Combined Multiplexed Phage Display, High-Throughput Sequencing, and Functional Assays as a Platform for Identifying Modulatory VHHs Targeting the FSHR.

Developing modulatory antibodies against G protein-coupled receptors is challenging. In this study, we targeted the follicle-stimulating hormone receptor (FSHR), a significant regulator of reproduction, with variable domains of heavy chain-only antibodies (VHHs). We built two immune VHH libraries and submitted them to multiplexed phage display approaches.

Chaperone-mediated autophagy protects against hyperglycemic stress.

Chaperone-mediated autophagy (CMA) is a major pathway of lysosomal proteolysis critical for cellular homeostasis and metabolism, and whose defects have been associated with several human pathologies. While CMA has been well described in mammals, functional evidence has only recently been documented in fish, opening up new perspectives to tackle this function under a novel angle. Now we propose to explore CMA functions in the rainbow trout (RT, ), a fish species recognized as a model organism of glucose intolerance and characterized by the presence of two paralogs of the CMA-limiting factor Lamp2A (lysosomal associated membrane protein 2A).

Are the Main Methionine Sources Equivalent? A Focus on DL-Methionine and DL-Methionine Hydroxy Analog Reveals Differences on Rainbow Trout Hepatic Cell Lines Functions.

The replacement of fishmeal by plant proteins in aquafeeds imposes the use of synthetic methionine (MET) sources to balance the amino acid composition of alternative diets and so to meet the metabolic needs of fish of agronomic interest such as rainbow trout (RT-). Nonetheless, debates still exist to determine if one MET source is more efficiently used than another by fish. To address this question, the use of fish cell lines appeared a convenient strategy, since it allowed to perfectly control cell growing conditions notably by fully depleting MET from the media and studying which MET source is capable to restore cell growth/proliferation and metabolism when supplemented back.

Two repeated motifs enriched within some enhancers and origins of replication are bound by SETMAR isoforms in human colon cells.

Setmar is a gene specific to simian genomes. The function(s) of its isoforms are poorly understood and their existence in healthy tissues remains to be validated. Here we profiled SETMAR expression and its genome-wide binding landscape in colon tissue.

The piggyBac-derived protein 5 (PGBD5) transposes both the closely and the distantly related piggyBac-like elements Tcr-pble and Ifp2.

The vertebrate piggyBac derived transposase 5 (PGBD5) encodes a domesticated transposase, which is active and able to transpose its distantly related piggyBac-like element (pble), Ifp2. This raised the question whether PGBD5 would be more effective at mobilizing a phylogenetically closely related pble element. We aimed to identify the pble most closely related to the pgbd5 gene.

The C-terminal Domain of piggyBac Transposase Is Not Required for DNA Transposition.

PiggyBac(PB)-like elements (pble) are members of a eukaryotic DNA transposon family. This family is of interest to evolutionary genomics because pble transposases have been domesticated at least 9 times in vertebrates. The amino acid sequence of pble transposases can be split into three regions: an acidic N-terminal domain (~100 aa), a central domain (~400 aa) containing a DD[D/E] catalytic triad, and a cysteine-rich domain (CRD; ~90 aa).

Variations in genome size between wild and domesticated lineages of fowls belonging to the Gallus gallus species.

Efforts to elucidate the causes of biological differences between wild fowls and their domesticated relatives, the chicken, have to date mainly focused on the identification of single nucleotide mutations. Other types of genomic variations have however been demonstrated to be important in avian evolution and associated to variations in phenotype. They include several types of sequences duplicated in tandem that can vary in their repetition number.

Sequence properties of certain GC rich avian genes, their origins and absence from genome assemblies: case studies.

Background: More and more eukaryotic genomes are sequenced and assembled, most of them presented as a complete model in which missing chromosomal regions are filled by Ns and where a few chromosomes may be lacking. Avian genomes often contain sequences with high GC content, which has been hypothesized to be at the origin of many missing sequences in these genomes. We investigated features of these missing sequences to discover why some may not have been integrated into genomic libraries and/or sequenced.

A simple PCR method for sexing Japanese quail Coturnix japonica at hatching.

1. The quail is a potentially important avian model for molecular studies; a major drawback is the inability to sex visually before 3 weeks of age. Molecular sexing is therefore an absolute requirement when animals are sampled before that age.

Mariner Transposons Contain a Silencer: Possible Role of the Polycomb Repressive Complex 2.

Transposable elements are driving forces for establishing genetic innovations such as transcriptional regulatory networks in eukaryotic genomes. Here, we describe a silencer situated in the last 300 bp of the Mos1 transposase open reading frame (ORF) which functions in vertebrate and arthropod cells. Functional silencers are also found at similar locations within three other animal mariner elements, i.

Effects of discontinuing anticholinergic treatment on movement disorders, cognition and psychopathology in patients with schizophrenia.

Background: Physicians have prescribed anticholinergic agents such as benztropine, procyclidine, biperiden and trihexyphenidyl for treatment and prophylaxis of antipsychotic-induced extrapyramidal symptoms (EPS) for decades. Anticholinergic agents can however worsen tardive dyskinesia and cause many adverse effects, including cognitive impairment. Previous studies of anticholinergic discontinuation in patients with schizophrenia receiving antipsychotics have yielded a wide range of EPS relapse rates.

Risperidone long-acting injection in the treatment of schizophrenia: 24-month results from the electronic Schizophrenia Treatment Adherence Registry in Canada.

Objective: To assess outcomes over 24 months in Canadian patients with schizophrenia initiated on risperidone long-acting injection (RLAI) and participating in the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

Materials And Methods: Patients with schizophrenia or schizoaffective disorder were enrolled from 24 sites after an independent decision to initiate RLAI. Subsequent patient management was based on usual clinical practice at each site and was not protocol-driven.

A non-canonical plant microRNA target site.

Plant microRNAs (miRNAs) typically form near-perfect duplexes with their targets and mediate mRNA cleavage. Here, we describe an unconventional miRNA target of miR398 in Arabidopsis, an mRNA encoding the blue copper-binding protein (BCBP). BCBP mRNA carries an miR398 complementary site in its 5'-untranslated region (UTR) with a bulge of six nucleotides opposite to the 5' region of the miRNA.

Anticholinergics in the era of atypical antipsychotics: short-term or long-term treatment?

Anticholinergic agents are usually prescribed to prevent or treat antipsychotic-induced extrapyramidal symptoms. Their long-term benefits are questionable and they carry diverse adverse effects, including cognitive impairment and worsening of tardive dyskinesia. This literature review explores the impact of anticholinergic medication discontinuation on movement disorders, cognition and psychopathology in patients receiving antipsychotics.

Switching from brand-name to generic psychotropic medications: a literature review.

Generic medications do not undergo the rigorous approval process required of original medications. Their effectiveness and safety is expected to be equal to that of their more expensive counterparts. However, several case reports and studies describe clinical deterioration and decreased tolerability with generic substitution.

Loss of response after switching from brand name to generic formulations: three cases and a discussion of key clinical considerations when switching.

Generic formulations of medications are marketed as therapeutically equivalent and less expensive than branded ones. Multiple studies and case reports have described relapses and worsening clinical outcome in patients after a switch from a brand name to a generic medication. Recent studies have shown that generics do not always lead to the expected costs savings, reducing the impetus to proceed with compulsory generic switching.

microRNA-directed cleavage and translational repression of the copper chaperone for superoxide dismutase mRNA in Arabidopsis.

microRNA398 (miR398) is a conserved miRNA of plants that targets two of the three copper/zinc superoxide dismutases (SOD) of Arabidopsis (CSD1 and CSD2) by triggering cleavage or inhibiting translation of their mRNAs. We analysed the transcriptomes of mutants impaired in miR398 production, and found that the mRNAs encoding the copper chaperone for superoxide dismutase (CCS1), which delivers copper to CSD1 and CSD2 apoproteins in different cellular compartments, are undiscovered targets of miR398. We identified the cleavage site in CCS1 mRNAs by 5'-RACE PCR.

Mutants of GABA transaminase (POP2) suppress the severe phenotype of succinic semialdehyde dehydrogenase (ssadh) mutants in Arabidopsis.

Background: The gamma-aminubutyrate (GABA) shunt bypasses two steps of the tricarboxylic acid cycle, and is present in both prokaryotes and eukaryotes. In plants, the pathway is composed of the calcium/calmodulin-regulated cytosolic enzyme glutamate decarboxylase (GAD), the mitochondrial enzymes GABA transaminase (GABA-T; POP2) and succinic semialdehyde dehydrogenase (SSADH). We have previously shown that compromising the function of the GABA-shunt, by disrupting the SSADH gene of Arabidopsis, causes enhanced accumulation of reactive oxygen intermediates (ROIs) and cell death in response to light and heat stress.

Invasion of the Arabidopsis genome by the tobacco retrotransposon Tnt1 is controlled by reversible transcriptional gene silencing.

Long terminal repeat (LTR) retrotransposons are generally silent in plant genomes. However, they often constitute a large proportion of repeated sequences in plants. This suggests that their silencing is set up after a certain copy number is reached and/or that it can be released in some circumstances.

Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: Incidence and management strategies in patients with schizophrenia.

Objective: Tardive dyskinesia (TD), the principal adverse effect of long-term conventional antipsychotic treatment, can be debilitating and, in many cases, persistent. We sought to explore the incidence and management of TD in the era of atypical antipsychotics because it remains an important iatrogenic adverse effect.

Methods: We conducted a review of TD incidence and management literature from January 1, 1965, to January 31, 2004, using the terms tardive dyskinesia, management, therapy, neuroleptics, antipsychotics, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole.

Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 1: pathophysiology and mechanisms of induction.

Objective: Tardive dyskinesia (TD) is the principal adverse effect of long-term treatment with conventional antipsychotic agents. Several mechanisms may exist for this phenomenon. Mechanisms for the lower incidence of TD with atypical antipsychotics also remain to be fully understood.