Azaspiracid-59 accumulation and transformation in mussels (Mytilus edulis) after feeding with Azadinium poporum (Dinophyceae).

Azaspiracid-59 (AZA-59) was detected in plankton in coastal waters of the Pacific Northwest USA. Given that bivalves metabolize and transform accumulated phycotoxins, a strain of Azadinium poporum isolated from the coast of Washington State that is a known producer of AZA-59 was used in a controlled feeding experiment with mussels (Mytilus edulis) to assess AZA-59 accumulation rates and transformation into shellfish metabolites. Mussels started feeding immediately after the addition of A.

Brain malformations and seizures by impaired chaperonin function of TRiC.

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures.

Non-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in late-onset Pompe disease.

Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls.

Towards a FHIR-Based Framework for Analyzing Nursing-Related Data in Smaller Sized Care Facilities.

Data-driven decision making can improve the situation for caregivers and residents in nursing homes. However, smaller facilities often lack the technical and personnel resources required to prepare and analyze data. We introduce a conceptual framework to enable data transformation and analyzation in smaller nursing homes.

Towards carbon neutrality and circular economy: an innovative combination of enhanced biogas production and nutrient recovery from sludge dewatering liquor at a municipal wastewater treatment plant in Germany.

An innovative circular economy (CE) system was implemented at the wastewater treatment plant (WWTP) in Brunswick. The performance of the CE system was evaluated for 4 years: the thermal pressure hydrolysis enhanced the methane production by 18% and increased the digestate dewaterability by 14%. Refractory COD formed in thermal hydrolysis and increased the COD concentration in the WWTP effluent by 4 mg L while still complying with the legal threshold.

Cold-water coral energy reserves and calcification in contrasting fjord environments.

The relationship between energy reserves of cold-water corals (CWCs) and their physiological performance remains largely unknown. In addition, it is poorly understood how the energy allocation to different metabolic processes might change with projected decreasing food supply to the deep sea in the future. This study explores the temporal and spatial variations of total energy reserves (proteins, carbohydrates and lipids) of the CWC Desmophyllum dianthus and their correlation with its calcification rate.

T1 mapping in patients with cervical spinal canal stenosis with and without decompressive surgery: A longitudinal study.

Background And Purpose: Cervical spinal canal stenosis (cSCS) is a common cause of spinal impairment in the elderly. With conventional magnetic resonance imaging (MRI) suffering from various limitations, high-resolution single-shot T1 mapping has been proposed as a novel MRI technique in cSCS diagnosis. In this study, we investigated the effect of conservative and surgical treatment on spinal cord T1 relaxation times in cSCS.

Why Temporal Inference Stimulation May Fail in the Human Brain: A Pilot Research Study.

Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG).

Doppler flow morphology characteristics of epiaortic arteries in aortic valve pathologies: a retrospective study on a cohort of patients with ischemic stroke.

Background And Aims: Neurovascular ultrasound (nvUS) of the epiaortic arteries is an integral part of the etiologic workup in patients with ischemic stroke. Aortic valve disease shares similar vascular risk profiles and therefore not only presents a common comorbidity, but also an etiologic entity. The aim of this study is to investigate the predictive value of specific Doppler curve flow characteristics in epiaortic arteries and the presence of aortic valve disease.

Identification of high-risk patients with a seven-biomarker prognostic signature for adjuvant treatment trial recruitment in American Joint Committee on Cancer v8 stage I-IIA cutaneous melanoma.

Purpose: Many patients with resected American Joint Committee on Cancer (AJCC) early-stage cutaneous melanoma nonetheless die of melanoma; additional risk stratification approaches are needed.

Patients And Methods: Using prospectively-collected whole-tissue sections, we assessed in consecutive stage I-IIA patients (N = 439), a previously-validated, immunohistochemistry-based, 7-biomarker signature to prognosticate disease-free survival (DFS), melanoma-specific survival (MSS; primary end-point) and overall survival (OS), independent of AJCC classification.

Results: Seven-marker signature testing designated 25.

Exploring the Therapeutic Potential of Ectoine in Duchenne Muscular Dystrophy: Comparison with Taurine, a Supplement with Known Beneficial Effects in the Mouse.

Duchenne Muscular Dystrophy (DMD) is a debilitating muscle disorder that condemns patients to year-long dependency on glucocorticoids. Chronic glucocorticoid use elicits many unfavourable side-effects without offering satisfying clinical improvement, thus, the search for alternative treatments to alleviate muscle inflammation persists. Taurine, an osmolyte with anti-inflammatory effects, mitigated pathological features in the mouse model for DMD but interfered with murine development.

Evidence of Two Novel Variants in a Patient With Muscular Dystrophy: Facing the Challenges of a Certain Diagnosis.

Background: Benefits and challenges resulting from advances in genetic diagnostics are two sides of the same coin. Facilitation of a correct and timely diagnosis is paralleled by challenges in interpretation of variants of unknown significance (VUS). Focusing on an individual VUS-re-classification pipeline, this study offers a diagnostic approach for clinically suspected hereditary muscular dystrophy by combining the expertise of an interdisciplinary team.

The Evolution of Complex Muscle Cell In Vitro Models to Study Pathomechanisms and Drug Development of Neuromuscular Disease.

Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies.

DNA damage-induced phosphorylation of CtIP at a conserved ATM/ATR site T855 promotes lymphomagenesis in mice.

CtIP is a DNA end resection factor widely implicated in alternative end-joining (A-EJ)-mediated translocations in cell-based reporter systems. To address the physiological role of CtIP, an essential gene, in translocation-mediated lymphomagenesis, we introduced the T855A mutation at murine CtIP to nonhomologous end-joining and Tp53 double-deficient mice that routinely succumbed to lymphomas carrying A-EJ-mediated IgH-Myc translocations. T855 of CtIP is phosphorylated by ATM or ATR kinases upon DNA damage to promote end resection.

Mouse Models of Germinal Center Derived B-Cell Lymphomas.

Over the last decades, the revolution in DNA sequencing has changed the way we understand the genetics and biology of B-cell lymphomas by uncovering a large number of recurrently mutated genes, whose aberrant function is likely to play an important role in the initiation and/or maintenance of these cancers. Dissecting how the involved genes contribute to the physiology and pathology of germinal center (GC) B cells -the origin of most B-cell lymphomas- will be key to advance our ability to diagnose and treat these patients. Genetically engineered mouse models (GEMM) that faithfully recapitulate lymphoma-associated genetic alterations offer a valuable platform to investigate the pathogenic roles of candidate oncogenes and tumor suppressors , and to pre-clinically develop new therapeutic principles in the context of an intact tumor immune microenvironment.

Distinct Molecular Mechanisms of Altered HLA Class II Expression in Malignant Melanoma.

Background: The human leukocyte antigen (HLA) class II molecules are constitutively expressed in some melanoma, but the underlying molecular mechanisms have not yet been characterized.

Methods: The expression of HLA class II antigen processing machinery (APM) components was determined in melanoma samples by qPCR, Western blot, flow cytometry and immunohistochemistry. Immunohistochemical and TCGA datasets were used for correlation of HLA class II expression to tumor grading, T-cell infiltration and patients' survival.

Physical distancing ≠ physical inactivity.

During this time of global health crisis, physical distancing, along with mask wearing, has emerged as the sine qua non social practice to protect ourselves and others from COVID-19. But as physical distancing ensues and all eyes remain fixed on the novel coronavirus, another, albeit careworn, pandemic rages on. Physical inactivity, the world's fourth leading cause of death, may indeed be exacerbated by physical distancing measures, such as sheltering at home and closing or limiting access to recreation and exercise facilities.

Fluorescence measurements of the marine flatworm Macrostomum lignano during exposure to TNT and its derivatives 2-ADNT and 4-ADNT.

Fluorescence measurements of the marine flatworm Macrostomum lignano were performed during exposure to the explosive TNT and its main derivatives 2-ADNT and 4-ADNT, using calcein AM, the acetoxymethylester of calcein, and the autofluorescence of its food (diatoms). Lethality was found to depend on temperature and exposure time. After 12 days of exposure to a concentration of 33,3 mg/L 2-ADNT and 4-ADNT, the lethality at 30 °C (100%) was strongly increased compared to 21 °C (~60%).

Unique and Shared Epigenetic Programs of the CREBBP and EP300 Acetyltransferases in Germinal Center B Cells Reveal Targetable Dependencies in Lymphoma.

Inactivating mutations of the CREBBP and EP300 acetyltransferases are among the most common genetic alterations in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). Here, we examined the relationship between these two enzymes in germinal center (GC) B cells, the normal counterpart of FL and DLBCL, and in lymphomagenesis by using conditional GC-directed deletion mouse models targeting Crebbp or Ep300. We found that CREBBP and EP300 modulate common as well as distinct transcriptional programs implicated in separate anatomic and functional GC compartments.

CO leakage alters biogeochemical and ecological functions of submarine sands.

Subseabed CO storage is considered a future climate change mitigation technology. We investigated the ecological consequences of CO leakage for a marine benthic ecosystem. For the first time with a multidisciplinary integrated study, we tested hypotheses derived from a meta-analysis of previous experimental and in situ high-CO impact studies.

Land-use and fire drive temporal patterns of soil solution chemistry and nutrient fluxes.

Land-use type and ecosystem disturbances are important drivers for element cycling and bear the potential to modulate soil processes and hence ecosystem functions. To better understand the effect of such drivers on the magnitude and temporal patterns of organic matter (OM) and associated nutrient fluxes in soils, continuous flux monitoring is indispensable but insufficiently studied yet. We conducted a field study to elucidate the impact of land-use and surface fires on OM and nutrient fluxes with soil solution regarding seasonal and temporal patterns analyzing short (<3months) and medium-term (3-12months) effects.