Publication

Synaptic reorganization response in the cochlear nucleus following intense noise exposure.

The cochlear nucleus, located in the brainstem, receives its afferent auditory input exclusively from the auditory nerve fibers of the ipsilateral cochlea. Noise-induced neurodegenerative changes occurring in the auditory nerve stimulate a cascade of neuroplastic changes in the cochlear nucleus resulting in major changes in synaptic structure and function.

Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during progression into dormancy.

Relapses of Plasmodium dormant liver hypnozoites compromise malaria eradication efforts. New radical cure drugs are urgently needed, yet the vast gap in knowledge of hypnozoite biology impedes drug discovery. We previously unraveled the transcriptome of 6 to 7 day-old P. cynomolgi liver stages, highlighting pathways associated with hypnozoite dormancy (Voorberg-van der Wel, 2017). We now extend these findings by transcriptome profiling of 9 to 10 day-old liver stage parasites, thus revealing for the first time the maturation of the dormant stage over time.

A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors.

Inhibition of the PARP superfamily tankyrase enzymes suppresses Wnt/b-catenin
signalling in tumour cells. Here, we describe here a novel, drug-like small molecule
inhibitor of tankyrase MSC2504877 that inhibits the growth of APC mutant colorectal
tumour cells. Parallel siRNA and drug sensitivity screens showed that the clinical CDK4/6
inhibitor palbociclib, causes enhanced sensitivity to MSC2504877. This tankyrase
inhibitor-CDK4/6 inhibitor combinatorial effect is not limited to palbociclib and

PD-L1 expression and association with malignant behavior in pheochromocytomas/paragangliomas.

The immunosuppressive effect of the programmed death (PD)-1/PD-L1 pathway plays an important role in the treatment of a variety of tumors, such as lung and breast cancer, but there is little literature about PD-1/PD-L1 in pheochromocytomas/paragangliomas (PCC/PGLs). We explored the relationship of PD-L1 and malignant behavior in 77 cases of PCC/PGL using immunohistochemistry (IHC) to assess protein expression and RNAscope to detect mRNA expression in 20 cases.

Dendritic targeted mRNA expression via a cis-acting RNA UTR element.

Local translation in neurites is considered as an important mechanism to modulate synaptic plasticity of neurons. However, it is hard to specifically express a protein-coding gene in neurites. Recently, the 5'-UTR of Tick-borne encephalitis virus (TBEV) is reported to be able to drive its RNA to the dendrites of infected neurons, as a cis-acting RNA element. To construct a neurite specific gene expression system, present study tested the ability of 5'-UTR of TBEV to bring a mRNA (mCherry CDS) to the neurites for targeted expression.

Dermal Condensate Niche Fate Specification Occurs Prior to Formation and Is Placode Progenitor Dependent.

Cell fate transitions are essential for specification of stem cells and their niches, but the precise timing and sequence of molecular events during embryonic development are largely unknown. Here, we identify, with 3D and 4D microscopy, unclustered precursors of dermal condensates (DC), signaling niches for epithelial progenitors in hair placodes. With population-based and single-cell transcriptomics, we define a molecular time-lapse from pre-DC fate specification through DC niche formation and establish the developmental trajectory as the DC lineage emerges from fibroblasts.

Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD.

Abstract
BACKGROUND:
IL10 receptor (IL10R) deficiency causes severe infantile-onset inflammatory bowel disease. Intact IL10R-dependent signals have been shown to be important for innate and adaptive immune cell functions in mice. We have previously reported a key role of IL10 in the generation and function of human anti-inflammatory macrophages. Independent of innate immune cell defects, the aim of the current study was to determine the role of IL10R signaling in regulating human CD4 T-cell function.

Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder.

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls.

RVFV Infection in Goats by Different Routes of Inoculation.

Rift Valley fever virus (RVFV) is a zoonotic arbovirus of the Phenuiviridae family. Infection causes abortions in pregnant animals, high mortality in neonate animals, and mild to severe symptoms in both people and animals. There is currently an ongoing effort to produce safe and efficacious veterinary vaccines against RVFV in livestock to protect against both primary infection in animals and zoonotic infections in people. To test the efficacy of these vaccines, it is essential to have a reliable challenge model in relevant target species, including ruminants.

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