About
73
Publications
9,221
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
3,146
Citations
Current institution
VICBR
Publications
Publications (73)
Diffusion tensor imaging in the courtroom: Distinction between scientific specificity and legally admissible evidence 4477 van Velkinburgh JC, Herbst MD, Casper SM
Interest and uptake of science and medicine peer-reviewed literature by readers outside of a paper's topical subject, field or even discipline is ever-expanding. While the application of knowledge from one field or discipline to others can stimulate innovative solutions to problems facing modern society, it is also fraught with danger for misuse. I...
A relatively low scientific research output is not unique to Libya and unfortunately persists as compared to more economically developed countries.[1],[2] Recent data have revealed the very low-productivity rate of research from Libya, compared to other Arab and North African nations.[1],[3],[4] In 2003, Libya's hierarchal ranking among 20 Arabic c...
The blood glycoprotein von Willebrand factor (vWF) is involved in coagulopathy and inflammation; however, its role in the pathogenesis of acute liver failure, as suggested by its higher expression levels in such patients, remains unknown. In this study, vWF-knockout (KO) mice showed more severe carbon tetrachloride (CCl4)-induced liver injury than...
Understanding the publication output of a country’s biomedical research can provide information
for strengthening its policies, economy, and educational systems. Yet, this is the first bibliometric
study to date to analyze and provide an in-depth discussion of the biomedical research productivity
from Libyan academic institutions. The biomedical re...
Castration-resistant prostate cancer (CRPC) has greater intratumoral testosterone concentrations than similar tumors from eugonadal men; simple diffusion does not account for this observation. This study was undertaken to ascertain the androgen uptake kinetics, functional, and clinical relevance of de novo expression of the steroid hormone transpor...
Despite little evidence for the therapeutic benefits of a high-fiber diet for diverticulitis, it is commonly recommended as part of the clinical management. The ongoing uncertainty of the cause(s) of diverticulitis confounds attempts to determine the validity of this therapy. However, the features of a high-fiber diet represent a logical contradict...
The increased prevalence of obesity worldwide has been accompanied by increases in risk and rates of obesity-associated metabolic dysfunctions, such as insulin resistance. The chronic, low-grade inflammatory condition of obesity highlights the pathophysiological link between the immune system and the metabolic system, which has yet to be fully unde...
Background:
Auditory and vestibular disorders are prevalent sensory disabilities caused by genetic and environmental (noise, trauma, chemicals) factors that often damage mechanosensory hair cells of the inner ear. Development of treatments for inner ear disorders of hearing and balance relies on the use of animal models such as fish, amphibians, r...
Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, that play distinctive roles in the immune system. Development, differentiation, and function of thymocytes...
Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are m...
A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated gre...
Innate lymphoid cells (ILCs) are involved in the development of mucosal-associated lymphoid tissues and serve as a rapid and early source of the effector cytokines that are typically associated with the T helper cell subsets in response to pathogen-induced changes in the microenvironment. Recent research has implicated ILCs as potential contributin...
Innate lymphoid cells (ILCs) promptly initiate cytokine responses to pathogen exposure in the mucosa and mucosal-associated lymphoid tissues. ILCs were recently categorized as being of the lymphoid lineage and have been classified into three groups. ILCs play important roles in immunity against pathogens, and an anti-tumor immune-related function w...
Brucellosis is a global bacterial zoonosis responsible for high morbidity in humans and significant livestock economic losses. While brucellosis remains a public health concern worldwide, its global geographic distribution is variable, largely due to different management schemes; however, paucity of information renders the status of brucellosis unc...
Sepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical characterizations fail to identify those at greatest risk of progression and mortality.
The Community Acquir...
The functional interaction of progesterone receptor (PR) isoforms PRA and PRB regulates myometrial transition from the resting state to excitation-contraction to initiate parturition. However, the regulatory mechanisms responsible for maintenance and functional alteration of the PRA and PRB expression levels during human pregnancy and term labor, r...
Unlabelled:
Hepatitis B virus (HBV) alters the expression of host cellular genes to support its replication and survival and to promote the liver cell injury. However, the underlying mechanism remained incompletely understood. In this study, we investigated HBV-induced epigenetic changes in HepG2 cells by profiling the landscapes of the active his...
Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and wi...
Effects of chloroquine on the function of mDCs. (A) Monocytes were isolated from PBMCs of healthy blood donors and mDCs were induced by culturing for five days in the presence of GM-CSF (50 ng/mL) and recombinant human IL-4 (5 ng/mL). Then, mDCs were stimulated by 24 hours of exposure to LPS alone or together with chloroquine (10 mM). FCM was used...
Endocytosis-independent IL-23 production from DCs stimulated by HBcAg. (A) Monocytes were isolated from PBMCs of healthy blood donors and mDCs were induced by five days of culturing in the presence of GM-CSF (50 ng/mL) and recombinant human IL-4 (5 ng/mL). mDCs were then stimulated by HBcAg alone or in the presence of ammonium chloride (10 µM), chl...
IL-23 is indispensable for HBV antigen-stimulated IL-17 production and Th17 differentiation. The mDCs and naïve CD4+ T cells from PBMCs of healthy blood donors (1.5∶1) were cultured for seven days in the presence of HBsAg (2 µg/mL), IL-23-blocking antibody (500 µg/mL) or rhIL-23 (20 ng/mL). The concentration of secreted IL-17 in the supernatant was...
Expression of IL-17 receptor in liver tissue. (A) Protein expression of IL-17R detected by Western blotting of liver tissues from healthy controls and patients with hepatitis B. Error bars indicate SD. *P<0.05; **P<0.01. (B) The expression of IL-17R in liver tissues from CHB patients detected by immunohistochemical staining (magnification 100×). (C...
IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV) causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infe...
Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host respond...
Bacterial challenge experiments. (A) Survival curves for A/J and C57BL/6J mice following an intra-peritoneal infection with S. aureus (1×107 CFU/g) or E. coli (6×104 CFU/g). Principal Components Analysis plots of the samples in the dataset. Samples are colored by infection status and pathogen. (B) S. aureus infection by time after inoculation (n =...
Heat maps of genes contributing to the murine S. aureus classifier. (A) Genes within the top five factors contributing to the murine S. aureus classifier were identified and ranked by p-value after Bonferroni correction. A subset of genes (393 after removing duplicates) is depicted here, stratified by pathogen. (B) The same genes depicted in part (...
Sixteen murine factors independently associated with S. aureus infection projected onto healthy controls (left panel, black circles), animals with E. coli infection (middle panel, blue triangles), and animals with S. aureus infection (right panel, red “x”). The y-axis represents the factor score.
(DOC)
Venn diagram demonstrating the number of overlapping probes in each murine experimental group pairwise comparison. Probes were included that had significantly different levels of expression after Bonferroni correction.
(DOC)
Seventeen human factors independently associated with S. aureus BSI projected onto healthy controls (left panel, black circles), subjects with E. coli BSI (middle panel, blue triangles), and subjects with S. aureus BSI (right panel, red “x”). The y-axis represents the factor score.
(DOC)
Probes, ranked by p-value, that were differentially expressed (after Bonferroni correction) in mice with S. aureus infection vs. Healthy controls; S. aureus vs. E. coli infection; and E. coli vs. Healthy controls. Also presented is the average probe expression in each comparator group and the fold-change within the pairwise comparison.
(XLSX)
Probes and corresponding genes that were differentially expressed (after Bonferroni correction) in mice with MRSA vs. MSSA infection.
(DOC)
Venn diagram demonstrating the number of overlapping probes in each human experimental group pairwise comparison. Probes were included that had significantly different levels of expression after Bonferroni correction. No probes met this cutoff for the S. aureus vs. E. coli comparison.
(DOC)
Pathway analysis for the genes from pairwise comparisons in the mouse and human study. Top 50 ranked pathways from GeneGo MetaCore pathway analysis based upon p-value. Shaded text corresponds to pathways that are present in both the mouse and human response to the specified pathogen.
(XLSX)
A factor-based classifier distinguishes MRSA from MSSA infection in mice. An ROC curve is shown for this classification.
(DOC)
Heat map of genes contributing to the human S. aureus classifier. Genes within the top two factors contributing to the human S. aureus classifier were identified and ranked by p-value after Bonferroni correction. A subset of genes (86 after removing duplicates) is depicted here, stratified by pathogen.
(DOC)
Probes, ranked by p-value, that were differentially expressed (after Bonferroni correction) in humans with S. aureus infection vs. Healthy controls; S. aureus vs. E. coli infection; and E. coli vs. Healthy controls. Also presented is the average probe expression in each comparator group and the fold-change within the pairwise comparison.
(XLSX)
Genes in pathways common to murine and human responses to infection. Human genes are in the shaded cells. Murine genes are in the unshaded cells.
(XLSX)
A detailed description of microarray preparation.
(DOC)
The lymphocyte-derived helper T (Th) cells are critical regulators of the adaptive immune response and are associated with inflammatory disease. The most recently recognized Th-cell lineage, Th17, plays an important role in host defense against extracellular pathogens by secreting the proinflammatory cytokine, interleukin 17, and recruiting reactiv...
Background:
It is well known that both heat shock protein (HSP) and Toll-like receptor (TLR)3 agonist polyinosinic:polycytidylic acid (poly(I:C)) are capable of promoting the antigen-specific immune responses. In the current study, we assessed whether the anti-tumor effects of the HPV16E7(49-57)-based vaccine can be elevated by combined applicatio...
T helper 17 (Th17) cells are a newly identified subset of T helper cells that play important roles in host defense against extracellular bacteria, as well as in the pathogenesis of autoimmune disease. Research interest in these cells was piqued when hepatitis B virus (HBV)-infected patients were found to have significantly elevated Th17 cell freque...
Antimicrobial-resistant bacteria represent a major threat to human and animal health. We compared equine fecal samples (n=264) from 138 horses from hospital and nonhospital (livery stable and riding school) premises in North West England to determine the prevalence of Escherichia coli, Salmonella, and Campylobacter and rates of antimicrobial-resist...
Real-time PCR analysis of known target sites enriched by H3K4me3. ChIP assays were performed with Tregs and aTconv cells as described. DNA fragments binding to H3K4me3 histones were immunoprecipitated using antibodies directed against H3K4me3. The rabbit isotype immunoglobulin G (IgG) served as control, IgGa was a control for Treg and IgGb was a co...
Summary data for ChIP-seq regions enriched in H3K4me1 or H3K4me3.
(DOC)
H3K4me3 and H3K4me1modifications of signature genes and common genes in Treg and aTconv T cells. Shown are the following tracks (from top to bottom): Genes location; ChIP-seq tag counts for H3K4me3 or H3K4mel modifications in Treg cells; ChIP-seq tag counts for H3K4me3 or H3K4mel modifications in aTconv cells; UCSC Genes Based on Refseq; mammalian...
Real-time PCR analysis of known target sites after sequencing. ChIP assays were performed with Tregs and aTconv cells as described. DNA fragments binding to H3K4me1 histones were immunoprecipitated using antibodies directed against H3K4me1. The rabbit isotype immunoglobulin G (IgG) served as control, IgGa was a control for Treg and IgGb was a contr...
Primers for the amplification of H3K4me1 or H3k4me3 enriched regions.
(DOC)
Real-time PCR primers for the promoters of known genes.
(DOC)
Real-time PCR primers for mRNA expression of known genes.
(DOC)
Regulatory T cells (Treg) contribute to the crucial immunological processes of self-tolerance and immune homeostasis. Genomic mechanisms that regulate cell fate decisions leading to Treg or conventional T cells (Tconv) lineages and those underlying Treg function remain to be fully elucidated, especially at the histone modification level. We generat...
Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.
To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis.
PCT, CRP, and IL-6 were...
Monozygotic or 'identical' twins have been widely studied to dissect the relative contributions of genetics and environment in human diseases. In multiple sclerosis (MS), an autoimmune demyelinating disease and common cause of neurodegeneration and disability in young adults, disease discordance in monozygotic twins has been interpreted to indicate...
Aggressive diagnosis and treatment of patients presenting to the emergency department (ED) with septic shock has been shown to reduce mortality. To enhance the ability to intervene in patients with lesser illness severity, a better understanding of the natural history of the early progression from simple infection to more severe illness is needed....
Pdx-1 (pancreatic-duodenal homeobox-1), a MODY4 homeodomain transcription factor, serves as a master regulator in the pancreas because of its importance during
organogenesis and in adult islet insulin-producing β cell activity. Here, we show that KLF11, an SP/Krüppel-like (SP/KLF) transcription factor, mutated in French maturity onset diabetes of t...
Sepsis is caused by a heterogeneous group of infectious etiologies. Early diagnosis and the provision of appropriate antimicrobial therapy correlate with positive clinical outcomes. Current microbiological techniques are limited in their diagnostic capacities and timeliness. Multiplex PCR has the potential to rapidly identify bloodstream infections...
Generation II DNA sequencing has been widely heralded as a disruptive technology, generating tens of millions of random short sequences at efficiencies up to 20,000-fold greater than Generation I (Sanger) sequencing. This review addresses the technical specifications of the leading Generation II sequencing technologies and current applications of r...
High-throughput DNA sequencing has enabled systems biology to begin to address areas in health, agricultural and basic biological research. Concomitant with the opportunities is an absolute necessity to manage significant volumes of high-dimensional and inter-related data and analysis. Alpheus is an analysis pipeline, database and visualization sof...
Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobia...
Schizophrenia (SCZ) is a common, disabling mental illness with high heritability but complex, poorly understood genetic etiology. As the first phase of a genomic convergence analysis of SCZ, we generated 16.7 billion nucleotides of short read, shotgun sequences of cDNA from post-mortem cerebellar cortices of 14 patients and six, matched controls. A...
This chapter summarizes our studies on the three toll-like receptor pathways, namely TLR4, TLR2, and TLR3, induced by lipopolysaccharides (LPS), peptidoglycan (PGN), and double-stranded RNA (dsRNA) in antigen presenting cells (APC). The particular emphasis is on the activation of human innate immune responses via cytokine and chemokine production....
PDX-1 regulates transcription of genes involved in islet beta cell function and pancreas development. Islet-specific expression is controlled by 5'-flanking sequences from base pair (bp) -2917 to -1918 in transgenic experiments, which encompasses both conserved (i.e. Area I (bp -2761/-2457), Area II (bp -2153/-1923)) and non-conserved pdx-1 sequenc...
The pancreas and duodenum homeobox protein 1 (PDX-1) homeodomain-containing transcription factor affects both pancreatic endocrine cell development and adult islet beta-cell function. Cell-type-specific expression is controlled by sequences 5' flanking the pdx-1 gene transcription start site. One principal control region is located roughly between...
Salmonella enterica serovar Typhimurium is resistant to the action of bile salts, and resistance to bile is enhanced in strains in which the
PhoP-PhoQ (PhoPQ) two-component regulatory system has been activated. To identify genes necessary for bile resistance, MudJ
transposon mutagenesis was performed on a strain containing a phoP mutation that resu...
The two-component regulatory system PmrA-PmrB confers resistance ofSalmonella spp. to cationic antimicrobial peptides (AP) such as polymyxin (PM), bactericidal/permeability-increasing protein, and azurocidin.
This resistance occurs by transcriptional activation of two loci termed pmrE and pmrHFIJKLM. BothpmrE and pmrHFIJKLM produce products require...
As enteric pathogens, Salmonella spp. are resistant to the actions of bile. Salmonella typhimurium and Salmonella typhi strains were examined to better define the bile resistance phenotype. The MICs of bile for wild-type S. typhimurium and S. typhi were 18 and 12%, respectively, and pretreatment of log-phase S. typhimurium with 15% bile dramaticall...
Johne’s Disease (JD), a ruminant infectious disease caused by Mycobacterium avium subspecies paratuberculosis (MAP), is characterized by a long latent period followed by an aggressive acute phase in which the animal experiences diarrhea and extreme wasting. The absence of symptoms and low levels of bacterial shedding during the latent period make e...
