Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer.

Unlabelled: Cancer-induced skeletal muscle defects differ in severity between individuals with the same cancer type. Cancer subtype-specific genomic aberrations are suggested to mediate these differences, but experimental validation studies are very limited. We utilized three different breast cancer patient-derived xenograft (PDX) models to correlate cancer subtype with skeletal muscle defects.

New Ref-1/APE1 targeted inhibitors demonstrating improved potency for clinical applications in multiple cancer types.

AP endonuclease-1/Redox factor-1 (APE1/Ref-1 or Ref-1) is a multifunctional protein that is overexpressed in most aggressive cancers and impacts various cancer cell signaling pathways. Ref-1's redox activity plays a significant role in activating transcription factors (TFs) such as NFκB, HIF1α, STAT3 and AP-1, which are crucial contributors to the development of tumors and metastatic growth. Therefore, development of potent, selective inhibitors to target Ref-1 redox function is an appealing approach for therapeutic intervention.

Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression.

Purpose: Plexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) associated with neurofibromatosis type 1 (NF1). Despite similar histologic appearance, these neoplasms exhibit diverse evolutionary trajectories, with a subset progressing to malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through the development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathologic features and CDKN2A copy-number loss.

Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene.

Unlabelled: Single-cell transcriptomics studies have begun to identify breast epithelial cell and stromal cell specific transcriptome differences between BRCA1/2 mutation carriers and non-carriers. We generated a single-cell transcriptome atlas of breast tissues from BRCA1, BRCA2 mutation carriers and compared this single-cell atlas of mutation carriers with our previously described single-cell breast atlas of healthy non-carriers. We observed that BRCA1 but not BRCA2 mutations altered the ratio between basal (basal-myoepithelial), luminal progenitor (luminal adaptive secretory precursor, LASP), and mature luminal (luminal hormone sensing) cells in breast tissues.

Effects of Non-monetary Incentives in Physician Groups-A Systematic Review.

Healthcare expenditures in western countries have been rising for many years. This leads many countries to develop and test new reimbursement systems. A systematic review about monetary incentives in group settings indicated that a sole focus on monetary aspects does not necessarily result in better care at lower costs.

Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma.

Purpose: Plexiform neurofibromas (PNF) are peripheral nerve sheath tumors that cause significant morbidity in persons with neurofibromatosis type 1 (NF1), yet treatment options remain limited. To identify novel therapeutic targets for PNF, we applied an integrated multi-omic approach to quantitatively profile kinome enrichment in a mouse model that has predicted therapeutic responses in clinical trials for NF1-associated PNF with high fidelity.

Experimental Design: Utilizing RNA sequencing combined with chemical proteomic profiling of the functionally enriched kinome using multiplexed inhibitor beads coupled with mass spectrometry, we identified molecular signatures predictive of response to CDK4/6 and RAS/MAPK pathway inhibition in PNF.

Ptr1 and ZAR1 immune receptors confer overlapping and distinct bacterial pathogen effector specificities.

Some nucleotide-binding and leucine-rich repeat receptors (NLRs) indirectly detect pathogen effectors by monitoring their host targets. In Arabidopsis thaliana, RIN4 is targeted by multiple sequence-unrelated effectors and activates immune responses mediated by RPM1 and RPS2. These effectors trigger cell death in Nicotiana benthamiana, but the corresponding NLRs have yet not been identified.

TONSL Is an Immortalizing Oncogene and a Therapeutic Target in Breast Cancer.

Unlabelled: Study of genomic aberrations leading to immortalization of epithelial cells has been technically challenging due to the lack of isogenic models. To address this, we used healthy primary breast luminal epithelial cells of different genetic ancestry and their hTERT-immortalized counterparts to identify transcriptomic changes associated with immortalization. Elevated expression of TONSL (Tonsoku-like, DNA repair protein) was identified as one of the earliest events during immortalization.

Machine-learning-aided application of high-gravity technology to enhance ammonia recovery of fresh waste leachate.

Stripping is widely applied for the removal of ammonia from fresh waste leachate. However, the development of air stripping technology is restricted by the requirements for large-scale equipment and long operation periods. This paper describes a high-gravity technology that improves ammonia stripping from actual fresh waste leachate and a machine learning approach that predicts the stripping performance under different operational parameters.

The Phytophthora capsici RxLR effector CRISIS2 triggers cell death via suppressing plasma membrane H+-ATPase in the host plant.

Pathogen effectors can suppress various plant immune responses, suggesting that they have multiple targets in the host. To understand the mechanisms underlying plasma membrane-associated and effector-mediated immunity, we screened the Phytophthora capsici RxLR cell death-inducer suppressing immune system (CRISIS). We found that the cell death induced by the CRISIS2 effector in Nicotiana benthamiana was inhibited by the irreversible plasma membrane H+-ATPase (PMA) activator fusicoccin.

RxLR Effector PITG06478 Hijacks 14-3-3 to Suppress PMA Activity Leading to Necrotrophic Cell Death.

Pathogens often induce cell death for their successful proliferation in the host plant. Plasma membrane H-ATPases (PMAs) are targeted by either pathogens or plant immune receptors in immune response regulation. Although PMAs play pivotal roles in host cell death, the molecular mechanism of effector-mediated regulation of PMA activity has not been described.

Integration of Risk Scores and Integration Capability in Electronic Patient Records.

Background: Digital availability of patient data is continuously improving with the increasing implementation of electronic patient records in physician practices. The emergence of digital health data defines new fields of application for data analytics applications, which in turn offer extensive options of using data. Common areas of data analytics applications include decision support, administration, and fraud detection.

Non-negligible greenhouse gas emissions from non-sewered sanitation systems: A meta-analysis.

Current methods for estimating sanitation emissions underestimate the significance of methane emissions from non-sewered sanitation systems (NSSS), which are prevalent in many countries. NSSS play a vital role in the safe management of fecal sludge, accounting for approximately half of all existing sanitation provisions. We analyzed the distribution of global NSSS and used IPCC accounting methods to estimate the total methane emissions profiles from these systems.

On a remarkable geometric-mechanical synergism based on a novel linear eigenvalue problem.

The vertices of two specific eigenvectors, obtained from a novel linear eigenvalue problem, describe two curves on the surface of an -dimensional unit hypersphere. denotes the number of degrees of freedom in the framework of structural analysis by the Finite Element Method. The radii of curvature of these two curves are 0 and 1.

Plasma membrane-localized plant immune receptor targets H -ATPase for membrane depolarization to regulate cell death.

The hypersensitive response (HR) is a robust immune response mediated by nucleotide-binding, leucine-rich repeat receptors (NLRs). However, the early molecular event that links activated NLRs to cell death is unclear. Here, we demonstrate that NLRs target plasma membrane H -ATPases (PMAs) that generate electrochemical potential, an essential component of living cells, across the plasma membrane.

Comparative analysis of de novo genomes reveals dynamic intra-species divergence of NLRs in pepper.

Background: Peppers (Capsicum annuum L.) containing distinct capsaicinoids are the most widely cultivated spices in the world. However, extreme genomic diversity among species represents an obstacle to breeding pepper.

Operating status of public toilets in the Hutong neighborhoods of Beijing: An empirical study.

The provision of sanitation services for fast-growing urban populations is one of the world's urgent challenges. Hutong neighborhoods in Beijing, capital of China, cannot be rebuilt due to the protection of historical heritage, while residents still need to keep the habit of defecating in public toilets. One hundred public toilets with non-sewered sanitation in the Hutong neighborhoods of Beijing were visited to investigate the actual operating status in response to the "toilet revolution" campaign.

Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans.

Background: Idiopathic nodular mesangial sclerosis, also called idiopathic nodular glomerulosclerosis (ING), is a rare clinical entity with an unclear pathogenesis. The hallmark of this disease is the presence of nodular mesangial sclerosis on histology without clinical evidence of diabetes mellitus or other predisposing diagnoses. To achieve insights into its pathogenesis, we queried the clinical, histopathologic and transcriptomic features of ING and nodular diabetic nephropathy (DN).

Occurrence of typical antibiotics, representative antibiotic-resistant bacteria, and genes in fresh and stored source-separated human urine.

Human urine is a source of fertilizer and, with proper management, it can be reused in agriculture. Determining the contamination issue of antibiotics in source-separated urine is important because the majority of antibiotics are excreted with urine. In this study, source-separated urine samples were randomly collected from a male toilet in a university building and analyzed in terms of 30 typical antibiotics (including 14 sulfonamides, 4 tetracyclines, and 12 fluoroquinolones) and tetracycline-resistant Escherichia coli, as well as its antibiotic-resistant genes to determine the contamination characteristics of antibiotic-related pollution in fresh and stored urine.

Using system dynamics to assess the complexity of rural toilet retrofitting: Case study in eastern China.

Rural toilet retrofitting (RTR) is a complex, dynamic system that is affected by many factors and the positive/negative feedback relationships between subsystems and variables. Traditional technologies and management methods face challenges in fundamentally describing and solving problems in RTR. To bridge this gap, this study utilizes system dynamics and causal loop diagrams to explain such problems based on data collected from the stakeholders of the RTR in Jiaozhou from 2018 to 2019.

Application-oriented fundamental research on concrete and reinforced concrete structures: selected findings from an Austro-Chinese research project.

In this paper, the significance of application-oriented fundamental research on concrete and reinforced concrete structures for progress regarding practical applications to structural design is addressed based on four examples. They were treated in a joint research project of Vienna University of Technology and Tongji University. The first topic refers to sudden heating or cooling of concrete structures, the second one to high-dynamic strength of specimens made of cementitious materials, the third one to structural analysis of segmental tunnel rings used in mechanized tunneling, and the fourth one to serviceability and ultimate limit states of concrete hinges used in integral bridge construction.

TGFam-Finder: a novel solution for target-gene family annotation in plants.

Whole-genome annotation error that omits essential protein-coding genes hinders further research. We developed Target Gene Family Finder (TGFam-Finder), an alternative tool for the structural annotation of protein-coding genes containing target domain(s) of interest in plant genomes. TGFam-Finder took considerably reduced annotation run-time and improved accuracy compared to conventional annotation tools.

[Screening for 4MRGN in German emergency departments].

Background: Multiresistant Gram-negative bacteria (MRGN) are a growing clinical problem. The practical implementation of the recommendation of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) for screening according to 4MRGN (MRGN resistant to all four categories of antibiotics), however, varies considerably between emergency departments.

Objectives: This study is intended to give an overview of the status quo and the quality assurance of 4MRGN screening and to show possibilities for process optimization.