Molecular architecture of basement membranes

Basement membranes are specialized extracellular matrices with support, sieving, and cell regulatory functions. The molecular architectures of these matrices are created through specific binding interactions between unique glycoprotein and proteoglycan protomers. Type IV collagen chains, using NH2-terminal, COOH-terminal, and lateral association, form a covalently stabilized polygonal framework. Laminin, a four-armed glycoprotein, self-assembles through terminal-domain interactions to form a second polymer network, Entactin/nidogen, a dumbbell-shaped sulfated glycoprotein, binds laminin near its center and interacts with type IV collagen, bridging the two. A large heparan sulfate proteoglycan, important for charge-dependent molecular sieving, is firmly anchored in the basement membrane and can bind itself through a core-protein interaction to form dimers and oligomers and bind laminin and type IV collagen through its glycosaminoglycan chains. Heterogeneity of structure and function occur in different tissues, in development, and in response to different physiological needs. The molecular architecture of these matrices may be regulated during or after primary assembly through variations in compositions, isoform substitutions, and the modifying influence of exogenous macromolecules such as heparin and heparan sulfate.

The human vestibular cortex revealed by coordinate-based activation likelihood estimation meta-analysis.

The vestibular system contributes to the control of posture and eye movements and is also involved in various cognitive functions including spatial navigation and memory. These functions are subtended by projections to a vestibular cortex, whose exact location in the human brain is still a matter of debate (Lopez and Blanke, 2011). The vestibular cortex can be defined as the network of all cortical areas receiving inputs from the vestibular system, including areas where vestibular signals influence the processing of other sensory (e.g. somatosensory and visual) and motor signals. Previous neuroimaging studies used caloric vestibular stimulation (CVS), galvanic vestibular stimulation (GVS), and auditory stimulation (clicks and short-tone bursts) to activate the vestibular receptors and localize the vestibular cortex. However, these three methods differ regarding the receptors stimulated (otoliths, semicircular canals) and the concurrent activation of the tactile, thermal, nociceptive and auditory systems. To evaluate the convergence between these methods and provide a statistical analysis of the localization of the human vestibular cortex, we performed an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies using CVS, GVS, and auditory stimuli. We analyzed a total of 352 activation foci reported in 16 studies carried out in a total of 192 healthy participants. The results reveal that the main regions activated by CVS, GVS, or auditory stimuli were located in the Sylvian fissure, insula, retroinsular cortex, fronto-parietal operculum, superior temporal gyrus, and cingulate cortex. Conjunction analysis indicated that regions showing convergence between two stimulation methods were located in the median (short gyrus III) and posterior (long gyrus IV) insula, parietal operculum and retroinsular cortex (Ri). The only area of convergence between all three methods of stimulation was located in Ri. The data indicate that Ri, parietal operculum and posterior insula are vestibular regions where afferents converge from otoliths and semicircular canals, and may thus be involved in the processing of signals informing about body rotations, translations and tilts. Results from the meta-analysis are in agreement with electrophysiological recordings in monkeys showing main vestibular projections in the transitional zone between Ri, the insular granular field (Ig), and SII.

Eosinophils

In 1846, T. Wharton-Jones described a coarsely granular stage in the development of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze redefined the coarsely granular cells as a type distinct from finely granular cells, rather than just a developmental stage. It was, however, not until 1879, when Paul Ehrlich introduced a method to distinguish granular cells by the staining properties of their granules, that a classification became possible. An intensive staining for eosin, among other aniline dyes, was eponymous for the coarsely granular cell type, which thereupon became referred to as eosinophil granulocyte. Eosinophilia had already been described in many diseases by the late 19th century. The role of these cells, however, today remains a matter of continuing speculation and investigation. Many functions have been attributed to the eosinophil over the years, often linked to increasing knowledge about the granular and cytoplasmatic contents. A better understanding of the regulatory mechanisms of eosinopoiesis has led to the development of knock-out mice strains as well as therapeutic strategies for reducing the eosinophil load in patients. The effect of these therapeutics and the characterization of the knock-out phenotypes have led to a great increase in the knowledge of the role of the eosinophil in disease. Today we think of the eosinophil as a multifunctional cell involved in host defense, tissue damage and remodeling, as well as immunomodulation.

Recent improvements in antigene technology

DNA triple helix based approaches to control and modulate cellular functions on the level of genomic DNA (antigene technology) suffered in the past from a stepmother like treatment in comparison to the flourishing field of oligonucleotide based control of translation (antisense technology). This was mostly due to lack of affinity of triplex forming oligonucleotides (TFOs) to their DNA target, to sequence restriciton constraints imposed by the triple helical recogniton motifs and by open questions to the accessibility of the target DNA. Recent developments in the area have brought about new bases that specifically recognize pyrimidine-purine inversion sites as well as sugar modifications, e.g. the 2'-aminoethoxy-oligonucleotides or oligonucleotides based on the locked nucleic acid (LNA) sugar unit, that greatly enhance triplex stability and alleviate in part the sequence restriction constraints. With this, sequence specific genomic DNA manipulation starts to become a useful tool in biotechnology

The Influence of Pre-stimulus EEG Activity on Reaction Time During a Verbal Sternberg Task is Related to Musical Expertise

Abstract Previous work highlighted the possibility that musical training has an influence on cognitive functioning. The suggested reason for this influence is the strong recruitment of attention, planning, and working memory functions during playing a musical instrument. The purpose of the present work was twofold, namely to evaluate the general relationship between pre-stimulus electrophysiological activity and cognition, and more specifically the influence of musical expertise on working memory functions. With this purpose in mind, we used covariance mapping analyses to evaluate whether pre-stimulus electroencephalographic activity is predictive for reaction time during a visual working memory task (Sternberg paradigm) in musicians and non-musicians. In line with our hypothesis, we replicated previous findings pointing to a general predictive value of pre-stimulus activity for working memory performance. Most importantly, we also provide first evidence for an influence of musical expertise on working memory performance that could distinctively be predicted by pre-stimulus spectral power. Our results open novel perspectives for better comprehending the vast influences of musical expertise on cognition.

Evaluation of soil salinity amelioration technologies in Timpaki, Crete

Salinization is a soil threat that adversely affects ecosystem services and diminishes soil functions in many arid and semi-arid regions. Soil salinity management depends on a range of factors, and can be complex expensive and time demanding. Besides taking no action, possible management strategies include amelioration and adaptation measures. The WOCAT Technologies Questionnaire is a standardized methodology for monitoring, evaluating and documenting sustainable land management practices through interaction with the stakeholders. Here we use WOCAT for the systematic analysis and evaluation of soil salinization amelioration measures, for the RECARE project Case Study in Greece, the Timpaki basin, a semi-arid region in south-central Crete where the main land use is horticulture in greenhouses irrigated by groundwater. Excessive groundwater abstractions have resulted in a drop of the groundwater level in the coastal part of the aquifer, thus leading to seawater intrusion and in turn to soil salinization due to irrigation with brackish water. Amelioration technologies that have already been applied in the case study by the stakeholders are examined and classified depending on the function they promote and/or improve. The documented technologies are evaluated for their impacts on ecosystem services, cost and input requirements. Preliminary results show that technologies which promote maintaining existing crop types while enhancing productivity and decreasing soil salinity such as composting, mulching, rain water harvesting and seed biopriming are preferred by the stakeholders. Further work will include result validation using qualitative approaches.

Transcriptional regulation of tenascin genes

Extracellular matrix proteins of the tenascin family resemble each other in their domain structure, and also share functions in modulating cell adhesion and cellular responses to growth factors. Despite these common features, the 4 vertebrate tenascins exhibit vastly different expression patterns. Tenascin-R is specific to the central nervous system. Tenascin-C is an "oncofetal" protein controlled by many stimuli (growth factors, cytokines, mechanical stress), but with restricted occurrence in space and time. In contrast, tenascin-X is a constituitive component of connective tissues, and its level is barely affected by external factors. Finally, the expression of tenascin-W is similar to that of tenascin-C but even more limited. In accordance with their highly regulated expression, the promoters of the tenascin-C and -W genes contain TATA boxes, whereas those of the other 2 tenascins do not. This article summarizes what is currently known about the complex transcriptional regulation of the 4 tenascin genes in development and disease.

An interferon-inducible protein, p202, in cancer gene therapy

Interferons (IFNs) have been shown to exert antiviral, cell growth regulatory, and immunomodulatory effects on target cells. Both type I (α and β) and type II (γ) IFNs regulate cellular activities by specifically inducing the expression or activation of endogenous proteins that perform distinct biological functions. p202 is a 52 kDa nuclear phosphoprotein known to be induced by IFNs. p202 interacts with a variety of cellular transcription and growth regulatory factors and affects their functions. ^ In this report, we showed that the expression of p202 was associated with an anti-proliferative effect on human prostate cancer cells. Cells that expressed p202 showed reduced ability to grow in soft-agar, indicating a loss of transformation phenotype. More importantly, p202 expression reduced the tumorigenicity of human prostate cancer cells. p202-expressing cells exhibit an elevated level of hypophosphorylated form of pRb, and reduced level of cyclin B1 and p55CDC. ^ Our data suggest that p202 is a growth inhibitor gene in prostate cancer cells and its expression may also suppress transformation phenotype and tumorigenicity of prostate cancer cells. ^ In addition to inhibiting in vitro cell growth, suppressing the tumorigenicity of breast cancer cells in vivo, p202 expression could sensitize breast cancer cells to apoptosis induced by TNF-α treatment. One possible mechanism contributing to this sensitization is the inactivation of NF-κB by its interaction with p202. These results provide a scientific basis for a novel therapeutic strategy that combines p202 and TNF-α treatment against breast cancer. ^ It has been reported that NF-κB is constitutively active in human pancreatic cancer cells. Since p202 interacts with NF-κB and inhibits its activity, we examined a potential p202-mediated anti-tumor activity in pancreatic cancer. We used both ectopic and orthotopic xenograft models and demonstrated that p202 expression is associated with multiple anti-tumor activities that include inhibition of tumor growth, reduced tumorigenicity, prolonged survival, and remarkably, suppression of metastasis and angiogenesis. In vitro invasion assay also showed that p202-expressing pancreatic cancer cells are less invasive than those without p202 expression. That observation was supported by the findings that p202-expressing tumors showed reduced expression of angiogenic factors such as IL-8, and VEGF by inhibiting their transcription, and p202-expressing pancreatic cancer cells have reduced level of MAP-2 activity, a secreted protease activity important for metastasis. Together, our results strongly suggest that p202 expression mediates multiple anti-tumor activities against pancreatic cancer, and that may provide a scientific basis for developing a p202-based gene therapy in pancreatic cancer treatment. ^ Importantly, we demonstrated a treatment efficacy by using p202/SN2 liposome complex in a nude mice orthotopic breast cancer, and an ectopic pancreatic cancer xenograft model, through systemic and intra-tumor injection respectively. These results suggest a feasibility of using p202/SN2 liposome in future pre-clinical gene therapy experiments. ^

Confocal analysis of synaptic connectivity of the rod pathway in the rabbit retina

The retina is a specialized neuronal structure that transforms the optical image into electrical signals which are transmitted to the brain via the optic nerve. As part of the strategy to cover a stimulus range as broad as 10 log units, from dim starlight to bright sunlight, retinal circuits are broadly divided into rod and cone pathways, responsible for dark and light-adapted vision, respectively. ^ In this dissertation, confocal microscopy and immunocytochemical methods were combined to study the synaptic connectivity of the rod pathway from the level of individual synapses to whole populations of neurons. The study was focused on synaptic interactions at the rod bipolar terminal. The purpose is to understand the synaptic structure of the dyad synapse made by rod bipolar terminals, including the synaptic components and connections, and their physiological functions in the rod pathway. In addition, some additional components and connections of the rod pathway were also studied in these experiments. The major results can be summarized as following: At the dyad synapse of rod bipolar terminals, three postsynaptic components—processes of All amacrine cells and the varicosities of S1 or S2 amacrine cells express different glutamate receptor subunits, which may underlie the functional diversity of these postsynaptic neurons. A reciprocal feedback system is formed by rod bipolar terminals and S1/S2 amacrine cells. Analysis showed these two wide-field GABA amacrine cells have stereotyped synaptic connections with the appropriate morphology and distribution to perform specific functions. In addition, S1 and S2 cells have different coupling patterns and, in general, there is no coupling between the two types. Besides the classic rod pathway though rod bipolar cells and All amacrine cells, the finding of direct connections between certain types of OFF cone bipolar cells and rods indicates the presence of an alternative rod pathway in the rabbit retina. ^ In summary, this dissertation presents a detailed view of the connection and receptors at rod bipolar terminals. Based on the morphology, distribution and coupling, different functional roles were identified for S1 and S2 amacrine cells. Finally, an alternative to the classic rod pathway was found in the rabbit retina. ^

Guessing Solutions to the H-atom Schrodinger Equation

In teaching elementary quantum chemistry, the concept of eigenfunctionality is explored using the H-atom's Hamiltonian and various guessed functions. This is done in Cartesian coordinates, in Spherical Polar coordinates, and in Confocal Elliptical coordinates.

The INO80 chromatin remodeling complex is involved in the nucleotide excision repair pathway

The genomic DNA of eukaryotic cells is well organized into chromatin structures. However, these repressed structures present barriers that block the access of regulatory factors to the genome during various nuclear events. To overcome the obstacle, two major cellular processes, post-modification of histone tails and ATP-dependent chromatin remodeling, are involved in reconfiguring chromatin structure and creating accessible DNA. Despite the current research progress, much remains to be explored concerning the relationship between chromatin remodeling and DNA repair. Recently, one member of the ATP-dependent chromatin remodeling complexes, INO80, has been found to play a crucial role in DNA damage repair. However, the functions of this complex in higher eukaryotes have yet to be determined. The goal of my study is to generate a human somatic INO80 conditional knockout model and investigate the functions of Ino80 in damage repair.^ By homologous targeting of the INO80 locus in human HCT116 colon epithelial cells, I established a human somatic INO80 conditional knockout model. I have demonstrated that the conditional INO80 cells exhibited a sufficiently viable period when the INO80 protein is removed. Moreover, I found that loss of INO80 resulted in deficient UV lesion repair in response to UV while the protein levels of the NER factors such as XPC, XPA, XPD were not affected. And in vitro repair synthesis assay showed that the NER incision and repair synthesis activities were intact in the absence of INO80. Examination on the damage recognition factor XPC showed its recruitment to damage sites was impaired in the INO80 mutant cells. Loss of INO80 also led to reduced enrichment of XPA at the site of UV lesions. Despite the reduced recruitment of XPC and XPA observed in INO80 mutants, no direct interaction was detected. Meanwhile, direct interaction between INO80 and DDB1, the initial UV lesion detector, was detected by coimmunoprecipitation. UV-induced chromosome relaxation was reduced in cells devoid of INO80. These results demonstrate the INO80 complex may participates in the NER by interacting with DDB1 and having a critical role of in creating DNA accessibility for the nucleotide excision pathway. ^

Trehalose 6,6'-dimycolate promotes the survival of Mycobacterium tuberculosis in murine macrophages

The survival of Mycobacterium tuberculosis (MTB) in macrophages largely plays upon its ability to manipulate the host immune response to its benefit. Trehalose 6,6'-dimycolate (TDM) is a glycolipid found abundantly on the surface of MTB. Preliminary studies have shown that MTB lacking TDM have a lower survival rate compared to wild-type MTB in infection experiments, and that lysosomal colocalization with the phagosome occurs more readily in delipidated MTB infections. The purpose of this dissertation is to identify the possible mechanistic roles of TDM and its importance to the survival of MTB in macrophages. Our hypothesis is that TDM promotes the survival of MTB by targeting specific immune functions in host macrophages. Our first specific aim is to evaluate the effects of TDM on MTB in surface marker expression and antigen presentation in macrophages. We characterized the surface marker response in murine macrophages infected with either TDM-intact or TDM-removed MTB. We found that the presence of TDM on MTB inhibited the expression of surface markers which are important for antigen presentation and costimulation to T cells. Then we measured and compared the ability of macrophages infected by MTB with or without TDM to present Antigen 85B to hybridoma T cells. Macrophages infected with TDM-intact MTB were found to be less efficient at antigen presentation than TDM-removed MTB. Our second aim is to identify molecular mechanisms which may be targeted by TDM to promote MTB survival in macrophages. We measured macrophage responsiveness to IFN-γ before or after MTB infection and correlated SOCS production to the presence of TDM on MTB. Macrophages infected with TDM-intact MTB were found to be less responsive to IFN-γ. This may be attributed to the TDM-driven production of SOCS, which was found to affect phosphorylation of the JAK-STAT signaling pathway. We also identified the importance of TLR2 and TLR4 in the initiation of SOCS by TDM-intact MTB in host macrophages. In conclusion, our studies reveal new insights into how TDM regulates macrophages and their immune functions to aid in the survival of MTB.^

Políticas de maternidad durante el período peronista : Quiebres y continuidades en las relaciones de género

En este trabajo, nos proponemos realizar un balance sobre el modo en que la historiografía ha descripto y analizado las políticas públicas que, durante el primer y segundo gobierno peronista, se implementaron en relación con la maternidad así como los debates conceptuales, analíticos e historiográficos que ha suscitado de manera, a veces, implícita. Este abordaje, nos permitirá estudiar cómo se constituyeron históricamente las identidades femeninas y cómo se prescribieron roles, funciones y relaciones de poder que legitimaron distinciones generizadas basadas en diferencias biológicas, que naturalizaron la centralidad de la maternidad en cuanto función reproductora en la vida de las mujeres o que, aún sosteniendo esas construcciones de género binarias, consideraron limitar los alcances de los roles maternales, pero no menos los paternos.

Los modelos de explicación para las novedades del desarrollo

Este trabajo examina los marcos epistémicos y su modus operandi sobre los modelos explicativos en la psicología del desarrollo. En primer lugar, los rasgos del marco epistémico de la escisión y su intervención en el modo ?legítimo? de explicar las competencias, habilidades y funciones psicológicas. En segundo lugar, se muestran las dificultades de dicho modelo, aún predominante entre los investigadores, cuando se pretende dar cuenta de la emergencia de comportamientos, sistemas conceptuales y funciones que son estrictamente novedosas, esto es, que no están dadas dentro del aparato mental ni fuera del propio proceso. En tercer lugar, se exploran las características de una explicación sistémica para dichas novedades, enmarcándola en una ontología y una epistemología relacional. Se identifican las características del modelo sistémico y se evalúa su eficacia respecto de la emergencia de sistemas conceptuales y funciones psicológicas nuevas en el desarrollo. Finalmente, se identifican dos versiones de dicha explicación: el sistema complejo del constructivismo y la perspectiva vigotskyana de la explicación, estableciendo una fuerte diferencia respecto de un sistema de interacciones no dialéctico

Adolescencia y escuelas: Interpelando a Vygotsky en el siglo XXI : Unidades de análisis que entrelazan tramas y recorridos, encuentros y desencuentro

El objetivo es presentar categorías construidas por Vigotsky desde un enfoque psicológico y educativo, para enriquecer perspectivas sobre relaciones entre adolescentes y escuelas, integrando el contexto social e histórico en el que se inscriben. Se problematiza la concepción de fracaso escolar y de educabilidad de los sujetos, que los reduce a problemas individuales. Los textos de Vigotsky en Paidología del adolescente , escritos hace casi ochenta años, anticipan y proveen insumos significativos para la agenda de problemas contemporáneos sobre el desarrollo de los sujetos y las prácticas educativas. Se enfocan las unidades de análisis en el estudio de fenómenos psicoeducativos, para explicar y comprender conductas, funciones y procesos, desde planos personales, interpersonales y socioculturales. El recorrido del autor, pionero del enfoque socio-histórico-cultural, abarca dimensiones complejas, como intereses, pensamiento conceptual, imaginación y personalidad, analizando los procesos psíquicos superiores como desarrollos de la historia cultural de los adolescentes. Se articula el análisis de la obra con la revisión que autores contemporáneos post-vigotskianos realizan de la categoría de Zona de Desarrollo Próximo. La lectura puede ampliar la perspectiva de agentes psicoeducativos sobre problemas y estrategias de intervención, tomando distancia de una lógica aplicacionista y enriqueciendo las lógicas de implicación y transformación situacional