Ewen McLean - Profile on Academia.edu (original) (raw)

Papers by Ewen McLean

Mitochondrial STRs

CRC Press eBooks, May 31, 2023

Structure of DNA and Why We Use DNA in Forensic Science

CRC Press eBooks, May 31, 2023

How STRs Are Analyzed in a Forensic Laboratory

CRC Press eBooks, May 31, 2023

Forensic Serology

CRC Press eBooks, May 31, 2023

Sex Determination by STR

CRC Press eBooks, May 31, 2023

A Simple Guide for Understanding the Value of DNA Results

CRC Press eBooks, May 31, 2023

How Cells Divide and Why It Is Important to Know the Process

CRC Press eBooks, May 31, 2023

Capillary Gel Electrophoresis to Analyze DNA in a Crime Lab

CRC Press eBooks, May 31, 2023

Y-STR and Paternal Ancestry

CRC Press eBooks, May 31, 2023

How to Extract DNA from a Biological Sample at a Crime Scene

CRC Press eBooks, May 31, 2023

Forensic DNA Analyses Made Simple

Complexities of Sex Determination

CRC Press eBooks, May 31, 2023

What Are Autosomal Dominant, Recessive, and X-Linked Dominant and Recessive Traits?

CRC Press eBooks, May 31, 2023

The Combined DNA Index System (CODIS)

CRC Press eBooks, May 31, 2023

The Cell

CRC Press eBooks, May 31, 2023

Libyan Journal of Medicine, 2021

Zika virus (ZIKV) is a serious public health concern that may lead to neurological disorders in a... more Zika virus (ZIKV) is a serious public health concern that may lead to neurological disorders in affected individuals. The virus can be transmitted from an infected mother to her fetus, via mosquitoes, or sexually. ZIKV infections are associated with increased risk for Guillain-Barré syndrome (GBS) and congenital microcephaly in newborns infected prenatally. Dysregulations of intracellular microRNAs (miRNAs) in infected neurons have been linked to different neurological diseases. To determine the potential role of miRNAs in ZIKV infection we developed a chronically infected neuroblastoma cell line and carried out differential expression analyses of miRNAs with reference to an uninfected neuroblastoma cell line. A total of 3192miRNAs were evaluated and 389 were found to be upregulated < 2-fold and 1291 were downregulated < 2-fold. In particular, we determined that hsa-mir-431-5p, hsa-mir-3687, hsamir-4655-5p, hsa-mir-6071, hsa-mir-762, hsa-mir-5787, and hsa-mir-6825-3p were significantly downregulated, ranging from-5711 to-660-fold whereas, has-mir-4315, hsa-mir-5681b, hsamir-6511a-3p, hsa-mir-1264, hsa-mir-4418, hsa-mir-4497, hsa-mir-4485-3p, hsa-mir-4715-3p, hsamir-4433-3p, hsa-mir-4708-3p, hsa-mir-1973 and hsa-mir-564 were upregulated, ranging from 20-0.8-fold. We carried out target gene alignment of these miRNAs with the ZIKV genome to predict the function of the differentially expressed miRNAs and their potential impact on ZIKV pathogenesis. These miRNAs might prove useful as novel diagnostic or therapeutic markers and targets for further research on ZIKV infection and neuronal injury resulting from ZIKV infectivity in developing fetal brain neurons.

Zika, miRNAs, and microcephaly genes

Elsevier eBooks, 2021

Abstract An increasingly diverse literature has established that microRNAs (miRNAs) are expansive... more Abstract An increasingly diverse literature has established that microRNAs (miRNAs) are expansively engaged in typical brain development, function, and dysfunction. They are comprehensively involved in the genesis of the hippocampus, frontal cortex, cerebellum, midbrain, and other nervous tissues. miRNA dysfunction has been demonstrated to lead to nerve-related pathologies. Deciphering the roles of miRNAs in response to diseases, such as Zika, provides an approach to discover key pathways connected to illness, including the role of essential genes that may be silenced, repressed, activated, and/or enhanced.

EBioMedicine, Aug 1, 2016

Background: Epidemiological data strongly suggest that microcephaly cases in Brazil are associate... more Background: Epidemiological data strongly suggest that microcephaly cases in Brazil are associated with the ongoing epidemic of Zika virus (ZIKV). In order to further solidify the possible link, we investigated the infectivity of ZIKV using various neuroblastoma (NB) cell lines. Methods: Six undifferentiated, two terminally differentiated and two retinoic acid (RA)-induced, partially differentiated cell lines were exposed to ZIKV strain PRVABC59, which is genetically similar to the French Polynesia strain, with 97-100% genetic homology to the current ZIKV strain found in Brazil. All infections were confirmed by real-time PCR (RT-qPCR), immunofluorescence assay (IFA) probing with anti-flavivirus E antibody, and evaluation of cytopathic effects. Findings: ZIKV infected all six undifferentiated NB cell lines. In five out of six NB cell lines, between 90 and 70% cells were positive by IFA whereas for one cell line, CCL-127,~80% of cells were positive for ZIKV as determined by IFA but showed persistent infection. Two differentiated cell lines, JFEN and T-268, were highly resistant to ZIKV with b1% of the cells being susceptible, as determined by IFA and confirmed by qRT-PCR. Two retinoic acid (RA)-induced NB partially differentiated cell lines showed no difference in permissiveness as compared to their undifferentiated mother cell lines. Interpretation: These findings strengthen the reported association between high incidences of microcephaly and ZIKV infection in newborns in Brazil. Our results suggest that the undifferentiated neurons are highly permissive to ZIKV infection, as one would expect during the early stages of neurogenesis in fetal brains; whereas differentiated neurons, representative of adult brain neurons, are relatively resistant to the virus, which explains the rare occurrence of neurological complications in adults infected with ZIKV. Our studies confirm the neurotropism of the ZIKV strain closely related to the current epidemic in Latin America.

Infectivity of Human Olfactory Neurons to SARS-CoV-2: A Link to Anosmia

Oman Medical Journal, Sep 30, 2021

Objectives: We sought to determine whether SARS-CoV-2 infections are associated with anosmia and ... more Objectives: We sought to determine whether SARS-CoV-2 infections are associated with anosmia and if this virus infects other neuronal cells. We utilized male and female olfactory neuronal cell lines and other olfactory cell lines to determine the viral targets. Methods: We used four undifferentiated and two partially differentiated human developing neuronal cell lines. Infectivity was confirmed by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), immunofluorescence assay (IFA) probing with anti-SARS-CoV-2 antibody, evaluation of cytopathic effects, and neurite formation. We induced partial differentiation of all cell lines (since both olfactory cell lines were terminally differentiated) with retinoic acid (RA) to determine whether differentiation was a factor in viral permissiveness. The expression of serine protease, transmembrane serine protease 2 (TMPRSS2), and angiotensin-converting enzyme II (ACE2) receptors were examined by RT-qPCR and IFA to determine the mechanism of viral entry. Results: Four to five days after exposure, both olfactory cell lines exhibited morphological evidence of infection; IFA analyses indicated that ~30% of the neurons were SARS-CoV-2 positive. At two weeks, 70–80% were positive for SARS-CoV-2 antigens. The partially differentiated (CRL-2266 and CRL-2267) and undifferentiated cell lines (CRL-2142, CRL-2149, CRL-127, and CDL-2271) were essentially non-permissive. After RA treatment, only CRL-127 exhibited slight permissiveness (RT-qPCR). The TMPRSS2 receptor showed high expression in olfactory neurons, but low expression in RA treated CRL-127. ACE2 exhibited high expression in olfactory neurons, whereas other cell lines showed low expression, including RA-treated cell lines. ACE2 expression slightly increased in CRL-127 post RA-treatment. Conclusions: Our studies confirm neurotropism of SARS-CoV-2 to olfactory neurons with viral entry likely mediated by TMPRSS2/ACE2. Other neuronal cell lines were non-permissive. Our results established that the nerve cells were infected regardless of male or female origin and strengthened the reported association of COVID-19 with loss of smell in infected individuals.

Libyan Journal of Medicine, 2017

Background Zika virus (ZIKV) has been associated with a variety of neuropathologies, including mi... more Background Zika virus (ZIKV) has been associated with a variety of neuropathologies, including microcephaly. We hypothesize that ZIKV genes activate host microRNAs (miRNAs) causing dysfunctional development of human fetal brains. Objectives/methods A bioinformatics search for miRNA genome-wide binding sites in the prototypic ZIKV (strain MR766) was undertaken to hunt for miRNAs with significant similarities with MCPH genetic sequences responsible for inducing MCHP in human fetal brains. Results Six ZIKV miRNAs were found to share mutual homology with 12 MCPH genetic sequences responsible for inducing MCPH. Noteworthy was miR-1304, which expressed 100% identity to six different MCPH genes. Conclusions We suggest that following infection of fetal neurons ZIKV may modulate the action of various miRNAs, and miR-1304 in particular, resulting in microcephaly.

Mitochondrial STRs

CRC Press eBooks, May 31, 2023

Structure of DNA and Why We Use DNA in Forensic Science

CRC Press eBooks, May 31, 2023

How STRs Are Analyzed in a Forensic Laboratory

CRC Press eBooks, May 31, 2023

Forensic Serology

CRC Press eBooks, May 31, 2023

Sex Determination by STR

CRC Press eBooks, May 31, 2023

A Simple Guide for Understanding the Value of DNA Results

CRC Press eBooks, May 31, 2023

How Cells Divide and Why It Is Important to Know the Process

CRC Press eBooks, May 31, 2023

Capillary Gel Electrophoresis to Analyze DNA in a Crime Lab

CRC Press eBooks, May 31, 2023

Y-STR and Paternal Ancestry

CRC Press eBooks, May 31, 2023

How to Extract DNA from a Biological Sample at a Crime Scene

CRC Press eBooks, May 31, 2023

Forensic DNA Analyses Made Simple

Complexities of Sex Determination

CRC Press eBooks, May 31, 2023

What Are Autosomal Dominant, Recessive, and X-Linked Dominant and Recessive Traits?

CRC Press eBooks, May 31, 2023

The Combined DNA Index System (CODIS)

CRC Press eBooks, May 31, 2023

The Cell

CRC Press eBooks, May 31, 2023

Libyan Journal of Medicine, 2021

Zika virus (ZIKV) is a serious public health concern that may lead to neurological disorders in a... more Zika virus (ZIKV) is a serious public health concern that may lead to neurological disorders in affected individuals. The virus can be transmitted from an infected mother to her fetus, via mosquitoes, or sexually. ZIKV infections are associated with increased risk for Guillain-Barré syndrome (GBS) and congenital microcephaly in newborns infected prenatally. Dysregulations of intracellular microRNAs (miRNAs) in infected neurons have been linked to different neurological diseases. To determine the potential role of miRNAs in ZIKV infection we developed a chronically infected neuroblastoma cell line and carried out differential expression analyses of miRNAs with reference to an uninfected neuroblastoma cell line. A total of 3192miRNAs were evaluated and 389 were found to be upregulated < 2-fold and 1291 were downregulated < 2-fold. In particular, we determined that hsa-mir-431-5p, hsa-mir-3687, hsamir-4655-5p, hsa-mir-6071, hsa-mir-762, hsa-mir-5787, and hsa-mir-6825-3p were significantly downregulated, ranging from-5711 to-660-fold whereas, has-mir-4315, hsa-mir-5681b, hsamir-6511a-3p, hsa-mir-1264, hsa-mir-4418, hsa-mir-4497, hsa-mir-4485-3p, hsa-mir-4715-3p, hsamir-4433-3p, hsa-mir-4708-3p, hsa-mir-1973 and hsa-mir-564 were upregulated, ranging from 20-0.8-fold. We carried out target gene alignment of these miRNAs with the ZIKV genome to predict the function of the differentially expressed miRNAs and their potential impact on ZIKV pathogenesis. These miRNAs might prove useful as novel diagnostic or therapeutic markers and targets for further research on ZIKV infection and neuronal injury resulting from ZIKV infectivity in developing fetal brain neurons.

Zika, miRNAs, and microcephaly genes

Elsevier eBooks, 2021

Abstract An increasingly diverse literature has established that microRNAs (miRNAs) are expansive... more Abstract An increasingly diverse literature has established that microRNAs (miRNAs) are expansively engaged in typical brain development, function, and dysfunction. They are comprehensively involved in the genesis of the hippocampus, frontal cortex, cerebellum, midbrain, and other nervous tissues. miRNA dysfunction has been demonstrated to lead to nerve-related pathologies. Deciphering the roles of miRNAs in response to diseases, such as Zika, provides an approach to discover key pathways connected to illness, including the role of essential genes that may be silenced, repressed, activated, and/or enhanced.

EBioMedicine, Aug 1, 2016

Background: Epidemiological data strongly suggest that microcephaly cases in Brazil are associate... more Background: Epidemiological data strongly suggest that microcephaly cases in Brazil are associated with the ongoing epidemic of Zika virus (ZIKV). In order to further solidify the possible link, we investigated the infectivity of ZIKV using various neuroblastoma (NB) cell lines. Methods: Six undifferentiated, two terminally differentiated and two retinoic acid (RA)-induced, partially differentiated cell lines were exposed to ZIKV strain PRVABC59, which is genetically similar to the French Polynesia strain, with 97-100% genetic homology to the current ZIKV strain found in Brazil. All infections were confirmed by real-time PCR (RT-qPCR), immunofluorescence assay (IFA) probing with anti-flavivirus E antibody, and evaluation of cytopathic effects. Findings: ZIKV infected all six undifferentiated NB cell lines. In five out of six NB cell lines, between 90 and 70% cells were positive by IFA whereas for one cell line, CCL-127,~80% of cells were positive for ZIKV as determined by IFA but showed persistent infection. Two differentiated cell lines, JFEN and T-268, were highly resistant to ZIKV with b1% of the cells being susceptible, as determined by IFA and confirmed by qRT-PCR. Two retinoic acid (RA)-induced NB partially differentiated cell lines showed no difference in permissiveness as compared to their undifferentiated mother cell lines. Interpretation: These findings strengthen the reported association between high incidences of microcephaly and ZIKV infection in newborns in Brazil. Our results suggest that the undifferentiated neurons are highly permissive to ZIKV infection, as one would expect during the early stages of neurogenesis in fetal brains; whereas differentiated neurons, representative of adult brain neurons, are relatively resistant to the virus, which explains the rare occurrence of neurological complications in adults infected with ZIKV. Our studies confirm the neurotropism of the ZIKV strain closely related to the current epidemic in Latin America.

Infectivity of Human Olfactory Neurons to SARS-CoV-2: A Link to Anosmia

Oman Medical Journal, Sep 30, 2021

Objectives: We sought to determine whether SARS-CoV-2 infections are associated with anosmia and ... more Objectives: We sought to determine whether SARS-CoV-2 infections are associated with anosmia and if this virus infects other neuronal cells. We utilized male and female olfactory neuronal cell lines and other olfactory cell lines to determine the viral targets. Methods: We used four undifferentiated and two partially differentiated human developing neuronal cell lines. Infectivity was confirmed by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), immunofluorescence assay (IFA) probing with anti-SARS-CoV-2 antibody, evaluation of cytopathic effects, and neurite formation. We induced partial differentiation of all cell lines (since both olfactory cell lines were terminally differentiated) with retinoic acid (RA) to determine whether differentiation was a factor in viral permissiveness. The expression of serine protease, transmembrane serine protease 2 (TMPRSS2), and angiotensin-converting enzyme II (ACE2) receptors were examined by RT-qPCR and IFA to determine the mechanism of viral entry. Results: Four to five days after exposure, both olfactory cell lines exhibited morphological evidence of infection; IFA analyses indicated that ~30% of the neurons were SARS-CoV-2 positive. At two weeks, 70–80% were positive for SARS-CoV-2 antigens. The partially differentiated (CRL-2266 and CRL-2267) and undifferentiated cell lines (CRL-2142, CRL-2149, CRL-127, and CDL-2271) were essentially non-permissive. After RA treatment, only CRL-127 exhibited slight permissiveness (RT-qPCR). The TMPRSS2 receptor showed high expression in olfactory neurons, but low expression in RA treated CRL-127. ACE2 exhibited high expression in olfactory neurons, whereas other cell lines showed low expression, including RA-treated cell lines. ACE2 expression slightly increased in CRL-127 post RA-treatment. Conclusions: Our studies confirm neurotropism of SARS-CoV-2 to olfactory neurons with viral entry likely mediated by TMPRSS2/ACE2. Other neuronal cell lines were non-permissive. Our results established that the nerve cells were infected regardless of male or female origin and strengthened the reported association of COVID-19 with loss of smell in infected individuals.

Libyan Journal of Medicine, 2017

Background Zika virus (ZIKV) has been associated with a variety of neuropathologies, including mi... more Background Zika virus (ZIKV) has been associated with a variety of neuropathologies, including microcephaly. We hypothesize that ZIKV genes activate host microRNAs (miRNAs) causing dysfunctional development of human fetal brains. Objectives/methods A bioinformatics search for miRNA genome-wide binding sites in the prototypic ZIKV (strain MR766) was undertaken to hunt for miRNAs with significant similarities with MCPH genetic sequences responsible for inducing MCHP in human fetal brains. Results Six ZIKV miRNAs were found to share mutual homology with 12 MCPH genetic sequences responsible for inducing MCPH. Noteworthy was miR-1304, which expressed 100% identity to six different MCPH genes. Conclusions We suggest that following infection of fetal neurons ZIKV may modulate the action of various miRNAs, and miR-1304 in particular, resulting in microcephaly.

Plagues, a word derived from the Latin plaga, meaning a blow, stroke or wound, have infested Euro... more Plagues, a word derived from the Latin plaga, meaning a blow, stroke or wound, have infested Europe throughout history. The first plagues were, by all accounts, devastating in human terms and the high mortalities associated with early plagues resulted due to the "first contact" effect.

This document was a www presentation from 1999 developed as part of a lecture for Biotechnology students.