The genetic implications of age-dependent penetrance in manic-depressive illness

An age dependent penetrance function was derived for manic-depressive illness, using age-of-onset data from sixty-one affected probands. The function used was a one-hit model, with earliest age-of-onset at about 14 yr, and a steadily increasing probability of manifesting the illness thereafter. The utility of the penetrance function for pedigree analysis was illustrated, using the families of the sixty-one probands. A sex-linked dominant model of inheritance was about eighty-nine times more likely than an autosomal dominant model, and both were far more likely than autosomal recessive or sex-linked recessive models. The more general single major locus model and the polygenic model cannot be ruled out, but would seem to be unnecessarily over-parameterized for the data at hand. The sex-linked dominant and autosomal dominant models were also compared, by means of the age specific morbidity risks and sibs and children. Both models provided a fairly close fit of expectation and observation, but the sex-linked model was preferable. Although the genetic conclusions cannot automatically be applied to other material, the analytical techniques should be useful elsewhere. Other uses of the penetrance function were indicated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23042/1/0000614.pd

Age- and sex-based variation in helminth infection of helmeted guineafowl (Numida meleagris) with comments on Swainson's spurfowl (Pternistis swainsonii) and Orange River francolin (Scleroptila levaillantoides)

Gastrointestinal tracts from 48 helmeted guineafowl (Numida meleagris), five Swainson's spurfowl (Pternistis swainsonii) and a single Orange River francolin (Scleroptila levaillantoides) were examined for helminth parasites. Twelve species of helminths were found in helmeted guineafowl, comprising six nematodes, five cestodes and a single acanthocephalan. Six species of nematodes were recovered from Swainson's spurfowl and a single nematode was recovered from the Orange River francolin. First-year guineafowl had more than twice the intensity of infection than did adult guineafowl, particularly regarding the acanthocephalan Mediorhynchus gallinarum, the caecal nematodes Subulura dentigera and S. suctoria, and the cestodes Octopetalum numida, Hymenolepis cantaniana and Numidella numida. Female guineafowl had significantly higher intensities of infection than males, especially concerning M. gallinarum, S. dentigera and N. numida and the nematode Gongylonema congolense. The recovery of the cestode Retinometra sp. from helmeted guineafowl constitutes a new host-parasite record

Brief report: Search for DNA markers in two autistic males with the fragile X syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44601/1/10803_2005_Article_BF02211885.pd

Phototrophic Fe(II)-oxidation in the chemocline of a ferruginous meromictic lake

© 2014 Walter, Picazo, Miracle, Vicente, Camacho, Aragno and Zopfi. Precambrian Banded Iron Formation (BIF) deposition was conventionally attributed to the precipitation of iron-oxides resulting from the abiotic reaction of ferrous iron (Fe(II)) with photosynthetically produced oxygen. Earliest traces of oxygen date from 2.7 Ga, thus raising questions as to what may have caused BIF precipitation before oxygenic photosynthesis evolved. The discovery of anoxygenic phototrophic bacteria thriving through the oxidation of Fe(II) has provided support for a biological origin for some BIFs, but despite reports suggesting that anoxygenic phototrophs may oxidize Fe(II) in the environment, a model ecosystem of an ancient ocean where they are demonstrably active was lacking. Here we show that anoxygenic phototrophic bacteria contribute to Fe(II) oxidation in the water column of the ferruginous sulfate-poor, meromictic lake La Cruz (Spain). We observed in-situ photoferrotrophic activity through stimulation of phototrophic carbon uptake in the presence of Fe(II), and determined light-dependent Fe(II)-oxidation by the natural chemocline microbiota. Moreover, a photoferrotrophic bacterium most closely related to Chlorobium ferrooxidans was enriched from the ferruginous water column. Our study for the first time demonstrates a direct link between anoxygenic photoferrotrophy and the anoxic precipitation of Fe(III)-oxides in a ferruginous water column, providing a plausible mechanism for the bacterial origin of BIFs before the advent of free oxygen. However, photoferrotrophs represent only a minor fraction of the anoxygenic phototrophic community with the majority apparently thriving by sulfur cycling, despite the very low sulfur content in the ferruginous chemocline of Lake La Cruz

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

HIV-1 Residual Viremia Correlates with Persistent T-Cell Activation in Poor Immunological Responders to Combination Antiretroviral Therapy

BACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14(high) CD16(-) and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ T-cell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14(high) CD16(-) monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. CONCLUSIONS:Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART

Comment letters to the National Commission on Commission on Fraudulent Financial Reporting, 1987 (Treadway Commission) Vol. 1

https://egrove.olemiss.edu/aicpa_sop/1661/thumbnail.jp

Detrital zircon age and provenance constraints on late Paleozoic ice-sheet growth and dynamics in Western and Central Australia

U–Pb dating and Hf-isotope provenance analysis of detrital zircons from the glaciogenic lower Permian Grant Group of the Canning Basin indicate sources principally from basement terranes in central Australia, with subordinate components from terranes to the south and north. Integrating these data with field outcrop and subsurface evidence for ice sheets, including glacial valleys and striated pavements along the southern and northern margins of the basin, suggests that continental ice sheets extended over several Precambrian upland areas of western and central Australia during the late Paleozoic ice age (LPIA). The youngest zircons constrain the maximum age for contemporaneous ice sheet development to the late Carboniferous (Kasimovian), whereas palynology provides a minimum age of early Permian (Asselian–Sakmarian). Considering the palynological age of the Grant Group within the context of regional and global climate proxies, the main phase of continental ice sheet growth was possibly in the Ghzelian–Asselian. The presence of ice sheets older than Kasimovian in western and central Australia remains difficult to prove given a regional gap in deposition possibly covering the mid-Bashkirian to early Ghzelian within the main depocentres and even larger along basin margins, and the poor evidence for older Carboniferous glacial facies. There is also no evidence for extensive glacial facies younger than mid-Sakmarian in this region as opposed to eastern Australia where the youngest regional glacial phase was Guadalupian

Comparison of in silico strategies to prioritize rare genomic variants impacting RNA splicing for the diagnosis of genomic disorders

From Springer Nature via Jisc Publications RouterHistory: received 2021-03-09, accepted 2021-09-13, registration 2021-10-01, online 2021-10-18, pub-electronic 2021-10-18, collection 2021-12Publication status: PublishedFunder: Wellcome Trust; Grant(s): RP-2016-07-011, 200990/Z/16/ZFunder: Health Education EnglandAbstract: The development of computational methods to assess pathogenicity of pre-messenger RNA splicing variants is critical for diagnosis of human disease. We assessed the capability of eight algorithms, and a consensus approach, to prioritize 249 variants of uncertain significance (VUSs) that underwent splicing functional analyses. The capability of algorithms to differentiate VUSs away from the immediate splice site as being ‘pathogenic’ or ‘benign’ is likely to have substantial impact on diagnostic testing. We show that SpliceAI is the best single strategy in this regard, but that combined usage of tools using a weighted approach can increase accuracy further. We incorporated prioritization strategies alongside diagnostic testing for rare disorders. We show that 15% of 2783 referred individuals carry rare variants expected to impact splicing that were not initially identified as ‘pathogenic’ or ‘likely pathogenic’; one in five of these cases could lead to new or refined diagnoses