Tunable high-energy ion source via oblique laser pulse incidence on a double-layer target

The laser-driven acceleration of high quality proton beams from a double-layer target, comprised of a high-Z ion layer and a thin disk of hydrogen, is investigated with three-dimensional particle-in-cell simulations in the case of oblique incidence of a laser pulse. It is shown that the proton beam energy reaches its maximum at a certain incidence angle of the laser pulse, where it can be much greater than the energy at normal incidence. The proton beam propagates at some angle with respect to the target surface normal, as determined by the proton energy and the incidence angle

Skuteczność terapii złożonej polegającej na podaniu blokera kanału IKr oraz wykonaniu blokady zwoju gwiaździstego w leczeniu opornych arytmii komorowych u chorych z zatrzymaniem krążenia

Wstęp: W poprzednich doniesieniach autorzy niniejszej pracy dowiedli, że współczynnik skuteczności defibrylacji przy jednoczesnym dożylnym podaniu chlorowodorku nifekalantu (NIF) - selektywnego blokera kanałów szybkiej składowej opóźnionego prostującego prądu potasowego (IKr) wynosił powyżej 75% dla opornego na lignokainę częstoskurczu lub migotania komór (VT/VF) w przebiegu pozaszpitalnego zatrzymania krążenia (CPA). Jednakże dla pozostałych 25% chorych, u których wykonana defibrylacja okazała się nieskuteczna, nie znaleziono efektywnych metod leczenia. Autorzy niniejszej pracy sugerują, że zastosowanie złożonej terapii polegającej na dożylnym podaniu NIF oraz wykonaniu blokady lewego zwoju gwiaździstego (LSGB) jest użyteczne w przypadku defibrylacji VT/VF opornego na działanie NIF. Na podstawie własnych badań retrospektywnych podjęto także próbę oceny skuteczności tej terapii. Metody i wyniki: Do badania włączono kolejnych 272 chorych przyjętych do Kliniki Kardiologii Uniwersytetu Tokai w okresie od kwietnia do grudnia 2006 roku z powodu pozaszpitalnego zatrzymania krążenia. U 55 pacjentów (podczas przyjęcia lub też w przebiegu resuscytacji krążeniowo-oddechowej) stwierdzono VT/VF. Zgodnie z samodzielnie wypracowanymi przez autorów pracy algorytmami prowadzenia resuscytacji krążeniowo-oddechowej NIF (w dawce 0,15-0,3 mg/kg) podawano dożylnie po pierwszej próbie kardiowersji. Oporne na działanie NIF częstoskurcze komorowe/migotania komór wystąpiły u 15 spośród 55 pacjentów. U 11 chorych z powyższej grupy wykonano LSGB oraz podano dożylnie NIF. U 7 osób (64%) po zabiegu LSGB uzyskano powrót rytmu zatokowego. Całkowity powrót do zdrowia zanotowano u 2 chorych. Jednakże w grupie, w której nie wykonano zabiegu blokady lewego zwoju gwiaździstego (grupa nie-LSBG), zmarli wszyscy pacjenci. Wnioski: Terapia złożona polegająca na dożylnym podaniu NIF oraz wykonaniu LSGB okazała się użyteczna w przypadku defibrylacji opornego VT/VF. Jest to potencjalna i innowacyjna strategia leczenia opornego na selektywne blokery kanałów IKr częstoskurczu komorowego/ migotania komór. (Folia Cardiologica Excerpta 2007; 2: 524-536

Identification of a Regulatory T Cell Specific Cell Surface Molecule that Mediates Suppressive Signals and Induces Foxp3 Expression

Regulatory T (Treg) cells control immune activation and maintain tolerance. How Tregs mediate their suppressive function is unclear. Here we identified a cell surface molecule, called GARP, (or LRRC32), which within T cells is specifically expressed in Tregs activated through the T cell receptor (TCR). Ectopic expression of GARP in human naïve T (TN) cells inhibited their proliferation and cytokine secretion upon TCR activation. Remarkably, GARP over-expression in TN cells induced expression of Treg master transcription factor Foxp3 and endowed them with a partial suppressive function. The extracellular but not the cytoplasmic region of GARP, was necessary for these functions. Silencing Foxp3 in human Treg cells reduced expression of GARP and attenuated their suppressive function. However, GARP function was not affected when Foxp3 was downregulated in GARP-overexpressing cells, while silencing GARP in Foxp3-overexpressing cells reduced their suppressive activity. These findings reveal a novel cell surface molecule-mediated regulatory mechanism, with implications for modulating aberrant immune responses

Upregulation of MMP-13 and TIMP-1 expression in response to mechanical strain in MC3T3-E1 osteoblastic cells

<p>Abstract</p> <p>Background</p> <p>Mechanical strain plays a significant role in the regulation of bone matrix turnover, which is mediated in part by matrix metalloproteinase (MMP)-13 and tissue inhibitors of matrix metalloproteinase (TIMP)-1. However, little is known about the correlation between mechanical strain and osteoblastic cell activities, including extracellular matrix (ECM) metabolism. Herein, we determined the effect of different magnitudes of cyclic tensile strain (0%, 6%, 12%, and 18%) on MMP-13 and TIMP-1 mRNA and protein expression in MC3T3-E1 osteoblasts. Furthermore, we employed specific inhibitors to examine the role of distinct signal transduction pathways known to mediate cellular responses to mechanical strain.</p> <p>Results</p> <p>We identified a magnitude-dependent increase in MMP-13 and TIMP-1 mRNA and protein levels in response to mechanical strains corresponding to 6%, 12%, and 18% elongation. The strain-induced increases in MMP-13 and TIMP-1 mRNA expression were inhibited by PD098059 and cycloheximide, respectively.</p> <p>Conclusions</p> <p>Our results suggest a mechanism for the regulation of bone matrix metabolism mediated by the differential expression of MMP-13 and TIMP-1 in response to increasing magnitudes of mechanical strain.</p

Strategies for the Use of Fallback Foods in Apes

Researchers have suggested that fallback foods (FBFs) shape primate food processing adaptations, whereas preferred foods drive harvesting adaptations, and that the dietary importance of FBFs is central in determining the expression of a variety of traits. We examine these hypotheses in extant apes. First, we compare the nature and dietary importance of FBFs used by each taxon. FBF importance appears greatest in gorillas, followed by chimpanzees and siamangs, and least in orangutans and gibbons (bonobos are difficult to place). Next, we compare 20 traits among taxa to assess whether the relative expression of traits expected for consumption of FBFs matches their observed dietary importance. Trait manifestation generally conforms to predictions based on dietary importance of FBFs. However, some departures from predictions exist, particularly for orang-utans, which express relatively more food harvesting and processing traits predicted for consuming large amounts of FBFs than expected based on observed dietary importance. This is probably due to the chemical, mechanical, and phenological properties of the apes’ main FBFs, in particular high importance of figs for chimpanzees and hylobatids, compared to use of bark and leaves—plus figs in at least some Sumatran populations—by orang-utans. This may have permitted more specialized harvesting adaptations in chimpanzees and hylobatids, and required enhanced processing adaptations in orang-utans. Possible intercontinental differences in the availability and quality of preferred and FBFs may also be important. Our analysis supports previous hypotheses suggesting a critical influence of the dietary importance and quality of FBFs on ape ecology and, consequently, evolution

HCV+ Hepatocytes Induce Human Regulatory CD4+ T Cells through the Production of TGF-β

Background: Hepatitis C Virus (HCV) is remarkably efficient at establishing persistent infection and is associated with the development of chronic liver disease. Impaired T cell responses facilitate and maintain persistent HCV infection. Importantly, CD4 + regulatory T cells (Tregs) act by dampening antiviral T cell responses in HCV infection. The mechanism for induction and/or expansion of Tregs in HCV is unknown. Methodology/Principal Findings: HCV-expressing hepatocytes were used to determine if hepatocytes are able to induce Tregs. The infected liver environment was modeled by establishing the co-culture of the human hepatoma cell line, Huh7.5, containing the full-length genome of HCV genotype 1a (Huh7.5-FL) with activated CD4 + T cells. The production of IFN-c was diminished following co-culture with Huh7.5-FL as compared to controls. Notably, CD4 + T cells in contact with Huh7.5-FL expressed an increased level of the Treg markers, CD25, Foxp3, CTLA-4 and LAP, and were able to suppress the proliferation of effector T cells. Importantly, HCV + hepatocytes upregulated the production of TGF-b and blockade of TGF-b abrogated Treg phenotype and function. Conclusions/Significance: These results demonstrate that HCV infected hepatocytes are capable of directly inducing Tregs development and may contribute to impaired host T cell responses

Impact of the TCR Signal on Regulatory T Cell Homeostasis, Function, and Trafficking

Signaling through the T cell antigen receptor (TCR) is important for the homeostasis of naïve and memory CD4+ T cells. The significance of TCR signaling in regulatory T (Treg) cells has not been systematically addressed. Using an Ox40-cre allele that is prominently expressed in Treg cells, and a conditional null allele of the gene encoding p56Lck, we have examined the importance of TCR signaling in Treg cells. Inactivation of p56Lck resulted in abnormal Treg homeostasis characterized by impaired turnover, preferential redistribution to the lymph nodes, loss of suppressive function, and striking changes in gene expression. Abnormal Treg cell homeostasis and function did not reflect the involvement of p56Lck in CD4 function because these effects were not observed when CD4 expression was inactivated by Ox40-cre.The results make clear multiple aspects of Treg cell homeostasis and phenotype that are dependent on a sustained capacity to signal through the TCR

Weaned age variation in the Virunga mountain gorillas (Gorilla beringei beringei)

The final publication is available at Springer via http://dx.doi.org/10.1007/s00265-016-2066-6Weaning marks an important milestone during life history in mammals indicating nutritional independence from the mother. Age at weaning is a key measure of maternal investment and care, affecting female reproductive rates, offspring survival and ultimately the viability of a population. Factors explaining weaned age variation in the endangered mountain gorilla are not yet well understood. This study investigated the impact of group size, group type (one-male versus multi-male), offspring sex, as well as maternal age, rank, and parity on weaned age variation in the Virunga mountain gorilla population. The status of nutritional independence was established in 69 offspring using long-term suckling observations. A Cox-regression with mixed effects was applied to model weaned age and its relationship with covariates. Findings indicate that offspring in one-male groups are more likely to be weaned earlier than offspring in multi-male groups, which may reflect a female reproductive strategy to reduce higher risk of infanticide in one-male groups. Inferior milk production capacity and conflicting resource allocation between their own and offspring growth may explain later weaning in primiparous mothers compared to multiparous mothers. Sex-biased weaned age related to maternal condition defined by parity, rank, and maternal age will be discussed in the light of the Trivers-Willard hypothesis. Long-term demographic records revealed no disadvantage of early weaning for mother or offspring. Population growth and two peaks in weaned age within the Virunga population encourage future studies on the potential impact of bamboo shoots as a weaning food and other environmental factors on weaning