Many proteins that bind specific DNA sequences search the genome by combining three-dimensional diffusion with one-dimensional sliding on nonspecific DNA
. Here we combine resonance energy transfer ...and fluorescence correlation measurements to characterize how individual lac repressor (LacI) molecules explore the DNA surface during the one-dimensional phase of target search. To track the rotation of sliding LacI molecules on the microsecond timescale, we use real-time single-molecule confocal laser tracking combined with fluorescence correlation spectroscopy (SMCT-FCS). The fluctuations in fluorescence signal are accurately described by rotation-coupled sliding, in which LacI traverses about 40 base pairs (bp) per revolution. This distance substantially exceeds the 10.5-bp helical pitch of DNA; this suggests that the sliding protein frequently hops out of the DNA groove, which would result in the frequent bypassing of target sequences. We directly observe such bypassing using single-molecule fluorescence resonance energy transfer (smFRET). A combined analysis of the smFRET and SMCT-FCS data shows that LacI hops one or two grooves (10-20 bp) every 200-700 μs. Our data suggest a trade-off between speed and accuracy during sliding: the weak nature of nonspecific protein-DNA interactions underlies operator bypassing, but also speeds up sliding. We anticipate that SMCT-FCS, which monitors rotational diffusion on the microsecond timescale while tracking individual molecules with millisecond resolution, will be applicable to the real-time investigation of many other biological interactions and will effectively extend the accessible time regime for observing these interactions by two orders of magnitude.
We show the existence of breathing edge modes in the Su-Schrieffer-Heeger model with cubic (Kerr) on-site nonlinearity, bifurcating from stationary edge solitons with propagation constant inside the ...topological gap of the linear model. These edge breathers are exact solutions to the nonlinear equations of motion, with time-periodic intensity oscillations and tails exponentially decaying from the edge. They bifurcate from two localized internal eigenmodes of the stationary edge soliton, having eigenfrequencies inside the topological gap and all higher harmonics above the linear spectrum. Numerical Floquet analysis for solutions obtained from a Newton scheme shows that edge breathers may be linearly stable even in regimes of large-amplitude oscillations, mainly manifested as time-periodic power exchange between the edge site and its next-nearest neighbor.
•Breathing edge solitons are exact solutions to a nonlinear SSH model.•Edge breathers with large-amplitude oscillations may be linearly stable.•In a breather, power oscillates between the edge site and its next-nearest neighbor.
Classical Crabbé type SN2' substitutions of propargylic substrates has served as one of the standard methods for the synthesis of allenes. However, the stereospecific version of this transformation ...often requires either stoichiometric amounts of organocopper reagents or special functional groups on the substrates, and the chirality transfer efficiency is also capricious. Herein, we report a sustainable methodology for the synthesis of diverse 1,3‐di and tri‐substituted allenes by using a simple and cheap cellulose supported heterogeneous nanocopper catalyst (MCC‐Amp‐Cu(I/II)). This approach represents the first example of heterogeneous catalysis for the synthesis of chiral allenes. High yields and excellent enantiospecificity (up to 97 % yield, 99 % ee) were achieved for a wide range of di‐ and tri‐substituted allenes bearing various functional groups. It is worth noting that the applied heterogeneous catalyst could be recycled at least 5 times without any reduced reactivity. To demonstrate the synthetic utility of the developed protocol, we have applied it to the total synthesis of several chiral allenic natural products.
A highly efficient and stereospecific cross‐coupling of propargylic mesylates and Grignard reagents for the synthesis of diverse chiral allenes catalyzed by a recyclable heterogeneous nanocopper catalyst is reported. The synthetic utility of this sustainable methodology was further demonstrated by its application to the asymmetric total synthesis of 5 valuable allenic natural products.
We analyze certain aspects of the classical dynamics of a one-dimensional discrete nonlinear Schrödinger model with inter-site as well as on-site nonlinearities. The equation is derived from a mixed ...Klein–Gordon/Fermi–Pasta–Ulam chain of anharmonic oscillators coupled with anharmonic inter-site potentials, and approximates the slow dynamics of the fundamental harmonic of discrete small-amplitude modulational waves. We give explicit analytical conditions for modulational instability of travelling plane waves, and find in particular that sufficiently strong inter-site nonlinearities may change the nature of the instabilities from long-wavelength to short-wavelength perturbations. Further, we describe thermodynamic properties of the model using the grand-canonical ensemble to account for two conserved quantities: norm and Hamiltonian. The available phase space is divided into two separated parts with qualitatively different properties in thermal equilibrium: one part corresponding to a normal thermalized state with exponentially small probabilities for large-amplitude excitations, and another part typically associated with the formation of high-amplitude localized excitations, interacting with an infinite-temperature phonon bath. A modulationally unstable travelling wave may exhibit a transition from one region to the other as its amplitude is varied, and thus modulational instability is not a sufficient criterion for the creation of persistent localized modes in thermal equilibrium. For pure on-site nonlinearities the created localized excitations are typically pinned to particular lattice sites, while for significant inter-site nonlinearities they become mobile, in agreement with well-known properties of localized excitations in Fermi–Pasta–Ulam-type chains.
A diverse set of more than 40 highly functionalized biaryls was synthesized successfully through the Suzuki–Miyaura cross‐coupling reaction catalyzed by Pd nanoparticles supported in a functionalized ...mesoporous MOF (8 wt % Pd@MIL‐101(Cr)‐NH2). This could be achieved under some of the mildest conditions reported to date and a strong control over the leaching of metallic species could be maintained, despite the presence of diverse functional groups and/or several heteroatoms. Some of the targeted molecules are important intermediates in the synthesis of pharmaceuticals and we clearly exemplify the versatility of this catalytic system, which affords better yields than currently existing commercial procedures. Most importantly, Pd@MIL‐101‐NH2 was packed in a micro‐flow reactor, which represents the first report of metallic nanoparticles supported on MOFs employed in flow chemistry for catalytic applications. A small library of 11 isolated compounds was created in a continuous experiment without replacing the catalyst, demonstrating the potential of the catalyst for large‐scale applications.
MOFember: A robust heterogeneous catalytic system is proposed for the Suzuki–Miyaura cross‐coupling reaction, and consists of palladium nanoparticles immobilized on the metal–organic framework MIL‐101‐NH2. A set of highly functionalized biaryls is synthesized under mild reaction conditions. By packing Pd@MIL‐101‐NH2 in a micro‐flow reactor, the system can be successfully adapted for operation under continuous‐flow conditions.
The organocatalytic asymmetric transfer hydrogenation of N-alkyl aryl imino esters for the direct synthesis of N-alkylated arylglycinate esters is reported. High yields and enantiomeric ratios were ...obtained, and tolerance to a diverse set of functional groups facilitated the preparation of more complex molecules as well as intermediates for active pharmaceuticals. A simple recycling protocol was developed for the Brønsted acid catalyst which could be reused through five cycles with no loss of activity or selectivity.
Selective reduction strategies based on abundant‐metal catalysts are very important in the production of chemicals. In this paper, a method for the electrochemical semihydrogenation and ...semideuteration of alkynes to form Z‐alkenes was developed, using a simple nickel foam as catalyst and H3O+ or D3O+ as sources of hydrogen or deuterium. Good yields and excellent stereoselectivities (Z/E up to 20 : 1) were obtained under very mild reaction conditions. The reaction proceeded with terminal and nonterminal alkynes, and also with alkynes containing easily reducible functional groups, such as carbonyl groups, as well as aryl chlorides, bromides, and even iodides. The nickel‐foam electrocatalyst could be recycled up to 14 times without any change in its catalytic properties.
Foam catalyst: Commercially available nickel foam is an excellent catalyst for the electrochemical semihydrogenation/semideuteration of functionalized alkynes in diluted sulfuric acid under ambient conditions. Here, the applicability of this catalyst for the stereoselective synthesis of Z‐alkenes and Z‐alkenes‐d2 is presented. The nickel foam is recyclable up to 14 times without losing its catalytic properties.
At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel ...have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of cotranslational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins.
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•Cotranslational folding is studied by arrest-peptide-mediated force measurements•Single-molecule measurements show that a pulling force prevents ribosome stalling•A ribosome-tethered zinc-finger domain is visualized by cryo-EM (electron microscopy)•The zinc-finger domain is shown to fold deep inside the ribosome exit tunnel
Nilsson et al. present an integrated approach to the study of cotranslational protein folding, in which the folding transition is mapped by arrest-peptide-mediated force measurements, molecular dynamics simulations, and cryo-EM (electron microscopy). The small zinc-finger domain ADR1a is shown to fold deep inside the ribosome exit tunnel.
Abstract
Background
Internet-based treatment has emerged as a cost-effective option for reaching people who for different reasons are not reached by traditional treatment. Internet-based treatment ...for problematic alcohol use, specifically, has been found to show results on par with other forms of treatment. However, in-depth knowledge of users’ experiences is required to understand what works, and what needs further development. The aim of this study is to investigate the help-seeking motives among users of an internet-based service for problematic alcohol use, as well as the users’ experiences of the support available through the service.
Method
The study consists of a thematic analysis of interviews with 38 former users of the internet-based intervention Alkoholhjälpen.
Results
The analysis shows that health and relationship factors, as well as feelings of shame, were important motives for the users’ decisions to reduce their drinking. Availability and anonymity seem to have been important reasons for choosing internet-based support. The different treatment components, i.e. ICBT program, therapist support and discussion forum, were each perceived as helpful by some users but not by others. Treatment components were described as more useful when users were able to personally identify with the content, and when it helped them reflect on their own alcohol consumption.
Conclusions
There are several aspects that are relevant, beyond the comparison between components, if we want to understand what works and for whom in internet-based treatment. Internet-based treatment services should be generous in terms of options for the users.
Abstract
Background
Stress reflects physical and psychological reactions to imposing demands and is often measured using self-reports. A widely-used instrument is the Perceived Stress Scale (PSS), ...intended to capture more general aspects of stress. A Swedish translation of the PSS is available but has not previously been examined using modern test theory approaches. The aim of the current study is to apply Rasch analysis to further the understanding of the PSS’ measurement properties, and, in turn, improve its utility in different settings.
Methods
Data from 793 university students was used to investigate the dimensionality of different version of the PSS (14, 10, and 4 items) as well as potential response patterns among the participants.
Results
The current study demonstrates that the PSS-14 has two separate factors, divided between negatively worded items (perceived stress) and positively worded items (perceived lack of control), although with only the negative subscale exhibiting good reliability. Response patterns were analyzed using Differential Item Functioning, which did not find an influence of gender on any of the items, but for age regarding the positive subscale (items 6 and 9). The PSS-10 also demonstrated adequate reliability for the negative subscale, but the PSS-4 was not deemed suitable as a unidimensional scale.
Conclusions
Based on the results, none of the versions of the PSS should be used by sum-scoring all of the items. Only the negative items from the PSS-14 or PSS-10 can be used as unidimensional scales to measure general aspects of stress. As for different response patterns, gender may nevertheless be important to consider, as prior research has found differences on several items. Meanwhile, content validity is discussed, questioning the relevance of anger and being upset when measuring more general aspects of stress. Finally, a table to convert the PSS-7 (i.e., negative items) ordinal sum scores to interval level scores is provided.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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