Elliottevans9539

Purpose The nature of the relationship between memory and sentence comprehension in school-age children with developmental language disorder (DLD) has been unclear. We present a novel perspective that highlights the relational influences of fluid intelligence, controlled attention, working memory (WM), and long-term memory (LTM) on sentence comprehension in children with and without DLD. This perspective has new and important implications for theory, assessment, and intervention. Method We review a large-scale study of children with and without DLD that focused on the connections between cognition, memory, and sentence comprehension. We also summarize a new model of these relationships. Results Our new model suggests that WM serves as a conduit through which syntactic knowledge in LTM, controlled attention, and general pattern recognition indirectly influence sentence comprehension in both children with DLD and typically developing children. For typically developing children, language-based LTM and fluid intelligence indirectly influence sentence comprehension. ARRY-575 manufacturer However, for children with DLD, controlled attention plays a larger indirect role. Conclusions WM plays a key role in children's ability to apply their syntactic knowledge when comprehending canonical and noncanonical sentences. Our new model has important implications for the assessment of sentence comprehension and for the treatment of larger sentence comprehension deficits.[Figure see text].Activation of T cells leads to the formation of the immunological synapse (IS) with antigen presenting cells. This requires T cell polarization and coordination between the actomyosin and microtubule cytoskeletons. The interactions between these two cytoskeletal components during T cell activation are not well understood. Here, we elucidate the interactions between microtubules and actin at the IS with high-resolution fluorescence microscopy. We show that microtubule growth dynamics in the peripheral actin-rich region are distinct from those in the central actin-free region. We further demonstrate that these differences arise from differential involvement of Arp2/3- and formin-nucleated actin structures. Formin inhibition results in a moderate decrease in microtubule growth rates, which is amplified in the presence of integrin engagement. In contrast, Arp2/3 inhibition leads to an increase in microtubule growth rates. We find that microtubule filaments are more deformed and exhibit greater shape fluctuations in the periphery of the IS compared to the center. Using small molecule inhibitors, we show that actin dynamics and actomyosin contractility play key roles in defining microtubule deformations and shape fluctuations. Our results indicate a mechanical coupling between the actomyosin and microtubule systems during T cell activation, whereby different actin structures influence microtubule dynamics in distinct ways. [Media see text] [Media see text] [Media see text] [Media see text] [Media see text].Lipid droplets (LDs) are neutral lipid-containing organelles enclosed in a single monolayer of phospholipids. LD formation begins with the accumulation of neutral lipids within the bilayer of the endoplasmic reticulum (ER) membrane. It is not known how the sites of formation of nascent LDs in the ER membrane are determined. Here we show that multiple C2 domain-containing transmembrane proteins, MCTP1 and MCTP2, are at sites of LD formation in specialized ER subdomains. We show that the transmembrane domain (TMD) of these proteins is similar to a reticulon homology domain. Like reticulons, these proteins tubulate the ER membrane and favor highly curved regions of the ER. Our data indicate that the MCTP TMDs promote LD biogenesis, increasing LD number. MCTPs colocalize with seipin, a protein involved in LD biogenesis, but form more stable microdomains in the ER. The MCTP C2 domains bind charged lipids and regulate LD size, likely by mediating ER-LD contact sites. Together, our data indicate that MCTPs form microdomains within ER tubules that regulate LD biogenesis, size, and ER-LD contacts. Interestingly, MCTP punctae colocalized with other organelles as well, suggesting that these proteins may play a general role in linking tubular ER to organelle contact sites.After growing on surfaces, including those of medical and industrial importance, fungal biofilms self-generate internal microenvironments. We previously reported that gaseous microenvironments around founder Aspergillus nidulans cells change during biofilm formation causing microtubules to disassemble under control of the hypoxic transcription factor SrbA. Here we investigate if biofilm formation might also promote changes to structures involved in exocytosis and endocytosis. During biofilm formation, the endoplasmic reticulum (ER) remained intact but ER exit sites and the Golgi apparatus were modified as were endocytic actin patches. The biofilm-driven changes required the SrbA hypoxic transcription factor and could be triggered by nitric oxide, further implicating gaseous regulation of biofilm cellular architecture. By tracking green fluorescent protein (GFP)-Atg8 dynamics, biofilm founder cells were also observed to undergo autophagy. Most notably, biofilm cells that had undergone autophagy were triggered into further autophagy by spinning disk confocal light. Our findings indicate that fungal biofilm formation modifies the secretory and endocytic apparatus and show that biofilm cells can also undergo autophagy that is reactivated by light. The findings provide new insights into the changes occurring in fungal biofilm cell biology that potentially impact their unique characteristics, including antifungal drug resistance.

The financial toxicity of cancer care is a source of significant distress for patients with cancer. The purpose of this study is to understand factors associated with financial toxicity in three distinct care systems.

We conducted a cross-sectional survey of patients in three care systems, Stanford Cancer Institute (SCI), VA Palo Alto Health Care System (VAPAHCS), and Santa Clara Valley Medical Center (SCVMC), from October 2017 to May 2019. We assessed demographic factors, employment status, and out-of-pocket costs (OOPCs) and administered the validated COmprehensive Score for financial Toxicity tool. We calculated descriptive statistics and conducted linear regression models to analyze factors associated with financial toxicity.

Four hundred forty-four of 578 patients (77%) completed the entire COmprehensive Score for financial Toxicity tool and were included in the analysis. Most respondents at SCI were White, with annual household income (AHI) > $50,000 USD and Medicare insurance. At the VAPAHCS, most were White, with AHI ≤ $50,000 USD and insured by the Veterans Administration.