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Hibernation with rhythmicity:the circadian clock and hormonal adaptations of the hibernating Asiatic toads(Bufo gargarizans)

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Integrative Zoology 2022年第4期17卷 656-669页

作者： Zhigang XIE Ibrahim M.AHMAD Lirong ZUO Feng XIAO Yongpeng WANG Dongming LI Zhejiang Academy of Agricultural Sciences HangzhouChina College of Chemistry and Life Science Zhejiang Normal UniversityJinhuaChina Ministry of Education Key Laboratory of molecular and cellular Biology Key Laboratory of Animal PhysiologyBiochemistry and Molecular Biology of Hebei ProvinceCollege of Life SciencesHebei Normal UniversityShijiazhuangChina

Hibernation is one of the fundamental strategies in response to cold environmental temperatures.During hibernation,the endocrine and circadian systems ensure minimal expenditure of energy for survival.The circadian rhythms of key hormones,melatonin(MT),corticosterone(CORT),triiodothyronine(T3),and thyroxine(T4),and the underlying molecular regulatory mechanisms of hibernation have been well determined in mammals but not in ectotherms.Here,a terrestrial hibernating species,Asiatic toad(Bufo gargarizans),was employed to investigate the plasma CORT,MT,T3,and T4;and the retina,brain,and liver mRNA expression of the core clock genes,including circadian locomotor output cycles kaput(Clock),brain and muscle ARNT-like 1(Bmal1),cryptochrome(Cry)1 and 2,and period(Per)1 and 2,at 7-time points over a 24-h period under acute cold(1 day at 4℃),and hibernation(45 days at 4℃).Our results showed that the circadian rhythms of the core clock genes were rather unaffected by acute cold exposure in the retina,unlike the brain and liver.In contrast,during hibernation,the liver clock genes displayed significant circadian oscillations,while those in the retina and brain stopped ticking.Furthermore,plasma CORT expressed circadian oscillations in both groups,and T3 in acute cold exposure group,whereas T4 and MT did not.Our results reveal that the plasma CORT and the liver sustain rhythmicity when the brain was not,indicating that the liver clock along with the adrenal clock synergistically maintains the metabolic requirements to ensure basic survival in hibernating Asiatic toads.

关键词： Asiatic toad circadian rhythm clock genes cold exposure hibernation metabolic hormones

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Guidelines for application of high-content screening in traditional Chinese medicine:concept,equipment,and troubleshooting

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Acupuncture and Herbal Medicine 2024年第1期4卷 1-15页

作者： Xuechun Chen Lu Li Mingxu Zhang Jian Yang ChunMing Lyu Yizhou Xu Yang Yang Yi Wang Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina Department of cardiology Hangzhou First People’s HospitalHangzhouChina National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxingChina molecular Devices Shanghai Corporation ShanghaiChina National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Science and Technology Experiment Center Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Innovative Anticancer Drugs Ministry of Educationhangzhou China

High-content screening(HCS)technology combines automated high-speed imaging hardware and single-cell quantitative analysis.It can greatly accelerate data acquisition in cellular fluorescence imaging and is a powerful research technique in traditional Chinese medicine(TCM).An increasing number of laboratories and platforms,including TCM laboratories,have begun utilizing HCS systems.However,this technology is still in its infancy in TCM research and there is a lack of sufficient experience with the associated concepts,instrument configurations,and analysis methods.To improve the understanding of HCS among researchers in the field of TCM,this paper summarizes the concept of HCS,software and hardware configuration,the overall research process,as well as common problems and related solutions of HCS in TCM research based on our team’s previous research experience,providing several research examples and an outlook on future perspectives,aiming to provide a technical guide for HCS in TCM research.

关键词： High-content imaging High-content screening Traditional Chinese medicine

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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason Department of physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to Earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Protein regulation mechanism of cold tolerance in Haemaphysalis longicornis

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Insect Science 2023年第3期30卷 725-740页

作者： Ningmei Wang Aimeng Ji Abolfazl Masoudi Shuang Li Yuhong Hu Yefei Zhang Zhijun Yu Han Wang Hui Wang Jingze Liu Ministry of Education Key Laboratory of molecular and cellular Biology Hebei Key Laboratory of Animal PhysiologyBiochemistry and Molecular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuangChina Instrumental Analysis Center Hebei Normal UniversityShjiazhuangChina Hebei Xiaowutai Mountain National Nature Reserve Management Center ZhangjiakouHebei ProvinceChina

Ticks are external parasitic arthropods that can transmit a variety of pathogens by sucking blood.Low-temperature tolerance is essential for ticks to survive during the cold winter.Exploring the protein regulation mechanism of low-temperature tolerance of Haemaphysalis longicornis could help to explain how ticks survive in winter.In this study,the quantitative proteomics of several tissues of H.longicornis exposed to low temperature were studied by data independent acquisition technology.Totals of 3699,3422,and 1958 proteins were identified in the salivary gland,midgut,and ovary,respectively.The proteins involved in energy metabolism,cell signal transduction,protein synthesis and repair,and cytoskeleton synthesis changed under low-temperature stress.The comprehensive analysis of the protein regulation of multiple tissues of female ticks exposed to low temperature showed that maintaining cell homeostasis,maintaining cell viability,and enhancing cell tolerance were the most important means for ticks to maintain vital signs under low temperature.The expression of proteins involved in and regulating the above cell activities was the key to the survival of ticks under low temperatures.Through the analysis of a large amount of data,we found that the expression levels of arylamine N-acetyltransferase,inositol polyphosphate multikinase,and dual-specificity phosphatase were up-regulated under low temperature.We speculated that they might have important significance in low-temperature tolerance.Then,we performed RNA interference on the mRNA of these 3 proteins,and the results showed that the ability of female ticks to tolerate low temperatures decreased significantly.

关键词： low-temperature tolerance protein regulation tick survival strategy

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FMO3-TMAO axis modulates the clinical outcome in chronic heart-failure patients with reduced ejection fraction:evidence from an Asian population

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Frontiers of Medicine 2022年第2期16卷 295-305页

作者： Haoran Wei Mingming Zhao Man Huang Chenze Li Jianing Gao Ting Yu Qi Zhang Xiaoqing Shen Liang Ji Li Ni Chunxia Zhao Zeneng Wang Erdan Dong Lemin Zheng Dao Wen Wang Division of cardiology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science&Technology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersWuhan 430030China Department of cardiology and Institute of Vascular Medicine Peking University Third HospitalNHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China The Institute of Cardiovascular Sciences Peking UniversityKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing 100191China Department of cardiology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of cellular and molecular Medicine Lerner Research InstituteCleveland ClinicClevelandOH 44195USA

The association among plasma trimethylamine-N-oxide(TMAO),FMO3 polymorphisms,and chronic heart failure(CHF)remains to be elucidated.TMAO is a microbiota-dependent metabolite from dietary choline and carnitine.A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction,with the longest follow-up of 7 years.The concentrations of plasma TMAO and its precursors,namely,choline and carnitine,were determined by liquid chromatography-mass spectrometry,and the FMO3 E158K polymorphisms(rs2266782)were genotyped.The top tertile of plasma TMAO was associated with a significant increment in hazard ratio(HR)for the composite outcome of cardiovascular death or heart transplantation(HR=1.47,95%CI=1.13-1.91,P=0.004)compared with the lowest tertile.After adjustments of the potential confounders,higher TMAO could still be used to predict the risk of the primary endpoint(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).This result was also obtained after further adjustment for carnitine(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).The FM03 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort,and lower TMAO levels were found in the AA-genotype.Thus,higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders,and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.

关键词： chronic heart failure trimethylamine-N-oxide flavin monooxygenase 3 single nucleotide polymorphism

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Pathology-induced NG2 proteoglycan expression in microglia

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Neural Regeneration Research 2023年第4期18卷 801-802页

作者： Erika Meyer Anja Scheller molecular physiology Center for Integrative Physiology and Molecular MedicineUniversity of SaarlandHomburgGermany(Meyer EScheller A)Laboratory of Brain Ischemia and NeuroprotectionDepartment of Pharmacology and TherapeuticsState University of MaringáMaringáBrazil

Oligodendrocyte precursor cells(OPCs)and microglia are two very fascinating cell types with a multitude of important but different functions.At a first glance,they appear not to share many cellular properties,nor are directly related to one another or derived from a common ancestor.Despite all differences,emerging data show that both cell types express the protein nerve/glial antigen 2(NG2)after pathological insults(Figure 1).For years,it remained controversial whether microglia really could express NG2 upon injury,with contradictory results reported among different disease models.Addressing this question,we could recently show by using triple transgenic knock-in mice and either an acute injury model(stab wound injury)or the middle cerebral artery occlusion combined with immunohistochemistry that a subset of microglia activates the cspg4 gene in a disease dependent manner leading to a bonafide microglia-specific NG2 protein expression besides OPCs and pericytes.Our data show that the cspg4 gene not only gets transcribed in microglia based on reporter expression after recombination,but also the protein itself is expressed(Huang et al.,2020).

关键词： NG2 wound Figure

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Chromatin and epigenetic regulation of the telomerase reverse transcriptase gene

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Protein & Cell 2010年第1期1卷 22-32页

作者： Jiyue Zhu Yuanjun Zhao Shuwen Wang Department of cellular and molecular physiology Pennsylvania State University College of MedicineHersheyPA 17033USA

Telomerase expression and telomere maintenance are critical for long-term cell proliferation and survival,and they play important roles in development,aging,and cancer.Cumulating evidence has indicated that regulation of the rate-limiting subunit of human telomerase reverse transcriptase gene(hTERT)is a complex process in normal cells and many cancer cells.In addition to a number of transcriptional activators and repressors,the chromatin environment and epigenetic status of the endogenous hTERT locus are also pivotal for its regulation in normal human somatic cells and in tumorigenesis.

关键词： telomerase transcriptional regulation chromatin epigenetic regulation cancer

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Role of fatty acids and calcium in male reproduction

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Reproductive and Developmental Medicine 2022年第1期6卷 57-64页

作者： Taniya Naz Srinjoy Chakraborty Sudipta Saha molecular Reproductive physiology Laboratory Amity Institute of Physiology and Allied SciencesAmity University Uttar PradeshNoida 201313India

Both fatty acids (FAs) and calcium ions play important roles in contraceptive cyclesvia several systems. Polyunsaturated FAs (PUFAs) act as precursors for prostaglandin production and can alter the expression of numerous crucial catalysts that are involved in prostaglandin and steroid digestion. Lipids are essential components of cell membranes. A diet rich in PUFAs enhances sperm motility and viability. It also improves testis development and spermatogenesis in several domesticated animal species. Increased PUFA content in spermatozoa increases plasma membrane fluidity, which is important for fertilization. However, the major drawback of high dietary PUFA intake is that it increases the levels of reactive oxygen species in the body. An increase in reactive oxygen species levels markedly affects fertility. Calcium is an important component that acts as an intra-cellular secondary messenger and plays an important role in some of the physiological processes that occur in male gametes. Some of these processes include spermatogenesis, sperm motility, capacitation, acrosome response, and fusion of gametes. These processes are associated with calcium influx through ion protein channels. Dietary fat intake is associated with increased intestinal calcium absorption. In this review, we discuss the impact of lipids, particularly PUFAs and monounsaturated FAs, and calcium ions on male reproduction, along with their effects on each other.

关键词： Infertility treatment Male infertility Motility regulation Polyunsaturated fatty acids Sperm motility

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From neurogenesis to neuronal regeneration: the amphibian olfactory system as a model to visualize neuronal development in vivo

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Neural Regeneration Research 2015年第6期10卷 872-874页

作者： Ivan Manzini Institute of Neurophysiology and cellular Biophysics University of Gottingen Center for Nanoscale Microscopy and molecular physiology of the Brain (CNMPB)

How do individual neurons develop and how are they in- tegrated into neuronal circuitry？ To answer this question is essential to understand how the nervous system develops and how it is maintained during the adult life. A neural stem cell must go through several stages of maturation, including proliferation, migration, differentiation, and integration, to become fully embedded to an existing neuronal circuit. The knowledge on this topic so far has come mainly from cell culture studies. Studying the development of individual neurons within intact neuronal networks in vivo is inherently difficult. Most neurons are generated form neural stem cells during embryonic and early postnatal development.

关键词： the amphibian olfactory system as a model to visualize neuronal development in vivo Figure

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Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice:effects of 4-aminopyridine

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Neural Regeneration Research 2023年第2期18卷 439-444页

作者： Jung Il Lee M A Hassan Talukder Zara Karuman Anagha A.Gurjar Prem Kumar Govindappa Jagadeeshaprasad M.Guddadarangaiah Kristen M.Manto Grant D.Wandling John P.Hegarty David L.Waning John C.Elfar Department of Orthopaedics and Rehabilitation Center for Orthopaedic Research and Translational ScienceThe Pennsylvania State University College of MedicineHersheyPAUSA Department of Orthopaedic Surgery Korea University Guro HospitalSeoulSouth Korea Department of cellular and molecular physiology The Pennsylvania State University College of MedicineHersheyPAUSA

We recently demonstrated a repurposing beneficial effect of 4-aminopyridine(4-AP),a potassium channel blocker,on functional recove ry and muscle atrophy after sciatic nerve crush injury in rodents.However,this effect of 4-AP is unknown in nerve transection,gap,and grafting models.To evaluate and compare the functional recovery,nerve morphology,and muscle atrophy,we used a novel stepwise nerve transection with gluing(STG),as well as 7-mm irreparable nerve gap(G-7/0)and 7-mm isografting in 5-mm gap(G-5/7)models in the absence and presence of 4-AP treatment.Following surgery,sciatic functional index was determined wee kly to evaluate the direct in vivo global motor functional recovery.After 12 weeks,nerves were processed for whole-mount immunofluorescence imaging,and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber crosssectional area and minimal Feret's diameter.Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model.4-AP did not affect the sciatic functional index recovery in any model.Compared to STG,nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting.While muscle weight,cross-sectional area,and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7,4-AP treatment significantly increased right TA muscle mass,cross-sectional area,and minimal Feret's diameter in G-7/0 model.These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap,and 4-AP exerts diffe rential effects on functional recove ry and muscle atrophy.

关键词： 4-aminopyridine functional recovery muscle atrophy nerve gap nerve grafting nerve imaging nerve transection

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