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The increasing incidence of hepatitis C virus (HCV) infections underscores the need for an effective vaccine. Successful vaccines to other viruses generally depend on a long-lasting humoral response. However, data on the half-life of HCV-specific responses are lacking. Here we study archived sera and mononuclear cells that were prospectively collected up to 18 years after cure of chronic HCV infection to determine the role of HCV antigen in maintaining neutralizing antibody and B cell responses. We show that HCV-neutralizing activity decreases rapidly in potency and breadth after curative treatment. In contrast, HCV-specific memory B cells persist, and display a restored resting phenotype, normalized chemokine receptor expression and preserved ability to differentiate into antibody-secreting cells. The short half-life of HCV-neutralizing activity is consistent with a lack of long-lived plasma cells. The persistence of HCV-specific memory B cells and the reduced inflammation after cure provide an opportunity for vaccination to induce protective immunity against re-infection. Long-term dynamics of the humoral response to HCV in cured individuals aren’t well understood. Here, Nishio et al. show that virus-neutralizing antibody levels decrease in potency and breadth after cure of chronic hepatitis C, while HCV-specific memory B cells persist.

The complexity of intracellular signalling requires both a diversity of molecular players and the sequestration of activity to unique compartments within the cell. Recent findings on the role of liquid–liquid phase separation provide a distinct mechanism for the spatial segregation of proteins to regulate signalling pathway crosstalk. Here, we discover that DACT1 is induced by TGFβ and forms protein condensates in the cytoplasm to repress Wnt signalling. These condensates do not localize to any known organelles but, rather, exist as phase-separated proteinaceous cytoplasmic bodies. The deletion of intrinsically disordered domains within the DACT1 protein eliminates its ability to both form protein condensates and suppress Wnt signalling. Isolation and mass spectrometry analysis of these particles revealed a complex of protein machinery that sequesters casein kinase 2—a Wnt pathway activator. We further demonstrate that DACT1 condensates are maintained in vivo and that DACT1 is critical to breast and prostate cancer bone metastasis. Esposito et al. show that TGF-β-induced DACT1 forms biomolecular condensates that sequester CK2 to repress Wnt signalling and modulate bone metastasis in cancer.

The purpose of this study is to report the utility of a universal depression screening in a student-run free clinic (SRFC) to improve bridging to psychiatric care. Patients (n = 224) seen by an SRFC between April 2017 and November 2022 were screened for depression in the patient’s primary language using the standardized Patient Health Questionnaire (PHQ-9). A PHQ-9 score greater or equal to 5 prompted psychiatry referral. Retrospective chart review was conducted to determine clinical characteristics and length of psychiatry follow-up. Out of 224 patients screened, 77 patients had positive depression screens and were referred to the SRFC’s adjacent psychiatry clinic. Of these 77 patients, 56 patients (73%) were female, the average age was 43.7 (SD = 14.5), and the mean PHQ score was 10 (SD = 5.13). Thirty-seven patients (48%) accepted referral, while 40 (52%) declined or were lost to follow-up. There were no statistical differences in age or number of medical comorbidities between the two groups. Patients who accepted referrals were more likely to be female, as well as to have psychiatric histories, higher PHQ-9 scores, and a history of trauma. Reasons for declining and being lost to follow-up included transition to insurance, geographic relocation and deferral due to hesitancy in seeking psychiatric care. Implementation of a standardized depression screening reveals a significant rate of depressive symptoms among an urban uninsured primary care population. Universal screening may serve as a tool to improve the delivery of psychiatric care to underserved patients.

The complexity of intracellular signalling requires both a diversity of molecular players and the sequestration of activity to unique compartments within the cell. Recent findings on the role of liquid-liquid phase separation provide a distinct mechanism for the spatial segregation of proteins to regulate signalling pathway crosstalk. Here, we discover that DACT1 is induced by TGF[beta] and forms protein condensates in the cytoplasm to repress Wnt signalling. These condensates do not localize to any known organelles but, rather, exist as phase-separated proteinaceous cytoplasmic bodies. The deletion of intrinsically disordered domains within the DACT1 protein eliminates its ability to both form protein condensates and suppress Wnt signalling. Isolation and mass spectrometry analysis of these particles revealed a complex of protein machinery that sequesters casein kinase 2–a Wnt pathway activator. We further demonstrate that DACT1 condensates are maintained in vivo and that DACT1 is critical to breast and prostate cancer bone metastasis.

  The movie is told in a series of flashbacks as Mia recounts episodes in her life that show the beauty of her relationships with loved ones. The laid-back and happy ambiance of Mia's family home is comforting. The scenes with Adam (though too tacky for my tastes) are sweet. Mia chronicles her life's joy and conflicts, showing how they might influence her decision to die or fight to stay alive.

In Lois Lowry's popular 1993 children's novel, The Giver, a 12-year-old boy named Jonas lives in a world of \"sameness\" with no pain, suffering, love or deeper emotions. Although his diction is simple, his story is dynamic. With language targeted to younger readers, Lowry artistically weaves a tale that reveals a deeper truth about idyllic \"utopias\" and the flaw behind the concept of \"perfection.\" Similar to Ray Bradbury's Fahrenheit 451 and Aldous Huxley's Brave New World, The Giver offers an insightful introduction into the realm of dystopian literature.

  Award: Students admitted through National College Match receive a full-ride scholarship to their \"matched\" Questbridge partner college. Finalists who are not matched receive fee waivers when applying to partner schools and have the option of forwarding their Questbridge application either as a supplement to or in lieu of their common application. Princeton University, Stanford University, The University of Chicago and Pomona College are just a few of the partner schools. Eligibility requirements: Demonstrated need; U.S. citizen or permanent resident in Colorado, New Mexico, Utah or Wyoming Eligibility requirements: A GED diploma or minimum GPA of 3.3; status as U.S. citizen, U.S permanent resident or foreign national. Must be African American, American Indian/Alaska Native, Asian Pacific Islander American or Hispanic.