Norepinephrine Protects against Methamphetamine Toxicity through β2-Adrenergic Receptors Promoting LC3 Compartmentalization

Norepinephrine (NE) neurons and extracellular NE exert some protective effects against a variety of insults, including methamphetamine (Meth)-induced cell damage. The intimate mechanism of protection remains difficult to be analyzed in vivo. In fact, this may occur directly on target neurons or as the indirect consequence of NE-induced alterations in the activity of trans-synaptic loops. Therefore, to elude neuronal networks, which may contribute to these effects in vivo, the present study investigates whether NE still protects when directly applied to Meth-treated PC12 cells. Meth was selected based on its detrimental effects along various specific brain areas. The study shows that NE directly protects in vitro against Meth-induced cell damage. The present study indicates that such an effect fully depends on the activation of plasma membrane β2-adrenergic receptors (ARs). Evidence indicates that β2-ARs activation restores autophagy, which is impaired by Meth administration. This occurs via restoration of the autophagy flux and, as assessed by ultrastructural morphometry, by preventing the dissipation of microtubule-associated protein 1 light chain 3 (LC3) from autophagy vacuoles to the cytosol, which is produced instead during Meth toxicity. These findings may have an impact in a variety of degenerative conditions characterized by NE deficiency along with autophagy impairment.

The Role of Grass MUTE Orthologs in GMC Progression and GC Morphogenesis

Stomata arose about 400 million years ago when plants left their aquatic environment. The last step of stomatal development is shared by all plant groups, and it implies a symmetrical cell division from the guard mother cell (GMC) to produce two guard cells (GCs) flanking a pore. In Arabidopsis, the basic helix-loop-helix transcription factor MUTE controls this step, upregulating cell-cycle regulators of the GMC division, and immediately afterward, repressors of theses regulators like FAMA and FOUR LIPS. Recently, three grass MUTE orthologs (BdMUTE from Brachypodium distachyon, OsMUTE from rice, and ZmMUTE from maize) have been identified and characterized. Mutations in these genes disrupt GMC fate, with bdmute also blocking GC morphogenesis. However, because these genes also regulate subsidiary cell recruitment, which takes place before GMC division, their functions regulating GMC division and GC morphogenesis could be an indirect consequence of that inducing the recruitment of subsidiary cells. Comprehensive data evaluation indicates that BdMUTE, and probably grass MUTE orthologs, directly controls GMC fate. Although grass MUTE proteins, whose genes are expressed in the GMC, move between cells, they regulate GMC fate from the cells where they are transcribed. Grass MUTE genes also regulate GC morphogenesis. Specifically, OsMUTE controls GC shape by inducing OsFAMA expression. In addition, while SCs are not required for GMC fate progression, they are for GC maturation.

Assessing local drivers influencing Land Use Cover Change (LUCC) in Southwestern Ghana: A Mixed-Method Approach (MMA) Analyses.

Changes in land cover have persisted throughout the history of mankind, and are the direct and indirect consequence of human actions to secure essential resources. Understanding direct and indirect factors that influence land use cover change (LUCC) is essential for modelling future LUCC in developing countries. The study analyses local drivers of LUCC in Southwestern Ghana using the mixed-method approach. The approach aided in identifying key drivers of LUCC, using different research strategies for comparisons through confidence level analysis and Analytic Hierarchy Process (AHP). We used expert interviews, literature review and geostatistical tools to ascertain causative factors triggering such unprecedented changes. Geospatial analysis depicted a decline in forests (-1.65 km2yr-1.) and areas covered by water bodies (-0.55 km2yr-1.). A remarkable increase in built-up (+25.77 km2yr-1.) and farmlands/shrubs (+7.4km2yr-1.) areas were also observed. Population growth, expansion of settlements and infrastructure, coupled with agricultural expansion are at the centre of the LUCC-environment nexus, based on the confidence level table. A steady increase in surface temperature can be attributed to the unprecedented LUCC over the past 50 years. Socio-economic development in Southwestern Ghana is fuelling interest in the relation between LUCC and environmental change. Biophysical, cultural and technological factors are also considered key drivers despite the “medium-to-very low confidence” in results generated. They could potentially impact climate-sensitive sectors that significantly modify land-use systems from the pessimists and optimist’s perspective. We, therefore, propose further analyses of LUCC drivers with medium to very low confidence levels.

Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression

Neurotransmitter transporters limit spillover between synapses and maintain the extracellular neurotransmitter concentration at low yet physiologically meaningful levels. They also exert a key role in providing precursors for neurotransmitter biosynthesis. In many cases, neurons and astrocytes contain a large intracellular pool of transporters that can be redistributed and stabilized in the plasma membrane following activation of different signaling pathways. This means that the uptake capacity of the brain neuropil for different neurotransmitters can be dynamically regulated over the course of minutes, as an indirect consequence of changes in neuronal activity, blood flow, cell-to-cell interactions, etc. Here we discuss recent advances in the mechanisms that control the cell membrane trafficking and biophysical properties of transporters for the excitatory, inhibitory and modulatory neurotransmitters glutamate, GABA, and dopamine.

A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans

Fluctuations in TOR, AMPK and MAP-kinase signalling maintain cellular homeostasis and coordinate growth and division with environmental context. We have applied quantitative, SILAC mass spectrometry to map TOR and nutrient-controlled signalling in the fission yeast Schizosaccharomyces pombe . Phosphorylation levels at more than 1000 sites were altered following nitrogen stress or Torin1 inhibition of the TORC1 and TORC2 networks that comprise TOR signalling. One hundred and thirty of these sites were regulated by both perturbations, and the majority of these (119) new targets have not previously been linked to either nutritional or TOR control in either yeasts or humans. Elimination of AMPK inhibition of TORC1, by removal of AMPK α ( ssp2::ura4 + ), identified phosphosites where nitrogen stress-induced changes were independent of TOR control. Using a yeast strain with an ATP analogue-sensitized Cdc2 kinase, we excluded sites that were changed as an indirect consequence of mitotic control modulation by nitrogen stress or TOR signalling. Nutritional control of gene expression was reflected in multiple targets in RNA metabolism, while significant modulation of actin cytoskeletal components points to adaptations in morphogenesis and cell integrity networks. Reduced phosphorylation of the MAPKK Byr1, at a site whose human equivalent controls docking between MEK and ERK, prevented sexual differentiation when resources were sparse but not eliminated.

Effects of channel engineering on flood dynamics along the middle and lower Rhône over the last two centuries.

<p>The Rhône River has undergone many anthropogenic transformations to improve his navigability and produce hydroelectricity since the mid-19th century. From the longitudinal dikes of the 1850’s to the hydroelectric diversion schemes of the 1950’s and 1960’s, these structures had a direct impact on the channel geometry along the 300km of river course between Lyon (France) and the Mediterranean Sea. An indirect consequence could be a change in the flood dynamics along the channel course, caused by the simplification of the channel patterns and the floodplain accretion. This communication aims to assess the potential changes in the flood propagation along the middle and lower Rhône valley throughout a century of anthropogenic reconfigurations of the channel. The possible impact of these human pressures on the inundation risk and the attenuation of the flood peak discharge is also discussed. Through the use of digitized hydrometric data recorded since 1840 on multiple stream gauges of the Rhône river, a variety of floods of the same type and magnitude are selected. The oceanic flood types (as described by Pardé, 1925) that take their origin from heavy rainfalls upstream of the area of interest are preferred. Thus, complex flood waves due to floods from the lower Rhône valley tributaries are avoided, to keep the analysis as simple as possible. The flood travel time and the peak discharge attenuation of the selected events are compared over the years of channel transformations, permitting us to estimate the impact of anthropogenic pressures on the flood dynamics.</p>

Migraciones, deportaciones, colonización y geopolítica durante las guerras dácicas de Trajano (101-106 d.C.)

The Trajanic Dacian Wars (101-106 AD) implied multiple expansionist population movements by all contestants, that affected the development and result of the conflict, conditioning many of the implied powers’ decisions. In the same way, the intensity and scale of a conflagration that spreaded throughout Danubian and Pontic Europe, finished with heavy population losses as a direct and indirect consequence of armed clashes. Finally, the consolidation of Roman power in Dacia after its conquest and its particularities supposed the deportation and intentional displacement of native population groups, migrations to zones free from Roman occupation and other sociopolitical and demographical problems solved by the Roman Empire through a planned colonization and the varied diplomatic agreements signed on 119 AD. In this essay we are going to deal, through literary, epigraphic, numismatic, archaeological and iconographical fonts, with this demographical processes, the actualities derived from them and its consequences in the framework of Trajan’s Dacian Wars, processes that conditioned the region’s geopolitics and, therefore, the future composition of Eastern Europe.

Iodinated contrast medium: Is there a re(n)al problem? A clinical vignette-based review

As we were taught, for decades, that iodinated contrast-induced acute kidney injury should be dreaded, considerable efforts were made to find out effective measures in mitigating the renal risk of iodinated contrast media. Imaging procedures were frequently either downgraded (unenhanced imaging) or deferred as clinicians felt that the renal risk pertaining to contrast administration outweighed the benefits of an enhanced imaging. However, could we have missed the point? Among the abundant literature about iodinated contrast-associated acute kidney injury, recent meaningful advances may help sort out facts from false beliefs. Hence, there is increasing evidence that the nephrotoxicity directly attributable to modern iodinated CM has been exaggerated. Failure to demonstrate a clear benefit from most of the tested prophylactic measures might be an indirect consequence. However, the toxic potential of iodinated contrast media is well established experimentally and should not be overlooked completely when making clinical decisions. We herein review these advances in disease and pathophysiologic understanding and the associated clinical crossroads through a typical case vignette in the critical care setting.

The Crossroads between Infection and Bone Loss

Bone homeostasis, based on a tight balance between bone formation and bone degradation, is affected by infection. On one hand, some invading pathogens are capable of directly colonizing the bone, leading to its destruction. On the other hand, immune mediators produced in response to infection may dysregulate the deposition of mineral matrix by osteoblasts and/or the resorption of bone by osteoclasts. Therefore, bone loss pathologies may develop in response to infection, and their detection and treatment are challenging. Possible biomarkers of impaired bone metabolism during chronic infection need to be identified to improve the diagnosis and management of infection-associated osteopenia. Further understanding of the impact of infections on bone metabolism is imperative for the early detection, prevention, and/or reversion of bone loss. Here, we review the mechanisms responsible for bone loss as a direct and/or indirect consequence of infection.