Publications by authors named "Salma Begum"

32 Publications

Application of Machine Learning in Intensive Care Unit (ICU) Settings Using MIMIC Dataset: Systematic Review.

Informatics (MDPI) 2021 Mar 3;8(1). Epub 2021 Mar 3.

Department of Biomedical Informatics, University of Arkansas for Medical Sciences (UAMS), Little Rock, Arkansas 72205, USA.

Modern Intensive Care Units (ICUs) provide continuous monitoring of critically ill patients susceptible to many complications affecting morbidity and mortality. ICU settings require a high staff-to-patient ratio and generates a sheer volume of data. For clinicians, the real-time interpretation of data and decision-making is a challenging task. Machine Learning (ML) techniques in ICUs are making headway in the early detection of high-risk events due to increased processing power and freely available datasets such as the Medical Information Mart for Intensive Care (MIMIC). We conducted a systematic literature review to evaluate the effectiveness of applying ML in the ICU settings using the MIMIC dataset. A total of 322 articles were reviewed and a quantitative descriptive analysis was performed on 61 qualified articles that applied ML techniques in ICU settings using MIMIC data. We assembled the qualified articles to provide insights into the areas of application, clinical variables used, and treatment outcomes that can pave the way for further adoption of this promising technology and possible use in routine clinical decision-making. The lessons learned from our review can provide guidance to researchers on application of ML techniques to increase their rate of adoption in healthcare.
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http://dx.doi.org/10.3390/informatics8010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112729PMC
March 2021

Implications for preeclampsia: hypoxia-induced Notch promotes trophoblast migration.

Reproduction 2021 05 14;161(6):681-696. Epub 2021 May 14.

Department of Obstetrics, Gynecology and Reproductive Health, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA.

In the first trimester of human pregnancy, low oxygen tension or hypoxia is essential for proper placentation and placenta function. Low oxygen levels and activation of signaling pathways have been implicated as critical mediators in the promotion of trophoblast differentiation, migration, and invasion with inappropriate changes in oxygen tension and aberrant Notch signaling both individually reported as causative to abnormal placentation. Despite crosstalk between hypoxia and Notch signaling in multiple cell types, the relationship between hypoxia and Notch in first trimester trophoblast function is not understood. To determine how a low oxygen environment impacts Notch signaling and cellular motility, we utilized the human first trimester trophoblast cell line, HTR-8/SVneo. Gene set enrichment and ontology analyses identified pathways involved in angiogenesis, Notch and cellular migration as upregulated in HTR-8/SVneo cells exposed to hypoxic conditions. DAPT, a γ-secretase inhibitor that inhibits Notch activation, was used to interrogate the crosstalk between Notch and hypoxia pathways in HTR-8/SVneo cells. We found that hypoxia requires Notch activation to mediate HTR-8/SVneo cell migration, but not invasion. To determine if our in vitro findings were associated with preeclampsia, we analyzed the second trimester chorionic villous sampling (CVS) samples and third trimester placentas. We found a significant decrease in expression of migration and invasion genes in CVS from preeclamptic pregnancies and significantly lower levels of JAG1 in placentas from pregnancies with early-onset preeclampsia with severe features. Our data support a role for Notch in mediating hypoxia-induced trophoblast migration, which may contribute to preeclampsia development.
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http://dx.doi.org/10.1530/REP-20-0483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403268PMC
May 2021

API Driven On-Demand Participant ID Pseudonymization in Heterogeneous Multi-Study Research.

Healthc Inform Res 2021 Jan 31;27(1):39-47. Epub 2021 Jan 31.

Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Objectives: To facilitate clinical and translational research, imaging and non-imaging clinical data from multiple disparate systems must be aggregated for analysis. Study participant records from various sources are linked together and to patient records when possible to address research questions while ensuring patient privacy. This paper presents a novel tool that pseudonymizes participant identifiers (PIDs) using a researcher-driven automated process that takes advantage of application-programming interface (API) and the Perl Open-Source Digital Imaging and Communications in Medicine Archive (POSDA) to further de-identify PIDs. The tool, on-demand cohort and API participant identifier pseudonymization (O-CAPP), employs a pseudonymization method based on the type of incoming research data.

Methods: For images, pseudonymization of PIDs is done using API calls that receive PIDs present in Digital Imaging and Communications in Medicine (DICOM) headers and returns the pseudonymized identifiers. For non-imaging clinical research data, PIDs provided by study principal investigators (PIs) are pseudonymized using a nightly automated process. The pseudonymized PIDs (P-PIDs) along with other protected health information is further de-identified using POSDA.

Results: A sample of 250 PIDs pseudonymized by O-CAPP were selected and successfully validated. Of those, 125 PIDs that were pseudonymized by the nightly automated process were validated by multiple clinical trial investigators (CTIs). For the other 125, CTIs validated radiologic image pseudonymization by API request based on the provided PID and P-PID mappings.

Conclusions: We developed a novel approach of an ondemand pseudonymization process that will aide researchers in obtaining a comprehensive and holistic view of study participant data without compromising patient privacy.
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http://dx.doi.org/10.4258/hir.2021.27.1.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921568PMC
January 2021

Role of Machine Learning Techniques to Tackle the COVID-19 Crisis: Systematic Review.

JMIR Med Inform 2021 Jan 11;9(1):e23811. Epub 2021 Jan 11.

Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

Background: SARS-CoV-2, the novel coronavirus responsible for COVID-19, has caused havoc worldwide, with patients presenting a spectrum of complications that have pushed health care experts to explore new technological solutions and treatment plans. Artificial Intelligence (AI)-based technologies have played a substantial role in solving complex problems, and several organizations have been swift to adopt and customize these technologies in response to the challenges posed by the COVID-19 pandemic.

Objective: The objective of this study was to conduct a systematic review of the literature on the role of AI as a comprehensive and decisive technology to fight the COVID-19 crisis in the fields of epidemiology, diagnosis, and disease progression.

Methods: A systematic search of PubMed, Web of Science, and CINAHL databases was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify all potentially relevant studies published and made available online between December 1, 2019, and June 27, 2020. The search syntax was built using keywords specific to COVID-19 and AI.

Results: The search strategy resulted in 419 articles published and made available online during the aforementioned period. Of these, 130 publications were selected for further analyses. These publications were classified into 3 themes based on AI applications employed to combat the COVID-19 crisis: Computational Epidemiology, Early Detection and Diagnosis, and Disease Progression. Of the 130 studies, 71 (54.6%) focused on predicting the COVID-19 outbreak, the impact of containment policies, and potential drug discoveries, which were classified under the Computational Epidemiology theme. Next, 40 of 130 (30.8%) studies that applied AI techniques to detect COVID-19 by using patients' radiological images or laboratory test results were classified under the Early Detection and Diagnosis theme. Finally, 19 of the 130 studies (14.6%) that focused on predicting disease progression, outcomes (ie, recovery and mortality), length of hospital stay, and number of days spent in the intensive care unit for patients with COVID-19 were classified under the Disease Progression theme.

Conclusions: In this systematic review, we assembled studies in the current COVID-19 literature that utilized AI-based methods to provide insights into different COVID-19 themes. Our findings highlight important variables, data types, and available COVID-19 resources that can assist in facilitating clinical and translational research.
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http://dx.doi.org/10.2196/23811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806275PMC
January 2021

Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy.

Int J Mol Sci 2020 Sep 5;21(18). Epub 2020 Sep 5.

Department of Obstetrics, Gynecology and Reproductive Health, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.

Maternal spiral arteries and newly formed decidual capillaries support embryonic development prior to placentation. Previous studies demonstrated that Notch signaling is active in endothelial cells of both decidual capillaries and spiral arteries, however the role of Notch signaling in physiologic decidual angiogenesis and maintenance of the decidual vasculature in early mouse pregnancy has not yet been fully elucidated. We used the () mouse model to delete Notch ligand, , in maternal endothelial cells during post-implantation, pre-placentation mouse pregnancy. Loss of endothelial leads to increased expression of Notch effectors, and and increased endothelial Notch signaling activity in areas of the decidua with remodeling angiogenesis. This correlated with an increase in Dll4 expression in capillary endothelial cells, but not spiral artery endothelial cells. Consistent with increased Dll4/Notch signaling, we observed decreased VEGFR2 expression and endothelial cell proliferation in angiogenic decidual capillaries. Despite aberrant Dll4 expression and Notch activation in mutants, pregnancies were maintained and the decidual vasculature was not altered up to embryonic day 7.5. Thus, Jag1 functions in the newly formed decidual capillaries as an antagonist of endothelial Dll4/Notch signaling during angiogenesis, but Jag1 signaling is not necessary for early uterine angiogenesis.
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http://dx.doi.org/10.3390/ijms21186477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554752PMC
September 2020

Toolkit to Compute Time-Based Elixhauser Comorbidity Indices and Extension to Common Data Models.

Healthc Inform Res 2020 Jul 31;26(3):193-200. Epub 2020 Jul 31.

Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Objective: The time-dependent study of comorbidities provides insight into disease progression and trajectory. We hypothesize that understanding longitudinal disease characteristics can lead to more timely intervention and improve clinical outcomes. As a first step, we developed an efficient and easy-to-install toolkit, the Time-based Elixhauser Comorbidity Index (TECI), which pre-calculates time-based Elixhauser comorbidities and can be extended to common data models (CDMs).

Methods: A Structured Query Language (SQL)-based toolkit, TECI, was built to pre-calculate time-specific Elixhauser comorbidity indices using data from a clinical data repository (CDR). Then it was extended to the Informatics for Integrating Biology and the Bedside (I2B2) and Observational Medical Outcomes Partnership (OMOP) CDMs.

Results: At the University of Arkansas for Medical Sciences (UAMS), the TECI toolkit was successfully installed to compute the indices from CDR data, and the scores were integrated into the I2B2 and OMOP CDMs. Comorbidity scores calculated by TECI were validated against: scores available in the 2015 quarter 1-3 Nationwide Readmissions Database (NRD) and scores calculated using the comorbidities using a previously validated algorithm on the 2015 quarter 4 NRD. Furthermore, TECI identified 18,846 UAMS patients that had changes in comorbidity scores over time (year 2013 to 2019). Comorbidities for a random sample of patients were independently reviewed, and in all cases, the results were found to be 100% accurate.

Conclusion: TECI facilitates the study of comorbidities within a time-dependent context, allowing better understanding of disease associations and trajectories, which has the potential to improve clinical outcomes.
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http://dx.doi.org/10.4258/hir.2020.26.3.193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438698PMC
July 2020

Polymerization in MOF-Confined Nanospaces: Tailored Architectures, Functions, and Applications.

Langmuir 2020 Sep 27;36(36):10657-10673. Epub 2020 Aug 27.

Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Hermann-von Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany.

This feature article describes recent trends and advances in structuring network polymers using a coordination-driven metal-organic framework (MOF)-based template approach to demonstrate the concept of crystal-controlled polymerization in confined nanospaces, forming tailored architectures ranging from simple linear one-dimensional macromolecules to tunable three-dimensional cross-linked network polymers and interwoven molecular architectures. MOF-templated network polymers combine the characteristics and advantages of crystalline MOFs (high porosity, structural regularity, and designability) with the intrinsic behaviors of soft polymers (flexibility, processability, stability, or biocompatibility) with widespread application possibilities and tunable properties. The article ends with a summary of the remaining challenges to be addressed, and future research opportunities in this field are discussed.
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http://dx.doi.org/10.1021/acs.langmuir.0c01832DOI Listing
September 2020

An IFT20 mechanotrafficking axis is required for integrin recycling, focal adhesion dynamics, and polarized cell migration.

Mol Biol Cell 2020 08 10;31(17):1917-1930. Epub 2020 Jun 10.

Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, New York, NY 10032.

Directional cell migration drives embryonic development, cancer metastasis, and tissue repair and regeneration. Here, we examine the role of intraflagellar transport (IFT) 20 (Ift20) during polarized migration of epidermal cells. IFT20 is implicated in regulating cell migration independently of the primary cilium, but how IFT proteins integrate with the cell migration machinery is poorly understood. We show that genetic ablation of IFT20 in vitro slows keratinocyte migration during wound healing. We find that this phenotype is independent of the primary cilium and instead can be attributed to alterations in integrin-mediated mechanotransduction and focal adhesion (FA) dynamics. Loss of Ift20 resulted in smaller and less numerous FAs and reduced the levels of activated FA kinase. Studies of FA dynamics during microtubule-induced FA turnover demonstrated that Ift20 loss specifically impaired the reformation, but not the disassembly, of FAs. In the absence of Ift20 function, β1 integrins endocytosed during FA disassembly are not transferred out of Rab5 (+) endosomes. This defective transit from the early endosome disrupts eventual recycling of β1 integrins back to the cell surface, resulting in defective FA reformation. In vivo, conditional ablation of Ift20 in hair follicle stem cells (HF-SCs) similarly impairs their ability to invade and migrate during epidermal wound healing. Using explant studies, lineage tracing, and clonal analysis, we demonstrate that Ift20 is required for HF-SC migration and their contribution to epidermal regeneration. This work identifies a new Ift20 mechanotrafficking mechanism required for polarized cell migration and stem cell-driven tissue repair.
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http://dx.doi.org/10.1091/mbc.E20-04-0232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525813PMC
August 2020

2D and Heterostructure Nanomaterial Based Strategies for Combating Drug-Resistant Bacteria.

ACS Omega 2020 Feb 13;5(7):3116-3130. Epub 2020 Feb 13.

Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi 39217, United States.

In the last three decades, there has been a huge increase in the number of antibiotic-resistant bacterial strains, which is becoming a serious threat to public health. Since the discovery of new effective antibiotics has dramatically decreased in last ten years, there are huge initiatives to develop new antimicrobial approaches to fight drug-resistant bacterial infections. In the last decade, a new nanoparticle-based tool has emerged to combat deadly bacterial infections, which may overcome the barriers faced by antibiotic resistance. The current mini-review highlights recent reports on two-dimensional (2D) graphene oxide (GO), 2D transition metal dichalcogenides (TMD), 2D MXenes, and 2D heterostructure material-based approaches to tackle bacteria. Notably, we discuss the major design criteria which have been used to develop novel antimicrobial 2D and heterostructure materials to eliminate bacterial infections. Next, details on the various mechanisms underlying antibacterial activity for 2D and heterostructure materials such as physical/mechanical damage, lipid extraction, oxidative stress, and photothermal/photodynamic effects have been discussed. Finally, we highlight the promises, major challenges, and prospects of nanomaterial-based approaches to combat multidrug-resistant bacterial infections.
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http://dx.doi.org/10.1021/acsomega.9b03919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045323PMC
February 2020

Dynamic Expression of Interleukin-33 and ST2 in the Mouse Reproductive Tract Is Influenced by Superovulation.

J Histochem Cytochem 2020 04 28;68(4):253-267. Epub 2020 Feb 28.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Women's Health, Rutgers Biomedical and Health Sciences, Newark, NJ.

Interleukin-33 (IL-33) is an IL-1 family cytokine with pleiotropic effects on diverse cell types. Dysregulated IL-33 signaling has been implicated in pregnancy-related disorders, including preeclampsia and recurrent pregnancy loss, and in ovarian function in women undergoing controlled ovarian stimulation for in vitro fertilization. To date, expression of IL-33 and its receptor subunit, ST2, in the female reproductive tract remains poorly characterized. We identify IL-33-expressing oocytes surrounded by ST2-expressing granulosa cells at all stages of follicular development, in addition to IL-33 and ST2 non-endothelial cells in the ovarian stroma and theca layer in ovaries from adult mice. These expression patterns are similar in estrus- and diestrus-stage adults and in pubescent mice, suggesting a role for IL-33 signaling in ovarian function throughout development and in the estrous cycle. In the uterus, we find expression of IL-33 and ST2 in glandular and luminal epithelia during estrus and at the initiation of pregnancy. Uterine IL-33 expression was modulated by the estrous cycle and was reduced in pubescent females. Last, superovulation increases transcripts for IL-33 and the soluble form of ST2 (sST2) in ovaries, and for IL-33 in uteri. Collectively, our findings lay the foundation for studies identifying cell type-specific requirements for IL-33/ST2 signaling in the establishment and maintenance of mouse pregnancy.
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http://dx.doi.org/10.1369/0022155420911049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132822PMC
April 2020

Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation.

J Clin Invest 2020 01;130(1):83-93

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.

The mineralocorticoid aldosterone is produced in the adrenal zona glomerulosa (ZG) under the control of the renin-angiotensin II (AngII) system. Primary aldosteronism (PA) results from renin-independent production of aldosterone and is a common cause of hypertension. PA is caused by dysregulated localization of the enzyme aldosterone synthase (Cyp11b2), which is normally restricted to the ZG. Cyp11b2 transcription and aldosterone production are predominantly regulated by AngII activation of the Gq signaling pathway. Here, we report the generation of transgenic mice with Gq-coupled designer receptors exclusively activated by designer drugs (DREADDs) specifically in the adrenal cortex. We show that adrenal-wide ligand activation of Gq DREADD receptors triggered disorganization of adrenal functional zonation, with induction of Cyp11b2 in glucocorticoid-producing zona fasciculata cells. This result was consistent with increased renin-independent aldosterone production and hypertension. All parameters were reversible following termination of DREADD-mediated Gq signaling. These findings demonstrate that Gq signaling is sufficient for adrenocortical aldosterone production and implicate this pathway in the determination of zone-specific steroid production within the adrenal cortex. This transgenic mouse also provides an inducible and reversible model of hyperaldosteronism to investigate PA therapeutics and the mechanisms leading to the damaging effects of aldosterone on the cardiovascular system.
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http://dx.doi.org/10.1172/JCI127429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934213PMC
January 2020

Synthesis, Transfer, and Gas Separation Characteristics of MOF-Templated Polymer Membranes.

Membranes (Basel) 2019 Sep 20;9(10). Epub 2019 Sep 20.

Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Hermann-von Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.

This paper discusses the potential of polymer networks, templated by crystalline metal-organic framework (MOF), as novel selective layer material in thin film composite membranes. The ability to create mechanically stable membranes with an ultra-thin selective layer of advanced polymer materials is highly desirable in membrane technology. Here, we describe a novel polymeric membrane, which is synthesized via the conversion of a surface anchored metal-organic framework (SURMOF) into a surface anchored gel (SURGEL). The SURGEL membranes combine the high variability in the building blocks and the possibility to control the network topology and membrane thickness of the SURMOF synthesis with high mechanical and chemical stability of polymers. Next to the material design, the transfer of membranes to suitable supports is also usually a challenging task, due to the fragile nature of the ultra-thin films. To overcome this issue, we utilized a porous support on top of the membrane, which is mechanically stable enough to allow for the easy membrane transfer from the synthesis substrate to the final membrane support. To demonstrate the potential for gas separation of the synthesized SURGEL membranes, as well as the suitability of the transfer method, we determined the permeance for eight gases with different kinetic diameters.
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http://dx.doi.org/10.3390/membranes9100124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835741PMC
September 2019

Designing Highly Crystalline Multifunctional Multicolor Luminescence Nanosystem for Tracking Breast Cancer Heterogeneity.

Nanoscale Adv 2019 Mar 26;1(3):1021-1034. Epub 2018 Nov 26.

Department of Physics and Astronomy, University of Texas at San Antonio, San Antonio, Texas 78249, USA.

Breast tumor heterogeneity is responsible for the death of ~ 40,000 women in 2017 in USA. Triple-negative breast cancers (TNBCs) are very aggressive and it is the only breast cancer subgroup still lacking effective therapeutic. As a result, early stage detection of TNBC is vital and it will have huge significant in the clinics. Driven by the need, here we report the design of highly crystalline antibody-conjugated multifunctional multicolor luminescence nanosystem derived from naturally available popular tropical fruits mango and prune, which have capability to track breast cancer heterogeneity via selective separation and accurate identification of TNBC and HER-2 (+) or ER/PR (+) breast cancer cells selectively and simultaneously. A detailed synthesis and characterization of multifunctional multicolor nanosystems from tropical fruits has been reported. Experimental results show that by changing the fruits, multicolor luminescent carbon dots (LCDs) can be developed and is mainly due to the formation of highly crystalline nano dots with different heavy metal doping and also due to the presence of different types of surface functional groups. Experimental data presented show that multifunctional multicolor nanoprobe can be used for highly selective and simultaneous capturing of targeted TNBCs, HER2(+) or ER(+) breast cancer cells and the capture efficiency can be as high as 98%. Reported data indicate that multicolor fluorescence imaging can be used for mapping hetergenous breast cancer cells simultaneously, and it can distinguish targeted TNBCs from non-targeted HER-2 (+) or ER/PR (+) breast cancer. Our finding suggests excellent possibility of designing multicolor nanosystems from natural fruits for tracking cancer heterogeneity in clinics.
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http://dx.doi.org/10.1039/C8NA00089ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753951PMC
March 2019

Giant Chemical and Excellent Synergistic Raman Enhancement from a 3D MoS O -Gold Nanoparticle Hybrid.

ACS Omega 2019 Jun 25;4(6):11112-11118. Epub 2019 Jun 25.

Department of Chemistry and Biochemistry, Jackson State University, Jackson 39217, Mississippi, United States.

Raman spectroscopy fingerprinting features many technological applications. For this purpose, the weak Raman signals need to be boosted dramatically by surface-enhanced Raman spectroscopy (SERS), which provides immense Raman enhancement via plasmonic and chemical mechanisms (CM). In this manuscript, we reveal the giant chemical as well as extremely high SERS enhancement from a three-dimensional MoS O -gold nanoparticle (GNP) hybrid, which has capability for ultrasensitive label-free sensing of chemical and biological molecules. Notably, reported data show that the chemical enhancement for the MoS O surface is ∼10, which is comparable with the plasmonic enhancement factor (EF) by GNP. Reported data show that the total Raman EF is ∼10 from the GNP-MoS O hybrid. Intriguingly, combined experimental and theoretical finite difference time domain stimulation modeling findings show that the synergistic effect of electromagnetic mechanism and CM is responsible for huge SERS enhancement. Experimental results demonstrate that a proposed hybrid SERS platform can be used for fingerprint sensing of different multiple drug resistance bacteria at 5 cfu/mL concentration. Importantly, the current manuscript provides a good strategy for manipulating the SERS sensitivity to 13 orders of magnitude, which is instrumental for next-generation technological applications of Raman spectroscopy.
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http://dx.doi.org/10.1021/acsomega.9b00866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648720PMC
June 2019

Intra- and interpersonal agency: Resuming occupational participation among persons with spinal cord injury after discharge from in-patient rehabilitation.

Scand J Occup Ther 2020 Jan 22;27(1):66-79. Epub 2019 Jun 22.

Department of Occupational Therapy, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.

This research aim was to understand and describe how changes occur in occupational participation among persons with spinal cord injury (SCI) following discharge from a rehabilitation center in Bangladesh. Using a selected ethnographical research design, nineteen participants were selected following a purposive sampling technique, then interviewed and observed on three occasions. Data analysis consisted of an iterative approach combining thematic narrative and narrative slopes analyses. Eight themes determined the transitional progress, regression and stability, in which, three of the eight themes characterized the ascending slopes, namely developing affirmative attitudes, adapting the occupational environments and working on identities. Three themes characterized the descending slopes, which were reducing confidence created difficulties, becoming bored in daily life, and declining health reduced social connections. The final two themes characterized periods of stability, namely, maintaining daily life through skills and helplessness to participate in occupations. Each of participants' transitions unfolded in unique, complex patterns. The processes directions of the transitions were understood as waning and waxing of agency. This agency could be individual, and shared with or dedicated by others, when participants and other persons combined their skills or when participants were supported by others.
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http://dx.doi.org/10.1080/11038128.2019.1628298DOI Listing
January 2020

Metal-Organic Framework-Templated Biomaterials: Recent Progress in Synthesis, Functionalization, and Applications.

Acc Chem Res 2019 06 12;52(6):1598-1610. Epub 2019 Apr 12.

Institute of Functional Interfaces , Karlsruhe Institute of Technology , Hermann-von Helmholtz-Platz 1 , D-76344 Eggenstein-Leopoldshafen , Germany.

The integration of a porous crystalline framework with soft polymers to create novel biomaterials has tremendous potential yet remains very challenging to date. Metal-organic framework (MOF)-templated polymers (MTPs) have emerged as persistent modular materials that can be tailored for desired biofunctions. These represent a novel class of hierarchically structured assemblies that combine the advantages of MOFs (precisely controlled structure, enormous diversity in framework topology, and high porosity) with the intrinsic behaviors of polymers (soft texture, flexibility, biocompatibility, and improved stability under physiological conditions). Transformation of surface-anchored MOFs (SURMOFs) via orthogonal covalent cross-linking yields surface-anchored polymeric gels (SURGELs) that open up exciting new opportunities to create soft nanoporous materials. SURGELs overcome the main drawbacks of SURMOFs, such as their limited stability under physiological conditions and their potential to release toxic metal ions, a substantial problem for applications in life sciences. MOF (SURMOF)-templated polymerization processes control the synthesis on a molecular level. Additionally, the morphology of the original MOF crystal template is replicated in the final network polymers. The MOF-templated polymerization can be induced by light, a catalyst, or temperature using several types of reactions, including thiol-ene, metal-free alkyne-azide click reactions, and Glaser-Hay coupling. In the case of photoinduced reactions, the cross-linking process can be locally confined, allowing control of the macroscopic patterning of the resulting network polymer. The use of layer-by-layer (lbl) techniques in the SURMOF synthesis serves the purpose of precise, layer-selective incorporation of functionalities via the combination of the postsynthetic modification and heteroepitaxy strategies. Transforming the functionalized SURMOF into a SURGEL allows the fabrication of polymers with desired bioactive functions at the internal or external surfaces. This Account highlights our ongoing research and inspiring progress in transforming SURMOFs into persistent, modular nanoporous materials tailored with biofunctions. Using cell culture studies, we present various aspects of SURGEL materials, such as the ability to deliver bioactive molecules to adhering cells on SURGEL surfaces, applications to advanced drug delivery systems, the ability to tune cell adhesion via surface modification, and the development of porphyrin-based SURGEL thin films with antimicrobial properties. Then we critically examine the challenges and limitations of current systems and discuss future research directions and new approaches for advancing MOF-templated biocompatible materials, emphasizing the need to include responsive and adaptive functionalities into the system. We emphasize that the hierarchical structure, ranging from the molecular to the macroscopic scale, allows for optimization of the material properties across all length scales relevant for cell-material interactions.
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http://dx.doi.org/10.1021/acs.accounts.9b00039DOI Listing
June 2019

The ciliary GTPase Arl3 maintains tissue architecture by directing planar spindle orientation during epidermal morphogenesis.

Development 2019 05 10;146(9). Epub 2019 May 10.

Department of Pathology and Cell Biology, Columbia University Medical Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA

Arl/ARF GTPases regulate ciliary trafficking, but their tissue-specific functions are unclear. Here, we demonstrate that ciliary GTPase Arl3 is required for mitotic spindle orientation of mouse basal stem cells during skin development. Arl3 loss diminished cell divisions within the plane of the epithelium, leading to increased perpendicular divisions, expansion of progenitor cells and loss of epithelial integrity. These observations suggest that an Arl3-dependent mechanism maintains cell division polarity along the tissue axis, and disruption of planar spindle orientation has detrimental consequences for epidermal architecture. Defects in planar cell polarity (PCP) can disrupt spindle positioning during tissue morphogenesis. Upon Arl3 loss, the PCP signaling molecules Celsr1 and Vangl2 failed to maintain planar polarized distributions, resulting in defective hair follicle angling, a hallmark of disrupted PCP. In the absence of Celsr1 polarity, frizzled 6 lost its asymmetrical distribution and abnormally segregated to the apical cortex of basal cells. We propose that Arl3 regulates polarized endosomal trafficking of PCP components to compartmentalized membrane domains. Cell-cell communication via ciliary GTPase signaling directs mitotic spindle orientation and PCP signaling, processes that are crucial for the maintenance of epithelial architecture.
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http://dx.doi.org/10.1242/dev.161885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526718PMC
May 2019

Multifunctional Biochar for Highly Efficient Capture, Identification, and Removal of Toxic Metals and Superbugs from Water Samples.

ACS Omega 2017 Nov 9;2(11):7730-7738. Epub 2017 Nov 9.

Department of Chemistry and Biochemistry, Jackson State University, 1400 J. R. Lynch Street, P.O. Box 17910, Jackson, Mississippi 39217-0510, United States.

According to the World Health Organization, more than two billion people in our world use drinking water sources which are not free from pathogens and heavy metal contamination. Unsafe drinking water is responsible for the death of several millions in the 21st century. To find facile and cost-effective routes for developing multifunctional materials, which has the capability to resolve many of the challenges associated with drinking water problem, here, we report the novel design of multifunctional fluorescence-magnetic biochar with the capability for highly efficient separation, identification, and removal of pathogenic superbugs and toxic metals from environmental water samples. Details of synthesis and characterization of multifunctional biochar that exhibits very good magnetic properties and emits bright blue light owing to the quantum confinement effect are reported. In our design, biochar, a carbon-rich low-cost byproduct of naturally abundant biomass, which exhibits heterogeneous surface chemistry and strong binding affinity via oxygen-containing group on the surface, has been used to capture pathogens and toxic metals. Biochar dots (BCDs) of an average of 4 nm size with very bright photoluminescence have been developed for the identification of pathogens and toxic metals. In the current design, magnetic nanoparticles have been incorporated with BCDs which allow pathogens and toxic metals to be completely removed from water after separation by an external magnetic field. Reported results show that owing to the formation of strong complex between multifunctional biochar and cobalt(II), multifunctional biochar can be used for the selective capture and removal of Co(II) from environmental samples. Experimental data demonstrate that multifunctional biochar can be used for the highly efficient removal of methicillin-resistant (MRSA) from environmental samples. Reported results also show that melittin, an antimicrobial peptide-attached multifunctional biochar, has the capability to completely disinfect MRSA superbugs after magnetic separation. A possible mechanism for the selective separation of Co(II), as well as separation and killing of MRSA, has been discussed.
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http://dx.doi.org/10.1021/acsomega.7b01386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044975PMC
November 2017

Multifunctional hybrid graphene oxide for circulating tumor cell isolation and analysis.

Adv Drug Deliv Rev 2018 02 10;125:21-35. Epub 2018 Jan 10.

Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS, USA. Electronic address:

Even in 21st century, >90% cancer-associated deaths are caused by metastatic disease. Circulating tumor cells (CTCs), which circulate in the blood stream after release from primary tumors, extravasate and form fatal metastases in different organs. Several clinical trials indicate that CTCs can be used as a liquid biopsy of tumors for early diagnosis of cancers. Since CTCs are extremely rare and exhibit heterogeneous biology due to epithelial-mesenchymal transition (EMT), oncologists continue to face enormous challenges in using CTCs as a true "liquid biopsy" for cancer patients. Recent advancements in nanoscience allow us to design nano-architectures with the capability of targeted CTCs isolation and identification. In the current review, we discuss contribution from different groups on the development of graphene oxide based nanoarchitecture for effective isolation and accurate identification of CTCs from whole blood. In the last few years, using zero-dimensional (0D), two dimensional (2D) and three dimensional (3D) multifunctional hybrid graphene oxide (GO), different types of nanoarchitectures have been designed. These nanoarchitectures represent a highly powerful platform for CTC diagnosis. We discuss the major design criteria that have been used to develop hybrid GO nanoarchitectures for selective capture and accurate identification of heterogeneous CTCs from whole blood. At the end, we conclude with the promises, major challenges, and prospect to clinically translate the identification of CTCs using GO based nanotechnology.
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http://dx.doi.org/10.1016/j.addr.2018.01.004DOI Listing
February 2018

A bio-conjugated chitosan wrapped CNT based 3D nanoporous architecture for separation and inactivation of Rotavirus and Shigella waterborne pathogens.

J Mater Chem B 2017 Dec 30;5(48):9522-9531. Epub 2017 Nov 30.

Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS, USA.

The United Nations (UN) estimates that more than one billion people in this world do not have access to safe drinking water due to microbial hazards and it kills more than 7.6 million children every year via waterborne diseases. Driven by the need for the removal and inactivation of waterborne pathogens in drinking water, we report the chemical design and details of microscopic characterization of a bio-conjugated chitosan attached carbon nanotube based three dimensional (3D) nanoporous architecture, which has the capability for effective separation and complete disinfection of waterborne pathogens from environmental water samples. In the reported design, chitosan, a biodegradable antimicrobial polysaccharide with an architecture-forming ability has been used for the formation of 3D pores as channels for water passage, as well as to increase the permeability on the inner and outer architectures for killing Rotavirus and Shigella waterborne pathogens. On the other hand, due to their large surface area, CNTs have been wrapped by chitosan to enhance the adsorption capability of the architecture for the separation and removal of pathogens from water. The reported data show that the anti-Rotavirus VP7 antibody and LL-37 antimicrobial peptide conjugated chitosan-CNT architecture can be used for efficient separation, identification and 100% eradication of Rotavirus and Shigella waterborne pathogens from water samples of different sources. A detailed mechanism for the separation and inactivation of waterborne pathogens using the bio-conjugated chitosan based 3D architecture has been discussed using microscopic and spectroscopic studies. Reported experimental data demonstrate that the multifunctional bio-conjugated 3D architecture has good potential for use in waterborne pathogen separation and inactivation technology.
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http://dx.doi.org/10.1039/c7tb02815fDOI Listing
December 2017

High Antimicrobial Activity of Metal-Organic Framework-Templated Porphyrin Polymer Thin Films.

ACS Appl Mater Interfaces 2018 Jan 5;10(2):1528-1533. Epub 2018 Jan 5.

Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT) , Hermann-von Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.

Development of surface coatings with high antimicrobial activity is urgently required to fight bacteria and other microorganisms on technical and hygiene relevant surfaces. Control over structure and topology of the surface coatings, combined with the ability to include functional molecules within the structure, is crucial for optimizing their performance. Herein, we describe a novel strategy to synthesize structurally well-defined porphyrin polymer thin films via a template approach. In this approach, bisazido-functionalized porphyrin molecules are preorganized within a metal-organic framework (MOF) structure. Afterward, porphyrin units within the MOF are covalently connected via a secondary linker. Removal of the metal ions of the MOF results in water-stable porphyrin polymer thin films that demonstrate high antibacterial activity against pathogens via visible-light-promoted generation of reactive oxygen species. In addition, this approach offers the inherent possibility to incorporate guest molecules within the structures, to functionalize the surface with biomolecules, and to create hierarchically structured materials.
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http://dx.doi.org/10.1021/acsami.7b14866DOI Listing
January 2018

Three-dimensional context rather than NLS amino acid sequence determines importin α subtype specificity for RCC1.

Nat Commun 2017 10 17;8(1):979. Epub 2017 Oct 17.

Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA, 19107, USA.

Active nuclear import of Ran exchange factor RCC1 is mediated by importin α3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin α3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin α1, although the two isoforms share an identical NLS-binding groove. Importin α3 uses its greater conformational flexibility to wedge the RCC1 β-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core. Removing the β-propeller, or inserting a linker between NLS and β-propeller, disrupts specificity for importin α3, demonstrating the structural context rather than NLS sequence determines selectivity for isoform 3. We propose importin α3 evolved to recognize topologically complex NLSs that lie next to bulky domains or are masked by quaternary structures.Importin α3 facilitates the nuclear transport of the Ran guanine nucleotide exchange factor RCC1. Here the authors reveal the molecular basis for the selectivity of RCC1 for importin α3 vs the generic importin α1 and discuss the evolution of importin α isoforms.
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http://dx.doi.org/10.1038/s41467-017-01057-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645467PMC
October 2017

Recent progress on the development of anisotropic gold nanoparticles: Design strategies and growth mechanism.

J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2017 Jan;35(1):47-66

a Department of Chemistry and Biochemistry , Jackson State University , Jackson , Mississippi , USA.

This review summarizes recent advances on design strategies for shape-controlled anisotropic gold nanoparticles. Detailed chemical mechanism has been discussed to understand the anisotropic growth. The effect of various chemical parameters and surface facets for the formation of different shaped anisotropic nanoparticles have been addressed.
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http://dx.doi.org/10.1080/10590501.2017.1280264DOI Listing
January 2017

MEISENHEIMER COMPLEX BETWEEN 2,4,6-TRINITROTOLUENE AND 3-AMINOPROPYLTRIETHOXYSILANE AND ITS USE FOR A PAPER-BASED SENSOR.

Sens Biosensing Res 2015 Sep;5:37-41

Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS 39217.

2,4,6-Trinitrotoluene (TNT) forms a red-colored Meisenheimer complex with 3-aminopropyltrenthoxysilane (APTES) both in solution and on solid phase. The TNT-APTES complex is unique since it forms yellow-colored complexes with 2,4,6-trinitrophenol and 4-nitrophenol, and no complex with 2,4-dinitrotoluene. The absorption spectrum of TNT-APTES has two absorption bands at 530 and 650 nm, while APTES complexes with 2,4,6-trinitrophenol and 4-nitrophenol have absorption maxima at around 420 nm, and no absorption change for 2,4-dinitrotoluene. The TNT-APTES complex facilitates the exchange of the TNT-CH proton/deuteron with solvent molecules. The red color of TNT-APTES is immediately visible at 1 µM of TNT.
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http://dx.doi.org/10.1016/j.sbsr.2015.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566156PMC
September 2015

A revision of the Indian species of Oligosita Walker (Hymenoptera: Trichogrammatidae).

Zootaxa 2015 Jun 19;3973(3):401-24. Epub 2015 Jun 19.

Department of Zoology, Aligarh Muslim University, Aligarh 202002, India; Email: unknown.

The Indian species of the genus Oligosita Walker, 1851 (Hymenoptera: Trichogrammatidae) are revised. One new species, Oligosita aseta Begum & Anis, sp. nov., is described based on specimens collected from Kerala, India. A key to the 16 Indian species of the genus is also given.
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http://dx.doi.org/10.11646/zootaxa.3973.3.1DOI Listing
June 2015

Water-mediated proton conduction in a robust triazolyl phosphonate metal-organic framework with hydrophilic nanochannels.

Chemistry 2014 Jul 17;20(29):8862-6. Epub 2014 Jun 17.

Fakultät für Chemie und Mineralogie, Universität Leipzig, Johannisallee 29, 04103 Leipzig (Germany).

The development of water-mediated proton-conducting materials operating above 100 °C remains challenging because the extended structures of existing materials usually deteriorate at high temperatures. A new triazolyl phosphonate metal-organic framework (MOF) [La3L4(H2O)6]Cl⋅x H2O (1, L(2-) = 4-(4H-1,2,4-triazol-4-yl)phenyl phosphonate) with highly hydrophilic 1D channels was synthesized hydrothermally. Compound 1 is an example of a phosphonate MOF with large regular pores with 1.9 nm in diameter. It forms a water-stable, porous structure that can be reversibly hydrated and dehydrated. The proton-conducting properties of 1 were investigated by impedance spectroscopy. Magic-angle spinning (MAS) and pulse field gradient (PFG) NMR spectroscopies confirm the dynamic nature of the incorporated water molecules. The diffusivities, determined by PFG NMR and IR microscopy, were found to be close to that of liquid water. This porous framework accomplishes the challenges of water stability and proton conduction even at 110 °C. The conductivity in 1 is proposed to occur by the vehicle mechanism.
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http://dx.doi.org/10.1002/chem.201402886DOI Listing
July 2014

Diverse functional networks of Tbx3 in development and disease.

Wiley Interdiscip Rev Syst Biol Med 2012 May-Jun;4(3):273-83. Epub 2012 Feb 14.

Department of Genetics and Development, Columbia University Medical Center, New York, NY, USA.

The T-box transcription factor Tbx3 plays multiple roles in normal development and disease. In order to function in different tissues and on different target genes, Tbx3 binds transcription factors or other cofactors specific to temporal or spatial locations. Examining the development of the mammary gland, limbs, and heart as well as the biology of stem cells and cancer provides insights into the diverse and common functions that Tbx3 can perform. By either repressing or activating transcription of target genes in a context-dependent manner, Tbx3 is able to modulate differentiation of immature progenitor cells, control the rate of cell proliferation, and mediate cellular signaling pathways. Because the direct regulators of these cellular processes are highly context-dependent, it is essential that Tbx3 has the flexibility to regulate transcription of a large group of targets, but only become a active on a small cohort of them at any given time or place. Moreover, Tbx3 must be responsive to the variety of different upstream factors that are present in different tissues. Only by understanding the network of genes, proteins, and molecules with which Tbx3 interacts can we hope to understand the role that Tbx3 plays in normal development and how its aberrant expression can lead to disease. Because of its myriad functions in disparate developmental and disease contexts, Tbx3 is an ideal candidate for a systems-based approach to genetic function and interaction.
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http://dx.doi.org/10.1002/wsbm.1162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328642PMC
January 2013

Dynamic expression of Tbx2 and Tbx3 in developing mouse pancreas.

Gene Expr Patterns 2011 Dec 17;11(8):476-83. Epub 2011 Aug 17.

Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.

Tbx2 and Tbx3 are closely related members of the T-box family of transcription factors that are important regulators during normal development as well as major contributors to human developmental syndromes when mutated. Although there is evidence for the involvement of Tbx2 and Tbx3 in pancreatic cancer, so far there are no reports characterizing the normal expression pattern of these genes in the pancreas. In this study, we examined spatial and temporal expression of Tbx2 and Tbx3 in mouse pancreas during development and in the adult using in situ hybridization and immunohistochemistry. Our results show that Tbx2 and Tbx3 are both expressed in the pancreatic mesenchyme throughout development beginning at embryonic day (E) 9.5. In addition, Tbx2 is expressed in pancreatic vasculature during development and in epithelial-derived endocrine and ductal cells during late fetal stages, postnatal development and in adult pancreas. In contrast, Tbx3 is expressed in exocrine tissue in the postnatal and adult pancreas. Further our results demonstrate that Tbx2 and Tbx3 are expressed in tumor-derived endocrine and exocrine cell lines, respectively. These dynamic changes in the expression pattern of these transcription factors lay the foundation for investigation of potential roles in pancreas development.
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http://dx.doi.org/10.1016/j.gep.2011.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200443PMC
December 2011

Remission of type 1 diabetes after anti-CD3 antibody treatment and transplantation of embryonic pancreatic precursors.

Endocrinology 2009 Oct 9;150(10):4512-20. Epub 2009 Jul 9.

Department of Genetics and Development, HHSC 1402, Columbia University, New York, New York 10032, USA.

Type 1 diabetes (T1D) mellitus is characterized by progressive autoimmune destruction of insulin producing beta-cells of the pancreatic islets of Langerhans. Cure of the disease will require control of autoimmunity to halt the destruction of beta-cells in the pancreas and restoration of beta-cell mass. We have built on the success of preclinical and clinical trials of anti-CD3 antibody treatment in modulating the immune response of T1D by the induction of tolerance and combined this treatment, using the nonobese diabetic mouse model, with a transplantation approach using fetal pancreatic anlagen as a source of beta-cell precursor or progenitor cells. Here we report that transplantation of pancreatic anlagen into diabetic nonobese diabetic mice rendered tolerant to the autoimmune process by treatment with anti-CD3 antibody resulted in long-term recovery from diabetes with restored metabolic control. Using a green fluorescent protein marker that made it possible to unequivocally identify the cells derived from the transplanted tissue, we show that the transplanted anlagen cells migrate to the host pancreas and provide a major source of insulin leading to restoration of normal glucose tolerance. Our results contrast with other studies that showed restoration of endogenous islets after infusion of spleen cells in mice treated with Freund's complete adjuvant and suggest that pancreatic fetal tissue has a tropism for the pancreatic site. This study suggests a novel mechanism of beta-cell restoration by the migration of precursor cells or their progeny to the host pancreas and highlights the feasibility of using pancreatic precursors in combination with immune modulation as a treatment to effect long-term remission of T1D.
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http://dx.doi.org/10.1210/en.2009-0287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754682PMC
October 2009

Promotion of beta-cell differentiation in pancreatic precursor cells by adult islet cells.

Endocrinology 2009 Feb 9;150(2):570-9. Epub 2008 Oct 9.

Department of Immunobiology and Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.

It is thought that differentiation of beta-cell precursors into mature cells is largely autonomous, but under certain conditions differentiation can be modified by external factors. The factors that modify beta-cell differentiation have not been identified. In this study, we tested whether adult islet cells can affect the differentiation process in mouse and human pancreatic anlage cells. We assessed beta-cell proliferation and differentiation in mouse and human pancreatic anlage cells cocultured with adult islet cells or betaTC3 cells using cellular, molecular, and immunohistochemical methods. Differentiation of murine anlage cells into beta-cells was induced by mature islet cells. It was specific for beta-cells and not a general feature of endodermal derived cells. beta-Cell differentiation required cell-cell contact. The induced cells acquired features of mature beta-cells including increased expression of beta-cell transcription factors and surface expression of receptor for stromal cell-derived factor 1 and glucose transporter-2 (GLUT-2). They secreted insulin in response to glucose and could correct hyperglycemia in vivo when cotransplanted with vascular cells. Human pancreatic anlage cells responded in a similar manner and showed increased expression of pancreatic duodenal homeobox 1 and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A and increased production of proinsulin when cocultured with adult islets. We conclude that mature beta-cells can modify the differentiation of precursor cells and suggest a mechanism whereby changes in differentiation of beta-cells can be affected by other beta-cells.
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http://dx.doi.org/10.1210/en.2008-1009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646532PMC
February 2009
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