Positive Depression Screening at the First Prenatal Visit in a Low-Income Primarily Black Population.

This study documents prevalence of positive depression screens at the first prenatal visit in an urban, low-income, and primarily Black population as part of initiatives to strengthen mental health services in a region with high rates of race disparities in infant and maternal mortality. We conducted a cross-sectional chart review of 500 patients, collecting demographics, medical histories, and scores of the Edinburgh Postnatal Depression Scale (EPDS), the instrument recommended for use during pregnancy by national United States organizations. Of those with a completed EPDS (n=414), 32% screened positive (n=131). These women were more likely to have smoked (p=.02), used illicit drugs (p=.01), or had depression (p<.0001), anxiety (p=.0004), bipolar disorder (p=.02), or postpartum depression for the subgroup with prior pregnancies (p<.0001). A high percentage of patients had positive EPDS screens, highlighting the need for better integration of mental health services into prenatal care for vulnerable populations.

PAK2 links cell survival to mechanotransduction and metabolism.

Too little or too much force can trigger cell death, yet factors that ensure the survival of cells remain largely unknown. Here, we demonstrate that E-cadherin responds to force by recruiting and activating p21-activated protein kinase 2 (PAK2) to allow cells to stiffen, metabolize, and survive. Interestingly, PAK2 activation and its control of the apoptotic response are specific for the amplitude of force applied. Specifically, under low amplitudes of physiological force, PAK2 is protected from proteolysis, thereby ensuring cell survival. In contrast, under higher amplitudes of physiological force, PAK2 is left unprotected and stimulates apoptosis, an effect that is prevented by cleavage-resistant forms of the protein. Finally, we demonstrate that PAK2 protection is conferred by direct binding of AMPK. Thus, PAK2 mediates the survival of cells under force. These findings reveal an unexpected paradigm for how mechanotransduction, metabolism, and cell survival are linked.

Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK.

The response of cells to mechanical force is a major determinant of cell behaviour and is an energetically costly event. How cells derive energy to resist mechanical force is unknown. Here, we show that application of force to E-cadherin stimulates liver kinase B1 (LKB1) to activate AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. LKB1 recruits AMPK to the E-cadherin mechanotransduction complex, thereby stimulating actomyosin contractility, glucose uptake and ATP production. The increase in ATP provides energy to reinforce the adhesion complex and actin cytoskeleton so that the cell can resist physiological forces. Together, these findings reveal a paradigm for how mechanotransduction and metabolism are linked and provide a framework for understanding how diseases involving contractile and metabolic disturbances arise.

Interplay between tight junctions & adherens junctions.

Cell-cell adhesions are critical for the development and maintenance of tissues. Present at sites of cell-cell contact are the adherens junctions and tight junctions. The adherens junctions mediate cell-cell adhesion via the actions of nectins and cadherins. The tight junctions regulate passage of ions and small molecules between cells and establish cell polarity. Historically, the adherens and tight junctions have been thought of as discrete complexes. However, it is now clear that a high level of interdependency exists between the two junctional complexes. The adherens junctions and tight junctions are physically linked, by the zonula occludens proteins, and linked via signaling molecules including several polarity complexes and actin cytoskeletal modifiers. This review will first describe the individual components of both the adherens and tight junctions and then discuss the coupling of the two complexes with an emphasis on the signaling links and physical interactions between the two junctional complexes.