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1.  Scaling of Geometric Quantum Discord Close to a Topological Phase Transition 
Scientific Reports  2014;4:4473.
Quantum phase transition is one of the most interesting aspects in quantum many-body systems. Recently, geometric quantum discord has been introduced to signature the critical behavior of various quantum systems. However, it is well-known that topological quantum phase transition can not be described by the conventional Landau's symmetry breaking theory, and thus it is unknown that whether previous study can be applicable in this case. Here, we study the topological quantum phase transition in Kitaev's 1D p-wave spinless quantum wire model in terms of its ground state geometric quantum discord. The derivative of geometric quantum discord is nonanalytic at the critical point, in both zero temperature and finite temperature cases. The scaling behavior and the universality are verified numerically. Therefore, our results clearly show that all the key ingredients of the topological phase transition can be captured by the nearest neighbor and long-range geometric quantum discord.
doi:10.1038/srep04473
PMCID: PMC3966051  PMID: 24667280
2.  Pharmacological characteristics and efficacy of a novel anti-angiogenic antibody FD006 in corneal neovascularization 
BMC Biotechnology  2014;14:17.
Background
Vascular endothelial growth factor (VEGF) is a key angiogenic factors. It plays an important role in both physiologic and pathologic angiogenesis and increases permeability across the vessels. Using antibody phage display technology, we obtained a novel anti-VEGFA IgG, named as FD006. In this study, the pharmacological characteristics and efficacy of FD006 in corneal neovascularization (CoNV) were evaluated.
Results
FD006 was predicted to have similar binding mode to bevacizumab. Experimental analysis showed that the binding ability of FD006 seemed a little stronger than bevacizumab, for the EC50 of FD006 to bind VEGF analyzed by ELISA was about 0.037 μg/mL while that of bevacizumab was 0.18 μg/mL. Binding kinetics assays showed similar results that FD006 possessed 2-fold higher affinity to bind VEGF than bevacizumab due to slower dissociation rate of FD006; meanwhile, FD006 inhibited the VEGF-induced proliferation of HUVEC with an IC50 value of 0.031 ± 0.0064 μg/ml, which seemed similar or a litter better than bevacizumab (0.047 ± 0.0081 μg/ml). The subconjunctival administration of FD006, bevacizumab or dexamethasone could significantly inhibit the growth of CoNV contrasting to N.S (p < 0.01). At the early stage, FD006 showed better inhibitory effect on the growth of CoNV compared with bevacizumab (p < 0.05). Western blot analysis showed that FD006 could inhibit the expression of VEGF, VEGFR-1, VEGFR-2, MMP-9 and ICAM-1, which could explain its favorable anti-angiogenic activity.
Conclusions
The pharmacological characteristics of FD006 were similar or even a little better than bevacizumab in inhibiting corneal neovascularization.
doi:10.1186/1472-6750-14-17
PMCID: PMC3942068  PMID: 24575750
Neovascularization; Cornea; Bevacizumab; Angiogenesis; Anti-angiogenic treatment
3.  Modeling recent human evolution in mice by expression of a selected EDAR variant 
Cell  2013;152(4):691-702.
Summary
An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in Central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knock-in mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify novel biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans.
doi:10.1016/j.cell.2013.01.016
PMCID: PMC3575602  PMID: 23415220
4.  Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A 
Background
This study aims to introduce the diagnosis and surgical treatment of the rare disease multiple endocrine neoplasia type 2A (MEN 2A).
Methods
Thirteen cases of MEN 2A were diagnosed as medullary thyroid carcinoma (MTC) and pheochromocytoma by biochemical tests and imaging examination. They were treated by bilateral adrenal tumor excision or laparoscopic surgery.
Results
Nine patients were treated by bilateral adrenal tumor excision and the remaining four were treated by laparoscopic surgery for pheochromocytoma. Ten patients were treated by total thyroidectomy and bilateral lymph nodes dissection and the remaining three were treated by unilateral thyroidectomy for MTC. Up to now, three patients have died of MTC distant metastasis.
Conclusions
We confirmed that MEN 2A can be diagnosed by biochemical tests and imaging examination when genetic testing is not available. Surgical excision is the predominant way to treat MEN 2A; pheochromocytoma should be excised at first when pheochromocytoma and MTC occur simultaneously.
doi:10.1186/1477-7819-12-8
PMCID: PMC3895851  PMID: 24400812
Diagnosis; Multiple endocrine neoplasia type 2A; Surgical excision; Treatment
5.  Detecting Genetic Association of Common Human Facial Morphological Variation Using High Density 3D Image Registration 
PLoS Computational Biology  2013;9(12):e1003375.
Human facial morphology is a combination of many complex traits. Little is known about the genetic basis of common facial morphological variation. Existing association studies have largely used simple landmark-distances as surrogates for the complex morphological phenotypes of the face. However, this can result in decreased statistical power and unclear inference of shape changes. In this study, we applied a new image registration approach that automatically identified the salient landmarks and aligned the sample faces using high density pixel points. Based on this high density registration, three different phenotype data schemes were used to test the association between the common facial morphological variation and 10 candidate SNPs, and their performances were compared. The first scheme used traditional landmark-distances; the second relied on the geometric analysis of 15 landmarks and the third used geometric analysis of a dense registration of ∼30,000 3D points. We found that the two geometric approaches were highly consistent in their detection of morphological changes. The geometric method using dense registration further demonstrated superiority in the fine inference of shape changes and 3D face modeling. Several candidate SNPs showed potential associations with different facial features. In particular, one SNP, a known risk factor of non-syndromic cleft lips/palates, rs642961 in the IRF6 gene, was validated to strongly predict normal lip shape variation in female Han Chinese. This study further demonstrated that dense face registration may substantially improve the detection and characterization of genetic association in common facial variation.
Author Summary
Heritability of human facial appearance is an intriguing question to the general public and researchers. Although it is known that some facial features are highly heritable, the exact genetic basis is unknown. Previous studies used simple linear measurements such as landmark distances, to evaluate the facial shape variation. Such approaches, although easy to carry out, may lack statistical power and miss complex morphological changes. In this study, we utilized a new 3D face registration method that enables subtle differences to be detected at high resolution 3D images. Based on this, we tried to test and characterize the associations of 10 candidate genetic variants to common facial morphological variations. Different types of phenotype data were extracted and compared in the association tests. Our results show that geometry based data performed better than simple distance based data. Furthermore, high density geometric data outstood the others in capturing small shape changes and modeling the 3D face visualization. Interestingly, a genetic variant from IRF6 gene, which is also a well-known risk factor of non-syndrome cleft lip, was found to strongly predispose the mouth shape in Han Chinese females.
doi:10.1371/journal.pcbi.1003375
PMCID: PMC3854494  PMID: 24339768
6.  Somatostatin Receptor-Based Molecular Imaging and Therapy for Neuroendocrine Tumors 
BioMed Research International  2013;2013:102819.
Neuroendocrine tumors (NETs) are tumors originated from neuroendocrine cells in the body. The localization and the detection of the extent of NETs are important for diagnosis and treatment, which should be individualized according to the tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity and specificity is achieved by nuclear medicine method using single photon-emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor imaging (SRI) using SPECT or PET as a whole-body imaging technique has become a crucial part of the management of NETs. The radiotherapy with somatostatin analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium-90, has been proved to be an option of therapy for patients with unresectable and metastasized NETs. Molecular imaging can deliver an important message to improve the outcome for patients with NETs by earlier diagnosis, better choice of the therapeutic method, and evaluation of the therapeutic response.
doi:10.1155/2013/102819
PMCID: PMC3784148  PMID: 24106690
7.  Neurofibrosarcoma of the gallbladder: a case report 
Sarcoma of the gallbladder is a rare entity. This report presents an extremely rare clinical case of a neurofibrosarcoma of the gallbladder. On examination, a mass was felt in the right hypochondrium. An ultrasound of the abdomen showed a mass in the gallbladder. Computed tomography (CT) scan of the abdomen showed a grossly distended gallbladder with soft tissue mass in the gallbladder. The mass was diagnosed as carcinoma of the gallbladder and an extended cholecystectomy was performed. Histopathological examination revealed spindle-cell proliferation and the possibility of a malignant tumor of mesenchymal origin.
doi:10.1186/1477-7819-11-189
PMCID: PMC3765290  PMID: 23938157
Gallbladder; Neurofibrosarcoma
8.  Automatic landmark annotation and dense correspondence registration for 3D human facial images 
BMC Bioinformatics  2013;14:232.
Background
Traditional anthropometric studies of human face rely on manual measurements of simple features, which are labor intensive and lack of full comprehensive inference. Dense surface registration of three-dimensional (3D) human facial images holds great potential for high throughput quantitative analyses of complex facial traits. However there is a lack of automatic high density registration method for 3D faical images. Furthermore, current approaches of landmark recognition require further improvement in accuracy to support anthropometric applications.
Result
Here we describe a novel non-rigid registration method for fully automatic 3D facial image mapping. This method comprises two steps: first, seventeen facial landmarks are automatically annotated, mainly via PCA-based feature recognition following 3D-to-2D data transformation. Second, an efficient thin-plate spline (TPS) protocol is used to establish the dense anatomical correspondence between facial images, under the guidance of the predefined landmarks. We demonstrate that this method is highly accurate in landmark recognition, with an average RMS error of ~1.7 mm. The registration process is highly robust, even for different ethnicities.
Conclusion
This method supports fully automatic registration of dense 3D facial images, with 17 landmarks annotated at greatly improved accuracy. A stand-alone software has been implemented to assist high-throughput high-content anthropometric analysis.
doi:10.1186/1471-2105-14-232
PMCID: PMC3724574  PMID: 23870191
3D face; Facial morphology; Registration; Landmark localization; Dense correspondence
9.  Human Infection with Candidatus Neoehrlichia mikurensis, China 
Emerging Infectious Diseases  2012;18(10):1636-1639.
To identify Candidatus Neoehrlichia mikurensis infection in northeastern China, we tested blood samples from 622 febrile patients. We identified in 7 infected patients and natural foci for this bacterium. Field surveys showed that 1.6% of ticks and 3.8% of rodents collected from residences of patients were also infected.
doi:10.3201/eid1810.120594
PMCID: PMC3471638  PMID: 23017728
Candidatus Neoehrlichia mikurensis; bacteria; human infection; ticks; rodents; vector-borne infections; China
10.  Genome Patterns of Selection and Introgression of Haplotypes in Natural Populations of the House Mouse (Mus musculus) 
PLoS Genetics  2012;8(8):e1002891.
General parameters of selection, such as the frequency and strength of positive selection in natural populations or the role of introgression, are still insufficiently understood. The house mouse (Mus musculus) is a particularly well-suited model system to approach such questions, since it has a defined history of splits into subspecies and populations and since extensive genome information is available. We have used high-density single-nucleotide polymorphism (SNP) typing arrays to assess genomic patterns of positive selection and introgression of alleles in two natural populations of each of the subspecies M. m. domesticus and M. m. musculus. Applying different statistical procedures, we find a large number of regions subject to apparent selective sweeps, indicating frequent positive selection on rare alleles or novel mutations. Genes in the regions include well-studied imprinted loci (e.g. Plagl1/Zac1), homologues of human genes involved in adaptations (e.g. alpha-amylase genes) or in genetic diseases (e.g. Huntingtin and Parkin). Haplotype matching between the two subspecies reveals a large number of haplotypes that show patterns of introgression from specific populations of the respective other subspecies, with at least 10% of the genome being affected by partial or full introgression. Using neutral simulations for comparison, we find that the size and the fraction of introgressed haplotypes are not compatible with a pure migration or incomplete lineage sorting model. Hence, it appears that introgressed haplotypes can rise in frequency due to positive selection and thus can contribute to the adaptive genomic landscape of natural populations. Our data support the notion that natural genomes are subject to complex adaptive processes, including the introgression of haplotypes from other differentiated populations or species at a larger scale than previously assumed for animals. This implies that some of the admixture found in inbred strains of mice may also have a natural origin.
Author Summary
Although there is abundant evidence for phenotypic adaptation in natural populations, it is still a challenge to understand the underlying genetic processes. House mice have colonized the world in several successive waves, the most recent ones in the wake of the spread of human agriculture and trans-oceanic shipping. They have adapted to many habitats and climates, and their populations provide a rich source of opportunities for studying the impact of adaptation and positive selection on the genome. By scanning the whole genome of four natural populations of mice, we detect abundant evidence for recent positive selection, including loci that are known to be involved in genetic diseases in humans. Unexpectedly, we also find a high proportion of gene exchange between populations that have long been separated. This finding supports the notion that hybridization and transfer of alleles can significantly contribute to new genetic material subject to positive selection.
doi:10.1371/journal.pgen.1002891
PMCID: PMC3431316  PMID: 22956910
11.  Effect of Low Tube Voltage on Image Quality, Radiation Dose, and Low-Contrast Detectability at Abdominal Multidetector CT: Phantom Study 
Purpose. To investigate the effect of low tube voltage (80 kV) on image quality, radiation dose, and low-contrast detectability (LCD) at abdominal computed tomography (CT). Materials and Methods. A phantom containing low-contrast objects was scanned with a CT scanner at 80 and 120 kV, with tube current-time product settings at 150–650 mAs. The differences between image noise, contrast-to-noise ratio (CNR), and scores of LCD obtained with 80 kV at 150–650 mAs and those obtained with 120 kV at 300 mAs were compared respectively. Results. The image noise substantially increased with low tube voltage. However, with identical dose, use of 80 kV resulted in higher CNR compared with CNR at 120 kV. There were no statistically significant difference in CNR and scores of LCD between 120 kV at 300 mAs and 80 kV at 550–650 mAs (P > 0.05). The relative dose delivered at 80 kV ranged from 58% at 550 mAs to 68% at 650 mAs. Conclusion. With a reduction of the tube voltage from 120 kV to 80 kV at abdominal CT, the radiation dose can be reduced by 32% to 42% without degradation of CNR and LCD.
doi:10.1155/2012/130169
PMCID: PMC3347747  PMID: 22619490
12.  Promising Rabies Vaccine for Postexposure Prophylaxis in Developing Countries, a Purified Vero Cell Vaccine Produced in China▿  
We evaluated the immunogenicity, safety, and antibody persistence of a Vero cell rabies vaccine manufactured in China, compared with those of Verorab. Adequate titers of antibody were observed for the two vaccines. ChengDa rabies vaccine could be a promising alternative vaccine for many developing countries which cannot afford expensive rabies vaccines.
doi:10.1128/CVI.00433-09
PMCID: PMC2849343  PMID: 20147495
13.  Poly[tetra-μ-cyanido-dipyridine­cadmium(II)zinc(II)] 
In the title coordination polymer, [CdZn(CN)4(C5H5N)2]n, the ZnII atom (site symmetry 222) adopts a distorted ZnC4 tetra­hedral geometry, being coordinated by four crystallographically equivalent cyanide ions. The cyanide ion bridges to a CdII centre via its N atom. The Cd atom (site symmetry 2/m) coordination is a distorted CdN6 octa­hedron, arising from four cyanide N atoms and two pyridine N atoms. The complete pyridine mol­ecule is generated by m symmetry, with the N atom and one C atom lying on the reflecting plane. In the crystal, the bridging cyanide ions result in a three-dimensional network.
doi:10.1107/S1600536809054579
PMCID: PMC2979792  PMID: 21579598
14.  Genetic Variation and Recent Positive Selection in Worldwide Human Populations: Evidence from Nearly 1 Million SNPs 
PLoS ONE  2009;4(11):e7888.
Background
Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world.
Methodology
We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH). When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental) level.
Conclusions
Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO) analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.
doi:10.1371/journal.pone.0007888
PMCID: PMC2775638  PMID: 19924308
15.  Recent positive selection of a human androgen receptor/ectodysplasin A2 receptor haplotype and its relationship to male pattern baldness 
Human Genetics  2009;126:255-264.
Genetic variants in the human androgen receptor gene (AR) are associated with male pattern baldness (androgenetic alopecia, AGA) in Europeans. Previous observations of long-range linkage disequilibrium at the AR locus are consistent with the hypothesis of recent positive selection. Here, we further investigate this signature and its relationship to the AGA risk haplotype. The haplotype homozygosity suggests that the AGA risk haplotype was driven to high frequency by positive selection in Europeans although a low meiotic recombination rate contributed to the high haplotype homozygosity. Further, we find high levels of population differentiation as measured by FST and a series of fixed derived alleles along an extended region centromeric to AR in the Asian HapMap sample. The predominant AGA risk haplotype also carries the putatively functional variant 57K in the flanking ectodysplasin A2 receptor gene (EDA2R). It is therefore probable that the AGA risk haplotype rose to high frequency in combination with this EDA2R variant, possibly by hitchhiking on a positively selected 57K haplotype.
Electronic supplementary material
The online version of this article (doi:10.1007/s00439-009-0668-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s00439-009-0668-z
PMCID: PMC3774421  PMID: 19373488
16.  Natural selection and the molecular basis of electrophoretic variation at the coagulation F13B locus 
Electrophoretic analysis of protein variation at the coagulation F13B locus has previously revealed three alleles, with alleles 1, 2, and 3 each being at high frequency in European, African, and Asian populations, respectively. To determine if this unusual pattern of interpopulation differentiation reflects local natural selection or neutral genetic drift, we re-sequenced 4.6 kb of the gene, encompassing all exons, splice junctions, and 1.4 kb of the promoter, in African, European, and Asian samples. These analyses revealed three major lineages, which correspond to the common protein alleles and differ from each other at a non-synonymous substitution in exon 3 and a novel splice acceptor in intron K. There is previous evidence that these lineages are not functionally equivalent; we therefore carried out case–control analyses and confirmed that variability at F13B modulates susceptibility and/or survivorship in coronary artery disease (P<0.05) and type II diabetes within the coronary artery disease cohort (P<0.01). Tajima's D and Fu and Li's tests did not indicate significant departures from neutral expectations. However, publicly available data from SeattleSNPs and HapMap do indicate highly unusual levels of population differentiation (P=0.003) and an excess of allele-specific, extended haplotype homozygosity within the African population (P=0.0125). Possible causes of this putative signal of selection include hematophagous organisms, infection by pathogens that cause disseminated intravascular coagulation, and metabolic or dietary factors.
doi:10.1038/ejhg.2008.137
PMCID: PMC2986062  PMID: 18716611
coagulation factors; population genetics; classical marker genetics; natural selection; alternative splicing
17.  Tetra-μ-2,5-difluoro­benzoato-bis­[(2,2′-bipyridine)(2,5-difluoro­benzoato)gadolinium(III)] 
In the centrosymmetric title compound, [Gd2(C7H3F2O2)6(C10H8N2)2], the asymmetric unit comprises one cation chelated by two 2,5-difluoro­benzoate and one 2,2′-bipyridine. Two cations are linked into dimers via three bridging carboxyl­ate groups from three 2,5-difluoro­benzoic acid units. The GdIII ion is nine-coord­inated by seven O atoms and two N atoms.
doi:10.1107/S1600536808023507
PMCID: PMC2960618  PMID: 21201598
18.  Tris[2-(propyl­imino­meth­yl)phenolato-κ2 N,O]cobalt(III) 
The title compound, [Co(C10H12NO)3], was synthesized from cobalt(III) fluoride and 2-(propyl­imino­meth­yl)phenol in refluxing methanol. The CoIII ion is hexa­coordinated by three N and three O atoms from three bidentate Schiff base ligands in an octa­hedral geometry.
doi:10.1107/S1600536808014074
PMCID: PMC2961544  PMID: 21202506
19.  Bis{μ-2,2′-[ethane-1,2-diylbis(nitrilo­methyl­idyne)]diphenolato}bis­[(thio­cyanato)manganese(III)] 
The reported structure is a monoclinic polymorph of the title compound, [Mn2(C16H14N2O2)2(NCS)2], which has been characterized previously in an ortho­rhom­bic form. Each MnIII atom is chelated by a tetra­dentate 2,2′-[ethane-1,2-diylbis(nitrilo­methyl­idyne)]diphenolate ligand and by the N atom of a thio­cyanate anion, in a square-pyramidal arrangement. The complexes form centrosymmetric dimers, with an Mn—O contact of 2.557 (3) Å trans to each thio­cyanate anion, completing a distorted octa­hedral coordination geometry.
doi:10.1107/S1600536808003577
PMCID: PMC2960991  PMID: 21202001
20.  Tetra­kis(μ-2,4-difluoro­benzoato)bis­[(2,4-difluoro­benzoato)(1,10-phenanthroline)gadolinium(III)] 
In the title compound, [Gd2(C7H3F2O2)6(C12H8N2)2], the asymmetric unit comprises one Gd3+ cation chelated by two 2,4-difluoro­benzoate and one 1,10-phenanthroline ligands. Two cations are linked into a centrosymmetric dimer via three bridging carboxyl­ate groups of 2,4-difluoro­benzoate ligands. Each Gd3+ ion is nine-coordinated by seven O atoms and two N atoms.
doi:10.1107/S1600536808004431
PMCID: PMC2960912  PMID: 21201985
21.  Parallel Selection on TRPV6 in Human Populations 
PLoS ONE  2008;3(2):e1686.
We identified and examined a candidate gene for local directional selection in Europeans, TRPV6, and conclude that selection has acted on standing genetic variation at this locus, creating parallel soft sweep events in humans. A novel modification of the extended haplotype homozygosity (EHH) test was utilized, which compares EHH for a single allele across populations, to investigate the signature of selection at TRPV6 and neighboring linked loci in published data sets for Europeans, Asians and African-Americans, as well as in newly-obtained sequence data for additional populations. We find that all non-African populations carry a signature of selection on the same haplotype at the TRPV6 locus. The selective footprints, however, are significantly differentiated between non-African populations and estimated to be younger than an ancestral population of non-Africans. The possibility of a single selection event occurring in an ancestral population of non-Africans was tested by simulations and rejected. The putatively-selected TRPV6 haplotype contains three candidate sites for functional differences, namely derived non-synonymous substitutions C157R, M378V and M681T. Potential functional differences between the ancestral and derived TRPV6 proteins were investigated by cloning the ancestral and derived forms, transfecting cell lines, and carrying out electrophysiology experiments via patch clamp analysis. No statistically-significant differences in biophysical channel function were found, although one property of the protein, namely Ca2+ dependent inactivation, may show functionally relevant differences between the ancestral and derived forms. Although the reason for selection on this locus remains elusive, this is the first demonstration of a widespread parallel selection event acting on standing genetic variation in humans, and highlights the utility of between population EHH statistics.
doi:10.1371/journal.pone.0001686
PMCID: PMC2246018  PMID: 18301763
22.  Platelet amyloid precursor protein processing: A bio-marker for Alzheimer's disease 
The amyloid precursor protein (APP) in brain is processed either by an amyloidogenic pathway by β-secretase and γ-secretase to yield Aβ (β-amyloid 4 kDa) peptide or by α-secretase within the β-amyloid domain to yield non-amyloidogenic products. We have studied blood platelet levels of a 22-kDa fragment containing the Aβ (β-amyloid 4 kDa) peptide, β-secretase (BACE1), α-secretase (ADAM10), and APP isoform ratios of the 120–130 kDa to 110 kDa peptides from 31 Alzheimer's disease (AD) patients and 10 age-matched healthy control subjects. We found increased levels of Aβ4, increased activation of β-secretase (BACE1), decreased activation of α-secretase (ADAM10) and decreased APP ratios in AD patients compared to normal control subjects. These observations indicate that the blood platelet APP is processed by the same amyloidogenic and non-amyloidogenic pathways as utilized in brain and that APP processing in AD patients is altered compared to control subjects and may be a useful bio-marker for the diagnosis of AD, the progression of disease and for monitoring drug responses in clinical trials.
doi:10.1016/j.jns.2005.09.002
PMCID: PMC1479090  PMID: 16256140
Alzheimer's disease; Platelets; β-Amyloid; β-Secretase; α-Secretase; APP
23.  μ-Oxido-bis­{chlorido[tris­(2-pyridylmeth­yl)amine]chromium(III)} bis(hexafluoridophosphate) 
The title compound, [Cr2Cl2O(C18H18N4)2](PF6)2, is isostructural with the VIII analogue. Each CrIII atom is chelated by the tetra­dentate tris­(2-pyridylmeth­yl)amine ligand via four N atoms, and further coordinated by one Cl atom and one bridging O atom, giving a slightly distorted octa­hedral coordination geometry. The dinuclear complex is centrosymmetric, with the bridging O atom lying on a centre of inversion.
doi:10.1107/S1600536807061296
PMCID: PMC2914886  PMID: 21200546
24.  Diazido­bis(2,2′-biimidazole)cobalt(II) 
In the title compound, [Co(N3)2(C6H6N4)2], the CoII atom lies on a centre of inversion and is bonded to two azide ions and two bidentate 2,2′-biimidizole ligands, giving a slightly distorted octa­hedral CoN6 coordination geometry. In the crystal structure, inter­molecular N—H⋯N hydrogen bonds exist between the 2,2′-biimidizole ligands and the azide ions, linking the complexes into sheets.
doi:10.1107/S1600536807062873
PMCID: PMC2914954  PMID: 21200644
25.  A New Approach for Using Genome Scans to Detect Recent Positive Selection in the Human Genome  
PLoS Biology  2007;5(7):e171.
Genome-wide scanning for signals of recent positive selection is essential for a comprehensive and systematic understanding of human adaptation. Here, we present a genomic survey of recent local selective sweeps, especially aimed at those nearly or recently completed. A novel approach was developed for such signals, based on contrasting the extended haplotype homozygosity (EHH) profiles between populations. We applied this method to the genome single nucleotide polymorphism (SNP) data of both the International HapMap Project and Perlegen Sciences, and detected widespread signals of recent local selection across the genome, consisting of both complete and partial sweeps. A challenging problem of genomic scans of recent positive selection is to clearly distinguish selection from neutral effects, given the high sensitivity of the test statistics to departures from neutral demographic assumptions and the lack of a single, accurate neutral model of human history. We therefore developed a new procedure that is robust across a wide range of demographic and ascertainment models, one that indicates that certain portions of the genome clearly depart from neutrality. Simulations of positive selection showed that our tests have high power towards strong selection sweeps that have undergone fixation. Gene ontology analysis of the candidate regions revealed several new functional groups that might help explain some important interpopulation differences in phenotypic traits.
Author Summary
The evolution of new functions and adaptation to new environments occurs by positive selection, whereby beneficial mutations increase in frequency and eventually become fixed in a population. Detecting such selection in humans is crucial for understanding the importance of past genetic adaptations and their role in contemporary common diseases. Methods have already been developed for detecting the signature of positive selection in large, genome-scale datasets (such as the “HapMap”). Positive selection is expected to more rapidly increase the frequency of an allele, and hence, the length of the haplotype (extent of DNA segment) associated with the selected allele, relative to those that are not under selection. Such methods compare haplotype lengths within a single population. Here, we introduce a new method that compares the lengths of haplotypes associated with the same allele in different populations. We demonstrate that our method has greater power to detect selective sweeps that are fixed or nearly so, and we construct a statistical framework that shows that our method reliably detects positive selection. We applied our method to the HapMap data and identified approximately 500 candidate regions in the human genome that show a signature of recent positive selection. Further targeted studies of these regions should reveal important genetic adaptations in our past.
The authors present a novel genome-scan approach for detecting local positive selection. The approach is designed to detect selective events that have resulted in complete or near-complete fixation of a beneficial allele.
doi:10.1371/journal.pbio.0050171
PMCID: PMC1892573  PMID: 17579516

Results 1-25 (25)