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Many species of soil fungi grow in the form of branched networks that enable long-range communication and mass flow of nutrient. These networks play important roles in the soil ecosystem as a major decomposer of organic materials. While there have been investigations on the branching of the fungal networks, their long-term growth dynamics in space and time is still not very well understood. In this study, we monitor the spatio-temporal growth dynamics of the plant-promoting filamentous fungus Serendipita indica for several days in a controlled environment within a microfluidic chamber. We find that S. indica cells display synchronized growth oscillations with the onset of sporulation and at a period of 3 h. Quantifying this experimental synchronization of oscillatory dynamics, we show that the synchronization can be recapitulated by the nearest neighbour Kuramoto model with a millimetre-scale cell-cell coupling. The microfluidic set-up presented in this work may aid the future characterization of the molecular mechanisms of the cell-cell communication, which could lead to biophysical approaches for controlling fungi growth and reproductive sporulation in soil and plant health management.

Climate warming is causing shifts in reproductive phenology, a crucial life history trait determining offspring survival and population productivity. Evaluating these impacts on exploited marine resources is essential for implementing adaptive measures from an ecosystemic approach. This study introduces a statistical model designed to predict fish spawning phenology from sea surface temperature profiles, integrating mortality-corrected hatch-date distributions inferred from fishery-dependent samplings, along with the gonadosomatic index of adult individuals. When applied to different dolphinfish (Coryphaena hippurus) populations across a broad latitudinal range, the model reasonably predicts the spawning phenology across its extensive thermal ranges, elucidating a direct relationship between mean annual temperature and the breadth of the spawning season. Despite the varying thermal profiles, results show a consistent timing of spawning peaks approximately 49 days before the peak in temperature. Importantly, these findings account for the impact of fishery constraints, such as seasonal closures or different sampling schedules, offering a robust tool for adjusting management practices in response to inter-annual temperature variations. These insights are critical for both short-term fishery management, including the strategic planning of seasonal closures, and long-term projections of spawning phenology shifts under changing thermal regimes. By enhancing our ability to predict spawning times, this research contributes significantly to the sustainable management of fish populations and the adaptive response to environmental changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Multivalent interactions are common in biology at many different length scales, and can result in the directional motion of multivalent cargo along substrates. Here, a general analytical model has been developed that can describe the directional motion of multivalent cargo as a response to position dependence in the binding and unbinding rates exhibited by their interaction sites. Cargo exhibit both an effective velocity, which acts in the direction of increasing cargo-substrate binding rate and decreasing cargo-substrate unbinding rate, and an effective diffusivity. This model can reproduce previously published experimental findings using only the binding and unbinding rate distributions of cargo interaction sites, and without any further parameter fitting. Extension of the cargo binding model to two dimensions reveals an effective velocity with the same properties as that derived for the one-dimensional case.

Objective: Vital sign scoring systems that alert providers of clinical deterioration prior to critical illness have been proposed as a means of reducing maternal risk. This study examined the predictive ability of established maternal early warning systems (MEWS)-as well as their component vital sign thresholds-for different types of maternal morbidity, to discern an optimal early warning system., Study Design: This retrospective cohort study analyzed all patients admitted to the obstetric services of a four-hospital urban academic system in 2018. Three sets of published MEWS criteria were evaluated. Maternal morbidity was defined as a composite of hemorrhage, infection, acute cardiac disease, and acute respiratory disease ascertained from the electronic medical record data warehouse and administrative data. The test characteristics of each MEWS, as well as for heart rate, blood pressure, and oxygen saturation were compared., Results: Of 14,597 obstetric admissions, 2,451 patients experienced the composite morbidity outcome (16.8%) including 980 cases of hemorrhage (6.7%), 1,337 of infection (9.2%), 362 of acute cardiac disease (2.5%), and 275 of acute respiratory disease (1.9%) (some patients had multiple types of morbidity). The sensitivities (15.3-64.8%), specificities (56.8-96.1%), and positive predictive values (22.3-44.5%) of the three MEWS criteria ranged widely for overall morbidity, as well as for each morbidity subcategory. Of patients with any morbidity, 28% met criteria for the most liberal vital sign combination, while only 2% met criteria for the most restrictive parameters, compared with 14 and 1% of patients without morbidity, respectively. Sensitivity for all combinations was low (maximum 28.2%), while specificity for all combinations was high, ranging from 86.1 to 99.3%., Conclusion: Though all MEWS criteria demonstrated poor sensitivity for maternal morbidity, permutations of the most abnormal vital signs have high specificity, suggesting that MEWS may be better implemented as a trigger tool for morbidity reduction strategies in the highest risk patients, rather than a general screen., Key Points: · MEWS have poor sensitivity for maternal morbidity.. · MEWS can be optimized for high specificity using modified criteria.. · MEWS could be better used as a trigger tool.., Competing Interests: None declared., (Thieme. All rights reserved.)

Study Objective: To analyze hysterectomy trends and vaginal cuff dehiscence (VCD) rates by mode of surgery at a tertiary care medical center and to describe characteristics of VCD cases., Design: Observational retrospective cohort study., Setting: Large academic hospital and affiliated community hospital., Patients: 4722 patients who underwent hysterectomy at Columbia University Irving Medical Center between January 2010 and August 2021., Interventions: Current Procedural Terminology and International Classification of Diseases codes identified hysterectomies and VCD cases. Hysterectomy trends and VCD rates were calculated by mode of surgery. Relative risks of VCD for each mode were compared with total abdominal hysterectomy (TAH). Clinical characteristics of VCDs were reviewed., Measurements and Main Results: There were 4059 total hysterectomies. Laparoscopic hysterectomies, including total laparoscopic hysterectomies (TLHs), laparoscopic-assisted vaginal hysterectomies, and robot-assisted TLHs (RA-TLHs), increased from 41.9% in 2010 to 65.9% in 2021 (p <.001). RA-TLH increased from 5.7% in 2010 to 40.2% in 2021. Supracervical hysterectomies followed similar trends and were excluded from VCD analysis. There were 15 VCDs (overall rate 0.37%). VCD was highest after RA-TLH (0.66%), followed by TLH (0.32%) and TAH (0.27%), with no VCDs after laparoscopic-assisted vaginal hysterectomy or total vaginal hysterectomy. Compared with TAH, the relative risk for VCD after RA-TLH was 2.44 (95% confidence interval 0.66-9.00) and after TLH was 1.18 (95% confidence interval 0.24-5.83), which were not statistically significant. The mean time to dehiscence was 39 days (range 8-145 days). The most common trigger event was coitus (41%)., Conclusion: VCD rates were low (<1%) for all modes of hysterectomy, and rates after robotic and laparoscopic hysterectomy were much lower than previously reported. Although VCD rates trended higher after robotic and laparoscopic hysterectomy compared with abdominal hysterectomy, the difference was not significant. It is difficult to determine whether this finding represents true lack of difference vs a lack of power to detect a significant difference given the rarity of VCD., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Self-organisation is the spontaneous emergence of spatio-temporal structures and patterns from the interaction of smaller individual units. Examples are found across many scales in very different systems and scientific disciplines, from physics, materials science and robotics to biology, geophysics and astronomy. Recent research has highlighted how self-organisation can be both mediated and controlled by confinement. Confinement is an action over a system that limits its units' translational and rotational degrees of freedom, thus also influencing the system's phase space probability density; it can function as either a catalyst or inhibitor of self-organisation. Confinement can then become a means to actively steer the emergence or suppression of collective phenomena in space and time. Here, to provide a common framework and perspective for future research, we examine the role of confinement in the self-organisation of soft-matter systems and identify overarching scientific challenges that need to be addressed to harness its full scientific and technological potential in soft matter and related fields. By drawing analogies with other disciplines, this framework will accelerate a common deeper understanding of self-organisation and trigger the development of innovative strategies to steer it using confinement, with impact on, e.g. , the design of smarter materials, tissue engineering for biomedicine and in guiding active matter.

Understanding the out-of-equilibrium properties of noisy microscale systems and the extent to which they can be modulated externally, is a crucial scientific and technological challenge. It holds the promise to unlock disruptive new technologies ranging from targeted delivery of chemicals within the body to directed assembly of new materials. Here we focus on how active matter can be harnessed to transport passive microscopic systems in a statistically predictable way. Using a minimal active-passive system of weakly Brownian particles and swimming microalgae, we show that spatial confinement leads to a complex non-monotonic steady-state distribution of colloids, with a pronounced peak at the boundary. The particles' emergent active dynamics is well captured by a space-dependent Poisson process resulting from the space-dependent motion of the algae. Based on our findings, we then realise experimentally the de-mixing of the active-passive suspension, opening the way for manipulating colloidal objects via controlled activity fields., (© 2022. The Author(s).)

Plastics, when entering the environment, are immediately colonised by microorganisms. This modifies their physico-chemical properties as well as their transport and fate in natural ecosystems, but whom pioneers this colonisation in marine ecosystems? Previous studies have focused on microbial communities that develop on plastics after relatively long incubation periods (i.e., days to months), but very little data is available regarding the earliest stages of colonisation on buoyant plastics in marine waters (i.e., minutes or hours). We conducted a preliminary study where the earliest hours of microbial colonisation on buoyant plastics in marine coastal waters were investigated by field incubations and amplicon sequencing of the prokaryotic and eukaryotic communities. Our results show that members of the Bacteroidetes group pioneer microbial attachment to plastics but, over time, their presence is masked by other groups - Gammaproteobacteria at first and later by Alphaproteobacteria. Interestingly, the eukaryotic community on plastics exposed to sunlight became dominated by phototrophic organisms from the phylum Ochrophyta, diatoms at the start and brown algae towards the end of the three-day incubations. This study defines the pioneering microbial community that colonises plastics immediately when entering coastal marine environments and that may set the seeding Plastisphere of plastics in the oceans., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To provide a systematic review of pregnancy outcomes after radiofrequency ablation (RFA) of uterine myomas., Data Sources: A literature search was conducted using PubMed, Cochrane Library, Scopus, Web of Science, and Embase, from database inception to October 2021., Methods of Study Selection: Two reviewers conducted independent literature searches. Studies that met the criteria based on title and abstract underwent full-text review. Publications were included if they reported pregnancies and obstetric outcomes after laparoscopic or transcervical RFA of myomas., Tabulation, Integration, and Results: A total of 405 publications were initially identified and screened, 39 underwent full-text review, and 10 publications were ultimately included. There were 50 pregnancies reported among 923 RFA patients: 40 pregnancies after 559 laparoscopic RFAs and 10 pregnancies after 364 transcervical RFAs. The number of patients from these studies actively trying to conceive after RFA is unknown. Among the RFA patients who conceived, the average age at ablation was 37 years old (range, 27-46 years). Most patients had between 1 and 3 myomas ablated, and myomas size ranged from <2 cm to 12.5 cm. There were 6 spontaneous abortions (12%) and 44 full-term pregnancies (88%), of which 24 were vaginal deliveries and 20 were cesarean deliveries. There were only 2 complications among 44 deliveries: one placenta previa that underwent an uncomplicated cesarean delivery and 1 delayed postpartum hemorrhage with expulsion of a degenerated myoma, with no long-term sequelae. There were no cases of uterine rupture, uterine window, or invasive placentation and no fetal complications. The spontaneous abortion rate was comparable with the general obstetric population., Conclusion: Almost all pregnancies after RFA of myomas were full-term deliveries with no maternal or neonatal complications. These findings add to the literature that radiofrequency myoma ablation may offer a safe and effective alternative to existing treatments for women who desire future fertility., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have declared they have no conflicts of interest.

Obstetric physiology may alter lactate metabolism and affect the ability to use lactate as a discriminator of critical illness in pregnancy. This prospective, cross-sectional study describes venous lactate levels in women presenting for acute care during pregnancy as well as characteristics associated with elevated lactate. Obstetric patients >20-week gestation presenting for acute evaluation were included and a venous lactate sample was drawn for each patient. Elevated lactate was defined as ≥2 mmol/L. One hundred two women were enrolled and venous lactate samples were obtained for 100 participants. Median lactate level was 1.22 (IQR 0.95-1.49) and 86% of patients had normal lactate. Six patients presented with infectious complaints, none of whom had sepsis or elevated lactate. Of the 14 patients with elevated lactate, all presented with labor complaints and 10 (71.4%) were admitted in labor. Elevated lactate level was significantly associated with labor complaints and admission in labor ( p  < .01). Thus, lactate may not be able to discriminate severe infection consistently in pregnancy as it is confounded by labor. Further research is necessary to clarify how lactate may be used more effectively in pregnant patients and to identify alternate strategies for sepsis screening.

How oligotrophic marine cyanobacteria position themselves in the water column is currently unknown. The current paradigm is that these organisms avoid sinking due to their reduced size and passive drift within currents. Here, we show that one in four picocyanobacteria encode a type IV pilus which allows these organisms to increase drag and remain suspended at optimal positions in the water column, as well as evade predation by grazers. The evolution of this sophisticated floatation mechanism in these purely planktonic streamlined microorganisms has important implications for our current understanding of microbial distribution in the oceans and predator-prey interactions which ultimately will need incorporating into future models of marine carbon flux dynamics.

Self-organized multicellular behaviors enable cells to adapt and tolerate stressors to a greater degree than isolated cells. However, whether and how cellular communities alter their collective behaviors adaptively upon exposure to stress is largely unclear. Here, we investigate this question using Bacillus subtilis , a model system for bacterial multicellularity. We discover that, upon exposure to a spatial gradient of kanamycin, swarming bacteria activate matrix genes and transit to biofilms. The initial stage of this transition is underpinned by a stress-induced multilayer formation, emerging from a biophysical mechanism reminiscent of motility-induced phase separation (MIPS). The physical nature of the process suggests that stressors which suppress the expansion of swarms would induce biofilm formation. Indeed, a simple physical barrier also induces a swarm-to-biofilm transition. Based on the gained insight, we propose a strategy of antibiotic treatment to inhibit the transition from swarms to biofilms by targeting the localized phase transition., Competing Interests: IG, MP, MA No competing interests declared, (© 2021, Grobas et al.)

Objective: This study aimed to evaluate temporal trends in opioid use disorder (OUD) during antepartum and postpartum hospitalizations., Study Design: This repeated cross-sectional analysis analyzed data from the National (Nationwide) Inpatient Sample. Women aged 15 to 54 years admitted antepartum or postpartum were identified. The presence of OUD was determined based on a diagnosis of opioid abuse, opioid dependence, or opioid overdose. Temporal trends in OUD were evaluated using the Rao-Scott chi-square test. Temporal trends in opioid overdose were additionally evaluated., Results: An estimated 7,336,562 antepartum hospitalizations and 1,063,845 postpartum readmissions were included in this analysis. The presence of an OUD diagnosis during antepartum hospitalizations increased from 0.7% of patients in 1998 to 1999 to 2.9% in 2014 ( p  < 0.01) and during postpartum hospitalizations increased from 0.8% of patients in 1998 to 1999 to 2.1% of patients in 2014 ( p  < 0.01). Risk of overdose diagnoses increased significantly for both antepartum hospitalizations, from 22.7 per 100,000 hospitalizations in 1998 to 2000 to 70.3 per 100,000 hospitalizations in 2013 to 2014 ( p  < 0.001), and postpartum hospitalizations, from 18.8 per 100,000 hospitalizations in 1998 to 2000 to 65.2 per 100,000 hospitalizations in 2013 to 2014 ( p  = 0.02)., Discussion: Risk of OUD diagnoses and overdoses increased over the study period for both antepartum and postpartum hospitalizations., Competing Interests: J.D.W. has served as a consultant for Tesaro and Clovis Oncology. The other authors did not report any potential conflicts of interest., (Thieme. All rights reserved.)

The persistent motility of individual constituents in microbial suspensions represents a prime example of the so-called active matter systems. Cells consume energy, exert forces and move, overall releasing the constraints of equilibrium statistical mechanics of passive elements and allowing for complex spatio-temporal patterns to emerge. Moreover, when subject to physico-chemical stimuli their collective behaviour often drives large-scale instabilities of a hydrodynamic nature, with implications for biomixing in natural environments and incipient industrial applications. In turn, our ability to exert external control of these driving stimuli could be used to govern the emerging patterns. Light, being easily manipulable and, at the same time, an important stimulus for a wide variety of microorganisms, is particularly well suited to this end. In this paper, we will discuss the current state, developments and some of the emerging advances in the fundamentals and applications of light-induced bioconvection with a focus on recent experimental realizations and modelling efforts. This article is part of the theme issue 'Stokes at 200 (part 2)'.

The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood because of difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and fast acquisition rates, we detect and image individual membrane-attached actin filaments diffusing within the acto-myosin network and follow individual myosin II filament dynamics. We quantify myosin II filament dwell times and processivity as functions of ATP concentration, providing experimental evidence for the predicted ensemble behavior of myosin head domains. Our results show how decreasing ATP concentrations lead to both increasing dwell times of individual myosin II filaments and a global change from a remodeling to a contractile state of the acto-myosin network., (Copyright © 2020 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Despite their importance in many biological, ecological, and physical processes, microorganismal fluid flows under tight confinement have not been investigated experimentally. Strong screening of Stokelets in this geometry suggests that the flow fields of different microorganisms should be universally dominated by the 2D source dipole from the swimmer's finite-size body. Confinement therefore is poised to collapse differences across microorganisms, which are instead well established in bulk. We combine experiments and theoretical modeling to show that, in general, this is not correct. Our results demonstrate that potentially minute details like microswimmer spinning and the physical arrangement of the propulsion appendages have in fact a leading role in setting qualitative topological properties of the hydrodynamic flow fields of microswimmers under confinement. This is well captured by an effective 2D model, even under relatively weak confinement. These results imply that active confined hydrodynamics is much richer than in bulk and depends in a subtle manner on the size, shape, and propulsion mechanisms of the active components.

Microorganismal motility is often characterized by complex responses to environmental physico-chemical stimuli. Although the biological basis of these responses is often not well understood, their exploitation already promises novel avenues to directly control the motion of living active matter at both the individual and collective level. Here we leverage the phototactic ability of the model microalga Chlamydomonas reinhardtii to precisely control the timing and position of localized cell photoaccumulation, leading to the controlled development of isolated bioconvective plumes. This novel form of photobioconvection allows a precise, fast, and reconfigurable control of the spatiotemporal dynamics of the instability and the ensuing global recirculation, which can be activated and stopped in real time. A simple continuum model accounts for the phototactic response of the suspension and demonstrates how the spatiotemporal dynamics of the illumination field can be used as a simple external switch to produce efficient bio mixing.

Background: Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival., Methods: Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL - fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF - fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations., Results: Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 μm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and β-myosin heavy chain did not differ between groups., Conclusion: Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.

Despite evidence for a hydrodynamic origin of flagellar synchronization between different eukaryotic cells, recent experiments have shown that in single multi-flagellated organisms, coordination hinges instead on direct basal body connections. The mechanism by which these connections lead to coordination, however, is currently not understood. Here, we focus on the model biflagellate Chlamydomonas reinhardtii , and propose a minimal model for the synchronization of its two flagella as a result of both hydrodynamic and direct mechanical coupling. A spectrum of different types of coordination can be selected, depending on small changes in the stiffness of intracellular couplings. These include prolonged in-phase and anti-phase synchronization, as well as a range of multi-stable states induced by spontaneous symmetry breaking of the system. Linking synchrony to intracellular stiffness could lead to the use of flagellar dynamics as a probe for the mechanical state of the cell., (© 2018 The Author(s).)

Phototaxis is an important reaction to light displayed by a wide range of motile microorganisms. Flagellated eukaryotic microalgae in particular, like the model organism Chlamydomonas reinhardtii, steer either towards or away from light by a rapid and precisely timed modulation of their flagellar activity. Cell steering, however, is only the beginning of a much longer process which ultimately allows cells to determine their light exposure history. This process is not well understood. Here we present a first quantitative study of the long timescale phototactic motility of Chlamydomonas at both single cell and population levels. Our results reveal that the phototactic strategy adopted by these microorganisms leads to an efficient exposure to light, and that the phototactic response is modulated over typical timescales of tens of seconds. The adaptation dynamics for phototaxis and chlorophyll fluorescence show a striking quantitative agreement, suggesting that photosynthesis controls quantitatively how cells navigate a light field.

A change in regioselectivity has been observed in the hydrogen atom transfer (HAT) reactions from 4-alkyl-N,N-dimethylbenzylamines (alkyl = ethyl, isopropyl, and benzyl) to the phthalimide N-oxyl radical (PINO) by effect of protonation. This result can be rationalized on the basis of an acid-induced deactivation of the C-H bonds α to nitrogen toward HAT to PINO as evidenced by the 10 4 -10 7 -fold decrease in the HAT rate constants in acetonitrile following addition of 0.1 M HClO 4 . This acid-induced change in regioselectivity has been successfully applied for selective functionalization of the less activated benzylic C-H bonds para to the CH 2 N(CH 3 ) 2 group in the aerobic oxidation of 4-alkyl-N,N-dimethylbenzylamines catalyzed by N-hydroxyphthalimide in acetic acid.

Eukaryotic cilia and flagella are chemo-mechanical oscillators capable of generating long-range coordinated motions known as metachronal waves. Pair synchronization is a fundamental requirement for these collective dynamics, but it is generally not sufficient for collective phase-locking, chiefly due to the effect of long-range interactions. Here we explore experimentally and numerically a minimal model for a ciliated surface: hydrodynamically coupled oscillators rotating above a no-slip plane. Increasing their distance from the wall profoundly affects the global dynamics, due to variations in hydrodynamic interaction range. The array undergoes a transition from a traveling wave to either a steady chevron pattern or one punctuated by periodic phase defects. Within the transition between these regimes the system displays behavior reminiscent of chimera states.

The incessant activity of swimming microorganisms has a direct physical effect on surrounding microscopic objects, leading to enhanced diffusion far beyond the level of Brownian motion with possible influences on the spatial distribution of non-motile planktonic species and particulate drifters. Here we study in detail the effect of eukaryotic flagellates, represented by the green microalga Chlamydomonas reinhardtii, on microparticles. Macro- and microscopic experiments reveal that microorganism-colloid interactions are dominated by rare close encounters leading to large displacements through direct entrainment. Simulations and theoretical modelling show that the ensuing particle dynamics can be understood in terms of a simple jump-diffusion process, combining standard diffusion with Poisson-distributed jumps. This heterogeneous dynamics is likely to depend on generic features of the near-field of swimming microorganisms with front-mounted flagella.

Interactions between microorganisms and solid boundaries play an important role in biological processes, such as egg fertilization, biofilm formation, and soil colonization, where microswimmers move within a structured environment. Despite recent efforts to understand their origin, it is not clear whether these interactions can be understood as being fundamentally of hydrodynamic origin or hinging on the swimmer's direct contact with the obstacle. Using a combination of experiments and simulations, here we study in detail the interaction of the biflagellate green alga Chlamydomonas reinhardtii, widely used as a model puller microorganism, with convex obstacles, a geometry ideally suited to highlight the different roles of steric and hydrodynamic effects. Our results reveal that both kinds of forces are crucial for the correct description of the interaction of this class of flagellated microorganisms with boundaries.

Groups of eukaryotic cilia and flagella are capable of coordinating their beating over large scales, routinely exhibiting collective dynamics in the form of metachronal waves. The origin of this behavior--possibly influenced by both mechanical interactions and direct biological regulation--is poorly understood, in large part due to a lack of quantitative experimental studies. Here we characterize in detail flagellar coordination on the surface of the multicellular alga Volvox carteri, an emerging model organism for flagellar dynamics. Our studies reveal for the first time that the average metachronal coordination observed is punctuated by periodic phase defects during which synchrony is partial and limited to specific groups of cells. A minimal model of hydrodynamically coupled oscillators can reproduce semi-quantitatively the characteristics of the average metachronal dynamics, and the emergence of defects. We systematically study the model's behaviour by assessing the effect of changing intrinsic rotor characteristics, including oscillator stiffness and the nature of their internal driving force, as well as their geometric properties and spatial arrangement. Our results suggest that metachronal coordination follows from deformations in the oscillators' limit cycles induced by hydrodynamic stresses, and that defects result from sufficiently steep local biases in the oscillators' intrinsic frequencies. Additionally, we find that random variations in the intrinsic rotor frequencies increase the robustness of the average properties of the emergent metachronal waves.

Flows generated by ensembles of flagella are crucial to development, motility and sensing, but the mechanisms behind this striking coordination remain unclear. We present novel experiments in which two micropipette-held somatic cells of Volvox carteri, with distinct intrinsic beating frequencies, are studied by high-speed imaging as a function of their separation and orientation. Analysis of time series shows that the interflagellar coupling, constrained by lack of connections between cells to be hydrodynamical, exhibits a spatial dependence consistent with theory. At close spacings it produces robust synchrony for thousands of beats, while at increasing separations synchrony is degraded by stochastic processes. Manipulation of the relative flagellar orientation reveals in-phase and antiphase states, consistent with dynamical theories. Flagellar tracking with exquisite precision reveals waveform changes that result from hydrodynamic coupling. This study proves unequivocally that flagella coupled solely through a fluid can achieve robust synchrony despite differences in their intrinsic properties.DOI: http://dx.doi.org/10.7554/eLife.02750.001., (Copyright © 2014, Brumley et al.)

Lung cancer remains the most common cause of cancer-related death worldwide and it continues to lack effective treatment. The increasingly large and diverse public databases of lung cancer gene expression constitute a rich source of candidate oncogenic drivers and therapeutic targets. To define novel targets for lung adenocarcinoma, we conducted a large-scale meta-analysis of genes specifically overexpressed in adenocarcinoma. We identified an 11-gene signature that was overexpressed consistently in adenocarcinoma specimens relative to normal lung tissue. Six genes in this signature were specifically overexpressed in adenocarcinoma relative to other subtypes of non-small cell lung cancer (NSCLC). Among these genes was the little studied protein tyrosine kinase PTK7. Immunohistochemical analysis confirmed that PTK7 is highly expressed in primary adenocarcinoma patient samples. RNA interference-mediated attenuation of PTK7 decreased cell viability and increased apoptosis in a subset of adenocarcinoma cell lines. Further, loss of PTK7 activated the MKK7-JNK stress response pathway and impaired tumor growth in xenotransplantation assays. Our work defines PTK7 as a highly and specifically expressed gene in adenocarcinoma and a potential therapeutic target in this subset of NSCLC., (©2014 American Association for Cancer Research.)

Groups of beating flagella or cilia often synchronize so that neighboring filaments have identical frequencies and phases. A prime example is provided by the unicellular biflagellate Chlamydomonas reinhardtii, which typically displays synchronous in-phase beating in a low-Reynolds number version of breaststroke swimming. We report the discovery that ptx1, a flagellar-dominance mutant of C. reinhardtii, can exhibit synchronization in precise antiphase, as in the freestyle swimming stroke. High-speed imaging shows that ptx1 flagella switch stochastically between in-phase and antiphase states, and that the latter has a distinct waveform and significantly higher frequency, both of which are strikingly similar to those found during phase slips that stochastically interrupt in-phase beating of the wild-type. Possible mechanisms underlying these observations are discussed.

Interactions between swimming cells and surfaces are essential to many microbiological processes, from bacterial biofilm formation to human fertilization. However, despite their fundamental importance, relatively little is known about the physical mechanisms that govern the scattering of flagellated or ciliated cells from solid surfaces. A more detailed understanding of these interactions promises not only new biological insights into structure and dynamics of flagella and cilia but may also lead to new microfluidic techniques for controlling cell motility and microbial locomotion, with potential applications ranging from diagnostic tools to therapeutic protein synthesis and photosynthetic biofuel production. Due to fundamental differences in physiology and swimming strategies, it is an open question of whether microfluidic transport and rectification schemes that have recently been demonstrated for pusher-type microswimmers such as bacteria and sperm cells, can be transferred to puller-type algae and other motile eukaryotes, because it is not known whether long-range hydrodynamic or short-range mechanical forces dominate the surface interactions of these microorganisms. Here, using high-speed microscopic imaging, we present direct experimental evidence that the surface scattering of both mammalian sperm cells and unicellular green algae is primarily governed by direct ciliary contact interactions. Building on this insight, we predict and experimentally verify the existence of optimal microfluidic ratchets that maximize rectification of initially uniform Chlamydomonas reinhardtii suspensions. Because mechano-elastic properties of cilia are conserved across eukaryotic species, we expect that our results apply to a wide range of swimming microorganisms.

From unicellular ciliates to the respiratory epithelium, carpets of cilia display metachronal waves, long-wavelength phase modulations of the beating cycles, which theory suggests may arise from hydrodynamic coupling. Experiments have been limited by a lack of organisms suitable for systematic study of flagella and the flows they create. Using time-resolved particle image velocimetry, we report the discovery of metachronal waves on the surface of the colonial alga Volvox carteri, whose large size and ease of visualization make it an ideal model organism for these studies. An elastohydrodynamic model of weakly coupled compliant oscillators, recast as interacting phase oscillators, reveals that orbit compliance can produce fast, robust synchronization in a manner essentially independent of boundary conditions, and offers an intuitive understanding of a possible mechanism leading to the emergence of metachronal waves.

A fundamental issue in the biology of eukaryotic flagella is the origin of synchronized beating observed in tissues and organisms containing multiple flagella. Recent studies of the biflagellate unicellular alga Chlamydomonas reinhardtii provided the first evidence that the interflagellar coupling responsible for synchronization is of hydrodynamic origin. To investigate this mechanism in detail, we study here synchronization in Chlamydomonas as its flagella slowly regrow after mechanically induced self-scission. The duration of synchronized intervals is found to be strongly dependent on flagellar length. Analysis within a stochastic model of coupled phase oscillators is used to extract the length dependence of the interflagellar coupling and the intrinsic beat frequencies of the two flagella. Physical and biological considerations that may explain these results are proposed.

Swimming microorganisms create flows that influence their mutual interactions and modify the rheology of their suspensions. While extensively studied theoretically, these flows have not been measured in detail around any freely-swimming microorganism. We report such measurements for the microphytes Volvox carteri and Chlamydomonas reinhardtii. The minute (∼0.3%) density excess of V. carteri over water leads to a strongly dominant Stokeslet contribution, with the widely-assumed stresslet flow only a correction to the subleading source dipole term. This implies that suspensions of V. carteri have features similar to suspensions of sedimenting particles. The flow in the region around C. reinhardtii where significant hydrodynamic interaction is likely to occur differs qualitatively from a puller stresslet, and can be described by a simple three-Stokeslet model.

It has long been conjectured that hydrodynamic interactions between beating eukaryotic flagella underlie their ubiquitous forms of synchronization; yet there has been no experimental test of this connection. The biflagellate alga Chlamydomonas is a simple model for such studies, as its two flagella are representative of those most commonly found in eukaryotes. Using micromanipulation and high-speed imaging, we show that the flagella of a C. reinhardtii cell present periods of synchronization interrupted by phase slips. The dynamics of slips and the statistics of phase-locked intervals are consistent with a low-dimensional stochastic model of hydrodynamically coupled oscillators, with a noise amplitude set by the intrinsic fluctuations of single flagellar beats.

The coordination of eukaryotic flagella is essential for many of the most basic processes of life (motility, sensing, and development), yet its emergence and regulation and its connection to locomotion are poorly understood. Previous studies show that the unicellular alga Chlamydomonas, widely regarded as an ideal system in which to study flagellar biology, swims forward by the synchronous action of its two flagella. Using high-speed imaging over long intervals, we found a richer behavior: A cell swimming in the dark stochastically switches between synchronous and asynchronous flagellar beating. Three-dimensional tracking shows that these regimes lead, respectively, to nearly straight swimming and to abrupt large reorientations, which yield a eukaryotic version of the "run-and-tumble" motion of peritrichously flagellated bacteria.

We describe an efficient technique for measuring the effective interaction potential for pairs of colloidal particles. The particles to be tested are confined in an extended optical trap, also known as a line tweezer, that is projected with the holographic optical trapping technique. Their diffusion along the line reflects not only their intrinsic interactions with each other, but also the influence of the line's potential energy landscape and interparticle interactions mediated by scattered light. We demonstrate that measurements of the particles' trajectories at just two laser powers can be used to correct explicitly for optically induced forces and that statistically optimal analysis for optically induced forces yields autocalibrated measurements of the particles' intrinsic interactions with remarkably few statistically independent measurements of the particles' separation.

Like-charged colloidal spheres dispersed in de-ionized water are supposed to repel each other. Instead, artifact-corrected video microscopy measurements reveal an anomalous long-ranged like-charge attraction in the interparticle pair potential when the spheres are confined to a layer by even a single-charged glass surface. These attractions can be masked by electrostatic repulsions at low ionic strengths. Coating the bounding surfaces with a conducting gold layer suppresses the attraction. These observations suggest a possible mechanism for the anomalous confinement-induced attractions.

We study the dynamic critical behavior of the Chayes-Machta dynamics for the Fortuin-Kasteleyn random-cluster model, which generalizes the Swendsen-Wang dynamics for the q-state Potts model to noninteger q, in two and three spatial dimensions, by Monte Carlo simulation. We show that the Li-Sokal bound z >or= alpha/nu is close to but probably not sharp in d = 2 and is far from sharp in d = 3, for all q. The conjecture z >or= beta/nu is false (for some values of q) in both d = 2 and d = 3.

Colloidal spheres localized in an array of harmonic wells form a thermally excited, viscously damped dynamical system capable of supporting propagating elastic waves. Experimentally realized with micrometer-scale polystyrene spheres localized in a line of holographic optical traps, the hydrodynamically coupled array's behavior is quantitatively explained by a model based on the Oseen superposition approximation. The spheres' purely dissipative coupling is predicted to mediate a crossover to a regime of underdamped propagating elastic waves with uniformly negative group velocities that has yet to be verified experimentally.

Holographic optical traps use the forces exerted by computer-generated holograms to trap, move and otherwise transform mesoscopically textured materials. This article introduces methods for optimizing holographic optical traps' efficiency and accuracy, and an optimal statistical approach for characterizing their performance. This combination makes possible real-time adaptive optimization.

We demonstrate that a cycle of three holographic optical trapping patterns can implement a thermal ratchet for diffusing colloidal spheres and that the ratchet-driven transport displays flux reversal as a function of the cycle frequency and the intertrap separation. Unlike previously described ratchet models, the approach we describe involves three equivalent states, each of which is locally and globally spatially symmetric, with spatiotemporal symmetry being broken by the sequence of states.