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Kang Jin, Kathy Hiu Laam Po, Wang Yeuk Kong, Chung Hei Lo, Chun Wah Lo, Ho Yin Lam, Amaya Sirinimal, Jonathan Avraham Reuven, Sheng Chen, Xuechen Li
Teixobactin is a structurally and mechanistically novel antimicrobial peptide with potent activities against Gram-positive pathogens. It contains l-allo-enduracididine (End) residue which is not readily accessible. In this report, we have used convergent Ser Ligation as the key step to prepare a series of teixobactin analogues with End being substituted with its non-isostere moieties. Among these analogues, compounds T16, T27 and T29 exhibited the best antimicrobial activities against different Gram-positive bacteria with MICs ranging from 0...
March 1, 2018: Bioorganic & Medicinal Chemistry
Kathy Hiu Laam Po, Edward Wai Chi Chan, Sheng Chen
This work investigated the molecular events driving the evolution of the CTX-M-type β-lactamases by the use of DNA shuffling of fragments of the bla CTX-M-14 and bla CTX-M-15 genes. Analysis of a total of 51 hybrid enzymes showed that enzymatic activity could be maintained in most cases, yet hybrids that were active possessed fewer amino acid substitutions than those that were inactive, suggesting that point mutations in the constructs rather than reshuffling of the fragments of the two target genes would more likely cause disruption of CTX-M activity...
December 2017: Antimicrobial Agents and Chemotherapy
Kang Jin, Kathy Hiu Laam Po, Shengxi Wang, Jonathan Avraham Reuven, Chi Nga Wai, Ho Ting Lau, Ting Ho Chan, Sheng Chen, Xuechen Li
Convergent Ser/Thr ligation has been used to prepare a series of teixobactin analogues (28 in total) to establish a structure-activity relationship of teixobactin. anti-bacterial evaluations of these synthetic analogues have revealed the critical amino acid residues and the sites tolerable of modifications. These studies will shed lights on the further development of teixobactin analogues with improved antibacterial activities.
September 15, 2017: Bioorganic & Medicinal Chemistry
David A L Newcombe, Andrew A Somogyi, Felix Bochner, Jason M White
Tolerance to the psychomotor impairing effects of opioid drugs is expected to develop with repeated dosing, but may be incomplete. The relationship between plasma opioid concentration and psychomotor function in opioid-dependent patients was examined to determine whether impairment was more likely at the time of highest plasma drug concentration. Sixteen patients participating in a cross-over trial comparing methadone and LAAM completed a tracking task (OSPAT) 11 times over the dosing-interval for methadone (24-hrs) and LAAM (48-hrs)...
June 2017: Experimental and Clinical Psychopharmacology
Roy Chun-Laam Ng, Koon-Ho Chan
The adipocyte-secreted protein adiponectin (APN) has several protective functions in the peripheral tissues including insulin sensitizing, anti-inflammatory and anti-oxidative effects that may benefit neurodegenerative diseases such as Alzheimer's disease (AD). In addition, dysregulation of cerebral insulin sensitivities and signaling activities have been implicated in AD. Emerging insights into the mechanistic roles of adiponectin and AD highlight the potential therapeutic effects for AD through insulin signaling...
March 9, 2017: International Journal of Molecular Sciences
Laam Li, Sébastien P Faucher
The water-borne Gram-negative bacterium Legionella pneumophila (Lp) is the causative agent of Legionnaires' disease. Lp is typically transmitted to humans from water systems, where it grows inside amoebae. Survival of Lp in water is central to its transmission to humans. A transcriptomic study previously identified many genes induced by Lp in water. One such gene, lpg2524, encodes a putative LuxR family transcriptional regulator. It was hypothesized that this gene could be involved in the survival of Lp in water...
June 2017: Canadian Journal of Microbiology
W Bradford DeLong, Nayak L Polissar, Moni B Neradilek, Leslie A Laam
No abstract text is available yet for this article.
January 2017: World Neurosurgery
Lin Yang, Hairong Nan, Jun Liang, Yin Hang Chan, Laam Chan, Rita Wing Man Sum, Yee Mei Kwan, Feifei Zhou, Huaiqing Meng, Lorna Kwai Ping Suen
BACKGROUND: People with diabetes are at a higher risk of influenza infections and severe complications. The vaccination of close contacts could offer indirect protection to people with diabetes; this is known as "herd immunity." The aim of this study is to investigate the vaccination rates of people with diabetes and their household contacts in Hong Kong. RESEARCH DESIGN AND METHODS: Face-to-face interviews with 158 patients diagnosed with Type 2 diabetes and aged ⩾65years were conducted in clinics...
February 7, 2017: Vaccine
Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling Lam, Koon Ho Chan
BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM...
November 25, 2016: Molecular Neurodegeneration
W Bradford DeLong, Nayak L Polissar, Moni B Neradilek, Leslie A Laam
STUDY DESIGN AND OBJECTIVES: This study by Srikandarajah et al is a retrospective cohort study of 200 CES patients. Although parts of the study appear to be well done we identified serious problems that impacted their conclusions. SUMMARY OF BACKGROUND DATA: There is strong consensus that patients with incomplete cauda equina syndrome (CESI) should be operated upon expeditiously to prevent progression to CES with urinary retention (CESR). There is controversy concerning optimal timing of surgery in patients who have entered CESR...
November 15, 2016: Spine
Laam Li, Sébastien P Faucher
The water-borne pathogen Legionella pneumophila (Lp) strongly expresses the lpg1659 gene in water. This gene encodes a hypothetical protein predicted to be a membrane protein using in silico analysis. While no conserved domains were identified in Lpg1659, similar proteins are found in many Legionella species and other aquatic bacteria. RT-qPCR showed that lpg1659 is positively regulated by the alternative sigma factor RpoS, which is essential for Lp to survive in water. These observations suggest an important role of this novel protein in the survival of Lp in water...
2016: Frontiers in Cellular and Infection Microbiology
W Bradford DeLong, Nayak L Polissar, Moni B Neradilek, Leslie A Laam
No abstract text is available yet for this article.
September 2016: World Neurosurgery
Kang Jin, Iek Hou Sam, Kathy Hiu Laam Po, Du'an Lin, Ebrahim H Ghazvini Zadeh, Sheng Chen, Yu Yuan, Xuechen Li
To cope with the global bacterial multidrug resistance, scientific communities have devoted significant efforts to develop novel antibiotics, particularly those with new modes of actions. Teixobactin, recently isolated from uncultured bacteria, is considered as a promising first-in-class drug candidate for clinical development. Herein, we report its total synthesis by a highly convergent Ser ligation approach and this strategy allows us to prepare several analogues of the natural product.
August 3, 2016: Nature Communications
Suzanne Nielsen, Briony Larance, Louisa Degenhardt, Linda Gowing, Chyanne Kehler, Nicholas Lintzeris
BACKGROUND: There are increasing concerns regarding pharmaceutical opioid harms including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. OBJECTIVES: To assess the effects of maintenance agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence...
May 9, 2016: Cochrane Database of Systematic Reviews
Jennifer R Tanner, Laam Li, Sébastien P Faucher, Ann Karen C Brassinga
The bacterium Legionella pneumophila is capable of intracellular replication within freshwater protozoa as well as human macrophages, the latter of which results in the serious pneumonia Legionnaires' disease. A primary factor involved in these host cell interactions is the Dot/Icm Type IV secretion system responsible for translocating effector proteins needed to establish and maintain the bacterial replicative niche. Several regulatory factors have been identified to control the expression of the Dot/Icm system and effectors, one of which is the CpxRA two-component system, suggesting essentiality for virulence...
June 2016: Molecular Microbiology
Kathy Hiu Laam Po, Edward Wai Chi Chan, Sheng Chen
This study assessed the functional importance of residues located at the i(-2) position of face 4 of the tandem repeat loops of the quinolone resistance protein QnrVC7 through mutagenesis studies. The i(-2) position of face 4 on different coils required residues with different natures. Some substitutions reduced the protective activity of QnrVC7, while some of them increased it. These findings advanced our understanding on the detailed structural organization and functional requirements of Qnr proteins.
January 11, 2016: Antimicrobial Agents and Chemotherapy
Laam Li, Nilmini Mendis, Hana Trigui, Sébastien P Faucher
BACKGROUND: Legionella pneumophila (Lp) is a water-borne opportunistic pathogen. In water, Lp can survive for an extended period of time until it encounters a permissive host. Therefore, identifying genes that are required for survival in water may help develop strategies to prevent Legionella outbreaks. RESULTS: We compared the global transcriptomic response of Lp grown in a rich medium to that of Lp exposed to an artificial freshwater medium (Fraquil) for 2, 6 and 24 hours...
2015: BMC Genomics
Manuel Grana, Darya Chyzhyk
Multivariate mathematical morphology (MMM) aims to extend the mathematical morphology from gray scale images to images whose pixels are high-dimensional vectors, such as remote sensing hyperspectral images and functional magnetic resonance images (fMRIs). Defining an ordering over the multidimensional image data space is a fundamental issue MMM, to ensure that ensuing morphological operators and filters are mathematically consistent. Recent approaches use the outputs of two-class classifiers to build such reduced orderings...
September 2016: IEEE Transactions on Neural Networks and Learning Systems
Brittany B Dennis, Monica Bawor, James Paul, Michael Varenbut, Jeff Daiter, Carolyn Plater, Guillaume Pare, David C Marsh, Andrew Worster, Dipika Desai, Lehana Thabane, Zainab Samaan
BACKGROUND: The consequences of opioid relapse among patients being treated with opioid substitution treatment (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Chronic pain is a major risk factor for opioid relapse within the addiction treatment setting. There exist a number of opioid maintenance therapies including methadone, buprenorphine, naltrexone, and levomethadyl acetate (LAAM), of which the mediating effects of pain on treatment attrition, substance use behavior, and social functioning may differ across therapies...
April 16, 2015: Systematic Reviews
Darya Chyzhyk, Manuel Graña, Döst Öngür, Ann K Shinn
Auditory hallucinations (AH) are a symptom that is most often associated with schizophrenia, but patients with other neuropsychiatric conditions, and even a small percentage of healthy individuals, may also experience AH. Elucidating the neural mechanisms underlying AH in schizophrenia may offer insight into the pathophysiology associated with AH more broadly across multiple neuropsychiatric disease conditions. In this paper, we address the problem of classifying schizophrenia patients with and without a history of AH, and healthy control (HC) subjects...
May 2015: International Journal of Neural Systems
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