3D Collaboration Spaces for Enterprise Work: A Thought Leaders’ Dialogue and Conference Summary Paper UPENN Virtual Organizational Dynamics Design Laboratory

On February 8th, 6pm to 10pm Eastern, presenters from CCL’s Innovation Group, IBM’s Center for Advanced Learning (CAL), Stanford’s Project Based Learning Lab (PBL) and Proton Media/PPD 3D joined UPenn’s Virtual OD Design Lab for our first fully immersive 3D Peer learning Conference, hosted and supported by Proton Media in ProtoSphere. In this exciting event, the Lab team engaged thought leaders in real time dialogue about their state-of- the-art cases covering advanced uses of 3D immersive technologies for leadership and organization development, collaboration and global enterprise training

Genetic Variability for Yield, Physiological and Quality Traits in Novel Super-Early Pigeonpea (Cajanus cajan (L.) Millsp.)

Super-early pigeonpea are novel genotypes that are reported to be photoperiod insensitive making it possible to grow it in non-traditional regions. Estimation of genetic parameters would be useful in developing appropriate selection and breeding strategies. A study was conducted to evaluate 37 super-early pigeonpea genotypes to access the magnitude of variability and to study heritable component of variation present in the yield, physiological and quality traits. The results revealed that traits leaf area duration between 60 DAS & maturity followed by leaf area & leaf area index at maturity, net assimilation between 60 DAS & maturity, leaf area index & leaf area at 60 DAS, leaf area duration between 60 DAS & maturity and plant height had high had higher PCV and GCV values. In general, phenotypic coefficients of variation (PCV) estimates were higher than genotypic coefficients of variation (GCV) estimates for all the characters under study, but the difference was relatively small indicating that these characters were less influenced by the environment and selection to improve those traits might be effective. High heritability combined with high genetic advance as a percent of mean was noted for all the traits except protein content conveying the governance of additive gene on trait expression. Anticipating these traits as selection index reaps competent improvement in yield, physiological and quality traits in early maturing pigeonpea

Genetic Divergence for Yield, Physiological and Quality Traits in Super-Early Pigeon pea (Cajanus cajan. (l.) Millsp.)

The present investigation aimed to study genetic divergence and clustering pattern of 37super-early pigeon pea genotypes. Analysis of variance and hierarchical cluster analysis of tocher’s method revealed significant differences among the genotypes for all the traits under study. Based on genetic distance (D2 value), the 37 genotypes were grouped into 9 distinctive clusters, of which cluster I and II formed the largest clusters with 10 genotypes in each. Among all the characters understudy, leaf area index(LAI) at 60 DAS contributed more to the divergence followed by leaf area (17.02) and leaf area index (12.71) at maturity. Based on the average inter-cluster distance, the cluster III and IX (66.93) tailed by cluster III and VIII (64.86) and cluster VI and VIII (64.06) showed higher inter-cluster distance depicting the wider divergence. Trait-wise selection of diverse parents from the above clusters aids in exploitation of heterosis in superearly pigeon pea

Cortical β-amyloid burden, neuropsychiatric symptoms, and cognitive status: the Mayo Clinic Study of Aging

Abstract Neuropsychiatric symptoms (NPS) are a risk factor for cognitive impairment and are associated with cortical β-amyloid (Aβ) deposition. We conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging to examine the frequency of NPS among cognitively unimpaired (CU) and mild cognitive impairment (MCI) participants who either have normal (A−) or abnormal (A+) Aβ deposition. We also investigated whether combined presence of MCI and amyloid positivity (MCI/A+) is associated with greater odds of having NPS as compared to CU/A− (defined as reference group). Participants were 1627 CU and MCI individuals aged ≥ 50 years (54% males; median age 73 years). All participants underwent NPS assessment (Neuropsychiatric Inventory Questionnaire (NPI-Q); Beck Depression Inventory II (BDI-II); Beck Anxiety Inventory (BAI)) and 11C-PiB-PET. Participants with an SUVR > 1.42 were classified as A+. We conducted multivariable logistic regression analyses adjusted for age, sex, education, and APOE ε4 genotype status. The sample included 997 CU/A−, 446 CU/A+, 78 MCI/A−, and 106 MCI/A+ persons. For most NPS, the highest frequency of NPS was found in MCI/A+ and the lowest in CU/A−. The odds ratios of having NPS, depression (BDI ≥ 13), or anxiety (BAI ≥ 8, ≥ 10) were consistently highest for MCI/A+ participants. In conclusion, MCI with Aβ burden of the brain is associated with an increased risk of having NPS as compared to MCI without Aβ burden. This implies that the underlying Alzheimer’s disease biology (i.e., cerebral Aβ amyloidosis) may drive both cognitive and psychiatric symptoms

Unbiased Proteomic Approach Identifies Unique and Coincidental Plasma Biomarkers in Repetitive mTBI and AD Pathogenesis

The relationship between repetitive mild traumatic brain injury (r-mTBI) and Alzheimer’s disease (AD) is well-recognized. However, the precise nature of how r-mTBI leads to or precipitates AD pathogenesis is currently not understood. Plasma biomarkers potentially provide non-invasive tools for detecting neurological changes in the brain, and can reveal overlaps between long-term consequences of r-mTBI and AD. In this study we address this by generating time-dependent molecular profiles of response to r-mTBI and AD pathogenesis in mouse models using unbiased proteomic analyses. To model AD, we used the well-validated hTau and PSAPP(APP/PS1) mouse models that develop age-related tau and amyloid pathological features, respectively, and our well-established model of r-mTBI in C57BL/6 mice. Plasma were collected at different ages (3, 9, and 15 months-old for hTau and PSAPP mice), encompassing pre-, peri- and post-“onset” of the cognitive and neuropathological phenotypes, or at different timepoints after r-mTBI (24 h, 3, 6, 9, and 12 months post-injury). Liquid chromatography/mass spectrometry (LC-MS) approaches coupled with Tandem Mass Tag labeling technology were applied to develop molecular profiles of protein species that were significantly differentially expressed as a consequence of mTBI or AD. Mixed model ANOVA after Benjamini–Hochberg correction, and a stringent cut-off identified 31 proteins significantly changing in r-mTBI groups over time and, when compared with changes over time in sham mice, 13 of these were unique to the injured mice. The canonical pathways predicted to be modulated by these changes were LXR/RXR activation, production of nitric oxide and reactive oxygen species and complement systems. We identified 18 proteins significantly changing in PSAPP mice and 19 proteins in hTau mice compared to their wild-type littermates with aging. Six proteins were found to be significantly regulated in all three models, i.e., r-mTBI, hTau, and PSAPP mice compared to their controls. The top canonical pathways coincidently changing in all three models were LXR/RXR activation, and production of nitric oxide and reactive oxygen species. This work suggests potential biomarkers for TBI and AD pathogenesis and for the overlap between these two, and warrant targeted investigation in human populations. Data are available via ProteomeXchange with identifier PXD010664

Defining imaging biomarker cut points for brain aging and Alzheimer's disease

AbstractIntroductionOur goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness.MethodsWe examined five methods for determining cut points.ResultsThe reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal.DiscussionIn the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method

Proximal Sessile Serrated Adenomas Are More Prevalent in Caucasians, and Gastroenterologists Are Better Than Nongastroenterologists at Their Detection

Background and Aim. Proximal sessile serrated adenomas (PSSA) leading to colorectal cancer (CRC) represent an alternate pathway for CRC development. In this study, we aim to determine the prevalence of PSSAs and the impact of patient, colonoscopy, and endoscopist-related factors on PSSA detection. Methods. Patients ≥ 50 years of age undergoing a screening colonoscopy between 2012 and 2014 were included. Detection rates based on patient gender, race, colonoscopy timing, fellow participation, bowel preparation quality, and specialty of the endoscopist were calculated. t-tests were used to compare detection rates and a multivariate-adjusted analysis was performed. Results. 140 PSSAs were detected from 4151 colonoscopies, with a prevalence of 3.4%. Detection rate was higher in Caucasians compared to African-Americans (AA) (3.7 ± 4.1 versus 0.96 ± 3.5; p<0.001). Gastroenterologists detected more PSSAs compared to nongastroenterologists (3.9 ± 3.5 versus 2.2 ± 3.0; p=0.028). These findings were still significant after adjusted multivariate analysis. The rest of the factors did not make significant difference in PSSA detection rate. Conclusions. PSSAs are more prevalent in Caucasians compared to AAs. Racial difference in prevalence of PSSAs is intriguing and warrants further investigation. Gastroenterologists have a significantly higher PSSADR compared to nongastroenterologists. Educational measures should be implemented in nongastroenterologists to improve their PSSA detection rates

Molecular Pathobiology of the Cerebrovasculature in Aging and in Alzheimers Disease Cases With Cerebral Amyloid Angiopathy

Cerebrovascular dysfunction and cerebral amyloid angiopathy (CAA) are hallmark features of Alzheimer's disease (AD). Molecular damage to cerebrovessels in AD may result in alterations in vascular clearance mechanisms leading to amyloid deposition around blood vessels and diminished neurovascular-coupling. The sequelae of molecular events leading to these early pathogenic changes remains elusive. To address this, we conducted a comprehensive in-depth molecular characterization of the proteomic changes in enriched cerebrovessel fractions isolated from the inferior frontal gyrus of autopsy AD cases with low (85.5 ± 2.9 yrs) vs. high (81 ± 4.4 yrs) CAA score, aged-matched control (87.4 ± 1.5 yrs) and young healthy control (47 ± 3.3 yrs) cases. We employed a 10-plex tandem isobaric mass tag approach in combination with our ultra-high pressure liquid chromatography MS/MS (Q-Exactive) method. Enriched cerebrovascular fractions showed very high expression levels of proteins specific to endothelial cells, mural cells (pericytes and smooth muscle cells), and astrocytes. We observed 150 significantly regulated proteins in young vs. aged control cerebrovessels. The top pathways significantly modulated with aging included chemokine, reelin, HIF1α and synaptogenesis signaling pathways. There were 213 proteins significantly regulated in aged-matched control vs. high CAA cerebrovessels. The top three pathways significantly altered from this comparison were oxidative phosphorylation, Sirtuin signaling pathway and TCA cycle II. Comparison between low vs. high CAA cerebrovessels identified 84 significantly regulated proteins. Top three pathways significantly altered between low vs. high CAA cerebrovessels included TCA Cycle II, Oxidative phosphorylation and mitochondrial dysfunction. Notably, high CAA cases included more advanced AD pathology thus cerebrovascular effects may be driven by the severity of amyloid and Tangle pathology. These descriptive proteomic changes provide novel insights to explain the age-related and AD-related cerebrovascular changes contributing to AD pathogenesis. Particularly, disturbances in energy bioenergetics and mitochondrial biology rank among the top AD pathways altered in cerebrovessels. Targeting these failed mechanisms in endothelia and mural cells may provide novel disease modifying targets for developing therapeutic strategies against cerebrovascular deterioration and promoting cerebral perfusion in AD. Our future work will focus on interrogating and validating these novel targets and pathways and their functional significance