DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons.

Disturbed motor control is a hallmark of Parkinson's disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats.

CD4+ T cells are the major predictor of HCMV control in allogeneic stem cell transplant recipients on letermovir prophylaxis.

Introduction: Human cytomegalovirus (HCMV) causes significant morbidity and mortality in allogeneic stem cell transplant (alloSCT) recipients. Recently, antiviral letermovir prophylaxis during the first 100 days after alloSCT replaced PCR-guided preemptive therapy as the primary standard of care for HCMV reactivations. Here, we compared NK-cell and T-cell reconstitution in alloSCT recipients receiving preemptive therapy or letermovir prophylaxis in order to identify potential biomarkers predicting prolonged and symptomatic HCMV reactivation.

Dimethylnonacethrene - to a magnetic switch.

Dimethylnonacethrene is the first derivative of the cethrene family that is energetically more stable than the product of its electrocyclic ring closure. Compared to the shorter homologue dimethylcethrene, the new system is EPR-active, because of a significantly lowered singlet-triplet gap, and displays remarkable stability. Our results suggest that adjustment of the steric bulk in the fjord region can enable realisation of diradicaloid-based magnetic photoswitches.

Intravenous injection of cyclosporin A loaded lipid nanocapsules fights inflammation and immune system activation in a mouse model of diabetic retinopathy.

Inflammation and immune system activation are key pathologic events in the onset and escalation of diabetic retinopathy (DR). Both are driven by cytokines and complement originating from the retinal pigment epithelium (RPE). Despite the RPE's pivotal role, there is no therapeutic tool to specifically interfere with the RPE-related pathomechanism.

USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer.

SREBP2 is a master regulator of the mevalonate pathway (MVP), a biosynthetic process that drives the synthesis of dolichol, heme A, ubiquinone and cholesterol and also provides substrates for protein prenylation. Here, we identify SREBP2 as a novel substrate for USP28, a deubiquitinating enzyme that is frequently upregulated in squamous cancers. Our results show that silencing of USP28 reduces expression of MVP enzymes and lowers metabolic flux into this pathway.

Timing of Ketogenic Dietary Therapy (KDT) Introduction and Its Impact on Cognitive Profiles in Children with Glut1-DS-A Preliminary Study.

Unlabelled: The aim of this research was to characterize cognitive abilities in patients with Glut1-Deficiency syndrome (Glut1DS) following ketogenic diet therapy (KDT).

Methods: The cognitive profiles of eight children were assessed using the Wechsler Intelligence Scale (WISC-IV). The effect of ketogenic diet therapy (KDT) on individual subareas of intelligence was analyzed considering the potential influence of speech motor impairments.

Handmade spacers for two-stage exchange at the hip.

Objective: Two-stage exchange with implantation of a temporary spacer is the gold standard treatment for chronic periprosthetic joint infection of the hip. This article describes a simple and safe technique for handmade spacers at the hip.

Indication: Periprosthetic joint infection of the hip.

Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors-A Comprehensive Reactivity and Selectivity Study.

Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding.

Prospective single-center study of health-related quality of life after COVID-19 in ICU and non-ICU patients.

Long-term sequelae in hospitalized Coronavirus Disease 2019 (COVID-19) patients may result in limited quality of life. The current study aimed to determine health-related quality of life (HRQoL) after COVID-19 hospitalization in non-intensive care unit (ICU) and ICU patients. This is a single-center study at the University Hospital of Wuerzburg, Germany.

Solution and solid-state studies of hydrogen and halogen bonding with N-heterocyclic carbene supported nickel(II) fluoride complexes.

Nickel fluoride complexes of the type [Ni(F)(L)(Ar)] (L = phosphine, Ar = fluorinated arene) are well-known to form strong halogen and hydrogen bonds in solution and in the solid state. A comprehensive study of such non-covalent interactions using bis(carbene) complexes as acceptors and suitable halogen and hydrogen bond donors is presented. In solution, the complex [Ni(F)(iPrIm)(CF)] forms halogen and hydrogen bonds with iodopentafluorobenzene and indole, respectively, which have formation constants () an order of magnitude greater than those of structurally related phosphine supported nickel fluorides.

Automated classification of polyps using deep learning architectures and few-shot learning.

Background: Colorectal cancer is a leading cause of cancer-related deaths worldwide. The best method to prevent CRC is a colonoscopy. However, not all colon polyps have the risk of becoming cancerous.

Tailoring baker's yeast Saccharomyces cerevisiae for functional testing of channelrhodopsin.

Channelrhodopsin 2 (ChR2) and its variants are the most frequent tools for remote manipulation of electrical properties in cells via light. Ongoing attempts try to enlarge their functional spectrum with respect to ion selectivity, light sensitivity and protein trafficking by mutations, protein engineering and environmental mining of ChR2 variants. A shortcoming in the required functional testing of large numbers of ChR2 variants is the lack of an easy screening system.

Orbital-resolved observation of singlet fission.

Singlet fission may boost photovoltaic efficiency by transforming a singlet exciton into two triplet excitons and thereby doubling the number of excited charge carriers. The primary step of singlet fission is the ultrafast creation of the correlated triplet pair. Whereas several mechanisms have been proposed to explain this step, none has emerged as a consensus.

Anomalous deep-red luminescence of perylene black analogues with strong π-π interactions.

Perylene bisimide (PBI) dyes are known as red, maroon and black pigments, whose colors depend on the close π-π stacking arrangement. However, contrary to the luminescent monomers, deep-red and black PBI pigments are commonly non- or only weakly fluorescent due to (multiple) quenching pathways. Here, we introduce N-alkoxybenzyl substituted PBIs that contain close π stacking arrangement (exhibiting d ≈ 3.

Direct Stochastic Optical Reconstruction Microscopy (dSTORM) of Peroxisomes.

Peroxisomes are central metabolic organelles whose maturation and function depend on efficient and accurate targeting of peroxisomal membrane proteins (PMPs). Ultrastructural imaging of the PMPs is a quite difficult task as it requires high spatial and temporal resolution. Further, the spatial resolution of conventional light microscopy is limited due to the diffraction of light.

Comparative in vitro treatment of mesenchymal stromal cells with GDF-5 and R57A induces chondrogenic differentiation while limiting chondrogenic hypertrophy.

Purpose: Hypertrophic cartilage is an important characteristic of osteoarthritis and can often be found in patients suffering from osteoarthritis. Although the exact pathomechanism remains poorly understood, hypertrophic de-differentiation of chondrocytes also poses a major challenge in the cell-based repair of hyaline cartilage using mesenchymal stromal cells (MSCs). While different members of the transforming growth factor beta (TGF-β) family have been shown to promote chondrogenesis in MSCs, the transition into a hypertrophic phenotype remains a problem.

Distinct phenotypes of stimulation-induced dysarthria represent different cortical networks in STN-DBS.

Background: Deep brain stimulation of the subthalamic nucleus is an effective treatment of Parkinson's disease, yet it is often associated with a general deterioration of speech intelligibility. Clustering the phenotypes of dysarthria has been proposed as a strategy to tackle these stimulation-induced speech problems.

Methods: In this study, we examine a cohort of 24 patients to test the real-life application of the proposed clustering and attempt to attribute the clusters to specific brain networks with two different approaches of connectivity analysis.

What is behind partial repetition costs? Event-files do not fully occupy bound feature codes.

Feature binding accounts state that features of perceived and produced events are bound into event-files. Performance while responding to an event is impaired when some, as opposed to all or none, of this event's features already belong to a previous event-file. While these partial repetition costs are generally considered to be indicators of feature binding, their cause is still unclear.

Nickel boryl complexes and nickel-catalyzed alkyne borylation.

The first nickel bis-boryl complexes -[Ni( PrIm)(Bcat)], -[Ni( PrIm)(Bpin)] and -[Ni( PrIm)(Beg)] are reported, which were prepared the reaction of a source of [Ni( PrIm)] with the diboron(4) compounds Bcat, Bpin and Beg ( PrIm = 1,3-di-iso-propyl-4,5-dimethylimidazolin-2-ylidene; Bcat = bis(catecholato)diboron; Bpin = bis(pinacolato)diboron; Beg = bis(ethylene glycolato)diboron). X-ray diffraction and DFT calculations strongly suggest that a delocalized, multicenter bonding scheme dictates the bonding situation of the NiB moiety in these square planar complexes, reminiscent of the bonding situation of "non-classical" H complexes. [Ni( PrIm)] also efficiently catalyzes the diboration of alkynes using Bcat as the boron source under mild conditions.

Demographics and Etiology for Lower Extremity Amputations-Experiences of an University Orthopaedic Center in Germany.

: Currently, the worldwide incidence of major amputations in the general population is decreasing whereas the incidence of minor amputations is increasing. The purpose of our study was to analyze whether this trend is reflected among orthopaedic patients treated with lower extremity amputation in our orthopaedic university institution. : We conducted a single-center retrospective study and included patients referred to our orthopaedic department for lower extremity amputation (LEA) between January 2007 and December 2019.

Determinants of satisfaction with acute pain therapy during and after childbirth.

Background: An important task in obstetrics is to offer patients adequate pain management after vaginal delivery (VD) and after cesarean section (CS). The aim of the present analysis was to assess pain intensity at the day after childbirth, after 3 and 6 months in women after VD and after CS. Additionally, it was planned to identify determinants of maternal satisfaction with acute pain therapy following VD and CS.

Multifaceted behavior of a doubly reduced arylborane in B-H-bond activation and hydroboration catalysis.

Alkali-metal salts of 9,10-dimethyl-9,10-dihydro-9,10-diboraanthrancene (M[DBA-Me]; M = Li, Na, K) activate the H-B bond of pinacolborane (HBpin) in THF already at room temperature. For M = Na, K, the addition products M[4] are formed, which contain one new H-B and one new B-Bpin bond; for M = Li, the H ion is instantaneously transferred from the DBA-Me unit to another equivalent of HBpin to afford Li[5]. Although Li[5] might commonly be considered a [Bpin] adduct of neutral DBA-Me, it donates a [Bpin] cation to Li[SiPh], generating the silyl borane PhSi-Bpin; Li[DBA-Me] with an aromatic central BC ring acts as the leaving group.