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Stem cell treatment improves post stroke neurological outcomes:a comparative study in male and female rats

Stroke & Vascular Neurology 2021年第4期6卷 519-527,I0005-I0010页

作者： Koteswara Rao Nalamolu Bharath Chelluboina Casimir A Fornal Siva Reddy Challa David M Pinson david Z Wang Jeffrey D Klopfenstein Krishna Kumar Veeravalli Cancer Biology and Pharmacology College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Pharmaceutical and Biomedical Sciences California Health Sciences UniversityClovisCaliforniaUSA Neurological Surgery University of Wisconsin-MadisonMadisonWisconsinUSA Health Sciences Education College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Neurology College of MedicineUniversity of IllinoisPeoriaIllinoisUSA Neurology Barrow Neurological InstitutePhoenixArizonaUSA Neurosurgery College of MedicineUniversity of IllinoisPeoriaIllinoisUSA OSF HealthCare Illinois Neurological Institute PeoriaIllinoisUSA Pediatrics College of MedicineUniversity of IllinoisPeoriaIllinoisUSA

Background and purpose The therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial.Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells(mSC)in a rodent stroke model.We hypothesised that mSC treatment would effectively promote the recovery of sensory and motor function in both males and females,despite any apparent sex differences in post stroke brain injury.methods Transient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery.Following the procedure,male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling.Additional groups of stroke-induced male and female rats were treated with mSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests(modified Neurological Severity Score assessment,adhesive tape removal,beam walk and rotarod).The tests were administered at regular intervals(at days 1,3,5,7 and 14)after reperfusion to determine the time course of neurological and functional recovery after stroke.Results The infarct volume and extent of swelling of the ischaemic brain were similar in males and females.Despite similar pathological stroke lesions,the clinical manifestations of stroke were more pronounced in males than females,as indicated by the neurological scores and other tests.mSC treatment significantly improved the recovery of sensory and motor function in both sexes,and it demonstrated efficacy in both moderate stroke(females)and severe stroke(males).Conclusions Despite sex differences in the severity of post stroke outcomes,mSC treatment promoted the recovery of sensory and motor function in male and female rats,suggesting that it may be a promising treatment for stroke.

关键词： neurological female rats

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Post-stroke mRNA expression profile of mmPs:effect of genetic deletion of mmP-12

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Stroke & Vascular Neurology 2018年第3期3卷 153-159页

作者： Koteswara Rao Nalamolu Bharath Chelluboina Ian B magruder Diane N Fru Adithya mohandass Ishwarya Venkatesh Jeffrey D Klopfenstein David M Pinson Krishna m Boini Krishna Kumar Veeravalli Department of Cancer Biology and Pharmacology University of Illinois College of MedicinePeoriaIllinoisUSA Department of Neurosurgery University of Illinois College of MedicinePeoriaIllinoisUSA Comprehensive Stroke Center Illinois Neurological InstituteOSF HealthCare SystemSaint Francis Medical CenterPeoriaIllinoisUSA Department of Pathology University of Illinois College of MedicinePeoriaIllinoisUSA Department of Pharmacological and Pharmaceutical Sciences College of PharmacyUniversity of HoustonHoustonTexasUSA Department of Neurology University of Illinois College of MedicinePeoriaIllinoisUSA

background and purpose Recent reports from our laboratory demonstrated the post-ischaemic expression profile of various matrix metalloproteinases(mmPs)in rats and the detrimental role of mmP-12 in post-stroke brain damage.We hypothesise that the post-stroke dysregulation of mmPs is similar across species and that genetic deletion of mmP-12 would not affect the post-stroke expression of other mmPs.We tested our hypothesis by determining the pre-ischaemic and post-ischaemic expression profile of mmPs in wild-type and mmP-12 knockout mice.methods Focal cerebral ischaemia was induced in wildtype and mmP-12 knockout mice by middle cerebral artery occlusion procedure by insertion of a monofilament suture.One hour after ischaemia,reperfusion was initiated by removing the monofilament.One day after reperfusion,ischaemic brain tissues from various groups of mice were collected,and total RNA was isolated and subjected to cDNA synthesis followed by PCR analysis.results Although the post-stroke expression profile of mmPs in the ischaemic brain of mice is different from rats,there is a clear species similarity in the expression of mmP-12,which was found to be predominantly upregulated in both species.Further,the post-stroke induction or inhibition of various mmPs in mmP-12 knockout mice is different from their respective expression profile in wild-type mice.moreover,the brain mRNA expression profile of various mmPs in mmP-12 knockout mice under normal conditions is also different to their expression in wild-type mice.Conclusions In the ischaemic brain,mmP-12 upregulates several fold higher than any other mmP.mice derived with the genetic deletion of mmP-12 are constitutive and have altered mmP expression profile both under normal and ischaemic conditions.

关键词： mmPs removing hypothesis

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Energy and Economic Assessment of Blast Furnace Ironmaking Operated under Nitrogen Free and Top Gas Recycling Conditions

Energy and Economic Assessment of Blast Furnace Ironmaking O...

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Asia Steel International Conference 2012(Asia Steel 2012)

作者： pinson david BlueScope Steel Research BlueScope Steel Ltd.Australia

Blast furnace ironmaking is the major route for iron production and likely to remain competitive against alternative ironmaking processes for the coming decades.Further blast furnace development targets decreasing coke consumption and overall CO emissions and nitrogen-free blast and top gas recycling are two potential measures to achieve these purposes.This paper analyses the effects of nitrogen free blast and top gas recycling on the operation of a blast furnace in comparison with a conventional blast furnace.The results show that recycling of top gas consisting of CO and CO is an effective measure to control the raceway combustion temperature.However,recycling of top gas will require the combination of an oxyfuel gasifier in which gasification of carbon by CO will occur and the generated reducing gas heated to 1400 -1700℃.It not only utilises the reduction capability of the top gas,but also is expected to reduce operating costs by up to US$5/THm.

关键词： blast furnace ironmaking pure oxygen blast,top gas recycling,oxyfuel gasifier

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Precision medicine in chronic obstructive pulmonary disease

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Chinese medical Journal 2022年第10期135卷 1156-1162页

作者： david m.G.Halpin University of Exeter medical School College of Medicine and HealthUniversity of ExeterExeterUK.

Over the last 20 years, it has become possible to use a precision medicine approach to the management of chronic obstructive pulmonary disease (COPD). Clinical and physiological features as well as a blood biomarker can be used to target treatments to patients most likely to benefit and avoid treatment in patients less likely to benefit. Future advances in a precision medicine approach to COPD will depend on more precise characterization of individual patients, possibly using quantitative imaging, new physiological techniques, novel biomarkers and genetic profiling. Precision medicine has led to significant improvements in the management of COPD and clinicians should use all available information to optimize the treatment of individual patients.

关键词： Chronic obstructive pulmonary disease(COPD) Precision medicine Biomarkers microbiome Comorbidity

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The embryology of persistent cloaca and urogenital sinus malformations

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Asian Journal of Andrology 2020年第2期22卷 124-128页

作者： david F m Thomas University of Leeds LeedsWest Yorkshire LS29JTUK

Cloacal malformations are characterized by the confluence of the lower urinary tract,the female reproductive tract,and the rectum to create a common channel with a single opening on the perineum.The presence of a cloaca is a normal phase of early human embryological development.Between the 4^th and 7^th weeks of gestation,the cloaca undergoes subdivision to form the hindgut and urogenital sinus.Failure of this process results in the congenital anomaly termed persistent cloaca(PC).The term urorectal septum malformation sequence(URSmS)is also used to describe this anomaly.The classic description of this process which is still cited in many standard textbooks dates from the 19th century.However,this has been increasingly called into question by the findings of studies using modern scientific methodology.Urogenital sinus anomalies are defined by the confluence of the urethra and vagina to form a common channel of varying length with a single perineal opening.In this condition,the anorectal canal opens separately on the perineum.The presence of a urogenital sinus represents a transient phase of the normal development of the lower genital tract in the female fetus.However,the form of urogenital sinus most commonly encountered in the developed world is a feature of disordered sexual differentiation and does not arise simply from the persistence of the anatomical structure which is a feature of normal fetal development.

关键词： cloaca embryology urogenital sinus

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Duplication and diversification of insulin genes in ray-finned fish

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Zoological Research 2019年第3期40卷 185-197页

作者： david m.Irwin Department of Laboratory medicine and Pathobiology University of Toronto Banting and Best Diabetes Centre University of Toronto

Insulin is a key hormone for the regulation of metabolism in vertebrates.Insulin is produced by pancreatic islet cells in response to elevated glucose levels and leads to the uptake of glucose by tissues such as liver and adipose tissue to store energy.Insulin also has additional functions in regulating development.Previous work has shown that the proglucagon gene,which encodes hormones counter regulating insulin,is duplicated in teleost fish,and that the peptide hormones encoded by these genes have diversified in function.I sought to determine whether similar processes have occurred to insulin genes in these species.Searches of fish genomes revealed an unexpected diversity of insulin genes.A triplication of the insulin gene occurred at the origin of teleost fish,however one of these three genes,insc,has been lost in most teleost fish lineages.The two other insulin genes,insa and insb,have been retained but show differing levels of selective constraint suggesting that they might have diversified in function.Intriguingly,a duplicate copy of the insa gene,which I named insab,is found in many fish.The coding sequenee encoded by insab genes is under weak selective constraint,with its predicted protein sequences losing their potential to be processed into a two-peptide hormone.However,these sequences have retained perfectly conserved cystine residues,suggesting that they maintain insulin's three-dimensional structure and therefore might modulate the processing and secretion of insulin produced by the other genes.

关键词： Insulin Teleost fish Gene duplicati on Adaptive evolution Gene loss

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Communication,Computation,and Governance:A multiscalar Vantage on the Prehispanic mesoamerican World

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Journal of Social Computing 2022年第1期3卷 91-118页

作者： Gary m.Feinman david m.Carballo the Negaunee Integrative Research Center Field Museum of Natural HistoryChicagoIL 60605USA Anthropology Archaeologyand Latin American StudiesBoston UniversityBostonMA 02215USA

Writing has often been put forth as one indicator of civilization.This correspondence dovetails with the even broader cross-species expectation that the degrees of social complexity and levels of computational communication should closely correlate.Although in a general sense across human cooperative arrangements,a basic relationship between these variables undoubtedly exists,more detailed and fine-grained analyses indicate important axes of variability.Here,our focus is on prehispanic mesoamerica and the means of computation and communication employed over more than three millennia(ca.1500 BCE-1520 CE).We take a multiscalar and diachronic analytical frame,in which we look at 30 central places,six macroregions,and mesoamerica as whole.By unraveling elements of“social complexity”,and decoupling computation from communication,we illustrate that institutional differences in governance had a marked effect on the specific modes and technologies through which prehispanic mesoamerican peoples communicated across time and space.Demographic and spatial scale,though relevant,do not alone determine time/space diversity in media of computational communication.This article is part of the theme issue“Evolution of Collective Computational Abilities of(Pre)Historic Societies”.

关键词： mesoamerica archaeology communication computation writing polity scale calendrics maya Aztec

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Slc7a5 regulation of neural development

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Neural Regeneration Research 2021年第10期16卷 1994-1995页

作者： Aidan m.Sokolov david m.Feliciano Department of Biological Sciences Clemson UniversityClemsonSCUSA

membrane transport proteins are appreciated for their ability to transport molecules across biological membranes and have received a renewed focus for their role in nervous system disorders.One such group of transporters are members of the solute carrier(SLC)family.SLC transporters shuttle various molecules,including neurotransmitters,fatty acids,amino acids,and inorganic ions.As such,they play an integral role in supplying cells with essential resources.An example is that amino acids are transported by SLC family members.Slc7a5 is a SLC family member that transports essential amino acids important for neuronal development,as well as other biological molecules including thyroid hormones T3,T4,and L-Dopa.Slc7a5 forms a heterodimer with Slc3a2 that facilitates the subcellular distribution of Slc7a5.Amino acids including leucine,glutamine,and arginine support cell growth by activating the protein kinase,mammalian target of rapamycin complex 1(mTORC1)(Liu et al.,2020).Consistent with this notion is that Slc7a5 transport of amino acids regulates mTORC1 activity in numerous cell types(Nicklin et al.,2009).A recent manuscript expands upon these findings to demonstrate that Slc7a5 plays a previously unrecognized and critical role in the regulation of mTORC1 activity and neuron development(Sokolov et al.,2020).

关键词： inorganic solute notion

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macrophages and the maintenance of homeostasis

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Cellular & molecular Immunology 2021年第3期18卷 579-587页

作者： david m.mosser Kajal Hamidzadeh Ricardo Goncalves The Department of Cell Biology and molecular Genetics The University of MarylandCollege ParkMD 20742USA The Department of General Pathology Federal University of Minas GeraisBelo HorizonteMGBrazil

There have been many chapters written about macrophage polarization.These chapters generally focus on the role of macrophages in orchestrating immune responses by highlighting the T-cell-derived cytokines that shape these polarizing responses.This bias toward immunity is understandable,given the importance of macrophages to host defense.However,macrophages are ubiquitous and are involved in many different cellular processes,and describing them as immune cells is undoubtedly an oversimplification.It disregards their important roles in development,tissue remodeling,wound healing,angiogenesis,and metabolism,to name just a few processes.In this chapter,we propose that macrophages function as transducers in the body.According to Wikipedia,WA transducer is a device that converts energy from one form to another.^The word transducer is a term used to describe both the"sensor,which can interpret a wide range of energy forms,and the"actuator,which can switch voltages or currents to affect the environment.macrophages are able to sense a seemingly endless variety of inputs from their environment and transduce these inputs into a variety of different response outcomes.Thus,rather than functioning as immune cells,they should be considered more broadly as cellular transducers that interpret microenvironmental changes and actuate vital tissue responses.In this chapter,we will describe some of the sensory stimuli that macrophages perceive and the responses they make to these stimuli to achieve their prime directive,which is the maintenance of homeostasis.

关键词： macrophages polarization cytokines development inflammation

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Functional diversity of small-mammal postcrania is linked to both substrate preference and body size

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Current Zoology 2020年第5期66卷 539-553页

作者： Lucas N.Weaver david m.Grossnickle Department of Biology Life Sciences BuildingUniversity of WashingtonSeattleWA 98195USA

Selective pressures favor morphologies that are adapted to distinct ecologies,resulting in trait partition!ng among ecomorphotypes.However,the effects of these selective pressures vary across taxa,especially because morphology is also influenced by factors such as phylogeny,body size,and functional trade-offs.In this study,we examine how these factors impact functional diversification in mammals.It has been proposed that trait partitioning among mammalian ecomorphotypes is less pronoun ced at small body sizes due to biomecha nical,energetic,and environ mental factors that favor a"generalist"body plan,whereas larger taxa exhibit more substantial functional adaptations.We title this the Diverge nee Hypothesis(DH)because it predicts greater morphological divergence among ecomorphotypes at larger body sizes.We test DH by using phylogenetic comparative methods to examine the postcranial skeletons of 129 species of taxonomically diverse,small-tomedium-sized(mammals,which we categorize as either"tree-dwellers"or"ground-dwellers."In some analyses,the morphologies of ground-dwellers and tree-dwellers suggest greater between-group differentiation at larger sizes,providing some evidence for DH.However,this trend is n either particularly strong nor supported by all an alyses.In stead,a more pronoun ced patter n emerges that is distinct from the predictions of DH:within-group phenotypic disparity increases with body size in both ground-dwellers and tree-dwellers,driven by morphological outliers among"medium'-sized mammals.Thus,evolutionary increases in body size are more closely linked to increases in within-locomotor-group disparity tha n to in creases in betwee n-group disparity.We discuss biomechanical and ecological factors that may drive these evolutionary patter ns,and we emphasize the significant evolutionary influences of ecology and body size on phenotypic diversity.

关键词： adaptive landscapes ecomorphology morphometries phenotypic diversity phylogenetic comparative methods trait partitioning

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