First order Fermi acceleration driven by magnetic reconnection

A box model is used to study first order Fermi acceleration driven by magnetic reconnection. It is shown, at least in this simple model, that the spectral index of the accelerated particles is related to the total compression in the same way as in diffusive shock acceleration and is not, as has been suggested, a universal $E^{-5/2}$ spectrum. The acceleration time-scale is estimated and some comments made about the applicability of the process.Comment: Accepted for MNRA

MicroRNAs in lung cancer

Lung cancer (LC) is a serious public health problem responsible for the majority of cancer deaths and comorbidities in developed countries. Tobacco smoking is considered the main risk factor for LC; however, only a few smokers will be affected by this cancer. Current screening methods are focused on identifying the early stages of this malignancy. Thus, new data concerning the roles of microRNA alterations in inflammation, epithelial-mesenchymal transition and lung disease have increased hope about LC pathogenesis, diagnosis, treatment and prognosis. MicroRNA mechanisms include angiogenesis promotion, cell cycle regulation by modulating cellular proliferation and apoptosis, and migration and invasion inhibition. In this context, this manuscript reviews the current information about many important microRNAs as they relate to the initiation and progression of LC.info:eu-repo/semantics/publishedVersio

Contrasting changes in palatability following senescence of the lichenized fungi Lobaria pulmonaria and L. scrobiculata

Epiphytic lichens can contribute significantly to ecosystem nutrient input because they efficiently accumulate atmospheric mineral nutrients and, in the case of cyanolichens, also fix nitrogen. The rate at which carbon and other nutrients gained by lichens enters the ecosystem is determined by lichen litter decomposability and by invertebrate consumption of lichen litter. In turn, these processes are driven by the secondary compounds present in senesced lichens. Therefore, we explored how lichen palatability and concentrations of secondary compounds change with tissue senescence for Lobaria pulmonaria, a green algal lichen with cyanobacterial cephalodia, and L. scrobiculata, a cyanobacterial lichen. During senescence both lichens lost 38-48% of their stictic acid chemosyndrome, while m-scrobiculin and usnic acid in L. scrobiculata remained unchanged. Snails preferred senesced rather than fresh L. pulmonaria, while senesced L. scrobiculata were avoided. This provides evidence that species with labile secondary compounds will have higher turnover rates, through consumption and decomposition, than those producing more stable secondary compounds

In vivo expression of natural killer cell inhibitory receptors by human melanoma-specific cytolytic T lymphocytes.

Natural killer (NK) receptor signaling can lead to reduced cytotoxicity by NK cells and cytolytic T lymphocytes (CTLs) in vitro. Whether T cells are inhibited in vivo remains unknown, since peptide antigen-specific CD8(+) T cells have so far not been found to express NK receptors in vivo. Here we demonstrate that melanoma patients may bear tumor-specific CTLs expressing NK receptors. The lysis of melanoma cells by patient-derived CTLs was inhibited by the NK receptor CD94/NKG2A. Thus, tumor-specific CTL activity may be decreased through NK receptor triggering in vivo

Fermi~I particle acceleration in converging flows mediated by magnetic reconnection

Context. Converging flows with strong magnetic fields of different polarity can accelerate particles through magnetic reconnection. If the particle mean free path is longer than the reconnection layer is thick, but much shorter than the entire reconnection structure, the particle will mostly interact with the incoming flows potentially with a very low escape probability. Aims. We explore, in general and also in some specific scenarios, the possibility of particles to be accelerated in a magnetic reconnection layer by interacting only with the incoming flows. Methods. We characterize converging flows that undergo magnetic reconnection, and derive analytical estimates for the particle energy distribution, acceleration rate, and maximum energies achievable in these flows. We also discuss a scenario, based on jets dominated by magnetic fields of changing polarity, in which this mechanism may operate. Results. The proposed acceleration mechanism operates if the reconnection layer is much thinner than its transversal characteristic size, and the magnetic field has a disordered component. Synchrotron losses may prevent electrons from entering in this acceleration regime. The acceleration rate should be faster, and the energy distribution of particles harder than in standard diffusive shock acceleration. The interaction of obstacles with the innermost region of jets in active galactic nuclei and microquasars may be suitable sites for particle acceleration in converging flows.Comment: 4 pages, 2 figures, Reserch Note, in press, A&A (final version

Heterogeneity assessment of functional T cell avidity.

The potency of cellular immune responses strongly depends on T cell avidity to antigen. Yet, functional avidity measurements are rarely performed in patients, mainly due to the technical challenges of characterizing heterogeneous T cells. The mean functional T cell avidity can be determined by the IFN-γ Elispot assay, with titrated amounts of peptide. Using this assay, we developed a method revealing the heterogeneity of functional avidity, represented by the steepness/hillslope of the peptide titration curve, documented by proof of principle experiments and mathematical modeling. Our data show that not only natural polyclonal CD8 T cell populations from cancer patients, but also monoclonal T cells differ strongly in their heterogeneity of functional avidity. Interestingly, clones and polyclonal cells displayed comparable ranges of heterogeneity. We conclude that besides the mean functional avidity, it is feasible and useful to determine its heterogeneity (hillslope) for characterizing T cell responses in basic research and patient investigation

A tetravalent nanovaccine that inhibits growth of HPV-associated head and neck carcinoma via dendritic and T cell activation.

The global incidence of human papillomavirus (HPV) associated head and neck carcinoma is on the rise, in response to this a tetravalent therapeutic vaccine named Qβ-HPVag was developed. This vaccine, utilizing virus-like particles (VLPs) loaded with toll-like receptor ligands and chemically coupled to four HPV16-derived peptides, demonstrated strong anti-tumor effects in a murine head and neck cancer model. Qβ-HPVag impeded tumor progression, increased infiltration of HPV-specific T cells, and significantly improved survival. The vaccine`s efficacy was associated with immune repolarization in the tumor microenvironment, characterized by expanded activated dendritic cell subsets (cDC1, cDC2, DC3). Notably, mice responding to treatment exhibited a higher percentage of migratory DC3 cells expressing CCR7. These findings suggest promising prospects for optimized VLP-based vaccines in treating HPV-associated head and neck cancer

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia consists of a heterogenous group of inherited disorders due to enzymatic defects in the biosynthetic pathway of cortisol and/or aldosterone. This results in glucocorticoid deficiency, mineralocorticoid deficiency, and androgen excess. 95% of CAH cases are due to 21-hydroxylase deficiency. Clinical forms range from the severe, classical CAH associated with complete loss of enzyme function, to milder, non-classical forms (NCAH). Androgen excess affects the pilosebaceous unit, causing cutaneous manifestations such as acne, androgenetic alopecia and hirsutism. Clinical differential diagnosis between NCAH and polycystic ovary syndrome may be difficult. In this review, the evaluation of patients with suspected CAH, the clinical presentation of CAH forms, with emphasis on the cutaneous manifestations of the disease, and available treatment options, will be discussed

Inflammatory B cells correlate with failure to checkpoint blockade in melanoma patients.

The understanding of the role of B cells in patients with solid tumors remains insufficient. We found that circulating B cells produced TNFα and/or IL-6, associated with unresponsiveness and poor overall survival of melanoma patients treated with anti-CTLA4 antibody. Transcriptome analysis of B cells from melanoma metastases showed enriched expression of inflammatory response genes. Publicly available single B cell data from the tumor microenvironment revealed a negative correlation between TNFα expression and response to immune checkpoint blockade. These findings suggest that B cells contribute to tumor growth via the production of inflammatory cytokines. Possibly, these B cells are different from tertiary lymphoid structure-associated B cells, which have been described to correlate with favorable clinical outcome of cancer patients. Further studies are required to identify and characterize B cell subsets and their functions promoting or counteracting tumor growth, with the aim to identify biomarkers and novel treatment targets

UHECRs from magnetic reconnection in relativistic jets

Ultra-high energy cosmic rays (UHECRs) may be produced in active galactic nuclei (AGN) or gamma-ray burst (GRB) jets. I argue that magnetic reconnection in jets can accelerate UHECRs rather independently of physical processes in the magnetic dissipation region. First order Fermi acceleration can efficiently take place in the region where the unreconnected (upstream) magnetized fluid converges into the reconnection layer. I find that protons can reach energies up to E~10^{20} eV in GRB and powerful AGN jets while iron nuclei can reach similar energies in AGN jets of more moderate luminosity.Comment: 5 pages, 2 figures, MNRAS Letters, in press, Sect. 3.3 added to match the published versio