Miracle-dz/UniFAR-FTUs huggingface dataset:
Polimorfismo Val158Met de COMT y esquizofrenia: estudio de asociación en una muestra de pacientes españoles

Fundamento y objetivo La enzima catecol-O-metiltransferasa (COMT) interviene de un modo significativo en la regulacion del sistema dopaminergico, especialmente en la corteza prefrontal. Estudios previos han evaluado la asociacion entre la actividad enzimatica de la COMT y la esquizofrenia, aunque los resultados no han sido concluyentes. El gen COMT contiene un polimorfismo funcional que ocasiona, en la posicion 158 del peptido, el cambio de valina por metionina y la modificacion de la actividad enzimatica, de forma que la COMT -valina muestra una capacidad de degradacion postsinaptica de la dopamina significativamente superior a la COMT -metionina. El objetivo de este trabajo es realizar un estudio de asociacion genetica con el polimorfismo funcional Val 158 Met del gen COMT en pacientes con esquizofrenia y en controles sanos espanoles. Pacientes y metodo Se ha realizado un estudio de casos y controles con una muestra de 177 pacientes y 141 controles. Los pacientes del estudio –115 varones y 62 mujeres, con una edad entre 27 y 49 anos; media (desviacion estandar) de 38 (10,7) anos– se incluyeron consecutivamente segun acudieron a las consultas del Servicio de Psiquiatria del Hospital Universitario 12 de Octubre y si cumplian criterios DSM-IV (cuarta edicion del Diagnostic and Statistical Manual of Mental Disorders) para esquizofrenia (n = 162) o trastorno esquizoafectivo (n = 15). Asimismo, se incluyo a 141 controles evaluados, sanos y libres de enfermedad medica o psiquiatrica –92 varones y 49 mujeres, con una edad entre 26 y 47 anos, media de 36 (9,4) anos–. La identificacion del genotipo se llevo a cabo por medio de tecnicas de genetica molecular humana que asociaron la reaccion en cadena de la polimerasa del ADN al estudio de la conformacion de la hebra simple del ADN ( single strand conformational polymorphism ; SSCP) del polimorfismo Val 158 Met de COMT . Resultados No se encontraron diferencias significativas en las frecuencias de los alelos para este polimorfismo al comparar controles y pacientes. Sin embargo, en el analisis por genotipos y desde un modelo de herencia recesivo (Val/Val frente a Val/Met y Met/Met), se detecto una posible tendencia a la significacion. Nuestros resultados no permiten confirmar la posible contribucion de variaciones del gen COMT en la etiopatogenia de la esquizofrenia, pero ofrecen indicios que permiten sospechar su participacion en algunos grupos concretos de pacientes. Conclusiones Con los resultados obtenidos en este estudio, la posible contribucion del gen COMT en la etiopatogenia de la esquizofrenia no puede descartarse. El debate sobre el posible efecto del polimorfismo Val 158 Met de COMT en la esquizofrenia se mantendria abierto; de ahi la necesidad de reproducir los estudios en muestras mayores que permitan analisis estratificados de subgrupos de pacientes.
Claudin5 genes encoding tight junction proteins are required for Xenopus heart formation

Claudin proteins are the major components of tight junctions connecting adjacent cells, where they regulate a variety of cellular activities. In the present paper we identified two Xenopus claudin5 genes (cldn5a and 5b), which are expressed early in the developing cardiac region. Precocious cldn5 expression was observed in explants of non‐heart‐forming mesoderm under inhibition of the canonical Wnt pathway. Cardiogenesis was severely perturbed by antisense oligonucleotides against cldn5 or by Cldn5 proteins lacking the cytoplasmic domain. Results of light‐ and electron‐microscopic observations suggested that cldn5a and 5b are required for Xenopus heart tube formation through epithelialization of the precardiac mesoderm.
Antioxidant defense and apoptotic effectors in ascorbic acid and β‐glycerophosphate‐induced osteoblastic differentiation

MC3T3‐E1 cells grown in the presence of ascorbic acid and β‐glycerophosphate (AA/β‐GP) express alkaline phosphatase and produce an extensive collagenous extracellular matrix. Differentiated MC3T3‐E1 cells are more sensitive to hydrogen peroxide‐induced oxidative stress than undifferentiated cells. In this study, we compared the profile of antioxidant enzymes and molecular markers of apoptosis in undifferentiated and differentiated MC3T3‐E1 cells (cell differentiation was induced by treatment with AA/β‐GP). Differentiated osteoblasts showed lower expression and activity of catalase, glutathione S‐transferase and glutathione peroxidase. The total superoxide dismutase activity and the expression of Cu/Zn superoxide dismutase were also lower, while the expression of Mn superoxide dismutase was higher in differentiated osteoblasts. The level of malondialdehyde, a widely used marker for oxidative stress, was lower in the AA/β‐GP group compared with control cells, but this difference was not significant. Western blotting showed that treatment with AA/β‐GP increased the Bax/Bcl‐2 ratio used as an index of cellular vulnerability to apoptosis. In addition, the activities of caspases 3, 8 and 9 and cleaved poly (ADP) ribose polymerase were significantly higher in differentiated cells. These findings provide new insights into how changes in the activities of major antioxidant enzymes and in the signaling pathways associated with apoptosis may influence the susceptibility of bone cells to oxidative stress.
Interaction between Maternal and Paternal SHMT1 C1420T Predisposes to Neural Tube Defects in the Fetus: Evidence from Case-Control and Family-Based Triad Approaches.

BACKGROUND Neural tube defects (NTDs) are caused by the failure of neural tube formation which occurs during early embryonic development. NTDs are the most severe and leading cause of fetal mortality. Serine hydroxymethyl transferase (SHMT1) provides one-carbon units necessary for embryogenesis and defects in one-carbon production result in specific pathological conditions during pregnancy. The present study is aimed to evaluate the association of SHMT1 C1420T with NTD risk in the fetus using fetal, maternal and paternal groups by applying both case-control and family-based triad approaches. METHODS A total of 924 subjects including 124 NTD case-parent trios (n = 124 × 3 = 372) and 184 healthy control-parent trios (n = 184 × 3 = 552) from Telangana State, South India were analyzed. DNA from umbilical cord tissues and parental blood samples were extracted, and genotyped by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis used were SPSS, parent-of-origin effect (POE) analysis. RESULTS Case-control study design demonstrated fetuses with homozygous variant genotype (TT) to be at risk toward spina bifida subtype (p = 0.022). Among parents, fathers with TT genotype were associated with anencephaly (p = 0.018) and spina bifida subtypes (p = 0.027) in the offspring. Of interest, maternal-paternal-offspring genotype incompatibility revealed maternal CT genotype in combination with paternal TT genotype increased risk for NTDs in the fetus (CTxTT = TT; p = 0.021). Family-based parent-of-origin effect linkage analysis revealed significant maternal over-transmission of variant allele to NTD fetuses (p < 0.01). CONCLUSION The present study, using both case-control and family-based triad approach is the first report to demonstrate parental association of SHMT1 C1420T variant in conferring NTD risk in the fetus. Birth Defects Research 109:1020-1029, 2017. © 2017 Wiley Periodicals, Inc.
Nicotinamide N-methyl transferase (NNMT) gene polymorphisms and risk for spina bifida.

BACKGROUND Moderate hyperhomocysteinemia is a known risk factor for NTDs in a variety of experimental model systems and is believed to be important in humans as well. The enzyme nicotinamide N-methyl transferase (NNMT) was identified in a genome-wide linkage scan as being an important regulator of homocysteine homeostasis in a Spanish population, making it an interesting candidate gene for NTDs. METHODS We evaluated 11 SNPs (single nucleotide polymorphism) of the NNMT gene in our study population. In this study, 252 cases (infants with spina bifida) and 335 controls (nonmalformed infants), born during the period 1983-1986 in selected counties in California, were genotyped for variants of the NNMT gene. Allelic, genotype, and haplotype associations with spina bifida risk were evaluated and analyzed. RESULTS None of the SNPs studied alone showed allelic or genotypic associations with spina bifida. However, the TCAG haplotype for block 3 (rs2852447, ra2852425, rs4646337, and rs11569688) showed a decreased risk for spina bifida among non-Hispanic Whites (OR 0.4; 95%CI: 0.1-1.0). CONCLUSIONS No association was found between infant NNMT gene variants and risk for spina bifida in our study population. However, small sample sizes for most variant groups and for phase-unknown haplotype data limited the power of the study.
Development of the nervous system in hatchlings of Spadella cephaloptera (Chaetognatha), and implications for nervous system evolution in Bilateria

Chaetognaths (arrow worms) play an important role as predators in planktonic food webs. Their phylogenetic position is unresolved, and among the numerous hypotheses, affinities to both protostomes and deuterostomes have been suggested. Many aspects of their life history, including ontogenesis, are poorly understood and, though some aspects of their embryonic and postembryonic development have been described, knowledge of early neural development is still limited. This study sets out to provide new insights into neurogenesis of newly hatched Spadella cephaloptera and their development during the following days, with attention to the two main nervous centers, the brain and the ventral nerve center. These were examined with immunohistological methods and confocal laser‐scan microscopic analysis, using antibodies against tubulin, FMRFamide, and synapsin to trace the emergence of neuropils and the establishment of specific peptidergic subsystems. At hatching, the neuronal architecture of the ventral nerve center is already well established, whereas the brain and the associated vestibular ganglia are still rudimentary. The development of the brain proceeds rapidly over the next 6 days to a state that resembles the adult pattern. These data are discussed in relation to the larval life style and behaviors such as feeding. In addition, we compare the larval chaetognath nervous system and that of other bilaterian taxa in order to extract information with phylogenetic value. We conclude that larval neurogenesis in chaetognaths does not suggest an especially close relationship to either deuterostomes or protostomes, but instead displays many apomorphic features.
Predictors of Difficult Intubation in Patients With Cervical Spine Limitations

Background Cervical spine function is of paramount importance to the management of the airway. What has not been reported in the literature is a systematic analysis of airway management in patients with cervical spine limitation (CSL) compared with their normal counterparts or a predictive model of difficult intubation (DI) in patients with CSL. Methods We reviewed the electronic charts of 14,053 patients and identified those with CSL based on the preoperative airway evaluation. We then compared various airway parameters in patients with CSL to those without CSL and further assessed risk factors for DI in patients with CSL. We develop a predictive model on the basis of multivariate analysis of such risk factors. Results Of the cohort studied, 1145 or 8.1% of patients were documented as having some form of CSL, with an average age of 60. In the <60 population, CSL was associated with a statistically significant increase in difficult and impossible mask ventilation, difficult laryngoscopy, and DI. In the population ≥60 years old, CSL was associated with a statistically significant increase in difficult laryngoscopy and DI. There were no significant differences in mask ventilation between normal and CSL patients in the population ≥60. Multivariate modeling revealed age ≥48, Mallampati 3 or 4, and thyromental distance <6 cm as independent preoperative risk factors of DI in patients with CSL. A predictive model is developed on the basis of these findings. Conclusions Limitations of cervical spine mobility are relatively common and increase the incidence of difficulty throughout the spectrum of airway management. DI should be anticipated in CSL patients who are ≥48 years old, have a Mallampati class 3 or 4, and a thyromental distance of <6 cm.
Survival and disability in a cohort of neural tube defect births in Dublin, Ireland.

BACKGROUND Neural tube defects (NTDs) are a major cause of death and disability. Periconceptional folic acid prevents up to 70% of these malformations but public health campaigns to increase use of supplements have had disappointing results: The proposed mandatory fortification of bread products in Ireland has raised concerns about possible side effects. We examined data collected on a cohort of children born with NTDs in an era before fortification/supplementation to illustrate the serious consequences in terms of survival and disability. METHODS All 623 infants born with NTDs in the Dublin area between 1976 and 1987 were included. Information was collected on mortality and length of survival for those who died, and for those who survived at least 5 years, interview-based data were collected on age, place of residence, prevalence of hydrocephalus, degree of disability, schooling, and IQ. RESULTS Seventy-four births (12%) were stillborn. Of the livebirths only 41% were alive at 5 years. Factors associated with mortality were type of lesion, level of lesion, presence of other defects, hydrocephalus, year of birth, and gestation. Of the children who survived to 5 years or more, 75% had a disability and 56% were severely disabled. Type of lesion and level of lesion influenced disability risk. Of the survivors, 51% of children had mobility limitations, 59% were incontinent, 42% had hydrocephalus, and 17% had intellectual disability. CONCLUSIONS These findings illustrate the devastating consequences of NTDs and underline the importance of effective intervention programs with folic acid for prevention.
GABAergic interneuron migration and the evolution of the neocortex

A neocortex is present in all mammals but is not present in other classes of vertebrates, and the neocortex is extremely elaborate in humans. Changes in excitatory projection neurons and their progenitors within the developing dorsal pallium in the most recent common ancestor of mammals are thought to have been involved in the evolution of the neocortex. Our recent findings suggest that changes in the migratory ability of inhibitory interneurons derived from outside the neocortex may also have been involved in the evolution of the neocortex. In this article we review the literature on the migratory profile of inhibitory interneurons in several different species and the literature on comparisons between the intrinsic migratory ability of interneurons derived from different species. Finally, we propose a hypothesis about the mammalian‐specific evolution of the migratory ability of interneurons and its potential contribution to the establishment of a functional neocortex.
Clinical beak and feather disease virus infection in wild juvenile eastern rosellas of New Zealand; biosecurity implications for wildlife care facilities

Abstract CASE HISTORY: Four juvenile eastern rosellas (Platycercus eximius) were admitted to two separate wildlife care facilities in the Auckland region by members of the public. They had missing or dystrophic wing and tail feathers that rendered them flightless, suggestive of beak and feather disease virus (BFDV) infection. Two were subject to euthanasia after failing to re-grow their feathers, with samples taken for histopathology and PCR analysis. Blood samples were obtained from the other two birds at the time of examination, however these individuals were lost to follow up. PATHOLOGICAL AND MOLECULAR FINDINGS: Basophilic inclusion bodies were observed in histological sections of the feather bulb, typical of BFDV infection, from the two euthanised individuals. Blood from all four birds tested positive by PCR for BFDV, and analysis of the recovered full BFDV genomes identified them as belonging to the BFDV-A strain. DIAGNOSIS: Beak and feather disease virus infection. CLINICAL RELEVANCE: This report highlights the clinical impacts of BFDV in juvenile eastern rosellas that may result in their admission to wildlife care facilities, creating a biosecurity risk in institutions that may host other native parrots intended for release. The environmental stability of BFDV and resistance to disinfection requires strict quarantine procedures to prevent contamination and spread within a facility. It is recommended that high-risk species such as wild eastern rosella be excluded from facilities that may also house native parrots.
An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1).

BACKGROUND Spina bifida is a class of neural tube defects, which are congenital malformations of the central nervous system with a prevalence of 0.5 to 12 per 1000 births globally. In this article we attempt to identify genes related to folate and its metabolic pathways that are involved in the etiology of spina bifida. METHODS We selected 50 folate metabolism-related genes and genotyped polymorphisms in those genes. Eighty-seven polymorphisms in 45 genes passed quality controls. Associations with spina bifida were investigated in 180 patients and 190 controls. For those polymorphisms that were nominally associated with spina bifida risk, the relation with serum and red blood cell folate, vitamin B(12), and homocysteine was evaluated in controls. RESULTS A polymorphism in CUBN was significantly associated with decreased spina bifida risk, after correction for multiple testing, and was related to increased vitamin B(12) (p = 0.039) and red blood cell folate (p = 0.001). The CUBN gene encodes the intrinsic factor-cobalamin receptor (or cubilin), a peripheral membrane protein that acts as a receptor for intrinsic factor-vitamin B(12) complexes. Vitamin B(12) is an important cofactor in the folate metabolism, and low B(12) status in mothers has been linked to neural tube defects in children. Other interesting findings include nominally significant associations with polymorphisms in TRDMT1, ALDH1L1, SARDH, and SLCA19A1 (RFC1). CONCLUSION Our study indicates interesting new candidate genes and functional pathways for further study and confirms earlier findings. None of the genes CUBN, TRDMT1, ALDH1L1, or SARDH have been investigated previously for association with spina bifida.
Parasite management extension – challenging traditional practice through adoption of a systems approach

The drivers for anthelmintic use today are substantial and anthelmintic use has become an embedded normalised behaviour. The cheapness and easy availability of anthelmintic products has meant that New Zealand farmers have had access to easy “solutions” for dealing with parasites and minimal forward planning or system redesign has been required. Despite 30 years of messaging about the emerging issue of anthelmintic resistance, management to reduce parasitism and the need to change behaviour, farmer practice has largely remained unchanged. Traditional approaches to extension, particularly around parasite management, appear to have been quite ineffective, apart from encouraging change in anthelmintic products and a switch to use of anthelmintics in combination. More effective approaches are required. The evolving nature of anthelmintic resistance and sustainable management of parasitism require attitudes, knowledge and behaviour to change. This is a challenge for all players in the industry; researchers, manufacturers and sellers, advisors and farmers. Looking beyond agriculture to the health sector provides some insight into models of decision making and behaviour change that can inform future strategies. Features in the health belief model including concepts of self-efficacy and cues to action appear to align with the issues, challenges and culture prevailing in farming, and parasite management in particular. Programmes through which farmers have made substantial beneficial behaviour change and the lessons learnt are discussed. Effecting consistent behaviour change around parasite management will involve new approaches by all participants in the process. And the process itself also needs to change. It requires an understanding of whole-farm systems, and the consideration of all the sources of influence on the farmer and the other participants in the process. The process of knowledge sharing involving the farmer should be based on equality; each person in the process brings their own expertise and knowledge and that needs to be valued and integrated into new practices. In effect, a multi-disciplinary team approach is required through which knowledge is shared and developed, confidence and understanding is developed, practice and behaviour is reflected on and positive behaviours are given affirmation.
Nonsyndromic cleft lip and palate: CRISPLD genes and the folate gene pathway connection.

BACKGROUND Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect that has a multifactorial etiology. Despite having substantial genetic liability, <15% of the genetic contribution to NSCLP has been delineated. In our efforts to dissect the genetics of NSCLP, we found that variation in the CRISPLD2 (cysteine-rich secretory protein LCCL domain containing 2) gene is associated with NSCLP and that the protein is expressed in the developing murine craniofacies. In addition, we found suggestive linkage of NSCLP (LOD > 1.0) to the chromosomal region on 8q13.2-21.13 that contains the CRISPLD1 gene. The protein products of both CRISPLD1 and CRISPLD2 contain more cysteine residues than comparably sized proteins. Interestingly, the folic acid pathway produces endogenous cysteines, and variation in genes in this pathway is associated with NSCLP. Based on these observations, we hypothesized that variation in CRISPLD1 contributes to NSCLP and that both CRISPLD genes interact with each other and genes in the folic acid pathway. METHODS Single nucleotide polymorphisms (SNPs) in CRISPLD1 were genotyped in our non-Hispanic white and Hispanic multiplex and simplex NSCLP families. RESULTS There was little evidence for a role of variation for CRISPLD1 alone in NSCLP. However, interactions were detected between CRISPLD1/CRISPLD2 SNPs and variation in folate pathway genes. Altered transmission of one CRISPLD1 SNP was detected in the NHW simplex families. Importantly, interactions were detected between SNPs in CRISPLD1 and CRISPLD2 (15 interactions, 0.0031 ≤p < 0.05). CONCLUSION These novel findings suggest that CRISPLD1 plays a role in NSCLP through the interaction with CRISPLD2 and folate pathway genes.
STUDIES CONCERNING DIABETES

The work, of which this paper will give a synopsis, is the continuation of an experimental study of diabetes described in detail elsewhere.1Certain of the results of the previous investigation, bearing on the present topic, may be summarized under the following four headings: Production of Diabetes: Removal of portions of the dog's pancreas produces a lowering of the sugar tolerance. Removal of nine-tenths of the gland results in severe diabetes. When the remnant is larger (for instance, one-eighth), milder types of diabetes result. The course is chronic, extending over months, and the end fatal. Such animals furnish a closer imitation of human diabetes than is produced by total pancreatectomy. Pathologic Anatomy of Diabetes: In the foregoing procedure, duct communication between the pancreatic remnant and the duodenum is preserved. Therefore the acinar tissue does not atrophy, and in some cases it may hypertrophy. The islands of Langerhans show typical