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Article ; Online: Silencing Srsf6 does not modulate incomplete splicing of the huntingtin gene in Huntington’s disease models

Michael A. Mason / Casandra Gomez-Paredes / Kirupa Sathasivam / Andreas Neueder / Aikaterini-Smaragdi Papadopoulou / Gillian P. Bates

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 12

Abstract: ... by manipulating SRSF6 levels in Huntington’s disease models in which an expanded CAG repeat had been knocked ... that SRSF6 is not required for the incomplete splicing of HTT in Huntington’s disease. ...

Abstract	Abstract We have previously shown that the incomplete splicing of exon 1 to exon 2 of the HTT gene results in the production of a small polyadenylated transcript (Httexon1) that encodes the highly pathogenic exon 1 HTT protein. There is evidence to suggest that the splicing factor SRSF6 is involved in the mechanism that underlies this aberrant splicing event. Therefore, we set out to test this hypothesis, by manipulating SRSF6 levels in Huntington’s disease models in which an expanded CAG repeat had been knocked in to the endogenous Htt gene. We began by generating mice that were knocked out for Srsf6, and demonstrated that reduction of SRSF6 to 50% of wild type levels had no effect on incomplete splicing in zQ175 knockin mice. We found that nullizygosity for Srsf6 was embryonic lethal, and therefore, to decrease SRSF6 levels further, we established mouse embryonic fibroblasts (MEFs) from wild type, zQ175, and zQ175::Srsf6 +/− mice and transfected them with an Srsf6 siRNA. The incomplete splicing of Htt was recapitulated in the MEFs and we demonstrated that ablation of SRSF6 did not modulate the levels of the Httexon1 transcript. We conclude that SRSF6 is not required for the incomplete splicing of HTT in Huntington’s disease.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Antibacterial Potential of Bacopa monnieri (L.) Wettst. and Its Bioactive Molecules against Uropathogens—An In Silico Study to Identify Potential Lead Molecule(s) for the Development of New Drugs to Treat Urinary Tract Infections

Jyoti Mehta / Kumar Utkarsh / Shivkanya Fuloria / Tejpal Singh / Mahendran Sekar / Deeksha Salaria / Rajan Rolta / M. Yasmin Begum / Siew Hua Gan / Nur Najihah Izzati Mat Rani / Kumarappan Chidambaram / Vetriselvan Subramaniyan / Kathiresan V. Sathasivam / Pei Teng Lum / Subasini Uthirapathy / Olatomide A. Fadare / Oladoja Awofisayo / Neeraj Kumar Fuloria

Molecules, Vol 27, Iss 15, p

2022 Volume 4971

Abstract: Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and ... ...

Abstract	Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. Bacopa monnieri is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of B. monnieri leaves and its bioactive molecules against UTIs that are caused by Klebsiella pneumoniae and Proteus mirabilis . This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of B. monnieri leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the Klebsiella pneumoniae fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of B. monnieri revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against K. pneumoniae with the use of increasing concentrations. In the case of P. mirabilis activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. ...
Keywords	Bacopa monnieri ; antimicrobial ; agar well diffusion ; molecular docking ; MD simulation ; urinary tract infection ; Organic chemistry ; QD241-441
Subject code	541 ; 540
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington’s disease mice

Marie K. Bondulich / Nelly Jolinon / Georgina F. Osborne / Edward J. Smith / Ivan Rattray / Andreas Neueder / Kirupa Sathasivam / Mhoriam Ahmed / Nadira Ali / Agnesska C. Benjamin / Xiaoli Chang / James R. T. Dick / Matthew Ellis / Sophie A. Franklin / Daniel Goodwin / Linda Inuabasi / Hayley Lazell / Adam Lehar / Angela Richard-Londt /

Jim Rosinski / Donna L. Smith / Tobias Wood / Sarah J. Tabrizi / Sebastian Brandner / Linda Greensmith / David Howland / Ignacio Munoz-Sanjuan / Se-Jin Lee / Gillian P. Bates

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 14

Abstract: Abstract Huntington’s disease (HD) is an inherited neurodegenerative disorder ... in wild type and R6/2 mice but did little to modulate the extensive Huntington’s disease-associated ...

Abstract	Abstract Huntington’s disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD. Weekly administration from 5 to 11 weeks of age prevented body weight loss, skeletal muscle atrophy, muscle weakness, contractile abnormalities, the loss of functional motor units in EDL muscles and delayed end-stage disease. Inhibition of myostatin/activin A signaling activated transcriptional profiles to increase muscle mass in wild type and R6/2 mice but did little to modulate the extensive Huntington’s disease-associated transcriptional dysregulation, consistent with treatment having little impact on HTT aggregation levels. Modalities that inhibit myostatin signaling are currently in clinical trials for a variety of indications, the outcomes of which will present the opportunity to assess the potential benefits of targeting this pathway in HD patients.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correlation of Preoperative Anemia Subtypes with Tumor Characteristics, Systemic Inflammation and Immediate Postoperative Outcomes in Gastrointestinal Cancer Patients - A Prospective Observational Study.

Mahalingam, Sudharshan / Amaranathan, Anandhi / Sathasivam, Sureshkumar / Udayakumar, Karthikrajan Parasuraman

Journal of gastrointestinal cancer

2023 Volume 54, Issue 4, Page(s) 1220–1230

Abstract: Purpose: Patients with gastrointestinal (GI) malignancies more frequently present with anemia. A large proportion of them exhibit a systemic inflammatory response causing anemia of chronic disease. Although tumor factors play an essential role in ... ...

Abstract	Purpose: Patients with gastrointestinal (GI) malignancies more frequently present with anemia. A large proportion of them exhibit a systemic inflammatory response causing anemia of chronic disease. Although tumor factors play an essential role in determining the prognosis, studies have also reported the role of host factors in the outcome. This study was done to determine the association between systemic inflammation, tumor characteristics, and immediate postoperative outcome among various anemia subgroups. Methods: This was a single-center, prospective observational study of patients undergoing treatment for GI cancers. The modified Glasgow Prognostic Score (mGPS) was calculated, and patients were followed up until discharge regarding postoperative complications, length of the hospital, ICU stay, and mortality. The patient demographics, tumor characteristics, systemic inflammation, and postoperative complications were studied among different subtypes of anemia. Results: A total of 209 patients were analyzed, and a higher prevalence of normocytic anemia (52.63%) and systemic inflammatory response (62.21%) was observed among the study population. Systemic inflammation was significantly associated with a higher nodal stage (p = 0.02) and margin positivity (p = 0.006). Patients with higher mGPS had significantly higher requirements for blood transfusion (p = 0.003), superficial SSI (p = 0.03), and sepsis (p = 0.02); however, other postoperative complications were comparable among patients without an inflammatory response. Conclusion: Higher prevalence of normocytic anemia is observed among patients with gastrointestinal cancer. Normocytic anemia is significantly associated with systemic inflammation with no significant difference in tumor characters and immediate postoperative outcomes.
MeSH term(s)	Humans ; Anemia/epidemiology ; Prognosis ; Inflammation/complications ; Gastrointestinal Neoplasms/complications ; Gastrointestinal Neoplasms/surgery ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Systemic Inflammatory Response Syndrome/diagnosis ; Systemic Inflammatory Response Syndrome/epidemiology ; Systemic Inflammatory Response Syndrome/etiology ; Retrospective Studies
Language	English
Publishing date	2023-01-12
Publishing country	United States
Document type	Observational Study ; Journal Article
ZDB-ID	2452514-5
ISSN	1941-6636 ; 1559-0739 ; 1941-6628 ; 1537-3649
ISSN (online)	1941-6636 ; 1559-0739
ISSN	1941-6628 ; 1537-3649
DOI	10.1007/s12029-022-00902-3
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Article: Parasitization of the pedicle: a rare form of TRAM flap recurrence.

Binks, Matthew J / Guo, CiCi / Sabanathan, Danusha / Sathasivam, Sivapirabu / Edirimanne, Senarath

Journal of surgical case reports

2023 Volume 2023, Issue 7, Page(s) rjad322

Abstract: Local recurrence after mastectomy and autologous breast reconstruction is uncommon and tends to occur predictably within the superficial tissues or at the chest wall. We present a unique case of breast cancer recurrence involving the superficial and deep ...

Abstract	Local recurrence after mastectomy and autologous breast reconstruction is uncommon and tends to occur predictably within the superficial tissues or at the chest wall. We present a unique case of breast cancer recurrence involving the superficial and deep tissues. By parasitizing the pedicle of a free transverse rectus abdominis myocutaneous flap pedicle, the tumour was seen to extend through the chest wall to the right pleura.
Language	English
Publishing date	2023-07-31
Publishing country	England
Document type	Case Reports
ZDB-ID	2580919-2
ISSN	2042-8812
ISSN	2042-8812
DOI	10.1093/jscr/rjad322
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Article ; Online: Visible-Light-Active Iodide-Doped BiOBr Coatings for Sustainable Infrastructure.

Wang, Mingyue / Quesada-Cabrera, Raul / Sathasivam, Sanjayan / Blunt, Matthew O / Borowiec, Joanna / Carmalt, Claire J

ACS applied materials & interfaces

2023 Volume 15, Issue 42, Page(s) 49270–49280

Abstract: The search for efficient materials for sustainable infrastructure is an urgent challenge toward potential negative emission technologies and the global environmental crisis. Pleasant, efficient sunlight-activated coatings for applications in self- ... ...

Abstract	The search for efficient materials for sustainable infrastructure is an urgent challenge toward potential negative emission technologies and the global environmental crisis. Pleasant, efficient sunlight-activated coatings for applications in self-cleaning windows are sought in the glass industry, particularly those produced from scalable technologies. The current work presents visible-light-active iodide-doped BiOBr thin films fabricated using aerosol-assisted chemical vapor deposition. The impact of dopant concentration on the structural, morphological, and optical properties was studied systematically. The photocatalytic properties of the parent materials and as-deposited doped films were evaluated using the smart ink test. An optimized material was identified as containing 2.7 atom % iodide dopant. Insight into the photocatalytic behavior of these coatings was gathered from photoluminescence and photoelectrochemical studies. The optimum photocatalytic performance could be explained from a balance between photon absorption, charge generation, carrier separation, and charge transport properties under 450 nm irradiation. This optimized iodide-doped BiOBr coating is an excellent candidate for the photodegradation of volatile organic pollutants, with potential applications in self-cleaning windows and other surfaces.
Language	English
Publishing date	2023-10-12
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.3c11525
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Article ; Online: Transparent and conducting boron doped ZnO thin films grown by aerosol assisted chemical vapor deposition.

Zhao, Donglei / Sathasivam, Sanjayan / Wang, Mingyue / Carmalt, Claire J

RSC advances

2022 Volume 12, Issue 51, Page(s) 33049–33055

Abstract: ZnO based transparent conducting oxides are important as they provide an alternative to the more expensive Sn : ... ...

Abstract	ZnO based transparent conducting oxides are important as they provide an alternative to the more expensive Sn : In
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Journal Article
ISSN	2046-2069
ISSN (online)	2046-2069
DOI	10.1039/d2ra05895b
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Fabrication of C-Doped Titanium Dioxide Coatings with Improved Anti-icing and Tribological Behavior.

Wang, Keli / Wu, Yang / Sathasivam, Sanjayan / Zhang, Xia

Langmuir : the ACS journal of surfaces and colloids

2021 Volume 38, Issue 1, Page(s) 576–583

Abstract: The accumulation of ice on solid surfaces can cause serious losses and accidents. Current anti-icing/deicing coatings find it difficult to maintain their properties under frequent mechanical wear. In this work, the aerosol-assisted chemical vapor ... ...

Abstract	The accumulation of ice on solid surfaces can cause serious losses and accidents. Current anti-icing/deicing coatings find it difficult to maintain their properties under frequent mechanical wear. In this work, the aerosol-assisted chemical vapor deposition method was employed to prepare C-doped titanium dioxide coatings that have both photothermal properties and excellent wear resistance. The temperature of the sample surface reached 37.6 °C after 2 sun (2 kW/m
Language	English
Publishing date	2021-12-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.1c03107
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Article ; Online: Statin induced myotoxicity.

Sathasivam, Sivakumar

European journal of internal medicine

2012 Volume 23, Issue 4, Page(s) 317–324

Abstract: Statins are an effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, myotoxicity induced by statins is a common adverse event and a major barrier to maximising cardiovascular risk reduction. The ... ...

Abstract	Statins are an effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, myotoxicity induced by statins is a common adverse event and a major barrier to maximising cardiovascular risk reduction. The clinical spectrum of statin induced myotoxicity includes asymptomatic rise in creatine kinase concentration, myalgia, myositis and rhabdomyolysis. In certain cases, the cessation of statin therapy does not result in the resolution of muscular symptoms or the normalization of creatine kinase, raising the possibility of necrotizing autoimmune myopathy. There is increasing understanding and recognition of the pathophysiology and risk factors of statin induced myotoxicity. Careful history and physical examination in conjunction with selected investigations such as creatine kinase measurement, electromyography and muscle biopsy in appropriate clinical scenario help diagnose the condition. The management of statin induced myotoxicity involves statin cessation, the use of alternative lipid lowering agents or treatment regimes, and in the case of necrotizing autoimmune myopathy, immunosuppression.
MeSH term(s)	Cytochrome P-450 Enzyme System/physiology ; Genetic Predisposition to Disease ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Hyperlipidemias/drug therapy ; Hypolipidemic Agents/therapeutic use ; Muscular Diseases/chemically induced ; Muscular Diseases/epidemiology ; Muscular Diseases/genetics ; Muscular Diseases/physiopathology ; Myositis/chemically induced ; Myositis/physiopathology ; Rhabdomyolysis/chemically induced ; Risk Factors
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypolipidemic Agents ; Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2012-06
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2012.01.004
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Zs.A 2608: Show issues

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Article: Motor neurone disease: clinical features, diagnosis, diagnostic pitfalls and prognostic markers.

Sathasivam, S

Singapore medical journal

2010 Volume 51, Issue 5, Page(s) 367–72; quiz 373

Abstract: Motor neurone disease (MND) is a rapidly progressive adult-onset neurodegenerative disorder. In recent years, there has been an increased understanding regarding the epidemiology and clinical features of the different variants of MND. In addition, new ... ...

Abstract	Motor neurone disease (MND) is a rapidly progressive adult-onset neurodegenerative disorder. In recent years, there has been an increased understanding regarding the epidemiology and clinical features of the different variants of MND. In addition, new diagnostic criteria have been proposed to increase the sensitivity of the diagnosis. This review highlights these new concepts and discusses the differential diagnoses of MND, highlighting the common pitfalls and misdiagnoses. It also discusses the prognostic markers for MND and a possible change in the natural history of the disease course.
MeSH term(s)	Biomarkers ; Diagnosis, Differential ; Diagnostic Errors ; Electromyography ; Health Status Indicators ; Humans ; Magnetic Resonance Imaging ; Motor Neuron Disease/diagnosis ; Motor Neuron Disease/epidemiology ; Motor Neuron Disease/physiopathology ; Neural Conduction ; Prognosis ; Risk Factors
Chemical Substances	Biomarkers
Language	English
Publishing date	2010-05
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	604319-7
ISSN	0037-5675
ISSN	0037-5675
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