Role of brain IL-1beta on fatigue after exercise-induced muscle damage

Brain cytokines, induced by various inflammatory challenges, have been linked to sickness behaviors, including fatigue. However, the relationship between brain cytokines and fatigue after exercise is not well understood. Delayed recovery of running performance after muscle-damaging downhill running is associated with increased brain IL-1beta concentration compared with uphill running. However, there has been no systematic evaluation of the direct effect of brain IL-1beta on running performance after exercise-induced muscle damage. This study examined the specific role of brain IL-1beta on running performance (either treadmill or wheel running) after uphill and downhill running by manipulating brain IL-1beta activity via intracerebroventricular injection of either IL-1 receptor antagonist (ra; downhill runners) or IL-1beta (uphill runners). Male C57BL/6 mice were assigned to the following groups: uphill-saline, uphill-IL-1beta, downhill-saline, or downhill-IL-1ra. Mice initially ran on a motor-driven treadmill at 22 m/min and -14% or +14% grade for 150 min. After the run, at 8 h (wheel cage) or 22 h (treadmill), uphill mice received intracerebroventricular injections of IL-1beta (900 pg in 2 microl saline) or saline (2 microl), whereas downhill runners received IL-1ra (1.8 microg in 2 microl saline) or saline (2 microl). Later (2 h), running performance was measured (wheel running activity and treadmill run to fatigue). Injection of IL-1beta significantly decreased wheel running activity in uphill runners (P<0.01), whereas IL-1ra improved wheel running in downhill runners (P<0.05). Similarly, IL-1beta decreased and Il-1ra increased run time to fatigue in the uphill and downhill runners, respectively (P<0.01). These results support the hypothesis that increased brain IL-1beta plays an important role in fatigue after muscle-damaging exercise.     

The effects of reaction conditions on the production of γ-cyclodextrin from tapioca starch by using a novel recombinant engineered CGTase

A novel mutant enzyme namely H43T CGTase can produce up to 39% γ-cyclodextrin (γ-CD) compared to the native enzyme which produces only 10% γ-CD. The effect of the reaction conditions on γ-CD production was studied using this mutant CGTase. The effects of substrate–buffer combination, starch pretreatment and concentration, pH, additives and finally the use of a debranching enzyme improved the γ-CD ratio further. The tapioca–acetate pair gave the highest conversion (16% conversion) among four types of starch and four buffer system combinations. Gelatinized starch was preferred compared to raw tapioca starch in producing a high percentage of γ-CD and conversion rate. Higher pH especially pH 8–9 led to a higher proportion of γ-CD, and was relatively more apparent when the concentration of starch was increased. Forty-six percent γ-CD was produced using 2.5% gelatinized tapioca starch at pH 8. Pullulanase enzyme was found to be useful in reducing the viscosity of tapioca starch paste thus increasing the efficiency of utilization of starch by CGTase by at least 20- to 30-fold. Up to 48% γ-CD can be produced when 4% pullulanase-pretreated tapioca starch was reacted with the CGTase mutant. It was also found that the supplementation of the reaction mixture with glucose, toluene, or cyclododecanone improved the γ-CD yield by 42.2, 46.4, 43.4, and 43.4%, respectively. All the parameters involved have been shown to affect the product specificity of the mutant H43T CGTase transglycosylation mechanism.     

Characterization of asparaginyl endopeptidase, legumain induced by blood feeding in the ixodid tick Haemaphysalis longicornis

We characterize here a cDNA from the ixodid tick Haemaphysalis longicornis, which encodes an asparaginyl endopeptidase, legumain (HlLgm), that was present as a functional molecule in the midgut of this tick. Endogenous HlLgm was detected as a 38-kDa antigen in H. longicornis extracts and was seen throughout all developmental stages. Endogenous HlLgm was mainly localized in the midgut epithelium by immunohistochemistry, and was shown to be up-regulated by the host blood-feeding process. Recombinant HlLgm (rHlLgm) produced in Escherichia coli was shown to hydrolyze the synthetic substrate Z-Ala-Ala-Asn-MCA at the rate of 6.42x10(-4)mumol/min/mg protein. Its activity was inhibited by the thiol blocking reagents iodoacetamide and N-ethylmaleimide. The enzyme was shown to possess a unique feature of having an autocatalyzed cleavage at asparagines(364-365) at the C-terminus of both endogenous HlLgm and rHlLgm. rHlLgm degraded bovine hemoglobin and bovine serum albumin (BSA) showing its strict specificity for hydrolysis of the peptide on the carboxyl side of the asparagines, as demonstrated by internal amino acid sequence analysis of proteolytic product of BSA cleavage. These results suggest that HlLgm plays an important role in host blood-meal digestion and may be critical for the final process of digestion of blood components.     

Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one

The synthesis and exploration of novel butyrophenones have led to the identification of a diazepane analogue of haloperidol, 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one (compound 13) with an interesting multireceptor binding profile. Compound 13 was evaluated for its binding affinities at DA subtype receptors, 5HT subtype receptors, H-1, M-1 receptors and at NET, DAT, and SERT transporters. At each of these receptors, compound 13 was equipotent or better than several of the standards currently in use. In in vivo mouse and rat models to evaluate its efficacy and propensity to elicit catalepsy and hence EPS in humans, compound 13 showed similar efficacy as clozapine and did not produce catalepsy at five times its ED(50) value.     

Silicon Application to Rice Root Zone Influenced the Phytohormonal and Antioxidant Responses Under Salinity Stress

Silicon (Si) application shows beneficial effects on plant growth; however, its effects on the phytohormone and enzymatic antioxidant regulation have not been fully understood. We studied the effects of short-term (6, 12, and 24 h) silicon (0.5, 1.0, and 2.0 mM) application on salinity (NaCl)-induced phytohormonal [abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA)] and antioxidant regulation in Oryza sativa. The results showed that Si treatments significantly increased rice plant growth compared to controls under salinity stress. Si treatments reduced the sodium accumulation resulting in low electrolytic leakage and lipid peroxidation compared to control plants under salinity stress. Enzymatic antioxidant (catalase, peroxidase and polyphenol oxidase) responses were more pronounced in control plants than in Si-treated plants under salinity stress. Stress- and defense-related phytohormones like JA were significantly downregulated and SA was irregular after short-term Si applications under salinity stress compared to control. Conversely, ABA was significantly higher after 6 and 12 h but insignificant after 24 h in Si-treated plants under salinity stress. After 6 and 12 h, Si and salinity stress resulted in upregulation of zeaxanthin epoxidase and 9-cis-epoxycarotenoid dioxygenase 1 and 4 (NCED1 and 4), whereas 24-h treatments significantly downregulated the expressions of these genes compared to those in the control. NCED3 expression increased after 6 and 24 h but it was insignificant after 12 h of Si application compared to control. The current findings indicate that increasing the Si concentrations for longer periods of time can regulate the salinity-induced stress by modulating phytohormonal and enzymatic antioxidants’ responses.     

The function of GluR1 and GluR2 in cerebellar and hippocampal LTP and LTD is regulated by interplay of phosphorylation and O‐GlcNAc modification

Long‐term potentiation (LTP) and long‐term depression (LTD) are the current models of synaptic plasticity and widely believed to explain how different kinds of memory are stored in different brain regions. Induction of LTP and LTD in different regions of brain undoubtedly involve trafficking of AMPA receptor to and from synapses. Hippocampal LTP involves phosphorylation of GluR1 subunit of AMPA receptor and its delivery to synapse whereas; LTD is the result of dephosphorylation and endocytosis of GluR1 containing AMPA receptor. Conversely the cerebellar LTD is maintained by the phosphorylation of GluR2 which promotes receptor endocytosis while dephosphorylation of GluR2 triggers receptor expression at the cell surface and results in LTP. The interplay of phosphorylation and O‐GlcNAc modification is known as functional switch in many neuronal proteins. In this study it is hypothesized that a same phenomenon underlies as LTD and LTP switching, by predicting the potential of different Ser/Thr residues for phosphorylation, O‐GlcNAc modification and their possible interplay. We suggest the involvement of O‐GlcNAc modification of dephosphorylated GluR1 in maintaining the hippocampal LTD and that of dephosphorylated GluR2 in cerebral LTP. J. Cell. Biochem. 109: 585–597, 2010. © 2010 Wiley‐Liss, Inc.     

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients with PAH (9 women; 54 ± 12 years) were studied: 10 with idiopathic PAH and 5 with a connective tissue disorder. We measured hemodynamics, as well as radiolabeled and endogenous concentrations of arterial and coronary sinus norepinephrine (NE). These measures were repeated after inhaled nitric oxide (NO). Measurement of transcardiac NE concentrations and the cardiac extraction of radiolabeled NE allowed calculation of the corrected transcardiac gradient of NE (CTCG of NE). Comparative data were collected from 15 patients (9 women: 55 ± 12 yr) with normal LV function and 15 patients with CHF (10 women; 53 ± 12 yr). PAH patients had elevated arterial NE concentrations compared with those with normal LV function but were similar to those with CHF. The CTCG of NE was higher in those with PAH than in the normal LV group (3.6 ± 2.2 vs. 1.5 ± 0.9 pmol/ml; P < 0.01) but similar to that seen in those with CHF (3.3 ± 1.4; P = NS). Inhaled NO, which reduced pulmonary artery pressure and increased cardiac output, had no effect on cardiac sympathetic activity. Therefore, cardiac sympathetic activation occurs in PAH. The mechanism of this activation remains uncertain but does not involve elevations in left heart filling pressure.     

Pharyngodonidae (Oxyuroidea; Nematoda) of Agama yemenensis in Saudi Arabia: hypothesis on the origin of pharyngodonids of herbivorous reptiles

Summary Five new species of pharyngodonid (Oxyuroidea) nematodes are described from the posterior gut of Agama yemenensis (Agamidae) in Saudi Arabia: Tachygonetria paradentata n.sp., a member of the T. dentata complex, most closely resembles T. quentini Petter, 1966 from Testudo tentoria verreauxi from South Africa in the form and disposition of cephalic sense organs; it is distinguished by having caudal alae, an anterior anal lip in the male formed by two sharply-elbowed lobes and by the fact that the terminal spine on the caudal appendage of the male is much shorter than that in T. quentini. Alaeuris asirensis n.sp. is most similar to a species described as Thelandros sexlabiata Ortlepp, 1933 from Testudo tentoria verreauxi from South Africa: the last pair of caudal papillae in the male is subterminal, and there are six lips and a slight prevulvar swelling in the female. Males of the two species are easily distinguished by the presence of caudal alae and a longer caudal appendage in A. asirensis females are distinguished by the fact that lips are less developed in the new species. The fact that two such similar species cannot be included in the same genus reflects the need for a redefinition of Alaeuris. Thelandros agama n.sp. resembles T. alatus Wedl, 1862 from Uromastix sp. in North Africa in the cephalic structure of the female and in the shape of the peduncles supporting adanal papillae in males; the new species is distinguished by its longer spicule and by the presence of caudal alae and the absence of lips in males. T. masaae n.sp. resembles T. taylori Chatterji, 1935 and T. baylisi Chatterji, 1935 from Agama sp. and Uromastix sp. in India in that the peduncles supporting the caudal papillae in the male are elongate; it differs from both and from all other members of the genus in that the vulva is located at the end of a long tube-like exvagination of the body wall and the anterior anal lip of the male is simple rather than fringed. T. petterae n.sp. resembles T. taylori and T. baylisi in having well-developed caudal alae in males and six prominent lips in females; it is distinguished from both by its flask-shaped adanal peduncles in the male. Thelandros is redefined to include only those species in which the pre- and adanal papillae are pedunculate and the opening to the spicular pouch is markedly postanal. The nine genera of the Pharyngodonidae in herbivorous and omnivorous reptiles form an evolutionary line distinct from that in insectivorous reptiles. It is suggested that this line arose in tortoises in Laurasia in the Eocene, spread with these hosts to Africa, Madagascar and South America, and subsequently underwent evolutionary radiations in each of these regions. Pharyngodonids of A. yemenensis have a double origin: the Thelandros spp. probably evolved with agamids whereas species of Tachygonetria and Alaeuris are likely captures from tortoises. ac]19831111     

Force-induced Unfolding of the Focal Adhesion Targeting Domain and the Influence of Paxillin Binding

Membrane-bound integrin receptors are linked to intracellular signaling pathways through focal adhesion kinase (FAK). FAK tends to colocalize with integrin receptors at focal adhesions through its C-terminal focal adhesion targeting (FAT) domain. Through recruitment and binding of intracellular proteins, FAs transduce signals between the intracellular and extracellular regions that regulate a variety of cellular processes including cell migration, proliferation, apoptosis and detachment from the ECM. The mechanism of signaling through the cell is of interest, especially the transmission of mechanical forces and subsequent transduction into biological signals. One hypothesis relates mechanotransduction to conformational changes in intracellular proteins in the force transmission pathway, connecting the extracellular matrix with the cytoskeleton through FAs. To assess this hypothesis, we performed steered molecular dynamics simulations to mechanically unfold FAT and monitor how force-induced changes in the molecular conformation of FAT affect its binding to paxillin.