Carnian (Triassic) aridization on the Levant margin: evidence from the M1 member, Mohilla Formation, Makhtesh Ramon, south Israel

The Carnian Pluvial Event was followed by extreme aridity around the Mediterranean region, but the relationship between these climatic modes and the evaporite deposits of the north Arabian margin has not been established. The Mohilla Formation in Israel was deposited on the rifted Levant margin of the Neotethyan seaway during the Carnian (Late Triassic). The lowermost member, M1 (carbonate, shale, minor evaporite), records sea-level and climate change of the transition from open-marine deposits to the thick evaporite of the overlying M2 member. Field, petrographic and cathodoluminescence investigation of the M1 member exposed at Makhtesh Ramon, southern Israel, enabled tracking of changing paleoenvironments. The M1 member can be subdivided into six sea-level controlled sedimentary cycles, each terminating in subaerial exposure. Open-marine, lagoonal, and supratidal belts are represented, but environments become increasingly restricted upwards. Three of the exposure horizons are marked by well-developed early diagenetic features, including dissolution porosity and meteoric cements. These changing facies belts and the superposed diagenetic modes formed under an oscillating climate regime of three relatively humid episodes dominated by deposition of carbonate, alternating with evaporitic sediments indicating aridity. Deposition of the M1 member can be correlated with the transition in the western Tethys from the Carnian pluvial episode to aridity. This transition in the Levant region is characterized by an oscillatory climate that culminated in a thick evaporite unit from the extreme arid phase. The oscillations may be attributed to shifting global climate belts, overprinted by monsoonal strengthening and weakening, in the equatorial belt.     

Photosynthetic reaction center-functionalized electrodes for photo-bioelectrochemical cells

During the last few years, intensive research efforts have been directed toward the application of several highly efficient light-harvesting photosynthetic proteins, including reaction centers (RCs), photosystem I (PSI), and photosystem II (PSII), as key components in the light-triggered generation of fuels or electrical power. This review highlights recent advances for the nano-engineering of photo-bioelectrochemical cells through the assembly of the photosynthetic proteins on electrode surfaces. Various strategies to immobilize the photosynthetic complexes on conductive surfaces and different methodologies to electrically wire them with the electrode supports are presented. The different photoelectrochemical systems exhibit a wide range of photocurrent intensities and power outputs that sharply depend on the nano-engineering strategy and the electroactive components. Such cells are promising candidates for a future production of biologically-driven solar power.     

Drivers of extinction risk in African mammals: the interplay of distribution state,human pressure,conservation response and species biology

Although conservation intervention has reversed the decline of some species, our success is outweighed by a much larger number of species moving towards extinction. Extinction risk modelling can identify correlates of risk and species not yet recognized to be threatened. Here, we use machine learning models to identify correlates of extinction risk in African terrestrial mammals using a set of variables belonging to four classes: species distribution state, human pressures, conservation response and species biology. We derived information on distribution state and human pressure from satellite-borne imagery. Variables in all four classes were identified as important predictors of extinction risk, and interactions were observed among variables in different classes (e.g. level of protection, human threats, species distribution ranges). Species biology had a key role in mediating the effect of external variables. The model was 90% accurate in classifying extinction risk status of species, but in a few cases the observed and modelled extinction risk mismatched. Species in this condition might suffer from an incorrect classification of extinction risk (hence require reassessment). An increased availability of satellite imagery combined with improved resolution and classification accuracy of the resulting maps will play a progressively greater role in conservation monitoring.     

DJ‐1 deficiency triggers microglia sensitivity to dopamine toward a pro‐inflammatory phenotype that is attenuated by rasagiline

DJ‐1 is an oxidative stress sensor that localizes to the mitochondria when the cell is exposed to oxidative stress. DJ‐1 mutations that result in gene deficiency are linked to increased risk of Parkinson's disease (PD). Activation of microglial stress conditions that are linked to PD may result in neuronal death. We postulated that DJ‐1 deficiency may increase microglial neurotoxicity. We found that down‐regulation of DJ‐1 in microglia using an shRNA approach increased cell sensitivity to dopamine as measured by secreted pro‐inflammatory cytokines such as IL‐1β and IL‐6. Furthermore, we discovered that DJ‐1‐deficient microglia had increased monoamine oxidase activity that resulted in elevation of intracellular reactive oxygen species and nitric oxide leading to increased dopaminergic neurotoxicity. Rasagaline, a monoamine oxidase inhibitor approved for treatment of PD, reduced the microglial pro‐inflammatory phenotype and significantly reduced neurotoxicity. Moreover, we discovered that DJ‐1‐deficient microglia have reduced expression of triggering receptor expressed on myeloid cells 2 (TREM2), previously suggested as a risk factor for pro‐inflammation in neurodegenerative diseases. Further studies of DJ‐1‐mediated cellular pathways in microglia may contribute useful insights into the development of PD providing future avenues for therapeutic intervention.

     

mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse

The mammalian (or mechanistic) target of rapamycin (mTOR) complex 1 (mTORC1) is a serine and threonine kinase that regulates cell growth, survival, and proliferation. mTORC1 is a master controller of the translation of a subset of mRNAs. In the central nervous system mTORC1 plays a crucial role in mechanisms underlying learning and memory by controlling synaptic protein synthesis. Here, we review recent evidence suggesting that the mTORC1 signaling pathway promotes neuroadaptations following exposure to a diverse group of drugs of abuse including stimulants, cannabinoids, opiates, and alcohol. We further describe potential molecular mechanisms by which drug‐induced mTORC1 activation may alter brain functions. Finally, we propose that mTORC1 is a focal point shared by drugs of abuse to mediate drug‐related behaviors such as reward seeking and excessive drug intake, and offer future directions to decipher the contribution of the kinase to mechanisms underlying addiction.

     

Physiological arousal for companion dogs working with their owners in animal-assisted activities and animal-assisted therapy

This study investigated the physiological reactions of companion dogs (Canis familiaris) used in animal-assisted activities and animal-assisted therapy by measuring salivary cortisol concentrations. The dog caregivers (owners) collected saliva samples (a) at 3 control days without therapeutic work, (b) directly before and after each therapeutic session during 3 consecutive months, and (c) again at 3 control days without therapeutic work. The study used an enzyme immunoassay to analyze the samples. Cortisol concentrations were significantly higher during therapy days than on control days. Dogs working during the first half of the day produced higher cortisol concentrations after therapeutic sessions than before, whereas dogs working in the afternoon produced lower cortisol concentrations. Cortisol concentrations were higher in short sessions than in long ones and increased relative to the number of therapeutic sessions done during the sampling period. The results indicate that therapeutic work was physiologically arousing for the dogs in this study. Whether these physiological responses are indicative of potentially negative stress or of positive excitement remains an open question.     

Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy

The essential micronutrient selenium is found in proteins as selenocysteine (Sec), the only genetically encoded amino acid whose biosynthesis occurs on its cognate tRNA in humans. In the final step of selenocysteine formation, the essential enzyme SepSecS catalyzes the conversion of Sep-tRNA to Sec-tRNA. We demonstrate that SepSecS mutations cause autosomal-recessive progressive cerebellocerebral atrophy (PCCA) in Jews of Iraqi and Moroccan ancestry. Both founder mutations, common in these two populations, disrupt the sole route to the biosynthesis of the 21st amino acid, Sec, and thus to the generation of selenoproteins in humans.     

Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling

Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis.     

Versatile and Simple Approach to Determine Astrocyte Territories in Mouse Neocortex and Hippocampus

Background

Besides their neuronal support functions, astrocytes are active partners in neuronal information processing. The typical territorial structure of astrocytes (the volume of neuropil occupied by a single astrocyte) is pivotal for many aspects of glia–neuron interactions.

Methods

Individual astrocyte territorial volumes are measured by Golgi impregnation, and astrocyte densities are determined by S100β immunolabeling. These data are compared with results from conventionally applied methods such as dye filling and determination of the density of astrocyte networks by biocytin loading. Finally, we implemented our new approach to investigate age-related changes in astrocyte territories in the cortex and hippocampus of 5- and 21-month-old mice.

Results

The data obtained by our simplified approach based on Golgi impregnation were compared to previously published dye filling experiments, and yielded remarkably comparable results regarding astrocyte territorial volumes. Moreover, we found that almost all coupled astrocytes (as indicated by biocytin loading) were immunopositive for S100β. A first application of this new experimental approach gives insight in age-dependent changes in astrocyte territorial volumes. They increased with age, while cell densities remained stable. In 5-month-old mice, the overlap factor was close to 1, revealing little or no interdigitation of astrocyte territories. However, in 21-month-old mice, the overlap factor was more than 2, suggesting that processes of adjacent astrocytes interdigitate.

Conclusion

Here we verified the usability of a simple, versatile method for assessing astrocyte territories and the overlap factor between adjacent territories. Second, we found that there is an age-related increase in territorial volumes of astrocytes that leads to loss of the strict organization in non-overlapping territories. Future studies should elucidate the physiological relevance of this adaptive reaction of astrocytes in the aging brain and the methods presented in this study might be a powerful tool to do so.     

Completing the Results of the 2013 Boston Marathon

The 2013 Boston marathon was disrupted by two bombs placed near the finish line. The bombs resulted in three deaths and several hundred injuries. Of lesser concern, in the immediate aftermath, was the fact that nearly 6,000 runners failed to finish the race. We were approached by the marathon''s organizers, the Boston Athletic Association (BAA), and asked to recommend a procedure for projecting finish times for the runners who could not complete the race. With assistance from the BAA, we created a dataset consisting of all the runners in the 2013 race who reached the halfway point but failed to finish, as well as all runners from the 2010 and 2011 Boston marathons. The data consist of split times from each of the 5 km sections of the course, as well as the final 2.2 km (from 40 km to the finish). The statistical objective is to predict the missing split times for the runners who failed to finish in 2013. We set this problem in the context of the matrix completion problem, examples of which include imputing missing data in DNA microarray experiments, and the Netflix prize problem. We propose five prediction methods and create a validation dataset to measure their performance by mean squared error and other measures. The best method used local regression based on a K-nearest-neighbors algorithm (KNN method), though several other methods produced results of similar quality. We show how the results were used to create projected times for the 2013 runners and discuss potential for future application of the same methodology. We present the whole project as an example of reproducible research, in that we are able to make the full data and all the algorithms we have used publicly available, which may facilitate future research extending the methods or proposing completely different approaches.