The dynamical transition in proteins and non-Gaussian behavior of low frequency modes in Self Consistent Normal Mode Analysis

Self Consistent Normal Mode Analysis (SCNMA) is applied to heme c type cytochrome f to study temperature dependent protein motion. Classical Normal Mode Analysis (NMA) assumes harmonic behavior and the protein Mean Square Displacement (MSD) has a linear dependence on temperature. This is only consistent with low temperature experimental results. To connect the protein vibrational motions between low temperature and physiological temperature, we have incorporated a fitted set of anharmonic potentials into SCNMA. In addition, Quantum Harmonic Oscillator (QHO) theory has been used to calculate the displacement distribution for individual vibrational modes. We find that the modes involving soft bonds exhibit significant non-Gaussian dynamics at physiological temperature, which suggests it may be the cause of the non-Gaussian behavior of the protein motions probed by Elastic Incoherent Neutron Scattering (EINS). The combined theory displays a dynamical transition caused by the softening of few "torsional" modes in the low frequency regime (< 50cm-1or 0.6ps). These modes change from Gaussian to a classical distribution upon heating. Our theory provides an alternative way to understand the microscopic origin of the protein dynamical transition.Comment: 17 pages, 6 figures, 1 tabl

Collective dynamics of strain-coupled nanomechanical pillar resonators

Semiconductur nano- and micropillars represent a promising platform for hybrid nanodevices. Their ability to couple to a broad variety of nanomechanical, acoustic, charge, spin, excitonic, polaritonic, or electromagnetic excitations is utilized in fields as diverse as force sensing or optoelectronics. In order to fully exploit the potential of these versatile systems e.g. for metamaterials, synchronization or topologically protected devices an intrinsic coupling mechanism between individual pillars needs to be established. This can be accomplished by taking advantage of the strain field induced by the flexural modes of the pillars. Here, we demonstrate strain-induced, strong coupling between two adjacent nanomechanical pillar resonators. Both mode hybridization and the formation of an avoided level crossing in the response of the nanopillar pair are experimentally observed. The described coupling mechanism is readily scalable, enabling hybrid nanomechanical resonator networks for the investigation of a broad range of collective dynamical phenomena

Glass transition in biomolecules and the liquid-liquid critical point of water

Using molecular dynamics simulations, we investigate the relation between the dynamic transitions of biomolecules (lysozyme and DNA) and the dynamic and thermodynamic properties of hydration water. We find that the dynamic transition of the macromolecules, sometimes called a ``protein glass transition'', occurs at the temperature of dynamic crossover in the diffusivity of hydration water, and also coincides with the maxima of the isobaric specific heat $C_P$ and the temperature derivative of the orientational order parameter. We relate these findings to the hypothesis of a liquid-liquid critical point in water. Our simulations are consistent with the possibility that the protein glass transition results from crossing the Widom line, which is defined as the locus of correlation length maxima emanating from the hypothesized second critical point of water.Comment: 10 Pages, 12 figure

Human Adipose Stromal Cells Increase Survival and Mesenteric Perfusion Following Intestinal Ischemia and Reperfusion Injury

OBJECTIVE: Intestinal ischemia can quickly escalate to bowel necrosis and perforation. Transplantation of stem cells presents a novel treatment modality for this problem. We hypothesized that: human adipose-derived stromal cells (hASCs) would increase survival and mesenteric perfusion to a greater degree compared with differentiated cellular controls following ischemic intestinal injury, and improved outcomes with hASC therapy would be associated with preservation of intestinal histological and tight junction architecture, and lower levels of systemic inflammation following intestinal injury. METHODS: hASCs and keratinocytes (differentiated cellular control) were cultured on polystyrene flasks at 37°C in 5% CO2 in air. Adult male C57Bl6J mice were anesthetized and a midline laparotomy performed. The intestines were eviscerated, the small bowel mesenteric root identified, and intestinal ischemia was established by temporarily occluding the superior mesenteric artery for 60 min with a noncrushing vascular clamp. Following ischemia, the clamp was removed, and the intestines were returned to the abdominal cavity. Before abdominal closure, 2 million hASCs or keratinocytes in 250 μL of phosphate-buffered saline (carrier for cells and control solution) were infused into the peritoneum. Animals were allowed to recover for 12 or 24 h (perfusion, histology, cytokine, and immunofluoresence studies), or 7 days (survival studies). Intestinal perfusion was assessed by laser Doppler imaging. Intestinal tissue segments were stained with hematoxylin and eosin, as well as antibodies for the tight junction protein claudin-1. Separate aliquots of intestine, liver, and lung tissue were homogenized and assessed for inflammatory cytokines via multiplex beaded assay. RESULTS: Animals administered hASCs following intestinal ischemia and reperfusion (I/R) injury had significantly greater 7-day survival and better postischemic recovery of mesenteric perfusion compared with vehicle or keratinocyte therapy. hASCs also abated intestinal mucosal destruction, facilitated preservation of intestinal tight junctions, and decreased the systemic inflammatory response to injury. CONCLUSIONS: Human adipose-derived stromal cells improved survival and mesenteric perfusion and attenuated the mucosal damage associated with intestinal I/R injury. hASCs should be considered as a plausible cell source for novel cellular treatment plans following intestinal ischemia

S100A12 in Digestive Diseases and Health: A Scoping Review

Calgranulin proteins are an important class of molecules involved in innate immunity. These members of the S100 class of the EF-hand family of calcium-binding proteins have numerous cellular and antimicrobial functions. One protein in particular, S100A12 (also called EN-RAGE or calgranulin C), is highly abundant in neutrophils during acute inflammation and has been implicated in immune regulation. Structure-function analyses reveal that S100A12 has the capacity to bind calcium, zinc, and copper, processes that contribute to nutritional immunity against invading microbial pathogens. S100A12 is a ligand for the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), and CD36, which promote cellular and immunological pathways to alter inflammation. We conducted a scoping review of the existing literature to define what is known about the association of S100A12 with digestive disease and health. Results suggest that S100A12 is implicated in gastroenteritis, necrotizing enterocolitis, gastritis, gastric cancer, Crohn’s disease, irritable bowel syndrome, inflammatory bowel disease, and digestive tract cancers. Together, these results reveal S100A12 is an important molecule broadly associated with the pathogenesis of digestive diseases

Evidence of coexistence of change of caged dynamics at Tg and the dynamic transition at Td in solvated proteins

Mossbauer spectroscopy and neutron scattering measurements on proteins embedded in solvents including water and aqueous mixtures have emphasized the observation of the distinctive temperature dependence of the atomic mean square displacements, , commonly referred to as the dynamic transition at some temperature Td. At low temperatures, increases slowly, but it assume stronger temperature dependence after crossing Td, which depends on the time/frequency resolution of the spectrometer. Various authors have made connection of the dynamics of solvated proteins including the dynamic transition to that of glass-forming substances. Notwithstanding, no connection is made to the similar change of temperature dependence of obtained by quasielastic neutron scattering when crossing the glass transition temperature Tg, generally observed in inorganic, organic and polymeric glass-formers. Evidences are presented to show that such change of the temperature dependence of from neutron scattering at Tg is present in hydrated or solvated proteins, as well as in the solvents used unsurprisingly since the latter is just another organic glass-formers. The obtained by neutron scattering at not so low temperatures has contributions from the dissipation of molecules while caged by the anharmonic intermolecular potential at times before dissolution of cages by the onset of the Johari-Goldstein beta-relaxation. The universal change of at Tg of glass-formers had been rationalized by sensitivity to change in volume and entropy of the beta-relaxation, which is passed onto the dissipation of the caged molecules and its contribution to . The same rationalization applies to hydrated and solvated proteins for the observed change of at Tg.Comment: 28 pages, 10 figures, 1 Tabl

How resilient is your team? Exploring healthcare providers’ well-being during the COVID-19 pandemic

Background: The global COVID-19 pandemic has placed tremendous physical and mental strain on the US healthcare system. Studies examining the effects of outbreaks have demonstrated both an increased prevalence and long-term development of Post-Traumatic Stress Disorder (PTSD) symptoms in healthcare providers. We sought to assess the impact of the COVID-19 pandemic on the psychological well-being of medical providers, medical trainees, and administrators at a large academic center to identify stressors and moderators to guide future mental health and hospital-system interventions. Methods: A 42-item survey examining specific stressors, grit, and resilience was widely distributed to physicians, residents, fellows, and administrators a large academic institution for departmental distribution. Survey results were analyzed using descriptive statistics, ANOVA, and multivariate linear regressions. A p-value <0.05 was considered statistically significant. Results: A total of 785 participants completed the survey. The majority of respondents rated their stress to be significantly increased during the pandemic. Respondents’ fear of transmitting the virus to their family members was a significant stressor. Higher resilience was associated with lower stress, anxiety, fatigue, and sleep disturbances. Overall, respondents felt supported by their departments and institution and felt contingency plans and personal protective equipment were adequate. Conclusions: Healthcare workers have increased resilience in the face of heightened stress during a pandemic. Higher resilience and grit were protective factors in managing personal and system-level stressors at the peak of the COVID-19 pandemic in our institution. Implementing an intervention designed to enhance healthcare workers’ resilience in response to the COVID-19 pandemic is warranted

Metastable Dynamics of the Hard-Sphere System

The reformulation of the mode-coupling theory (MCT) of the liquid-glass transition which incorporates the element of metastability is applied to the hard-sphere system. It is shown that the glass transition in this system is not a sharp one at the special value of the density or the packing fraction, which is in contrast to the prediction by the conventional MCT. Instead we find that the slowing down of the dynamics occurs over a range of values of the packing fraction. Consequently, the exponents governing the sequence of time relaxations in the intermediate time regime are given as functions of packing fraction with one additional parameter which describes the overall scale of the metastable potential energy for defects in the hard-sphere system. Implications of the present model on the recent experiments on colloidal systems are also discussed.Comment: 21 pages, 5 figures (available upon request), RevTEX3.0, JFI Preprint

Metastable Dynamics above the Glass Transition

The element of metastability is incorporated in the fluctuating nonlinear hydrodynamic description of the mode coupling theory (MCT) of the liquid-glass transition. This is achieved through the introduction of the defect density variable $n$ into the set of slow variables with the mass density $\rho$ and the momentum density ${\bf g}$. As a first approximation, we consider the case where motions associated with $n$ are much slower than those associated with $\rho$. Self-consistently, assuming one is near a critical surface in the MCT sense, we find that the observed slowing down of the dynamics corresponds to a certain limit of a very shallow metastable well and a weak coupling between $\rho$ and $n$. The metastability parameters as well as the exponents describing the observed sequence of time relaxations are given as smooth functions of the temperature without any evidence for a special temperature. We then investigate the case where the defect dynamics is included. We find that the slowing down of the dynamics corresponds to the system arranging itself such that the kinetic coefficient $\gamma_v$ governing the diffusion of the defects approaches from above a small temperature-dependent value $\gamma^c_v$.Comment: 38 pages, 14 figures (6 figs. are included as a uuencoded tar- compressed file. The rest is available upon request.), RevTEX3.0+eps

Dynamics of hydration water in deuterated purple membranes explored by neutron scattering

The function and dynamics of proteins depend on their direct environment, and much evidence has pointed to a strong coupling between water and protein motions. Recently however, neutron scattering measurements on deuterated and natural-abundance purple membrane (PM), hydrated in H2O and D2O, respectively, revealed that membrane and water motions on the ns–ps time scale are not directly coupled below 260 K (Wood et al. in Proc Natl Acad Sci USA 104:18049–18054, 2007). In the initial study, samples with a high level of hydration were measured. Here, we have measured the dynamics of PM and water separately, at a low-hydration level corresponding to the first layer of hydration water only. As in the case of the higher hydration samples previously studied, the dynamics of PM and water display different temperature dependencies, with a transition in the hydration water at 200 K not triggering a transition in the membrane at the same temperature. Furthermore, neutron diffraction experiments were carried out to monitor the lamellar spacing of a flash-cooled deuterated PM stack hydrated in H2O as a function of temperature. At 200 K, a sudden decrease in lamellar spacing indicated the onset of long-range translational water diffusion in the second hydration layer as has already been observed on flash-cooled natural-abundance PM stacks hydrated in D2O (Weik et al. in J Mol Biol 275:632–634, 2005), excluding thus a notable isotope effect. Our results reinforce the notion that membrane-protein dynamics may be less strongly coupled to hydration water motions than the dynamics of soluble proteins