African-American mitochondrial DNAs often match mtDNAs found in multiple African ethnic groups

BACKGROUND: Mitochondrial DNA (mtDNA) haplotypes have become popular tools for tracing maternal ancestry, and several companies offer this service to the general public. Numerous studies have demonstrated that human mtDNA haplotypes can be used with confidence to identify the continent where the haplotype originated. Ideally, mtDNA haplotypes could also be used to identify a particular country or ethnic group from which the maternal ancestor emanated. However, the geographic distribution of mtDNA haplotypes is greatly influenced by the movement of both individuals and population groups. Consequently, common mtDNA haplotypes are shared among multiple ethnic groups. We have studied the distribution of mtDNA haplotypes among West African ethnic groups to determine how often mtDNA haplotypes can be used to reconnect Americans of African descent to a country or ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA hypervariable segment I (HVS-I) usually provides sufficient information to assign a particular mtDNA to the proper haplogroup, and it contains most of the variation that is available to distinguish a particular mtDNA haplotype from closely related haplotypes. In this study, samples of general African-American and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches recorded for each sample. RESULTS: When two independent African-American samples were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly matched common haplotypes that were shared among multiple African ethnic groups. Another 40% did not match any sequence in the database, and fewer than 10% were an exact match to a sequence from a single African ethnic group. Differences in the regional distribution of haplotypes were observed in the African database, and the African-American haplotypes were more likely to match haplotypes found in ethnic groups from West or West Central Africa than those found in eastern or southern Africa. Fewer than 14% of the African-American mtDNA sequences matched sequences from only West Africa or only West Central Africa. CONCLUSION: Our database of sub-Saharan mtDNA sequences includes the most common haplotypes that are shared among ethnic groups from multiple regions of Africa. These common haplotypes have been found in half of all sub-Saharan Africans. More than 60% of the remaining haplotypes differ from the common haplotypes at a single nucleotide position in the HVS-I region, and they are likely to occur at varying frequencies within sub-Saharan Africa. However, the finding that 40% of the African-American mtDNAs analyzed had no match in the database indicates that only a small fraction of the total number of African haplotypes has been identified. In addition, the finding that fewer than 10% of African-American mtDNAs matched mtDNA sequences from a single African region suggests that few African Americans might be able to trace their mtDNA lineages to a particular region of Africa, and even fewer will be able to trace their mtDNA to a single ethnic group. However, no firm conclusions should be made until a much larger database is available. It is clear, however, that when identical mtDNA haplotypes are shared among many ethnic groups from different parts of Africa, it is impossible to determine which single ethnic group was the source of a particular maternal ancestor based on the mtDNA sequence

A model of direction selectivity in the starburst amacrine cell network

Displaced starburst amacrine cells (SACs) are retinal interneurons that exhibit GABAA receptor-mediated and Cl− cotransporter-mediated, directionally selective (DS) light responses in the rabbit retina. They depolarize to stimuli that move centrifugally through the receptive field surround and hyperpolarize to stimuli that move centripetally through the surround (Gavrikov et al, PNAS 100(26):16047–16052, 2003, PNAS 103(49):18793–18798, 2006). They also play a key role in the activity of DS ganglion cells (DS GC; Amthor et al, Vis Neurosci 19:495–509 2002; Euler et al, Nature 418:845–852, 2002; Fried et al, Nature 420:411– 414, 2002; Gavrikov et al, PNAS 100(26):16047–16052, 2003, PNAS 103(49):18793–18798, 2006; Lee and Zhou, Neuron 51:787–799 2006; Yoshida et al, Neuron 30:771–780, 2001). In this paper we present a model of strong DS behavior of SACs which relies on the GABA-mediated communication within a tightly interconnected network of these cells and on the glutamate signal that the SACs receive from bipolar cells (a presynaptic cell that receives input from cones). We describe how a moving light stimulus can produce a large, sustained depolarization of the SAC dendritic tips that point in the direction that the stimulus moves (i.e., centrifugal motion), but produce a minimal depolarization of the dendritic tips that point in the opposite direction (i.e., centripetal motion). This DS behavior, which is quantified based on the relative size and duration of the depolarizations evoked by stimulus motion at dendritic tips pointing in opposite directions, is robust to changes of many different parameter values and consistent with experimental data. In addition, the DS behavior is strengthened under the assumptions that the Cl− cotransporters Na + -K + -Cl − and K + -Cl − are located in different regions of the SAC dendritic tree (Gavrikov et al, PNAS 103(49):18793–18798, 2006) and that GABA evokes a long-lasting response (Gavrikov et al, PNAS 100(26):16047–16052, 2003, PNAS 103(49):18793–18798, 2006; Lee and Zhou, Neuron 51:787–799, 2006). A possible mechanism is discussed based on the generation of waves of local glutamate and GABA secretion, and their postsynaptic interplay as the waves travel between cell compartments

Serum Uric Acid and Adiposity: Deciphering Causality Using a Bidirectional Mendelian Randomization Approach

Background: Although the relationship between serum uric acid (SUA) and adiposity is well established, the direction of the causality is still unclear in the presence of conflicting evidences. We used a bidirectional Mendelian randomization approach to explore the nature and direction of causality between SUA and adiposity in a population-based study of Caucasians aged 35 to 75 years. Methods and Findings: We used, as instrumental variables, rs6855911 within the SUA gene SLC2A9 in one direction, and combinations of SNPs within the adiposity genes FTO, MC4R and TMEM18 in the other direction. Adiposity markers included weight, body mass index, waist circumference and fat mass. We applied a two-stage least squares regression: a regression of SUA/adiposity markers on our instruments in the first stage and a regression of the response of interest on the fitted values from the first stage regression in the second stage. SUA explained by the SLC2A9 instrument was not associated to fat mass (regression coefficient [95 % confidence interval]: 0.05 [20.10, 0.19] for fat mass) contrasting with the ordinary least square estimate (0.37 [0.34, 0.40]). By contrast, fat mass explained by genetic variants of the FTO, MC4R and TMEM18 genes was positively and significantly associated to SUA (0.31 [0.01, 0.62]), similar to the ordinary least square estimate (0.27 [0.25, 0.29]). Results were similar for the other adiposity markers. Conclusions: Using a bidirectional Mendelian randomization approach in adult Caucasians, our findings suggest tha

Polymorphisms in the Presumptive Promoter Region of the SLC2A9 Gene Are Associated with Gout in a Chinese Male Population

BACKGROUND: Glucose transporter 9 (GLUT9) is a high-capacity/low-affinity urate transporter. To date, several recent genome-wide association studies (GWAS) and follow-up studies have identified genetic variants of SLC2A9 associated with urate concentrations and susceptibility to gout. We therefore investigated associations between gout and polymorphisms and haplotypes in the presumptive promoter region of GLUT9 in Chinese males. METHODOLOGY/PRINCIPAL FINDINGS: The approximately 2000 bp presumptive promoter region upstream of the start site of exon 1 of GLUT9 was sequenced and subjected to genetic analysis. A genotype-phenotype correlation was performed and polymorphisms-induced changes in transcription factor binding sites were predicted. Of 21 SNPs identified in GLUT9, five had not been previously reported. Two of the SNPs (rs13124007 and rs6850166) were associated with susceptibility to gout (p = 0.009 and p = 0.042, respectively). The C allele of rs13124007 appeared to be the risk allele for predisposition to gout (p = 0.006, OR 1.709 [95% CI 1.162-2.514]). For rs6850166, an increased risk of gout was associated with the A allele (p = 0.029, OR 1.645 [95% CI 1.050-2.577]). After Bonferroni correction, there was statistically difference in rs13124007 allele frequencies between gout cases and controls (P = 0.042). Haplotype analyses showed that haplotype GG was a protective haplotype (p = 0.0053) and haplotype CA was associated with increased risk of gout (p = 0.0326). Genotype-phenotype analysis among gout patients revealed an association of rs13124007 with serum triglycerides levels (P = 0.001). The C to G substitution in polymorphism rs13124007 resulted in a loss of a binding site for transcription factor interferon regulatory factor 1 (IRF-1). CONCLUSIONS/SIGNIFICANCE: Polymorphisms rs13124007 and rs6850166 are associated with susceptibility to gout in Chinese males

Topological Qubits with Majorana Fermions in Trapped Ions

We propose a method of encoding a topologically-protected qubit using Majorana fermions in a trapped-ion chain. This qubit is protected against major sources of decoherence, while local operations and measurements can be realized. Furthermore, we show that an efficient quantum interface and memory for arbitrary multiqubit photonic states can be built, encoding them into a set of entangled Majorana-fermion qubits inside cavities.Comment: 9 pages, 2 figure

Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog

Allantoin is the end product of purine catabolism in all mammals except humans, great apes, and one breed of dog, the Dalmatian. Humans and Dalmatian dogs produce uric acid during purine degradation, which leads to elevated levels of uric acid in blood and urine and can result in significant diseases in both species. The defect in Dalmatians results from inefficient transport of uric acid in both the liver and renal proximal tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, an interbreed backcross was used. Linkage mapping localized the huu trait to CFA03, which excluded the obvious urate transporter 1 gene, SLC22A12. Positional cloning placed the locus in a minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of 333 kb containing only four genes was homozygous in all Dalmatians. Sequence and expression analyses of the SLC2A9 gene indicated three possible mutations, a missense mutation (G616T;C188F) and two promoter mutations that together appear to reduce the expression levels of one of the isoforms. The missense mutation is associated with hyperuricosuria in the Dalmatian, while the promoter SNPs occur in other unaffected breeds of dog. Verification of the causative nature of these changes was obtained when hyperuricosuric dogs from several other breeds were found to possess the same combination of mutations as found in the Dalmatian. The Dalmatian dog model of hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for uric acid transport in mammals

Engaging diverse underserved communities to bridge the mammography divide

<p>Abstract</p> <p>Background</p> <p>Breast cancer screening continues to be underutilized by the population in general, but is particularly underutilized by traditionally underserved minority populations. Two of the most at risk female minority groups are American Indians/Alaska Natives (AI/AN) and Latinas. American Indian women have the poorest recorded 5-year cancer survival rates of any ethnic group while breast cancer is the number one cause of cancer mortality among Latina women. Breast cancer screening rates for both minority groups are near or at the lowest among all racial/ethnic groups. As with other health screening behaviors, women may intend to get a mammogram but their intentions may not result in initiation or follow through of the examination process. An accumulating body of research, however, demonstrates the efficacy of developing 'implementation intentions' that define when, where, and how a specific behavior will be performed. The formulation of intended steps in addition to addressing potential barriers to test completion can increase a person's self-efficacy, operationalize and strengthen their intention to act, and close gaps between behavioral intention and completion. To date, an evaluation of the formulation of implementation intentions for breast cancer screening has not been conducted with minority populations.</p> <p>Methods/Design</p> <p>In the proposed program, community health workers will meet with rural-dwelling Latina and American Indian women one-on-one to educate them about breast cancer and screening and guide them through a computerized and culturally tailored "implementation intentions" program, called <it>Healthy Living Kansas - Breast Health</it>, to promote breast cancer screening utilization. We will target Latina and AI/AN women from two distinct rural Kansas communities. Women attending community events will be invited by CHWs to participate and be randomized to either a mammography "implementation intentions" (<b>MI</b>^<b>2</b>) intervention or a comparison general breast cancer prevention informational intervention (<b>C</b>). CHWs will be armed with notebook computers loaded with our Healthy Living Kansas - Breast Health program and guide their peers through the program. Women in the <b>MI</b>^{<b>2 </b>}condition will receive assistance with operationalizing their screening intentions and identifying and addressing their stated screening barriers with the goal of guiding them toward accessing screening services near their community. Outcomes will be evaluated at 120-days post randomization via self-report and will include mammography utilization status, barriers, and movement along a behavioral stages of readiness to screen model.</p> <p>Discussion</p> <p>This highly innovative project will be guided and initiated by AI/AN and Latina community members and will test the practical application of emerging behavioral theory among minority persons living in rural communities.</p> <p>Trial Registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267110">NCT01267110</a></p

Conflicted Emotions Following Trust-based Interaction

We investigated whether 20 emotional states, reported by 170 participants after participating in a Trust game, were experienced in a patterned way predicted by the “Recalibrational Model” or Valence Models. According to the Recalibrational Model, new information about trust-based interaction outcomes triggers specific sets of emotions. Unlike Valence Models that predict reports of large sets of either positive or negative emotional states, the Recalibrational Model predicts the possibility of conflicted (concurrent positive and negative) emotional states. Consistent with the Recalibrational Model, we observed reports of conflicted emotional states activated after interactions where trust was demonstrated but trustworthiness was not. We discuss the implications of having conflicted goals and conflicted emotional states for both scientific and well-being pursuits