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Fulltext Caught in the web: a review of web-based suicide prevention

Lai MH, Maniam T, Chan LF, Ravindran AV

J Med Internet Res, 2014;16(1):e30.
PMID: 24472876 DOI: 10.2196/jmir.2973

Suicide is a serious and increasing problem worldwide. The emergence of the digital world has had a tremendous impact on people's lives, both negative and positive, including an impact on suicidal behaviors.
Fulltext N-glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues

Everest-Dass AV, Briggs MT, Kaur G, Oehler MK, Hoffmann P, Packer NH

Mol Cell Proteomics, 2016 09;15(9):3003-16.
PMID: 27412689 DOI: 10.1074/mcp.M116.059816

Ovarian cancer is a fatal gynaecological malignancy in adult women with a five-year overall survival rate of only 30%. Glycomic and glycoproteomic profiling studies have reported extensive protein glycosylation pattern alterations in ovarian cancer. Therefore, spatio-temporal investigation of these glycosylation changes may unearth tissue-specific changes that occur in the development and progression of ovarian cancer. A novel method for investigating tissue-specific N-linked glycans is using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) on formalin-fixed paraffin-embedded (FFPE) tissue sections that can spatially profile N-glycan compositions released from proteins in tissue-specific regions. In this study, tissue regions of interest (e.g. tumor, stroma, adipose tissue and necrotic areas) were isolated from FFPE tissue sections of advanced serous ovarian cancers (n = 3). PGC-LC-ESI-MS/MS and MALDI-MSI were used as complementary techniques to firstly generate structural information on the tissue-specific glycans in order to then obtain high resolution images of the glycan structure distribution in ovarian cancer tissue. The N-linked glycan repertoires carried by the proteins in these tissue regions were structurally characterized for the first time in FFPE ovarian cancer tissue regions, using enzymatic peptide-N-glycosidase F (PNGase F) release of N-glycans. The released glycans were analyzed by porous graphitized carbon liquid chromatography (PGC-LC) and collision induced electrospray negative mode MS fragmentation analysis. The N-glycan profiles identified by this analysis were then used to determine the location and distribution of each N-glycan on FFPE ovarian cancer sections that were treated with PNGase F using high resolution MALDI-MSI. A tissue-specific distribution of N-glycan structures identified particular regions of the ovarian cancer sections. For example, high mannose glycans were predominantly expressed in the tumor tissue region whereas complex/hybrid N-glycans were significantly abundant in the intervening stroma. Therefore, tumor and non-tumor tissue regions were clearly demarcated solely on their N-glycan structure distributions.
The impact of anticancer drugs on the ocular surface

Chiang JCB, Zahari I, Markoulli M, Krishnan AV, Park SB, Semmler A, et al.

Ocul Surf, 2020 07;18(3):403-417.
PMID: 32344148 DOI: 10.1016/j.jtos.2020.03.008

Cancer is a global health problem and is one of the leading causes of death worldwide. Pleasingly, the rate of survival has improved and continues in an upward trend mainly due to better diagnosis and treatment modalities. In particular, the development of anticancer drugs including cytotoxic chemotherapy, hormonal agents and targeted therapies have provided the most effective treatment options in combatting cancerous cells. However, the antineoplastic mechanisms of these drugs can also lead to undesirable systemic and ocular side effects resulting from cytotoxicity, inflammation and neurotoxicity. While survival rates are projected to increase with time, the number of patients presenting with these side effects that can substantially impact quality of life will also rise. The current paper reviews the ocular surface and adnexal side effects of anticancer drugs, the appropriate management and possible interactions between drugs for ocular surface pathology treatment and the anticancer drugs.
N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues

Briggs MT, Ho YY, Kaur G, Oehler MK, Everest-Dass AV, Packer NH, et al.

Rapid Commun Mass Spectrom, 2017 May 30;31(10):825-841.
PMID: 28271569 DOI: 10.1002/rcm.7845

RATIONALE: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. In the last few years, MALDI-MSI of the N-glycome has emerged as a novel MALDI-MSI technique. To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins.
METHODS AND RESULTS: Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS.
CONCLUSIONS: Our protocol provides groups that are new to this technique with instructions how to establish N-glycan MALDI-MSI in their laboratory. Furthermore, the method assigns N-glycan structural detail to the masses obtained in the MALDI-MS image. Copyright © 2017 John Wiley & Sons, Ltd.
MALDI Mass Spectrometry Imaging of Early- and Late-Stage Serous Ovarian Cancer Tissue Reveals Stage-Specific N-Glycans

Briggs MT, Condina MR, Ho YY, Everest-Dass AV, Mittal P, Kaur G, et al.

Proteomics, 2019 11;19(21-22):e1800482.
PMID: 31364262 DOI: 10.1002/pmic.201800482

Epithelial ovarian cancer is one of the most fatal gynecological malignancies in adult women. As studies on protein N-glycosylation have extensively reported aberrant patterns in the ovarian cancer tumor microenvironment, obtaining spatial information will uncover tumor-specific N-glycan alterations in ovarian cancer development and progression. matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is employed to investigate N-glycan distribution on formalin-fixed paraffin-embedded ovarian cancer tissue sections from early- and late-stage patients. Tumor-specific N-glycans are identified and structurally characterized by porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry (PGC-LC-ESI-MS/MS), and then assigned to high-resolution images obtained from MALDI-MSI. Spatial distribution of 14 N-glycans is obtained by MALDI-MSI and 42 N-glycans (including structural and compositional isomers) identified and structurally characterized by LC-MS. The spatial distribution of oligomannose, complex neutral, bisecting, and sialylated N-glycan families are localized to the tumor regions of late-stage ovarian cancer patients relative to early-stage patients. Potential N-glycan diagnostic markers that emerge include the oligomannose structure, (Hex)6 + (Man)3 (GlcNAc)2 , and the complex neutral structure, (Hex)2 (HexNAc)2 (Deoxyhexose)1 + (Man)3 (GlcNAc)2 . The distribution of these markers is evaluated using a tissue microarray of early- and late-stage patients.
Translating N-Glycan Analytical Applications into Clinical Strategies for Ovarian Cancer

Briggs MT, Condina MR, Klingler-Hoffmann M, Arentz G, Everest-Dass AV, Kaur G, et al.

Proteomics Clin Appl, 2019 05;13(3):e1800099.
PMID: 30367710 DOI: 10.1002/prca.201800099

Protein glycosylation, particularly N-linked glycosylation, is a complex posttranslational modification (PTM), which plays an important role in protein folding and conformation, regulating protein stability and activity, cell-cell interaction, and cell signaling pathways. This review focuses on analytical techniques, primarily MS-based techniques, to qualitatively and quantitatively assess N-glycosylation while successfully characterizing compositional, structural, and linkage features with high specificity and sensitivity. The analytical techniques explored in this review include LC-ESI-MS/MS and MALDI time-of-flight MS (MALDI-TOF-MS), which have been used to analyze clinical samples, such as serum, plasma, ascites, and tissue. Targeting the aberrant N-glycosylation patterns observed in MALDI-MS imaging (MSI) offers a platform to visualize N-glycans in tissue-specific regions. The studies on the intra-patient (i.e., a comparison of tissue-specific regions from the same patient) and inter-patient (i.e., a comparison of tissue-specific regions between different patients) variation of early- and late-stage ovarian cancer (OC) patients identify specific N-glycan differences that improve understanding of the tumor microenvironment and potentially improve therapeutic strategies for the clinic.
Fulltext SARS-CoV-2 spike protein: Site-specific breakpoints for the development of COVID-19 vaccines

Velusamy P, Kiruba K, Su CH, Arun V, Anbu P, Gopinath SCB, et al.

J King Saud Univ Sci, 2021 Dec;33(8):101648.
PMID: 34690467 DOI: 10.1016/j.jksus.2021.101648

SARS-CoV2 is a member of human coronaviruses and is the causative agent of the present pandemic COVID-19 virus. In order to control COVID-19, studies on viral structure and mechanism of infectivity and pathogenicity are sorely needed. The spike (S) protein is comprised of S1 & S2 subunits. These spike protein subunits enable viral attachment by binding to the host cell via ACE-2 (angiotensin converting enzyme-2) receptor, thus facilitating the infection. During viral entry, one of the key steps is the cleavage of the S1-S2 spike protein subunits via surface TMPRSS2 (transmembrane protease serine 2) and results in viral infection. Hence, the S-protein is critical for the viral attachment and penetration into the host. The rapid advancement of our knowledge on the structural and functional aspects of the spike protein could lead to development of numerous candidate vaccines against SARS-CoV2. Here the authors discuss about the structure of spike protein and explore its related functions. Our aim is to provide a better understanding that may aid in fighting against CoVID-19 and its treatment.