Resolving the two-body problem: A postulated role for the V0 sector of the V0V1-ATPase in exosome biogenesis and multivesicular body fate.

Because the discovery of the multivesicular body (MVB) as the origin of secreted vesicles or exosomes, the question arose and still looms-what distinguishes an MVB destined for fusion with the plasma membrane (EXO-MVB) facilitating exosome release from an MVB involved in transport of content to the lysosome (LYSO-MVB). Do they have independent origins? Hence, the two-body problem. We hypothesize that a key to this conundrum is the membrane spanning V0 sector of the proton pump, V0V1-ATPase.

High interobserver variability of PTEN immunohistochemistry defining PTEN status in low- to intermediate-risk prostate cancer: results of the first German ring trial.

The prognostication of individual disease trajectory and selection of optimal therapy in patients with localized, low-grade prostate cancer often presents significant difficulty. The phosphatase and tensin homolog on chromosome 10 (PTEN) has emerged as a potential novel biomarker in this clinical context, based on its demonstrated prognostic significance in multiple retrospective studies. Incorporation into standard clinical practice necessitates exceptional diagnostic accuracy, and PTEN's binary readout-retention or loss-suggests its suitability as a biomarker.

Standalone single- and bi-layered human skin 3D models supported by recombinant silk feature native spatial organization.

Physiologically relevant human skin models that include key skin cell types can be used fordrug testing, skin pathology studies, or clinical applications such as skin grafts. However, there is still no golden standard for such a model. We investigated the potential of a recombinant functionalized spider silk protein, FN-silk, for the construction of a dermal, an epidermal, and a bilayered skin equivalent (BSE).

High-resolution infrared spectra and rovibrational analysis of the ν band of propylene oxide.

The high-resolution infrared spectrum of the fundamental band ν (ring breathing) of the chiral molecule propylene oxide (CHCHCHO) was recorded at room temperature and under jet-cooled conditions using a quantum cascade laser at 8 μm. The observed lines with quantum numbers ≤ 55 and ≤ 21 were assigned to strong - and -type bands, and some low transitions were classified as weak -type transitions. The lines were fitted using a Watsons A-reduced Hamiltonian in the I representation.

Living with glioblastoma - the need for integrated support based on experiences of chaos, loss of autonomy, and isolation in both patients and their relatives.

Purpose: The aim of this study was to investigate the experiences of living with glioblastoma from the perspective of patients themselves as well as their closest relatives, focusing on the changes in the life situation and the need for support.

Methods: Twenty-two semi-structured interviews were conducted with 12 patients (mean age 61 years, 7 male, 5 female) and 10 relatives (mean age 56 years, 3 male, 7 female). The relatives comprised of partners (n = 7), child (n = 1), sister (n = 1), or friend (n = 1).

Merging of a Supramolecular Ligand with a Switchable Luminophore - Light-Responsiveness, Photophysics and Bioimaging.

In this contribution we report on a novel approach towards luminescent light-responsive ligands. To this end, cyanostilbene- guanidiniocarbonyl-pyrrole hybrids were designed and investigated. Merging of a luminophore with a supramolecular bioactive ligand bears numerous advantages by overcoming the typical drawbacks of drug-labelling, influencing the overall performance of the active species by attachment of a large luminophore.

A comparison of Polysorbates and Alternative Surfactants for Interfacial Stress Protection and Mitigation of Fatty Acid Particle Formation in the Presence of an Esterase.

The hydrolysis of polysorbate surfactants in large molecule drug product formulations caused by residual host cell proteins presents numerous stability concerns for pharmaceuticals. The fatty acids (FA) released by polysorbate hydrolysis can nucleate into particulates or challenge the conformational stability of the proteinaceous active pharmaceutical ingredient (API). The loss of intact polysorbate may also leave the Drug Product (DP) vulnerable to interfacial stresses.

The Role of SCARA5 as a Potential Biomarker in Squamous Cell Carcinoma of the Lung.

Lung cancer is the leading cause of cancer-related deaths in the western world. Squamous cell carcinoma is one of the most common histological subtypes of this malignancy. For squamous cell carcinoma of the lung (LSCC), prognostic and predictive markers still are largely missing.

Mapping spatially resolved transcriptomes in human and mouse pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. Here we generated spatially resolved transcriptome maps of human IPF (n = 4) and bleomycin-induced mouse pulmonary fibrosis (n = 6) to address these limitations.

Asymmetric pulses delivered by a cochlear implant allow a reduction in evoked firing rate and in spatial activation in the guinea pig auditory cortex.

Despite that fact that the cochlear implant (CI) is one of the most successful neuro-prosthetic devices which allows hearing restoration, several aspects still need to be improved. Interactions between stimulating electrodes through current spread occurring within the cochlea drastically limit the number of discriminable frequency channels and thus can ultimately result in poor speech perception. One potential solution relies on the use of new pulse shapes, such as asymmetric pulses, which can potentially reduce the current spread within the cochlea.

A novel entity of massive multifocal osteolyses in the elderly.

Osteolyses are common findings in elderly patients and most frequently represent malignant or locally aggressive bone tumors, infection, inflammatory and endocrine disorders, histiocytoses, and rare diseases such as Gorham-Stout syndrome. We here report on a novel entity of massive multifocal osteolyses in both shoulders, the right hip and left knee joint and the dens of an 83-year-old patient not relatable to any previously known etiopathology of bone disorders. The soft tissue mass is of myxoid stroma with an unspecific granulomatous inflammatory process, aggressively destroying extensive cortical and cancellous bone segments and encroaching on articulating bones in diarthrodial large joints.

[InspeCKD - Analysis of the use of diagnostics in patients at high risk for chronic kidney disease in German general practitioner (GP) practices].

Background: Despite the high prevalence of chronic kidney disease (CKD) in Germany, only a small proportion of patients are currently diagnosed with CKD. Patients with hypertension, diabetes mellitus, and/or cardiovascular disease have a significantly increased risk of developing CKD and rapid disease progression and should therefore be screened and monitored in accordance with the guidelines.

Objectives: The aim of this retrospective, cross-sectional study was to gain insights into appropriate diagnosis of patients at risk for CKD in German general practitioner practices.

Extracellular vesicles - on the cusp of a new language in the biological sciences.

Extracellular vesicles (EVs) play a key role both in physiological balance and homeostasis and in disease processes through their ability to participate in intercellular signaling and communication. An ever-expanding knowledge pool and a myriad of functional properties ascribed to EVs point to a new language of communication in biological systems that has opened a path for the discovery and implementation of novel diagnostic applications. EVs originate in the endosomal network and via non-random shedding from the plasma membrane by mechanisms that allow the packaging of functional cargoes, including proteins, lipids, and genetic materials.

Lokatt: a hybrid DNA nanopore basecaller with an explicit duration hidden Markov model and a residual LSTM network.

Background: Basecalling long DNA sequences is a crucial step in nanopore-based DNA sequencing protocols. In recent years, the CTC-RNN model has become the leading basecalling model, supplanting preceding hidden Markov models (HMMs) that relied on pre-segmenting ion current measurements. However, the CTC-RNN model operates independently of prior biological and physical insights.

Semla: a versatile toolkit for spatially resolved transcriptomics analysis and visualization.

Summary: Spatially resolved transcriptomics technologies generate gene expression data with retained positional information from a tissue section, often accompanied by a corresponding histological image. Computational tools should make it effortless to incorporate spatial information into data analyses and present analysis results in their histological context. Here, we present semla, an R package for processing, analysis, and visualization of spatially resolved transcriptomics data generated by the Visium platform, that includes interactive web applications for data exploration and tissue annotation.

Spatial transcriptomics of human placentas reveal distinct RNA patterns associated with morphology and preeclampsia.

Spatial transcriptomics (ST) maps RNA level patterns within a tissue. This technology has not been previously applied to human placental tissue. We demonstrate analysis of human placental samples with ST.

THSD7A Positivity Predicts Poor Survival and Is Linked to High FAK Expression and FGFR1-Wildtype in Female Patients with Squamous Cell Carcinoma of the Lung.

Lung cancer is the leading cause of cancer-related deaths in the western world, with squamous cell carcinoma being one of the most common histological subtypes. Prognostic and predictive markers are still largely missing for squamous cell carcinoma of the lung (LSCC). Several studies indicate that THSD7A might at least play a role in the prognosis of different tumors.

SCARA5 Is Overexpressed in Prostate Cancer and Linked to Poor Prognosis.

Prostate cancer is one of the most common malignancies worldwide, showing a wide range of clinical behaviors. Therefore, several treatment options arise out of the diagnosis "prostate cancer". For this reason, it is desirable to find novel prognostic and predictive markers.

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.

An integrated single cell and spatial transcriptomic map of human white adipose tissue.

To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells.

What Is the Benefit of Ramped Pulse Shapes for Activating Auditory Cortex Neurons? An Electrophysiological Study in an Animal Model of Cochlear Implant.

In all commercial cochlear implant (CI) devices, the activation of auditory nerve fibers is performed with rectangular pulses that have two phases of opposite polarity. Recently, several papers proposed that ramped pulse shapes could be an alternative shape for efficiently activating auditory nerve fibers. Here, we investigate whether ramped pulse shapes can activate auditory cortex (ACx) neurons in a more efficient way than the classical rectangular pulses.