Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously been implicated in the pathogenesis of polyglutamine expansion diseases. Our findings link this gene to XLMR and shed more light on the pathogenesis of this common disorder.     

Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs

Duchenne muscular dystrophy remains an untreatable genetic disease that severely limits motility and life expectancy in affected children. The only animal model specifically reproducing the alterations in the dystrophin gene and the full spectrum of human pathology is the golden retriever dog model. Affected animals present a single mutation in intron 6, resulting in complete absence of the dystrophin protein, and early and severe muscle degeneration with nearly complete loss of motility and walking ability. Death usually occurs at about 1 year of age as a result of failure of respiratory muscles. Here we report that intra-arterial delivery of wild-type canine mesoangioblasts (vessel-associated stem cells) results in an extensive recovery of dystrophin expression, normal muscle morphology and function (confirmed by measurement of contraction force on single fibres). The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients.     

Germline KRAS mutations cause Noonan syndrome

Noonan syndrome (MIM 163950) is characterized by short stature, facial dysmorphism and cardiac defects. Heterozygous mutations in PTPN11, which encodes SHP-2, cause approximately 50% of cases of Noonan syndrome. The SHP-2 phosphatase relays signals from activated receptor complexes to downstream effectors, including Ras. We discovered de novo germline KRAS mutations that introduce V14I, T58I or D153V amino acid substitutions in five individuals with Noonan syndrome and a P34R alteration in a individual with cardio-facio-cutaneous syndrome (MIM 115150), which has overlapping features with Noonan syndrome. Recombinant V14I and T58I K-Ras proteins show defective intrinsic GTP hydrolysis and impaired responsiveness to GTPase activating proteins, render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage-specific manner. These studies establish germline KRAS mutations as a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is, in large part, due to hyperactive Ras.     

Action of thalidomide on endosteal ossification in the pigeon

Riassunto Ricerche condotte sulla ossificazione endosteale indotta con ormone follicolare in piccioni trattati con talidomide hanno messo in evidenza che la talidomide interferisce con azione ormonale; la talidomide non inibisce la formazione delle trabecole ossee, ma provoca un notevole riassorbimento delle trabecole stesse tra il 10° e il 15° giorno di trattamento; tale riassorbimento non è imputabile ad un aumento del numéro di osteoclasti nel periodo corrispondente.     

Whole-genome sequence of Schistosoma haematobium

Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.     

Using Soft Systems Methodology to Fight Against Info-Exclusion: The Experience of a Brazilian University

The aim of this paper is to apply a systemic methodology to analyse the concept of info-inclusion which can guide strategic actions of institutions within civil society and within several levels of government. The paper provides a plan of action that, integrated with other tools, aims at fighting the technological and social gap. We apply Soft System Methodology (SSM), because it provides a holistic approach to info-exclusion. SSM is often used to analyse and resolve problems in complex social studies such as info-exclusion. An info-exclusion reduction project, developed by a university in the country region of Sao Paulo will be provided as a case study. This project is one of the several Brazilian initiatives to solve the problem of limited access to information technology tools. We start by contextualising info-exclusion in Brazil and follow with a review of SSM. We then introduce the concept of info-inclusion and apply SSM to it. We end with a discussion of the results obtained and with some suggestions for action and possible improvements.     

Diagnosis of Organizational Soft Problems in a Peruvian Financial Institution by Systemic Thinking

Managing financial institutions in an underdeveloped economic context has become a real challenge nowadays. In order to reach the organization’s planned goals, they have to deal with structural, behavioral and informational problems. From the systemic point of view, this situation gets even worse when the company does not present organizational boundaries and a cohesive identification for their stakeholders. Thus, European countries have some special financial lines in order to help the development of micro credit in Latin communities in an attempt to help the local economy. However, institutions like Caixa dos Andes in Peru present management problems when dealing with this complexity. Based on this, how can the systemic eye help in the diagnosis of soft problems of a Peruvian financial company? This study aims to diagnose soft problems of a Peruvian financial company based on soft variables like identity, communication and autonomy and also intends to identify possible ways to redesign its basic framework. The (VSM––Viable System Model) method from Beer (1967), applied in this diagnostic study, was used in a practical way as a management tool for organizations’ analysis and planning. By describing the VSM’s five systems, the creation of a systemic vision or a total vision is possible, showing the organization’s complexity from the inside. Some company’s soft problems like double control, inefficient use of physical and human resources, low information flows, slowness, etc. The VSM presented an organizational diagnosis indicating effective solutions that do integrate its five systems.     

Systemic Model for Diagnosis of the Micro,Small and Medium Enterprises from Two Cities from the Countryside of the State of <Emphasis Type="Italic">São Paulo</Emphasis> in Brazil

This article presents a proposal of a systemic model composed for the micro and small companies (MSE) of the region of Ribeirão Preto and the agents which influenced their environment. The proposed model was based on Stafford Beer’s (Diagnosing the system for organizations. Chichester, Wiley, 1985) systemic methodologies VSM (Viable System Model) and on Werner Ulrich’s (1983) CSH (Critical Systems Heuristics). The VSM is a model for the diagnosis of the structure of an organization and of its flows of information through the application of the cybernetics concepts (Narvarte, In El Modelo del Sistema Viable—MSV: experiencias de su aplicación en Chile. Proyecto Cerebro Colectivo del IAS, Santiago, 2001). On the other hand, CSH focus on the context of the social group applied to the systemic vision as a counterpoint to the organizational management view considered by the VSM. MSE of Ribeirão Preto and Sertãozinho had been analyzed as organizations inserted in systems that relate and integrate with other systems concerning the public administration, entities of representation and promotion agencies. The research questions: which are the bonds of interaction among the subsystems in this process and who are the agents involved? The systemic approach not only diagnosed a social group, formed by MSE of Ribeirão Preto and Sertãozinho, public authorities and support entities, but could also delineate answers that aimed the clarification of obscure questions generating financial assistance to the formularization of efficient actions for the development of this system.