Molecular ontogeny of the stomach in the catshark Scyliorhinus canicula.

The origin of extracellular digestion in metazoans was accompanied by structural and physiological alterations of the gut. These adaptations culminated in the differentiation of a novel digestive structure in jawed vertebrates, the stomach. Specific endoderm/mesenchyme signalling is required for stomach differentiation, involving the growth and transcription factors: 1) Shh and Bmp4, required for stomach outgrowth; 2) Barx1, Sfrps and Sox2, required for gastric epithelium development and 3) Cdx1 and Cdx2, involved in intestinal versus gastric identity.

Mutational mechanism for DAB1 (ATTTC) insertion in SCA37: ATTTT repeat lengthening and nucleotide substitution.

Dynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC) insertion within an (ATTTT) in a noncoding region of DAB1.

Choosing not to know: accounts of non-engagement with pre-symptomatic testing for Machado-Joseph disease.

This paper reports accounts from people at-risk for, or affected by, Machado-Joseph disease, and their family members, about their decisions not to seek pre-symptomatic testing, therefore remaining (for the time) uninformed about their genetic status. We draw on individual and family semi-structured interviews with participants recruited through a national patient's association (n = 25). Qualitative thematic analysis revealed three main categories of accounts: (1) justifying the decision "not to know", because either no clinical benefit was expected or predictive knowledge was anticipated as psychologically burdensome; (2) prioritizing everyday life, maintaining hope and the goal of living a valid life; and (3) the wish to know: ambivalence and conflict within the family.

Polymorphisms in DNA methylation-related genes are linked to the phenotype of Machado-Joseph disease.

DNA methylation has been reported as an important regulator of genomic structure stability, including large tandem repeats. To test the modulation effect of variants in DNA methylation-related genes on distribution of expanded (CAG) alleles and age at onset (AO) of patients with Machado-Joseph disease (MJD), we conducted an association analysis on 23 selected SNPs in these genes in 613 patients with MJD and 581 controls. There were significant differences in the distribution of rs12957023 between patients and controls (OR = 1.

Genetic modifiers of age-at-onset in polyglutamine diseases.

Polyglutamine (polyQ) diseases are a group of clinically and genetically heterogeneous neurodegenerative diseases. Expansion size correlates with age-at-onset (AO) and severity, and shows a critical threshold for each polyQ disease. Although an expanded CAG tract is sufficient to trigger disease, not all variation in AO is explained by (CAG) length, which suggests the contribution of other modifying factors.

Anti-TTR Nanobodies Allow the Identification of TTR Neuritogenic Epitope Associated with TTR-Megalin Neurotrophic Activities.

Transthyretin (TTR) has intrinsic neurotrophic physiological activities independent from its thyroxine ligands, which involve activation of signaling pathways through interaction with megalin. Still, the megalin binding motif on TTR is unknown. Nanobodies (Nb) have the ability to bind "hard to reach" epitopes being useful tools for protein/structure function.

Recontacting patients in clinical genetics services: recommendations of the European Society of Human Genetics.

Technological advances have increased the availability of genomic data in research and the clinic. If, over time, interpretation of the significance of the data changes, or new information becomes available, the question arises as to whether recontacting the patient and/or family is indicated. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with research groups from the UK and the Netherlands, developed recommendations on recontacting which, after public consultation, have been endorsed by ESHG Board.

Phylogeny and comprehensive revision of mugiliform-infecting myxobolids (Myxozoa, Myxobolidae), with the morphological and molecular redescription of the cryptic species Myxobolus exiguus.

Mullets inhabit a wide range of habitats from tropical to temperate regions and play a critical role in their ecosystems. This commercially important fish group constitutes a significant source of food in several geographic regions, and the production of some species for consumption is an increasing trend. About 64 myxosporean species have been reported in mullets, some of which are cryptic, as is the case of Myxobolus exiguus, and M.

The Global State of the Genetic Counseling Profession.

The profession of genetic counseling (also called genetic counselling in many countries) began nearly 50 years ago in the United States, and has grown internationally in the past 30 years. While there have been many papers describing the profession of genetic counseling in individual countries or regions, data remains incomplete and has been published in diverse journals with limited access. As a result of the 2016 Transnational Alliance of Genetic Counseling (TAGC) conference in Barcelona, Spain, and the 2017 World Congress of Genetic Counselling in the UK, we endeavor to describe as fully as possible the global state of genetic counseling as a profession.

Investigation on modulation of DNA repair pathways in Chinese MJD patients.

It has been reported that DNA repair pathways could modify age at onset (AO) in Huntington disease (HD) and spinocerebellar ataxias. We genotyped 22 SNPs from DNA repair pathways in a large cohort of 798 Chinese Machado-Joseph disease patients to investigate the association with AO, and no significant finding was observed. Our findings did not provide a strong evidence for the modulatory effect of DNA repair pathways on the AO of Chinese Machado-Joseph disease patients.

MouR controls the expression of the Listeria monocytogenes Agr system and mediates virulence.

The foodborne pathogen Listeria monocytogenes (Lm) causes invasive infection in susceptible animals and humans. To survive and proliferate within hosts, this facultative intracellular pathogen tightly coordinates the expression of a complex regulatory network that controls the expression of virulence factors. Here, we identified and characterized MouR, a novel virulence regulator of Lm.

Genome Sequence of Listeria monocytogenes 2542, a Serotype 4b Strain from a Cheese-Related Outbreak in Portugal.

We report here the draft genome sequence of 2542, a serotype 4b clinical strain recovered from a placental sample during a cheese-related listeriosis outbreak in Portugal.

A repeat-primed PCR assay for pentanucleotide repeat alleles in spinocerebellar ataxia type 37.

Spinocerebellar ataxia 37 (SCA37) is caused by an (ATTTC) insertion in a polymorphic ATTTT repeat in the non-coding region of DAB1. The non-pathogenic alleles have a configuration [(ATTTT)], whereas pathogenic alleles have a complex structure of [(ATTTT)(ATTTC)(ATTTT)]. Molecular diagnosis of SCA37 is laborious because about 7% of the pentanucleotide repeat alleles in DAB1 are larger than 30 units and, thus, fail to amplify with standard PCR conditions, resulting in apparently homoallelism or in complete lack of PCR amplification in several cases.

Recontacting or not recontacting? A survey of current practices in clinical genetics centres in Europe.

Advances in genomic medicine are improving diagnosis and treatment of some health conditions, and the question of whether former patients should be recontacted is therefore timely. The issue of recontacting is becoming more important with increased integration of genomics in 'mainstream' medicine. Empirical evidence is needed to advance the discussion over whether and how recontacting should be implemented.

In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum.

There is an urgent need for the discovery of new antileishmanial drugs with a new mechanism of action. Type 2 NADH dehydrogenase from (NDH2) is an enzyme of the parasite's respiratory system, which catalyzes the electron transfer from NADH to ubiquinone without coupled proton pumping. In previous studies of the related NADH: ubiquinone oxidoreductase crystal structure from , two ubiquinone-binding sites (UQ and UQ) were identified and shown to play an important role in the NDH-2-catalyzed oxidoreduction reaction.

Delivery of an anti-transthyretin Nanobody to the brain through intranasal administration reveals transthyretin expression and secretion by motor neurons.

Transthyretin (TTR) is a transport protein of retinol and thyroxine in serum and CSF, which is mainly secreted by liver and choroid plexus, and in smaller amounts in other cells throughout the body. The exact role of TTR and its specific expression in Central Nervous System (CNS) remains understudied. We investigated TTR expression and metabolism in CNS, through the intranasal and intracerebroventricular delivery of a specific anti-TTR Nanobody to the brain, unveiling Nanobody pharmacokinetics to the CNS.

Analysis of (CAG) expansion in ATXN1, ATXN2 and ATXN3 in Chinese patients with multiple system atrophy.

Multiple system atrophy (MSA) is a complex and multifactorial neurodegenerative disease, and its pathogenesis remains uncertain. Patients with MSA or spinocerebellar ataxia (SCA) show overlapping clinical phenotypes. Previous studies have reported that intermediate or long CAG expansions in SCA genes have been associated with other neurodegenerative disease.

Clinical spectrum of C9orf72 expansion in a cohort of Huntington's disease phenocopies.

The expansion in the C9orf72 gene has been recently reported as a genetic cause of Huntington's disease (HD) phenocopies. We aim to assess the frequency of the C9orf72 gene expansion in a Portuguese HD phenocopies cohort. Twenty HD phenotype-like patients without diagnosis were identified in our institutional database.

Origins and Spread of Machado-Joseph Disease Ancestral Mutations Events.

Machado-Joseph disease (MJD) is the most common autosomal dominant spinocerebellar ataxia reported worldwide, but it shows marked geographic differences in prevalence. The study of ancestral origins and spreading routes of MJD mutational events has contributed to explain such differences. During human evolution, at least two independent de novo MJD expansions occurred in distinct haplotype backgrounds: TTACAC and GTGGCA (named Joseph and Machado lineages).

Psychopathological dimensions in subjects with hereditary ATTR V30M amyloidosis and their relation with life events due to the disease.

Background: Chronic physical illness has been associated with emotional distress. Chronic diseases may change usual family patterns with economic, social and family losses. Hereditary ATTR V30M amyloidosis is a rare, fatal inherited systemic amyloidosis, with chronic evolution and beginning in adulthood.

How practical experiences, educational routes and multidisciplinary teams influence genetic counselors' clinical practice in Europe.

The main objective of our study was to explore whether, and to what extent, genetic counselors' characteristics impact on their tasks in practice. Specifically, we explored the complementariness between genetic counselors and medical geneticists and therefore looked at the most relevant tasks of genetic counselors, according to genetic counselors themselves and according to the medical geneticists they work with. A total of 104 genetic counselors and 29 medical geneticists from 15 countries completed a purposefully designed questionnaire.

Psychopathological Dimensions in Portuguese Subjects with Transthyretin Familial Amyloid Polyneuropathy.

Background: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a fatal, chronic, progressive disease. It is a rare hereditary amyloidosis, which manifests as a sensorimotor neuropathy and autonomic dysfunction. It begins during adulthood.

Rare Neurodegenerative Diseases: Clinical and Genetic Update.

More than 600 human disorders afflict the nervous system. Of these, neurodegenerative diseases are usually characterised by onset in late adulthood, progressive clinical course, and neuronal loss with regional specificity in the central nervous system. They include Alzheimer's disease and other less frequent dementias, brain cancer, degenerative nerve diseases, encephalitis, epilepsy, genetic brain disorders, head and brain malformations, hydrocephalus, stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS or Lou Gehrig's Disease), Huntington's disease, and Prion diseases, among others.

Persistent postoperative pain after cardiac surgery: a systematic review with meta-analysis regarding incidence and pain intensity.

Persistent postoperative pain (PPP) has been described as a complication of cardiac surgery (CS). We aimed to study PPP after CS (PPPCS) by conducting a systematic review of the literature regarding its incidence, intensity, location, and the presence of neuropathic pain, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The review comprised 3 phases: a methodological assessment of 6 different databases identifying potential articles and screening for inclusion criteria by 2 independent reviewers; data extraction; and study quality assessment.