| 1. |
- Jaromin, Anna, et al.
(författare)
-
Liposomal formulation of a new antifungal hybrid compound provides protection against Candida auris in the ex vivo skin colonization model.
- 2024
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 68:1
-
Tidskriftsartikel (refereegranskat)abstract
- The newly emerged pathogen, Candida auris, presents a serious threat to public health worldwide. This multidrug-resistant yeast often colonizes and persists on the skin of patients, can easily spread from person to person, and can cause life-threatening systemic infections. New antifungal therapies are therefore urgently needed to limit and control both superficial and systemic C. auris infections. In this study, we designed a novel antifungal agent, PQA-Az-13, that contains a combination of indazole, pyrrolidine, and arylpiperazine scaffolds substituted with a trifluoromethyl moiety. PQA-Az-13 demonstrated antifungal activity against biofilms of a set of 10 different C. auris clinical isolates, representing all four geographical clades distinguished within this species. This compound showed strong activity, with MIC values between 0.67 and 1.25 µg/mL. Cellular proteomics indicated that PQA-Az-13 partially or completely inhibited numerous enzymatic proteins in C. auris biofilms, particularly those involved in both amino acid biosynthesis and metabolism processes, as well as in general energy-producing processes. Due to its hydrophobic nature and limited aqueous solubility, PQA-Az-13 was encapsulated in cationic liposomes composed of soybean phosphatidylcholine (SPC), 1,2-dioleoyloxy-3-trimethylammonium-propane chloride (DOTAP), and N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl- sn-glycero-3-phosphoethanolamine, sodium salt (DSPE-PEG 2000), and characterized by biophysical and spectral techniques. These PQA-Az-13-loaded liposomes displayed a mean size of 76.4 nm, a positive charge of +45.0 mV, a high encapsulation efficiency of 97.2%, excellent stability, and no toxicity to normal human dermal fibroblasts. PQA-Az-13 liposomes demonstrated enhanced antifungal activity levels against both C. auris in in vitro biofilms and ex vivo skin colonization models. These initial results suggest that molecules like PQA-Az-13 warrant further study and development.
|
|
| 2. |
- Markovic, Slobodan B., et al.
(författare)
-
Geomorphological evolution of the Petrovaradin Fortress Palaeolithic site (Novi Sad, Serbia)
- 2021
-
Ingår i: Quaternary Research. - : Cambridge University Press. - 0033-5894 .- 1096-0287. ; 103, s. 21-34
-
Tidskriftsartikel (refereegranskat)abstract
- Two phases of archaeological investigation were performed in the Novi Sad City Museum at Petrovaradin Fortress. In this study, we summarize the results of geo-archaeological investigations of the second period of excavation inside the Novi Sad City Museum building. The fortress is situated on a Danube terrace with the top of the bedrock at ca.123 m asl. The investigated section consists of undisturbed fine-sandy silt. The grain-size distribution of the sediments indicates clearly its alluvial reworking but shows also a general similarity with typical primary loess in the region. All analyzed proxies indicate slightly stronger weathering in the upper part of the profile. Luminescence ages suggest that the investigated sequence covers the last glacial period and the terrace presumably formed during MIS 4. Subsequently, the Danube started its incision at the start of the next warmer period (MIS 3) onward. This terrace age and elevation enable us to derive an uplift rate of the terrace of ca. 0.73 mm/a for the last 60 ka, which seems to increase towards the present. Basal loessic material, in which artifacts occur, likely in the reworked position, indicate that the area close to today's Petrovaradin Fortress was already inhabited in MIS 5.
|
|
| 3. |
- Potter, Stephan, et al.
(författare)
-
Disentangling Sedimentary Pathways for the Pleniglacial Lower Danube Loess Based on Geochemical Signatures
- 2021
-
Ingår i: Frontiers in Earth Science. - : Frontiers Media S.A.. - 2296-6463. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- The source of aeolian sediments such as loess has been investigated since decades. Reliable knowledge on potential dust sources is crucial to understand past climatic and environmental conditions accompanying the dispersal of early modern humans (EMH) into Europe. Provenance studies are usually performed on small sample sets and most established methods are expensive and time-consuming. Here, we present the results of high-resolution geochemical analyses performed on five loess-palaeosol sequences from the Lower Danube Basin (LDB), a region, despite its importance as a trajectory for EMH, largely underrepresented in loess provenance studies. We compare our results with geochemical data of loess-palaeosol sequences from Austria, Hungary, Serbia, and Ukraine. Based on published literature, we thus evaluate five plausible sedimentary pathways for the LDB loess: 1) the Danube alluvium (DA) pathway, which constrains the transport and re-deposition of detrital material by the Danube and its tributaries; 2) the Carpathian Bending (CB) pathway, where sediment is mainly transported from the Cretaceous to Neogene flysch of the Eastern Carpathian Bending; 3) the Eastern Carpathian (EC) pathway, in which sediment is eroded from the flysch of the Outer Eastern Carpathians, transported by rivers, and deflated by northwesterly to westerly winds; 4) the glaciofluvial (GF) pathway, where dust is deflated from glacial outwash plains in nowadays Ukraine, and 5) the Black Sea (BS) pathway, where dust originates from the exposed shelf of the Black Sea. Based on geochemical data, we consider the DA pathway to be the major sediment trajectory for loess in the LDB. Especially the sequences located close to the Danube and the Dobrogea show similarities to sites in Central and Northeast Hungary as well as Northern Serbia. For the northeastern part of the LDB, we demonstrate that dust input is mainly sourced from primary material from the Eastern Carpathians. Mineralogical estimations and geochemical data render the CB pathway as an additional substantial source of detrital material for the loess of this area. We consider the influence of the GF pathway in the LDB as negligible, whereas some minor influences of the BS pathway cannot be ruled out based on geochemical data.
|
|
| 4. |
- Sümegi, Pál, et al.
(författare)
-
Comparison of High-Resolution 14C and Luminescence-Based Chronologies of the MIS 2 Madaras Loess/Paleosol Sequence, Hungary : Implications for Chronological Studies
- 2022
-
Ingår i: Quaternary. - : MDPI. - 2571-550X. ; 5:4
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous loess/paleosol sequences (LPS) in the Carpathian Basin span the period of Marine Isotope Stage (MIS) 2 and the last glacial maximum (LGM). Nevertheless, only two known records-Madaras and Dunaszekcso-preserve highly resolved records with absolute chronologies with minimal uncertainties, which enable the meaningful assessment of feedbacks and short-term climatic fluctuations over this period. The Madaras profile is located at the northern margin fringe of the Bacska loess plateau; Dunaszekcso, located on the Danube to its west, yields a chronology built on over 100 C-14 dates yet spans only part of MIS 2, missing half of the LGM including its peak. Here, we add to the previously published C-14 chronology for Madaras (15 dates) with an additional 17 C-14 and luminescence ages. Resulting age models built solely on quartz OSL and feldspar pIRIRSL data underestimate the C-14 based chronology, which is likely based on inaccuracies related to luminescence signal behavior; we observe age underestimations associated with unusual quartz behavior and significant signal loss, a phenomenon also observed in Serbian and Romanian loess, which may relate to non-sensitized grains from proximal sources. Our new chronology provides higher resolution than hitherto possible, yielding consistent 2 sigma uncertainties of similar to 150-200 years throughout the entire sequence. Our study indicates that the addition of further dates may not increase the chronological precision significantly. Additionally, the new age model is suitable for tackling centennial-scale changes. The mean sedimentation rate based on our new age-depth model (10.78 +/- 2.34 years/cm) is the highest yet recorded in the Carpathian Basin for MIS 2. The resolution of our age model is higher than that for the Greenland NGRIP ice core record. The referred horizons in our profile are all characterized by a drop in accumulation and a higher sand input, the latter most likely deriving from nearby re-exposed sand dunes.
|
|
