Paternal mtDNA and Maleness Are Co-Inherited but Not Causally Linked in Mytilid Mussels

BACKGROUND: In marine mussels of the genus Mytilus there are two mitochondrial genomes. One is transmitted through the female parent, which is the normal transmission route in animals, and the other is transmitted through the male parent which is an unusual phenomenon. In males the germ cell line is dominated by the paternal mitochondrial genome and the somatic cell line by the maternal. Research to date has not allowed a clear answer to the question of whether inheritance of the paternal genome is causally related to maleness. METHODOLOGY/PRINCIPAL FINDINGS: Here we present results from hybrid crosses, from triploid mussels and from observations of sperm mitochondria in fertilized eggs which clearly show that maleness and presence of the paternal mitochondrial genome can be decoupled. These same results show that the female mussel has exclusive control of whether her progeny will inherit the mitochondrial genome of the male parent. CONCLUSIONS/SIGNIFICANCE: These findings are important in our efforts to understand the mechanistic basis of this unusual mode of mitochondrial DNA inheritance that is common among bivalves

Effect of Body Mass Index on pregnancy outcomes in nulliparous women delivering singleton babies

Peer reviewedPublisher PD

Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones

ACKNOWLEDGMENTS This work was funded by The BBSRC (BB/D004659/1) the Wellcome Trust (080980/Z/06/Z) and the Medical Research Council (G0701003).Peer reviewedPublisher PD

Biodiversity of the Deep-Sea Continental Margin Bordering the Gulf of Maine (NW Atlantic): Relationships among Sub-Regions and to Shelf Systems

Background: In contrast to the well-studied continental shelf region of the Gulf of Maine, fundamental questions regarding the diversity, distribution, and abundance of species living in deep-sea habitats along the adjacent continental margin remain unanswered. Lack of such knowledge precludes a greater understanding of the Gulf of Maine ecosystem and limits development of alternatives for conservation and management. Methodology/Principal Findings: We use data from the published literature, unpublished studies, museum records and online sources, to: (1) assess the current state of knowledge of species diversity in the deep-sea habitats adjacent to the Gulf of Maine (39–43uN, 63–71uW, 150–3000 m depth); (2) compare patterns of taxonomic diversity and distribution of megafaunal and macrofaunal species among six distinct sub-regions and to the continental shelf; and (3) estimate the amount of unknown diversity in the region. Known diversity for the deep-sea region is 1,671 species; most are narrowly distributed and known to occur within only one sub-region. The number of species varies by sub-region and is directly related to sampling effort occurring within each. Fishes, corals, decapod crustaceans, molluscs, and echinoderms are relatively well known, while most other taxonomic groups are poorly known. Taxonomic diversity decreases with increasing distance from the continental shelf and with changes in benthic topography. Low similarity in faunal composition suggests the deep-sea region harbours faunal communities distinct from those of the continental shelf. Non-parametric estimators of species richness suggest a minimum of 50% of the deep-sea species inventory remains to be discovered. Conclusions/Significance: The current state of knowledge of biodiversity in this deep-sea region is rudimentary. Our ability to answer questions is hampered by a lack of sufficient data for many taxonomic groups, which is constrained by sampling biases, life-history characteristics of target species, and the lack of trained taxonomists

Doubly Uniparental Inheritance of Mitochondria As a Model System for Studying Germ Line Formation

BACKGROUND: Doubly Uniparental Inheritance (DUI) of mitochondria occurs when both mothers and fathers are capable of transmitting mitochondria to their offspring, in contrast to the typical Strictly Maternal Inheritance (SMI). DUI was found in some bivalve molluscs, in which two mitochondrial genomes are inherited, one through eggs, the other through sperm. During male embryo development, spermatozoon mitochondria aggregate in proximity of the first cleavage furrow and end up in the primordial germ cells, while they are dispersed in female embryos. METHODOLOGY/PRINCIPAL FINDINGS: We used MitoTracker, microtubule staining and transmission electron microscopy to examine the mechanisms of this unusual distribution of sperm mitochondria in the DUI species Ruditapes philippinarum. Our results suggest that in male embryos the midbody deriving from the mitotic spindle of the first division concurs in positioning the aggregate of sperm mitochondria. Furthermore, an immunocytochemical analysis showed that the germ line determinant Vasa segregates close to the first cleavage furrow. CONCLUSIONS/SIGNIFICANCE: In DUI male embryos, spermatozoon mitochondria aggregate in a stable area on the animal-vegetal axis: in organisms with spiral segmentation this zone is not involved in cleavage, so the aggregation is maintained. Moreover, sperm mitochondria reach the same embryonic area in which also germ plasm is transferred. In 2-blastomere embryos, the segregation of sperm mitochondria in the same region with Vasa suggests their contribution in male germ line formation. In DUI male embryos, M-type mitochondria must be recognized by egg factors to be actively transferred in the germ line, where they become dominant replacing the Balbiani body mitochondria. The typical features of germ line assembly point to a common biological mechanism shared by DUI and SMI organisms. Although the molecular dynamics of the segregation of sperm mitochondria in DUI species are unknown, they could be a variation of the mechanism regulating the mitochondrial bottleneck in all metazoans

Evidence for a Fourteenth mtDNA-Encoded Protein in the Female-Transmitted mtDNA of Marine Mussels (Bivalvia: Mytilidae)

BACKGROUND: A novel feature for animal mitochondrial genomes has been recently established: i.e., the presence of additional, lineage-specific, mtDNA-encoded proteins with functional significance. This feature has been observed in freshwater mussels with doubly uniparental inheritance of mtDNA (DUI). The latter unique system of mtDNA transmission, which also exists in some marine mussels and marine clams, is characterized by one mt genome inherited from the female parent (F mtDNA) and one mt genome inherited from the male parent (M mtDNA). In freshwater mussels, the novel mtDNA-encoded proteins have been shown to be mt genome-specific (i.e., one novel protein for F genomes and one novel protein for M genomes). It has been hypothesized that these novel, F- and M-specific, mtDNA-encoded proteins (and/or other F- and/or M-specific mtDNA sequences) could be responsible for the different modes of mtDNA transmission in bivalves but this remains to be demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: We investigated all complete (or nearly complete) female- and male-transmitted marine mussel mtDNAs previously sequenced for the presence of ORFs that could have functional importance in these bivalves. Our results confirm the presence of a novel F genome-specific mt ORF, of significant length (>100aa) and located in the control region, that most likely has functional significance in marine mussels. The identification of this ORF in five Mytilus species suggests that it has been maintained in the mytilid lineage (subfamily Mytilinae) for ∼13 million years. Furthermore, this ORF likely has a homologue in the F mt genome of Musculista senhousia, a DUI-containing mytilid species in the subfamily Crenellinae. We present evidence supporting the functionality of this F-specific ORF at the transcriptional, amino acid and nucleotide levels. CONCLUSIONS/SIGNIFICANCE: Our results offer support for the hypothesis that "novel F genome-specific mitochondrial genes" are involved in key biological functions in bivalve species with DUI

Health sector spending and spending on HIV/AIDS, tuberculosis, and malaria, and development assistance for health: progress towards Sustainable Development Goal 3

Background: Sustainable Development Goal (SDG) 3 aims to “ensure healthy lives and promote well-being for all at all ages”. While a substantial effort has been made to quantify progress towards SDG3, less research has focused on tracking spending towards this goal. We used spending estimates to measure progress in financing the priority areas of SDG3, examine the association between outcomes and financing, and identify where resource gains are most needed to achieve the SDG3 indicators for which data are available. Methods: We estimated domestic health spending, disaggregated by source (government, out-of-pocket, and prepaid private) from 1995 to 2017 for 195 countries and territories. For disease-specific health spending, we estimated spending for HIV/AIDS and tuberculosis for 135 low-income and middle-income countries, and malaria in 106 malaria-endemic countries, from 2000 to 2017. We also estimated development assistance for health (DAH) from 1990 to 2019, by source, disbursing development agency, recipient, and health focus area, including DAH for pandemic preparedness. Finally, we estimated future health spending for 195 countries and territories from 2018 until 2030. We report all spending estimates in inflation-adjusted 2019 US$, unless otherwise stated. Findings: Since the development and implementation of the SDGs in 2015, global health spending has increased, reaching$7·9 trillion (95% uncertainty interval 7·8–8·0) in 2017 and is expected to increase to $11·0 trillion (10·7–11·2) by 2030. In 2017, in low-income and middle-income countries spending on HIV/AIDS was$20·2 billion (17·0–25·0) and on tuberculosis it was $10·9 billion (10·3–11·8), and in malaria-endemic countries spending on malaria was$5·1 billion (4·9–5·4). Development assistance for health was $40·6 billion in 2019 and HIV/AIDS has been the health focus area to receive the highest contribution since 2004. In 2019,$374 million of DAH was provided for pandemic preparedness, less than 1% of DAH. Although spending has increased across HIV/AIDS, tuberculosis, and malaria since 2015, spending has not increased in all countries, and outcomes in terms of prevalence, incidence, and per-capita spending have been mixed. The proportion of health spending from pooled sources is expected to increase from 81·6% (81·6–81·7) in 2015 to 83·1% (82·8–83·3) in 2030. Interpretation: Health spending on SDG3 priority areas has increased, but not in all countries, and progress towards meeting the SDG3 targets has been mixed and has varied by country and by target. The evidence on the scale-up of spending and improvements in health outcomes suggest a nuanced relationship, such that increases in spending do not always results in improvements in outcomes. Although countries will probably need more resources to achieve SDG3, other constraints in the broader health system such as inefficient allocation of resources across interventions and populations, weak governance systems, human resource shortages, and drug shortages, will also need to be addressed. Funding: The Bill & Melinda Gates Foundatio

Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing

Purpose We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). Methods Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis. Results There was no evidence for usefulness of old criteria “glioma“ or “neurofibroma.” “Ependymoma” had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%. Conclusions The present study confirms important deficiencies in NF2 diagnostic criteria. The term “glioma” should be dropped and replaced by “ependymoma.” Similarly “neurofibroma” should be removed. Dropping “sibling” from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS