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311.
Philippa Gander Hannah M. Mulrine Margo J. van den Berg Lora Wu Alexander Smith Leigh Signal 《Chronobiology international》2016,33(8):982-994
On trips with multiple transmeridian flights, pilots experience successive non-24 h day/night cycles with circadian and sleep disruption. One study across a 9-day sequence of transpacific flights (no in-flight sleep, 1-day layovers between flights) reported an average period in the core body temperature rhythm of 24.6 h (circadian drift). Consequently, pilots were sometimes flying through the circadian performance nadir and had to readapt to home base time at the end of the trip. The present study examined circadian drift in trip patterns with longer flights and in-flight sleep. Thirty-nine B747-400 pilots (19 captains, 20 first officers, mean age = 55.5 years) were monitored on 9- to 13-day trips with multiple return flights between East Coast USA and Japan (in 4-pilot crews) and between Japan and Hawaii (in 3-pilot crews), with 1-day layovers between each flight. Measures included total in-flight sleep (actigraphy, log books) and top of descent (TOD) measures of sleepiness (Karolinska Sleepiness Scale), fatigue (Samn–Perelli Crew Status Check) and psychomotor vigilance task (PVT) performance. Circadian rhythms of individual pilots were not monitored. To detect circadian drift, mixed-model analysis of variance examined whether for a given flight, total in-flight sleep and TOD measures varied according to when the flight occurred in the trip sequence. In addition, sleep propensity curves for pre-trip and post-trip days were examined (Chi-square periodogram analyses). Limited data suggest that total in-flight sleep of relief crew at landing may have decreased across successive East Coast USA–Japan (flights 1, 3, 5 or 7; median arrival 03:45 Eastern Daylight Time (EDT)). However, PVT response speed at TOD was faster on East Coast USA–Japan flights later in the trip. On these flights, circadian drift would result in flights later in the trip landing closer to the evening wake maintenance zone, when sleep is difficult and PVT response speeds are fastest. On Japan–East Coast USA flights (flights 2, 4, 6 or 8; median arrival time 14:52 EDT), PVT response speeds were slower on flight 8 than on flight 2. Circadian drift would move these arrivals progressively earlier in the SCN pacemaker cycle, where PVT response speeds are slower. Across the five post-trip days, 12 pilots (Group A) immediately resumed their pre-trip sleep pattern of a single nocturnal sleep episode; 9 pilots (Group B) had a daytime nap on most days that moved progressively earlier until it merged with nocturnal sleep and 17 pilots (Group C) had nocturnal sleep and intermittent naps. Chi-square periodogram analyses of the sleep propensity curves for each group across baseline and post-trip days suggest full adaptation to EDT from post-trip day 1 (dominant period = 24 h). However, in Groups B and C, the patterns of split sleep post-trip compared to pre-trip suggest that this may be misleading. We conclude that the trends in total in-flight sleep and significant changes in PVT performance speed at TOD provide preliminary evidence for circadian drift, as do persistent patterns of split sleep post-trip. However, new measures to track circadian rhythms in individual pilots are needed to confirm these findings. 相似文献
312.
Nelson G Kozlova-Zwinderman O Collis AJ Knight MR Fincham JR Stanger CP Renwick A Hessing JG Punt PJ van den Hondel CA Read ND 《Molecular microbiology》2004,52(5):1437-1450
Calcium signalling is little understood in filamentous fungi largely because easy and routine methods for calcium measurement in living hyphae have previously been unavailable. We have developed the recombinant aequorin method for this purpose. High levels of aequorin expression were obtained in Neurospora crassa, Aspergillus niger and Aspergillus awamori by codon optimization of the aequorin gene. Three external stimuli (mechanical perturbation, hypo-osmotic shock and high external calcium) were found transiently to increase [Ca(2+)](c). Each of the calcium signatures associated with these physico-chemical treatments was unique, suggesting the involvement of three distinct calcium-mediated signal transduction pathways. The fungal calcium channel blocker KP4 inhibited the [Ca(2+)](c) responses to hypo-osmotic shock and high external calcium, but not to mechanical perturbation. The divalent cation chelator BAPTA inhibited [Ca(2+)](c) responses to mechanical perturbation and hypo-osmotic shock. The calcium agonists A23187 and cyclopiazonic acid increased [Ca(2+)](c) levels. 相似文献
313.
Marinaki AM Champion M Kurian MA Simmonds HA Marie S Vincent MF van den Berghe G Duley JA Fairbanks LD 《Nucleosides, nucleotides & nucleic acids》2004,23(8-9):1231-1233
A deficiency of adenylosuccinate lyase (ASDL) is characterised by the accumulation of SAICAriboside (SAICAr) and succinyladenosine (S-Ado) in body fluids. The severity of the clinical presentation correlates with a low S-Ado/SAICAr ratio in body fluids. We report the first British case of ADSL deficiency. The patient presented at 14 days with a progressive neonatal encephalopathy and seizures. There was marked axial and peripheral hypotonia. Brain MRI showed widespread white matter changes. She died at 4 weeks of age. Concentrations of SAICAr and SAdo were markedly elevated in urine, plasma and CSF and the SAdo/SAICAr ratio was low, consistent with the severe phenotype. The patient was compound heterozygous for 2 novel ADSL mutations; c.9 G>C (A3P) and c.572 C>T (R190X). 相似文献
314.
Sara Rosati Ewald TJ van den Bremer Janine Schuurman Paul WHI Parren Johannis P Kamerling Albert JR Heck 《MABS-AUSTIN》2013,5(6):917-924
Here, we describe a fast, easy-to-use, and sensitive method to profile in-depth structural micro-heterogeneity, including intricate N-glycosylation profiles, of monoclonal antibodies at the native intact protein level by means of mass spectrometry using a recently introduced modified Orbitrap Exactive Plus mass spectrometer. We demonstrate the versatility of our method to probe structural micro-heterogeneity by describing the analysis of three types of molecules: (1) a non-covalently bound IgG4 hinge deleted full-antibody in equilibrium with its half-antibody, (2) IgG4 mutants exhibiting highly complex glycosylation profiles, and (3) antibody-drug conjugates. Using the modified instrument, we obtain baseline separation and accurate mass determination of all different proteoforms that may be induced, for example, by glycosylation, drug loading and partial peptide backbone-truncation. We show that our method can handle highly complex glycosylation profiles, identifying more than 20 different glycoforms per monoclonal antibody preparation and more than 30 proteoforms on a single highly purified antibody. In analyzing antibody-drug conjugates, our method also easily identifies and quantifies more than 15 structurally different proteoforms that may result from the collective differences in drug loading and glycosylation. The method presented here will aid in the comprehensive analytical and functional characterization of protein micro-heterogeneity, which is crucial for successful development and manufacturing of therapeutic antibodies 相似文献
315.
Thomas van Hengstum Susanne Lachmuth J. Gerard B. Oostermeijer Hans C. M. den Nijs Patrick G. Meirmans Peter H. van Tienderen 《Plant Systematics and Evolution》2012,298(6):1119-1131
Endemic genera on oceanic islands often evolved striking morphological and ecological differences among species, with weak postzygotic reproductive isolation. Human activities can lead to increased connectivity and can thereby promote secondary contact and hybridization between previously isolated species. We studied this phenomenon in three species of the genus Pericallis (Asteraceae) on Tenerife, Canary Islands. A total of 53 populations was sampled, including morphologically uniform as well as mixed populations containing morphologically diverse individuals. All plants were analyzed both genetically using AFLP markers and morphometrically. As expected, morphological analysis clearly separated the plants from the uniform populations in three clusters, with distinguishing characters corresponding to those used in species identification. The three species were also grouped into distinct genetic clusters in a structure analysis, although no private alleles were observed. Adding the mixed population data to the analyses provided evidence for extensive hybridization among species, predominantly between P. cruenta and P. echinata, and between P. cruenta and P. tussilaginis, and morphological and genetic signals were congruent. The mixed populations were geographically located in between the uniform populations and were found in road verges significantly more often than the uniform populations. The observed distribution strongly suggests that hybridization between originally isolated species is recent, promoted by secondary contact due to human disturbance and the construction of roads. 相似文献
316.
M. Van den Mooter M. Steenackers C. Maertens F. Gosselé P. De Vos J. Swings K. Kersters J. De Ley 《Journal of Phytopathology》1987,118(2):135-156
A numerical analysis of 257 phenotypic features of 45 bacterial isolates from grasses, revealed three phenons corresponding to (i) X. campestris pv. graminis (ISPP List 1980), (ii) X. campestris pv. phleipratensis (ISPP List 1980) and (iii) X. campestris pv. poae Egli and Schmidt 1982 and X. campestris pv. arrhenatheri Egli and Schmidt 1982. In each phenon, the strains clustered together regardless of the geographical origin of the isolates orthe year of isolation. Polyacrylamide gel electrophoresis of soluble proteins and host range studies, revealed four groups corresponding to the pathovars mentioned above. The four pathovars constitute definite biological entities that can be differentiated by phenotypic, gel electrophoretic and host range features. 相似文献
317.
Wijnhoven TJ van de Westerlo EM Smits NC Lensen JF Rops AL van der Vlag J Berden JH van den Heuvel LP van Kuppevelt TH 《Glycoconjugate journal》2008,25(2):177-185
Heparinoids are used in the clinic as anticoagulants. A specific pentasaccharide in heparinoids activates antithrombin III,
resulting in inactivation of factor Xa and–when additional saccharides are present–inactivation of factor IIa. Structural
and functional analysis of the heterogeneous heparinoids generally requires advanced equipment, is time consuming, and needs
(extensive) sample preparation. In this study, a novel and fast method for the characterization of heparinoids is introduced
based on reactivity with nine unique anti-heparin antibodies. Eight heparinoids were biochemically analyzed by electrophoresis
and their reactivity with domain-specific anti-heparin antibodies was established by ELISA. Each heparinoid displayed a distinct
immunoprofile matching its structural characteristics. The immunoprofile could also be linked to biological characteristics,
such as the anti-Xa/anti-IIa ratio, which was reflected by reactivity of the heparinoids with antibodies HS4C3 (indicative
for 3-O-sulfates) and HS4E4 (indicative for domains allowing anti-factor IIa activity). In addition, the immunoprofile could be indicative
for heparinoid-induced side-effects, such as heparin-induced thrombocytopenia, as illustrated by reactivity with antibody
NS4F5, which defines a very high sulfated domain. In conclusion, immunoprofiling provides a novel, fast, and simple methodology
for the characterization of heparinoids, and allows high-throughput screening of (new) heparinoids for defined structural
and biological characteristics. 相似文献
318.
Collagen XVII (COL17) is a transmembrane glycoprotein that is expressed on the basal surface of basal epidermal keratinocytes. Previous observations have led to the hypothesis that an interaction between COL17 and laminin 332, an extracellular matrix protein, contributes to the attachment of the basal keratinocyte to the basement membrane. In order to isolate and manipulate COL17 interactions with ECM components, we induced COL17 expression in two cells lines, SK-MEL1 and K562, that exhibit little or no capacity to attach to our test substrates, including laminin 332, types I and IV collagen, and fibronectin. Cells expressing high levels of COL17 preferentially adhered to a laminin 332 matrix, and, to a lesser extent, type IV collagen, while showing little or no binding to type I collagen or fibronectin. A quantitative analysis of cell adhesive forces revealed that, compared with COL17-negative cells, COL17-positive cells required over 7-fold greater force to achieve 50% detachment from a laminin 332 substrate. When a cell preparation (either K562 or SK-MEL1) with heterogeneous COL17 expression levels was allowed to attach to a laminin 332 matrix, the COL17-positive and COL17-negative cells differentially sorted to the bound and unbound cell fractions, respectively. COL17-dependent attachment to laminin 332 could be reduced or abolished by siRNA-mediated knock-down of COL17 expression or by adding to the assay wells specific antibodies against COL17 or laminin 332. These findings provide strong support for the hypothesis that cell surface COL17 can interact with laminin 332 and, together, participate in the adherence of a cell to the extracellular matrix. 相似文献
319.
320.
Summary A review of 569 male patients with X-chromosome polysomies (544 Klinefelter and 25 patients with other types of X-chromosome polysomy) is presented here. These patients were detected among the 77000 persons karyotyped in the Leuven cytogenetic center between the years 1966 and 1987. In the group of 544 Klinefelter patients special attention was paid to (1) the age at diagnosis, (2) social and marital status of the postpubertal males, (3) physical and intellectual abilities of the prepubertal boys, (4) delineation of the concurrence of Klinefelter syndrome and fragile X syndrome, and (5) the frequency of malignancies. In 25 patients with other X-chromosome polysomies (2 n48 chromosomes) genotype/phenotype correlation is reviewed, especially for the patients with 48,XXYY and 49,XXXXY karyotypes. Finally, double aneuploidy and rare structural X-chromosome aberrations are briefly discussed. 相似文献