Seed micromorphology and its taxonomic evidence in subfamily Alsinoideae (Caryophyllaceae)

Seed micromorphology of 13 species, belonging to four genera of subfamily Alsinoideae (Caryophyllaceae) were investigated with scanning electron microscopy (SEM), in order to assess their diagnostic significance at generic level and provide additional evidence on species delimitation, as well as correct identification and phylogenetic position. Genera and species of subfamily Alsinoideae exhibit great variation in ultrastructure and a high diversity of novel micromorphological characters were observed. Variation in seed shape, color, hilum, anticlinal wall, epidermal cell, cell surface, margins, and quantitative characters as length and width were studied in detail, compared, illustrated, and their taxonomic significant were discussed. Seed shapes of the species were classified as reniform, round, angular, subcircular, subreniform, and elliptical pyriform, with sub‐central, central, basal, and nearly basal hilum. Wavy, irregular, tetragonal, and elongated epidermal cells structure has been observed as an exomorphological character. The present findings show that the micromorphology of subfamily Alsinoideae provides taxonomic information and is helpful to distinguish different species. The results also explained that SEM morphology of seeds provide important data about affinity among taxa and give potential characters in delimitation of members of subfamily Alsinoideae at generic and species level. A principal component analysis allowed to highlight the most outsiders among seed micromorphology with a possible explanation. Taxonomic keys were developed based on micromorphological characters to delimit the species and useful for their quick identification within subfamily Alsinoideae.     

Immunohistochemical Analysis of DNA Repair- and Drug-Efflux-Associated Molecules in Tumor and Peritumor Areas of Glioblastoma

Glioblastoma (GBM), the most commonly occurring primary tumor arising within the central nervous system, is characterized by high invasiveness and poor prognosis. In spite of the improvement in surgical techniques, along with the administration of chemo- and radiation therapy and the incessant investigation in search of prospective therapeutic targets, the local recurrence that frequently occurs within the peritumoral brain tissue makes GBM the most malignant and terminal type of astrocytoma. In the current study, we investigated both GBM and peritumoral tissues obtained from 55 hospitalized patients and the expression of three molecules involved in the onset of resistance/unresponsiveness to chemotherapy: O6-methylguanine methyltransferase (MGMT), breast cancer resistance protein (BCRP1), and A2B5. We propose that the expression of these molecules in the peritumoral tissue might be crucial to promoting the development of early tumorigenic events in the tissue surrounding GBM as well as responsible for the recurrence originating in this apparently normal area and, accordingly, for the resistance to treatment with the standard chemotherapeutic regimen. Notably, the inverse correlation found between MGMT expression in peritumoral tissue and patients’ survival suggests a prognostic role for this protein.     

A threshold heating rate for single-stage heat treatments in glass-ceramics containing seed formers

The development of glass-ceramic materials is often achieved using an elementary microstructural strategy that splits the tasks of seed formation and functionality between two types of crystals. This strategy requires customized time-temperature ceramization protocols, which have been so far implemented using empirical parameters. Here, a more fundamental approach is proposed: the extent of overlap O_e between seed formation and volume crystallization is evaluated by calorimetric and dilatometric measurements, targeting the computation of a threshold heating rate q_t for effective single-stage heat treatments. The applicability of this novel parameter is tested in TiO₂-doped lithium magnesium aluminosilicate glass-ceramics, whose seed formation stage is thoroughly characterized by Raman spectroscopy and STEM. High-temperature X-ray diffraction demonstrates that insufficient seeding results in potentially weaker performances of the final products, due to large sizes and silica deficiency of the functional quartz solid solution crystals.     

Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation

Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds ( 7 and 10 ) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies.     

Effect of Regiochemistry and Methylation on the Anticancer Activity of a Ferrocene-Containing Organometallic Nucleoside Analogue

Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group and either a thyminyl or methylthyminyl group have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1 -(S,R_p), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1 -(S,R_p), which only differs from the lead compound in being substituted on two cyclopentadienyl rings rather than one, was over 20 times less cytotoxic. On the other hand, methylated derivatives of 1 -(S,R_p) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1 -(S,R_p) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity.     

Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB

Natural products are widely used as source for drugs development. An interesting example is represented by natural drugs developed against human topoisomerase IB, a ubiquitous enzyme involved in many cellular processes where several topological problems occur due the formation of supercoiled DNA. Human topoisomerase IB, involved in the solution of such problems relaxing the DNA cleaving and religating a single DNA strand, represents an important target in anticancer therapy. Several natural compounds inhibiting or poisoning this enzyme are under investigation as possible new drugs. This review summarizes the natural products that target human topoisomerase IB that may be used as the lead compounds to develop new anticancer drugs. Moreover, the natural compounds and their derivatives that are in clinical trial are also commented on.     

Cardiovascular adjustments to high- and low-intensity exercise do not regulate temporary threshold shifts

Sixteen adults cycled for 10 min at low and high intensities--with and without noise. The noise consisted of a 1/3 octave band-filtered noise with a 2,000 Hz center frequency at 104 dB SPL. Regardless of whether or not noise was present, systolic blood pressure increased 14% and 40% above rest during low- and high-intensity exercise, respectively. Heart rate also increased above rest (36% and 90%) during low- and high-intensity exercise, respectively. Temporary threshold shifts (TTS) at 3,000, 4,000 and 6,000 Hz could not be differentiated following low- and high-intensity exercise when noise was not present. We report significant TTS at the three frequencies following 10 min of noise exposure with or without low- or high-intensity exercise. TTS was not influenced by either the 14-40% increase in blood pressure or the 36-90% increase in heart rate induced by exercise. The inability of noise alone to influence either blood pressure or heart rate appears to implicate systems other than the cardiovascular in the regulation of hearing sensitivity.     

The toxicology and prevention of the risks of occupational exposure to aromatic polycyclic hydrocarbons. I. Guide lines for the prevention of the risks of occupational exposure to aromatic polycyclic hydrocarbons. Società Italiana Valori di Riferimento and Cattedra di Medicina del Lavoro, Università di Brescia]

AIM: Patients with various disorders of gastric function were studied with radiolabeled test meals of different consistency to elaborate the effect of ingested media on gastric peristalsis and emptying. METHODS: In 12 patients parameters of gastric function were intraindividually compared after ingestion of a semiliquid and a solid test meal. In addition to the standard evaluation derived from time activity curves condensed images were established from two fixed time intervals (early and late period). These images were used to evaluate the amplitude and frequency of gastric contractions using Fourier analysis. RESULTS: As expected gastric emptying was influenced by the consistency of the test meal. Mean emptying rates for the solid meal were significant lower than those for the semiliquid one (p < 0.01). The amplitude and frequency of gastric contractions, however, did not depend on the consistency of the test meal. Within the course of the examination contraction amplitudes significantly increased (p < 0.05) from the early to the late period using both, solid as well as semiliquid test meals. The frequency of gastric contractions remained unchanged. CONCLUSION: As shown by an intraindividual data comparison amplitude and frequency of gastric contractions seem to be independent of the consistency of ingested test meals whereas gastric emptying is significantly influenced by the administered media. Semiliquid meals offer advantages with respect to the shorter examination time and simpler preparation and therefore may be preferred for routine use. Since amplitudes seem to vary within the observation period standardized acquisition protocols are recommended for the evaluation of this parameter.     

A multi-objective sequential method for manufacturing cost and structural optimization of modular steel towers

This paper proposes a methodological approach for the multi-objective optimization of steel towers made from prefabricated cylindrical stacks that are typically used in the oil and gas sector. The goal is to support engineers in designing economical products while meeting structural requirements. The multi-objective optimization approach involves the minimization of the weights and costs related to the manufacturing and assembly phases. The method is based on three optimization levels. The first is used in the preliminary design phase when a company receives a request for proposal. Here, minimal information on the order is available, and the time available to formulate an offer is limited. Thus, parametric cost models and simplified 1-D geometries are used in the optimization loop performed by genetic algorithms. The second phase, the embodiment design phase, starts when an offer becomes an order based on the results of the first stage. Simplified shell geometries and advanced parametric cost models are used in the optimization loop, which present a restricted problem domain. In the last phase involving detailed design, a full 3-D computer-aided design model is generated, and specific finite-element method simulations are performed. The cost estimations, given the high levels of detail considered, are analytic and are performed using dedicated software.