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The insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis. We discovered a set of genera in early-life associated with CTS and defined a 16-genus signature that accurately predicted CTS, the majority of which were correlated with human CRCs. We identified 547 SNPs associated with abundances of these genera. Mediation analysis revealed GM as mediators partially exerting the effect of SNP UNC3869242 within Duox2 on CTS. Intestine cell-specific depletion of Duox2 altered GM composition and contribution of Duox2 depletion to CTS was significantly influenced by GM. Our findings provide potential novel targets for personalized CRC prevention and treatment.

31 Dec 2024·Geoenergy

Field tests of geological storage of CO ₂ at the Otway International Test Centre, Australia: trapping and monitoring the migrating plumes

Author: Dodds, Kevin ; Sidenko, Evgenii ; Wood, Todd ; Popik, Sofya ; Glubokovskikh, Stanislav ; Jackson, Samuel J. ; Green, Chris ; Wilkins, Andrew ; Tertyshnikov, Konstantin ; Gurevich, Boris ; Isaenkov, Roman ; Dance, Tess ; Yavuz, Sinem ; Yurikov, Alexey ; Barraclough, Paul ; Paterson, Lincoln ; Shulakova, Valeriya ; Correa, Julia ; Singh, Rajindar ; Popik, Dmitry ; Freifeld, Barry ; Raab, Matthias ; Gunning, James ; Shashkin, Pavel ; Jenkins, Charles ; Zhang, Yingqi ; Pevzner, Roman ; Watson, Max ; Ennis-King, Jonathan

The capture and geological storage of CO 2 is essential for net zero. Large volumes of secure subsurface storage will be required, much in unexplored saline aquifers. At the Otway International Test Centre we have executed a series of storage tests, including geophysical surveys, geochemical and petrophysical characterization, drilling and instrumenting six deep wells and conducting two intensively monitored injections each of 15 Kt CO 2 . We summarize the execution and outcomes to draw out the implications for larger-scale storage and for migration trapping of CO 2 plumes. Immobilization of most of the plume is essential for long-term safety. Suitable saline aquifers should have sealing caprocks but need not have structural traps. Buoyant CO 2 could move kilometres beneath the seal, with immobilization occurring by capillary forces and dissolution. Predicting and monitoring plume behaviour with practical methods integrated with risk management will be necessary. We characterized and monitored migration trapping, demonstrated plume immobilization, and tested monitoring methods tailored to large saline aquifers. We developed pressure tomography and continuous seismic monitoring; these provide less detailed information than conventional methods but can be targeted at risks. Passive methods, such as the seismic response to earthquakes, can also act as sentinels for specific events. These methods can bridge the ‘monitoring gap’ between detailed but infrequent methods and more frequent but simpler methods and the results will enable better trade-offs between cost, complexity and risk for a technology crucial for controlling CO 2 levels in the atmosphere. Supplementary material : Detailed descriptions of unpublished modelling are available at https://doi.org/10.6084/m9.figshare.c.7148197

01 Dec 2024·Neurobiology of Aging

Modeling the progression of neuropsychiatric symptoms in Alzheimer’s disease with PET-based Braak staging

Article

Author: Macedo, Arthur C. ; Bellaver, Bruna ; Lussier, Firoza Z. ; Therriault, Joseph ; Aumont, Étienne ; Zimmer, Eduardo R. ; Chamoun, Mira ; Stevenson, Jenna ; Ismail, Zahinoor ; Pascoal, Tharick A. ; Rosa-Neto, Pedro ; Ferrari-Souza, João Pedro ; Fernandez-Arias, Jaime ; Vermeiren, Marie ; Socualaya, Kely Quispialaya ; Gauthier, Serge ; Rahmouni, Nesrine ; Vitali, Paolo ; Hosseini, Seyyed Ali ; Macedo, Arthur C ; Pascoal, Tharick A ; Ferreira, Pâmela C.L. ; Lussier, Firoza Z ; Ferreira, Pâmela C L ; Wang, Yi-Ting ; Leffa, Douglas Teixeira ; Servaes, Stijn ; Zimmer, Eduardo R ; Bezgin, Gleb ; Tissot, Cécile ; Ng, Kok Pin

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum. Participants were assigned a Braak stage at baseline and followed for 1.97 (s.d. 0.62) years. NPS were investigated using the Mild Behavioral Impairment Checklist (MBI-C) and the Neuropsychiatric Inventory Questionnaire severity (NPI-Q-S) and distress (NPI-Q-D) scales. Multiple linear regressions (MLR) assessed the association of Braak stages with baseline NPS and the annual change in NPS scores. At baseline, stages I-II, III-IV, and V-VI were associated with higher MBI-C, NPI-Q-S, and NPI-Q-D scores. Stages V-VI were associated with a significant annual increase in MBI-C scores. These findings suggest that tau accumulation may manifest clinically with an increase in NPS, which seems to be an early event in AD pathophysiology. Moreover, PET-based Braak staging appears to be a good predictor of NPS severity progression.

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Pipeline Snapshot as of 07 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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