CO2: Editorial Board/Subscription info.

Publication date: December 2017
Source:Progress in Neurobiology, Volume 159





http://ift.tt/2k8jPFy

HDAC11 is a regulator of diverse immune functions

Publication date: Available online 6 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Cansu Yanginlar, Colin Logie
Histone deacetylases deacetylate histone and non-histone protein targets. Aberrant HDAC expression and function have been observed in several diseases, which makes these enzymes attractive treatment targets. Here, we summarize recent literature that addresses the roles of HDAC11 on the regulation of different immune cells including neutrophils, myeloid derived suppressor cells and T-cells. HDAC11 was initially identified as a negative regulator of the well-known anti-inflammatory cytokine IL-10. Hence, antagonizing HDAC11 activity may have anti-tumor potential, whereas activating HDAC11 may be useful to treat chronic inflammation or autoimmunity. However, to anticipate biological side-effects of HDAC11 modulators, more molecular insights will be required.



http://ift.tt/2B2QNBP

Regulation of tRNA biogenesis in plants and its link to plant growth and response to pathogens

Publication date: Available online 6 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Adriana Santos Soprano, Juliana Helena Costa Smetana, Celso Eduardo Benedetti
tRNA biology has fascinated scientists over the years. Besides their fundamental role in protein translation, new evidence indicates that tRNA-derived molecules also regulate gene expression and protein synthesis in all domains of life. In this review, we will highlight some of the recent findings linking tRNA transcription and modification with plant cell growth and response to pathogens. In fact, mutations in proteins directly involved in tRNA synthesis and modification most often lead to pleiotropic effects on plant growth and immunity. As plants need to optimize and balance their energy and nutrient resources towards growth and defense, regulatory pathways that play a central role in integrating tRNA transcription and protein translation with cell growth control and organ development, such as the auxin-TOR signaling pathway, also influence the plant immune response against pathogens. As a consequence, distinct pathogens employ an array of effector molecules including tRNA fragments to target such regulatory pathways to exploit the plant's translational capacity, gain access to nutrients and evade defenses. An example includes the RNA polymerase III repressor MAF1, a conserved component of the TOR signaling pathway that controls ribosome biogenesis and tRNA synthesis required for plant growth and which is targeted by a pathogen effector molecule to promote disease. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.



http://ift.tt/2AEcNAb

PARP1 facilitates EP300 recruitment to the promoters of the subset of RBL2-dependent genes

Publication date: Available online 5 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Agnieszka Robaszkiewicz, Ewelina Wiśnik, Zsolt Regdon, Kinga Chmielewska, László Virág
Differentiation of human monocytes is associated with proliferation arrest resulting from activation of the inter alia retinoblastoma protein family of gene repressors, which target gene promoters in an E2F-dependent manner. To investigate RBL2 contribution to defining monocyte phenotype and function, we used primer libraries. We identified genes encoding two surface receptors (CXCR1 and IL17RE) and two TLR signaling mediators (CD86 and NFKB2) that are repressed by the RBL2-E2F4-HDAC1-BRM complex. Surprisingly, PARP1 co-regulated 24 out of the 28 identified genes controlled by RBL2. Upon RBL2 silencing, PARP1 was recruited to one subset of RBL2-dependent genes, represented by MAP2K6 and MAPK3. RBL2 silencing also restored PARP1 transcription. Gene promoters enriched in PARP1 were characterized by increased histone acetylation and the replacement of HDAC1 with EP300. While PARP1 was dispensable for HDAC1 dissociation, EP300 was found only at gene promoters enriched in PARP1. EP300 activated transcription of PARP1/RBL2 co-regulated genes, but not genes solely controlled by RBL2. DNA was a prerequisite to the formation of an immunoprecipitated PARP1-EP300 complex, suggesting that PARP1 enabled EP300 binding, which in turn activated gene transcription. Notably, PARP1 overexpression failed to overcome the inhibitory effect of RBL2 on MAP2K6 and MAPK3 transcription. The same interdependence was observed in proliferating cancer cells; the low abundance of RBL2 resulted in PARP1-mediated EP300 recruitment to promoters of the MAP2K6 and MAPK3 genes. We conclude that RBL2 may indirectly regulate transcription of some genes by controlling PARP1-mediated EP300 recruitment.

Graphical abstract

http://ift.tt/2B2QM0J

Cooperativity between different tRNA modifications and their modification pathways

Publication date: Available online 5 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Mikołaj Sokołowski, Roland Klassen, Alexander Bruch, Raffael Schaffrath, Sebastian Glatt
Ribonucleotide modifications perform a wide variety of roles in synthesis, turnover and functionality of tRNA molecules. The presence of particular chemical moieties can refine the internal interaction network within a tRNA molecule, influence its thermodynamic stability, contribute novel chemical properties and affect its decoding behavior during mRNA translation. As the lack of specific modifications in the anticodon stem and loop causes disrupted proteome homeostasis, diminished response to stress conditions, and the onset of human diseases, the underlying modification cascades have recently gained particular scientific and clinical interest. Nowadays, a complicated but conclusive image of the interconnectivity between different enzymatic modification cascades and their resulting tRNA modifications emerges. Here we summarize the current knowledge in the field, focusing on the known instances of cross talk among the enzymatic tRNA modification pathways and the consequences on the dynamic regulation of the tRNA modificome by various factors. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.



http://ift.tt/2AZLXoE

5-Azacytidine engages an IRE1α-EGFR-ERK1/2 signaling pathway that stabilizes the LDL receptor mRNA

Publication date: Available online 5 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Nourhen Mnasri, Maya Mamarbachi, Bruce G. Allen, Gaétan Mayer
Hepatic low-density lipoprotein receptor (LDLR) is the primary conduit for the clearance of plasma LDL-cholesterol and increasing its expression represents a central goal for treating cardiovascular disease. However, LDLR mRNA is unstable and undergoes rapid turnover mainly due to the three AU-rich elements (ARE) in its proximal 3′-untranslated region (3′-UTR). Herein, our data revealed that 5-azacytidine (5-AzaC), an antimetabolite used in the treatment of myelodysplastic syndrome, stabilizes the LDLR mRNA through a previously unrecognized signaling pathway resulting in a strong increase of its protein level in human hepatocytes in culture. 5-AzaC caused a sustained activation of the inositol-requiring enzyme 1α (IRE1α) kinase domain and c-Jun N-terminal kinase (JNK) independently of endoplasmic reticulum stress. This resulted in activation of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase1/2 (ERK1/2) that, in turn, stabilized LDLR mRNA. Systematic mutation of the AREs (ARE1-3) in the LDLR 3′UTR and expression of each mutant coupled to a luciferase reporter in Huh7 cells demonstrated that ARE1 is required for rapid LDLR mRNA decay and 5-AzaC-induced mRNA stabilization via the IRE1α-EGFR-ERK1/2 signaling cascade. The characterization of this pathway will help to reveal potential targets to enhance plasma LDL clearance and novel cholesterol-lowering therapeutic strategies.



http://ift.tt/2AGcaWW

Regulation of tRNA gene transcription by the chromatin structure and nucleosome dynamics

Publication date: Available online 5 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Ashutosh Shukla, Purnima Bhargava
The short, non-coding genes transcribed by the RNA polymerase (pol) III, necessary for survival of a cell, need to be repressed under the stress conditions in vivo. The pol III-transcribed genes have adopted several novel chromatin-based regulatory mechanisms to their advantage. In the budding yeast, the sub-nucleosomal size tRNA genes are found in the nucleosome-free regions, flanked by positioned nucleosomes at both the ends. With their chromosomes-wide distribution, all tRNA genes have a different chromatin context. A single nucleosome dynamics controls the accessibility of the genes for transcription. This dynamics operates under the influence of several chromatin modifiers in a gene-specific manner, giving the scope for differential regulation of even the isogenes within a tRNA gene family. The chromatin structure around the pol III-transcribed genes provides a context conducive for steady-state transcription as well as gene-specific transcriptional regulation upon signaling from the environmental cues.This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.



http://ift.tt/2AZLUsY

tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: Location, location, location

Publication date: Available online 28 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Kunal Chatterjee, Regina T. Nostramo, Yao Wan, Anita K. Hopper
Although tRNAs participate in the essential function of protein translation in the cytoplasm, tRNA transcription and numerous processing steps occur in the nucleus. This subcellular separation between tRNA biogenesis and function requires that tRNAs be efficiently delivered to the cytoplasm in a step termed "primary tRNA nuclear export". Surprisingly, tRNA nuclear-cytoplasmic traffic is not unidirectional, but, rather, movement is bidirectional. Cytoplasmic tRNAs are imported back to the nucleus by the "tRNA retrograde nuclear import" step which is conserved from budding yeast to vertebrate cells and has been hijacked by viruses, such as HIV, for nuclear import of the viral reverse transcription complex in human cells. Under appropriate environmental conditions cytoplasmic tRNAs that have been imported into the nucleus return to the cytoplasm via the 3rd nuclear-cytoplasmic shuttling step termed "tRNA nuclear re-export", that again is conserved from budding yeast to vertebrate cells. We describe the 3 steps of tRNA nuclear-cytoplasmic movements and their regulation. There are multiple tRNA nuclear export and import pathways. The different tRNA nuclear exporters appear to possess substrate specificity leading to the tantalizing possibility that the cellular proteome may be regulated at the level of tRNA nuclear export. Moreover, in some organisms, such as budding yeast, the pre-tRNA splicing heterotetrameric endonuclease (SEN), which removes introns from pre-tRNAs, resides on the cytoplasmic surface of the mitochondria. Therefore, we also describe the localization of the SEN complex to mitochondria and splicing of pre-tRNA on mitochondria, which occurs prior to the participation of tRNAs in protein translation. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.



http://ift.tt/2AEyK22

Elongator—a tRNA modifying complex that promotes efficient translational decoding

Publication date: Available online 21 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Marcus J.O. Johansson, Fu Xu, Anders S. Byström
Naturally occurring modifications of the nucleosides in the anticodon region of tRNAs influence their translational decoding properties. Uridines present at the wobble position in eukaryotic cytoplasmic tRNAs often contain a 5-carbamoylmethyl (ncm⁵) or 5-methoxycarbonylmethyl (mcm⁵) side-chain and sometimes also a 2-thio or 2′-O-methyl group. The first step in the formation of the ncm⁵ and mcm⁵ side-chains requires the conserved six-subunit Elongator complex. Although Elongator has been implicated in several different cellular processes, accumulating evidence suggests that its primary, and possibly only, cellular function is to promote modification of tRNAs. In this review, we discuss the biosynthesis and function of modified wobble uridines in eukaryotic cytoplasmic tRNAs, focusing on the in vivo role of Elongator-dependent modifications in Saccharomyces cerevisiae. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.



http://ift.tt/2AZBJEL

Vaginoplasty and Perineoplasty

No abstract available

http://ift.tt/2j0AD4y

The Fine Wire Technique for Flexor Tenolysis

Background: Flexor tenolysis surgery for flexor digitorum profundus and superficialis adhesions is a common procedure performed by hand surgeons. Releasing these adhered tendons can greatly improve hand function and improve quality of life. Recent evidence, however, has shown that the outcomes of tenolysis surgeries are often suboptimal and can result in relapsing adhesions or even tendon ruptures. Methods: This article describes a new technique with potential for reduced complication rates: The Fine Wire Technique for Flexor Tenolysis (FWT). Results: Following FWT, the patient detailed in this article had an excellent recovery of function and no complications: including tendon rupture, infection, hematomas, or any other complications. She reported a major improvement from her preoperative functionality and continues to have this level of success. The wire's thinness allows for a swift tenolysis. Conclusions: The FWT is a new option available to the hand surgeon associated with good functional results. The wire is readily available to the clinician and is also inexpensive.

http://ift.tt/2j0AIoS

Dynamic Model of Applied Facial Anatomy with Emphasis on Teaching of Botulinum Toxin A

Background: The use of botulinum toxin type A is considered one of the most revolutionary and promising face rejuvenation methods. Although rare, most of the complications secondary to the use of botulinum toxin A are technician dependent. Among the major shortcomings identified in the toxin administration education is unfamiliarity with applied anatomy. This article proposes the use of body painting as an innovative method of teaching the application of botulinum toxin A. Methods: Using the body painting technique, facial anatomy was represented on the face of a model showing the major muscle groups of botulinum toxin A targets. Photographic records and films were made for documentation of represented muscles at rest and contraction. Results: Using the body painting technique, each of the muscles involved in facial expression and generation of hyperkinetic wrinkles can be faithfully reproduced on the model's face. The documentation of the exact position of the points of application, the distribution of the feature points in the muscular area, the proper angulation and syringe grip, as well as the correlation of the points of application with the presence of hyperkinetic wrinkles, could be properly registered, providing professional training with information of great practical importance, development of highly effective treatments, and low complication rates. Conclusion: By making it possible to interrelate anatomy of a function, body painting is proposed in the present study as an innovative method, which in a demonstrative and highly didactic manner presents great potential as a teaching tool in the application of botulinum toxin A.

http://ift.tt/2j17iXN

Potential vulnerability of oak forests to climate change-induced flooding: effects of mild oxygen deficiency on Quercus robur and Quercus petraea seedling physiology

Abstract

Flooding is characterized by saturation of soil pores with water, leading to hypoxic conditions which affect plant root development and metabolism. We investigated the oxygen deficiency tolerance observed in Quercus robur and Quercus petraea and seek to understand whether it can be explained by enhanced efficiency in oxygen use in the roots, as estimated through radial oxygen loss visualization in relation to growth measurements and root apex respiration. The study showed that root growth, under oxygen deficiency conditions, was significantly reduced only in Q. robur seedlings. Root respiration was maintained in Q. robur, whereas it was decreased in Q. petraea. Both species set up a barrier against radial oxygen loss, though measurement of apex oxygen leakage showed greater oxygen efficiency in Q. robur seedlings. This strategy might allow Q. robur to maintain its respiration and thus to survive longer under oxygen deficiency conditions by facilitating the seedling establishment in transient flooded soils.

http://ift.tt/2AXxB8v

Revisiting the alerting effect of light; a systematic review

Light plays an essential role in maintaining alertness levels. Like other non-image-forming responses, the alerting effect of light is influenced by its spectral wavelength, duration and intensity. Alertness levels are also dependent on circadian rhythm (Process C) and homeostatic sleep pressure (Process S), consistent with the classic two-process model of sleep regulation. Over the last decade, there has been increasing recognition of an additional process (referred to as the third process) in sleep regulation.

http://ift.tt/2AncnkU

Muscle recruitment and coordination during upper-extremity functional tests

Publication date: Available online 7 December 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Keshia M. Peters, Valerie E. Kelly, Tasha Chang, Madeline C. Weismann, Sarah Westcott-McCoy, Katherine M. Steele
Performance-based tests, such as the Jebsen Taylor Hand Function Test or Chedoke Arm and Hand Activity Inventory, are commonly used to assess functional performance after neurologic injury. However, the muscle activity required to execute these tasks is not well understood, even for unimpaired individuals. The purpose of this study was to evaluate unimpaired muscle recruitment and coordination of the dominant and non-dominant limbs during common clinical tests. Electromyography (EMG) recordings from eight arm muscles were monitored bilaterally for twenty unimpaired participants while completing these tests. Average signal magnitudes, activation times, and cocontraction levels were calculated from the filtered EMG data, normalized by maximum voluntary isometric contractions (MVICs). Overall, performance of these functional tests required low levels of muscle activity, with average EMG magnitudes less than 6.5% MVIC for all tests and muscles, except the extensor digitorum, which had higher activations across all tasks (11.7±2.7% MVIC, dominant arm). When averaged across participants, cocontraction was between 25-62% for all tests and muscle pairs. Tasks evaluated by speed of completion, rather than functional quality of movement demonstrated higher levels of muscle recruitment. These results provide baseline measurements that can be used to evaluate muscle-specific deficits after neurologic injury and track recovery using common clinical tests.



http://ift.tt/2ky0Fwy

Alteration of autophagy-related proteins in peripheral blood mononuclear cells of patients with Parkinson's disease

Publication date: March 2018
Source:Neurobiology of Aging, Volume 63
Author(s): Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6). Reverse transcription–polymerase chain reaction and Western blot analysis confirmed significantly increased protein levels of upstream autophagy (ULK1, Beclin1, and autophagy/beclin1 regulator 1) with negative feedback of mRNA expression for these proteins in PD. These protein levels were correlated with increased levels of α-synuclein in PBMCs. The expression level of the oligomeric form of α-synuclein in PBMCs paralleled the clinical severity of PD and the degeneration of cardiac sympathetic nerves. Basal activity of autophagy can be lower in patients with PD. Alteration of basal autophagy may be a fundamental aspect of PD.



http://ift.tt/2jrv6kR

Striking a chord with healthy aging: memory system cooperation is related to preserved configural response learning in older adults

Publication date: March 2018
Source:Neurobiology of Aging, Volume 63
Author(s): Michelle W. Voss, Rachel Clark, Michael Freedberg, Timothy Weng, Eliot Hazeltine
Evidence from tasks that primarily tap either hippocampal- or striatal-based memory systems suggests that although these systems often compete for control of behavior, aging is associated with greater cooperation between them. This may stem from altered prefrontal cortex function. Here, we use a configural response task designed to engage both memory systems to test how age affects their interaction with cortical regions including the prefrontal cortex. We found that although older and younger adults learned just as well, older adults showed greater initial activation in cortical networks associated with visuospatial-action mapping and resolving conflict for competing memory representations. Older adults also showed greater functional coupling of the striatum with the left inferior frontal gyrus, in parallel with similar hippocampal coupling to ventral visual regions as young adults. Overall, our results support the proposal that aging is associated with more cooperative memory systems, but we did not find that greater cooperation is associated with less interaction between the prefrontal cortex and core memory system structures during learning.



http://ift.tt/2ADLUyv

Assessment of debris inputs from land into the river in the Three Gorges Reservoir Area, China

Abstract

Riverine debris in the Three Gorges Reservoir Area (TGRA) poses a threat to electricity generation, ship navigation, and water environment. Quantifying riverine debris inputs from land into the river is a foundation for modeling of the transport and accumulation of floating debris on the water surface in the TGRA. However, this has not been researched to date. In this study, debris inputs from land into the river in the TGRA were assessed according to the response relationship between debris inputs and surface runoff. The land-based debris inputs in the TGRA were estimated using simulated surface runoff which was simulated by the Soil and Water Assessment Tool (SWAT) model. Results showed that 15.32 × 10⁶ kg of land-based debris was inputted into the main channel of the TGRA in 2015 which accounted for 9.74% of total debris inputs (the monitoring data of river-sourced and land-sourced debris inputs was 157.27 × 10⁶ kg). Debris inputs varied seasonally and peaked in the summer season (July to September). Compared with monthly measured data, the average relative errors in 2015 were below 30%. In addition, areas with higher debris pollution inputs were mainly located in the upper section of the TGRA, between the Tang River Basin and the Long River Basin. The proposed method was tested and determined to be reliable; thus, it can be used to quickly estimate debris inputs from land into the river by surface runoff of the outlets in a river basin. Moreover, this method provides new insight into the estimation of land-based debris inputs into rivers.

http://ift.tt/2iAZBUr

Time resolution requirements for civilian radioxenon emission data for the CTBT verification regime

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): Pieter De Meutter, Johan Camps, Andy Delcloo, Benoît Deconninck, Piet Termonia
The capability of the noble gas component of the International Monitoring System as a verification tool for the Comprehensive Nuclear-Test-Ban Treaty is deteriorated by a background of radioxenon emitted by civilian sources. One of the possible approaches to deal with this issue, is to simulate the daily radioxenon concentrations from these civilian sources at noble gas stations by using atmospheric transport models. In order to accurately quantify the contribution from these civilian sources, knowledge on the releases is required. However, such data are often not available and furthermore it is not clear what temporal resolution such data should have. In this paper, we assess which temporal resolution is required to best model the ¹³³Xe contribution from civilian sources at noble gas stations in an operational context. We consider different sampling times of the noble gas stations and discriminate between nearby and distant sources. We find that for atmospheric transport and dispersion problems on a scale of 1000 km or more, emission data with subdaily temporal resolution is generally not necessary. However, when the source-receptor distance decreases, time-resolved emission data become more important. The required temporal resolution of emission data thus depends on the transport scale of the problem. In the context of the Comprehensive Nuclear-Test-Ban Treaty, where forty noble gas stations will monitor the whole globe, daily emission data are generally sufficient, but for certain meteorological conditions, better temporally resolved emission data are required.



http://ift.tt/2BKWpxf

Chemical properties and colors of fermenting materials in salmon fish sauce production

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Mitsutoshi Nakano, Yoshimasa Sagane, Ryosuke Koizumi, Yozo Nakazawa, Masao Yamazaki, Toshihiro Watanabe, Katsumi Takano, Hiroaki Sato
This data article reports the chemical properties (moisture, pH, salinity, and soluble solid content) and colors of fermenting materials in salmon fish sauce products. The fish sauce was produced by mixing salt with differing proportions of raw salmon materials and fermenting for three months; the salmon materials comprised flesh, viscera, an inedible portion, and soft roe. Chemical properties and colors of the unrefined fish sauce (moromi), and the refined fish sauce, were analyzed at one, two, and three months following the start of fermentation. Data determined for all products are provided in table format.



http://ift.tt/2nGqr2M