Utility of state-level influenza disease burden and severity estimates to investigate an apparent increase in reported severe cases of influenza A(H1N1) pdm09 - Arizona, 2015-2016.

The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015-2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015-2016 were higher than the previous two seasons. However, ratios of severe disease to community illness were similar. Arizona experienced overall increased disease burden in 2015-2016, but not increased severity compared with prior seasons. Timely estimates of state-specific burden and severity are potentially feasible and may provide important information during seemingly unusual influenza seasons or pandemic situations.

Pressure-induced stacking disorder in boehmite.

The structure of an aluminum layered hydroxide, boehmite (γ-AlOOH), as a function of pressure was studied by using in situ synchrotron X-ray and neutron diffraction. Peak broadening, which is only found for hkl (h ≠ 0) peaks in the X-ray diffraction patterns, is explained by stacking disorder accompanying a continuously increasing displacement of the AlO6 octahedral layer along the a-axis. This finding could be the first experimental result for pressure-induced stacking disorder driven by continuous layer displacement. The magnitude of the layer displacement was estimated from the X-ray scattering profile calculation based on the stacking disordered structure model. Hydrogen bond geometries of boehmite, obtained by structure refinements of the observed neutron diffraction patterns for the deuterated sample up to 10 GPa, show linearly approaching O-D covalent and DO hydrogen bond distances and they merge below 26 GPa. Pressure-induced stacking disorder makes the electrostatic potential of hydrogen bonds asymmetric, yielding less chance for proton-tunnelling.

A case-control study of risk factors for death from 2009 pandemic influenza A(H1N1): is American Indian racial status an independent risk factor?

Historically, American Indian/Alaska Native (AI/AN) populations have suffered excess morbidity and mortality from influenza. We investigated the risk factors for death from 2009 pandemic influenza A(H1N1) in persons residing in five states with substantial AI/AN populations. We conducted a case-control investigation using pandemic influenza fatalities from 2009 in Alaska, Arizona, New Mexico, Oklahoma and Wyoming. Controls were outpatients with influenza. We reviewed medical records and interviewed case proxies and controls. We used multiple imputation to predict missing data and multivariable conditional logistic regression to determine risk factors. We included 145 fatal cases and 236 controls; 22% of cases were AI/AN. Risk factors (P 45 years vs. <18 years], pre-existing medical conditions (mOR 7·1), smoking (mOR 3·0), delayed receipt of antivirals (mOR 6·5), and barriers to healthcare access (mOR 5·3). AI/AN race was not significantly associated with death. The increased influenza mortality in AI/AN individuals was due to factors other than racial status. Prevention of influenza deaths should focus on modifiable factors (smoking, early antiviral use, access to care) and identifying high-risk persons for immunization and prompt medical attention.

Detection and differentiation of Fusarium oxysporum f. sp. lycopersici race 1 using loop-mediated isothermal amplification with three primer sets.

UNLABELLED: Fusarium oxysporum f. sp. lycopersici (Fol) causes tomato wilt. Based on the difference in pathogenicity towards tomato cultivars, Fol is classified into three races. In this study, a rapid method is developed for the detection and discrimination of Fol race 1 using a loop-mediated isothermal amplification (LAMP) assay with two primer sets targeting a region of the nucleotide sequence of the SIX4 gene specific for race 1 and a primer set targeting the SIX5 gene, conserved in all known Fol isolates. Upon LAMP reaction, amplification using all three primer sets was observed only when DNA of Fol race 1 was used as a template, and not when DNA of other Fol races or other fungal species was used. This method could detect 300 fg of Fol race 1 DNA, a 100-fold higher sensitivity than that obtained by conventional PCR. The method can also detect DNA extracted from soil artificially infested with Fol race 1. It is now possible to detect Fol race 1 in colonies and infected tomato stems without DNA isolation. This method is a rapid and simple tool for discrimination of Fol race 1. SIGNIFICANCE AND IMPACT OF THE STUDY: This study developed a loop-mediated isothermal amplification (LAMP) assay for detection and differentiation of Fusarium oxysporum f. sp. lycopersici (Fol) race 1 by using three primer sets targeting for the SIX4 and SIX5 genes. These genes are present together only in Fol race 1. This method can detect Fol race 1 in infected tomato stems without DNA extraction, affording an efficient diagnosis of Fusarium wilt on tomatoes in the field.

Positional cloning of the gene for Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT) variant, is an autosomal recessive disorder characterized by microcephaly, growth retardation, severe combined immunodeficiency and a high incidence of lymphoid cancers. Cells from NBS patients display chromosome instability, hypersensitivity to ionizing radiation and abnormal cell-cycle regulation after irradiation, all of which are characteristics shared with AT. Recently, the NBS locus was mapped at 8q21 by two independent approaches, complementation studies and linkage analysis. Here, we report the positional cloning of the NBS gene, NBS1, from an 800-kb candidate region. The gene comprises 50 kb and encodes a protein of 754 amino acids. The amino-terminal region of the protein shows weak homology to the yeast XRS2, MEK1, CDS1 and SPK1 proteins. The gene is expressed at high levels in the testes, suggesting that it might be involved in meiotic recombination. We detected the same 5-bp deletion in 13 individuals, and conclude that it is likely to be a founder mutation.

Formation of NaCl-type monodeuteride LaD by the disproportionation reaction of LaD2.

Previous x-ray diffraction measurements revealed the pressure-induced decomposition of an fcc LaH2.3 into H-rich and H-poor fcc phases around 11 GPa. The present neutron diffraction measurements on LaD2 confirm the formation of NaCl-type LaD as a counterpart of the D-rich LaD2+δ by disproportionation. First-principles enthalpy and lattice dynamic calculations demonstrate that the NaCl-type LaH is stabilized at high pressures and can be recovered at ambient conditions. Finding the NaCl-type LaH will pave the way for investigations on the site-dependent nature of hydrogen-metal interactions.

Completeness of West Nile virus testing in patients with meningitis and encephalitis during an outbreak in Arizona, USA.

Accurate data on West Nile virus (WNV) cases help guide public health education and control activities, and impact regional WNV blood product screening procedures. During an outbreak of WNV disease in Arizona, records from patients with meningitis or encephalitis were reviewed to determine the proportion tested for WNV. Of 60 patients identified with meningitis or encephalitis, 24 (40%) were tested for WNV. Only 12 (28%) of 43 patients aged <50 years were tested for WNV compared to 12 (71%) of 17 patients aged ≥50 years (P<0·01). Patients with clinical signs of weakness or paralysis, elevated CSF protein, admitted to an inpatient facility, or discharged to a rehabilitation facility were also more likely to have WNV testing performed. The lack of testing in younger age groups and in those with less severe disease probably resulted in substantial underestimates of WNV neuroinvasive disease burden.

Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis.

DNA damage induces apoptosis through a signalling pathway that can be suppressed by the BCL-2 protein, but the mechanism by which DNA damage does this is unknown. Here, using yeast two-hybrid and co-immunoprecipitation studies, we show that RAD9, a human protein involved in the control of a cell-cycle checkpoint, interacts with the anti-apoptotic Bcl-2-family proteins BCL-2 and BCL-x L, but not with the pro-apoptotic BAX and BAD. When overexpressed in mammalian cells, RAD9 induces apoptosis that can be blocked by BCL-2 or BCL-x L. Conversely, antisense RAD9 RNA suppresses cell death induced by methyl methanesulphonate. These findings indicate that RAD9 may have a new role in regulating apoptosis after DNA damage, in addition to its previously described checkpoint-control and other radioresistance-promoting functions.

Interaction potential and infrared absorption of endohedral H2 in C60.

We have measured the temperature dependence of the infrared spectra of a hydrogen molecule trapped inside a C(60) cage, H(2)@C(60), in the temperature range from 6 to 300 K and analyzed the excitation spectrum by using a five-dimensional model of a vibrating rotor in a spherical potential. The electric dipole moment is induced by the translational motion of endohedral H(2) and gives rise to an infrared absorption process where one translational quantum is created or annihilated, ΔN = ±1. Some fundamental transitions, ΔN = 0, are observed as well. The rotation of endohedral H(2) is unhindered but coupled to the translational motion. The isotropic and translation-rotation coupling part of the potential are anharmonic and different in the ground and excited vibrational states of H(2). The vibrational frequency and the rotational constant of endohedral H(2) are smaller than those of H(2) in the gas phase. The assignment of lines to ortho- and para-H(2) is confirmed by measuring spectra of a para enriched sample of H(2)@C(60) and is consistent with the earlier interpretation of the low temperature infrared spectra [Mamone et al., J. Chem. Phys. 130, 081103 (2009)].

Infrared spectroscopy of endohedral HD and D2 in C60.

We report on the dynamics of two hydrogen isotopomers, D(2) and HD, trapped in the molecular cages of a fullerene C(60) molecule. We measured the infrared spectra and analyzed them using a spherical potential for a vibrating rotor. The potential, vibration-rotation Hamiltonian, and dipole moment parameters are compared with previously studied H(2)@C(60) parameters [M. Ge, U. Nagel, D. Hüvonen, T. Rõõm, S. Mamone, M. H. Levitt, M. Carravetta, Y. Murata, K. Komatsu, J. Y.-C. Chen, and N. J. Turro, J. Chem. Phys. 134, 054507 (2011)]. The isotropic part of the potential is similar for all three isotopomers. In HD@C(60), we observe mixing of the rotational states and an interference effect of the dipole moment terms due to the displacement of the HD rotation center from the fullerene cage center.

Novel anaerobic digestion process with sludge ozonation for economically feasible power production from biogas.

A novel process scheme was developed to achieve economically feasible energy recovery from anaerobic digestion. The new process scheme employs a hybrid configuration of mesophilic and thermophilic anaerobic digestion with sludge ozonation: the ozonated sludge is first degraded in a thermophilic digester and then further degraded in a mesophilic digester. In small-scale pilot experiments of the new process scheme, degradation of VSS improved by 3.5% over the control (mesophilic-only configuration) with 20% less ozone consumption. Moreover, biogas conversion also improved by 7.1% over the control. Selective enrichment of inorganic compounds during centrifugation produced a dewatered sludge cake with very low water content (59.4%). This low water content in the sludge cake improved its auto-thermal combustion potential during incineration and added to the overall energy savings. We conducted a case study to evaluate power generation from biogas for a municipal wastewater treatment plant with an average dry weather flow of 43,000 m3/d. Electricity production cost was 5.2 ¢/kWh for the advanced process with power generation, which is lower than the current market price of 7.2 ¢/kWh. The new anaerobic digestion scheme with power generation may reduce greenhouse gas emissions by about 1,000 t-CO(2)/year compared with the conventional process without power generation.

Nutrients cause grassland biomass to outpace herbivory.

Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs ('consumer-controlled'). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ('resource-controlled'). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.

Rotor in a cage: Infrared spectroscopy of an endohedral hydrogen-fullerene complex.

We report the observation of quantized translational and rotational motion of molecular hydrogen inside the cages of C(60). Narrow infrared absorption lines at the temperature of 6 K correspond to vibrational excitations in combination with translational and rotational excitations and show well-resolved splittings due to the coupling between translational and rotational modes of the endohedral H(2) molecule. A theoretical model shows that H(2) inside C(60) is a three-dimensional quantum rotor moving in a nearly spherical potential. The theory provides both the frequencies and the intensities of the observed infrared transitions. Good agreement with the experimental results is obtained by fitting a small number of empirical parameters to describe the confining potential, as well as the relative concentration of ortho- and para-H(2).

Sandwich ELISA system for cartilage oligomeric matrix protein in equine synovial fluid and serum.

REASONS FOR PERFORMING STUDY: Measurement of cartilage oligomeric matrix protein (COMP) in serum has potential for diagnosis of equine osteoarthritis (OA), but clinical use is currently limited by the lack of specificity of an inhibition ELISA as well as by baseline increases due to exercise. Improved methods for ELISA with increased antigen specificity and sensitivity are therefore required for reliable measurement. HYPOTHESIS: Measurement of the serum level of COMP by sandwich ELISA allows identification of horses with OA. METHODS: New monoclonal antibodies (mAbs) were elicited against equine cartilage COMP, their epitopes were determined and a sandwich ELISA was developed. The concentrations of COMP in synovial fluid (SF; n=100) and sera (n=100) from OA cases were measured by sandwich ELISA as well as by inhibition ELISA and compared with concentrations in normal joints (n=95) and horses (n=50). RESULTS: Immunoblots of enzymatically cleaved COMP showed that the new mAbs recognised different epitopes located on a 20 kDa fragment between K63 and K238 of the EGF-like repeats. Inhibition ELISA with any mAb detected significantly increased levels of COMP in OA SF compared with normal SF, whereas no significant difference was detected between serum levels of COMP in OA and normal horses. Conversely, sandwich ELISA with the combination of unlabelled 2A11 x biotinylated 11F10 mAbs detected a significant increase in COMP levels in both serum and SF from OA cases compared with levels in normal animals. CONCLUSIONS AND POTENTIAL RELEVANCE: Measurement of serum COMP with sandwich ELISA may be useful in identifying horses with OA.

Homologous recombination repair is regulated by domains at the N- and C-terminus of NBS1 and is dissociated with ATM functions.

The proteins responsible for radiation sensitive disorders, NBS1, kinase ataxia-telangiectasia-(A-T)-mutated (ATM) and MRE11, interact through the C-terminus of NBS1 in response to the generation of DNA double-strand breaks (DSBs) and are all implicated in checkpoint regulation and DSB repair, such as homologous recombination (HR). We measured the ability of several NBS1 mutant clones and A-T cells to regulate HR repair using the DR-GFP or SCneo systems. ATM deficiency did not reduce the HR repair frequency of an induced DSB, and it was confirmed by findings that HR frequencies are only slightly affected by deletion of ATM-binding site at the extreme C-terminus of NBS1. In contrast, The HR-regulating ability is dramatically reduced by deletion of the MRE11-binding domain at the C-terminus of NBS1 and markedly inhibited by mutations in the FHA/BRCT domains at the N-terminus. This impaired capability in HR is consistent with a failure to observe MRE11 foci formation. Furthermore, normal HR using sister chromatid was completely inhibited by the absence of FHA/BRCT domains. These results suggested that the N- and C-terminal domains of NBS1 are the major regulatory domains for HR pathways, very likely through the recruitment and retention of the MRE11 nuclease to DSB sites in an ATM-independent fashion.

NBS1 prevents chromatid-type aberrations through ATM-dependent interactions with SMC1.

Nijmegen breakage syndrome shares several common cellular features with ataxia telangiectasia, including chromosomal instability and aberrant S- and G2-phase checkpoint regulation. We show here that after irradiation, NBS1 interacts physically with both BRCA1 and SMC1, a component of the cohesin complex, and that their interactions are completely abolished in AT cells. It is noted that BRCA1 is required for the interaction of NBS1 with SMC1, whereas the reverse is not the case, since BRCA1 is able to bind to NBS1 in the absence of an NBS1/SMC1 interaction as observed in MRE11- or RAD50-deficient cells. This indicates that ATM and BRCA1 are upstream of the NBS1/SMC1 interaction. Furthermore, the interaction of NBS1 with SMC1 requires both conserved domains of NBS in the N-terminus and the C-terminus, since they are indispensable for binding of NBS1 to BRCA1 and to MRE11/ATM, respectively. The interaction of NBS1 with SMC1 and the resulting phosphorylation are compromised in the clones lacking either the N- or C-terminus of NBS1, and as a consequence, chromatid-type aberrations are enhanced after irradiation. Our results reveal that ATM plays a fundamental role in promoting the radiation-induced interaction of NBS1 with SMC1 in the presence of BRCA1, leading to the maintenance of chromosomal integrity.

Degradation of noncollagenous components by neutrophil elastase reduces the mechanical strength of rat periodontal ligament.

BACKGROUND AND OBJECTIVE: We have previously shown that increases in neutrophil elastase in periodontal ligament with chronic periodontitis results in degradation of the noncollagenous components. The purpose of this study was to investigate whether the destruction of noncollagenous components by treatment with elastase in vitro causes changes in the mechanical properties of the periodontal ligament. MATERIAL AND METHODS: The transverse sections of mandibular first molars, prepared from male Wistar rats at 6 wk of age, were digested with 0-50 microg/mL of neutrophil elastase at 37 degrees C for 4 h. Then, their mechanical properties and morphological features were examined. RESULTS: Digestion with elastase dose-dependently decreased the maximum shear stress and failure strain energy density of the periodontal ligament (p < 0.05-0.01). The histological observations after digestion revealed marked degradation of oxytalan fibers, but no marked changes of the collagen fibers, which was confirmed by the detection of very low quantities of hydroxyproline in the digest. The light and scanning electron micrographs showed that the elastase degraded the interfibrillar substances in the periodontal ligament and exposed individual collagen fibrils. CONCLUSION: These results suggest that the increased neutrophil elastase observed in periodontal disease degrades the oxytalan fibers and interfibrillar substances in the periodontal ligament to decrease its mechanical strength.

Long-term effects of local pretreatment with alendronate on healing of replanted rat teeth.

BACKGROUND AND OBJECTIVE: Our previous study showed that topical alendronate, an inhibitor of bone resorption, reduces root resorption and ankylosis for 21 d after replantation of rat teeth. The aim of the present study was to evaluate the long-term inhibitory effects of topical alendronate in the replanted teeth. MATERIAL AND METHODS: The rat maxillary first molars were extracted, placed in saline containing 1 mm alendronate (alendronate group) or saline (saline group) for 5 min and then replanted. The maxillae were dissected at 60 and 120 d. Microcomputed tomography horizontal sections at three root levels were analyzed for root and bone resorption, ankylosis and pulp mineralization. RESULTS: In the alendronate group at 60 and 120 d, the frequencies of resorption of roots and bone were lower than those in the saline group. The p values show statistical significances of lower frequencies in the alendronate group than in the saline group by chi-square test (see Table 1). Ankylosis and pulp mineralization occurred in the alendronate and saline groups. Bone marrow spaces were narrowed in conjunction with bone tissue expansion around the replanted teeth in the alendronate group. CONCLUSION: The inhibitory effects of topical alendronate were retained on root and bone resorption, but not on ankylosis and pulp mineralization, in the replanted teeth for 4 mo. Alendronate might also stimulate bone formation around the rat replanted teeth.

Evaluation of state variable interface between the Activated Sludge Models and Anaerobic Digestion Model no 1.

For plant wide modelling of wastewater treatment, it is necessary to develop a suitable state variables interface for integrating state of the art models of ASM and ADM1. ADM1 currently describes such an interface, however, its suitability needs to be experimentally evaluated. In this study, we characterised activated sludge under aerobic and anaerobic conditions to obtain representative state variables for both models. ASM state variables of X(S), X(H) and X(I) (as obtained from aerobic tests) and ADM1 state variables of X(C) and X(I) (as obtained from anaerobic tests) were then correlated to assess the suitability of current interface. Based on the seven datasets of this study and seven datasets from literatures, it was found that in general ASM state variables were well correlated to the state variables of ADM1. The ADM1 state variable of X(C) could be correlated to the sum of state variables of X(S) and X(H), while X(I) in both the models showed direct correspondence. It was also observed that the degradation kinetics of X(C) under anaerobic condition could be better described by individual degradation kinetics of X(S) and X(H). Therefore, to establish a one to one correspondence between ASM and ADM1 state variables and better description of degradation kinetics in ADM1, replacing the composite variable of X(C) by the state variables of X(S) and X(H) is recommended.