Little is known about the history of click-speaking populations in Africa. Prior genetic studies revealed that the click-speaking Hadza of eastern Africa are as distantly related to click speakers of southern Africa as are most other African populations. The Sandawe, who currently live within 150 km of the Hadza, are the only other population in eastern Africa whose language has been classified as part of the Khoisan language family. Linguists disagree on whether there is any detectable relationship between the Hadza and Sandawe click languages. We characterized both mtDNA and Y chromosome variation of the Sandawe, Hadza, and neighboring Tanzanian populations. New genetic data show that the Sandawe and southern African click speakers share rare mtDNA and Y chromosome haplogroups; however, common ancestry of the 2 populations dates back >35,000 years. These data also indicate that common ancestry of the Hadza and Sandawe populations dates back >15,000 years. These findings suggest that at the time of the spread of agriculture and pastoralism, the click-speaking populations were already isolated from one another and are consistent with relatively deep linguistic divergence among the respective click languages. 相似文献
Sexual diversity expressed by Curcurbitaceae species is a primary example of developmental plasticity in plants. Ethylene,
which promotes femaleness (carpel development), plays a key role in sex determination. We sought to determine the critical
location for ethylene perception in developing floral primodia. The dominant negative Arabidopsis ethylene response mutant
gene, etr1-1, was introduced into melon (Cucumis melo L.) plants under control of the constitutive cauliflower mosaic virus (CaMV) 35S promoter, or floral-targeted Apetela3 (AP3) and Crab’s Claw (CRC) promoters, which in Arabidopsis, promote expression in petal and stamen, and carpel and nectary primordia, respectively.
Based on effects of exogenous ethylene, it was predicted that inhibition of ethylene perception by carpel primordia would
inhibit carpel development. Constitutive expression of etr1-1 caused several phenotypes associated with ethylene insensitivity, verifying that etr1-1 inhibits ethylene perception in the heterologous melon system. Carpel-bearing bud production was essentially abolished in
35S::etr1-1 melons, providing direct demonstration of the requirement for ethylene perception for carpel development. CRC::etr1-1 plants, however, showed enhanced femaleness as manifested by earlier and increased number of carpel-bearing buds, and production
of female (rather than bisexual) buds. Despite increased carpel-bearing bud formation, a greater proportion of the CRC::etr1-1 carpel-bearing buds aborted before anthesis. AP3::etr1-1 plants showed increased maleness by nearly exclusive staminate flower production, and poorly developed carpels in the rare
bisexual flowers. These results indicate that ethylene perception by the stamen (or petal) primordia plays a critical role
in promoting carpel development at the time of sex determination, while ethylene perception by the carpel is important for
maturation of carpel-bearing flowers to anthesis. 相似文献
Developmental abnormalities of myelination are observed in the brains of laminin-deficient humans and mice. The mechanisms by which these defects occur remain unknown. It has been proposed that, given their central role in mediating extracellular matrix (ECM) interactions, integrin receptors are likely to be involved. However, it is a non-integrin ECM receptor, dystroglycan, that provides the key linkage between the dystrophin-glycoprotein complex (DGC) and laminin in skeletal muscle basal lamina, such that disruption of this bridge results in muscular dystrophy. In addition, the loss of dystroglycan from Schwann cells causes myelin instability and disorganization of the nodes of Ranvier. To date, it is unknown whether dystroglycan plays a role during central nervous system (CNS) myelination. Here, we report that the myelinating glia of the CNS, oligodendrocytes, express and use dystroglycan receptors to regulate myelin formation. In the absence of normal dystroglycan expression, primary oligodendrocytes showed substantial deficits in their ability to differentiate and to produce normal levels of myelin-specific proteins. After blocking the function of dystroglycan receptors, oligodendrocytes failed both to produce complex myelin membrane sheets and to initiate myelinating segments when co-cultured with dorsal root ganglion neurons. By contrast, enhanced oligodendrocyte survival in response to the ECM, in conjunction with growth factors, was dependent on interactions with beta-1 integrins and did not require dystroglycan. Together, these results indicate that laminins are likely to regulate CNS myelination by interacting with both integrin receptors and dystroglycan receptors, and that oligodendrocyte dystroglycan receptors may have a specific role in regulating terminal stages of myelination, such as myelin membrane production, growth, or stability. 相似文献
Hemipteran insect vectors transmit the majority of plant pathogens. Acquisition of pathogenic bacteria by these piercing/sucking insects requires intimate associations between the bacterial cells and insect surfaces. Lipopolysaccharide (LPS) is the predominant macromolecule displayed on the cell surface of Gram-negative bacteria and thus mediates bacterial interactions with the environment and potential hosts. We hypothesized that bacterial cell surface properties mediated by LPS would be important in modulating vector-pathogen interactions required for acquisition of the bacterial plant pathogen Xylella fastidiosa, the causative agent of Pierce''s disease of grapevines. Utilizing a mutant that produces truncated O antigen (the terminal portion of the LPS molecule), we present results that link this LPS structural alteration to a significant decrease in the attachment of X. fastidiosa to blue-green sharpshooter foreguts. Scanning electron microscopy confirmed that this defect in initial attachment compromised subsequent biofilm formation within vector foreguts, thus impairing pathogen acquisition. We also establish a relationship between O antigen truncation and significant changes in the physiochemical properties of the cell, which in turn affect the dynamics of X. fastidiosa adhesion to the vector foregut. Lastly, we couple measurements of the physiochemical properties of the cell with hydrodynamic fluid shear rates to produce a Comsol model that predicts primary areas of bacterial colonization within blue-green sharpshooter foreguts, and we present experimental data that support the model. These results demonstrate that, in addition to reported protein adhesin-ligand interactions, O antigen is crucial for vector-pathogen interactions, specifically in the acquisition of this destructive agricultural pathogen. 相似文献
Through a multi-center collaboration study, we here report six individuals from five unrelated families, with mutations in KAT6A/MOZ detected by whole-exome sequencing. All five different de novo heterozygous truncating mutations were located in the C-terminal transactivation domain of KAT6A: {"type":"entrez-nucleotide","attrs":{"text":"NM_001099412.1","term_id":"150378462","term_text":"NM_001099412.1"}}NM_001099412.1: c.3116_3117 delCT, p.(Ser1039∗); c.3830_3831insTT, p.(Arg1278Serfs∗17); c.3879 dupA, p.(Glu1294Argfs∗19); c.4108G>T p.(Glu1370∗) and c.4292 dupT, p.(Leu1431Phefs∗8). An additional subject with a 0.23 MB microdeletion including the entire KAT6A reading frame was identified with genome-wide array comparative genomic hybridization. Finally, by detailed clinical characterization we provide evidence that heterozygous mutations in KAT6A cause a distinct intellectual disability syndrome. The common phenotype includes hypotonia, intellectual disability, early feeding and oromotor difficulties, microcephaly and/or craniosynostosis, and cardiac defects in combination with subtle facial features such as bitemporal narrowing, broad nasal tip, thin upper lip, posteriorly rotated or low-set ears, and microretrognathia. The identification of human subjects complements previous work from mice and zebrafish where knockouts of Kat6a/kat6a lead to developmental defects. 相似文献
Individuals at risk of developing Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability. A growing body of evidence suggests that perturbations in the glutamatergic tripartite synapse may underlie this hyperexcitability. Here, we used a tau mouse model of AD (rTg(TauP301L)4510) to examine the effects of tau pathology on hippocampal glutamate regulation. We found a 40% increase in hippocampal vesicular glutamate transporter, which packages glutamate into vesicles, and has previously been shown to influence glutamate release, and a 40% decrease in hippocampal glutamate transporter 1, the major glutamate transporter responsible for removing glutamate from the extracellular space. To determine whether these alterations affected glutamate regulation in vivo, we measured tonic glutamate levels, potassium‐evoked glutamate release, and glutamate uptake/clearance in the dentate gyrus, cornu ammonis 3(CA3), and cornu ammonis 1(CA1) regions of the hippocampus. P301L tau expression resulted in a 4‐ and 7‐fold increase in potassium‐evoked glutamate release in the dentate gyrus and CA3, respectively, and significantly decreased glutamate clearance in all three regions. Both release and clearance correlated with memory performance in the hippocampal‐dependent Barnes maze task. Alterations in mice expressing P301L were observed at a time when tau pathology was subtle and before readily detectable neuron loss. These data suggest novel mechanisms by which tau may mediate hyperexcitability.
While several studies have examined the accuracy of direct genomic
breeding values (DGV) within and across purebred cattle populations, the accuracy
of DGV in crossbred or multi-breed cattle populations has been less well examined.
Interest in the use of genomic tools for both selection and management has
increased within the hybrid seedstock and commercial cattle sectors and research
is needed to determine their efficacy. We predicted DGV for six traits using
training populations of various sizes and alternative Bayesian models for a
population of 3240 crossbred animals. Our objective was to compare alternate
models with different assumptions regarding the distributions of single nucleotide
polymorphism (SNP) effects to determine the optimal model for enhancing
feasibility of multi-breed DGV prediction for the commercial beef industry.
Results
Realized accuracies ranged from 0.40 to 0.78. Randomly assigning 60
to 70% of animals to training (n ≈ 2000 records) yielded DGV accuracies with the
smallest coefficients of variation. Mixture models (BayesB95, BayesCπ) and models
that allow SNP effects to be sampled from distributions with unequal variances
(BayesA, BayesB95) were advantageous for traits that appear or are known to be
influenced by large-effect genes. For other traits, models differed little in
prediction accuracy (~0.3 to 0.6%), suggesting that they are mainly controlled by
small-effect loci.
Conclusions
The proportion (60 to 70%) of data allocated to training that
optimized DGV accuracy and minimized the coefficient of variation of accuracy was
similar to large dairy populations. Larger effects were estimated for some SNPs
using BayesA and BayesB95 models because they allow unequal SNP variances. This
substantially increased DGV accuracy for Warner-Bratzler Shear Force, for which
large-effect quantitative trait loci (QTL) are known, while no loss in accuracy
was observed for traits that appear to follow the infinitesimal model. Large
decreases in accuracy (up to 0.07) occurred when SNPs that presumably tag
large-effect QTL were over-regressed towards the mean in BayesC0 analyses. The DGV
accuracies achieved here indicate that genomic selection has predictive utility in
the commercial beef industry and that using models that reflect the genomic
architecture of the trait can have predictive advantages in multi-breed
populations.
Electronic supplementary material
The online version of this article (doi:10.1186/s12711-015-0106-8) contains supplementary material, which is available to authorized
users. 相似文献