Multivalent Calixarene-Based Liposomes as Platforms for Gene and Drug Delivery

The formation of calixarene-based liposomes was investigated, and the characterization of these nanostructures was carried out using several techniques. Four amphiphilic calixarenes were used. The length of the hydrophobic chains attached to the lower rim as well as the nature of the polar group present in the upper rim of the calixarenes were varied. The lipid bilayer was formed with one calixarene and with the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, DOPE. The cytotoxicity of the liposomes for various cell lines was also studied. From the results obtained, the liposomes formed with the least cytotoxic calixarene, (TEAC12)4 , were used as nanocarriers of both nucleic acids and the antineoplastic drug doxorubicin, DOX. Results showed that (TEAC12)4/DOPE/p-EGFP-C1 lipoplexes, of a given composition, can transfect the genetic material, although the transfection efficiency substantially increases in the presence of an additional amount of DOPE as coadjuvant. On the other hand, the (TEAC12)4/DOPE liposomes present a high doxorubicin encapsulation efficiency, and a slow controlled release, which could diminish the side effects of the drugThis work was financed by the Consejería de Conocimiento, Innovación y Universidades de la Junta de Andalucía (FQM-206, FQM-274, and PY20-01234), the VI Plan Propio Universidad de Sevilla (PP2019/00000748), RTI2018-100692-B-100; P18-RT-1271; PI18-0005-2018; VI-PP AY.SUPLEM2019; RYC-2015-18670, The R+D+I grant PID2019-104195G from the Spanish Ministry of Science and Innovation-Agencia Estatal de Investigación/10.13039/501100011033 (P.H.) and the European Union (Feder Funds). The authors thank the University of Seville for the grant VPPI-US. J.A.L. also thanks the Fundación ONCE funded by the Fondo Social Europe

Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia

International audienc

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies $E>E_{th}=5.5\times 10^{19}$ eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at $E>E_{th}$ are heavy nuclei with charge $Z$, the proton component of the sources should lead to excesses in the same regions at energies $E/Z$. We here report the lack of anisotropies in these directions at energies above $E_{th}/Z$ (for illustrative values of $Z=6,\ 13,\ 26$). If the anisotropies above $E_{th}$ are due to nuclei with charge $Z$, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

Endogenous formaldehyde is a hematopoietic stem cell genotoxin and metabolic carcinogen

Endogenous formaldehyde is produced by numerous biochemical pathways fundamental to life, and it can crosslink both DNA and proteins. However, the consequences of its accumulation are unclear. Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5−/− mice therefore accumulate formaldehyde adducts in DNA. The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein. Adh5−/−Fancd2−/− mice reveal an essential requirement for these protection mechanisms in hematopoietic stem cells (HSCs), leading to their depletion and precipitating bone marrow failure. More widespread formaldehyde-induced DNA damage also causes karyomegaly and dysfunction of hepatocytes and nephrons. Bone marrow transplantation not only rescued hematopoiesis but, surprisingly, also preserved nephron function. Nevertheless, all of these animals eventually developed fatal malignancies. Formaldehyde is therefore an important source of endogenous DNA damage that is counteracted in mammals by a conserved protection mechanism

Production of excited beauty states in Z decays

A data sample of about 3.0 million hadronic Z decays collected by the ALEPH experiment at LEP in the years 1991 through 1994, is used to make an inclusive selection of B~hadron events. In this event sample 4227 \pm 140 \pm 252 B^* mesons in the decay B^* \to B \gamma and 1944 \pm 108 \pm 161 B^{**} mesons decaying into a B~meson and a charged pion are reconstructed. For the well established B^* meson the following quantities areobtained: \Delta M = M_{B^*} - M_{B} = (45.30\pm 0.35\pm 0.87)~\mathrm{MeV}/c^2 and N_{B^*}/(N_B+N_{B^*}) = (77.1 \pm 2.6 \pm 7.0)\%. The angular distribution of the photons in the B^* rest frame is used to measure the relative contribution of longitudinal B^* polarization states to be \sigma_L/(\sigma_L + \sigma_T)= (33 \pm 6 \pm 5)\%. \\ Resonance structure in the M(B\pi)-M(B) mass difference is observed at (424 \pm 4 \pm 10)~\mathrm{MeV}/c^2. Its shape and position is in agreement with the expectation for B^{**}_{u,d} states decaying into B_{u,d}^{(*)} \pi^\pm. The signal is therefore interpreted as arising from them. The relative production rate is determined to be \frac{BR(Z \to b \to B_{u,d}^{**})}{BR(Z \to b \to B_{u,d})} = [27.9 \pm 1.6(stat) \pm 5.9(syst) \phantom{a}^{+3.9}_{-5.6}(model)]\%. where the third error reflects the uncertainty due to different production and decay models for the broad B_{u,d}^{**} states

Tau hadronic branching ratios

From 64492 selected \tau-pair events, produced at the Z^0 resonance, the measurement of the tau decays into hadrons from a global analysis using 1991, 1992 and 1993 ALEPH data is presented. Special emphasis is given to the reconstruction of photons and \pi^0's, and the removal of fake photons. A detailed study of the systematics entering the \pi^0 reconstruction is also given. A complete and consistent set of tau hadronic branching ratios is presented for 18 exclusive modes. Most measurements are more precise than the present world average. The new level of precision reached allows a stringent test of \tau-\mu universality in hadronic decays, g_\tau/g_\mu \ = \ 1.0013 \ \pm \ 0.0095, and the first measurement of the vector and axial-vector contributions to the non-strange hadronic \tau decay width: R_{\tau ,V} \ = \ 1.788 \ \pm \ 0.025 and R_{\tau ,A} \ = \ 1.694 \ \pm \ 0.027. The ratio (R_{\tau ,V} - R_{\tau ,A}) / (R_{\tau ,V} + R_{\tau ,A}), equal to (2.7 \pm 1.3) \ \%, is a measure of the importance of QCD non-perturbative contributions to the hadronic \tau decay widt