Miracle-dz/UniFAR-FTUs huggingface dataset:
Myosin lever arm directs collective motion on cellular actin network

Significance Myosins function as groups of motors anchored to a cellular scaffold that interacts with neighboring actin filaments patterned in complex three-dimensional networks. Although much is known about the function of individual myosin molecules, the contribution of intermotor interactions to collective movement is poorly understood. We used a precisely engineered biomimetic system to investigate how the mechanics of a structural element in the individual myosin influences the collective motion of groups of motors. Stochastic simulations suggest that the interplay between intramolecular strain on the motor lever arm and intermotor tension dictates trajectory shapes in groups of identical and antagonistic motors. Our study provides a general approach to dissecting emergence in cellular processes with applications for the efficient synthetic design of molecular transport systems. The molecular motor myosin teams up to drive muscle contraction, membrane traffic, and cell division in biological cells. Myosin function in cells emerges from the interaction of multiple motors tethered to a scaffold, with surrounding actin filaments organized into 3D networks. Despite the importance of myosin function, the influence of intermotor interactions on collective motion remains poorly understood. In this study, we used precisely engineered myosin assemblies to examine emergence in collective myosin movement. We report that tethering multiple myosin VI motors, but not myosin V motors, modifies their movement trajectories on keratocyte actin networks. Single myosin V and VI dimers display similar skewed trajectories, albeit in opposite directions, when traversing the keratocyte actin network. In contrast, tethering myosin VI motors, but not myosin V motors, progressively straightens the trajectories with increasing myosin number. Trajectory shape of multimotor scaffolds positively correlates with the stiffness of the myosin lever arm. Swapping the flexible myosin VI lever arm for the relatively rigid myosin V lever increases trajectory skewness, and vice versa. A simplified model of coupled motor movement demonstrates that the differences in flexural rigidity of the two myosin lever arms is sufficient to account for the differences in observed behavior of groups of myosin V and VI motors. In accordance with this model trajectory, shapes for scaffolds containing both myosin V and VI are dominated by the myosin with a stiffer lever arm. Our findings suggest that structural features unique to each myosin type may confer selective advantages in cellular functions.
Neuroimmune mechanisms in Krabbe's disease

Neuroinflammation, activation of innate immune components of the nervous system followed by an adaptive immune response, is observed in most leukodystrophies and coincides with white matter pathology, disease progression, and morbidity. Despite this, there is a major gap in our knowledge of the contribution of the immune system to disease phenotype. Inflammation in Krabbe's disease has been considered a secondary effect, resulting from cell‐autonomous oligodendroglial cell death or myelin loss resulting from psychosine accumulation. However, recent studies have shown immune activation preceding clinical symptoms and white matter pathology. Moreover, the therapeutic effect underlying hematopoietic stem cell transplantation, the only treatment for Krabbe's disease, has been demonstrated to occur via immunomodulation. This Review highlights recent advances in elaboration of the immune cascade involved in Krabbe's disease. Mechanistic insight into the inflammatory pathways participating in myelin and axon loss or preservation may lead to novel therapeutic approaches for this disorder. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Some Observations on the Cured Shape of Thin Unsymmetric Laminates

This paper discusses the fact that the cured shape of thin unsymmetric laminates do not conform to the predictions of classical lamination theory. Rather than being saddle shaped, as predicted by the classical theory, the paper shows that thin unsymmetric laminates cure into a shape of a right circular cylinder. This anomalous behavior has been observed by many but the paper serves to quantify the effect and to inspire investigators to begin thinking about using the phenomenon to advantage. The paper indicates that the anomalous behavior is repeatable and that thicker laminates con form to the predictions of the classical theory. Laminates of the [0/902 /θ ] T, [02 /θ2 ] T and [04 /θ4 ] T families are investigated for this be havior and it is shown the principal curvature directions of the cylindrical shapes are predictable.
Neutrophil histamine contributes to inflammation in mycoplasma pneumonia

Mycoplasmas cause chronic inflammation and are implicated in asthma. Mast cells defend against mycoplasma infection and worsen allergic inflammation, which is mediated partly by histamine. To address the hypothesis that mycoplasma provokes histamine release, we exposed mice to Mycoplasma pulmonis, comparing responses in wild-type and mast cell–deficient KitW-sh/KitW-sh (W-sh) mice. Low histamine levels in uninfected W-sh mice confirmed the conventional wisdom that mast cells are principal sources of airway and serum histamine. Although mycoplasma did not release histamine acutely in wild-type airways, levels rose up to 50-fold above baseline 1 week after infection in mice heavily burdened with neutrophils. Surprisingly, histamine levels also rose profoundly in infected W-sh lungs, increasing in parallel with neutrophils and declining with neutrophil depletion. Furthermore, neutrophils from infected airway were highly enriched in histamine compared with naive neutrophils. In vitro, mycoplasma directly stimulated histamine production by naive neutrophils and strongly upregulated mRNA encoding histidine decarboxylase, the rate-limiting enzyme in histamine synthesis. In vivo, treatment with antihistamines pyrilamine or cimetidine decreased lung weight and severity of pneumonia and tracheobronchitis in infected W-sh mice. These findings suggest that neutrophils, provoked by mycoplasma, greatly expand their capacity to synthesize histamine, thereby contributing to lung and airway inflammation.
A Feasible Method to Enhance and Maintain the Health of Elderly Living in Long-Term Care Facilities Through Long-Term, Simplified Tai Chi Exercises

&NA; Practicing Tai Chi offers the potential to enhance the physical and mental health of older adults. Identifying a feasible way to encourage regular Tai Chi practice is essential if Tai Chi is to be promoted as a long-term, daily activity for elderly care facility residents. The purpose of this study was to test the effectiveness and feasibility of using an audiovisual, simplified Tai Chi exercise module to enhance and maintain the health of long-term care facility residents. A quasi-experimental, one-group, time-series design was used. Data were collected six times (twice before the intervention; four times after intervention started) at three-month intervals. Fifty-one elderly male subjects were recruited by convenience sampling. A 50-minute Simplified Tai-Chi Exercise Program (STEP) was implemented in two small groups three times a week for 12 months. During the first six-month period, participants received guidance from an actual instructor. During the second six-month period, guidance was delivered via a video tape and displayed on a television screen. Results indicated that participants' physical health (cardio-respiratory function, lower body flexibility, and hand-gripping strength) and mental health (quality of sleep) had both improved significantly six months after intervention started, with improvements maintained throughout the end of the 12-month study (all p values < .05). Instructor-led STEP training followed by practice using appropriate audiovisual aids represents a feasible and effective method to implement a long-term activity program in long-term elderly care facilities.
Immunogold localization of the NodC and NodA proteins of Rhizobium meliloti

Monospecific, polyclonal antibodies to the nodC and nodA gene products of Rhizobium meliloti were used in combination with immunogold labeling and transmission electron microscopy to localize the NodC and NodA proteins in cultures of R. meliloti. Both NodC and NodA were detected in the cytoplasm and cell envelope in thin sections of free-living rhizobia treated with luteolin, a known inducer of nod gene expression; however, only NodC was detected on cell surfaces when immunolabeling was performed with intact induced cells. In view of biochemical data characterizing NodC as an outer membrane protein with a large extracellular domain, the pattern of immunolabeling on thin sections suggests that NodC is produced on free cytoplasmic ribosomes prior to assembly in the membrane. The pattern of NodA labeling on thin sections is consistent with biochemical data detecting NodA in both soluble and membrane fractions of NodA-overexpressing strains of R. meliloti.
Incidence of Coronary Events and Case Fatality Rate in Relation to Blood Lymphocyte and Neutrophil Counts

Objective—Elevated levels of blood leukocytes have been associated with acute coronary events (CEs), but data on leukocyte subclasses are limited. This study aimed to explore whether blood lymphocyte and neutrophil counts are associated with incidence of CEs and with fatal outcome in subjects who subsequently experienced a first CE. Methods and Results—Neutrophil and lymphocyte counts were measured in 27 419 subjects from the general population without a history of CEs, heart failure, or atrial fibrillation. Incidence of CEs was studied in relation to leukocyte counts during a mean follow-up of 13.6 years. Neutrophil but not lymphocyte counts were significantly associated with incidence of CEs. After adjustments for confounding factors, the hazard ratios (95% confidence interval) were 1.00 (reference), 1.07 (0.94–1.23), 1.09 (0.95–1.25), and 1.39 (1.22–1.59) for subjects with neutrophils in the first, second, third, and fourth (highest) sex-specific quartiles, respectively (P for trend <0.001). Of the 1965 subject who had a CE, 471 subjects died on the first day of the CE, in- or outside hospital. The proportions of subjects who died the first day were 19%, 21%, 25%, and 28%, respectively in the first, second, third, and fourth quartiles (P for trend <0.001). Conclusion—Increased neutrophil counts are associated with incidence of CEs and increased case-fatality rate after a CE.
Accrual of arguments in defeasible argumentation

In this paper we address an often overlooked problem in defeasible argumentation: how do we deal with arguments that are on their own defeated, but together remain undefeated? Pollock (1991) finds this accrual of arguments a na tural supposition, but t hen surprisingly denies its existence. We think that arguments do a ccrue. To hand le the accrual of arguments, we introduce compound defeat of arguments. We call the defeat of arguments compound, if groups of arguments can b e defeated b y other groups of arguments. The formalism presented in this paper is based on this notion o f compound defeat. It adequately handles the accrual of arguments.
Montelukast reduces ischaemia/reperfusion‐induced bladder dysfunction and oxidant damage in the rat

The present study aimed to investigate the possible beneficial effects of the cysteinyl leukotriene‐1 receptor antagonist montelukast on contractility and oxidant damage after ischaemia/reperfusion (I/R) of rat urinary bladder. The abdominal aorta of Sprague‐Dawley rats was occluded to induce I/R. Montelukast (10 mg kg−1) or saline was administered intraperitoneally before I/R. In the sham‐operated group, the abdominal aorta was left intact and the animals were treated with montelukast or saline. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for biochemical assays. In the I/R group, the isometric contractile responses of the bladder strips to carbachol (10−8‐10−4 M) were lower than those of the control group and were reversed by treatment with montelukast. Lipid peroxidation and myeloperoxidase activity of the bladder tissues in the I/R group were greater than in the sham‐operated group. Montelukast treatment in the I/R group decreased these parameters compared with I/R alone. Similarly, the significant decrease in tissue glutathione level in the I/R group compared with controls was also prevented by montelukast. Treatment with montelukast almost completely reversed the low contractile responses of rat urinary bladder to carbachol and prevented oxidative tissue damage following I/R.
Hotel Brand Strategy

Few dispute the value that a brand brings to a hotel property, but questions remain regarding exactly how the brand creates guest loyalty and how it creates value. Over the past twenty-five years, a brand flag has become an essential element of arranging a hotel development deal. Because of this, researchers have examined how brands influence top- and bottom-line revenues and overall asset value. Moreover, the effect of the brand on customer satisfaction seems to be affected by the brand’s franchising strategy.
Risk factors of mortality during the first year after low energy osteoporosis fracture: a retrospective case-control study.

INTRODUCTION Osteoporotic fractures are a major public health problem because of the morbidity and mortality of fracture complications. The objective of this study was to examine predictive factors of mortality during the first year after an osteoporotic fracture. METHODS It is a retrospective case-control study using data of a group of 1081 patients aged over 50 years with severe osteoporotic fractures by the Rennes university hospital emergency department from August 2007 to September 2008. Patients (cases) who died during the year following the fracture were compared with others who had survived (controls) one year after the fracture, matched on age, sex and type of fracture. Pre-fracture comorbidities and complications after the fractures were studied. RESULTS Forty-two cases and 126 controls were analyzed without significant differences in age, sex or type of fracture. On univariate analysis, previous neoplasia, neurodegenerative disease, walking aids, thromboembolic complication, post fracture infection, post fracture heart failure, post fracture acute respiratory failure were associated with more mortality after osteoporotic fracture. After multivariate analysis, only previous neoplasia (OR = 4.63 [1.79 - 11.95]; p = 0.02) and acute respiratory failure after fracture (OR = 28.15 [5.75 - 137.9]; p<0.001) were retained as predictive factors during the year following the fracture. CONCLUSION Patients died more often from their co-morbidities than direct complications of their fractures. Osteoporotic fracture seems to be a marker of poor health status and a factor which may hasten the death.
Single-Dose, Preoperative Vitamin-D Supplementation Decreases Infection in a Mouse Model of Periprosthetic Joint Infection

Background: Despite recent advances, infection remains the most common etiology of arthroplasty failure. Recent work suggests that 25-hydroxyvitamin D (25D) deficiency correlates with the frequency of periprosthetic joint infection (PJI). We endeavored to examine whether 25D3 deficiency leads to increased bacterial burden in vivo in an established mouse model of PJI and, if so, whether this effect can be reversed by preoperative 25D3 supplementation. Methods: Mice (lys-EGFP) possessing fluorescent neutrophils were fed a vitamin D3-sufficient (n = 20) or deficient (n = 40) diet for 6 weeks. A group of 25D3-deficient mice (n = 20) were “rescued” with 1 intraperitoneal dose of 25D3 at 3 days before surgery. A stainless steel implant was inserted into the knee joint and the joint space was inoculated with bioluminescent Staphylococcus aureus (1 × 103 colony forming units [CFUs]). In vivo imaging was used to monitor bacterial burden and neutrophil infiltration. Blood was drawn to confirm 25D3 levels 3 days before surgery and on postoperative days (PODs) 0 and 14. Mice were killed at POD 21, and CFUs were quantified after culture. Myeloperoxidase (MPO) and &bgr;-N-acetylglucosaminidase (NAG) were assayed to look at neutrophil infiltration and activated tissue macrophage recruitment, respectively. Results: Serum values confirmed 25D3 deficiency and repletion of the 25D3-rescued group. Bacterial bioluminescence and neutrophil fluorescence were significantly greater (p < 0.05) in the 25D3-deficient group. CFU counts from the joint tissue and implant were also significantly greater in this group (p < 0.05). Rescue treatment significantly decreased bacterial burden and neutrophil infiltration (p < 0.05). Compared with the 25D3-sufficient and 25D3-rescued groups, MPO activity was higher (p < 0.02) and NAG activity was lower (p < 0.03) in the 25D3-deficient group. Conclusions: This study demonstrated in vivo in a mouse model of PJI that (1) 25D3 deficiency results in increased bacterial burden and neutrophil infiltration, and (2) this effect can be reversed with preoperative repletion of 25D3. Clinical Relevance: Considering that >65% of patients undergoing arthroplasty have insufficient or low levels of total 25D and that 25D levels can be replenished with ease using a U.S. Food and Drug Administration (FDA)-approved, oral 25D3 product, 25D deficiency may be an important modifiable risk factor in humans undergoing joint replacement.
Analysis of pressure fluctuations in swirling turbulent flows

Turbulent flows display intermittent pressure drops associated with vorticity concentrations. Using wavelet transform, we characterize these low pressure events and study some of their statistical characteristics in a flow generated between the gap of two counter- rotating disks. We show that the mean frequency of intermittent pressure drops decreases with increasing Reynolds number.
Antibodies to a Single, Conserved Epitope in Anopheles APN1 Inhibit Universal Transmission of Plasmodium falciparum and Plasmodium vivax Malaria

ABSTRACT Malaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of the Plasmodium parasite, the Anopheles mosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission of Plasmodium falciparum and Plasmodium vivax across distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria.
Intracellular Ph Regulation by Na+/H+ Exchange Requires Phosphatidylinositol 4,5-Bisphosphate

The carrier-mediated, electroneutral exchange of Na+ for H+ across the plasma membrane does not directly consume metabolic energy. Nevertheless, acute depletion of cellular ATP markedly decreases transport. We analyzed the possible involvement of polyphosphoinositides in the metabolic regulation of NHE1, the ubiquitous isoform of the Na+/H+ exchanger. Depletion of ATP was accompanied by a marked reduction of plasmalemmal phosphatidylinositol 4,5-bisphosphate (PIP2) content. Moreover, sequestration or hydrolysis of plasmalemmal PIP2, in the absence of ATP depletion, was associated with profound inhibition of NHE1 activity. Examination of the primary structure of the COOH-terminal domain of NHE1 revealed two potential PIP2-binding motifs. Fusion proteins encoding these motifs bound PIP2 in vitro. When transfected into antiport-deficient cells, mutant forms of NHE1 lacking the putative PIP2-binding domains had greatly reduced transport capability, implying that association with PIP2 is required for optimal activity. These findings suggest that NHE1 activity is modulated by phosphoinositides and that the inhibitory effect of ATP depletion may be attributable, at least in part, to the accompanying net dephosphorylation of PIP2.
Activation of MyD88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules

Ligands binding to Toll-like receptor (TLR), interleukin 1 receptor (IL-1R), or IFN-γR1 are known to trigger MyD88-mediated signaling, which activates pro-inflammatory cytokine responses. Recently we reported that staphylococcal enterotoxins (SEA or SEB), which bind to MHC class II molecules on APCs and cross link T cell receptors, activate MyD88- mediated pro-inflammatory cytokine responses. We also reported that MyD88−/− mice were resistant to SE- induced toxic shock and had reduced levels of serum cytokines. In this study, we investigated whether MHC class II- SE interaction by itself is sufficient to activate MyD88 in MHC class II+ cells and induce downstream pro-inflammatory signaling and production of cytokines such as TNF-α and IL-1β. Here we report that human monocytes treated with SEA, SEB, or anti-MHC class II monoclonal antibodies up regulated MyD88 expression, induced activation of NF-kB, and increased expression of IL-1R1 accessory protein, TNF-α and IL-1β. MyD88 immunoprecipitated from cell extracts after SEB stimulation showed a greater proportion of MyD88 phosphorylation compared to unstimulated cells indicating that MyD88 was a component of intracellular signaling. MyD88 downstream proteins such as IRAK4 and TRAF6 were also up regulated in monocytes after SEB stimulation. In addition to monocytes, primary B cells up regulated MyD88 in response to SEA or SEB stimulation. Importantly, in contrast to primary B cells, MHC class II deficient T2 cells had no change of MyD88 after SEA or SEB stimulation, whereas MHC class II-independent activation of MyD88 was elicited by CpG or LPS. Collectively, these results demonstrate that MHC class II utilizes a MyD88-mediated signaling mechanism when in contact with ligands such as SEs to induce pro-inflammatory cytokines.
Algal blooms reduce the uptake of toxic methylmercury in freshwater food webs

Mercury accumulation in fish is a global public health concern, because fish are the primary source of toxic methylmercury to humans. Fish from all lakes do not pose the same level of risk to consumers. One of the most intriguing patterns is that potentially dangerous mercury concentrations can be found in fish from clear, oligotrophic lakes whereas fish from greener, eutrophic lakes often carry less mercury. In this study, we experimentally tested the hypothesis that increasing algal biomass reduces mercury accumulation at higher trophic levels through the dilution of mercury in consumed algal cells. Under bloom dilution, as algal biomass increases, the concentration of mercury per cell decreases, resulting in a lower dietary input to grazers and reduced bioaccumulation in algal-rich eutrophic systems. To test this hypothesis, we added enriched stable isotopes of Hg to experimental mesocosms and measured the uptake of toxic methylmercury (CH3200Hg+) and inorganic 201Hg2+ by biota at several algal concentrations. We reduced absolute spike detection limits by 50–100 times compared with previous techniques, which allowed us to conduct experiments at the extremely low aqueous Hg concentrations that are typical of natural systems. We found that increasing algae reduced CH3Hg+ concentrations in zooplankton 2–3-fold. Bloom dilution may provide a mechanistic explanation for lower CH3Hg+ accumulation by zooplankton and fish in algal-rich relative to algal-poor systems.