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Supplying the trip to antibody production-nutrients,signaling,and the programming of cellular metabolism in the mature B lineage

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Cellular & Molecular Immunology 2022年第3期19卷 352-369页

作者： mark R.Boothby Shawna k.Brookens Ariel L.Raybuck Sung Hoon Cho Department of Pathology Microbiology&ImmunologyMolecular Pathogenesis DivisionVanderbilt University Medical CenterNashvilleTN37232USA Department of Medicine Rheumatology&Immunology DivisionVanderbilt University Medical CenterNashvilleTN37232USA Cancer Biology Program Vanderbilt UniversityNashvilleTN37232USA Vanderbilt Institute of Infection Inflammationand ImmunologyNashvilleTN37232USA

The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody(Ab)secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against *** this backdrop,it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise,persist,and meet the challenge of secreting vast amounts of these *** plasmablasts and plasma cells(PCs)are the primary sources of secreted Abs,the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential *** each step,cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for *** in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription,translation,and *** review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab *** findings of this group and others,sometimes exhibiting differences,will be summarized with regard to the journey to a distinctive metabolic program in PCs.

关键词： B lymphocyte Plasma cell Intermediary metabolism Glucose Glutamine Fatty acid Signal transduction

Improved thromboresistance and analytical performance of intravascular amperometric glucose sensors using optimized nitric oxide release coatings

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Chinese Chemical Letters 2015年第4期26卷 464-468页

作者： Alexander k.Wolf Yu Qin Terry C.Major mark E.Meyerhoff Department of Chemistry University of Michigan Department of Chemistry Nanjing University Department of Surgery University of Michigan

In this work, nitric oxide （NO） release coatings designed for intravenous amperometric glucose sensors are optimized through the use ofa polylactic acid （PLA） layer doped with a lipophilic diazeniumdiolated species that releases NO through a proton-driven mechanism. An Elast-Eon E2As polyurethane coating is used to both moderate NO release from the sensor surface and increase the sensor＇s linear detection range toward glucose. These sensors were evaluated for thromboresistance and in vivo glucose performance through implantation in rabbit veins. By maintaining NO flux on a similar scale to endogenous endothelial cells, implanted glucose sensors exhibited reduced surface clot formation which enables more accurate quantitative glucose measurements continuously. An in vivo time trace of implanted venous sensors demonstrated glucose values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. The raw measured currents from the implanted glucose sensors over 7 h time periods were converted to glucose concentration through use of both a one-point in vivo calibration and a calibration curve obtained in vitro within a bovine serum solution. Control sensors, assembled without NO release functionality, exhibit distinctive surface clotting over the 7 h in vivo implantation period.

关键词： Nitric oxide release coatingsGlucose sensorsPolylactic acid layerQuantitative glucose measurements

Enduring legacy of coal mining on the fungal community in a High Arctic soil after five decades

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Pedosphere 2022年第5期32卷 698-706页

作者： Dorsaf kERFAHI kevin k.NEWSHAM ke DONG Hokyung SONG mark TIBBETT Jonathan M.ADAMS School of Natural Sciences Department of Biological SciencesKeimyung UniversityDaegu 42601(Republic of Korea) NERC British Antarctic Survey Madingley RoadCambridge CB3 OET(UK) Department of Life Science Kyonggi UniversitySuwon-si 16227(Republic of Korea) School of Earth and Environmental Sciences The University of ManchesterManchester M139PL(UK) Department of Sustainable Land Management&Soil Research Center School of AgriculturePolicy and DevelopmentUniversity of ReadingReading RG66AR(UK) School of Geographic and Oceanographic Sciences Nanjing UniversityNanjing 210008(China)

Mineral extraction is known to affect soil fungi in polar environments,but it is unknown how long these effects ***,by amplifying the internal transcribed spacer regions of rRNA genes in soil fungi,we compared soil fungal community in intact natural tundra with that in a nearby former coal mining area,abandoned 52 years previously,on Svalbard in the High *** with those in intact tundra,soils in the former mining area were more acidic and had lower plant *** of similar diversity in the two areas,the fungal community was dominated by Basidiomycota in the intact tundra,but by Ascomycota in the former mining *** genera formed a major part of the tundra community,but were notably less abundant in the mining *** principal variation among samples was soil ***,network connectivity analysis indicated that the fungal community in the former mining area had greater network connectivity than that in the tundra ***,the ecosystem in the former mining area has made only limited recovery towards the natural tundra state even after more than five *** is unclear whether the recovery of the fungal community is limited more by the low primary productivity,slow migration of fungi and plants,or slow changes in soil *** findings emphasize the susceptibility of polar ecosystems to disturbance,given their particularly slow recovery back towards the natural state.

关键词： abandoned mining site ectomycorrhizal fungi intact tundra mine tailings mineral extraction polar ecosystem recovery

A diagnosis with a twist:Ultrasonographic sensitivity and predictors of pediatric ovarian torsion within a large pediatric hospital

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World Journal of Emergency Medicine 2022年第3期13卷 229-231页

作者： mark k.Hewitt Jesse E.Marshall-Sheppard April J.kam Department of Medicine Division of Emergency MedicineMcMaster UniversityHamilton L8S 4L8Canada Department of Family Medicine University of TorontoToronto M5S1A1Canada Department of Pediatrics Division of Pediatric Emergency MedicineMcMaster UniversityHamilton 8S 4L8Canada

The diagnosis of ovarian torsion(OT)in girls is challenging compared to that of testicular torsion in boys for many reasons,but it behooves the medical community to continue to strive to better identify this uncommon but clinically important pathology^([1]) OT occurs when the ovary and associated structures rotate around its vascular pedicle,leading to eventually irreversible necrosis.^([2,3])Studies attempting to identify clinical features for early diagnosis have not reached a consensus on the best clinical predictors of this condition,making radiographic imaging of the ovaries even more crucial.^([4,5])

关键词： diagnosis pediatric torsion

Are the well-fed less thirsty?Effects of drought and salinity on New Zealand mangroves

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Journal of Plant Ecology 2022年第1期15卷 85-99页

作者： Sridevi Ravi Martin k-FBader Tim Young mark Duxbury Michael Clearwater Cate Macinnis-Ng Sebastian Leuzinger School of Science Auckland University of TechnologyAucklandNew Zealand Department of Forestry and Wood Technology Linnaeus UniversityVäxjöSweden Centre for Biomedical and Chemical Sciences School of ScienceAuckland University of TechnologyAucklandNew Zealand School of Science and Environmental Research Institute University of WaikatoPrivate Bag 3105HamiltonNew Zealand School of Biological Sciences and Te Pūnaha Matatini University of AucklandAucklandNew Zealand

Despite a large number of studies examining the effects of abiotic stress factors on plants,the mechanistic explanations of drought-induced tree mortality remain inconclusive and even less is known about how multiple stressors *** role of non-structural carbohydrates(NSCs)in preventing or postponing drought mortality is gaining ***,we tested the role of NSCs in mitigating the effects of drought and salinity in New Zealand mangroves,Avicennia marina *** experimentally manipulated plant NSC levels,prior to subjecting them to combinations of drought and *** growth and survival rates were 2-and 3-fold higher in the high-NSC(H-NSC)group than in the low-NSC(L-NSC)group under high salinity and drought conditions,*** 12 weeks under high salinity-high drought conditions,the H-NSC group showed higher stem hydraulic conductivity(281±50 mmol cm^(−1)s^(−1)MPa^(−1))compared with the L-NSC group(134±40 mmol cm^(−1)s^(−1)MPa^(−1)).Although starch levels remained relatively constant,we found a 20%increase in soluble sugars in the stems of H-NSC group under high drought and high salinity in week 8 compared with week *** results suggest(i)an important role of NSCs in mitigating the effects of low soil water potential caused by drought and salinity,and(ii)sink-limited growth under conditions of combined salinity and drought.

关键词： non-structural carbohydrates Avicennia marina subsp.australasica drought and salt tolerance carbon limitation temperate mangroves

Neonatal cholestasis and hepatosplenomegaly caused by congenital dyserythropoietic anemia type 1: A case report

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World Journal of Hepatology 2019年第5期11卷 477-482页

作者： Catalina Jaramillo Anna k Ermarth Angelica R Putnam mark Deneau Department of Pediatrics University of UtahSalt Lake CityUT 84113United States Department of Pathology University of UtahSalt Lake CityUT 84113United States

BACkGROUND Congenital dyserythropoietic anemia type 1(CDA1)is an autosomal recessive disorder of ineffective erythropoiesis,resulting in increased iron ***1 is usually diagnosed in children and adolescents but can rarely present in the neonatal period with severe anemia at *** are no prior reports of neonatal liver histologic findings of *** report a case of CDA1 in a newborn presenting with severe anemia,cholestasis and liver failure,where liver biopsy helped confirm the *** SUMMARY A term infant,born via emergency Cesarean section,presented with cholestasis,hepatosplenomegaly,multiorgan failure and severe anemia at birth.A prior pregnancy was significant for fetal demise at 35 wk without autopsy or known etiology for the fetal *** are both healthy and there is no history of *** further evaluation,the patient was found to have severe ferritin elevation and pulmonary *** extensive infectious and metabolic work-up was *** gland biopsy was negative for iron *** 2 wk of age,a liver biopsy showed findings consistent with CDA1.A genome rapid sequencing panel revealed novel variants in the CDAN1 *** patient’s liver dysfunction,cholestasis and organomegaly resolved,however she remains *** We report liver pathology findings of CDA1 with a novel genetic mutation for the first time in a newborn.

关键词： Congenital dyserythropoietic anemia Hemochromatosis Pulmonary hypertension Jaundice Case report

Less common etiologies of exocrine pancreatic insufficiency

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World Journal of Gastroenterology 2017年第39期23卷 7059-7076页

作者： Vikesh k Singh mark E Haupt David E Geller Jerry A Hall Pedro M Quintana Diez Division of Gastroenterology Johns Hopkins University School of MedicineBaltimoreMD 21287United States Medical Affairs AbbVie Inc.North ChicagoIL 60064United States Cystic Fibrosis Clinical Development AbbVie Inc.North ChicagoIL 60064United States CREON^(█) Clinical Development AbbVie Inc.North ChicagoIL 60064United States CREON^(█) Development AbbVie Inc.North ChicagoIL 60064United States

Exocrine pancreatic insufficiency(EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases(diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin(CCk); celiac or inflammatory bowel disease(IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery(asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy(PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI(66%-92%). EPI occurs in patients with type 1(26%-57%) or type 2 diabetes(20%-36%) and is typically mild to moderate; by definition, all patients with type 3 c(pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease(4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD(14%-74%) and up to 100% of gastrointestinal surgery patients(47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.

关键词： Celiac disease Inflammatory bowel disease Exocrine pancreatic insufficiency Malabsorption Epidemiology Pancreas Pancreatic cancer Secretion/absorption Surgery

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANkk (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (kB220) and Antibacterial Therapies

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Open Journal of Immunology 2024年第3期14卷 60-86页

作者： kenneth Blum Igor Elman David Han Colin Hanna David Baron Ashim Gupta Shan kazmi Jag khalsa Debasis Bagchi Thomas McLaughlin Rajendra D. Badgaiyan Edward J. Modestino Drew Edwards Catherine A. Dennen Eric R. Braverman Abdalla Bowirrat keerthy Sunder kevin Murphy Nicole Jafari Foojan Zeine Paul R. Carney mark S. Gold kai-Uwe Lewandowski Alireza Sharafshah Aryeh R. Pollack Panayotis k. Thanos Division of Addiction Research & Education Center for Sports and Mental Health Western University of Health Sciences Pomona CA USA Department of Psychiatry Boonshoft School of Medicine Wright State University and Dayton VA Medical Centre Dayton OH USA Division of Nutrigenomics Victory Nutrition International Lederoch PA USA Institute of Psychology ELTE Etvs Lornd University Budapest Hungary Department of Psychiatry School of Medicine University of Vermont Burlington VT USA The kenneth Blum Behavioral & Neurogenetic Institute LLC. Austin TX USA Department of Molecular Biology Adelson School of Medicine Ariel University Ariel Israel Division of Neuromodulation Research Karma Doctors & Karma TMS Palm Springs CA USA Division of Personalized Interventions Peak Logic Del Mar CA USA Division of Personalized Medicine Cross-Cultural Research & Educational Institute San Clemente CA USA Awareness Integration Institute San Clemente CA USA Division of Personalized Pain Therapy Center for Advanced Spine Care of Southern Arizona Tucson AZ USA Department of Psychiatry Harvard School of Medicine Cambridge MA USA Department of Management Science and Statistics University of Texas San Antonio TX USA Behavioral Neuropharmacology and Neuroimaging Laboratory Clinical Research Institute on Addictions Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo NY USA Future Biologics Lawrenceville GA USA Department of Microbiology Immunology & Tropic Diseases School of Medicine Georgetown University Washington DC USA Department of Pharmaceutical Sciences College of Pharmacy Texas Southern University Houston TX USA Department of Psychiatry School of Medicine Case Western University Cleveland OH USA Brain and Behavior Laboratory Curry College Milton MA USA The Neurogenesis Project Jacksonville FL USA Department of Family Medicine Jefferson Health Northeast Philadelphia PA USA Departmen

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (kB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANkk (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-kB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing kB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and kB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as

关键词： PANDAS CANS Genetic Addiction Risk Testing (GARS) Pro-Dopamine Regulation Hypodopaminergia Polymorphisms Antibacterial Therapy Infections

Experimental design and model reduction in systems biology

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Frontiers of Electrical and Electronic Engineering in China 2018年第4期6卷 287-306页

作者： Jenny E.Jeong Qinwei Zhuang mark k.Transtrum Enlu Zhou Peng Qiu School of Electrical and Computer Engineering Georgia Institute of TechnologyAtlantaGA 30318USA School of Biological Sciences Georgia Institute of TechnologyAtlantaGA 30318USA Department of Physics and Astronomy Brigham Young UniversityProvoUT 84602USA School of Industrial and Systems Engineering Georgia Institute of TechnologyAtlantaGA 30318USA Department of Biomedical Engineering Georgia Institute of TechnologyAtlantaGA 30318USA、Emory UniversityAtlanta GA 30322USA

Background: In systems biology, the dynamics of biological networks are often modeled with ordinary differential equations (ODEs) that encode interacting components in the systems, resulting in highly complex models. In contrast, the amount of experimentally available data is almost always limited, and insufficient to constrain the parameters. In this situation, parameter estimation is a very challenging problem. To address this challenge, two intuitive approaches are to perform experimental design to generate more data, and to perform model reduction to simplify the model. Experimental design and model reduction have been traditionally viewed as two distinct areas, and an extensive literature and excellent reviews exist on each of the two areas. Intriguingly, however, the intrinsic connections between the two areas have not been recognized. Results: Experimental design and model reduction are deeply related, and can be considered as one unified framework. There are two recent methods that can tackle both areas, one based on model manifold and the other based on profile likelihood. We use a simple sum-of-two-exponentials example to discuss the concepts and algorithmic details of both methods, and provide Matlab-based code and implementation which are useful resources for the dissemination and adoption of experimental design and model reduction in the biology community. Conclusions: From a geometric perspective, we consider the experimental data as a point in a high-dimensional data space and the mathematical model as a manifold living in this space. Parameter estimation can be viewed as a projection of the data point onto the manifold. By examining the singularity around the projected point on the manifold, we can perform both experimental design and model reduction. Experimental design identifies new experiments that expand the manifold and remove the singularity, whereas model reduction identifies the nearest boundary, which is the nearest singularity that suggest

关键词： experimental design model reduction model manifold profile likelihood systems biology Experimental Design Reduced order model Manifolds