Twirling and Whirling: Viscous Dynamics of Rotating Elastica

Motivated by diverse phenomena in cellular biophysics, including bacterial flagellar motion and DNA transcription and replication, we study the overdamped nonlinear dynamics of a rotationally forced filament with twist and bend elasticity. Competition between twist injection, twist diffusion, and writhing instabilities is described by a novel pair of coupled PDEs for twist and bend evolution. Analytical and numerical methods elucidate the twist/bend coupling and reveal two dynamical regimes separated by a Hopf bifurcation: (i) diffusion-dominated axial rotation, or twirling, and (ii) steady-state crankshafting motion, or whirling. The consequences of these phenomena for self-propulsion are investigated, and experimental tests proposed.Comment: To be published in Physical Review Letter

Coiling Instability of Multilamellar Membrane Tubes with Anchored Polymers

We study experimentally a coiling instability of cylindrical multilamellar stacks of phospholipid membranes, induced by polymers with hydrophobic anchors grafted along their hydrophilic backbone. Our system is unique in that coils form in the absence of both twist and adhesion. We interpret our experimental results in terms of a model in which local membrane curvature and polymer concentration are coupled. The model predicts the occurrence of maximally tight coils above a threshold polymer occupancy. A proper comparison between the model and experiment involved imaging of projections from simulated coiled tubes with maximal curvature and complicated torsions.Comment: 11 pages + 7 GIF figures + 10 JPEG figure

Evidence for a singularity in ideal magnetohydrodynamics: implications for fast reconnection

Numerical evidence for a finite-time singularity in ideal 3D magnetohydrodynamics (MHD) is presented. The simulations start from two interlocking magnetic flux rings with no initial velocity. The magnetic curvature force causes the flux rings to shrink until they come into contact. This produces a current sheet between them. In the ideal compressible calculations, the evidence for a singularity in a finite time $t_c$ is that the peak current density behaves like $|J|_\infty \sim 1/(t_c-t)$ for a range of sound speeds (or plasma betas). For the incompressible calculations consistency with the compressible calculations is noted and evidence is presented that there is convergence to a self-similar state. In the resistive reconnection calculations the magnetic helicity is nearly conserved and energy is dissipated.Comment: 4 pages, 4 figure

The Viscous Nonlinear Dynamics of Twist and Writhe

Exploiting the "natural" frame of space curves, we formulate an intrinsic dynamics of twisted elastic filaments in viscous fluids. A pair of coupled nonlinear equations describing the temporal evolution of the filament's complex curvature and twist density embodies the dynamic interplay of twist and writhe. These are used to illustrate a novel nonlinear phenomenon: ``geometric untwisting" of open filaments, whereby twisting strains relax through a transient writhing instability without performing axial rotation. This may explain certain experimentally observed motions of fibers of the bacterium B. subtilis [N.H. Mendelson, et al., J. Bacteriol. 177, 7060 (1995)].Comment: 9 pages, 4 figure

Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors

Universality in Bacterial Colonies

The emergent spatial patterns generated by growing bacterial colonies have been the focus of intense study in physics during the last twenty years. Both experimental and theoretical investigations have made possible a clear qualitative picture of the different structures that such colonies can exhibit, depending on the medium on which they are growing. However, there are relatively few quantitative descriptions of these patterns. In this paper, we use a mechanistically detailed simulation framework to measure the scaling exponents associated with the advancing fronts of bacterial colonies on hard agar substrata, aiming to discern the universality class to which the system belongs. We show that the universal behavior exhibited by the colonies can be much richer than previously reported, and we propose the possibility of up to four different sub-phases within the medium-to-high nutrient concentration regime. We hypothesize that the quenched disorder that characterizes one of these sub-phases is an emergent property of the growth and division of bacteria competing for limited space and nutrients.Comment: 12 pages, 5 figure

Erasmus Language students in a British University – a case study

Students’ assessment of their academic experience is actively sought by Higher Education institutions, as evidenced in the National Student Survey introduced in 2005. Erasmus students, despite their growing numbers, tend to be excluded from these satisfaction surveys, even though they, too, are primary customers of a University. This study aims to present results from bespoke questionnaires and semi-structured interviews with a sample of Erasmus students studying languages in a British University. These methods allow us insight into the experience of these students and their assessment as a primary customer, with a focus on language learning and teaching, university facilities and student support. It investigates to what extent these factors influence their levels of satisfaction and what costs of adaptation if any, they encounter. Although excellent levels of satisfaction were found, some costs affect their experience. They relate to difficulties in adapting to a learning methodology based on a low number of hours and independent learning and to a guidance and support system seen as too stifling. The results portray this cohort’s British University as a well-equipped and well-meaning but ultimately overbearing institution, which may indicate that minimising costs can eliminate some sources of dissatisfaction

Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies

Sequence variants at the TERT-CLPTM1L locus in chromosome 5p have been recently associated with disposition for various cancers. Here we show that this locus including the gene encoding the telomerase reverse-transcriptase TERT at 5p13.33 is rarely but recurrently targeted by somatic chromosomal translocations to IGH and non-IG loci in B-cell neoplasms, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. In addition, cases with genomic amplification of TERT locus were identified. Tumors bearing chromosomal aberrations involving TERT showed higher TERT transcriptional expression and increased telomerase activity. These data suggest that deregulation of TERT gene by chromosomal abnormalities leading to increased telomerase activity might contribute to B-cell lymphomagenesis

Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer

There is a subtype of breast cancer characterized by the overexpression of the oncogene HER2. Although most patients with this diagnosis benefit from HER2-targeted treatments, some do not respond to these therapies and others develop resistance with time. New tools are therefore warranted for the treatment of this patient population, and for early identification of those individuals at a higher risk of developing innate or acquired resistance to current treatments. Here, we show that HER2 forms heteromer complexes with the cannabinoid receptor CB2R, the expression of these structures correlates with poor patient prognosis, and their disruption promotes antitumor responses. Collectively, our results support HER2–CB2R heteromers as new therapeutic targets and prognostic tools in HER2+ breast cancer

Kinetics of superoxide reactions with dissolved organic matter in tropical Atlantic surface waters near Cape Verde (TENATSO)

The decay kinetics of superoxide (O2−) reacting with organic matter was examined in oligotrophic waters at, and nearby, the TENATSO ocean observatory adjacent to the Cape Verde archipelago. Superoxide is the short-lived primary photochemical product of colored dissolved organic matter (CDOM) photolysis and also reacts with CDOM or trace metals (Cu, Fe) to form H2O2. In the present work we focused our investigations on reactions between CDOM and superoxide. O2− decay kinetics experiments were performed by adding KO2 to diethylenetriaminepentaacetic acid (DTPA) amended seawater and utilizing an established chemiluminescence technique for the detection of O2− at nM levels. In Cape Verdean waters we found a significant reactivity of superoxide with CDOM with maximal rates adjacent to the chlorophyll maximum, presumably from production of new CDOM from bacteria/phytoplankton. This work highlights a poorly understood process which impacts on the biogeochemical cycling of CDOM and trace metals in the open ocean