Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

3D spiny AlF_(3)/Mullite heterostructure nanofiber as solid-state polymer electrolyte fillers with enhanced ionic conductivity and improved interfacial compatibility

Lithium metal batteries assembled with solid-state electrolyte can offer high safety and volumetric energy density compared to liquid electrolyte.The polymer solid-state electrolytes of poly(ethylene oxide)(PEO)are widely used in lithium metal solid-state batteries due to their unique properties.However,there are still some defects such as low ionic conductivity at room temperature and weak inhibition of lithium dendrite growth.Herein,the spiny inorganic nanofibers heterostructure with mullite whiskers grown on the surface of aluminum fluoride(AlF_(3))nanofibers are introduced into the PEOLi TFSI electrolytes for the first time to prepare composite solid-state electrolytes.The AlF_(3)as a strong Lewis acid can adsorb anions and promote the dissociation of Li salts.Besides,the specially threedimensional(3D)structure enlarges the effective contacting interface with the PEO polymer,which allows the lithium ions to be transported not only along the large aspect ratio of AlF3nanofibers,but also along the mullite phase in the transmembrane direction rapidly.Thereby,the transport channel of lithium ions at the spiny inorganic nanofibers-polymer interface is further improved.Benefiting from these advantages,the obtained composite solid-state electrolyte has a high ionic conductivity of 1.58×10^(-4)S cm^(-1)at 30℃and the lithium ions transfer number of 0.53.In addition,the AlF3has strong binding energy with anions,low electronic conductivity and wide electrochemical stability window,and reduced nucleation overpotential of lithium during cycling,which is positive for lithium dendrite suppression in solid-state electrolytes.Thus,the assembled symmetric Li/Li symmetric batteries exhibit stable cycling performance at different area capacities of 0.15,0.2,0.3 and 0.4 m A h cm^(-2).More importantly,the LiFePO_(4)(LFP)/Li battery still has 113.5 m A h g-1remaining after 400 cycles at 50℃and the Coulomb efficiency is nearly 100%during the long cycle.Overall,the interconnected structure of 3D spiny inorganic heterostructure nanofiber constitutes fast and uninterrupted lithium ions transport channels,maximizing the synergistic effect of interfacial transport of inorganic fillers and reducing PEO crystallinity,thus providing a novel approach to high performance solid-state electrolytes.

Genetic Diversity and Population Structure for the Conservation of Giant Spiny Frog(Quasipaa spinosa)Using Microsatellite Loci and Mitochondrial DNA

The giant spiny frog （Quasipaa spinosa） is an endangered species with a relatively small distribution limited to southern China and Northern Vietnam. This species is becoming increasingly threatened because of over-exploitation and habitat degradation. This study provides data on the genetic diversity and population genetic structure of the giant spiny frog to facilitate the further development of effective conservation recommendations for this economically important but threatened species. We examined 10 species-specific microsatellite loci and Cyt b genes （562 bp） collected from 13 wild populations across the entire range of this species. Results of 10 microsatellite loci analysis showed a generally high level of genetic diversity. Moreover, the genetic differentiation among all 12 populations was moderate to large （overall Fs7= 0.1057）. A total of 51 haplotypes were identified for Cyt b, which suggests high haplotype nucleotide diversities. Phylogeographic and population structure analyses using both DNA markers suggested that the wild giant spiny frog can be divided into four distinct major clades, i.e., Northern Vietnam, Western China, Central China, and Eastern China. The clades with significant genetic divergence are reproductively isolated, as evidenced by a high number of private alleles and strong incidence of failed amplification in microsatellite loci. Our research, coupled with other studies, suggests that Q. spinosa might be a species complex within which no detectable morphological variation has been revealed. The four phylogenetic clades and some subclades with distinct geographical distribution should be regarded as independent management units for conservation purposes.

Functional Autapses Form in Striatal Parvalbumin Interneurons but not Medium Spiny Projection Neurons

Autapses selectively form in specific cell types in many brain regions.Previous studies have also found putative autapses in principal spiny projection neurons(SPNs)in the striatum.However,it remains unclear whether these neurons indeed form physiologically functional autapses.We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release(AR)of neurotransmitters after bursts of high-frequency action potentials(APs).Surprisingly,we found no autaptic AR in SPNs,even in the presence of Sr^(2+).However,robust autaptic AR was recorded in parvalbumin(PV)-expressing neurons.The autaptic responses were mediated by GABA_(A) receptors and their strength was dependent on AP frequency and number.Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations.Together,our results indicate that PV neurons,but not SPNs,form functional autapses,which may play important roles in striatal functions.

Therapeutic advances in neural regeneration for Huntington’s disease

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, numerous have been the attempts in several preclinical models of Huntington’s disease to evaluate the feasibility of invasive and non-invasive approaches. Thus, the aim of this review is to offer an overview of the most appealing approaches spanning from stem cell-based cell therapy to extracellular vesicles such as exosomes in light of promoting neurogenesis, discussing the results obtained so far, their limits and the future perspectives regarding the neural regeneration in the context of Huntington’s disease.

A Three-row Opposed Gripping Mechanism with Bioinspired Spiny Toes for Wall-climbing Robots

This paper presents a study of a three-row opposed gripping mechanism made of bioinspired spiny toes.An insect Serica orientalis Motschulsky's tarsal system was first described and studied.A compliant single spiny toe model was established assuming that the contact asperities were spheres.Following the single toe contact model,a spiny toe array's contact model was then developed using asperity height's distribution fiinction.By studying the cngaging and disengaging process of the single toe,the mechanical behavior of the toe and toe array were addressed.The toes as well as the arrays were manufacturcd via rapid prototyping.A customized apparatus using dis-placement-control method has been carried out to measure the pull-in forces and pull-ofT positions of the single toe and toe array undcr various compression conditions.Based on the understanding,a three-row opposed gripping mechanism with radial configuration for wall-climbing robots was designed and fabricated according to the mechanical behaviors of the toe and array.Using an opposed spoke con figuration with 3 rows of 31 toes on each linkage array,the mechanism designed as a foot of climbing robots can vertically resist at least 1 kg of load on rough inverted surface,while the maximum normal load is as high as 31 N.The findings may provide a way in developing a high payload wall-climbing robot system for practical applications.

A Track-type Inverted Climbing Robot with Bio-inspired Spiny Grippers

To enable the capacity of climbing robots to work on steep surfaces,especially on inverted surfaces,is a fundamental but challenging task.This capacity can extend the reachable workspace and applications of climbing robots.A track-type inverted climbing robot called SpinyCrawler was developed in this paper.Using a spiny track with an opposed gripping mechanism,the robot was experimentally demonstrated to have the ability of generating considerable adhesion to achieve stable inverted climbing.First,to guarantee reliable attachment of the robot on rough ceilings,a spiny gripper inspired by the opposed gripping prolegs of caterpillars is designed,and a gripping model of the interaction between spines and the ceiling asperities is established and analyzed.Second,a spiny track is developed by assembling dozens of spiny grippers to enable continuous attachment.A cam mechanism is introduced in the robot design without extra actuators to achieve stable attachment and easy detachment during continuous climbing.Finally,climbing experiments are conducted on different surfaces,using a SpinyCrawler prototype.Experimental results demonstrated stable climbing ability on various rough inverted and vertical surfaces,including concrete walls,crushed stone walls,sandpaper walls,brick walls,and brick ceilings.

Effect of conspecific and heterospecific urine odors on the foraging behavior of the golden spiny mouse

The common spiny mouse(Acomys cahirinus)inhibits the foraging activity of the golden spiny mouse(A.russatus).These two sympatric species of spiny mice,which are considered habitat competitors,occur in extreme arid environments.To test this theory of competition,the influence of urinary odors of both conspecific and heterospecific mice on the foraging behavior of A.russatus was studied under controlled laboratory conditions.Twenty adult males,born in captivity and unfamiliar to the odors of the donor mice,were tested in 3 experimental conditions choosing between 2 seed patches that were scented with urine of either heterospecifics(A.cahirinus),conspecifics(A.russatus)or controls(odors of the tested individual).Of the 20 males,12 were also tested with urine of unfamiliar gerbils,bushy-tailed jird,considered as competitors in the field.Both conspecific and heterospecific urine samples from Acomys significantly reduced foraging behavior of A.russatus when compared to the control odor.The inhibitory effect of the Acomys urine does not result from the novelty of chemical stimuli of the urine because no effect was shown with unfamiliar gerbil urine.The findings are in accordance with the general theory that A.cahirinus dominates the foraging activity of A.russatus.We hypothesize that chemical cues in the urine of Acomys spp.might induce a negative effect on the foraging behavior of A.russatus.

Homeobox Gene Six3 is Required for the Differentiation of D2-Type Medium Spiny Neurons

Medium spiny neurons(MSNs)in the striatum,which can be divided into D1 and D2 MSNs,originate from the lateral ganglionic eminence(LGE).Previously,we reported that Six3 is a downstream target of Sp8/Sp9 in the transcriptional regulatory cascade of D2 MSN development and that conditionally knocking out Six3 leads to a severe loss of D2 MSNs.Here,we showed that Six3 mainly functions in D2 MSN precursor cells and gradually loses its function as D2 MSNs mature.Conditional deletion of Six3 had little effect on cell proliferation but blocked the differentiation of D2 MSN precursor cells.In addition,conditional overexpression of Six3 promoted the differentiation of precursor cells in the LGE.We measured an increase of apoptosis in the postnatal striatum of conditional Six3-knockout mice.This suggests that,in the absence of Six3,abnormally differentiated D2 MSNs are eliminated by programmed cell death.These results further identify Six3 as an important regulatory element during D2 MSN differentiation.

Repetitive DNA Sequences from the X Chromosome of the Spiny Eel (Mastacembelus aculeatus)

To investigate the characters of repetitive DNA sequence in the sex chromosomes of the spiny eel （Mastacembelus aculeatus）, the X chromosomal library was screened and a family of repetitive sequence, consisting of Ma 1-Ma 6, was isolated. The fluorescence in situ hybridization （FISH） result confirmed that Ma 1- Ma 5 dispersed over sex chromosomes and all autosomes, whereas, Ma 6 is sex chromosome-specific and distributed only on the C-band positive regions of X chromosome, and Ma 6 maybe the main components of the heterochromatic regions of X chromosome. This study provides additional information about the evolution of sex chromosomes in lower vertebrates such as fish.

Generating a reporter mouse line marking medium spiny neurons in the developing striatum driven by Arpp21 cis-regulatory elements

The striatum, as the primary input nucleus in the basal ganglion,plays an important role in neural circuits crucial for the control of critical motivation, motor planning and procedural learning(Kreitzer and Malenka, 2008). Most cells in the striatum are GABAergic, including a large population (90%-95%) of medium spiny neurons (MSNs) and a small population of interneurons.

The adjustment of γ-aminobutyric acid_A tonic subunits in Huntington＇s disease：from transcription to translation to synaptic levels into the neostriatum

γ-Aminobutyric acid（GABA）,plays a key role in all stages of life,also is considered the main inhibitory neurotransmitter.GABA activates two kind of membrane receptors known as GABAA and GABAB,the first one is responsible to render tonic inhibition by pentameric receptors containing α4-6,β3,δ,or ρ1-3 subunits,they are located at perisynaptic and/or in extrasynaptic regions.The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation.On this basis,GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington＇s disease.Huntington＇s disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein.For experimental studies of Huntington＇s disease mouse models have been developed,such as R6/1,R6/2,Hdh Q92,Hdh Q150,as well as YAC128.In all of them,some key experimental reports are focused on neostriatum.The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures,its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively,they display strong expression of many types of GABAA receptors,including tonic subunits.The studies about of GABAA tonic subunits and Huntington＇s disease into the neostriatum are rising in recent years,suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition,a hallmark of Huntington＇s disease.

Morphological Characterization of <i>Amaranthus palmeri</i>x <i>A. spinosus</i>Hybrids

The growth of clones of seven Amaranthus palmeri x A. spinosus hybrids was compared to type specimens of A. palmeri and A. spinosus. The hybrids came from the field where they were originally discovered and clones of the type specimens and hybrids were established under greenhouse conditions and used to compare growth rates. A. palmeri had the highest growth rate and A. spinosus the lowest growth rate based on height, node counts, and dry weight accumulation. A. palmeri also had the greatest number of days to flowering and A. spinosus the fewest. Hybrids had intermediary growth rates and days to flowering, but differed from each other with regard to sex identity. The hybrids were either dioecious like A. palmeri or, if monoecious, had patterns unlike A. spinosus. Spine length and texture also varied in hybrids and some were without spines. Hybrid 16Ci was short compared to all others and had succulent leaves and stems, which easily separated from the plant body. These hybridizations resulted in morphologically distinct types with acquisition of physical traits intermediate to the type specimens which may drive evolution of these species.

Integrative taxonomy helps to reveal the mask of the genus Gynandropaa (Amphibia: Anura: Dicroglossidae)

Species of the genus Gynandropaa within the family Dicroglossidae are typical spiny frogs whose taxonomic status has long been in doubt.We used integrative methods,involving morphological and molecular analyses,to elucidate the phylogenetic relationships,and to determine identities and the geographic distribution of each val­id species.We obtained DNA sequence data of 5 species of Gynandropaa(complete sequences of the mitochon­drial NADH dehydrogenase subunit 2[ND2]gene,and 890 bp of 12S rRNA and 16S rRNA partial sequences)from 37 localities(including the topotypes of 5 described species)and constructed Bayesian and maximum-like­lihood trees to examine the patterns of phylogeography.A total of 28 morphological variables were taken on 624 specimens.Three clades with clear geographic patterns were recognized:clade C(from south-western Sich­uan Province and central Yunnan Province),clade E(western Guizhou Province and eastern to central Yunnan Province)and clade W(western to southern Yunnan Province).Integrating morphological characteristics and distribution information,the clades W,E and C represent Gynandropaa yunnanensis,G.phrynoides and G.si­chuanensis,respectively.We draw the following conclusions:(i)the taxon G.phrynoides,formerly evaluated as a junior synonym of G.yunnanensis,is revalidated herein at the rank of species;(ii)G.liui is a junior synonym of G.sichuanensis;and(iii)G.yunnanensis is a valid species while G.bourreti is probably a subspecies of G.yunnanensis,with the distribution range from Vietnam to southern Yunnan Province.This study clears up the taxonomic status of Gynandropaa and provides important information for understanding the evolution and con­servation of these spiny frogs.

Parkinson’s disease and translational research

Parkinson's disease(PD)is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity,and when these symptoms respond to dopaminergic medications.Yet in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states with associated pathology in various regions of the nervous system.In this review we discuss current concepts of two major alterations found during the course of the disease:cytoplasmic aggregates of the protein a-synuclein and the degeneration of dopaminergic neurons.We provide an overview of new approaches in this field based on current concepts and latest literature.In many areas,translational research on PD has advanced the understanding of the disease but there is still a need for more effective therapeutic options based on the insights into the basic biological phenomena.

Genome-wide signatures of mammalian skin covering evolution

Animal body coverings provide protection and allow for adaptation to environmental pressures such as heat,ultraviolet radiation,water loss,and mechanical forces.Here,using a comparative genomics analysis of 39 mammal species spanning three skin covering types(hairless,scaly and spiny),we found some genes(e.g.,UVRAG,POLH,and XPC)involved in skin inflammation,skin innate immunity,and ultraviolet radiation damage repair were under selection in hairless ocean mammals(e.g.,whales and manatees).These signatures might be associated with a high risk of skin diseases from pathogens and ultraviolet radiation.Moreover,the genomes from three spiny mammal species shared convergent genomic regions(EPHB2,EPHA4,and NIN)and unique positively selected genes(FZD6,INVS,and CDC42)involved in skin cell polarity,which might be related to the development of spines.In scaly mammals,the shared convergent genomic regions(e.g.,FREM2)were associated with the integrity of the skin epithelium and epidermal adhesion.This study identifies potential convergent genomic features among distantly related mammals with the same skin covering type.

Single Exposure to Cocaine Impairs Reinforcement Learning by Potentiating the Activity of Neurons in the Direct Striatal Pathway in Mice

Plasticity in the glutamatergic synapses on striatal medium spiny neurons(MSNs)is not only essential for behavioral adaptation but also extremely vulnerable to drugs of abuse.Modulation on these synapses by even a single exposure to an addictive drug may interfere with the plasticity required by behavioral learning and thus produce impairment.In the present work,we found that the negative reinforcement learning,escaping mild foot-shocks by correct nose-poking,was impaired by a single in vivo exposure to 20 mg/kg cocaine 24 h before the learning in mice.Either a single exposure to cocaine or reinforcement learning potentiates the glutamatergic synapses on MSNs expressing the striatal dopamine 1(D1)receptor(D1-MSNs).However,24 h after the cocaine exposure,the potentiation required for reinforcement learning was disrupted.Specific manipulation of the activity of striatal D1-MSNs in D1-cre mice demonstrated that activation of these MSNs impaired reinforcement learning in normal D1-cre mice,but inhibition of these neurons reversed the reinforcement learning impairment induced by cocaine.The results suggest that cocaine potentiates the activity of direct pathway neurons in the dorsomedial striatum and this potentiation might disrupt the potentiation produced during and required for reinforcement learning.

Biodiversity studies of myxomycetes in Madagascar

The results of the first comprehensive study of myxomycetes from the island of Madagascar,a world biodiversity hotspot,are reported in this paper.The island is of continental origin,the fourth largest in the world,and has been geographically isolated for more than 160 million years,since its separation from Gondwanaland.The isolation,size and topography of Madagascar have triggered the development of a great variety of different habitats and favoured multiple evolutionary pathways,resulting in many animals and plants that exist nowhere else on earth.Fieldwork for the biodiversity survey of the central and southern parts of the island took place in May 2009,to coincide with the end of the rainy season.Tropical moist forest,sclerophyll forest and dry forest were selected for sampling in Ranomafana,Andringitra,Andohahela and L’Isalo National Parks.Some unique vegetation was sampled in the spiny dry forest and succulent scrub with plants from the genera Alluaudia,Euphorbia,Kalanchoe and Pachypodium.The survey produced 124 species from 22 different genera in more than 750 myxomycete collections.In this paper one species,Perichaena madagascariensis,is described as new to science,21 species are new records for Africa,and 106 are reported for the first time from Madagascar.Some unusual collections included Physarum lakhanpalii that appeared on Ravenala madagascariensis,Fuligo intermedia and Licea nannengae found on Adansonia grandidieri,Perichaena pulcherrima,Physarum dictyosporum,and P.echinosporum on Euphorbia and Licea rufocuprea on bark.The scope,methods and results of this survey are included in this paper,and comments are made on the ecology,distribution and substrate association of the myxomycetes of these areas of Madagascar.Macrographs,micrographs and SEM images of interesting species are included.The results indicate that the island of Madagascar has a unique assemblage of species of myxomycetes,different from neighbouring islands and from similar but distant environments.