The System Design, Engineering Architecture, and Preliminary Results of a Lower-Cost High-Sensitivity High-Resolution Positron Emission Mammography Camera.
A lower-cost high-sensitivity high-resolution positron emission mammography (PEM) camera is developed. It consists of two detector modules with the planar detector bank of 20 × 12 cm(2). Each bank has 60 low-cost PMT-Quadrant-Sharing (PQS) LYSO blocks arranged in a 10 × 6 array with two types of geometries. One is the symmetric 19.36 × 19.36 mm(2) block made of 1.5 × 1.5 × 10 mm(3) crystals in a 12 × 12 array. The other is the 19.36 × 26.05 mm(2) asymmetric block made of 1.5 × 1.9 × 10 mm(3) crystals in 12 × 13 array. One row (10) of the elongated blocks are used along one side of the bank to reclaim the half empty PMT photocathode in the regular PQS design to reduce the dead area at the edge of the module. The bank has a high overall crystal packing fraction of 88%, which results in a very high sensitivity. Mechanical design and electronics have been developed for low-cost, compactness, and stability purposes. Each module has four Anger-HYPER decoding electronics that can handle a count-rate of 3 Mcps for single events. A simple two-module coincidence board with a hardware delay window for random coincidences has been developed with an adjustable window of 6 to 15 ns. Some of the performance parameters have been studied by preliminary tests and Monte Carlo simulations, including the crystal decoding map and the 17% energy resolution of the detectors, the point source sensitivity of 11.5% with 50 mm bank-to-bank distance, the 1.2 mm-spatial resolutions, 42 kcps peak Noise Equivalent Count Rate at 7.0-mCi total activity in human body, and the resolution phantom images. Those results show that the design goal of building a lower-cost, high-sensitivity, high-resolution PEM detector is achieved.


[An analysis of local similarities in the primary structures of protein hormones].
An analysis of primary structures for local similarities has been performed for a number of protein hormones. The statistical MacLachlan's technique and three matrices of amino acids similarities: in respect to the genetic code (M1), physico-chemical properties (M2), interchangeability of amino acids in homologous proteins (M3) have been used. When comparing prolactin and growth hormones, four zones of high structural similarity have been found. Comparison of beta-subunits of interstitial-cell and thyroid-stimulating hormones has shown two zones of high similarity. Using M3 matrice, non-homogeneity of the self local similarity of structure has been shown for prolactin, growth hormone, beta-lipotropin, proinsulin and parathormone. For the latter three hormones, the high evolutionary conservative regions coincide with the active sites of structure. It is suggested that such regions in the structures of prolactin and growth hormone also provide the active function.


Risk of mortality and complications in patients with schizophrenia and diabetes mellitus: population-based cohort study.
Schizophrenia patients have markedly elevated prevalence of diabetes compared with the general population. However, risk of mortality and diabetes-related complications among schizophrenia patients with co-occurring diabetes is understudied. We investigated whether schizophrenia increased the risk of overall mortality, complications and post-complication mortality in people with diabetes. This population-based, propensity-score matched (1:10) cohort study identified 6991 patients with incident diabetes and pre-existing schizophrenia and 68 682 patients with incident diabetes only between 2001 and 2016 in Hong Kong using a medical record database of public healthcare services. Association between schizophrenia and all-cause mortality was examined with a Cox proportional hazards model. Effect of schizophrenia on first-year complication occurrence following diabetes diagnosis and post-complication mortality rates were evaluated. Schizophrenia was associated with increased all-cause mortality (adjusted hazards ratio [aHR] 1.11, 95% CI 1.05-1.18), particularly among men and older age groups. Schizophrenia patients with diabetes had higher metabolic complication rate (aHR 1.99, 95% CI 1.63-2.42), lower microvascular complication rate (aHR 0.75, 95% CI 0.65-0.86) and comparable macrovascular complication rate (aHR 0.93, 95% CI 0.85-1.03), relative to patients with diabetes only. Among patients with diabetes complications, schizophrenia was associated with elevated all-cause mortality after macrovascular (aHR 1.19, 95% CI 1.04-1.37) and microvascular (aHR 1.33, 95% CI 1.08-1.64) complications. Gender-stratified analyses revealed that a significant effect of schizophrenia on heightened post-complication mortality was observed in men only. Schizophrenia patients with co-occurring diabetes are at increased risk of excess mortality, including post-complication mortality. Further research identifying effective interventions is warranted to optimise diabetes-related outcomes in this vulnerable population.


Clinicopathologic analysis of localized nasal/paranasal diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) comprises 2 molecularly distinct subgroups of non-germinal center B-cell-like (non-GCB) and germinal center B-cell-like (GCB) DLBCLs, with the former showing relatively poor prognosis. In the present study, we analyzed the clinicopathological features of 39 patients with localized nasal/paranasal DLBCL. Immunohistochemistry-based subclassification revealed that 11 patients (28%) were of the GCB-type according to Hans' algorithm and 11 (28%) were of the GCB-type according to Choi's algorithm. According to both Hans' and Choi's algorithms, the non-GCB type was predominant. Nevertheless, prognosis was good. Overall survival did not differ significantly between the GCB and non-GCB subgroups (Hans' algorithm: p = 0.57, Choi's algorithm: p = 0.99). Furthermore, the prognosis of localized nasal/paranasal DLBCL was better than that of other localized extranodal DLBCLs. The prognosis of extranodal DLBCL is usually considered poorer than that of nodal DLBCL. However, in our study, no difference was noted between patients with localized nasal/paranasal DLBCL and patients with localized nodal DLBCL. In conclusion, although the non-GCB subtype is thought to show poor prognosis, in our study, the prognosis for localized nasal/paranasal DLBCL patients was good irrespective of subclassification.


[Development of a questionnaire to evaluate sugar abuse and dependence].
This study describes the development of a questionnaire to evaluate the potential abuse of (and dependence on) non-milk extrinsic sugar (NMES). Recent studies have shown that excessive NMES consumption can cause alterations in the central nervous system due to the influence of these substances in the neurochemical reward system. The questionnaire was originally developed from a summary of reports from four focus groups utilizing the "L" module of the MINI-Plus questionnaire. Addiction specialists subsequently evaluated the draft of the questionnaire and altered the original instrument's content, substituting terms in order to better fit the substance used in this study. However, the original structure of 20 questions on abuse and dependence was maintained. It is hoped that an instrument to evaluate NMES abuse and dependence will help health professionals prevent and treat problems related to over-consumption of sugars. However, the diagnosis of sugar abuse and dependence and the instrument's potential psychometric properties require further study by the scientific community.


A latent class analysis of drug abuse in a national Swedish sample.
Drug abuse (DA) is a clinically heterogeneous syndrome. Using medical, legal, death and pharmacy records covering the entire population of Sweden, could we uncover meaningful subtypes of DA? We performed a latent class analysis (LCA) on all individuals in Sweden born 1950–1993 who were registered with DA or its consequences (n=192,501) and then validated these classes using demographics, patterns of co-morbidity with alcohol use disorder (AUD), non-DA crime and psychiatric illness, and the pattern of aggregation and co-aggregation in sibling pairs. The best-fit LCA had six classes : (1) low-frequency pure criminal, (2) high-frequency medical criminal, (3) low-frequency pure medical, (4) high-frequency medical, (5) prescription and (6) death. Each class had a distinct pattern of demographic features and co-morbidity and aggregated within sibling pairs with at least moderate specificity. For example, class 2 was characterized by early age at registration, low educational attainment, high male preponderance, high rates of AUDs, strong resemblance within sibling pairs [odds ratio (OR) 12.6] and crime and the highest risk for DA in siblings (20.0%). By contrast, class 5 had a female preponderance, late age at registration, low rates of crime and AUDs, high rates of psychiatric illness, high familiality within sibling pairs (OR 14.7) but the lowest observed risk for DA in siblings (8.9%). DA as assessed by public records is a heterogeneous syndrome. Familial factors contribute substantially to this heterogeneity. Advances in our understanding of etiological processes leading to DA will be aided by a consideration of this heterogeneity.


Circumventing recombination events encountered with production of a clinical-grade adenoviral vector with a double-expression cassette.
Delivery of multiple exogenous genes into target cells is important for a broad range of gene therapy applications, including combined therapeutic gene expression and noninvasive imaging. Previous studies ( Mol Ther 4: 223-231, 2001 ) have described the adenoviral vector RGDTKSSTR with a double-expression cassette that encodes herpes simplex virus thymidine kinase (HSVtk) for molecular chemotherapy and human somatostatin receptor subtype-2 (hSSTR2) for indirect imaging. In this vector, both genes are inserted in place of the E1 region of the adenoviral genome and expressed independently from two cytomegalovirus (CMV) promoters. During production of clinical-grade RGDTKSSTR, we found that the CMV promoters and simian virus 40 (SV40) poly(A) regions located in both expression cassettes provoked homologous recombination and deletion of one of the cassettes. To resolve this problem, we designed a strategy for substituting the duplicate promoters and poly(A) regions. We placed the hSSTR2 gene in the new Ad5.SSTR/TK.RGD vector under the control of a CMV promoter with a bovine growth hormone poly(A) region, whereas the SV40 promoter, enhancer, and poly(A) signal controlled HSVtk expression. This use of different regulatory sequences allowed independent expression of both transgenes from a single adenoviral vector and circumvented the recombination problem. Reconstruction of the vector with a double-expression cassette enables its use in human clinical trials.


Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition.
(-)-Quinine-catalyzed intramolecular oxo-Michael addition (IMA) of 7-hydroxy-5-methoxy-8-tigloylcoumarins was developed for the enantioselective construction of 2,3-dimethyl-4-chromanone systems in the context of the asymmetric synthesis of anti-HIV-1 active Calophyllum coumarins. Combination of the IMA and MgI(2)-assisted demethylation of the 5-methoxy group along with isomerization of the formed chromanone systems as key steps successfully led to the concise synthesis of (+)-inophyllum B and (+)-calanolide A, possible candidates for AIDS drugs. Further examination of the asymmetric IMA with cinchona alkaloids lacking a methoxy group on the quinoline skeleton suggested the influence of the methoxy substituent on stereoselectivity at the stereogenic centers of the chromanone systems.


[Architecture of collagen fibers in the meniscus of the human knee joint, with special reference to the medial meniscus and its connection to the articular ligaments].
1. To understand the meniscus-tears the architecture of their collagenic fibers is of interest, particularly so the connection of the fibers of the medial meniscus with the collateral ligament. 2. The ligaments of 12 knee joints have been studied macroscopically and with the aid of thick serial sections under polarized light. 3. The main portion of the tibial collateral ligament passes the articular space without any connection with the capsule or the meniscus. The upper oblique portion of the ligament runs inside the external zone of the meniscus to the posterior attachment of the latter. Immediately inferior to the articular space the oblique fibers have another attachment. 4. The findings in respect of the arrangement of the fibers in the menisci differ from those in earlier studies. Only in the external zone the fibers run approximately parallel to the outer border. After leaving the external zone the fibers run in an arched way through the middle zone. In the internal zone these fibers have nearly a radial direction. 5. The architecture of the menisci is discussed under functional aspects. It does not correspond to a "spring" but to a tendon, which is extended over a hypomochlion. 6. Forms and localisations of meniscus-tears have been discussed under viewpoint of architecture and compared with clinical results: The typical tear of the posterior segment of the medial meniscus is the horizontal cleavage. The present opinion according to which longitudinal tears are the typical meniscus lesion, seems to be doubtful.


Problems of operation and main reasons for failure of membranes in tertiary treatment systems.
This paper presents the results of the long-term operation and monitoring of membrane fouling at several full-scale MF/RO water recycling facilities operated by Agbar in Spain. It was demonstrated that membranes give very reliable treatment enabling the production of high-grade recycled water, well disinfected and with the removal of all priority substances. The high organic and salt concentrations of raw wastewater combined to extremely high variations justified the implementation of sand filtration to protect MF/RO membranes. Membrane autopsy was used to better understand the predominant fouling mechanisms and optimise down-stream operation and membrane cleaning strategy. The main membrane pathologies are described with recommendation of an adequate cleaning strategy.


Endogenous dopamine can modulate inhibition of substantia nigra pars reticulata neurons elicited by GABA iontophoresis or striatal stimulation.
Previous reports from this laboratory have described an ability of iontophoretically applied dopamine to attenuate the inhibitory effects of iontophoresed GABA on neurons of the substantia nigra pars reticulata. This finding raised the question of whether endogenous dopamine, released from dendrites of neighboring pars compacta dopamine neurons, might act as a neuromodulator which diminishes the inhibition of pars reticulata neurons evoked by either GABA iontophoresis or electrical stimulation of the striatonigral GABAergic pathway. Extracellular, single-unit activity of pars reticulata neurons was recorded in male rats anesthetized with chloral hydrate. In one set of studies, d-amphetamine, a drug reported to release dopamine from nigral dendrites, was administered intravenously (1.6 mg/kg) during regular, intermittent iontophoretic pulses of GABA. As had been previously observed with iontophoresed dopamine, i.v. amphetamine significantly lessened the inhibition of reticulata neurons produced by GABA application. This change was reflected by a decrease in GABA's inhibitory potency by 22% relative to the control level of inhibition achieved prior to amphetamine administration. Amphetamine caused no decreases in GABA's effectiveness, however, in animals that had previously received treatments that depleted or destroyed nigral dopamine stores, i.e., in rats pretreated with reserpine and alpha-methyl-p-tyrosine, or in rats with 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway. In a second set of experiments, amphetamine or dopamine was delivered iontophoretically while monitoring the GABA-mediated (bicuculline-reversible) inhibition of reticulata neurons that can be elicited by striatal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Gastroprotective effect of orexin-A and heme oxygenase system.
Orexin-A, besides playing an important role in the mechanism of food intake, exhibits a potent gastroprotective action against the formation of acute gastric mucosal injury. The aim of the present study was to determine the effect of administered orexin-A against ischemia-reperfusion (I/R)-induced gastric injury on the expression of heme oxygenase (HO)-1 and HO-2 in gastric tissue. Wistar rats were subjected to 30 min of ischemia followed by 3 h reperfusion. Orexin-A was infused at a dose of 500 pmol/kg/min during the I/R period. The lesion area was measured by stereomicroscope. The myeloperoxidase activity and 4-hydroxinonenol-malondialdehyde content of gastric mucosa were evaluated spectrophotometrically, and the gastric tumor necrosis factor-α was measured by enzyme linked immune sorbent assay. The expression of HO-1 and HO-2 was determined by Western blotting analysis. Orexin-A significantly decreased the I/R-induced gastric lesions, myeloperoxidase activity, and 4-hydroxinonenol-malondialdehyde concentration in gastric tissue exposed to I/R. The gastroprotective effect of orexin-A in gastric I/R model was accompanied by the increase in HO-2 expression and the decrease in HO-1 expression. Orexin-A exerts a protective action on gastric mucosa subjected to I/R, and this effect is associated with the reduction of neutrophil infiltration and lipid peroxidation in gastric tissue in addition to the increase in HO-2 expression due to the administration of orexin-A.


[Videoendosurgical diagnosis and treatment of abdominal injuries in combined trauma].
Experience with videolaparoscopy in 1332 patients with combined abdominal trauma is analyzed. The original method of diagnosis of traumatic abdominal multitraumas in shock patients was proposed and patented. Diagnostic and treatment algorithm for hemoperitoneum in patients with abdominal multitrauma based on USE or CT data on liquid in the abdominal cavity has been developed. Videolaparoscopy helped to avoid open surgery in 73.3% patients with dominating abdominal trauma.


Carrier optical vortex interferometer using segmentation demodulation method for dynamic measurement of axisymmetric surface deformation.
The dynamic measurement of surface deformation with an axisymmetric profile at nanometer- to micrometer-scale is of great interest in understanding micromechanical and thermophysical dynamics. We propose a carrier optical vortex interferometer (COVI) to measure such surface deformation dynamically by segmentation demodulation of the petal-like interferogram that is produced by the coaxial superposition of conjugated p-radial order Laguerre-Gaussian beams. Specifically, a rotating chopper placed at the exit of the interferometer introduces a carrier frequency in the absence of surface deformation. A camera placed behind the chopper uses a multi-ring segmentation detection scheme to produce a Doppler shift relative to the carrier frequency at the radius of each ring in the presence of axisymmetric surface deformation. Locating the Doppler shifts gives the surface deformation velocities at those radii. Thus, the dynamic surface deformation profile can be obtained by integrating the velocities over time. We reveal the basic principles of the carrier frequency and the Doppler shifts in the COVI theoretically. As a proof-of-concept, an external force-induced axisymmetric mechanical surface deformation is measured dynamically to demonstrate the validity of the COVI. The results show that the measurement error of the surface deformation velocity is within (-2.1, 1.1 nm/s) for the velocity ranging from 20 to 86 nm/s. The lower limit of the measurable velocity can reach 20 nm/s. The measurement error of the surface deformation profile is less than 2.5 nm for the amplitude of the surface deformation of 500 nm.


[Turnover of potential-dependent ion channels in the membrane of neuroblastoma cells studied using the protein synthesis inhibitor cycloheximide].
The influence of cycloheximide on currents through sodium and potassium channels in dialysed neuroblastoma cells of clone N18A-1 has been studied under voltage clamp conditions. When cells are incubated with cycloheximide, the conductance of sodium decreases, whereas that of potassium changes only slightly, if at all. The cycloheximide concentration, at which sodium conductance is reduced by 50% during 24 hours incubation, was about 0.5 microgram/ml. The half-time of inhibition at the concentration of 15 microgram/ml was about 9 hours, with the time of 50% inhibition of sodium being more complex than single exponential. The density of sodium channels in control and after the maximal inhibition was estimated to be about 25 and 2.2 micron-2, respectively. The sodium-potassium selectivity and the gating mechanism parameters were shown to be unchanged following cycloheximide treatment.


Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of oxidative stress.
Animal studies suggest that reactive oxygen species (ROS) play an important role in the development of diabetic cardiomyopathy. Matrix metalloproteinase-2 (MMP-2) is activated by ROS and contributes to the acute loss of myocardial contractile function by targeting and cleaving susceptible proteins including troponin I (TnI) and alpha-actinin. Using the streptozotocin-induced diabetic rat model, we evaluated the effect of daily in vivo administration of sodium selenate (0.3 mg/kg; DMS group), or a pure omega-3 fish oil with antioxidant vitamin E (omega-3E; 50 mg/kg; DMFA group), which has antioxidant-like effects, for 4 weeks on heart function and on several biochemical parameters related to oxidant stress and MMP-2. Although both treatments prevented the diabetes-induced depression in left ventricular developed pressure (LVDP) as well as the rates of changes in developed pressure (+/-dP/dt) (P<.001), the improvement in LVDP of the DMS group was greater compared to that of the DMFA group (P<.001). Moreover, these treatments reduced the diabetes-induced increase in myocardial oxidized protein sulfhydryl and nitrite concentrations (P<.001). Gelatin zymography and Western blot data indicated that the diabetes-induced changes in myocardial levels of MMP-2 and tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) and the reduction in TnI and alpha-actinin protein levels were improved in both the DMS and DMFA groups (P<.001). These results suggest that diabetes-induced alterations in MMP-2 and TIMP-4 contribute to myocardial contractile dysfunction by targeting TnI and alpha-actinin and that sodium selenate or omega-3E could have therapeutic benefits in diabetic cardiomyopathy.


A beta-thalassemia lesion abolishes the same Mst II site as the sickle mutation.
Digestion of DNA from a patient with homozygous beta zero thalassemia from Calabria, Italy with the restriction endonuclease Mst II produced a pattern similar to the one obtained with sickle cell trait DNA in that the Mst II site at the beta 6 position on one chromosome was abolished. We cloned the DNA from this beta-thalassemia chromosome and performed sequence analysis. The deletion of a single nucleotide (A) at the GAG codon of the beta 6 position results in a frame shift and early beta-globin chain termination. This mutation occurs on a chromosome with a haplotype similar to two other Mediterranean beta-thalassemia lesions. The Mst II enzyme is useful for prenatal diagnosis of beta thalassemia in this population.


Exploring the Prototypical Definitions of Intelligent Engineers Held by Irish and Swedish Higher Education Engineering Students.
Males are generally overrepresented in higher education engineering. However, the magnitude of this variance differs between countries and engineering fields. Evidence associated with the field-specific ability beliefs hypothesis suggests that perceptions of intelligence held by actors within engineering affects the engagement of underrepresented groups. This study examined perceptions of an intelligent engineer held by undergraduate and postgraduate engineering students in Ireland and Sweden, countries selected based on their levels of female representation in engineering education. It was hypothesised that there would be a significant difference in perceptions between countries. A survey methodology was employed in which a random sample of Irish and Swedish university students completed two surveys. The first asked respondents to list characteristics of an intelligent engineer, and the second asked for ratings of importance for each unique characteristic. The results indicate that an intelligent engineer was perceived to be described by seven factors; practical problem solving, conscientiousness, drive, discipline knowledge, reasoning, negative attributes, and inquisitiveness when the data was analysed collectively, but only the five factors of practical problem solving, conscientiousness, drive, discipline knowledge and negative attributes were theoretically interpretable when the data from each country was analysed independently. A gender × country interaction effect was observed for each of these five factors. The results suggest that the factors which denote intelligence in engineering between Irish and Swedish males and females are similar, but differences exist in terms of how important these factors are in terms group level definitions. Future work should consider the self-concepts held by underrepresented groups with respect to engineering relative to the factors observed in this study.


Hyperactivated PI3Kδ promotes self and commensal reactivity at the expense of optimal humoral immunity.
Gain-of-function mutations in the gene encoding the phosphatidylinositol-3-OH kinase catalytic subunit p110δ (PI3Kδ) result in a human primary immunodeficiency characterized by lymphoproliferation, respiratory infections and inefficient responses to vaccines. However, what promotes these immunological disturbances at the cellular and molecular level remains unknown. We generated a mouse model that recapitulated major features of this disease and used this model and patient samples to probe how hyperactive PI3Kδ fosters aberrant humoral immunity. We found that mutant PI3Kδ led to co-stimulatory receptor ICOS-independent increases in the abundance of follicular helper T cells (TFH cells) and germinal-center (GC) B cells, disorganized GCs and poor class-switched antigen-specific responses to immunization, associated with altered regulation of the transcription factor FOXO1 and pro-apoptotic and anti-apoptotic members of the BCL-2 family. Notably, aberrant responses were accompanied by increased reactivity to gut bacteria and a broad increase in autoantibodies that were dependent on stimulation by commensal microbes. Our findings suggest that proper regulation of PI3Kδ is critical for ensuring optimal host-protective humoral immunity despite tonic stimulation from the commensal microbiome.


Detection of circulating cytokeratin-positive cells in the blood of breast cancer patients using immunomagnetic enrichment and digital microscopy.
To examine the feasibility for identifying and enumerating cytokeratin positive (CK+) cells in the peripheral blood of breast cancer patients. Blood specimens from 34 normal donors (negative controls), 15 samples to which carcinoma cells were added (positive controls), and 84 breast cancer patients [27 node-negative (N-), 29 node-positive (N+), and 28 metastatic] were studied. RBCs were lysed with ammonium chloride and the resulting cell suspension incubated with anti-EpCAM-conjugated immunomagnetic beads for carcinoma cell enrichment. Immunomagnetically selected cells were placed on slides; stained for CKs 8, 18, and 19; and evaluated with an automated digital microscopy system that rapidly scanned the slide and collected images of cells meeting predefined staining and cytomorphological criteria. A montage of the CK+ cells was reviewed to confirm tumor cell morphology. Eighteen specimens (9 normal, 2 N-, 4 N+, and 3 metastatic) were excluded because of poor cytomorphology or staining artifact. All 15 of the positive controls [95% confidence interval (CI), 78-100%] and none of the 25 negative controls (95% CI, 0-14%) demonstrated CK+ cells. Twenty-one of the 75 (28%; 95% CI, 18-40%) samples from breast cancer patients demonstrated CK+ cells including 76% of patients with metastatic disease (95% CI, 55-91%), 8% with N+ disease (95% CI, 1-26%), and none of those with N- disease (95% CI, 0-14). The mean number of CK+ cells detected in the 21 CK+ patients was 18.4 (range, 1-120). Breast carcinoma cells can be detected in the blood from a significant fraction of metastatic breast cancer patients using immunomagnetic cell enrichment and digital microscopy. The incidence of CK+ cells was low in those with resected N+ disease (at most 26%) and those with resected N- breast cancer (at most 14%). This technique could be used in large prospective studies of patients with breast cancer to learn whether the detection of rare carcinoma cells is a useful predictive or prognostic factor.


Differential pulse voltammetric determination of eugenol at a pencil graphite electrode.
In this study, the electrochemical behavior of eugenol, a widely used herbal drug, was investigated at a pencil graphite electrode (PGE). A low-cost, disposable, sensitive and selective electrochemical sensor is proposed for the determination of eugenol by recording its differential pulse voltammograms in Britton-Robinson buffer solution containing 0.1 M KCl with pH of 2.0 at the PGE. The PGE displayed a very good electrochemical behavior with significant enhancement of the peak current compared to a glassy carbon electrode. Under experimental conditions, the PGE had a linear response range from 0.3 μM to 50.0 μM eugenol with a detection limit of 0.085 μM (based on 3S(b)). Relative standard deviations of 2.4 and 4.8% were obtained for five successive determinations of 30.0 and 5.0 μM eugenol, respectively, which indicate acceptable repeatability. This voltammetric method was successfully applied for the direct determination of eugenol in real samples. The effect of various interfering compounds on the eugenol peak current was also studied.


Polyaniline decorated Bi2MoO6 nanosheets with effective interfacial charge transfer as photocatalysts and optical limiters.
Polyaniline (PANI)-decorated Bi2MoO6 nanosheets (BMO/PANI) were prepared by a facile solvothermal method. Different characterization techniques, including X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, diffuse reflectance ultraviolet-visible spectroscopy, photoluminescence spectroscopy, electrochemical impedance spectroscopy, photocurrent spectroscopy, and nanosecond time-resolved emission studies, have been employed to investigate the structure, optical and electrical properties of the BMO/PANI composites. The wide absorption of the samples in the visible light region makes them suitable for nonlinear transmission and photocatalytic activity studies. The associated photocatalytic activity and optical nonlinearities for the BMO/PANI composites are shown to be dependent on the PANI loadings. The rational mechanisms responsible for deteriorating pollutants and improving optical nonlinearities were also proposed, which could be mainly attributed to the efficient interfacial charge transfer and the interfacial electronic interactions between PANI and Bi2MoO6. The photoluminescence spectroscopy, electrochemical impedance spectroscopy, and photocurrent spectroscopy studies confirmed that the interface charge separation efficiency was greatly improved by coupling Bi2MoO6 with PANI. The tuning of photocatalysis and nonlinear optical behaviors with variation in the content of PANI provides an easy way to attain tunable properties, which are exceedingly required in optoelectronics applications.


Metabolic setpoint control mechanisms in different physiological systems at rest and during exercise.
Using a number of different homeostatic control mechanisms in the brain and peripheral physiological systems, metabolic activity is continuously regulated at rest and during exercise to prevent catastrophic system failure. Essential for the function of these regulatory processes are baseline "setpoint" levels of metabolic function, which can be used to calculate the level of response required for the maintenance of system homeostasis after system perturbation, and to which the perturbed metabolic activity levels are returned to at the end of the regulatory process. How these setpoint levels of all the different metabolic variables in the different peripheral physiological systems are created and maintained, and why they are similar in different individuals, has not been well explained. In this article, putative system regulators of metabolic setpoint levels are described. These include that: (i) innate setpoint values are stored in a certain region of the central nervous system, such as the hypothalamus; (ii) setpoint values are created and maintained as a response to continuous external perturbations, such as gravity or "zeitgebers", (iii) setpoint values are created and maintained by complex system dynamical activity in the different peripheral systems, where setpoint levels are regulated by the ongoing feedback control activity between different peripheral variables; (iv) human anatomical and biomechanical constraints contribute to the creation and maintenance of metabolic setpoints values; or (v) a combination of all these four different mechanisms occurs. Exercise training and disease processes can affect these metabolic setpoint values, but the setpoint values are returned to pre-training or pre-disease levels if the training stimulus is removed or if the disease process is cured. Further work is required to determine what the ultimate system regulator of metabolic setpoint values is, why some setpoint values are more stringently protected by homeostatic regulatory mechanisms than others, and the role of conscious decision making processes in determining the regulation of metabolic setpoint values.


Comparison of Clinical and Radiographic Outcomes After Standalone Versus Cage and Plate Constructs for Anterior Cervical Discectomy and Fusion.
Anterior cervical discectomy and fusion (ACDF) has conventionally been performed using an allograft cage with a plate-and-screw construct. Recently, standalone cages have gained popularity due to theorized decreases in operative time and postoperative dysphagia. Few studies have compared these outcomes. Here, we directly compare the outcomes of plated versus standalone ACDF constructs. A single-center retrospective review of patients undergoing ACDF after June 2011 with at least 6 months of follow up was conducted. Clinical outcomes were analyzed and compared between standalone and plated constructs. Multivariate regression analysis of the primary outcome, need for revision surgery, as well as several secondary outcomes, procedure duration, estimated blood loss (EBL), length of hospital stay, disposition, and incidence of dysphagia, hoarseness, or surgical site infection, was completed. A total of 321 patients underwent ACDF and met inclusion-exclusion criteria, with mean follow-up duration of 20 months. Forty-six (14.3%) patients received standalone constructs, while 275 (85.7%) received plated constructs. Fourteen (4.4%) total revisions were necessary, 4 in the standalone group and 10 in the plated group, yielding revision rates of 8.7% and 3.6%, respectively (P = .125). Mean EBL was 98 mL in the standalone group and 63 mL in the plated group (P = .001). Mean procedure duration was 147 minutes in the standalone group and 151 minutes in the plated group (P = .800). Mean hospital stay was 3.6 days in the standalone group and 2.5 days in the plated group (P = .270). There was no significant difference in incidence of dysphagia (P = .700) or hoarseness (P = .700). Standalone ACDF demonstrates higher, but not statistically significant, revision rates than plate-and-screw constructs, without the hypothesized decreased incidence of dysphagia or hoarseness and without decreased procedure duration or EBL. Surgeons may consider limiting use of these constructs to cases of adjacent segment disease. Larger studies with longer follow up are necessary to make more definitive conclusions. 4. This study will help spine surgeons decide between using standalone or cage-and-plate constructs for ACDF.


Found: The missing discriminators of cell-surface auxin receptors.
An Arabidopsis cell-surface auxin receptor that mediates rapid elongation consists of transmembrane kinases (TMKs) and an auxin-binding co-receptor. Auxin-binding protein 1 (ABP1) is one identified TMK co-receptor, but abp1 mutants have no elongation phenotypes. Yu et al. use structural analysis of the ABP1-binding pocket to identify functional ABP1-like (ABL) TMK co-receptors that regulate rapid growth.


Drosophila melanogaster as an organism model for studying cystic fibrosis and its major associated microbial infections.
Cystic fibrosis (CF) is a human genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene that encodes a chloride channel. The most severe clinical manifestation is associated with chronic pulmonary infections by pathogenic and opportunistic microbes. Drosophila melanogaster has become the invertebrate model of choice for modeling microbial infections and studying the induced innate immune response. Here, we review its contribution to the understanding of infections with six major pathogens associated with CF (Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, Mycobacterium abscessus, Streptococcus pneumoniae, and Aspergillus fumigatus) together with the perspectives opened by the recent availability of two CF models in this model organism.


'The lesser devil you don't know': a qualitative study of smokers' responses to messages communicating comparative risk of electronic and combusted cigarettes.
Communicating to smokers that e-cigarettes deliver lower levels of harmful chemicals than combusted cigarettes is a challenging issue. This study qualitatively explored smokers' interpretations of messages communicating the risk of e-cigarettes relative to cigarettes (comparative risk messages). We developed 12 print comparative risk messages and evaluated them in 12 focus groups with 72 adult smokers (18+ years old) in Atlanta, Georgia. Participants interpreted uncertainty about health effects of e-cigarettes as an indicator of significant unknown risks, which some believed to be potentially more severe than the known effects of cigarettes (such as cancer and heart disease). Also, participants were sceptical about the lower risk claims. Some participants misinterpreted what 'switching completely' or 'switching 100% of the time' means, perceiving switching from e-cigarettes to combusted cigarettes as comparable with the use of both products. When chemicals in e-cigarettes were mentioned (eg, nicotine or formaldehyde), participants viewed e-cigarettes as very harmful and had difficulty reconciling this belief with the reduced risk claim. Comparative risk messages emphasising smoking risks were perceived as effective. Participants also appreciated being given an option to switch if they cannot quit. Participants suggested the inclusion of more facts and statistics and a credible message source (eg, public health agencies) to increase message effectiveness. Comparative risk messages may be more acceptable to smokers if they show direct comparisons of the number of toxic chemicals in cigarettes and e-cigarettes, are attributed to a credible source(s), and emphasise smoking risks.


T cell antigen receptor expression in athymic (nu/nu) mice. Evidence for an oligoclonal beta chain repertoire.
The expression of T cell antigen receptors (TCR) in congenitally athymic (nude) mice has been investigated. Lymph node T cells from 4-5-mo-old athymic mice expressed full-length transcripts for the TCR alpha and beta chains at a level two-to three-fold lower than normal littermate (nu/+) controls. Low levels of expression of TCR protein at the surface of a proportion of nude T cells was demonstrated by staining with monoclonal antibodies KJ16-133 and F23.1 (directed against protein products of a family of TCR beta chain variable region genes known as V beta 8). Immunoprecipitation studies confirmed that F23.1 reacted with a similar molecular species on nude and nu/+ T cells. Studies with individual nude mice revealed a striking heterogeneity in the proportion of T cells expressing KJ16/F23.1 that was not seen in normal animals. This heterogeneity correlated with the expression of mRNA specific for V beta 8 but not with total expression of full-length beta chain transcripts. Analysis of Lyt-2+ and L3T4+ T cell subsets in individual nude mice further demonstrated that F23.1 expression was frequently associated with only one subset, and several cases were seen in which all L3T4+ cells expressed F23.1. In contrast, a similar (and constant) proportion of Lyt-2+ or L3T4+ T cells expressed F23.1 in control mice. Southern blotting of Hind III-digested DNA from nude T cells with a C beta probe revealed a more restricted pattern of TCR beta chain rearrangements than was seen for normal T cells. Taken together, these data provide compelling evidence that TCR gene rearrangement and expression can occur extrathymically. Furthermore, they suggest a model according to which the restricted functional repertoire of T cells previously observed in individual nude mice results from an oligoclonal expansion of T cells that have randomly rearranged and expressed TCR beta chain genes.


A Large Multiethnic Genome-Wide Association Study of Adult Body Mass Index Identifies Novel Loci.
Body mass index (BMI), a proxy measure for obesity, is determined by both environmental (including ethnicity, age, and sex) and genetic factors, with > 400 BMI-associated loci identified to date. However, the impact, interplay, and underlying biological mechanisms among BMI, environment, genetics, and ancestry are not completely understood. To further examine these relationships, we utilized 427,509 calendar year-averaged BMI measurements from 100,418 adults from the single large multiethnic Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We observed substantial independent ancestry and nationality differences, including ancestry principal component interactions and nonlinear effects. To increase the list of BMI-associated variants before assessing other differences, we conducted a genome-wide association study (GWAS) in GERA, with replication in the Genetic Investigation of Anthropomorphic Traits (GIANT) consortium combined with the UK Biobank (UKB), followed by GWAS in GERA combined with GIANT, with replication in the UKB. We discovered 30 novel independent BMI loci (P < 5.0 × 10-8) that replicated. We then assessed the proportion of BMI variance explained by sex in the UKB using previously identified loci compared to previously and newly identified loci and found slight increases: from 3.0 to 3.3% for males and from 2.7 to 3.0% for females. Further, the variance explained by previously and newly identified variants decreased with increasing age in the GERA and UKB cohorts, echoed in the variance explained by the entire genome, which also showed gene-age interaction effects. Finally, we conducted a tissue expression QTL enrichment analysis, which revealed that GWAS BMI-associated variants were enriched in the cerebellum, consistent with prior work in humans and mice.


Epidemiology and factors associated with COVID-19 outbreak-related deaths in patients admitted to medical centers of Mazandaran University of Medical Sciences.
The first case of COVID-19 was reported in Iran on February 19, 2020, in Qom. Since Mazandaran is one of the high-risk provinces with many patients and deaths, this study was conducted to investigate the epidemiological characteristics of COVID-19-related deaths in Mazandaran. In this descriptive study, demographic information and clinical findings in patients who died following COVID-19 in the medical centers of Mazandaran University of Medical Sciences from February 8, 2020, to October 10, 2020, were extracted. Data were analyzed by using SPSS 21. Logistic regression was used to compare the data. P < 0.05 was considered as the significance level. Out of a total of 34,039 patients admitted during the 8 months, 2907 patients died. Of these, 1529 (52%) were male, and the rest were female. In terms of age, 10 cases in the age group of fewer than 15 years, 229 cases in the age group of 15-44 years, 864 patients in the age group of 45-64 years, and 1793 people in the age group of 65 years and over died. 2206 people (more than 75%) by personal visit referred to medical centers. The mortality rate was more than 8 cases per 100 hospitalized patients. Men were 16% more likely to die from COVID-19 than women. Older adults over 65 have the highest incidence and death rate due to this disease. The incidence rate was higher in women, and the death rate was higher in men, which differs from the national pattern.


Measurement of conductivity and permittivity on samples sealed in nuclear magnetic resonance tubes.
We present a broadband impedance spectroscopy instrument designed to measure conductivity and∕or permittivity for samples that are sealed in glass tubes, such as the standard 5 mm tubes used for nuclear magnetic resonance experiments. The calibrations and corrections required to extract the dielectric properties of the sample itself are outlined. It is demonstrated that good estimates of the value of dc-conductivity can be obtained even without correcting for the effects of glass or air on the overall impedance. The approach is validated by comparing data obtained from samples sealed in nuclear magnetic resonance tubes with those from standard dielectric cells, using glycerol and butylmethylimidazolium-hexafluorophosphate as respective examples of a molecular and an ionic liquid. This instrument and approach may prove useful for other studies of permittivity and conductivity where contact to the metal electrodes or to the ambient atmosphere needs to be avoided.


The shape of pterosaur evolution: evidence from the fossil record.
Although pterosaurs are a well-known lineage of Mesozoic flying reptiles, their fossil record and evolutionary dynamics have never been adequately quantified. On the basis of a comprehensive data set of fossil occurrences correlated with taxon-specific limb measurements, we show that the geological ages of pterosaur specimens closely approximate hypothesized patterns of phylogenetic divergence. Although the fossil record has expanded greatly in recent years, collectorship still approximates a sigmoid curve over time as many more specimens (and thus taxa) still remain undiscovered, yet our data suggest that the pterosaur fossil record is unbiased by sites of exceptional preservation (lagerstätte). This is because as new species are discovered the number of known formations and sites yielding pterosaur fossils has also increased - this would not be expected if the bulk of the record came from just a few exceptional faunas. Pterosaur morphological diversification is, however, strongly age biased: rarefaction analysis shows that peaks of diversity occur in the Late Jurassic and Early Cretaceous correlated with periods of increased limb disparity. In this respect, pterosaurs appear unique amongst flying vertebrates in that their disparity seems to have peaked relatively late in clade history. Comparative analyses also show that there is little evidence that the evolutionary diversification of pterosaurs was in any way constrained by the appearance and radiation of birds.


Fragile X syndrome at the turn of the century.
Fragile X syndrome is not only the most common form of inherited cognitive impairment, it is also one of the most frequent single gene disorders. It is caused by a stretch of CGG-repeats within the fragile X gene, which increases in length as it is transmitted from generation to generation. Once the repeat exceeds a threshold length, no fragile X protein is produced and disease results. Since the mutation was discovered, nearly a decade of research has revealed a wealth of information regarding the fragile X gene and its possible function within the cell. The fragile X story also provides a sobering example of how much time and effort might be necessary to develop beneficial treatment through understanding gene function.


Actions Speak Louder than Words: How Characters' Effectiveness as Message Sources Depend on Their Story Experiences.
A television (TV) character's actions and the consequences of these actions in TV storylines can shape the audience's own behavioral intentions, especially if the audience identifies with that character. The current research examines how storylines depicting positive versus negative consequences of drinking affect youths' drinking intentions, and whether post-narrative intervention messages delivered by story characters alter these influences. Results indicate that a post-narrative intervention can correct drinking intentions shaped by a pro-alcohol storyline, but the effectiveness depends on the source: a peripheral character is more effective than the main character at delivering a corrective message. This research pinpoints the role of identification with the main character as a key driver of stories' influence and a key focus of health intervention efforts to correct these stories' potentially undesirable impact on vulnerable audiences.


Membrane backwash cleaning using CO2 nucleation.
Low pressure membranes, such as ultrafiltration (UF), are widely used in water treatment applications, including the pretreatment of reverse osmosis desalination. UF membranes produce a water of superior quality, in addition to reducing the footprint and the use of chemicals, compared to conventional methods. However, membrane fouling remains a major drawback, and frequent membrane cleanings are required to maintain the flux of water and its quality. Typically, after a series of backwashes using an UF permeate, a chemical cleaning process is applied to fully recover the membrane's permeability. However, frequent chemical cleanings negatively affect the lifetime of the membrane, the environment, and increase operational costs. Here, we introduce a novel cleaning method that uses a solution saturated with CO2 to clean the membranes through the backwash step. As the pressure drops, the CO2 solution becomes supersaturated, and bubbles start to nucleate within the membrane pores and on its surface, resulting in the effective removal of the deposited fouling material. These foulants are further helping the nucleation process as they are considered as imperfection sites with high creation and growth of bubbles. Investigations performed for different synthetic feed solutions of organic compounds (sodium alginate), colloidal matter (silica) and sea salts, at different concentrations, show that our new physical cleaning process using CO2 is more performant than the regular backwash using Milli-Q water. We obtain a 100% flux recovery, in a short time, even under severe irreversible fouling conditions. Based on these results, we conclude that replacing water by a solution saturated with CO2 for the backwash cleaning of filtration membranes provides significant benefits to existing cleaning processes, and represent a promising alternative for improving and lowering the frequency of conventional chemical cleaning methods.


Supralinear Ca2+ influx into dendritic tufts of layer 2/3 neocortical pyramidal neurons in vitro and in vivo.
Pyramidal neurons in layer 2/3 of the neocortex are central to cortical circuitry, but the intrinsic properties of their dendrites are poorly understood. Here we study layer 2/3 apical dendrites in parallel experiments in acute brain slices and in anesthetized rats using whole-cell recordings and Ca2+ imaging. We find that backpropagation of action potentials into the dendritic arbor is actively supported by Na+ channels both in vitro and in vivo. Single action potentials evoke substantial Ca2+ influx in the apical trunk but little or none in the dendritic tuft. Supralinear Ca2+ influx is produced in the tuft, however, when an action potential is paired with synaptic input. This dendritic supralinearity enables layer 2/3 neurons to integrate ascending sensory input from layer 4 and associative input to layer 1.


Comparison of a new anti-glutamic acid decarboxylase (GAD) enzyme-linked immunosorbent assay (ELISA) with radioimmunoassay methods: a multicenter study.
Several methods are available for the measurement of antibodies to glutamic acid decarboxylase (anti GAD). These antibodies are valuable tools for the immunodiagnosis of insulin-dependent (type 1) diabetes mellitus (IDDM) and for the assessment of risk for the future development of IDDM. We here describe a new enzyme-linked immunosorbent assay (ELISA) for the detection of anti-GAD which was tested in a multicenter study. The results of the new anti-GAD ELISA correlate well with those obtained by radioimmunoassays (RIA) and they have a higher sensitivity (69%) and specificity (98%) compared to other anti-GAD enzyme immunoassays as determined in the IDW Proficiency Test Program for the detection of GAD antibodies. The new ELISA is simple and easy to perform, with convenient handling of the reagents. Quantitative and reproducible test results are available within approximately four hours. The new anti-GAD ELISA can be used for large scale population screening to indicate a prediabetic state as well as to diagnose autoimmune diabetes in adults (LADA) and the risk for IDDM in pregnant women with gestational diabetes.


Length-dependent sensitivity at lengths greater than Lmax in vascular smooth muscle.
Previous work has shown that vascular smooth muscle sensitivity depends on muscle length (arterial circumference) at lengths equal to and less than that for maximum active force (Lmax). In the present study dose-response curves were obtained from dog anterior tibial artery rings at lengths equal to or longer than Lmax. The curves were compared with dose-response curves obtained at lengths less than Lmax. The agonist concentration for half maximal response (ED50) was determined by graphical estimation and by calculation from a best-fit curve. The results show that with norepinephrine (NE) stimulation 1) ED50 decreased significantly at each step when the rings were stretched from Lmax to 1.15 Lmax and then to 1.30 Lmax; 2) ED50 increased significantly when length was decreased from 1.15 to 1.00 Lmax; 3) ED50 decreased significantly at each step when the rings were stretched from 0.70 Lmax to Lmax and then to 1.30 Lmax; and 4) for NE concentration greater than the ED50 at Lmax, active stress was significantly higher at Lmax than at 0.70 Lmax or 1.30 Lmax. For an NE concentration less than the ED50 at Lmax, the active stress at 1.30 Lmax was higher than the active stress at Lmax and at 0.70 Lmax. The results show that sensitivity of vascular smooth muscle continually increases with stretch and does not have a maximum at the length for maximum active force.


Prevalence and characteristics of talon cusps in Turkish population.
Talon cusp is a rare dental anomaly characterized by a cusp-like projection, often including the palatal surface of the affected tooth. The aim of the present study was to investigate the prevalence and characteristics of talon cusps in a group of Turkish children. The study population consisted of 14,400 subjects who attended the clinics of the Department of Pediatric Dentistry at the Istanbul University, Istanbul, Turkey. Subjects ranged in age from 1 to 14 years with a mean age of 10.5 ± 2.55 years. Talon cusps were mainly categorized by visual examination according to the classification of Hattab et al. The distribution and frequency of talon cusps were calculated with respect to dentition type, tooth type, talon type, the affected surface, associated dental anomalies, and clinical complications. Statistical analysis included descriptive statistics, frequencies, and crosstabs with Chi-square analysis. Talon cusps were detected in 49 subjects (26 males and 23 females) of 14,400 (0.34%). A total of 108 teeth showed talon cusps. Distribution of talon cusps according to gender showed no statistically significant differences. The incidence of talon cusps was found to be greater in maxillary lateral incisors (53.7%) than central incisors (29.62%). Regarding the type of talon cusp, 47.22% of teeth showed a Type III talon cusp, whereas 30.55% of teeth demonstrated a Type II talon and 22.22% of teeth demonstrated a Type I talon cusp. Nine patients (18.36%) with talon cups also exhibited other developmental dental anomalies. Clinical complications associated with talon cusps were detected as caries formation and occlusal interference. This is the most comprehensive study of the prevalence of talon cusps in Turkish population using the largest sample size to date. Also, taurodontism associated with a talon cusp has been reported here for the 1(st) time. Clinical complications associated with talon cusps need more investigations.


Evidence that invasion-inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein-1 (MSP-1 19) can play a protective role against blood-stage Plasmodium falciparum infection in individuals in a malaria endemic area of Africa.
The C-terminal 19-kDa fragment of Plasmodium falciparum merozoite surface protein-1 (MSP-1(19)) is a target of protective Abs against blood-stage infection and a leading candidate for inclusion in a human malaria vaccine. However, the precise role, relative importance, and mechanism of action of Abs that target this protein remain unclear. To examine the potential protective role of Abs to MSP-1(19) in individuals naturally exposed to malaria, we conducted a treatment time to infection study over a 10-wk period in 76 residents of a highland area of western Kenya during a malaria epidemic. These semi-immune individuals were not all equally susceptible to reinfection with P. falciparum following drug cure. Using a new neutralization assay based on transgenic P. falciparum expressing the P. chabaudi MSP-1(19) orthologue, individuals with high-level MSP-1(19)-specific invasion-inhibitory Abs (>75th percentile) had a 66% reduction in the risk of blood-stage infection relative to others in the population (95% confidence interval, 3-88%). In contrast, high levels of MSP-1(19) IgG or IgG subclass Abs measured by enzyme immunoassay with six different recombinant MSP-1(19) Ags did not correlate with protection from infection. IgG Abs measured by serology and functional invasion-inhibitory activity did not correlate with each other. These findings implicate an important protective role for MSP-1(19)-specific invasion inhibitory Abs in immunity to blood-stage P. falciparum infection, and suggest that the measurement of MSP-1(19) specific inhibitory Abs may serve as an accurate correlate of protection in clinical trials of MSP-1-based vaccines.


Cultural competence policies and other predictors of asthma care quality for Medicaid-insured children.
More than half of Medicaid enrollees are now in managed care. Scant information exists about which policies of practice sites improve quality of care in managed Medicaid. Children with asthma are a sentinel group for Medicaid quality monitoring because they are at elevated risk for adverse outcomes. The objective of this study was to identify practice-site policies and features associated with quality of care for Medicaid-insured children with asthma. A prospective cohort study with 1-year follow-up was conducted in 5 health plans in California, Washington, and Massachusetts. Data were collected via telephone interviews with parents at baseline and 1 year, surveys of practice sites and clinicians, and computerized databases. The practice site survey asked about policies to promote cultural competence, the use of several types of reports to clinicians, support for self-management of asthma, case management and care coordination, and access to and continuity of care. Quality of care was evaluated on the basis of 5 measures: 1) preventive medication underuse based on parent report; 2) the parent's rating of asthma care; 3) the 1-year change in the child's asthma physical status based on a standardized measure; 4) preventive medication underprescribing based on computerized data; and 5) the occurrence of a hospital-based episode. Of the 1663 children in the study population, 67% had persistent asthma at baseline based on parent report of symptoms and medications. At 1-year follow-up, 65% of the children with persistent asthma were underusing preventive medication based on parent report. In multivariate analyses, patients of practice sites with the highest cultural competence scores were less likely to be underusing preventive asthma medications based on parent report at follow-up (odds ratio [OR]: 0.15; 95% confidence interval [CI]: 0.06-0.41 for the highest vs lowest categories) and had better parent ratings of care. The use of asthma reports to clinicians was predictive of less preventive medication underprescribing based on computerized data (OR: 0.33; 95% CI: 0.16-0.69), better parent ratings of care, and better asthma physical status at follow-up. Patients of practice sites with policies to promote access and continuity had less underuse of preventive medications (OR: 0.56; 95% CI: 0.34-0.93). Among the 83 practice sites, the practice site's size, organizational type, percentage of patients insured by Medicaid, mechanism of payment for specialty care, and other primary care features were not consistently associated with quality measures. Practice-site policies to promote cultural competence, the use of reports to clinicians, and access and continuity predicted higher quality of care for children with asthma in managed Medicaid.


Effectiveness of five insecticides for the control of adults and young stages of Cacopsylla melanoneura (Förster) (Hemiptera: Psyllidae) in a semi-field trial.
Cacopsylla melanoneura (Förster) is a vector of Candidatus Phytoplasma mali, the causal agent of one of the most serious diseases in European apple orchards, apple proliferation (AP). The aim of this study was to evaluate the toxicity of five insecticides from different chemical groups (carbamates, chitin inhibitors, insect growth regulators, organophosphates and pyrethroids) towards overwintered adults and young stages of C. melanoneura under semi-field conditions. The organophosphate chlorpyrifos and the pyrethroid etofenprox caused higher mortality of overwintered adults than diflubenzuron, fenoxycarb and abamectin, with mortality values exceeding 90%. All the pesticides tested reduced the number of progeny per female and, except for abamectin, were highly effective against young stages, with a long-lasting effect. An integrated management of the vector is currently required to prevent the spread of AP. The reference insecticides, chlorpyrifos and etofenprox, have a strong toxicity and persistence against all stages of the vector. In apple orchard IPM programmes, the chitin inhibitors and the insect growth regulators could be part of an alternative and more sustainable strategy for the control of C. melanoneura owing to their effectiveness against immature stages.


Postoperative Outcome of Robot-Assisted Transforaminal Lumbar Interbody Fusion: A Pilot Study.
Transforaminal lumbar interbody fusion (TLIF) surgery is well established for the treatment of discopathy, foraminal disc herniation, and recurrent disc herniation. At the Amiens university medical center, we have been using a robot-assisted technique for performing the TLIF. The purpose of this study is to evaluate the radiological and clinical outcome, specifically pain, of patients having undergone robot-assisted TLIF. We performed a retrospective analysis of prospectively collected data of patients having undergone minimally invasive (MI) robot-assisted TLIF between November 2014 and July 2018 in a French university medical center. In clinical consultations at 6 weeks, 12 months, and 24 months posttreatment, patients were assessed for back and leg pain (on a visual analog scale), breached screws, and sagittal parameters. A total of 136 pedicle screws were inserted with robot guidance into 32 patients. Four of the patients required laminectomy before fusion. No pedicle breach occurred for 94% of the screws, and no joint violation was observed for 90%. Lordosis was improved in 78% of the cases. The robot provides valuable assistance during MI arthrodesis; it facilitates the surgical procedure by preplanning the trajectory, providing instantaneous navigation and tracking, and thus assure the accuracy of screw positioning.


Identification of a novel Fcalpha receptor expressed by human mesangial cells.
IgA nephropathy (IgAN) is characterized by mesangial deposits of polymeric IgA (pIgA). The pathological consequences of IgA deposition are believed to center on direct interaction between IgA and the glomerular mesangial cell (MC). We have characterized a novel mesangial receptor that recognizes the Fc portion of IgA. Five primary MC cultures were evaluated for IgA binding by flow cytometry, and specificity of binding was determined by competitive inhibition. Relative affinities of the receptor for all IgA isoforms were also determined, and binding of pIgA1 was compared to monomer. The identified Fc receptor was then compared with CD89, hitherto the only other Fcalpha receptor reported. CD89 protein and mRNA expression were detected by conventional and intracellular flow cytometry, sequencing of reverse transcription-polymerase chain reaction (RT-PCR) products, and Northern blotting. All MCs constitutively expressed a receptor that bound IgA in an Fcalpha-dependent fashion. The receptor recognized secretory and serum IgA1 and IgA2 equally, but pIgA bound with much greater affinity than monomer. At no time were we able to detect CD89 synthesis, although three novel CD89-related mRNA transcripts were identified by RT-PCR. We have clearly demonstrated that MCs consistently express an FcalphaR distinct from the myeloid FcalphaR CD89. This novel receptor binds pIgA with high affinity and may therefore mediate the mesangial injury that follows IgA deposition in IgAN. While immunogenically distinct, the mesangial Fcalpha receptor may share some molecular homology with CD89, as mRNA transcripts with partial identity to CD89 were found in all five MC cultures.


Invited commentary: a sunbed epidemic?
The Icelandic study of melanoma trends by Héry et al. in this issue of the Journal (Am J Epidemiol. 2010;172(7):762-767) is a fascinating analysis of an ecologic association. The authors noted a sharp increase in melanoma incidence that appeared to lag a few years behind the increased prevalence of sunbeds in Iceland. Caution, however, must be exercised in interpreting the data because of the lack of understanding of emissions of ultraviolet radiation from sunbeds and the ecologic nature of the data.


Recombinant human C5a-induced bronchoconstriction in the guinea pig: inhibition by an H1 antagonist after depletion of circulating granulocytes and platelets.
Recombinant human C5a (rHuC5a) causes an intense bronchoconstriction very quickly after i.v. injection into the guinea pig. In addition, it causes a biphasic blood pressure response characterized by a small hypotensive phase followed by a larger transient hypertensive phase. The overall goal was to determine the role of circulating cells in the bronchoconstriction and changes in blood pressure induced by rHuC5a. Intravenous injection of rHuC5a causes a transient granulocytopenia and thrombocytopenia, suggesting that these cells may be important targets of C5a action. However, the magnitude of granulocytopenia does not directly correlate with the magnitude of the bronchoconstriction, suggesting no direct connection between the events. Our studies continued to determine if depletion of circulating granulocytes and/or platelets altered the magnitude of, or the participation of histamine in, C5a-induced bronchoconstriction in the guinea pig. Selective depletion of circulating granulocytes, circulating platelets or both with specific antisera did not alter the severity, time of onset or duration of the rHuC5a-induced bronchoconstriction. The rHuC5a-induced hypertensive blood pressure response was significantly reduced only in guinea pigs depleted of just granulocytes. After depletion of both circulating granulocytes and platelets, histamine plays an important role in mediating the rHuC5a-induced bronchoconstriction as evidenced by the effectiveness of an H1 antagonist in inhibiting the response. This is in contrast to the ineffectiveness of the same H1 antagonist in inhibiting rHuC5a-induced bronchoconstriction in guinea pigs with normal numbers of circulating granulocytes and platelets or guinea pigs depleted of granulocytes only or platelets only.(ABSTRACT TRUNCATED AT 250 WORDS)


Motion blurring with decaying detector response.
The spread function and optical transfer function associated with image motion relative to the recording medium are derived and generalized to cover media whose response changes with time. Specific expressions are derived for an exponentially decaying response and three types of image motion: linear, sinusoidal, and random walk. An expression for the blurring in flying spot scanners using cathode ray tubes, caused by the finite decay time of the phosphor, is also derived.


Advancing opportunities for children's informal STEM learning transfer through parent-child narrative reflection.
This study examined whether families' conversational reflections after a STEM (science, technology, engineering, and mathematics)-related experience in a museum promoted learning transfer. 63 children (M = 6.93 years; 30 girls; 57% White, 17.5% Latinx, 8% Asian, 5% African American, 9.5% mixed, 3% missing race/ethnicity) and their parents received an engineering demonstration, engaged in a building activity, and either recorded a photo-narrative reflection about their building experience or not at the museum. Thirty-six of these families completed a building activity with different materials weeks later at home, and the majority (77%) evidenced learning transfer of the building principle demonstrated at the museum. Those who participated in the photo-narrative reflection at the museum also showed learning transfer by talking more about STEM during the home building activity.


Effects of selective inhibition of thromboxane synthesis on renal function in humans.
Thromboxane A2, a potent vasoconstrictor, is a major metabolite of arachidonic acid in the human kidney. To determine the role of thromboxanes in renal hemodynamics, we administered the new thromboxane inhibitor dazmegrel or placebo to 20 healthy volunteers for 14 days in a double-blind protocol. Dazmegrel reduced urinary thromboxane B2 by an average of 68% and serum thromboxane B2 by 79%, without affecting urinary excretion of the prostacyclin metabolite 6-ketoprostaglandin F 1 alpha. Neither p-aminohippurate clearance nor inulin clearance were altered by thromboxane inhibition. Thus it is unlikely that thromboxane A2 plays a major role in the regulation of glomerular function in healthy humans.


Schlieren-cinematographic and holographic diagnostic of a laser-produced plasma in xenon.
We have studied extensively a gas breakdown in xenon produced by a giant pulse ruby laser with a power <100 MW. Detailed information concerning the structure of the laser plasma formation and of the following expansion has been obtained by different optical methods, including schlieren techniques (single frames and ultra high speed cinematography) and holography. The high quality of the holographic pictures was achieved by the use of a monomode laser. With this we were able to visualize the plasma history and to determine the velocities of the boundary layer and of the blast wave with utmost accuracy. Investigations of the electron density and electron temperature showed that a relaxation time of about 10 nsec is necessary to establish local thermodynamic equilibrium states. After this relaxation time it is then possible to carry out thermodynamic calculations, applying the shock-wave theory, to relate the optically measured expansion velocity with the plasma parameters involved. The mean specific internal energy epsilon , for instance, attained values in excess of 10(12) erg/g which decayed rapidly during the first 100 nsec to about 5. 10(10) erg/g. By comparing the results to theoretical calculations of we obtained a first estimate of the temperature, taking into consideration the partial densities n(j) as well as the partition functions Z(j)((i)) of the xenon atoms, the single-charged ions, and the double-charged ones. Furthermore, a two-step iteration computer program was used to give more detailed and more accurate results on the variations of the pressure, temperature, partial densities, and enthalpy as a function of time.


Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women.
In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes. Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age-matched men (n = 11; 59 +/- 2 years) and post-menopausal women (n = 10; 60 +/- 1 years). mRNA expression of several genes involved in glucose and lipid metabolism was higher in skeletal muscle biopsies from female vs. male donors, but unaltered between the sexes in cultured myotubes. Basal and insulin-stimulated glucose uptake, as well as glucose incorporation into glycogen, was similar in myotube cultures derived from male vs. female donors. In males vs. females, insulin increased glucose uptake (1.3 +/- 0.1 vs. 1.5 +/- 0.1-fold respectively) and incorporation into glycogen (2.3 +/- 0.3 vs. 2.0 +/- 0.3-fold respectively) to the same extent. Basal fatty acid oxidation and rate of uptake/accumulation was similar between sexes. In response to the 5'AMP-activated protein kinase activator AICAR, lipid oxidation was increased to the same extent in myotubes established from male vs. female donors (1.6 +/- 0.6 vs. 2.0 +/- 0.3-fold respectively). Moreover, the AICAR-induced rate of uptake/accumulation was similar between sexes. Differences in metabolic parameters and gene expression profiles between age-matched men and post-menopausal women noted in vivo are not observed in cultured human skeletal muscle cells. Thus, the sexual dimorphism in glucose and lipid metabolism is likely a consequence of systemic whole body factors, rather than intrinsic differences in the skeletal muscle proper.


Annual variation in the levels of transcripts of sex-specific genes in the mantle of the common mussel, Mytilus edulis.
Mytilus species are used as sentinels for the assessment of environmental health but sex or stage in the reproduction cycle is rarely considered even though both parameters are likely to influence responses to pollution. We have validated the use of a qPCR assay for sex identification and related the levels of transcripts to the reproductive cycle. A temporal study of mantle of Mytilus edulis found transcripts of male-specific vitelline coat lysin (VCL) and female-specific vitelline envelope receptor for lysin (VERL) could identify sex over a complete year. The levels of VCL/VERL were proportional to the numbers of sperm/ova and are indicative of the stage of the reproductive cycle. Maximal levels of VCL and VERL were found in February 2009 declining to minima between July - August before increasing and re-attaining a peak in February 2010. Water temperature may influence these transitions since they coincide with minimal water temperature in February and maximal temperature in August. An identical pattern of variation was found for a cryptic female-specific transcript (H5) but a very different pattern was observed for oestrogen receptor 2 (ER2). ER2 varied in a sex-specific way with male > female for most of the cycle, with a female maxima in July and a male maxima in December. Using artificially spawned animals, the transcripts for VCL, VERL and H5 were shown to be present in gametes and thus their disappearance from mantle is indicative of spawning. VCL and VERL are present at equivalent levels in February and July-August but during gametogenesis (August to January) and spawning (March to June) VCL is present at lower relative amounts than VERL. This may indicate sex-specific control mechanisms for these processes and highlight a potential pressure point leading to reduced reproductive output if environmental factors cause asynchrony to gamete maturation or release.


Self-assembled ZnO microspheres coated with carbon dot-doped CoNi LDH wrinkled films as electrochemical sensors for highly sensitive detection of hydrazine.
In this study, a 3D surface-folded composite was prepared in situ as a hydrazine sensor by loading a hybrid film of CoNi-layered double hydroxides (LDHs) with nitrogen-doped carbon dots on self-assembled ZnO microspheres. The nanocomposite was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), and the electrochemical behavior of the sensors was investigated by cyclic voltammetry (CV), amperometry and electrochemical impedance spectroscopy (EIS). The results showed that ZnO microspheres with nitrogen-doped carbon dots strongly coupled with LDHs can significantly reduce the charge transfer resistance, accelerate the oxidation kinetics of hydrazine, and effectively increase the electrochemically active surface area (ECSA). The sensor achieved ultra-sensitive (13 040 μA mM-1 cm-2 (S/N = 3)) detection of hydrazine in the concentration range of 0.7 μM to 4 mM, exhibited excellent selectivity, reproducibility and high stability, and was successfully applied to the determination of hydrazine in actual environmental water samples and landfill leachate samples.


Insights into the effect of the interlayer spacings of bilayer graphene on the desolvation of H+, Li+, Na+, and K+ ions with water as a solvent: a first-principles study.
The desolvation effect of ions plays an important role in adjusting the capacity of supercapacitors and has attracted considerable attention after its discovery. Here, first-principles calculations were conducted to calculate the reaction energies of ions, water, and hydrated ions in bilayer graphene (BG) with different interlayer spacings (d) and to explore the desolvation behaviors of H+, Li+, Na+, and K+ ions. The calculated results showed that H+ can only exist in the state of H3O+ in AA-stacking BG, and desolvation exists only in the case of AB-stacking BG. The complete desolvation size for H+ ions in the AB-stacking system reached 5.6 Å, which was the largest desolvation size of the four ions studied. The critical desolvation sizes of Li+, Na+, and K+ in the BG layers of AA- and AB-stacking increased sharply as a consequence of the increasing ionic radius. However, the complete desolvation sizes of all three ions were in the range of 4-5 Å and with the increase in ionic radius, the complete desolvation sizes showed a reverse tendency. The complete desolvation size of Na+ in AB-stacking BG was slightly larger than that in AA-stacking BG. Further analysis presented that the ionic radii of H+, Li+, Na+, and K+ ions make a dominant contribution to the critical size of desolvation. Our present results provide useful information for improving the capacity of supercapacitors by precisely matching the pore structure and electrolyte through the adjustment of the pore structure of carbon materials.


The Effect of Resin and Monoterpenes on Spore Germination and Growth in Fusarium circinatum.
Resin obtained from Pinus radiata and five monoterpene components of resin (limonene, α-pinene, β-pinene, camphene, and myrcene) were tested to determine their effects on mycelial growth and germination and survival of spores of Fusarium circinatum, the cause of pitch canker in pine, and F. temperatum, which is interfertile with F. circinatum but not pathogenic to pine. Averaged across all treatments, F. temperatum sustained the greatest reduction in radial growth (16.9±0.02% of control). The greatest reduction in dry weight also occurred in F. temperatum (11.7±0.01% of control), and all isolates of F. circinatum were significantly less affected (P<0.05). Spore germination rates in a saturated atmosphere of monoterpenes were relatively high for all tested isolates but, when placed in direct contact with resin, spore survival was significantly greater for F. circinatum than for F. temperatum. Our results are consistent with the hypothesis that greater tolerance of resin is one factor distinguishing F. circinatum from the nonpathogenic F. temperatum. However, differential tolerance of monoterpene components of resin is not sufficient to explain the observed variation in virulence to pine in F. circinatum.


Nonnutritive factors in colostrum enhance myofibrillar protein synthesis in the newborn Pig.
Colostrum is a complex source of nutrients, immune factors, and bioactive substances consumed by newborn mammals. In previous work, we observed that protein synthesis in the skeletal muscle of newborn piglets is enhanced when they are fed colostrum rather than a nutrient-matched formula devoid of growth factors. To elucidate the mechanisms responsible for this response, we contrasted the fractional rates of sarcoplasmic and myofibrillar protein synthesis of newborn piglets that received only water with those fed for 24 h with colostrum, a nutrient-matched formula, or mature sow's milk. Compared with water, feeding resulted in a 2.5- to 3-fold increase in total skeletal muscle protein synthesis, and this increase was 28% greater in the colostrum-fed than either the formula- or mature milk-fed piglets. Feeding also stimulated muscle ribosome and total polyadenylated RNA accretion. Ribosomal translational efficiency, however, was similar across all fed groups. The greater stimulation of protein synthesis in colostrum-fed pigs was restricted entirely to the myofibrillar protein compartment and was associated with higher ribosome and myosin heavy chain mRNA abundance. Taken together, these data suggest that nonnutritive factors in colostrum enhance ribosomal accretion and muscle-specific gene transcription that, in turn, stimulate specifically the synthesis of myofibrillar proteins in the skeletal musculature of the newborn.


Weakly Coupled Piezoelectric MEMS Resonators for Aerosol Sensing.
This paper successfully demonstrates the potential of weakly coupled piezoelectric MEMS (Micro-Electro-Mechanical Systems) gravimetric sensors for the detection of ultra-fine particulates. As a proof-of-principle, the detection of diesel soot particles of 100 nanometres or less is demonstrated. A practical monitoring context also exists for diesel soot particles originating from combustion engines, as they are of serious health concern. The MEMS sensors employed in this work operate on the principle of vibration mode-localisation employing an amplitude ratio shift output metric for readout. Notably, gains are observed while comparing parametric sensitivities and the input referred stability for amplitude ratio and resonant frequency variations, demonstrating that the amplitude ratio output metric is particularly suitable for long-term measurements. The soot particle mass directly estimated using coupled MEMS resonators can be correlated to the mass, indirectly estimated using the condensation particle counter used as the reference instrument.


Does saffron supplementation have favorable effects on liver function indicators? A systematic review and meta-analysis of randomized controlled trials.
Several pharmaceutical and non-pharmaceutical approaches have been suggested to improve liver health. There is a large discrepancy in the effects of saffron supplementation on liver function in adults. To fill this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) assess the effects of saffron supplementation on liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A systematic search current to August 2020 was performed in PubMed/Medline, Scopus, Web of Science, and Google Scholar using relevant keywords to detect eligible articles. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine eligible trials were included in the final analysis. The pooled analysis revealed that serum ALT concentrations were significantly reduced using saffron compared to placebo (WMD: -2.39 U/L; 95% CI: -4.57 to -0.22; P = 0.03, I2= 87.9%, P < 0.001). However, saffron supplementation did not affect levels of serum AST (WMD: 1.12 U/L; 95% CI: -1.42 to 3.65; P = 0.39) or ALP (WMD: 4.32 U/L; 95% CI: -6.91 to 15.54; P = 0.78). In the dose-response analysis, we did not find a significant dose-response relationship between dosage and duration of saffron supplementation on serum levels of ALT, AST, and ALP. We found that saffron supplementation can reduce ALT serum concentrations without significant effects on other liver function indicators, including AST and ALP. Nevertheless, future large RCTs on diverse populations are needed to understand better the effects of saffron and its constituents on these enzymes.


Signet Ring Cell Carcinoma of Unknown Primary Origin Detected Incidentally by Lymph Node Purification for Thyroid Carcinoma.
A 63-year-old woman underwent thyroidectomy for papillary thyroid adenocarcinoma and cervical lymph node resection. Pathological analyses revealed the presence of signet cell carcinoma in a resected lymph node, which were apparently different from the pathological findings of thyroid carcinoma. No evidence of a primary tumor could be found elsewhere despite detailed examinations, including esophagogastroduodenoscopy, colonoscopy, capsule endoscopy, CT scan, and fluorodeoxyglucose-positron emission tomography. Two and half years later, the patient developed multiple bone metastases and the pathological findings confirmed the presence of signet cell carcinoma. The primary origin remained undetermined. Metastatic signet ring cell carcinoma of unknown primary origin is extremely rare.


Intrauterine coadministration of ERK1/2 inhibitor U0126 inhibits interferon TAU action in the endometrium and restores luteolytic PGF2alpha pulses in sheep.
In ruminants, prostaglandin F2 alpha (PGF2alpha) is synthesized and released in a pulsatile pattern from the endometrial luminal epithelial (LE) cells during the process of luteolysis. Interferon tau (IFNT) is a Type 1 IFN secreted by the trophoblast cells of the developing conceptus. IFNT acts locally on endometrial LE cells to inhibit pulsatile releases of PGF2alpha and thus establish an endocrine environment for recognition of pregnancy. Cell signaling pathways through which IFNT stimulates expression of multiple genes or proteins in endometrial LE are largely unknown. Results of the present investigation indicate that intrauterine administration of IFNT inhibits pulsatile release of PGF2alpha, while coadministration IFNT and ERK 1/2 inhibitor U0126 restores luteolytic PGF2alpha pulses in sheep. IFNT increases phosphorylation of ERK1/2 proteins and increases its interaction with PGT proteins in endometrial LE. Blockade of ERK1/2 pathways inhibits IFNT action, decreases pERK1/2 and PGT protein interactions, and re-establishes the spatial expression of the oxytocin receptor protein completely and the estrogen receptor protein partially without modulating the expression of interferon regulatory factor-2 (IRF-2) protein in endometrial LE. IFNT does not decrease expression of COX-2, PGDH, or PGT protein in endometrial LE. Our results provide important new insights into IFNT signaling and the molecular endocrine control of PGF2alpha release at the time of establishment of pregnancy in ruminants. This novel IFNT-ERK1/2 signaling module needs to be explored in future studies to understand molecular and cellular mechanisms of IFNT action in endometrial LE in ruminants.


Reconfiguration of a vertebrate motor network: specific neuron recruitment and context-dependent synaptic plasticity.
Motor networks typically generate several related output patterns or gaits where individual neurons may be shared or recruited between patterns. We investigate how a vertebrate locomotor network is reconfigured to produce a second rhythmic motor pattern, defining the detailed pattern of neuronal recruitment and consequent changes in the mechanism for rhythm generation. Hatchling Xenopus tadpoles swim if touched, but when held make slower, stronger, struggling movements. In immobilized tadpoles, a brief current pulse to the skin initiates swimming, whereas 40 Hz pulses produce struggling. The classes of neurons active during struggling are defined using whole-cell patch recordings from hindbrain and spinal cord neurons during 40 Hz stimulation of the skin. Some motoneurons and inhibitory interneurons are active in both swimming and struggling, but more neurons are recruited within these classes during struggling. In addition, and in contrast to a previous study, we describe two new classes of excitatory interneuron specifically recruited during struggling and define their properties and synaptic connections. We then explore mechanisms that generate struggling by building a network model incorporating these new neurons. As well as the recruitment of new neuron classes, we show that reconfiguration of the locomotor network to the struggling central pattern generator (CPG) reveals a context-dependent synaptic depression of reciprocal inhibition: the result of increased inhibitory neuron firing frequency during struggling. This provides one possible mechanism for burst termination not seen in the swimming CPG. The direct demonstration of depression in reciprocal inhibition confirms a key element of Brown's (1911) hypothesis for locomotor rhythmogenesis.


Formation and conversion of characteristic volatile compounds in grilled eel (Astroconger myriaster) during different processing steps.
The aroma of grilled eel is affected by three key processing steps: curing, steaming, and grilling. This study was aimed at the determination of the difference between the characteristic volatiles in each processing stage and their influence on the final aroma of grilled eel. A total of 92 volatile compounds were identified by purge and trap (P&T) combined with gas chromatography-mass spectrometry (GC-MS) throughout the processing. Alcohol, ketone, aromatic compounds and methylated compounds were the most important volatiles in the eel meat during processing. Pyrazine was generated gradually during the entire process, and 2,3-dimethylpyrazine was only found in the sample after grilling. Distinct odors among the raw and treated samples could be indirectly distinguished according to their volatile compounds, analyzed by heatmap. Together, these results indicate a relationship between the final aroma and the whole processing. The odor coding made from the odor activity value (OAV) could be as a reference benchmark for the grilled eel product.


Discovery of Enterovirus A71-like nonstructural genomes in recent circulating viruses of the Enterovirus A species.
Enterovirus A71 (EV-A71) is an important nonpolio enterovirus that causes severe neurological complications. In 1998, Taiwan experienced an EV-A71 outbreak that caused 78 deaths. Since then, periodic epidemics of EV-A71 associated with newly emerging strains have occurred. Several of these strains are known to be recombinant; however, how these strains arose within such a short period of time remains unknown. Here, we sequenced 64 full-length genomes from clinical isolates collected from 2005 to 2016 and incorporated all 91 Taiwanese genomes downloaded from the Virus Pathogen Resource to extensively analyze EV-A71 recombination in Taiwan. We found that the B3 subgenotype was a potential recombinant parent of the EV-A71 C2-like and C4 strains by intratypic recombination. Such B3-similar regions were also found in many cocirculating coxsackieviruses belonging to Enterovirus A species (EV-A) through a series of intertypic recombinations. Therefore, locally enriched outbreaks of cocirculating viruses from different genotypes/serotypes may facilitate recombination. Most recombination breakpoints we found had nonrandom distributions and were located within the region spanning from the boundary of P1 (structural gene) and P2 (nonstructural) to the cis-acting replication element at P2, indicating that specific genome reassembly of structural and nonstructural genes may be subject to natural selection. Through intensive recombination, 11 EV-A71-like signatures (including one in 3A, two in 3C, and eight in 3D) were found to be present in a variety of recently cocirculating EV-A viruses worldwide, suggesting that these viruses may be targets for wide-spectrum antiviral development.


Different potato virus Y strains frequently co-localize in single epidermal leaf cells and in the aphid stylet.
Single aphids can simultaneously or sequentially acquire and transmit multiple potato virus Y (PVY) strains. Multiple PVY strains are often found in the same field and occasionally within the same plant, but little is known about how PVY strains interact in plants or in aphid stylets. Immuno-staining and confocal microscopy were used to examine the spatial and temporal dynamics of PVY strain mixtures (PVYO and PVYNTN or PVYO and PVYN) in epidermal leaf cells of 'Samsun NN' tobacco and 'Goldrush' potato. Virus binding and localization was also examined in aphid stylets following acquisition. Both strains systemically infected tobacco and co-localized in cells of all leaves examined; however, the relative amounts of each virus changed over time. Early in the tobacco infection, when mosaic symptoms were observed, PVYO dominated the infection although PVYNTN was detected in some cells. As the infection progressed and vein necrosis developed, PVYNTN was prevalent. Co-localization of PVYO and PVYN was also observed in epidermal cells of potato leaves with most cells infected with both viruses. Furthermore, two strains could be detected binding to the distal end of aphid stylets following virus acquisition from a plant infected with a strain mixture. These data are in contrast with the traditional belief of spatial separation of two closely related potyviruses and suggest apparent non-antagonistic interaction between PVY strains that could help explain the multitude of emerging recombinant PVY strains discovered in potato in recent years.


The acetyltransferase Eco1 elicits cohesin dimerization during S phase.
Cohesin is a DNA-associated protein complex that forms a tripartite ring controlling sister chromatid cohesion, chromosome segregation and organization, DNA replication, and gene expression. Sister chromatid cohesion is established by the protein acetyltransferase Eco1, which acetylates two conserved lysine residues on the cohesin subunit Smc3 and thereby ensures correct chromatid separation in yeast (Saccharomyces cerevisiae) and other eukaryotes. However, the consequence of Eco1-catalyzed cohesin acetylation is unknown, and the exact nature of the cohesive state of chromatids remains controversial. Here, we show that self-interactions of the cohesin subunits Scc1/Rad21 and Scc3 occur in a DNA replication-coupled manner in both yeast and human cells. Using cross-linking MS-based and in vivo disulfide cross-linking analyses of purified cohesin, we show that a subpopulation of cohesin may exist as dimers. Importantly, upon temperature-sensitive and auxin-induced degron-mediated Eco1 depletion, the cohesin-cohesin interactions became significantly compromised, whereas deleting either the deacetylase Hos1 or the Eco1 antagonist Wpl1/Rad61 increased cohesin dimer levels by ∼20%. These results indicate that cohesin dimerizes in the S phase and monomerizes in mitosis, processes that are controlled by Eco1, Wpl1, and Hos1 in the sister chromatid cohesion-dissolution cycle. These findings suggest that cohesin dimerization is controlled by the cohesion cycle and support the notion that a double-ring cohesin model operates in sister chromatid cohesion.