Deep learning image analysis for filamentous fungi taxonomic classification: Dealing with small datasets with class imbalance and hierarchical grouping.

Deep learning applications in taxonomic classification for animals and plants from images have become popular, while those for microorganisms are still lagging behind. Our study investigated the potential of deep learning for the taxonomic classification of hundreds of filamentous fungi from colony images, which is typically a task that requires specialized knowledge. We isolated soil fungi, annotated their taxonomy using standard molecular barcode techniques, and took images of the fungal colonies grown in petri dishes ( = 606).

Multiomic analyses uncover immunological signatures in acute and chronic coronary syndromes.

Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered a key pathogenic driver of these diseases, but the underlying immune states and their clinical implications remain poorly understood. Multiomic factor analysis (MOFA) allows unsupervised data exploration across multiple data types, identifying major axes of variation and associating these with underlying molecular processes.

Role of the small protein Mco6 in the mitochondrial sorting and assembly machinery.

The majority of mitochondrial precursor proteins are imported through the Tom40 β-barrel channel of the translocase of the outer membrane (TOM). The sorting and assembly machinery (SAM) is essential for β-barrel membrane protein insertion into the outer membrane and thus required for the assembly of the TOM complex. Here, we demonstrate that the α-helical outer membrane protein Mco6 co-assembles with the mitochondrial distribution and morphology protein Mdm10 as part of the SAM machinery.

Clinical Impact of Polygenic Risk Score for Breast Cancer Risk Prediction in 382 Individuals with Hereditary Breast and Ovarian Cancer Syndrome.

Single nucleotide polymorphisms are currently not considered in breast cancer (BC) risk predictions used in daily practice of genetic counselling and clinical management of familial BC in Germany. This study aimed to assess the clinical value of incorporating a 313-variant-based polygenic risk score (PRS) into BC risk calculations in a cohort of German women with suspected hereditary breast and ovarian cancer syndrome (HBOC). Data from 382 individuals seeking counselling for HBOC were analysed.

Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.

Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control and have been linked to various diseases. Different views exist on the composition of the human mitochondrial proteome. We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP).

Complete Native Stable Isotope Labeling by Amino Acids of Saccharomyces cerevisiae for Global Proteomic Analysis.

Knowledge about the functions of individual proteins on a system-wide level is crucial to fully understand molecular mechanisms underlying cellular processes. A considerable part of the proteome across all organisms is still poorly characterized. Mass spectrometry is an efficient technology for the global study of proteins.

Definition of a High-Confidence Mitochondrial Proteome at Quantitative Scale.

Mitochondria perform central functions in cellular bioenergetics, metabolism, and signaling, and their dysfunction has been linked to numerous diseases. The available studies cover only part of the mitochondrial proteome, and a separation of core mitochondrial proteins from associated fractions has not been achieved. We developed an integrative experimental approach to define the proteome of yeast mitochondria.

Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10.

The endoplasmic reticulum-mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level.

Dynamic organization of the mitochondrial protein import machinery.

Mitochondria contain elaborate machineries for the import of precursor proteins from the cytosol. The translocase of the outer mitochondrial membrane (TOM) performs the initial import of precursor proteins and transfers the precursors to downstream translocases, including the presequence translocase and the carrier translocase of the inner membrane, the mitochondrial import and assembly machinery of the intermembrane space, and the sorting and assembly machinery of the outer membrane. Although the protein translocases can function as separate entities in vitro, recent studies revealed a close and dynamic cooperation of the protein import machineries to facilitate efficient transfer of precursor proteins in vivo.

Mitochondrial OXA Translocase Plays a Major Role in Biogenesis of Inner-Membrane Proteins.

The mitochondrial inner membrane harbors three protein translocases. Presequence translocase and carrier translocase are essential for importing nuclear-encoded proteins. The oxidase assembly (OXA) translocase is required for exporting mitochondrial-encoded proteins; however, different views exist about its relevance for nuclear-encoded proteins.

Lam6 Regulates the Extent of Contacts between Organelles.

Communication between organelles is crucial for eukaryotic cells to function as one coherent unit. An important means of communication is through membrane contact sites, where two organelles come into close proximity allowing the transport of lipids and small solutes between them. Contact sites are dynamic in size and can change in response to environmental or cellular stimuli; however, how this is regulated has been unclear.

Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter.

ATP-binding cassette (ABC) transporters translocate substrates across cell membranes, using energy harnessed from ATP binding and hydrolysis at their nucleotide-binding domains. ABC exporters are present both in prokaryotes and eukaryotes, with examples implicated in multidrug resistance of pathogens and cancer cells, as well as in many human diseases. TmrAB is a heterodimeric ABC exporter from the thermophilic Gram-negative eubacterium Thermus thermophilus; it is homologous to various multidrug transporters and contains one degenerate site with a non-catalytic residue next to the Walker B motif.

The importance of order and complements: a new way to understand the Dutch and German health insurance reforms.

This article adds to recent theorizing on gradual institutional change by focusing on how institutional displacement occurs through sequential patterns of change. It argues that under certain conditions, reformist political actors may achieve systemic reform through sequences of incremental reforms. We illustrate our argument through a comparative analysis of systemic health care reforms in two Bismarckian health insurance systems, the Netherlands and Germany.

Non-motor phenotype of dopa-responsive dystonia and quality of life assessment.

Background: Dopa-responsive dystonia (DRD) is a young-onset neurometabolic disorder often presenting with a combination of parkinsonism and dystonia. The pathophysiology includes an impairment of dopaminergic and serotonergic neurotransmission. Uncontrolled reports suggest an increased frequency of neuropsychiatric abnormalities and sleep impairment.

Mdm10 is an ancient eukaryotic porin co-occurring with the ERMES complex.

Mitochondrial β-barrel proteins fulfill central functions in the outer membrane like metabolite exchange catalyzed by the voltage-dependent anion channel (VDAC) and protein biogenesis by the central components of the preprotein translocase of the outer membrane (Tom40) or of the sorting and assembly machinery (Sam50). The mitochondrial division and morphology protein Mdm10 is another essential outer membrane protein with proposed β-barrel fold, which has so far only been found in Fungi. Mdm10 is part of the endoplasmic reticulum mitochondria encounter structure (ERMES), which tethers the ER to mitochondria and associates with the SAM complex.

Activation and degradation of mitofusins: two pathways regulate mitochondrial fusion by reversible ubiquitylation.

Mitofusins are large GTPases essential for mitochondrial fusion. In this issue, Anton et al. (2013) report that two independent pathways of ubiquitylation/deubiquitylation control activation and degradation of mitofusins, revealing a sophisticated mechanism of regulating mitochondrial dynamics.

Workload and usefulness of daily, centralized home monitoring for patients treated with CIEDs: results of the MoniC (Model Project Monitor Centre) prospective multicentre study.

Aim: Automated, daily Home Monitoring (HM) of pacemaker and implantable cardioverter-defibrillator (ICD) patients can improve patient care. Yet, HM introduction to routine clinical practice is challenged by resource allocation for regular HM data review. We tested the feasibility, safety, workload, and clinical usefulness of a centralized HM model consisting of one monitor centre and nine satellite clinics.

Dopa-responsive dystonia revisited: diagnostic delay, residual signs, and nonmotor signs.

Objective: To investigate the delay in diagnosis, residual motor signs, and nonmotor signs of dopa-responsive dystonia (DRD) using literature and our own pilot data.

Design, Setting, And Patients: We searched the MEDLINE database for patients with clinically typical DRD and/or guanosine triphosphate cyclohydrolase I gene mutations from 1952 to 2011 and examined a pilot cohort of 23 outpatients with DRD and guanosine triphosphate cyclohydrolase I gene mutations.

Results: The literature search yielded 101 reports describing 576 cases.

Analytical and experimental position stability of the abutment in different dental implant systems with a conical implant-abutment connection.

Objectives: Position stability of the abutment should be investigated in four implant systems with a conical implant-abutment connection.

Materials And Methods: Previously developed formulas and an established experimental setup were used to determine the position stability of the abutment in the four implant systems with a conical implant-abutment connection and different positional index designs: The theoretical rotational freedom was calculated by using the dimensions of one randomly selected implant per system for approximated geometric models. Experimentally, the rotation, the vertical displacement, and canting moments of the abutment after multiple repositioning and hand tightening of the abutment screw were investigated.

Long-term benefit of implantable cardioverter/defibrillator therapy after elective device replacement: results of the INcidence free SUrvival after ICD REplacement (INSURE) trial--a prospective multicentre study.

Aims: Prevention of sudden cardiac death by means of the implantable cardioverter/defibrillator (ICD) is considered to be a lifelong therapy. However, it is still unresolved if patients who never experienced an appropriate ICD intervention during generator longevity really need to undergo device replacement.

Methods And Results: The INSURE trial was a multicentre prospective observational cohort study that enrolled patients at the time of their first ICD replacement.

Epidermal growth factor upregulates endometrial CYR61 expression via activation of the JAK2/STAT3 pathway.

Endometrial cysteine-rich protein 61 (CYR61, CCN1) is a growth factor-inducible gene whose expression is elevated during the proliferative phase of the menstrual cycle and which has been implicated in the pathogenesis of endometriosis. This study aimed to define the mediators of epidermal growth factor (EGF) signalling on CYR61 expression in spontaneously immortalised human endometrial epithelial cells (HES) as a model system. After 30 min of EGF treatment, the receptor was phosphorylated and internalised as well as mRNA CYR61 increased in HES cells.

Interproximal access efficacy of one vibrating and two powered oscillating-rotating toothbrushes.

Objective: A new toothbrush, with elongated fine bristles and a vibrating bristle field, has been designed and developed. In this study, the new product was compared to two commercially available powered, oscillating-rotating toothbrushes for efficacy using a laboratory method that has been predictive of clinical plaque removal.

Methods: Interproximal access efficacy (IAE) is a measure of the ability of toothbrush bristles to access interproximal sites and remove simulated plaque from these areas.

Cryoablation versus radiofrequency energy for the ablation of atrioventricular nodal reentrant tachycardia (the CYRANO Study): results from a large multicenter prospective randomized trial.

Background: Cryoablation has emerged as an alternative to radiofrequency catheter ablation (RFCA) for the treatment of atrioventricular (AV) nodal reentrant tachycardia (AVNRT). The purpose of this prospective randomized study was to test whether cryoablation is as effective as RFCA during both short-term and long-term follow-up with a lower risk of permanent AV block.

Methods And Results: A total of 509 patients underwent slow pathway cryoablation (n=251) or RFCA (n=258).

Myocardial scar extent evaluated by cardiac magnetic resonance imaging in ICD patients: relationship to spontaneous VT during long-term follow-up.

Patients with ischemic cardiomyopathy have an increased risk for ventricular arrhythmia, since myocardial infarction can be the substrate for re-entrant arrhythmias. Contrast-enhanced cardiac magnetic resonance imaging (CMR) has proven to reliably quantify myocardial infarction. Aim of our study was to evaluate correlations between functional and contrast-enhanced CMR findings and spontaneous ventricular tachy-arrhythmias in patients with ischemic cardiomyopathy who underwent implantable cardioverter-defibrillator (ICD) therapy.

Interproximal access efficacy of three manual toothbrushes with extended, x-angled or flat multitufted bristles.

Purpose: This laboratory research study was conducted to evaluate three manual toothbrushes for their ability to remove artificial plaque from interproximal sites.

Materials And Methods: Interproximal access efficacy (IAE) was evaluated using a pressure-sensitive artificial plaque substrate placed around simulated anterior and posterior teeth with horizontal and vertical brushing motions. Efficacy was determined as the maximum width of artificial plaque removed from around the teeth.