Ciliate Biology: The Graceful Hunt of a Shape-Shifting Predator

This is the final version. Available from Elsevier via the DOI in this record. Even single-celled eukaryotes are capable of highly complex behaviors. A new study reveals how one unicellular predator actively manipulates and remodels its unique cytoskeletal morphology to achieve rapid shape changes and a remarkable hunting strategy

Coordination of eukaryotic cilia and flagella

This is the final version. Available on open access from Portland Press via the DOI in this recordPropulsion by slender cellular appendages called cilia and flagella is an ancient means of locomotion. Unicellular organisms evolved myriad strategies to propel themselves in fluid environments, often involving significant differences in flagella number, localisation and modes of actuation. Remarkably, these appendages are highly conserved, occurring in many complex organisms such as humans, where they may be found generating physiological flows when attached to surfaces (e.g. airway epithelial cilia), or else conferring motility to male gametes (e.g. undulations of sperm flagella). Where multiple cilia arise, their movements are often observed to be highly coordinated. Here I review the two main mechanisms for motile cilia coordination, namely, intracellular and hydrodynamic, and discuss their relative importance in different ciliary systems.This work was supported by a startup grant from the Living Systems Institute, University of Exeter, and a Springboard Award from the Academy of Medical Sciences

Rhythmicity, Recurrence, and Recovery of Flagellar Beating

This is the final version of the article. Available from American Physical Society via the DOI in this recordThe eukaryotic flagellum beats with apparently unfailing periodicity, yet responds rapidly to stimuli. Like the human heartbeat, flagellar oscillations are now known to be noisy. Using the alga C. reinhardtii, we explore three aspects of nonuniform flagellar beating. We report the existence of rhythmicity, waveform noise peaking at transitions between power and recovery strokes, and fluctuations of interbeat intervals that are correlated and even recurrent, with memory extending to hundreds of beats. These features are altered qualitatively by physiological perturbations. Further, we quantify the recovery of periodic breaststroke beating from transient hydrodynamic forcing. These results will help constrain microscopic theories on the origins and regulation of flagellar beating.Financial support is acknowledged from the Engineering and Physical Sciences Research Council, European Research Council Advanced Investigator Grant No. 247333, and a Senior Investigator Award from the Wellcome Trust

Coordinated beating of algal flagella is mediated by basal coupling

This is the final version of the article. Available from National Academy of Sciences via the DOI in this recordCilia and flagella often exhibit synchronized behavior; this includes phase locking, as seen in Chlamydomonas, and metachronal wave formation in the respiratory cilia of higher organisms. Since the observations by Gray and Rothschild of phase synchrony of nearby swimming spermatozoa, it has been a working hypothesis that synchrony arises from hydrodynamic interactions between beating filaments. Recent work on the dynamics of physically separated pairs of flagella isolated from the multicellular alga Volvox has shown that hydrodynamic coupling alone is sufficient to produce synchrony. However, the situation is more complex in unicellular organisms bearing few flagella. We show that flagella of Chlamydomonas mutants deficient in filamentary connections between basal bodies display markedly different synchronization from the wild type. We perform micromanipulation on configurations of flagella and conclude that a mechanism, internal to the cell, must provide an additional flagellar coupling. In naturally occurring species with 4, 8, or even 16 flagella, we find diverse symmetries of basal body positioning and of the flagellar apparatus that are coincident with specific gaits of flagellar actuation, suggesting that it is a competition between intracellular coupling and hydrodynamic interactions that ultimately determines the precise form of flagellar coordination in unicellular algae.This work is supported by a Junior Research Fellowship from Magdalene College Cambridge (to K.Y.W.) and a Wellcome Trust Senior Investigator Award (to R.E.G.)

Time Irreversibility and Criticality in the Motility of a Flagellate Microorganism

This is the final version of the article. Available from American Physical Society via the DOI in this record.Active living organisms exhibit behavioral variability, partitioning between fast and slow dynamics. Such variability may be key to generating rapid responses in a heterogeneous, unpredictable environment wherein cellular activity effects continual exchanges of energy fluxes. We demonstrate a novel, noninvasive strategy for revealing nonequilibrium control of swimming—specifically, in an octoflagellate microalga. These organisms exhibit surprising features of flagellar excitability and mechanosensitivity, which characterize a novel, time-irreversible “run-stop-shock” motility comprising forward runs, knee-jerk shocks with dramatic beat reversal, and long stops during which cells are quiescent yet continue to exhibit submicron flagellar vibrations. Entropy production, associated with flux cycles arising in a reaction graph representation of the gait-switching dynamics, provides a direct measure of detailed balance violation in this primitive alga.Financial support is acknowledged from Magdalene College, Cambridge, through a Junior Research Fellowship (K. Y. W.), and Senior Investigator Grants No. 097855MA and No. 207510/Z/17/Z from the Wellcome Trust (R. E. G.). We thank Robert G. Endres and Eric Lauga for the discussions

Postablation stimulated thyroglobulin level is an important predictor of biochemical complete remission after reoperative cervical neck dissection in persistent/recurrent papillary thyroid carcinoma

BACKGROUND: The efficacy of reoperative cervical neck dissection (RND) in achieving biochemical complete remission (BCR) (or postreoperation stimulated thyroglobulin [sTg] of 2 ng/mL) were correlated with the postreoperation sTg levels after RNDs. Patients' clinicopathological characteristics, operative findings, and subsequent RNDs were compared between those with BCR after RNDs and those without. RESULTS: Those with postablation sTg levels of 2 ng/mL. Overall BCR gradually decreased after each subsequent RND. Postablation sTg significantly correlated with postreoperation sTg (rho = 0.509, p < 0.001). After adjusting for the number of metastatic lymph nodes excised at first RND and presence of extranodal extension, postablation sTg of </= 0.2 ng/mL was the only independent factor for BCR after one or more RNDs (odds ratio 37.0, 95 % confidence interval 5.68-250.0, p = 0.001). CONCLUSIONS: Only a third of patients who underwent one or more RNDs for persistent/recurrent PTC had BCR afterward. Postablation sTg level was an independent factor for BCR. Completeness of the initial operation is important for the subsequent success of RND.published_or_final_versio

Lag, lock, sync, slip: the many 'phases' of coupled flagella

This is the final version of the article. Available from the Royal Society via the DOI in this recordIn a multitude of life's processes, cilia and flagella are found indispensable. Recently, the biflagellated chlorophyte alga Chlamydomonas has become a model organism for the study of ciliary motility and synchronization. Here, we use high-speed, high-resolution imaging of single pipette-held cells to quantify the rich dynamics exhibited by their flagella. Underlying this variability in behaviour are biological dissimilarities between the two flagella—termed cis and trans, with respect to a unique eyespot. With emphasis on the wild-type, we derive limit cycles and phase parametrizations for self-sustained flagellar oscillations from digitally tracked flagellar waveforms. Characterizing interflagellar phase synchrony via a simple model of coupled oscillators with noise, we find that during the canonical swimming breaststroke the cis flagellum is consistently phase-lagged relative to, while remaining robustly phase-locked with, the trans flagellum. Transient loss of synchrony, or phase slippage, may be triggered stochastically, in which the trans flagellum transitions to a second mode of beating with attenuated beat envelope and increased frequency. Further, exploiting this alga's ability for flagellar regeneration, we mechanically induced removal of one or the other flagellum of the same cell to reveal a striking disparity between the beatings of the cis and trans flagella, in isolation. These results are evaluated in the context of the dynamic coordination of Chlamydomonas flagella.Financial support is acknowledged from the EPSRC, ERC Advanced Investigator Grant 247333, and a Senior Investigator Award from the Wellcome Trust (R.E.G.)

Establishment of a bortezomib-resistant Chinese human multiple myeloma cell line: MMLAL

published_or_final_versio

Classifying rational densities using two one-dimensional cellular automata

Given a (finite but arbitrarily long) string of zeros and ones, we report a way to determine if the number of ones is less than, greater than, or equal to a prescribed number by applying two sets of cellular automation rules in succession. Thus, we solve the general one-dimensional density classification problem using two cellular automata.published_or_final_versio

Long-Term Outcomes for Older Patients with Papillary Thyroid Carcinoma: Should Another Age Cutoff Beyond 45 Years Be Added?

© 2014, Society of Surgical Oncology. Background: Although an age cutoff of 45 years has often been adopted to stratify cancer risk in papillary thyroid carcinoma (PTC), both cancer-specific survival (CSS) and disease-specific survival (DFS) continue to worsen beyond this cutoff. This study aimed to determine whether advanced age (i.e., >60 years) at diagnosis was an independent predictor of CSS and DFS in older (≥45 years) patients. Methods: This study analyzed 407 PTC patients with a minimal follow-up period of 7 years. Standard protocol was followed. Both CSS and DFS were estimated using the Kaplan–Meier method and compared with the log-rank test. Variables shown to be significant by the log-rank test were entered into the Cox regression analysis. Results: During a median follow-up period of 15.1 years, 51 patients (12.5 %) died of PTC, whereas 80 (20.5 %) experienced at least one recurrence. For CSS, age beyond 60 years (hazard ratio [HR], 3.027; 95 % confidence interval [CI] 1.369–6.690; p = 0.006), tumor size greater than 4 cm (HR 2.043; 95 % CI 1.141–4.255; p = 0.049), central nodal metastases (HR 2.726; 95 % CI 1.198–6.200; p = 0.017), lateral nodal metastases (HR 5.247; 95 % CI 2.987–9.216; p < 0.001), and distant metastases (HR 4.297; 95 % CI 1.726–2.506; p = 0.002) were independent predictors. For DFS, only tumor size greater than 4 cm (HR 1.733; 95 % CI 1.030–3.058; p = 0.049), central nodal metastases (HR 2.362; 95 % CI 1.010–5.523; p = 0.047), and lateral nodal metastases (HR 4.383; 95 % CI 2.388–8.042; p < 0.001) were independent predictors. Conclusions: Advanced age was an independent predictor of CSS, and cancer-related death risk showed a continuing increase beyond the age of 60 years. However, advanced age was not an independent predictor of DFS. Therefore, having another age cutoff appears justifiable for stratifying risk of cancer-related death but less justifiable for disease recurrence. Tumor size as well as central and lateral nodal metastases independently predicted CSS and DFS.postprin