Characterization of antibiosis and antixenosis to the woolly poplar aphid (Hemiptera: Aphididae) in the bark of different poplar genotypes.
The woolly poplar aphid, Phloeomyzus passerinii (Signoret) (Hemiptera: Aphididae), is a major pest of poplar plantations in the Mediterranean basin and the Near East. Aphids colonize poplar trunks and feed upon the cortical parenchyma. Despite the economic importance of poplar, little is known about the mechanisms involved in poplar resistance to this pest. However, Populus x canadensis Moench genotypes show various levels of resistance to P. passerinii. This study has investigated the type of poplar resistance (antibiosis or antixenosis) by assessing aphid settlement, physiology (survival, development, and reproduction), and stylet penetration behavior (electrical penetration graph) on three P. x canadensis genotypes; '1214' (susceptible), 'Brenta' (resistant), and '145/51' (intermediate). Because settlement was reduced, the highly resistant genotype Brenta exhibited surface antixenosis. In addition, nymphal survival was null on Brenta, and twice less adult aphid initiated a sustained intracellular phase in the cortical parenchyma of that genotype compared with the other two genotypes. Thus, Brenta also showed parenchyma-located antixenosis coupled with antibiosis characteristic. In contrast, P. passerinii had no difficulty to initiate a sustained ingestion in the cortical parenchyma of the intermediate genotype 145/51, but decreased fecundity and lower intrinsic rate of natural increase were clear expressions of antibiosis.


Tuning the electronic properties and work functions of graphane/fully hydrogenated h-BN heterobilayers via heteronuclear dihydrogen bonding and electric field control.
Using density functional theory calculations with van der Waals correction, we show that the electronic properties (band gap and carrier mobility) and work functions of graphane/fully hydrogenated hexagonal boron nitride (G/fHBN) heterobilayers can be favorably tuned via heteronuclear dihydrogen bonding (C-HH-B and C-HH-N) and an external electric field. Our results reveal that G/fHBN heterobilayers have different direct band gaps of ∼1.2 eV and ∼3.5 eV for C-HH-B and C-HH-N bonds, respectively. In particular, these band gaps can be effectively modulated by altering the direction and strength of the external electric field (E-field), and correspondingly exhibit a semiconductor-metal transition. The conformation and stability of G/fHBN heterobilayers show a strong dependence on the heteronuclear dihydrogen bonding. Fantastically, these bonds are stable enough under a considerable external E-field as compared with other van der Waals (vdW) 2D layered materials. The mobilities of G/fHBN heterobilayers we predicted are hole-dominated, reasonably high (improvable up to 200 cm(2) V(-1) s(-1)), and extremely isotropic. We also demonstrate that the work function of G/fHBN heterobilayers is very sensitive to the external E-field and is extremely low. These findings make G/fHBN heterobilayers very promising materials for field-effect transistors and light-emitting devices, and inspire more efforts in the development of 2D material systems using weak interlayer interactions and electric field control.


Comparison of Outcomes of Hybrid and Surgical Correction for De Novo Arteriovenous Graft Occlusion.
This study aimed to compare surgical revisions and balloon angioplasty after surgical thrombectomy on thrombosed dialysis access as a first event. Records of patients undergoing creation of arteriovenous grafts (AVGs) at the Gachon University Gil Medical Center between March 2008 and February 2016 were reviewed. Among them, patients who underwent treatment on first-time thrombotic occlusion after AVG creation were identified. Outcomes were primary, primary-assisted, and secondary patency. The patency was generated using the Kaplan-Meier method, and patency rates were compared by log-rank test. A total of 59 de novo interventions (n=26, hybrid interventions; n=33, surgical revisions) for occlusive AVGs were identified. The estimated 1-year primary patency rates were 47% and 30% in the surgery and hybrid groups, respectively. The estimated primary patency rates were not different between the two groups (log-rank test, P=0.73). The Kaplan-Meier estimates of 6 and 12 months for primary-assisted patency rates were 68% and 57% in the surgery group and 56% and 56% in the hybrid group. The Kaplan-Meier estimates of 12 and 24 months secondary patency rates were 90% and 71% in the surgery group and 79% and 62% in the hybrid group. There were no differences in the estimated primary-assisted and secondary patency rates between the two groups. Our results showed no significant difference between the two groups in terms of primary patency (P=0.73), primary-assisted patency (P=0.85), and secondary patency (P=0.78). However, percutaneous transluminal angioplasty can give more therapeutic options for both surgeons and patients.


Beta-endorphin: a highly selective endogenous opioid agonist for presynaptic mu opioid receptors.
In the presence of physiological cations (in Krebs-4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid buffer) at 37 degrees C the Ki value's of beta-endorphin for mu- and delta-opioid receptor binding sites in rat neocortical membranes, labeled with [3H][D-Ala2,MePhe4,Gly- ol5]enkephalin (DAMGO) and [3H][D-Ala2-D-Leu5]enkephalin (in the presence of unlabeled DAMGO), respectively, amounted to about 9 and 22 nM. Surprisingly, a very different selectivity pattern for the endogenous opioid peptide was found when the affinity of beta-endorphin for functional presynaptic opioid receptors was examined. Thus, beta-endorphin strongly inhibited the electrically evoked release of [3H]NE from rat neocortical slices with an IC50 value of about 0.5 nM, whereas [14C] acetylcholine release from neostriatal slices was inhibited with an IC50 value of about 100 nM. On the other hand, the electrically evoked release of [3H]dopamine from striatal slices was not affected by beta-endorphin. The inhibitory effects of DAMGO and beta-endorphin on [3H]NE release from neocortical slices were equally well antagonized by naloxone. Moreover, 10 nM of the highly selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen- Thr-NH2 antagonized competitively the inhibitory effect of beta-endorphin on [3H]NE release.(ABSTRACT TRUNCATED AT 250 WORDS)


Intrarenal angiotensin II generation and renal effects of AT1 receptor blockade.
The intrarenal renin-angiotensin system plays a critical role in the paracrine regulation of renal function and the pathophysiology of hypertension. Angiotensin II (AngII) is formed intrarenally from systemically delivered angiotensin I (AngI) and intrarenally formed AngI. Intrarenal AngII content, which is greater than can be explained by the circulating AngII concentrations, is compartmentalized such that proximal tubule concentrations of AngI and AngII greatly exceed plasma concentrations. Proximal tubule cells are thought to secrete AngII or precursors of AngII into the tubular fluid to activate luminal AngII receptors. Recent immunohistochemical studies have demonstrated an abundance of AT1 receptors on the luminal surface of proximal and distal tubule cells and on afferent and efferent arteriolar vascular smooth muscle cells and mesangial cells of glomeruli. Activation of luminal AT1 receptors stimulates tubular sodium reabsorption rate. To evaluate the direct effects of AT1 receptor blockade on renal function in AngII-dependent hypertension, experiments were performed on two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. Although the nonclipped kidney is renin-depleted, the intrarenal AngII levels are not suppressed, and AngII concentrations in proximal tubular fluid remain high (10(-8) M). Candesartan was administered into the renal artery of nonclipped kidneys to avoid the confounding consequences of decreases in arterial pressure. Blockade of intrarenal AT1 receptors elicited significant increases in GFR, renal blood flow, sodium excretion, and fractional sodium excretion, suggesting synergistic actions on tubular transport and vascular smooth muscle cells.


Magnetic MOF microreactors for recyclable size-selective biocatalysis.
In this contribution we report a synthetic strategy for the encapsulation of functional biomolecules within MOF-based microcapsules. We employ an agarose hydrogel droplet Pickering-stabilised by UiO-66 and magnetite nanoparticles as a template around which to deposit a hierarchically structured ZIF-8 shell. The resulting microcapsules are robust, highly microporous and readily attracted to a magnet, where the hydrogel core provides a facile means to encapsulate enzymes for recyclable size-selective biocatalysis.


SRT1720 enhances maturity and quality of oocytes in aged mice.
This study aims to investigate the morphology and distribution of mitochondria, spindles, and chromosomes in oocytes of aged mice and examine the effects of SRT1720 on oocyte maturation. C57BL/6J mice were divided into young (4-8 weeks) and aged groups (48-52 weeks). In vitro maturation media contained (0.05, 0.1, and 1.0 μM) SRT1720 and 0.1-μM dimethyl sulfoxide (DMSO control). The rate of chromosome misalignment and spindle misorientation in oocytes of aged mice were significantly higher than that of young mice (P < 0.01). Fluorescence intensity of mitochondria from oocytes of aged mice was significantly lower than that of young mice (P < 0.01). SRT1720 at 0.1 μM significantly improved oocyte maturation, fertilization, and blastocyst formation in aged mice compared with young mice (P < 0.01). Additionally, immunofluorescence intensity of mitochondria, normal spindle morphology, and chromosome alignment were notably enhanced with SRT1720 when compared with the DSMO control group for metaphase II (MII)-stage oocytes matured in vitro (P < 0.01); 0.1-μM SRT1720 enhanced the expression level of SRIT1 in oocytes from aged mice. In summary, the aged mice oocytes showed increased nuclear and cytoplasmic defects, whereas SRT1720 enhanced oocyte maturation and quality. We concluded that 0.1-μM SRT1720 was an appropriate concentration for in vitro maturation media.


Trigeminal neuralgia associated with seizure and syncope. Case report.
A patient with trigeminal neuralgia experienced a generalized seizure and a prolonged syncopal episode. He was found to be asystolic during the syncopal episode. There was no recurrence of loss of consciousness after implantation of a pacemaker. Mechanical stimulation of the trigeminal nerve during craniotomy for microvascular decompression of the trigeminal nerve resulted in bradycardia. Since vascular decompression of the trigeminal nerve, there has been no recurrent facial pain, and no further syncope, seizures, or bradycardia. Syncope and seizures have not been previously reported in association with trigeminal neuralgia, although they are well described with glossopharyngeal neuralgia.


Hypertensive Crisis in a Pediatric Patient Experiencing Clonidine Withdrawal.
Clonidine, a central alpha-adrenoreceptor agonist, was initially developed as an antihypertensive. Though no longer commonly used for its original indication due to rebound hypertension after discontinuation, it is currently widely prescribed as a treatment for many pediatric indications including sleep disorders, behavioral concerns, and attention deficit hyperactivity disorder. Case Report. We describe a girl who developed prolonged symptoms of clonidine withdrawal, including hypertension and elevated serum metanephrines. Discussion. Clonidine withdrawal in pediatric patient can present with hypertensive urgency and other signs of sympathetic stimulation. Withdrawal can also lead to dramatic elevation in serum metanephrines. Treatment with a clonidine taper will reduce development of withdrawal symptoms. Given the rise in clonidine use in pediatric patients, clinicians should be aware of the risk of clonidine withdrawal and how to recognize and avoid its development.


Relationship between weight loss in obese knee osteoarthritis patients and serum biomarkers of cartilage breakdown: secondary analyses of a randomised trial.
To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population. 192 obese KOA patients followed a 16 week weight loss intervention and 52 weeks weight maintenance (ClinicalTrials.gov identifier: NCT00655941). Assessments were at 0, 8, 16 and 68 weeks. Serum Coll2-1 and Fib3-2 were determined with ELISA, and symptoms by the Knee Osteoarthritis Outcome Score (KOOS) questionnaire. Changes from week 0 and association between changes from baseline in body weight and Coll2-1, Fib3-2, and the 5 KOOS domains were assessed at all time points. Coll2-1 changes from baseline showed a decrease at week 8 (P = 0.0002), no change at week 16 (P = 0.49), and an increase at week 68 (P = 0.036). Fib3-2 showed an increase from baseline at week 8 (P = 0.0015) and 16 (P < 0.0001), but none at week 68 (P = 0.23). No statistically significant correlations were found between changes in body weight and Coll2-1 and Fib3-2 at any time point (r < 0.05; P > 0.49). At all time-points there were significant positive correlations between changes from baseline in Coll2-1 and in KOOSSports/Recreation (week 8, 16, 68: r = 0.17; P = 0.03; r = 0.16; P = 0.04; and r = 0.17; P = 0.04, respectively). The clinical improvement after a substantial weight loss and weight maintenance in KOA patients was not associated with decrease in markers of cartilage breakdown Coll2-1 or Fib3-2, even with indications of a slightly negative effect.


Head-to-head comparison of the accuracy of saliva and nasal rapid antigen SARS-CoV-2 self-testing: cross-sectional study.
The diagnostic accuracy of unsupervised self-testing with rapid antigen diagnostic tests (Ag-RDTs) is mostly unknown. We studied the diagnostic accuracy of a self-performed SARS-CoV-2 saliva and nasal Ag-RDT in the general population. This large cross-sectional study consecutively included unselected individuals aged ≥ 16 years presenting for SARS-CoV-2 testing at three public health service test sites. Participants underwent molecular test sampling and received two self-tests (the Hangzhou AllTest Biotech saliva self-test and the SD Biosensor nasal self-test by Roche Diagnostics) to perform themselves at home. Diagnostic accuracy of both self-tests was assessed with molecular testing as reference. Out of 2819 participants, 6.5% had a positive molecular test. Overall sensitivities were 46.7% (39.3-54.2%) for the saliva Ag-RDT and 68.9% (61.6-75.6%) for the nasal Ag-RDT. With a viral load cut-off (≥ 5.2 log10 SARS-CoV-2 E-gene copies/mL) as a proxy of infectiousness, these sensitivities increased to 54.9% (46.4-63.3%) and 83.9% (76.9-89.5%), respectively. For the nasal Ag-RDT, sensitivities were 78.5% (71.1-84.8%) and 22.6% (9.6-41.1%) in those symptomatic and asymptomatic at the time of sampling, which increased to 90.4% (83.8-94.9%) and 38.9% (17.3-64.3%) after applying the viral load cut-off. In those with and without prior SARS-CoV-2 infection, sensitivities were 36.8% (16.3-61.6%) and 72.7% (65.1-79.4%). Specificities were > 99% and > 99%, positive predictive values > 70% and > 90%, and negative predictive values > 95% and > 95%, for the saliva and nasal Ag-RDT, respectively, in most analyses. Most participants considered the self-performing and result interpretation (very) easy for both self-tests. The Hangzhou AllTest Biotech saliva self Ag-RDT is not reliable for SARS-CoV-2 detection, overall, and in all studied subgroups. The SD Biosensor nasal self Ag-RDT had high sensitivity in individuals with symptoms and in those without prior SARS-CoV-2 infection but low sensitivity in asymptomatic individuals and those with a prior SARS-CoV-2 infection which warrants further investigation.


The impact of splenectomy and diaphragmatic surgery on perioperative morbidity and overall survival of ovarian cancer patients.
The prognosis of ovarian cancer (OC), among other factors, depends on residual disease after primary debulking surgery (PDS) and initial disease advancement. The main aim of our study was to evaluate the survival benefits of splenectomy and diaphragmatic surgery in OC patients, when the procedures result in resection to no macroscopic residual disease or minimal residual disease [tumor nodules below 2.5 mm according to Sugarbaker's completeness of cytoreduction score (CC) = 1]. The study included 25 OC patients after splenectomy procedures, 28 patients after diaphragmatic surgery and 17 patients who had undergone both splenectomy and diaphragmatic surgery. Patients' overall survival (OS) was compared with residual disease-matched controls (47 patients) who had upper abdomen involvement but no requirement for splenectomy and/or diaphragmatic surgery. Overall survival of patients after splenectomy was not significantly different from OS of patients who did not required splenectomy (36.1 vs 31.6 months; p = 0.85). No differences in OS were observed between patients who did and did not require diaphragmatic surgery (31.3 vs 41.8; p = 0.33). Similarly, we found no differences in OS between patients who underwent both splenectomy and diaphragmatic surgery and those patients who did not require either procedure (20.1 vs 31.6 months; p = 0.45). Splenectomies and diaphragmatic surgeries were associated with prolonged hospitalization and length of surgery, however, no specific morbidity related to the procedures was observed. In the cases of advanced OC, diaphragm and spleen involvement do not hamper patient prognosis when adequately resected.


A cyclical wildfire pattern as the outcome of a coupled human natural system.
Over the past decades, wildfire has imposed a considerable cost on natural resources and human lives. In many regions, annual wildfire trends show puzzling oscillatory patterns with increasing amplitudes for burned areas over time. This paper aims to examine the potential causes of such patterns by developing and examining a dynamic simulation model that represents interconnected social and natural dynamics in a coupled system. We develop a generic dynamic model and, based on simulation results, postulate that the interconnection between human and natural subsystems is a source of the observed cyclical patterns in wildfires in which risk perception regulates activities that can result in more fire and development of vulnerable properties. Our simulation-based policy analysis points to a non-linear characteristic of the system, which rises due to the interconnections between the human side and the natural side of the system. This has a major policy implication: in contrast to studies that look for the most effective policy to contain wildfires, we show that a long-term solution is not a single action but is a combination of multiple actions that simultaneously target both human and natural sides of the system.


Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia.
Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) is a controversial diagnosis, as others propose that it represents chronic myelogenous leukemia in blast phase (CML-BP). NPM1 mutations occur in 25-35% of patients with AML but are absent in patients with CML. Conversely, ABL1 mutations occur in 25% of imatinib-naive patients with CML-BP but are not described in patients with AML. We analyzed for NPM1 and ABL1 mutations in nine Ph+ patients with AML and five patients with CML-BP initially presenting in BP. In six cases of Ph+ AML, we screened for a panel of gene mutations using Sequenome(®)-based methods including AKT1, AKT2, AKT3, BRAF, EGFR, GNAQ, GNAS, IDH1, IDH2, KRAS, MET, NRAS, PIK3CA and RET. Two of nine (22%) patients with Ph+ AML had NPM1 mutations and were alive 36 and 71 months after diagnosis. All cases of Ph+ AML were negative for ABL1 and other gene mutations. One (20%) patient with CML-BP had ABL1 mutation; no patients had NPM1 mutations. These data suggest that Ph+ AML is distinct from CML-BP.


Selective optical detection of aromatic vapors.
A sensitive layer system of amorphous Teflon AF on silver has been coated on a glass substrate. With a monochromatic light source the reflectivity of the layer system as a function of the angle of incidence exhibits the surface-plasmon resonance as well as a set of leaky-mode resonances. These optical resonance phenomena are sensitive to small refractive-index changes that may be induced by diffusion of particles into the Teflon AF layer. On the basis of this effect, the aromatic vapors benzene; toluene; and o-, p-, and m-xylene have been investigated with different vapor concentrations. By selection of a distinct angle at a particular resonance, dynamic measurements can be performed. Assuming a diffusion process in accordance with Fick's law, the diffusion profile can be calculated as a function of time. As described by the Lorentz-Lorenz relation a refractive-index profile is induced that consequently interacts with the electromagnetic fields of the optical modes. With the function of the diffusion-induced refractive-index profile the shift of the resonance lines can be calculated from the measured reflectivity change as a function of time. The characteristic diffusion coefficients of the particular vapor allow for a distinction between the different types of aromate, even between the different xylenes.


[Expression of erythroblastic leukemia viral oncogene homolog 3 (ErbB-3) binding protein-1, matrix metalloproteinases, eplthelial cadherin in adenoid cystic carcinoma and correlation analysis].
To investigate the expression of ErbB-3 binding protein-1 (EBP-1), matrix metalloproteinase 9 (MMP-9) and E-cadherin (E-cad) in adenoid cystic carcinoma and their correlation. Immunohistochemistry(PV6000 method) was used to detect EBP-1, MMP-9 and E-cad expression in 66 cases of adenoid cystic carcinoma tissues and matched para-cancerous normal tissues. In this study all cases were successfully followed up. The positive expression rate of EBP-1 in adenoid cystic carcinoma tissues was 85%. EBP-1 expression was significantly correlated to pathological pattern and clinical stage (P < 0.05), but not to gender and age. In addition, there was a negative correlation between EBP-1 and E-cad expression, and positive correlation between EBP-1 and MMP-9. EBP-1 and its correlation with MMP-9 and E-cad may be used as useful indicators for clinical assessment of tumor biological behavior and prognosis in patients with adenoid cystic carcinoma.


Epithelial Patterning, Morphogenesis, and Evolution: Drosophila Eggshell as a Model.
Understanding the mechanisms driving tissue and organ formation requires knowledge across scales. How do signaling pathways specify distinct tissue types? How does the patterning system control morphogenesis? How do these processes evolve? The Drosophila egg chamber, where EGF and BMP signaling intersect to specify unique cell types that construct epithelial tubes for specialized eggshell structures, has provided a tractable system to ask these questions. Work there has elucidated connections between scales of development, including across evolutionary scales, and fostered the development of quantitative modeling tools. These tools and general principles can be applied to the understanding of other developmental processes across organisms.


Nociceptive Sensory Neurons Mediate Inflammation Induced by Bacillus Anthracis Edema Toxin.
Bacterial products are able to act on nociceptive neurons during pathogenic infection. Neurogenic inflammation is an active part of pain signaling and has recently been shown to impact host-pathogen defense. Bacillus anthracis Edema Toxin (ET) produces striking edema in peripheral tissues, but the cellular mechanisms involved in tissue swelling are not completely understood. Here, we find that nociceptive neurons play a role in ET-induced edema and inflammation in mice. Subcutaneous footpad infection of B. anthracis Sterne caused ET-dependent local mechanical allodynia, paw swelling and body weight gain. Subcutaneous administration of ET induced paw swelling and vascular leakage, the early phases of which were attenuated in the absence of Trpv1+ or Nav1.8+ nociceptive neurons. Nociceptive neurons express the anthrax toxin receptor ANTXR2, but this did not mediate ET-induced edema. ET induced local cytokine expression and neutrophil recruitment, which were dependent in part on Trpv1+ nociceptive neurons. Ablation of Trpv1+ or Nav1.8+ nociceptive neurons also attenuated early increases in paw swelling and body weight gain during live B. anthracis infection. Our findings indicate that nociceptive neurons play an active role in inflammation caused by B. anthracis and Edema Toxin to potentially influence bacterial pathogenesis.


Scientific publications on orthopedic surgery from three major East Asian countries (2012-2021).
East Asia is the most dynamic region in the world and includes three major countries: Japan, South Korea and China. Due to rapid economic growth, orthopedics research in East Asia has achieved great advances during the past 10 years. However, the current status of orthopedic research in Japan, South Korea and China is still unclear. To understand the current status of orthopedic research in Japan, South Korea, and China. Journals listed in the ''Orthopedics'' category of Science Citation Index Expanded subject categories were included. The PubMed and Web of Knowledge electronic databases were searched to identify scientific publications from the selected journals written by researchers from Japan, South Korea and China. A systematic analysis was conducted to analyze orthopedic research articles published in the three countries based on the number of articles, study design, impact factors (IFs) and citations. Furthermore, we also ranked the top 10 countries worldwide with the highest publications in the past 10 years. Additionally, we ranked the top 10 countries with the highest number of publications in the world in the past 10 years. Statistical analyses were performed using SPSS 20.0 software (SPSS Inc., Chicago, IL, United States), and statistical results are given in Tables and Figures. The Kruskal-Wallis test and the Mann-Whitney test were used to detect differences between countries. The tendency regarding the number of articles was analyzed by curvilinear regression. A two-tailed P < 0.05 was considered significant. From 2012-2021, a total of 144518 articles were published in the 86 selected orthopedic journals. During this period, the number of worldwide published orthopedic articles has shown an annual increasing trend. A total of 27164 orthopedic research articles were published by Japan, South Korea and China during the past 10 years; 44.32% were from China, 32.98% were from Japan, and 22.70% were from South Korea. From 2012 to 2021, the annual number of articles markedly increased in each of the three countries. Over time, the worldwide share of articles increased substantially in South Korea (3.37% to 6.53%, P < 0.001) and China (5.29% to 9.61%, P < 0.001). However, the worldwide share of articles significantly decreased in Japan (5.22% to 3.80%, P < 0.001). The annual total IFs of articles from China were well above those of articles from Japan and South Korea (36597.69 vs 27244.48 vs 20657.83, P < 0.05). There was no significant difference among the articles in the top 10 high-IF orthopedics journals published from those three countries [South Korea (800) > China (787) > Japan (646), P > 0.05]. Over the past 10 years, China's scientific publications in orthopedic journals have shown an increasing trend. Considering the relative scale of the populations, Japan and South Korea have outpaced China with respect to quality.


Sterol response element binding protein and thyroid transcription factor-1 (Nkx2.1) regulate Abca3 gene expression.
The ATP-binding cassette (ABC) ABCA3 gene encodes a lipid transporter critical for surfactant function at birth. To identify transcription factors that regulate ABCA3 expression in the lung, we identified by bioinformatic and functional analyses two positive regulatory regions, located between bp -2591 and -1102 and bp -1102 and +11, relative to the exon 1 of the Abca3 gene promoter. The distal cassette contains consensus sequences predicting binding to lung transcription factors including FOXA2, CCAAT/enhancer binding protein-alpha (C/EBPalpha), GATA-6, thyroid transcription factor-1 (TTF-1 or Nkx2.1), and nuclear factor of activated T cells-c3 (NFATc3). The activity of the distal region from bp -2591 to -1102 was assessed in HeLa and mouse lung epithelial MLE-15 cells. FOXA2, C/EBPalpha, GATA-6, TTF-1, and NFATc3 increased the activity of the Abca3 luciferase construct in a dose-dependent manner. The distal cassette conferred activation by FOXA2, C/EBPalpha, GATA-6, TTF-1, and NFATc3 in a position- and orientation-independent manner, serving as an enhancer-like regulatory element. The proximal Abca3 promoter region contained multiple sterol responsive element (SRE) binding sites. SRE binding protein (SREBP)-1c significantly increased the activity of the Abca3 luciferase construct in a dose-dependent manner, whereas SREBP-1a and SREBP-2 did not influence the Abca3 promoter activity. Chromatin immunoprecipitation (ChIP) analyses demonstrated the binding of SREBP-1c, C/EBPalpha, and TTF-1 to their respective regulatory elements. Conditional deletion of SREBP cleavage-activating protein (Scap) in respiratory epithelial cells in the mouse lung in vivo inhibited the expression of SREBPs in concert with Abca3. Abca3 gene expression is mediated by discrete cis-acting cassettes that mediate pulmonary cell- and lipid-sensitive pathways regulating surfactant homeostasis.


Hydration of Carboxyl Groups: A Route toward Molecular Recognition?
On Earth, water plays an active role in cellular life, over several scales of distance and time. At a nanoscale, water drives macromolecular conformation through hydrophobic forces and at short times acts as a proton donor/acceptor providing charge carriers for signal transmission. At longer times and larger distances, water controls osmosis, transport, and protein mobility. Neutron diffraction experiments augmented by computer simulation, show that the three-dimensional shape of the hydration shell of carboxyl and carboxylate groups belonging to different molecules is characteristic of each molecule. Different hydration shells identify and distinguish specific sites with the same chemical structure. This experimental evidence suggests an active role of water also in controlling, modulating, and mediating chemical reactions involving carboxyl and carboxylate groups.


Emissions of SO2, NO and N2O in a circulating fluidized bed combustor during co-firing coal and biomass.
This paper presents the experimental investigations of the emissions of SO2, NO and N20 in a bench scale circulating fluidized bed combustor for coal combustion and co-firing coal and biomass. The thermal capacity of the combustor is 30 kW. The setup is electrically heated during startup. The influence of the excess air, the degree of the air staging, the biomass share and the feeding position of the fuels on the emissions of SO2, NO and N2O were studied. The results showed that an increase in the biomass shares resulted in an increase of the CO concentration in the flue gas, probably due to the high volatile content of the biomass. In co-firing, the emission of SO2 increased with increasing biomass share slightly, however, non-linear increase relationship between SO2 emission and fuel sulfur content was observed. Air staging significantly decreased the NO emission without raising the SO2 level. Although the change of the fuel feeding position from riser to downer resulted in a decrease in the NO emission level, no obvious change was observed for the SO2 level. Taking the coal feeding position R as a reference, the relative NO emission could significantly decrease during co-firing coal and biomass when feeding fuel at position D and keeping the first stage stoichiometry greater than 0.95. The possible mechanisms of the sulfur and nitrogen chemistry at these conditions were discussed and the ways of simultaneous reduction of SO2, NO and N20 were proposed.


[Two novel TSC2 frameshift mutations in tuberous sclerosis complex].
High-throughput sequencing was performed for the peripheral blood DNA from two probands in the family with tuberous sclerosis complex (TSC) to determine the sequences of TSC-related genes TSC1 and TSC2 and their splicing regions and identify mutation sites. Amplification primers were designed for the mutation sites and polymerase chain reaction and Sanger sequencing were used to verify the sequences of peripheral blood DNA from the probands and their parents. The two probands had c.3981-3982 insA (p.Asp1327AspfsX87) and c.4013-4014 delCA (p.Ser1338Cysfs) heterozygous mutations, respectively, in the TSC2 gene. The parents of proband 1 had no abnormalities at these two loci; the mother of proband 2 had c.4013-4014 delCA heterozygous mutation in the TSC2 gene, while the father and the grandparents of proband 2 had no abnormalities. c.3981-3982 insA mutation may cause early coding termination of amino acid sequence at the 1413th site, and c.4013-4014 delCA mutation may cause early coding termination of amino acid sequence at the 1412th site. These two mutations are the pathogenic mutations for families 1 and 2, respectively, and both of them are novel frameshift mutations, but their association with the disease needs to be further verified by mutant protein function cell model and animal model.


Role of aquaglyceroporin (AQP1) gene and drug uptake in antimony-resistant clinical isolates of Leishmania donovani.
Antimonial-containing drugs are the first line of treatment against Leishmaniasis. Resistance to antimonials in Leishmania is proposed to be due to reduced uptake of trivalent antimony (SbIII) through the aquaglyceroporin (AQP1). We investigated the uptake of SbIII and involvement of aquaglyceroporin in developing antimony resistance phenotype in Leishmania donovani clinical isolates. SbIII accumulation, copy number of AQP1 gene, and transcript levels were compared in antimony-sensitive versus -resistant isolates. Antimony-resistant field isolates showed reduced uptake of SbIII. The copy number of AQP1 gene showed higher copy number in the antimony-resistant isolates when compared with the sensitive isolates and did not correlate to the reduced uptake of SbIII. Downregulation of AQP1 RNA levels was not consistently found in the antimony-resistant isolates. Our studies indicate that while downregulation of AQP1 may be one of the mechanisms of antimony resistance, it is however not an invariable feature.


Use of dermal-fat flaps in treating abdominal scars, in abdominoplasty, and in subtrochanteric lipectomy.
Triangular dermal-fat flaps can be used in the excision of adherent vertical scars in the lower abdomen to prevent a recurrence of the depressed adhesion. Also, several such flaps can be used on the upper margin of an abdominoplasty, and one on the lower edge (above the pubis), to equalize the thickness and the lengths of the two edges. This results in a better final appearance. Finally, the use of a single triangular dermal-fat flap on the lower margin when doing a lipectomy for "subtrochanterric lipodystrophy" (or a "plastic on buttock") gives the buttock a more normal shape--round in the medial two-thirds and almost flat in the lateral one-third.


Fibritin encoded by bacteriophage T4 gene wac has a parallel triple-stranded alpha-helical coiled-coil structure.
The bacteriophage T4 late gene wac (whisker's antigen control) encodes a fibrous protein which forms a collar/whiskers complex. Whiskers function as a helper protein for the long tail fibres assembly and plays a role in regulating retraction of the long tail fibres in response to environmental conditions. In this work we show that expression of the cloned wac gene in Escherichia coli yields a protein oligomer of 53 nm length which we call fibritin, and which is able to complement gpwac T4 particles in vitro. CD spectroscopy of fibritin indicates a 90% alpha-helical content, and scanning calorimetry shows that the protein has several distinct domains. The analysis of the 486 amino acid sequence of fibritin reveals three structural components: a 408 amino acid region that contains 12 putative coiled-coil segments with a canonical heptad (a-b-c-d-e-f-g)n substructure where the "a" and "d" positions are preferentially occupied by apolar residues, and the N and C-terminal domains (47 and 29 amino acid residues, respectively) have no heptad substructure. The distribution of hydrophobic residues within heptads is more similar to a triple than to a double coiled-coil. The alpha-helical segments are separated by short "linker" regions, variable in length, that have a high proportion of glycine and proline residues. Each coiled-coil segment has, on the borders with linker regions, residues that are common to the N and C-terminal caps of the alpha-helices. Full-length and amino-terminally truncated fibritins can be reassembled in vitro after temperature-induced denaturation. Co-assembly of full-length fibritin and the N-terminal deletion mutant, as well as analytical centrifugation, indicates that the protein is a parallel triple-standard alpha-helical coiled-coil. Deletions of various N-terminal portions of fibritin did not block trimerisation but the mutant trimers are unable to bind to T4 particles. The last 18 C-terminal residues of fibritin are required for correct trimerisation of gpwac monomers in vivo. We propose that fibritin might serve as a convenient model for the investigation of folding and assembly mechanisms of alpha-fibrous proteins.


Hepatitis delta virus ribonucleoproteins shuttle between the nucleus and the cytoplasm.
Hepatitis delta virus (HDV) infection of individuals infected with hepatitis B virus (HBV) is associated with more severe liver damage and an increased risk of fulminant disease. HDV is a single-stranded RNA virus that encodes a single protein, the delta antigen, which is expressed in two forms, small (S-HDAg) and large (L-HDAg). Here we show that although HDV ribonucleoproteins are mainly detected in the nucleus, they are also present in the cytoplasm of cells infected with HDV or transfected with HDV cDNA. Making use of an heterokaryon assay, we demonstrate that HDV ribonucleoproteins shuttle continuously between the nucleus and the cytoplasm. In the absence of HDV RNA, both forms of the delta antigen are retained in the nucleus, whereas in the absence of the delta antigen, HDV RNA is predominantly detected in the cytoplasm. Coexpression of HDV RNA and S-HDAg (which binds to the viral RNA and contains a nuclear localization signal) results in nuclear accumulation of the viral RNA. This suggests that HDV RNA mediates export of viral particles to the cytoplasm whereas the delta antigen triggers their reimport into the nucleus.


A detailed morphologic and immunohistochemical comparison of pre- and postmenopausal endometriosis.
Endometriosis depends on oestrogenic stimulation for its continued growth, accounting for its prevalence during reproductive years. There is doubt among clinicians regarding its existence in postmenopausal women in the absence of exogenous or endogenous sex hormones. We postulated that endometriosis occurring in postmenopausal women would show a different morphologic and immunohistochemical profile to the disease occurring in premenopausal women. We reviewed the most recent 100 cases of endometriosis in our department plus all cases occurring in women aged > or =50 dating back to 1999. Cases were divided into <50 (n = 91), 50-59 (8) and > or =60 (6), and analysed for extent of disease, proportions of epithelium and stroma, and amount of haemorrhage. Immunohistochemistry for oestrogen receptor (OR), progesterone receptor (PR) and CD10 was performed and analysed on all cases aged > or =50 and on controls <50. There was statistically less disease in older women when cases occurring in the cervix and in scars were excluded (p = 0.0191). There was no statistical difference in the proportions of epithelium or stroma, but there was a statistical difference in the amount of haemorrhage (p = 0.0154) with older women showing less haemorrhage. There was no significant difference in immunohistochemical profile. Endometriosis does occur in postmenopausal women but is less common, is present in smaller volumes, and is less active. It has the same immunohistochemical profile as the disease occurring in premenopausal women and we infer from this that it has the potential to reactivate given the appropriate stimulation.


A restriction-free method for gene reconstitution using two single-primer PCRs in parallel to generate compatible cohesive ends.
Restriction-free (RF) cloning, a PCR-based method for the creation of custom DNA plasmids, allows for the insertion of any sequence into any plasmid vector at any desired position, independent of restriction sites and/or ligation. Here, we describe a simple and fast method for performing gene reconstitution by modified RF cloning. Double-stranded inserts and acceptors were first amplified by regular PCR. The amplified fragments were then used as the templates in two separate linear amplification reactions containing either forward or reverse primer to generate two single-strand reverse-complement counterparts, which could anneal to each other. The annealed inserts and acceptors with 5' and 3' cohesive ends were sealed by ligation reaction. Using this method, we made 46 constructs containing insertions of up to 20 kb. The average cloning efficiency was higher than 85%, as confirmed by colony PCR and sequencing of the inserts. Our method provides an alternative cloning method capable of inserting any DNA fragment of up to at least 20 kb into a plasmid, with high efficiency. This new method does not require restriction sites or alterations of the plasmid or the gene of interest, or additional treatments. The simplicity of both primer design and the procedure itself makes the method suitable for high-throughput cloning and structural genomics.


Caffeine intake, short bouts of physical activity, and energy expenditure: a double-blind randomized crossover trial.
PA energy expenditure (PAEE) is the most variable component of Total Energy Expenditure (TEE) and largely due to the balance of sedentary time (SedT) and low intensity physical activity (LIPA). There has been an emergence for seeking an understanding of factors which determine variations in SedT, LIPA, and PAEE. Sedentary behavior and physical activity are relatively resistant to change by experimental dietary treatments and significant body weight changes. Although caffeine (Caf) is by far the most heavily used nutritional agent ingested to promote a sense of vigor/alertness, it is still unknown if Caf is effective in increasing PAEE and physical activity. The aim of the study was to test the hypothesis that 2 daily doses of Caf (as a capsule to blind the treatment and divided equally during breakfast and lunch) increase PAEE and TEE, and it would do so through increasing the frequent and brief bouts of physical activity (~1-5 min long) through the day as measured by accelerometry. In 21 low Caf users (<100 mg day(-1)), we used a double-blind crossover trial (ClinicalTrials.govID;NCT01477294) with two conditions (4-day each with a 3-day washout period) randomly ordered as 5 mg kg(-1) day(-1) of Caf and maltodextrin as placebo (Plc). Resting energy expenditure (REE) by indirect calorimetry, total energy expenditure (TEE) from doubly labeled water, PAEE calculated as TEE-(REE+0.1TEE), and accelerometry measurements of both LIPA and MVPA were not different between conditions. However, regardless of caffeine or placebo, there were several significant relationships between brief bouts of LIPA and MVPA with PAEE. In conclusion, this double-blind study found that low and moderate-vigorous activity as well as the total volume of PAEE in free-living conditions is resistant to dietary caffeine intake that was equivalent to 5 cups of espresso or 7 cups of tea. ClinicalTrials.gov NCT01477294.


Glycosyltransferase mechanisms: impact of a 5-fluoro substituent in acceptor and donor substrates on catalysis.
In glycosyltransferase-catalyzed reactions a new carbohydrate-carbohydrate bond is formed between a carbohydrate acceptor and the carbohydrate moiety of either a sugar nucleotide donor or lipid-linked saccharide donor. It is currently believed that most glycosyltransferase-catalyzed reactions occur via an electrophilic activation mechanism with the formation of an oxocarbenium ion-like transition state, a hypothesis that makes clear predictions regarding the charge development on the donor (strong positive charge) and acceptor (minimal negative charge) substrates. To better understand the mechanism of these enzyme-catalyzed reactions, we have introduced a strongly electron-withdrawing group (fluorine) at C-5 of both donor and acceptor substrates in order to explore its effect on catalysis. In particular, we have investigated the effects of the 5-fluoro analogues on the kinetics of two glycosyltransferase-catalyzed reactions mediated by UDP-GlcNAc:GlcNAc-P-P-Dol N-acetylglucosaminyltransferase (chitobiosyl-P-P-lipid synthase, CLS) and beta-N-acetylglucosaminyl-beta-1,4 galactosyltransferase (GalT). The 5-fluoro group has a marked effect on catalysis when inserted into the UDP-GlcNAc donor, with the UDP(5-F)-GlcNAc serving as a competitive inhibitor of CLS rather than a substrate. The (5-F)-GlcNAc beta-octyl glycoside acceptor, however, is an excellent substrate for GalT. Both of these results support a weakly associative transition state for glycosyltransferase-catalyzed reactions that proceed with inversion of configuration.


Value of database linkage: are patients at risk of familial colorectal cancer being referred for genetic counselling and testing?
Unique research opportunities are being created in an era of increasingly sophisticated data collection and data linkage. There are Familial Cancer Clinics (FCC) to counsel patients and families about risk reduction strategies and to carry out genetic testing where appropriate. There is currently no objective evidence as to whether appropriate patients are being referred to the FCC. Using a unique resource, the BIO21:MMIM informatics platform, we were able to link data from a prospective colorectal cancer (CRC) database at four Melbourne hospitals with the FCC database for the 4-year period from 2002 to 2005. We determined the number of patients that, on the basis of at least one risk factor suggestive of hereditary CRC, could have been considered for FCC referral, the number that was referred and the number that attended. Of the 829 new diagnoses of CRC 228 (27.5%) would potentially have benefited from FCC referral. Of these, 50 persons (21.9%) were referred and 32 (14.0%) attended. The highest referral rates were in young, early-stage CRC patients with a family history and the lowest in late-stage and multiple-polyp patients. Patient sex, language and insurance status did not influence referral or attendance. The database linkage capability provided by MMIM has enabled us to carry out a unique study. The results suggest that the rate of appropriate FCC referral is low, that certain subgroups are at particular risk of non-referral and that many referred patients do not ultimately attend. Interventions that increase referral rates and encourage attendance need to be considered.


Evaluation of Left Main Coronary Artery Using Optical Frequency Domain Imaging and Its Pitfalls.
We aimed to assess the quality of optical frequency domain imaging (OFDI) of the left main (LM) arterial wall and describe and analyse potential artefacts in this setting. OFDI is increasingly used to assess ambiguous lesions and optimize LM percutaneous coronary intervention. However, its ability to provide artefact-free high-quality images of coronary ostia and large segments such as the LM remains uncertain. We included 42 consecutive patients who underwent OFDI, including LM imaging. Each OFDI frame was subdivided into four quadrants and analysed. The number of quadrants with artifacts was calculated within the proximal, mid, and distal LM and the first 5 mm of the left anterior descending artery (LAD) and/or left circumflex artery (LCX). The quadrants analysis showed an overall artifact rate of 8.9%, mostly out-of-field (45.1%) or residual blood (44.7%) artefacts. Most artifacts were located in the proximal LM (18.6%) with a stepwise reduction of artifact rates towards distal segments (mid LM 5.8%; distal LM 3.6%, ostial LAD 2.6%, and ostial LCX 0%; p < 0.001). While 20 (48.8%) patients had angiographically visible plaques, OFDI showed plaques in 32 patients (76.2%; p=0.007). OFDI can accurately evaluate the LM and detect and assess angiographically unvisualized atherosclerotic plaques providing accurate assessment of >90% of the quadrants of the LM and the ostia of its bifurcation branches. However, artifacts mainly located in the proximal LM and decreasing distally in a stepwise fashion should be considered in the interpretation of OFDI in this setting.


Assessment of brain growth in early childhood using deformation-based morphometry.
We present methods for the quantitative analysis of brain growth based on the registration of longitudinal MR image data with the use of Jacobian determinant maps to characterise neuroanatomical changes. The individual anatomies, growth maps and tissue classes are also spatially normalised in an 'average space' and aggregated to provide atlases for the population at each timepoint. The average space representation is obtained using the average intersubject transformation within each timepoint. In an exemplar study, this approach is used to assess brain development in 25 infants between 1 and 2 years, and we show consistency in growth estimates between registration and segmentation approaches.


Towards excimer-laser-based stereolithography: a rapid process to fabricate rigid biodegradable photopolymer scaffolds.
We demonstrate high-resolution photocross-linking of biodegradable poly(propylene fumarate) (PPF) and diethyl fumarate (DEF) using UV excimer laser photocuring at 308 nm. The curing depth can be tuned in a micrometre range by adjusting the total energy dose (total fluence). Young's moduli of the scaffolds are found to be a few gigapascal, high enough to support bone formation. The results presented here demonstrate that the proposed technique is an excellent tool for the fabrication of stiff and biocompatible structures on a micrometre scale with defined patterns of high resolution in all three spatial dimensions. Using UV laser photocuring at 308 nm will significantly improve the speed of rapid prototyping of biocompatible and biodegradable polymer scaffolds and enables its production in a few seconds, providing high lateral and horizontal resolution. This short timescale is indeed a tremendous asset that will enable a more efficient translation of technology to clinical applications. Preliminary cell tests proved that PPF : DEF scaffolds produced by excimer laser photocuring are biocompatible and, therefore, are promising candidates to be applied in tissue engineering and regenerative medicine.


Molecular cloning of a putative receptor protein kinase gene encoded at the self-incompatibility locus of Brassica oleracea.
Self-recognition between pollen and stigma during pollination in Brassica oleracea is genetically controlled by the multiallelic self-incompatibility locus (S). We describe the S receptor kinase (SRK) gene, a previously uncharacterized gene that resides at the S locus. The nucleotide sequences of genomic DNA and of cDNAs corresponding to SRK predict a putative transmembrane receptor having serine/threonine-specific protein kinase activity. Its extracellular domain exhibits striking homology to the secreted product of the S-locus glycoprotein (SLG) gene and is connected via a single pass transmembrane domain to a protein kinase catalytic center. SRK alleles derived from different S-locus genotypes are highly polymorphic and have apparently evolved in unison with genetically linked alleles of SLG. SRK directs the synthesis of several alternative transcripts, which potentially encode different protein products, and these transcripts were detected exclusively in reproductive organs. The identification of SRK may provide new perspectives into the signal transduction mechanism underlying pollen recognition.


A smoke-free medical campus in Jerusalem: data for action.
Establishing smoke-free environments is a major component of tobacco control policy. The introduction of a smoke-free policy in medical campuses may serve as a role model for other educational and health institutions but little has been published about their prevalence or impact. In 2012, the Faculty of Medicine at Hebrew University-Hadassah in Jerusalem, Israel launched a smoke-free Medical Campus initiative. This study examined smoking behaviours, cigarette smoke exposure and attitudes towards the smoke-free campus policy among students and employees. Using a self-administered questionnaire, data was collected from medical, dental and pharmacy students, as well as employees of the school of pharmacy. We approached the entire target population in 2013 (N = 449), with a response rate of 72.5 % (N = 313). The rate of smoking was 8.3 % (95 % CI 5.5-11.9 %). Most participants reported daily exposure or exposure several times a week to cigarette smoke (65.8 %). Overall, 98.0 % had reported seeing people smoke in open campus areas and 27.2 % indoors. Most participants supported the smoking ban inside buildings (94.2 %) but fewer supported (40.8 %) a complete ban of smoking throughout the campus, including outside areas. Only 18.4 % agreed that a policy prohibiting smoking was unfair to smokers. A multivariable analysis showed that support for a complete ban on smoking on campus was higher among non-smokers than for smokers (OR = 9.5, 95 % CI 2.2-31.5, p = 0.02). The smoke-free policy does not have total compliance, despite the strong support among both students and employees for a smoke-free medical campus. The data collected will assist policy makers move towards a total smoke-free medical campus and will aid tobacco control efforts in Israel and other countries.


Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence.
The small GTPase Rab7 promotes fusion events between late endosomes and lysosomes. Rab7 activity is regulated by extrinsic signals, most likely via effects on its guanine nucleotide exchange factor (GEF) or GTPase-activating protein (GAP). Based on their homology to the yeast proteins that regulate the Ypt7 GTP binding state, TBC1D15, and mammalian Vps39 (mVps39) have been suggested to function as the Rab7 GAP and GEF, respectively. We developed an effector pull-down assay to test this model. TBC1D15 functioned as a Rab7 GAP in cells, reducing Rab7 binding to its effector protein RILP, fragmenting the lysosome, and conferring resistance to growth factor withdrawal-induced cell death. In a cellular context, TBC1D15 GAP activity was selective for Rab7. TBC1D15 overexpression did not inhibit transferrin internalization or recycling, Rab7-independent processes that require Rab4, Rab5, and Rab11 activation. TBC1D15 was thus renamed Rab7-GAP. Contrary to expectations for a Rab7 GEF, mVps39 induced lysosomal clustering without increasing Rab7 GTP binding. Moreover, a dominant-negative mVps39 mutant fragmented the lysosome and promoted growth factor independence without decreasing Rab7-GTP levels. These findings suggest that a protein other than mVps39 serves as the Rab7 GEF. In summary, although only TBC1D15/Rab7-GAP altered Rab7-GTP levels, both Rab7-GAP and mVps39 regulate lysosomal morphology and play a role in maintaining growth factor dependence.


Synthesis and anti-human immunodeficiency virus activity of 4'-branched (+/-)-4'-thiostavudines.
Motivated by our recent finding that 4'-ethynylstavudine (4) is a promising anti-human immunodeficiency virus type 1 (HIV-1) agent, we synthesized its 4'-thio analogue, as well as other 4'-thiostavudines having a carbon substituent at the 4'-position, as racemates in this study. Methyl 3-oxo-tetrahydrothiophen-2-carboxylate (5) was used as a starting material to construct the requisite 4-thiofuranoid glycal (13). Introduction of a thymine base was carried out by an electrophilic addition reaction to 13 using N-iodosuccinimide (NIS) and bis(trimethylsilyl)thymine. The desired beta-anomer (16beta) obtained as a major product in this reaction underwent ready elimination with activated Zn to give the 4'-carbomethoxy derivative (18). By using 18 as a common intermediate, 4'-carbon-substituted (CH2OH, CO2Me, CONH2, CH=CH2, CN, and C(triple bond)CH) 4'-thiostavudines were prepared. Among these six compounds, 4'-cyano (28) and 4'-ethynyl (29) analogues were found to show inhibitory activity against HIV-1 with ED50 values of 7.6 and 0.74 microM, respectively. The activity of 29 was comparable to that of stavudine, but 29 was not as active as 4. Optical resolution of 29 was briefly examined.


Role of growth-hormone and insulin-like growth-factor-binding proteins.
Some peptide hormones are associated with specific, high-affinity plasma proteins. The major binding protein (BP) for growth hormone (GH) in humans is a circulating fragment of the GH membrane receptor, consisting of the hydrophilic, extracellular portion of that transmembrane glycoprotein. The circulating levels of GH-BP mirror the levels of GH receptors. There are 4 well-characterized insulin-like growth factor (IGF)-BPs. One IGF-binding component in plasma is a fragment of the extracellular portion of the IGF-II/mannose-6-phosphate receptor, analogous to the GH-BP. The 3 other cloned IGF-BPs form a homologous family of proteins with differences in structure, glycosylation and hormonal control that suggest differences in function. The GH- and IGF-BPs play a major role in the metabolism and biological action of these peptide hormones.


In vitro studies to show sequestration of matrix metalloproteinases by silver-containing wound care products.
Excess or "uncontrolled" proteinase activity in the wound bed has been implicated as one factor that may delay or compromise wound healing. One proteinase group--matrix metalloproteinases--includes collagenases, elastase, and gelatinases and can be endogenous (cell) or exogenous (bacterial) in origin. A study was conducted to assess the ability of five silver-containing wound care products to reduce a known matrix metalloproteinase supernatant concentration in vitro. Four silver-containing wound dressings (a carboxy-methyl cellulose, a nanocrystalline, a hydro-alginate, and a collagen/oxidized regenerated cellulose composite dressing), along with a 0.5% aqueous silver nitrate [w/v] solution and controls for matrix metalloproteinase-2 and matrix metalloproteinase-9 sourced from ex vivo dermal tissue and blood monocytes, respectively, were used. Extracts were separated and purified using gelatine-Sepharose column chromatography and dialysis and polyacrylamide gel electrophoretic zymography was used to analyze specific matrix metalloproteinase activity. All dressings and the solution were shown to sequester both matrix metalloproteinases. The silver-containing carboxy-methyl cellulose dressing showed significantly greater sequestration for matrix metalloproteinase-2 at 6 and 24 hours (P< 0.001) compared to the other treatments. For matrix metalloproteinase-9, both the carboxy-methyl cellulose dressing and the oxidized regenerated cellulose dressing achieved significant sequestration when compared to the other treatments at 24 hours (P <0.001), which was maintained to 48 hours (P < 0.001). Results from this study show that silver-containing dressings are effective in sequestering matrix metalloproteinase-2 and -9 and that this can be achieved without a sacrificial protein (eg, collagen). Although the varying ability of wound dressings to sequester matrix metalloproteinases has been shown in vitro, further in vivo evidence is required to confirm these findings.


Capacitive micromachined ultrasonic Lamb wave transducers using rectangular membranes.
This paper details the theory, fabrication, and characterization of a new Lamb wave device. Built using capacitive micromachined ultrasonic transducers (CMUTs), the structure described uses rectangular membranes to excite and receive Lamb waves on a silicon substrate. An equivalent circuit model for the transducer is proposed that produces results, which match well with those observed by experiment. During the derivation of this model, emphasis is placed on the resistance presented to the transducer membranes by the Lamb wave modes. Finite element analysis performed in this effort shows that the dominant propagating mode in the device is the lowest order antisymmetric flexural wave (A0). Furthermore, most of the power that couples into the Lamb wave is due to energy in the vibrating membrane that is transferred to the substrate through the supporting posts of the device. The manufacturing process of the structure, which relies solely on fundamental IC-fabrication techniques, is also discussed. The resulting device has an 18-microm-thick substrate that is almost entirely made up of crystalline silicon and operates at a frequency of 2.1 MHz. The characterization of this device includes S-parameter and laser vibrometer measurements as well as delay-line transmission data. The insertion loss, as determined by both S-parameter and delay-line transmission measurements, is 20 dB at 2.1 MHz. When configured as a delay-line oscillator, the device functions well as a sensor with sensitivity to changes in the mass loading of its substrate.


Differential growth dynamics control aerial organ geometry.
How gene activities and biomechanics together direct organ shapes is poorly understood. Plant leaf and floral organs develop from highly similar initial structures and share similar gene expression patterns, yet they gain drastically different shapes later-flat and bilateral leaf primordia and radially symmetric floral primordia, respectively. We analyzed cellular growth patterns and gene expression in young leaves and flowers of Arabidopsis thaliana and found significant differences in cell growth rates, which correlate with convergence sites of phytohormone auxin that require polar auxin transport. In leaf primordia, the PRESSED-FLOWER-expressing middle domain grows faster than adjacent adaxial domain and coincides with auxin convergence. In contrast, in floral primordia, the LEAFY-expressing domain shows accelerated growth rates and pronounced auxin convergence. This distinct cell growth dynamics between leaf and flower requires changes in levels of cell-wall pectin de-methyl-esterification and mechanical properties of the cell wall. Data-driven computer model simulations at organ and cellular levels demonstrate that growth differences are central to obtaining distinct organ shape, corroborating in planta observations. Together, our study provides a mechanistic basis for the establishment of early aerial organ symmetries through local modulation of differential growth patterns with auxin and biomechanics.


Zika autoimmunity and Guillain-Barré syndrome.
To summarize the recent data regarding Guillain-Barré syndrome (GBS) as an autoimmune disorder following infection with Zika virus (ZIKV) infection, including the proposed pathogenic mechanisms and the role of autoantibodies. The loss of self-tolerance that leads to autoimmune diseases is a multifactorial process that may be illustrated as 'the mosaic of autoimmunity'. Infectious agents may contribute to the development of autoimmunity by several proposed mechanisms. One of the central mechanisms is molecular mimicry, which is also the most plausible mechanism in the case of ZIKV-induced autoimmune disorders.A recent meta-analysis found a low prevalence of GBS associated with ZIKV infection. Nevertheless, the estimated cost of illness for patients with GBS associated with ZIKV are tremendous and exceed 4.7 million dollars per year in Brazil alone. Currently, there is sufficient data to indicate that ZIKV infection is one of many triggers and factors that may contribute to the development GBS. Thus, it is advised to evaluate and determine ZIKV exposure and infection in the management of potential GBS patients.


Hierarchical task organization in dual tasks: evidence for higher level task representations.
To examine whether hierarchical higher level task representations comprising the task sets of Task 1 (T1) and Task 2 (T2) are activated within each trial in dual-task situations, we combined the psychological refractory period (PRP) paradigm with the task-pair switching logic (Hirsch et al. 2017). In Experiment 1, in which subjects switched between task-pairs including a varying T1 and a constant T2, we found a PRP effect (i.e., worse performance with short stimulus onset asynchrony [SOA] than with long SOA) and task-pair switch costs in T1 and T2 (impaired performance in task-pair switches compared to task-pair repetitions). However, since in Experiment 1 there were no forward and backward response-response compatibility effects that indicated interference between T1 and T2, we could not exclude that the activation of T1 persisted into the next trial despite the intervening T2, and hence, that task-pair switch costs are due to repetition-priming effects of T1 across task-pairs rather than due to persisting activation of task-pair representations. In Experiment 2, we used a modified task-pair switching logic with a constant T1 and a varying T2, and replicated task-pair switch costs under conditions that not only rule out repetition-priming effects of T1 across task-pairs as the source of task-pair switch costs but also disentangle the effects of switching task-pairs from those of switching T1. These effects were associated in previous studies using the original task-pair switching logic. Thus, the findings of the present study strongly suggest that hierarchical higher level task representations are activated during dual-task processing.


Action of YM155 on clear cell renal cell carcinoma does not depend on survivin expression levels.
The dioxonapthoimidazolium YM155 is a survivin suppressant which has been investigated as an anticancer agent in clinical trials. Here, we investigated its growth inhibitory properties on a panel of immortalized and patient derived renal cell carcinoma (RCC) cell lines which were either deficient in the tumour suppressor von Hippel-Lindau (VHL) protein or possessed a functional copy. Neither the VHL status nor the survivin expression levels of these cell lines influenced their susceptibility to growth inhibition by YM155. Of the various RCC lines, the papillary subtype was more resistant to YM155, suggesting that the therapeutic efficacy of YM155 may be restricted to clear cell subtypes. YM155 was equally potent in cells (RCC786.0) in which survivin expression had been stably silenced or overexpressed, implicating a limited reliance on survivin in the mode of action of YM155. A follow-up in-vitro high throughput RNA microarray identified possible targets of YM155 apart from survivin. Selected genes (ID1, FOXO1, CYLD) that were differentially expressed in YM155-sensitive RCC cells and relevant to RCC pathology were validated with real-time PCR and western immunoblotting analyses. Thus, there is corroboratory evidence that the growth inhibitory activity of YM155 in RCC cell lines is not exclusively mediated by its suppression of survivin. In view of the growing importance of combination therapy in oncology, we showed that a combination of YM155 and sorafenib at ½ x IC50 concentrations was synergistic on RCC786.0 cells. However, when tested intraperitoneally on a murine xenograft model derived from a nephrectomised patient with clear cell RCC, a combination of suboptimal doses of both drugs failed to arrest tumour progression. The absence of synergy in vivo highlighted the need to further optimize the dosing schedules of YM155 and sorafenib, as well as their routes of administration. It also implied that the expression of other oncogenic proteins which YM155 may target is either low or absent in this clear cell RCC.


In silico study the inhibition of angiotensin converting enzyme 2 receptor of COVID-19 by Ammoides verticillata components harvested from Western Algeria.
The objective of this present study is to focus on the in silico study to screen for an alternative drug that can block the activity of the angiotensin converting enzyme 2 (ACE2) as a receptor for SARS-CoV-2, potential therapeutic target of the COVID-19 virus using natural compounds (Isothymol, Thymol, Limonene, P-cymene and γ-terpinene) derived from the essential oil of the antiviral and antimicrobial plant Ammoides verticillata (Desf.) Briq. which is located in the occidental Algeria areas. This study reveals that Isothymol, a major component of this plant, gives the best docking scores, compared to, the co-crystallized inhibitor β-D-mannose of the enzyme ACE2, to Captropil drug as good ACE2 inhibitor and to Chloroquine antiviral drug also involved in other mechanisms as inhibition of ACE2 cellular receptor. In silico (ADME), drug-likeness, PASS & P450 site of metabolism prediction, pharmacophore Mapper showed that the compound Isothymol has given a good tests results compared to the β-D-mannose co-crystallized inhibitor, to Captopril and Chloroquine drugs. Also the other natural compounds gave good results. The Molecular Dynamics Simulation study showed good result for the Isotymol- ACE2 docked complex. This study revealed for the first time that Isothymol is a functional inhibitor of angiotensin converting enzyme 2 activity and the components of essential oils Ammoides verticillata can be used as potential inhibitors to the ACE2 receptor of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.


Comparative single-dose kinetics of oxazolam, prazepam, and clorazepate: three precursors of desmethyldiazepam.
Twelve healthy volunteers received a single 40-mg oral dose of the benzodiazepine derivative oxazolam, which serves primarily as a precursor of the active substance desmethyldiazepam (DMDZ). Concentrations of DMDZ were measured in multiple serum samples drawn for up to two weeks after the dose. Peak serum DMDZ concentrations averaged 115 ng/ml, measured at 8.6 hours after dosage. Mean DMDZ elimination half-life averaged 61 hours. Three of the subjects also received 40 mg each of prazepam and clorazepate, two other DMDZ precursors, on separate occasions. Although DMDZ elimination half-life was similar, total area under the curve (AUC) for DMDZ was larger for clorazepate, known to be completely transformed into DMDZ, than for oxazolam or prazepam the extent of whose conversion to DMDZ has not been previously established. After correcting for the different molar equivalent of DMDZ available from each preparation, the DMDZ ratio averaged 0.22 for oxazolam vs. clorazepate and 0.51 for prazepam vs. clorazepate. Thus, both oxazolam and prazepam lead to slow appearance of DMDZ in the systemic circulation. Furthermore the extent of DMDZ formation from oxazolam and prazepam is either incomplete or the drugs are incompletely absorbed. Equivalent doses of oxazolam, prazepam, and clorazepate should not be interchanged in clinical practice.


Management of neonatal abstinence syndrome in neonates born to opioid maintained women.
Neonates born to opioid-maintained mothers are at risk of developing neonatal abstinence syndrome (NAS), which often requires pharmacological treatment. This study examined the effect of opioid maintenance treatment on the incidence and timing of NAS, and compared two different NAS treatments (phenobarbital versus morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers were included in this study. The mothers received methadone (n=22), slow-release oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective of maintenance treatment, all neonates showed APGAR scores comparable to infants of non-opioid dependent mothers. No difference was found between the three maintenance groups regarding neonatal weight, length or head circumference. Sixty percent (n=32) of neonates required treatment for NAS [68% in the methadone-maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in the buprenorphine-maintained group (n=3)]. The mean duration from birth to requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for the buprenorphine-maintained group and 58 h for the methadone-maintained group. In neonates requiring NAS treatment, those receiving morphine required a significantly shorter mean duration of treatment (9.9 days) versus those treated with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is preferable for neonates suffering NAS due to opioid withdrawal.


Oral magnesium load test in patients with migraine.
To determine whether migraineurs may have a systemic deficiency of magnesium. Magnesium deficiency has been shown to play a potential role in the pathogenesis of migraine, but there are no data on total body magnesium status in migraineurs. An oral magnesium load test was performed by giving 3000 mg of magnesium lactate during a 24-hour interictal period to 20 patients with migraine (15 women and 5 men; mean age, 37.9 years) and 20 healthy volunteers (16 women and 4 men; mean age, 39.6 years). Baseline and postload magnesium concentrations were determined from serum and 24-hour urine specimens. There was no significant difference between the groups in the baseline serum and urine magnesium concentrations, although the latter tended to be lower (P = .064) in the migraine group. The postload magnesium concentrations were significantly higher within both the migraine (P < .0001 and P < .0001) and the control (P = .0009 and P < .0001) groups compared to the baseline values. After loading, the 24-hour urinary magnesium excretions were significantly lower (P = .0007) in the patients with migraine than in the controls, but serum values did not differ. Magnesium retention occurs in patients with migraine after oral loading, suggesting a systemic magnesium deficiency.


Evidence for linkage of murine beta 2-microglobulin to H-3 and Ly-4.
Murine beta 2-microglobulin exists in 2 electrophoretically distinct forms; C57BL/6 mice possess the basic allele whereas BALB/c, CBA, AKR, and NZB possess the acidic allele. Mice heterozygous for beta 2-microglobulin express both alleles. Analysis of recombinant inbred mice suggests linkage of beta 2-microglobulin to H-2 or H-3. B10.C (28NX) mice (which possess the H-3c allele of BALB/c on a C57BL/10 background) possess the acid allele. Taken together, these results are consistent with the beta 2-microglobulin gene lying on chromosome 2, and being linked to H-3 and Ly-4.


Prenatal maternal cortisol measures predict learning and short-term memory performance in 3- but not 5-month-old infants.
Little is known about relations between maternal prenatal stress and specific cognitive processes-learning and memory-in infants. A modified crib-mobile task was employed in a longitudinal design to test relations between maternal prenatal cortisol, prenatal subjective stress and anxiety, psychosocial variables, and learning and memory in 3- and 5-month-old infants. Results revealed that maternal prenatal cortisol was affected by particular psychosocial variables (e.g., maternal age, whether or not the infant's grandmother provided childcare, financial status), but was unrelated to measures of maternal depression, anxiety, and stress. Although maternal prenatal cortisol was not predictive of learning or memory performance in 5-month-old infants, higher levels of basal maternal cortisol and reduced prenatal cortisol response was predictive of some learning and short-term memory measures in 3-month-old infants. These results suggest an influence of maternal neuroendocrine functioning on fetal neurological development, and the importance of separate examination of subjective and biological measures of stress.


Differential involvement of reactive oxygen species in a mouse model of capsaicin-induced secondary mechanical hyperalgesia and allodynia.
Intradermally injected capsaicin induces secondary mechanical hyperalgesia and allodynia outside the primary (i.e., capsaicininjected) site. This secondary mechanical hypersensitivity is attributed to central sensitization in which reactive oxygen species (ROS) play a key role. We examined whether ROS would be differentially involved in secondary mechanical hyperalgesia and allodynia using a mouse intraplantar capsaicin injection model. In mice, capsaicin-induced secondary mechanical hyperalgesia outlasted its allodynia counterpart. Unlike the hyperalgesia, the allodynia was temporarily abolished by an anesthetic given at the capsaicin-injected site. The ROS scavenger phenyl-N-tert-butylnitrone slowed the development of both secondary mechanical hyperalgesia and allodynia when administered before intraplantar capsaicin injection, whereas it inhibited only the allodynia when administered after capsaicin had already induced secondary mechanical hyperalgesia and allodynia. Intrathecal injection of the ROS donor KO2 induced both mechanical hyperalgesia and allodynia with the former outlasting the latter. Metformin, an activator of redox-sensitive adenosine monophosphate-activated protein kinase, selectively inhibited capsaicin-induced secondary mechanical allodynia and intrathecal KO2-induced mechanical allodynia. These results suggest that ROS is required for rapid activation of central sensitization mechanisms for both secondary mechanical hyperalgesia and allodynia after intraplantar capsaicin injection. Once activated, the mechanism for the hyperalgesia is longlasting without being critically dependent on ongoing afferent activities arising from the capsaicin-injected site and the continuous presence of ROS. On the contrary, the ongoing afferent activities, ROS presence and adenosine monophosphate-activated protein kinase inhibition are indispensable for the maintenance mechanism for capsaicin-induced secondary mechanical allodynia.


Characteristics of skeletal muscle growth and protein turnover in a fast-growing rat strain.
1. Protein turnover and muscle composition has been studied in rat skeletal muscle throughout development in a relatively-fast-growing rat strain. 2. Muscle growth involved an increase in the total DNA and in the DNA-unit size as indicated by proteins: DNA. As a result of the latter increase together with no change in RNA: DNA, the RNA concentration fell throughout development. 3. Rates of protein synthesis measured in vivo by the continuous intravenous infusion method fell throughout development from 15.6%/d at 25 d to 4.46%/d at 320 d, and these changes reflected mainly the fall in RNA concentration, since there was no marked change in the rate of protein synthesis per unit RNA. 4. The rate of protein degradation, measured as the difference between rates of protein synthesis and growth, fell from 9.82%/d at 25 d to 4.46%/d at 320 d. 5. When these changes in protein turnover throughout development are compared with measurements made previously in a slow-growing strain it would appear that the faster growth was achieved as a result of increased efficiency of protein synthesis (defined as net synthesis: over-all synthesis) and this occurred mainly because of lower rates of protein degradation.


Acceptability and feasibility of mini-clinical evaluation exercise as a formative assessment tool for workplace-based assessment for surgical postgraduate students.
Despite an increasing emphasis on workplace-based assessment (WPBA) during medical training, the existing assessment system largely relies on summative assessment while formative assessment is less valued. Various tools have been described for WPBA, mini-clinical evaluation exercise (mini-CEX) being one of them. Mini-CEX is well accepted in Western countries, however, reports of its use in India are scarce. We conducted this study to assess acceptability and feasibility of mini-CEX as a formative assessment tool for WPBA of surgical postgraduate students in an Indian setting. Faculty members and 2nd year surgical residents were sensitized toward mini-CEX and requisite numbers of exercises were conducted. The difficulties during conduction of these exercises were identified, recorded, and appropriate measures were taken to address them. At the conclusion, the opinion of residents and faculty members regarding their experience with mini-CEX was taken using a questionnaire. The results were analyzed using simple statistical tools. Nine faculty members out of 11 approached participated in the study (81.8%). All 16 2nd year postgraduate surgical residents participated (100%). Sixty mini-CEX were conducted over 7 months. Each resident underwent 3-5 encounters. The mean time taken by the assessor for observation was 12.3 min (8-30 min) while the mean feedback time was 4.2 min (3-10 min). The faculty reported good overall satisfaction with mini-CEX and found it acceptable as a formative assessment tool. Three faculty members (33.3%) reported mini-CEX as more time-consuming while 2 (22.2%) found it difficult to carry the exercises often. All residents accepted mini-CEX and most of them reported good to high satisfaction with the exercises conducted. Mini-CEX is well accepted by residents and faculty as a formative assessment tool. It is feasible to utilize mini-CEX for WPBA of postgraduate students of surgery.


Integrated Smartphone-App-Chip System for On-Site Parts-Per-Billion-Level Colorimetric Quantitation of Aflatoxins.
We demonstrate herein an integrated, smartphone-app-chip (SPAC) system for on-site quantitation of food toxins, as demonstrated with aflatoxin B1 (AFB1), at parts-per-billion (ppb) level in food products. The detection is based on an indirect competitive immunoassay fabricated on a transparent plastic chip with the assistance of a microfluidic channel plate. A 3D-printed optical accessory attached to a smartphone is adapted to align the assay chip and to provide uniform illumination for imaging, with which high-quality images of the assay chip are captured by the smartphone camera and directly processed using a custom-developed Android app. The performance of this smartphone-based detection system was tested using both spiked and moldy corn samples; consistent results with conventional enzyme-linked immunosorbent assay (ELISA) kits were obtained. The achieved detection limit (3 ± 1 ppb, equivalent to μg/kg) and dynamic response range (0.5-250 ppb) meet the requested testing standards set by authorities in China and North America. We envision that the integrated SPAC system promises to be a simple and accurate method of food toxin quantitation, bringing much benefit for rapid on-site screening.


Anti-VDRL antibodies by ELISA in cerebrospinal fluid and its value in the differential diagnosis of abnormalities of the cerebrospinal fluid.
Enzyme-linked immunoabsorbent assay (ELISA) techniques for the detection of antibodies to the Venereal Disease Research Laboratories (VDRL) antigen as well as for the estimation of antibodies to cardiolipin (aCL) in cerebrospinal fluid (CSF) were performed in several groups of patients, including those with definite paretic neurosyphilis (DPNS, 10 patients), probable paretic neurosyphilis (PPNS, 19 patients), systemic lupus erythematosus (SLE, 71 patients), and miscellaneous neurologic disorders (30 patients), and normal subjects (11 patients). In the DPNS group, all demonstrated positive VDRL by ELISA, and 7 also had positive aCL tests, whereas only 7 of the 10 had positive CSF fluorescent treponemal antibody absorption (FTA-ABS) and Treponema pallidum hemagglutination assay (TPH A) tests. Three had positive VDRL tests by flocculation. In the PPNS group, no patients had positive FTA-ABS, TPH A, or VDRL flocculation tests in CSF. However, 18 of the 19 had positive CSF VDRL by ELISA; two of these also had positive aCL tests. Four SLE patients had positive CSF aCL tests (three with positive ELISA VDRL). Only one patient in the miscellaneous group had positive CSF aCL (Guillain-Barre syndrome), and one had positive IgM VDRL tests (bacterial meningitis). The value of VDRL ELISA in the diagnosis of neurosyphilis in the face of other negative conventional tests is established by our study and had important therapeutic consequences in patients with possible/probable neurosyphilis. The aCL test often may be positive in patients with DPNS but is less useful in the PPNS group.


Control of saccades in Parkinson's disease.
Parkinson's patients (PD) made pro- and antisaccades: In the no-delay condition, the target appeared concurrent with the GO signal. In the delay condition, the target appeared before the signal for movement. Second, we probed spatial working memory in PD. Subjects looked to the remembered locations of sequential targets. In the no-delay prosaccade condition, PD had faster reaction times, made more express saccades, and exhibited hypometria. In the no-delay antisaccade condition, PD had longer reaction times and made more direction errors. In the delay tasks, PD made more direction errors and had more difficulty withholding a movement. PD made more sequencing errors in the spatial working memory task. These findings are consistent with a basal ganglia pathophysiology influencing eye movement processing in the frontal cortex.


STATISTICAL TESTS OF HOST-PARASITE COSPECIATION.
A history of cospeciation (synchronous speciation) among ecologically associated, but otherwise distantly related, species is often revealed by a strong correspondence of their phylogenies. In this paper, we present several tests of cospeciation that use maximum-likelihood and Bayesian methods of phylogenetic estimation. The hypotheses tested include: (1) topological agreement of phylogenies for coevolving groups; (2) identical speciation times of associated species; and (3) identical evolutionary rates in genes of associated species. These tests are applied to examine a possible instance of host-parasite coevolution among pocket gophers and lice using mitochondrial COI DNA sequences. The observed differences between gopher and louse trees cannot be explained by sampling error and are consistent with a rate of host switching about one-third the host speciation rate. A subset of the gopher-louse data is consistent with a common history of evolution (i.e., the topologies and speciation times are identical). However, the relative rate of nucleotide substitution is two to four times higher in the lice than in the gophers.


Media use, sports activities, and motor fitness in childhood and adolescence.
Physical activity is one of the key determinants of physical, mental, and social health of children and adolescents. Therefore, the early development of health-relevant behavior patterns is of high relevance. To examine the impact of selected socioeconomic factors as well as media consumption, on sports activities and the motor skills of 10- to 14-year-old secondary school students. Body height and body weight were measured. The motor skills were determined with the Deutschen Motorik Test (DMT 6‑18; German Motor Test). Information about media use, media equipment, recreational sports activities, migration status, and the parents' profession was collected by means of a standardized questionnaire. A total of 391 adolescents have been tested (male 235; female 156). Body mass index (BMI) types are evenly distributed on gender. On a weekday, the pupils spend 10.3 h using media (SD ± 9.1 h). On weekends, media use increases up to 12 h per day on average (SD ± 9.7 h). The number of available media is independent from the age of the respondents and the social status of their families. According to bivariate correlations, heavy media use, a high BMI as well as migration status correlate negatively with both sports activities and motor skills. BMI seems to have the strongest influence on athletic performance (b = 0.41). Media use is an important determinant of juvenile sports activity and motor performance, being part of a complex juvenile leisure behavior.


Morphological, ultrastructural, genetic characteristics and remarkably low prevalence of macroscopic Sarcocystis species isolated from sheep and goats in Kurdistan region, Iraq.
Sarcocystis is a genus of cyst-forming parasites that infest both humans and livestock. Some parasites cause clinical and subclinical diseases in their hosts, resulting in economic losses. Esophagus, diaphragm, and skeletal muscle from slaughtered sheep and goats were examined macroscopically, microscopically, and ultrastructurally and subjected to DNA analysis. We isolated macrocysts of S. gigantea and of S. caprafelis moulei from naturally infected sheep (Ovis aries) and goats (Capra hircus). The macrocyst wall thickness was 18.9 µm in sheep and 15.3 µm in goats, and consisted of an inner Periodic acid Schiff- (PAS) negative primary wall and an outer glycoconjugates containing i.e. PAS-positive secondary wall. The walls inner surface was compartmentalized and filled with bradyzoites. In S. gigantea the bradyzoites were approximently 12.3 x 2.6 µm in size, while in S. caprafelis moulei they were 13.9 x 4.4 µm. Ultrastructurally, both species have nearly identical morphology: cauliflower-like protrusions with numerous microtubules and often dendritic-like filaments, branching from the primary wall. The 18S rRNA gene in S. gigantea was 85.9% identical to that in S. medusiformis and 80.4% to the S. caprafelis moulei gene. The 28S rRNA gene in S. gigantea was 94.6% identical to that in S. medusiformis and 97.3% to the S. caprafelis moulei. This study is the first to (i) detail the ultrastructure of the macrocyst wall of S. caprafelis moulei, (ii) identify S. medusiformis in Iraqi sheep, and (iii) compare the prevalence of macroscopic Sarcocystis at different time periods within the same region. A positive finding was the reduction of macroscopic sarcocystosis occurrences (0.01% in sheep and 0.02% in goats) compared to our previous data from 1992 (4.1%: sheep, 33.6%: goats).


Liquid Marbles Based on Magnetic Upconversion Nanoparticles as Magnetically and Optically Responsive Miniature Reactors for Photocatalysis and Photodynamic Therapy.
Magnetic liquid marbles have recently attracted extensive attention for various potential applications. However, conventional liquid marbles based on iron oxide nanoparticles are opaque and inadequate for photo-related applications. Herein, we report the first development of liquid marbles coated with magnetic lanthanide-doped upconversion nanoparticles (UCNPs) that can convert near-infrared light into visible light. Apart from their excellent magnetic and mechanical properties, which are attractive for repeatable tip opening and magnetically directed movements, the resultant UCNP-based liquid marbles can act as ideal miniature reactors for photodynamic therapy of cancer cells. This work opens new ways for the development of liquid marbles, and shows great promise for liquid marbles based on UCNPs to be used in a large variety of potential applications, such as photodynamic therapy for accelerated drug screening, magnetically guided controlled drug delivery and release, and multifunctional actuation.


[Factors correlated with left ventricular mass in hypertensive patients].
Left ventricular hypertrophy (LVH) is an independent risk factor in hypertensive patient. Of our study is to evaluate prospectively the relationship between left ventricular mass and clinical, echocardiographical and ambulatory blood pressure data in hypertensive subjects. We studied 88 hypertensive patient who underwent clinical and laboratory investigation, echocardiography and 24 hours ambulatory blood pressure monitoring. Correlations were made between these data and left ventricular mass. Clinical data, which correlated well with left ventricular mass, were duration of hypertension, systolic arterial pressure and pulse arterial pressure. In echocardiography left atrial area and left ventricular dysfunction correlated significatively with left ventricular mass. Data from 24 hours blood pressure monitoring as daytime systolic pressure, nighttimes diastolic pressure, ambulatory systolic pressure and ambulatory pulse pressure. In hypertensive patient, left ventricular mass correlated well with left atrial dilation and diastolic left ventricular dysfunction. It also correlated with 24 hours ambulatory blood pressure monitoring data.


Non-radioactive in vitro PINK1 Kinase Assays Using Ubiquitin or Parkin as Substrate.
This protocol describes the in vitro phosphorylation of ubiquitin and Parkin by the kinase PINK1 using recombinant proteins. Both substrates, ubiquitin and Parkin, are phosphorylated at the conserved serine 65 residue (pS65-ubiquitin and pS65-Parkin). The protocol also includes the use of monomeric and K48- and K63-linked poly-ubiquitin chains as alternative substrates. Although there are commercially available antibodies, we have not tested their performance in this assay since, but used validated antibodies from our laboratory. An alternative antibody-independent method, the use of phostag gels to detect pS65-ubiquitin and pS65-Parkin, is described in addition.


Efficacy of different feeding levels of monensin in the control of coccidiosis in broilers.
The feed level of monensin which gave maximal protection from coccidial infection in broilers reared in floor pens depended on the severity of the coccidial exposure and the criteria of infection studied. With indirect seeding of pens with coccidia (light coccidial exposure), 40 ppm was as efficacious as 100 ppm in improving weight gain, lesion score, and feed conversion. Statistical analysis with direct seeding (seeder birds; severe coccidial exposure) showed that feed levels of 84 and 102 ppm gave maximal improvement of weight gain and 4-week feed conversion, respectively. Further increasing the monensin level from 100 to 121 ppm did not improve weight gain and feed conversion at 8 weeks. Conversely, the relationship of plasma pigmentation and total lesion scores to monensin feed levels indicated that increasing the dosage of monensin from 100 to 121 ppm improved the performance of the broilers on the basis of these 2 infection indicators.


Clinical features of ocular trauma in emergency department.
This study analyzed a hospital-based study to investigate the incidence and clinical features of ocular traumatic emergencies in Korea. Over a 6-year period, 1809 patients with ocular traumatic emergency each individually underwent clinical study including subject characteristics, type of ocular emergency, disease severity, etiology of ocular trauma, injury location, cause of decreased visual acuity, management of ocular injury, and final visual acuity. The homogeneity of each finding of the clinical features of ocular traumatic emergency was tested by an X2 test at a 95% level of certainty. During follow-up periods ranging from 3 days to 23 months (mean 2.0 months), the 1809 patients with ocular traumatic emergency, 1183 males (65.4%) and 626 females (34.6%), were studied. The incidence of ocular emergencies peaked in the third decade of life, irrespective of gender (P < 0.05). Corneal abrasion was the most common etiology among 1,552 (85.8%) closed injuries, and corneal laceration among 257 (14.2%) open injuries (P < 0.05). There were 542 cases (30%) of severe ocular injury, such as penetrating ocular injury, blow out fracture, and intraocular foreign body (IOF), and 1267 (70%) of less severe ocular injury, such as superficial ocular injury or contusion. The most common etiology of severe ocular injury was penetrating ocular injury, and that of less severe injury was corneal injury (P < 0.05). The main causative activity of ocular injuries was work in 631 cases (34.9%), assault in 398 (22.0%), play in 278 (15.4%), traffic accidents in 145 (8.0%) and sports in 128 (7.1%). Five hundred and fifty-four cases (32.5%) underwent surgical intervention. There was an improvement of visual acuity in 502 cases (70.1%), no change in 122 (17.0%), and worsening in 92 (12.9%). We suggest that preventive educational measures be instigated at workplaces to reduce the incidence of ocular traumatic emergency, especially severe ocular injury.


A Model of Gravity Vector Measurement Noise for Estimating Accelerometer Bias in Gravity Disturbance Compensation.
Compensation of gravity disturbance can improve the precision of inertial navigation, but the effect of compensation will decrease due to the accelerometer bias, and estimation of the accelerometer bias is a crucial issue in gravity disturbance compensation. This paper first investigates the effect of accelerometer bias on gravity disturbance compensation, and the situation in which the accelerometer bias should be estimated is established. The accelerometer bias is estimated from the gravity vector measurement, and a model of measurement noise in gravity vector measurement is built. Based on this model, accelerometer bias is separated from the gravity vector measurement error by the method of least squares. Horizontal gravity disturbances are calculated through EGM2008 spherical harmonic model to build the simulation scene, and the simulation results indicate that precise estimations of the accelerometer bias can be obtained with the proposed method.