Non-Markovian Configurational Diffusion and Reaction Coordinates for Protein Folding

The non-Markovian nature of polymer motions is accounted for in folding kinetics, using frequency-dependent friction. Folding, like many other problems in the physics of disordered systems, involves barrier crossing on a correlated energy landscape. A variational transition state theory (VTST) that reduces to the usual Bryngelson-Wolynes Kramers approach when the non-Markovian aspects are neglected is used to obtain the rate, without making any assumptions regarding the size of the barrier, or the memory time of the friction. The transformation to collective variables dependent on the dynamics of the system allows the theory to address the controversial issue of what are ``good'' reaction coordinates for folding.Comment: 9 pages RevTeX, 3 eps-figures included, submitted to PR

Controls on short-term variations in Greenland glacier dynamics

Short-term ice-dynamical processes at Greenland’s Jakobshavn and Kangerdlugssuaq glaciers were studied using a 3 day time series of synthetic aperture radar data acquired during the 2011 European Remote-sensing Satellite-2 (ERS-2) 3 day repeat campaign together with modelled meteorological parameters. The time series spans the period March–July 2011 and captures the first 30% of the summer melting season. In both study areas, we observe velocity fluctuations at the lower 10 km of the glacier. At Jakobshavn Isbræ, where our dataset covers the first part of the seasonal calving-front retreat, we identify ten calving episodes, with a mean calving-front area loss of 1.29 0.4km2. Significant glacier speed-up was observed in the near-terminus area following all calving episodes. We identify changes in calving-front geometry as the dominant control on velocity fluctuations on both glaciers, apart from

Syntheses, characterization, density functional theory calculations, and activity of tridentate SNS zinc pincer complexes

A series of tridentate SNS ligand precursors were metallated with ZnCl2 to give new tridentate SNS pincer zinc complexes. The zinc complexes serve as models for the zinc active site in liver alcohol dehydrogenase (LADH) and were characterized with single crystal X-ray diffraction, 1H, 13C, and HSQC NMR spectroscopies and electrospray mass spectrometry. The bond lengths and bond angles of the zinc complexes correlate well to those in horse LADH. The zinc complexes feature SNS donor atoms and pseudotetrahedral geometry about the zinc center, as is seen for liver alcohol dehydrogenase. The SNS ligand precursors were characterized with 1H, 13C, and HSQC NMR spectroscopies and cyclic voltammetry, and were found to be redox active. Gaussian calculations were performed and agree quite well with the experimentally observed oxidation potential for the pincer ligand. The zinc complexes were screened for the reduction of electron poor aldehydes in the presence of a hydrogen donor, 1-benzyl-1,4-dihydronicotinamide (BNAH). The zinc complexes enhance the reduction of electron poor aldehydes. Density functional theory calculations were performed to better understand why the geometry about the zinc center is pseudo-tetrahedral rather than pseudo-square planar, which is seen for most pincer complexes. For the SNS tridentate pincer complexes, the data indicate that the pseudo-tetrahedral geometry was 43.8 kcal/mol more stable than the pseudo-square planar geometry. Density functional theory calculations were also performed on zinc complexes with monodentate ligands and the data indicate that the pseudo-tetrahedral geometry was 30.6 kcal/mol more stable than pseudo-square planar geometry. Overall, the relative stabilities of the pseudo-tetrahedral and pseudo-square planar systems are the same for this coordination environment whether the ligand set is a single tridentate SNS system or is broken into three separate units. The preference of a d10 Zn center to attain a tetrahedral local environment trumps any stabilization gained by removal of constraints within the ligand set

Computer Simulations of Supercooled Liquids and Glasses

After a brief introduction to the dynamics of supercooled liquids, we discuss some of the advantages and drawbacks of computer simulations of such systems. Subsequently we present the results of computer simulations in which the dynamics of a fragile glass former, a binary Lennard-Jones system, is compared to the one of a strong glass former, SiO_2. This comparison gives evidence that the reason for the different temperature dependence of these two types of glass formers lies in the transport mechanism for the particles in the vicinity of T_c, the critical temperature of mode-coupling theory. Whereas the one of the fragile glass former is described very well by the ideal version of mode-coupling theory, the one for the strong glass former is dominated by activated processes. In the last part of the article we review some simulations of glass formers in which the dynamics below the glass transition temperature was investigated. We show that such simulations might help to establish a connection between systems with self generated disorder (e.g. structural glasses) and quenched disorder (e.g. spin glasses).Comment: 37 pages of Latex, 11 figures, to appear as a Topical Review article in J. Phys.: Condens. Matte

Beaked whales respond to simulated and actual navy sonar

This article is distributed under the terms of the Creative Commons Public Domain declaration. The definitive version was published in PLoS One 6 (2011): e17009, doi:10.1371/journal.pone.0017009.Beaked whales have mass stranded during some naval sonar exercises, but the cause is unknown. They are difficult to sight but can reliably be detected by listening for echolocation clicks produced during deep foraging dives. Listening for these clicks, we documented Blainville's beaked whales, Mesoplodon densirostris, in a naval underwater range where sonars are in regular use near Andros Island, Bahamas. An array of bottom-mounted hydrophones can detect beaked whales when they click anywhere within the range. We used two complementary methods to investigate behavioral responses of beaked whales to sonar: an opportunistic approach that monitored whale responses to multi-day naval exercises involving tactical mid-frequency sonars, and an experimental approach using playbacks of simulated sonar and control sounds to whales tagged with a device that records sound, movement, and orientation. Here we show that in both exposure conditions beaked whales stopped echolocating during deep foraging dives and moved away. During actual sonar exercises, beaked whales were primarily detected near the periphery of the range, on average 16 km away from the sonar transmissions. Once the exercise stopped, beaked whales gradually filled in the center of the range over 2–3 days. A satellite tagged whale moved outside the range during an exercise, returning over 2–3 days post-exercise. The experimental approach used tags to measure acoustic exposure and behavioral reactions of beaked whales to one controlled exposure each of simulated military sonar, killer whale calls, and band-limited noise. The beaked whales reacted to these three sound playbacks at sound pressure levels below 142 dB re 1 µPa by stopping echolocation followed by unusually long and slow ascents from their foraging dives. The combined results indicate similar disruption of foraging behavior and avoidance by beaked whales in the two different contexts, at exposures well below those used by regulators to define disturbance.The research reported here was financially supported by the United States (U.S.) Office of Naval Research (www.onr.navy.mil) Grants N00014-07-10988, N00014-07-11023, N00014-08-10990; the U.S. Strategic Environmental Research and Development Program (www.serdp.org) Grant SI-1539, the Environmental Readiness Division of the U.S. Navy (http://www.navy.mil/local/n45/), the U.S. Chief of Naval Operations Submarine Warfare Division (Undersea Surveillance), the U.S. National Oceanic and Atmospheric Administration (National Marine Fisheries Service, Office of Science and Technology) (http://www.st.nmfs.noaa.gov/), U.S. National Oceanic and Atmospheric Administration Ocean Acoustics Program (http://www.nmfs.noaa.gov/pr/acoustics/), and the Joint Industry Program on Sound and Marine Life of the International Association of Oil and Gas Producers (www.soundandmarinelife.org)

Mechanical Strain Stabilizes Reconstituted Collagen Fibrils against Enzymatic Degradation by Mammalian Collagenase Matrix Metalloproteinase 8 (MMP-8)

Collagen, a triple-helical, self-organizing protein, is the predominant structural protein in mammals. It is found in bone, ligament, tendon, cartilage, intervertebral disc, skin, blood vessel, and cornea. We have recently postulated that fibrillar collagens (and their complementary enzymes) comprise the basis of a smart structural system which appears to support the retention of molecules in fibrils which are under tensile mechanical strain. The theory suggests that the mechanisms which drive the preferential accumulation of collagen in loaded tissue operate at the molecular level and are not solely cell-driven. The concept reduces control of matrix morphology to an interaction between molecules and the most relevant, physical, and persistent signal: mechanical strain.The investigation was carried out in an environmentally-controlled microbioreactor in which reconstituted type I collagen micronetworks were gently strained between micropipettes. The strained micronetworks were exposed to active matrix metalloproteinase 8 (MMP-8) and relative degradation rates for loaded and unloaded fibrils were tracked simultaneously using label-free differential interference contrast (DIC) imaging. It was found that applied tensile mechanical strain significantly increased degradation time of loaded fibrils compared to unloaded, paired controls. In many cases, strained fibrils were detectable long after unstrained fibrils were degraded.In this investigation we demonstrate for the first time that applied mechanical strain preferentially preserves collagen fibrils in the presence of a physiologically-important mammalian enzyme: MMP-8. These results have the potential to contribute to our understanding of many collagen matrix phenomena including development, adaptation, remodeling and disease. Additionally, tissue engineering could benefit from the ability to sculpt desired structures from physiologically compatible and mutable collagen

Using death to one's advantage: HIV modulation of apoptosis

Infection by human immunodeficiency virus (HIV) is associated with an early immune dysfunction and progressive destruction of CD4+ T lymphocytes. This progressive disappearance of T cells leads to a lack of immune control of HIV replication and to the development of immune deficiency resulting in the increased occurrence of opportunistic infections associated with acquired immune deficiency syndrome (AIDS). The HIV-induced, premature destruction of lymphocytes is associated with the continuous production of HIV viral proteins that modulate apoptotic pathways. The viral proteins, such as Tat, Env, and Nef, are associated with chronic immune activation and the continuous induction of apoptotic factors. Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+ T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and as a result, to lead to the destruction of healthy, non-infected T cells. Tat and Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by increasing anti-apoptotic proteins and down- regulating cell surface receptors recognized by immune system cells. This review will discuss the validity of the apoptosis hypothesis in HIV disease and the potential mechanism(s) that HIV proteins perform in the progressive T cell depletion observed in AIDS pathogenesis. Originally published Leukemia, Vol. 15, No. 3, Mar 200

Parent Mindfulness, Parenting, and Child Psychopathology in China

Objectives Considering the Western-Eastern cultural differences in parenting practices, as well as the relative paucity of research on the use of mindfulness-based programs by Chinese parents, we replicated a recently proposed Western model of mindfulness. The purpose of this study was to test the direct and indirect relations between parents’ dispositional mindfulness, mindful parenting, parenting practices, and child internalizing and externalizing behaviors. Method A total of 2237 Chinses parents (M = 38.46, SD = 4.43) of 6- to 12-year-old children participated in the current study. Results The results showed that parents’ dispositional mindfulness was indirectly associated with child internalizing and externalizing behaviors through mindful parenting and positive parenting practices, whereas this pathway was not significant through negative parenting practices. In addition, mothers and fathers demonstrated almost equal effects on direct and indirect pathways except that mothers showed stronger effects on the relationships between dispositional mindfulness and mindful parenting, as well as on the link between negative parenting practices and child externalizing behaviors. Conclusions These findings contribute to a better understanding of the mechanisms underlying how mindfulness and parenting associated with child internalizing and externalizing behaviors, and have important implications for research on interventions aimed at promoting children’s psychological well-being. Mindfulness refers to “the awareness that emerges through paying attention, on purpose, in the present moment, and nonjudgmentally to the unfolding of experience moment by moment” (Kabat-Zinn 2003, p. 145). Research has highlighted a number of benefits associated with increased mindfulness, including reduced depression and anxiety symptoms (Keng et al. 2011; Moreira and Canavarro 2018). In addition, comparable effectiveness has been observed between mindfulness-based programs and other evidence-based treatments (Goldberg et al. 2017) with promising results demonstrated across various settings and age groups. In recent years, increased attention has focused on the study of dispositional (e.g., Wang et al. 2017) or trait mindfulness (Brown et al. 2007) and mindful parenting (e.g., Parent et al. 2016). Dispositional mindfulness is an individual’s tendency or inner capacity to pay nonjudgmental attention to experiences and events occurring in the present moment (Brown and Ryan 2003). Research suggests that higher levels of dispositional mindfulness are associated with favorable outcomes, such as better emotion regulation (Baer et al. 2004; Pepping et al. 2013) and more effective coping strategies (Brown and Ryan 2003). In addition, a recent study reported that parents with higher levels of dispositional mindfulness are more likely to engage in mindful parenting with children (Parent et al. 2016). Mindful parenting consists of nonjudgmental and present-centered awareness during parent-child interactions (Bögels and Restifo 2014; Kabat-Zinn and Kabat-Zinn 1997). It involves listening to the child with full attention, maintaining an awareness of the child’s emotional experience, regulating one’s own emotions during the parenting process, maintaining a non-judgmental acceptance of parental functioning, and being compassionate both towards the child, as well as oneself (Duncan et al. 2009). Research has suggested that higher levels of dispositional mindfulness can increase the likelihood of parents’ engagement in mindful parenting behaviors (de Bruin et al. 2014; Parent et al. 2016). This may be due to mindful parents being better able to distinguish cognitive, affective, and behavioral experiences compared to their less mindful counterparts (Bishop et al. 2004), thus decreasing the likelihood of engaging in maladaptive interactions with children. Moreover, mindful parenting has been associated with more positive parenting practices (Bazzano et al. 2015; Bögels et al. 2013; Haydicky et al. 2015). During parent-child interactions, a mindful parent is more likely to be consistent with his/her values and goals (Duncan et al. 2009), non-judgmental, demonstrates present-moment awareness, and sensitive to the children’s needs. Thus, mindful parenting has been shown to be associated with lower levels of dysfunctional parenting styles (de Bruin et al. 2014). Parent et al. (2016) examined parents of children at varying developmental stages and reported similar results, suggesting that mindful parenting is directly related to higher levels of positive parenting practices (e.g., warmth and reinforcement) and lower levels of negative parenting practices (e.g., coercion or hostility). There is a substantial amount of literature establishing the relationship between parenting practices and child psychopathology in Western cultural contexts (Harold et al. 2012; Kawabata et al. 2011; Lindblom et al. 2017), with similar results in Eastern contexts (Baharudin et al. 2011; Lin et al. 2016). For instance, Chinese parents’ support for autonomy was associated with fewer depressive symptoms as reported by their middle-school-aged children (Yan et al. 2017). In addition, harsh parenting from fathers and mothers negatively contributed to children’s emotion regulation and peer aggression (Wang et al. 2017). However, little research has been conducted to delineate the processes through which dispositional mindfulness, mindful parenting, and parenting practices affect child psychopathology outside of Western cultures. This is an important area of exploration given the significant implications of early psychopathology for children’s long-term mental health, academic performance, and overall quality of life (e.g., Barkley et al. 2006; Yap and Jorm 2015). It has been suggested that over time all cultures derive unique concepts and values on effective parenting, and, therefore, the support for mindful parenting is likely to vary depending on cultural context (Smith and Dishion 2013). In addition, similar parenting practices may have varying effects on children of different cultures (Leung et al. 1998). For example, many researchers have argued that culture shapes how children’s emotional competence is defined and thus influences parenting behaviors, as well as child mental health outcomes (e.g., Friedlmeier et al. 2011). As such, it is of great importance to explore mindful parenting beyond Western cultures and to elucidate the process through which mindful parenting is associated with child outcomes in comparatively understudied cultural contexts (e.g., Chinese culture). Hofstede (1980) initially proposed the individualism-collectivism dimension to help describe the primary distinction between cultures, and this principle can be used to better understand parenting and the role of parenting in child adjustment beyond Western culture. In this context, Hofstede (1980) proposed that individualistic societies (e.g., the USA) value independence and tend to focus on the self, thus encouraging parenting practices (e.g., warmth) that foster children’s self-reliance. In contrast, collectivistic societies (e.g., China and India) emphasize interdependence and group harmony, thus encouraging parenting practices (e.g., training) that promote children’s obedience to group rules. Parents from individualistic and collectivistic cultures might adopt different parenting behaviors given the various and possibly divergent cultural norms and values related to these behaviors and the associated child outcomes. Little research has extended beyond the Western model of mindful parenting to explicitly discuss cultural issues pertaining to mindful parenting and related child outcomes; however, an emerging line of research has been conducted with Chinese parents that can help provide a foundation for this work. For example, Siu et al. (2016) found parental mindfulness had a negative indirect association on children’s emotional and behavioral problems through a series of positive factors related to the parent-child relationship. These emerging findings have been consistent across Western societies and suggest parents who mindfully interact with their children have higher quality relationships with their children than those who have less mindful interactions (Duncan et al. 2009). This, in turn, is related to greater psychological adjustment and fewer problem behaviors in children (Geurtzen et al. 2015; Parent et al. 2010; Williams and Wahler 2010). These findings across cultures might be explained by the recent proposition that while Chinese parenting is still largely influenced by traditional cultural values, a Western and child-centered approach has gradually been incorporated into contemporary Chinese parenting, particularly among more highly educated parents (Xu et al. 2014). Despite this preliminary evidence, studies have not delineated the processes through which parental mindfulness and parenting practices are associated with child outcomes using a large Chinese sample. Elucidating these processes with a Chinese sample will enable more nuanced research on the development and implementation of mindfulness-based program with Chinese families. Parent gender might also shape the processes by which parenting influences child psychopathology (Friedlmeier et al. 2011; Klimes-Dougan et al. 2010). For example, when compared to Western parents (both mothers and fathers) and Chinese mothers, Chinese fathers’ parenting practices (e.g., harsh parenting and physical control) are viewed as strong behavioral modeling for children, especially sons (Chen et al. 2000). Thus, it is important to consider the cultural expectations of mothers and fathers when examining the influence of parenting on their children. Furthermore, gender differences have only been evaluated in the Western context of mindful parenting (Gouveia et al. 2016; Medeiros et al. 2016). In these studies, mothers generally have shown higher level of mindful parenting compared to fathers (e.g., Gouveia et al. 2016), whereas fathers have displayed more supportive emotion socialization with children than mothers when they both participate in mindfulness programs (Coatsworth et al. 2015). The current study aimed to test the Parent et al. (2016) model of mindful parenting practices and child psychopathology with a large group of parents from Mainland China. The hypotheses of the current study take into consideration the potential impact of cultural context and parent gender (see Fig. 1). First, we hypothesized that parent dispositional mindfulness would be positively associated with mindful parenting and that mindful parenting would be associated with greater positive parenting practices and fewer negative parenting practices. Second, we hypothesized that positive parenting practices would be negatively associated with children’s internalizing and externalizing behavior, whereas negative parenting practices would be positively associated with children’s internalizing and externalizing behavior. Third, regarding the overall theoretical model, we hypothesized that parent dispositional mindfulness would have a negative indirect association with children’s internalizing and externalizing behavior through an increase in mindful parenting, resulting in positive parenting practices, as well as decreased negative parenting practices