Autophagy in hematopoietic stem/progenitor cells exposed to heavy metals: Biological implications and toxicological relevance

The inherent toxicity of many metal compounds, together with their widespread environmental distribution, raises concerns of potential health hazards. Little is known about the impact of these important environmental toxicants on adult stem/progenitor cells, necessary for tissue homeostasis and repair. We recently reported that autophagy is implicated in the response of hematopoietic stem/progenitor cells to toxic concentrations of hexavalent chromium (Cr[VI]) and cadmium (Cd), two well known carcinogenic heavy metal cations. Autophagy may lead to cell death if carried out too extensively, but also acts as a survival pathway in cells under stress. In stem/progenitor cells, an autophagic phenotype could mitigate metal-induced toxicity, contributing to the conservation of tissue renewal capability. Given the key role of toxic damage to adult stem/progenitor cells in cancer, it is necessary to investigate whether autophagic responses modulate the carcinogenic potential of exposure to heavy metals during stem/progenitor cell differentiation.     

Trypanosoma cruzi disrupts myofibrillar organization and intracellular calcium levels in mouse neonatal cardiomyocytes

Immunofluorescence studies of normal and Trypanosoma cruzi-infected primary cultures of heart muscle cells were performed to gather information about the arrangement of myofibrillar components during the intracellular life cycle of this parasite. By using a panel of monoclonal antibodies against various myofibrillar proteins, a progressive disruption and loss of contractile proteins (such myosin and actin) of the host cell was detected during infection. The host cell formed a loose network of myofibrillar proteins around the parasites. Breakdown of the myofibrils occurred in regions where the parasites were present, and heavily infected cells showed myofibrillar proteins at their periphery. In parallel, we investigated the effect of T. cruzi infection on intracellular calcium levels by using a Ca²⁺ fluorescent indicator (confocal microscopy). Infected cardiomyocytes displayed a marked impairment in contractility, and calcium influxes became irregular and less intense when compared with those of non-infected cells. Our results demonstrate that T. cruzi infection dramatically affects calcium fluxes and causes myofibrillar breakdown disturbing cardiomyocyte contractility.Financial support through grants and scholarships from the Brazilian funding agencies FAPESP, CNPq, and CAPES is gratefully acknowledged.     

Carbon-13 labelling strategy for studying the ATP metabolism in individual yeast cells by micro-arrays for mass spectrometry

Isotopic labelling of cellular metabolites, used in conjunction with high-density micro-arrays for mass spectrometry enables observation of ATP metabolism in single yeast cells.     

A biomechanical analysis on the impact of episiotomy during childbirth

Episiotomy is still a controversy issue among physicians, despite the enormous growth of clinical research. Therefore, the potential of numerical modeling of anatomical structures to simulate biomechanical processes was exploited to realize quantitatively the real effects of the episiotomy and its consequences on the pelvic floor muscle. As such, a numerical model was used composed of pelvic floor muscles, a surface delimiting the anterior region, and a fetus body. A normal vaginal delivery without and with different episiotomies was simulated with the fetus in vertex presentation and occipitoanterior position. According to our numerical results, a mediolateral episiotomy has a protective effect, reducing the stress on the muscles, and the force required to delivery successfully up to 52.2 %. The intervention also has benefits on muscle injury, reducing the damage to a small zone. This study demonstrates the feasibility of using a computational modeling approach to study parturition, namely the capability to isolate and evaluate the mechanical significance of a single feature. It must, however, be taken into account that the numerical model does not assess problems that may occur as blood loss, infections and others, so it is necessary to examine whether the benefits of an intervention outweigh the risks.     

Optimization of arsenic phytoremediation using Eichhornia crassipes

This study aimed to evaluate the pH, phosphate, and nitrate in the process of arsenic absorption by Eichhornia crassipes (water hyacinth), using the surface response methodology, in order to optimize the process. The plants were exposed to a concentration of arsenic of 0.5 mg L^?1 (NaAsO₂) over a period of 10 days. The results indicated optimal levels for the absorption of arsenic by E. crassipes at pH equal to 7.5, absence of phosphate, and minimum nitrate level of 0.0887 mmol L^?1. For the tested concentration, E. crassipes was able to accumulate 498.4 mg kg^?1 of As (dry base) in its plant tissue and to reduce 83% of the initial concentration present in the aqueous medium where it was cultivated. The concentration of phosphorus in solution linearly increased the phosphorus content in the plants and negatively influenced the absorption of arsenic. The concentration of 0.5 mg L^?1 of As did not significantly affect the relative growth rate (RGR) and the tolerance index (TI). 94% of As (III) initially solubilized in water was converted by the end of the experiment period into As (V). The water hyacinth was important in the phytoremediation of arsenic when cultivated under optimal conditions for its removal.     

In vitro efficacy of <Emphasis Type="Italic">Metarhizium anisopliae</Emphasis> sensu lato against unfed <Emphasis Type="Italic">Amblyomma parvum</Emphasis> (Acari: Ixodidae)

Amblyomma parvum Aragão (Acari: Ixodidae) is a tick species found with wide distribution in the Neotropical region. Even though it is a wildlife-related tick, it is also a frequent parasite of domestic animals, is aggressive to human beings and may harbor pathogenic microorganisms. Therefore, it is a target species for control on domestic animals, particularly those at the rural–wildlife interface. Herein, the efficacy of two isolates (E9 and IBCB 425) of an entomopathogenic fungus, Metarhizium anisopliae sensu lato, already evaluated for ticks that parasitize domestic animals, was tested against unfed A. parvum adults. Both isolates displayed high acaricidal efficacy after immersion in fungal conidial suspensions for 5 min. Isolate E9 killed all ticks by the 7th day post-treatment, and isolate IBCB 425 did so by the 11th day. Tick mortality of 80 and 90% was achieved as early as the 3rd and 4th days, respectively, with both treatments. Thus, if a commercial M. anisopliae s.l. acaricide against domestic animal ticks is developed, it would also be effective against A. parvum.     

Giant kelp (Macrocystis) fishery in Atacama (Northern Chile): biological basis for management of the integrifolia morph

In Bahia Chasco, Atacama, the integrifolia morph of Macrocystis forms one of the most important kelp forests in northern Chile. In order to determine effects of local harvesting policies, we evaluated the population dynamics of this resource in intact, frequently disturbed, and permanently and completely harvested areas. Recruitment, frond length, reproductive phenology and standing crop were assessed monthly. In intact areas, frond length and ratio of reproductive individuals were higher, but recruitment was poorly stimulated. On the other hand, complete harvest had an important effect on Macrocystis population dynamics. Whereas recruitment and growth were much higher after harvest events, reproductive phenology was lower. The harvest techniques with different frequencies practiced by Bahia Chasco fishermen were less harmful than complete harvest, and we conclude that current exploitation techniques applied in this location are not deleterious for the giant kelp beds. They even have favorable effects by renewing the population through stimulation of sexual reproduction, recruitment and growth of young individuals.     

Validation of Housekeeping Genes in the Brains of Rats Submitted to Chronic Intermittent Hypoxia,a Sleep Apnea Model

Obstructive sleep apnea (OSA) is a syndrome characterized by intermittent nocturnal hypoxia, sleep fragmentation, hypercapnia and respiratory effort, and it has been associated with several complications, such as diabetes, hypertension and obesity. Quantitative real-time PCR has been performed in previous OSA-related studies; however, these studies were not validated using proper reference genes. We have examined the effects of chronic intermittent hypoxia (CIH), which is an experimental model mainly of cardiovascular consequences of OSA, on reference genes, including beta-actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hypoxanthine guanine phosphoribosyl transferase and eukaryotic 18S rRNA, in different areas of the brain. All stability analyses were performed using the geNorm, Normfinder and BestKeeper software programs. With exception of the 18S rRNA, all of the evaluated genes were shown to be stable following CIH exposure. However, gene stability rankings were dependent on the area of the brain that was analyzed and varied according to the software that was used. This study demonstrated that CIH affects various brain structures differently. With the exception of the 18S rRNA, all of the tested genes are suitable for use as housekeeping genes in expression analyses.     

Suramin, a novel antitumor compound

Suramin, a polyanionic compound originally synthesized for use as an antiparasitic agent, has recently entered clinical trials for the treatment of a variety of human cancers refractory to conventional modalities of therapy. This is based on suramin's ability to bind and to inactivate growth factor and enzyme systems critical to cellular homeostasis and proliferation. In addition, this compound possesses adrenocorticolytic properties in vivo and exerts significant cytostatic and cytocidal effects against a variety of human tumor cell lines in vitro. Pilot studies using suramin have thus far been conducted in adrenocortical carcinoma, prostate cancer refractory to conventional hormonal manipulation and nodular lymphomas.