Polarization-dependence of anomalous scattering in brominated DNA and RNA molecules, and importance of crystal orientation in single- and multiple-wavelength anomalous diffraction phasing

In this paper the anisotropy of anomalous scattering at the Br K-absorption edge in brominated nucleotides is investigated, and it is shown that this effect can give rise to a marked directional dependence of the anomalous signal strength in X-ray diffraction data. This implies that choosing the correct orientation for crystals of such molecules can be a crucial determinant of success or failure when using single- and multiple-wavelength anomalous diffraction (SAD or MAD) methods to solve their structure. In particular, polarized absorption spectra on an oriented crystal of a brominated DNA molecule were measured, and were used to determine the orientation that yields a maximum anomalous signal in the diffraction data. Out of several SAD data sets, only those collected at or near that optimal orientation allowed interpretable electron density maps to be obtained. The findings of this study have implications for instrumental choices in experimental stations at synchrotron beamlines, as well as for the development of data collection strategy programs

Horizontal tuning for faces originates in high-level Fusiform Face Area

Recent work indicates that the specialization of face visual perception relies on the privileged processing of horizontal angles of facial information. This suggests that stimulus properties assumed to be fully resolved in primary visual cortex (V1; e.g., orientation) in fact determine human vision until high-level stages of processing. To address this hypothesis, the present fMRI study explored the orientation sensitivity of V1 and high-level face-specialized ventral regions such as the Occipital Face Area (OFA) and Fusiform Face Area (FFA) to different angles of face information. Participants viewed face images filtered to retain information at horizontal, vertical or oblique angles. Filtered images were viewed upright, inverted and (phase-)scrambled. FFA responded most strongly to the horizontal range of upright face information; its activation pattern reliably separated horizontal from oblique ranges, but only when faces were upright. Moreover, activation patterns induced in the right FFA and the OFA by upright and inverted faces could only be separated based on horizontal information. This indicates that the specialized processing of upright face information in the OFA and FFA essentially relies on the encoding of horizontal facial cues. This pattern was not passively inherited from V1, which was found to respond less strongly to horizontal than other orientations likely due to adaptive whitening. Moreover, we found that orientation decoding accuracy in V1 was impaired for stimuli containing no meaningful shape. By showing that primary coding in V1 is influenced by high-order stimulus structure and that high-level processing is tuned to selective ranges of primary information, the present work suggests that primary and high-level levels of the visual system interact in order to modulate the processing of certain ranges of primary information depending on their relevance with respect to the stimulus and task at hand

A novel gamma-N-methylaminobutyrate demethylating oxidase involved in catabolism of the tobacco alkaloid nicotine by Arthrobacter nicotinovorans pAO1

Nicotine catabolism, linked in Arthrobacter nicotinovorans to the presence of the megaplasmid pAO1, leads to the formation of gamma-N-methylaminobutyrate from the pyrrolidine ring of the alkaloid. Until now the metabolic fate of gamma-N-methylaminobutyrate has been unknown. pAO1 carries a cluster of ORFs with similarity to sarcosine and dimethylglycine dehydrogenases and oxidases, to the bifunctional enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase and to formyltetrahydrofolate deformylase. We cloned and expressed the gene carrying the sarcosine dehydrogenase-like ORF and showed, by enzyme activity, spectrophotometric methods and identification of the reaction product as gamma-aminobutyrate, that the predicted 89 395 Da flavoprotein is a demethylating gamma-N-methylaminobutyrate oxidase. Site-directed mutagenesis identified His67 as the site of covalent attachment of FAD and confirmed Trp66 as essential for FAD binding, for enzyme activity and for the spectral properties of the wild-type enzyme. A K-m of 140 mum and a k(cat) of 800 s(-1) was determined when gamma-N-methylaminobutyrate was used as the substrate. Sarcosine was also turned over by the enzyme, but at a rate 200-fold slower than gamma-N-methylaminobutyrate. This novel enzyme activity revealed that the first step in channelling the gamma-N-methylaminobutyrate generated from nicotine into the cell metabolism proceeds by its oxidative demethylation

Porin from the halophilic species Ectothiorhodospira vacuolata: cloning, structure of the gene and comparison with other porins

The gene coding for the anion-specific porin of the halophilic eubacterium Ectothiorhodospira (Ect.) vacuolata was cloned and sequenced, the first such gene so analyzed from a purple sulfur bacterium. It encodes a precursor protein consisting of 374 amino acid (aa)-residues including a signal peptide of 22-aa residues. Comparison with aa sequences of porins from several other members of the Proteobacteria revealed little homology. Only two regions showed local homology with the previously sequenced porins of Neisseria species, Comamonas acidovorans, Bordetella pertussis, Alcaligenes eutrophus, and Burkholderia cepacia. Genomic Southern blot hybridization studies were carried out with a probe derived from the 5′ end of the gene coding for the porin of Ect. vacuolata. Two related species, Ect. haloalkaliphila and Ect. shaposhnikovii, exhibited a clear signal, while the extremely halophilic bacterium Halorhodospira (Hlr.) halophila (formerly Ect. halophila) did not show any cross-hybridization even at low stringency. This result is in good accordance with a recently proposed reassignment within the family Ectothiorhodospiraceae, which included the separation of the extremely halophilic species into the new genus Halorhodospira

Social Difficulties in Youth with Autism With and Without Anxiety and ADHD Symptoms

Social difficulties inherent to autism spectrum disorder are often linked with co‐occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co‐occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co‐occurring symptom subgroups (Anxiety, ADHD, Both, Neither)—namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Lay Summary Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested

Social Difficulties in Youth with Autism With and Without Anxiety and ADHD Symptoms

Social difficulties inherent to autism spectrum disorder are often linked with co‐occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co‐occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co‐occurring symptom subgroups (Anxiety, ADHD, Both, Neither)—namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Lay Summary Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested

Multimorbidity: constellations of conditions across subgroups of midlife and older individuals, and related Medicare expenditures

Introduction: The Department of Health and Human Services’ 2010 Strategic Framework on Multiple Chronic Conditions called for the identification of common constellations of conditions in older adults. Objectives: To analyze patterns of conditions constituting multimorbidity (CCMM) and expenditures in a US representative sample of midlife and older adults (50–64 and ≥65 years of age, respectively). Design: A cross-sectional study of the 2010 Health and Retirement Study (HRS; n=17,912). The following measures were used: (1) count and combinations of CCMM, including (i) chronic conditions (hypertension, arthritis, heart disease, lung disease, stroke, diabetes, cancer, and psychiatric conditions), (ii) functional limitations (upper body limitations, lower body limitations, strength limitations, limitations in activities of daily living, and limitations in instrumental activities of daily living), and (iii) geriatric syndromes (cognitive impairment, depressive symptoms, incontinence, visual impairment, hearing impairment, severe pain, and dizziness); and (2) annualized 2011 Medicare expenditures for HRS participants who were Medicare fee-for-service beneficiaries (n=5,677). Medicaid beneficiaries were also identified based on their self-reported insurance status. Results: No large representations of participants within specific CCMM categories were observed; however, functional limitations and geriatric syndromes were prominently present with higher CCMM counts. Among fee-for-service Medicare beneficiaries aged 50–64 years, 26.7% of the participants presented with ≥10 CCMM, but incurred 48% of the expenditure. In those aged ≥65 years, these percentages were 16.9% and 34.4%, respectively. Conclusion: Functional limitations and geriatric syndromes considerably add to the MM burden in midlife and older adults. This burden is much higher than previously reported

The Influence of Multimorbidity on Leading Causes of Death in Older Adults With Cognitive Impairment

Objective: The aim of this study is to evaluate the relationship of leading causes of death with gradients of cognitive impairment and multimorbidity. Method: This is a population-based study using data from the linked 1992- 2010 Health and Retirement Study and National Death Index (n = 9,691). Multimorbidity is defined as a combination of chronic conditions, functional limitations, and geriatric syndromes. Regression trees and Random Forest identified which combinations of multimorbidity associated with causes of death. Results: Multimorbidity is common in the study population. Heart disease is the leading cause in all groups, but with a larger percentage of deaths in the mild and moderate/severe cognitively impaired groups than among the noncognitively impaired. The different “paths” down the regression trees show that the distribution of causes of death changes with different combinations of multimorbidity. Discussion: Understanding the considerable heterogeneity in chronic conditions, functional limitations, geriatric syndromes, and causes of death among people with cognitive impairment can target care management and resource allocation

Complex multimorbidity and health outcomes in older adult cancer survivors

Objective: To characterize complex multimorbidity among cancer survivors and evaluate the association between cancer survivorship, time since cancer diagnosis, and self-reported fair/poor health, self-rated worse health in 2 years, and 2-year mortality. Methods: We used the 2010–2012 Health and Retirement Study. Cancer survivors were individuals who reported a (nonskin) cancer diagnosis 2 years or more before the interview. We defined complex multimorbidity as the co-occurrence of chronic conditions, functional limitations, and/or geriatric syndromes. In addition to descriptive analyses, we used logistic regression to evaluate the independent association between cancer survivor status and health outcomes. We also examined whether cancer survivorship differed by the number of years since diagnosis. Results: Among 15,808 older adults (age ≥50 years), 11.8% were cancer survivors. Compared with cancer-free individuals, a greater percentage of cancer survivors had complex multimorbidity: co-occurring chronic conditions, functional limitations, and geriatric syndromes. Cancer survivorship was significantly associated with self-reported fair/poor health, self-rated worse health in 2 years, and 2-year mortality. These effects declined with the number of years since diagnosis for fair/ poor health and mortality but not for self-rated worse health. Conclusion: Cancer survivor status is independently associated with more complex multimorbidity, and with worse health outcomes. These effects attenuate with time, except for patient perception of being in worse health

Large uniaxial negative thermal expansion in pentacene due to steric hindrance

The uniaxial negative thermal expansion in pentacene crystals along $a$ is a particularity in the series of the oligoacenes, and exeptionally large for a crystalline solid. Full x-ray structure analysis from 120 K to 413 K reveals that the dominant thermal motion is a libration of the rigid molecules about their long axes, modifying the intermolecular angle which describes the herringbone packing within the layers. This herringbone angle increases with temperature (by 0.3 -- 0.6$^{\circ}$ per 100 K), and causes an anisotropic rearrangement of the molecules within the layers, i.e. an expansion in the $b$ direction, and a distinct contraction along $a$. Additionally, a larger herringbone angle improves the cofacial overlap between adjacent, parallel molecules, and thus enhances the attractive van der Waals forces