Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting.

Targeting of diseased cells is one of the most urgently needed prerequisites for a next generation of potent pharmaceuticals. Different approaches pursued fail mainly due to a lack of specific surface markers. Developing an RNA-based methodology, we can now ensure precise cell targeting combined with selective expression of effector proteins for therapy, diagnostics or cell steering.

Decisive role of mDia-family formins in cell cortex function of highly adherent cells.

Cortical formins, pivotal for the assembly of linear actin filaments beneath the membrane, exert only minor effects on unconfined cell migration of weakly and moderately adherent cells. However, their impact on migration and mechanostability of highly adherent cells remains poorly understood. Here, we demonstrate that loss of cortical actin filaments generated by the formins mDia1 and mDia3 drastically compromises cell migration and mechanics in highly adherent fibroblasts.

A single-nucleus transcriptomic atlas of medium spiny neurons in the rat nucleus accumbens.

Neural processing of rewarding stimuli involves several distinct regions, including the nucleus accumbens (NAc). The majority of NAc neurons are GABAergic projection neurons known as medium spiny neurons (MSNs). MSNs are broadly defined by dopamine receptor expression, but evidence suggests that a wider array of subtypes exist.

The angiotensin II receptors type 1 and 2 modulate astrocytes and their crosstalk with microglia and neurons in an in vitro model of ischemic stroke.

Background: Astrocytes are the most abundant cell type of the central nervous system and are fundamentally involved in homeostasis, neuroprotection, and synaptic plasticity. This regulatory function of astrocytes on their neighboring cells in the healthy brain is subject of current research. In the ischemic brain we assume disease specific differences in astrocytic acting.

A single-nucleus transcriptomic atlas of medium spiny neurons in the rat nucleus accumbens.

Neural processing of rewarding stimuli involves several distinct regions, including the nucleus accumbens (NAc). The majority of NAc neurons are GABAergic projection neurons known as medium spiny neurons (MSNs). MSNs are broadly defined by dopamine receptor expression, but evidence suggests that a wider array of subtypes exist.

Early Blood-Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice.

Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice.

Interaction between gestational plane of nutrition and lactation diet composition on lactation performance of Alpine goats of different parities.

A study was conducted with 48 multiparous and 31 primiparous Alpine goats to determine the effects of different nutritional planes during gestation and lactation on feed intake, body weight, body condition score and mass index, blood constituent concentrations, and milk yield and composition. Two gestation supplement treatments (GS; Moderate versus High) were imposed for approximately 5.5 months and two lactation diets (LD; Moderate vs.

PYY infused systemically or directly into the VTA attenuates fentanyl seeking in male rats.

More effective treatments for fentanyl use disorder are urgently needed. An emerging literature indicates that glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate voluntary opioid taking and seeking in rodents. However, GLP-1R agonists produce adverse malaise-like effects that may limit patient compliance.

Calcitonin receptor signaling in nucleus accumbens D1R- and D2R-expressing medium spiny neurons bidirectionally alters opioid taking in male rats.

The high rates of relapse associated with current medications used to treat opioid use disorder (OUD) necessitate research that expands our understanding of the neural mechanisms regulating opioid taking to identify molecular substrates that could be targeted by novel pharmacotherapies to treat OUD. Recent studies show that activation of calcitonin receptors (CTRs) is sufficient to reduce the rewarding effects of addictive drugs in rodents. However, the role of central CTR signaling in opioid-mediated behaviors has not been studied.

Mechanical activation of lung epithelial cells through the ion channel Piezo1 activates the metalloproteinases ADAM10 and ADAM17 and promotes growth factor and adhesion molecule release.

In the lung, pulmonary epithelial cells undergo mechanical stretching during ventilation. The associated cellular mechanoresponse is still poorly understood at the molecular level. Here, we demonstrate that activation of the mechanosensitive cation channel Piezo1 in a human epithelial cell line (H441) and in primary human lung epithelial cells induces the proteolytic activity of the metalloproteinases ADAM10 and ADAM17 at the plasma membrane.

Elastomeric Pillar Cages Modulate Actomyosin Contractility of Epithelial Microtissues by Substrate Stiffness and Topography.

Cell contractility regulates epithelial tissue geometry development and homeostasis. The underlying mechanobiological regulation circuits are poorly understood and experimentally challenging. We developed an elastomeric pillar cage (EPC) array to quantify cell contractility as a mechanoresponse of epithelial microtissues to substrate stiffness and topography.

Polarity signaling balances epithelial contractility and mechanical resistance.

Epithelia maintain a functional barrier during tissue turnover while facing varying mechanical stress. This maintenance requires both dynamic cell rearrangements driven by actomyosin-linked intercellular adherens junctions and ability to adapt to and resist extrinsic mechanical forces enabled by keratin filament-linked desmosomes. How these two systems crosstalk to coordinate cellular movement and mechanical resilience is not known.

Smuggling on the Nanoscale-Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo.

The efficient and biocompatible transfer of nucleic acids into mammalian cells for research applications or medical purposes is a long-standing, challenging task. Viral transduction is the most efficient transfer system, but often entails high safety levels for research and potential health impairments for patients in medical applications. Lipo- or polyplexes are commonly used transfer systems but result in comparably low transfer efficiencies.

Integrated model of primary and mental healthcare for the refugee population served by an academic medical centre.

Refugees are at increased risk for developing mental health concerns due to high rates of trauma exposure and postmigration stressors. Moreover, barriers to accessing mental health services result in ongoing suffering within this population. Integrated care-which combines primary healthcare and mental healthcare into one cohesive, collaborative setting-may improve refugees' access to comprehensive physical and mental health services to ultimately better support this uniquely vulnerable population.

PEGylation and folic-acid functionalization of cationic lipoplexes-Improved nucleic acid transfer into cancer cells.

Efficient and reliable transfer of nucleic acids for therapy applications is a major challenge. Stabilization of lipo- and polyplexes has already been successfully achieved by PEGylation. This modification reduces the interaction with serum proteins and thus prevents the lipoplexes from being cleared by the reticuloendothelial system.

Cell Stretcher Assay to Analyze Mechanoresponses to Cyclic Stretching.

In their natural environment, most cells and tissues are continuously exposed to cyclic mechanical strain. Sensing these stimuli by mechanosensory proteins and subsequent conversion into a variety of biological responses (referred to as mechanotransduction) are key processes for tissue homeostasis, survival, and differentiation. Perturbations of underlying signaling pathways lead to severe diseases in vivo (Urciuoli E, Peruzzi B, Int J Mol Sci 21(24).

ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development.

Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore, we created a magnetic shear strain device that enabled, for the first time, to analyze the instant shear strain response of human breast gland cells.

Membrane tension controls the phase equilibrium in fusogenic liposomes.

Fusogenic liposomes have been widely used for molecule delivery to cell membranes and cell interior. However, their physicochemical state is still little understood. We tested mechanical material behavior by micropipette aspiration of giant vesicles from fusogenic lipid mixtures and found that the membranes of these vesicles are fluid and under high mechanical tension even before aspiration.

Intrinsic cell rheology drives junction maturation.

A fundamental property of higher eukaryotes that underpins their evolutionary success is stable cell-cell cohesion. Yet, how intrinsic cell rheology and stiffness contributes to junction stabilization and maturation is poorly understood. We demonstrate that localized modulation of cell rheology governs the transition of a slack, undulated cell-cell contact (weak adhesion) to a mature, straight junction (optimal adhesion).

Technology-Based Responses to Technology-Facilitated Domestic and Family Violence: An Overview of the Limits and Possibilities of Tech-Based "Solutions".

It is increasingly common for domestic and family violence to have an element of technology-facilitated abuse (TFA). As a result, technology-based responses have emerged to address TFA. Using observations from several empirical research projects into TFA, it will be shown that technology-based responses are necessary without being sufficient, and that they have persistent limitations that need to be recognized.

Desmoplakin Maintains Transcellular Keratin Scaffolding and Protects From Intestinal Injury.

Background & Aims: Desmosomes are intercellular junctions connecting keratin intermediate filaments of neighboring cells. The cadherins desmoglein 2 (Dsg2) and desmocollin 2 mediate cell-cell adhesion, whereas desmoplakin (Dsp) provides the attachment of desmosomes to keratins. Although the importance of the desmosome-keratin network is well established in mechanically challenged tissues, we aimed to assess the currently understudied function of desmosomal proteins in intestinal epithelia.

A novel approach to treating opioid use disorders: Dual agonists of glucagon-like peptide-1 receptors and neuropeptide Y receptors.

The widespread misuse of opioids and opioid use disorder (OUD) together constitute a major public health crisis in the United States. The greatest challenge for successfully treating OUD is preventing relapse. Unfortunately, there are few FDA-approved medications to treat OUD and, while effective, these pharmacotherapies are limited by high relapse rates.

NSCs Under Strain-Unraveling the Mechanoprotective Role of Differentiating Astrocytes in a Cyclically Stretched Coculture With Differentiating Neurons.

The neural stem cell (NSC) niche is a highly vascularized microenvironment that supplies stem cells with relevant biological and chemical cues. However, the NSCs' proximity to the vasculature also means that the NSCs are subjected to permanent tissue deformation effected by the vessels' heartbeat-induced pulsatile movements. Cultivating NSCs under common culture conditions neglects the-yet unknown-influence of this cyclic mechanical strain on neural stem cells.

From Microspikes to Stress Fibers: Actin Remodeling in Breast Acini Drives Myosin II-Mediated Basement Membrane Invasion.

The cellular mechanisms of basement membrane (BM) invasion remain poorly understood. We investigated the invasion-promoting mechanisms of actin cytoskeleton reorganization in BM-covered MCF10A breast acini. High-resolution confocal microscopy has characterized actin cell protrusion formation and function in response to tumor-resembling ECM stiffness and soluble EGF stimulation.