Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

A 48-bp deletion upstream of LIGULELESS 1 alters rice panicle architecture

Panicle architecture is an agronomic determinant of crop yield and a target for cereal crop improvement.To investigate its molecular mechanisms in rice,we performed map-based cloning and characterization of OPEN PANICLE 1(OP1),a gain-of-function allele of LIGULELESS 1(LG1),controlling the spread-panicle phenotype.This allele results from a 48-bp deletion in the LG1 upstream region and promotes pulvinus development at the base of the primary branch.Increased OP1 expression and altered panicle phenotype in chimeric transgenic plants and upstream-region knockout mutants indicated that the deletion regulates spread-panicle architecture in the mutant spread panicle 1(sp1).Knocking out BRASSINOSTEROID UPREGULATED1(BU1)gene in the background of OP1 complementary plants resulted in compact panicles,suggesting OP1 may regulate inflorescence architecture via the brassinosteroid signaling pathway.We regard that manipulating the upstream regulatory region of OP1 or genes involved in BR signal pathway could be an efficient way to improve rice inflorescence architecture.

The UDP-glycosyltransferase OsUGT706D2 positively regulates cold and submergence stress tolerance in rice

In a genome-wide association study,we identified a rice UDP-glycosyltransferase gene,OsUGT706D2,whose transcription was activated in response to cold and submergence stress and to exogenous abscisic acid(ABA).OsUGT706D2 positively regulated the biosynthesis of tricin-4’-O-(syringyl alcohol)ether-7-O-glucoside at both the transcriptional and metabolic levels.OsUGT706D2 mediated cold and submergence tolerance by modulating the expression of stress-responsive genes as well as the abscisic acid(ABA)signaling pathway.Gain of function of OsUGT706D2 increased cold and submergence tolerance and loss of function of OsUGT706D2 reduced cold tolerance.ABA positively regulated OsUGT706D2-mediated cold tolerance but reduced submergence tolerance.These findings suggest the potential use of OsUGT706D2 for improving abiotic stress tolerance in rice.

Effects of Polygala fallax Hemsl Water Extract on a Mouse Model of Gastric Motility Disorders

[Objectives]To explore the effects of Polygona fallax Hemsl water extract on gastrointestinal motility in normal mice and gastric motility disorder model mice and approximate mechanism.[Methods]Using normal mice and mice with gastric motility disorders(modeled with atropine),the effects of different mass concentration groups of P.fallax Hemsl water extract(0.125,0.250,0.500 g/mL)and domperidone groups on gastric residual rate,small intestine propulsion rate,serum motilin(MLT),vasoactive intestinal peptide(VIP),and tissue morphology were studied.[Results]There was a highly significant difference(P<0.01)in the small intestine propulsion rate of liquid in normal mice among the different concentration groups of P.fallax Hemsl water extract compared to the blank group.The small intestine propulsion rate and gastric residue rate of semi-solid paste were statistically significant compared to the blank group(P<0.05).Among them,there was a highly significant difference between the high concentration group(67.75%±7.65%,46.5%±10.62%)and the medium concentration group(60.90%±5.87%,59.27%±7.82%)(P<0.01).There was statistical significance in normal mouse serum MLT content in the high concentration group(P<0.05).There was no effect on serum VIP levels in normal mice;no effect on the morphology of stomach and intestinal tissues of normal mice.The small intestine propulsion rate and gastric residue rate of liquid and semi-solid paste in mice with gastric motility disorders were statistically significant compared to the atropine group,with extremely significant differences(P<0.01).[Conclusions]P.fallax Hemsl water extract has a promoting effect on gastrointestinal motility.One of the specific mechanisms by which P.fallax Hemsl promotes gastrointestinal motility in normal mice may be related to the content of MLT in mouse serum.The mechanism of action in atropine induced gastric paresis mice may be related to the reactivation of M receptors,and the action mechanism of P.fallax Hemsl does not change the original histological basis.It can be inferred that P.fallax Hemsl water extract has a synergistic effect on promoting gastrointestinal motility through other mechanisms,but it is not fully understood and further in-depth research is needed.

Comparative efficacy of social media delivered health education on glycemic control: A meta-analysis

Objective:To compare outcomes associated with patient education about glycemic control via group chat versus patient education as usual among individuals with diabetes in China.Methods:We searched the following databases both in English and in Chinese languages:PubMed,CNKI,Wanfang database,VIP database,and CBM for articles published up to Jan 1,2018.The studies were screened by two independent reviewers.Using criteria from the risk of bias assessment tool developed by Cochrane Collaboration to assess the risk of bias of eligible studies.A meta-analysis of studies was performed using comprehensive meta-analysis version 3.0.Results:Twenty-five unique randomized clinical trials,including 2,838 patients,were identified.The education delivered via group chat had large overall pooled effect sizes in improving glucose control measured by hemoglobin A1c[Hedges'g=-0.81,95%CI:(-0.98,-0.64)],fasting blood glucose[Hedges'g=-1.11,95%CI:(-1.37,-0.85)],and 2 h postprandial blood glucose[Hedges'g=-0.98,95%CI:(-1.20,-0.76)].Additionally,patient education delivered via group chat has shown consistently superior outcomes in glucose control in short-term(0-3 months),mid-term(3-6 months)and longer-term(6-12 months).Conclusions:Educational interventions via group chat had a superior outcome in blood glucose control compared to education as usual in China.Educational interventions via group chat had superior shortterm,mid-term,and longer-term outcomes in blood glucose control compared to education as usual in China.

Optimizing pH-sensitive and time-dependent polymer formula of colonic pH-responsive pellets to achieve precise drug release

Time-sensitive and pH-dependent polymers are generally employed to prepare colon-site delivery system, and their coating thickness and order are very important in controlling the drug release. The traditional colon-site delivery systems consist of time-dependent polymers as inner layer and pH-sensitive polymers as outer layer. However, they suffer from low drug-loading rate and immature drug release. In this study, total alkaloids of sophora alopecuroides(TASA)-loaded pellets were prepared by extrusion-spheronization method and coated with Eudragit RS30D and Eudragit S100. Pellets using Eudragit RS30D as inner layer and Eudragit S100 as outer layer were named as ERS-ES100 TCO, while pellets with Eudragit S100 as inner layer and Eudragit RS30D as outer layer were ES100-ERS NCO. Both types of formulations with varying coating ratios and orders of Eudragit S100 and Eudragit RS30D were designed and prepared. The following in vitro drug release and SEM studies indicated that ERS-ES100 TCO(F2) with 12.8% Eudragit RS30D as inner layer and 21% Eudragit S100 as outer layer released up to 42% drug in 5 h. Interestingly, ES100-ERS NCO(F4) coated with 12.8% Eudragit S100 and 14.8% Eudragit RS30D showed optimal drug release in colon. In conclusion, ES100-ERS NCO colonic delivery system achieved reduced coating thickness and improved colonic targeting compared with traditional delivery system(ERS-ES100 TCO). In addition, the similarity factors( f 2) value of sophoridine and matrine for investigated formulation were within 50–100 and > 80, demonstrating that sophoridine and matrine in all formulations achieved a synchronous release.

Fast ISAR imaging method based on scene segmentation

Although compressed sensing inverse synthetic aperture radar(ISAR) imaging methods are widely used in radar signal processing, its reconstructing time and memory storage space requirements are very high. The main reason is that large scene reconstruction needs a higher dimension of the sensing matrix. To reduce this limitation, a fast high resolution ISAR imaging method,which is based on scene segmentation for random chirp frequencystepped signals, is proposed. The idea of scene segmentation is used to solve the problems aforementioned. In the method,firstly, the observed scene is divided into multiple sub-scenes and then the sub-scenes are reconstructed respectively. Secondly, the whole image scene can be obtained through the stitching of the sub-scenes. Due to the reduction of the dimension of the sensing matrix, the requirement of the memory storage space is reduced substantially. In addition, due to the nonlinear superposition of the reconstructed time of the segmented sub-scenes, the reconstruction time is reduced, and the purpose of fast imaging is achieved.Meanwhile, the feasibility and the related factors which affect the performance of the proposed method are also analyzed, and the selection criterion of the scene segmentation is afforded. Finally,theoretical analysis and simulation results demonstrate the feasibility and effectiveness of the proposed method.

The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity

Royal jelly(RJ)is a biologically active substance secreted by the hypopharyngeal and mandibular glands of worker honeybees.It is widely claimed that RJ reduces oxidative stress.However,the antioxidant activity of RJ has mostly been determined by in vitro chemical detection methods or by external administration drugs that cause oxidative stress.Whether RJ can clear the endogenous production of reactive oxygen species(ROS)in cells remains largely unknown.Here,we systematically investigated the antioxidant properties of RJ using several endogenous oxidative stress models of Drosophila.We found that RJ enhanced sleep quality of aging Drosophila,which is decreased due to an increase of oxidative damage with age.RJ supplementation improved survival and suppressed ROS levels in gut cells of flies upon exposure to hydrogen peroxide or to the neurotoxic agent paraquat.Moreover,RJ supplementation moderated levels of ROS in endogenous gut cells and extended lifespan after exposure of flies to heat stress.Sleep deprivation leads to accumulation of ROS in the gut cells,and RJ attenuated the consequences of oxidative stress caused by sleep loss and prolonged lifespan.Mechanistically,RJ prevented cell oxidative damage caused by heat stress or sleep deprivation,with the antioxidant activity in vivo independent of Keap1/Nrf2 signaling.RJ supplementation activated oxidoreductase activity in the guts of flies,suggesting its ability to inhibit endogenous oxidative stress and maintain health,possibly in humans.

面孔吸引力对经济决策的影响机制

面孔吸引力影响人类的经济决策,人们对高吸引力和低吸引力博弈对象的决策不同.大量研究报告美貌溢价效应,另一些研究则发现美貌惩罚效应.前人提出经济学、社会心理学和进化心理学3个取向来解释面孔吸引力影响决策的原因.经济学取向和社会心理学取向都只提供了描述性解释,忽略了性别的作用.进化心理学取向则提出更深层次的解释,认为人类对高吸引力面孔的偏好主要受到择偶动机的驱使,且人们更偏爱高吸引力的异性.虽然这3个理论体系的解释层级不同,但并不互斥,它们在预测不存在性别差异的美貌溢价现象时有共同的解释力.电生理研究进一步从决策过程中面孔吸引力的认知加工和对公平以及风险的感知的影响方面揭示面孔吸引力影响经济决策的神经生物学机制,发现高吸引力面孔在决策过程中能诱发较大的晚期正成分,并激活伏隔核、眶额叶皮层、腹侧纹状体等与奖赏加工有关的脑区.未来研究应探究真实经济决策情境中,面孔与嗓音、气味等多通道吸引力的交互作用,建立不同面孔吸引力水平的动态连续变化模型,并将电生理研究与现有理论体系整合,全面阐释吸引力影响经济决策的神经机制,并充分挖掘面孔吸引力影响决策的中介变量和调节变量,为控制招聘等活动中的外貌偏见提供理论依据.

全球变暖加剧青藏高原湖泊效应

Lake-effect snowfall(LES)occurs when cold air moves across open lakes.LES is expected to occur more frequently over the TP,due to the intensified lake expansion caused by intensified global warming.Thus,there is an urgent need to comprehensively assess the LES over the TP.Here,we revealed that the LES is triggered by westerly southward shift leading to the drop in air temperature and is positively correlated with lake area,wind speed and longitude across 12 large lakes(>300 km^(2))based on satellite observations and reanalysis data.Using a sensitivity model simulation,we determined that large lakes in the southern TP contributed to more than 50%of the snowfall in the downwind area in 2013.Projections indicate that the westerly-triggered LES will increase under the future RCP4.5 climate warming scenario,highlighting the importance of developing adaptive policies to address the growing risks associated with future LES.

孤独症儿童生活和学习能力的正向干预模式

目前,对孤独症儿童的干预模式逐步由医学模式转向社会模式,孤独症儿童更需要人文精神与社会情怀,需要生命观、伦理观来解读.孤独症领域的实证研究成果转化为适应社会生活为目的的实操体系才能最终使患儿及其家庭受益,同时也确保理论有效普及.某种意义上,协助患儿适应生活与生存即为"治疗".本文通过文献及个案研究,进行了孤独症儿童生活和学习能力正向干预模式的前期探索.

抑郁症患者的表情及微表情识别

选取不同程度的临床抑郁症患者和与之匹配的健康人为被试,采用宏表情识别测验、短暂表情识别测验和微表情识别测验3个研究范式,分别从宏表情、短暂表情和微表情3个方面考察被试识别表情及微表情的能力,探究抑郁症患者与健康人之间表情及微表情识别的差异.结果显示,抑郁症患者表情识别正确率普遍低于健康人,微表情识别绩效低于宏表情,并且表情及微表情的识别绩效与HAMD抑郁量表得分存在负相关.这些结果说明,临床抑郁症患者的表情加工缺陷不受表情呈现时长的影响,对表情及微表情的识别绩效在某种程度上反映了抑郁严重程度.

社会规范对情绪感染的影响及其潜在机制

情绪感染是情绪从表达者传递到接收者并致使接收者情绪体验与表达者趋于一致的过程,适宜的情绪感染能促进社会关系和合作.情绪模仿和社会评价被认为是情绪感染的主要途径,但在社会情境中,社会评价的作用更为突出.然而,以往研究主要集中在群际关系(如内外群、竞争合作)等,而作为社会评价过程中的关键因素之一,社会规范如何影响情绪感染以及可能涉及的机制却未引起重视.本文梳理了情绪感染的含义与测量,情绪感染的心理机制,社会评价与社会规范之间的关系,社会规范的概念与分类、操纵与测量;归纳总结了社会规范影响情绪感染的相关理论基础和实证研究,提出了社会规范作用于情绪感染可能的心理机制以及该过程中可能涉及的神经基础,并对未来研究方向进行了展望.

A robust but variable lake expansion on the Tibetan Plateau

Lakes on the Tibetan Plateau(TP)are an indicator and sentinel of climatic changes[1].We extended lake area changes on the TP from 2010[2]to 2018,and provided a long and dense lake observations between the 1970s and 2018.We found that the number of lakes,with area larger than 1 km2,has in creased to?1,400 in 2018 from?1,000 in the 1970s.The total area of these lakes decreased between the 1970s and?1995,and then showed a robust increase,with the exception of a slight decrease in 2015.This expansion of the lakes on the highest plateau in rhe world is a response to a hydrological cycle intensified by recent climate changes[3].

Cognitive mechanism related to line drawings and its applications in intelligent process of visual media： a survey

Line drawings, as a concise form, can be recognized by infants and even chimpanzees. Recently, how the visual system processes line-drawings attracts more and more attention from psychology, cognitive science and computer science. The neuroscientific studies revealed that line drawings generate similar neural actions as color photographs, which give insights on how to efficiently process big media data. In this paper, we present a comprehensive survey on line drawing studies, including cognitive mechanism of visual perception, computational models in computer vision and intelligent process in diverse media applications. Major debates, challenges and solutions that have been addressed over the years are discussed. Finally some of the ensuing challenges in line drawing studies are outlined.

CRISPR/Cas9-mediated knockout of period reveals its function in the circadian rhythms of the diamondback moth Plutella xylostella

Circadian clocks control the rhythmicity of many behaviors and physiological features of insects.To study the circadian clock of the moth Plutella xylostella,we employed CRISPR/Cas9-mediated genome editing to investigate the effect of loss of the clock gene period on the circadian rhythms.P.xylostella harbors a single copy of period.Phylogenetic analysis showed that P.xylostella PERIOD is more homologous to mouse PERIOD than the PERIOD proteins from bees,flies,mosquitos,and many other Lepidoptera,such as Danaus plexippus and Bombyx mori.The circadian rhythms in adult locomotor activity were altered in the period knockout strain of P.xylostella under light–dark(LD)and continuous dark(DD)conditions.Under the LD cycle,the wild-type moths displayed nocturnal activity with activity peaking very early after lights off and quickly declining after lights on.In contrast,the period knockout strain had no peak in activity when the lights were turned off and exhibited steady activity throughout the hours of darkness.Interestingly,under DD conditions,our results showed that the locomotor rhythm can be maintained without period gene,but at a lower rhythmicity ratio than wild-type.In addition,knockout of period in P.xylostella changed circadian rhythms patterns related to pupal eclosion,mating,egg-laying,and egg hatching.Mechanistically,loss of PERIOD disrupted the molecular rhythm of period and changed the clock transcription rhythm in the heads of the moths under LD and DD conditions.Together,our study indicates that the PERIOD is required for normal expression of many behavioral rhythms in P.xylostella.