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Byline: German Reig, Maria E. Cabrejos, Miguel L. Concha Keywords: Homeodomain; BarH; Barhl; FIL domains; Central nervous system; Eye; Development; Vertebrates; Drosophila Abstract: This paper reviews the developmental role of a group of homeobox-containing genes firstly described in the early nineties as critical factors regulating eye development in Drosophila. These genes received the name of BarH due to the Drosophila 'Bar' mutant phenotype and, since then, vertebrate homologues (named BarH-like or Barhl) have been described in a number of species of fish, amphibians and mammals. During embryonic development, BarH/Barhl are expressed primarily in the central nervous system where they play essential roles in decisions of cell fate, migration and survival. Transcriptional regulation mediated by these proteins involves either repression or activation mechanisms. In Drosophila, BarH is involved in morphogenesis and fate determination of the eye and external sensory organs, in regional prepatterning of the notum, and in formation and specification of distal leg segments. Vertebrate Barhl shares some functional properties with the fly counterparts, such as the ability to interact with basic helix-loop-helix (bHLH) proneural proteins, and plays crucial roles during cell type specification within the retina, acquisition of commissural neuron identity in the spinal cord, migration of cerebellar cells, and in cell survival within the neural plate, cochlea and cerebellum. Author Affiliation: Anatomy and Developmental Biology Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Independencia 1027, Santiago, Chile Article History: Received 5 July 2006; Revised 6 September 2006; Accepted 5 October 2006

Vertebrates have internal asymmetries along the left-right (L-R) axis revealed by organ placement about the midline. In zebrafish, Nodal signaling components are expressed asymmetrically on the left in the lateral plate mesoderm (LPM) and in the diencephalon (DI). The zebra fish gene one-eyed-pinhead (oep) is a member of the EGF-CFC family of proteins that are required cofactors for Nodal signaling. Oep embryos rescued by RNA injection for an early requirement for oep appear wild type but have defects in L-R organ placement in the viscera and the brain. Additionally, asymmetric gene expression in the LPM and DI is never established in these embryos. Similar results were obtained in zebrafish schmalspur mutants that have defects in the Nodal transducer Fast1. In both of these mutants, organs still obtain asymmetric positions, but these positions are randomized with respect to the midline. This indicates that Nodal signaling is not required for the generation of asymmetry per se, but is required to direct these asymmetries. Our analysis suggests a model where an early Nodal signaling event leads to a repression of gene expression in the LPM and DI. A later oep-dependent step is required to overcome this repression and allow for gene expression to occur. In addition, we are mapping and cloning several genes that affect L-R development in the zebra fish, and our recent results on this work will be presented.

We have recently reported that in vitro low dose of ultraviolet B radiation (UVB, 100–200 J per m2) directly impaired the antigen‐presenting function of human Langerhans cells. In this study, we analyzed the effect of UVB irradiation on the Langerhans cells expression of several accessory molecules, namely CD54, CD80, and CD86. Langerhans cells phenotype was determined either immediately after UVB exposure (100 J per m2) or after a 2 d culture. No modification in cell surface antigen levels was observed immediately after irradiation. Prior UVB exposure did not modify the levels of CD80 at the Langerhans cells surface after a 2 d culture. In contrast, CD54 and, above all, CD86 expression were significantly decreased. Addition of exogenous anti‐CD28 monoclonal antibodies partly restored the allostimulatory property of irradiated Langerhans cells in mixed epidermal cell‐lymphocyte reaction, demonstrating that impairment of CD86 upregulation contributes to the UVB‐induced immunosuppressive effect. Furthermore, we found that UVB irradiation at 200 J per m2 significantly reduced the number of viable Langerhans cells after 2 d of culture. UVB‐induced cytotoxicity was due to apoptotic cell death, as demonstrated by typical morphologic alterations and by DNA fragmentation yielding a classical ladder pattern on gel electrophoresis. Interestingly, interaction of Langerhans cells with CD40‐ligand transfected L cells improved the viability of irradiated Langerhans cells, counteracted the inhibition of CD86 expression, and efficiently reduced the number of apoptotic cells after a 2 d culture. Collectively, these results demonstrate that in vitro UVB exposure affects Langerhans cells via at least two distinct pathways: (i) decreased CD86 costimulatory molecule upregulation; and (ii) induction of Langerhans cells apoptosis, a phenomenon partly prevented by CD40 triggering. [ABSTRACT FROM AUTHOR]

Physical interaction between Langerhans cells and T cells is an essential requirement for antigen presentation. In this study we report the ultrastructural characteristics of the antigen-specific physical interactions that occur in vitro between murine Langerhans cells and T cells. Epidermal Langerhans cells enriched to 78% purity by a panning method were pulsed with 2,4-dinitrophenyl-Limulus polyphemus hemocyanin and co-incubated with syngeneic T lymphocytes primed in vivo with the same antigen. A substantial number of conjugates constituted by Langerhans cells surrounded by three or more lymphocytes were obtained after 60 min of incubation at 4°C. Electron microscopy of the conjugates revealed that Langerhans cells and T lymphocytes interacted by two type of contacts. Type I was characterized by glycocalyx-glycocalyx interaction that occurred in relation to protrusions or microvilli of both cells. Type II was characterized by wide and tight areas of close apposition between Langerhans cells and T-lymphocyte plasma membranes. In these areas there were zones with intercellular bridges and small septilaminar junctions highly suggestive of gap junctions. An electron-immunogold procedure demonstrated the presence of DNP-LPH antigen on the type I contact. Our findings suggest that type I contact may represent the locus for antigen presentation whereas the type II contact may be involved in keeping adhesiveness between Langerhans cells and lymphocytes during antigen presentation. [ABSTRACT FROM AUTHOR]

Summary CD40 is expressed in normal human keratinocytes, especially in the basal cell layer. We have recently reported that CD40 ligation strongly inhibits keratinocyte proliferation and induces their differentiation. In this study, the CD40 pathway that prevents keratinocyte growth was investigated. We first reported that interferon-γ treatment potentiated the CD40-mediated inhibition of keratinocyte proliferation. CD40–CD40 ligand interactions, in the presence or absence of interferon-γ, neither enhanced spontaneous keratinocyte apoptosis, nor did it enhance apoptosis induced by various agents. More importantly, we showed that CD40 signaling altered the keratinocyte cell cycle, as demonstrated by a decreasing number of cells in the G1 and S phases and an accumulation in G2/M phase of the cell cycle. Furthermore, western blot analysis of cell cycle regulatory proteins, showed a decrease in cyclin A and E expression in CD40-activated keratinocytes. Collectively, these results indicate that CD40 ligation inhibits keratinocyte renewal by a mechanism independent of cell apoptosis and that modulation of the keratinocyte cell cycle is an additional outcome of CD40 signaling. [ABSTRACT FROM AUTHOR]

Fog is an important water resource, especially in arid and semi-arid zones. The usual method to collect fog water is placing a rectangular mesh perpendicular to the wind which traps fog droplets. The collector catches a fraction of the fog’s water droplets, allowing them to grow by coalescence until large enough to fall by gravity for collection. Fog events can last from minutes to hours, or even longer. This study aimed to evaluate the efficiency (η) of a standard fog collector (SFC) to gather fog water. Efficiency is defined as the ratio between the water reaching the collector’s gutter (CW) and the liquid water flux (LWF) normal to the collector’s mesh, integrated in a period of time. After a fog event begins, mesh collectors require some time to reach saturation and begin dripping; further, the system does not achieve a stationary state at field conditions. Therefore, we considered entire fog events when evaluating efficiency. The CW was measured using a rain gauge, and the LWF was calculated based on the liquid water content (LWC) obtained through a fog droplet spectrometer, and data of wind velocity registered by a meteorological station. The duration of the analyzed events ranged from 20 min to 11 h 40 min. A lag of up to one hour between the arrival of fog and the beginning of the measured water output was observed. Both processes started simultaneously when preceded by another fog event. For the analyzed events, η ranged between 0% and 36.8%. Isolated events of up to 30 minutes resulted in zero CW measurements because the mesh requires time to become saturated before dripping. Furthermore, η was zero if the mean dew point depression (DPD) was above 0.2 °C or the mean LWC was below 0.045 g m −3 . We found that η decreases with increasing mean volume diameter (MVD) for MVD ≳ 10 μm. Finally, η increased with wind speed for events in which the MVD > 12 μm. [ABSTRACT FROM AUTHOR]

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. [ABSTRACT FROM AUTHOR]

Abstract: BarH (Barhl) genes encode for highly conserved homeodomain-containing transcription factors involved in critical functions during development, including cell fate specification, migration and survival. Here, we report the dynamic and restricted expression of three zebrafish barhl within the developing central nervous system. barhl2 becomes expressed in the late gastrula as a transverse diencephalic domain located immediately caudal to the prospective eyes. At early somitogenesis, barhl1.1 and barhl1.2 are expressed in the diencephalon in domains that partially overlap with the ventral and dorsal aspects of barhl2 expression, respectively. At later stages, expression of all zebrafish barhl shows large extent of overlap in the pretectum, tectum and dorsal hindbrain. The presence of a unique territory of barhl2 expression in the dorsal telencephalon and the high levels of expression in the retina are both consistent with expression reports of other Barhl2 orthologues, and support the subdivision of vertebrate Barhl into two paralogue groups based on the phylogenetic analysis of nucleotide and amino acid sequences. [Copyright &y& Elsevier]

Kinins are key pro-inflammatory peptides that exhibit mitogenic effects in tissue-specific cellular systems. Since the life span of the keratinocyte is regulated by receptors that control proliferation and differentiation, and since both processes are affected during wound healing, we have examined the consequence of kinin B2 receptors (B2R) activation in cultured human keratinocytes. Stimulation of keratinocytes by Lys-bradykinin (LBK) induced a rapid and sustained phosphorylation of 42/44 mitogen-activated protein kinase (MAPK) that translocated to the nucleus, and decreased only after 120 min of stimulation. Kinin B1 and B2 receptor (B1R and B2R) antagonists showed that phosphorylation was mainly because of B2R activation. The GF109203X inhibitor almost completely abolished the effect of LBK, suggesting the involvement of protein kinase C in the signal cascade. MAPK phosphorylation was partially dependent on epidermal growth factor receptor transactivation as assessed by the selective inhibitor, AG1478. LBK stimulation did not result in cell proliferation, but produced a rapid c-Fos expression, nuclear translocation of nuclear factor-κB, and a moderated (pro)filaggrin synthesis, indicating that it may modulate cell differentiation. Our results support the view that kinins may affect the life span of human keratinocytes and highlight the importance that kinin peptides may have in the pathogenesis and/or progression of skin diseases. [ABSTRACT FROM AUTHOR]

The isocortex is a distinctive feature of the mammalian brain, with no clear counterpart in other amniotes. There have been long controversies regarding possible homologues of this structure in reptiles and birds. The brains of the latter are characterized by the presence of a structure termed dorsal ventricular ridge (DVR), which receives ascending auditory and visual projections, and has been postulated to be homologous to parts of the mammalian isocortex (i.e., the auditory and the extrastriate visual cortices). Dissenting views, now supported by molecular evidence, claim that the DVR originates from a region termed ventral pallium, while the isocortex may arise mostly from the dorsal pallium (in mammals, the ventral pallium relates to the claustroamygdaloid complex). Although it is possible that in mammals the embryonic ventral pallium contributes cells to the developing isocortex, there is no evidence yet supporting this alternative. The possibility is raised that the expansion of the cerebral cortex in the origin of mammals was product of a generalized dorsalizing influence in pallial development, at the expense of growth in ventral pallial regions. Importantly, the evidence suggests that organization of sensory projections is significantly different between mammals and sauropsids. In reptiles and birds, some sensory pathways project to the ventral pallium and others project to the dorsal pallium, while in mammals sensory projections end mainly in the dorsal pallium. We suggest a scenario for the origin of the mammalian isocortex which relies on the development of associative circuits between the olfactory, the dorsal and the hippocampal cortices in the earliest mammals. [Copyright &y& Elsevier]