Determinarea rezistenţei la medicamente a Mycobacterium tuberculosis în materialul post-operator În prezent, odată cu îmbunătăţirea indicatorilor epidemiologici a tuberculozei, numărul pacienţilor cu ...forme de tuberculoză rezistente la medicamente este în creştere, ceea ce complică şi prelungeşte tratamentul acestor pacienţi. Scopul lucrării este de a studia rezistenţa la medicamente a Mycobacterium tuberculosis obţinută din material chirurgical. Materiale şi metode: Studiul a inclus 74 de pacienţi cu operaţii medicale şi diagnostice pe organele toracice. Toţi pacienţii au fost examinaţi prin metode standard: spută şi microscopie BAL cu bronhoscopie (în timpul procedurii), metode genetice moleculare, cultură pe medii nutritive dense şi lichide. Diagnosticul de tuberculoză a fost confirmat morfologic la toţi pacienţii prin examinarea histologică a materialului chirurgical. La analiza rezultatelor rezistenţei la medicamente, s-a constatat că, printre pacienţii nou identificaţi, mai mult de jumătate (59,3%) au avut rezistenţe multiple (44,6%) p <0,005 şi rezistenţă la medicamente pe scară largă (14,7%) p = 0,003. În acelaşi timp, 74,5% (n = 35/47) dintre pacienţi nu aveau MBT în spută înainte de operaţie. Se prezintă frecvenţa dezvoltării rezistenţei la medicamente la medicamentele antibacteriene de primă necesitate şi de rezervă, structura rezistenţei la medicamente în funcţie de grupul de înregistrare la dispensar. A fost efectuată o analiză comparativă a testării sensibilităţii la medicamente a MBT izolat din spută înainte de operaţie şi din material chirurgical. Rezultatele studiului au arătat un procent ridicat de rezistenţă la medicamente MBT obţinut în materialul de operaţie la pacienţii cu teste MBT negative. Mai mult de jumătate dintre pacienţii care nu au primit terapie antibacteriană înainte de intervenţia chirurgicală au rezistenţă multiplă la medicamente şi rezistenţă la medicamente pe scară largă, ceea ce sugerează o rezistenţă la medicamente primară regională ridicată a Mycobacterium tuberculosis
Amyloid aggregates of the calcium-binding EF-hand proteins, S100A8 and S100A9, have been found in the corpora amylacea of patients with prostate cancer and may play a role in carcinogenesis. Here we ...present a novel model system using the yeast Saccharomyces cerevisiae to study human S100A8 and S100A9 aggregation and toxicity. We found that S100A8, S100A9 and S100A8/9 cotransfomants form SDS-resistant non-toxic aggregates in yeast cells. Using fluorescently tagged proteins, we showed that S100A8 and S100A9 accumulate in foci. After prolonged induction, S100A8 foci localized to the cell vacuole, whereas the S100A9 foci remained in the cytoplasm when present alone, but entered the vacuole in cotransformants. Biochemical analysis of the proteins indicated that S100A8 and S100A9 alone or coexpressed together form amyloid-like aggregates in yeast. Expression of S100A8 and S100A9 in wild type yeast did not affect cell viability, but these proteins were toxic when expressed on a background of unrelated metastable temperature-sensitive mutant proteins, Cdc53-1p, Cdc34-2p, Srp1-31p and Sec27-1p. This finding suggests that the expression and aggregation of S100A8 and S100A9 may limit the capacity of the cellular proteostasis machinery. To test this hypothesis, we screened a set of chaperone deletion mutants and found that reducing the levels of the heat-shock proteins Hsp104p and Hsp70p was sufficient to induce S100A8 and S100A9 toxicity. This result indicates that the chaperone activity of the Hsp104/Hsp70 bi-chaperone system in wild type cells is sufficient to reduce S100A8 and S100A9 amyloid toxicity and preserve cellular proteostasis. Expression of human S100A8 and S100A9 in yeast thus provides a novel model system for the study of the interaction of amyloid deposits with the proteostasis machinery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A number of novel heteroligand Zn(II) complexes (
-
) of the general type (L
)Zn(NN) containing O,N,O'-, O,N,S-donor redox-active Schiff bases and neutral N,N'-chelating ligands (NN) were ...synthesized. The target Schiff bases L
H
were obtained as a result of the condensation of 3,5-di-
-butyl-2-hydroxybenzaldehyde with substituted
-aminophenols or
-aminothiophenol. These ligands with combination with 2,2'-bipyridine, 1,10-phenanthroline, and neocuproine are able to form stable complexes upon coordination with zinc(II) ion. The molecular structures of complexes
∙H
O,
, and
in crystal state were determined by means of single-crystal X-ray analysis. In the prepared complexes, the redox-active Schiff bases are in the form of doubly deprotonated dianions and act as chelating tridentate ligands. Complexes
and
possess a strongly distorted pentacoordinate geometry while
∙H
O is hexacoordinate and contains water molecule coordinated to the central zinc atom. The electrochemical properties of zinc(II) complexes were studied by the cyclic voltammetry. For the studied complexes, O,N,O'- or O,N,S-donor Schiff base ligands are predominantly involved in electrochemical transformations in the anodic region, while the N,N'-coordinated neutral nitrogen donor ligands demonstrate the electrochemical activity in the cathode potential range. A feature of complexes
and
with sterically hindered
-butyl groups is the possibility of the formation of relatively stable monocation and monoanion forms under electrochemical conditions. The values of the energy gap between the boundary redox orbitals were determined by electrochemical and spectral methods. The parameters obtained in the first case vary from 1.97 to 2.42 eV, while the optical bang gap reaches 2.87 eV.
New CoII substituted malonate field-induced molecular magnets {Rb6Co3(cpdc)6(H2O)12∙6H2O}n (1) and Cs2Co(cpdc)2(H2O)6n (2) (where cpdc2− stands for cyclopropane-1,1-dicarboxylic acid dianions) were ...synthesized. Both compounds contain mononuclear bischelate fragments {CoII(cpdc)2(H2O)2}2− where the quasi-octahedral cobalt environment (CoO6) is complemented by water molecules in apical positions. The alkali metal atoms play the role of connectors between the bischelate fragments to form 3D and 2D polymeric structures for 1 and 2, respectively. Analysis of dc magnetic data using the parametric Griffith Hamiltonian for high-spin CoII supported by ab initio calculations revealed that both compounds have an easy axis of magnetic anisotropy. Compounds 1 and 2 exhibit slow magnetic relaxation under an external magnetic field (HDC = 1000 and 1500 Oe, respectively).
A series of Ba-M
II
complexes with allylmalonic acid anions (Amal) BaM
II
(Amal)
2
(H
2
O)
3
n
(M
II
= Mn (
1
), Co (
2
), Cu (
3
), and Zn (
4
)) were synthesized by the reaction of the ...corresponding transition metal sulfates and barium allylmalonate. The complexes were characterized by IR and EPR spectroscopy, elemental analysis, magnetochemical and solid phase thermal decomposition studies as well as powder and single-crystal X-ray crystallography. The main structural block {M
II
(Amal)
2
(H
2
O)
x
} (
x
= 1 for M = Cu,
x
= 2 for M = Mn, Co, and Zn) in
1-4
is formed by two chelate allylmalonate anions and water molecule(s), which are surrounded by Ba
2+
ions. The magnetic measurements of paramagnetic compounds revealed weak ferromagnetic interactions between copper(
ii
) ions in
3
, and slow magnetic relaxation in non-zero field (
H
DC
= 1500 Oe) for
2
. According to the TGA data of
1-4
, they are decomposed
via
different pathways in the case of Mn
II
, Co
II
, Cu
II
, and Zn
II
since the metal ions catalyze different types of processes. However, all the complexes undergo polymerization of the allyl fragment.
A series of Ba-M
II
complexes with allylmalonic acid anions BaM
II
(Amal)
2
(H
2
O)
3
n
(M
II
= Mn, Co, Cu, and Zn) were synthesized. The magnetic measurements revealed slow magnetic relaxation in non-zero field (
H
DC
= 1500 Oe) for Co
II
ions.
The tetranuclear heterometallic complex Li2Zn2(piv)6(py)2 (1, where piv– = pivalate and py = pyridine) has been successfully employed as a presynthesized node for the construction of four porous ...metal–organic frameworks (MOFs) Li2Zn2(R-bdc)3(bpy)·solv (2-R, R-bdc2–; R = H, Br, NH2, NO2) by reaction with 4,4′-bipyridine (bpy) and terephthalate anionic linkers. The Li2Zn2 node is retained in the products, representing a rare example of the rational step-by-step design of isoreticular MOFs based on complex heterometallic building units. The permanent porosity of the activated frameworks was confirmed by gas adsorption isotherm measurements (N2, CO2, CH4). Three compounds, 2-H, 2-Br, and 2-NH 2 (but not 2-NO 2 ), feature extensive hysteresis between the adsorption and desorption curves in the N2 isotherms at low pressures. The substituents R decorate the inner surface and also control the aperture of the channels, the volume of the micropores, and the overall surface area, thus affecting both the gas uptake and adsorption selectivity. The highest CO2 absorption at ambient conditions (105 cm3·g–1 or 21 wt % at 273 K and 1 bar for 2-NO 2 ) is above the average values for microporous MOFs. The photoluminescent properties of the prototypic 2-H as well as the corresponding host–guest compounds with various aromatic molecules (benzene, toluene, anisole, and nitrobenzene) were systematically investigated. We discovered a rather complex pattern in the emission response of this material depending on the wavelength of excitation as well as the nature of the guest molecules. On the basis of the crystal structure of 2-H, a mechanism for these luminescent properties is proposed and discussed.
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