Laminin-332 (Laminin-5) is the major motility ligand for B cell chronic lymphocytic leukemia.

Cell adhesion and motility are central aspects in the pathophysiology of B cell chronic lymphocytic leukemia (B-CLL), but the role of specific extracellular matrix proteins is still to be completely unveiled. Purified peripheral blood neoplastic cells of B-CLL patients migrated poorly on laminins-111,-411,-511, but showed pronounced motility on laminin (LM)-332 in a high percentage of cases. B-CLL cell motility on LM-332 was mediated by the alpha3beta1 integrin and was preferentially observed in cells carrying a mutated IgV(H) gene profile. Within normal lymph nodes, LM-332 was circumscribed around blood vessels and to areas corresponding to marginal zones, where it was deposited in a pattern reminiscent of reticular fibers. Conversely, in B-CLL involved lymph nodes, a positive LM-332 reticular mesh was diffusely evident, throughout the disrupted nodal architecture. In the present study we identified LM-332 as a crucial motility-promoting factor for B-CLL lymphocytes and as a potential constituent favoring the dissemination of B-CLL lymphocytes through vascular basement membranes and possibly lymph node compartments.     

Zebrafish Danio rerio shows behavioural cross-context consistency at larval and juvenile stages but no consistency between stages

Coping style is defined as a set of individual physiological and behavioural characteristics that are consistent across time and context. In the zebrafish Danio rerio, as well as in many other animals, several covariations have been established among behavioural, physiological and molecular responses. Nonetheless, not many studies have addressed the consistency in behavioural responses over time starting at the larval stage. Therefore, this study aimed to improve the understanding of behavioural consistency across contexts and over time in zebrafish from the larval to juvenile stages. Two distinct experiments were conducted: a larval stage experiment (from 8 to 21 days post fertilization, dpf) and a juvenile stage experiment (from 21 to 60 dpf). On one hand, the larval experiment allows to focus on the transition between 8 and 21 dpf, marked by significant morphological changes related to the end of larval stage and initiation of metamorphosis. On the other hand, the juvenile experiment allows to properly cover the period extending from the end of larval stage to the juvenile stage (60 dpf), including metamorphosis which is itself completed around 45 dpf. Within each experiment, boldness was determined using a group risk-taking test to identify bold and shy individuals. A novel environment test was then performed at the same age to evaluate consistency across contexts. Groups of fish (either bold or shy) were bathed in an alizarin red S solution for later identification of their initially determined coping style to evaluate behavioural consistency over time. Fish were then reared under common garden conditions and challenged again with the same behavioural tests at a later age (21 and 60 dpf in the larval and juvenile experiments, respectively). Behavioural consistency was observed across contexts, with bold fish being more active and expressing higher thigmotaxis regardless of age. There was, however, little behavioural consistency over age, suggesting behavioural plasticity during development. Moreover, the use of alizarin red S to conduct this experiment provides new perspectives for the further study of the longitudinal evolution of various traits, including behaviour, over life stages in fish.     

Suppression Effects on Pineapple Soil-Borne Pathogens by <i>Crotalaria juncea</i>, Dolomitic Lime and Plastic Mulch Cover on MD-2 Hybrid Cultivar

The development and implementation of sustainable and environmentally friendly agricultural practices are indispensable as alternatives to pesticide use and to keep populations of soil-borne plant pathogens at levels that do not affect crop productivity. The present research evaluates the incidence of soil-borne phytopathogens on the pineapple variety MD-2, which was subjected to different treatments: Incorporation of Crotalaria juncea into the soil (organic amendment), application of dolomitic lime to soil (inorganic amendment), and the use of plastic mulch covering the soil. During the crop cycle (15 months), the following variables were evaluated: plant height (cm), fruit weight (kg·plant⁻¹ ), crop yield (ton·ha⁻¹ ), the bud root disease incidence caused by Phytophthora nicotianae, number of soil phytoparasitic nematodes and colony-forming-units (CFUs) of soil fungi and oomycetes. The results indicate that Crotalaria juncea treatment reduced the pathogen population (nematode and oomycetes) at levels that did not affect crop development, so that yield increased (18–20%). The incorporation of C. juncea into the soil as an organic amendment favors the populations of fungi disease suppressors (Trichoderma-Aspergillus). The phytoparasitic nematodes (Meloidogyne sp., Pratylenchus sp., and Mesocriconema sp.) and oomycetes (Phytophthora spp., and Pythium spp.) showed a reduction of their population levels by effects of organic amendment (C. juncea). The plastic mulch was also effective, probably due to the maintenance of optimal condition to crop growth and weed control. However, the dolomitic lime application had the poorest effect under the conditions of the study area on the variables analyzed. The described observations are characteristics of a system-based approach for the potential management of soil-borne pathogens of pineapple MD-2 in Veracruz, México.     

Reward Sensitivity Is Associated with Brain Activity during Erotic Stimulus Processing

The behavioral approach system (BAS) from Gray’s reinforcement sensitivity theory is a neurobehavioral system involved in the processing of rewarding stimuli that has been related to dopaminergic brain areas. Gray’s theory hypothesizes that the functioning of reward brain areas is modulated by BAS-related traits. To test this hypothesis, we performed an fMRI study where participants viewed erotic and neutral pictures, and cues that predicted their appearance. Forty-five heterosexual men completed the Sensitivity to Reward scale (from the Sensitivity to Punishment and Sensitivity to Reward Questionnaire) to measure BAS-related traits. Results showed that Sensitivity to Reward scores correlated positively with brain activity during reactivity to erotic pictures in the left orbitofrontal cortex, left insula, and right ventral striatum. These results demonstrated a relationship between the BAS and reward sensitivity during the processing of erotic stimuli, filling the gap of previous reports that identified the dopaminergic system as a neural substrate for the BAS during the processing of other rewarding stimuli such as money and food.     

Nephrology Referral and Outcomes in Critically Ill Acute Kidney Injury Patients

Background

Delayed nephrology consultation (NC) seems to be associated with worse prognosis in critically ill acute kidney injury (AKI) patients.

Design, Setting, Participants, & Measurements

The aims of this study were to analyze factors related with timing of NC and its relation with AKI patients'' outcome in intensive care units of a tertiary hospital. AKI was defined as an increase ≥50% in baseline serum creatinine (SCr). Early NC and delayed NC were defined as NC performed before and two days after AKI diagnosis day. Multivariable logistic regression and propensity scores (PS) were used to adjust for confounding and selection biases. Hospital mortality and dialysis dependence on hospital discharge were the primary outcomes.

Results

A total of 366 AKI patients were analyzed and NCs were carried out in 53.6% of the patients. Hospital mortality was 67.8% and dialysis required in 31.4% patients (115/366). Delayed NCs (34%) occurred two days after AKI diagnosis day. This group presented higher mortality (OR: 4.04/CI: 1.60–10.17) and increased dialysis dependence (OR: 3.00/CI: 1.43–6.29) on hospital discharge. Four variables were retained in the PS model for delayed NC: diuresis (1000 ml/24 h - OR: 1.92/CI: 1.27–2.90), SCr (OR: 0.49/CI: 0.32–0.75), surgical AKI (OR: 3.67/CI: 1.65–8.15), and mechanical ventilation (OR: 2.82/CI: 1.06–7.44). After correction by PS, delayed NC was still associated with higher mortality (OR: 3.39/CI: 1.24–9.29) and increased dialysis dependence (OR: 3.25/CI: 1.41–7.51). Delayed NC was associated with increased mortality either in dialyzed patients (OR: 1.54/CI: 1.35–1.78) or non-dialyzed patients (OR: 2.89/CI: 1.00–8.35).

Conclusion

Delayed NC was associated with higher mortality and increased dialysis dependence rates in critically ill AKI patients at hospital discharge. Further studies are necessary to ascertain whether this effect is due to delayed nephrology intervention or residual confounding factors.     

Hypertrophic Cardiomyopathy in Owl Monkeys (Aotus spp.)

Cardiac hypertrophy is a common postmortem finding in owl monkeys. In most cases the animals do not exhibit clinical signs until the disease is advanced, making antemortem diagnosis of subclinical disease difficult and treatment unrewarding. We obtained echocardiograms, electrocardiograms, and thoracic radiographs from members of a colony of owl monkeys that previously was identified as showing a 40% incidence of gross myocardial hypertrophy at necropsy, to assess the usefulness of these modalities for antemortem diagnosis. No single modality was sufficiently sensitive and specific to detect all monkeys with cardiac hypertrophy. Electrocardiography was the least sensitive method for detecting owl monkeys with hypertrophic cardiomyopathy. Thoracic radiographs were more sensitive than was electrocardiography in this context but cannot detect animals with concentric hypertrophy without an enlarged cardiac silhouette. Echocardiography was the most sensitive method for identifying cardiac hypertrophy in owl monkeys. The most useful parameters suggestive of left ventricular hypertrophy in our owl monkeys were an increased average left ventricular wall thickness to chamber radius ratio and an increased calculated left ventricular myocardial mass. Parameters suggestive of dilative cardiomyopathy were an increased average left ventricular myocardial mass and a decreased average ratio of left ventricular free wall thickness to left ventricular chamber radius. When all 4 noninvasive diagnostic modalities (physical examination, echocardiography, electrocardiography, and thoracic radiography) were used concurrently, the probability of detecting hypertrophic cardiomyopathy in owl monkeys was increased greatly.Abbreviations: LVFWTd, left ventricular free wall thickness at end-diastole; STd, interventricular septal thickness at end-diastole; EDD, left ventricular chamber diameter at end-diastole; ESD, left ventricular chamber diameter at end-systole; VHS, vertebral heart scaleOwl monkeys (Aotus spp.) are maintained and used primarily as a nonhuman primate model for the study of malaria.^17,38,45 These neotropical monkeys have also been shown to be useful for the study of visceral leishmaniasis,⁵ various viruses,^1,20-22,27 streptotrichosis,¹⁹ campylobacteriosis,¹⁶ and toxoplasmosis.³⁴ Owl monkeys are naturally susceptible to a variety of internal parasites,^37,39 hemolytic anemia, and glomerulonephritis.^8,13,40Approximately 40% of Aotus monkeys dying from all causes in a colony maintained for dispersement to investigators for the study of malaria have gross evidence of myocardial hypertrophy at necropsy.⁴⁰ This incidence is similar to the 41% mortality ascribed to cardiovascular disease in captive adult lowland gorillas,²⁵ and the report that, in humans, cardiovascular disease represents 42% of all deaths in the United States.⁹ The hypertrophy in owl monkeys almost obliterates the left ventricular chamber and causes marked thickening of the left ventricular free wall and interventricular septum. A similar incidence of myocardial hypertrophy has previously been reported in other owl monkey colonies.^13,31,32Most of the deaths in the owl monkey colony at our institution can be attributed to various identifiable causes typical for this species.⁴⁰ However, several monkeys in this colony had gross evidence of myocardial hypertrophy at death but had shown no clinical signs of disease and displayed no gross or microscopic etiology for death. A prominent feature of the spontaneous deaths within this particular colony of Aotus monkeys was ‘sudden death,’ particularly during periods of high physical and psychologic stress.⁴⁰ Ventricular arrhythmias have been hypothesized as possible cause of sudden death in chimpanzees with cardiomyopathy,¹⁰ and a similar mechanism might be responsible for sudden death in captive owl monkeys.Gross hypertrophy of the left ventricle has many causes in humans and animals. In the absence of gross evidence of resistive lesions (that is, coarctation of the aorta, aortic stenosis) or shunting lesions (that is, ventricular septal defect, patent ductus arteriosus, atrial septal defect), hypertrophic cardiomyopathy and hypertension are the 2 most likely causes of or stimulus for the left ventricular hypertrophy observed in our colony.^4,18 Because no gross lesions that contribute to myocardial hypertrophy have been found at necropsy, we presumed that the hypertrophic changes in our monkeys are due to hypertrophic cardiomyopathy or to increased afterload secondary to hypertension. Spontaneous hypertension has been reported as causing dilated cardiomyopathy in wooly monkeys,¹¹ and vitamin E deficiency is a cause of cardiomyopathy (primarily dilative) in gelada baboons as well as other primates.^23,24 Cardiac changes secondary to experimental trypanosomiasis have occurred in vervet²⁸ and squirrel monkeys²⁹ and after group A streptococcal infection in rhesus monkeys.²⁶ However, only a few reports detail spontaneous myocardial hypertrophic changes in nonhuman primates.^3,10,13,32 Because of the high incidence of cardiac hypertrophy in clinically normal owl monkeys, it is difficult to establish ‘normal’ reference values for the species. One group of authors³¹ was reluctant to suggest reference intervals for normal echocardiographic variables in owl monkeys due to inability to confirm that monkeys classified as normal were free of cardiac disease.The left ventricular hypertrophy in the owl monkey colony we present has been speculated to be the result of renal-induced hypertension. Many of these monkeys have evidence of glomerular lesions at necropsy. Spontaneous primary systemic hypertension has been suggested as the etiology of the cardiomyopathy and renal disease in owl monkeys,¹³ however, no relationship between antemortem blood pressure and the presence or absence of renal lesions and myocardial hypertrophy in these monkeys had been established until recently. A recent study³⁵ using chronically implanted pressure transducers in A. nancymae found that 30% of the monkeys had resting mean arterial pressures in the hypertensive range (>110 mm Hg), and all animals had exaggerated pressor responses in response to routine husbandry procedures (mean arterial pressure, 125 to 196 mm Hg). These same authors concluded that the hypertension observed was consistent with a neural-based essential hypertension that possibly was engendered by the frequent hyperreactive responses of the sympathetic nervous system of these animals to environmental events.³⁵This study was undertaken to identify individual owl monkeys with left ventricular hypertrophy by using noninvasive diagnostic techniques antemortem. Physical examination, echocardiography, electrocardiography, and thoracic radiography were selected as potential diagnostic modalities with the greatest probability of yielding sensitive and specific information regarding left ventricular hypertrophy in individual monkeys prior to postmortem examination.     

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

The effect of the treatment with glycolipid derivatives on the metabolic profile of intact glioma cells and tumor tissues, investigated using proton high resolution magic angle spinning (¹H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, is reported here. Two compounds were used, a glycoside and its thioglycoside analogue, both showing anti-proliferative activity on glioma C6 cell cultures; however, only the thioglycoside exhibited antitumor activity in vivo. At the drug concentrations showing anti-proliferative activity in cell culture (20 and 40 µM), significant increases in choline containing metabolites were observed in the ¹H NMR spectra of the same intact cells. In vivo experiments in nude mice bearing tumors derived from implanted C6 glioma cells, showed that reduction of tumor volume was associated with significant changes in the metabolic profile of the same intact tumor tissues; and were similar to those observed in cell culture. Specifically, the activity of the compounds is mainly associated with an increase in choline and phosphocholine, in both the cell cultures and tumoral tissues. Taurine, a metabolite that has been considered a biomarker of apoptosis, correlated with the reduction of tumor volume. Thus, the results indicate that the mode of action of the glycoside involves, at least in part, alteration of phospholipid metabolism, resulting in cell death.     

Testing the Accuracy of Different A-Axis Types for Measuring the Orientation of Bones in the Archaeological and Paleontological Record

Orientation of archaeological and paleontological materials plays a prominent role in the interpretation of site formation processes. Allochthony and authochthony are frequently assumed from orientation patterns or lack thereof. Although it is still debated to what extent orientation of items can be produced in original depositional contexts, the recent use of GIS tools to measure orientations has highlighted several ways of reproducing A-axes with which to address these taphonomic issues. In the present study, the three most relevant A-axis types are compared to test their accuracy in reproducing water current direction. Although results may be similar in specific bone shapes, differences are important in other shapes. As known in engineering working with wind and fluid mechanics (developing shape optimization), longitudinal symmetrical axes (LSA) are the one that best orient structures against or in the same direction of wind and water. The present work shows that this is also the case for bones (regardless of shape), since LSA produce the most accurate estimates of flow direction. This has important consequences for the interpretation of orientation patterns at sites, since this type of axis is still not properly reproduced by GIS available tools.