Parental communicative input as a protective factor in Bangladeshi families living in poverty: A multi-dimensional perspective.

Studies from high-income populations have shown that stimulating, supportive communicative input from parents promote children's cognitive and language development. However, fewer studies have identified specific features of input supporting the healthy development of children growing up in low- or middle-income countries. The current study proposes and tests a multi-dimensional framework for understanding whether and how caregiver communicative input mediates the associations between socio-economic conditions and early development. We also examine how caregiver conceptual scaffolding and autonomy support uniquely and synergistically explain variation in child outcomes. Participants were 71 Bangladeshi families with five-year-olds who were exposed to a range of biological and psychosocial hazards from birth. Caregiver-child interactions during snack sharing and semi-structured play were coded for caregiver conceptual scaffolding, autonomy support, and child engagement. Findings indicate that the two dimensions of input were correlated, suggesting that caregivers who provided richer conceptual scaffolds were simultaneously more supportive of children's autonomy. Notably, conceptual scaffolding and autonomy support each mediated associations between maternal education and child verbal intelligence quotient (IQ) scores. Further, caregivers who supported greater autonomy in their children had children who participated in conversations more actively, and these children in turn had higher performance IQ scores. When considered simultaneously, conceptual scaffolding was associated with verbal IQ over and above autonomy support, whereas autonomy support related to child engagement, controlling for conceptual scaffolding. These findings shed new light on how environmental factors may support early development, contributing to the design of family-centered, culturally authentic interventions. A video abstract of this article can be viewed at https://youtu.be/9v_8sIv7ako RESEARCH HIGHLIGHTS: Studies from high-income countries have identified factors mitigating the impacts of socio-economic risks on development. Such research is scarce in low- and middle-income countries. The present study conceptualized and evaluated caregiver communicative input in Bangladeshi families along two interrelated yet distinct dimensions: conceptual scaffolding and autonomy support. Conceptual scaffolding and autonomy support individually mediated associations between maternal education and child verbal IQ, shedding light on protective factors in families living in poverty. Parents providing richer conceptual scaffolds were simultaneously more supportive of children's autonomy. However, the two dimensions each related to cognition and language through unique pathways.

Tumor microtubes connect pancreatic cancer cells in an Arp2/3 complex-dependent manner.

Actin-based tubular connections between cells have been observed in many cell types. Termed "tunneling nanotubes (TNTs)," "membrane nanotubes," "tumor microtubes (TMTs)," or "cytonemes," these protrusions interconnect cells in dynamic networks. Structural features in these protrusions vary between cellular systems, including tubule diameter and the presence of microtubules. We find tubular protrusions, which we classify as TMTs, in a pancreatic cancer cell line, Dartmouth-Hitchcock Pancreatic Cancer (DHPC)-018. TMTs are present in DHPC-018-derived tumors in mice, as well as in a mouse model of pancreatic cancer and a subset of primary human tumors. DHPC-018 TMTs have heterogeneous diameter (0.39-5.85 µm, median 1.92 µm) and contain actin filaments, microtubules, and cytokeratin 19-based intermediate filaments. TMTs do not allow intercellular transfer of cytoplasmic GFP. Actin filaments are cortical within the protrusion, as opposed to TNTs, in which filaments run down the center. TMTs are dynamic in length, but are long lived (median >60 min). Inhibition of actin polymerization, but not microtubules, results in TMT loss. Extracellular calcium is necessary for TMT maintenance. A second class of tubular protrusion, which we term cell-substrate protrusion, has similar width range and cytoskeletal features but makes contact with the substratum as opposed to another cell. Similar to previous work on TNTs, we find two assembly mechanisms for TMTs, which we term "pull-away" and "search-and-capture." Inhibition of Arp2/3 complex inhibits TMT assembly by both mechanisms. This work demonstrates that the actin architecture of TMTs in pancreatic cancer cells is fundamentally different from that of TNTs and demonstrates the role of Arp2/3 complex in TMT assembly.

Cyfip1 Regulates SynGAP1 at Hippocampal Synapses.

In humans, copy number variations in CYFIP1 appear to have sweeping physiological and structural consequences in the brain, either producing or altering the severity of intellectual disability, autism, and schizophrenia. Independently, SynGAP1 haploinsufficiency produces intellectual disability and, frequently, autism. Cyfip1 inhibits protein translation and promotes actin polymerization, and SynGAP1 is a synaptically localized Ras/Rap GAP. While these proteins are clearly distinct, studies investigating their functions in mice have shown that each regulates the maturation of synapses in the hippocampus and haploinsufficiency for either produces an exaggerated form of mGluR-dependent long-term depression, suggesting that some signaling pathways converge. In this study, we examined how Cyfip1 haploinsufficiency impacts SynGAP1 levels and localization, as well as potential sites for mechanistic interaction in mouse hippocampus. The data show that synaptic, but not total, levels of SynGAP1 in Cyfip1 +/- mice were abnormally low during early postnatal development and in adults. This may be in response to a shift in the balance of kinases that activate SynGAP1 as levels of Cdk5 were reduced and those of activated CaMKII were maintained in Cyfip1 +/- mice compared to wild-type mice. Alternatively, this could reflect altered actin dynamics as Rac1 activity in Cyfip1 +/- hippocampus was boosted significantly compared to wild-type mice, and levels of synaptic F-actin were generally enhanced due in part to an increase in the activity of the WAVE regulatory complex. Decreased synaptic SynGAP1 coupled with a CaMKII-mediated bias toward Rap1 inactivation at synapses is also consistent with increased levels of synaptic GluA2, increased AMPA receptor-mediated responses to stimulation, and increased levels of synaptic mGluR1/5 compared to wild-type mice. Collectively, our data suggest that Cyfip1 regulates SynGAP1 and the two proteins work coordinately at synapses to appropriately direct actin polymerization and GAP activity.

Human Gut Microbiota: Toward an Ecology of Disease.

Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.

Modeling ring/chain equilibrium in nanoconfined sulfur.

The effect of nanoconfinement on the thermodynamics of free radical polymerization of sulfur is examined. We extend Tobolsky and Eisenberg's model of bulk sulfur polymerization to nanopores accounting for the confinement entropy of the chains and ring using scaling reported in literature. The model quantitatively captures literature data from Yannopoulos and co-workers for the extent of polymerization versus temperature for bulk sulfur polymerization and for polymerization in 20, 7.5, and 2.5 nm diameter Gelsil nanopores, assuming that the change of entropy of nanoconfined chains scales with molecular size to the second power and with nanopore diameter to either the -3.0 or -3.8 power, the former of which fits slightly better. The scaling, which is valid for strong confinement in spherical pores, predicts that the propagation equilibrium constant will depend on both nanopore size and chain length, such that the average chain length decreases significantly upon confinement.