Muscle transcriptome adaptations with mild eccentric ergometer exercise

The muscle has a wide range of possibilities to adapt its phenotype. Repetitive submaximal concentric exercise (i.e., shortening contractions) mainly leads to adaptations of muscle oxidative metabolism and endurance while eccentric exercise (i.e., lengthening contractions) results in muscle growth and gain of muscle strength. Modified gene expression is believed to mediate these exercise-specific muscle adjustments. In the present study, early alterations of the gene expression signature were monitored by a muscle-specific microarray. Transcript profiling was performed on muscle biopsies of vastus lateralis obtained from six male subjects before and in a 24-h time course after a single bout of mild eccentric ergometer exercise. The eccentric exercise consisted of 15min of eccentric cycling at 50% of the individual maximal concentric power output leading to muscle soreness (5.9 on a 0-10 visual analogue scale) and limited muscle damage (1.7-fold elevated creatine kinase activity). Muscle impairment was highlighted by a transient reduction in jumping height after the eccentric exercise. On the gene expression level, we observed a general early downregulation of detected transcripts, followed by a slow recovery close to the control values within the first 24h post exercise. Only very few regulatory factors were increased. This expression signature is different from the signature of a previously published metabolic response after an intensive endurance-type concentric exercise as well as after maximal eccentric exercise. This is the first description of the time course of changes in gene expression as a consequence of a mild eccentric stimulu

Intercepting second-messenger signaling by rationally designed peptides sequestering c-di-GMP

The bacterial second messenger cyclic diguanylate (c-di-GMP) regulates a wide range of cellular functions from biofilm formation to growth and survival. Targeting a second-messenger network is challenging because the system involves a multitude of components with often overlapping functions. Here, we present a strategy to intercept c-di-GMP signaling pathways by directly targeting the second messenger. For this, we developed a c-di-GMP-sequestering peptide (CSP) that was derived from a CheY-like c-di-GMP effector protein. CSP binds c-di-GMP with submicromolar affinity. The elucidation of the CSP⋅c-di-GMP complex structure by NMR identified a linear c-di-GMP-binding motif, in which a self-intercalated c-di-GMP dimer is tightly bound by a network of H bonds and π-stacking interactions involving arginine and aromatic residues. Structure-based mutagenesis yielded a variant with considerably higher, low-nanomolar affinity, which subsequently was shortened to 19 residues with almost uncompromised affinity. We demonstrate that endogenously expressed CSP intercepts c-di-GMP signaling and effectively inhibits biofilm formation in Pseudomonas aeruginosa , the most widely used model for serious biofilm-associated medical implications

Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Mammalian Molecular Clocks

As a consequence of the Earth's rotation, almost all organisms experience day and night cycles within a 24-hr period. To adapt and synchronize biological rhythms to external daily cycles, organisms have evolved an internal time-keeping system. In mammals, the master circadian pacemaker residing in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus generates circadian rhythmicity and orchestrates numerous subsidiary local clocks in other regions of the brain and peripheral tissues. Regardless of their locations, these circadian clocks are cell-autonomous and self-sustainable, implicating rhythmic oscillations in a variety of biochemical and metabolic processes. A group of core clock genes provides interlocking molecular feedback loops that drive the circadian rhythm even at the single-cell level. In addition to the core transcription/translation feedback loops, post-translational modifications also contribute to the fine regulation of molecular circadian clocks. In this article, we briefly review the molecular mechanisms and post-translational modifications of mammalian circadian clock regulation. We also discuss the organization of and communication between central and peripheral circadian oscillators of the mammalian circadian clock

Pest categorisation of Scirtothrips citri

The Panel on Plant Health performed a pest categorisation of the citrus thrips, Scirtothrips citri (Moulton) (Thysanoptera: Thripidae), for the European Union (EU). This is a well-de fi ned and distinguishable species, occurring in North America and Asia. Its precise distribution in Asia is uncertain. S. citri is a pest of citrus and blueberries and has been cited on over 50 different host species in 33 plant families. Whether all plants reported as hosts are true hosts, allowing population development of S. citri , is uncertain. S. citri feeds exclusively on young actively growing foliage and fruit. It is not known to occur in the EU and is listed in Annex IIAI of 2000/29/EC as a harmful organism. The international trade of hosts, as either plants for planting or cut fl owers, provide potential pathways into the EU. However, current EU legislation prohibits the import of citrus plants for planting. Furthermore, measures aimed at the import of plants for planting in a dormant stage (no young foliage or fruits present) with no soil/growing medium attached, decreases the likelihood of the pest ’ s entry via other hosts. Considering that there are regional climatic similarities where S. citri occurs in the USA with climates in the EU, and taking EU host distribution into account, S. citri has the potential to establish in the EU, especially in citrus and blueberry growing regions around the Mediterranean where quality losses in citrus and yield losses in blueberry could occur. Phytosanitary measures are available to inhibit the likelihood of introduction of S. citri from infested countries. Considering the criteria within the remit of EFSA to assess its status as a potential Union quarantine pest (QP) or as a potential regulated non-quarantine pest (RNQP), S. citri meets with no uncertainties the criteria assessed by EFSA for consideration as a potential Union QP

Pest categorisation of Toxoptera citricida

23The European Commission requested EFSA to conduct a pest categorisation of Toxoptera citricida (Hemiptera: Aphididae), an oligophagous aphid developing and reproducing parthenogenetically on tender leaf and flower flush of citrus (Rutaceae). T.citricida is a taxonomic entity with reliable methods available for detection and identification. It is regulated in the EU by Council Directive 2000/29/EC where it is listed in Annex IIAI as a harmful organism whose introduction and spread into the EU shall be banned. T.citricida is native to tropical regions of Southeast Asia and has spread to most citrus-growing areas worldwide, except California and the Mediterranean basin, causing significant damage to citrus as it is the most efficient vector of the Citrus tristeza virus (CTV). T.citricida occurs in Madeira and, with a restricted distribution, in the north-west of the Iberian Peninsula, mostly on backyard citrus trees. This may have hindered the effectiveness of the official control measures in these areas. There are further phytosanitary measures in place in the EU in order to limit entry via traded commodities. Citrus plants for planting are regulated and are a closed pathway. However, there is uncertainty regarding host status of some non-rutaceous plants on which this aphid has been recorded and so other plant genera may provide additional pathways. The EFSA Plant Health Panelconcludes that the establishment of T.citricida in the main EU citrus growing areas around the Mediterranean would have significant impacts because of its ability to vector CTV. Considering the criteria within the remit of EFSA to assess the status as a potential Union quarantine pest (QP), as a potential protected zone quarantine pest (PZQP) or as a potential regulated non-quarantine pest (RNQP), T.citricida meets with no uncertainties the criteria assessed by EFSA for consideration as a potential Union QP.openopenJeger, Michael; Bragard, Claude; Caffier, David; Candresse, Thierry; Chatzivassiliou, Elisavet; Dehnen‐Schmutz, Katharina; Gilioli, Gianni; Grégoire, Jean‐Claude; Jaques Miret, Josep Anton; Navarro, Maria Navajas; Niere, Björn; Parnell, Stephen; Potting, Roel; Rafoss, Trond; Rossi, Vittorio; Urek, Gregor; Van Bruggen, Ariena; Van der Werf, Wopke; West, Jonathan; Winter, Stephan; Gardi, Ciro; Bergeretti, Filippo; MacLeod, AlanJeger, Michael; Bragard, Claude; Caffier, David; Candresse, Thierry; Chatzivassiliou, Elisavet; Dehnen‐schmutz, Katharina; Gilioli, Gianni; Grégoire, Jean‐claude; Jaques Miret, Josep Anton; Navarro, Maria Navajas; Niere, Björn; Parnell, Stephen; Potting, Roel; Rafoss, Trond; Rossi, Vittorio; Urek, Gregor; Van Bruggen, Ariena; Van der Werf, Wopke; West, Jonathan; Winter, Stephan; Gardi, Ciro; Bergeretti, Filippo; Macleod, Ala

Pest categorisation of Longidorus diadecturus

The Panel on Plant Health performed a pest categorisation of Longidorus diadecturus (Nematoda: Longidoridae) for the EU. The nematode is a well-defined taxon and was described from Ontario, Canada and later reported from some states in the USA. The nematode is not present in the EU. It is regulated by Council Directive 2000/29/EC, listed in Annex I A I as L. diadecturus Eveleigh and Allen. It is a migratory ectoparasitic nematode species puncturing cells of plant roots thereby able to transmit the nepovirus Peach rosette mosaic virus (PRMV). The pest is found in soil associated with plant species belonging to different families. L. diadecturus is able to cause direct damage to plants, but its main damage is caused by vectoring PRMV. Soil is a potential pathway for this nematode for entry into the EU. The nematode is able to survive adverse conditions, but the virus may not persist inside the nematode for extended periods. Climatic conditions in the EU are similar to those found in the countries where the pest is currently present. Hosts of the nematode (and the associated virus) are, e.g. peaches and grapes; those crops are also widely cultivated in the EU. The nematode only moves short distances (around 1 m) but may be spread with soil moving activities. Measures are available to inhibit entry via soil as such. Entry of the nematode with soil attached to plants for planting that are not regulated is possible. L. diadecturus does satisfy all the criteria that are within the remit of EFSA to assess to be regarded as a potential Union quarantine pest