Multivalent GU-rich oligonucleotides sequester TDP-43 in the nucleus by inducing high molecular weight RNP complexes.

TDP-43 nuclear clearance and cytoplasmic aggregation are hallmarks of TDP-43 proteinopathies. We recently demonstrated that binding to endogenous nuclear GU-rich RNAs sequesters TDP-43 in the nucleus by restricting its passive nuclear export. Here, we tested the feasibility of synthetic RNA oligonucleotide-mediated augmentation of TDP-43 nuclear localization.

Elevated nuclear TDP-43 induces constitutive exon skipping.

Background: Cytoplasmic inclusions and loss of nuclear TDP-43 are key pathological features found in several neurodegenerative disorders, suggesting both gain- and loss-of-function mechanisms of disease. To study gain-of-function, TDP-43 overexpression has been used to generate in vitro and in vivo model systems.

Methods: We analyzed RNA-seq datasets from mouse and human neurons overexpressing TDP-43 to explore species specific splicing patterns.

Elevated nuclear TDP-43 induces constitutive exon skipping.

Cytoplasmic inclusions and loss of nuclear TDP-43 are key pathological features found in several neurodegenerative disorders, suggesting both gain- and loss-of-function mechanisms of disease. To study gain-of-function, TDP-43 overexpression has been used to generate and model systems. Our study shows that excessive levels of nuclear TDP-43 protein lead to constitutive exon skipping that is largely species-specific.

Microstructural and Mechanical Characterization of Al Nanocomposites Using GCNs as a Reinforcement Fabricated by Induction Sintering.

High-energy ball milling is a process suitable for producing composite powders whose achieved microstructure can be controlled by the processing parameters. Through this technique, it is possible to obtain a homogeneous distribution of reinforced material into a ductile metal matrix. In this work, some Al/CGNs nanocomposites were fabricated through a high-energy ball mill to disperse nanostructured graphite reinforcements produced in situ in the Al matrix.

Cell-specific regulation of gene expression using splicing-dependent frameshifting.

Precise and reliable cell-specific gene delivery remains technically challenging. Here we report a splicing-based approach for controlling gene expression whereby separate translational reading frames are coupled to the inclusion or exclusion of mutated, frameshifting cell-specific alternative exons. Candidate exons are identified by analyzing thousands of publicly available RNA sequencing datasets and filtering by cell specificity, conservation, and local intron length.

In vitro model of postoncosphere development, and in vivo infection abilities of Taenia solium and Taenia saginata.

Taenia solium is known to cause human cysticercosis while T. saginata does not. Comparative in vitro and in vivo studies on the oncosphere and the postoncospheral (PO) forms of T.

Axonal swellings and spheroids: a new insight into the pathology of neurocysticercosis.

Neurocysticercosis is a parasitic brain disease caused by the larval form (Cysticercus cellulosae) of Taenia solium and is the leading cause of preventable epilepsy worldwide. However, the pathophysiology and relation to the wide range of clinical features remains poorly understood. Axonal swelling is emerging as an important early pathological finding in multiple neurodegenerative diseases and as a cause of brain injury, but has not been well described in neurocysticercosis.

Blood-brain barrier disruption and angiogenesis in a rat model for neurocysticercosis.

Neurocysticercosis (NCC) is a helminth infection affecting the central nervous system caused by the larval stage (cysticercus) of Taenia solium. Since vascular alteration and blood-brain barrier (BBB) disruption contribute to NCC pathology, it is postulated that angiogenesis could contribute to the pathology of this disease. This study used a rat model for NCC and evaluated the expression of two angiogenic factors called vascular endothelial growth factor (VEGF-A) and fibroblast growth factor (FGF2).

Low frequency of renal function impairment during one-year of therapy with tenofovir-containing regimens in the real-world: a case-control study.

Concern exists about the risk of nephrotoxicity using tenofovir (TDF) in HIV-infected patients. We performed a retrospective case-control study including 122 consecutive TDF-naive patients who started treatment with TDF-containing regimens and 194 patients receiving antiretroviral therapy with other antiretroviral drugs. During a 12-month observation period 5 (4.

Neuropsychological functioning in methadone maintenance patients versus abstinent heroin abusers.

Several studies have reported on neuropsychological status as an important contributing variable in drug abuse rehabilitation outcomes. However, few studies have dealt with cognitive impairment in methadone maintenance patients (MMP), despite the fact that methadone is the most frequently used opioid substitution treatment in European countries. The objective of the present study is to contrast the neuropsychological performance of MMP with that of abstinent heroin abusers (AHA).