A decolonized mental health framework for black women and birthing people.

Black perinatal mental health is an area that has received less focus in psychotherapy research in the United States. This area is especially important as recent attacks on Reproductive Justice impact not only birthing people's rights and freedoms but also their mental health and emotional well-being. Current psychotherapy interventions are rooted in evidence-based treatments (EBTs) that may not always align with the values and practices of frameworks like radical healing and liberation psychology that are meant to emphasize collective healing and empower individuals. To date, psychological research involving radical healing and liberation psychology approaches have not had a specific focus on birthing people. Psychotherapeutic interventions have also largely excluded the unique intersectional identities and healing of Black birthing people. In moving toward decolonizing psychotherapy, this conceptual paper will propose a multi-pronged framework for addressing racial stressors and other mental health concerns during the perinatal period. The proposed framework, The Three Cs of Decolonization, includes three components: Community, Creativity, and Connection to Self. These components of the framework are meant to address and highlight culturally relevant ways of healing for Black birthing people. Larger systemic changes are needed and necessary for the desired change across mental health, medical, and other integrated systems of care that have been impacted by racism and discrimination. The current framework is dedicated to healing and empowering Black birthing people with approaches and considerations that are consistent with Reproductive Justice.

'Sleep-dependent' memory consolidation? Brief periods of post-training rest and sleep provide an equivalent benefit for both declarative and procedural memory.

Sleep following learning facilitates the consolidation of memories. This effect has often been attributed to sleep-specific factors, such as the presence of sleep spindles or slow waves in the electroencephalogram (EEG). However, recent studies suggest that simply resting quietly while awake could confer a similar memory benefit. In the current study, we examined the effects of sleep, quiet rest, and active wakefulness on the consolidation of declarative and procedural memory. We hypothesized that sleep and eyes-closed quiet rest would both benefit memory compared with a period of active wakefulness. After completing a declarative and a procedural memory task, participants began a 30-min retention period with PSG (polysomnographic) monitoring, in which they either slept (n = 24), quietly rested with their eyes closed (n = 22), or completed a distractor task (n = 29). Following the retention period, participants were again tested on their memory for the two learning tasks. As hypothesized, sleep and quiet rest both led to better performance on the declarative and procedural memory tasks than did the distractor task. Moreover, the performance advantages conferred by rest were indistinguishable from those of sleep. These data suggest that neurobiology specific to sleep might not be necessary to induce the consolidation of memory, at least across very short retention intervals. Instead, offline memory consolidation may function opportunistically, occurring during either sleep or stimulus-free rest, provided a favorable neurobiological milieu and sufficient reduction of new encoding.

Novel class 1 integron harboring antibiotic resistance genes in wastewater-derived bacteria as revealed by functional metagenomics.

Combatting antibiotic resistance is critical to our ability to treat infectious diseases. Here, we identified and characterized diverse antimicrobial resistance genes, including potentially mobile elements, from synthetic wastewater treatment microcosms exposed to the antibacterial agent triclosan. After seven weeks of exposure, the microcosms were subjected to functional metagenomic selection across 13 antimicrobials. This was achieved by cloning the combined genetic material from the microcosms, introducing this genetic library into E. coli, and selecting for clones that grew on media supplemented with one of the 13 antimicrobials. We recovered resistant clones capable of growth on media supplemented with a single antimicrobial, yielding 13 clones conferring resistance to at least one antimicrobial agent. Antibiotic susceptibility analysis revealed resistance ranging from 4 to >50 fold more resistant, while one clone showed resistance to multiple antibiotics. Using both Sanger and SMRT sequencing, we identified the predicted active gene(s) on each clone. One clone that conferred resistance to tetracycline contained a gene encoding a novel tetA-type efflux pump that was named TetA(62). Three clones contained predicted active genes on class 1 integrons. One integron had a previously unreported genetic arrangement and was named In1875. This study demonstrated the diversity and potential for spread of resistance genes present in human-impacted environments.

Towards an Understanding of the Molecular Mechanisms of Variable Unnatural Base-Pair Behavior: A Biophysical Analysis of dNaM-dTPT3.

The series of unnatural base pairs (UBPs) developed by the Romesberg lab, which pair via hydrophobic and packing interactions have been replicated, transcribed, and translated inside of a living organism. However, as to why these UBPs exhibit variable fidelity and efficiency when used in different contexts is not clear. In an effort to gain some insights, we investigated the thermal stability and pairing selectivity of the (d)NaM-(d)TPT3 UBP in 11nt duplexes via UV spectroscopy and the effects on helical structure via CD spectroscopy. We observed that while the duplexes containing a UBP are less stable than fully natural duplexes, they are generally more stable than duplexes containing natural mispairs. This work provides the first insights connecting the thermal stability of the (d)NaM-(d)TPT3 UBP to the molecular mechanisms for varying replication fidelity in different sequence contexts in DNA, asymmetrical transcription fidelity, and codon:anticodon interactions and can assist in future UBP development.

Identification of a Novel Plasmid-Borne Gentamicin Resistance Gene in Nontyphoidal Salmonella Isolated from Retail Turkey.

The spread of antibiotic-resistant bacteria presents a global health challenge. Efficient surveillance of bacteria harboring antibiotic resistance genes (ARGs) is a critical aspect to controlling the spread. Increased access to microbial genomic data from many diverse populations informs this surveillance but only when functional ARGs are identifiable within the data set. Current, homology-based approaches are effective at identifying the majority of ARGs within given clinical and nonclinical data sets for several pathogens, yet there are still some whose identities remain elusive. By coupling phenotypic profiling with genotypic data, these unknown ARGs can be identified to strengthen homology-based searches. To prove the efficacy and feasibility of this approach, a published data set from the U.S. National Antimicrobial Resistance Monitoring System (NARMS), for which the phenotypic and genotypic data of 640 Salmonella isolates are available, was subjected to this analysis. Six isolates recovered from the NARMS retail meat program between 2011 and 2013 were identified previously as phenotypically resistant to gentamicin but contained no known gentamicin resistance gene. Using the phenotypic and genotypic data, a comparative genomics approach was employed to identify the gene responsible for the observed resistance in all six of the isolates. This gene, grdA, is harbored on a 9,016-bp plasmid that is transferrable to Escherichia coli, confers gentamicin resistance to E. coli, and has never before been reported to confer gentamicin resistance. Bioinformatic analysis of the encoded protein suggests an ATP binding motif. This work demonstrates the advantages associated with coupling genomics technologies with phenotypic data for novel ARG identification.

Single-cell mass spectrometry with multi-solvent extraction identifies metabolic differences between left and right blastomeres in the 8-cell frog (Xenopus) embryo.

Single-cell metabolic mass spectrometry enables the discovery (untargeted) analysis of small molecules in individual cells. Using single-cell capillary electrophoresis high-resolution mass spectrometry (CE-HRMS), we recently uncovered small-molecule differences between embryonic cells located along the animal-vegetal and dorsal-ventral axes of the 16-cell frog (Xenopus laevis) embryo, raising the question whether metabolic cell heterogeneity also exists along the left-right body axis. To address this question, we here advance single-cell CE-HRMS for identifying and quantifying metabolites in higher analytical sensitivity, and then use the methodology to compare metabolite production between left and right cells. Our strategy utilizes multiple solvents with complementary physicochemical properties to extract small molecules from single cells and improve electrophoretic separation, increasing metabolite ion signals for quantification and tandem HRMS. As a result, we were able to identify 55 different small molecules in D1 cells that were isolated from 8-cell embryos. To quantify metabolite production between left and right cells, we analyzed n = 24 different D1 cells in technical duplicate-triplicate measurements. Statistical and multivariate analysis based on 80 of the most repeatedly quantified compounds revealed 10 distinct metabolites that were significantly differentially accumulated in the left or right cells (p < 0.05 and fold change ≥1.5). These metabolites were enriched in the arginine-proline metabolic pathway in the right, but not the left D1 cells. Besides providing analytical benefits for single-cell HRMS, this work provides new metabolic data on the establishment of normal body asymmetry in the early developing embryo.

"A Judgment-Free Zone": Adaptation and Pilot Study of a Virtual Wellness Group for African American Mothers with Young Children.

The COVID-19 pandemic has been particularly challenging for the mental health of African American (AA) birthing people. The pandemic necessitated shifting mental health care to online interventions. The goals of this study were to (1) describe an adapted evidence-based group preventive intervention for AA mothers with young children within a pediatric setting and (2) evaluate the feasibility, acceptability, and preliminary effectiveness of this virtual intervention. Phase 1 describes the adaptation of the HealthySteps Mom's Virtual Wellness Group, including eight weekly sessions based on the Mothers and Babies Course. Phase 2 was a mixed-methods, pre-post intervention design. Six AA mothers with young children completed questionnaires related to depression, anxiety, and parenting competence at three time points: pre-intervention (T1), post-intervention (T2), and 3 months post-intervention (T3). The participants also completed a focus group post-T2 to gather qualitative feedback regarding the intervention. The median scores for depression were lower at T2 and increased at T3, and for anxiety, they increased at T2 and decreased at T3. The median scores for parenting competence increased across the three time points. The participants attended a mean of 7.2 sessions (SD = 0.74). The qualitative results indicate that the participants gained a sense of empowerment, enjoyed connecting with other mothers, and acquired information. This pilot study suggests that a virtual intervention is feasible, acceptable, and can increase parenting competence and support among AA mothers with young children.

Mothers and Babies Online Course: Participant Characteristics and Behaviors in a Web-Based Prevention of Postpartum Depression Intervention.

Despite the availability of evidence-based postpartum depression (PPD) prevention and treatment interventions, perinatal persons continue to suffer. eHealth and mHealth tools to address mental health issues have grown exponentially, especially given the ubiquity of technology and the increased demand for telemental health resources. The Mothers and Babies Online Course (eMB), an 8-lesson prevention of PPD intervention, was digitally adapted to expand the reach of evidence-based interventions to perinatal persons with limited access to maternal mental health resources. This report describes the characteristics, behaviors, and feedback provided by users of the updated eMB website. Two hundred eight predominantly English-speaking U.S. residents enrolled in the eMB. Thirty-seven percent were either pregnant (n = 38) or postpartum (n = 39) women interested in learning skills to manage changes in their mood during and after pregnancy; 63% were health providers (n = 131) interested in learning how to support their patient communities. Seventy-six percent (n = 159) viewed at least one of the eight eMB lessons, with 50.9% exclusively viewing Lesson 1. Few (4.4%) viewed all eight lessons. The lessons were rated favorably on usefulness and understanding. Perinatal women engaged with interactive content at higher rates than health providers. Examining user behaviors and feedback is an essential developmental step before empirically testing the efficacy of digital tools. Future iterations of the eMB will incorporate these preliminary findings to provide perinatal persons with accessible web-based interventions that will hopefully reduce the incidence and negative consequences of postpartum depression.

Expansion of the genetic code via expansion of the genetic alphabet.

Current methods to expand the genetic code enable site-specific incorporation of non-canonical amino acids (ncAAs) into proteins in eukaryotic and prokaryotic cells. However, current methods are limited by the number of codons possible, their orthogonality, and possibly their effects on protein synthesis and folding. An alternative approach relies on unnatural base pairs to create a virtually unlimited number of genuinely new codons that are efficiently translated and highly orthogonal because they direct ncAA incorporation using forces other than the complementary hydrogen bonds employed by their natural counterparts. This review outlines progress and achievements made towards developing a functional unnatural base pair and its use to generate semi-synthetic organisms with an expanded genetic alphabet that serves as the basis of an expanded genetic code.

Optimization of a ß-Lactam Scaffold for Antibacterial Activity via the Inhibition of Bacterial Type I Signal Peptidase.

ß-Lactam antibiotics, one of the most important class of human therapeutics, act via the inhibition of penicillin-binding proteins (PBPs). The unparalleled success in their development has inspired efforts to develop them as inhibitors of other targets. Bacterial type I signal peptidase is evolutionarily related to the PBPs, but the stereochemistry of its substrates and its catalytic mechanism suggest that ß-lactams with the 5S stereochemistry, as opposed to the 5R stereochemistry of the traditional ß-lactams, would be required for inhibition. We report the synthesis and evaluation of a variety of 5S penem derivatives and identify several with promising activity against both a Gram-positive and a Gram-negative bacterial pathogen. To our knowledge these are the first 5S ß-lactams to possess significant antibacterial activity and the first ß-lactams imparted with antibacterial activity via optimization of the inhibition of a target other than a PBP. Along with the privileged status of their scaffold and the promise of bacterial signal peptidase I (SPase) as a target, this activity makes these compounds promising leads for development as novel therapeutics.

Synthetic Biology Parts for the Storage of Increased Genetic Information in Cells.

To bestow cells with novel forms and functions, the goal of synthetic biology, we have developed the unnatural nucleoside triphosphates dNaMTP and dTPT3TP, which form an unnatural base pair (UBP) and expand the genetic alphabet. While the UBP may be retained in the DNA of a living cell, its retention is sequence-dependent. We now report a steady-state kinetic characterization of the rate with which the Klenow fragment of E. coli DNA polymerase I synthesizes the UBP and its mispairs in a variety of sequence contexts. Correct UBP synthesis is as efficient as for a natural base pair, except in one sequence context, and in vitro performance is correlated with in vivo performance. The data elucidate the determinants of efficient UBP synthesis, show that the dNaM-dTPT3 UBP is the first generally recognized natural-like base pair, and importantly, demonstrate that dNaMTP and dTPT3TP are well optimized and standardized parts for the expansion of the genetic alphabet.