Eccentricity pacing and rapid termination of the early Antarctic ice ages.

Earth's obliquity and eccentricity cycles are strongly imprinted on Earth's climate and widely used to measure geological time. However, the record of these imprints on the oxygen isotope record in deep-sea benthic foraminifera (δO) shows contradictory signals that violate isotopic principles and cause controversy over climate-ice sheet interactions. Here, we present a δO record of high fidelity from International Ocean Drilling Program (IODP) Site U1406 in the northwest Atlantic Ocean.

In Vivo Assessment of Deep Vascular Patterns in Murine Colitis Using Optoacoustic Mesoscopic Imaging.

The analysis of vascular morphology and functionality enables the assessment of disease activity and therapeutic effects in various pathologies. Raster-scanning optoacoustic mesoscopy (RSOM) is an imaging modality that enables the visualization of superficial vascular networks in vivo. In murine models of colitis, deep vascular networks in the colon wall can be visualized by transrectal absorber guide raster-scanning optoacoustic mesoscopy (TAG-RSOM).

Screen printed 3D microfluidic paper-based and modifier-free electroanalytical device for clozapine sensing.

The increasing demand in healthcare for accessible and cost-effective analytical tools is driving the development of reliable platforms to the customization of therapy according to individual patient drug serum levels, of anti-psychotics in schizophrenia. A modifier-free microfluidic paper-based electroanalytical device (μPED) holds promise as a portable, sensitive, and affordable solution. While many studies focus on the working electrode catalysts, improvements by engineering aspects of the electrode arrangement are less reported.

How enoxaparin underdosing and sex contribute to achieving therapeutic anti-Xa levels.

Introduction: Anti-Xa serves as a clinical surrogate for assessing the efficacy and bleeding risk in patients treated with enoxaparin for thromboembolic events. Evidence from the literature and empirical observations suggest that patients are underdosed in clinical practice to avoid bleeding complications. This study aimed to investigate such underdosing of enoxaparin and its potential impact on achieving therapeutic anti-Xa levels.

Iron deficiency in athletes: Prevalence and impact on VO peak.

Background: Iron is an important micronutrient in pathways of energy production, adequate nutrient intake and its balance is essential for optimal athletic performance. However, large studies elucidating the impact of iron deficiency on athletes' performance are sparse.

Methods: Competitive athletes of any age who presented for preparticipation screening 04/2020-10/2021 were included in this study and stratified for iron deficiency (defined as ferritin level <20 µg/l with and without mild anemia [hemoglobin levels ≥11 g/dl]).

Levosimendan's Effects on Length-Dependent Activation in Murine Fast-Twitch Skeletal Muscle.

Levosimendan's calcium sensitizing effects in heart muscle cells are well established; yet, its potential impact on skeletal muscle cells has not been evidently determined. Despite controversial results, levosimendan is still expected to interact with skeletal muscle through off-target sites (further than troponin C). Adding to this debate, we investigated levosimendan's acute impact on fast-twitch skeletal muscle biomechanics in a length-dependent activation study by submersing single muscle fibres in a levosimendan-supplemented solution.

Characterization of two different alginate-based bioinks and the influence of melanoma growth within.

Extrusion-based bioprinting is an established method in biofabrication. Suitable bioinks have fundamentally different compositions and characteristics, which should be examined, in order to find a perfect model system. Here, we investigate the effect of two alginate-based, yet unalike 3D-printed bioinks, pre-crosslinked alginate-dialdehyde gelatin (ADA-GEL) and a mixture of alginate, hyaluronic acid, and gelatin (Alg/HA/Gel), on the melanoma cell line Mel Im and vice versa in terms of stiffness, shrinkage, cellular behavior and colony formation over 15 days.

Effects of Adjuvant Exercise and Nutrition Therapy on Muscle Fibre Biomechanics in Gastrointestinal Cancer Patients.

Patients with aggressive cancer, e.g., gastrointestinal cancer, are prone (≥50% chance) to developing cancer cachexia (CC).

Access to Artemisinin-Triazole Antimalarials Organo-Click Reaction: High / Activity against Multi-Drug-Resistant Malaria Parasites.

Malaria is one of the most widespread diseases worldwide. Besides a growing number of people potentially threatened by malaria, the consistent emergence of resistance against established antimalarial pharmaceuticals leads to an urge toward new antimalarial drugs. Hybridization of two chemically diverse compounds into a new bioactive product is a successful concept to improve the properties of a hybrid drug relative to the parent compounds and also to overcome multidrug resistance.

High-content method for mechanosignaling studies using IsoStretcher technology and quantitative Ca imaging applied to Piezo1 in cardiac HL-1 cells.

The importance of mechanosensory transduction pathways in cellular signalling has prominently come to focus in the last decade with the discovery of the Piezo ion channel family. Mechanosignaling involving Piezo1 ion channels in the function of the heart and cardiovascular system has only recently been identified to have implications for cardiovascular physiology and pathophysiology, in particular for heart failure (i.e.

Stretch response of the mechano-gated channel TMEM63A in membrane patches and single cells.

The recently discovered ion channel TMEM63A has biophysical features distinctive for mechano-gated cation channels, activating at high pressures with slow kinetics while not inactivating. However, some biophysical properties are less clear, including no information on its function in whole cells. The aim of this study is to expand the TMEM63A biophysical characterization and examine the function in whole cells.

ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo.

Objective: Mucosal T cells play a major role in inflammatory bowel disease (IBD). However, their immunometabolism during intestinal inflammation is poorly understood. Due to its impact on cellular metabolism and proinflammatory immune cell function, we here focus on the enzyme ATP citrate lyase (ACLY) in mucosal T cell immunometabolism and its relevance for IBD.

Effect of insulin insufficiency on ultrastructure and function in skeletal muscle.

Background: Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with β-cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals.

SEMPAI: a Self-Enhancing Multi-Photon Artificial Intelligence for Prior-Informed Assessment of Muscle Function and Pathology.

Deep learning (DL) shows notable success in biomedical studies. However, most DL algorithms work as black boxes, exclude biomedical experts, and need extensive data. This is especially problematic for fundamental research in the laboratory, where often only small and sparse data are available and the objective is knowledge discovery rather than automation.

A 104-Ma record of deep-sea Atelostomata (Holasterioda, Spatangoida, irregular echinoids) - a story of persistence, food availability and a big bang.

Deep-sea macrobenthic body fossils are scarce due to the lack of deep-sea sedimentary archives in onshore settings. Therefore, hypothesized migrations of shallow shelf taxa into the deep-sea after phases of mass extinction (onshore-offshore pattern in the literature) due to anoxic events is not constrained by the fossil record. To resolve this conundrum, we investigated 1,475 deep-sea sediment samples from the Atlantic, Pacific and Southern oceans (water depth ranging from 200 to 4,700 m), providing 41,460 spine fragments of the crown group Atelostomata (Holasteroida, Spatangoida).

3D printing of piezoelectric and bioactive barium titanate-bioactive glass scaffolds for bone tissue engineering.

Bone healing is a complex process orchestrated by various factors, such as mechanical, chemical and electrical cues. Creating synthetic biomaterials that combine several of these factors leading to tailored and controlled tissue regeneration, is the goal of scientists worldwide. Among those factors is piezoelectricity which creates a physiological electrical microenvironment that plays an important role in stimulating bone cells and fostering bone regeneration.

Partner, Neighbor, Housekeeper and Dimension: 3D versus 2D Glomerular Co-Cultures Reveal Drawbacks of Currently Used Cell Culture Models.

Signaling-pathway analyses and the investigation of gene responses to different stimuli are usually performed in 2D monocultures. However, within the glomerulus, cells grow in 3D and are involved in direct and paracrine interactions with different glomerular cell types. Thus, the results from 2D monoculture experiments must be taken with caution.

Former SARS-CoV-2 Infection Was Related to Decreased VO Peak and Exercise Hypertension in Athletes.

The impact of former COVID-19 infection on the performance of athletes is not fully understood. We aimed to identify differences in athletes with and without former COVID-19 infections. Competitive athletes who presented for preparticipation screening between April 2020 and October 2021 were included in this study, stratified for former COVID-19 infection, and compared.

Optimized Method of 3D Scaffold Seeding, Cell Cultivation, and Monitoring Cell Status for Bone Tissue Engineering.

The cultivation of cells in 3D systems is commonly regarded to be more physiological than in 2D as it comes much closer to the natural situation in tissues in many different aspects. However, 3D cell culture is much more complex. Cells within the pores of a printed 3D scaffold face a special situation concerning cell-material interaction and cell adhesion, cell proliferation, and supply of medium and oxygen into the core of the scaffolds.

Second Harmonic Generation Morphometry of Muscle Cytoarchitecture in Living Cells.

The architectural structure of cells is essential for the cells' function, which becomes especially apparent in the highly "structure functionally" tuned skeletal muscle cells. Here, structural changes in the microstructure can have a direct impact on performance parameters, such as isometric or tetanic force production. The microarchitecture of the actin-myosin lattice in muscle cells can be detected noninvasively in living cells and in 3D by using second harmonic generation (SHG) microscopy, forgoing the need to alter samples by introducing fluorescent probes into them.

Assessment of Cell Viability in Electrically Excitable Muscle Cells Through Intact Twitch Stimulation.

Muscle cells (i.e. skeletal muscle fibers) are fully viable and functional when their excitation-contraction (EC) coupling machinery is intact.

Quantitative Live-Cell Ca Imaging During Isotropic Cell Stretch.

Cell viability of many cell types strongly relies on their ability to adjust to mechanical conditions and alterations. Cellular mechanisms for sensing and responding to mechanical forces and pathophysiological variations in these processes have become an emerging research field in recent years. An important signaling molecule involved in mechanotransduction as in many cellular processes is Ca.

Assaying Proliferation Characteristics of Cells Cultured Under Static Versus Periodic Conditions.

Two-dimensional in vitro culture models are widely being employed for assessing a vast variety of biological questions in different scientific fields. Common in vitro culture models are typically maintained under static conditions, where the surrounding culture medium is replaced every few days-typically every 48 to 72 h-with the aim to remove metabolites and to replenish nutrients. Although this approach is sufficient for supporting cellular survival and proliferation, static culture conditions do mostly not reflect the in vivo situation where cells are continuously being perfused by extracellular fluid, and thus, create a less-physiological environment.