Differential interaction patterns of opioid analgesics with µ opioid receptors correlate with ligand-specific voltage sensitivity.

The µ opioid receptor (MOR) is the key target for analgesia, but the application of opioids is accompanied by several issues. There is a wide range of opioid analgesics, differing in their chemical structure and their properties of receptor activation and subsequent effects. A better understanding of ligand-receptor interactions and the resulting effects is important. Here, we calculated the respective binding poses for several opioids and analyzed interaction fingerprints between ligand and receptor. We further corroborated the interactions experimentally by cellular assays. As MOR was observed to display ligand-induced modulation of activity due to changes in membrane potential, we further analyzed the effects of voltage sensitivity on this receptor. Combining in silico and in vitro approaches, we defined discriminating interaction patterns responsible for ligand-specific voltage sensitivity and present new insights into their specific effects on activation of the MOR.

Trends in the neurological emergency room, focusing on persons with seizures.

BACKGROUND AND PURPOSE: Previous studies in neurological emergency rooms (nERs) have reported many non-acute, self-presenting patients, patients with delayed presentation of stroke, and frequent visits of persons with seizures (PWS). The aim of this study was to evaluate trends during the last decade, with special focus on PWS. METHODS: We retrospectively analyzed patients who presented to our specialized nER during the course of 5 months in 2017 and 2019, and included information on admission/referral, hospitalization, discharge diagnosis, and diagnostic tests/treatment in the nER. RESULTS: A total of 2791 patients (46.6% male, mean age 57 ± 21 years) were included. The most common diagnoses were cerebrovascular events (26.3%), headache (14.1%), and seizures (10.5%). Most patients presented with symptoms lasting >48 h (41.3%). The PWS group included the largest proportion of patients presenting within 4.5 h of symptom onset (171/293, 58.4%), whereas only 37.1% of stroke patients presented within this time frame (273/735). Self-presentation was the most common admission pathway (31.1%), followed by emergency service referral (30.4%, including the majority of PWS: 197/293, 67.2%). Despite known diagnosis of epilepsy in 49.2%, PWS more often underwent accessory diagnostic testing including cerebral imaging, compared to the overall cohort (accessory diagnostics 93.9% vs. 85.4%; cerebral imaging 70.1% vs. 64.1%). Electroencephalography in the nER was only performed in 20/111 patients (18.0%) with a first seizure. Nearly half of the patients (46.7%) were discharged home after nER work-up, including most self-presenters (632/869, 72.7%) and headache patients (377/393, 88.3%), as well as 37.2% (109/293) of PWS. CONCLUSION: After 10 years, nER overuse remains a problem. Stroke patients still do not present early enough, whereas PWS, even those with known epilepsy, often seek acute and extensive assessment, indicating gaps in pre-hospital management and possible over-assessment.

Monolithic Zirconium-Based Metal-Organic Frameworks for Energy-Efficient Water Adsorption Applications.

Space cooling and heating, ventilation, and air conditioning (HVAC) accounts for roughly 10% of global electricity use and are responsible for ca. 1.13 gigatonnes of CO2 emissions annually. Adsorbent-based HVAC technologies have long been touted as an energy-efficient alternative to traditional refrigeration systems. However, thus far, no suitable adsorbents have been developed which overcome the drawbacks associated with traditional sorbent materials such as silica gels and zeolites. Metal-organic frameworks (MOFs) offer order-of-magnitude improvements in water adsorption and regeneration energy requirements. However, the deployment of MOFs in HVAC applications has been hampered by issues related to MOF powder processing. Herein, three high-density, shaped, monolithic MOFs (UiO-66, UiO-66-NH2 , and Zr-fumarate) with exceptional volumetric gas/vapor uptake are developed-solving previous issues in MOF-HVAC deployment. The monolithic structures across the mesoporous range are visualized using small-angle X-ray scattering and lattice-gas models, giving accurate predictions of adsorption characteristics of the monolithic materials. It is also demonstrated that a fragile MOF such as Zr-fumarate can be synthesized in monolithic form with a bulk density of 0.76 gcm-3 without losing any adsorption performance, having a coefficient of performance (COP) of 0.71 with a low regeneration temperature (≤ 100 °C).

The externalities of energy production in the context of development of clean energy generation.

In this paper, we present a comparative review of the externalities of electricity production. First of all, the environmental impact is considered. A discussion of the influence of various electricity production processes on human health follows. The studies are conducted in the context of historical development. Current trends, as well as a historical background that resulted in the changes that can be observed today, are presented. The considerations are supported by a few case studies. Analysis of perspectives for the development of electricity generation methods, in particular the indication of clean energy sources and the perspectives of their exploitation, is the main aim of this paper.

A metal-organic framework for efficient water-based ultra-low-temperature-driven cooling.

Efficient use of energy for cooling applications is a very important and challenging field in science. Ultra-low temperature actuated (Tdriving < 80 °C) adsorption-driven chillers (ADCs) with water as the cooling agent are one environmentally benign option. The nanoscale metal-organic framework [Al(OH)(C6H2O4S)] denoted CAU-23 was discovered that possess favorable properties, including water adsorption capacity of 0.37 gH2O/gsorbent around p/p0 = 0.3 and cycling stability of at least 5000 cycles. Most importantly the material has a driving temperature down to 60 °C, which allows for the exploitation of yet mostly unused temperature sources and a more efficient use of energy. These exceptional properties are due to its unique crystal structure, which was unequivocally elucidated by single crystal electron diffraction. Monte Carlo simulations were performed to reveal the water adsorption mechanism at the atomic level. With its green synthesis, CAU-23 is an ideal material to realize ultra-low temperature driven ADC devices.

CD146 (MCAM) in human cs-DLK1-/cs-CD34+ adipose stromal/progenitor cells.

To precisely characterize CD146 in adipose stromal/progenitor cells (ASCs) we sorted the stromal vascular faction (SVF) of human abdominal subcutaneous white adipose tissue (sWAT) according to cell surface (cs) expression of CD146, DLK1 and CD34. This test identified three main SVF cell populations: ~50% cs-DLK1-/cs-CD34+/cs-CD146- ASCs, ~7.5% cs-DLK1+/cs-CD34dim/+/cs-CD146+ and ~7.5% cs-DLK1+/cs-CD34dim/+/cs-CD146- cells. All cells contained intracellular CD146. Whole mount fluorescent IHC staining of small vessels detected CD146+ endothelial cells (CD31+/CD34+/CD146+) and pericytes (CD31-/CD34-/CD146+ ASCs). The cells in the outer adventitial layer showed the typical ASC morphology, were strongly CD34+ and contained low amounts of intracellular CD146 protein (CD31-/CD34+/CD146+). Additionally, we detected wavy CD34-/CD146+ and CD34dim/CD146+ cells. CD34dim/CD146+ cells were slightly more bulky than CD34-/CD146+ cells. Both CD34-/CD146+ and CD34dim/CD146+ cells were detached from the inner pericyte layer and protruded into the outer adventitial layer. Cultured early passage ASCs contained low levels of CD146 mRNA, which was expressed in two different splicing variants, at a relatively high amount of the CD146-long form and at a relatively low amount of the CD146-short form. ASCs contained low levels of CD146 protein, which consisted predominantly long form and a small amount of short form. The CD146 protein was highly stable, and the majority of the protein was localized in the Golgi apparatus. In conclusion, the present study contributes to a better understanding of the spatial localization of CD34+/CD146+ and CD34-/CD146+ cells in the adipose niche of sWAT and identifies CD146 as intracellular protein in cs-DLK1-/cs-CD34+/cs-CD146- ASCs.