A Role for Casein Kinase 2 in the Mechanism Underlying Circadian Temperature Compensation

SummaryTemperature compensation of circadian clocks is an unsolved problem with relevance to the general phenomenon of biological compensation. We identify casein kinase 2 (CK2) as a key regulator of temperature compensation of the Neurospora clock by determining that two long-standing clock mutants, chrono and period-3, displaying distinctive alterations in compensation encode the β1 and α subunits of CK2, respectively. Reducing the dose of these subunits, particularly β1, significantly alters temperature compensation without altering the enzyme's Q10. By contrast, other kinases and phosphatases implicated in clock function do not play appreciable roles in temperature compensation. CK2 exerts its effects on the clock by directly phosphorylating FREQUENCY (FRQ), and this phosphorylation is compromised in CK2 hypomorphs. Finally, mutation of certain putative CK2 phosphosites on FRQ, shown to be phosphorylated in vivo, predictably alters temperature compensation profiles effectively phenocopying CK2 mutants

The usefulness of rapid diagnostic tests in the new context of low malaria transmission in zanzibar.

BACKGROUND\ud \ud We assessed if histidine-rich-protein-2 (HRP2) based rapid diagnostic test (RDT) remains an efficient tool for Plasmodium falciparum case detection among fever patients in Zanzibar and if primary health care workers continue to adhere to RDT results in the new epidemiological context of low malaria transmission. Further, we evaluated the performance of RDT within the newly adopted integrated management of childhood illness (IMCI) algorithm in Zanzibar.\ud \ud METHODS AND FINDINGS\ud \ud We enrolled 3890 patients aged ≥2 months with uncomplicated febrile illness in this health facility based observational study conducted in 12 primary health care facilities in Zanzibar, between May-July 2010. One patient had an inconclusive RDT result. Overall 121/3889 (3.1%) patients were RDT positive. The highest RDT positivity rate, 32/528 (6.1%), was found in children aged 5-14 years. RDT sensitivity and specificity against PCR was 76.5% (95% CI 69.0-83.9%) and 99.9% (95% CI 99.7-100%), and against blood smear microscopy 78.6% (95% CI 70.8-85.1%) and 99.7% (95% CI 99.6-99.9%), respectively. All RDT positive, but only 3/3768 RDT negative patients received anti-malarial treatment. Adherence to RDT results was thus 3887/3889 (99.9%). RDT performed well in the IMCI algorithm with equally high adherence among children <5 years as compared with other age groups.\ud \ud CONCLUSIONS\ud \ud The sensitivity of HRP-2 based RDT in the hands of health care workers compared with both PCR and microscopy for P. falciparum case detection was relatively low, whereas adherence to test results with anti-malarial treatment was excellent. Moreover, the results provide evidence that RDT can be reliably integrated in IMCI as a tool for improved childhood fever management. However, the relatively low RDT sensitivity highlights the need for improved quality control of RDT use in primary health care facilities, but also for more sensitive point-of-care malaria diagnostic tools in the new epidemiological context of low malaria transmission in Zanzibar.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT01002066

Estimation of Biological Oxygen Demand and Chemical Oxygen Demand for Combined Sewer Systems Using Synchronous Fluorescence Spectra

Real-time monitoring of water quality for sewer system is required for efficient sewer network design because it provides information on the precise loading of pollutant to wastewater treatment facilities and the impact of loading on receiving water. In this study, synchronous fluorescence spectra and its first derivatives were investigated using a number of wastewater samples collected in sewer systems in urban and non-urban areas, and the optimum fluorescence feature was explored for the estimation of biochemical oxygen demand (BOD) and chemical oxygen demand (COD) concentrations of sewer samples. The temporal variations in BOD and COD showed a regular pattern for urban areas whereas they were relatively irregular for non-urban areas. Irrespective of the sewer pipes and the types of the areas, two distinct peaks were identified from the synchronous fluorescence spectra, which correspond to protein-like fluorescence (PLF) and humic-like fluorescence (HLF), respectively. HLF in sewer samples appears to be associated with fluorescent whitening agents. Five fluorescence characteristics were selected from the synchronous spectra and the first-derivatives. Among the selected fluorescence indices, a peak in the PLF region (i.e., Index I) showed the highest correlation coefficient with both BOD and COD. A multiple regression approach based on suspended solid (SS) and Index I used to compensate for the contribution of SS to BOD and COD revealed an improvement in the estimation capability, showing good correlation coefficients of 0.92 and 0.94 for BOD and COD, respectively

Attosecond control of electrons emitted from a nanoscale metal tip

Attosecond science is based on steering of electrons with the electric field of well-controlled femtosecond laser pulses. It has led to, for example, the generation of XUV light pulses with a duration in the sub-100-attosecond regime, to the measurement of intra-molecular dynamics by diffraction of an electron taken from the molecule under scrutiny, and to novel ultrafast electron holography. All these effects have been observed with atoms or molecules in the gas phase. Although predicted to occur, a strong light-phase sensitivity of electrons liberated by few-cycle laser pulses from solids has hitherto been elusive. Here we show a carrier-envelope (C-E) phase-dependent current modulation of up to 100% recorded in spectra of electrons laser-emitted from a nanometric tungsten tip. Controlled by the C-E phase, electrons originate from either one or two sub-500as long instances within the 6-fs laser pulse, leading to the presence or absence of spectral interference. We also show that coherent elastic re-scattering of liberated electrons takes place at the metal surface. Due to field enhancement at the tip, a simple laser oscillator suffices to reach the required peak electric field strengths, allowing attosecond science experiments to be performed at the 100-Megahertz repetition rate level and rendering complex amplified laser systems dispensable. Practically, this work represents a simple, exquisitely sensitive C-E phase sensor device, which can be shrunk in volume down to ~ 1cm3. The results indicate that the above-mentioned novel attosecond science techniques developed with and for atoms and molecules can also be employed with solids. In particular, we foresee sub-femtosecond (sub-) nanometre probing of (collective) electron dynamics, such as plasmon polaritons, in solid-state systems ranging in size from mesoscopic solids via clusters to single protruding atoms.Comment: Final manuscript version submitted to Natur

Allergic Asthma and Rhinitis Caused by Household Rabbit Exposure: Identification of Serum-Specific IgE and Its Allergens

Although rabbits are common domestic pets, severe respiratory allergic reactions to rabbits in households are unusual. Ory c 1, a 17-kDa glycoprotein found in saliva and fur, has previously been identified as a major rabbit allergen. In this report, we describe the cases of three patients with rabbit allergy who presented with asthma and/or rhinitis while living in households with detectable levels of serum-specific IgE and major IgE binding components. Three patients with rabbit allergy and 18 unexposed nonatopic healthy controls were enrolled. Enzyme-linked immunosorbent assays (ELISA) for serum-specific IgE and IgG4 to rabbit epithelium and inhibition ELISA were performed followed by sodium dodecye sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and IgE immunoblotting. All three patients with rabbit allergy had high serum-specific IgE antibody levels compared with controls. The results of the inhibition ELISA showed significant inhibition with the addition of rabbit epithelium, whereas no significant inhibition was noted with the addition of cat and dog epithelia. Two IgE-binding components with molecular weights of 16 kDa and 67.5 kDa were identified by IgE immunoblotting. In conclusion, rabbit exposure may induce IgE-mediated bronchial asthma and/or rhinitis in domestic settings

Proper Orthogonal Decomposition as a technique for identifying two-phase flow pattern based on electrical impedance tomography

Collecting of very large amount of data from experimental measurement is a common practice in almost every scientific domains. There is a great need to have specific techniques capable of extracting synthetic information, which is essential for understanding and modelling the specific phenomena. The Proper Orthogonal Decomposition (POD) is one of the most powerful data analysis methods for multivariate and nonlinear phenomena. Generally, POD is a procedure that takes a given collection of input experimental or numerical data and creates an orthogonal basis constituted by functions estimated as the solutions of an integral eigenvalue problem known as a Fredholm equation. This paper proposes a novel approach by utilising POD to identify flow structure in horizontal pipeline, specially, for slag, plug and wavy stratified air-water flow regimes, , in which POD technique extends the current evaluation procedure of electrical impedance tomography [31]. This capability is extended by the implementation of POD as an identifier for typical horizontal two phase flow regimes. Direct POD method introduced by Lumley and Snapshot POD method introduced by Sirovich are applied The POD snapshot matrices are reconstructed from electrical tomography measurement under specific flow conditions. It is expected that this study may provide new knowledge on two phase flow dynamics in a horizontal pipeline and useful information for further prediction of multiphase flow regime

A new conceptual framework for the transformation of groundwater dissolved organic matter

Groundwater comprises 95% of the liquid fresh water on Earth and contains a diverse mix of dissolved organic matter (DOM) molecules which play a significant role in the global carbon cycle. Currently, the storage times and degradation pathways of groundwater DOM are unclear, preventing an accurate estimate of groundwater carbon sources and sinks for global carbon budgets. Here we reveal the transformations of DOM in aging groundwater using ultra-high resolution mass spectrometry combined with radiocarbon dating. Long-term anoxia and a lack of photodegradation leads to the removal of oxidised DOM and a build-up of both reduced photodegradable formulae and aerobically biolabile formulae with a strong microbial signal. This contrasts with the degradation pathway of DOM in oxic marine, river, and lake systems. Our findings suggest that processes such as groundwater extraction and subterranean groundwater discharge to oceans could result in up to 13 Tg of highly photolabile and aerobically biolabile groundwater dissolved organic carbon released to surface environments per year, where it can be rapidly degraded. These findings highlight the importance of considering groundwater DOM in global carbon budgets

Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3.

Misfolded endoplasmic reticulum (ER) proteins are retro-translocated through the membrane into the cytosol, where they are poly-ubiquitinated, extracted from the ER membrane, and degraded by the proteasome1-4, a pathway termed ER-associated protein degradation (ERAD). Proteins with misfolded domains in the ER lumen or membrane are discarded through the ERAD-L and -M pathways, respectively. In S. cerevisiae, both pathways require the ubiquitin ligase Hrd1, a multi-spanning membrane protein with a cytosolic RING finger domain5,6. Hrd1 is the crucial membrane component for retro-translocation7,8, but whether it forms a protein-conducting channel is unclear. Here, we report a cryo-electron microscopy (cryo-EM) structure of S. cerevisiae Hrd1 in complex with its ER luminal binding partner Hrd3. Hrd1 forms a dimer within the membrane with one or two Hrd3 molecules associated at its luminal side. Each Hrd1 molecule has eight trans-membrane segments, five of which form an aqueous cavity extending from the cytosol almost to the ER lumen, while a segment of the neighboring Hrd1 molecule forms a lateral seal. The aqueous cavity and lateral gate are reminiscent of features in protein-conducting conduits that facilitate polypeptide movement in the opposite direction, that is, from the cytosol into or across membranes9-11. Our results suggest that Hrd1 forms a retro-translocation channel for the movement of misfolded polypeptides through the ER membrane

A new species of cosmocercoides (Nematoda; cosmocercidae) and other helminths in leptodactylus latrans (anura; leptodactylidae) from Argentina

Cosmocercoides latrans n. sp. (Cosmocercidae) from the small intestine of Leptodactylus latrans (Anura: Leptodactylidae) from Northeastern Province of Buenos Aires, Argentina is described. The new species can be distinguished from their congeners by a combination of the characters, among which stands out the number of rosette papillae, the lack of gubernaculum and the presence of lateral alae in both sexes. There are over 20 species in the genus Cosmocercoides, and Cosmocercoides latrans n. sp. represents the third species from the Neotropical realm and the second for Argentina. Additionally, seven previously known taxa are reported; Pseudoacanthocephalus cf. lutzi, Catadiscus uruguayensis, Rauschiella palmipedis, Aplectana hylambatis, Cosmocerca parva, Schrankiana sp. and Rhabdias elegans; providing literature records and information on distribution and host-parasite relationships.Fil: Draghi, Regina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Drago, Fabiana Beatriz. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Invertebrados; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Lunaschi, Lía Inés. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Invertebrados; Argentin

Mycoplasma pneumoniae infection in patients with Kawasaki disease

PurposeKawasaki disease (KD) is the main cause of acquired heart disease in children. In addition to cardiovascular involvement, many complications have been recognized in KD. However, respiratory complications have been rarely reported. We investigated the differences in clinical characteristics, laboratory findings, radiography findings, and echocardiography findings of Mycoplasma pneumoniae infection and other types of pneumonia in KD patients.MethodsAmong 358 patients with KD, 54 developed concurrent pneumonia. Among the 54 patients, 12 (22.2%) with high titers of anti-M. pneumoniae antibody (AMA) (>1:640) were grouped in the M. pneumoniae group and 42 were included in the control group. Serum AMA was measured in each patient. Clinical laboratory findings and total duration of fever were analyzed.ResultsThe duration of fever, serum hemoglobin, white blood cell count, platelet count, erythrocyte sedimentation rate, C-reactive protein level, albumin level, and the incidence of coronary arterial lesions showed no statistical difference in the 2 groups. Neutrophil count was significantly higher in the M. pneumoniae group than in the control group. Among various radiography findings observed in pneumonia, consolidation and pleural effusion were more frequent in the M. pneumoniae group than in the control group. On the other hand, parahilar peribronchial opacification, diffuse interstitial lesion, and normal findings prevailed in the control group.ConclusionKD patients can have concurrent infections, especially pulmonary symptoms. The cause of KD is likely to be associated with M. pneumoniae infection. Thus, immediate treatment of M. pneumoniae infection in KD patients is very important