Investigation of Acute Neutrophil Response in Malaria Infection and Characterization of the CS Tag

Much progress has been made in malaria research and malaria-related mortality has been declining throughout the years, yet malaria remains to be a global threat given the lack of an effective vaccine and spread of reoccurring drug-resistant parasites. Hence, better understanding of how malaria infection progresses and how human immunity response combats infection is paramount in achieving malaria elimination. This thesis has been divided into two parts. One is to explore how neutrophil infiltration impacts the earliest phase of Plasmodium infection. Although the role of neutrophils combating different pathogens has been investigated extensively, no study has explored their roles in Plasmodium sporozoites in the skin phase, which is critical in understanding the innate immune response against malaria infection in the pre-erythrocytic stage. The other part of the thesis investigates whether a tag composed of a portion of the circumsporozoite protein can be used as a more sensitive and specific protein tag. Many commonly used protein tags, such as His (HHHHHHHH), HA (YPYDVPDYA), FLAG (DYKDDDDK), and Myc (EQKLISLEEDL) tags, provide satisfactory results but unable to reach the required sensitivity and specificity for better work flow. Hence, a novel CS tag with potentially better sensitivity and specificity can benefit greatly in the biotechnology field.

The role of p53 in the alternation of vascular functions

Ageing is a risk factor for many degenerative diseases. Cardiovascular diseases (CVDs) are usually big burdens for elderly, caregivers and the health system. During the aging process, normal functions of vascular cells and tissue progressively lost and eventually develop vascular diseases. Endothelial dysfunction, reduced bioavailability of endothelium-derived nitric oxide are usual phenomena observed in patients with cardiovascular diseases. Myriad of studies have been done to investigate to delay the vascular dysfunction or improve the vascular function to prolong the aging process. Tumor suppressor gene p53, also a transcription factor, act as a gatekeeper to regulate a number of genes to maintain normal cell function including but not limited to cell proliferation, cell apoptosis. p53 also crosstalk with other key transcription factors like hypoxia-inducible factor 1 alpha that contribute to the progression of cardiovascular diseases. Therefore, in recent three decades, p53 has drawn scientists’ attention on its effects in vascular function. Though the role of tumor suppressor gene p53 is still not clear in vascular function, it is found to play regulatory roles and may involve in vascular remodeling, atherosclerosis or pulmonary hypertension. p53 may have a divergent role in endothelial and vascular muscle cells in those conditions. In this review, we describe the different effects of p53 in cardiovascular physiology. Further studies on the effects of endothelial cell-specific p53 deficiency on atherosclerotic plaque formation in common animal models are required before the therapeutic potential can be realized

Constraining Tidal Dissipation in Stars from The Destruction Rates of Exoplanets

We use the distribution of extrasolar planets in circular orbits around stars with surface convective zones detected by ground based transit searches to constrain how efficiently tides raised by the planet are dissipated on the parent star. We parameterize this efficiency as a tidal quality factor (Q*). We conclude that the population of currently known planets is inconsistent with Q*<10^7 at the 99% level. Previous studies show that values of Q* between 10^5 and 10^7 are required in order to explain the orbital circularization of main sequence low mass binary stars in clusters, suggesting that different dissipation mechanisms might be acting in the two cases, most likely due to the very different tidal forcing frequencies relative to the stellar rotation frequency occurring for star--star versus planet--star systems.Comment: 12 pages, 6 figures accepted for publication in Ap

WASP-50b: a hot Jupiter transiting a moderately active solar-type star

We report the discovery by the WASP transit survey of a giant planet in a close orbit (0.0295+-0.0009 AU) around a moderately bright (V=11.6, K=10) G9 dwarf (0.89+-0.08 M_sun, 0.84+-0.03 R_sun) in the Southern constellation Eridanus. Thanks to high-precision follow-up photometry and spectroscopy obtained by the telescopes TRAPPIST and Euler, the mass and size of this planet, WASP-50b, are well constrained to 1.47+-0.09 M_jup and 1.15+-0.05 R_jup, respectively. The transit ephemeris is 2455558.6120 (+-0.0002) + N x 1.955096 (+-0.000005) HJD_UTC. The size of the planet is consistent with basic models of irradiated giant planets. The chromospheric activity (log R'_HK = -4.67) and rotational period (P_rot = 16.3+-0.5 days) of the host star suggest an age of 0.8+-0.4 Gy that is discrepant with a stellar-evolution estimate based on the measured stellar parameters (rho_star = 1.48+-0.10 rho_sun, Teff = 5400+-100 K, [Fe/H]= -0.12+-0.08) which favours an age of 7+-3.5 Gy. This discrepancy could be explained by the tidal and magnetic influence of the planet on the star, in good agreement with the observations that stars hosting hot Jupiters tend to show faster rotation and magnetic activity (Pont 2009; Hartman 2010). We measure a stellar inclination of 84 (-31,+6) deg, disfavouring a high stellar obliquity. Thanks to its large irradiation and the relatively small size of its host star, WASP-50b is a good target for occultation spectrophotometry, making it able to constrain the relationship between hot Jupiters' atmospheric thermal profiles and the chromospheric activity of their host stars proposed by Knutson et al. (2010).Comment: 9 pages, 8 figures. Accepted for publication in Astronomy & Astrophysic

Oral health of community dwelling elders in Hong Kong

Introduction: The world’s population is ageing and the elders are vulnerable to oral health problems. This project aimed to observe the oral health status of community dwelling elders in Hong Kong, investigate the oral health impact on their quality of life and nutritional status, and provide oral health education and preventive service. Methods: Community dwelling elders (65 or above) were recruited from five community centers. An interviewer-administered questionnaire was completed to collect information on their socio-demographic background and oral health perception/practice. Their oral health related quality of life (OHQoL) and nutritional status were measured by using the Geriatric Oral Health Assessment Index (GOHAI) and Mini-Nutritional Assessment (MNA), respectively. Their tooth and periodontal status, oral hygiene and soft tissues were examined. Individualized advice, oral health education and scaling were provided. Results: A total of 195 elders participated. Despite their sound knowledge on dental caries, their awareness of the causes and risk factors of periodontal diseases was low. Several misconceptions of oral health were common and their expectation towards oral health was low. Although 81% brush their teeth at least twice a day, over 75% did not perform interdental cleaning mainly due to unawareness of the necessity (32%) and lack of skills (42%). Their dental visits were treatment-driven and mainly for pain-relieving and emergency care. Only 19% were regular dental attendees. The mean (SD) DMFT was 8.9 (7.8). Over 60% had periodontal pockets; 6% were edentulous and 38% had fewer than 20 teeth. The mean (SD) total GOHAI score was 56.4 (8.0); 60% reported negative impact of oral health on their quality of life. The mean (SD) MNA score was 25.2 (2.9); 30% had malnutrition or were at risk. Multivariate analysis showed that tooth loss and untreated decayed teeth (DT) were significant determinants of poor OHQoL; older age, higher education level, and poorer OHQoL were significantly associated with higher risk of malnutrition (all p<0.05). Conclusions: Oral health problems are common among community dwelling elders in Hong Kong. Their oral health awareness and practice are yet to be improved. Tooth loss and unmet treatment need for dental caries significantly compromise elders’ quality of life, which in turn increases their risk for malnutrition. Outreach oral health education and service are well received by the community.published_or_final_versio

Is alcohol dependence best viewed as a chronic relapsing disorder?

This 'For Debate' paper starts by recognizing the growing trend towards considering alcohol dependence as a chronic relapsing disorder. We argue that the adoption of this model results from focusing on those in treatment for alcohol dependence rather than considering the larger number of people in the general population who meet criteria for alcohol dependence at some point in their lives. The majority of the general population who ever experience alcohol dependence do not behave as though they have a chronic relapsing disorder: they do not seek treatment, resolve their dependence themselves and do not relapse repeatedly. We suggest that caution is therefore needed in using the chronic relapsing disorder label. Our primary concerns are that this formulation privileges biological aspects of dependence to the detriment of psychological and social contributions, it inhibits much-needed developments in understanding alcohol dependence and leads to inefficient distributions of public health and clinical care resources for alcohol dependence. We invite debate on this issue

A review of the pharmacological effects of Arctium lappa (burdock)

Abstract Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in traditional Chinese medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to &quot;detoxify&quot; blood in terms of TCM and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and antidiabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects and potent inhibitory effects on the growth of tumors such as pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases such as cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock

An ultrasensitive SiO2-encapsulated alloyed CdZnSeS quantum dot-molecular beacon nanobiosensor for norovirus

AbstractUltrasensitive, rapid and selective diagnostic probes are urgently needed to overcome the limitations of traditional probes for norovirus (NV). Here, we report the detection of NV genogroup II via nucleic acid hybridization technology using a quantum dot (QD)-conjugated molecular beacon (MB) probe. To boost the sensitivity of the MB assay system, an ultrasensitive QD fluorophore with unique optical properties was synthesized, characterized and exploited as a fluorescence signal generator. Alloyed thioglycolic (TGA)-capped CdZnSeS QDs with a high photoluminescence (PL) quantum yield (QY) value of 92% were synthesized, and a modified silanization method was employed to encapsulate the thiol-capped QDs in a silica layer. The resulting highly luminescent alloyed SiO2-coated CdZnSeS QDs had a remarkable PL QY value of 98%. Transmission electron microscopy and dynamic light scattering confirmed the monodispersity of the alloyed nanocrystals, and zeta potential analysis confirmed their colloidal stability. Powder X-ray diffraction and PL lifetime measurements confirmed the surface modification of the QDs. The alloyed TGA-capped and SiO2-coated CdZnSeS QD-conjugated MB bioprobes detected extremely low concentrations of NV RNA. Ultrasensitive detection of low concentrations of NV RNA with a limit of detection (LOD) of 8.2copies/mL in human serum and a LOD of 9.3 copies/mL in buffer was achieved using the SiO2-coated CdZnSeS QD-MB probes, an increase in sensitivity of 3-fold compared with the detection limit for NV RNA using TGA-capped CdZnSeS QD-MBs. The additional merits of our detection system are rapidity, specificity and improved sensitivity over conventional molecular test probes

An essential role for dNTP homeostasis following CDK-induced replication stress

Replication stress is a common feature of cancer cells, and thus a potentially important therapeutic target. Here, we show that cyclindependent kinase (CDK)-induced replication stress, resulting from Wee1 inactivation, is synthetic lethal with mutations disrupting dNTP homeostasis in fission yeast. Wee1 inactivation leads to increased dNTP demand and replication stress through CDK-induced firing of dormant replication origins. Subsequent dNTP depletion leads to inefficient DNA replication, DNA damage and to genome instability. Cells respond to this replication stress by increasing dNTP supply through histone methyltransferase Set2-dependent MBF-induced expression of Cdc22, the catalytic subunit of ribonucleotide reductase (RNR). Disrupting dNTP synthesis following Wee1 inactivation, through abrogating Set2-dependent H3K36 trimethylation or DNA integrity checkpoint inactivation results in critically low dNTP levels, replication collapse and cell death, which can be rescued by increasing dNTP levels. These findings support a ‘dNTP supply and demand’ model in which maintaining dNTP homeostasis is essential to prevent replication catastrophe in response to CDK-induced replication stress