.32 nm. The cellular-uptake results showed that IF-7-MNC could be significantly internalized by A549 cells and HUVEC cells, while the penetration of IF-7-MNC could be more prominent into the 3D-tumor spheroids compared with that of MNC. The biodistribution results displayed that the fluorescence of IF-7-MNC in the tumor site at 24 hrs was 4.5-fold stronger than that of MNC. The results of anti-tumor growth demonstrated that IF-7-MNC was more favorable for the tumor therapy than MNC, where the inhibitory rate of tumor growth was 88.29% in the PTX-loaded IF-7-MNC (IF-7-PMNC) treated group, significantly greater than PMNC treatment group (p<0.05).
Analysis of Promoter-Associated Chromatin Interactions Reveals Biologically Relevant Candidate Target Genes at Endometrial Cancer Risk Loci

The identification of target genes at genome-wide association study (GWAS) loci is a major obstacle for GWAS follow-up. To identify candidate target genes at the 16 known endometrial cancer GWAS risk loci, we performed HiChIP chromatin looping analysis of endometrial cell lines. To enrich for enhancer-promoter interactions, a mechanism through which GWAS variation may target genes, we captured loops associated with H3K27Ac histone, characteristic of promoters and enhancers. Analysis of HiChIP loops contacting promoters revealed enrichment for endometrial cancer GWAS heritability and intersection with endometrial cancer risk variation identified 103 HiChIP target genes at 13 risk loci. Expression of four HiChIP target genes (SNX11, SRP14, HOXB2 and BCL11A) was associated with risk variation, providing further evidence for their regulation. Network analysis functionally prioritized a set of proteins that interact with those encoded by HiChIP target genes, and this set was enriched for pan-cancer and endometrial cancer drivers. Lastly, HiChIP target genes and prioritized interacting proteins were over-represented in pathways related to endometrial cancer development. In summary, we have generated the first global chromatin looping data from endometrial cells, enabling analysis of all known endometrial cancer risk loci and identifying biologically relevant candidate target genes.
Restriction of anthropogenic foods alters a top predator's diet and intraspecific interactions

Anthropogenic foods are utilized by many animals around the world, and these resources could impact dietary preferences and intra- and interspecific interactions. Under a quasi-Before-After-Control-Impact experimental design, we assessed how dingoes (Canis dingo) responded to a decline in anthropogenic foods in the Tanami Desert, central Australia. We did so by assessing dingo diets close to and away from human influence during a period when food waste was available at two rubbish tips, and then during a period when food waste was restricted at one of the tips. Our results demonstrate that access to anthropogenic foods can alter a top predator's diet. Namely, dingoes showed a preference for eating the desert mouse (Pseudomys desertor) in areas where food waste was restricted, whereas dingo diets did not reflect ambient prey availability at areas where food waste was constantly available. Reduced availability of food waste also affected interactions between dingoes, with cannibalism decreasing where food waste was removed, and it may have increased consumption of a subordinate mesopredator, the feral cat (Felis catus). By implication, efforts to manage food waste could reestablish or strengthen interactions between predators and their wild prey with possible cascading consequences for ecosystems.
Microbial community dissimilarity for source tracking with application in forensic studies

Microbial source-tracking is a useful tool for trace evidence analysis in Forensics. Community-wide massively parallel sequencing profiles can bypass the need for satellite microbes or marker sets which are unreliable when handling unstable samples. We propose a method utilizing Aitchison distance to select important suspects/sources and then propose several methods to estimate the proportions of microbial communities/samples coming from important suspects/sources. A series of comprehensive simulation studies show that these methods are capable of accurate selection and improve the performance of current methods Bayesian SourceTracker and FEAST in the presence of noise microbial sources.
The complete mitochondrial genome of Semnopithecus schistaceus

Abstract Semnopithecus schistaceus Hodgson, 1840 belongs to subfamily Colobinae, family Cercopithecidae. This species was once mixed with S. entellus. The conservation status of this species is Least Concern (LC) in IUCN. In China, this species has been considered as Critically Endangered (CR) by the Red List of China’s vertebrates. In this study, the complete mitogenome of S. schistaceus was determined. The mitogenome is a circular molecule of 16,534 bp in length, containing 13 protein－coding genes, 2 ribosome RNA genes, 1 light strand replication origin (OL), 22 transfer RNA genes, and 1 non－coding region. We reconstructed a phylogenetic tree based on Bayesian inference for 19 primates species. The Cyt b p-distance is 0.029 between S. schistaceu and S. entellus. Thus, the taxonomic status of these two species remains to be further studied.
RESULTS OF Fc-PROTEIN FUSION TECHNOLOGY APPLICATION FOR VACCINE DESIGN AGAINST INFECTIOUS DISEASES OF ANIMALS AND HUMAN

The main criteria for current vaccines design are effectiveness, efficaciousness and safety. Increasing requirements for vaccine safety and purity push forward not only classical vaccine development, but also new generation vaccine technology, including sub-unit, recombinant, antiidiotypic, DNA vaccines etc. This recombinant technology has already demonstrated its advantage, efficaciousness and safety in a large field of therapeutic and curative drug development for animal and human (S. Khan et al., 2016). In 2011, six novel drugs were created based on the new Fc-fusion protein technology. Most of the newly developed drugs affect receptor-ligand interactions, acting as antagonists by blocking direct receptor binding, i.e. Enbrel (etanercept; Amgen, USA), Zaltrap (aflibercept; Sanofi, France), Arcalyst (rilonacept; Regeneron, USA), or as agonists for direct stimulation of receptor function which augment immune response as Amevive (alefacept, Astellas, USA) does, or decrease immune response as Nplate (romiplostim; Amgen, USA) does. In this review, we pay attention to the most relevant results from the last few years for virus and bacterial vaccine designed based on Fc-fusion technology. The Fc-chimeras are hybrid sequences in which Fc-fragment of IgG (Fc-IgG) and targeted therapeutic protein are fused in an entire protein molecule (V. Pechtner et al., 2017). In this fusion, the hinge region of Fc-IgG is a flexible spacer between therapeutic protein and conservative part of IgG. It helps to minimize potential negative effect of two functional domains to each other. Therapeutic drugs based on Fc-fusion proteins are divided in three types, the receptor-Fc, peptide-Fc, and monomer-Fc. The Fc-fused proteins have tremendous therapeutic potential, since Fc domain in this molecules helps to specifically augment the pharmacodynamics values. Presence of Fc-domain in hybrid molecules prolongs half elimination of protein from plasma, which extends drug therapeutic activity and slows down kidney clearance for large molecules. Here, we summarize the most significant experimental data of Fc-fusion technology application against such pathogens as human immunodeficiency virus (D. Capon et al., 1989), Ebola virus (K. Konduru et al., 2011), Dengue virus (M.Y. Kim et al., 2018), influenza virus (L. Du et al., 2011), Mycobacterium tuberculosis (S. Soleimanpour et al., 2015), classical swine fever virus (Z. Liu et al., 2017). We also discuss the critical aspects of mechanism of action, drug design and Fc-fused protein production. Targeted activation of effector systems boosts protective potential of immunogenic molecules and broadens its application. The interest of this review is focused on an application of Fc-fused proteins as potential vaccines against infectious human and animal diseases. We also briefly discuss the perspectives of Fc-fused antigens for novel effective medicine developments using African swine fever virus as an example.
Does Wolbachia Change Diapause and Energy Reserves of Trichogramma brassicae in Response to Light Wavelengths

The present study examined the light wavelengths effect on the diapause percentage of progeny and energy reserves of maternal generation in sexual and asexual Trichogramma brassicae that had been reared under different light wavelengths before oviposition. Photoperiod has a maternal effect on the diapause induction in Trichogramma wasps; however, the light wavelengths effect on their diapause has not been studied. In this study, we reared the maternal generation of both strains under five light wavelengths including blue (455~475 nm), green (515~535 nm), orange (585~595 nm), red (620~630 nm), and white (5,000~10,000 K), and allowed 24 hours old females to oviposit in Ephestia kuehniella eggs. The diapausing generation was placed at 10°C and absolute darkness for two months. The results showed that Wolbachia infection and light wavelengths had significant effects on the diapause percentage and energy reserves of T. brassicae, excepting glycogen contents. The maximum and minimum diapause percentage was observed under green and white light in asexual, and under white and green light in sexual strain. The data showed that the sexual strain had lower lipid and protein levels than the asexual strain, except when exposed under white light. The diapause percentage in the sexual strain was higher than in the asexual strain under all light wavelengths, and the reaction of parasitoids toward light wavelengths was different in the two strains. Therefore, Wolbachia can cause a different reaction to light wavelengths in both diapause percentage and pattern of the parasitoid. These results should be considered to improve mass-rearing and long-term storage of this parasitoid.
Identification of Platform-Independent Diagnostic Biomarker Panel for Hepatocellular Carcinoma Using Large-Scale Transcriptomics Data

The high mortality rate of hepatocellular carcinoma (HCC) is primarily due to its late diagnosis. In the past numerous attempts have been made to design genetic biomarkers for the identification of HCC; unfortunately, most of the studies are based on a small dataset obtained from a specific platform or lack of their reasonable validation performance on the external datasets. In order to identify a universal expression-based diagnostic biomarker panel for HCC that can be applicable across multiple platforms; we have employed large scale transcriptomic profiling datasets containing a total of 2,306 HCC and 1,655 non-tumorous tissue samples. These samples were obtained from 29 studies generated by mainly four types of profiling techniques include Affymetrix, Illumina, Agilent and High-throughput-seq, which implemented a wide range of platforms. Firstly, we scrutinized 26 genes that are differentially expressed or regulated in uniform pattern among numerous datasets. Subsequently, we identified three genes (FCN3, CLEC1B, & PRC1) panel-based HCC biomarker using different machine learning techniques include Simple-threshold based approach, Extra Trees, Support Vector Machine, Random Forest, K Neighbors Classifier, Logistic Regression etc. Three-genes panel-based HCC biomarker classified HCC samples and non-tumorous samples of training and three external validation datasets with an accuracy between 93 to 98% and AUROC (Area Under Receiver Operating Characteristic curve) in a range of 0.97 to 1.0. Furthermore, the prognostic potential of these genes was evaluated on TCGA cohort and GSE14520 cohort using univariate survival analysis revealed that these genes are independent prognostic indicators for various types of the survivals, i.e. OS (Overall Survival), PFS (Progression-Free Survival), DFS/RFS (Disease-Free Survival/Recurrence-Free Survival) and DSS (Disease-Specific Survival) of HCC patients and significantly stratify high-risk and low-risk HCC patients (p-value <0.05). In conclusion, we identified a universal platform-independent three genes-based biomarker that can predict HCC patients with high precision; also possess significant prognostic potential. Eventually, to provide service to the scientific community, we developed a webserver HCCPred based on the above study (http://webs.iiitd.edu.in/raghava/hccpred/).
Simplification of Ribosomes in Bacteria with Tiny Genomes

The ribosome is an essential cellular machine performing protein biosynthesis. Its structure and composition are highly conserved in all species. However, some bacteria have been reported to have an incomplete set of ribosomal proteins. We have analyzed ribosomal protein composition in 214 small bacterial genomes (< 1 Mb) and found that although the ribosome composition is fairly stable, some ribosomal proteins may be absent, especially in bacteria with dramatically reduced genomes. The protein composition of the large subunit is less conserved than that of the small subunit. We have identified the set of frequently lost ribosomal proteins and demonstrated that they tend to be situated on the ribosome surface and have fewer contacts to other ribosome components. Moreover, loss of some proteins is correlated, at least in one case leading to the loss of a complete functional block. Additionally, the reduction of rRNA is also common in bacteria with short genomes, and deletions mostly occur in free loops. The loss of ribosomal protein uL24 occurs simultaneously with the loss of the corresponding binding site in rRNA. Finally, the loss of the anti-Shine-Dalgarno sequence is not correlated with the genome size or the loss of particular ribosomal proteins.
Adjusting ADJUST: Optimizing the ADJUST Algorithm for Pediatric Data Using Geodesic Nets

A major challenge for electroencephalograph (EEG) studies on pediatric populations is that large amounts of data are lost due to artifacts (e.g., movement and blinks). Independent component analysis (ICA) can separate artifactual and neural activity, allowing researchers to remove such artifactual activity and retain a greater percentage of EEG data for analyses. However, manual identification of artifactual components is time consuming and requires subjective judgment. Automated algorithms, like ADJUST and ICLabel, have been validated on adults using the international 10-20 system, but to our knowledge no such algorithms have been optimized for the geodesic sensor net, which is often used with infants and children. Therefore, in an attempt to automate artifact selection for pediatric data collected with geodesic nets, we modified ADJUST’s algorithm. Our “adjusted-ADJUST” algorithm was compared to the “original-ADJUST” algorithm and ICLabel in adults, children, and infants on three different performance measures: respective classification agreement with expert coders, the number of trials retained following artifact removal, and the reliability of the EEG signal after pre-processing with each algorithm. Overall, the adjusted-ADJUST algorithm performed better than the original-ADJUST algorithm and no ICA correction with adult and pediatric data. Moreover, it performed better than ICLabel for pediatric data. These results indicate that optimizing existing algorithms for data collected with a geodesic net improves artifact classification and retains more trials, potentially facilitating EEG studies with pediatric populations.
Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma

Alternative polyadenylation (APA) is a gene regulatory process that dictates mRNA 3’-UTR length, resulting in changes in mRNA stability and localization. APA is frequently disrupted in cancer and promotes tumorigenesis through altered expression of oncogenes and tumor suppressors. Pan-cancer analyses have revealed common APA events across the tumor landscape; however, little is known about tumor type-specific alterations that may uncover novel events and vulnerabilities. Here we integrate RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA) to comprehensively analyze APA events in 148 pancreatic ductal adenocarcinomas (PDAs). We report widespread, recurrent and functionally relevant 3’-UTR alterations associated with gene expression changes of known and newly identified PDA growth-promoting genes and experimentally validate the effects of these APA events on expression. We find enrichment for APA events in genes associated with known PDA pathways, loss of tumor-suppressive miRNA binding sites, and increased heterogeneity in 3’-UTR forms of metabolic genes. Survival analyses reveal a subset of 3’-UTR alterations that independently characterize a poor prognostic cohort among PDA patients. Finally, we identify and validate the casein kinase CK1α as an APA-regulated therapeutic target in PDA. Knockdown or pharmacological inhibition of CK1α attenuates PDA cell proliferation and clonogenic growth. Our single-cancer analysis reveals APA as an underappreciated driver of pro-tumorigenic gene expression in PDA via the loss of miRNA regulation.
Magainin 2 and PGLa in Bacterial Membrane Mimics II: Membrane Fusion and Sponge Phase Formation

We studied the synergistic mechanism of equimolar mixtures of magainin 2 (MG2a) and PGLa in phosphatidylethanolamine/phosphatidylglycerol mimics of Gram-negative cytoplasmic membranes. In a preceding paper [Pachler et al., Biophys. J. 2019 xxx], we reported on the early onset of parallel heterodimer formation of the two antimicrobial peptides already at low concentrations and the resulting defect formation in membranes. Here, we focus on the structures of the peptide/lipid aggregates occurring in the synergistic regime at elevated peptide concentrations. Using a combination of calorimetric, scattering, electron microscopic and in silico techniques, we demonstrate that the two peptides, even if applied individually, transform originally large unilamellar vesicles into multilamellar vesicles, with a collapsed interbilayer spacing resulting from peptide induced adhesion. Interestingly, the adhesion does not lead to a peptide induced lipid separation of charged and charge neutral species. In addition to this behavior, equimolar mixtures of MG2a and PGLa formed surface-aligned fibril-like structures, which induced adhesion zones between the membranes and the formation of transient fusion stalks in molecular dynamics simulations and a coexisting sponge phase observed by small-angle X-ray scattering. The previously reported increased leakage of lipid vesicles of identical composition in the presence of MG2a/PGLa mixtures is therefore related to a peptide-induced cross-linking of bilayers. STATEMENT OF SIGNIFICANCE We demonstrate that the synergistic activity of the antimicrobial peptides MG2a and PGLa correlates to the formation of surface-aligned fibril-like peptide aggregates, which cause membrane adhesion, fusion and finally the formation of a sponge phase.
Identification of orthotropic material parameters for acute, necrotic, fibrotic and remodelling myocardial infarcts in the rat

Finite element (FE) models have been effectively utilized in studying biomechanical aspects of myocardial infarction (MI). Although the rat is a widely used animal model for MI, there is a lack of material parameters based on anisotropic constitutive models for rat myocardial infarcts in literature. This study aimed at employing inverse methods to identify the parameters of an orthotropic constitutive model for myocardial infarcts in the acute, necrotic, fibrotic and remodelling phases utilizing the biaxial mechanical data developed in a previous study. FE model was developed mimicking the setup of the biaxial tensile experiment. The orthotropic case of the generalized Fung constitutive model was utilized to model the material properties of the infarct. The parameters of Fung model were optimized so that the FE solution best fitted the biaxial experimental stress-strain data. A genetic algorithm was used to minimize the objective function. Fung orthotropic material parameters for different infarct stages were identified. The FE model predictions best approximated the experimental data of the 28 days infarct stage with 3.0% mean absolute percentage error. The worst approximation was for the 7 days stage with 3.6% error. This study demonstrated that the experimental biaxial stress-strain data of healing rat infarcts could be successfully approximated using inverse FE methods and genetic algorithms. The material parameters identified in this study will provide an essential platform for FE investigations of biomechanical aspects of MI and the development of therapies.
Revision of the species of Meromyza Meigen (Diptera, Chloropidae) from Finland

The Finnish species of the genus Meromyza are revised. Three new species M. ingrica sp. n. , M. lidiae sp. n. and M. zimzerla sp. n. are described using material from adjacent parts of Russia, Estonia and Latvia. The total number of Finnish Meromyza species is 16. Illustrations of the male genitalia, maps of records in Finland for all the species and a key to the known species from Finland are provided.
LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility

Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from Lis1-deficient mutants. Lis1-deficient neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with mislocalization of furrow-associated markers, associated with actomyosin dysfunction and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility is tightly controlled to execute proper daughter cell separation.