Response Fluctuations Research Articles

Dynamic Changes in Disney Stock Return under the Uncertain Situation

As the Federal Reserve raises the key interest rate, the exchange rate and the financial market will change. This paper studies how exchange rate change will influence one of the largest entertainment companies’ stock returns. This paper builds VAR model and ARMA-GARCH model to show the influence and finds that the stock return will increase in the short term but significantly shows fluctuations in response to exchange rate changes. So, the paper gives some suggestions for this discovery. The policymakers of the central bank should treat the volatility seriously and think carefully about adjusting the interest rate and the Disney company should create more good products to attract consumers and investors to keep the increase of the return and avoid loss of revenues because of exchange rate changes and fluctuation of the stock return. Investors should also treat the changes in money and financial markets carefully to avoid losses. This research provides some methods to predict the stock return in the future and find the influence of several variables, which can be used in many areas.

Selection of suitable internal control gene for assaying gene expression in rice through qRT-PCR during sheath blight infection

qRT-PCR is a globally accepted technique for assaying gene expression in relative terms which compares the difference between critical threshold (CT) values of a gene calculated form two independently isolated RNA samples. Independent RNA isolations, however, include error due to batch effect which must be normalized for error-free calculation of relative gene expression. Hence, CT values of internal control (IC) genes are used for normalization during the calculation of expression fold-change in gene expression analysis. The expression of ICs genes expected to be stable in all the experimental conditions. However, it is almost impossible to find such a gene which do not depict expression fluctuation in response to the changes in experimental conditions. Hence, it is necessary to identify suitable IC gene(s) for any given experimental condition before conducting any particular gene expression study. Here, we examined the suitability of eight candidate IC genes, namely glyceraldehyde 3-phosphate dehydrogenase (GAPDH), eukaryotic elongation factor-1 (eEF-1α), 25 S rRNA (25 S), 18 S rRNA (18 S), ubiquitin C E2 ligase (UBC), Actin (Act), ubiquitin 5 (UBQ5) and ubiquitin 10 (UBQ10), for assaying gene expression in rice during sheath blight infection. Our analysis suggest that GAPDH might be the IC of choice when expression studies include contrasting genotypes differing in their tolerance to sheath blight pathogen as well as progressive infection time. While if expression analysis have to be performed only in one genotype but under progressive sheath blight infection, UBQ5 might be chosen as IC because of its high expression stability under the proposed experimental setup.

A Single-Event-Hardened Scheme of Phase-Locked Loop Microsystems for Aerospace Applications.

In order to improve the ability of the phase-locked loop (PLL) microsystem applied in the aerospace environment to suppress the irradiation effect, this study presents an efficient charge pump hardened scheme by using the radiation-hardened-by-design (RHBD) technology. In this study, the sensitivity analysis of the single-event transient (SET) at different nodes of charge pump and different bombardment energies is carried out. Without changing the original structure and loop parameters, a hardened scheme of phase-locked loop to suppress the single-event effect is proposed. A digital control circuit is added between the charge pump and low-pass filter, which greatly reduces the sensitivity of the charge pump to the SET. The classical double-exponential current pulse model is used to simulate the SET effect on the unreinforced and reinforced phase-locked loops, and the reliability of the proposed reinforcement scheme is verified. The simulation results based on the SMIC 130 nm standard complementary metal-oxide-semiconductor (CMOS) process show that the peak value of the transient response fluctuation of the phase-locked loop using the proposed single-event-hardened scheme decreased by 94.2%, the lock recovery time increased by 75.3%, and the maximum phase shift decreased by 90.8%. This shows that the hardened scheme can effectively reduce the sensitivity of the PLL microsystems to the SET effects.

Differences in Weekly Training Load, Well-Being, and Hormonal Responses between European- and National-Level Professional Male Basketball Players during the Pre-Season Phase.

This study aimed to compare the weekly fluctuation in training load (sRPE-load), well-being (perceived fatigue, stress, mood, sleep, and muscle soreness), and hormonal responses [testosterone (T) and cortisol (C)] during the pre-season phase in European- and national-level professional male basketball players. Twenty-one professional male basketball players belonging to European-level (n = 11, age: 25.5 ± 3.6 yr; stature: 199.2 ± 7.1 cm; body mass: 94.1 ± 8.5 kg) and national-level (n = 10, age: 23.5 ± 4.7 yr; stature: 198.0 ± 5.6 cm; body mass: 94.0 ± 8.8 kg) teams were monitored during a 5-week pre-season phase. The European-level team showed higher sRPE-load in week 5 compared to week 3 (within-team difference, p = 0.049; ES = -1.44 [-2.38, -0.5], large) and week 1 (p = 0.018; ES = 1.62 [0.64, 2.61], large), week 4 (p = 0.005; ES = 1.79 [0.78, 2.81], large) and week 5 (p = 0.001; ES = 1.96 [0.92, 3.01], large) of the national-level team. The national-level team documented the lowest sRPE-load in week 5, which was statistically different compared to week 2 (p = 0.022; ES = 1.59 [0.61, 2.58], large) and week 4 (p = 0.001; ES = 1.94 [0.9, 2.98], large) of the European-level team. Moreover, higher stress (p < 0.001; ES = 1.94 [0.93, 2.95], large) and better mood (p = 0.003; ES = 1.79 [0.8, 2.78], large) were found in week 1 compared to week 5 within the European-level team. Additionally, higher values of salivary C were found in week 1 for the European-level team compared to week 2 (p = 0.020; ES = 1.6 [0.61, 2.58], large) and week 4 (p = 0.018; ES = 1.66 [0.64, 2.67], large) of the national-level team. Our results can provide reference values for basketball practitioners regarding the fluctuations of weekly load, well-being, and hormones across the pre-season period in professional male teams competing at European and national levels.

Quality of Life and Motor Outcomes in Patients With Parkinson’s Disease 12 Months After Deep Brain Stimulation in China

BackgroundLong-term levodopa use is frequently associated with fluctuations in motor response and can have a serious adverse effect on the quality of life (QoL) of patients with Parkinson’s disease (PD). Deep brain stimulation (DBS) is effective in improving symptoms of diminished levodopa responsiveness. QoL improvements with DBS have been shown in several randomized control trials, mostly in Europe and the United States; however, there is a need for evidence from regions around the world. ObjectiveThe study aimed to demonstrate improvement in PD-related QoL in patients undergoing DBS in a prospective, multicenter study conducted in China. Materials and MethodsTo evaluate the effect of neurostimulation on the QoL of patients with PD, a Parkinson’s Disease Questionnaire (PDQ-8); Unified Parkinson’s Disease Rating Scale (UPDRS) I, II, III, and IV; and EuroQol 5-dimension questionnaire (EQ-5D) were administered at baseline and 12 months after DBS implantation. The mean change and percent change from baseline were reported for these clinical outcomes. ResultsAssessments were completed for 85 of the 89 implanted patients. DBS substantially improved patients’ QoL and function. Implanted patients showed statistically significant mean improvement in PDQ-8 and UPDRS III (on stimulation/off medication). In the patients who completed the 12-month follow-up visit, the percent change was −22.2% for PDQ-8 and −51.6% for UPDRS III (on stimulation/off medication). Percent change from baseline to 12 months for UPDRS I, II, III, and IV and EQ-5D were −16.8%, −39.4%, −18.5%, and −50.0% and 22.7%, respectively. The overall rate of incidence for adverse events was low at 15.7%. Favorable outcomes were also reported based on patient opinion; 95.3% were satisfied with DBS results. ConclusionsThese data were comparable to other studies around the world and showed alignment with the ability of DBS to meaningfully improve the QoL of patients with PD. More studies investigating DBS therapy for patients with PD are necessary to accurately characterize clinical outcomes for the global PD population. Clinical Trial RegistrationThe ClinicalTrials.gov registration number for this study is NCT02937688.

Horizontal two-dimensional groundwater-level fluctuations in response to the combined actions of tide and rainfall in an unconfined coastal aquifer

Horizontal two-dimensional groundwater-level fluctuations in response to the combined actions of tide and rainfall in an unconfined coastal aquifer

Numerical assessment of the nanocomposite sector annular plates with the aim of promoting their mixed-form thermal shock response

As practical research, this study assesses the resistance of the radially-graded graphene-platelets reinforced (RG-GPLR) nanocomposite annular sector plates against thermal shock. Three-dimensional declaration of the elasticity theory is the base for defining the governing equations of the system. Discrete singular convolution technique (DSCT) is applied as an efficient solution to determine the stress and defection variation of the clamped plate against the instantaneous thermal shock. For the first time, this study considers the effect of thermal shock induced by the radical temperature gradient, heat flux, and the mixed form. Laplace transform combined with the extended Dubner and Abate's technique to find the time history of the system's thermomechanical behavior. The accuracy of the solution is inspected through a comparative analysis between the present and published studies’ results. As a valuable outcome, it is revealed that the fluctuations of the system's response around their ultimate constant values would be damped faster when the applied heat flux is higher.

The pharmacokinetics of continuous subcutaneous levodopa/carbidopa infusion: Findings from the ND0612 clinical development program.

While treatment with levodopa remains the cornerstone of Parkinson's disease (PD) management, chronic oral therapy is often associated with the development of motor complications, that correlate to fluctuating levodopa plasma concentrations, limiting its clinical utility. Continuous infusion is considered to be the optimal delivery route for treating PD patients with motor fluctuations, but current infusion systems require invasive surgery. Subcutaneous infusion of (SC) levodopa has the potential to provide a better tolerated and more convenient route of continuous levodopa delivery. ND0612 is in development as a combination product providing continuous levodopa/carbidopa via a minimally invasive, subcutaneous delivery system for PD patients experiencing motor response fluctuations. We present pharmacokinetic results from a series of studies that analyzed plasma concentrations after SC levodopa delivery with ND0612 to inform the clinical development program. We performed a series of six Phase I and II studies to characterize the pharmacokinetics of levodopa and carbidopa derived from ND0612 infusion with/without adjunct oral therapy of the same ingredients. These studies were conducted in healthy volunteers and in PD patients experiencing motor response fluctuations while on their current levodopa therapy regimen. Taken together, the results demonstrate dose-proportionality dependent on rate of subcutaneous levodopa infusion leading to stable and sustained plasma concentrations of levodopa. Subcutaneous infusion of ND0612 administered with oral levodopa/carbidopa maintained near-constant, therapeutic levodopa plasma concentrations, thereby avoiding the troughs in levodopa plasma concentrations that are associated with OFF time in PD. The data generated in this series of studies also confirmed that a levodopa/carbidopa dose ratio of 8:1 would be the most reasonable choice for ND0612 development. This series of clinical pharmacokinetic studies have demonstrated that ND0612, administered continuously with a levodopa concentration of 60 mg/ml combined with carbidopa 7.5 mg/ml, and complemented with oral levodopa/carbidopa, is suitable for 24 h continuous administration in patients with PD. The stable plasma concentrations of levodopa achieved predict utility of ND0612 as a parenteral formulation for achieving clinically useful delivery of levodopa for PD patients.

Chemiresistive NH Sensor of Cotton-Stalk- Based Carbon@MoS Composites Promoted by Heterojunction

Under the background of the global low carbon development, in order to prevent the carbon in cotton stalks from returning to the atmospheric environment in the form of greenhouse gas, cotton stalks were used as a carbon source to prepare cotton straw-based carbon (CSC). Furthermore, CSC@MoS2 composites were prepared by hydrothermal reaction and used as a gas sensor for the first time. The structure and morphology of the CSC and CSC@MoS2 composites were characterized by scanning electron microscope, transmission electron microscope, X-ray diffraction, Raman spectroscopy, and Fourier transform infrared spectroscopy. The CSC@MoS2 sensor exhibits a high sensitivity to NH3, fast response (< 26 s), and recovery (< 2.2 s). No matter whether after three months or in different humidity environments, the response fluctuation of the CSC@MoS2 sensor to NH3 is less than 5%, showing good long-term stability and antihumidity interference ability. Good repeatability is also shown between the different CSC@MoS2 sensors. This study not only provides a new reference for the low-carbon treatment and resource utilization of crop straw represented by cotton stalk but also provides a new path for the development of the gas sensor.

Levodopa Response in Patients With Early Parkinson Disease: Further Observations of the LEAP Study.

The Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease. The LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations. A total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early- and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was -0.33 for bradykinesia, -0.29 for rigidity, and -0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively, -0.49, -0.36, and -0.44 (small to medium effect); and from baseline to week 40, respectively, -0.32, -0.19, and -0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01). In patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier. This study provides Class II evidence that the effect of levodopa on bradykinesia, rigidity, and tremor is larger after 22 weeks compared with 4 weeks of treatment. ISRCTN30518857, EudraCT number 2011-000678-72.

Cortical response variability is driven by local excitability changes with somatotopic organization

Identical sensory stimuli can lead to different neural responses depending on the instantaneous brain state. Specifically, neural excitability in sensory areas may shape the brain´s response already from earliest cortical processing onwards. However, whether these dynamics affect a given sensory domain as a whole or occur on a spatially local level is largely unknown. We studied this in the somatosensory domain of 38 human participants with EEG, presenting stimuli to the median and tibial nerves alternatingly, and testing the co-variation of initial cortical responses in hand and foot areas, as well as their relation to pre-stimulus oscillatory states. We found that amplitude fluctuations of initial cortical responses to hand and foot stimulation – the N20 and P40 components of the somatosensory evoked potential (SEP), respectively – were not related, indicating local excitability changes in primary sensory regions. In addition, effects of pre-stimulus alpha (8-13 Hz) and beta (18-23 Hz) band amplitude on hand-related responses showed a robust somatotopic organization, thus further strengthening the notion of local excitability fluctuations. However, for foot-related responses, the spatial specificity of pre-stimulus effects was less consistent across frequency bands, with beta appearing to be more foot-specific than alpha. Connectivity analyses in source space suggested this to be due to a somatosensory alpha rhythm that is primarily driven by activity in hand regions while beta frequencies may operate in a more hand-region-independent manner. Altogether, our findings suggest spatially distinct excitability dynamics within the primary somatosensory cortex, yet with the caveat that frequency-specific processes in one sub-region may not readily generalize to other sub-regions.

Collective organization from cellular disorder

In biology, form follows function. Spatial organization of cells within tissues is a critical aspect of this form. Injuries, drugs, and genetic mutations that perturb cellular organization disrupt tissue and organ functions. Indeed, the high degree of order and organization in tissues like heart muscle and bone is one impressive aspect of histological images. The influence of entropic crowding in cell monolayersIppolito et al.Biophysical JournalAugust 23, 2022In BriefCell-cell interaction dictates cell morphology and organization, which play a crucial role in the micro-architecture of tissues that guides their biological and mechanical functioning. Here, we investigate the effect of cell density on the responses of cells seeded on flat substrates using a novel statistical thermodynamics framework. The framework recognizes the existence of nonthermal fluctuations in cellular response and thereby naturally captures entropic interactions between cells in monolayers. Full-Text PDF Open Access

In situ electrosynthetic bacterial growth using electricity generated by a deep-sea hydrothermal vent

Electroautotrophic microorganisms have attracted great attention since they exhibit a new type of primary production. Here, in situ electrochemical cultivation was conducted using the naturally occurring electromotive forces at a deep-sea hydrothermal vent. The voltage and current generation originating from the resulting microbial activity was observed for 12 days of deployment, with fluctuation in response to tidal cycles. A novel bacterium belonging to the genus Thiomicrorhabdus dominated the microbial community specifically enriched on the cathode. Metagenomic analysis provided the draft genome of the bacterium and the gene repertoire indicated that the bacterium has the potential for thio-autotrophic growth, which is a typical physiological feature of the members of the genus, while the bacterium had a unique gene cluster encoding multi-heme cytochrome c proteins responsible for extracellular electron transfer. Herein, we propose this bacterium as a new species, specifically enriched during electricity generation, as ‘Candidatus Thiomicrorhabdus electrophagus’. This finding suggests the natural occurrence of electrosynthetic microbial populations using the geoelectricity in deep-sea hydrothermal environments.

Life after death? Exploring biochemical and molecular changes following organismal death in green turtles, Chelonia mydas (Linnaeus, 1758)

Green turtles, Chelonia mydas, have been included in biomonitoring efforts given its status as an endangered species. Many studies, however, rely on samples from stranded animals, raising the question of how death affects important biochemical and molecular biomarkers. The goal of this study was to investigate post mortem fluctuations in the antioxidant response and metabolism of carbohydrates in the liver of C. mydas. Liver samples were obtained from six green turtles which were submitted to rehabilitation and euthanized due to the impossibility of recovery. Samples were collected immediately after death (t = 0) and at various time intervals (1, 2, 3, 4, 5, 6, 12, 18 and 24 h post mortem), frozen in liquid nitrogen and stored at −80 °C. The activities of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH) were analyzed, as were the levels of lipid peroxidation, glycogen concentration, RNA integrity (RNA IQ) and transcript levels of carbonic anhydrase and pyruvate carboxylase genes. Comparison between post mortem intervals showed a temporal stability for all the biomarkers evaluated, suggesting that changes in biochemical and molecular parameters following green turtle death are not immediate, and metabolism may remain somewhat unaltered up to 24 h after death. Such stability may be associated with the overall lower metabolism of turtles, especially under an oxygen deprivation scenario such as organismal death. Overall, this study supports the use of biomarkers in sea turtles sampled within a period of 24 h post mortem for biomonitoring purposes, though it is recommended that post mortem fluctuations of particular biomarkers be evaluated prior to their application, given that proteins may show varying degrees of susceptibility to proteolysis.

Influence of Karst Reservoir Capacity on Flood in Lijiang Basin Based on Modified HEC-HMS through Soil Moisture Accounting Loss

The objective of this work was to modify the HEC-HMS flood prediction for the karstic watershed of the Lijiang River, South China, through the quantitative inclusion into the model of the available reservoir capacity of karst (ARCK) as a case study. Due to the complexities caused by hidden drainage networks in karst hydrology, as a new approach, soil moisture accounting loss was used to reflect the ARCK in flood forecasting. The soil moisture loss was analyzed against daily rainfall runoff data across 1.5 years by using an artificial neural network via phyton programming. Through the correlations found among the amounts of soil moisture and river flow fluctuations in response to precipitation and its intervals, coefficients were introduced to the model for output modifications. ARCK analysis revealed that while heavy rainfalls with longer intervals (i.e., 174 mm/2d after 112 days of the dry season) may not cause considerable changes in the river flow magnitude (0.1–0.64 higher owing to high ARCK), relatively small rainfalls with higher frequency (i.e., 83 mm/4d during the wet season) can cause drastic raise of river flow (10–20 times greater at different stations) due to lower ARCK. Soil moisture accounting loss coefficients did enhance the model’s simulated hydrographs accuracy (NSE) up to 16% on average as compared to the initial forecasting via real data. However, the modifications were valid for flood events within a few years from the soil moisture observation period. Our result suggested that the inclusion of ARCK in modeling through soil moisture accounting loss can lead to increased prediction accuracy through consistent monitoring.

Monitoring gait at home with radio waves in Parkinson's disease: A marker of severity, progression, and medication response.

Parkinson's disease (PD) is the fastest-growing neurological disease in the world. A key challenge in PD is tracking disease severity, progression, and medication response. Existing methods are semisubjective and require visiting the clinic. In this work, we demonstrate an effective approach for assessing PD severity, progression, and medication response at home, in an objective manner. We used a radio device located in the background of the home. The device detected and analyzed the radio waves that bounce off people's bodies and inferred their movements and gait speed. We continuously monitored 50 participants, with and without PD, in their homes for up to 1 year. We collected over 200,000 gait speed measurements. Cross-sectional analysis of the data shows that at-home gait speed strongly correlates with gold-standard PD assessments, as evaluated by the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III subscore and total score. At-home gait speed also provides a more sensitive marker for tracking disease progression over time than the widely used MDS-UPDRS. Further, the monitored gait speed was able to capture symptom fluctuations in response to medications and their impact on patients' daily functioning. Our study shows the feasibility of continuous, objective, sensitive, and passive assessment of PD at home and hence has the potential of improving clinical care and drug clinical trials.

Estimation of the time fluctuation of polysynaptic responses evoked by constant spinal cord stimulation

Abstract Polysynaptic activity is necessary to engage the neural circuitry that controls the motor behaviour and is crucial to the recovery after spinal cord injury (SCI) [1]. Polysynaptic responses can be elicited with spinal cord stimulation, and there are few reports on these types of responses in human electrophysiology, most of them describing them as constant to fixed stimuli. However, we have observed that the responses fluctuate in amplitude and time. Amplitude variations can be analysed with statistical methods. However, time fluctuations are more complex due to the multiple parameters involved. This work describes a methodology to analyse the time fluctuation in the responses of each pulse. It is based on the calculation of the signal temporal centroid, representing the whole activity, weighted by its latency, in a single time value. This value is then used to model the temporal fluctuation with linear regression. The methodology was verified with an electromyography dataset from a discomplete spinal cord injured patient with spinal cord stimulation. The parameter is able to follow small changes in the responses' distribution. Examples of how the temporal centroid and linear model identify the fluctuations are presented. Once fitted in a linear model, the fluctuation coefficient describes time fluctuations in the interneuron processing and, together with amplitude metrics, can characterise changes in polysynaptic responses during the application of fixed stimulation parameters.

Protein expression profiling, in silico classification and pathway analysis of cariogenic bacteria Streptococcus mutans under bacitracin stress conditions.

Introduction. Streptococcus mutans is a cariogenic bacterium that causes dental caries as well as being implicated in other dental pathologies and infective endocarditis. Bacitracin is a bactericidal antibiotic that induces cell wall stress in Gram-positive bacteria.Gap Statement. S. mutans is among the most characterized Gram-positive bacteria. However, the transcriptome and proteome of S. mutans have received less attention, and they are actually key in understanding the pathogenesis of any bacteria. In this study, we extracted the whole proteome of S. mutans grown under bacitracin stress. Such a proteome is anticipated to offer deep insights related to physiological dynamic fluctuations and, consequently, it may provide 'proteomic signatures' to be identified as potential targets.Aim. The aim of the study is to explore the general stress response that S. mutans exhibits at the proteome level when cell wall stress is imposed on it.Methodology. A sub-MIC concentration of bacitracin was added to the growth media of S. mutans followed by whole-cell protein extraction. The proteome was then subjected to high-throughput proteomics analysis, i.e. liquid chromatography tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins obtained through LC-MS/MS underwent analyses such as gene ontology, KEGG (Kyoto Encyclopaedia of Genes and Genomes) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analysis, and STRING for functional annotation, pathway enrichment and protein-protein interaction (PPI) networks, respectively. These proteins were also categorized into functional classes using the PANTHER (Protein Annotation Through Evolutionary Relationship) classification system.Result. LC-MS/MS produced data from 321 identified proteins. From these, 41 and 30 were found to be significantly over- (≥2 fold change) and underexpressed (≤0.4 fold change), respectively. In the upregulated proteins we mostly observed sortases and proteins involved in the EPS biosynthesis pathway, whereas among the downregulated proteins the majority related to glycolysis.Conclusion. The sortase family of proteins appear to be potential targets because they regulate various virulence factors and therefore can be targeted to inhibit multiple virulence pathways simultaneously. This study offers an understanding of proteomic fluctuations in response to cell wall stress and can thus help in identifying key players mediating virulence.

The influence of entropic crowding in cell monolayers

Cell-cell interaction dictates cell morphology and organization, which play a crucial role in the micro-architecture of tissues that guides their biological and mechanical functioning. Here, we investigate the effect of cell density on the responses of cells seeded on flat substrates using a novel statistical thermodynamics framework. The framework recognizes the existence of nonthermal fluctuations in cellular response and thereby naturally captures entropic interactions between cells in monolayers. In line with observations, the model predicts that cell area and elongation decrease with increasing cell seeding density—both are a direct outcome of the fluctuating nature of the cellular response that gives rise to enhanced cell-cell interactions with increasing cell crowding. The modeling framework also predicts the increase in cell alignment with increasing cell density: this cellular ordering is also due to enhanced entropic interactions and is akin to nematic ordering in liquid crystals. Our simulations provide physical insights that suggest that entropic cell-cell interactions play a crucial role in governing the responses of cell monolayers.

Light/Dark and Temperature Cycling Modulate Metabolic Electron Flow in Pseudomonas aeruginosa Biofilms.

ABSTRACTSunlight drives phototrophic metabolism, which affects redox conditions and produces substrates for nonphototrophs. These environmental parameters fluctuate daily due to Earth’s rotation, and nonphototrophic organisms can therefore benefit from the ability to respond to, or even anticipate, such changes. Circadian rhythms, such as daily changes in body temperature, in host organisms can also affect local conditions for colonizing bacteria. Here, we investigated the effects of light/dark and temperature cycling on biofilms of the opportunistic pathogen Pseudomonas aeruginosa PA14. We grew biofilms in the presence of a respiratory indicator dye and found that enhanced dye reduction occurred in biofilm zones that formed during dark intervals and at lower temperatures. This pattern formation occurred with cycling of blue, red, or far-red light, and a screen of mutants representing potential sensory proteins identified two with defects in pattern formation, specifically under red light cycling. We also found that the physiological states of biofilm subzones formed under specific light and temperature conditions were retained during subsequent condition cycling. Light/dark and temperature cycling affected expression of genes involved in primary metabolic pathways and redox homeostasis, including those encoding electron transport chain components. Consistent with this, we found that cbb3-type oxidases contribute to dye reduction under light/dark cycling conditions. Together, our results indicate that cyclic changes in light exposure and temperature have lasting effects on redox metabolism in biofilms formed by a nonphototrophic, pathogenic bacterium.