Legal Pluralism & Women\u27s Rights: A Study in Post-Colonial Tanzania

Recognizing a dearth of legal research on Zanzibar, the authors explore the complex legal and cultural landscape of this archipelago and its relationship to mainland Tanzania. The article discusses the problems that arise when multicultural societies adopt a pluralist system of justice in order to preserve the traditions of its diverse communities. Although the article focuses on Tanzania, the problems that arise from multicultural accommodations affect not only young, postcolonial nations in Africa and Asia, but also individuals in cosmopolitan, economically-developed countries such as Israel and the United States. As countries wrestle with ever diversifying ethnic and religious populations, such a study is an important tool in ensuring that equal rights are provided to all citizens

Depth-dependent δ13 C trends in platform and slope settings of the Campbellrand-Malmani carbonate platform and possible implications for Early Earth oxygenation

Highlights • Carbon cycle of Neoarchean carbonate platform and potential oxygen oasis. • Carbon isotopes reveal a shift to aerobic biosphere and increasing oxidation state. • Rare earth element patterns reveal decrease in open ocean water influx. • Rimmed margin architecture was crucial for evolution of aerobic ecosystems. Abstract The evolution of oxygenic photosynthesis is widely seen as the major biological factor for the profound shift from reducing to slightly oxidizing conditions in Earth’s atmosphere during the Archean-Proterozoic transition period. The delay from the first biogenic production of oxygen and the permanent oxidation of Earth’s atmosphere during the early Paleoproteorozoic Great Oxidation Event (GOE) indicates that significant environmental modifications were necessary for an effective accumulation of metabolically produced oxygen. Here we report a distinct temporal shift to heavier carbon isotope signatures in lagoonal and intertidal carbonates (δ13Ccarb from -1.6 to +0.2 ‰, relative to VPDB) and organic matter (δ13Corg from about -40 to -25 ‰, relative to VPDB) from the 2.58–2.50 Gy old shallow–marine Campbellrand-Malmani carbonate platform (South Africa). This indicates an increase in the burial rate of organic matter caused by enhanced primary production as well as a change from an anaerobic to an aerobic ecosystem. Trace element data indicate limited influx of reducing species from deep open ocean water into the platform and an increased supply of nutrients from the continent, both supporting primary production and an increasing oxidation state of the platform interior. These restricted conditions allowed that the dissolved inorganic carbon (DIC) pool in the platform interior developed differently than the open ocean. This is supported by coeval carbonates from the marginal slope setting, which had a higher interaction with open ocean water and do not record a comparable shift in δ13Ccarb throughout the sequence. We propose that the emergence of stable shallow-water carbonate platforms in the Neoarchean provided ideal conditions for the evolution of early aerobic ecosystems, which finally led to the full oxidation of Earth’s atmosphere during the GOE

Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome

Purpose: Variants in the DNA mismatch repair (MMR) gene MSH6, identified in individuals suspected of Lynch syndrome, are difficult to classify owing to the low cancer penetrance of defects in that gene. This not only obfuscates personalized health care but also the development of a rapid and reliable classification procedure that does not require clinical data. Methods: The complete in vitro MMR activity (CIMRA) assay was calibrated against clinically classified MSH6 variants and, employing Bayes’ rule, integrated with computational predictions of pathogenicity. To enable the validation of this two-component classification procedure we have employed a genetic screen to generate a large set of inactivating Msh6 variants, as proxies for pathogenic variants. Results: The genetic screen-derived variants established that the two-component classification procedure displays high sensitivities and specificities. Moreover, these inactivating variants enabled the direct reclassification of human variants of uncertain significance (VUS) as (likely) pathogenic. Conclusion: The two-component classification procedure and the genetic screens provide complementary approaches to rapidly and cost-effectively classify the large majority of human MSH6 variants. The approach followed here provides a template for the classification of variants in other disease-predisposing genes, facilitating the translation of personalized genomics into personalized health care

The High Diagnostic Yield of Prenatal Exome Sequencing Followed by 3400 Gene Panel Analysis in 629 Ongoing Pregnancies With Ultrasound Anomalies

Background: The aim of this study was to evaluate the diagnostic yield of routine exome sequencing (ES) in fetuses with ultrasound anomalies. Methods: We performed a retrospective analysis of the ES results of 629 fetuses with isolated or multiple anomalies referred in 2019–2022. Variants in a gene panel consisting of approximately 3400 genes associated with multiple congenital anomalies and/or intellectual disability were analyzed. We used trio analysis and filtering for de novo variants, compound heterozygous variants, homozygous variants, X-linked variants, variants in imprinted genes, and known pathogenic variants. Results: Pathogenic and likely pathogenic variants (class five and four, respectively) were identified in 14.0% (88/629, 95% CI 11.5%–16.9%) of cases. In the current cohort, the probability of detecting a monogenetic disorder was ∼1:7 (88/629, 95% CI 1:8.7–1:5.9), ranging from 1:9 (49/424) in cases with one major anomaly to 1:5 (32/147) in cases with multiple system anomalies. Conclusions: Our results indicate that a notable number of fetuses (1:7) with ultrasound anomalies and a normal chromosomal microarray have a (likely) pathogenic variant that can be detected through prenatal ES. These results warrant implementation of exome sequencing in selected cases, including those with an isolated anomaly on prenatal ultrasound.</p

A research roadmap for quantifying non-state and subnational climate mitigation action

Non-state and subnational climate actors have become central to global climate change governance. Quantitatively assessing climate mitigation undertaken by these entities is critical to understand the credibility of this trend. In this Perspective, we make recommendations regarding five main areas of research and methodological development related to evaluating non-state and subnational climate actions: defining clear boundaries and terminology; use of common methodologies to aggregate and assess non-state and subnational contributions; systematically dealing with issues of overlap; estimating the likelihood of implementation; and addressing data gaps