Childhood adversity and psychosis: examinig whether the association is due to genetic confounding using a monozygotic twin differences approach

Purpose: To test whether the association between childhood adversity and positive and negative psychotic experiences is due to genetic confounding. Method: Childhood adversity and psychotic experiences were assessed in a sample of 226 twins from the general population. A monozygotic (MZ) twin differences approach was used to assess possible genetic confounding. Results: In the whole sample, childhood adversity was significantly associated with positive (β =.45; SE=.16; p=.008) and negative psychotic experiences (β=.77; SE=.18; p<.01). Within-pair MZ twin differences in exposure to childhood adversity were significantly associated with differences in positive (β =.71; SE=.29; p=.016) and negative psychotic experiences (β =.98; SE=.38; p=.014) in a subsample of 86 MZ twin pairs. Conclusions: Individuals exposed to childhood adversity are more likely to report psychotic experiences. Furthermore, our findings indicate that unique environmental effects of childhood adversity contribute to the development of psychotic experiences.

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Altered nitrogen balance and decreased urea excretion in male rats fed cafeteria diet are related to arginine availability

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids.We analyzed whether reduced urea excretion was a consequence of higherNO ; (nitrite,nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion.There were no differences in plasma nitrate or nitrite. NO and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithinewhen comparedwith controls,whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

1,2-Dimethylindole-3-sulfonyl (MIS) as protecting group for the side chain of arginine

The protection of arginine (Arg) side chains is a crucial issue in peptide chemistry because of the propensity of the basic guanidinium group to produce side reactions. Currently, sulfonyl-type protecting groups, such as 2,2,5,7,8-pentamethylchroman (Pmc) and 2,2,4,6,7-pentamethyldihydrobenzofurane (Pbf), are the most widely used for this purpose. Nevertheless, Arg side chain protection remains problematic as a result of the acid stability of these two compounds. This issue is even more relevant in Arg-rich sequences, acid-sensitive peptides and large-scale syntheses. The 1,2-dimethylindole-3-sulfonyl (MIS) group is more acid-labile than Pmc and Pbf and can therefore be a better option for Arg side chain protection. In addition, MIS is compatible with tryptophan-containing peptides.

Protein loop compaction and the origin of the effect of arginine and glutamic acid mixtures on solubility, stability and transient oligomerization of proteins

Addition of a 50 mM mixture of l-arginine and l-glutamic acid (RE) is extensively used to improve protein solubility and stability, although the origin of the effect is not well understood. We present Small Angle X-ray Scattering (SAXS) and Nuclear Magnetic Resonance (NMR) results showing that RE induces protein compaction by collapsing flexible loops on the protein core. This is suggested to be a general mechanism preventing aggregation and improving resistance to proteases and to originate from the polyelectrolyte nature of RE. Molecular polyelectrolyte mixtures are expected to display long range correlation effects according to dressed interaction site theory. We hypothesize that perturbation of the RE solution by dissolved proteins is proportional to the volume occupied by the protein. As a consequence, loop collapse, minimizing the effective protein volume, is favored in the presence of RE.

Birth Weight, Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study.

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.

Altered nitrogen balance and decreased urea excretion in male rats fed cafeteria diet are related to arginine availability

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids.We analyzed whether reduced urea excretion was a consequence of higherNO ; (nitrite,nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion.There were no differences in plasma nitrate or nitrite. NO and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithinewhen comparedwith controls,whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

Parametrization of spectral surfaces of a class of periodic 5-diagonal matrices

The main result of this work is a parametric description of the spectral surfaces of a class of periodic 5-diagonal matrices, related to the strong moment problem. This class is a self-adjoint twin of the class of CMV matrices. Jointly they form the simplest possible classes of 5-diagonal matrices.

Bases genètiques de la malformació de Chiari

La Malformació de Chiari tipus I (MCI) ha estat definida tradicionalment com la herniació de les amígdales cerebel•loses d’almenys 5mm, a través del forat mange. En general, els símptomes es posen de manifest durant la segona o tercera dècada de vida, tot i que s’han descrit casos pediàtrics. Donada la complexitat del quadre clínic, per realitzar un diagnòstic adient es requereix avaluació clínica i estudi de neuroimatge. La tècnica de preferència és la ressonància magnètica d’imatge, considerant-se actualment com a pacients de MCI aquells que presenten un descens de les amígdales superior a 3mm per sota del forat magne. L'existència de casos asimptomàtics dificulta establir una prevalença concreta, però s’ha estimat que podria estar entre 1/1000 a 1/5000 sent major en dones que en homes (2:1 aproximadament). Fins el moment, es desconeix l’etiologia de la malaltia però la hipòtesi més acceptada és que MCI és deguda al desenvolupament insuficient del mesoderm paraxial. Diferents estudis realitzats fins el moment evidencien que almenys, un subgrup de pacients amb MCI són deguts a contribució genètica: 1) casos d’agregació familiar amb afectes en tres generacions; 2) estudis de bessons 3) associació amb síndromes genètics coneguts amb herència mendeliana produïts per anomalies óssies que donen suport a la hipòtesi de la insuficiència del mesoderm com a causa de MCI. Davant l’evidència clara d’un component genètic com a principal causant de l’etiologia de MCI, l’objectiu del projecte va ser la identificació de les bases genètiques de la MCI, tant en gens responsables de les formes mendelianes com en gens responsables de les formes complexes de MCI mitjançant dues estratègies: 1-Identificació de variants genètiques de susceptibilitat en pacients amb MCI mitjançant estudis d’associació de tipus cas-control. 2-Anàlisi genètic de formes monogèniques mitjançant l’anàlisi de lligament a marcardors polimòrfics i la seqüenciació del DNA a gran escala.

Characterization and simulation of a CdTe detector for use in PET

The Voxel Imaging PET (VIP) Path nder project got the 4 year European Research Council FP7 grant in 2010 to prove the feasibility of using CdTe detectors in a novel conceptual design of PET scanner. The work presented in this thesis is a part of the VIP project and consists of, on the one hand, the characterization of a CdTe detector in terms of energy resolution and coincidence time resolution and, on the other hand, the simulation of the setup with the single detector in order to extend the results to the full PET scanner. An energy resolution of 0.98% at 511 keV with a bias voltage of 1000 V/mm has been measured at low temperature T=-8 ºC. The coincidence time distribution of two twin detectors has been found to be as low as 6 ns FWHM for events with energies above 500 keV under the same temperature and bias conditions. The measured energy and time resolution values are compatible with similar ndings available in the literature and prove the excellent potential of CdTe for PET applications. This results have been presented in form of a poster contribution at the IEEE NSS/MIC & RTSD 2011 conference in October 2011 in Valencia and at the iWoRID 2012 conference in July 2012 in Coimbra, Portugal. They have been also submitted for publication to "Journal of Instrumentation (JINST)" in September 2012.

Children in the welfare state. A social investment approach

Children occupy centre-stage in any new welfare equilibrium. Failure to support families may produce either of two undesirable scenarios. We shall see a society without children if motherhood remains incompatible with work. A new family policy needs to recognize that children are a collective asset and that the cost of having children is rising. The double challenge is to eliminate the constraints on having children in the first place, and to ensure that the children we have are ensured optimal opportunities. The simple reason why a new social contract is called for is that fertility and child quality combine both private utility and societal gains. And like no other epoch in the past, the societal gains are mounting all-the-while that families’ ability to produce these social gains is weakening.In the following 1 analyze the twin challenges of fertility and child development. I then examine which kind of policy mix will ensure both the socially desired level of fertility and investment in our children? The task is to identify a Paretian optimum that will maximize efficiency gains and social equity simultaneously.

PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27Kip1

P27(Kip1) (p27) is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors. Recently, a new function of p27 as transcriptional regulator has been reported. It has been shown that p27 regulates the expression of target genes mostly involved in splicing, cell cycle, respiration and translation. We report here that p27 directly binds to the transcriptional coactivator PCAF by a region including amino acids 91-120. PCAF associates with p27 through its catalytic domain and acetylates p27 at lysine 100. Our data showed that overexpression of PCAF induces the degradation of p27 whereas in contrast, the knockdown of PCAF stabilizes the protein. A p27 mutant in which K100 was substituted by arginine (p27-K100R) cannot be acetylated by PCAF and has a half-life much higher than that of p27WT. Moreover, p27-K100R remains stable along cell-cycle progression. Ubiquitylation assays and the use of proteasome inhibitors indicate that PCAF induces p27 degradation via proteasome. We also observed that knockdown of skp2 did not affect the PCAF induced degradation of p27. In conclusion, our data suggest that the p27 acetylation by PCAF regulates its stability.

Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.