The Pseudomonas syringae type III-secreted protein HopPtoD2 possesses protein tyrosine phosphatase activity and suppresses programmed cell death in plants

The bacterial plant pathogen Pseudomonas syringae possesses a type III protein secretion system that delivers many virulence proteins into plant cells. A subset of these proteins (called Avr proteins) is recognized by the plant’s innate immune system and triggers defences. One defence-associated response is the hypersensitive response (HR), a programmed cell death (PCD) of plant tissue. We have previously identified HopPtoD2 as a type III secreted protein from P. s. pv. tomato DC3000. Sequence analysis revealed that an N-terminal domain shared homology with Avr- PphD and a C-terminal domain was similar to protein tyrosine phosphatases (PTPs). We demonstrated that purified HopPtoD2 possessed PTP activity and this activity required a conserved catalytic Cys residue (Cys 378 ). Interestingly, HopPtoD2 was capable of suppressing the HR elicited by an avirulent P. syringae strain on Nicotiana benthamiana . HopPtoD2 derivatives that lacked Cys 378 no longer suppressed the HR indicating that HR suppression required PTP activity. A constitutively active MAPK kinase, called NtMEK2 DD , is capable of eliciting an HR-like cell death when transiently expressed in tobacco. When NtMEK2 DD and HopPtoD2 were co-delivered into plant cells, the HR was suppressed indicating that HopPtoD2 acts downstream of NtMEK2 DD . DC3000 hopPtoD2 mutants were slightly reduced in their ability to multiply in planta and displayed an enhanced ability to elicit an HR. The identification of HopPtoD2 as a PTP and a PCD suppressor suggests that the inactivation of MAPK pathways is a virulence strategy utilized by bacterial plant pathogens

A Review on the Special Radiotherapy Techniques of Colorectal Cancer

Colorectal cancer is one of the commonest cancers worldwide. Radiotherapy has been established as an indispensable component of treatment. Although conventional radiotherapy provides good local control, radiotherapy treatment side-effects, local recurrence and distant metastasis remain to be the concerns. With the recent technological advancements, various special radiotherapy treatment options have been offered. This review article discusses the recently-developed special radiotherapy treatment modalities for various conditions of colorectal cancer ranging from early stage, locally advanced stage, recurrent, and metastatic diseases. The discussion focuses on the areas of feasibility, local control, and survival benefits of the treatment modalities. This review also provides accounts of the future direction in radiotherapy of colorectal cancer with emphasis on the coming era of personalized radiotherapy

Microstructured Fibre Taper with Constant Outer Diameter

Department of Electrical Engineerin

Surveillance of emerging drugs of abuse in Hong Kong: Validation of an analytical tool

© 2015, Hong Kong Academy of Medicine Press. All rights reserved. Objective: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Design: Cross-sectional study. Setting: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. Participants: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Main outcome measures: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. Results: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. Conclusions: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.Link_to_subscribed_fulltex

H.E.S.S. observations of gamma-ray bursts in 2003-2007

Very-high-energy (VHE; >~100 GeV) gamma-rays are expected from gamma-ray bursts (GRBs) in some scenarios. Exploring this photon energy regime is necessary for understanding the energetics and properties of GRBs. GRBs have been one of the prime targets for the H.E.S.S. experiment, which makes use of four Imaging Atmospheric Cherenkov Telescopes (IACTs) to detect VHE gamma-rays. Dedicated observations of 32 GRB positions were made in the years 2003-2007 and a search for VHE gamma-ray counterparts of these GRBs was made. Depending on the visibility and observing conditions, the observations mostly start minutes to hours after the burst and typically last two hours. Results from observations of 22 GRB positions are presented and evidence of a VHE signal was found neither in observations of any individual GRBs, nor from stacking data from subsets of GRBs with higher expected VHE flux according to a model-independent ranking scheme. Upper limits for the VHE gamma-ray flux from the GRB positions were derived. For those GRBs with measured redshifts, differential upper limits at the energy threshold after correcting for absorption due to extra-galactic background light are also presented.Comment: 9 pages, 4 tables, 3 figure

Discovery of VHE gamma-rays from the high-frequency-peaked BL Lac object RGB J0152+017

Aims: The BL Lac object RGB J0152+017 (z=0.080) was predicted to be a very high-energy (VHE; > 100 GeV) gamma-ray source, due to its high X-ray and radio fluxes. Our aim is to understand the radiative processes by investigating the observed emission and its production mechanism using the High Energy Stereoscopic System (H.E.S.S.) experiment. Methods: We report recent observations of the BL Lac source RGB J0152+017 made in late October and November 2007 with the H.E.S.S. array consisting of four imaging atmospheric Cherenkov telescopes. Contemporaneous observations were made in X-rays by the Swift and RXTE satellites, in the optical band with the ATOM telescope, and in the radio band with the Nancay Radio Telescope. Results: A signal of 173 gamma-ray photons corresponding to a statistical significance of 6.6 sigma was found in the data. The energy spectrum of the source can be described by a powerlaw with a spectral index of 2.95+/-0.36stat+/-0.20syst. The integral flux above 300 GeV corresponds to ~2% of the flux of the Crab nebula. The source spectral energy distribution (SED) can be described using a two-component non-thermal synchrotron self-Compton (SSC) leptonic model, except in the optical band, which is dominated by a thermal host galaxy component. The parameters that are found are very close to those found in similar SSC studies in TeV blazars. Conclusions: RGB J0152+017 is discovered as a source of VHE gamma-rays by H.E.S.S. The location of its synchrotron peak, as derived from the SED in Swift data, allows clearly classification it as a high-frequency-peaked BL Lac (HBL).Comment: Accepted for publication in A&A Letters (5 pages, 4 figures

Common Polymorphisms in MTNR1B, G6PC2 and GCK Are Associated with Increased Fasting Plasma Glucose and Impaired Beta-Cell Function in Chinese Subjects

BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals

Ideal timing to transfer from an acute care hospital to an interdisciplinary inpatient rehabilitation program following a stroke: an exploratory study

BACKGROUND: Timely accessibility to organized inpatient stroke rehabilitation services may become compromised since the demand for rehabilitation services following stroke is rapidly growing with no promise of additional resources. This often leads to prolonged lengths of stays in acute care facilities for individuals surviving a stroke. It is believed that this delay spent in acute care facilities may inhibit the crucial motor recovery process taking place shortly after a stroke. It is important to document the ideal timing to initiate intensive inpatient stroke rehabilitation after the neurological event. Therefore, the objective of this study was to examine the specific influence of short, moderate and long onset-admission intervals (OAI) on rehabilitation outcomes across homogeneous subgroups of patients who were admitted to a standardized interdisciplinary inpatient stroke rehabilitation program. METHODS: A total of 418 patients discharged from the inpatient neurological rehabilitation program at the Montreal Rehabilitation Hospital Network after a first stroke (79% of all cases reviewed) were included in this retrospective study. After conducting a matching procedure across these patients based on the degree of disability, gender, and age, a total of 40 homogeneous triads (n = 120) were formed according to the three OAI subgroups: short (less than 20 days), moderate (between 20 and 40 days) or long (over 40 days; maximum of 70 days) OAI subgroups. The rehabilitation outcomes (admission and discharge Functional Independence Measure scores (FIM), absolute and relative FIM gain scores, rehabilitation length of stay, efficiency scores) were evaluated to test for differences between the three OAI subgroups. RESULTS: Analysis revealed that the three OAI subgroups were comparable for all rehabilitation outcomes studied. No statistical difference was found for admission (P = 0.305–0.972) and discharge (P = 0.083–0.367) FIM scores, absolute (P = 0.533–0.647) and relative (P = 0.496–0.812) FIM gain scores, rehabilitation length of stay (P = 0.096), and efficiency scores (P = 0.103–0.674). CONCLUSION: OAI does not seem to affect significantly inpatient stroke rehabilitation outcomes of patients referred from acute care facilities where rehabilitation services are rapidly initiated after the onset of the stroke and offered throughout their stay. However, other studies considering factors such as the type and intensity of the rehabilitation are required to support those results

Single Cell Analysis Facilitates Staging of Blimp1-Dependent Primordial Germ Cells Derived from Mouse Embryonic Stem Cells

The cell intrinsic programming that regulates mammalian primordial germ cell (PGC) development in the pre-gonadal stage is challenging to investigate. To overcome this we created a transgene-free method for generating PGCs in vitro (iPGCs) from mouse embryonic stem cells (ESCs). Using labeling for SSEA1 and cKit, two cell surface molecules used previously to isolate presumptive iPGCs, we show that not all SSEA1+/cKit+ double positive cells exhibit a PGC identity. Instead, we determined that selecting for cKitbright cells within the SSEA1+ fraction significantly enriches for the putative iPGC population. Single cell analysis comparing SSEA1+/cKitbright iPGCs to ESCs and embryonic PGCs demonstrates that 97% of single iPGCs co-express PGC signature genes Blimp1, Stella, Dnd1, Prdm14 and Dazl at similar levels to e9.5–10.5 PGCs, whereas 90% of single mouse ESC do not co-express PGC signature genes. For the 10% of ESCs that co-express PGC signature genes, the levels are significantly lower than iPGCs. Microarray analysis shows that iPGCs are transcriptionally distinct from ESCs and repress gene ontology groups associated with mesoderm and heart development. At the level of chromatin, iPGCs contain 5-methyl cytosine bases in their DNA at imprinted and non-imprinted loci, and are enriched in histone H3 lysine 27 trimethylation, yet do not have detectable levels of Mvh protein, consistent with a Blimp1-positive pre-gonadal PGC identity. In order to determine whether iPGC formation is dependent upon Blimp1, we generated Blimp1 null ESCs and found that loss of Blimp1 significantly depletes SSEA1/cKitbright iPGCs. Taken together, the generation of Blimp1-positive iPGCs from ESCs constitutes a robust model for examining cell-intrinsic regulation of PGCs during the Blimp1-positive stage of development