Repurposing DPP4 Inhibition to Improve Hair Follicle Activation and Regeneration.

Skin injury and several diseases elicit fibrosis and induce hair follicle (HF) growth arrest and loss. The resulting alopecia and disfiguration represent a severe burden for patients, both physically and psychologically. Reduction of profibrotic factors such as dipeptidyl peptidase 4 (DPP4) might be a strategy to tackle this issue.

Single-cell trajectories of melanoma cell resistance to targeted treatment.

Objective: Cellular heterogeneity is regarded as a major factor affecting treatment response and resistance in malignant melanoma. Recent developments in single-cell sequencing technology have provided deeper insights into these mechanisms.

Methods: Here, we analyzed a -mutant melanoma cell line by single-cell RNA-seq under various conditions: cells sensitive to BRAF inhibition with BRAF inhibitor vemurafenib and cells resistant to BRAF inhibition with vemurafenib alone or vemurafenib in combination with the MEK1/2 inhibitors cobimetinib or trametinib.

Melanoma Single-Cell Biology in Experimental and Clinical Settings.

Cellular heterogeneity is regarded as a major factor for treatment response and resistance in a variety of malignant tumors, including malignant melanoma. More recent developments of single-cell sequencing technology provided deeper insights into this phenomenon. Single-cell data were used to identify prognostic subtypes of melanoma tumors, with a special emphasis on immune cells and fibroblasts in the tumor microenvironment.

Ultrastructural Imaging of Activity-Dependent Synaptic Membrane-Trafficking Events in Cultured Brain Slices.

Electron microscopy can resolve synapse ultrastructure with nanometer precision, but the capture of time-resolved, activity-dependent synaptic membrane-trafficking events has remained challenging, particularly in functionally distinct synapses in a tissue context. We present a method that combines optogenetic stimulation-coupled cryofixation ("flash-and-freeze") and electron microscopy to visualize membrane trafficking events and synapse-state-specific changes in presynaptic vesicle organization with high spatiotemporal resolution in synapses of cultured mouse brain tissue. With our experimental workflow, electrophysiological and "flash-and-freeze" electron microscopy experiments can be performed under identical conditions in artificial cerebrospinal fluid alone, without the addition of external cryoprotectants, which are otherwise needed to allow adequate tissue preservation upon freezing.

Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses.

Complexin (Cplx) proteins modulate the core SNARE complex to regulate exocytosis. To understand the contributions of Cplx to signaling in a well-characterized neural circuit, we investigated how Cplx3, a retina-specific paralog, shapes transmission at rod bipolar (RB)→AII amacrine cell synapses in the mouse retina. Knockout of Cplx3 strongly attenuated fast, phasic Ca(2+)-dependent transmission, dependent on local [Ca(2+)] nanodomains, but enhanced slower Ca(2+)-dependent transmission, dependent on global intraterminal [Ca(2+)] ([Ca(2+)]I).

KV 10.1 opposes activity-dependent increase in Ca²⁺ influx into the presynaptic terminal of the parallel fibre-Purkinje cell synapse.

Voltage-gated KV 10.1 potassium channels are widely expressed in the mammalian brain but their function remains poorly understood. We report that KV 10.

Human glioma-initiating cells show a distinct immature phenotype resembling but not identical to NG2 glia.

Glioma-initiating cells (GICs) represent a potential important therapeutic target because they are likely to account for the frequent recurrence of malignant gliomas; however, their identity remains unsolved. Here, we characterized the cellular lineage fingerprint of GICs through a combination of electrophysiology, lineage marker expression, and differentiation assays of 5 human patient-derived primary GIC lines. Most GICs coexpressed nestin, NG2 proteoglycan, platelet-derived growth factor receptor-α, and glial fibrillary acidic protein.

Behavioural and functional characterization of Kv10.1 (Eag1) knockout mice.

Kv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.

Reduced amygdala-prefrontal coupling in major depression: association with MAOA genotype and illness severity.

The amygdala plays a pivotal role in a cortico-limbic circuitry implicated in emotion processing and regulation. In the present study, functional connectivity of the amygdala with prefrontal areas involved in emotion regulation was investigated during a facial expression processing task in a sample of 34 depressed inpatients and 31 healthy controls. All patients were genotyped for a common functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the monoamine oxidase A gene (MAOA u-VNTR) which has been previously associated with major depression as well as reduced cortico-limbic connectivity in healthy subjects.

Association of MAO-A variant with complicated grief in major depression.

Background/aims: It has been suggested that monoamine oxidase A (MAO-A) activity is involved in the pathogenesis of major depression. Bereavement-related complicated grief significantly increases the risk of major depression and has been shown to be influenced by serotonergic tonus, possibly conferred by MAO-A activity. Complicated grief--whose inclusion in DSM-V as a separate mental disorder is under discussion--has been shown to be a distinct syndrome with symptoms not seen in depression.

Serotonin transporter polymorphism (5-HTTLPR) association with melancholic depression: a female specific effect?

Earlier studies yielded inconsistent results on the association between variation in the serotonin transporter (5-HTT) gene and depression, with evidence for a differential effect of the 5-HTTLPR on melancholic versus atypical depression. To further delineate the impact of 5-HTT gene variation on psychopathology in depression, in this analysis the influence of the 5-HTTLPR and the functionally closely related 5-HTT rs25531 was investigated in 340 Caucasian patients with a major depressive episode (DSM-IV) with particular attention to the subtype of depression (melancholic depression versus atypical depression) applying logistic regression models adjusted for age and gender. The homozygous, more active 5-HTTLPR LL genotype was significantly associated with melancholic depression (odds ratio, OR, 1.

Monoamine oxidase A variant influences antidepressant treatment response in female patients with Major Depression.

The monoamine oxidase A (MAO-A) has been suggested to be involved in the pathogenesis as well as the pharmacological treatment of Major Depression. In the present study, 340 patients with a Major Depressive Episode (f=194, m=146; DSM-IV) of Caucasian descent were genotyped for the functional MAO-A VNTR. The clinical response to antidepressive pharmacological treatment was assessed by weekly intra-individual changes of HAM-D-21 scores over six weeks.