Recombinant protein hydrazides: application to site-specific protein PEGylation.

Here, we describe a novel method for the site-specific C-terminal PEGylation of recombinant proteins. This general approach exploits chemical cleavage of precursor intein-fusion proteins with hydrazine to directly produce recombinant protein hydrazides. This unique functionality within the protein sequence then facilitates site-specific C-terminal modification by hydrazone-forming ligation reactions. This approach was used to generate folded, site-specifically C-terminal PEGylated IFNalpha2b and IFNbeta1b, which retained excellent antiviral activity, demonstrating the utility of this technology in the PEGylation of therapeutic proteins. As this methodology is straightforward to perform, is compatible with disulfide bonds, and is exclusively selective for the protein C-terminus, it shows great potential as general technology for the site-specific engineering and labeling of recombinant proteins.

Beyond Words/Signs: DHH Learners' Spatial Reasoning in Mathematics as Embodied Cognition.

Spatial reasoning is critical across the STEM disciplines. Examining deaf and hard of hearing (DHH) children's spatial reasoning in mathematics, particularly geometry, as an embodied phenomenon opens new possibilities for deaf education. The authors inquire into the embodied processes and forms of DHH learners' spatial reasoning, considering how such knowledge can expand access and conceptual opportunities for both DHH and hearing learners. The article focuses on the spatial reasoning of two grade 1 hard of hearing children as they complete a geometric task with a hearing peer in a mainstream classroom. Informed by research in cognitive science, mathematics, and the fields of deaf and general education, the authors explicate key spatial subcomponent processes of deconstructing and constructing as the children produce 2D and 3D figures. The findings of this qualitative study provide considerations for future research and pedagogy in both deaf and general education.

A New Stepping-Stone on the Path to Mathematics Success for DHH Learners.

Coeditors of a special issue of the American Annals of the Deaf on mathematics instruction in deaf education, the authors provide a context for the five featured articles. First, the authors establish the importance of mathematics. They then give a historical account of previously related "stepping-stones." Beginning at 1990, the authors follow key events in the field that have led to the special issue. They summarize each article, highlighting three common themes: deaf and hard of hearing (DHH) persons as distinct and capable mathematics learners, the significance of conceptual understanding of mathematics concepts, and the role of language as a key component of mathematics instruction and learning. The authors conclude with a call for further research that recognizes the heterogeneity of DHH learners.

Global music streaming data reveal diurnal and seasonal patterns of affective preference.

People manage emotions to cope with life's demands1,2. Previous research has identified affective patterns using self-reports3 and text analysis4,5, but these measures track the expression of affect, not affective preference for external stimuli such as music, which affects mood states and levels of emotional arousal1,6,7. We analysed a dataset of 765 million online music plays streamed by 1 million individuals in 51 countries to measure diurnal and seasonal patterns of affective preference. Findings reveal similar diurnal patterns across cultures and demographic groups. Individuals listen to more relaxing music late at night and more energetic music during normal business hours, including mid-afternoon when affective expression is lowest. However, there were differences in baselines: younger people listen to more intense music; compared with other regions, music played in Latin America is more arousing, while music in Asia is more relaxing; and compared with other chronotypes, 'night owls' (people who are habitually active or wakeful at night) listen to less-intense music. Seasonal patterns vary with distance from the equator and between Northern and Southern hemispheres and are more strongly correlated with absolute day length than with changes in day length. Taken together with previous findings on affective expression in text4, these results suggest that musical choice both shapes and reflects mood.

Single-Domain Antibody-Functionalized pH-Responsive Amphiphilic Block Copolymer Nanoparticles for Epidermal Growth Factor Receptor Targeted Cancer Therapy.

Biocompatible antibody-nanoparticle conjugates have attracted interest as anticancer agents due to their potential to selectively target therapeutic agents at disease sites. However, new formulation and conjugation approaches are urgently needed to improve their uniformity for clinical applications. Here, a pH-responsive benzaldehyde-functionalized poly[oligo(ethylene glycol) methacrylate-st-para-formyl phenyl methacrylate]-b-poly[2-(diisopropyl)aminoethyl methacrylate] [P(OEGMA-st-pFPMA)-b-PDPA] block copolymer, prepared by reversible addition-fragmentation chain transfer polymerization, produced PEGylated nanoparticles (pH ∼ 7.4) by a single emulsion-solvent evaporation formulation approach. Efficient site-specific attachment of an aminooxy-functionalized anti-EGFR single-domain antibody (sdAb) on these benzaldehyde-decorated nanoparticles is achieved by oxime bond formation. These nanoconjugates can specifically bind EGFR (modified ELISA) and have enhanced uptake over nonfunctionalized controls in EGFR-positive HeLa cells. Encapsulation of rhodamine 6G dye and its dispersion upon cellular uptake, consistent with nanoparticle stability loss at pH < 5.7, prove their ability to facilitate triggered release in endosomal compartments and highlight their potential for use as next-generation antibody-drug nanoconjugates for therapeutic drug delivery.

A comparison of mothers with co-occurring disorders and histories of violence living with or separated from minor children.

Data from the Women with Co-occurring Disorders and Histories of Violence Study are used to examine characteristics distinguishing mothers currently providing care for all their minor children (n = 558) from mothers separated from one or more minor children (n = 1396). Mothers are described and compared on background characteristics and experiences, well-being and current functioning, situational context, and services used. Analyses control for number of children, race, and years of education. Mothers separated from children have more children, less education, have more often been homeless, in juvenile detention or jail, and have lower incomes than mothers living with all their children. Mothers separated from children have more extensive experiences of traumatic and stressful life events, and the groups differ in current functioning and patterns of services used. While cross-sectional data do not allow causal inferences, challenges faced by mothers have significant implications for policy and programs.

Physical health burdens of women with trauma histories and co-occurring substance abuse and mental disorders.

This article documents the physical health burdens of participants in a large, federally funded cross-site study of specialized services for women with histories of trauma (physical or sexual abuse) and co-occurring substance abuse and mental health disorders. Nearly half of the 2729 women in the study (48%) reported serious physical illnesses that frequently limited their daily life activities or required them to use special equipment. Nearly half (46%) rated their health status as only fair or poor. Given the prevalence of physical illnesses in this population, behavioral service providers should discuss with clients their overall health and how it might hinder their participation in treatment for trauma, substance abuse, and mental illness, and policymakers should consider this need when designing behavioral health requirements, setting reimbursement rates, and allocating funds.