Multiple introductions and onward transmission of non-pandemic HIV-1 subtype B strains in North America and Europe

Most HIV-1 subtype B infections in North America and Europe seem to have resulted from the expansion of a single pandemic lineage (B PANDEMIC) disseminated from the United States (US). Some non-pandemic subtype B strains of Caribbean origin (B CAR) may have also reached North America and Europe, but their epidemiological relevance in those regions remains largely unknown. Here we analyze a total of 20,045 HIV-1 subtype B pol sequences from the US, Canada, and Europe, to estimate the prevalence and to reconstruct the spatiotemporal dynamics of dissemination of HIV-1 B CAR strains in those regions. We find that B CAR strains were probably disseminated from the Caribbean into North America and Europe at multiple times since the early 1970s onwards. The B CAR strains reached the US, Canada and at least 16 different European countries, where they account for a very low fraction (<5%) of subtype B infections, with exception of the Czech Republic (7.7%). We also find evidence of the onward transmission of B CAR clades in the US, Canada, the Czech Republic, Germany, Italy, Spain and the UK, as well as short-distance spreading of B CAR lineages between neighboring European countries from Central and Western Europe, and long-distance dissemination between the US and Europe

Effects of osmotic stress on antioxidative system of duckweed (Lemna minor L)

Background and Purpose: It is known that osmotic stress may cause damage to cells by inducing active oxygen species production or by disrupting detoxification mechanisms. We hypothesize that increased activity of antioxidant enzymes in duckweed (Lemna minor L.) provides a mechanism of tolerance to osmotic stress. Material and Methods: Plants were subjected to NaCl- (50 mM), mannitol- (50 and 100 mM) and polyethylene glycol-mediated osmotic stress (PEG, 50 mM) for a period of 15 days. The responses of antioxidative system including also changes in growth, proline content and the extent of oxidative damage in terms of malondialdehyde, H2O2 and chlorophyll a to chlorophyll b (chl a/b) and chlorophyll a+b to carotenoids (chl a+b/car) ratios were studied. Results and Conclusion: Iso-osmolar concentrations of salt and mannitol significantly reduced relative growth rate compared to control plants while osmotic shockmediated by PEG caused complete cessation of growth. Proline content increased with the severity of osmotic stress showing the highest values in PEG-treated plants. The proline accumulation upon PEG stress was paralleled by equal increase of ascorbic acid pool. Catalase, ascorbate peroxidase and non-specific peroxidase activities showed considerable increase under all osmotic agents, especially PEG. The increased enzyme activities coincided with unchanged H2O2 levels, chl a/b and chl a+b/car under mannitol and salt stress. Despite the highest induction of antioxidative defense, a marked increase in lipid peroxidation and H2O2 level as well as decrease of chl a/b and chl a+b/car accompanied PEG treatment. These results suggested that induction of antioxidant defences is at least one component of the tolerance mechanism of plants to long-term osmotic stress

Simulation of ab initio optical absorption spectrum of \beta-carotene with fully resolved S_{0} and S_{2} vibrational normal modes

Electronic absorption spectrum of beta-carotene (b-Car) is studied using quantum chemistry and quantum dynamics simulations. Vibrational normal modes were computed in optimized geometries of the electronic ground state S0 and the optically bright excited S2 state using the time-dependent density functional theory. By expressing the S2 state normal modes in terms of the ground state modes, we find that no one-to-one correspondence between the ground and excited state vibrational modes exists. Using the ab initio results, we simulated b-Car absorption spectrum with all 282 vibrational modes in a model solvent at 300K using the time-dependent Dirac-Frenkel variational principle (TDVP) and are able to qualitatively reproduce the full absorption lineshape. By comparing the 282-mode model with the prominent 2-mode model, widely used to interpret carotenoid experiments, we find that the full 282-mode model better describe the high frequency progression of carotenoid absorption spectra, hence, vibrational modes become highly mixed during the S0 -> S2 optical excitation. The obtained results suggest that electronic energy dissipation is mediated by numerous vibrational modes

Ne-termalni biopokazatelji izloženosti radiofrekvencijskom/mikrovalnom zračenju

This article gives a review or several hypotheses on the biological effects of non-thermal radiofrequency/microwave (RF/MW) radiation and discusses our own findings from animal and in vitro studies performed over the last decade. We have found that RF/MW radiation disturbs cell proliferation and leads to cell differentiation in the bone marrow, which is reflected in the peripheral blood of rats. Repeated RF/MW radiation can also temporarily disrupt melatonin turnover. The observed changes seem to be a sign of adaptation to stress caused by irradiation rather than of malfunction. The article looks further into the basic mechanisms of RF/MW biological action, including cell growth parameters, colony-forming ability, viability, and the polar and apolar protein cytoskeleton structures. The observed reversible cell changes significantly obstructed cell growth. In contrast to the apolar intermediate proteins, the intracellular polar microtubule and actin fibres were damaged by radiation in a time-dependent manner. These signifi cantly altered parameters can be considered as the biomarkers of exposure. Future research should combine dosimetry, experimental studies, and epidemiological data.Svrha rada je prikaz više hipoteza o biološkom djelovanju ne-termalnih razina radiofrekventnog/mikrovalnog (RF/MW) zračenja i rasprava o rezultatima vlastitih istraživanja na životinjama i in vitro. Istraživanje djelovanja elektromagnetskih polja na organizam uključilo je proučavanje hematopoieze u štakora povremeno izloženih ne-termalnom radiofrekventnom/mikrovalnom (RF/MW) zračenju tijekom supkroničnog pokusa. Rezultati su pokazali neravnotežu u proliferaciji i diferencijaciji stanica koštane srži što se odrazilo na stanične parametre u krvi štakora. U primijenjenim uvjetima zračenja nađeno je da RF/MW može privremeno destabilizirati metabolizam melatonina bez štetnog utjecaja na zdravlje životinja. Razmatrana je mogućnost aktivacije prilagodbenog mehanizma na stres izazvan zračenjem jer smatramo da su nađene promjene prije znak adaptacije nego štetnog učinka zračenja. Pristup temeljnim mehanizmima biološkog djelovanja RF/MW zračenja uključio je istraživanje parametara staničnog rasta, sposobnosti stvaranja kolonija, vijabilnosti te polarnih i nepolarnih proteinskih struktura citoskeleta nakon ozračivanja stanica. Reverzibilne promjene staničnih svojstava koje su nađene upućuju na značajnu opstrukciju staničnog rasta. Za razliku od nepolarnih intermedijarnih proteina, unutarstanična polarna vlakna mikrotubula i aktina su, ovisno o vremenu izloženosti, pokazala značajna oštećenja uzrokovana zračenjem. Statistički značajno promijenjeni parametri smatrani su biomarkerima izloženosti. Istaknuta je potreba za budućim istraživanjima koja uključuju epidemiološke, laboratorijske i dozimetrijske studije

TGF-β-responsive CAR-T cells promote anti-tumor immune function.

A chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF-β) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T-cell stimulant. However, clinical translation of TGF-β CAR-T cells for cancer therapy requires the ability to productively combine TGF-β responsiveness with tumor-targeting specificity. Furthermore, the potential concern that contaminating, TGF-β?producing regulatory T (Treg) cells may preferentially expand during TGF-β CAR-T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation. Here, we demonstrate that TGF-β CAR-T cells significantly improve the anti-tumor efficacy of neighboring cytotoxic T cells. Furthermore, the introduction of TGF-β CARs into mixed T-cell populations does not result in the preferential expansion of Treg cells, nor do TGF-β CAR-Treg cells cause CAR-mediated suppression of Teff cells. These results support the utility of incorporating TGF-β CARs in the development of adoptive T-cell therapy for cancer

De Finetti theorem on the CAR algebra

The symmetric states on a quasi local C*-algebra on the infinite set of indices J are those invariant under the action of the group of the permutations moving only a finite, but arbitrary, number of elements of J. The celebrated De Finetti Theorem describes the structure of the symmetric states (i.e. exchangeable probability measures) in classical probability. In the present paper we extend De Finetti Theorem to the case of the CAR algebra, that is for physical systems describing Fermions. Namely, after showing that a symmetric state is automatically even under the natural action of the parity automorphism, we prove that the compact convex set of such states is a Choquet simplex, whose extremal (i.e. ergodic w.r.t. the action of the group of permutations previously described) are precisely the product states in the sense of Araki-Moriya. In order to do that, we also prove some ergodic properties naturally enjoyed by the symmetric states which have a self--containing interest.Comment: 23 pages, juornal reference: Communications in Mathematical Physics, to appea

Fluctuations in the Alpha-Effect and Grand Solar Minima

Parameters of a special kind of \alpha-effect known in dynamo theory as the Babcock-Leighton mechanism are estimated using the data of sunspot catalogs. The estimates evidence the presence of the Babcock-Leighton \alpha-effect on the Sun. Fluctuations of the \alpha-effect are also estimated. The fluctuation amplitude appreciably exceeds the mean value, and the characteristic time for the fluctuations is comparable to the period of the solar rotation. Fluctuations with the parameters found are included in a numerical model for the solar dynamo. Computations show irregular changes in the amplitudes of the magnetic cycles on time scales of centuries and millennia. The calculated statistical characteristics of the grand solar minima and maxima agree with the data on solar activity over the Holocene.Comment: To appear in Astronomy Reports, 20 pages, 9 figure

Overexpression of beta-carotene hydroxylase enhances stress tolerance in Arabidopsis

Plant stress caused by extreme environmental conditions is already a principal reason for yield reduction in crops. The threat of global environment change makes it increasingly important to generate crop plants that will withstand such conditions. Stress, particularly stress caused by increased sunlight, leads to the production of reactive oxygen species that cause photo-oxidative cell damage. Carotenoids, which are present in the membranes of all photosynthetic organisms, help protect against such light-dependent oxidative damage. In plants, the xanthophyll cycle (the reversible interconversion of two carotenoids, violaxanthin and zeaxanthin) has a key photoprotective role and is therefore a promising target for genetic engineering to enhance stress tolerance. Here we show that in Arabidopsis thaliana overexpression of the chyB gene that encodes -carotene hydroxylase—an enzyme in the zeaxanthin biosynthetic pathway—causes a specific twofold increase in the size of the xanthophyll cycle pool. The plants are more tolerant to conditions of high light and high temperature, as shown by reduced leaf necrosis, reduced production of the stress indicator anthocyanin and reduced lipid peroxidation. Stress protection is probably due to the function of zeaxanthin in preventing oxidative damage of membranes