Quantum phase transition in the dioptase magnetic lattice

The study of quantum phase transitions, which are zero-temperature phase transitions between distinct states of matter, is of current interest in research since it allows for a description of low-temperature properties based on universal relations. Here we show that the crystal green dioptase Cu_6Si_6O_18 . 6H_2O, known to the ancient Roman as the gem of Venus, has a magnetic crystal structure, formed by the Cu(II) ions, which allows for a quantum phase transition between an antiferromagnetically ordered state and a quantum spin liquid.Comment: 6 pages, 5 figures, EPL, in pres

Construction and validation of a patient- and user-friendly nursing home version of the Geriatric Depression Scale.

Objective To construct a patient- and user-friendly shortened version of the Geriatric Depression Scale (GDS) that is especially suitable for nursing home patients. Methods The study was carried out on two different data bases including 23 Dutch nursing homes. Data on the GDS (n¼410), the Mini Mental State Examination (n¼410) and a diagnostic interview (SCAN; n¼333), were collected by trained clinicians. Firstly, the items of the GDS-15 were judged on their clinical applicability by three clinical experts. Subsequently, items that were identified as unsuitable were removed using the data of the Assess project (n¼77), and internal consistency was calculated. Secondly, with respect to criterion validity (sensitivity, specitivity, area under ROC and positive and negative predictive values), the newly constructed shortened GDS was validated in the AGED data set (n¼333), using DSM-IV diagnosis for depression as measured by the SCAN as ‘gold standard’. Results The eight-item GDS that resulted from stage 1 showed good internal consistency in both the Assess data set (a¼0.86) and the AGED dataset (a¼0.80). In the AGED dataset, high sensitivity rates of 96.3% for major depression and 83.0% for minor depression were found, with a specificity rate of 71.7% at a cut-off point of 2/3. Conclusion The GDS-8 has good psychometric properties. Given that the GDS-8 is less burdening for the patient, more comfortable to use and less time consuming, it may be a more feasible screening test for the frail nursing home population

Influenza Vaccination Rates, and Barriers to Influenza Vaccination, in People who are Homeless

Background: Influenza is a highly infectious virus which is endemic in most high-income countries. People experiencing homelessness are at an increased risk of contracting influenza, and often have poorer outcomes associated with hospitalisation and mortality. Annual influenza vaccination is recommended for all adults, and highly recommended for ‘at-risk’ groups, including people who are homeless. Despite this, the vaccination uptake within the homeless community is low. This systematic review will identify influenza vaccination rates, and barriers to influenza vaccination, in people who are homeless.   Methods: This review will consider primary studies about influenza vaccination in people who are homeless. Searches will be undertaken on five electronic databases and managed in EndNote X9. The literature will be screened by title/abstract, then by full-text, and citation chaining will be completed. Data about the influenza vaccination rates and barriers will be extracted. Each task, primarily the screening and extraction of data, will be completed by one researcher, and checked by at least one other.     Discussion: This review will identify influenza vaccination rates, and barriers to influenza vaccination, in people experiencing homelessness. This will inform vaccination delivery and funding, and may contribute to reducing the health disparities in this at-risk, hard-to-reach population.&nbsp

The FeMoco-deficient MoFe Protein Produced by a nifH Deletion Strain of Azotobacter vinelandii Shows Unusual P-cluster Features

The His-tag MoFe protein expressed by the nifH deletion strain Azotobacter vinelandii DJ1165 (Delta nifH MoFe protein) was purified in large quantity. The alpha 2beta 2 tetrameric Delta nifH MoFe protein is FeMoco-deficient based on metal analysis and the absence of the S = 3/2 EPR signal, which arises from the FeMo cofactor center in wild-type MoFe protein. The Delta nifH MoFe protein contains 18.6 mol Fe/mol and, upon reduction with dithionite, exhibits an unusually strong S = 1/2 EPR signal in the g approx 2 region. The indigo disulfonate-oxidized Delta nifH MoFe protein does not show features of the P2+ state of the P-cluster of the Delta nifB MoFe protein. The oxidized Delta nifH MoFe protein is able to form a specific complex with the Fe protein containing the [4Fe-4S]1+ cluster and facilitates the hydrolysis of MgATP within this complex. However, it is not able to accept electrons from the [4Fe-4S]1+ cluster of the Fe protein. Furthermore, the dithionite-reduced Delta nifH MoFe can be further reduced by Ti(III) citrate, which is quite unexpected. These unusual catalytic and spectroscopic properties might indicate the presence of a P-cluster precursor or a P-cluster trapped in an unusual conformation or oxidation state

Cofactor specificity motifs and the induced fit mechanism in class I ketol-acid reductoisomerases

Although most sequenced members of the industrially important ketol-acid reductoisomerase (KARI) family are class I enzymes, structural studies to date have focused primarily on the class II KARIs, which arose through domain duplication. In the present study, we present five new crystal structures of class I KARIs. These include the first structure of a KARI with a six-residue β2αB (cofactor specificity determining) loop and an NADPH phosphate-binding geometry distinct from that of the seven- and 12-residue loops. We also present the first structures of naturally occurring KARIs that utilize NADH as cofactor. These results show insertions in the specificity loops that confounded previous attempts to classify them according to loop length. Lastly, we explore the conformational changes that occur in class I KARIs upon binding of cofactor and metal ions. The class I KARI structures indicate that the active sites close upon binding NAD(P)H, similar to what is observed in the class II KARIs of rice and spinach and different from the opening of the active site observed in the class II KARI of Escherichia coli. This conformational change involves a decrease in the bending of the helix that runs between the domains and a rearrangement of the nicotinamide-binding site

Genetic markers of Munc13 protein family member, BAIAP3, are gender-specifically associated with anxiety and benzodiazepine abuse in mouse and man

Anxiety disorders and substance abuse, including benzodiazepine use disorder, frequently occur together. Unfortunately, treatment of anxiety disorders still includes benzodiazepines, and patients with an existing comorbid benzodiazepine use disorder or a genetic susceptibility for benzodiazepine use disorder may be at risk of adverse treatment outcomes. The identification of genetic predictors for anxiety disorders, and especially for benzodiazepine use disorder, could aid the selection of the best treatment option and improve clinical outcomes. The brain-specific angiogenesis inhibitor I–associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in amygdalae, hypothalamus and periaqueductal gray. Deletion of Baiap3 in mice leads to enhanced seizure propensity and increased anxiety, with the latter being more pronounced in female than in male animals. We hypothesized that genetic variation in human BAIAP3 may also be associated with anxiety. By using a phenotype-based genetic association study, we identified two human BAIAP3 single-nucleotide polymorphism risk genotypes (AA for rs2235632, TT for rs1132358) that show a significant association with anxiety in women and, surprisingly, with benzodiazepine abuse in men. Returning to mice, we found that male, but not female, Baiap3 knockout (KO) mice develop tolerance to diazepam more quickly than control animals. Analysis of cultured Baiap3 KO hypothalamus slices revealed an increase in basal network activity and an altered response to diazepam withdrawal. Thus, Baiap3/BAIAP3 is gender specifically associated with anxiety and benzodiazepine use disorder, and the analysis of Baiap3/BAIAP3-related functions may help elucidate mechanisms underlying the development of both disorders

Transdisciplinary research in support of land and water management in China and Southeast Asia : evaluation of four research projects

Unidad de excelencia María de Maeztu MdM-2015-0552Transdisciplinary research (TDR) aims at identifying implementable solutions to difficult sustainability problems and at fostering social learning. It requires a wellmanaged collaboration among multidisciplinary scientists and multisectoral stakeholders. Performing TDR is challenging, particularly for foreign researchers working in countries with different institutional and socio-cultural conditions. There is a need to synthesize and share experience among researchers as well as practitioners regarding how TDR can be conducted under specific contexts. In this paper, we aim to evaluate and synthesize our unique experience in conducting TDR projects in Asia. We applied guiding principles of TDR to conduct a formative evaluation of four consortium projects on sustainable land and water management in China, the Philippines, and Vietnam. In all projects, local political conditions restricted the set of stakeholders that could be involved in the research processes. The set of involved stakeholders was also affected by the fact that stakeholders in most cases only participate if they belong to the personal network of the project leaders. Language barriers hampered effective communication between foreign researchers and stakeholders in all projects and thus knowledge integration. The TDR approach and its specific methods were adapted to respond to the specific cultural, social, and political conditions in the research areas, also with the aim to promote trust and interest of the stakeholders throughout the project. Additionally, various measures were implemented to promote collaboration among disciplinary scientists. Based on lessons learned, we provide specific recommendations for the design and implementation of TDR projects in particular in Asia

Dissociation of accumulated genetic risk and disease severity in patients with schizophrenia

Genotype–phenotype correlations of common monogenic diseases revealed that the degree of deviation of mutant genes from wild-type structure and function often predicts disease onset and severity. In complex disorders such as schizophrenia, the overall genetic risk is still often >50% but genotype–phenotype relationships are unclear. Recent genome-wide association studies (GWAS) replicated a risk for several single-nucleotide polymorphisms (SNPs) regarding the endpoint diagnosis of schizophrenia. The biological relevance of these SNPs, however, for phenotypes or severity of schizophrenia has remained obscure. We hypothesized that the GWAS ‘top-10' should as single markers, but even more so upon their accumulation, display associations with lead features of schizophrenia, namely positive and negative symptoms, cognitive deficits and neurological signs (including catatonia), and/or with age of onset of the disease prodrome as developmental readout and predictor of disease severity. For testing this hypothesis, we took an approach complementary to GWAS, and performed a phenotype-based genetic association study (PGAS). We utilized the to our knowledge worldwide largest phenotypical database of schizophrenic patients (n>1000), the GRAS (Göttingen Research Association for Schizophrenia) Data Collection. We found that the ‘top-10' GWAS-identified risk SNPs neither as single markers nor when explored in the sense of a cumulative genetic risk, have any predictive value for disease onset or severity in the schizophrenic patients, as demonstrated across all core symptoms. We conclude that GWAS does not extract disease genes of general significance in schizophrenia, but may yield, on a hypothesis-free basis, candidate genes relevant for defining disease subgroups

Violent aggression predicted by multiple pre-adult environmental hits

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention