Myeloid/T-cell acute lymphoblastic leukemia in children and adults

Until recently, few molecular aberrations were recognized in T-cell acute lymphoblastic leukemia (T-ALL) and they were restricted to aberrations involving the T-cell receptor (TCR). The introduction of powerful technologies has allowed to identify novel rearrangements. In this context, we have performed a gene expression profiling analysis on a relatively large cohort (n=69) of adult patients with a diagnosis of T-ALL. By unsupervised clustering, we identified 5 subgroups. Of these, one branch included 7 patients (10%) whose gene expression profile resembled that of AML. These cases were characterized by the overexpression of a large set of myeloid-related genes, as well as of miR-223. Finally, these patients appear to have an unfavorable clinical course. This newly identified subset of T-ALL cases partly resembles the so-called ETP (early T-precursor) pediatric subgroup: both age groups have in fact a peculiar gene expression profile, an unfavorable outcome and an incidence of about 10%

Design of decorated self-assembling peptide hydrogels as architecture for mesenchymal stem cells

Hydrogels from self-assembling ionic complementary peptides have been receiving a lot of interest from the scientific community as mimetic of the extracellular matrix that can offer three-dimensional supports for cell growth or can become vehicles for the delivery of stem cells, drugs or bioactive proteins. In order to develop a 3D "architecture" for mesenchymal stem cells, we propose the introduction in the hydrogel of conjugates obtained by chemoselective ligation between a ionic-complementary self-assembling peptide (called EAK) and three different bioactive molecules: an adhesive sequence with 4 Glycine-Arginine-Glycine-Aspartic Acid-Serine-Proline (GRGDSP) motifs per chain, an adhesive peptide mapped on h-Vitronectin and the growth factor Insulin-like Growth Factor-1 (IGF-1). The mesenchymal stem cell adhesion assays showed a significant increase in adhesion and proliferation for the hydrogels decorated with each of the synthesized conjugates; moreover, such functionalized 3D hydrogels support cell spreading and elongation, validating the use of this class of self-assembly peptides-based material as very promising 3D model scaffolds for cell cultures, at variance of the less realistic 2D ones. Furthermore, small amplitude oscillatory shear tests showed that the presence of IGF-1-conjugate did not alter significantly the viscoelastic properties of the hydrogels even though differences were observed in the nanoscale structure of the scaffolds obtained by changing their composition, ranging from long, well-defined fibers for conjugates with adhesion sequences to the compact and dense film for the IGF-1-conjugate

Self-fluorescent antibiotic MoOx–hydroxyapatite: a nano-theranostic platform for bone infection therapies

Nowadays, the repair of large-size bone defects represents a huge medical challenge. A line of attack is the construction of advanced biomaterials having multifunctional properties. In this work, we show the creation of biocompatible MoOx-hydroxyapatite nanoparticles (nano-HA/MoOx) that simultaneously exhibit self-activated fluorescence and antibiotic skills. Along this text, we demonstrate that the insertion of molybdenum, an essential trace element, into the non-stoichiometric calcium deficient hydroxyapatite lattice generates intrinsic electronic point defects that exacerbate its epifluorescence blue emission and provokes new red emissions, preserving, always, its bioactivity. Furthermore, these point defects, acting as electron acceptors, stimulate the materials´ biological redox status and promote the death of pathogen microorganisms after their direct contact. A putative mechanism, by which bacteria lose electrons from their metabolic circuit that alter the function of their cytoplasmic membrane and potentially die, agrees with our results. Our findings highlight the importance of tuning the electronic communications between biomaterial interfaces and biological units, and support the use of self-fluorescent MoOx-hydroxyapatite nanoparticles as fundamental building blocks for new real-time imaging platforms against bone infection.Fil: Placente, Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Ruso, Juan Manuel. Universidad de Santiago de Compostela; EspañaFil: Baldini, Monica Diana. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Laiuppa, Juan Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Sieben, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química. Instituto de Electroquímica y Corrosión; ArgentinaFil: Santillán, Graciela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Messina, Paula Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

A Contribution of Beef to Human Health: A Review of the Role of the Animal Production Systems

Meat and meat products constitute important source of protein, fat, and several functional compounds. Although beef consumption may implicate possible negative impacts on human health, its consumption can also contribute to human health. Quality traits of beef, as well as its nutritional properties, depend on animal genetics, feeding, livestock practices, and post mortem procedures. Available data show that emerging beef production systems are able to improve both, quality and nutritional traits of beef in a sustainable way. In this context, Argentina’s actions are aimed at maximising beef beneficial effects and minimising its negative impact on human health, in a way of contributing to global food security.Fil: Pighín, Darío Gabriel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina. Universidad de Morón; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pazos, Adriana Alejandra. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina. Universidad de Morón; ArgentinaFil: Chamorro, Monica Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; ArgentinaFil: Paschetta, María Fernanda. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; ArgentinaFil: Cunzolo, Sebastian Abel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina. Universidad de Morón; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Godoy, Maria Fernanda. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; ArgentinaFil: Messina, Valeria Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Pordomingo, Anibal Javier. Instituto Nacional de Tecnología Agropecuaria. Centro Regional La Pampa-San Luis. Estación Experimental Agropecuaria Anguil; ArgentinaFil: Grigioni, Gabriela Maria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina. Universidad de Morón; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Turning renewable feedstocks into a valuable and efficient chiral phosphate salt catalyst

Solketal, the chiral acetonide of glycerol, has been employed as the starting material in the design of a novel punctually chiral phosphate sodium salt for catalytic applications in organic and asymmetric synthesis. The racemate and the two enantiomers of the substrate are economic and commercially available, straightforwardly prepared in high yields from naturally occurring feedstocks. Therefore, remarkably, both enantiomers of the final catalyst can be synthesized by simple procedures in high yield and in compliance with several principles of green chemistry. To further demonstrate the usefulness of the novel catalyst, its application in a solventless protocol for cyanohydrin synthesis from a series of aldehydes has been presented

Volatile organic compounds: instrumental and canine detections link an individual to the crime scene

Background: Whenever a crime is committed, forensic personnel are requested to collect every kind of evidence to establish the relationship between the suspects and the crime. When any evidence is accidentally destroyed or not found, there is one type of latent evidence that is always deposited at the crime scene: unique human scent. Recently, the use of trained canines to detect selective human scent at a crime scene has increased. To consolidate this kind of evidence, it is essential to have an exact knowledge and an awareness of the chemical signature of the volatile compounds that could indicate the presence of the alleged offender at the crime scene. This experimental study aims to detect the volatile organic compounds (VOCs) released from subjects who handled scent-articles to imprint their odor on. After handling, each scent-article was wrapped in sterile and VOC-free cotton gauzes for 48 h for secondary transfer. VOCs were detected by headspace/solid-phase microextraction-gas chromatography/mass spectrometry (HS/SPME-GC/MS) and well-trained dogs, at different time points (up to 15 days). Furthermore, the possibility of further DNA detection after contact was also investigated to propose a novel approach able to identify a subject from this latent forensic trace. Results: Data show that inter-individual human scent composition includes different VOCs, but dogs were able to discriminate the individual who touched the object at the crime scene. The dog training procedure showed excellent sensitivity (between 99.48 and 100%) and specificity (between 60 and 100%), having a positive predictive value (PPV) ranging between 97.94 and 100% and a negative predictive value (NPV) ranging between 85.71 and 100%. Preliminary work on DNA analysis released after contact yielded positive results, even if further studies are necessary, expanding the same experimentation to a larger sample with the aim of obtaining a statistically significant result. Conclusion: Data show that human scent is a good source of VOCs and a good target for canine training. The well-trained dog represents a specialized biological device able to discriminate personal human odor from any contaminants in the mixture detected by instrumental analysis. Furthermore, this study proposes the use of human scent as a forensic latent trace for DNA profiling

Smart drugs and neuroenhancement: what do we know?

Introduction: Smart drugs are among the most common drugs used by students. It is estimated that they are second in incidence after cannabis. Although they are usually used for diseases such as attention deficit hyperactivity disorder (ADHD) and dementia, in most cases the use of smart drugs is illegal and without a prescription. Methodological issues: A systematic review was conducted according to PRISMA guidelines. SCOPUS, Medline (using PubMed as a search engine), Embase, Web of Sciences, and Google Scholar were used as search engines from January 1, 1980 to June 1, 2021 to evaluate the association between smart drugs and neuro-enhancement. A total of 4715 articles were collected. Of these, 295 duplicates were removed. A total of 4380 articles did not meet the inclusion criteria. In conclusion, 48 articles were included in the present systematic review. Results: Most of the studies were survey studies, 1 was a prospective longitudinal study, 1 was a cross-over study, and 1 was an experimental study in an animal model (rats). The largest group of consumers was school or university students. The most frequent reasons for using smart drugs were: better concentration, neuro enhancement, stress reduction, time optimization, increased wake time, increased free time, and curiosity. There are conflicting opinions, in fact, regarding their actual functioning and benefit, it is not known whether the benefits reported by consumers are due to the drugs, the placebo effect or a combination of these. The real prevalence is underestimated: it is important that the scientific community focus on this issue with further studies on animal models to validate their efficacy

Transcranial Magnetic Stimulation as a Tool to Investigate Motor Cortex Excitability in Sport

Transcranial magnetic stimulation, since its introduction in 1985, has brought important innovations to the study of cortical excitability as it is a non-invasive method and, therefore, can be used both in healthy and sick subjects. Since the introduction of this cortical stimulation technique, it has been possible to deepen the neurophysiological aspects of motor activation and control. In this narrative review, we want to provide a brief overview regarding TMS as a tool to investigate changes in cortex excitability in athletes and highlight how this tool can be used to investigate the acute and chronic responses of the motor cortex in sport science. The parameters that could be used for the evaluation of cortical excitability and the relative relationship with motor coordination and muscle fatigue, will be also analyzed. Repetitive physical training is generally considered as a principal strategy for acquiring a motor skill, and this process can elicit cortical motor representational changes referred to as use-dependent plasticity. In training settings, physical practice combined with the observation of target movements can enhance cortical excitability and facilitate the process of learning. The data to date suggest that TMS is a valid technique to investigate the changes in motor cortex excitability in trained and untrained subjects. Recently, interest in the possible ergogenic effect of non-invasive brain stimulation in sport is growing and therefore in the future it could be useful to conduct new experiments to evaluate the impact on learning and motor performance of these techniques

Guinea worm wrap-up

Sudan has reported 21,433 cases of dracunculiasis in January-July 2002, which is 73% of the global total of cases reported for that period. Whereas 36% of 8,058 endemic villages reported in January-July 2001, 62% of 6,224 endemic villages reported during the same period of 2002. The latest update on the status of the program was discussed during the annual Program Review of the Guinea Worm Eradication Programs of Sudan, Ethiopia and Uganda, which was held in Nairobi, Kenya on September 30 \ue2\u20ac\u201c October 2. The percentage of known endemic villages with nylon filters in every household increased from 29% to 58% between 2001 and 2002, and over 7 million pipe filters were distributed in 2001. Health education talks by village volunteers have increased from 50% to 83% of endemic villages, and are increasingly supplemented by radio broadcasts in local languages. Abate usage is still limited in all but the northern states of the country

IL-4 Protects Tumor Cells from Anti-CD95 and Chemotherapeutic Agents via Up-Regulation of Antiapoptotic Proteins

We recently proposed that Th1 and Th2 cytokines exert opposite effects on the pathogenesis and clinical outcome of organ-specific autoimmunity by altering the expression of genes involved in target cell survival. Because a Th2 response against tumors is associated with poor prognosis, we investigated the ability of IL-4 to protect tumor cells from death receptor- and chemotherapy-induced apoptosis. We found that IL-4 treatment significantly reduced CD95 (Fas/APO-1)- and chemotherapeutic drug-induced apoptosis in prostate, breast, and bladder tumor cell lines. Analysis of antiapoptotic protein expression revealed that IL-4 stimulation resulted in up-regulation of cellular (c) FLIP/FLAME-1 and Bcl-xL. Exogenous expression of cFLIP/FLAME-1 inhibited apoptosis induced by CD95 and to a lesser extent by chemotherapy, while tumor cells transduced with Bcl-xLwere substantially protected both from CD95 and chemotherapeutic drug stimulation. Moreover, consistent IL-4 production and high expression of both cFLIP/FLAME-1 and Bcl-xLwere observed in primary prostate, breast, and bladder cancer in vivo. Finally, primary breast cancer cells acquired sensitivity to apoptosis in vitro only in the absence of IL-4. Thus, IL-4 protects tumor cells from CD95- and chemotherapy-induced apoptosis through the up-regulation of antiapoptotic proteins such as cFLIP/FLAME-1 and Bcl-xL. These findings may provide useful information for the development of therapeutic strategies aimed at restoring the functionality of apoptotic pathways in tumor cells