Inotropic action of the puberty hormone kisspeptin in rat, mouse and human: cardiovascular distribution and characteristics of the kisspeptin receptor

Kisspeptins, the ligands of the kisspeptin receptor known for its roles in reproduction and cancer, are also vasoconstrictor peptides in atherosclerosis-prone human aorta and coronary artery. The aim of this study was to further investigate the cardiovascular localisation and function of the kisspeptins and their receptor in human compared to rat and mouse heart. Immunohistochemistry and radioligand binding techniques were employed to investigate kisspeptin receptor localisation, density and pharmacological characteristics in cardiac tissues from all three species. Radioimmunoassay was used to detect kisspeptin peptide levels in human normal heart and to identify any pathological changes in myocardium from patients transplanted for cardiomyopathy or ischaemic heart disease. The cardiac function of kisspeptin receptor was studied in isolated human, rat and mouse paced atria, with a role for the receptor confirmed using mice with targeted disruption of Kiss1r. The data demonstrated that kisspeptin receptor-like immunoreactivity localised to endothelial and smooth muscle cells of intramyocardial blood vessels and to myocytes in human and rodent tissue. [¹²⁵I]KP-14 bound saturably, with subnanomolar affinity to human and rodent myocardium (K(D) = 0.12 nM, human; K(D) = 0.44 nM, rat). Positive inotropic effects of kisspeptin were observed in rat, human and mouse. No response was observed in mice with targeted disruption of Kiss1r. In human heart a decrease in cardiac kisspeptin level was detected in ischaemic heart disease. Kisspeptin and its receptor are expressed in the human, rat and mouse heart and kisspeptins possess potent positive inotropic activity. The cardiovascular actions of the kisspeptins may contribute to the role of these peptides in pregnancy but the consequences of receptor activation must be considered if kisspeptin receptor agonists are developed for use in the treatment of reproductive disorders or cancer.This work was supported by grants from the Medical Research Council (http://www.mrc.ac.uk) and the British Heart Foundation (http://www.bhf.org.uk). (Grant numbers PS/02/001 and PG/09/050/27734.)

Vertebral rotation measurement: a summary and comparison of common radiographic and CT methods

Current research has provided a more comprehensive understanding of Adolescent Idiopathic Scoliosis (AIS) as a three-dimensional spinal deformity, encompassing both lateral and rotational components. Apart from quantifying curve severity using the Cobb angle, vertebral rotation has become increasingly prominent in the study of scoliosis. It demonstrates significance in both preoperative and postoperative assessment, providing better appreciation of the impact of bracing or surgical interventions. In the past, the need for computer resources, digitizers and custom software limited studies of rotation to research performed after a patient left the scoliosis clinic. With advanced technology, however, rotation measurements are now more feasible. While numerous vertebral rotation measurement methods have been developed and tested, thorough comparisons of these are still relatively unexplored. This review discusses the advantages and disadvantages of six common measurement techniques based on technology most pertinent in clinical settings: radiography (Cobb, Nash-Moe, Perdriolle and Stokes' method) and computer tomography (CT) imaging (Aaro-Dahlborn and Ho's method). Better insight into the clinical suitability of rotation measurement methods currently available is presented, along with a discussion of critical concerns that should be addressed in future studies and development of new methods

Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function $F_{jj}^D$ of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in $\bar pp$ collisions at $\sqrt s=630$ GeV at the Fermilab Tevatron. The ratio of $F_{jj}^D$ at $\sqrt s=630$ GeV to $F_{jj}^D$ obtained from a similar measurement at $\sqrt s=1800$ GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the $\xi$ ($x$-Pomeron) and $\beta$ ($x$ of parton in Pomeron) dependence of $F_{jj}^D$ at $\sqrt s=1800$ GeV. In the region $0.035<\xi<0.095$, $|t|<1$ GeV$^2$ and $\beta<0.5$, $F_{jj}^D(\beta,\xi)$ is found to be of the form $\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}$, which obeys $\beta$-$\xi$ factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter

Modeling the Violation of Reward Maximization and Invariance in Reinforcement Schedules

It is often assumed that animals and people adjust their behavior to maximize reward acquisition. In visually cued reinforcement schedules, monkeys make errors in trials that are not immediately rewarded, despite having to repeat error trials. Here we show that error rates are typically smaller in trials equally distant from reward but belonging to longer schedules (referred to as “schedule length effect”). This violates the principles of reward maximization and invariance and cannot be predicted by the standard methods of Reinforcement Learning, such as the method of temporal differences. We develop a heuristic model that accounts for all of the properties of the behavior in the reinforcement schedule task but whose predictions are not different from those of the standard temporal difference model in choice tasks. In the modification of temporal difference learning introduced here, the effect of schedule length emerges spontaneously from the sensitivity to the immediately preceding trial. We also introduce a policy for general Markov Decision Processes, where the decision made at each node is conditioned on the motivation to perform an instrumental action, and show that the application of our model to the reinforcement schedule task and the choice task are special cases of this general theoretical framework. Within this framework, Reinforcement Learning can approach contextual learning with the mixture of empirical findings and principled assumptions that seem to coexist in the best descriptions of animal behavior. As examples, we discuss two phenomena observed in humans that often derive from the violation of the principle of invariance: “framing,” wherein equivalent options are treated differently depending on the context in which they are presented, and the “sunk cost” effect, the greater tendency to continue an endeavor once an investment in money, effort, or time has been made. The schedule length effect might be a manifestation of these phenomena in monkeys

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Expanding the clinical phenotype of IARS2-related mitochondrial disease.

BACKGROUND: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. METHODS: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. RESULTS: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. CONCLUSIONS: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia

Supported housing programs for persons with serious mental illness in rural northern communities: A mixed method evaluation

Background: During the past two decades, consumers, providers and policy makers have recognized the role of supported housing intervention for persons diagnosed with serious mental illness (SMI) to be able to live independently in the community. Much of supported housing research to date, however, has been conducted in large urban centers rather than northern and rural communities. Northern conditional and contextual issues such as rural poverty, lack of accessible mental health services, small or non-existing housing markets, lack of a continuum of support or housing services, and in some communities, a poor quality of housing challenge the viability of effective supported housing services. The current research proposal aims to describe and evaluate the processes and outcomes of supported housing programs for persons living with SMI in northern and rural communities from the perspective of clients, their families, and community providers. Methods: This research will use a mixed method design guided by participatory action research. The study will be conducted over two years, in four stages. Stage I will involve setting up the research in each of the four northern sites. In Stage II a descriptive cross-sectional survey will be used to obtain information about the three client outcomes: housing history, quality of life and housing preference. In Stage III two participatory action strategies, focus groups and photo-voice, will be used to explore perceptions of supported housing services. In the last stage findings from the study will be re-presented to the participants, as well as other key community individuals in order to translate them into policy. Conclusion: Supported housing intervention is a core feature of mental health care, and it requires evaluation. The lack of research in northern and rural SMI populations heightens the relevance of research findings for health service planning. The inclusion of multiple stakeholder groups, using a variety of data collection approaches, contributes to a comprehensive, systems-level examination of supported housing in smaller communities. It is anticipated that the study\u27s findings will not only have utility across Ontario, but also Canada