Entropic Tension in Crowded Membranes

Unlike their model membrane counterparts, biological membranes are richly decorated with a heterogeneous assembly of membrane proteins. These proteins are so tightly packed that their excluded area interactions can alter the free energy landscape controlling the conformational transitions suffered by such proteins. For membrane channels, this effect can alter the critical membrane tension at which they undergo a transition from a closed to an open state, and therefore influence protein function \emph{in vivo}. Despite their obvious importance, crowding phenomena in membranes are much less well studied than in the cytoplasm. Using statistical mechanics results for hard disk liquids, we show that crowding induces an entropic tension in the membrane, which influences transitions that alter the projected area and circumference of a membrane protein. As a specific case study in this effect, we consider the impact of crowding on the gating properties of bacterial mechanosensitive membrane channels, which are thought to confer osmoprotection when these cells are subjected to osmotic shock. We find that crowding can alter the gating energies by more than $2\;k_BT$ in physiological conditions, a substantial fraction of the total gating energies in some cases. Given the ubiquity of membrane crowding, the nonspecific nature of excluded volume interactions, and the fact that the function of many membrane proteins involve significant conformational changes, this specific case study highlights a general aspect in the function of membrane proteins.Comment: 20 pages (inclduing supporting information), 4 figures, to appear in PLoS Comp. Bio

Development of a New Tacaribe Arenavirus Infection Model and Its Use to Explore Antiviral Activity of a Novel Aristeromycin Analog

Background A growing number of arenaviruses can cause a devastating viral hemorrhagic fever (VHF) syndrome. They pose a public health threat as emerging viruses and because of their potential use as bioterror agents. All of the highly pathogenic New World arenaviruses (NWA) phylogenetically segregate into clade B and require maximum biosafety containment facilities for their study. Tacaribe virus (TCRV) is a nonpathogenic member of clade B that is closely related to the VHF arenaviruses at the amino acid level. Despite this relatedness, TCRV lacks the ability to antagonize the host interferon (IFN) response, which likely contributes to its inability to cause disease in animals other than newborn mice. Methodology/Principal Findings Here we describe a new mouse model based on TCRV challenge of AG129 IFN-α/β and -γ receptor-deficient mice. Titration of the virus by intraperitoneal (i.p.) challenge of AG129 mice resulted in an LD50 of ∼100 fifty percent cell culture infectious doses. Virus replication was evident in the serum, liver, lung, spleen, and brain 4–8 days after inoculation. MY-24, an aristeromycin derivative active against TCRV in cell culture at 0.9 µM, administered i.p. once daily for 7 days, offered highly significant (P\u3c0.001) protection against mortality in the AG129 mouse TCRV infection model, without appreciably reducing viral burden. In contrast, in a hamster model of arenaviral hemorrhagic fever based on challenge with clade A Pichinde arenavirus, MY-24 did not offer significant protection against mortality. Conclusions/Significance MY-24 is believed to act as an inhibitor of S-adenosyl-L-homocysteine hydrolase, but our findings suggest that it may ameliorate disease by blunting the effects of the host response that play a role in disease pathogenesis. The new AG129 mouse TCRV infection model provides a safe and cost-effective means to conduct early-stage pre-clinical evaluations of candidate antiviral therapies that target clade B arenaviruses

MscS-like mechanosensitive channels in plants and microbes

The challenge of osmotic stress is something all living organisms must face as a result of environmental dynamics. Over the past three decades, innovative research and cooperation across disciplines have irrefutably established that cells utilize mechanically gated ion channels to release osmolytes and prevent cell lysis during hypoosmotic stress. Early electrophysiological analysis of the inner membrane of Escherichia coli identified the presence of three distinct mechanosensitive activities. The subsequent discoveries of the genes responsible for two of these activities, the mechanosensitive channels of large (MscL) and small (MscS) conductance, led to the identification of two diverse families of mechanosensitive channels. The latter of these two families, the MscS family, consists of members from bacteria, archaea, fungi, and plants. Genetic and electrophysiological analysis of these family members has provided insight into how organisms use mechanosensitive channels for osmotic regulation in response to changing environmental and developmental circumstances. Furthermore, determining the crystal structure of E. coli MscS and several homologues in several conformational states has contributed to our understanding of the gating mechanisms of these channels. Here we summarize our current knowledge of MscS homologues from all three domains of life and address their structure, proposed physiological functions, electrophysiological behaviors, and topological diversity

Wpływ podłoży na wzrost, plonowanie oraz zawartość polifenoli w owocach borówki niskiej (Vaccinium angustifolium Ait.) odmiany ‘Emil’

The experiment was carried out in the years 2007–2008 in the Experimental Pomological Station at Rajkowo near Szczecin. In 2005 the plants of lowbush blueberry, ‘Emil’ cv. were planted in peat (acid muck soil), sawdust (previously composted), and cocoa husk substrate (a by-product from chocolate confectionary plant) at spacing 1.0 × 2.5 m. Plant growth, quantity, quality, and chemical composition of yield were assessed. No effect of substrate was observed regarding plant height tested in the substrates however, the bushes planted in peat and cocoa husk had bigger leaves and one-year shoots. Further, the bushes grown in these substrates yielded best and their fruits were largest, showed highest firmness as well as highest content of soluble solids, organic acids, and phenol compounds.Doświadczenie przeprowadzono w latach 2007-2008 w Sadowniczej Stacji Badawczej Katedry Sadownictwa, gdzie w 2005 roku posadzono krzewy borówki niskiej odmiany 'Emil' w rozstawie 1,0 × 2,5 m w glebie murszowej (torf) o odczynie kwaśnym, przekompostowanych trocinach z drzew iglastych oraz w łusce z ziarna kakaowego, która jest odpadem przy produkcji czekolady. Określano wzrost roślin oraz ilość, jakość oraz skład chemiczny plonu. Nie stwierdzono wpływu zastosowanych podłoży na wysokość roślin, jednak krzewy posadzone w torfie oraz łusce kakaowej miały większe liście oraz dłuższe pędy jednoroczne. Krzewy, które rosły w tych podłożach, również plonowały najlepiej a owoce z nich uzyskane były największe i najbardziej jędrne. Ponadto owoce z tych krzewów charakteryzowały się największą zawartością ekstraktu, kwasów organicznych oraz związków polifenolowych

Wpływ stosowania trzech biopreparatów na plon oraz jakość owoców trzech odmian malin

There was tested an influence of three biostymulants Atonik SL, Biochikol 020 PC and Tytanit on yield and fruits quality of three fruiting repeating Polish raspberry cultivars: Pokusa, Polka and Poranna Rosa during years of 2005–2006. These agents had a positive influence on fruits quality and yielding to all tested cultivars. The fruits with exception of Tytanit treated fruit especially in the beginning of harvest, were characterized by better firmness and were bigger. However, Tytanit treatment increased soluble solids content in fruits and reduced in Polka cv. nitrates concentration. Among tested cultivars, cv. Polka was characterized by the highest yield, that was of c. a. 50% greater that of cv. Pokusa, which was characterized by the gratest fruits sizes. The ‘Poranna Rosa’ shawed the least soluble solids and vitamin C content and had the highest acidity.W latach 2005–2006 określono wpływu trzech bioregulatorów, Atonic, Biochikol 020 PC i Tytanit, na plon oraz jako owoców trzech powtarzających owocowanie polskich odmian malin: Pokusa, Polka i Poranna Rosa. Zastosowane środki u wszystkich badanych odmian wpłynęły pozytywnie na plonowanie i jako owoców. Owoce roślin traktowanych bioregulatorami (z wyjątkiem stosowania Tytanitu), zwłaszcza na początku zbiorów, były większe oraz jędrniejsze. Zastosowanie Tytanitu przyczyniło się natomiast do zwiększenia zawartości ekstraktu w owocach i zmniejszenia, u odmiany Polka, koncentracji azotanów. Spośród trzech przebadanych odmian najlepiej plonowała odmiana Polka, plon był o 50% większy, natomiast największymi owocami charakteryzowała się Pokusa. Żółte owoce Porannej Rosy zawierały najmniej ekstraktu i witaminy C i miały największą kwasowość

Effect of substrate type on the field performance and chemical composition of highbush blueberry cv.Patriot

The aim of a 3-year study was to compare the effect of substrate type (peat, sawdust and cocoa husk) on the yield, fruit quality, general and phenolic composition, and antioxidant activity of highbush blueberry (Vaccinium corymbosum L.) cultivar Patriot. The largest berries and the highest yield were obtained from bushes grown in sawdust (3.661 kg ha-1). Berries from bushes grown in cocoa husk had the highest content of N (14.25 g kg-1), P (1.17 g kg-1), K (6.51 g kg-1), and Zn (8.78 mg kg-1), as well as P (1.26 g kg-1) and K (6.99 g kg-1) in the leaves. Both the leaves and fruits of plants grown in sawdust had higher Cu concentrations (3.89 and 3.01 mg kg-1). Berries from sawdust-grown bushes had the highest soluble solids (13.1%) and total sugar (10.80 g 100 g-1) content. The fruits obtained from peat-grown bushes exhibited enhanced antioxidant capacity (38.6 ìmol Trolox g-1). However, the highest levels of phenolics were noted in berries produced in the cocoa husk (208.29 mg 100 g-1) and peat-bed system (174.07 mg 100 g-1). Regardless of the type of substrate used, the following phenols were identified (in descending order): anthocyanins>chlorogenic acid>flavonols. Delphinidin-glycosides were the most abundant pigments, and cyanidin, peonidin, petunidin, and malvidin-glycosides were also detected. Total flavonol content (quercetin derivatives and kaempferol 3-rutinoside) was not significantly affected by the type of substrate.