Sec6 mutations and the Drosophila exocyst complex

To allow a detailed analysis of exocyst function in multicellular organisms, we have generated sec6 mutants in Drosophila. We have used these mutations to compare the phenotypes of sec6 and sec5 in the ovary and nervous system, and we find them to be similar. We also find that Sec5 is mislocalized in sec6 mutants. Additionally, we have generated an epitope-tagged Sec8 that localized with Sec5 on oocyte membranes and was mislocalized in sec5 and sec6 germ-line clones. This construct further revealed a genetic interaction of sec8 and sec5. These data, taken together, provide new information about the organization of the exocyst complex and suggest that Sec5, Sec6 and Sec8 act as a complex, each member dependent on the others for proper localization and function

Drosophila Importin-α2 Is Involved in Synapse, Axon and Muscle Development

Nuclear import is required for communication between the cytoplasm and the nucleus and to enact lasting changes in gene transcription following stimuli. Binding to an Importin-α molecule in the cytoplasm is often required to mediate nuclear entry of a signaling protein. As multiple isoforms of Importin-α exist, some may be responsible for the entry of distinct cargoes rather than general nuclear import. Indeed, in neuronal systems, Importin-α isoforms can mediate very specific processes such as axonal tiling and communication of an injury signal. To study nuclear import during development, we examined the expression and function of Importin-α2 in Drosophila melanogaster. We found that Importin-α2 was expressed in the nervous system where it was required for normal active zone density at the NMJ and axonal commissure formation in the central nervous system. Other aspects of synaptic morphology at the NMJ and the localization of other synaptic markers appeared normal in importin-α2 mutants. Importin-α2 also functioned in development of the body wall musculature. Mutants in importin-α2 exhibited errors in muscle patterning and organization that could be alleviated by restoring muscle expression of Importin-α2. Thus, Importin-α2 is needed for some processes in the development of both the nervous system and the larval musculature

Negotiation, Email, and Internet Reverse Auctions: How Sourcing Mechanisms Deployed by Buyers Affect Suppliers’ Trust

The Internet has made a wealth of new tools available to the industrial buyer. However, researchers have suggested that computer mediated interaction with suppliers may not be conducive to strong supplier relationships in general and to trust in particular. This paper compares two computer-mediated sourcing tools (email negotiation and Internet reverse auctions) with face-to-face negotiation. Information richness theory suggests that the different media will produce different impacts relating to sellers’ trust in buyers. Data are generated with a simulation experiment using 117 subjects. We found that information richness affects seller-buyer trust: Sellers who used face-to-face negotiation, the richest medium in the study, always reported higher trust in their buyer counterparts than did sellers using Internet reverse auctions. There were also some trust advantages of face-to-face negotiation over email and limited advantages of email over reverse auctions. We also found that procurement complexity influences the relationship between information richness and trust. As hypothesized, when face-to-face negotiation is used, procurement complexity has no effect on seller trust. When reverse auctions are utilized, the greater the complexity of the purchase, the less the seller trust. However, when email is used, greater procurement complexity is associated with greater seller trust, and there are no differences in trust between the email and face-to-face channels. Finally, we found that sellers’ trust in buyers is positively associated with sellers’ desire for future dealings with the buyer

‘Writes a fair hand and appears to be well qualified’ : the recruitment of Bank of England clerks, 1800-1815

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly citedThe financial strains of the Revolutionary and Napoleonic Wars had a significant impact on the Bank of England. In its position as banker to the state and manager of the state’s debt, it experienced a significant increase in workload and thus was forced rapidly to expand its workforce. From a complement of around 300 in the mid-1780s, the number of clerks employed had increased to over 900 in 1815. Using a unique set of records preserved in the Bank’s archives, this article investigates the backgrounds and skills of the men recruited during the expansion of the early nineteenth century. It finds a significant gap between the skills required by the Bank and the skills possessed by its potential workforce.Peer reviewedFinal Published versio

A first-principles comparison of the electronic properties of MgC_{y}Ni_{3} and ZnC_{y}Ni_{3} alloys

First-principles, density-functional-based electronic structure calculations are employed to study the changes in the electronic properties of ZnC_{y}Ni_{3} and MgC_{y}Ni_{3} using the Korringa-Kohn-Rostoker coherent-potential approximation method in the atomic sphere approximation (KKR-ASA CPA). As a function of decreasing C at%, we find a steady decrease in the lattice constant and bulk modulus in either alloys. However, the pressure derivative of the bulk modulus displays an opposite trend. Following the Debye model, which relates the pressure derivative of the bulk modulus with the average phonon frequency of the crystal, it can thus be argued that ZnCNi_{3} and its disordered alloys posses a different phonon spectra in comparison to its MgCNi_{3} counterparts. This is further justified by the marked similarity we find in the electronic structure properties such as the variation in the density of states and the Hopfield parameters calculated for these alloys. The effects on the equation of state parameters and the density of states at the Fermi energy, for partial replacement of Mg by Zn are also discussed.Comment: 19 pages, 15 figure

Cytoskeletal variations in an asymmetric cell division support diversity in nematode sperm size and sex ratios

Asymmetric partitioning is an essential component of many developmental processes. As spermatogenesis concludes, sperm are streamlined by discarding unnecessary cellular components into cellular wastebags called residual bodies (RBs). During nematode spermatogenesis, this asymmetric partitioning event occurs shortly after anaphase II, and both microtubules and actin partition into a central RB. Here, we use fluorescence and transmission electron microscopy to elucidate and compare the intermediate steps of RB formation in Caenorhabditis elegans, Rhabditis sp. SB347 (recently named Auanema rhodensis) and related nematodes. In all cases, intact microtubules reorganize and move from centrosomal to non-centrosomal sites at the RB-sperm boundary whereas actin reorganizes through cortical ring expansion and clearance from the poles. However, in species with tiny spermatocytes, these cytoskeletal changes are restricted to one pole. Consequently, partitioning yields one functional sperm with the X-bearing chromosome complement and an RB with the other chromosome set. Unipolar partitioning may not require an unpaired X, as it also occurs in XX spermatocytes. Instead, constraints related to spermatocyte downsizing may have contributed to the evolution of a sperm cell equivalent to female polar bodies

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

Self-Assembled Triply Periodic Minimal Surfaces as moulds for Photonic Band Gap Materials

We propose systems with structures defined by self-assembled triply periodic minimal surfaces (STPMS) as candidates for photonic bandgap materials. To support our proposal we have calculated the photonic bands for different STPMS and we have found that, at least, the double diamond and gyroid structures present full photonic bandgaps. Given the great variety of systems which crystalize in these structures, the diversity of possible materials that form them and the range of lattice constants they present, the construction of photonic bandgap materials with gaps in the visible range may be presently within reach.Comment: 3 pages, 2 figures, RevTe