BORIS – It’s never too late to start a repository

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Late-acting self-incompatibility in Capparis retusa (Capparaceae), a species of Chaco woodland in NE Argentina

The reproductive biology of Capparis retusa was studied by means of controlled pollination experiments and fluorescence microscopy observations of post-pollination events. Self-pollinated flowers mostly failed to form fruits despite the fact that self-pollen tubes grew to the ovary and penetrated ovules within 24 h. Since embryo development to globular stage was observed in some self-fertilized ovules it was concluded that control of self-fertilization in this species occurs by some kind of post-zygotic mechanism.

The DNA puff BhB10-1 gene is differentially expressed in various tissues of Bradysia hygida late larvae and constitutively transcribed in transgenic Drosophila

We extended the characterization of the DNA puff BhB10-1 gene of Bradysia hygida by showing that, although its mRNA is detected only at the end of the fourth larval instar, BhB10-1 expression is not restricted to the salivary gland, the tissue in which this gene is amplified. Different amounts of BhB10-1 mRNA were detected in other larval tissues such as gut, Malpighian tubules, fat body, brain and cuticle, suggesting that this gene is expressed differentially in the various tissues analyzed. Analysis of transgenic Drosophila carrying the BhB10-1 transcription unit and flanking sequences revealed that the tested fragment promotes transcription in a constitutive manner. We suggest that either cis-regulatory elements are missing in the transgene or factors that temporally regulate the BhB10-1 gene in B. hygida are not conserved in Drosophila.

Clinical assessment of the effect of digital filtering on the detection of ventricular late potentials

Ventricular late potentials are low-amplitude signals originating from damaged myocardium and detected on the body surface by ECG filtering and averaging. Digital filters present in commercial equipment may interfere with the ability of arrhythmia stratification. We compared 40-Hz BiSpec (BI) and classical 40- to 250-Hz band-pass Butterworth bidirectional (BD) filters in terms of impact on time domain variables and diagnostic properties. In a transverse retrospective age-adjusted case-control study, 221 subjects with sinus rhythm without bundle branch block were divided into three groups after signal-averaged ECG acquisition: GI (N = 40), clinically normal controls, GII (N = 158), subjects with coronary heart disease without sustained monomorphic ventricular tachycardia (SMVT), and GIII (N = 23), subjects with heart disease and documented SMVT. Conventional variables analyzed from vector magnitude data after averaging to 0.3 µV final noise were obtained by application of each filter to the averaged signal, and evaluated in pairs by numerical comparison and by diagnostic agreement assessment, using conventional and optimized thresholds of normality. Significant differences were found between BI and BD variables in all groups, with diagnostic results showing significant disagreement between both filters [kappa value of 0.61 (P<0.05) for GII and 0.31 for GIII (P = NS)]. Sensitivity for SMVT was lower with BI than with BD (65.2 vs 91.3%, respectively, P<0.05). Filters provided significantly different numerical and diagnostic results and the BI filter showed only limited clinical application to risk stratification of ventricular arrhythmia.

Sleep-wake pattern of medical students: early versus late class starting time

The sleep-wake cycle of students is characterized by delayed onset, partial sleep deprivation and poor sleep quality. Like other circadian rhythms, the sleep-wake cycle is influenced by endogenous and environmental factors. The aim of the present study was to determine the effects of different class starting times on the sleep-wake pattern of 27 medical students. The data were collected during two medical school semesters having different class starting times. All subjects answered the Portuguese version of the Horne and Östberg Morningness/Eveningness Questionnaire, the Pittsburgh Sleep Quality Index (PSQI) and kept a sleep diary for two weeks during each semester. Better sleep quality (PSQI = 5.3 vs 3.4), delayed sleep onset (23:59 vs 0:54 h) and longer sleep duration (6 h and 55 min vs 7 h and 25 min) were observed with the late schedule. We also found reduced sleep durations during weekdays and extended sleep durations during weekends. This pattern was more pronounced during the semester with the early class schedule, indicating that the students were more sleep deprived when their classes began earlier in the morning. These results require further investigation regarding the temporal organization of our institutions.

Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians

The genetic basis for dementias is complex. A common polymorphism in the apolipoprotein E (APOE) gene is considered to be the major risk factor in families with sporadic and late-onset Alzheimer's disease as well as in the general population. The distribution of alleles and genotypes of the APOE gene in late-onset Alzheimer's disease (N = 68), other late-life dementias (N = 39), and in cognitively normal controls (N = 58) was determined, as also was the risk for Alzheimer's disease associated with the epsilon4 allele. Peripheral blood samples were obtained from a total of 165 individuals living in Brazil aged 65-82 years. Genomic DNA was amplified by the polymerase chain reaction and the products were digested with HhaI restriction enzyme. APOE epsilon2 frequency was considerably lower in the Alzheimer's disease group (1%), and the epsilon3 allele and epsilon3/epsilon3 genotype frequencies were higher in the controls (84 and 72%, respectively) as were the epsilon4 allele and epsilon3/epsilon4 genotype frequencies in Alzheimer's disease (25 and 41%, respectively). The higher frequency of the epsilon4 allele in Alzheimer's disease confirmed its role as a risk factor, while epsilon2 provided a weak protection against development of the disease. However, in view of the unexpectedly low frequency of the epsilon4 allele, additional analyses in a more varied Brazilian sample are needed to clarify the real contribution of apolipoprotein E to the development of Alzheimer's disease in this population.

Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study

The relevance of the relationship between cardiac disease and depressive symptoms is well established. White matter hyperintensity, a bright signal area in the brain on T2-weighted magnetic resonance imaging scans, has been separately associated with cardiovascular risk factors, cardiac disease and late-life depression. However, no study has directly investigated the association between heart failure, major depressive symptoms and the presence of hyperintensities. Using a visual assessment scale, we have investigated the frequency and severity of white matter hyperintensities identified by magnetic resonance imaging in eight patients with late-life depression and heart failure, ten patients with heart failure without depression, and fourteen healthy elderly volunteers. Since the frontal lobe has been the proposed site for the preferential location of white matter hyperintensities in patients with late-life depression, we focused our investigation specifically on this brain region. Although there were no significant group differences in white matter hyperintensities in the frontal region, a significant direct correlation emerged between the severity of frontal periventricular white matter hyperintensity and scores on the Hamilton scale for depression in the group with heart failure and depression (P = 0.016, controlled for the confounding influence of age). There were no significant findings in any other areas of the brain. This pattern of results adds support to a relationship between cardiovascular risk factors and depressive symptoms, and provides preliminary evidence that the presence of white matter hyperintensities specifically in frontal regions may contribute to the severity of depressive symptoms in cardiac disease.

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group) underwent left coronary artery ligation (infarcted, Inf) or sham-operation (Sham). Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e) and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 ± 6; Inf 3 = 130 ± 9; Inf 30 = 92 ± 7 mmHg; P < 0.05). The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 ± 3; Inf 3 = 45 ± 2; Inf 30 = 29 ± 3 mmHg; P < 0.05), while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.

Clinical and pathological challenges in the diagnosis of late-onset biliary atresia: four case studies

Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age.

Challenges of user-driven innovations on late stages of innovation process: evidence from ICT companies

The goal of this thesis is to study user-driven innovations and user involvement throughout the innovation process in context of B2B companies. Significant emphasis in the analysis put onto the late stages of innovation process and commercialization of innovations. Thesis includes detailed review of theoretical concepts and underlying frameworks of innovation process, lead users and user-driven innovations. The empirical part of the thesis consist of interviews of the four companies from ICT industry, followed by the comprehensive analysis and comparison of the results. The presented findings indicate common challenges, which ICT companies face, when shifting towards innovation by users paradigm. Linkages and connections among current situation and theoretical frameworks presented in the discussion part of the thesis allow to draw practical managerial implications. The results of the research emphasize valuable insights and challenges of user interactions within innovation process as well as output and participation related benefits for the companies and users. The research points out current state of the user involvement techniques and tools used for user interactions as well as suggests the possibilities for improvement in the future.

A case of late-onset oligomeganephronia

A 33-year old caucasian man was investigated for pain in the right flank, proteinuria, hemathuria and an elevated serum creatinine level. He also presented an abnormal ultrasonography, which revealed asymmetric kidneys. Through renal biopsy, the diagnosis of oligomeganephronia (OMN) was confirmed. OMN is a very rare form of renal hypoplasia, and late-onset in adulthood is even rarer. In the pediatric population, OMN leads to end-stage-renal-failure(ESRF) in a few years. This is the sixth case related in the literature of a late-onset OMN who have not yet developed ESRF.

Late-onset spinal motor neuronopathy- a new neuromuscular disease

The aim of this study was to clarify the clinical phenotype of late-onset spinal motor neuronopathy (LOSMoN), an adult-onset autosomal dominant lower motor neuron disorder identified first in two families in Eastern Finland, in order to clarify its genetic background. Motor neuron disorders (MNDs) are characterized by dysfunction and premature death of motor neurons in the brain and spinal cord. MNDs can manifest at any age of the human lifespan, ranging from pre- or neonatal forms such as spinal muscular atrophy type I (SMA I) to those preferentially affecting the older age groups exemplified by sporadic amyotrophic lateral sclerosis (ALS). With a combination of genetic linkage analysis and genome sequencing using DNA from a total of 55 affected members of 17 families and a whole genome scan, we were able to show that LOSMoN is caused by the c.197G>T p.G66V mutation in the gene CHCHD10. This study showed that LOSMoN has very characteristic features that help to differentiate it from other more malignant forms of motor neuron disease, such as ALS, which was erroneously diagnosed in many patients in our cohort. Lack of fibrillations in the first dorsal interosseus muscle on EMG and extensive grouping of non-atrophic type IIA/2A fibers on muscle biopsy were shown to be common findings in LOSMoN, but rare or absent in ALS patients. The results of this study will help clinicians recognize the characteristic phenotype of LOSMoN disease and thus improve their diagnostic accuracy, and will also allow physicians to provide adequate genetic counseling for patients.