6,109 research outputs found
Characterisation of ATP-Dependent Mur Ligases Involved in the Biogenesis of Cell Wall Peptidoglycan in Mycobacterium tuberculosis
No full textATP-dependent Mur ligases (Mur synthetases) play essential roles in the biosynthesis of cell wall peptidoglycan (PG) as they catalyze the ligation of key amino acid residues to the stem peptide at the expense of ATP hydrolysis, thus representing potential targets for antibacterial drug discovery. In this study we characterized the division/cell wall (dcw) operon and identified a promoter driving the co-transcription of mur synthetases along with key cell division genes such as ftsQ and ftsW. Furthermore, we have extended our previous investigations of MurE to MurC, MurD and MurF synthetases from Mycobacterium tuberculosis. Functional analyses of the pure recombinant enzymes revealed that the presence of divalent cations is an absolute requirement for their activities. We also observed that higher concentrations of ATP and UDP-sugar substrates were inhibitory for the activities of all Mur synthetases suggesting stringent control of the cytoplasmic steps of the peptidoglycan biosynthetic pathway. In line with the previous findings on the regulation of mycobacterial MurD and corynebacterial MurC synthetases via phosphorylation, we found that all of the Mur synthetases interacted with the Ser/Thr protein kinases, PknA and PknB. In addition, we critically analyzed the interaction network of all of the Mur synthetases with proteins involved in cell division and cell wall PG biosynthesis to re-evaluate the importance of these key enzymes as novel therapeutic targets in anti-tubercular drug discovery
mur
No full textmurre 2 nTurpentine on trees is called 'mur'. Mur is put on cuts to cause a cure.Turpentine on treesDNE-citW KirwinUsed IUsed IUsed I[see 'balsam' etc.] 'myrrh' 'mirr
mur
No full textmurre 1 nI shot a sea-bird, called in Newfoundland a mur, which is, I believe ; some species of mergulus....PRINTED ITEM DNE-citUsed I and SupUsed IUsed
Odkrivanje potencialnih aktinobakterijskih inhibitorjev za ligaze Mur bakterije Clostridium difficile
No full textClostridium difficile is one of the major public health treats nowadays as C. difficile infections (CDI) represent the majority of health-care associated infections. This is due to the standard treatment with broad-spectrum antibiotics, vancomycin and metronidazole. Treatment results in disrupted microbiota and that leads to decreased defence ability and increased reoccurrence of infections with C. difficile. Provided that, many studies in last decade are focused on finding new antimicrobial substances that would inhibit C. difficile and would not have a broad impact on gut microbiota. Mur ligases catalyse the initial steps on peptidoglycan assembly. Already known antimicrobials are mostly directed towards peptidoglycan machinery involved in the last part of peptidoglycan biosynthesis. In this reason, Mur ligase are representing a great target for new antimicrobials as this first steps of peptidoglycan assembly are not targeted by antimicrobials yet. Mur ligases could be used as multi target drug to increase the therapeutic effectiveness. This study is focused on detection of new potential inhibitors of Mur ligases from C. difficile. Genes for Mur ligases were obtained from native and synthetic DNA. Mur ligases genes were cloned into appropriate vectors and expressed in prokaryotic and eukaryotic system. The goal was to obtain active, recombinant protein. This part of the study was rather unsuccessful with native origin of C. difficile DNA. This was not surprising as C. difficile is known as genetically difficult to modify. The further work was proceeded with synthetic DNA of Mur ligases. Proteins of interest were successfully expressed and purified. After purification, MurE protein was selected for further analysis. Purified MurE ligase was concentrated and positively tested for its activity. Afterwards, several inhibitors from genus Streptomyces and clinically used antimicrobials, fosfomycin and D-cycloserin, were used in last step of the study, inhibitory assay.Bakterija Clostridium difficile v današnjem času predstavlja eno izmed večjih groženj javnemu zdravju, saj so infekcije s C. difficile eden od glavnih razlogov bolnišničnih okužb. Vzrok za to je predvsem zdravljenje infekcij s široko spektralnima antibiotikoma, vankomicinom in metronidazolom. Uporaba omenjenih antibiotikov podre ravnovesje črevesne mikrobiote in zmanjša zmožnost obrambe, ter posledično poveča možnost za ponoven pojav okužbe s C. difficile. Veliko zanimanje je zato usmerjeno v iskanje novih potencialnih tarč protimikrobnih sredstev, ki bi delovali bolj ozkospektralno in ne bi imeli velikega vpliva na črevesno mikrobioto. Mur ligaze so encimi, ki katalizirajo začetne korake sinteze peptidoglikana. Do sedaj znana antimikrobna sredstva so usmerjena predvsem na zadnje stopnje sinteze peptidoglikana, prvi koraki pa so še redko ciljani. V ta namen Mur ligaze predstavljajo velik potencial v iskanju novih protimikrobnih učinkovin. Ta študija se osredotoča na odkrivanje potencialnih inhibitorjev Mur ligaz iz C. difficile. Geni za Mur ligaze so bili pridobljeni iz naravne in sintetične DNA. Geni za Mur ligaze so bili klonirani v ustrezne vektorje za ekspresijo v prokariontskem in evkariontskem sistemu. Cilj je bil pridobiti aktivne rekombinantne Mur ligaze. Ta del študije je bil precej neuspešen z nativno DNA C. difficile. Nadaljnje delo je tako potekalo zgolj s sintetično DNA Mur ligaz. Ligaze so bile uspešno izražene in prečiščene. Po proteinski ekspresiji smo študijo osredotočili na MurE protein. Očiščeno MurE ligazo smo koncentrirali in testirali njeno aktivnost. S tem smo potrdili naše predvidevanje, saj smo pridobili aktivno, rekombinantno MurE ligazo. V zadnjem koraku študije smo izvedli test inhibicije z več različnimi inhibitorji iz rodu Streptomyces, ter dva antibiotika v klinični uporabi, fosfomicin in D-cikloserin
Chagas Disease after Heart Transplant in an endemic Country
No full textIntroducción:
La enfermedad de Chagas es una causa de falla cardiaca avanzada en Colombia y es la tercera causa de trasplante en nuestro centro. Los pacientes trasplantados requieren terapia inmunomoduladora, la cual podría aumentar el riesgo de reactivación de enfermedad infecciosas en el receptor; como la enfermedad de Chagas. La estimación de la prevalencia de este fenómeno en países como el nuestro es crucial con el fin de mejorar la atención de pacientes trasplantados.
Métodos:
Desarrollamos una cohorte retrospectiva de pacientes con trasplante cardiaco debido a cardiomiopatía Chagásica. El desenlace primario fue la prevalencia de reactivación de la enfermedad. Los desenlaces secundarios incluyeron la descripción de manifestaciones clínicas, la terapia inmunomoduladora usada en los pacientes con y sin reactivación y el tiempo transcurrido desde el trasplante a la reactivación. La reactivación fue definida como una prueba de RT - PCR positiva para T. Cruzi posterior al trasplante o una biopsia endomiocárdica compatible. La RT - PCR fue realizada en los pacientes con deterioro clínico, disfunción ventricular o según criterio del clínico.
Resultados:
En total 15 pacientes fueron incluidos en el análisis. El promedio de edad al momento del trasplante fue de 54 años (rango: 43 - 56 años), la mayoría hombres (67%). Reactivación de la enfermedad de Chagas fue diagnóstica en el 67% de los pacientes. La mediana de tiempo al momento de la reactivación posterior al trasplante fue de 12 meses (95% IC: 3,16 - 20,8 meses). La mortalidad durante el seguimiento fue de 0% y el seguimiento más largo fue de 11 años.
Los medicamentos más frecuentemente usados en los pacientes con reactivación fueron ciclosporina, tacrolimus y corticoides. Todos los pacientes con reactivación recibieron benznidazole.
Conclusiones:
Existe una alta prevalencia de reactivación de la enfermedad de Chagas en pacientes con trasplante cardiaco por cardiopatía chagásica; especialmente durante el primer año. Es necesario crear protocolos de seguimiento para un adecuado cuidado de estos pacientes; que contemplen la realización de pruebas de RT - PCR y biopsia endomiocárdica.Fundación Cardioinfantil - Instituto del CorazónUniversidad del RosarioUniversidad el BosqueEspecialista en Cardiología de AdultosEspecializaciónIntroduction
Chagas disease is a common cause of advanced heart failure in Colombia and is the third cause of heart transplant in our center. For transplanted patients, one of the mainstays is the immunomodulatory therapy, but that therapy makes the patients susceptible to Chagas disease reactivation. The estimation of this phenomenon in endemic countries like ours is crucial to improve its management.
Methods
We performed a retrospective cohort study of patients with heart transplant due to chagasic cardiomyopathy.
The primary outcome was the prevalence of Chagas disease reactivation. Secondary outcomes included the description of clinical manifestations, the immunomodulatory therapies previously used in the patients with and without reactivation and the time elapsed since the transplant until the reactivation.
Reactivation was defined as a positive RT-PCR for T.cruzi after heart transplant or a compatible endomyocardial biopsy. The RT-PCR test was performed when the patients presented clinical deterioration, ventricular disfunction, or either randomly according to physician criteria.
Results
Fifteen patients were included in the analysis. The mean age at the moment of the transplant was 54 YO (43-56), most of them were men (67%). Chagas disease reactivation was diagnosed in the 67% of patients. The median of the time to Chagas disease reactivation after the transplant is 12 months (95%-CI:3,16–20,8). The mortality during follow-up was 0% and the longest follow-up time was 11 years.
The most frequently used drugs in patients with reactivation were cyclosporine, tacrolimus and corticosteroids. All of the patients with reactivation received benznidazole.
Discussion
There is a high prevalence of Chagas disease reactivation in heart transplanted patients due to Chagasic cardiomyopathy, especially during the first year. Protocols for screening of these condition are necessary for an adequate care of these patients. RT-PCR test and myocardial biopsy role must be considered
Influence of various zooplankton taxa on the structure of phytoplankton community
No full textNamen magistrskega dela je ugotoviti učinke različnih zooplanktonskih taksonov
na strukturo fitoplanktonske združbe in povezave s spremembami koncentracij
nutrientov. Na jezeru Klostersee smo vzpostavili sistem 35 mezokozmosov s 7
različnimi okolji zooplanktonskih taksonov, prefiltriranih i z omenjenega jezera.
V obdobju od 14.7. do 2.8.2021 smo v teh okoljih vzorčili in določali količine
hranil, fitoplanktona in zooplanktona. Hranila in fitoplankton smo vzorčili zjutraj
z integriranim vzorčevalnikom z globine 4 m in 1 m. Zooplankton smo vzorčili
ponoči z vertikalnim dviganjem z globine 4 m. Ugotovili smo, da je pogostost
cianobakterij (Cyanophyta) naraščala zaradi selektivne paše herbivorega taksona
Eudiaptomus gracilis. Največje zmanjšanje gostote fitoplanktona, oziroma ple-
njenje s stranih herbivorov je bilo v okoljih s prevladujočim taksonom Cladocera
in v okoljih s taksonoma Cladocera in Copepoda. V okolju, kjer je bil priso-
ten predatorski takson Chaoborus spp., je bil takson Copepoda manj plenjen kot
takson Cladocera. Opazili smo upad koncentracije silikata in nato diatomej.The main goal of the master’s thesis was to investigate the influence of various
zooplankton taxa on the structure of phytoplankton community according to va-
riations in nutrient concentrations. A system of 35 mesocosms with 7 different
treatments was established on the Klostersee lake and filled with zooplankton
taxa from it. Experiment was performed from 14.7. to 2.8.2021, where nutrients,
phytoplankton and zooplankton were sampled and later analyzed. Nutrients and
phytoplankton were sampled in the mornings with the integrated sampler from 4
m and 1 m depth. Zooplankton was towed in the night time from 4 m depth. We
found that the frequency of cyanobacteria (Cyanophyta) increased due to selec-
tive grazing of the herbivorous taxa Eudiaptomus gracilis. The greatest decrease
of the phytoplankton density (herbivore predation) was in the treatments domi-
nated by Cladocera taxa and Cladocera taxa combined with Copepoda taxa. In
the treatments with carnivore taxa Chaoborus spp., the Copepoda taxa was less
preyed compared to the Cladocera taxa. A decline in the silica concentration and
later diatoms was noticed
mur
No full textmyrrh n"Only on the east coast of Newfoundland is the word 'mur' used instead of 'frankentine' which is found on fur trees." (sic)Used I and SupUsed INot use
mur bladders
No full textmyrrh n. . . I was/seen running for the house with the blood streaming down my leg. Solomon X, . . . happened to be at our house at the time. He hurried into the nearby woods and in a few moments came back with a handfull of mur bladders. These he squeezed out and mixed with molasses. The cut (about 1/2 inch deep) was covered with this mixture and wrapped with white cloth. In just one week my leg was completely healed. "Mur-bladders and molasses" was a very commonly used remedy up until a few years ago. Some still use it. As for myself I believe it to be a 100% perfect cure.DNE-citJH 6/71Used I and SupUsed IUsed I[see 'myrrh bladders'
Note de M. Lefebvre sur la découverte d'un mur couvert de graffitis grecs à Abydos (Égypte)
No full textCroiset Maurice. Note de M. Lefebvre sur la découverte d'un mur couvert de graffitis grecs à Abydos (Égypte). In: Comptes rendus des séances de l'Académie des Inscriptions et Belles-Lettres, 57ᵉ année, N. 7, 1913. pp. 465-468
Une traversée maritime, destination l'Europe: “Mur Méditerranée” de Louis-Philippe Dalembert
No full textEtude du roman "Mur Méditerranée" de Louis-Philippe Dalembert: structures et thèmes
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