Browse publications by year: 2013

Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function

Al-Salahi OS, Kit-Lam C, Majid AM, Al-Suede FS, Mohammed Saghir SA, Abdullah WZ, et al.

Microvasc Res, 2013 Nov;90:30-9.
PMID: 23899415 DOI: 10.1016/j.mvr.2013.07.007

Targeting angiogenesis could be an excellent strategy to combat angiogenesis-dependent pathophysiological conditions such as cancer, rheumatoid arthritis, obesity, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis. Recently a number of clinical investigations are being undertaken to assess the potential therapeutic application of various anti-angiogenic agents. Many of these angiogenesis inhibitors are directed against the functions of endothelial cells, which are considered as the building blocks of blood vessels. Similarly, roots of a traditional medicinal plant, Eurycoma longifolia, can be used as an alternative treatment to prevent and treat the angiogenesis-related diseases. In the present study, antiangiogenic potential of partially purified quassinoid-rich fraction (TAF273) of E. longifolia root extract was evaluated using ex vivo and in vivo angiogenesis models and the anti-angiogenic efficacy of TAF273 was investigated in human umbilical vein endothelial cells (HUVEC). TAF273 caused significant suppression in sprouting of microvessels in rat aorta with IC50 11.5μg/ml. TAF273 (50μg/ml) showed remarkable inhibition (63.13%) of neovascularization in chorioallantoic membrane of chick embryo. Tumor histology also revealed marked reduction in extent of vascularization. In vitro, TAF273 significantly inhibited the major angiogenesis steps such as proliferation, migration and differentiation of HUVECs. Phytochemical analysis revealed high content of quassinoids in TAF273. Specially, HPLC characterization showed that TAF273 is enriched with eurycomanone, 13α(21)-epoxyeurycomanone and eurycomanol. These results demonstrated that the antiangiogenic activity of TAF273 may be due to its inhibitory effect on endothelial cell proliferation, differentiation and migration which could be attributed to the high content of quassinoids in E. longifolia.

MeSH terms: Animals; Cell Differentiation/drug effects; Cell Movement/drug effects; Chick Embryo; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Leukemia, Erythroblastic, Acute/drug therapy; Leukemia, Erythroblastic, Acute/pathology; Humans; Male; Phytotherapy; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Plant Extracts/isolation & purification; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Plants, Medicinal; Time Factors; Rats, Sprague-Dawley; Plant Roots; Neovascularization, Physiologic/drug effects; K562 Cells; Angiogenesis Inhibitors/isolation & purification; Angiogenesis Inhibitors/pharmacology*; Angiogenesis Inhibitors/chemistry; Xenograft Model Antitumor Assays; Eurycoma*; Quassins/isolation & purification; Quassins/pharmacology*; Quassins/chemistry; Endothelial Cells/drug effects*; Chorioallantoic Membrane/blood supply; Chorioallantoic Membrane/drug effects; Cell Proliferation/drug effects; Mice; Rats; Human Umbilical Vein Endothelial Cells/drug effects
Fulltext Review of emotion recognition in stroke patients

Yuvaraj R, Murugappan M, Norlinah MI, Sundaraj K, Khairiyah M

Dement Geriatr Cogn Disord, 2013;36(3-4):179-96.
PMID: 23899462 DOI: 10.1159/000353440

OBJECTIVE: Patients suffering from stroke have a diminished ability to recognize emotions. This paper presents a review of neuropsychological studies that investigated the basic emotion processing deficits involved in individuals with interhemispheric brain (right, left) damage and normal controls, including processing mode (perception) and communication channels (facial, prosodic-intonational, lexical-verbal).
METHODS: An electronic search was conducted using specific keywords for studies investigating emotion recognition in brain damage patients. The PubMed database was searched until March 2012 as well as citations and reference lists. 92 potential articles were identified.
RESULTS: The findings showed that deficits in emotion perception were more frequently observed in individuals with right brain damage than those with left brain damage when processing facial, prosodic and lexical emotional stimuli.
CONCLUSION: These findings suggest that the right hemisphere has a unique contribution in emotional processing and provide support for the right hemisphere emotion hypothesis.
SIGNIFICANCE:
This robust deficit in emotion recognition has clinical significance. The extent of emotion recognition deficit in brain damage patients appears to be correlated with a variety of interpersonal difficulties such as complaints of frustration in social relations, feelings of social discomfort, desire to connect with others, feelings of social disconnection and use of controlling behaviors.

MeSH terms: Communication; Decision Making; Emotions/physiology*; Empathy; Facial Expression; Humans; Neuropsychological Tests; Social Perception; Treatment Outcome; Stroke/psychology*; Recognition (Psychology)/physiology*
Temperature differentially regulates the two kisspeptin systems in the brain of zebrafish

Shahjahan M, Kitahashi T, Ogawa S, Parhar IS

Gen Comp Endocrinol, 2013 Nov 1;193:79-85.
PMID: 23899715 DOI: 10.1016/j.ygcen.2013.07.015

Kisspeptins encoded by the kiss1 and kiss2 genes play an important role in reproduction through the stimulation of gonadotropin-releasing hormone (GnRH) secretion by activating their receptors (KissR1 EU047918 and KissR2 EU047917). To understand the mechanism through which temperature affects reproduction, we examined kiss1 and kiss2 and their respective receptor (kissr1 and kissr2) gene expression in the brain of male zebrafish exposed to a low temperature (15°C), normal temperature (27°C), and high temperature (35°C) for 7-days. kiss1 mRNA levels in the brain were significantly increased (2.9-fold) in the low temperature compared to the control (27°C), while no noticeable change was observed in the high temperature conditions. Similarly, kissr1 mRNA levels were significantly increased (1.5-2.2-folds) in the low temperature conditions in the habenula, the nucleus of the medial longitudinal fascicle, oculomotor nucleus, and the interpeduncular nucleus. kiss2 mRNA levels were significantly decreased (0.5-fold) in the low and high temperature conditions, concomitant with kissr2 mRNA levels (0.5-fold) in the caudal zone of the periventricular hypothalamus and the posterior tuberal nucleus. gnrh3 but not gnrh2 mRNA levels were also decreased (0.5-fold) in the low and high temperature conditions. These findings suggest that while the kiss1/kissr1 system is sensitive to low temperature, the kiss2/kissr2 system is sensitive to both extremes of temperature, which leads to failure in reproduction.

MeSH terms: Animals; Brain/metabolism*; Female; Male; Reproduction/genetics; Reproduction/physiology; Temperature; Zebrafish/genetics; Zebrafish/metabolism*; Zebrafish/physiology; Zebrafish Proteins/metabolism*; Kisspeptins/metabolism*
Fulltext Aporphine alkaloids from the leaves of Phoebe grandis (Nees) Mer. (Lauraceae) and their cytotoxic and antibacterial activities

Omar H, Hashim NM, Zajmi A, Nordin N, Abdelwahab SI, Azizan AH, et al.

Molecules, 2013 Jul 29;18(8):8994-9009.
PMID: 23899833 DOI: 10.3390/molecules18088994

The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,9,11,12-tetrahydromecambrine (3) and hexahydromecambrine A (4) were isolated from the leaves of Phoebe grandis (Nees) Merr. (Lauraceae). Compounds 2 and 3 were first time isolated as new naturally occurring compounds from plants. The NMR data for the compounds 2-4 have never been reported so far. Compounds 1 and 2 showed significant cytotoxic activity against a MCF7 (human estrogen receptor (ER+) positive breast cancer) cell line with IC₅₀ values of 26 and 60 µg/mL, respectively. Furthermore, in vitro cytotoxic activity against HepG2 (human liver cancer) cell line was evaluated for compounds 1-4 with IC₅₀ values of 27, 14, 81 and 20 µg/mL, respectively. Lysicamine (1) displayed strong antibacterial activity against Bacillus subtilis (B145), Staphylococcus aureus (S1434) and Staphylococus epidermidis (a clinically isolated strain) with inhibition zones of 15.50 ± 0.57, 13.33 ± 0.57 and 12.00 ± 0.00 mm, respectively. However, none of the tested pathogenic bacteria were susceptible towards compounds 2 and 3.

MeSH terms: Alkaloids/administration & dosage*; Alkaloids/isolation & purification; Alkaloids/chemistry; Anti-Bacterial Agents/administration & dosage; Anti-Bacterial Agents/chemistry; Aporphines/administration & dosage*; Aporphines/isolation & purification; Aporphines/chemistry; Bacteria/drug effects*; Cytotoxins/administration & dosage; Cytotoxins/chemistry; Humans; Plant Extracts/administration & dosage; Plant Extracts/chemistry; Plant Leaves/chemistry; Saturn; Cell Proliferation/drug effects*; Hep G2 Cells/drug effects; MCF-7 Cells/drug effects
Influential factors in stability of lower-limb amputees

Kamali M, Karimi MT, Eshraghi A, Omar H

Am J Phys Med Rehabil, 2013 Dec;92(12):1110-8.
PMID: 23900009 DOI: 10.1097/PHM.0b013e31829b4b7a

Lower-limb amputation is mainly a result of trauma, vascular disease, diabetes, or congenital disorders. Persons with amputation lose their ability to stand and walk on the basis of the level of amputation. Contribution of level of amputation, type of amputation, or cause of amputation to balance impairment has not been clearly defined. Furthermore, it is controversial how much the mentioned parameters influence standing stability. Therefore, the aim of this review article was to find the relationship between the abovementioned factors and balance impairment in the available literature. It was also aimed to find the possibility of improving standing stability by the use of different prosthesis components.

MeSH terms: Amputation; Amputees/rehabilitation*; Artificial Limbs; Postural Balance/physiology*; Humans; Walking/physiology*; Lower Extremity/physiopathology*; Lower Extremity/surgery*
Fulltext Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7

Motaghed M, Al-Hassan FM, Hamid SS

Pharmacognosy Res, 2013 Jul;5(3):200-6.
PMID: 23900121 DOI: 10.4103/0974-8490.112428

Nigella sativa or black seed extract has been reported to show various medicinal benefits. Thymoquinone which is an active compound of its seed has been reported to contain anti-cancer properties.

MeSH terms: Neoplasms; Seeds; Benzoquinones; Nigella sativa
Fulltext Usage of glucometer is associated with improved glycaemic control in type 2 diabetes mellitus patients in Malaysian public primary care clinics: an open-label, randomised controlled trial

Ismail M, Teng CL, Teng CL, Omar M, Ho BK, Kusiar Z, et al.

Singapore Med J, 2013 Jul;54(7):391-5.
PMID: 23900469

INTRODUCTION: Self-monitoring of blood glucose (SMBG) has been underutilised. We conducted an open-label, randomised controlled trial to assess the feasibility of introducing SMBG in primary care clinics in Malaysia.

METHODS: This was an open-label, randomised controlled trial conducted in five public primary care clinics in Malaysia. Patients with type 2 diabetes mellitus (age range 35-65 years) not performing SMBG at the time of the study were randomised to receive either a glucometer for SMBG or usual care. Both groups of patients received similar diabetes care from the clinics.

RESULTS: A total of 105 patients with type 2 diabetes mellitus were enrolled. Of these, 58 and 47 were randomised to intervention and control groups, respectively. After six months, the glycated haemoglobin (HbA1c) level in the intervention group showed a statistically significant improvement of 1.3% (p = 0.001; 95% confidence interval 0.6-2.0), relative to the control group that underwent usual care. The percentages of patients that reached the HbA1c treatment target of ≤ 7% were 14.0% and 32.1% in the control and intervention groups (p = 0.036), respectively.

CONCLUSION: The usage of a glucometer improved glycaemic control, possibly due to the encouragement of greater self-care in the intervention group.

MeSH terms: Adult; Aged; Diabetes Mellitus, Type 2/blood*; Female; Hemoglobin A, Glycosylated/analysis; Humans; Malaysia; Male; Middle Aged; Primary Health Care*; Blood Glucose Self-Monitoring*
Fulltext Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancers

Tiong KH, Mah LY, Leong CO

Apoptosis, 2013 Dec;18(12):1447-68.
PMID: 23900974 DOI: 10.1007/s10495-013-0886-7

The fibroblast growth factor receptors (FGFRs) regulate important biological processes including cell proliferation and differentiation during development and tissue repair. Over the past decades, numerous pathological conditions and developmental syndromes have emerged as a consequence of deregulation in the FGFRs signaling network. This review aims to provide an overview of FGFR family, their complex signaling pathways in tumorigenesis, and the current development and application of therapeutics targeting the FGFRs signaling for treatment of refractory human cancers.

MeSH terms: Animals; Antineoplastic Agents/therapeutic use; Humans; Neoplasms/drug therapy; Neoplasms/genetics; Neoplasms/metabolism*; Neoplasms/physiopathology; Signal Transduction*; Apoptosis; Receptors, Fibroblast Growth Factor/genetics; Receptors, Fibroblast Growth Factor/metabolism*
Hybrid learning control for improving suppression of hand tremor

As'arry A, Md Zain MZ, Mailah M, Hussein M

Proc Inst Mech Eng H, 2013 Nov;227(11):1171-80.
PMID: 23901066 DOI: 10.1177/0954411913494325

Patients with hand tremors may find routine activities such as writing and holding objects affected. In response to this problem, an active control technique has been examined in order to lessen the severity of tremors. In this article, an online method of a hybrid proportional-integral control with active force control strategy for tremor attenuation is presented. An intelligent mechanism using iterative learning control is incorporated into the active force control loop to approximate the estimation mass parameter. Experiments were conducted on a dummy hand model placed horizontally in a tremor test rig. When activated by a shaker in the vertical direction, this resembles a postural tremor condition. In the proportional-integral plus active force control, a linear voice coil actuator is used as the main active tremor suppressive element. A sensitivity analysis is presented to investigate the robustness of the proposed controller in a real-time control environment. The findings of this study demonstrate that the intelligent active force control and iterative learning controller show excellent performance in reducing tremor error compared to classic pure proportional, proportional-integral and hybrid proportional-integral plus active force control controllers.

MeSH terms: Adult; Artificial Intelligence*; Biomechanical Phenomena; Biomedical Engineering/instrumentation*; Hand/physiopathology; Humans; Male; Models, Biological; Parkinson Disease/physiopathology; Parkinson Disease/therapy; Software; Tremor/physiopathology*; Tremor/therapy*
Carbon dioxide conversion over carbon-based nanocatalysts

Khavarian M, Chai SP, Mohamed AR

J Nanosci Nanotechnol, 2013 Jul;13(7):4825-37.
PMID: 23901504

The utilization of carbon dioxide for the production of valuable chemicals via catalysts is one of the efficient ways to mitigate the greenhouse gases in the atmosphere. It is known that the carbon dioxide conversion and product yields are still low even if the reaction is operated at high pressure and temperature. The carbon dioxide utilization and conversion provides many challenges in exploring new concepts and opportunities for development of unique catalysts for the purpose of activating the carbon dioxide molecules. In this paper, the role of carbon-based nanocatalysts in the hydrogenation of carbon dioxide and direct synthesis of dimethyl carbonate from carbon dioxide and methanol are reviewed. The current catalytic results obtained with different carbon-based nanocatalysts systems are presented and how these materials contribute to the carbon dioxide conversion is explained. In addition, different strategies and preparation methods of nanometallic catalysts on various carbon supports are described to optimize the dispersion of metal nanoparticles and catalytic activity.

MeSH terms: Carbon/chemistry*; Carbon Dioxide/chemistry*; Catalysis; Metal Nanoparticles/chemistry*
The effect of oleic acid stabilizer on the surface properties of bimetallic PtNi catalysts

Abu Bakar NH, Abu Bakar M, Bettahar MM, Ismail J, Monteverdi S

J Nanosci Nanotechnol, 2013 Jul;13(7):5034-43.
PMID: 23901527

A detailed study on the surface properties of oleic acid-stabilized PtNi nanoparticles supported on silica is reported. The oleic acid-stabilized PtNi nanoparticles were synthesized using NaBH4 as the reducing agent at various temperatures and oleic acid concentrations, prior to incorporation onto the silica support. X-ray diffraction studies of the unsupported oleic acid-stabilized PtNi particles revealed that the PtNi existed as alloys. Upon incorporation onto silica support, surface properties of the catalysts were investigated using H2-temperature reduction (H2-TPR), H2-temperature desorption (H2-TPD) and H2-chemisorption techniques. It was found that for the bimetallic catalysts, no oxides or very little oxidation occurred. Furthermore, these catalysts exhibited both Pt and Ni active sites on its surface though the availability of Ni active sites was dominant. A comparison of the surface properties of these materials with those prepared without oleic acid in our previous work [N. H. H. Abu Bakar et al., J. Catal. 265, 63 (2009)] and how they affect the hydrogenation of benzene is also discussed.

MeSH terms: Alloys/chemistry; Catalysis; Excipients/chemistry; Materials Testing; Nickel/chemistry*; Oxidation-Reduction; Platinum/chemistry*; Surface Properties; Oleic Acid/chemistry*; Metal Nanoparticles/chemistry*
Fulltext Increased detection of Plasmodium knowlesi in Sandakan division, Sabah as revealed by PlasmoNex™

Goh XT, Lim YA, Vythilingam I, Chew CH, Lee PC, Ngui R, et al.

Malar J, 2013 Jul 31;12:264.
PMID: 23902626 DOI: 10.1186/1475-2875-12-264

BACKGROUND: Plasmodium knowlesi is a simian malaria parasite that is widespread in humans in Malaysian Borneo. However, little is known about the incidence and distribution of this parasite in the Sandakan division, Malaysian Borneo. Therefore, the aim of the present epidemiological study was to investigate the incidence and distribution of P. knowlesi as well as other Plasmodium species in this division based on a most recent developed hexaplex PCR system (PlasmoNex™).
METHODS: A total of 189 whole blood samples were collected from Telupid Health Clinic, Sabah, Malaysia, from 2008 to 2011. All patients who participated in the study were microscopically malaria positive before recruitment. Complete demographic details and haematological profiles were obtained from 85 patients (13 females and 72 males). Identification of Plasmodium species was conducted using PlasmoNex™ targeting the 18S ssu rRNA gene.
RESULTS: A total of 178 samples were positive for Plasmodium species by using PlasmoNex™. Plasmodium falciparum was identified in 68 samples (38.2%) followed by 64 cases (36.0%) of Plasmodium vivax, 42 (23.6%) cases of P. knowlesi, two (1.1%) cases of Plasmodium malariae and two (1.1%) mixed-species infections (i e, P. vivax/P. falciparum). Thirty-five PlasmoNex™ positive P. knowlesi samples were misdiagnosed as P. malariae by microscopy. Plasmodium knowlesi was detected in all four districts of Sandakan division with the highest incidence in the Kinabatangan district. Thrombocytopaenia and anaemia showed to be the most frequent malaria-associated haematological complications in this study.
CONCLUSIONS: The discovery of P. knowlesi in Sandakan division showed that prospective studies on the epidemiological risk factors and transmission dynamics of P. knowlesi in these areas are crucial in order to develop strategies for effective malaria control. The availability of advanced diagnostic tool PlasmoNex™ enhanced the accuracy and accelerated the speed in the diagnosis of malaria.

MeSH terms: Adolescent; Adult; Blood/parasitology; Child; Child, Preschool; Female; Humans; Malaria/epidemiology*; Malaria/parasitology*; Malaysia/epidemiology; Male; Middle Aged; Incidence; Prevalence; DNA, Protozoan/genetics; Plasmodium knowlesi/classification; Plasmodium knowlesi/genetics; Plasmodium knowlesi/isolation & purification*; Young Adult; Multiplex Polymerase Chain Reaction/methods
Fulltext Comparative analysis of Mafriwal (Bos taurus × Bos indicus) and Kedah Kelantan (Bos indicus) sperm proteome identifies sperm proteins potentially responsible for higher fertility in a tropical climate

Ashrafzadeh A, Nathan S, Karsani SA

Int J Mol Sci, 2013;14(8):15860-77.
PMID: 23903046 DOI: 10.3390/ijms140815860

The fertility of zebu cattle (Bos indicus) is higher than that of the European purebred (Bos taurus) and crossbred (Bos taurus × Bos indicus) cattle in tropical areas. To identify proteins related to the higher thermo-tolerance and fertility of Zebu cattle, this study was undertaken to identify differences in sperm proteome between the high fertile Malaysian indigenous zebu cattle (Kedah Kelantan) and the sub-fertile crossbred cattle (Mafriwal). Frozen semen from three high performance bulls from each breed were processed to obtain live and pure sperm. Sperm proteins were then extracted, and two-dimensional gel electrophoresis performed to compare proteome profiles. Gel image analysis identified protein spots of interest which were then identified by liquid chromatography mass spectrometry quadrupole time-of-flight (LC MS/MS Q-TOF). STRING network analysis predicted interactions between at least 20 of the identified proteins. Among the identified proteins, a number of motility and energy related proteins were present in greater abundance in Kedah Kelantan. Sperm motility evaluation by Computer Assisted Semen Analysis (CASA) confirmed significantly higher motility in Kedah Kelantan. While results from this study do identify proteins that may be responsible for the higher fertility of Kedah Kelantan, functional characterization of these proteins is warranted to reinforce our understanding of their roles in sperm fertility.

MeSH terms: Animals; Cattle; Chromatography, High Pressure Liquid; Fertility; Male; Sperm Motility; Spermatozoa/metabolism*; Tropical Climate; Electrophoresis, Gel, Two-Dimensional; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*; Computational Biology; Proteome/analysis*
Fulltext Modification of oil palm mesocarp fiber characteristics using superheated steam treatment

Nordin NI, Ariffin H, Andou Y, Hassan MA, Shirai Y, Nishida H, et al.

Molecules, 2013 Jul 30;18(8):9132-46.
PMID: 23903185 DOI: 10.3390/molecules18089132

In this study, oil palm mesocarp fiber (OPMF) was treated with superheated steam (SHS) in order to modify its characteristics for biocomposite applications. Treatment was conducted at temperatures 190-230 °C for 1, 2 and 3 h. SHS-treated OPMF was evaluated for its chemical composition, thermal stability, morphology and crystallinity. OPMF treated at 230 °C exhibited lower hemicellulose content (9%) compared to the untreated OPMF (33%). Improved thermal stability of OPMF was found after the SHS treatment. Moreover, SEM and ICP analyses of SHS-treated OPMF showed that silica bodies were removed from OPMF after the SHS treatment. XRD results exhibited that OPMF crystallinity increased after SHS treatment, indicating tougher fiber properties. Hemicellulose removal makes the fiber surface more hydrophobic, whereby silica removal increases the surface roughness of the fiber. Overall, the results obtained herewith suggested that SHS is an effective treatment method for surface modification and subsequently improving the characteristics of the natural fiber. Most importantly, the use of novel, eco-friendly SHS may contribute to the green and sustainable treatment for surface modification of natural fiber.

MeSH terms: Hot Temperature*; Polysaccharides/chemistry*; Steam*; Spectroscopy, Fourier Transform Infrared; Arecaceae/chemistry*; Hydrophobic and Hydrophilic Interactions
Exploring the structural insights on human laforin mutation K87A in Lafora disease--a molecular dynamics study

Srikumar PS, Rohini K

Appl Biochem Biotechnol, 2013 Oct;171(4):874-82.
PMID: 23904258 DOI: 10.1007/s12010-013-0393-x

Lafora disease (LD) is an autosomal recessive, progressive form of myoclonus epilepsy which affects worldwide. LD occurs mainly in countries like southern Europe, northern Africa, South India, and in the Middle East. LD occurs with its onset mainly in teenagers and leads to decline and death within 2 to 10 years. The genes EPM2A and EPM2B are commonly involved in 90 % of LD cases. EPM2A codes for protein laforin which contains an amino terminal carbohydrate binding module (CBM) belonging to the CBM20 family and a carboxy terminal dual specificity phosphatase domain. Mutations in laforin are found to abolish glycogen binding and have been reported in wet lab methods. In order to investigate on structural insights on laforin mutation K81A, we performed molecular dynamics (MD) simulation studies for native and mutant protein. MD simulation results showed loss of stability due to mutation K87A which confirmed the structural reason for conformational changes observed in laforin. The conformational change of mutant laforin was confirmed by analysis using root mean square deviation, root mean square fluctuation, solvent accessibility surface area, radius of gyration, hydrogen bond, and principle component analysis. Our results identified that the flexibility of K87A mutated laforin structure, with replacement of acidic amino acid to aliphatic amino acid in functional CBM domain, have more impact in abolishing glycogen binding that favors LD.

MeSH terms: Humans; Mutation; Protein Structure, Secondary; Lafora Disease/genetics*; Lafora Disease/metabolism*; Principal Component Analysis; Protein Tyrosine Phosphatases, Non-Receptor/genetics*; Protein Tyrosine Phosphatases, Non-Receptor/metabolism; Protein Tyrosine Phosphatases, Non-Receptor/chemistry*; Molecular Dynamics Simulation*
Fulltext Evaluation of anti-bacterial and anti-oxidant potential of andrographolide and echiodinin isolated from callus culture of Andrographis paniculata Nees

Arifullah M, Namsa ND, Mandal M, Chiruvella KK, Vikrama P, Gopal GR

Asian Pac J Trop Biomed, 2013 Aug;3(8):604-10; discussion 609-10.
PMID: 23905016 DOI: 10.1016/S2221-1691(13)60123-9

To evaluate the anti-bacterial and anti-oxidant activity of andrographolide (AND) and echiodinin (ECH) of Andrographis paniculata.

MeSH terms: Anti-Bacterial Agents/pharmacology*; Antioxidants/pharmacology*; Cells, Cultured; Diterpenes/pharmacology*; Drug Resistance, Microbial; Gram-Negative Bacteria/drug effects; Gram-Positive Bacteria/drug effects; Microbial Sensitivity Tests; Plant Extracts/chemistry*; Yeasts/drug effects; Plant Leaves/chemistry; Andrographis/chemistry*; Flavones/pharmacology*; Mesophyll Cells/chemistry
Fulltext Social isolation in older Malaysians: prevalence and risk factors

Ibrahim R, Abolfathi Momtaz Y, Hamid TA

Psychogeriatrics, 2013 Jun;13(2):71-9.
PMID: 23909963 DOI: 10.1111/psyg.12000

Social isolation is one of the most important emerging issues among ageing populations, as it reduces well-being, health and quality of life. The purpose of this study was to identify prevalence and risk factors of social isolation in older Malaysians.

MeSH terms: Aged; Aged, 80 and over; Aging/psychology*; Female; Health Surveys; Humans; Malaysia/epidemiology; Male; Middle Aged; Personal Satisfaction; Quality of Life/psychology*; Surveys and Questionnaires; Risk Factors; Social Isolation/psychology*; Social Support; Socioeconomic Factors; Prevalence; Logistic Models
Fulltext Identification of small molecule inhibitors of p27(Kip1) ubiquitination by high-throughput screening

Ooi LC, Watanabe N, Futamura Y, Sulaiman SF, Darah I, Osada H

Cancer Sci, 2013 Nov;104(11):1461-7.
PMID: 23910095 DOI: 10.1111/cas.12246

Dysregulation of p27(Kip1) due to proteolysis that involves the ubiquitin ligase (SCF) complex with S-phase kinase-associated protein 2 (Skp2) as the substrate-recognition component (SCF(Skp2)) frequently results in tumorigenesis. In this report, we developed a high-throughput screening system to identify small-molecule inhibitors of p27(Kip1) degradation. This system was established by tagging Skp2 with fluorescent monomeric Azami Green (mAG) and CDK subunit 1 (Cks1) (mAGSkp2-Cks1) to bind to p27(Kip1) phosphopeptides. We identified two compounds that inhibited the interaction between mAGSkp2-Cks1 and p27(Kip1): linichlorin A and gentian violet. Further studies have shown that the compounds inhibit the ubiquitination of p27(Kip1) in vitro as well as p27(Kip1) degradation in HeLa cells. Notably, both compounds exhibited preferential antiproliferative activity against HeLa and tsFT210 cells compared with NIH3T3 cells and delayed the G1 phase progression in tsFT210 cells. Our approach indicates a potential strategy for restoring p27(Kip1) levels in human cancers.

MeSH terms: Amino Acid Sequence; Animals; Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry; Drug Screening Assays, Antitumor; Gentian Violet/pharmacology*; Gentian Violet/chemistry; HeLa Cells; Humans; Molecular Sequence Data; Peptide Fragments/chemistry; Sesquiterpenes/pharmacology*; Sesquiterpenes/chemistry; Cyclin-Dependent Kinases/antagonists & inhibitors; Cyclin-Dependent Kinases/metabolism; NIH 3T3 Cells; Cell Proliferation/drug effects; Cyclin-Dependent Kinase Inhibitor p27/metabolism*; Cyclin-Dependent Kinase Inhibitor p27/chemistry; Mice; Small Molecule Libraries; Ubiquitination/drug effects*; Protein Stability; High-Throughput Screening Assays; Cell Cycle Checkpoints; Proteolysis/drug effects
Fulltext Reliable, verifiable and efficient monitoring of biodiversity via metabarcoding

Ji Y, Ashton L, Pedley SM, Edwards DP, Tang Y, Nakamura A, et al.

Ecol Lett, 2013 Oct;16(10):1245-57.
PMID: 23910579 DOI: 10.1111/ele.12162

To manage and conserve biodiversity, one must know what is being lost, where, and why, as well as which remedies are likely to be most effective. Metabarcoding technology can characterise the species compositions of mass samples of eukaryotes or of environmental DNA. Here, we validate metabarcoding by testing it against three high-quality standard data sets that were collected in Malaysia (tropical), China (subtropical) and the United Kingdom (temperate) and that comprised 55,813 arthropod and bird specimens identified to species level with the expenditure of 2,505 person-hours of taxonomic expertise. The metabarcode and standard data sets exhibit statistically correlated alpha- and beta-diversities, and the two data sets produce similar policy conclusions for two conservation applications: restoration ecology and systematic conservation planning. Compared with standard biodiversity data sets, metabarcoded samples are taxonomically more comprehensive, many times quicker to produce, less reliant on taxonomic expertise and auditable by third parties, which is essential for dispute resolution.

MeSH terms: Animals; Arthropods/physiology; Automatic Data Processing*; Ecology/methods*; Environmental Monitoring/methods*; Computational Biology; Biodiversity*
The pandemic potential of Nipah virus

Luby SP

Antiviral Res, 2013 Oct;100(1):38-43.
PMID: 23911335 DOI: 10.1016/j.antiviral.2013.07.011

Nipah virus, a paramyxovirus whose wildlife reservoir is Pteropus bats, was first discovered in a large outbreak of acute encephalitis in Malaysia in 1998 among persons who had contact with sick pigs. Apparently, one or more pigs was infected from bats, and the virus then spread efficiently from pig to pig, then from pigs to people. Nipah virus outbreaks have been recognized nearly every year in Bangladesh since 2001 and occasionally in neighboring India. Outbreaks in Bangladesh and India have been characterized by frequent person-to-person transmission and the death of over 70% of infected people. Characteristics of Nipah virus that increase its risk of becoming a global pandemic include: humans are already susceptible; many strains are capable of limited person-to-person transmission; as an RNA virus, it has an exceptionally high rate of mutation: and that if a human-adapted strain were to infect communities in South Asia, high population densities and global interconnectedness would rapidly spread the infection. Appropriate steps to estimate and manage this risk include studies to explore the molecular and genetic basis of respiratory transmission of henipaviruses, improved surveillance for human infections, support from high-income countries to reduce the risk of person-to-person transmission of infectious agents in low-income health care settings, and consideration of vaccination in communities at ongoing risk of exposure to the secretions and excretions of Pteropus bats.

MeSH terms: Animals; Humans; India/epidemiology; Malaysia/epidemiology; Swine; Swine Diseases/epidemiology; Swine Diseases/transmission; Swine Diseases/virology*; Zoonoses/epidemiology; Zoonoses/transmission; Zoonoses/virology*; Nipah Virus/isolation & purification*; Nipah Virus/physiology; Henipavirus Infections/epidemiology*; Henipavirus Infections/transmission; Henipavirus Infections/virology; Pandemics

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