A toolbox of nanobodies developed and validated for use as intrabodies and nanoscale immunolabels in mammalian brain neurons.

Nanobodies (nAbs) are small, minimal antibodies that have distinct attributes that make them uniquely suited for certain biomedical research, diagnostic and therapeutic applications. Prominent uses include as intracellular antibodies or intrabodies to bind and deliver cargo to specific proteins and/or subcellular sites within cells, and as nanoscale immunolabels for enhanced tissue penetration and improved spatial imaging resolution. Here, we report the generation and validation of nAbs against a set of proteins prominently expressed at specific subcellular sites in mammalian brain neurons. We describe a novel hierarchical validation pipeline to systematically evaluate nAbs isolated by phage display for effective and specific use as intrabodies and immunolabels in mammalian cells including brain neurons. These nAbs form part of a robust toolbox for targeting proteins with distinct and highly spatially-restricted subcellular localization in mammalian brain neurons, allowing for visualization and/or modulation of structure and function at those sites

The endogenous heat-stable glucocorticoid receptor stabilizing factor and the H-2 locus

It has recently been suggested that the level of the endogenous glucocorticoid receptor stabilizing factor in mouse liver is regulated by the major hisiocompatibility, H-2. complex (Katsumata et al. [1]). We have developed an asssay for the activity of the endogenous heat-stable factor in mouse liver and have assayed this factor in liver cytosols prepared from two pairs of two H-2 congenic mouse strains. Our results show that the amount of the endogenous factor is the same in all four mouse strains and that it is not regulated by the H-2 locus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23932/1/0000178.pd

Applying a participatory approach to the promotion of a culture of respect during childbirth

Disrespect and abuse (D&A) during facility-based childbirth is a topic of growing concern and attention globally. Several recent studies have sought to quantify the prevalence of D&A, however little evidence exists about effective interventions to mitigate disrespect and abuse, and promote respectful maternity care. In an accompanying article, we describe the process of selecting, implementing, and evaluating a package of interventions designed to prevent and reduce disrespect and abuse in a large urban hospital in Tanzania. Though that study was not powered to detect a definitive impact on reducing D&A, the results showed important changes in intermediate outcomes associated with this goal. In this commentary, we describe the factors that enabled this effect, especially the participatory approach we adopted to engage key stakeholders throughout the planning and implementation of the program. Based on our experience and findings, we conclude that a visible, sustained, and participatory intervention process; committed facility leadership; management support; and staff engagement throughout the project contributed to a marked change in the culture of the hospital to one that values and promotes respectful maternity care. For these changes to translate into dignified care during childbirth for all women in a sustainable fashion, institutional commitment to providing the necessary resources and staff will be needed

Mitigating disrespect and abuse during childbirth in Tanzania: an exploratory study of the effects of two facility-based interventions in a large public hospital

Background: There is emerging evidence that disrespect and abuse (D&A) during facility-based childbirth is prevalent in countries throughout the world and a barrier to achieving good maternal health outcomes. However, much work remains in the identification of effective interventions to prevent and eliminate D&A during facility-based childbirth. This paper describes an exploratory study conducted in a large referral hospital in Dar es Salaam, Tanzania that sought to measure D&A, introduce a package of interventions to reduce its incidence, and evaluate their effectiveness. Methods: After extensive consultation with critical constituencies, two discrete interventions were implemented: (1) Open Birth Days (OBD), a birth preparedness and antenatal care education program, and (2) a workshop for healthcare providers based on the Health Workers for Change curriculum. Each intervention was designed to increase knowledge of patient rights and birth preparedness; increase and improve patient-provider and provider-administrator communication; and improve women’s experience and provider attitudes. The effects of the interventions were assessed using a pre-post design and a range of tools: pre-post questionnaires for OBD participants and pre-post questionnaires for workshop participants; structured interviews with healthcare providers and administrators; structured interviews with women who gave birth at the study facility; and direct observations of patient-provider interactions during labor and delivery. Results: Comparisons before and after the interventions showed an increase in patient and provider knowledge of user rights across multiple dimensions, as well as women’s knowledge of the labor and delivery process. Women reported feeling better prepared for delivery and provider attitudes towards them improved, with providers reporting higher levels of empathy for the women they serve and better interpersonal relationships. Patients and providers reported improved communication, which direct observations confirmed. Additionally, women reported feeling more empowered and confident during delivery. Provider job satisfaction increased substantially from baseline levels, as did user reports of satisfaction and perceptions of care quality. Conclusions: Collectively, the outcomes of this study indicate that the tested interventions have the potential to be successful in promoting outcomes that are prerequisite to reducing disrespect and abuse. However, a more rigorous evaluation is needed to determine the full impact of these interventions

Theoretical study of the absorption spectra of the sodium dimer

Absorption of radiation from the sodium dimer molecular states correlating to Na(3s)-Na(3s) is investigated theoretically. Vibrational bound and continuum transitions from the singlet X Sigma-g+ state to the first excited singlet A Sigma-u+ and singlet B Pi-u states and from the triplet a Sigma-u+ state to the first excited triplet b Sigma-g+ and triplet c Pi-g states are studied quantum-mechanically. Theoretical and experimental data are used to characterize the molecular properties taking advantage of knowledge recently obtained from ab initio calculations, spectroscopy, and ultra-cold atom collision studies. The quantum-mechanical calculations are carried out for temperatures in the range from 500 to 3000 K and are compared with previous calculations and measurements where available.Comment: 19 pages, 8 figures, revtex, eps

Effectiveness of a multivitamin supplementation program among HIV-infected adults in Tanzania

Objective: The objective of this study was to assess the effectiveness of a routine multivitamin supplementation program for adults living with HIV in Tanzania. Design: We conducted a retrospective cohort study of 67,707 adults enrolled in the Dar es Salaam HIV care and treatment program during 2004-2012. Methods: The Dar es Salaam HIV care and treatment program intended to provide all adult patients with multivitamin supplements (vitamins B-complex, C, and E) free of charge; however, intermittent stockouts and other implementation issues did not afford universal coverage. We use Cox proportional hazard models to assess the time-varying association of multivitamin supplementation with mortality and clinical outcomes. Results: The study cohort contributed 41,540 and 129,315 person-years of follow-up time to the ART-naïve and ART-experienced analyses, respectively. Among 48,207 ART-naïve adults, provision of multivitamins reduced the risk of mortality (adjusted hazard ratio (aHR): 0.69; 95% CI: 0.59-0.81), incident tuberculosis (TB) (aHR: 0.83; 0.76-0.91), and meeting ART eligibility criteria (aHR: 0.78; 95% CI: 0.73-0.83) after adjustment for time-varying confounding. Among 46,977 ART-experienced patients, multivitamins reduced mortality (HR: 0.86; 95% CI: 0.80-0.92), incident TB (aHR: 0.78; 95% CI: 0.73-0.84), and immunologic failure (aHR: 0.70; 95% CI: 0.67-0.73). The survival benefits associated with provision multivitamins appeared to be greatest during the first year of ART and declined over time (p-value \u3c0.001). Conclusion: Multivitamin supplementation appears to be a simple, effective, safe, and scalable program to improve survival, reduce incidence of TB, and improve treatment outcomes for adult HIV patients in Tanzania

Ferroelectric Solitons Crafted in Epitaxial Bismuth Ferrite Superlattices

In ferroelectrics, complex interactions among various degrees of freedom enable the condensation of topologically protected polarization textures. Known as ferroelectric solitons, these particle-like structures represent a new class of materials with promise for beyond CMOS technologies due to their ultrafine size and sensitivity to external stimuli. Such polarization textures have scarcely been reported in multiferroics. Here, we report a range of soliton topologies in bismuth ferrite strontium titanate superlattices. High-resolution piezoresponse force microscopy and Cs-corrected high-angle annular dark-field scanning transmission electron microscopy reveal a zoo of topologies, and polarization displacement mapping of planar specimens reveals center-convergent and divergent topological defects as small as 3 nm. Phase field simulations verify that some of these topologies can be classed as bimerons, with a topological charge of plus and minus one, and first-principles-based effective Hamiltonian computations show that the co-existence of such structures can lead to non-integer topological charges, a first observation in a BiFeO3-based system. Our results open new opportunities in multiferroic topotronics

Alanine Scanning mutagenesis of the prototypic cyclotide reveals a cluster of residues essential for bioactivity

The cyclotides are stable plant-derived mini-proteins with a topologically circular peptide backbone and a knotted arrangement of three disulfide bonds that form a cyclic cystine knot structural framework. they display a wide range of pharmaceutically important bioactivities, but their natural function is in plant defense as insecticidal agents