A New Era of Racial Equity in Community Development Finance: Leveraging Private and Philanthropic Commitments in the PostGeorge Floyd Period

The brief first reflects on gaps in economic opportunity for capital access and wealth accrual in disadvantaged communities and by race, explaining why it is essential to align community development finance and corporate and philanthropic commitments to community need if the country is to successfully unlock more equitable opportunity for all. Part 1 then examines racial equity commitments made between June 2020 and May 2021; the types of organizations and priorities targeted by these financial commitments; adherence to disbursement timelines; and changes in financial products, services, and grantmaking approaches. Part 2 looks at the uses of community development capital, the role of community development finance in supporting disinvested communities, challenges reported in capital deployment, and 11 potential solutions for addressing these challenges equitably. In part 3, "The Path Forward," we discuss how the federal government can more effectively mobilize the private sector and share four strategies for the corporate and philanthropic sectors, in turn. These steps include strategies to maximize current resources and sustain momentum—such as greater transparency and collaboration and embedding equity in investment decisions—and those that can support longer-term, systemic change that extends more flexible and patient financing, responding to the needs with an even bolder commitment, and embracing equity as a business imperative

Accounting Profession in France; Professional Accounting in Foreign Country Series

https://egrove.olemiss.edu/aicpa_guides/1677/thumbnail.jp

Progenitor Cell Therapy for Sensorineural Hearing Loss in Infants

Typical language development requires typical hearing. With sensorineural hearing loss (SNHL), the damaged hair cells of the organ of Corti within the cochlea interfere with typical hearing and, as a result, cause impaired language development. Untreated SNHL causes significant neurocognitive differences in affected children. SNHL is a permanent sensory disorder affecting more than 270 million people worldwide. Congenital SNHL is found in 4 of 1000 newborns. Approximately half of congenital SNHL is hereditary and is the result of genetic mutations causing improper development of cochlear hair cells. Non-genetic congenital SNHL is thought to be the result of an injury to the cochlea typically from premature birth, infection, or exposure to ototoxic medications or noise. In mammals, the cochlea is postmitotic at birth, and no spontaneous repair occurs thereafter. Existing treatments for SNHL (hearing aids and cochlear implants) function by augmenting the damaged organ of Corti. No reparative treatments currently exist. In preclinical and clinical studies, progenitor cell therapy (cord blood and mesenchymal stem cells) has shown promise in reversing the underlying pathology of SNHL, the loss of cochlear sensory hair cells. Progenitor cell therapy may also allow functional reorganization of the auditory pathways including primary auditory cortex (Heschl’s gyrus). We will present a summary of the effect of hearing loss on auditory development, existing preclinical and clinical data on progenitor cell therapy, and its potential role in the (re)habilitation of non-genetic SNHL

A Different Perspective on Breast Cancer Risk Factors: Some Implications of the Nonattributable Risk

Many risk factors for breast cancer are known, but each makes a relatively small contribution to individual risk. Nearly a dozen risk factors taken together accounted for only about 25% of total risk in a population of 570,000 women enrolled in the American Cancer Society's Cancer Prevention Study I (1959-66). This study was considered path-breaking in 1982. Nevertheless, breast cancer remains the leading cause of cancer in US women three decades later

EM-mosaic detects mosaic point mutations that contribute to congenital heart disease.

BackgroundThe contribution of somatic mosaicism, or genetic mutations arising after oocyte fertilization, to congenital heart disease (CHD) is not well understood. Further, the relationship between mosaicism in blood and cardiovascular tissue has not been determined.MethodsWe developed a new computational method, EM-mosaic (Expectation-Maximization-based detection of mosaicism), to analyze mosaicism in exome sequences derived primarily from blood DNA of 2530 CHD proband-parent trios. To optimize this method, we measured mosaic detection power as a function of sequencing depth. In parallel, we analyzed our cohort using MosaicHunter, a Bayesian genotyping algorithm-based mosaic detection tool, and compared the two methods. The accuracy of these mosaic variant detection algorithms was assessed using an independent resequencing method. We then applied both methods to detect mosaicism in cardiac tissue-derived exome sequences of 66 participants for which matched blood and heart tissue was available.ResultsEM-mosaic detected 326 mosaic mutations in blood and/or cardiac tissue DNA. Of the 309 detected in blood DNA, 85/97 (88%) tested were independently confirmed, while 7/17 (41%) candidates of 17 detected in cardiac tissue were confirmed. MosaicHunter detected an additional 64 mosaics, of which 23/46 (50%) among 58 candidates from blood and 4/6 (67%) of 6 candidates from cardiac tissue confirmed. Twenty-five mosaic variants altered CHD-risk genes, affecting 1% of our cohort. Of these 25, 22/22 candidates tested were confirmed. Variants predicted as damaging had higher variant allele fraction than benign variants, suggesting a role in CHD. The estimated true frequency of mosaic variants above 10% mosaicism was 0.14/person in blood and 0.21/person in cardiac tissue. Analysis of 66 individuals with matched cardiac tissue available revealed both tissue-specific and shared mosaicism, with shared mosaics generally having higher allele fraction.ConclusionsWe estimate that ~ 1% of CHD probands have a mosaic variant detectable in blood that could contribute to cardiac malformations, particularly those damaging variants with relatively higher allele fraction. Although blood is a readily available DNA source, cardiac tissues analyzed contributed ~ 5% of somatic mosaic variants identified, indicating the value of tissue mosaicism analyses

Motor Learning Induces Plasticity in the Resting Brain—Drumming Up a Connection

Neuroimaging methods have recently been used to investigate plasticity-induced changes in brain structure. However, little is known about the dynamic interactions between different brain regions after extensive coordinated motor learning such as drumming. In this article, we have compared the resting-state functional connectivity (rs-FC) in 15 novice healthy participants before and after a course of drumming (30-min drumming sessions, 3 days a week for 8 weeks) and 16 age-matched novice comparison participants. To identify brain regions showing significant FC differences before and after drumming, without a priori regions of interest, a multivariate pattern analysis was performed. Drum training was associated with an increased FC between the posterior part of bilateral superior temporal gyri (pSTG) and the rest of the brain (i.e., all other voxels). These regions were then used to perform seed-to-voxel analysis. The pSTG presented an increased FC with the premotor and motor regions, the right parietal lobe and a decreased FC with the cerebellum. Perspectives and the potential for rehabilitation treatments with exercise-based intervention to overcome impairments due to brain diseases are also discussed

Cardiomyocyte Proliferative Capacity Is Restricted in Mice With Lmna Mutation

LMNA is one of the leading causative genes of genetically inherited dilated cardiomyopathy (DCM). Unlike most DCM-causative genes, which encode sarcomeric or sarcomere-related proteins, LMNA encodes nuclear envelope proteins, lamin A and C, and does not directly associate with contractile function. However, a mutation in this gene could lead to the development of DCM. The molecular mechanism of how LMNA mutation contributes to DCM development remains largely unclear and yet to be elucidated. The objective of this study was to clarify the mechanism of developing DCM caused by LMNA mutation.Methods and Results: We assessed cardiomyocyte phenotypes and characteristics focusing on cell cycle activity in mice with Lmna mutation. Both cell number and cell size were reduced, cardiomyocytes were immature, and cell cycle activity was retarded in Lmna mutant mice at both 5 weeks and 2 years of age. RNA-sequencing and pathway analysis revealed “proliferation of cells” had the most substantial impact on Lmna mutant mice. Cdkn1a, which encodes the cell cycle regulating protein p21, was strongly upregulated in Lmna mutants, and upregulation of p21 was confirmed by Western blot and immunostaining. DNA damage, which is known to upregulate Cdkn1a, was more abundantly detected in Lmna mutant mice. To assess the proliferative capacity of cardiomyocytes, the apex of the neonate mouse heart was resected, and recovery from the insult was observed. A restricted cardiomyocyte proliferating capacity after resecting the apex of the heart was observed in Lmna mutant mice.Conclusions: Our results strongly suggest that loss of lamin function contributes to impaired cell proliferation through cell cycle defects. The inadequate inborn or responsive cell proliferation capacity plays an essential role in developing DCM with LMNA mutation

Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy

BACKGROUND: Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy and a proposed substrate for arrhythmias and heart failure. In animal models, profibrotic genetic pathways are activated early, before hypertrophic remodeling. Data showing early profibrotic responses to sarcomere-gene mutations in patients with hypertrophic cardiomyopathy are lacking. METHODS: We used echocardiography, cardiac magnetic resonance imaging (MRI), and serum biomarkers of collagen metabolism, hemodynamic stress, and myocardial injury to evaluate subjects with hypertrophic cardiomyopathy and a confirmed genotype. RESULTS: The study involved 38 subjects with pathogenic sarcomere mutations and overt hypertrophic cardiomyopathy, 39 subjects with mutations but no left ventricular hypertrophy, and 30 controls who did not have mutations. Levels of serum C-terminal propeptide of type I procollagen (PICP) were significantly higher in mutation carriers without left ventricular hypertrophy and in subjects with overt hypertrophic cardiomyopathy than in controls (31% and 69% higher, respectively; P<0.001). The ratio of PICP to C-terminal telopeptide of type I collagen was increased only in subjects with overt hypertrophic cardiomyopathy, suggesting that collagen synthesis exceeds degradation. Cardiac MRI studies showed late gadolinium enhancement, indicating myocardial fibrosis, in 71% of subjects with overt hypertrophic cardiomyopathy but in none of the mutation carriers without left ventricular hypertrophy. CONCLUSIONS: Elevated levels of serum PICP indicated increased myocardial collagen synthesis in sarcomere-mutation carriers without overt disease. This profibrotic state preceded the development of left ventricular hypertrophy or fibrosis visible on MRI. (Funded by the National Institutes of Health and others.