Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that the neurobeachin (NBEA) gene is disrupted in human patients with idiopathic autism ( Castermans et al., 2003 ). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein ( Savelyeva et al., 2006 ). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. ( Medrihan et al., 2009 ; Savelyeva et al., 2006 ). Rugose (rg) is the Drosophila homolog of the mammalian and human NBEA. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways ( Shamloula et al., 2002 ). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate that Drosophila NBEA (rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs.

Santa Clara de Nanay: the MAL-ED cohort in Peru.

The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study communities in Peru are located in Loreto province, in a rural area 15 km from the city of Iquitos. This riverine population of approximately 5000 individuals is fairly representative of Loreto. The province lags behind the rest of the country in access to water and sanitation, per capita income, and key health indicators including infant mortality (43.0 vs 16.0 per 1000 nationwide) and under-5 mortality (60.6 vs 21.0 per 1000). Total fertility rates are higher than elsewhere in the country (4.3 vs 2.6). Nationwide, the prevalence of human immunodeficiency virus is estimated at 0.45%, the prevalence of tuberculosis is 117 per 100 000, and the incidence of malaria is 258 per 100 000. Stunting in this community is high, whereas acute undernutrition is relatively uncommon. The population suffers from high rates of diarrheal disease. Prevalent enteric pathogens include Ascaris, Giardia, enterotoxigenic Escherichia coli, Shigella, and Campylobacter.

Complex pattern of interaction between in utero hypoxia-ischemia and intra-amniotic inflammation disrupts brain development and motor function.

BACKGROUND: Infants born preterm commonly suffer from a combination of hypoxia-ischemia (HI) and infectious perinatal inflammatory insults that lead to cerebral palsy, cognitive delay, behavioral issues and epilepsy. Using a novel rat model of combined late gestation HI and lipopolysaccharide (LPS)-induced inflammation, we tested our hypothesis that inflammation from HI and LPS differentially affects gliosis, white matter development and motor impairment during the first postnatal month. METHODS: Pregnant rats underwent laparotomy on embryonic day 18 and transient systemic HI (TSHI) and/or intra-amniotic LPS injection. Shams received laparotomy and anesthesia only. Pups were born at term. Immunohistochemistry with stereological estimates was performed to assess regional glial loads, and western blots were performed for protein expression. Erythropoietin ligand and receptor levels were quantified using quantitative PCR. Digigait analysis detected gait deficits. Statistical analysis was performed with one-way analysis of variance and post-hoc Bonferonni correction. RESULTS: Microglial and astroglial immunolabeling are elevated in TSHI + LPS fimbria at postnatal day 2 compared to sham (both P < 0.03). At postnatal day 15, myelin basic protein expression is reduced by 31% in TSHI + LPS pups compared to shams (P < 0.05). By postnatal day 28, white matter injury shifts from the acute injury pattern to a chronic injury pattern in TSHI pups only. Both myelin basic protein expression (P < 0.01) and the phosphoneurofilament/neurofilament ratio, a marker of axonal dysfunction, are reduced in postnatal day 28 TSHI pups (P < 0.001). Erythropoietin ligand to receptor ratios differ between brains exposed to TSHI and LPS. Gait analyses reveal that all groups (TSHI, LPS and TSHI + LPS) are ataxic with deficits in stride, paw placement, gait consistency and coordination (all P < 0.001). CONCLUSIONS: Prenatal TSHI and TSHI + LPS lead to different patterns of injury with respect to myelination, axon integrity and gait deficits. Dual injury leads to acute alterations in glial response and cellular inflammation, while TSHI alone causes more prominent chronic white matter and axonal injury. Both injuries cause significant gait deficits. Further study will contribute to stratification of injury mechanisms in preterm infants, and guide the use of promising therapeutic interventions.

Pneumothorax, Pneumomediastinum, and Cervical and Facial Massive Emphysema Secondary to Colonoscopy: A Rare Complication of Colonoscopy.

Background: Colonoscopy is a resource used for the diagnosis, treatment, and monitoring of benign and malignant colorectal pathologies. The incidence of perforation is 0.03%-0.65% in diagnostic colonoscopy; however, the incidence can be up to 10 times higher in therapeutic interventions, such as polypectomies, increasing the risk of complications up to 0.07-2.1%. Materials and methods. Case report of a 71-year-old female who presents a rare complication due to a perforation in the sigmoid which developed pneumoperitoneum, pneumomediastinum, pneumothorax, and massive subcutaneous emphysema as a complication of a diagnostic colonoscopy where a biopsy of a friable lesion was performed. Results: A 71-year-old female that went to the emergency room due to acute generalized abdominal colic spasm pain with a duration of 7 hours, associated with significant abdominal distension, malaise, diaphoresis, progressive dyspnea, and massive subcutaneous emphysema that developed after performing panendoscopy and colonoscopy for diverticulosis follow-up. An abdominal CT scan with double contrast was performed, reporting suggestive data of hollow viscus perforation, pneumoperitoneum, pneumomediastinum, pneumothorax, and massive subcutaneous emphysema in the thorax, neck, and skull base. She underwent an exploratory laparotomy finding a perforation in the sigmoid for which sigmoidectomy was performed, and for the pneumothorax and pneumomediastinum, endopleural tubes were placed in both hemithoraxes. The massive subcutaneous emphysema subsided with observation and oxygen. Conclusion: A rare complication of the use of colonoscopy as a diagnostic and therapeutic method is presented. The purpose of presenting this case is for the doctor who performs these interventions to suspect this complication in a timely manner, not delaying the diagnosis and carrying out an urgent therapeutic approach as in this case with exploratory laparotomy, finding the perforation site and carrying out the corresponding surgical management. We demonstrated that massive subcutaneous emphysema can be managed with observation if there is no other alarm data evident that required another surgical approach.

Chronic Encapsulated Sclerosing Peritonitis: A Case Report.

Chronic encapsulated sclerosing peritonitis (CESP) is a very rare cause of intestinal obstruction that has been associated with certain chronic conditions. It is characterized by the thickening of the peritoneum, generating a membrane that covers the intestinal loops and prevents their adequate mobilization. Most cases present as a surgical emergency, leading to a diagnosis during surgery; however, imaging studies can support the pre-surgical diagnosis. Treatment is based on the clinical context of the patient, based on medical management with corticosteroids in a stable patient, or surgical management when it presents as an acute complication. The morbidity and mortality associated with this condition are high and epidemiological data are scarce. There is still a lack of studies to describe the associated demographic data, diagnosis, and treatment.

Isolation of high-quality total RNA from leaves of Myrciaria dubia "CAMU CAMU".

Myrciaria dubia is a main source of vitamin C for people in the Amazon region. Molecular studies of M. dubia require high-quality total RNA from different tissues. So far, no protocols have been reported for total RNA isolation from leaves of this species. The objective of this research was to develop protocols for extracting high-quality total RNA from leaves of M. dubia. Total RNA was purified following two modified protocols developed for leaves of other species (by Zeng and Yang, and by Reid et al.) and one modified protocol developed for fruits of the studied species (by Silva). Quantity and quality of purified total RNA were assessed by spectrophotometric and electrophoretic analysis. Additionally, quality of total RNA was evaluated with reverse-transcription polymerase chain reaction (RT-PCR). With these three modified protocols we were able to isolate high-quality RNA (A260nm/A280nm >1.9 and A260nm/A230nm >2.0). Highest yield was produced with the Zeng and Yang modified protocol (384±46µg ARN/g fresh weight). Furthermore, electrophoretic analysis showed the integrity of isolated RNA and the absence of DNA. Another proof of the high quality of our purified RNA was the successful cDNA synthesis and amplification of a segment of the M. dubia actin 1 gene. We report three modified protocols for isolation total RNA from leaves of M. dubia. The modified protocols are easy, rapid, low in cost, and effective for high-quality and quantity total RNA isolation suitable for cDNA synthesis and polymerase chain reaction.

Dormia basket impacted during ERCP, resolved by laparoscopic bile duct approach: Case report.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is the method of choice for treating and removing common bile duct (CBD) stones with high success rates. Among the adverse effects, impaction of the Dormia basket when removing the stones is an unusual complication. CASE PRESENTATION: Two cases of choledocholithiasis with endoscopic treatment by ERCP and Dormia basket impaction, resolved by a laparoscopic approach to the bile duct. DISCUSSION: Laparoscopic common bile duct exploration (LCBDE) has been developed as a technique to treat choledocholithiasis and simultaneously vesicular lithiasis by laparoscopy. LCBDE can be by means of a transcystic approach or by choledochotomy. The success of the treatment depends on surgical experience and the availability of adequate equipment, with high effectiveness to eliminate CBD stones and a success rate greater than 95%, it is equally effective for the resolution of adverse events during ERCP. CONCLUSION: LCBDE provides an alternative therapy where there is no other type of treatment for the resolution of complications of ERCP. It is a safe, effective and reliable technique with high success rates, which offers the benefits of a minimally invasive approach.

Total gastrectomy in a case of complicated gastric volvulus: Case report and review of literature.

INTRODUCCIóN: Gastric volvulus is characterized by a rotation, in its long or short axis, generating various degrees of obstruction, which can occur acutely or chronically. CASE: A 45-year-old female. Refers to the performance of laparoscopic Nissen fundoplication 4 years ago. In December 2018, she presented a recurrence of the symptoms associated with reflux, for which a new laparoscopic fundoplication was performed (outside our medical unit) without eventualities or apparent complications. Six months later, he was admitted to our medical unit due to intolerance to the oral route. Thoraco-abdomino-pelvic tomography reports images suggestive of gastric volvulus and mixed hiatal hernia with protrusion of colon, stomach, duodenum, jejunum and mesenteric vessels, with data suggestive of complication or ischemia of these structures. An emergency operating room was requested to perform an exploratory laparotomy. Gastric volvulus, ischemia and gastric necrosis were observed in the cavity, for which a total gastrectomy and restitution of the intestinal transit were carried out by means of an esophagus-jejunum end-to-side Roux-en-Y anastomosis. DISCUSSION: There is no scientific evidence or algorithms described for the management of this condition, according to the management described in the literature, decision-making by our team surgical procedure matches current recommendations. CONCLUSION: In accordance with what is described in the literature, we consider it important to carry out a retrospective study that describes the bases for standardizing the management of this complication, and assessing models for conducting prospective multicenter studies that allow the creation of an algorithm and clinical guideline.

Zaragoza technique of laparoscopic appendicectomy.

INTRODUCTION: Appendectomy is one of the most frequent emergency surgical procedures, currently with a preference for laparoscopic management worldwide. OBJECTIVE: To report a new laparoscopic appendectomy technique and its results. MATERIAL AND METHODS: Cohort study of patients with a diagnosis of appendicitis who are managed laparoscopically. In a total 1063 patients, 148 were operated on with the Zaragoza technique during the period from January 2002 to December 2018. The technique consists of making a window in the appendicular base between the meso and the appendicular wall, two prolene or silk sutures are placed, and the cecal appendix is cut between the two sutures, finally the mesoappendix is sectioned with a harmonic scalpel or bipolar clamp. RESULTS: From our results, we had 1.4% residual abscesses, 1.4% umbilical surgical wound infection and 0% mortality. DISCUSSION: Various laparoscopic management methods for appendectomy are reported in the literature, with a wide range in the results. We have obtained good results in patients subjected to our technique. CONCLUSIONS: The Zaragoza technique for laparoscopic appendectomy is an effective and safe option that prevents excessive manipulation of the inflamed appendix and is easily reproducible.

GIST associated with von recklinghausen disease: Report of two cases and review of literature.

INTRODUCTION AND IMPORTANCE: Neurofibromatosis type 1 (NF1), or Von Recklinghausen's disease, is an autosomal dominant condition that affects the central nervous system. Gastrointestinal stromal tumor (GIST) refers to non-epithelial tumors of the gastrointestinal tract lacking smooth muscle structural features and schwann cell immunohistochemical characteristics. The risk of patients with NF1 to develop a GIST is 7%. CASE PRESENTATION: GIST is a soft tissue sarcoma that probably arises from the interstitial Cajal cells of the intestine. GIST associated with NF1 syndrome appears to have a distinct phenotype, occurring in younger patients compared to sporadic GIST. CLINICAL DISCUSSION: The clinical presentation can be highly variable, the association of gastrointestinal tumors associated with Von Recklinghausen's disease is up to 7%, postoperative treatment with imatinib is reserved for patients with a high risk of recurrence. CONCLUSION: The treatment of primary GIST is complete surgical resection with free microscopic margins and an intact pseudocapsule.

Perpendicular duodenum jejunum anastomosis for conventional postoperative endoscopic access in biliodigestive diversions in Roux in Y.

BACKGROUND: Cholecystectomy is one of the most performed abdominal surgical procedures, with approximately 1.5 million procedures performed annually in the United States of america. Most of the biliary duct injuries during laparoscopic cholecystectomy are due to a wrong perception of the anatomy. Two thirds of postsurgical stenosis develop within two and three years after repairing and the other third in the following ten years. OBJECTIVE: To show the adequacy for postoperative endoscopic access in Roux-in-Y biliodigestive diversions. METHOD: The best technique to repair biliary duct injuries is the Roux-in-Y hepaticojejunostomy or choledochojejunostomy, from this procedure we propose a surgical technique that consists to perform a perpendicular anastomosis between the defunctionalized jejunum loop and the duodenum for later endoscopic access of the Roux-en-Y biliodigestive diversion. RESULTS: The duodenal-jejunal perpendicular anastomosis procedure was performed in four patients with Roux-Y biliodigestive diversion. CONCLUSIONS: With the technique that is proposed, we have that advantage of keeping the anastomosis permanently open due to its rhomboidal design and because of the pylorus is kept intact alkaline reflux would not be a problem.

ANTECEDENTES: La colecistectomía es una de las cirugías más frecuentes, con aproximadamente 1.2 millones de procedimientos realizados anualmente solo en los Estados Unidos de América. La mayoría de las disrupciones biliares durante la colecistectomía laparoscópica se deben a una percepción errónea de la anatomía. Dos tercios de las estenosis posquirúrgicas se desarrollan 2-3 años después de la reparación y el otro tercio en los 10 años siguientes. OBJETIVO: Mostrar la adecuación para un acceso endoscópico posoperatorio en las derivaciones biliodigestivas en Y de Roux. MÉTODO: La mejor técnica quirúrgica reportada para la reparación de las disrupciones biliares es la anastomosis hepático-yeyuno o anastomosis colédoco-yeyuno en Y de Roux. Partiendo de este procedimiento, la variante quirúrgica que proponemos consiste en realizar una anastomosis perpendicular entre el asa desfuncionalizada de yeyuno y el duodeno para el posterior acceso endoscópico de la derivación biliodigestiva en Y de Roux. RESULTADOS: Se realizó el procedimiento en cuatro pacientes con derivación biliodigestiva en Y de Roux. CONCLUSIONES: El procedimiento que proponemos tiene la ventaja de mantener abierta la anastomosis debido a su diseño romboidal, y como el píloro se encuentra indemne, el reflujo gástrico alcalino no sería ningún problema.

A theoretical chemistry-based strategy for the rational design of new luminescent lanthanide complexes: an approach from a multireference SOC-NEVPT2 method.

Theoretical methods of the SOC-NEVPT2 type combined with a molecular fragmentation scheme have been proven to be a powerful tool that allows explaining the luminescence sensitization mechanism in Ln(III) coordination compounds through the antenna effect. In this work, we have used this strategy to predict luminescence in a family of compounds of the Eu(R-phen)(BTA)3 type where R-phen = 5-methyl-1,10-phenanthroline (Me-phen), 5-nitro-1,10-71 phenanthroline (Nitro-phen), 4,5-diazafluoren-9-one (One-phen), or 5,6-epoxy-5,6-dihydro-1,10-72 phenanthroline (Epoxy-phen); and BTA = fluorinated ß-diketone. Possible sensitization pathways were elucidated from the energy difference between the ligand-centered triplet (3T) states and the emissive excited states of the Eu(III) fragments (Latva rules). Calculations show that the most probable mechanism occurs through the triplet state of the BTA which should be enriched by several parallel energy transfer pathways from R-phen substituents. The complexes were synthesized and structurally characterized by X-ray crystallography and various other physicochemical and spectroscopic methods to realize their optical properties and energy transfer pathways from dual antennae. Experimental results were in good agreement with the theoretical predictions, which reinforces the predictive power of the used theoretical methodology.

Instrumentation for Testing Whether the Icy Moons of the Gas and Ice Giants Are Inhabited.

Evidence of life beyond Earth may be closer than we think, given that the forthcoming missions to the jovian system will be equipped with instruments capable of probing Europa's icy surface for possible biosignatures, including chemical biomarkers, despite the strong radiation environment. Geochemical biomarkers may also exist beyond Europa on icy moons of the gas giants. Sulfur is proposed as a reliable geochemical biomarker for approved and forthcoming missions to the outer solar system. Key Words: JUICE mission-Clipper mission-Geochemical biomarkers-Europa-Moons of the ice giants-Geochemistry-Mass spectrometry. Astrobiology 17, 958-961.

Evolution of substrate specificity in a retained enzyme driven by gene loss.

The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.

Effects of movement imitation training in Parkinson's disease: A virtual reality pilot study.

BACKGROUND: Hypometria is a clinical motor sign in Parkinson's disease. Its origin likely emerges from basal ganglia dysfunction, leading to an impaired control of inhibitory intracortical motor circuits. Some neurorehabilitation approaches include movement imitation training; besides the effects of motor practice, there might be a benefit due to observation and imitation of un-altered movement patterns. In this sense, virtual reality facilitates the process by customizing motor-patterns to be observed and imitated. OBJECTIVE: To evaluate the effect of a motor-imitation therapy focused on hypometria in Parkinson's disease using virtual reality. METHODS: We carried out a randomized controlled pilot-study. Sixteen patients were randomly assigned in experimental and control groups. Groups underwent 4-weeks of training based on finger-tapping with the dominant hand, in which imitation was the differential factor (only the experimental group imitated). We evaluated self-paced movement features and cortico-spinal excitability (recruitment curves and silent periods in both hemispheres) before, immediately after, and two weeks after the training period. RESULTS: Movement amplitude increased significantly after the therapy in the experimental group for the trained and un-trained hands. Motor thresholds and silent periods evaluated with transcranial magnetic stimulation were differently modified by training in the two groups; although the changes in the input-output recruitment were similar. CONCLUSIONS: This pilot study suggests that movement imitation therapy enhances the effect of motor practice in patients with Parkinson's disease; imitation-training might be helpful for reducing hypometria in these patients. These results must be clarified in future larger trials.

Cribado poblacional de aneurismas de la aorta abdominal. Estudio piloto en Salamanca / Population screening for abdominal aortic aneurysms. Pilot study in Salamanca

Introducción: una estrategia para reducir la mortalidad de los aneurismas de la aorta abdominal es conocer su existencia en fase asintomática. Así podremos clasificar los pacientes, en función del tamaño del aneurisma, en candidatos a cirugía programada o a seguimiento periódico. Objetivos: conocer la eficacia, la seguridad y la aceptabilidad de un programa piloto de cribado de aneurismas de la aorta abdominal mediante ecografía abdominal realizada en una población de riesgo. Material y métodos: programa organizado por la Real Academia de Medicina y el Instituto de Investigación Biomédica y ejecutado por el Servicio de Angiología, Cirugía Vascular y Endovascular del Hospital Universitario de Salamanca. El cribado se realizó hace un año, en dos carpas situadas en una céntrica plaza de Salamanca. El análisis incluyó a 295 varones ≥ 65 años, residentes en Salamanca capital, de forma libre y gratuita. Se excluyeron aquellos con aneurisma aórtico conocido. Se realizaron: 1) registro de datos; 2) eco Doppler color por especialistas en angiología y cirugía vascular, y 3) encuesta de satisfacción. Todos firmaron un consentimiento informado. Resultados: el diámetro transversal medio de la aorta abdominal fue de 1,81 ± 0,36 cm. Se detectaron 2 aneurismas (diámetro mayor: ≥ 3,0 cm; 3,1 y 4,7 cm) y 3 ectasias aórticas (diámetro ≥ 2,5 y < 3,0 cm). El 98,3 % (290 varones) no presentó ectasia o aneurisma (aorta < 2,5 cm). Tres individuos (obesidad o aire intrabdominal) fueron reevaluados posteriormente. Se analizaron los factores de riesgo y los antecedentes de la población cribada. 180 participantes del cribado (61,0 %) rellenaron anónimamente una encuesta de satisfacción, con resultados muy positivos. Conclusión: si bien el rendimiento de detección fue bajo, la estrategia y el método empleado fueron satisfactorios para el equipo explorador y la población explorada. Este estudio piloto nos permitirá planificar y organizar un segundo cribado más amplio y de nuevos objetivos.(AU)

Introduction: a strategy to reduce the mortality of abdominal aortic aneurysms is to know their existence in theasymptomatic phase. This way we can classify patients, mainly according to the size of the aneurysm, into candi-dates for scheduled elective surgery or periodic follow-up.Objectives: to determine the effectiveness, safety, and acceptability of a pilot screening program for abdominalaortic aneurysms, using abdominal ultrasound, performed in a risk population.Material and methods: program organized by the Royal Academy of Medicine and the Biomedical ResearchInstitute, and carried out by the Angiology and Vascular Surgery service of the University Hospital of Salamanca.The screening was carried out a year ago, in two tents located in a central square in Salamanca. The study included295 men over 65 years of age, residents of Salamanca capital, free of charge. Those with known aortic aneurysmwere excluded. The following were carried out: 1) data recording; 2) color echo-Doppler, by specialists in angiologyand vascular surgery; and 3) satisfaction survey. All signed an informed consent.Results: the mean transverse diameter of the abdominal aorta was 1.81 ± 0.36 cm. Two aneurysms were detect-ed (largest diameter ≥ 3.0 cm; 3.1 and 4.7 cm), and 3 aortic ectasias (diameter ≥ 2.5 and < 3.0 cm). The 98.3 %(290 men) did not present ectasia or aneurysm (aorta < 2.5 cm). Three individuals (obesity or intra-abdominal air) weresubsequently re-evaluated. The risk factors and background of the screened population were analyzed. A satisfactionsurvey was completed freely and anonymously by 180 screening participants (61.0 %) with very positive results.Conclusion: although the detection performance was low, the strategy and method used were satisfactory for theexploring team and the population explored. The present pilot study will allow us to plan and organize a second,broader screening with new objectives.(AU)

Drosophila-Cdh1 (Rap/Fzr) a regulatory subunit of APC/C is required for synaptic morphology, synaptic transmission and locomotion.

The assembly of functional synapses requires the orchestration of the synthesis and degradation of a multitude of proteins. Protein degradation and modification by the conserved ubiquitination pathway has emerged as a key cellular regulatory mechanism during nervous system development and function (Kwabe and Brose, 2011). The anaphase promoting complex/cyclosome (APC/C) is a multi-subunit ubiquitin ligase complex primarily characterized for its role in the regulation of mitosis (Peters, 2002). In recent years, a role for APC/C in nervous system development and function has been rapidly emerging (Stegmuller and Bonni, 2005; Li et al., 2008). In the mammalian central nervous system the activator subunit, APC/C-Cdh1, has been shown to be a regulator of axon growth and dendrite morphogenesis (Konishi et al., 2004). In the Drosophila peripheral nervous system (PNS), APC2, a ligase subunit of the APC/C complex has been shown to regulate synaptic bouton size and activity (van Roessel et al., 2004). To investigate the role of APC/C-Cdh1 at the synapse we examined loss-of-function mutants of Rap/Fzr (Retina aberrant in pattern/Fizzy related), a Drosophila homolog of the mammalian Cdh1 during the development of the larval neuromuscular junction in Drosophila. Our cell biological, ultrastructural, electrophysiological, and behavioral data showed that rap/fzr loss-of-function mutations lead to changes in synaptic structure and function as well as locomotion defects. Data presented here show changes in size and morphology of synaptic boutons, and, muscle tissue organization. Electrophysiological experiments show that loss-of-function mutants exhibit increased frequency of spontaneous miniature synaptic potentials, indicating a higher rate of spontaneous synaptic vesicle fusion events. In addition, larval locomotion and peristaltic movement were also impaired. These findings suggest a role for Drosophila APC/C-Cdh1 mediated ubiquitination in regulating synaptic morphology, function and integrity of muscle structure in the peripheral nervous system.

Motor facilitation during real-time movement imitation in Parkinson's disease: a virtual reality study.

BACKGROUND: Impaired temporal stability and poor motor unit recruitment are key impairments in Parkinsonian motor control during a whole spectrum of rhythmic movements, from simple finger tapping to gait. Therapies based on imitation can be designed for patients with motor impairments and virtual-reality (VR) offers a new perspective. Motor actions are known to depend upon the dopaminergic system, whose involvement in imitation is unknown. We sought to understand this role and the underlying possibilities for motor rehabilitation, by observing the execution of different motor-patterns during imitation in a VR environment in subjects with and without dopaminergic deficits. METHODS: 10 OFF-dose idiopathic Parkinson's Disease patients (PD), 9 age-matched and 9 young-subjects participated. Subjects performed finger-tapping at their "comfort" and "slow-comfort" rates, while immersed in VR presenting their "avatar" in 1st person perspective. Imitation was evaluated by asking subjects to replicate finger-tapping patterns different to their natural one. The finger-pattern presented matched their comfort and comfort-slow rates, but without a pause on the table (continuously moving). RESULTS: Patients were able to adapt their finger-tapping correctly, showing that in comparison with the control groups, the dopaminergic deficiency of PD did not impair imitation. During imitation the magnitude of EMG increased and the temporal variability of movement decreased. CONCLUSIONS: PD-patients have unaltered ability to imitate instructed motor-patterns, suggesting that a fully-functional dopaminergic system is not essential for such imitation. It should be further investigated if imitation training over a period of time induces positive off-line motor adaptations with transfer to non-imitation tasks.

Virtual reality as a tool for evaluation of repetitive rhythmic movements in the elderly and Parkinson's disease patients.

This work presents an immersive Virtual Reality (VR) system to evaluate, and potentially treat, the alterations in rhythmic hand movements seen in Parkinson's disease (PD) and the elderly (EC), by comparison with healthy young controls (YC). The system integrates the subjects into a VR environment by means of a Head Mounted Display, such that subjects perceive themselves in a virtual world consisting of a table within a room. In this experiment, subjects are presented in 1(st) person perspective, so that the avatar reproduces finger tapping movements performed by the subjects. The task, known as the finger tapping test (FT), was performed by all three subject groups, PD, EC and YC. FT was carried out by each subject on two different days (sessions), one week apart. In each FT session all subjects performed FT in the real world (FT(REAL)) and in the VR (FT(VR)); each mode was repeated three times in randomized order. During FT both the tapping frequency and the coefficient of variation of inter-tap interval were registered. FT(VR) was a valid test to detect differences in rhythm formation between the three groups. Intra-class correlation coefficients (ICC) and mean difference between days for FT(VR) (for each group) showed reliable results. Finally, the analysis of ICC and mean difference between FT(VR) vs FT(REAL), for each variable and group, also showed high reliability. This shows that FT evaluation in VR environments is valid as real world alternative, as VR evaluation did not distort movement execution and detects alteration in rhythm formation. These results support the use of VR as a promising tool to study alterations and the control of movement in different subject groups in unusual environments, such as during fMRI or other imaging studies.

Assays for the in vitro establishment of Swietenia macrophylla and Cedrela odorata / Ensayos para el establecimiento in vitro de Swietenia macrophyllay Cedrela odorata

Recalcitrance and contamination in Mahogany (Swietenia macrophylla King) and Spanish cedar (Cedrela odorata L.) stem tissues are the main causes of its ineffective in vitro propagation. The objectives of this research were: a) to evaluate sodium hypochlorite (NaOCl) and plant preservative mixture (PPM®) as surface disinfectants and/or added to the culture medium for the in vitro establishment of nodal explants taken from 10-year-old Mahogany and Spanish cedar plants, and b) to evaluate the in vitro response of such explants treated with N6-benzylaminopurine (BAP) (0, 2.2, 4.4, 8.8, 17.7 μM), silver nitrate (AgNO3) (0, 3 mg l-1), activated charcoal (0, 1 g l-1) and vented caps. All the experiments were arranged in a completely randomized design. The NaOCl at 15%, for 20 min, as a surface sterilization or PPM® at 2 ml l-1 into the culture medium, were the best treatments to reduce contamination for both species. For Mahogany explants, BAP at 17.7 μM resulted in higher percentages of bud breaks than Spanish cedar (64% and 25%, respectively). Leaves on elongated shoots dropped off by 20 days after starting the explants in culture and neither the activated charcoal nor the AgNO3 alone or combined prevented leaf abscission. The AgNO3 decreased contamination, but also increased leaf abscission. Bud breaks was two-fold higher for nodal explants established in vessels with vented caps than with normal caps. Mahogany nodal explants were easier to surface sterilize and more buds broke from BAP treated explants than Spanish cedar treated explants in the in vitro establishment.

La contaminación y la recalcitrancia de tejidos de tallo de Caoba (Swietenia macrophylla King) y Cedro español (Cedrela odorata L.) son las causas principales de su inefectiva micro-propagación. Los objetivos de la investigación fueron: a) evaluar el hipoclorito de sodio (NaClO) y una mezcal preservadora de plantas (PPM®) como desinfectantes superficiales y/o agregados al medio de cultivo para el establecimiento in vitro de explantes nodales de Caoba y Cedro español de 10 años de edad; b) evaluar la respuesta in vitro de tales explantes tratados con N6-benzylaminopurine (BAP) (0, 2.2, 4.4, 8.8, 17.7 μM), nitrato de plata (AgNO3) (0, 3 mg l-1), carbón activado (0, 1 g l-1) y tapas porosas. Los experimentos fueron establecidos bajo un diseño completamente al azar. La contaminación se redujo en ambas especies con NaOCl al 15% durante 20 min como desinfección superficial o con PPM® (2 ml l-1) agregado al medio de cultivo. El mayor porcentaje de brotación de explantes se obtuvo con BAP a 17.7 μM en caoba (64%) comparado con cedro (25%). Los brotes se defoliaron a los 20 días de cultivo y ni el carbón activado ni el AgNO3, solos o combinados evitaron la defoliación. El AgNO3 disminuyó la contaminación, pero incrementó la defoliación. La brotación fue dos veces mayor en los explantes nodales establecidos en recipientes con tapas porosas que cuando se utilizaron tapas normales. Los explantes nodales de Caoba respondieron mejor a la desinfección superficial y a los tratamientos de BAP comparados con los de Cedro español en el establecimiento in vitro.