Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
1,582
result(s) for
"Martinez, Jonathan"
Sort by:
The last age of magic
\"Led by Wonder Woman this team of Zatanna, Swamp Thing, Man-Bat and Detective Chimp must bring the fight against all supernatural foes too big for the World's Greatest Super Heroes! Earth's magic once belonged to them. Now they want the magic back. But who exactly are they? It's up to the new Justice League Dark to find out and stop this nightmarish new threat at all costs! After the events of NO JUSTICE, Wonder Woman guides the misfit magic mix against enemies too fantastic even for the Justice League. Plus, what awful things are coming through the Tree of Wonder? Dark days ahead.\"-- Provided by publisher.
Book
Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions
The therapeutic efficacy of systemic drug-delivery vehicles depends on their ability to evade the immune system, cross the biological barriers of the body and localize at target tissues. White blood cells of the immune system—known as leukocytes—possess all of these properties and exert their targeting ability through cellular membrane interactions. Here, we show that nanoporous silicon particles can successfully perform all these actions when they are coated with cellular membranes purified from leukocytes. These hybrid particles, called leukolike vectors, can avoid being cleared by the immune system. Furthermore, they can communicate with endothelial cells through receptor–ligand interactions, and transport and release a payload across an inflamed reconstructed endothelium. Moreover, leukolike vectors retained their functions when injected
in vivo
, showing enhanced circulation time and improved accumulation in a tumour.
Camouflaging nanoporous silicon particles by functionalizing them with membranes isolated from white blood cells can delay their removal from the body and improve their accumulation in tumours.
Journal Article
Lysyl oxidase engineered lipid nanovesicles for the treatment of triple negative breast cancer
In the field of oncology research, a deeper understanding of tumor biology has shed light on the role of environmental conditions surrounding cancer cells. In this regard, targeting the tumor microenvironment has recently emerged as a new way to access this disease. In this work, a novel extracellular matrix (ECM)-targeting nanotherapeutic was engineered using a lipid-based nanoparticle chemically linked to an inhibitor of the ECM-related enzyme, lysyl oxidase 1 (LOX), that inhibits the crosslinking of elastin and collagen fibers. We demonstrated that, when the conjugated vesicles were loaded with the chemotherapeutic epirubicin, superior inhibition of triple negative breast cancer (TNBC) cell growth was observed both in vitro and in vivo. Moreover, in vivo results displayed prolonged survival, minimal cytotoxicity, and enhanced biocompatibility compared to free epirubicin and epirubicin-loaded nanoparticles. This all-in-one nano-based ECM-targeting chemotherapeutic may provide a key-enabling technology for the treatment of TNBC.
Journal Article
Crystal structure of the HMGA AT-hook 1 domain bound to the minor groove of AT-rich DNA and inhibition by antikinetoplastid drugs
High mobility group (HMG) proteins are intrinsically disordered nuclear non-histone chromosomal proteins that play an essential role in many biological processes by regulating the expression of numerous genes in eukaryote cells. HMGA proteins contain three DNA binding motifs, the “AT-hooks”, that bind preferentially to AT-rich sequences in the minor groove of B-form DNA. Understanding the interactions of AT-hook domains with DNA is very relevant from a medical point of view because HMGA proteins are involved in different conditions including cancer and parasitic diseases. We present here the first crystal structure (1.40 Å resolution) of the HMGA AT-hook 1 domain, bound to the minor groove of AT-rich DNA. In contrast to AT-hook 3 which bends DNA and shows a larger minor groove widening, AT-hook 1 binds neighbouring DNA molecules and displays moderate widening of DNA upon binding. The binding affinity and thermodynamics of binding were studied in solution with surface plasmon resonance (SPR)-biosensor and isothermal titration calorimetry (ITC) experiments. AT-hook 1 forms an entropy-driven 2:1 complex with (TTAA)
2
-containing DNA with relatively slow kinetics of association/dissociation. We show that
N
-phenylbenzamide-derived antikinetoplastid compounds (
1
–
3
) bind strongly and specifically to the minor groove of AT-DNA and compete with AT-hook 1 for binding. The central core of the molecule is the basis for the observed sequence selectivity of these compounds. These findings provide clues regarding a possible mode of action of DNA minor groove binding compounds that are relevant to major neglected tropical diseases such as leishmaniasis and trypanosomiasis.
Journal Article
Hyaluronic acid coatings as a simple and efficient approach to improve MSC homing toward the site of inflammation
A major challenge in regenerative medicine is to improve therapeutic cells’ delivery and targeting using an efficient and simple protocol. Mesenchymal stem cells (MSC) are currently employed for the treatment of inflammatory-based diseases, due to their powerful immunosoppressive potential. Here we report a simple and versatile method to transiently overexpress the hyaluronic acid (HA) receptor, CD44, on MSC membranes, to improve their homing potential towards an inflammatory site without affecting their behavior. The effect of HA-coatings on murine MSC was functionally determined both,
in vitro
and
in vivo
as a consequence of the transient CD44 overexpression induced by HA. Data obtained from the
in vitro
migration assay demonstrated a two-fold increase in the migratory potential of HA-treated MSC compared to untreated cells. In an LPS-induced inflamed ear murine model, HA-treated MSC demonstrated a significantly higher inflammatory targeting as observed at 72 hrs as compared to untreated cells. This increased accumulation for HA-treated MSC yielded a substantial reduction in inflammation as demonstrated by the decrease in the expression of pro-inflammatory markers and by the induction of a pro-regenerative environment.
Journal Article
Are Forecasts of the Tropical Cyclone Radius of Maximum Wind Skillful?
The radius of maximum wind (RMW) defines the location of the maximum winds in a tropical cyclone and is critical to understanding intensity change as well as hazard impacts. A comparison between the Hurricane Analysis and Forecast System (HAFS) models and two statistical models based off the National Hurricane Center official forecast is conducted relative to a new baseline climatology to better understand whether models have skill in forecasting the RMW of North Atlantic tropical cyclones. On average, the HAFS models are less skillful than the climatology and persistence baseline and two statistically derived RMW estimates. The performance of the HAFS models is dependent on intensity with better skill for stronger tropical cyclones compared to weaker tropical cyclones. To further improve guidance of tropical cyclone hazards, more work needs to be done to improve forecasts of tropical cyclone structure. Plain Language Summary The radius of maximum wind (RMW) is a key structural parameter of tropical cyclones that describes how far the strongest winds are from the storm's center. The RMW is closely tied to significant hazards such as wind, storm surge, and rainfall. However, little forecast guidance is provided for the RMW resulting in forecasters using climatological estimates to help communicate hazard risk. In order to better forecast the RMW, we need to understand the performance of the few guidance techniques available. We compare RMW forecasts from the Hurricane Analysis and Forecast System (HAFS) to two statistical models and a climatological estimate. Forecasts of the RMW from HAFS are not competitive with statistical derivations of the RMW with marginally better to comparable skill for stronger tropical cyclones. The results indicate that there is a strong need for future improvements to better predict tropical cyclone structure in addition to track and intensity. Key Points Forecasting the radius of maximum wind (RMW) is important for forecasting tropical cyclone hazards A RMW climatology and persistence model is created to determine forecast skill Statistical RMW forecasts are skillful and outperform dynamical model guidance
Journal Article
Teachers’ Emotional Exhaustion Scale (TEES): Development and Psychometric Validation
Emotional exhaustion in schoolteachers is a critical issue due to its detrimental effects on teachers’ mental health and its potential negative impact on students’ academic outcomes. This study aimed to develop and validate the Teachers’ Emotional Exhaustion Scale (TEES). The research was conducted in three phases. First, the scale items were developed and evaluated by expert judges using Aiken’s V for content validation. Second, an exploratory factor analysis (EFA) was performed on a sample of 153 teachers to identify the scale’s factor structure. Finally, a confirmatory factor analysis (CFA) was conducted with a sample of 473 Chilean teachers to validate the factor structure. The EFA revealed a two-factor structure comprising Emotional Fatigue (EF) and Emotional Hopelessness (EH), which was subsequently confirmed in the CFA. The model demonstrated a satisfactory fit to the data: χ2(32) = 142.383, p < 0.001; CMIN/DF = 1.651. The goodness-of-fit indices were robust (GFI = 0.933, NFI = 0.952, IFI = 0.981, TLI = 0.974, CFI = 0.980), and the RMSEA was 0.065, indicating an acceptable model fit. The TEES is a valid and reliable instrument for assessing emotional exhaustion in teachers. These findings are particularly relevant in the Chilean educational context, where teachers’ mental health and its implications for the education system are of increasing concern. The TEES can serve as a valuable tool for the early identification of emotional exhaustion, ultimately contributing to teacher retention and the improvement of educational quality.
Journal Article
The influence of parents and schools on developmental trajectories of antisocial behaviors in Caucasian and African American youths
African American youths are overrepresented in the American juvenile justice system relative to Caucasians. Yet, research on antisocial behaviors (ASB) has focused on predominantly Caucasian populations. Furthermore, relatively little is known about how environmental factors, such as supportive parenting (e.g., how close adolescents feel to their parent) and school connectedness (e.g., how supported adolescents feel at school), affect trajectories of ASB in Caucasians versus African Americans. This study mapped developmental trajectories of ASB in Caucasians (n = 10,764) and African Americans (n = 4,091) separately, using four waves of data from the National Longitudinal Study of Adolescent to Adult Health. We then examined supportive parenting and school connectedness on the trajectories of ASB. Four trajectories of ASB were identified for both Caucasians and African Americans: negligible, adolescence-peaked, low-persistence, and high-persistence ASB, although prevalence rates differed by racial-ethnic status. Supportive parenting reduced the risk of membership into the adolescence-peaked trajectory for both Caucasians and African Americans. However, school connectedness was less protective for African Americans than for Caucasians because it only predicted a lower risk of adolescence-peaked membership for African Americans. Findings may reflect the complex social dynamics between race and schools in the development of ASB.
Journal Article
Development and Characterization of a New Oral Antileishmanial Bis(pyridine-2-Carboxamidine) Drug Through Innovative Dissolution Testing in Biorelevant Media Combined with Pharmacokinetic Studies
Background/Objectives: Currently there are very few effective oral antileishmanial treatments. In this study we evaluated a new bis(pyridine-2-carboxamidine) antileishmanial drug (JNII40_base) and its hydrochloride salt (JNII40_HCl). Methods: The characterization studies performed allowed us to determine the crystallinity, hydration water, and presence of hydrogen bonds in these drugs. Different dissolution methods were employed to predict intestinal absorption. A high-performance liquid chromatography–mass spectrophotometry (HPLC-MS/MS) method was developed for the determination of JNII40 in plasma. Results: Pharmacokinetic studies in rats of JNII40_base at 100 and 20 mg/kg, and JNII40_HCl at 20 mg/kg, showed a non-linear pharmacokinetic at high doses. An innovative biorelevant medium of phosphate buffer pH 6.8 with polysorbate 80 at 0.6% (w/v) showed high concentration values for JNII40_base at 30 min, which predicts good intestinal absorption. These results were consistent with the bioavailability data, which exhibited a significant (p < 0.05) increase in maximum plasma concentration (Cmax) and a slight delay in time to maximum (Tmax) compared to JNII40_HCl. Furthermore, the sustained release of JNII40_base in this biorelevant media was related to high plasma concentration values at 24 h (C24h) observed in bioavailability studies. These plasma concentrations of JNII40_base were above the half-maximal inhibitory concentration (IC50) against promastigote and amastigote forms of Leishmania donovani, which is indicative of effectiveness and should reduce the occurrence of drug resistance during treatments. Conclusions: The bioavailability and pharmacokinetic data support the consideration of this drug for further in vivo studies as an oral antileishmanial treatment.
Journal Article
