To achieve a detailed understanding of processes in biological systems, cellular features must be quantified in the three‐dimensional (3D) context of cells and organs. We described use of the ...intrinsic root coordinate system (iRoCS) as a reference model for the root apical meristem of plants. iRoCS enables direct and quantitative comparison between the root tips of plant populations at single‐cell resolution. The iRoCS Toolbox automatically fits standardized coordinates to raw 3D image data. It detects nuclei or segments cells, automatically fits the coordinate system, and groups the nuclei/cells into the root's tissue layers. The division status of each nucleus may also be determined. The only manual step required is to mark the quiescent centre. All intermediate outputs may be refined if necessary. The ability to learn the visual appearance of nuclei by example allows the iRoCS Toolbox to be easily adapted to various phenotypes. The iRoCS Toolbox is provided as an open‐source software package, licensed under the GNU General Public License, to make it accessible to a broad community. To demonstrate the power of the technique, we measured subtle changes in cell division patterns caused by modified auxin flux within the Arabidopsis thaliana root apical meristem.
Starting from the β-adrenoceptor agonist isoprenaline and beta-blocker carvedilol, we designed and synthesized three different chemotypes of agonist/antagonist hybrids. Investigations of ...ligand-mediated receptor activation using bioluminescence resonance energy transfer biosensors revealed a predominant effect of the aromatic head group on the intrinsic activity of our ligands, as ligands with a carvedilol head group were devoid of agonistic activity. Ligands composed of a catechol head group and an antagonist-like oxypropylene spacer possess significant intrinsic activity for the activation of Gαs, while they only show weak or even no β-arrestin-2 recruitment at both β1- and β2-AR. Molecular dynamics simulations suggest that the difference in G protein efficacy and β-arrestin recruitment of the hybrid (S)-22, the full agonist epinephrine, and the β2-selective, G protein-biased partial agonist salmeterol depends on specific hydrogen bonding between Ser5.46 and Asn6.55, and the aromatic head group of the ligands.
Lack of sleep has a considerable impact on vigilance: we perform worse, we make more errors, particularly at night, when we should be sleeping. Measures of brain functional connectivity suggest that ...decrease in vigilance during sleep loss is associated with an impaired cross-talk within the fronto-parietal cortex. However, fronto-parietal effective connectivity, which is more closely related to the causal cross-talk between brain regions, remains unexplored during prolonged wakefulness. In addition, no study has simultaneously investigated brain effective connectivity and wake-related changes in vigilance, preventing the concurrent incorporation of the two aspects. Here, we used electroencephalography (EEG) to record responses evoked by Transcranial Magnetic Stimulation (TMS) applied over the frontal lobe in 23 healthy young men (18–30 yr.), while they simultaneously performed a vigilance task, during 8 sessions spread over 29 h of sustained wakefulness. We assessed Response Scattering (ReSc), an estimate of effective connectivity, as the propagation of TMS-evoked EEG responses over the fronto-parietal cortex. Results disclose a significant change in fronto-parietal ReSc with time spent awake. When focusing on the night-time period, when one should be sleeping, participants with lower fronto-parietal ReSc performed worse on the vigilance task. Conversely, no association was detected during the well-rested, daytime period. Night-time fronto-parietal ReSc also correlated with objective EEG measures of sleepiness and alertness. These changes were not accompanied by variations in fronto-parietal response complexity. These results suggest that decreased brain response propagation within the fronto-parietal cortex is associated to increased vigilance failure during night-time prolonged wakefulness. This study reveals a novel facet of the detrimental effect on brain function of extended night-time waking hours, which is increasingly common in our societies.
•Fronto-parietal Response Scattering (ReSc) varies during prolonged wakefulness.•Lower fronto-parietal ReSc is associated with lower vigilance performance at night.•Lower fronto-parietal ReSc is associated with higher sleepiness measures at night.•Fronto-parietal response complexity does not change with time spent awake.•These findings reveal a novel facet of night-time wakefulness detrimental effects.
Most birds incubate their eggs to allow embryo development. This behaviour limits the ability of adults to perform other activities. Hence, incubating adults trade off incubation and nest protection ...with foraging to meet their own needs. Parents can either cooperate to sustain this tradeoff or incubate alone. The main cause of reproductive failure at this reproductive stage is predation and adults reduce this risk by keeping the nest location secret. Arctic sandpipers are interesting biological models to investigate parental care evolution as they may use several parental care strategies. The three main incubation strategies include both parents sharing incubation duties (‘biparental’), one parent incubating alone (‘uniparental’), or a flexible strategy with both uniparental and biparental incubation within a population (‘mixed’). By monitoring the incubation behaviour in 714 nests of seven sandpiper species across 12 arctic sites, we studied the relationship between incubation strategy and nest predation. First, we described how the frequency of incubation recesses (NR), their mean duration (MDR), and the daily total duration of recesses (TDR) vary among strategies. Then, we examined how the relationship between the daily predation rate and these components of incubation behaviour varies across strategies using two complementary survival analysis. For uniparental and biparental species, the daily predation rate increased with the daily total duration of recesses and with the mean duration of recesses. In contrast, daily predation rate increased with the daily number of recesses for biparental species only. These patterns may be attributed to two independent mechanisms: cryptic incubating adults are more difficult to locate than unattended nests and adults departing the nest or feeding close to the nest can draw predators’ attention. Our results demonstrate that incubation behaviour as mediated by incubation strategy has important consequences for sandpipers’ reproductive success.
Various bio-applications of mesoporous materials ( e.g. , the immobilization of enzymes or the delivery of biomolecules such as siRNA) require large pores for the successful adsorption of the rather ...large molecules of interest and protecting the fragile cargo from external forces such as degradation. We describe the facile synthesis of functionalized mesoporous silica nanoparticles with large pores (LP-MSNs) providing high loading capacity for the immobilization of two differently-sized enzymes. The synthesis procedure yields homogeneous core–shell particles of about 100 nm in size with large mesopores (about 7 nm in diameter) and an azide-functionality inside the pores. The LP-MSNs were synthesized employing a co-condensation approach with the rather large micellar template cetyltrimethylammonium p -toluenesulfonate (CTATos). Due to the azide functionality, the LP-MSNs are suitable for bio-orthogonal click chemistry reactions within the porous network. Two different acetylene-functionalized enzymes (sp-carbonic anhydrase (CA) and sp-horseradish peroxidase (HRP)) were immobilized in the pores of the obtained LP-MSNs by a copper-catalyzed 1,3-dipolar cycloaddition reaction. The covalent attachment of the enzymes within the mesopores allowed us to investigate the catalytic performance of the enzyme–silica systems. The enzymes are stable after bioconjugation with the silica support and show high catalytic activity over several cycles for the colorimetric reaction of guaiacol (2-methoxyphenol) in case of LP-MSN–HRP and the hydrolysis of 4-nitrophenyl acetate (NPA) by LP-MSN–CA.
This review summarizes the current state of the art of statistical and (survey) methodological research on measurement (non)invariance, which is considered a core challenge for the comparative social ...sciences. After outlining the historical roots, conceptual details, and standard procedures for measurement invariance testing, the paper focuses in particular on the statistical developments that have been achieved in the last 10 years. These include Bayesian approximate measurement invariance, the alignment method, measurement invariance testing within the multilevel modeling framework, mixture multigroup factor analysis, the measurement invariance explorer, and the response shift-true change decomposition approach. Furthermore, the contribution of survey methodological research to the construction of invariant measurement instruments is explicitly addressed and highlighted, including the issues of design decisions, pretesting, scale adoption, and translation. The paper ends with an outlook on future research perspectives.
Cortical excitability depends on sleep-wake regulation, is central to cognition, and has been implicated in age-related cognitive decline. The dynamics of cortical excitability during prolonged ...wakefulness in aging are unknown, however. Here, we repeatedly probed cortical excitability of the frontal cortex using transcranial magnetic stimulation and electroencephalography in 13 young and 12 older healthy participants during sleep deprivation. Although overall cortical excitability did not differ between age groups, the magnitude of cortical excitability variations during prolonged wakefulness was dampened in older individuals. This age-related dampening was associated with mitigated neurobehavioral consequences of sleep loss on executive functions. Furthermore, higher cortical excitability was potentially associated with better and lower executive performance, respectively, in older and younger adults. The dampening of cortical excitability dynamics found in older participants likely arises from a reduced impact of sleep homeostasis and circadian processes. It may reflect reduced brain adaptability underlying reduced cognitive flexibility in aging. Future research should confirm preliminary associations between cortical excitability and behavior and address whether maintaining cortical excitability dynamics can counteract age-related cognitive decline.
•Overall cortical excitability levels are similar in younger and older individuals.•Circadian dynamics in cortical excitability is dampened in older versus young adults.•Cortical excitability dynamics is associated with variation in executive performance.•Higher cortical excitability is associated with better performance in older adults.•In contrast, high cortical excitability correlates with low performance in the young.
Highlights • The clinical use is of benzodiazepines (BZDs) is limited due to adverse effects • Partial or subtype selective agonists at the BZD receptor may have advantages • One of these compounds, ...abecarnil, exerts anxiolytic activity in patients • Here, we compared abecarnil and flumazenil in patients with photosensitive epilepsy • Abecarnil was antiepileptic and significantly differed from both placebo and flumazenil
The study aimed to elucidate areas involved in recognizing tool-associated actions, and to characterize the relationship between recognition and active performance of tool use.We performed ...voxel-based lesion-symptom mapping in a prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male, age mean ± standard deviation, 65 ± 13 years; examination 4.4 ± 2 days post-stroke). In a video-based test, patients distinguished correct tool-related actions from actions with spatio-temporal (incorrect grip, kinematics, or tool orientation) or conceptual errors (incorrect tool-recipient matching, e.g., spreading jam on toast with a paintbrush). Moreover, spatio-temporal and conceptual errors were determined during actual tool use.Deficient spatio-temporal error discrimination followed lesions within a dorsal network in which the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were specifically relevant for assessing functional hand postures and kinematics, respectively. Conversely, impaired recognition of conceptual errors resulted from damage to ventral stream regions including anterior temporal lobe. Furthermore, LTC and IPL lesions impacted differently on action recognition and active tool use, respectively.In summary, recognition of tool-associated actions relies on a componential network. Our study particularly highlights the dissociable roles of LTC and IPL for the recognition of action kinematics and functional hand postures, respectively.
Reports of fading vole and lemming population cycles and persisting low populations in some parts of the Arctic have raised concerns about the spread of these fundamental changes to tundra food web ...dynamics. By compiling 24 unique time series of lemming population fluctuations across the circumpolar region, we show that virtually all populations displayed alternating periods of cyclic/non-cyclic fluctuations over the past four decades. Cyclic patterns were detected 55% of the time (
= 649 years pooled across sites) with a median periodicity of 3.7 years, and non-cyclic periods were not more frequent in recent years. Overall, there was an indication for a negative effect of warm spells occurring during the snow onset period of the preceding year on lemming abundance. However, winter duration or early winter climatic conditions did not differ on average between cyclic and non-cyclic periods. Analysis of the time series shows that there is presently no Arctic-wide collapse of lemming cycles, even though cycles have been sporadic at most sites during the last decades. Although non-stationary dynamics appears a common feature of lemming populations also in the past, continued warming in early winter may decrease the frequency of periodic irruptions with negative consequences for tundra ecosystems.
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