Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychiatric symptoms and disorders in old age: prevalence, course and diagnostic thresholds

The aim of this thesis was to study the epidemiology of some psychiatric disorders, as well as their corresponding subthreshold symptoms, in order to explore the border between psychopathology and normality in the general population of older people. Data came from population studies of older people in Gothenburg. Participants completed a semi-structured psychiatric interview and cognitive tests conducted by psychiatric research nurses. A key informant interview was also conducted. Psychiatric diagnoses were made using DSM-IV criteria. Dementia was an exclusion criterion for all studies. Study I examined the one-year prevalence of psychotic symptoms (delusions and hallucinations) in 70-82-year olds. The one-year prevalence of psychotic symptoms, as determined by expert review of available information, was 1.0% with no age or sex differences. Subthreshold symptoms (paranoid ideation and illusions) had a similar prevalence. A lower prevalence than in most previous studies may reflect methodological differences, age differences or secular changes in the prevalence of these symptoms. Study II and Study III examined the prevalence, correlates and course of specific phobia and subthreshold fears in 70-year olds followed-up at age 75 and 79 years. At age 70, specific phobia and subthreshold fears were present in 10% and 47%, respectively. Both were more common in women than in men. Specific phobia, but not subthreshold fears, was associated with other mental disorders. Specific phobia was associated with global functional impairment, but markedly less so than depression. The prevalence of specific phobia declined with age. Most individuals with specific phobia at age 70 did not have specific phobia during follow-up, but most had subthreshold fears, suggesting that these symptoms have a chronic course but with fluctuating severity and improvement with age. Study IV examined the prevalence and course of depression in 70-year olds who were followed-up at age 75 and/or age 79. At baseline and follow-up, participants were placed in one of four categories of depression (no depression, subsyndromal depressive symptoms, minor depression and major depression). The majority of baseline cases of major and minor depression were chronic or recurrent. Subsyndromal depressive symptoms at age 70 differed from no depression with respect to mental health correlates and prognosis. About half of individuals with major depression at follow-up had minor or subsyndromal depressive symptoms at age 70. These symptomatic risk groups could be suitable targets for prevention of major depression in older people.
UvA-DARE ( Digital Academic Repository ) Dopamine and the management of attentional resources : genetic markers of striatal D 2 dopamine predict individual differences in the attentional blink

■ The attentional blink (AB)—a deficit in reporting the second of two target stimuli presented in close succession in a rapid sequence of distracters—has been related to processing limitations in working memory. Given that dopamine (DA) plays a crucial role working memory, the present study tested whether individual differences in the size of the AB can be predicted by differences in genetic predisposition related to the efficiency of dopaminergic pathways. Polymorphisms related to mesocortical and nigrostriatal dopaminergic pathways were considered, as well as polymorphisms related to norepinephrine (NE), a transmitter system that has also been suspected to play a role in the AB. In a sample of 157 healthy adults, we studied the dependency of the individual magnitude of the AB and the C957T polymorphism at the DRD2 gene (associated with striatal DA/D2 receptors), the DARPP32 polymorphism (associated with striatal DA/D1), the COMT ValMet polymorphism (associated with frontal DA), DBH444 g/a and DBH50-ins/del polymorphisms (polymorphisms strongly correlated with DA beta hydroxylase, the enzyme catalyzing the DA–NE conversion) and NET T-182C (a polymorphism related to the NE transporter). DRD2 C957T T/T homozygotes showed a significantly smaller AB, whereas polymorphisms associated with frontal DA and NE were unrelated to performance. This outcome pattern suggests a crucial role of the nigrostriatal dopaminergic pathway and of nigrostriatal D2 receptors, in particular, in the management of attentional resources. ■
N-terminus oligomerization regulates the function of cardiac ryanodine receptors

Summary The ryanodine receptor (RyR) is an ion channel composed of four identical subunits mediating calcium efflux from the endo/sarcoplasmic reticulum of excitable and non-excitable cells. We present several lines of evidence indicating that the RyR2 N-terminus is capable of self-association. A combination of yeast two-hybrid screens, co-immunoprecipitation analysis, chemical crosslinking and gel filtration assays collectively demonstrate that a RyR2 N-terminal fragment possesses the intrinsic ability to oligomerize, enabling apparent tetramer formation. Interestingly, N-terminus tetramerization mediated by endogenous disulfide bond formation occurs in native RyR2, but notably not in RyR1. Disruption of N-terminal inter-subunit interactions within RyR2 results in dysregulation of channel activation at diastolic Ca2+ concentrations from ryanodine binding and single channel measurements. Our findings suggest that the N-terminus interactions mediating tetramer assembly are involved in RyR channel closure, identifying a crucial role for this structural association in the dynamic regulation of intracellular Ca2+ release.
Streptococcus suis Meningitis: A Systematic Review and Meta-analysis

Background Streptococcus suis is the most common cause of meningitis in pork consuming and pig rearing countries in South-East Asia. We performed a systematic review of studies on S. suis meningitis to define the clinical characteristics, predisposing factors and outcome. Methodology Studies published between January 1, 1980 and August 1, 2015 were identified from main literature databases and reference lists. Studies were included if they were written in West-European languages and described at least 5 adult patients with S. suis meningitis in whom at least one clinical characteristic was described. Findings We identified 913 patients with S. suis meningitis included in 24 studies between 1980 and 2015. The mean age was 49 years and 581 of 711 patients were male (82%). Exposure to pigs or pork was present in 395 of 648 patients (61%) while other predisposing factors were less common. 514 of 528 patients presented with fever (97%), 429 of 451 with headache (95%), 462 of 496 with neck stiffness (93%) and 78 of 384 patients (20%) had a skin injury in the presence of pig/pork contact. The case fatality rate was 2.9% and hearing loss was a common sequel occurring in 259 of 489 patients (53%). Treatment included dexamethasone in 157 of 300 (52%) of patients and was associated with reduced hearing loss in S. suis meningitis patients included in a randomized controlled trial. Conclusion S. suis meningitis has a clear association with pig and pork contact. Mortality is low, but hearing loss occurs frequently. Dexamethasone was shown to reduce hearing loss.
Dissection of complex protein dynamics in human thioredoxin

We report our direct study of complex protein dynamics in human thioredoxin by dissecting into elementary processes and determining their relevant time scales. By combining site-directed mutagenesis with femtosecond spectroscopy, we have distinguished four partly time-overlapped dynamical processes at the active site of thioredoxin. Using intrinsic tryptophan as a molecular probe and from mutation studies, we ascertained the negligible contribution to solvation by protein sidechains and observed that the hydration dynamics at the active site occur in 0.47–0.67 and 10.8–13.2 ps. With reduced and oxidized states, we determined the electron-transfer quenching dynamics between excited tryptophan and a nearby disulfide bond in 10–17.5 ps for three mutants. A robust dynamical process in 95–114 ps, present in both redox states and all mutants regardless of neighboring charged, polar, and hydrophobic residues around the probe, is attributed to the charge transfer reaction with its adjacent peptide bond. Site-directed mutations also revealed the electronic quenching dynamics by an aspartate residue at a hydrogen bond distance in 275–615 ps. The local rotational dynamics determined by the measurement of anisotropy changes with time unraveled a relatively rigid local configuration but implies that the protein fluctuates on the time scale of longer than nanoseconds. These results elucidate the temporal evolution of hydrating water motions, electron-transfer reactions, and local protein fluctuations at the active site, and show continuously synergistic dynamics of biological function over wide time scales.
A Triclade DNA Vaccine Designed on the Basis of a Comprehensive Serologic Study Elicits Neutralizing Antibody Responses against All Clades and Subclades of Highly Pathogenic Avian Influenza H5N1 Viruses

ABSTRACT Because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds, and potential human-to-human transmission, H5N1 influenza viruses remain a major global health concern. Their high degree of genetic diversity also poses enormous burdens and uncertainties in developing effective vaccines. To overcome this, we took a new approach, i.e., the development of immunogens based on a comprehensive serologic study. We constructed DNA plasmids encoding codon-optimized hemagglutinin (HA) from 17 representative strains covering all reported clades and subclades of highly pathogenic avian influenza H5N1 viruses. Using DNA plasmids, we generated the corresponding H5N1 pseudotypes and immune sera. We performed an across-the-board pseudotype-based neutralization assay and determined antigenic clusters by cartography. We then designed a triclade DNA vaccine and evaluated its immunogenicity and protection in mice. We report here that (sub)clades 0, 1, 3, 4, 5, 6, 7.1, and 9 were grouped into antigenic cluster 1, (sub)clades 2.1. 3.2, 2.3. 4, 2.4, 2.5, and 8 were grouped into another antigenic cluster, with subclade 2.2.1 loosely connected to it, and each of subclades 2.3.2.1 and 7.2 was by itself. Importantly, the triclade DNA vaccine encoding HAs of (sub)clades 0, 2.3.2.1, and 7.2 elicited broadly neutralizing antibody responses against all H5 clades and subclades and protected mice against high-lethal-dose heterologous H5N1 challenge. Thus, we conclude that broadly neutralizing antibodies against all H5 clades and subclades can indeed be elicited with immunogens on the basis of a comprehensive serologic study. Further evaluation and optimization of such an approach in ferrets and in humans is warranted.
Team Culture and Business Strategy Simulation Performance

Many capstone strategic management courses use computer-based simulations as core pedagogical tools. Simulations are touted as assisting students in developing much-valued skills in strategy formation, implementation, and team management in the pursuit of superior strategic performance. However, despite their rich nature, little is known regarding the relationship between team-level attributes and simulation performance. This research reports the findings of a multiyear study that uncovered a clear link between specific team cultural values, as measured by the Competing Values Framework, and simulation performance. It then explores how these findings may influence the pedagogical use of simulations in the strategy classroom in areas ranging from using culture as a performance tool to diagnosis and training.
Effects of Certain Lateral Dominance Traits, Music Aptitude, and Sex Differences with Instrumental Music Achievement

The effects of music aptitude, sex, handedness, eyedness, and footedness on music achievement and executive skills of elementary instrumental music students was explored. Handedness was defined for the present study as the observed preferred hand used for a specific set of familiar tasks; eyedness refers to sighting dominance; and footedness was defined as the observed foot preferred to perform selected familiar tasks. A five-way multivariate analysis (2×2×3×2×3) was employed to analyze the data. No conclusive evidence was found to show that combinations of eye and limb dominance, sex differences, and music aptitude variables affect music achievement or executive skill variables. Only music aptitude levels when considered alone strongly affected tonal, rhythmic, and performance achievement
Higher mRNA levels of chemokines and cytokines associated with macrophage activation in erythema migrans skin lesions in patients from the United States than in patients from Austria with Lyme borreliosis.

BACKGROUND Erythema migrans (EM) is caused primarily by Borrelia afzelii in Europe and solely by Borrelia burgdorferi in the United States. B. burgdorferi infection in the United States has previously been associated with faster expansion of EM lesions and with more associated symptoms, compared with B. afzelii infection in Europe. However, reasons for these differences are not yet known. METHODS We determined the Borrelia species infecting 67 US or Austrian patients with EM. The clinical pictures and chemokine and cytokine mRNA levels in lesional skin were then compared in the 19 B. burgdorferi-infected US patients and the 37 B. afzelii-infected Austrian patients, the 2 largest groups. RESULTS The 19 B. burgdorferi-infected US patients had faster-expanding EM lesions and a median of 4 associated signs and symptoms, whereas the 37 B. afzelii-infected Austrian patients had slower-expanding lesions and usually did not experience associated symptoms. Compared with the EM lesions of B. afzelii-infected Austrian patients, those of B. burgdorferi-infected US patients had significantly higher mRNA levels of chemokines associated with activation of macrophages, including chemoattractants for neutrophils (CXCL1), macrophages (CCL3 and CCL4), and T helper 1 cells (CXCL9, CXCL10, and CXCL11). In addition, compared with the EM lesions of Austrian patients, the EM lesions of US patients tended to have higher mRNA levels of the macrophage-associated proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha, and they had significantly higher mRNA expression of the antiinflammatory cytokines interleukin 10 and transforming growth factor beta. CONCLUSIONS The EM lesions of B. burgdorferi-infected US patients expanded faster, were associated with more symptoms, and had higher mRNA levels of macrophage-associated chemokines and cytokines than did the EM lesions of B. afzelii-infected Austrian patients.
When Being a Bad Friend Doesn't Hurt The Buffering Function of Gender Typicality Against Self-Esteem-Threatening Feedback

Research on domain-specific sociometer theory suggests that individual mate value has a great influence on self-esteem. In this study (N = 124), we investigated the notion that perceived high gender typicality increases one's perceived mate value and thus counteracts the usual decline in state self-esteem following negative feedback. The participants completed a fictitious personality test to assess their individual quality as a friend and received bogus negative feedback. Depending on the experimental condition, participants received a test score close to the mean test score attained by their own or the opposite gender and thus either gender-typical or gender- atypical. Additionally, we included a control condition in which no feedback was given. The results showed that participants in the gender-atypical condition reported lower state self-esteem than did participants in the gender-typical condition or the control condition. This buffer effect was mediated by perceived mate value.
Simultaneous evolution of multiple dispersal components and kernel

Global climate is changing rapidly and is accompanied by large-scale fragmentation and destruction of habitats. Since dispersal is the first line of defense for mobile organisms to cope with such adversities in their environment, it is important to understand the causes and consequences of evolution of dispersal. Although dispersal is a complex phenomenon involving multiple dispersal-traits like propensity (tendency to leave the natal patch) and ability (to travel long distances), the relationship between these traits is not always straight-forward, it is not clear whether these traits can evolve simultaneously or not, and how their interactions affect the overall dispersal profile. To investigate these issues, we subjected four large (N∼2500) outbred populations of Drosophila melanogaster to artificial selection for increased dispersal, in a setup that mimicked increasing habitat fragmentation over 33 generations. The propensity and ability of the selected populations were significantly greater than the non-selected controls and the difference persisted even in the absence of proximate drivers for dispersal. The dispersal kernel evolved to have significantly greater standard deviation and reduced values of skew and kurtosis, which ultimately translated into the evolution of a greater frequency of long-distance dispersers (LDDs). We also found that although sex-biased dispersal exists in Drosophila melanogaster, its expression can vary depending on which dispersal component is being measured and the environmental condition under which dispersal takes place. Interestingly though, there was no difference between the two sexes in terms of dispersal evolution. We discuss possible reasons for why some of our results do not agree with previous laboratory and field studies. The rapid evolution of multiple components of dispersal and the kernel, expressed even in the absence of stress, indicates that dispersal evolution cannot be ignored while investigating eco-evolutionary phenomena like speed of range expansion, disease spread, evolution of invasive species and destabilization of metapopulation dynamics. Data Accessibility Data will be deposited to dryad if accepted.
Mutual Forbearance: The Role of Intrafirm Integration and Rewards

Despite increasing attention given to mutual forbearance strategies (MFS), researchers have virtually ignored the internal arrangements necessary for their implementation. We argue that the design of the mutual forbearance competitor may pose some unique implementation challenges for the firm, theorize about the administrative mechanisms that we expect to characterize firms implementing MFS, and suggest that, to the extent that future researchers do not model the qualities theoretically necessary to implement MFS, the full competitive consequences of MFS will not be appreciated.
Research 177 on incomplete C budgets or on indirect measurements based on comparisons between belowground C allocation in mycorrhizal and nonmycorrhizal plants

• Direct measurement of the carbon (C) ‘cost’ of mycorrhizas is problematic. Although estimates have been made for arbuscular and ectomycorrhizal symbioses, these are based on incomplete budgets or indirect measurements. Furthermore, the conventional model of unidirectional plant-to-fungus C flux is too simplistic. Net fungus-to-plant C transfer supports seedling establishment in c. 10% of plant species, including most orchids, and bidirectional C flows occur in ectomycorrhiza utilizing soil amino acids. • Here, the C cost of mycorrhizas to the green orchid Goodyera repens was determined by measurement of simultaneous bidirectional fluxes of 14C labelled sources using a monoxenic system with the fungus Ceratobasidium cornigerum. • Transfer of C from fungus to plant (‘up-flow’) occurs in the photosynthesizing orchid G. repens (max. 0.06 μg) whereas over five times more current assimilate (min. 0.355 μg) is simultaneously allocated in the reverse direction to the mycorrhizal fungus (‘down-flow’) after 8 d. Carbon is transferred rapidly, being detected in plant–fungal respiration within 31 h of labelling. • This study provides the most complete C budget for an orchid–mycorrhizal symbiosis, and clearly shows net plant-to-fungus C flux. The rapidity of bidirectional C flux is indicative of dynamic transfer at an interfacial apoplast as opposed to reliance on digestion of fungal pelotons.
Conformally equivariant quantization

Let $(M,g)$ be a pseudo-Riemannian manifold and $F_\lambda(M)$ the space of densities of degree $\lambda$ on $M$. We study the space $D^2_{\lambda,\mu}(M)$ of second-order differential operators from $F_\lambda(M)$ to $F_\mu(M)$. If $(M,g)$ is conformally flat with signature $p-q$, then $D^2_{\lambda,\mu}(M)$ is viewed as a module over the group of conformal transformations of $M$. We prove that, for almost all values of $\mu-\lambda$, the $O(p+1,q+1)$-modules $D^2_{\lambda,\mu}(M)$ and the space of symbols (i.e., of second-order polynomials on $T^*M$) are canonically isomorphic. This yields a conformally equivariant quantization for quadratic Hamiltonians. We furthermore show that this quantization map extends to arbitrary pseudo-Riemannian manifolds and depends only on the conformal class $[g]$ of the metric. As an example, the quantization of the geodesic flow yields a novel conformally equivariant Laplace operator on half-densities, as well as the well-known Yamabe Laplacian. We also recover in this framework the multi-dimensional Schwarzian derivative of conformal transformations.
A Dual Function for SecA in the Assembly of Single Spanning Membrane Proteins in Escherichia coli*

The assembly of bacterial membrane proteins with large periplasmic loops is an intrinsically complex process because the SecY translocon has to coordinate the signal recognition particle-dependent targeting and integration of transmembrane domains with the SecA-dependent translocation of the periplasmic loop. The current model suggests that the ATP hydrolysis by SecA is required only if periplasmic loops larger than 30 amino acids have to be translocated. In agreement with this model, our data demonstrate that the signal recognition particle- and SecA-dependent multiple spanning membrane protein YidC becomes SecA-independent if the large periplasmic loop connecting transmembrane domains 1 and 2 is reduced to less than 30 amino acids. Strikingly, however, we were unable to render single spanning membrane proteins SecA-independent by reducing the length of their periplasmic loops. For these proteins, the complete assembly was always SecA-dependent even if the periplasmic loop was reduced to 13 amino acids. If, however, the 13-amino acid-long periplasmic loop was fused to a downstream transmembrane domain, SecA was no longer required for complete translocation. Although these data support the current model on the SecA dependence of multiple spanning membrane proteins, they indicate a novel function of SecA for the assembly of single spanning membrane proteins. This could suggest that single and multiple spanning membrane proteins are processed differently by the bacterial SecY translocon.