Age and growth of bluehead suckers and flannelmouth suckers in headwater tributaries, Wyoming

Bluehead sucker ( Catostomus discobolus ) and flannelmouth sucker ( Catostomus latipinnis ) populations are declining throughout these species’ native ranges in the Upper Colorado River Basin. In order to conserve these populations, an understanding of population dynamics is needed. Using age estimates from pectoral fin rays, we describe age and growth of these 2 species in 3 Wyoming stream systems: Muddy Creek, the Little Sandy River, and the Big Sandy River. Within all 3 stream systems, flannelmouth suckers were longer-lived than bluehead suckers, with maximum estimated ages of 16 years in Muddy Creek, 18 years in Little Sandy Creek, and 26 years in the Big Sandy River. Bluehead suckers had maximum estimated ages of 8 years in Muddy Creek, 10 years in Little Sandy Creek, and 18 years in the Big Sandy River. These maximum estimated ages were substantially greater than in other systems where scales have been used to estimate ages. Mean lengths at estimated ages were greater for flannelmouth suckers than for bluehead suckers in all 3 streams and generally less than values published from other systems where scales were used to estimate ages. Our observations of long life spans and slow growth rates among bluehead suckers and flannelmouth suckers were probably associated with our use of fin rays to estimate ages as well as the populations being in headwater tributaries near the northern edges of these species’ ranges.     

poCDIO: A Methodological Proposal for Promoting Active Participation in Social Engineering Projects

Currently, both public and private organizations, as well as the academic milieu are developing social projects in order to strengthen and improve the quality of life. This is the case of Engineers Without Borders Colombia (ISFCOL for its Spanish acronym), an organization formed by engineering teachers and students from Los Andes University and the Minuto de Dios University Corporation that develops engineering projects within communities in order to solve environmental and social problems. However, based in the group’s experience, a problem has been identified regarding the absence of a methodology that promotes the active and effective participation of all the parties involved, which can prevent the accomplishment of otherwise technically viable, socially responsible, and sustainable projects. Looking to address this issue, this paper presents a methodological proposal for promoting the active participation of all the parties involved in engineering projects that have a social impact. The proposal is structured following the stages of the oCDIO context (Observe, Conceive, Design, Implement and Operate), and is successfully applied during the development of an ISFCOL project in which the participation of all the parties involved becomes a key element for the effective accomplishment of the engineering proposal and for the generation of socially responsible impacts. Namely, the project “Fortalecimiento Negocios Verdes Comunitarios Provincia del Guavio” (Community Green Businesses Strengthening in the Guavio Province) whose main goal was to strengthen the innovation and the entrepreneurship in the Guavio region communities, consolidating thus an active participation network of 400 members made up by small entrepreneurs and students from rural communities close to the city of Bogota and from higher education institutions.     

Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain

The conserved formin homology 2 (FH2) domain nucleates actin filaments and remains bound to the barbed end of the growing filament. Here we report the crystal structure of the yeast Bni1p FH2 domain in complex with tetramethylrhodamine-actin. Each of the two structural units in the FH2 dimer binds two actins in an orientation similar to that in an actin filament, suggesting that this structure could function as a filament nucleus. Biochemical properties of heterodimeric FH2 mutants suggest that the wild-type protein equilibrates between two bound states at the barbed end: one permitting monomer binding and the other permitting monomer dissociation. Interconversion between these states allows processive barbed-end polymerization and depolymerization in the presence of bound FH2 domain. Kinetic and/or thermodynamic differences in the conformational and binding equilibria can explain the variable activity of different FH2 domains as well as the effects of the actin-binding protein profilin on FH2 function.     

The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold

The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits. These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components. However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding, and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5?? crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8?? crystal structure of EspG in complex with the autoinhibitory Iα3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a 'catalytic scaffold' that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex.     

Geological and palaeontological context of a Pliocene juvenile hominin at Dikika, Ethiopia

Since 1999, the Dikika Research Project (DRP; initiated by Z.A.) has conducted surveys and excavations in badlands that expose Pliocene and Pleistocene sediments south of the Awash River in Ethiopia, between surrounding hominin localities at Hadar, Gona and the Middle Awash region. Here we report our geological mapping and stratigraphic measurement of the DRP area, and the context of a remarkably well-preserved skeleton of the earliest known juvenile hominin at the Dikika DIK-1 locality. Our mapping of the DRP area permits a complete definition of the hominin-bearing Hadar Formation and provides a cohesive structural and tectonic framework defining its relationships to adjacent strata. Our findings reveal the basin-scale tectonic, depositional and palaeoenvironmental history of the area, as well as a clear taphonomic and palaeontological context for the juvenile hominin. Such data are crucial for understanding the environmental context of human evolution, and can be integrated into larger-scale tectonic and palaeoenvironmental studies. Our basin-scale approach to palaeoenvironments provides a means to elucidate the complex geological history occurring at the scale of temporally and geographically controlled fossil point localities, which occur within the rich tectonic and depositional history of the Awash Valley.     

Modelling schizophrenia using human induced pluripotent stem cells

Schizophrenia (SCZD) is a debilitating neurological disorder with a world-wide prevalence of 1%; there is a strong genetic component, with an estimated heritability of 80-85%. Although post-mortem studies have revealed reduced brain volume, cell size, spine density and abnormal neural distribution in the prefrontal cortex and hippocampus of SCZD brain tissue and neuropharmacological studies have implicated dopaminergic, glutamatergic and GABAergic activity in SCZD, the cell types affected in SCZD and the molecular mechanisms underlying the disease state remain unclear. To elucidate the cellular and molecular defects of SCZD, we directly reprogrammed fibroblasts from SCZD patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiated these disorder-specific hiPSCs into neurons (Supplementary Fig. 1). SCZD hiPSC neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of SCZD hiPSC neurons identified altered expression of many components of the cyclic AMP and WNT signalling pathways. Key cellular and molecular elements of the SCZD phenotype were ameliorated following treatment of SCZD hiPSC neurons with the antipsychotic loxapine. To date, hiPSC neuronal pathology has only been demonstrated in diseases characterized by both the loss of function of a single gene product and rapid disease progression in early childhood. We now report hiPSC neuronal phenotypes and gene expression changes associated with SCZD, a complex genetic psychiatric disorder.     

Overview upon miR-21 in lung cancer: focus on NSCLC

Considering the high mortality rate encountered in lung cancer, there is a strong need to explore new biomarkers for early diagnosis and also improved therapeutic targets to overcome this issue. The implementation of microRNAs as important regulators in cancer and other pathologies expanded the possibilities of lung cancer management and not only. MiR-21 represents an intensively studied microRNA in many types of cancer, including non-small cell lung cancer (NSCLC). Its role as an oncogene is underlined in multiple studies reporting the upregulated expression of this sequence in patients diagnosed with this malignancy; moreover, several studies associated this increased expression of miR-21 with a worse outcome within NSCLC patients. The same pattern is supported by the data existent in the Cancer Genome Atlas (TCGA). The carcinogenic advantage generated by miR-21 in NSCLC resides in the target genes involved in multiple pathways such as cell growth and proliferation, angiogenesis, invasion and metastasis, but also chemo- and radioresistance. Therapeutic modulation of miR-21 by use of antisense sequences entrapped in different delivery systems has shown promising results in impairment of NSCLC. Hereby, we review the mechanisms of action of miR-21 in cancer and the associated changes upon tumor cells together a focused perspective on NSCLC signaling, prognosis and therapy.     

GSK3 and β-catenin determines functional expression of sodium channels at the axon initial segment

Neuronal action potentials are generated through voltage-gated sodium channels, which are tethered by ankyrinG at the membrane of the axon initial segment (AIS). Despite the importance of the AIS in the control of neuronal excitability, the cellular and molecular mechanisms regulating sodium channel expression at the AIS remain elusive. Our results show that GSK3α/β and β-catenin phosphorylated by GSK3 (S33/37/T41) are localized at the AIS and are new components of this essential neuronal domain. Pharmacological inhibition of GSK3 or β-catenin knockdown with shRNAs decreased the levels of phosphorylated-β-catenin, ankyrinG, and voltage-gated sodium channels at the AIS, both “in vitro” and “in vivo”, therefore diminishing neuronal excitability as evaluated via sodium current amplitude and action potential number. Thus, our results suggest a mechanism for the modulation of neuronal excitability through the control of sodium channel density by GSK3 and β-catenin at the AIS.