Structural Characteristics and Phylogenetic Analysis of the Mitochondrial Genomes of Four Species (Hemiptera: Cicadellidae: Iassinae).

species are insects that have piercing-sucking mouthparts and belong to the Krisnini tribe in the Iassinae subfamily of leafhoppers in the Cicadellidae family. In this study, we sequenced and compared the mitochondrial genomes (mitogenomes) of four species. The results showed that all four mitogenomes were composed of cyclic double-stranded molecules and contained 13 protein-coding genes (PCGs) and 22 and 2 genes coding for tRNAs and rRNAs, respectively.

Transcriptional Dysregulations of Seven Non-Differentially Expressed Genes as Biomarkers of Metastatic Colon Cancer.

: Colon cancer (CC) is common, and the mortality rate greatly increases as the disease progresses to the metastatic stage. Early detection of metastatic colon cancer (mCC) is crucial for reducing the mortality rate. Most previous studies have focused on the top-ranked differentially expressed transcriptomic biomarkers between mCC and primary CC while ignoring non-differentially expressed genes.

Development of a New Class of CXCR4-Targeting Radioligands Based on the Endogenous Antagonist EPI-X4 for Oncological Applications.

The peptide fragment of human serum albumin that was identified as an inhibitor of C-X-C motif chemokine receptor 4 (CXCR4), termed EPI-X4, was investigated as a scaffold for the development of CXCR4-targeting radio-theragnostics. Derivatives of its truncated version JM#21 (ILRWSRKLPCVS) were conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and tested in Jurkat and Ghost-CXCR4 cells. Ligand-, -, -, -, -, -, and - were selected for radiolabeling.

Structural basis of ubiquitin-independent PP1 complex disassembly by p97.

The AAA+-ATPase p97 (also called VCP or Cdc48) unfolds proteins and disassembles protein complexes in numerous cellular processes, but how substrate complexes are loaded onto p97 and disassembled is unclear. Here, we present cryo-EM structures of p97 in the process of disassembling a protein phosphatase-1 (PP1) complex by extracting an inhibitory subunit from PP1. We show that PP1 and its partners SDS22 and inhibitor-3 (I3) are loaded tightly onto p97, surprisingly via a direct contact of SDS22 with the p97 N-domain.

The C-terminal 32-mer fragment of hemoglobin alpha is an amyloidogenic peptide with antimicrobial properties.

Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides.

Clp-targeting BacPROTACs impair mycobacterial proteostasis and survival.

The ClpC1:ClpP1P2 protease is a core component of the proteostasis system in mycobacteria. To improve the efficacy of antitubercular agents targeting the Clp protease, we characterized the mechanism of the antibiotics cyclomarin A and ecumicin. Quantitative proteomics revealed that the antibiotics cause massive proteome imbalances, including upregulation of two unannotated yet conserved stress response factors, ClpC2 and ClpC3.

IFNα primes cancer cells for Fusicoccin-induced cell death via 14-3-3 PPI stabilization.

The natural product family of the fusicoccanes (FCs) has been shown to display anti-cancer activity, especially when combined with established therapeutic agents. FCs stabilize 14-3-3 protein-protein interactions (PPIs). Here, we tested combinations of a small library of FCs with interferon α (IFNα) on different cancer cell lines and report a proteomics approach to identify the specific 14-3-3 PPIs that are induced by IFNα and stabilized by FCs in OVCAR-3 cells.

A Single Residue within the MCR-1 Protein Confers Anticipatory Resilience.

The envelope stress response (ESR) of Gram-negative enteric bacteria senses fluctuations in nutrient availability and environmental changes to avert damage and promote survival. It has a protective role toward antimicrobials, but direct interactions between ESR components and antibiotic resistance genes have not been demonstrated. Here, we report interactions between a central regulator of ESR , the two-component signal transduction system CpxRA (onjugative ilus epression), and the recently described mobile colistin resistance protein (MCR-1).

Gender-specific dysregulations of nondifferentially expressed biomarkers of metastatic colon cancer.

Colon cancer is a common cancer type in both sexes and its mortality rate increases at the metastatic stage. Most studies exclude nondifferentially expressed genes from biomarker analysis of metastatic colon cancers. The motivation of this study is to find the latent associations of the nondifferentially expressed genes with metastatic colon cancers and to evaluate the gender specificity of such associations.

Cationic Solution and Solid-State Emitters - Robust Imaging Agents for Cells, Bacteria, and Protists.

A library of eight different cationic emitters with emission properties in solution and in solid-state (solution and solid-state emitters - SSSE) is presented. These compounds, bearing either ammonium or pyridinium groups, have been investigated regarding their photophysical properties as well as their potential application in biological imaging. Besides high quantum yields as well as a high degree of stability during the imaging process, it was additionally revealed that a broad range of biological targets can be addressed, such as different bacterial strains, human cells as well as protists.

Tuning Nanobodies' Bioactivity: Coupling to Ultrasmall Gold Nanoparticles Allows the Intracellular Interference with Survivin.

Nanobodies are highly affine binders, often used to track disease-relevant proteins inside cells. However, they often fail to interfere with pathobiological functions, required for their clinical exploitation. Here, a nanobody targeting the disease-relevant apoptosis inhibitor and mitosis regulator Survivin (SuN) is utilized.

Systematic analysis of microtubule plus-end networks defines EB-cargo complexes critical for mitosis in budding yeast.

Microtubules are ubiquitous cytoskeletal polymers with essential functions in chromosome segregation, intracellular transport, and cellular morphogenesis. End-binding proteins (EBs) form the nodes of intricate microtubule plus-end interaction networks. Which EB binding partners are most critical for cell division and how cells organize a microtubule cytoskeleton in the absence of an EB protein are open questions.

Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription.

The human protease Taspase1 plays a pivotal role in developmental processes and cancerous diseases by processing critical regulators, such as the leukemia proto-oncoprotein MLL. Despite almost two decades of intense research, Taspase1's biology is, however, still poorly understood, and so far its cellular function was not assigned to a superordinate biological pathway or a specific signaling cascade. Our data, gained by methods such as co-immunoprecipitation, LC-MS/MS and Topoisomerase II DNA cleavage assays, now functionally link Taspase1 and hormone-induced, Topoisomerase IIβ-mediated transient DNA double-strand breaks, leading to active transcription.

Dual activity inhibition of threonine aspartase 1 by a single bisphosphate ligand.

Therapy resistance remains a challenge for the clinics. Here, dual-active chemicals that simultaneously inhibit independent functions in disease-relevant proteins are desired though highly challenging. As a model, we here addressed the unique protease threonine aspartase 1, involved in various cancers.

10q26 - The enigma in age-related macular degeneration.

Despite comprehensive research efforts over the last decades, the pathomechanisms of age-related macular degeneration (AMD) remain far from being understood. Large-scale genome wide association studies (GWAS) were able to provide a defined set of genetic aberrations which contribute to disease risk, with the strongest contributors mapping to distinct regions on chromosome 1 and 10. While the chromosome 1 locus comprises factors of the complement system with well-known functions, the role of the 10q26-locus in AMD-pathophysiology remains enigmatic.

Targeted Protein Unfolding at the Golgi Apparatus.

Maintaining protein homeostasis (proteostasis) is vital to cellular and organismal health. How the Golgi apparatus, the central protein maturation and sorting station in the cell, manages misfolded proteins to maintain proteostasis is still poorly understood. Here we present a strategy for targeted protein unfolding at the Golgi that enables studying Golgi-related protein quality control and stress-signaling pathways.

Advanced EPI-X4 Derivatives Covalently Bind Human Serum Albumin Resulting in Prolonged Plasma Stability.

Advanced derivatives of the ndogenous eptide nhibitor of CCR (EPI-X4) have shown therapeutic efficacy upon topical administration in animal models of asthma and dermatitis. Here, we studied the plasma stability of the EPI-X4 lead compounds WSC02 and JM#21, using mass spectrometry to monitor the chemical integrity of the peptides and a functional fluorescence-based assay to determine peptide function in a CXCR4-antibody competition assay. Although mass spectrometry revealed very rapid disappearance of both peptides in human plasma within seconds, the functional assay revealed a significantly higher half-life of 9 min for EPI-X4 WSC02 and 6 min for EPI-X4 JM#21.

Determination of antifungal activity and action mechanism of the modified Aurein 1.2 peptide derivatives.

Background: With the emergence of drug-resistant fungi and the increased population prone to fungal infections, more effective antifungal drugs are needed. Aurein 1.2 is a potent antimicrobial peptide.

Growth Rate and Thermal Properties of DNA Origami Filaments.

Synthetic DNA filaments exploit the programmability of the individual units and their predictable self-association to mimic the structural and dynamic features of natural protein filaments. Among them, DNA origami filamentous structures are of particular interest, due to the versatility of morphologies, mechanical properties, and functionalities attainable. We here explore the thermodynamic and kinetic properties of linear structures grown from a ditopic DNA origami unit, i.

Sensitive Determination of Trace 4-Nitrophenol in Ambient Environment Using a Glassy Carbon Electrode Modified with Formamide-Converted Nitrogen-Doped Carbon Materials.

Sensing trace amounts of 4-nitrophenol (4-NP) as a harmful substance to organisms even in small quantities is of great importance. The present study includes a sensitive and selective electrochemical sensor for detecting 4-NP in natural water samples using formamide-converted nitrogen-carbon materials (shortened to f-NC) as a new material for electrode modification. The structure and morphology of the f-NC were set apart by SEM, TEM, XRD, XPS, FTIR, Raman, and the electrochemical performance of the f-NC were set apart by CV, EIS and CC.

A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma.

Purpose: Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly targeting tumor cells that can survive, adapt, and subclonally expand under primary therapy.

Experimental Design: To identify candidate markers and to experimentally access dynamics of subclonal progression in glioblastoma, we established a discovery cohort of paired vital cell samples obtained before and after primary therapy.

Recognition of a Flexible Protein Loop in Taspase 1 by Multivalent Supramolecular Tweezers.

Many natural proteins contain flexible loops utilizing well-defined complementary surface regions of their interacting partners and usually undergo major structural rearrangements to allow perfect binding. The molecular recognition of such flexible structures is still highly challenging due to the inherent conformational dynamics. Notably, protein-protein interactions are on the other hand characterized by a multivalent display of complementary binding partners to enhance molecular affinity and specificity.

Superoxide Dismutase 1 Folding Stability as a Target for Molecular Tweezers in SOD1-Related Amyotrophic Lateral Sclerosis.

Protein misfolding and aggregation are hallmarks of many severe neurodegenerative diseases including Alzheimer's, Parkinson's and Huntington's disease. As a supramolecular ligand that binds to lysine and arginine residues, the molecular tweezer CLR01 was found to modify the aggregation pathway of disease-relevant proteins in vitro and in vivo with beneficial effects on toxicity. However, the molecular mechanisms of how tweezers exert these effects remain mainly unknown, hampering further drug development.