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https://www.readbyqxmd.com/read/27923041/crystal-structure-of-the-salmonella-typhimurium-effector-gtge
#1
Caishuang Xu, Guennadi Kozlov, Kathy Wong, Kalle Gehring, Miroslaw Cygler
Salmonella Typhimurium GtgE is an effector protein contributing to the virulence of this pathogen. It was shown to possess highly selective proteolytic activity against a subset of Rab proteins that helps in evasion of Salmonella-containing vacuole (SCV) fusion with lysosomes. Cys45, His151 and Asp169 are essential for proteolytic activity. The structure of a C-terminal fragment GtgE(79-214) indicated the presence of a papain-like fold. Here, we present the structure of GtgE(17-214) containing the fully assembled active site...
2016: PloS One
https://www.readbyqxmd.com/read/27921110/multifunctional-pei-entrapped-gold-nanoparticles-enable-efficient-delivery-of-therapeutic-sirna-into-glioblastoma-cells
#2
Lingdan Kong, Jieru Qiu, Wenjie Sun, Jia Yang, Mingwu Shen, Lu Wang, Xiangyang Shi
RNA interference (RNAi) has been considered as a promising strategy for effective treatment of cancer. However, the easy degradation of small interfering RNA (siRNA) limits its extensive applications in gene therapy. For safe and effective delivery of siRNA, a novel vector system possessing excellent biocompatibility, highly efficient transfection efficiency and specific targeting properties has to be considered. In this study, we report the use of polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) modified with an arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide via a poly(ethylene glycol) (PEG) spacer as a vector for Bcl-2 (B-cell lymphoma-2) siRNA delivery to glioblastoma cells...
December 6, 2016: Biomaterials Science
https://www.readbyqxmd.com/read/27920695/metastatic-alveolar-soft-part-sarcoma-responsive-to-pazopanib-after-progression-through-sunitinib-and-bevacizumab-two-cases
#3
William L Read, Felicia Williams
Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma with a propensity for lung metastases and indolent progression. ASPS is not responsive to chemotherapy, but there are case reports and small series describing benefit from drugs targeting the VEGF pathway. These drugs include sunitinib, cediranib and bevacizumab. There is no established second-line treatment for persons with ASPS progressing through first-line targeted therapy. We report two individuals with metastatic ASPS who obtained disease stabilization from sunitinib lasting over a year...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27918611/moisture-absorption-and-water-dynamics-in-the-powder-of-egg-albumen-peptide-met-pro-asp-ala-his-leu
#4
Shuailing Yang, Xuye Liu, Mingdi Zhang, Songyi Lin, Feng Chen
Moisture absorbed into the powder of Met-Pro-Asp-Ala-His-Leu (MPDAHL)-a novel egg albumen antioxidant peptide-profoundly affects its properties. In this study, we elucidated water dynamics in MPDAHL using DVS, DSC, and low-field (1) H NMR. Based on the DVS data, we found that MPDAHL sorption kinetics obey a parallel exponential model. DSC results indicated that both water and heating could change the microstructure of MPDAHL. The T2 parameters of NMR reflected the different phases of moisture absorption revealed that there were 4 categories of water with different states or mobility in the MPDAHL during the moisture absorption process...
December 5, 2016: Journal of Food Science
https://www.readbyqxmd.com/read/27917734/effective-antibiotic-conservation-by-emergency-antimicrobial-stewardship-during-a-drug-shortage
#5
Kevin Hsueh, Maria Reyes, Tamara Krekel, Ed Casabar, David J Ritchie, S Reza Jafarzadeh, Amanda J Hays, Michael A Lane, Michael J Durkin
We present the first description of an antimicrobial stewardship program (ASP) used to successfully manage a multi-antimicrobial drug shortage. Without resorting to formulary restriction, meropenem utilization decreased by 69% and piperacillin-tazobactam by 73%. During the shortage period, hospital mortality decreased (P=.03), while hospital length of stay remained unchanged. Infect Control Hosp Epidemiol 2016;1-4.
December 5, 2016: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/27917707/management-of-pneumonia-in-the-pediatric-critical-care-unit-an-area-for-antimicrobial-stewardship
#6
Aimee M Dassner, David P Nicolau, Jennifer E Girotto
Pediatric pneumonia is one of the most common causes of childhood infection requiring hospitalization and is a substantial driver of antimicrobial use among hospitalized children. About 12-20% of pediatric patients hospitalized with community-acquired pneumonia (CAP) require critical care. Additionally, nosocomial pneumonias (i.e. hospital-acquired and ventilator-associated pneumonias) are responsible for 15-53% of hospital-associated infections and are the most common indication for empiric antibiotics in the pediatric intensive care unit...
December 4, 2016: Current Pediatric Reviews
https://www.readbyqxmd.com/read/27915022/concentration-dependent-survival-and-neural-differentiation-of-murine-embryonic-stem-cells-cultured-on-polyethylene-glycol-dimethacrylate-hydrogels-possessing-a-continuous-concentration-gradient-of-n-cadherin-derived-peptide-his-ala-val-asp-lle
#7
Hyun Ju Lim, Matthew C Mosley, Yuki Kurosu, Laura A Smith Callahan
: N-cadherin cell-cell signaling plays a key role in the structure and function of the nervous system. However, few studies have incorporated bioactive signaling from n-cadherin into tissue engineering matrices. The present study uses a continuous gradient approach in polyethylene glycol dimethacrylate hydrogels to identify concentration dependent effects of n-cadherin peptide, His-Ala-Val-Asp-Lle (HAVDI), on murine embryonic stem cell survival and neural differentiation. The n-cadherin peptide was found to affect the expression of pluripotency marker, alkaline phosphatase, in murine embryonic stem cells cultured on n-cadherin peptide containing hydrogels in a concentration dependent manner...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27913975/clinical-impact-of-an-antibiotic-stewardship-program-at-a-children-s-hospital
#8
Brian R Lee, Jennifer L Goldman, Diana Yu, Angela L Myers, Leslie M Stach, Erin Hedican, Mary Anne Jackson, Jason G Newland
INTRODUCTION: Antibiotic stewardship programs (ASP) improve appropriate antibiotic use. Data are limited on the clinical benefit of ASPs in children's hospitals. This study's objective was to determine the impact of an ASP on length of stay (LOS) and readmission rate among patients admitted to children's hospitals. METHODS: Data from a prospective-audit-with-feedback ASP were used to examine the ASP review characteristics, including antibiotic(s) prescribed, clinical indication, recommendations made by the ASP, and agreement with recommendations...
December 2, 2016: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/27911737/the-conservation-of-phosphate-binding-residues-among-pht1-transporters-suggests-that-distinct-transport-affinities-are-unlikely-to-result-from-differences-in-the-phosphate-binding-site
#9
REVIEW
S Antony Ceasar, Alison Baker, Stephen P Muench, S Ignacimuthu, Stephen A Baldwin
The plant PHosphate Transporter 1 (PHT1) family of membrane proteins belongs to the major facilitator super family and plays a major role in the acquisition of inorganic phosphate (Pi) from the soil and its transport within the plant. These transporters have been well characterized for expression patterns, localization, and in some cases affinity. Furthermore, the crystal structure of a high-affinity eukaryotic phosphate transporter from the fungus Piriformospora indica (PiPT) has revealed important information on the residues involved in Pi transport...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911475/carboplatin-complexed-and-crgd-conjugated-unimolecular-nanoparticles-for-targeted-ovarian-cancer-therapy
#10
Yuyuan Wang, Liwei Wang, Guojun Chen, Shaoqin Gong
Platinum-based chemotherapy has been widely used to treat cancers including ovarian cancer; however, it suffers from dose-limiting toxicity. Judiciously designed drug nanocarriers can enhance the anticancer efficacy of platinum-based chemotherapy while reducing its systemic toxicity. Herein the authors report a stable and water-soluble unimolecular nanoparticle constructed from a hydrophilic multi-arm star block copolymer poly(amidoamine)-b-poly(aspartic acid)-b-poly(ethylene glycol) (PAMAM-PAsp-PEG) conjugated with both cRGD (cyclo(Arg-Gly-Asp-D-Phe-Cys) peptide and cyanine5 (Cy5) fluorescent dye as a platinum-based drug nanocarrier for targeted ovarian cancer therapy...
December 1, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27909427/biocombinatorial-synthesis-of-novel-lipopeptides-by-com-domain-mediated-reprogramming-of-the-plipastatin-nrps-complex
#11
Hongxia Liu, Ling Gao, Jinzhi Han, Zhi Ma, Zhaoxin Lu, Chen Dai, Chong Zhang, Xiaomei Bie
Both donors and acceptors of communication-mediating (COM) domains are essential for coordinating intermolecular communication within nonribosomal peptides synthetases (NRPSs) complexes. Different sets of COM domains provide selectivity, allowing NRPSs to utilize different natural biosynthetic templates. In this study, novel lipopeptides were synthesized by reprogramming the plipastatin biosynthetic machinery. A Thr-to-Asp point mutation was sufficient to shift the selectivity of the donor COM domain of ppsB toward that of ppsD...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27908619/correlation-of-dna-repair-gene-polymorphisms-with-clinical-outcome-in-patients-with-locally-advanced-non-small-cell-lung-cancer-receiving-induction-chemotherapy-followed-by-surgery
#12
Mariacarmela Santarpia, Jose Luis Ramirez, Itziar de Aguirre, Pilar Garrido, Maria Pérez Cano, Cristina Queralt, Jose Luis Gonzalez-Larriba, Amelia Insa, Mariano Provencio, Dolores Isla, Carlos Camps, Remei Blanco, Teresa Moran, Rafael Rosell
OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival...
November 9, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27906990/surveillance-of-helicobacter-pylori-antibiotic-susceptibility-in-indonesia-different-resistance-types-among-regions-and-with-novel-genetic-mutations
#13
Muhammad Miftahussurur, Ari Fahrial Syam, Iswan Abbas Nusi, Dadang Makmun, Langgeng Agung Waskito, Lukman Hakim Zein, Fardah Akil, Willy Brodus Uwan, David Simanjuntak, I Dewa Nyoman Wibawa, Jimmy Bradley Waleleng, Alexander Michael Joseph Saudale, Fauzi Yusuf, Syifa Mustika, Pangestu Adi, Ummi Maimunah, Hasan Maulahela, Yudith Annisa Ayu Rezkitha, Phawinee Subsomwong, Nasronudin, Dadik Rahardjo, Rumiko Suzuki, Junko Akada, Yoshio Yamaoka
Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes...
2016: PloS One
https://www.readbyqxmd.com/read/27905156/kinetics-of-the-competitive-reactions-of-isomerization-and-peptide-bond-cleavage-at-l-%C3%AE-and-d-%C3%AE-aspartyl-residues-in-an-%C3%AE-a-crystallin-fragment
#14
Kenzo Aki, Emiko Okamura
d-β-aspartyl (Asp) residue has been found in a living body such as aged lens crystallin, although l-α-amino acids are constituents in natural proteins. Isomerization from l-α- to d-β-Asp probably modulates structures to affect biochemical reactions. At Asp residue, isomerization and peptide bond cleavage compete with each other. To gain insight into how fast each reaction proceeds, the analysis requires the consideration of both pathways simultaneously and independently. No information has been provided, however, about these competitive processes because each reaction has been studied separately...
December 1, 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/27904082/design-and-synthesis-of-non-peptide-rgd-mimics-for-evaluation-of-their-utility-as-anti-platelet-agents
#15
Kazuhiro Higuchi, Hideki Hikita, Asumi Murayama, Daichi Yuri, Natsu Kobayakawa, Takashi Takahashi, Shigeru Kojima, Hiroko Ueno, Tomomi Hatakeyama, Airi Kato, Masanori Tayu, Etsuko Oyama, Shigeo Sugiyama, Kazuyuki Ishii, Hidenobu Takahashi, Tomomi Kawasaki
Arg-Gly-Asp (RGD) mimics were synthesized and their anti-platelet activity was evaluated. A concise method was developed for the synthesis of the target compounds from dehydroepiandrosterone and Wieland-Miescher and Hajos-Parrish ketones, which are suitable for readily available platform. Among the synthesized compounds, the perhydronaphthalene framework with a 3-(4-piperidinyl)propoxyl structure 3e possessed the highest anti-aggregative activity. The IC50 values of 3e were 0.91 mM (ADP initiation) and 0...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903891/cloning-independent-markerless-gene-editing-in-streptococcus-sanguinis-novel-insights-in-type-iv-pilus-biology
#16
Ishwori Gurung, Jamie-Lee Berry, Alexander M J Hall, Vladimir Pelicic
Streptococcus sanguinis, a naturally competent opportunistic human pathogen, is a Gram-positive workhorse for genomics. It has recently emerged as a model for the study of type IV pili (Tfp)-exceptionally widespread and important prokaryotic filaments. To enhance genetic manipulation of Streptococcus sanguinis, we have developed a cloning-independent methodology, which uses a counterselectable marker and allows sophisticated markerless gene editing in situ We illustrate the utility of this methodology by answering several questions regarding Tfp biology by (i) deleting single or mutiple genes, (ii) altering specific bases in genes of interest, and (iii) engineering genes to encode proteins with appended affinity tags...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903647/the-production-and-utilization-of-gdp-glucose-in-the-biosynthesis-of-trehalose-6-phosphate-by-streptomyces-venezuelae
#17
Matías D Asencion Diez, Farzana Miah, Clare E M Stevenson, David M Lawson, Alberto A Iglesias, Stephen Bornemann
Trehalose-6-phosphate synthase OtsA from streptomycetes is unusual in that it uses GDP-glucose as the donor substrate rather than the more commonly used UDP-glucose. We now confirm that OtsA from Streptomyces venezuelae has such a preference for GDP-glucose and can utilise ADP-glucose to some extent too. A crystal structure of the enzyme shows that it shares twin Rossmann-like domains with the UDP-glucose-specific OtsA from Escherichia coli However, it is structurally more similar to Streptomyces hygroscopicus VldE, a GDP-valienol-dependent pseudo-glycosyltransferase enzyme...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903075/australian-taipan-oxyuranus-spp-envenoming-clinical-effects-and-potential-benefits-of-early-antivenom-therapy-australian-snakebite-project-asp-25
#18
Christopher I Johnston, Nicole M Ryan, Margaret A O'Leary, Simon G A Brown, Geoffrey K Isbister
CONTEXT: Taipans (Oxyuranus spp.) are medically important venomous snakes from Australia and Papua New Guinea. The objective of this study was to describe taipan envenoming in Australian and its response to antivenom. METHODS: Confirmed taipan bites were recruited from the Australian Snakebite Project. Data were collected prospectively on all snakebites, including patient demographics, bite circumstances, clinical effects, laboratory results, complications and treatment...
November 30, 2016: Clinical Toxicology
https://www.readbyqxmd.com/read/27903001/right-in-front-of-our-eyes-evolution-of-streptococcal-toxic-shock-syndrome-with-ischemic-optic-neuropathy
#19
Salaheldin M Elhamamsy, Mazen O Al-Qadi, Taro Minami, Marguerite Neill
INTRODUCTION: Toxic shock syndrome occurs from dysregulation of host inflammatory responses. Toxin- producing strains of Group A streptococcus cause TSS. Ischemic optic neuropathy rarely complicates septic shock. We present a rare case of streptococcal pharyngitis complicated by septic arthritis and TSS with reversible blindness due to non-arteritic ischemic optic neuropathy. CASE: A 28-year-old man drove to our ED with exudative pharyngitis. A rapid streptococcal test was positive...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27903000/fournier-s-gangrene-of-the-penis-in-a-12-year-old-patient-secondary-to-phimosis
#20
Luther Ward, Daniel Eisenson, Jean-Louis Fils
We report a case of Fournier's gangrene in a 12-year-old boy from St. Boniface Hospital in Fond-des-Blancs, Haiti. Fournier's gangrene, a fulminant necrotizing fasciitis of the penis and scrotum, is a rare and life-threatening infection that requires hospitalization, broad-spectrum antibiotics, and surgical debridement.1-3 It is usually associated with impaired cellular immunity due to systemic disorders such as diabetes and liver disease.4,5 This patient had none of those risk factors, but had severe, longstanding phimosis, for which circumcision had been recommended many years before...
December 1, 2016: Rhode Island Medical Journal
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