Pigment dispersing hormone modulates spontaneous electrical activity of the cerebroid ganglion and synchronizes electroretinogram circadian rhythm in crayfish Procambarus clarkii

In crayfish, one very well-studied circadian rhythm is that of electroretinogram (ERG) amplitude. The cerebroid ganglion has been considered a plausible site for the circadian pacemaker of this rhythm and for the retinular photoreceptors, as the corresponding effectors. The pigment dispersing hormone (PDH) appears to synchronize ERG rhythm, but its characterization as a synchronizer cue remains incomplete. The main purposes of this work were a) to determine whether PDH acts on the cerebroid ganglion, and b) to complete its characterization as a non-photic synchronizer. Here we show that PDH increases the number of the spontaneous potentials of the cerebroid ganglion, reaching 149.92±6.42% of the activity recorded in the controls, and that daily application of PDH for 15 consecutive days adjusts the ERG circadian rhythm period to 24.0±0.2h and the end of the activity period of the rhythm coincides with the injection of the hormone. In this work, we hypothesized that in crayfish, PDH transmits the "day" signal to the ERG circadian system and acts upon both the presumptive circadian pacemaker and the corresponding effectors to reinforce the synchronization of the system.     

Immunohistochemical characterization of neoplastic cells of breast origin

ABSTRACT: BACKGROUND: After skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% corresponding to breast cancer. We selected an immunohistochemical panel with conventional and newer markers, such as mammaglobin, for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with an especial emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on Tissue Micro-Array. Methods. Twenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of other tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done. Results. Mammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48. Conclusions. The inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin increased the probability of detecting metastasis of breast cancer. For the diagnostic strategy with the highest positive predictive value (87.5%), hormone receptors and mammaglobin were considered in serial, non-parallel manner.     

Federated ontology-based queries over cancer data

BACKGROUND: Personalised medicine provides patients with treatments that are specific to their genetic profiles. It requires efficient data sharing of disparate data types across a variety of scientific disciplines, such as molecular biology, pathology, radiology and clinical practice. Personalised medicine aims to offer the safest and most effective therapeutic strategy based on the gene variations of each subject. In particular, this is valid in oncology, where knowledge about genetic mutations has already led to new therapies. Current molecular biology techniques (microarrays, proteomics, epigenetic technology and improved DNA sequencing technology) enable better characterisation of cancer tumours. The vast amounts of data, however, coupled with the use of different terms - or semantic heterogeneity - in each discipline makes the retrieval and integration of information difficult. RESULTS: Existing software infrastructures for data-sharing in the cancer domain, such as caGrid, support access to distributed information. caGrid follows a service-oriented model-driven architecture. Each data source in caGrid is associated with metadata at increasing levels of abstraction, including syntactic, structural, reference and domain metadata. The domain metadata consists of ontology-based annotations associated with the structural information of each data source. However, caGrid's current querying functionality is given at the structural metadata level, without capitalising on the ontology-based annotations. This paper presents the design of and theoretical foundations for distributed ontology-based queries over cancer research data. Concept-based queries are reformulated to the target query language, where join conditions between multiple data sources are found by exploiting the semantic annotations. The system has been implemented, as a proof of concept, over the caGrid infrastructure. The approach is applicable to other model-driven architectures. A graphical user interface has been developed, supporting ontology-based queries over caGrid data sources. An extensive evaluation of the query reformulation technique is included. CONCLUSIONS: To support personalised medicine in oncology, it is crucial to retrieve and integrate molecular, pathology, radiology and clinical data in an efficient manner. The semantic heterogeneity of the data makes this a challenging task. Ontologies provide a formal framework to support querying and integration. This paper provides an ontology-based solution for querying distributed databases over service-oriented, model-driven infrastructures.     

Intravenous grafts of amniotic fluid-derived stem cells induce endogenous cell proliferation and attenuate behavioral deficits in ischemic stroke rats

We recently reported isolation of viable rat amniotic fluid-derived stem (AFS) cells [1]. Here, we tested the therapeutic benefits of AFS cells in a rodent model of ischemic stroke. Adult male Sprague-Dawley rats received a 60-minute middle cerebral artery occlusion (MCAo). Thirty-five days later, animals exhibiting significant motor deficits received intravenous transplants of rat AFS cells or vehicle. At days 60-63 post-MCAo, significant recovery of motor and cognitive function was seen in stroke animals transplanted with AFS cells compared to vehicle-infused stroke animals. Infarct volume, as revealed by hematoxylin and eosin (H&E) staining, was significantly reduced, coupled with significant increments in the cell proliferation marker, Ki67, and the neuronal marker, MAP2, in the dentate gyrus (DG) [2] and the subventricular zone (SVZ) of AFS cell-transplanted stroke animals compared to vehicle-infused stroke animals. A significantly higher number of double-labeled Ki67/MAP2-positive cells and a similar trend towards increased Ki67/MAP2 double-labeling were observed in the DG and SVZ of AFS cell-transplanted stroke animals, respectively, compared to vehicle-infused stroke animals. This study reports the therapeutic potential of AFS cell transplantation in stroke animals, possibly via enhancement of endogenous repair mechanisms.     

The stress-response factor SigH modulates the interaction between Mycobacterium tuberculosis and host phagocytes

The Mycobacterium tuberculosis stress response factor SigH plays a crucial role in modulating the pathogen's response to heat, oxidative-stress, envelope damage and hypoxia. We hypothesized that the lack of this key stress response factor would alter the interaction between the pathogen and its host cells. We compared the interaction of Mtb, Mtb:Δ-sigH and a strain where the mutation had been genetically complemented (Mtb: Δ-sigH:CO) with primary rhesus macaque bone marrow derived macrophages (Rh-BMDMs). The expression of numerous inducible and homeostatic (CCL) β-chemokines and several apoptotic markers was induced to higher levels in the cells infected with Mtb:Δ-sigH, relative to Mtb or the complemented strain. The differential expression of these genes manifested into functional differences in chemotaxis and apoptosis in cells infected with these two strains. The mutant strain also exhibited reduced late-stage survival in Rh-BMDMs. We hypothesize that the product of one or more SigH-dependent genes may modulate the innate interaction of Mtb with host cells, effectively reducing the chemokine-mediated recruitment of immune effector cells, apoptosis of infected monocytes and enhancing the long-term survival and replication of the pathogen in this milieu The significantly higher induction of Prostaglandin Synthetase 2 (PTGS2 or COX2) in Rh-BMDMs infected with Mtb relative to Mtb: Δ-sigH may explain reduced apoptosis in Mtb-infected cells, as PTGS2 is known to inhibit p53-dependent apoptosis.The SigH-regulon modulates the innate interaction of Mtb with host phagocytes, perhaps as part of a strategy to limit its clearance and prolong its survival. The SigH regulon appears to be required to modulate innate immune responses directed against Mtb.     

The Social Behavior of Brown Spider Monkeys (Ateles hybridus) in a Fragmented Forest in Colombia

Forest fragmentation and habitat loss are two of the main drivers of wildlife population declines. Animals exposed to habitat disturbances must develop behavioral strategies to adapt to novel, rapidly fluctuating socioecological challenges. Understanding the behavioral flexibility of endangered primates as a response to ecological challenges, e.g., anthropogenic habitat disturbance, is a key element in the design of successful conservation initiatives for remaining populations. We studied the social behavior of a group of 11 adult and subadult brown spider monkeys (Ateles hybridus) living in a recently isolated and densely populated forest fragment in the Magdalena River Valley, Colombia, and compared their behavior to that of other wild spider monkey populations. From June 2009 to July 2010 we assessed diet, activity budgets, and the rates of affiliative and agonistic interactions initiated and received by adult male and female spider monkeys. The diet of our focal group was quite different from that in most previous studies of Ateles: leaves accounted for ca. 40?% of their diet, and fruits represented barely half of their diet, suggesting that this population has had to adjust its feeding strategies to the local ecological challenges. We found no sex differences in the time males and females spent resting, moving, and socializing, but females tended to invest more time in feeding than males did. Male-to-female aggression was the most common agonistic interaction, and same-sex aggressions were almost absent. We found no significant differences in rates of grooming or embracing between the different types of dyads. The resemblance of our results to those of similar studies in less disturbed habitats suggests that spider monkeys might adapt to certain levels of ecological and social disturbance, at least initially, and are a starting point to understand better the initial effects of fragmentation on the behavioral repertoire of these primates.     

The Phaseolus vulgaris miR159a precursor encodes a second differentially expressed microRNA

Plant microRNAs originate from a stem-loop structured single-stranded RNA precursor. Each stem-loop is processed to generate a mature microRNA that is recruited to an ARGONAUTE-containing multi-protein complex to direct silencing of its target mRNA. Here we report that the conserved plant miR159a precursor produces a second 21-nt long RNA with the properties of a microRNA. Its presence in different plant species is supported by its conservation in the stem-loop position and expression as determined by northern blot analysis. We show that successive processing by DCL1 produces this novel microRNA from the same precursor as miR159a. In contrast to the low levels observed in other plant models for the equivalent of miR159.2, in P. vulgaris, the accumulation of miR159.2 is easily detectable and when compared to miR159a, their expression patterns are distinct in different organs and growth conditions. Further evidence of the functionality of miR159.2 comes from its association with silencing complexes as demonstrated by co-immunoprecipitation experiments using an AGO1-specific antibody and processing of an artificial GFP reporter construct containing a complementary target sequence. These results indicate that the second small RNA corresponds to a microRNA, at least partially independent of miR159 activity, and that in plants a miRNA precursor may encode multiple regulatory small RNAs.     

Carabelli's trait revisited: An examination of mesiolingual features at the enamel-dentine junction and enamel surface of Pan and Homo sapiens upper molars

Carabelli’s trait is a morphological feature that frequently occurs on the mesiolingual aspect of Homo sapiens upper molars. Similar structures also referred to as Carabelli’s trait have been reported in apes and fossil hominins. However, the morphological development and homology of these mesiolingual structures among hominoids are poorly understood. In this study, we employ micro-computed tomography to image the enamel-dentine junction (EDJ) and outer enamel surface (OES) of Pan (n = 48) and H. sapiens (n = 52) upper molars. We investigate the developmental origin of mesiolingual features in these taxa and establish the relative contribution of the EDJ and enamel cap to feature expression. Results demonstrate that mesiolingual features of H. sapiens molars develop at the EDJ and are similarly expressed at the OES. Morphological variation at both surfaces in this taxon can satisfactorily be assessed using standards for Carabelli’s trait developed by the Arizona State University Dental Anthropology System (ASUDAS). Relative to H. sapiens, Pan has an even greater degree of correspondence in feature expression between the EDJ and OES. Morphological manifestations in Pan molars are not necessarily limited to the protocone and are best characterized by a lingual cingulum that cannot be captured by the ASUDAS. Cusp-like structures, similar to those seen in marked Carabelli’s trait expressions in H. sapiens, were not found in Pan. This study provides a foundation for further analyses on the evolutionary history of mesiolingual dental traits within the hominoid lineage. It also highlights the wealth of morphological data that can be obtained at the EDJ for understanding tooth development and for characterizing tooth crown variation in worn fossil teeth.