Mild cognitive impairment (MCI) is a transitional state between the cognitive changes in normal aging and Alzheimer's disease (AD), which induces abnormalities in specific brain regions. Previous ...studies showed that paired helical filaments Tau (PHF-Tau) protein is a potential pathogenic protein which may cause abnormal brain function and structure in MCI and AD patients. However, the understanding of the PHF-Tau protein network in MCI patients is limited. In this study, 225 subjects with PHF-Tau Positron Emission Tomography (PET) images were divided into four groups based on whether they carried Apolipoprotein E ε4 (APOE 4) or abnormal cerebrospinal fluid Total-Tau (CSF T-Tau). They are two important pathogenic factors that might cause cognitive function impairment. The four groups were: individuals harboring CSF T-Tau pathology but no APOE 4 (APOE 4-T+); APOE 4 carriers with normal CSF T-Tau (APOE 4+T-); APOE 4 carriers with abnormal CSF T-Tau (APOE 4+T+); and APOE 4 noncarriers with abnormal CSF T-Tau (APOE 4-T-). We explored the topological organization of PHF-Tau networks in these four groups and calculated five kinds of network properties: clustering coefficient, shortest path length,
value of modularity, nodal centrality and degree. Our findings showed that compared with APOE 4-T- group, the other three groups showed different alterations in the clustering coefficient, shortest path length,
value of modularity, nodal centrality and degree. Simultaneously, voxel-level analysis was conducted and the results showed that compared with APOE 4-T- group, the other three groups were found increased PHF-Tau distribution in some brain regions. For APOE 4+T+ group, positive correlation was found between the value of PHF-Tau distribution in altered regions and Functional Assessment Questionnaire (FAQ) score. Our results indicated that the effects of APOE 4 and abnormal CSF T-Tau may induce abnormalities of PHF-Tau protein and APOE 4 has a greater impact on PHF-Tau than abnormal CSF T-Tau. Our results may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI patients.
Evaluates the framing concept and its utility for communication research in conflict resolution. Defines frames as communicative, rather than cognitive, constructions. Provides a theoretical ...framework for explicating the communicative framing process and its potential issues in conflict. Explores the effects of particular framing patterns on actual conflict intervention. Finds a positive relationship between frame convergence and frequency of agreements. (PA)
Recognition of stop codons depends on the release factors RF1 and RF2 instead of tRNA. Yet the following basic questions have gone unanswered for more than 40 years: (i) Are the stop codons ...recognized directly by the release factors or indirectly through the ribosome? (ii) Is peptidyl‐tRNA hydrolysis catalyzed by the release factors or by the ribosome? (iii) How is stop codon recognition coupled to peptidyl‐tRNA hydrolysis with an error frequency as small as ~10−5in the absence of GTP‐dependent proofreading? We have solved the structures of ribosome termination complexes containing release factors RF1 (bound with UAG or UAA) and RF2 (bound with UAA) at resolutions between 3.0 and 3.2 Å. Together with the structure of an RF2 complex bound with a UGA codon from the Ramakrishnan laboratory, the structures of all of the four possible termination complexes are now known. We can now propose a mechanism for translation termination that provides answers to the three key questions.
Children with Autism Spectrum Disorder (ASD) are faced with many challenging behaviors that could impede their learning. One commonly reported problem behavior is noncompliance, which is often ...defined as a delay in response (latency), decrease in rate of responding (fluency), or failure to complete a task. This failure to comply in an appropriate amount of time has been noted as a primary factor for a child's exclusion from the community, poor social interactions, as well as limited instructional opportunities. This study examined the response latency, task completion, and accuracy in responding of an adolescent with ASD utilizing a changing criterion design. Reinforcement was provided only when the student answered a question or complied with an instruction accurately and within the preset criterion which was successively and gradually reduced. Results indicated that response latency decreased from an average of 4.6 seconds down to an average of 2.4 seconds and that there was a significant decrease in no responses. Findings show that differential reinforcement of short latencies resulted in a decrease in response latency and an increase in compliance. Thus, the study yielded positive results and paved the way for future research.
The advent of imatinib, and subsequently, other tyrosine kinase inhibitors (TKIs) has relegated allogeneic stem cell transplantation (SCT) to second-or third-line therapy for chronic phase-chronic ...myeloid leukemia (CML). A significant shortcoming of TKIs in the large majority of good-responder patients is the persistent detection of BCR-ABL transcripts despite achievement of complete cytogenetic response (CCyR) or major molecular response (greater than 3-log reduction of BCR-ABL levels below a standardized baseline in minimal residual disease (MRD) measurements from total mononuclear cells). The presence of this MRD, and the demonstration that primitive CD34+ cells from patients in CCyR still harbor BCR-ABL (Bhatia, et al, Blood 2003) strengthens the opinion that TKIs do not eradicate all CML cells. Conversely, SCT has apparently cured some CML patients with more than 20 years follow-up. Of note, MRD is also quite frequently found in CML patients more than 5 years post-SCT, and donor lymphocyte infusions (DLI) are usually given to patients who satisfy criteria for molecular relapse. We compared the level of BCR-ABL transcripts in primitive hematopoietic cells from patients who were treated with T-depleted SCT with scheduled T-cell addback from D+45 to D+100 post-SCT (n=34) with levels in those taking TKIs (n=4). CD34+ progenitor cells were isolated from leukapheresis collections at D+120 post-SCT (n=13), peripheral blood from D+60 – 66 months post-SCT (n=19), bone marrow aspirates in patients on long-term follow-up (4–10 years) post-SCT (n=8) or 15 – 18 months post-TKI treatment alone (n=4); serial post-SCT samples were available in 6 patients. Using fluorescence activated cell sorting, hematopoietic stem cells (HSC, CD34+CD38-Lin-CD90+), common myeloid progenitors (CMP, CD34+CD38+Lin-IL3Rα+CD45RA-) and granulocyte-macrophage progenitors (GMP, CD34+CD38+Lin-IL3Rα+CD45RA+) were collected. BCR-ABL expression in primitive CD34+ subpopulations and total leukocytes from peripheral blood (PB) was measured using real-time quantitative polymerase chain reaction, with the sensitivity to detect one BCR-ABL-positive cell in 106 normal cells. A median of 112 x 106 mononuclear cells (range 16 – 582 x 106) were available per patient sample, with a median of 3 x 106 CD34+ cells (range 1 – 90 x 106) sorted. There was no difference between the number of HSC, CMP or GMP CD34+ cells collected between MRD negative or MRD positive-post-SCT patients, or TKI-treated patients. All patients with negative MRD in PB (n=12 post-SCT, n=1 post-TKI) did not have detectable BCR-ABL transcripts in primitive CD34+ subpopulations. Furthermore, in PB MRD-positive patients, 3/21 (14%) post-SCT and 2/2 (100%) post-TKI did not have detectable BCR-ABL transcripts in HSC, CMP or GMP populations. 18/21 (86%) PB MRD-positive patients who were post-SCT had detectable BCR-ABL transcripts in at least one primitive CD34+ subpopulation. A rise in BCR-ABL levels in GMP populations tended to herald impending relapse. In post-SCT patients on long-term follow-up with persistent PB MRD positivity not fulfilling criteria for molecular relapse, the highest BCR-ABL levels were in HSC populations. In comparable patients with a major molecular response, post-SCT patients appeared to harbor a greater amount of residual leukemia cells in CD34+ subpopulations than TKI-treated patients. Our observations suggest that although SCT is a curative treatment for CML, the graft-versus-leukemia effect may eliminate only more mature leukemic CD34+ subpopulations in some patients who have enduring positive MRD post-SCT, with persistence of the most primitive leukemic HSCs, which are presumably constrained in patients who do not fulfill criteria for relapse. Conversely, TKI appears to reduce the number of BCR-ABL-positive primitive CD34+ subpopulations, especially GMPs and CMPs, more efficiently. Our data support TKI-treatment as an adjunct to DLI to treat CML relapse post-SCT, and concurrent vaccination strategies which are able to target surface proteins on HSC to eradicate disease.
Despite receiving a cancer diagnosis, many patients continue to use tobacco during treatment, negatively affecting their outcomes. We hypothesized that limited tobacco cessation (TC) discussion among ...patients and providers was partially the result of providers' lack of awareness of current TC resources available.
We surveyed the head and neck oncology providers (HNOPs) at Dana-Farber Cancer Institute to evaluate their awareness of existing TC resources within the community and performed a 6-month medical record review of active tobacco users (ATUs) to evaluate the frequency of documented TC discussions in clinic. We educated the HNOPs about available TC resources, developed a TC resource teaching sheet, placed a provider alert page in examination rooms as a reminder of TC discussions, and built a TC discussion template to ease documentation. Four weeks postintervention, we resurveyed providers and again performed medical record reviews of ATUs.
Preintervention, 13% of HNOPs were aware of TC resources available, and TC discussion documentation was 28%. Postintervention, 100% of HNOPs became aware of the TC resources available, and documentations increased to 56% at 5 months. Identification of ATUs increased from six to 13 per month to 17 to 33 per month post intervention. Eighty-eight percent of HNOPs felt the intervention prompted TC discussions in clinic with their ATUs.
The limited number of TC discussions among patients and providers was at least partially the result of unawareness of TC resources available within the community. Educating HNOPs and alerting them to ATUs at their clinic visits successfully prompted TC discussions in clinic.
We experimentally demonstrate a source of nearly pure single photons in arbitrary temporal shapes heralded from a parametric down-conversion (PDC) source at telecom wavelengths. The technology is ...enabled by the tailored dispersion of in-house fabricated waveguides with shaped pump pulses to directly generate the PDC photons in on-demand temporal shapes. We generate PDC photons in Hermite-Gauss and frequency-binned modes and confirm a minimum purity of 0.81, even for complex temporal shapes.
PDF
