176 research outputs found
Effect Of Zinc Cations On The Kinetics Of Supramolecular Assembly And The Chirality Of Porphyrin J-Aggregates
Dilute aqueous solutions of anionic meso-4-sulfonatophenyl-porphyrin (TPPS) extract zinc(ii) ions from glass or quartz surfaces at room temperature and efficiently form the corresponding metal complex (ZnTPPS). The partial or complete formation of ZnTPPS has been probed by UV/Vis spectroscopy and both static and time-resolved fluorescence. The source of zinc(ii) ions has been clearly identified through inductively coupled plasma optical emission spectrometry. The presence of increasing amounts of ZnTPPS slows down the rate of TPPS J-aggregate formation in acid solution. This influences the nucleation step and has a profound impact on the onset of chirality in these species. This evidence indicates the important role of this adventitious metal ion in the interpretation of various spectroscopic and kinetic data for the self-assembly of the TPPS porphyrin and provides some insights into controversial findings on their chirality. The use of this metal derivative as the starting compound for in situ formation of monomeric TPPS is suggested
Mechanism For Copper(II)-Mediated Disaggregation Of A Porphyrin J-Aggregate
J-aggregates of anionic meso-tetrakis(4-sulfonatophenyl)porphyrin form at intermediate pH (2.3–3.1) in the presence of NiSO₄ or ZnSO₄ (ionic strength, I.S. = 3.2 M). These aggregates convert to monomeric porphyrin units via metallation with copper(II) ions. The kinetics for the disassembly process, as monitored by UV/vis spectroscopy, exhibits zeroth-order behavior. The observed zeroth-order rate constants show a two-term dependence on copper(II) ion concentrations: linear and second order. Also observed is an inverse dependence on hydrogen ion concentration. Activation parameters have been determined for the disassembly process leading to ΔH^≠ = (+163 ± 15) kJ·mol⁻¹ and ΔS^≠ = (+136 ± 11) J·K⁻¹. A mechanism is proposed in which copper(II) cation is in pre-equilibrium with a reactive site at the rim of the J-aggregate. An intermediate copper species is thus formed that eventually leads to the final metallated porphyrin either through an assisted attack of a second metal ion or through a direct insertion of the metal cation into the macrocycle core
Variación morfológica y un nuevo y remarcable tipo de dimorfismo sexual en la población de Pseudocyclops xiphophorus del Lago Faro en el noreste de Sicilia
The population of P. xiphophorus in Lake Faro exhibits variation in the form of caudal seta V. In some specimens of both sexes, this seta is spatulate but in others it is slender and unmodified. Occasional specimens are asymmetrical. In addition to this variation in caudal seta form, the Lake Faro population displays variation in male body length and in the extent of the sexually dimorphic specialisation of the right swimming leg 2. The scale of these differences between the morphotypes might suggest their taxonomic treatment as distinct species. The modification of the distal two segments of the exopod of right leg 2 in the male is a unique sexual dimorphism. We infer, from the presence of this hook on the right exopod in adult males only, that it is involved in mating behaviour. Laboratory-based breeding experiments between females and males showing different combinations of these characters were also performed. Experiments comparing egg production rates in females that have mated with modified or unmodified males revealed no significant differences. It appears therefore that gene flow is not interrupted between the morphotypes and that reproductive segregation does not occur. Observations of male leg 5 morphology and musculature revealed no significant differences between the two P. xiphophorus morphotypes.La población de P. xiphophorus del Lago Faro muestra variación en la forma de la seda caudal V. En algunos especímenes de ambos sexos presenta una morfología espatulada, pero en otros es esbelta y sin modificaciones. Ocasionalmente, es asimétrica en un mismo individuo. La población del Lago Faro muestra también variabilidad en la longitud corporal del macho y en el grado de dimorfismo sexual de la segunda pata natatoria derecha. La escala de estas diferencias entre morfotipos podría sugerir un tratamiento específico diferente para ellos. La modificación en el macho de los dos segmentos distales del exópodo de la segunda pata natatoria derecha es un carácter desconocido en otras especies del género. La presencia de un gancho en el exópodo derecho de los machos sugiere que esta modificación está relacionada con el comportamiento de apareamiento. Se han realizado cruzamientos en laboratorio entre hembras y machos que mostraban diferentes combinaciones de estos caracteres. La comparación de las tasas de producción de huevos en hembras que se han cruzado con machos con o sin modificaciones no muestra diferencias significativas. Parece por tanto que el flujo génico entre morfotipos no está interrumpido y que no tiene lugar segregación reproductiva. La observación de la morfología y del patrón muscular de la pata quinta del macho no ha revelado tampoco diferencias significativas entre los dos morfotipos de P. xiphophorus
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Intracellular fate and impact on gene expression of doxorubicin/cyclodextrin-graphene nanomaterials at sub-toxic concentration
The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field
Reelin expression in human prostate cancer: a marker of tumor aggressiveness based on correlation with grade.
Reelin is a glycoprotein that plays a critical role in the regulation of neuronal migration during brain development and, since reelin has a role in the control of cell migration, it might represents an important factor in cancer pathology. In this study, 66 surgical specimens of prostate cancer were analyzed for reelin expression by immunohistochemical method. The reelin expression was correlated with Gleason score and individual Gleason patterns. Reelin expression was found in 39% prostate cancers. Stromal tissues, normal epithelial cells and prostate intraepithelial neoplasia (PIN) of any grade around and distant from cancer were always negative for reelin. Reelin was found in malignant prostatic epithelial glands of 50% cases Gleason score 10, 52% Gleason score 9, 56% Gleason score 8, 18% Gleason score 7, while no sample of prostate cancers with Gleason score 6 showed reelin expression (P=0,005). As reelin staining is frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns
The prevalence of triggers in paediatric migraine: a questionnaire study in 102 children and adolescents
The prevalence and characterization of migraine triggers have not been rigorously studied in children and adolescents. Using a questionnaire, we retrospectively studied the prevalence of 15 predefined trigger factors in a clinic-based population. In 102 children and adolescents fulfilling the Second Edition of The International Headache Classification criteria for paediatric migraine, at least one migraine trigger was reported by the patient and/or was the parents’ interpretation in 100% of patients. The mean number of migraine triggers reported per subject was 7. Mean time elapsed between exposure to a trigger factor and attack onset was comprised between 0 and 3 h in 88 patients (86%). The most common individual trigger was stress (75.5% of patients), followed by lack of sleep (69.6%), warm climate (68.6%) and video games (64.7%). Stress was also the most frequently reported migraine trigger always associated with attacks (24.5%). In conclusion, trigger factors were frequently reported by children and adolescents with migraine and stress was the most frequent
Molecular Characterization of the Mouse Superior Lateral Parabrachial Nucleus through Expression of the Transcription Factor Runx1
The ability to precisely identify separate neuronal populations is essential to the understanding of the development and function of different brain structures. This necessity is particularly evident in regions such as the brainstem, where the anatomy is quite complex and little is known about the identity, origin, and function of a number of distinct nuclei due to the lack of specific cellular markers. In this regard, the gene encoding the transcription factor Runx1 has emerged as a specific marker of restricted neuronal populations in the murine central and peripheral nervous systems. The aim of this study was to precisely characterize the expression of Runx1 in the developing and postnatal mouse brainstem.Anatomical and immunohistochemical studies were used to characterize mouse Runx1 expression in the brainstem. It is shown here that Runx1 is expressed in a restricted population of neurons located in the dorsolateral rostral hindbrain. These neurons define a structure that is ventromedial to the dorsal nucleus of the lateral lemniscus, dorsocaudal to the medial paralemniscal nucleus and rostral to the cerebellum. Runx1 expression in these cells is first observed at approximately gestational day 12.5, persists into the adult brain, and is lost in knockout mice lacking the transcription factor Atoh1, an important regulator of the development of neuronal lineages of the rhombic lip. Runx1-expressing neurons in the rostral hindbrain produce cholecystokinin and also co-express members of the Groucho/Transducin-like Enhancer of split protein family.Based on the anatomical and molecular characteristics of the Runx1-expressing cells in the rostral hindbrain, we propose that Runx1 expression in this region of the mouse brain defines the superior lateral parabrachial nucleus
Sex-Based Dimorphism of Anticancer Immune Response and Molecular Mechanisms of Immune Evasion
PURPOSE:
We previously demonstrated that sex influences response to immune checkpoint inhibitors. In this article, we investigate sex-based differences in the molecular mechanisms of anticancer immune response and immune evasion in patients with NSCLC.
EXPERIMENTAL DESIGN:
We analyzed (i) transcriptome data of 2,575 early-stage NSCLCs from seven different datasets; (ii) 327 tumor samples extensively characterized at the molecular level from the TRACERx lung study; (iii) two independent cohorts of 329 and 391 patients, respectively, with advanced NSCLC treated with anti–PD-1/anti–PD-L1 drugs.
RESULTS:
As compared with men, the tumor microenvironment (TME) of women was significantly enriched for a number of innate and adaptive immune cell types, including specific T-cell subpopulations. NSCLCs of men and women exploited different mechanisms of immune evasion. The TME of females was characterized by significantly greater T-cell dysfunction status, higher expression of inhibitory immune checkpoint molecules, and higher abundance of immune-suppressive cells, including cancer-associated fibroblasts, MDSCs, and regulatory T cells. In contrast, the TME of males was significantly enriched for a T-cell–excluded phenotype. We reported data supporting impaired neoantigens presentation to immune system in tumors of men, as molecular mechanism explaining the findings observed. Finally, in line with our results, we showed significant sex-based differences in the association between TMB and outcome of patients with advanced NSCLC treated with anti–PD-1/PD-L1 drugs.
CONCLUSIONS:
We demonstrated meaningful sex-based differences of anticancer immune response and immune evasion mechanisms, that may be exploited to improve immunotherapy efficacy for both women and men.
TRANSLATIONAL RELEVANCE:
It is well known that sex (i.e., the biological differences between men and women) and gender (i.e., behavioral differences associated with being male or female) are variables that affect immune responses to both foreign and selfantigens. Such sex- and gender-based dimorphism of immune system function, in turn reflects complex interactions between genes, hormones, the environment, and commensal microbiome composition. In our previous works, we showed that patients' sex is significantly associated with effectiveness of immune checkpoint inhibitors (ICIs) in patients with several solid tumors, including NSCLC. Here, we identified meaningful differences in molecular mechanisms that drive anticancer immune response as well as in immune evasion mechanisms exploited by NSCLCs arising in men and women. Importantly, we showed that all the findings reported, were not related to other variables potentially associated with sex such as patients' age, stage of disease, tumor histotype, and smoking status. The findings reported in this our work explain our previous clinical observations and can open this area to different immunotherapy strategies in males and females with NSCLC to further improve prognosis of both
Effect of sampling effort and sampling frequency on the composition of the planktonic crustacean assemblage: a case study of the river Danube
Although numerous studies have focused
on the seasonal dynamics of riverine zooplankton,
little is known about its short-term
variation. In order to examine the effects of sampling
frequency and sampling effort, microcrustacean
samples were collected at daily intervals
between 13 June and 21 July of 2007 in a parapotamal
side arm of the river Danube, Hungary.
Samples were also taken at biweekly intervals
from November 2006 to May 2008. After presenting
the community dynamics, the effect of
sampling effort was evaluated with two different
methods; the minimal sample size was also estimated.
We introduced a single index (potential
dynamic information loss; to determine the potential
loss of information when sampling frequency
is reduced. The formula was calculated for the total abundance, densities of the dominant taxa, adult/larva ratios of copepods and for two different diversity measures. Results suggest that abundances may experience notable fluctuations even within 1 week, as do diversities and adult/larva ratios
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