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The Ali Principles Of The Law Of Family Dissolution: Addressing Inequality Through Functional Regulation, Linda C. Mcclain, Douglas Nejamie

Faculty Scholarship

As part of a volume commemorating the American Law Institute on its centennial, this Essay reflects on the ALI Principles of the Law of Family Dissolution. We show how the Principles’ drafters intervened in cutting-edge issues at a time of flux in family law in ways that elaborated a progressive agenda that would continue to gain traction in the years after the Principles’ publication in 2000. Beginning from the assumption that family law should reflect how people actually live, the drafters developed a functional, rather than formal, approach to legal regulation. Such an approach, they believed, could vindicate commitments to …

Genetic Variation In Environmental Enteropathy And Stunting In Zambian Children: A Pilot Genome Wide Association Study Using The H3africa Chip, Monica N. Mweetwa, Talin Haritunians, Shishir Dube, Kanta Chandwe, Beatrice Amadi, Kanekwa Zyambo, Ta-Chiang Liu, Dermot Mcgovern, Paul Kelly

2020-Current year OA Pubs

PURPOSE: Stunting is known to be heavily influenced by environmental factors, so the genetic contribution has received little attention. Here we report an exploration of genetic influences in stunted Zambian children with environmental enteropathy.

METHOD: Children with stunting (LAZ < -2) were enrolled and given nutritional therapy. Those that were non-responsive to therapy were designated as cases, and children with good growth (LAZ > -1) from the same community as controls. Blood and stool samples were taken to measure biomarkers of intestinal inflammation, epithelial damage, and microbial translocation. Single nucleotide polymorphism array genotyping was carried out on saliva samples using the H3Africa consortium array.

RESULTS: Genome wide associations were analysed in 117 cases and 41 controls. While no significant associations with stunting were observed at …

Cytosolic Epcam Cooperates With H-Ras To Regulate Epithelial To Mesenchymal Transition Through Zeb1, Fatma A. Omar, Taylor C. Brown, William E. Gillanders, Timothy P. Fleming, Michael A. Smith, Ross M. Bremner, Narendra V. Sankpal

2020-Current year OA Pubs

Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that can transform normal cells into tumor cells. In this study, we investigated the role of altered localization of epithelial cell adhesion molecule (EpCAM) in Ras-expressing cells. Analysis of microarray data demonstrated that Ras expression induced EpCAM expression in normal breast epithelial cells. Fluorescent and confocal microscopy showed that H-Ras mediated transformation also promoted epithelial-to-mesenchymal transition (EMT) together with EpCAM. To consistently localize EpCAM in the cytosol, …

Evolution And Implementation Of Radiographic Response Criteria In Neuro-Oncology, Divya Ramakrishnan, Marc Von Reppert, Mark Krycia, Matthew Sala, Sabine Mueller, Sanjay Aneja, Ali Nabavizadeh, Norbert Galldiks, Philipp Lohmann, Cyrus Raji, Ichiro Ikuta, Fatima Memon, Brent D Weinberg, Mariam S Aboian

2020-Current year OA Pubs

Radiographic response assessment in neuro-oncology is critical in clinical practice and trials. Conventional criteria, such as the MacDonald and response assessment in neuro-oncology (RANO) criteria, rely on bidimensional (2D) measurements of a single tumor cross-section. Although RANO criteria are established for response assessment in clinical trials, there is a critical need to address the complexity of brain tumor treatment response with multiple new approaches being proposed. These include volumetric analysis of tumor compartments, structured MRI reporting systems like the Brain Tumor Reporting and Data System, and standardized approaches to advanced imaging techniques to distinguish tumor response from treatment effects. In …

Genetics Of Vegetarianism: A Genome-Wide Association Study, Nabeel R. Yaseen, Catriona L. K. Barnes, Lingwei Sun, Akiko Takeda, John P. Rice

2020-Current year OA Pubs

A substantial body of evidence points to the heritability of dietary preferences. While vegetarianism has been practiced for millennia in various societies, its practitioners remain a small minority of people worldwide, and the role of genetics in choosing a vegetarian diet is not well understood. Dietary choices involve an interplay between the physiologic effects of dietary items, their metabolism, and taste perception, all of which are strongly influenced by genetics. In this study, we used a genome-wide association study (GWAS) to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, we identified …

Risk And Protection Of Different Rare Protein-Coding Variants Of Complement Component C4a In Age-Related Macular Degeneration, Johanna M Seddon, Dikha De, William Casazza, Shun-Yun Cheng, Claudio Punzo, Mark Daly, Danlei Zhou, Samantha L Coss, John P Atkinson, Chack-Yung Yu

2020-Current year OA Pubs

No abstract provided.

The Association Of Radiation Dose With Overall Survival For Patients Treated With Prostate Stereotactic Body Radiation Therapy, Michael R. Waters, Neal Andruska, Benjamin W. Fischer-Valuck, Temitope Agabalogun, Randall J. Brenneman, Hiram Gay, Jeff M. Michalski, Brian Baumann

2020-Current year OA Pubs

Introduction Stereotactic body radiation therapy (SBRT) for prostate adenocarcinoma (PCa) has demonstrated excellent biochemical recurrence-free survival, with studies showing improved BRFS with higher-dose SBRT. However, current studies have been underpowered to evaluate the relationship of SBRT dose to overall survival (OS). In this retrospective study using the National Cancer Database (NCDB), we hypothesize that, given the low alpha/beta ratio of PCa, a relatively small increase in the dose-per-fraction would be associated with improved survival outcomes for intermediate-risk PCa (IR-PCa) comparing 36.25 Gy/5 fx [biologically equivalent dose (BEDα/β = 1.5 = 211.46 Gy vs. 35 Gy (BED1.5 = 198.33 Gy)]. Materials …

Open-Source Statistical And Data Processing Tools For Wide-Field Optical Imaging Data In Mice, Lindsey M. Brier, Joseph P. Culver

2020-Current year OA Pubs

SIGNIFICANCE: Wide-field optical imaging (WOI) can produce concurrent hemodynamic and cell-specific calcium recordings across the entire cerebral cortex in animal models. There have been multiple studies using WOI to image mouse models with various environmental or genetic manipulations to understand various diseases. Despite the utility of pursuing mouse WOI alongside human functional magnetic resonance imaging (fMRI), and the multitude of analysis toolboxes in the fMRI literature, there is not an available open-source, user-friendly data processing and statistical analysis toolbox for WOI data.

AIM: To assemble a MATLAB toolbox for processing WOI data, as described and adapted to combine techniques from …

Barriers To And Solutions For Representative Inclusion Across The Lifespan And In Life Course Research: The Need For Structural Competency Highlighted By The Covid-19 Pandemic, Madison N Lecroy, Ebony B Carter, Sarah S Farabi, Dominic N Reeds, Et Al.

2020-Current year OA Pubs

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating …

How Penalizing Substance Use In Pregnancy Affects Treatment And Research: A Qualitative Examination Of Researchers' Perspectives, Seema K Shah, Leishla Perez-Cardona, Khrystyna Helner, Suena H Massey, Ashish Premkumar, Renee Edwards, Elizabeth S Norton, Cynthia E Rogers, Emily S Miller, Christopher D Smyser, Matthew M Davis, Lauren S Wakschlag

2020-Current year OA Pubs

INTRODUCTION: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood.

METHODS: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis.

RESULTS: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal …

Microbiome-Targeting Therapies In The Neonatal Intensive Care Unit: Safety And Efficacy, Anna Deveaux, Jian Ryou, Gautam Dantas, Barbara B Warner, Phillip I Tarr

2020-Current year OA Pubs

Microbiome-targeting therapies have received great attention as approaches to prevent disease in infants born preterm, but their safety and efficacy remain uncertain. Here we summarize the existing literature, focusing on recent meta-analyses and systematic reviews that evaluate the performance of probiotics, prebiotics, and/or synbiotics in clinical trials and studies, emphasizing interventions for which the primary or secondary outcomes were prevention of necrotizing enterocolitis, late-onset sepsis, feeding intolerance, and/or reduction in hospitalization length or all-cause mortality. Current evidence suggests that probiotics and prebiotics are largely safe but conclusions regarding their effectiveness in the neonatal intensive care unit have been mixed. To …

Characterization Of Cerebrospinal Fluid (Csf) Microbiota At The Time Of Initial Surgical Intervention For Children With Hydrocephalus, Shailly Pandey, Kathryn B. Whitlock, Matthew R. Test, Paul Hodor, Christopher E. Pope, David D. Limbrick, Patrick J. Mcdonald, Jason S. Hauptman, Lucas R. Hoffman, Tamara D. Simon, Cerebrospinal Fluid Microbiota In Shunts (Climb) Study Group

2020-Current year OA Pubs

OBJECTIVE: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention.

STUDY DESIGN: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at -70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in …

Structural And Biophysical Characterization Of The Secreted, Β-Helical Adhesin Etpa Of Enterotoxigenic Escherichia Coli, Clifford Manyo Ntui, James M. Fleckenstein, Wolf-Dieter Schubert

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) is a diarrhoeal pathogen associated with high morbidity and mortality especially among young children in developing countries. At present, there is no vaccine for ETEC. One candidate vaccine antigen, EtpA, is a conserved secreted adhesin that binds to the tips of flagellae to bridge ETEC to host intestinal glycans. EtpA is exported through a Gram-negative, two-partner secretion system (TPSS, type Vb) comprised of the secreted EtpA passenger (TpsA) protein and EtpB (TpsB) transporter that is integrated into the outer bacterial membrane. TpsA proteins share a conserved, N-terminal TPS domain followed by an extensive C-terminal domain with …

Phosphorus Speciation And Heavy Metal Levels In Ogun River Sediments At Different Anthropogenic Locations In Abeokuta, Ogun State, Olayinka Oluwafunmilayo Olasunbo, Opatoyinbo Oluwabamise Esther, Olujimi Olarenwaju Olusoji, Azeez Jamiu Oladipupo, Oyebanji Adedayo Olamide

Applied Environmental Research

Phosphorus (P) is an essential nutrient for phytoplankton growth in water bodies and an important element in biochemical processes. Also, excessive P in river causes eutrophication which endangers aquatic organisms while sediment acts as sink for inorganic and organic pollutants and nutrients. To assess the availability of P and heavy metals (HMs) in Ogun River, surface sediment samples were collected at twelve anthropogenic sites for three months. The surface sediment samples were sequentially extracted to determine five phosphorus fractions [loosely-sorbed P (LS-P), iron-bound P (Fe-P), authigenic apatite, biogenic apatite and CaCO3-bound P (CFA-P), detrital apatite (Det-P) and other inorganic P …

Removal Of Diclofenac In Wastewater By Activated Sludge In Batch And Moving-Bed Biofilm Reactor Experiments, Keletso Chakalisa, Piriyakorn Injai, Kullapa Chanawanno, Panaya Kotchaplai, Pumis Thuptimdang

Applied Environmental Research

This study aimed to determine the diclofenac removal in wastewater by sludge taken from an operating wastewater treatment facility. Laboratory experiments were conducted in two parts: batch and moving-bed biofilm reactor (MBBR) experiments. Results from batch experiments showed that 0.1–2 mg L-1 of diclofenac could be removed more than 80% within 72 h, and the removal efficiency reduced to less than 60% for higher concentrations. The increase in the removal rate from 0.00058 to 0.16527 mg L-1 h-1 was observed when the initial diclofenac concentration increased from 0.1 to 10 mg L-1, respectively. The average first-order rate constants of 24-h …

The Role Of Bacteria And Factors Affecting The Decomposition Of Pollutants In The Biofilter Reactor: A Review, Muliyadi Muliyadi, Purwanto Purwanto, Sri Sumiyati, Sudarno Sudarno, Budiyono Budiyono, Budi Warsito, Hadiyanto Hadiyanto

Applied Environmental Research

The findings showed that several types of bacteria can help biodegrade organic pollutants, such as Comamonadacea, which can biodegrade volatile fatty acids and aromatic compounds. Proteobacteria, Bacteroidetes, and Actinobacteria can biodegrade ammonium. Burkholderiales can biodegrade ferric ions and hydrogen. Comamonas testosteroni is able to biodegrade nitrates. Pseudomonas taiwanensis, Acinetobacter guillouiae, and Klebsiella pneumoniae can reduce copper, chromium and zinc levels. Azolla biomass reduces strontium. Rhodospirillum sp. can biodegrade cadmium, mercury, lead, and nickel. Gallionella ferruginea and Leptothrix sp. can biodegrade arsenic and manganese. Gracilaria sp. can biodegrade aluminum, chromium, and zinc. Desulfovibrio sp. can …

Nonalcoholic Fatty Liver Disease Is A Risk Factor For Thiopurine Hepatotoxicity In Crohn's Disease, Alvin T George, Matthew Glover, Quazim Alayo, Maria Zulfiqar, Daniel R Ludwig, Matthew A Ciorba, Scott Mchenry, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

METHODS: In this prospective cohort analysis, CD patients at a single center were recruited 6/2017-5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a …

Efficacy Of Laser Interstitial Thermal Therapy For Biopsy-Proven Radiation Necrosis In Radiographically Recurrent Brain Metastases, Michael Chan, Albert H Kim, Eric Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.

METHODS: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.

RESULTS: Ninety patients met …

Necrotic Cardiac Myocytes Skew Macrophage Polarization Towards A Classically Activated Phenotype, Wenlong Jiang, Luigi Adamo, Kenji Lim, Scot J Matkovich, Sarah Evans, Cibele Rocha-Resende, Douglas L. Mann

2020-Current year OA Pubs

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide …

The History And Organization Of The Workshop On Population And Speciation Genomics, Julia M I Barth, Scott A Handley, Daniel Kintzl, Guy Leonard, Milan Malinsky, Michael Matschiner, Britta S Meyer, Walter Salzburger, Jan Stefka, Emiliano Trucchi

2020-Current year OA Pubs

With the advent of high-throughput genome sequencing, bioinformatics training has become essential for research in evolutionary biology and related fields. However, individual research groups are often not in the position to teach students about the most up-to-date methodology in the field. To fill this gap, extended bioinformatics courses have been developed by various institutions and provide intense training over the course of two or more weeks. Here, we describe our experience with the organization of a course in one of the longest-running extended bioinformatics series of workshops, the Evomics Workshop on Population and Speciation Genomics that takes place biennially in …

Apolipoprotein E Genetic Variation, Atherogenic Index And Cardiovascular Disease Risk Assessment In An African Population: An Analysis Of Hiv And Malaria Patients In Ghana, Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to …

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Armin Ghobadi, Amanda Cashen, Et Al.

2020-Current year OA Pubs

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Small Molecule Inhibiting Microglial Nitric Oxide Release Could Become A Potential Treatment For Neuroinflammation, Philipp Jordan, Amanda Costa, Et Al.

2020-Current year OA Pubs

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or …

Hydrogen Deuterium Exchange And Other Mass Spectrometry-Based Approaches For Epitope Mapping, Prashant N Jethva, Michael L Gross

2020-Current year OA Pubs

Antigen-antibody interactions are a fundamental subset of protein-protein interactions responsible for the "survival of the fittest". Determining the interacting interface of the antigen, called an epitope, and that on the antibody, called a paratope, is crucial to antibody development. Because each antigen presents multiple epitopes (unique footprints), sophisticated approaches are required to determine the target region for a given antibody. Although X-ray crystallography, Cryo-EM, and nuclear magnetic resonance can provide atomic details of an epitope, they are often laborious, poor in throughput, and insensitive. Mass spectrometry-based approaches offer rapid turnaround, intermediate structural resolution, and virtually no size limit for the …

Relationship Between Baseline Plasma P-Tau181 And Longitudinal Changes In Cognition And Structural Brain Measures In A Cohort Of Cognitively Unimpaired Older Adults, Marcos V Pais, Chia-Ling Kuo, Beau M Ances, Julie Loebach Wetherell, Eric J Lenze, Breno S Diniz

2020-Current year OA Pubs

INTRODUCTION: Preclinical Alzheimer's disease (AD) affects a significant proportion of cognitively unimpaired (CU) older adults. Currently, blood-based biomarkers detect very early changes in the AD continuum with great accuracy.

METHODS: We measured baseline plasma phosphorylated tau (p-tau)181 using electrochemiluminescence (ECL)-based assay (MesoScale Discovery) in 533 CU older adults. Follow-up lasted up to 18 months. Cognitive performance assessment included memory and cognitive control. Structural brain measures included cortical thickness, which includes the AD magnetic resonance imaging (AD MRI) signature, and hippocampal volume.

RESULTS: In this cohort of CU older adults, baseline plasma p-tau181 levels were not associated with short-term changes in …

Severe Central Nervous System Demyelination In Sanfilippo Disease, Mahsa Taherzadeh, Erjun Zhang, Irene Londono, Benjamin De Leener, Sophie Wang, Jonathan D Cooper, Timothy E Kennedy, Carlos R Morales, Zesheng Chen, Gregory A Lodygensky, Alexey V Pshezhetsky

2020-Current year OA Pubs

INTRODUCTION: Chronic progressive neuroinflammation is a hallmark of neurological lysosomal storage diseases, including mucopolysaccharidosis III (MPS III or Sanfilippo disease). Since neuroinflammation is linked to white matter tract pathology, we analyzed axonal myelination and white matter density in the mouse model of MPS IIIC

METHODS: Brain and spinal cord tissues of human MPS III patients, 6-month-old

RESULTS: Analyses of CC and spinal cord tissues by immunohistochemistry revealed substantially reduced levels of myelin-associated proteins including Myelin Basic Protein, Myelin Associated Glycoprotein, and Myelin Oligodendrocyte Glycoprotein. Furthermore, ultrastructural analyses revealed disruption of myelin sheath organization and reduced myelin thickness in the brains …

Defining Solute Carrier Transporter Signatures Of Murine Immune Cell Subsets, Tania Løve Aaes, Javier Burgoa Cardás, Kodi S Ravichandran

2020-Current year OA Pubs

Solute carrier (SLC) transporters are membrane-bound proteins that facilitate nutrient transport, and the movement across cellular membranes of various substrates ranging from ions to amino acids, metabolites and drugs. Recently, SLCs have gained increased attention due to their functional linkage to innate immunological processes such as the clearance of dead cells and anti-microbial defense. Further, the druggable nature of these transporters provides unique opportunities for improving outcomes in different immunological diseases. Although the SLCs represent the largest group of transporters and are often identified as significant hits in omics data sets, their role in immunology has been insufficiently explored. This …

The Actin-Bundling Protein, Pls3, Is Part Of The Mechanoresponsive Machinery That Regulates Osteoblast Mineralization, Samantha M Chin, Carmela Unnold-Cofre, Teri Naismith, Silvia Jansen

2020-Current year OA Pubs

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During …