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Abstract. Social bookmark tools are rapidly emerging on the Web. In such systems users are setting up lightweight conceptual structures called folksonomies. The reason for their immediate success is the fact that no specific skills are needed for participating. At the moment, however, the information retrieval support is limited. We present a formal model and a new search algorithm for folksonomies, called FolkRank, that exploits the structure of the folksonomy. The proposed algorithm is also applied to find communities within the folksonomy and is used to structure search results. All findings are demonstrated on a large scale dataset.

Alzheimer's disease (AD) is characterized by a substantial degeneration of pyramidal neurons and the appearance of neuritic plaques and neurofibrillary tangles. Here we present a novel transgenic mouse model, APP(SL)PS1KI that closely mimics the development of AD-related neuropathological features including a significant hippocampal neuronal loss. This transgenic mouse model carries M233T/L235P knocked-in mutations in presenilin-1 and overexpresses mutated human beta-amyloid (Abeta) precursor protein. Abeta(x-42) is the major form of Abeta species present in this model with progressive development of a complex pattern of N-truncated variants and dimers, similar to those observed in AD brain. At 10 months of age, an extensive neuronal loss (>50%) is present in the CA1/2 hippocampal pyramidal cell layer that correlates with strong accumulation of intraneuronal Abeta and thioflavine-S-positive intracellular material but not with extracellular Abeta deposits. A strong reactive astrogliosis develops together with the neuronal loss. This loss is already detectable at 6 months of age and is PS1KI gene dosage-dependent. Thus, APP(SL)PS1KI mice further confirm the critical role of intraneuronal Abeta(42) in neuronal loss and provide an excellent tool to investigate therapeutic strategies designed to prevent AD neurodegeneration.

Autism is characterized by qualitative abnormalities in behavior and higher order cognitive functions. Minicolumnar irregularities observed in autism provide a neurologically sound localization to observed clinical and anatomical abnormalities. This study corroborates the initial reports of a minicolumnopathy in autism within an independent sample. The patient population consisted of six age-matched pairs of patients (DSM-IV-TR and ADI-R diagnosed) and controls. Digital micrographs were taken from cortical areas S1, 4, 9, and 17. The image analysis produced estimates of minicolumnar width (CW), mean interneuronal distance, variability in CW (V (CW)), cross section of Nissl-stained somata, boundary length of stained somata per unit area, and the planar convexity. On average CW was 27.2 microm in controls and 25.7 microm in autistic patients (P = 0.0234). Mean neuron and nucleolar cross sections were found to be smaller in autistic cases compared to controls, while neuron density in autism exceeded the comparison group by 23%. Analysis of inter- and intracluster distances of a Delaunay triangulation suggests that the increased cell density is the result of a greater number of minicolumns, otherwise the number of cells per minicolumns appears normal. A reduction in both somatic and nucleolar cross sections could reflect a bias towards shorter connecting fibers, which favors local computation at the expense of inter-areal and callosal connectivity.

Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general.

Autism is currently viewed as a largely genetically determined neurodevelopmental disorder, although its underlying biological causes remain to be established. In this review, we examine the available neuropathological literature on autism and discuss the findings that have emerged. Classic neuropathological observations are rather consistent with respect to the limbic system (nine of 14 studied cases showed increased cell packing density and smaller neuronal size), the cerebellum (21 of 29 studied cases showed a decreased number of Purkinje cells, and in all of five cases that were examined for age-related morphological alterations, these changes were found in cerebellar nuclei and inferior olive) and the cerebral cortex (>50% of the studied cases showed features of cortical dysgenesis). However, all reported studies had to contend with the problem of small sample sizes, the use of quantification techniques not free of bias and assumptions, and high percentages of autistic subjects with comorbid mental retardation (at least 70%) or epilepsy (at least 40%). Furthermore, data from the limbic system and on age-related changes lack replication by independent groups. It is anticipated that future neuropathological studies hold great promise, especially as new techniques such as design-based stereology and gene expression are increasingly implemented and combined, larger samples are analysed, and younger subjects free of comorbidities are investigated.

The autism spectrum disorder (ASD) is among the most devastating disorders of childhood in terms of prevalence, morbidity, outcome, impact on the family, and cost to society. According to recent epidemiological data, ϳ1 child in 166 is affected with ASD, a considerable increase compared with estimates compiled 15-20 years ago (Fombonne, 2003a,b). Although at one time considered an emotional disturbance resulting from early attachment experiences (Bettelheim, 1967), ASD is now recognized as a disorder of prenatal and postnatal brain development. Although ASD is primarily a genetic disorder involving multiple genes, insights into underlying mechanisms will require a multidisciplinary approach. Assessment of the earliest clinical signs and symptoms and the functional and structural networks by neuroimaging and neuropathology can be used to identify the underlying brain regions, neural networks, and cellular systems. In turn, the efforts of human and animal geneticists and neuroscientists are needed to define molecular and protein signaling pathways that mediate normal as well as abnormal development of language, social interaction, and cognitive and motor routines. In this review, we focus on several issues: the earliest manifestations of ASD, reported abnormalities of brain growth, functional neural networks, and neuropathology. We also consider the possible etiological factors and the challenges of creating animal models for this uniquely human behavioral disorder. Autism spectrum disorder: phenotypes and clinical diagnosisASD comprises several different disorders as defined by deficits in social behaviors and interactions. These deficits prevent the development of normal interpersonal relationships of affected patients with their parents, siblings, and other children. Deficits in nonverbal communication include reduced eye contact, facial expression, and body gestures (American Psychiatric Association, 1994). These disorders include prototypic autistic disorder, Asperger syndrome, and pervasive developmental disorder-not otherwise specified (PDD-NOS). Autistic disorder has three core symptom domains: deficits in communication, abnormal social interactions, and restrictive and/or repetitive interests and behaviors. Autistic disorder is typically noticed in the first or second year of life. The manifestations include delay or abnormality in language and play, repetitive behaviors, such as spinning things or lining up small objects, or unusual interests such as preoccupations with stop signs or ceiling fans. Asperger syndrome also involves social symptoms but language development and non-

BackgroundExtracorporeal shock wave therapy (ESWT) is an effective and safe non-invasive treatment option for tendon and other pathologies of the musculoskeletal system.Sources of dataThis systematic review used data derived from the Physiotherapy Evidence Database (PEDro; , 23 October 2015, date last accessed).Areas of agreementESWT is effective and safe. An optimum treatment protocol for ESWT appears to be three treatment sessions at 1-week intervals, with 2000 impulses per session and the highest energy flux density the patient can tolerate.Areas of controversyThe distinction between radial ESWT as ‘low-energy ESWT’ and focused ESWT as ‘high-energy ESWT’ is not correct and should be abandoned.Growing pointsThere is no scientific evidence in favour of either radial ESWT or focused ESWT with respect to treatment outcome.Areas timely for developing researchFuture randomized controlled trials should primarily address systematic tests of the aforementioned optimum treatment protocol and direct comparisons between radial and focused ESWT.