Contributions of African-centered (Africentric) psychology: A call for inclusion in APA-accredited graduate psychology program curriculum.

Over the past few years, there has been increased visibility of, and attention paid to, enduring issues such as racial discrimination toward Black Americans. Black psychologists have been called upon to explain various race-related mental health issues to the public, as well as their colleagues and students. Discussions about how to heal from persistent, intergenerational, oppressive attacks on the African psyche are important, but the theories and treatments in which most practitioners are trained and considered "best practices" are Eurocentric in nature. African-centered (or Africentric) psychology is a well-established school of thought, predating the philosophies often discussed in Western/American psychology's History and Systems curriculum, that provides an authentic understanding of the psychology of people of African descent from an African perspective. In this article, we present the historical contention about the lack of inclusion of an African perspective in conceptualizing and addressing the psychological needs of people of African descent, provide an overview of African-centered psychology including its underlying worldview and philosophy, development, and key contributors, and advocate for the inclusion of Africentric psychology in APA-accredited psychology graduate programs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination.

BACKGROUND: Myelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires communicative axo-glial interactions, however, the molecular interactions that occur between oligodendrocytes and axons during developmental myelination and myelin maintenance remain to be fully elucidated. Our previous work identified G protein-coupled receptor 62 (Gpr62), an uncharacterized orphan g-protein coupled receptor, as being selectively expressed by mature oligodendrocytes within the CNS, suggesting a potential role in myelination or axoglial interactions. However, no studies to date have assessed the functional requirement for Gpr62 in oligodendrocyte development or CNS myelination. METHODS: To address this, we generated a knockout mouse strain lacking the Gpr62 gene. We assessed CNS myelination during both postnatal development and adulthood using immunohistochemistry, electron microscopy and western blot. In addition, we utilized AAV-mediated expression of a tagged Gpr62 in oligodendrocytes to determine the subcellular localization of the protein in vivo. RESULTS: We find that virally expressed Gpr62 protein is selectively expressed on the adaxonal myelin layer, suggestive of a potential role for Gpr62 in axo-myelinic signaling. Nevertheless, Gpr62 knockout mice display normal oligodendrocyte numbers and apparently normal myelination within the CNS during both postnatal development and adulthood. CONCLUSIONS: We conclude that in spite of being well-placed to mediate neuronal-oligodendrocyte communications, Gpr62 is overall dispensable for CNS myelination.

NT-proBNP levels and cardiopulmonary function in children with sickle cell disease.

Patients with sickle cell disease (SCD) are living longer and subsequently more apt to develop cardiopulmonary dysfunction. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels have been used in adults with SCD to assess for pulmonary hypertension and mortality. While the incidence of PH is low in pediatrics, it is reasonable to presume that NT-proBNP levels can be used to assess risk for the development of cardiopulmonary morbidity. We hypothesized that NT-proBNP levels would be increased in patients with SCD compared to age-adjusted healthy children; additionally, these levels would be associated with labs indicative of hemolysis and would demonstrate evidence of obstructive lung disease and cardiac dysfunction. We retrospectively evaluated patients with SCD, 8-18 years old, at a large, tertiary care children's hospital. NT-proBNP levels were assessed in correlation with hemolytic lab work, spirometry, and echocardiographic data. The age group 8-14 years old, 75% of our cohort's population, had a median NT-proBNP of 70 pg/ml, greater than their age-adjusted counterparts (52 pg/ml). NT-proBNP levels were associated with an increased degree of hemolysis when compared with hemoglobin (Hb) (r = -0.43, p < .0001), reticulocyte count (r = .25, p = .01) and lactate dehydrogenase levels (r = .47, p < .0001). An inverse trend was found between NT-proBNP and spirometric data. Finally, a positive correlation was found between NT-proBNP and diastolic left ventricular size (r = .28, p = .047]. The correlations found suggest that NT-proBNP may be used prospectively to identify patients with SCD at increased risk for the development of cardiopulmonary dysfunction.

Selective Role of the Putamen in Serial Reversal Learning in the Marmoset.

Fronto-striatal circuitry involving the orbitofrontal cortex has been identified as mediating successful reversal of stimulus-outcome contingencies. The region of the striatum that most contributes to reversal learning remains unclear, with studies in primates implicating both caudate nucleus and putamen. We trained four marmosets on a touchscreen-based serial reversal task and implanted each with cannulae targeting both putamen and caudate bilaterally. This allowed reversible inactivation of the two areas within the same monkeys, but across separate sessions, to directly investigate their respective contributions to reversal performance. Behavioral sensitivity to the GABAA agonist muscimol varied across subjects and between brain regions, so each marmoset received a range of doses. Intermediate doses of intra-putamen muscimol selectively impaired reversal performance, leaving the baseline discrimination phase unchanged. There was no effect of low doses and high doses were generally disruptive. By contrast, low doses of intra-caudate muscimol improved reversal performance, while high doses impaired both reversal and baseline discrimination performance. These data provide evidence for a specific role of the putamen in serial reversal learning, which may reflect the more habitual nature of repeated reversals using the same stimulus pair.

Generation of a human induced pluripotent stem cell line CERAi001-A-6 using episomal vectors.

We report the generation of the hiPSC line CERAi001-A-6 from primary human dermal fibroblasts. Reprogramming was performed using episomal vector delivery of OCT4, SOX2, KLF4, L-MYC, LIN28 and shRNA for p53.

Mitochondrial replacement in an iPSC model of Leber's hereditary optic neuropathy.

Cybrid technology was used to replace Leber hereditary optic neuropathy (LHON) causing mitochondrial DNA (mtDNA) mutations from patient-specific fibroblasts with wildtype mtDNA, and mutation-free induced pluripotent stem cells (iPSCs) were generated subsequently. Retinal ganglion cell (RGC) differentiation demonstrates increased cell death in LHON-RGCs and can be rescued in cybrid corrected RGCs.

Impostor feelings as a moderator and mediator of the relationship between perceived discrimination and mental health among racial/ethnic minority college students.

This study investigated whether impostor feelings would both moderate and mediate the relationship between perceived discrimination and mental health in a sample of diverse ethnic minority college students (106 African Americans, 102 Asian Americans, 108 Latino/a Americans) at an urban public university. African American students reported higher perceived discrimination than Asian American and Latino/a American students, while no racial/ethnic group differences were reported for impostor feelings. Analyses revealed that among African American students, high levels of impostor feelings moderated the perceived discrimination and depression relationship and mediated the perceived discrimination and anxiety relationship. Among Asian American students, impostor feelings mediated the relationship between perceived discrimination and both depression and anxiety. Among Latino/a American students low levels of impostor feelings moderated the relationship between perceived discrimination and both depression and anxiety, and partially mediated the relationship between perceived discrimination and anxiety. Multigroup path analyses revealed a significantly stronger impact of impostor feelings on depression among African American students and a stronger impact of perceived discrimination on impostor feelings among African American and Latino/a American students. Clinical implications and future research directions are discussed. (PsycINFO Database Record

Enriched retinal ganglion cells derived from human embryonic stem cells.

Optic neuropathies are characterised by a loss of retinal ganglion cells (RGCs) that lead to vision impairment. Development of cell therapy requires a better understanding of the signals that direct stem cells into RGCs. Human embryonic stem cells (hESCs) represent an unlimited cellular source for generation of human RGCs in vitro. In this study, we present a 45-day protocol that utilises magnetic activated cell sorting to generate enriched population of RGCs via stepwise retinal differentiation using hESCs. We performed an extensive characterization of these stem cell-derived RGCs by examining the gene and protein expressions of a panel of neural/RGC markers. Furthermore, whole transcriptome analysis demonstrated similarity of the hESC-derived RGCs to human adult RGCs. The enriched hESC-RGCs possess long axons, functional electrophysiological profiles and axonal transport of mitochondria, suggestive of maturity. In summary, this RGC differentiation protocol can generate an enriched population of functional RGCs from hESCs, allowing future studies on disease modeling of optic neuropathies and development of cell therapies.

Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset.

Two learning mechanisms contribute to decision-making: goal-directed actions and the "habit" system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior.

Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells.

Reprogramming of somatic cells into a pluripotent state is known to be accompanied by extensive restructuring of mitochondria and switch in metabolic requirements. Here we utilized Leber's hereditary optic neuropathy (LHON) as a mitochondrial disease model to study the effects of homoplasmic mtDNA mutations and subsequent oxidative phosphorylation (OXPHOS) defects in reprogramming. We obtained fibroblasts from a total of 6 LHON patients and control subjects, and showed a significant defect in complex I respiration in LHON fibroblasts by high-resolution respiratory analysis. Using episomal vector reprogramming, our results indicated that human induced pluripotent stem cell (hiPSC) generation is feasible in LHON fibroblasts. In particular, LHON-specific OXPHOS defects in fibroblasts only caused a mild reduction and did not significantly affect reprogramming efficiency, suggesting that hiPSC reprogramming can tolerate a certain degree of OXPHOS defects. Our results highlighted the induction of genes involved in mitochondrial biogenesis (TFAM, NRF1), mitochondrial fusion (MFN1, MFN2) and glycine production (GCAT) during reprogramming. However, LHON-associated OXPHOS defects did not alter the kinetics or expression levels of these genes during reprogramming. Together, our study provides new insights into the effects of mtDNA mutation and OXPHOS defects in reprogramming and genes associated with various aspects of mitochondrial biology.

MYRF is a membrane-associated transcription factor that autoproteolytically cleaves to directly activate myelin genes.

The myelination of axons is a crucial step during vertebrate central nervous system (CNS) development, allowing for rapid and energy efficient saltatory conduction of nerve impulses. Accordingly, the differentiation of oligodendrocytes, the myelinating cells of the CNS, and their expression of myelin genes are under tight transcriptional control. We previously identified a putative transcription factor, Myelin Regulatory Factor (Myrf), as being vital for CNS myelination. Myrf is required for the generation of CNS myelination during development and also for its maintenance in the adult. It has been controversial, however, whether Myrf directly regulates transcription, with reports of a transmembrane domain and lack of nuclear localization. Here we show that Myrf is a membrane-associated transcription factor that undergoes an activating proteolytic cleavage to separate its transmembrane domain-containing C-terminal region from a nuclear-targeted N-terminal region. Unexpectedly, this cleavage event occurs via a protein domain related to the autoproteolytic intramolecular chaperone domain of the bacteriophage tail spike proteins, the first time this domain has been found to play a role in eukaryotic proteins. Using ChIP-Seq we show that the N-terminal cleavage product directly binds the enhancer regions of oligodendrocyte-specific and myelin genes. This binding occurs via a defined DNA-binding consensus sequence and strongly promotes the expression of target genes. These findings identify Myrf as a novel example of a membrane-associated transcription factor and provide a direct molecular mechanism for its regulation of oligodendrocyte differentiation and CNS myelination.

Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS.

Although the transcription factors required for the generation of oligodendrocytes and CNS myelination during development have been relatively well established, it is not known whether continued expression of the same factors is required for the maintenance of myelin in the adult. Here, we use an inducible conditional knock-out strategy to investigate whether continued oligodendrocyte expression of the recently identified transcription factor myelin gene regulatory factor (MRF) is required to maintain the integrity of myelin in the adult CNS. Genetic ablation of MRF in mature oligodendrocytes within the adult CNS resulted in a delayed but severe CNS demyelination, with clinical symptoms beginning at 5 weeks and peaking at 8 weeks after ablation of MRF. This demyelination was accompanied by microglial/macrophage infiltration and axonal damage. Transcripts for myelin genes, such as proteolipid protein, MAG, MBP, and myelin oligodendrocyte glycoprotein, were rapidly downregulated after ablation of MRF, indicating an ongoing requirement for MRF in the expression of these genes. Subsequently, a proportion of the recombined oligodendrocytes undergo apoptosis over a period of weeks. Surviving oligodendrocytes gradually lose the expression of mature markers such as CC1 antigen and their association with myelin, without reexpressing oligodendrocyte progenitor markers or reentering the cell cycle. These results demonstrate that ongoing expression of MRF within the adult CNS is critical to maintain mature oligodendrocyte identity and the integrity of CNS myelin.

Utility of the AAMC's Graduation Questionnaire to study behavioral and social sciences domains in undergraduate medical education.

PURPOSE: The Institute of Medicine (IOM) report on social and behavioral sciences (SBS) indicated that 50% of morbidity and mortality in the United States is associated with SBS factors, which the report also found were inadequately taught in medical school. A multischool collaborative explored whether the Association of American Medical Colleges Graduation Questionnaire (GQ) could be used to study changes in the six SBS domains identified in the IOM report. METHOD: A content analysis conducted with the GQ identified 30 SBS variables, which were narrowed to 24 using a modified Delphi approach. Summary data were pooled from nine medical schools for 2006 and 2007, representing 1,126 students. Data were generated on students' perceptions of curricular experiences, attitudes related to SBS curricula, and confidence with relevant clinical knowledge and skills. The authors determined the sample sizes required for various effect sizes to assess the utility of the GQ. RESULTS: The 24 variables were classified into five of six IOM domains representing a total of nine analytic categories with cumulative scale means ranging from 60.8 to 93.4. Taking into account the correlations among measures over time, and assuming a two-sided test, 80% power, alpha at .05, and standard deviation of 4.1, the authors found that 34 medical schools would be required for inclusion to attain an estimated effect size of 0.50 (50%). With a sample size of nine schools, the ability to detect changes would require a very high effect size of 107%. CONCLUSIONS: Detecting SBS changes associated with curricular innovations would require a large collaborative of medical schools. Using a national measure (the GQ) to assess curricular innovations in most areas of SBS is possible if enough medical schools were involved in such an effort.