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1.
BMJ Open Respir Res ; 11(1)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637114

ABSTRACT

BACKGROUND: Although bronchiectasis is reported to be associated with cardiovascular disease, evidence for an association with cardiovascular events (CVEs) is lacking. METHODS: A territory-wide retrospective cohort study was conducted in Hong Kong involving all patients who had bronchiectasis diagnosed in public hospitals and clinics between 1 January 1993 and 31 December 2017 were included. Patients were allocated to be exacerbator or non-exacerbator group based on hospitalzied bronchiecsis history and CVEs over the next 5 years determined. Propensity score matching was used to balance baseline characteristics. RESULTS: 10 714 bronchiectasis patients (mean age 69.6±14.4 years, 38.9% men), including 1230 in exacerbator group and 9484 in non-exacerbator group, were analysed. At 5 years, 113 (9.2%) subjects in the exacerbator group and 87 (7.1%) in the non-exacerbator group developed composite CVEs. After adjustment for age, sex, smoking and risk factors for cardiovascular disease, bronchiectasis exacerbation was associated with increased risks for acute myocardial infarction (AMI), congestive heart failure (CHF) and CVE compared with those in the non-exacerbator group with adjusted HR of 1.602 (95% CI 1.006-2.552, p value=0.047), 1.371 (95% CI 1.016-1.851, p value=0.039) and 1.238 (95% CI 1.001-1.532, p=0.049) in the whole cohort. Findings were similar for the propensity score-matched cohort for AMI and CVE. CONCLUSION: Patients who were hospitalised for exacerbation of bronchiectasis were at significantly increased risk of AMI, CHF and CVE over a 5-year follow-up period.


Subject(s)
Bronchiectasis , Cardiovascular Diseases , Heart Failure , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Female , Retrospective Studies , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Risk Factors , Bronchiectasis/epidemiology , Heart Failure/epidemiology , Heart Failure/etiology , Hospitalization
2.
Phys Eng Sci Med ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38656437

ABSTRACT

Cervical cancer is a common cancer in women globally, with treatment usually involving radiation therapy (RT). Accurate segmentation for the tumour site and organ-at-risks (OARs) could assist in the reduction of treatment side effects and improve treatment planning efficiency. Cervical cancer Magnetic Resonance Imaging (MRI) segmentation is challenging due to a limited amount of training data available and large inter- and intra- patient shape variation for OARs. The proposed Masked-Net consists of a masked encoder within the 3D U-Net to account for the large shape variation within the dataset, with additional dilated layers added to improve segmentation performance. A new loss function was introduced to consider the bounding box loss during training with the proposed Masked-Net. Transfer learning from a male pelvis MRI data with a similar field of view was included. The approaches were compared to the 3D U-Net which was widely used in MRI image segmentation. The data used consisted of 52 volumes obtained from 23 patients with stage IB to IVB cervical cancer across a maximum of 7 weeks of RT with manually contoured labels including the bladder, cervix, gross tumour volume, uterus and rectum. The model was trained and tested with a 5-fold cross validation. Outcomes were evaluated based on the Dice Similarity Coefficients (DSC), the Hausdorff Distance (HD) and the Mean Surface Distance (MSD). The proposed method accounted for the small dataset, large variations in OAR shape and tumour sizes with an average DSC, HD and MSD for all anatomical structures of 0.790, 30.19mm and 3.15mm respectively.

3.
BMC Nurs ; 23(1): 84, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38303009

ABSTRACT

BACKGROUND: Providing informal care for individuals with dementia is frequently a challenging and demanding experience that can have detrimental effects on the psychological well-being of caregivers. Regrettably, community-based caregiver services often prove inadequate, highlighting the necessity for innovative approaches to support caregivers. AIM: To test the efficacy of e-bibliotherapy in improving the psychological well-being of informal caregivers of people with dementia. METHOD: The study is divided into two phases. In phase 1, the research team will co-design the e-bibliotherapy app with caregivers. In phase 2, a randomized controlled trial will be conducted among 192 informal caregivers of people with dementia in Hong Kong. Caregivers will be randomly assigned to either the e-bibliotherapy group or the control group using simple randomization. Outcome measures will encompass caregivers' psychological well-being, caregiving appraisal, mental health, saliva cortisol levels as an indicator of stress, and health-related quality of life for caregivers. Data will be collected at baseline, immediately post intervention, and 3 months and 6 months post intervention. General linear mixed model will be employed to analyze intervention effects. Qualitative interviews will be undertaken to explore caregiver experiences within this study and evaluate intervention acceptability using conventional content analysis methods. DISCUSSION: This study represents a pioneering effort in utilizing e-bibliotherapy to enhance the psychological well-being of informal caregivers of individuals with dementia, addressing the existing gap in caregiver services and facilitating knowledge dissemination within the community. TRIAL REGISTRATION: The trial has been registered on ClinicalTrial.gov (Ref: NCT05927805).

4.
Water Res ; 249: 120974, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38101044

ABSTRACT

Noctiluca scintillans (red) is a widely distributed heterotrophic dinoflagellate and a prominent red tide forming species. This study investigated the effects of Noctiluca blooms on marine microbial diversity and functionality using multi-omics approaches. Our findings revealed significant differences in the community composition of Noctiluca-associated bacteria compared to those associated with autotrophic plankton and free-living bacteria in the surrounding seawater. The dominant bacterial groups within the Noctiluca-associated community shifted at various bloom stages, which could be attributed to changes in prey composition of Noctiluca. During the non-bloom stage, Burkholderiaceae, Carnobacteriaceae, and Pseudomonadaceae dominated the community, while Vibrionaceae became dominant during the bloom stage, and Saprospiraceae, Crocinitomicaceae, and Pirellulaceae thrived during the post-bloom stage. Compared to the non-bloom stage, Noctiluca-associated bacterial community at the bloom stage exhibited significant down-regulation of genes related to complex carbohydrate metabolism, while up-regulation of genes related to glucose transportation and utilization. Furthermore, we identified Vibrio anguillarum, a potential pathogenic bacterium to marine fish, as a major component of the Vibrionaceae family during the bloom stage. The occurrence of V. anguillarum associated with Noctiluca blooms may be attributed to the increased availability of its preferred carbon sources and its high capabilities in glucose transportation, motility and chemotaxis. Moreover, the presence of Vibrio infection genes (hap, hlyA, rtxA) encoding vibriolysin, hemolysin, and RTX (Repeats-in-toxin) toxin in the V. anguillarum genome, with the hap gene showing high expression levels during Noctiluca blooms, indicates an elevated risk of infection. This study underscores the unique composition of the bacterial community associated with red tide forming heterotrophic dinoflagellates and suggests that Noctiluca cells may serve as reservoirs and vectors for pathogenic bacteria, potentially posing a threat to fish-farming and the health of other marine organisms.


Subject(s)
Dinoflagellida , Dinoflagellida/physiology , Harmful Algal Bloom/physiology , Bacteria , Carbohydrates , Glucose
5.
Sci Adv ; 9(26): eadh1321, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37390215

ABSTRACT

Soft robotics offer unusual bioinspired solutions to challenging engineering problems. Colorful display and morphing appendages are vital signaling modalities used by natural creatures to camouflage, attract mates, or deter predators. Engineering these display capabilities using traditional light emitting devices is energy expensive and bulky and requires rigid substrates. Here, we use capillary-controlled robotic flapping fins to create switchable visual contrast and produce state-persistent, multipixel displays that are 1000- and 10-fold more energy efficient than light emitting devices and electronic paper, respectively. We reveal the bimorphic ability of these fins, whereby they switch between straight or bent stable equilibria. By controlling the droplets temperature across the fins, the multifunctional cells simultaneously exhibit infrared signals decoupled from the optical signals for multispectral display. The ultralow power, scalability, and mechanical compliance make them suitable for curvilinear and soft machines.


Subject(s)
Animal Fins , Robotics , Animals , Capillary Action , Electronics , Engineering
6.
Viruses ; 15(3)2023 02 23.
Article in English | MEDLINE | ID: mdl-36992319

ABSTRACT

While molnupiravir (MOV) and nirmatrelvir-ritonavir (NMV-r) were developed for treatment of mild to moderate COVID-19 infection, there has been a lack of data on the efficacy among unvaccinated adult patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. A territory-wide retrospective cohort study was conducted in Hong Kong to investigate the efficacy of MOV and NMV-r against severe outcomes of COVID-19 in unvaccinated adult patients with chronic respiratory diseases. A total of 3267 patients were included. NMV-r was effective in preventing respiratory failure (66.6%; 95% CI, 25.6-85.0%, p = 0.007), severe respiratory failure (77.0%; 95% CI, 6.9-94.3%, p = 0.039) with statistical significance, and COVID-19 related hospitalization (43.9%; 95% CI, -1.7-69.0%, p = 0.057) and in-hospital mortality (62.7%; 95% CI, -0.6-86.2, p = 0.051) with borderline statistical significance. MOV was effective in preventing COVID-19 related severe respiratory failure (48.2%; 95% CI 0.5-73.0, p = 0.048) and in-hospital mortality (58.3%; 95% CI 22.9-77.4, p = 0.005) but not hospitalization (p = 0.16) and respiratory failure (p = 0.10). In summary, both NMV-r and MOV are effective for reducing severe outcomes in unvaccinated COVID-19 patients with chronic respiratory diseases.


Subject(s)
COVID-19 , Respiratory Insufficiency , Adult , Humans , Outpatients , Ritonavir/therapeutic use , Retrospective Studies , COVID-19 Drug Treatment , SARS-CoV-2 , Respiratory Insufficiency/drug therapy , Antiviral Agents/therapeutic use
7.
mSystems ; 8(1): e0110622, 2023 02 23.
Article in English | MEDLINE | ID: mdl-36622156

ABSTRACT

Cluster 5 Synechococcus is one of the most important primary producers on earth. However, ecotypes of this genus exhibit complex geographical distributions, and the genetic basis of niche partitioning is still not fully understood. Here, we report distinct distributions of subcluster 5.1 (SC5.1) and subcluster 5.2 (SC5.2) Synechococcus in estuarine waters, and we reveal that salinity is the main factor determining their distribution. Clade III (belonging to SC5.1) and CB4 (belonging to SC5.2) are dominant clades in the study region, with different ecological distributions. We further conducted physiological, genomic, and transcriptomic studies of Synechococcus strains YX04-3 and HK05, which are affiliated with clade III and CB4, respectively. Laboratory tests showed that HK05 could grow at low salinity (13 ppt), whereas the growth of YX04-3 was suppressed when salinity decreased to 13 ppt. Genomic and transcriptomic analysis suggested that euryhaline clade CB4 is capable of dealing with a sudden drop of salinity by releasing compatible solutes through mechanosensitive channels that are coded by the mscL gene, decreasing biosynthesis of organic osmolytes, and increasing expression of heat shock proteins and high light-inducible proteins to protect photosystem. Furthermore, CB4 strain HK05 exhibited a higher growth rate when growing at low salinity than at high salinity. This is likely achieved by reducing its biosynthesis of organic osmolyte activity and increasing its photosynthetic activity at low salinity, which allowed it to enhance the assimilation of inorganic carbon and nitrogen. Together, these results provide new insights regarding the ecological distribution of SC5.2 and SC5.1 ecotypes and their underlying molecular mechanisms. IMPORTANCE Synechococcus is a group of unicellular Cyanobacteria that are widely distributed in global aquatic ecosystems. Salinity is a factor that affects the distribution of microorganisms in estuarine and coastal environments. In this study, we studied the distribution pattern of Synechococcus community along the salinity gradient in a subtropical estuary. By using omic methods, we unveiled genetic traits that determine the niche partitioning of euryhaline and strictly marine Synechococcus. We also explored the strategies employed by euryhaline Synechococcus to cope with a sudden drop of salinity, and revealed possible mechanisms for the higher growth rate of euryhaline Synechococcus in low salinity conditions. This study provides new insight into the genetic basis of niche partitioning of Synechococcus clades.


Subject(s)
Synechococcus , Synechococcus/genetics , Seawater/microbiology , Ecosystem , Transcriptome/genetics , Salt Tolerance/genetics , Genomics
8.
Article in English | MEDLINE | ID: mdl-36698687

ABSTRACT

Background: While different COVID-19 vaccines have been developed, there has been lack of data on the efficacy comparison between mRNA and inactivated whole virus vaccine among patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. Methods: This was a retrospective case control study on the efficacy of BNT162b2 (mRNA vaccine) and CoronaVac (inactivated whole virus vaccine) against COVID-19 in patients with chronic respiratory diseases. A total of 327 patients were included, with 109 patients infected with COVID-19 matched with 218 patients without COVID-19. The co-primary outcomes were vaccine effectiveness against symptomatic COVID-19, COVID-19-related hospitalization and COVID-19-related respiratory failure. Vaccine effectiveness was calculated using the formula (1-adjusted odds ratio) x 100. Results: Patients who received at least 2 doses of CoronaVac had lower risk of being hospitalized for COVID-19 and developing respiratory failure than those who did not have vaccination, with adjusted odds ratio (OR) of 0.189 (95% CI = 0.050-0.714, p = 0.014) and 0.128 (95% CI = 0.026-0.638, p = 0.012) respectively. Patients who received at least 2 doses of BNT162b2 had lower risk of being hospitalized for COVID-19 and developing respiratory failure than those who did not have vaccination with adjusted OR of 0.207 (95% CI = 0.043-0.962, p = 0.050) and 0.093 (95% CI = 0.011-0.827, p = 0.033) respectively. There was no statistically significant difference in the risks of being hospitalized for COVID-19 and developing respiratory failure between patients who received at least 2 doses of CoronaVac or BNT162b2. Conclusion: BNT162b2 and CoronaVac vaccines are effective in preventing hospitalization for COVID-19 and respiratory failure complicating COVID-19 among patients with chronic respiratory diseases. Patients with chronic respiratory diseases should be encouraged to have COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Pulmonary Disease, Chronic Obstructive , Respiration Disorders , Respiratory Insufficiency , Humans , BNT162 Vaccine , Case-Control Studies , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Respiratory Insufficiency/therapy , Retrospective Studies , RNA, Messenger
9.
Sci Total Environ ; 798: 149208, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34375229

ABSTRACT

The marine Synechococcus is a major primary producer in the global oceans. It is phylogenetically highly diverse, and its major phylogenetic lineages display clear spatial segregation among different marine environments. Here, we showed that the composition of the associated bacterial communities was related to the geographic origin of the different Synechococcus strains, and it was stable during long-term lab incubation. Of all the Synechococcus cultures investigated, the Rhodobacteraceae had a relatively high abundance and was the core bacterial family of the associated bacterial communities. In contrast, the Flavobacteriaceae were only abundant in the cultures collected from the South China Sea (which is warm and oligotrophic), whereas those of the Alteromonadaceae were abundant in the cultures from the coastal waters off Hong Kong and Xiamen. We also found that the Rhodobacteraceae had more ABC transporters and utilized a wider spectrum of carbon sources than did the Flavobacteriaceae and Alteromonadaceae. Moreover, the Alteromonadaceae had more transporters for importing phosphate and amino acids, but fewer transporters for importing oligosaccharides, polyol, and lipid, than the Flavobacteriaceae. Furthermore, metagenomic analysis demonstrated that bacteria involved in nitrate-ammonification prevailed in all the cultures. These results imply that networks formed by phytoplankton and heterotrophic bacteria might vary across habitats, and that different dominant bacterial groups play different roles in the phycosphere. This study provides new insight into the unique interactive and interdependent bond between phytoplankton and their associated microbiome, which may enhance our understanding of carbon and nutrient cycling in marine environments.


Subject(s)
Microbiota , Synechococcus , Heterotrophic Processes , Phylogeny , Seawater , Synechococcus/genetics
10.
Sci Total Environ ; 711: 135107, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-31818556

ABSTRACT

Noctiluca scintillans is a bloom-forming dinoflagellate, which is widely distributed in the global coastal seas. Associated bacteria have been proven to be essential for the survival and growth of zooplanktons. However, the diversity and function of bacteria associated with Noctiluca scintillans are under studied and largely unknown. Here, we examined the diversity and function of bacteria associated with field-acquired and laboratory-maintained Noctiluca cells. Our results showed that the bacterial communities associated with the laboratory-maintained Noctiluca were dominated by Rhodobacterales, whereas those associated with the field-acquired Noctiluca varied over time. In addition, major Noctiluca-associated bacteria had low relative abundance in the ambient environment. We also observed that when field-acquired Noctiluca were cultivated with a mono-species food source, there was a shift in the associated bacterial communities. Metagenomic analysis showed that genes involved in DNA replication/repair and osmotic regulation were more abundant than other genes in the Noctiluca-associated bacterial community. Furthermore, the associated bacteria were able to degrade various complex carbohydrates and actively participate in the nitrogen cycle in their host cells. In addition, a draft genome of the Rickettsiaceae strain was recovered, and we showed that the genome did not contain genes encoding hexokinase and phosphoglucomutase, two key enzymes involved in glucose utilization. Instead, the primary energy sources of this bacteria were shown to be glutamate, glutamine and pyruvate, which might be obtained from the host. We suggest that in return, the Rickettsiaceae strain is likely to provide cofactors and amino acids to the host. This study highlights the spatial and temporal complexity of bacterial communities associated with Noctiluca, and provides valuable insights into the interaction between a host and its associated bacteria.


Subject(s)
Dinoflagellida , Seawater
11.
J Biol Chem ; 293(30): 11709-11726, 2018 07 27.
Article in English | MEDLINE | ID: mdl-29887526

ABSTRACT

Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses, the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/metabolism , Coronavirus/physiology , Heat-Shock Proteins/metabolism , Middle East Respiratory Syndrome Coronavirus/physiology , Virus Attachment , Animals , Cell Line , Chlorocebus aethiops , Dipeptidyl Peptidase 4/metabolism , Endoplasmic Reticulum Chaperone BiP , Host-Pathogen Interactions , Humans , Protein Interaction Maps , Receptors, Virus/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
12.
J Biol Chem ; 292(47): 19503-19520, 2017 11 24.
Article in English | MEDLINE | ID: mdl-28972161

ABSTRACT

Cytotoxin-producing Klebsiella oxytoca is the causative agent of antibiotic-associated hemorrhagic colitis (AAHC). Recently, the cytotoxin associated with AAHC was identified as tilivalline, a known pentacyclic pyrrolobenzodiazepine (PBD) metabolite produced by K. oxytoca Although this assertion of tilivalline's role in AAHC is supported by evidence from animal experiments, some key aspects of this finding appear to be incompatible with toxicity mechanisms of known PBD toxins. We therefore hypothesized that K. oxytoca may produce some other uncharacterized cytotoxins. To address this question, we investigated whether tilivalline alone is indeed necessary and sufficient to induce cytotoxicity or whether K. oxytoca also produces other cytotoxins. LC-MS- and NMR-based metabolomic analyses revealed the presence of an abundant tricyclic PBD, provisionally designated kleboxymycin, in the supernatant of toxigenic K. oxytoca strains. Moreover, by generating multiple mutants with gene deletions affecting tilivalline biosynthesis, we show that a tryptophanase-deficient, tilivalline-negative K. oxytoca mutant induced cytotoxicity in vitro similar to tilivalline-positive K. oxytoca strains. Furthermore, synthetic kleboxymycin exhibited greater than 9-fold higher cytotoxicity than tilivalline in TC50 cell culture assays. We also found that the biosynthetic pathways for kleboxymycin and tilivalline appear to overlap, as tilivalline is an indole derivative of kleboxymycin. In summary, our results indicate that tilivalline is not essential for inducing cytotoxicity observed in K. oxytoca-associated AAHC and that kleboxymycin is a tilivalline-related bacterial metabolite with even higher cytotoxicity.


Subject(s)
Apoptosis/drug effects , Benzodiazepinones/pharmacology , Cytotoxins/pharmacology , Enterocolitis, Pseudomembranous/pathology , Klebsiella oxytoca/metabolism , Laryngeal Neoplasms/pathology , Anti-Bacterial Agents/adverse effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/microbiology , Carcinoma, Squamous Cell/pathology , Enterocolitis, Pseudomembranous/chemically induced , Enterocolitis, Pseudomembranous/microbiology , Humans , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella oxytoca/drug effects , Laryngeal Neoplasms/drug therapy , Laryngeal Neoplasms/microbiology , Peptides/pharmacology , Tumor Cells, Cultured
13.
J Virol ; 90(20): 9114-27, 2016 10 15.
Article in English | MEDLINE | ID: mdl-27489282

ABSTRACT

UNLABELLED: The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface. IMPORTANCE: Infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with the highest mortality rate among all known human-pathogenic coronaviruses. Currently, there are no approved vaccines or therapeutics against MERS-CoV infection. The identification of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV advanced our knowledge on the cell binding biology of MERS-CoV. Importantly, CEACAM5 could potentiate the entry of MERS-CoV by functioning as an attachment factor. In this regard, CEACAM5 could serve as a novel target, in addition to dipeptidyl peptidase-4 (DPP4), in the development of antiviral strategies for MERS-CoV.


Subject(s)
Carcinoembryonic Antigen/metabolism , Middle East Respiratory Syndrome Coronavirus/physiology , Receptors, Virus/metabolism , Virus Attachment , Virus Internalization , Animals , Cell Line , GPI-Linked Proteins/metabolism , Humans
14.
Nature ; 495(7440): 223-6, 2013 Mar 14.
Article in English | MEDLINE | ID: mdl-23467090

ABSTRACT

Recognition of sweet, bitter and umami tastes requires the non-vesicular release from taste bud cells of ATP, which acts as a neurotransmitter to activate afferent neural gustatory pathways. However, how ATP is released to fulfil this function is not fully understood. Here we show that calcium homeostasis modulator 1 (CALHM1), a voltage-gated ion channel, is indispensable for taste-stimuli-evoked ATP release from sweet-, bitter- and umami-sensing taste bud cells. Calhm1 knockout mice have severely impaired perceptions of sweet, bitter and umami compounds, whereas their recognition of sour and salty tastes remains mostly normal. Calhm1 deficiency affects taste perception without interfering with taste cell development or integrity. CALHM1 is expressed specifically in sweet/bitter/umami-sensing type II taste bud cells. Its heterologous expression induces a novel ATP permeability that releases ATP from cells in response to manipulations that activate the CALHM1 ion channel. Knockout of Calhm1 strongly reduces voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells by taste stimuli. Thus, CALHM1 is a voltage-gated ATP-release channel required for sweet, bitter and umami taste perception.


Subject(s)
Calcium Channels/metabolism , Synaptic Transmission , Taste/physiology , Adenosine Triphosphate/metabolism , Animals , Calcium Channels/deficiency , Calcium Channels/genetics , Female , HeLa Cells , Humans , Ion Channel Gating , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mice , Mice, Knockout , Receptors, Purinergic/metabolism , Single-Cell Analysis , Taste/genetics , Taste Buds/cytology , Taste Buds/metabolism
15.
J Clin Microbiol ; 50(11): 3780-2, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22972831

ABSTRACT

Staphylococcus aureus can be distinguished from similar coagulase-positive staphylococci by its absence of ß-galactosidase activity. This is commonly tested using o-nitrophenyl-ß-D-galactopyranoside (ONPG) as the substrate. Unexpectedly, 111 and 58 of 123 isolates displayed apparent ß-galactosidase activity in the ONPG assay and on the Vitek 2 system, respectively. Compositional analysis showed that the yellow coloration of the positive ONPG assay resulted from production of 2-aminophenoxazin-3-one. Alternative ß-galactosidase substrates like X-Gal (5-bromo-4-chloro-3-indolyl-ß-D-galactopyranoside) should be used for testing staphylococci.


Subject(s)
False Positive Reactions , Oxazines/metabolism , Staphylococcus aureus/enzymology , Staphylococcus aureus/metabolism , beta-Galactosidase/analysis , Animals , Galactosides/metabolism , Humans , Indoles/metabolism , Nitrophenylgalactosides/metabolism , Staphylococcal Infections/diagnosis , Staphylococcal Infections/veterinary , Staphylococcus aureus/isolation & purification
16.
Article in English | MEDLINE | ID: mdl-22336225

ABSTRACT

We have previously demonstrated that activation of prostacyclin (IP) receptors in human erythroleukemia (HEL) cells phosphorylates the signal transducer and activator of transcription 3 (STAT3) via Gα(s) and Gα(16) hybrid signalling. This current study was designed to determine if functional responses to cicaprost in HEL cells were dependent on STAT3 phosphorylation. Cicaprost significantly enhanced the rapid change in HEL cell morphology induced by phorbol-12-myristate-13-acetate (PMA), and this effect was inhibited by the IP receptor antagonist RO1138452 and a STAT3 inhibitory peptide. Other indicators of PMA-induced HEL cell differentiation, such as increased expression of CD41/CD61 and an increase in cell complexity/granularity, were inhibited by cicaprost in an IP receptor-dependent and STAT3-dependent manner. Although thrombopoietic cytokines promote megakaryocytic differentiation and platelet production via activation of STAT3, the predominant STAT3-dependent effects of cicaprost in HEL cells were inhibitory towards the process of PMA-induced megakaryocytopoeisis.


Subject(s)
Cell Differentiation , Leukemia, Erythroblastic, Acute/pathology , Receptors, Epoprostenol/metabolism , STAT3 Transcription Factor/metabolism , Cell Line, Tumor , Cell Survival , Epoprostenol/analogs & derivatives , Epoprostenol/pharmacology , Humans , Integrin beta3/metabolism , Leukemia, Erythroblastic, Acute/metabolism , Platelet Membrane Glycoprotein IIb/metabolism , Platelet Membrane Glycoprotein IIb/pharmacology , Signal Transduction , Tetradecanoylphorbol Acetate/pharmacology
17.
J Bacteriol ; 193(7): 1783-4, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21278300

ABSTRACT

Staphylococcus pseudintermedius is a member of the coagulase-positive staphylococci and is the commonest cause of canine pyoderma. We report the first genome sequence of S. pseudintermedius, which shows the presence of numerous virulence factors akin to those of the related human pathogen Staphylococcus aureus.


Subject(s)
Dog Diseases/microbiology , Genome, Bacterial , Pyoderma/veterinary , Staphylococcal Skin Infections/veterinary , Staphylococcus/classification , Staphylococcus/genetics , Animals , Dogs , Molecular Sequence Data , Pyoderma/microbiology , Staphylococcal Skin Infections/microbiology
18.
J Bacteriol ; 192(5): 1471-2, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20047907

ABSTRACT

Staphylococcus lugdunensis is a member of the coagulase-negative staphylococci and commonly found as part of the human skin flora. It is a significant cause of catheter-related bacteremia and also causes serious infections like native valve endocarditis in previously healthy individuals. We report the complete genome sequence of this medically important bacterium.


Subject(s)
DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Genome, Bacterial , Molecular Sequence Data , Sequence Analysis, DNA , Staphylococcus/genetics , Humans , Staphylococcal Infections/microbiology
19.
J Colloid Interface Sci ; 339(2): 424-33, 2009 Nov 15.
Article in English | MEDLINE | ID: mdl-19716565

ABSTRACT

We report the details of our success in conferring photocatalytic self-cleaning properties on keratin fibers using modified sol-gel colloids. To the best of our knowledge, we studied for the first time the crucial effect of the concentration of titanium dioxide precursor on colloid composition, properties, and biocompatibility in an attempt to enhance the properties and application of anatase titanium dioxide colloid to keratins. The transparency, the particle size distribution, and the crystallinity of synthesized colloids were systematically investigated. The compatibility of the colloids and keratin substrates is thoroughly compared and discussed. The insights presented contribute to the further understanding of the structure-property-use relationship of titanium dioxide in biomaterial applications.


Subject(s)
Keratins/chemistry , Titanium/chemistry , Biocompatible Materials , Catalysis , Colloids/chemistry , Particle Size , Photochemical Processes
20.
Dalton Trans ; (24): 4741-6, 2009 Jun 28.
Article in English | MEDLINE | ID: mdl-19513484

ABSTRACT

A modular design approach has been utilized to develop molecular 'pockets' featuring three integrated components, namely a phosphorescent Pt(II)-pi(organic) moiety, a suitable receptor group, and a rigid, conjugated connecting backbone, and the cavities therein are examined by NMR spectroscopy and an X-ray crystal structure. Their photophysical properties have been investigated; unusually for Pt-terpyridine derivatives, the complexes are luminescent (near-red (3)MLCT emission) in solution at room temperature. It has been shown that their emissive characteristics are affected by the nature of the backbone component but not the receptor group.


Subject(s)
Luminescent Agents/chemistry , Luminescent Agents/chemical synthesis , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/chemical synthesis , Pyridines/chemistry , Chemistry Techniques, Analytical , Crystallography, X-Ray , Luminescent Measurements , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Molecular Structure , Spectrophotometry , Spectrophotometry, Ultraviolet
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