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Endosomal trafficking defects in patient cells with KIAA1109 biallelic variants

Genes & Diseases 2019年第1期6卷 56-67页

作者： megan s.kane Callie J.Diamonstein Natalie Hauser John F.Deeken John E.Niederhuber Thierry Vilboux Inova Translational Medicine Institute Inova Health SystemFairfaxVAUnited States Department of Medicine Virginia Commonwealth UniversityRichmondVAUnited States Department of Public Health sciences University of Virginia School of MedicineCharlottesvilleVAUnited States Department of Oncology and surgery Johns Hopkins University School of MedicineBaltimoreMDUnited States

The uncharacterized gene KIAA1109 has recently been associated with a congenital neurological malformation disorder that variably presents with arthrogryposis,craniofacial and/or cardiac *** have identified two additional patients with compound heterozygous KIAA1109 variants presenting with the same neurological *** mechanism whereby KIAA1109 loss of function causes this spectrum of disorders was the primary focus of our *** hypothesized that KIAA1109 function could be conserved relative to the fly gene tweek and examined endocytosis and endosome recycling in patient ***,we examined the structure of the cytoskeleton and cilia based on functional overlap with endocytosis and several known etiologies for neuronal migration *** primary dermal fibroblasts from one patient and a healthy donor,we performed immunofluorescence and endocytosis assays to examine the endosomal,cytoskeletal,and ciliary cellular *** found notable abnormalities in endosomal trafficking and endosome recycling *** also observed changes in the actin cytoskeleton and cilia structural *** conclude that the function of KIAA1109 in humans may indeed overlap with the function of the Drosophila ortholog,resulting in perturbations to endosomal trafficking and the actin *** alterations have ripple effects,altering many pathways that are critical for proper neuronal migration and embryonic development.

关键词： Cilia Endocytosis KIAA1109 Neurological malformation Vesicular trafficking

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Recent advances and future therapy development for Alzheimer’s disease and related disorders

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Neural Regeneration Research 2024年第9期19卷 1877-1878页

作者： megan Hong Gal Bitan Department of Neurology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCAUSA Department of Chemistry and Biochemistry University of California Los AngelesLos AngelesCAUSA Molecular Biology Institute University of California Los AngelesLos AngelesCAUSA Brain Research Institute University of CaliforniaLos AngelesCAUSA

Over 55 million people globally live with Alzheimer’s disease(AD)or related dementias(ADRD)and the number is expected to double every twenty *** i l recent l y,onl y symptomatic treatments were available to patients with AD,including acetylcholine esterase inhibitors,of which the last one,galantamine,was approved by the Us Food and Drug Administration(FDA)in 2001.

关键词： Alzheimer globally patients

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Restimate:Recovery Estimation Tool for Resilience Planning

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Journal of safety science and Resilience 2024年第1期5卷 47-63页

作者： scott Miles megan Ly Nick Terry Youngjun Choe Department of Human Centered Design&Engineering Campus Box 352315University of WashingtonSeattleWA 98195United States of America Department of Industrial&systems Engineering Box 352650University of WashingtonSeattleWA 98195United States of America

The *** Institute of standards and Technology(NIsT)published the Community Resilience Planning Guide in *** NIsT Guide advocates for a participatory process for developing a performance measurement framework for the jurisdiction’s resilience against a scenario *** framework centers around tables of expected and desired recovery times for selected community assets,such as electricity,water,and natural gas *** NIsT Guide does not provide a method for estimating the expected recovery ***,building high-fidelity computer models for such estimations requires substantial resources that even larger ju-risdictions cannot *** most promising approach to recovery time estimation is to systematically use data elicited from people to tap into the wisdom of the(knowledgeable)*** paper describes a novel research-through-design project to enable the computer-supported elicitation of recovery time series *** work is the first in the literature to examine people’s ability to estimate recovery curves and how design in-fluences such *** main contribution to resilience planning is three-fold:development of a new elicitation tool called Restimate,understanding its potential user base,and providing insights into how it can facilitate resilience *** is the first tool to enable evidence-based expert elicitation in any community with limited resources for resilience *** resilience planning,those who facilitate high-stakes planning activities under large uncertainties(e.g.,mission-critical system design and planning)will benefit from a similar research-through-design process.

关键词： expert elicitation disaster natural hazard infrastructure community resilience restoration user-centered design computer-supported cooperative work

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Detection and clearance in Alzheimer’s disease: leading with illusive chemical, structural and morphological features of the targets

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Neural Regeneration Research 2024年第3期19卷 497-498页

作者： Luís Gales i3s−Instituto de Investigação e Inovação em saúde Rua Alfredo AllenPortoPortugal(Gales L)IBMC−Instituto de Biologia Molecular e CelularUniversidade do PortoRua Alfredo AllenPortoPortugal ICBAs−Instituto de Ciências Biomédicas Abel salazar Rua de Jorge Viterbo FerreiraPortoPortugal

Highly specific interactions between biomolecules,such as antigen-antibody,protein-ligand,or nucleic acid base pair complementary are on the basis of the organization of complex *** same principles may be tentatively used in molecular medicine for diagnosis and therapeutics.A molecule can be designed to selectively bind a protease and thereby inhibit the production of a peptide that forms toxic aggregates in the brain or an antibody may be produced to bind specifically to that peptide for detection or clearance ***,interference in biological systems is not that *** a start there is the inhibition of the physiological role of the protease;moreover,several cleavage fragments may be produced,which may continue to diverge due to putative post-translational modification and self-assembly processes,hiding the toxic target in a“soup”of peptide species varying in size,structure and chemical composition.A perspective of the current status and challenges in targeting peptide species for diagnosis and treatment in the context of Alzheimer’s disease is given.

关键词： Alzheimer diagnosis thereby

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Implementation of an international medical student pen-pal club:survey outcomes of perceptions in cultural competency and global health

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Global Health Journal 2024年第1期8卷 11-15页

作者： Max J.Goodman Jennifer Livschitz Ji Won Kim megan L.schultz Medical College of Wisconsin MilwaukeeWI 53226USA Department of Pediatrics Division of Emergency MedicineMedical College of WisconsinMilwaukeeWI53226USA

Background:Pen-pal clubs(PPC)are used worldwide for students to learn about different cultures and other skillsets without the need for *** medical students are interested in global health opportunities abroad but costs,scheduling,and other barriers allow few to participate in such *** is important that medical students have nuanced global medical perspectives and can contribute to the global medical ***:The purpose of this study is to demonstrate that an international medical student PPC improves medical students'perspectives of cultural competency and global health ***:In 2021,a novel medical student PPC was established that began between an American and Japanese medical *** a shareholders meeting,it was decided that the number of medical schools involved globally be expanded through previous institutional affiliations and online *** total,the club connected 50 American medical students and 52 medical students from 17 high-and middle-income *** primary form of communication was online;pen-pals were encouraged to communicate monthly using provided topics,although frequency and way of communication was their *** February 2022,American PPC members were emailed a qualitative survey to assess the PPC's ***:The survey was completed by 42%of American PPC members,95%of which were 22-26 *** were preclinical medical students,60%whom were female and the majority either white(47%)or Asian(43%).Overall,the PPC positively influenced American medical students'perception of global medicine,medical education,and their cultural competency after joining the PPC compared to prior(P=0.004).Conclusion:PPCs encourage medical students to think from a global perspective and foster open-mindedness within varying social and cultural *** a global communication platform for students during medical school education may be an additional way to train aspiring global l

关键词： Pen-pals Medical student Global health Cultural competency

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An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads:Experimental studies and molecular dynamics analysis

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Acta Pharmaceutica sinica B 2024年第6期14卷 2669-2684页

作者： Jamie Anne Lugtu-Pe Xuning Zhang sako Mirzaie Hao Han R.Chang Nour AL-Mousawi Kuan Chen Yongqiang Li Anil kane Daniel Bar-shalom Xiao Yu Wu Advanced Pharmaceutics and Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoToronto M5S 3M2Canada Candoo Pharmatech Company Inc. Mississauga L5N 5M1Canada Department of Pharmacy University of CopenhagenCopenhagen DK-2100Denmark Patheon by Thermo Fisher scientific Toronto Region Operations(TRO)Mississauga L5N 3X4Canada

solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution ***,most new chemical entities exhibit poor water solubility,and hence are exempt from such *** combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage ***,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRAsD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)*** to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRAsD bead surface,and greater extent of celecoxib ***-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to *** work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRAsD.

关键词： Controlled release amorphous solid dispersion Poorly soluble drug Internal recrystallization Membrane-reservoir coated beads Molecular dynamics simulation Effect of pore formers Terpolymer nanogel Drug-polymer interactions

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Preventive Effect of an Extract of Terminalia avicennioides on Acetylcholine-Induced Tracheoconstriction in Wistar strain Rats

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Open Journal of Respiratory Diseases 2024年第2期14卷 60-68页

作者： Awa Ba-Diop Ndèye Absa Diaw Ibrahima Diouf Mbaye sène Ouafae Kechaba Mamadou sarr Modou Oumy kane Physiology Laboratory Department of Medicine Alioune Diop University of Bambey Bambey Senegal IRL3189 Environment Health Societies CNRS-UCAD Dakar Senegal Department of Physiology Laboratory Faculty of Medicine Cheikh Anta Diop University of Dakar Dakar Senegal Department of Physiology Laboratory Faculty of Medicine UFR Sante Assane SECK University of Ziguinchor Ziguinchor Senegal

Asthma is one of the most common chronic respiratory pathologies worldwide. The cost of its treatment, particularly for populations in developing countries like senegal, requires an alternative which consists of developing research into new therapeutic approaches with the use of plants from traditional pharmacopoeia. The objective of this study was to determine whether the hydroalcoholic extract of Terminalia avicennioides leaves has a preventive effect on the constriction of tracheal smooth muscle induced by Acetylcholine in Wistar strain rats. Methods: The species used in our experiments were male Wistar rats aged between 12 and 14 weeks. Rings of rat trachea were suspended in isolated organ chambers connected to tension sensors. Two pharmacological agents were used: acetylcholine, for its constrictor effect and adrenaline, for its dilating effect on the pulmonary trachea. Our plant material consisted of a hydroalcoholic extract of Terminalia avicennioides leaves. The experimental protocol was that of the preventive model which consisted of impregnating these rings with the extract at a defined concentration then testing its contractility in the presence of Acetylcholine which was the contractile agonist used in this study. The preventive effect of the extract was studied with an Acetylcholine contraction range on rings pre-incubated with Terminalia avicennioides extract. Results: The results showed that Acetylcholine contracts the trachea and the increase in its contractility was dependent on the dose of Ach added cumulatively (10sup>−5sup> to 4 × 10sup>−5sup> mol/l). The administration of the hydroalcoholic extract of Terminalia avicennioides leaves led to a modification of the contractile response to Acetylcholine. Indeed, this extract induced a significant attenuation of the contractile responses of the treated tracheal rings compared to those untreated. Conclusion: Terminalia avicennioides had a relaxing effect on tracheal smooth muscle and this effect

关键词： Bronchial Hyperreactivity Extract Hydroalcoholic of Terminalia Avicennioides Asthma

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Astrophysical s-factor and reaction rate for 15N(p,γ)16O within the modified potential cluster model

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Chinese Physics C 2024年第4期48卷 130-145页

作者： s.B.Dubovichenko A.s.Tkachenko R.Ya.Kezerashvili N.A.Burkova B.M.Yeleusheva Fesenkov Astrophysical Institute 050020 AlmatyKazakhstan New York City College of Technology City University of New YorkBrooklyn11201 New YorkUSA Graduate school and University Center City University of New York10016 New YorkUSA al-Farabi Kazakh National University 050040 AlmatyKazakhstan

We study radiative p^(15)N capture on the ground state of ^(16)O at stellar energies within the framework of a modified potential cluster model(MPCM)with forbidden states,including low-lying *** investigation of the ^(15)N(p,γ0)^(16)O reaction includes the consideration of ^(3)s_(1) resonances due to E1 transitions and the contribution of the ^(3)P_(1) scattering wave in the p+^(15)N channel due to the ^(3)P_(1)→^(3)P_(0)M1 *** calculated the astrophysical low-energy s-factor,and the extrapolated s(0)turned out to be within 34.7−40.4 keV·*** important role of the asymptotic constant(AC)for the ^(15)N(p,γ0)16O process with interfering ^(3)s_(1)(312)and ^(3)s_(1)(962)resonances is elucidated.A comparison of our calculation for the s-factor with existing experimental and theoretical data is addressed,and a reasonable agreement is *** reaction rate is calculated and compared with the existing *** has negligible dependence on the variation of AC but shows a strong impact of the interference of ^(3)s_(1)(312)and ^(3)s_(1)(962)resonances in reference to the CNO Gamow windows,especially at low *** estimate the contribution of cascade transitions to the reaction rate based on the exclusive experimental data from ***.C.85,065810(2012).The reaction rate enhancement due to the cascade transitions is observed from T_(9)>0.3 and reaches the maximum factor~1.3 at T_(9)=*** present the Gamow energy window and a comparison of rates for radiative proton capture reactions ^(12)N(p,γ)^(13)O,^(13)N(p,γ)^(14)O,^(14)N(p,γ)^(15)O,and ^(15)N(p,γ)^(16)O obtained in the framework of the MPCM and provide the temperature windows,prevalence,and significance of each process.

关键词： low and astrophysical energies p^(15)N system thermonuclear reaction rate potential cluster model CNO-cycle

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Identification of Antioxidant Additives in Food Products sold in Dakar Markets

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Open Journal of Applied sciences 2024年第1期14卷 51-62页

作者： Alé kane Papa Amadou Diakhaté sokhna Ndao Modou Dieng Mady Cisse Amadou Diop Laboratory of Biological Agronomic and Food Sciences and Complex Systems Modelling (LABAAM) University Gaston Berger (UGB) Saint-Louis Senegal UFR of Agronomic sciences Aquaculture and Food Technology (UFR S2ATA) UGB Saint-Louis Senegal Analytical Chemistry and Bromatology Laboratory University Cheikh Anta Diop of Dakar Dakar Senegal Department of Chemical Engineering and Applied Biology University Cheikh Anta Diop of Dakar Dakar Senegal

The use of food additives in industrial production has the advantage of improving sensory properties, technological quality and extending the shelf life of foods. Among the most widely used additives are antioxidants, which prevent oxidation, browning and rancidity reactions in foods. However, the strong presence of these additives on the market is not without risks for human health, and should be controlled to guarantee food safety. Analysis of the risks associated with consumption of foods containing these additives requires, among other things, information on the frequency of use of these additives in various consumer products. The aim of this study is therefore to identify the antioxidants present in industrial food products distributed in Dakar. The methodology adopted consists of a qualitative analysis based on the identification of additives from food labels. Investigations were carried out in 9 stores, 4 superettes and 2 supermarkets located in different districts of Dakar. The results revealed the presence of 12 antioxidant additives, dominated by citric acid (53%) and ascorbic acid (29%). These studies have also highlighted the simultaneous use of several antioxidants in the same food product. Moreover, for some artificial antioxidants identified antioxydant such as BHA and BHT, health risks are associated with their consumption. The results of this study open up prospects for the development of information databases on food additives.

关键词： Additives Antioxidant Food Products Market Risk

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Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti

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World Journal of Hepatology 2024年第7期16卷 1039-1050页

作者： sahal Darar Dirir Ambroise D Ahouidi Aboubacry Drame Warsama Osman Abdi Guelleh Youssouf Kayad Mohamed Houmed Aboubakar Makhtar Camara Coumba Toure kane Halimatou Diop Ndiaye Laboratoire Medical de la Caisse National de sécuritésocial de Djibouti Caisse National de SécuritéSocial de DjiboutiDjibouti BP 696Senegal Parasitology Institut de Recherche en santéde Surveillanceépidémiologique et de FormationDakar 7325Senegal Ecole Doctoral UniversitéAlioune Diop de BambeyDakar 7325Senegal Department of Des soins Caisse National de Securite SocialDjibouti 696Senegal Centre de soin Caisse National de Securite SocialDjibouti 696Senegal Laboratoire Medical Mer Rouge Djibouti 99399Senegal Centre Hospitalier Universitaire Aristide le Dantec Laboratoire Bactériologie-Virologie-Hôpital Aristide le DantecDakar 7325Senegal Department of Virology Institut de Recherche en Santéde Surveillanceépidémiologique et de FormationDakar 7325Senegal Bacteriology and Virology Laboratory Le Dantec University Teaching HospitalDakar BP 7325Senegal

BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected *** mother-to-child transmission(MTCT)of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1%by *** screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive *** To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen(HBsAg)-positive mothers in Djibouti *** We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their *** study ran from January 2021 to May 2022,and infants were followed up to 7 mo of *** serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay(Biomérieux,Paris,France)and the automated Amplix platform(Biosynex,strasbourg,France).All infants received hepatitis B immunoglobulin and were vaccinated against HBV at *** infants were closely monitored to assess their seroprotective response and for failure of *** logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine *** statistical analyses were performed with version 4.0.1 of the R *** Of the 50 pregnant women recruited,the median age was 31 years,ranging from 18 years to 41 *** MTCT rate in this cohort was 4%(2/50)in HBsAg-positive women and 67%(2/3)in hepatitis B e antigen-positive women with a viral load>200000 IU/*** the 48 infants who did not fail immunoprophylaxis,8(16%)became poor responders(anti-HBs B immunoglobulin,while 40(84%)infants achieved a good level of seroprotection(anti-HB>100 mIU/mL).Factors associated with this failure of immunoprophylaxis were maternal HBV DNA lev

关键词： Hepatitis B surface antigen Infants Hepatitis B immunoglobulin Hepatitis vaccine Djibouti

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