Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells

Cyclase-associated proteins (CAPs) are highly conserved actin monomer binding proteins present in all eukaryotes. However, the mechanism by which CAPs contribute to actin dynamics has been elusive. In mammals, the situation is further complicated by the presence of two CAP isoforms whose differences have not been characterized. Here, we show that CAP1 is widely expressed in mouse nonmuscle cells, whereas CAP2 is the predominant isoform in developing striated muscles. In cultured NIH3T3 and 1316171 cells, CAP1 is a highly abundant protein that colocalizes with cofilin-1 to dynamic regions of the cortical actin cytoskeleton. Analysis of CAP1 knockdown cells demonstrated that this protein promotes rapid actin filament depolymerization and is important for cell morphology, migration, and endocytosis. Interestingly, depletion of CAP1 leads to an accumulation of cofilin-1 into abnormal cytoplasmic aggregates and to similar cytoskeletal defects to those seen in cofilin-1 knockdown cells, demonstrating that CAP1 is required for proper subcellular localization and function of ADF/cofilin. Together, these data provide the first direct in vivo evidence that CAP promotes rapid actin dynamics in conjunction with ADF/cofilin and is required for several central cellular processes in mammals

Travertine precipitation in the Paleoproterozoic Kuetsjärvi Sedimentary Formation, Pechenga Greenstone Belt, NE Fennoscandian Shield

PES was supported by Väisälä Foundation (Finnish Academy of Science and Letters) and the Finnish Doctoral Program in Geology. ATB was supported by NERC grant NE/G00398X/1. VAM was supported by NFR grant 191530/V30 (projects 331000 and 802795). This is a contribution (paper) # 18 to the ICDP FAR-DEEP project.Peer reviewedPublisher PD

Reducing CSF partial volume effects to enhance diffusion tensor imaging metrics of brain microstructure

Technological advances over recent decades now allow for in vivo observation of human brain tissue through the use of neuroimaging methods. While this field originated with techniques capable of capturing macrostructural details of brain anatomy, modern methods such as diffusion tensor imaging (DTI) that are now regularly implemented in research protocols have the ability to characterize brain microstructure. DTI has been used to reveal subtle micro-anatomical abnormalities in the prodromal phase ofº various diseases and also to delineate “normal” age-related changes in brain tissue across the lifespan. Nevertheless, imaging artifact in DTI remains a significant limitation for identifying true neural signatures of disease and brain-behavior relationships. Cerebrospinal fluid (CSF) contamination of brain voxels is a main source of error on DTI scans that causes partial volume effects and reduces the accuracy of tissue characterization. Several methods have been proposed to correct for CSF artifact though many of these methods introduce new limitations that may preclude certain applications. The purpose of this review is to discuss the complexity of signal acquisition as it relates to CSF artifact on DTI scans and review methods of CSF suppression in DTI. We will then discuss a technique that has been recently shown to effectively suppress the CSF signal in DTI data, resulting in fewer errors and improved measurement of brain tissue. This approach and related techniques have the potential to significantly improve our understanding of “normal” brain aging and neuropsychiatric and neurodegenerative diseases. Considerations for next-level applications are discussed

Topological organization of whole-brain white matter in HIV infection

Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV− controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural network models were constructed using diffusion MRI-based multifiber tractography and T(1)-weighted MRI-based regional gray matter segmentation. Global network measures included whole-brain structural integration, connection strength, and structural segregation. Cognition was measured using a neuropsychological global deficit score (GDS) as well as individual cognitive domains. Results revealed that HIV+ participants exhibited significant disruptions to whole-brain networks, characterized by weaker structural integration (characteristic path length and efficiency), connection strength, and structural segregation (clustering coefficient) than HIV− controls (p < 0.05). GDSs and performance on learning/recall tasks were negatively correlated with the clustering coefficient (p < 0.05) in HIV+ participants. Results from this study indicate disruption to brain network integrity in treatment-limited HIV+ young adults with corresponding abnormalities in cognitive performance

Kinetics of a Diffusive Capture Process: Lamb Besieged by a Pride of Lions

The survival probability, S_N(t), of a diffusing prey (``lamb'') in the proximity of N diffusing predators (a ``pride of lions'') in one dimension is investigated. When the lions are all to one side of the lamb, the survival probability decays as a non-universal power law, S_N(t) is proportional to t^{-beta_N}, with the decay exponent beta_N proportional to ln N. The crossover behavior as a function of the relative diffusivities of the lions and the lamb is also discussed. When N--->oo, the lamb survival probability exhibits a log-normal decay, exp(-ln^2 t).Comment: 12 pages, no figures, macro files prepended, to be submitted to J. Phys.

Mechanism of action of probiotics

The modern diet doesn't provide the required amount of beneficial bacteria. Maintenance of a proper microbial ecology in the host is the main criteria to be met for a healthy growth. Probiotics are one such alternative that are supplemented to the host where by and large species of Lactobacillus, Bifidobacterium and Saccharomyces are considered as main probiotics. The field of probiotics has made stupendous strides though there is no major break through in the identification of their mechanism of action. They exert their activity primarily by strengthening the intestinal barrier and immunomodulation. The main objective of the study was to provide a deep insight into the effect of probiotics against the diseases, their applications and proposed mechanism of action

Transverse-field Ising spin chain with inhomogeneous disorder

We consider the critical and off-critical properties at the boundary of the random transverse-field Ising spin chain when the distribution of the couplings and/or transverse fields, at a distance $l$ from the surface, deviates from its uniform bulk value by terms of order $l^{-\kappa}$ with an amplitude $A$. Exact results are obtained using a correspondence between the surface magnetization of the model and the surviving probability of a random walk with time-dependent absorbing boundary conditions. For slow enough decay, $\kappa<1/2$, the inhomogeneity is relevant: Either the surface stays ordered at the bulk critical point or the average surface magnetization displays an essential singularity, depending on the sign of $A$. In the marginal situation, $\kappa=1/2$, the average surface magnetization decays as a power law with a continuously varying, $A$-dependent, critical exponent which is obtained analytically. The behavior of the critical and off-critical autocorrelation functions as well as the scaling form of the probability distributions for the surface magnetization and the first gaps are determined through a phenomenological scaling theory. In the Griffiths phase, the properties of the Griffiths-McCoy singularities are not affected by the inhomogeneity. The various results are checked using numerical methods based on a mapping to free fermions.Comment: 11 pages (Revtex), 11 figure

Appendicolith appendicitis is clinically complicated acute appendicitis – is it histopathologically different from uncomplicated acute appendicitis

Purpose: Acute appendicitis may present as uncomplicated and complicated and these disease forms differ both epidemiologically and clinically. Complicated acute appendicitis has traditionally been defined as an appendicitis complicated by perforation or a periappendicular abscess, and an appendicolith represents a predisposing factor of complicated disease. There are histopathological differences between uncomplicated acute appendicitis and the previously established traditional forms of complicated acute appendicitis, but to our knowledge, the histopathological differences between uncomplicated acute appendicitis and complicated acute appendicitis presenting with an appendicolith have not yet been reported. The study purpose was to assess these differences with two prospective patient cohorts: (1) computed tomography (CT) confirmed uncomplicated acute appendicitis patients enrolled in the surgical treatment arm of the randomized APPAC trial comparing appendectomy with antibiotics for the treatment of uncomplicated acute appendicitis and (2) patients with CT-verified acute appendicitis presenting with an appendicolith excluded from the APPAC trial.Methods: The following histopathological parameters were assessed: appendiceal diameter, depth of inflammation, micro-abscesses, density of eosinophils, and neutrophils in appendiceal wall and surface epithelium degeneration.Results: Using multivariable logistic regression models adjusted for age, gender, and symptom duration, statistically significant differences were detected in the depth of inflammation = 150/mm(2) (adjusted OR 0.97 (95%CI: 0.95-0.99, p=0.013), adjusted OR 3.04 (95%CI: 1.82-5.09, pConclusions: These results corroborate the known clinical association of an appendicolith to complicated acute appendicitis.</div

An isolate of human immunodeficiency virus type 1 originally classified as subtype I represents a complex mosaic comprising three different group M subtypes (A, G, and I)

Full-length reference clones and sequences are currently available for eight human immunodeficiency virus type 1 (HIV-1) group M subtypes (A through H), but none have been reported for subtypes I and J, which have only been identified in a few individuals. Phylogenetic information for subtype I, in particular, is limited since only about 400 bp of env gene sequences have been determined for just two epidemiologically linked viruses infecting a couple who were heterosexual intravenous drug users from Cyprus. To characterize subtype I in greater detail, we employed long-range PCR to clone a full-length provirus (94CY032.3) from an isolate obtained from one of the individuals originally reported to be infected with this subtype. Phylogenetic analysis of C2-V3 env gene sequences confirmed that 94CY032.3 was closely related to sequences previously classified as subtype I. However, analysis of the remainder of its genome revealed various regions in which 94CY032.3 was significantly clustered with either subtype A or subtype G. Only sequences located in vpr and nef, as well as the middle portions of pol and env, formed independent lineages roughly equidistant from all other known subtypes. Since these latter regions most likely have a common origin, we classify them all as subtype I. These results thus indicate that the originally reported prototypic subtype I isolate 94CY032 represents a triple recombinant (A/G/I) with at least 11 points of recombination crossover. We also screened HIV-1 recombinants with regions of uncertain subtype assignment for the presence of subtype I sequences. This analysis revealed that two of the earliest mosaics from Africa, Z321B (A/G/?) and MAL (A/D/?), contain short segments of sequence which clustered closely with the subtype I domains of 94CY032.3. Since Z321 was isolated in 1976, subtype I as well as subtypes A and G must have existed in Central Africa prior to that date... (D'après résumé d'auteur

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.Peer reviewe