Magnetotactic bacteria Magnetic navigation on the microscale

Magnetotactic bacteria are aquatic microorganisms with the ability to swim along the field lines of a magnetic field, which in their natural environment is provided by the magnetic field of the Earth. They do so with the help of specialized magnetic organelles called magnetosomes, vesicles containing magnetic crystals. Magnetosomes are aligned along cytoskeletal filaments to give linear structures that can function as intracellular compass needles. The predominant viewpoint is that the cells passively align with an external magnetic field, just like a macroscopic compass needle, but swim actively along the field lines, propelled by their flagella. In this minireview, we give an introduction to this intriguing bacterial behavior and discuss recent advances in understanding it, with a focus on the swimming directionality, which is not only affected by magnetic fields, but also by gradients of the oxygen concentration

Molecular therapies for HCC: Looking outside the box

Summary Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. In addition, trials of immune checkpoint inhibitors reported encouraging efficacy signals. However, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting. Other important phase II studies have tested molecular therapies directed against different novel targets, such as transforming growth factor-beta, MET (hepatocyte growth factor receptor), and fibroblast growth factor receptor 4. These studies integrated translational research with the aim of better defining the biological tumour profile and identifying tumour and blood biomarkers that select patients who may really benefit from a specific molecular therapy. Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC

Swinging of red blood cells under shear flow

We reveal that under moderate shear stress (of the order of 0.1 Pa) red blood cells present an oscillation of their inclination (swinging) superimposed to the long-observed steady tanktreading (TT) motion. A model based on a fluid ellipsoid surrounded by a visco-elastic membrane initially unstrained (shape memory) predicts all observed features of the motion: an increase of both swinging amplitude and period (1/2 the TT period) upon decreasing the shear stress, a shear stress-triggered transition towards a narrow shear stress-range intermittent regime of successive swinging and tumbling, and a pure tumbling motion at lower shear stress-values.Comment: 4 pages 5 figures submitted to Physical Review Letter

Effects of interphase boundary anisotropy on the three-phase growth dynamics in the β(In) – In 2 Bi – γ(Sn) ternary-eutectic system

International audienceWe present an experimental investigation on the effects of the interphase energy anisotropy on the formation of three-phase growth microstructures during directional solidification (DS) of the β(In)-In2Bi-γ(Sn) ternary-eutectic system. Standard DS and rotating directional solidification (RDS) experiments were performed using thin alloy samples with real-time observation. We identified two main types of eutectic grains (EGs): (i) quasi-isotropic EGs within which the solidification dynamics do not exhibit any substantial anisotropy effect, and (ii) anisotropic EGs, within which RDS microstructures exhibit an alternation of locked and unlocked microstructures. EBSD analyses revealed (i) a strong tendency to an alignment of the In2Bi and γ(Sn) crystals (both hexagonal) with respect to the thin-sample walls, and (ii) the existence of special crystal orientation relationships (ORs) between the three solid phases in both quasi-isotropic and anisotropic EGs. We initiate a discussion on the dominating locking effect of the In2Bi-β(In) interphase boundary during quasi steady-state solidification, and the existence of strong crystal selection mechanisms during early nucleation and growth stages

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response.

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent. METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib. RESULTS: Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg \u274-weeks on/2-weeks off\u27 schedule; n=86 \u2737.5 mg continuous daily dosing (CDD)\u27)) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6-12.2) and 5.4 months (95% CI 3.5-6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29-0.62); P CONCLUSIONS: A 10% reduction within marker lesions identifies pNET patients benefiting from sunitinib treatment with implications for maintenance of dose intensity and future trial design

Discovery Prospects for a Supernova Signature of Biogenic Origin

Approximately 2.8 Myr before the present our planet was subjected to the debris of a supernova explosion. The terrestrial proxy for this event was the discovery of live atoms of 60Fe in a deep-sea ferromanganese crust. The signature for this supernova event should also reside in magnetite Fe3O4 microfossils produced by magnetotactic bacteria extant at the time of the Earth-supernova interaction, provided the bacteria preferentially uptake iron from fine-grained iron oxides and ferric hydroxides. Using estimates for the terrestrial supernova 60Fe flux, combined with our empirically derived microfossil concentrations in a deep-sea drill core, we deduce a conservative estimate of the ^{60}{Fe} fraction as 60Fe/Fe ~ 3.6 x 10^{-15}. This value sits comfortably within the sensitivity limit of present accelerator mass spectrometry capabilities. The implication is that a biogenic signature of this cosmic event is detectable in the Earth's fossil record.Comment: As it appears in Icaru