New insights into the phosphorylation of the threonine motif of the β1 integrin cytoplasmic domain

Integrins require an activation step before ligand binding and signaling that is mediated by talin and kindlin binding to the beta integrin cytosolic domain (beta-tail). Conflicting reports exist about the contribution of phosphorylation of a conserved threonine motif in the beta 1-tail (beta 1-pT788/pT789) to integrin activation. We show that widely used and commercially available antibodies against beta 1-pT788/pT789 integrin do not detect specific beta 1-pT788/ pT789 integrin signals in immunoblots of several human and mouse cell lysates but bind bi-phosphorylated threonine resi-dues in numerous proteins, which were identified by mass spectrometry experiments. Furthermore, we found that fibro-blasts and epithelial cells expressing the phospho-mimicking beta 1-TT788/789DD integrin failed to activate beta 1 integrins and displayed reduced integrin ligand binding, adhesion initiation and cell spreading. These cellular defects are specifically caused by the inability of kindlin to bind beta 1-tail polypeptides carrying a phosphorylated threonine motif or phospho-mimicking TT788/789DD substitutions. Our findings indicate that the double-threonine motif in beta 1-class integrins is not a major phosphory-lation site but if phosphorylated would curb integrin function

INTERSEGMENTAL COORDINATION DIFFERENCES BETWEEN BEGINNING PERFORMERS EXECUTING A BADMINTON SMASH FOR ACCURACY OR VELOCITY

Proper coordination is generally accepted as a very important process in skilful execution of many movement activities. It is also believed ballistic skills will exhibit a sequential intersegmental coordination pattern. Yet, what we know about how intersegmental coordination develops is relatively minimal. The purpose of this investigation was to examine a new skill (badminton smash) under two conditions (accuracy and velocity) to determine which condition would elicit the most theoretically correct intersegmental coordination pattern (Work in progress)

Proteome-based plasma biomarkers for Alzheimer's disease

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and α-2-macroglobulin (α- 2M). Using semi-quantitative immunoblotting, the elevation of CFH and α- 2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as α- 2M may be a specific markers of this illness. © 2006 The Author(s).link_to_subscribed_fulltex

Feasibility of a combined mobile-health electrocardiographic and rapid diagnostic test screening for chagas-related cardiac alterations

Background: Chronic Chagas cardiomyopathy (CChC) is the most common cause of death related to Chagas disease (CD). The aim of this study was to assess the feasibility of a combined rapid diagnostic test (RDT) and electrocardiographic (ECG) screening in a remote rural village of the Bolivian Chaco, with a high prevalence of CChC. Methods: Consecutive healthy volunteers > 15 years were enrolled in the community of Palmarito (municipality of Gutierrez, Santa Cruz Department, Bolivia) in February 2019. All patients performed an RDT with Chagas Stat-Pak(®) (CSP, Chembio Diagnostic System, Medford, NY, USA) and an ECG by D-Heart(®) technology, a low-cost, user-friendly smartphone-based 8-lead Bluetooth ECG. RDTs were read locally while ECGs were sent to a cardiology clinic which transmitted reports within 24 h from recording. Results: Among 140 people (54 men, median age 38(interquartile range 23–54) years), 98 (70%) were positive for Trypanosoma cruzi infection, with a linear, age-dependent, increasing trend (p < 0.001). Twenty-five (18%) individuals showed ECG abnormalities compatible with CD. Prevalence of ECG abnormalities was higher in infected individuals and was associated with higher systolic blood pressure and smoking. Following screening, 22 (16%) individuals underwent clinical evaluation and chest X-ray and two were referred for further evaluation. At multivariate analysis, positive CSP results (OR = 4.75, 95%CI 1.08–20.96, p = 0.039) and smoking (OR = 4.20, 95%CI 1.18–14.92, p = 0.027) were independent predictors of ECG abnormalities. Overall cost for screening implementation was <10 $. Conclusions: Combined mobile-Health and RDTs was a reliable and effective low-cost strategy to identify patients at high risk of disease needing cardiologic assessment suggesting potential future applications

Might some gamma ray bursts be an observable signature of natural wormholes?

The extragalactic microlensing scenario for natural wormholes is examined. It is shown that the main features of wormhole lensing events upon the light of distant Active Galactic Nuclei (AGNs) are similar to some types of already observed Gamma Ray Bursts (GRBs). Using recent satellite data on GRBs, an upper limit to the negative mass density -- ${\cal O} (10^{-36})$ g cm$^{-3}$ -- under the form of wormhole-like objects is presented.Comment: extended version, additions on GRB physics, background sources and cosmological consequences. Two ps figures. Accpeted for publication in Phys. Rev.

Unsharp Quantum Reality

The positive operator (valued) measures (POMs) allow one to generalize the notion of observable beyond the traditional one based on projection valued measures (PVMs). Here, we argue that this generalized conception of observable enables a consistent notion of unsharp reality and with it an adequate concept of joint properties. A sharp or unsharp property manifests itself as an element of sharp or unsharp reality by its tendency to become actual or to actualize a specific measurement outcome. This actualization tendency-or potentiality-of a property is quantified by the associated quantum probability. The resulting single-case interpretation of probability as a degree of reality will be explained in detail and its role in addressing the tensions between quantum and classical accounts of the physical world will be elucidated. It will be shown that potentiality can be viewed as a causal agency that evolves in a well-defined way

Advanced adenoma diagnosis with FDG PET in a visibly normal mucosa: a case report

<p>Abstract</p> <p>Background</p> <p>An accurate, early diagnosis and treatment of adenomatous polyp can curtail progression to colorectal cancer. F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) reveals the biochemical changes associated with the development of many cancers which precede the appearance of gross anatomical changes that may be visualized during surgical resection or via imaging with MR or CT.</p> <p>Intervention</p> <p>We detail the history of a 64 year old female who had a whole-body FDG PET scan as a part of an employee wellness program. A dose of 12.2 mCi of F-18 labeled FDG was administered.</p> <p>Results</p> <p>A focal cecal uptake with a standardized uptake value (SUV) of 8.9 was found on the PET scan. Conversely, only normal mucosa was observed during a colonoscopy done 2 months after the PET scan. Motivated by the PET scan finding, the colonoscopist performed a biopsy which revealed a villous adenoma without high grade dysplasia. Pathology from tissue extracted during an exploratory laparatomy completed one month later found the lesion to be a villous adenoma with high grade dysplasia.</p> <p>Conclusion</p> <p>Whole-body FDG PET scan revealed the biochemical metabolic changes in malignancy that preceded the appearance of any gross anatomical abnormality. A positive FDG PET scan indicative of colorectal cancer should be followed up with a colonoscopy and biopsy even in a visibly normal mucosa.</p

Digital karyotyping reveals probable target genes at 7q21.3 locus in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is a worldwide malignant liver tumor with high incidence in China. Subchromosomal amplifications and deletions accounted for major genomic alterations occurred in HCC. Digital karyotyping was an effective method for analyzing genome-wide chromosomal aberrations at high resolution.</p> <p>Methods</p> <p>A digital karyotyping library of HCC was constructed and 454 Genome Sequencer FLX System (Roche) was applied in large scale sequencing of the library. Digital Karyotyping Data Viewer software was used to analyze genomic amplifications and deletions. Genomic amplifications of genes detected by digital karyotyping were examined by real-time quantitative PCR. The mRNA expression level of these genes in tumorous and paired nontumorous tissues was also detected by real-time quantitative RT-PCR.</p> <p>Results</p> <p>A total of 821,252 genomic tags were obtained from the digital karyotyping library of HCC, with 529,162 tags (64%) mapped to unique loci of human genome. Multiple subchromosomal amplifications and deletions were detected through analyzing the digital karyotyping data, among which the amplification of 7q21.3 drew our special attention. Validation of genes harbored within amplicons at 7q21.3 locus revealed that genomic amplification of SGCE, PEG10, DYNC1I1 and SLC25A13 occurred in 11 (21%), 11 (21%), 11 (21%) and 23 (44%) of the 52 HCC samples respectively. Furthermore, the mRNA expression level of SGCE, PEG10 and DYNC1I1 were significantly up-regulated in tumorous liver tissues compared with corresponding nontumorous counterparts.</p> <p>Conclusions</p> <p>Our results indicated that subchromosomal region of 7q21.3 was amplified in HCC, and SGCE, PEG10 and DYNC1I1 were probable protooncogenes located within the 7q21.3 locus.</p