Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, highangular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

Working the story : News curation in social media as a second save of citizen journalism

For the first decade of its existence, the concept of citizen journalism has described an approach which was seen as a broadening of the participant base in journalistic processes, but still involved only a comparatively small subset of overall society – for the most part, citizen journalists were news enthusiasts and “political junkies” (Coleman, 2006) who, as some exasperated professional journalists put it, “wouldn’t get a job at a real newspaper” (The Australian, 2007), but nonetheless followed many of the same journalistic principles. The investment – if not of money, then at least of time and effort – involved in setting up a blog or participating in a citizen journalism Website remained substantial enough to prevent the majority of Internet users from engaging in citizen journalist activities to any significant extent; what emerged in the form of news blogs and citizen journalism sites was a new online elite which for some time challenged the hegemony of the existing journalistic elite, but gradually also merged with it. The mass adoption of next-generation social media platforms such as Facebook and Twitter, however, has led to the emergence of a new wave of quasi-journalistic user activities which now much more closely resemble the “random acts of journalism” which JD Lasica envisaged in 2003. Social media are not exclusively or even predominantly used for citizen journalism; instead, citizen journalism is now simply a by-product of user communities engaging in exchanges about the topics which interest them, or tracking emerging stories and events as they happen. Such platforms – and especially Twitter with its system of ad hoc hashtags that enable the rapid exchange of information about issues of interest – provide spaces for users to come together to “work the story” through a process of collaborative gatewatching (Bruns, 2005), content curation, and information evaluation which takes place in real time and brings together everyday users, domain experts, journalists, and potentially even the subjects of the story themselves. Compared to the spaces of news blogs and citizen journalism sites, but also of conventional online news Websites, which are controlled by their respective operators and inherently position user engagement as a secondary activity to content publication, these social media spaces are centred around user interaction, providing a third-party space in which everyday as well as institutional users, laypeople as well as experts converge without being able to control the exchange. Drawing on a number of recent examples, this article will argue that this results in a new dynamic of interaction and enables the emergence of a more broadly-based, decentralised, second wave of citizen engagement in journalistic processes.

Food justice or food sovereignty? Understanding the rise of urban food movements in the USA

As world food and fuel prices threaten expanding urban populations, there is greater need for the urban poor to have access and claims over how and where food is produced and distributed. This is especially the case in marginalized urban settings where high proportions of the population are food insecure. The global movement for food sovereignty has been one attempt to reclaim rights and participation in the food system and challenge corporate food regimes. However, given its origins from the peasant farmers' movement, La Via Campesina, food sovereignty is often considered a rural issue when increasingly its demands for fair food systems are urban in nature. Through interviews with scholars, urban food activists, non-governmental and grassroots organizations in Oakland and New Orleans in the United States of America, we examine the extent to which food sovereignty has become embedded as a concept, strategy and practice. We consider food sovereignty alongside other dominant US social movements such as food justice, and find that while many organizations do not use the language of food sovereignty explicitly, the motives behind urban food activism are similar across movements as local actors draw on elements of each in practice. Overall, however, because of the different histories, geographic contexts, and relations to state and capital, food justice and food sovereignty differ as strategies and approaches. We conclude that the US urban food sovereignty movement is limited by neoliberal structural contexts that dampen its approach and radical framework. Similarly, we see restrictions on urban food justice movements that are also operating within a broader framework of market neoliberalism. However, we find that food justice was reported as an approach more aligned with the socio-historical context in both cities, due to its origins in broader class and race struggles.

Investigating the concept of potential quality: An exploratory study in the real estate industry

Purpose The purpose of this research is to examine the concept of “potential quality” – that is, a company's tangible search qualities (such as the physical servicescape and virtual servicescape) – within the context of the real‐estate industry in the USA. Design/methodology/approach This qualitative study collects data by conducting personal in‐depth interviews with 34 respondents who had been recent buyers or renters of property. The data are then coded and themed to identify quality dimensions relevant to this industry. Findings The results indicate that a buyer's perception of the overall service quality of real‐estate service consists of two components: the interaction with a realtor (process quality); and the virtual servicescape, especially the firm's website design and content (potential quality). The study concludes that existing scales (such as SERVQUAL and RESERV) fail to capture the tangible component of service quality sufficiently in the real‐estate industry. Research limitations/implications The study uses data from only one industry (real estate) and from only one demographic segment (professionals in higher education). Practical implications Service providers of intangible, high‐contact services must appreciate the importance of the virtual servicescape as a surrogate quality indicator that can help to reduce information asymmetries and consumers' uncertainty with regard to initiating a business relationship. Real estate firms need to pay attention to the training of agents and the design and content of their e‐service systems. Originality/value This study integrates potential quality, process quality, and outcome quality in a comprehensive proposed model. In particular, the study identifies “potential quality” as a combination of the attributes of the virtual service environment and the physical service environment.

Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming

Endoplasmatic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in trimming of peptides to an optimal length for presentation by major histocompatibility complex (MHC) class I molecules. Polymorphisms in ERAP1 have been associated with chronic inflammatory diseases, including ankylosing spondylitis (AS) and psoriasis, and subsequent in vitro enzyme studies suggest distinct catalytic properties of ERAP1 variants. To understand structure-activity relationships of this enzyme we determined crystal structures in open and closed states of human ERAP1, which provide the first snapshots along a catalytic path. ERAP1 is a zinc-metallopeptidase with typical H-E-X-X-H-(X)18-E zinc binding and G-A-M-E-N motifs characteristic for members of the gluzincin protease family. The structures reveal extensive domain movements, including an active site closure as well as three different open conformations, thus providing insights into the catalytic cycle. A K 528R mutant strongly associated with AS in GWAS studies shows significantly altered peptide processing characteristics, which are possibly related to impaired interdomain interactions.

Properties of the correlated electronic states of pyrene and hydrogenated pyrene

Approximate calculations are reported on pyrene within the PPP model Hamiltonian using a novel restricted CI scheme which employs both molecular orbital and valence bond techniques. Also reported are detailed full CI results of the PPP model on 2,7-dihydropyrene obtained using the valence bond method. Spectral studies, charge and spin density calculations in ground and excited states, and ring current calculations in the ground state of the molecules are presented. In pyrene, the calculated excitation energies are in good agreement with experiment. The closed structure pi-conjugated molecule pyrene appears to show smaller distortions from the ground state geometry compared with the open structure pi-conjugated molecule 2,7-dihydropyrene. The ground state equilibrium structure of 2,7-dihydropyrene can be viewed as two hexatriene molecules connected by a vinyl crosslink, as is evident from bond order and ring current calculations. This is consistent with the only Kekule resonant structure possible for this molecule.

Chiral molecular self-assembly of phospholipid tubules: A circular dichroism study

We report on spectroscopic studies of the chiral structure in phospholipid tubules formed in mixtures of alcohol and water. Synthetic phospholipids containing diacetylenic moieties in the acyl chains self-assemble into hollow, cylindrical tubules in appropriate conditions. Circular dichroism provides a direct measure of chirality of the molecular structure. We find that the CD spectra of tubules formed in mixtures of alcohol and water depends strongly on the alcohol used and the lipid concentration. The relative spectral intensity of different circular dichroism bands correlates with the number of bilayers observed using microscopy. The results provide experimental evidence that tubule formation is based on chiral packing of the lipid molecules and that interbilayer interactions are important to the tubule structure

DC-SIGN and alpha 2,6-sialylated IgG Fc interaction is dispensable for the anti-inflammatory activity of IVIg on human dendritic cells

Intravenous immunoglobulin (IVIg) is widely used to treat autoimmune diseases. Several mutually nonexclusive mechanisms are proposed to explain the beneficial effects of IVIg in patients (1, 2). Lately, Ravetch and colleagues (3) demonstrate that anti-inflammatory activity of IVIg is mediated mainly by antibodies that contain terminal _2,6-sialic acid linkages at the Asn297-linked glycan of Fc region.

Study of electron states of solids by techniques of electron spectroscopy

Studies of valence bands and core levels of solids by photoelectron spectroscopy are described at length. Satellite phenomena in the core level spectra have been discussed in some detail and it has been pointed out that the intensity of satellites appearing next to metal and ligand core levels critically depends on the metal-ligand overlap. Use of photoelectron spectroscopy in investigating metal-insulator transitions and spin-state transitions in solids is examined. It is shown that relative intensities of metal Auger lines in transition metal oxides and other systems provide valuable information on the valence bands. Occurrence of interatomic Auger transitions in competition with intraatomic transitions is discussed. Applications of electron energy loss spectroscopy and other techniques of electron spectroscopy in the study of gas-solid interactions are briefly presented.

Population genetics of the frog-killing fungus Batrachochytrium dendrobatidis

Global amphibian decline by chytridiomycosis is a major environmental disaster that has been attributed to either recent fungal spread or environmental change that promotes disease. Here, we present a population genetic comparison of Batrachochytrium dendrobatidis isolates from an intensively studied region of frog decline, the Sierra Nevada of California. In support of a novel pathogen, we find low diversity, no amphibian-host specificity, little correlation between fungal genotype and geography, local frog extirpation by a single fungal genotype, and evidence of human-assisted fungus migration. In support of endemism, at a local scale, we find some diverse, recombining populations. Therefore neither epidemic spread nor endemism alone explains this particular amphibian decline. Recombination raises the possibility of resistant sporangia and a mechanism for rapid spread as well as persistence that could greatly complicate global control of the pathogen.

An ultraviolet photoelectron spectroscopic study of the electron states of iodine complexes with electron donors

HeI photoelectron spectra of the vapour phase complexes of diethylether and diethylsulphide with iodine have been investigated for the first time. The iodine orbital ionization energy decreases on complexation while the donor lone-pair orbital ionization energy increases markedly; the shifts are considerably larger in the sulphide complex as expected on the basis of enthalpy considerations.

An investigation of bond formation in the weakly bound first excited 1Σ and lowest 3Σ states of HeH+

The role of the electronic kinetic energy and its Cartesian components is examined during the formation of the first excited 1�£ and the lowest 3�£ states of HeH+ employing wavefunctions of multi-configuration type with basis orbitals in elliptic coordinates. Results show that the bond formation in these states is preceded primarily by a charge transfer from H to He+ rather than by polarisation of the H-orbital by He+

Parallel packing of alpha-helices in crystals of the zervamicin IIA analog Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe.2H2O.

An apolar synthetic analog of the first 10 residues at the NH2-terminal end of zervamicin IIA crystallizes in the triclinic space group P1 with cell dimensions a = 10.206 +/- 0.002 A, b = 12.244 +/- 0.002 A, c = 15.049 +/- 0.002 A, alpha = 93.94 +/- 0.01 degrees, beta = 95.10 +/- 0.01 degrees, gamma = 104.56 +/- 0.01 degrees, Z = 1, C60H97N11O13 X 2H2O. Despite the relatively few alpha-aminoisobutyric acid residues, the peptide maintains a helical form. The first intrahelical hydrogen bond is of the 3(10) type between N(3) and O(0), followed by five alpha-helix-type hydrogen bonds. Solution 1H NMR studies in chloroform also favor a helical conformation, with seven solvent-shielded NH groups. Continuous columns are formed by head-to-tail hydrogen bonds between the helical molecules along the helix axis. The absence of polar side chains precludes any lateral hydrogen bonds. Since the peptide crystallizes with one molecule in a triclinic space group, aggregation of the helical columns must necessarily be parallel rather than antiparallel. The packing of the columns is rather inefficient, as indicated by very few good van der Waals' contacts and the occurrence of voids between the molecules.

Configuration mixing in the s-hole states of metal ions

Configuration interaction calculation have been carried out on the s-hole states of Mn2+ Fe2+ (both high- and low-spin configurations). Co2+, Ca2+, K+ and Na+ including configurations involving virtual orbitals. The results show good agreement with the multiplet structures found in X-ray photoelectron spectra of these ions.

Targeting biotypes of Dactylopius tomentosus to improve effective biocontrol of Cylindropuntia spp. in Australia

Seven Dactylopius tomentosus (Lamarck) biotypes were collected from a range of Cylindropuntia spp. in Mexico, South Africa and United States of America (USA) and imported into quarantine facilities at the Ecosciences Precinct. Host range trials were conducted for each biotype and further assessed against the Cylindropuntia species that are naturalised in Australia to determine the most effective biotype for each species. Host range was confined to the Cylindropuntia for all seven biotypes. In the efficacy trials, C. imbricata (Haw.) F.M.Knuth was killed by the ‘imbricata’ biotype within 16 weeks and C. kleiniae (DC.) F.M.Knuth died within 26 weeks. Cylindropuntia fulgida var. mamillata (DC.) Backeb. and C. imbricata were killed by the ‘fulgida’ biotype within 18 weeks. On-going trials suggest that C. rosea (DC.) Backeb. could be controlled by either the ‘acanthocarpa’ or the ‘acanthocarpa × echinocarpa’ biotypes. Cylindropuntia spinosior (Englem.) F.M.Knuth was not susceptible to any of the D. tomentosus biotypes assessed. A clear designation of which D. tomentosus biotype is most suited for each Cylindropuntia species will improve and increase the effectiveness of biological control of these weed species