Average-Case Optimal Approximate Circular String Matching

Approximate string matching is the problem of finding all factors of a text t of length n that are at a distance at most k from a pattern x of length m. Approximate circular string matching is the problem of finding all factors of t that are at a distance at most k from x or from any of its rotations. In this article, we present a new algorithm for approximate circular string matching under the edit distance model with optimal average-case search time O(n(k + log m)/m). Optimal average-case search time can also be achieved by the algorithms for multiple approximate string matching (Fredriksson and Navarro, 2004) using x and its rotations as the set of multiple patterns. Here we reduce the preprocessing time and space requirements compared to that approach

Circular pattern matching with k mismatches

The k-mismatch problem consists in computing the Hamming distance between a pattern P of length m and every length-m substring of a text T of length n, if this distance is no more than k. In many real-world applications, any cyclic shift of P is a relevant pattern, and thus one is interested in computing the minimal distance of every length-m substring of T and any cyclic shift of P. This is the circular pattern m

Sensitive detection of Aβ protofibrils by proximity ligation - relevance for Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Protein aggregation plays important roles in several neurodegenerative disorders. For instance, insoluble aggregates of phosphorylated tau and of Aβ peptides are cornerstones in the pathology of Alzheimer's disease. Soluble protein aggregates are therefore potential diagnostic and prognostic biomarkers for their cognate disorders. Detection of the aggregated species requires sensitive tools that efficiently discriminate them from monomers of the same proteins. Here we have established a proximity ligation assay (PLA) for specific and sensitive detection of Aβ protofibrils via simultaneous recognition of three identical determinants present in the aggregates. PLA is a versatile technology in which the requirement for multiple target recognitions is combined with the ability to translate signals from detected target molecules to amplifiable DNA strands, providing very high specificity and sensitivity.</p> <p>Results</p> <p>For specific detection of Aβ protofibrils we have used a monoclonal antibody, mAb158, selective for Aβ protofibrils in a modified PLA, where the same monoclonal antibody was used for the three classes of affinity reagents required in the assay. These reagents were used for detection of soluble Aβ aggregates in solid-phase reactions, allowing detection of just 0.1 pg/ml Aβ protofibrils, and with a dynamic range greater than six orders of magnitude. Compared to a sandwich ELISA setup of the same antibody the PLA increases the sensitivity of the Aβ protofibril detection by up to 25-fold. The assay was used to measure soluble Aβ aggregates in brain homogenates from mice transgenic for a human allele predisposing to Aβ aggregation.</p> <p>Conclusions</p> <p>The proximity ligation assay is a versatile analytical technology for proteins, which can provide highly sensitive and specific detection of Aβ aggregates - and by implication other protein aggregates of relevance in Alzheimer's disease and other neurodegenerative disorders.</p

Forest Fruit Production Is Higher on Sumatra Than on Borneo

BACKGROUND: Various studies have shown that the population densities of a number of forest vertebrates, such as orangutans, are higher on Sumatra than Borneo, and that several species exhibit smaller body sizes on Borneo than Sumatra and mainland Southeast Asia. It has been suggested that differences in forest fruit productivity between the islands can explain these patterns. Here we present a large-scale comparison of forest fruit production between the islands to test this hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: Data on fruit production were collated from Sumatran and Bornean sites. At six sites we assessed fruit production in three forest types: riverine, peat swamp and dryland forests. We compared fruit production using time-series models during different periods of overall fruit production and in different tree size classes. We examined overall island differences and differences specifically for fruiting period and tree size class. The results of these analyses indicate that overall the Sumatran forests are more productive than those on Borneo. This difference remains when each of the three forest types (dryland, riverine, and peat) are examined separately. The difference also holds over most tree sizes and fruiting periods. CONCLUSIONS/SIGNIFICANCE: Our results provide strong support for the hypothesis that forest fruit productivity is higher on Sumatra than Borneo. This difference is most likely the result of the overall younger and more volcanic soils on Sumatra than Borneo. These results contribute to our understanding of the determinants of faunal density and the evolution of body size on both islands

Cognitive and Socio-Emotional Deficits in Platelet-Derived Growth Factor Receptor-β Gene Knockout Mice

Platelet-derived growth factor (PDGF) is a potent mitogen. Extensive in vivo studies of PDGF and its receptor (PDGFR) genes have reported that PDGF plays an important role in embryogenesis and development of the central nervous system (CNS). Furthermore, PDGF and the β subunit of the PDGF receptor (PDGFR-β) have been reported to be associated with schizophrenia and autism. However, no study has reported on the effects of PDGF deletion on mice behavior. Here we generated novel mutant mice (PDGFR-β KO) in which PDGFR-β was conditionally deleted in CNS neurons using the Cre/loxP system. Mice without the Cre transgene but with floxed PDGFR-β were used as controls. Both groups of mice reached adulthood without any apparent anatomical defects. These mice were further examined by conducting several behavioral tests for spatial memory, social interaction, conditioning, prepulse inhibition, and forced swimming. The test results indicated that the PDGFR-β KO mice show deficits in all of these areas. Furthermore, an immunohistochemical study of the PDGFR-β KO mice brain indicated that the number of parvalbumin (calcium-binding protein)-positive (i.e., putatively γ-aminobutyric acid-ergic) neurons was low in the amygdala, hippocampus, and medial prefrontal cortex. Neurophysiological studies indicated that sensory-evoked gamma oscillation was low in the PDGFR-β KO mice, consistent with the observed reduction in the number of parvalbumin-positive neurons. These results suggest that PDGFR-β plays an important role in cognitive and socioemotional functions, and that deficits in this receptor may partly underlie the cognitive and socioemotional deficits observed in schizophrenic and autistic patients

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

Neck disorder influenced by occupational reward type: Results from effort-reward imbalance model based on IPWS

Effort-Reward Imbalance model is known as one of the survey method of occupational stress and also as an effective element on health condition according to its parameters. Due to types of rewards generally, and reward subscales in this model specifically, each one can have a distinctive effect on health perception, current study is aimed at determination of the most effective reward subscale for managing work-related neck disorder in industries. All of workers who participated in IPWS study (N = 1126), were entered in the statistical analysis stage. After completing personal and organizational information, they responded to Van Vegchel et al. Effort-Reward Imbalance and also Dutch questionnaires for their musculoskeletal disorders. Chi-square and t-test comparisons were performed and the final regression model was presented with a significance level of 0.05. The mean (Standard deviation) age of workers and musculoskeletal disorders prevalence in neck were 33.21 (7.63) years and 34 percent respectively. Also in workers with neck pain, odds ratio between effort and monetary reward, between effort and respect reward, and between effort and security reward in their jobs were 1.35, 2.07 and 1.32 respectively. After elimination of confounders in final regression model, significant correlation was remained only between effort and job respect reward. According to high prevalence of musculoskeletal disorders in neck and also large amount of effort-reward imbalance in Iranian workers, implementing interventions are recommended. Based on results of present study, it is suggested that main intervention must be focused on respect and esteem reward in jobs. © Springer Nature Switzerland AG 2019

A pharmacological organization of G protein–coupled receptors

Protein classification typically uses structural, sequence, or functional similarity. Here we introduce an orthogonal method that organizes proteins by ligand similarity, focusing here on the class A G protein-coupled receptor (GPCR) protein family. Comparing a ligand-based dendogram to a sequence-based one, we sought examples of GPCRs that were distantly linked by sequence but neighbors by ligand similarity. Experimental testing of compounds predicted to link three of these new pairs confirmed the predicted association, with potencies ranging from the low-nanomolar to low-micromolar. We then identified hundreds of non-GPCRs closely related to GPCRs by ligand similarity, including the CXCR2 chemokine receptor to Casein kinase I, the cannabinoid receptors to epoxide hydrolase 2, and the α2 adrenergic receptor to phospholipase D. These, too, were confirmed experimentally. Ligand similarities among these targets may reflect a chemical integration in the time domain of molecular signaling

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans