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Shaffer, C.

Publications and source records attributed to Shaffer, C..

4 recordsLinked to original sources

When attention falters: brain, breathing, and behavioral signals of lapses in interoceptive attention

Mindlbody practices like meditation and yoga involve paying attention to breathing sensations. During these practices, individuals report "interoceptive lapses," moments when attention drifts away from internal bodily sensations. While lapses in attention to the external world have been widely studied, little is known about the physiological and neural mechanisms of interoceptive lapses. Interoceptive lapses may share markers with exteroceptive lapses--such as reaction time variability and default-mode network (DMN) connectivity--but may also depend on distinct brain systems and breathing physiology. Here we examined behavioral, physiological and neural signals preceding lapses in a sample of 93 adolescents enriched for GAD and depression symptoms. Participants performed a 20-minute breath counting task in the fMRI scanner with simultaneous breath recordings. Lapses were defined as moments when counting errors occurred. The sample was split into training and validation sets to test machine learning models predicting attentional lapses. The strongest predictors were timing and variability of button responses (AUCs > 0.75). Breathing variability and breathing-behavior synchronization showed smaller but generalizable predictive value (AUCs < 0.65). Whole-brain connectivity models also predicted lapses (AUC {approx} 0.65), incorporating the DMN, dorsal and ventral attention, and somatomotor networks. Further, models that included brain connectivity marginally outperformed behavior-only models. Comparisons to previous exteroceptive findings indicate some common markers (e.g., reaction time variability) and some unique markers (e.g., selective perceptual coupling with attentional networks). Although limited by the clinical sample and lack of a control task, these results highlight brain-body markers of interoceptive attention that may inform real-time monitoring during mind-body interventions.

neuroscience↗

Generation of human induced pluripotent stem cell (hiPSC) lines from patients with extreme high and low polygenic scores for QT interval

Long QT syndrome (LQTS) is an inherited cardiac arrhythmia syndrome with congenital and drug-induced presentations and known monogenic and polygenic contributions. LQTS represents a significant clinical challenge due to its complex genetic underpinning and propensity for fatal arrhythmias. In this study, we generated induced pluripotent stem cells (iPSCs) reprogrammed from peripheral blood mononuclear cells (PBMCs) of six patients with extreme polygenic scores for short and long corrected QT intervals. iPSC lines were rigorously validated for genomic integrity through karyotyping and targeted mutation analysis specific to a lengthened or shortened QT interval. Pluripotency was confirmed by expression of key markers TRA 1-60, TRA 1-81, SOX2, OCT4, NANOG, and REX1 via quantitative PCR and immunofluorescence. Subsequent cardiac induction successfully generated cardiomyocytes that were further characterized. This patient-specific approach will enable us to better understand variable expressivity and penetrance of LQTS. Rigorously validated iPSC lines serve as a vital resource for elucidating the molecular mechanisms underlying LQTS. Our study provides a robust and clinically relevant resource to facilitate our understanding the genetic and cellular complexity of LQTS.

genetics↗

A novel widespread bacterial structure related to the flagellar type III secretion system

The flagellar type III secretion system (fT3SS) is a suite of membrane-embedded and cytoplasmic proteins responsible for building the bacterial flagellar motility machinery. Homologous proteins form the injectisome machinery bacteria use to deliver effector proteins into eukaryotic cells, and other family members have recently been reported to be involved in the formation of membrane nanotubes. Here we describe a novel, ubiquitous and evolutionarily widespread hat-shaped structure embedded in the inner membrane of bacteria, of yet-unidentified function, that is related to the fT3SS, adding to the already rich repertoire of this family of nanomachines.

microbiology↗

In situ imaging of bacterial membrane projections and associated protein complexes using electron cryo-tomography

The ability to produce membrane projections in the form of tubular membrane extensions (MEs) and membrane vesicles (MVs) is a widespread phenomenon among bacteria. Despite this, our knowledge of the ultrastructure of these extensions and their associated protein complexes remains limited. Here, we surveyed the ultrastructure and formation of MEs and MVs, and their associated protein complexes, in tens of thousands of electron cryo-tomograms of [~] 90 bacterial species that we have collected for various projects over the past 15 years (Jensen lab database), in addition to data generated in the Briegel lab. We identified MEs and MVs in 13 species and classified several major ultrastructures: 1) tubes with a uniform diameter (with or without an internal scaffold), 2) tubes with irregular diameter, 3) tubes with a vesicular dilation at their tip, 4) pearling tubes, 5) connected chains of vesicles (with or without neck-like connectors), 6) budding vesicles and nanopods. We also identified several protein complexes associated with these MEs and MVs which were distributed either randomly or exclusively at the tip. These complexes include a secretin-like structure and a novel crown-shaped structure observed primarily in vesicles from lysed cells. In total, this work helps to characterize the diversity of bacterial membrane projections and lays the groundwork for future research in this field.

molecular biology↗