Random walk models in the life sciences: including births, deaths and local interactions.

Random walks and related spatial stochastic models have been used in a range of application areas, including animal and plant ecology, infectious disease epidemiology, developmental biology, wound healing and oncology. Classical random walk models assume that all individuals in a population behave independently, ignoring local physical and biological interactions. This assumption simplifies the mathematical description of the population considerably, enabling continuum-limit descriptions to be derived and used in model analysis and fitting.

Explaining the monoaural directional hearing of the moth .

(Fabricius, 1794) (Lepidoptera: Pyralidae) is a pyralid moth with two ears in its abdomen that it uses for detecting mates and predators. Despite no connection between the two ears having been found and no other elements having been observed through X-ray scans of the moth, it seems to be capable of directional hearing with just one ear when one of them is damaged. It is therefore suspected that the morphology of the eardrum can provide directional cues for sound localization.

Reconstructing dinosaur locomotion.

Dinosaur locomotor biomechanics are of major interest. Locomotion of an animal affects many, if not most, aspects of life reconstruction, including behaviour, performance, ecology and appearance. Yet locomotion is one aspect of non-avian dinosaurs that we cannot directly observe.

Awakening not associated with an increased rate of cortisol secretion.

Cortisol is released upon activation of the hypothalamic-pituitary-adrenal axis, varies across the day, possesses an underlying diurnal rhythm and is responsive to stressors. The endogenous circadian peak of cortisol occurs in the morning, and increases in cortisol observed post-awakening have been named the cortisol awakening response (CAR) based on the belief that the act of waking up stimulates cortisol secretion. However, objective evidence that awakening induces cortisol secretion is limited.

Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing.

Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury.

Neuronal mechanisms of nociceptive-evoked gamma-band oscillations in rodents.

Gamma-band oscillations (GBOs) in the primary somatosensory cortex (S1) play key roles in nociceptive processing. Yet, one crucial question remains unaddressed: what neuronal mechanisms underlie nociceptive-evoked GBOs? Here, we addressed this question using a range of somatosensory stimuli (nociceptive and non-nociceptive), neural recording techniques (electroencephalography in humans and silicon probes and calcium imaging in rodents), and optogenetics (alone or simultaneously with electrophysiology in mice). We found that (1) GBOs encoded pain intensity independent of stimulus intensity in humans, (2) GBOs in S1 encoded pain intensity and were triggered by spiking of S1 interneurons, (3) parvalbumin (PV)-positive interneurons preferentially tracked pain intensity, and critically, (4) PV S1 interneurons causally modulated GBOs and pain-related behaviors for both thermal and mechanical pain.

Contextualizing the Upper Paleolithic of the Armenian Highlands: New data from Solak-1, central Armenia.

As a potential corridor connecting Southwest Asia with western and northern Europe, the Armenian Highlands and southern Caucasus hold great potential for increasing our understanding of Upper Paleolithic behavioral and cultural variability. However, given the dearth of Upper Paleolithic sites, we lack the data necessary to answer basic questions regarding the timing and nature of the Upper Paleolithic in this region. Solak-1 is an open-air site located along the upper Hrazdan Valley (1635 m above sea level) in central Armenia.

Unveiling the interplay between soluble guanylate cyclase activation and redox signalling in stroke pathophysiology and treatment.

Soluble guanylate cyclase (sGC) stands as a pivotal regulatory element in intracellular signalling pathways, mediating the formation of cyclic guanosine monophosphate (cGMP) and impacting diverse physiological processes across tissues. Increased formation of reactive oxygen species (ROS) is widely recognized to modulate cGMP signalling. Indeed, oxidatively damaged, and therefore inactive sGC, contributes to poor vascular reactivity and more severe neurological damage upon stroke.

Graded porous scaffold mediates internal fluidic environment for 3D in vitro mechanobiology.

Most cell types are mechanosensitive, their activities such as differentiation, proliferation and apoptosis, can be influenced by the mechanical environment through mechanical stimulation. In three dimensional (3D) mechanobiological in vitro studies, the porous structure of scaffold controls the local mechanical environment that applied to cells. Many previous studies have focused on the topological design of homogeneous scaffold struts.

Analysis of the haemodynamic changes caused by surgical and transcatheter aortic valve replacements by means fluid-structure interaction simulations.

Aortic valve replacements, both surgical and transcatheter, are nowadays widely employed treatments. Although clinically effective, these procedures are correlated with potentially severe clinical complications which can be associated with the non-physiological haemodynamics that they establish. In this work, the fluid dynamics changes produced by surgical and transcatheter aortic valve replacements are analysed and compared with an ideal healthy native valve configuration, employing advanced fluid-structure interaction (FSI) simulations.

The formation and architecture of surface-initiated polymer brush gene delivery complexes.

Understanding the architecture and mechanism of assembly of polyelectrolyte-nucleic acid complexes is critical to the rational design of their performance for gene delivery. Surface-initiated polymer brushes were recently found to be particularly effective at delivering oligonucleotides and maintaining high knock down efficiencies for prolonged periods of time, in highly proliferative cells. However, what distinguishes their binding capacity for oligonucleotides from that of larger therapeutic macromolecules remains unknown.

Adsorption of Eu and Gd on high-charge micas as inner-sphere complexes.

High-charge micas exhibit improved adsorption properties and are a promising alternative clay material for the engineered barrier in deep geological repositories. When combined with Eu cations, they serve as an in situ luminescent probe for tracking the physical-chemical changes occurring in this engineered barrier over the long term. Therefore, a better understanding of the local environment of the lanthanide is highly desirable to comprehend the specific behavior of these systems.

Neighborhood environment and cognitive functioning in middle-aged and older population: A mediating role of physical activity.

Background: Evidence on the impact of complex neighborhood environment, including air pollution, greenness, and neighborhood socioeconomic deprivation (nSED) on cognitive health in older adults remains scarce. Both cognition and neighborhood environment are associated with physical activity, but little is known about the potential mediating role of physical activity in this association.

Methods: Cross-sectional data of the Czech arm of the HAPIEE cohort study examined 4,178 participants (55.

Hydrophobic PU fabric with synergistic conductive networks for boosted high sensitivity, wide linear-range wearable strain sensor.

Strain sensing fabrics are able to sense the deformation of the outside world, bringing more accurate and real-time monitoring and feedback to users. However, due to the lack of clear sensing mechanism for high sensitivity and high linearity carbon matrix composites, the preparation of high performance strain sensing fabric weaving is still a major challenge. Here, an elastic polyurethane(PU)-based conductive fabric(GCPU) with high sensitivity, high linearity and good hydrophobicity is prepared by a novel synergistic conductive network strategy.

How I diagnose and treat systemic mastocytosis with an associated hematologic neoplasm.

Over the last decade significant advances have been made by honing in on the diagnostic evaluation and the significance of molecular profiles in patients with systemic mastocytosis (SM), non-advanced and advanced.This is reflected in the 2022 iterations of the World Health Organization Edition 5 and International Consensus Criteria classifications.The impact of targeted KIT inhibitor therapies on patients treated within global trials has demonstrated significant improvements in the prognosis and overall survival for patients, leading to a change the treatment paradigm.

Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial.

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months.

Randomized Comparison of Magnetic Resonance Imaging Versus Transurethral Resection for Staging New Bladder Cancers: Results From the Prospective BladderPath Trial.

Purpose: Transurethral resection of bladder tumor (TURBT) is the initial staging procedure for new bladder cancers (BCs). For muscle-invasive bladder cancers (MIBCs), TURBT may delay definitive treatment. We investigated whether definitive treatment can be expedited for MIBC using flexible cystoscopic biopsy and multiparametric magnetic resonance imaging (mpMRI) for initial staging.

Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.

The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.

Design, Synthesis, and Pharmacological Evaluation of Nonsteroidal Tricyclic Ligands as Modulators of GABA Receptors.

GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.

Psychological detachment from work predicts mental wellbeing of working-age adults: Findings from the 'Wellbeing of the Workforce' (WoW) prospective longitudinal cohort study.

Background: There is an urgent need to better understand the factors that predict mental wellbeing in vocationally active adults during globally turbulent times.

Aim: To explore the relationship between psychological detachment from work (postulated as a key recovery activity from work) in the first national COVID-19 lockdown with health, wellbeing, and life satisfaction of working age-adults one year later, within the context of a global pandemic.

Methods: Wellbeing of the Workforce (WoW) was a prospective longitudinal cohort study, with two waves of data collection (Time 1, April-June 2020: T1 n = 337; Time 2, March-April 2021: T2 = 169) corresponding with the first and third national COVID-19 lockdowns in the UK.

Creation of Piezoelectricity in Quadruple Perovskite Oxides by Harnessing Cation Defects and Their Application in Piezo-Photocatalysis.

Quadruple perovskite oxides have received extensive attention in electronics and catalysis, owing to their cation-ordering structure and intriguing physical properties. However, their repertoires still remain limited. In particular, piezoelectricity from quadruple perovskites has been rarely reported due to the frustrated symmetry-breaking transition in A-site-ordered perovskite structures, disabling their piezoelectric applications.