1,960 research outputs found
Environmental control of microtubule-based bidirectional cargo-transport
Inside cells, various cargos are transported by teams of molecular motors.
Intriguingly, the motors involved generally have opposite pulling directions,
and the resulting cargo dynamics is a biased stochastic motion. It is an open
question how the cell can control this bias. Here we develop a model which
takes explicitly into account the elastic coupling of the cargo with each
motor. We show that bias can be simply controlled or even reversed in a
counterintuitive manner via a change in the external force exerted on the cargo
or a variation of the ATP binding rate to motors. Furthermore, the
superdiffusive behavior found at short time scales indicates the emergence of
motor cooperation induced by cargo-mediated coupling
Fluctuation effects in bidirectional cargo transport
We discuss a theoretical model for bidirectional cargo transport in
biological cells, which is driven by teams of molecular motors and subject to
thermal fluctuations. The model describes explicitly the directed motion of the
molecular motors on the filament. The motor-cargo coupling is implemented via
linear springs. By means of extensive Monte Carlo simulations we show that the
model describes the experimentally observed regimes of anomalous diffusion,
i.e. subdiffusive behavior at short times followed by superdiffusion at
intermediate times. The model results indicate that subdiffuse regime is
induced by thermal fluctuations while the superdiffusive motion is generated by
correlations of the motors' activity. We also tested the efficiency of
bidirectional cargo transport in crowded areas by measuring its ability to pass
barriers with increased viscosity. Our results show a remarkable gain of
efficiency for high viscosities.Comment: 10 pages, 6 figure
The good and the bad of T cell cross-reactivity: challenges and opportunities for novel therapeutics in autoimmunity and cancer
T cells are main actors of the immune system with an essential role in protection against pathogens and cancer. The molecular key event involved in this absolutely central task is the interaction of membrane-bound specific T cell receptors with peptide-MHC complexes which initiates T cell priming, activation and recall, and thus controls a range of downstream functions. While textbooks teach us that the repertoire of mature T cells is highly diverse, it is clear that this diversity cannot possibly cover all potential foreign peptides that might be encountered during life. TCR cross-reactivity, i.e. the ability of a single TCR to recognise different peptides, offers the best solution to this biological challenge. Reports have shown that indeed, TCR cross-reactivity is surprisingly high. Hence, the T cell dilemma is the following: be as specific as possible to target foreign danger and spare self, while being able to react to a large spectrum of body-threatening situations. This has major consequences for both autoimmune diseases and cancer, and significant implications for the development of T cell-based therapies. In this review, we will present essential experimental evidence of T cell cross-reactivity, implications for two opposite immune conditions, i.e. autoimmunity vs cancer, and how this can be differently exploited for immunotherapy approaches. Finally, we will discuss the tools available for predicting cross-reactivity and how improvements in this field might boost translational approaches
Les femmes et l’approche du Buen Vivir en Bolivie : entre l’absence et l’émergence
Au début du XXIe siècle, le gouvernement bolivien a redonné une place prépondérante au mode de vie indigène, s’inspirant de l’approche du Buen Vivir, posée comme une alternative au paradigme dominant du développement. Cette approche a été constitutionnalisée et promue auprès des citoyens. Qu’en est-il de la situation des femmes dans ce contexte ? Selon le vocabulaire de B. de Sousa Santos, les Boliviennes indigènes constituent des « absences » dans l’« émergence » qu’est le Buen Vivir. Utilisant l’approche de la géographie féministe, nous avons interrogé des femmes expertes ainsi que des indigènes. Nous avons recueilli leur point de vue sur les répercussions des politiques gouvernementales et de la résurgence du Buen Vivir.At the beginning of the XXIe century, the Bolivian government gave a prominent place to the indigenous lifestyle, inspired by the Buen Vivir approach. This approach was raised as an alternative to the dominant western paradigm of development. It was constitutionalized and promoted as a way of life in Bolivia. What is the place of women in this new context? According to B. de Sousa Santos, Bolivian indigenous women are ’absent’ from the ’emergent’ approach which is the Buen Vivir. From a feminist geography perspective, we met Bolivian women, professionals as well as indigenous, and we asked them about the repercussions of the implementation of Buen Vivir on their lives
Fine-specificity of cytotoxic T lymphocytes which recognize conserved epitopes of the Gag protein of human immunodeficiency virus type 1
Human immunodeficiency virus type 1 (HIV-1) Gag-specific cytotoxic T lymphocyte (CTL) responses were studied in seven seropositive long-term asymptomatic individuals (CDC A1)with stable CD4 counts for more than 8 years. Using a set of partially overlapping peptides covering the whole Gag, five 15-20-mer peptides were found to contain CTL epitopes. Further characterization of these epitopes revealed a new HLA-A25-restricted CTL epitope in p24, p24203-212 ETINEEAAEW. This region of Gag highly conserved in clades B and D of HIV-1. Naturally occurring amino acid sequences, containing p24203D (consensus HIV-1 clades A, C, F, G and H) or p24204I(HIV-2(ROD)) were not recognized by CTL recognizing the index peptide. No virus variants with mutations in this sequence were found in peripheral blood mononuclear cells from the HIV-1-infected individual concerned during the 8 year observation period, indicating that the virus had not escaped from the observed CTL response.</p
Long-term quality of life in adult survivors of pediatric differentiated thyroid carcinoma
Context: Little is known about long-term quality of life (QoL) of survivors of pediatric differentiated
thyroid carcinoma. Therefore, this study aimed to evaluate generic health-related QoL (HRQoL),
fatigue, anxiety, and depression in these survivors compared with matched controls, and to evaluate
thyroid cancer–specific HRQoL in survivors only.
Design: Survivors diagnosed between 1970 and 2013 at age #18 years, were included. Exclusion
criteria were a follow-up ,5 years, attained age ,18 years, or diagnosis of DTC as a second
malignant neoplasm (SMN). Controls were matched by age, sex, and socioeconomic status. Survivors
and controls were asked to complete 3 questionnaires [Short-Form 36 (HRQoL), Multidimensional
Fatigue Inventory 20 (fatigue), and Hospital Anxiety and Depression Scale (anxiety/depression)].
Survivors completed a thyroid cancer–specific HRQoL questionnaire.
Results: Sixty-seven survivors and 56 controls. Median age of survivors at evaluation was
34.2 years (range, 18.8 to 61.7). Median follow-up was 17.8 years (range, 5.0 to 44.7). On most
QoL subscales, scores of survivors and controls did not differ significantly. However, survivors
had more physical problems (P = 0.031), role limitations due to physical problems (P = 0.021),
and mental fatigue (P = 0.016) than controls. Some thyroid cancer–specific complaints (e.g.,
sensory complaints and chilliness) were present in survivors. Unemployment and more extensive
disease or treatment characteristics were most frequently associated with worse QoL.
Conclusions: Overall, long-term QoL in survivors of pediatric DTC was normal. Survivors experienced
mild impairment of QoL in some domains (physical problems, mental fatigue, and various thyroid
cancer–specific complaints). Factors possibly affecting QoL need further exploration
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