bluuebunny/crossref_metadata_2025 huggingface dataset:
Threshold electrolyte concentration and dispersive potential in relation to CROSS in dispersive soils
Authors: Marchuk Alla , Rengasamy Pichu
Published: September 2012

We have used the newly developed concept of CROSS (cation ratio of soil structural stability) instead of SAR (sodium adsorption ratio) in our study on dispersive soils. CROSS incorporates the differential dispersive powers of Na and K and the differences in the flocculating effects of Ca and Mg. The CROSS of the dispersed soil solutions, from the differently treated soils of three soil types varying in clay content, mineralogy, and organic matter, was highly correlated with the amount of clay dispersed. The relation between CROSS and exchangeable cation ratio depended on soil type, and particularly organic matter and the content and mineralogy of clay. Threshold electrolyte concentration of the flocculated suspensions was significantly correlated with CROSS of the dispersed suspensions. The cationic flocculating charge of the flocculated suspensions, which incorporates the individual flocculating powers of the cations, was significantly correlated with CROSS. However, these types of relations will depend on several soil factors even within a given soil class. Therefore, we have derived the dispersive potential of an individual soil from which we calculated the required cationic amendments to maintain flocculated soils and their structural integrity.
Prolonged myelination in human neocortical evolution
Authors: Miller Daniel J. , Duka Tetyana , Stimpson Cheryl D. , Schapiro Steven J. , Baze Wallace B. , McArthur Mark J. , Fobbs Archibald J. , Sousa André M. M. , Šestan Nenad , Wildman Derek E. , Lipovich Leonard , Kuzawa Christopher W. , Hof Patrick R. , Sherwood Chet C.
Published: September 2012

Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N= 20) and humans (N= 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.
Mammalian transcription factor A is a core component of the mitochondrial transcription machinery
Authors: Shi Yonghong , Dierckx Anke , Wanrooij Paulina H. , Wanrooij Sjoerd , Larsson Nils-Göran , Wilhelmsson L. Marcus , Falkenberg Maria , Gustafsson Claes M.
Published: September 2012

Transcription factor A (TFAM) functions as a DNA packaging factor in mammalian mitochondria. TFAM also binds sequence-specifically to sites immediately upstream of mitochondrial promoters, but there are conflicting data regarding its role as a core component of the mitochondrial transcription machinery. We here demonstrate that TFAM is required for transcription in mitochondrial extracts as well as in a reconstituted in vitro transcription system. The absolute requirement of TFAM can be relaxed by conditions that allow DNA breathing, i.e., low salt concentrations or negatively supercoiled DNA templates. The situation is thus very similar to that described in nuclear RNA polymerase II-dependent transcription, in which the free energy of supercoiling can circumvent the need for a subset of basal transcription factors at specific promoters. In agreement with these observations, we demonstrate that TFAM has the capacity to induce negative supercoils in DNA, and, using the recently developed nucleobase analog FRET-pair tC
O
–tC
nitro
, we find that TFAM distorts significantly the DNA structure. Our findings differ from recent observations reporting that TFAM is not a core component of the mitochondrial transcription machinery. Instead, our findings support a model in which TFAM is absolutely required to recruit the transcription machinery during initiation of transcription.
Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome
Authors: Gordon Leslie B. , Kleinman Monica E. , Miller David T. , Neuberg Donna S. , Giobbie-Hurder Anita , Gerhard-Herman Marie , Smoot Leslie B. , Gordon Catherine M. , Cleveland Robert , Snyder Brian D. , Fligor Brian , Bishop W. Robert , Statkevich Paul , Regen Amy , Sonis Andrew , Riley Susan , Ploski Christine , Correia Annette , Quinn Nicolle , Ullrich Nicole J. , Nazarian Ara , Liang Marilyn G. , Huh Susanna Y. , Schwartzman Armin , Kieran Mark W.
Published: September 2012

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in
LMNA
that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.
Small-molecule histone methyltransferase inhibitors display rapid antimalarial activity against all blood stage forms inPlasmodium falciparum
Authors: Malmquist Nicholas A. , Moss Thomas A. , Mecheri Salah , Scherf Artur , Fuchter Matthew J.
Published: September 2012

Epigenetic factors such as histone methylation control the developmental progression of malaria parasites during the complex life cycle in the human host. We investigatedPlasmodium falciparumhistone lysine methyltransferases as a potential target class for the development of novel antimalarials. We synthesized a compound library based upon a known specific inhibitor (BIX-01294) of the human G9a histone methyltransferase. Two compounds, BIX-01294 and its derivative TM2-115, inhibitedP. falciparum3D7 parasites in culture with IC50values of ∼100 nM, values at least 22-fold more potent than their apparent IC50toward two human cell lines and one mouse cell line. These compounds irreversibly arrested parasite growth at all stages of the intraerythrocytic life cycle. Decrease in parasite viability (>40%) was seen after a 3-h incubation with 1 µM BIX-01294 and resulted in complete parasite killing after a 12-h incubation. Additionally, mice with patentPlasmodium bergheiANKA strain infection treated with a single dose (40 mg/kg) of TM2-115 had 18-fold reduced parasitemia the following day. Importantly, treatment ofP. falciparumparasites in culture with BIX-01294 or TM2-115 resulted in significant reductions in histone H3K4me3 levels in a concentration-dependent and exposure time-dependent manner. Together, these results suggest that BIX-01294 and TM2-115 inhibit malaria parasite histone methyltransferases, resulting in rapid and irreversible parasite death. Our data position histone lysine methyltransferases as a previously unrecognized target class, and BIX-01294 as a promising lead compound, in a presently unexploited avenue for antimalarial drug discovery targeting multiple life-cycle stages.
Direct observation of proteolytic cleavage at the S2 site upon forced unfolding of the Notch negative regulatory region
Authors: Stephenson Natalie L. , Avis Johanna M.
Published: September 2012

The conserved Notch signaling pathway plays crucial roles in developing and self-renewing tissues. Notch is activated upon ligand-induced conformation change of the Notch negative regulatory region (NRR) unmasking a key proteolytic site (S2) and facilitating downstream events. Thus far, the molecular mechanism of this signal activation is not defined. However, strong indirect evidence favors a model whereby transendocytosis of the Notch extracellular domain, in tight association with ligand into the ligand-bearing cell, exerts a force on the NRR to drive the required structure change. Here, we demonstrate that force applied to the human Notch2 NRR can indeed expose the S2 site and, crucially, allow cleavage by the metalloprotease TACE (TNF-alpha-converting enzyme). Molecular insight into this process is achieved using atomic force microscopy and molecular dynamics simulations on the human Notch2 NRR. The data show near-sequential unfolding of its constituent LNR (Lin12-Notch repeat) and HD (heterodimerization) domains, at forces similar to those observed for other protein domains with a load-bearing role. Exposure of the S2 site is the first force “barrier” on the unfolding pathway, occurring prior to unfolding of any domain, and achieved via removal of the LNRA∶B linker region from the HD domain. Metal ions increase the resistance of the Notch2 NRR to forced unfolding, their removal clearly facilitating unfolding at lower forces. The results provide direct demonstration of force-mediated exposure and cleavage of the Notch S2 site and thus firmly establish the feasibility of a mechanotransduction mechanism for ligand-induced Notch activation.
Massively parallel measurements of molecular interaction kinetics on a microfluidic platform
Authors: Geertz Marcel , Shore David , Maerkl Sebastian J.
Published: September 2012

Quantitative biology requires quantitative data. No high-throughput technologies exist capable of obtaining several hundred independent kinetic binding measurements in a single experiment. We present an integrated microfluidic device (k-MITOMI) for the simultaneous kinetic characterization of 768 biomolecular interactions. We applied k-MITOMI to the kinetic analysis of transcription factor (TF)—DNA interactions, measuring the detailed kinetic landscapes of the mouse TF Zif268, and the yeast TFs Tye7p, Yox1p, and Tbf1p. We demonstrated the integrated nature of k-MITOMI by expressing, purifying, and characterizing 27 additional yeast transcription factors in parallel on a single device. Overall, we obtained 2,388 association and dissociation curves of 223 unique molecular interactions with equilibrium dissociation constants ranging from 2 × 10
-6
 M to 2 × 10
-9
 M, and dissociation rate constants of approximately 6 s
-1
to 8.5 × 10
-3
 s
-1
. Association rate constants were uniform across 3 TF families, ranging from 3.7 × 10
6
 M
-1
 s
-1
to 9.6 × 10
7
 M
-1
 s
-1
, and are well below the diffusion limit. We expect that k-MITOMI will contribute to our quantitative understanding of biological systems and accelerate the development and characterization of engineered systems.
Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes
Authors: Chen Naiyan , Sugihara Hiroki , Sharma Jitendra , Perea Gertrudis , Petravicz Jeremy , Le Chuong , Sur Mriganka
Published: September 2012

Although cholinergic innervation of the cortex by the nucleus basalis (NB) is known to modulate cortical neuronal responses and instruct cortical plasticity, little is known about the underlying cellular mechanisms. Using cell-attached recordings in vivo, we demonstrate that electrical stimulation of the NB, paired with visual stimulation, can induce significant potentiation of visual responses in excitatory neurons of the primary visual cortex in mice. We further show with in vivo two-photon calcium imaging, ex vivo calcium imaging, and whole-cell recordings that this pairing-induced potentiation is mediated by direct cholinergic activation of primary visual cortex astrocytes via muscarinic AChRs. The potentiation is absent in conditional inositol 1,4,5 trisphosphate receptor type 2 KO mice, which lack astrocyte calcium activation, and is stimulus-specific, because pairing NB stimulation with a specific visual orientation reveals a highly selective potentiation of responses to the paired orientation compared with unpaired orientations. Collectively, these findings reveal a unique and surprising role for astrocytes in NB-induced stimulus-specific plasticity in the cerebral cortex.
Hydra
meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans
Authors: Fraune Johanna , Alsheimer Manfred , Volff Jean-Nicolas , Busch Karoline , Fraune Sebastian , Bosch Thomas C. G. , Benavente Ricardo
Published: September 2012

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms
Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster,
and
Mus musculus
revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan
Hydra
. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans.
Leadership is associated with lower levels of stress
Authors: Sherman Gary D. , Lee Jooa J. , Cuddy Amy J. C. , Renshon Jonathan , Oveis Christopher , Gross James J. , Lerner Jennifer S.
Published: September 2012

As leaders ascend to more powerful positions in their groups, they face ever-increasing demands. As a result, there is a common perception that leaders have higher stress levels than nonleaders. However, if leaders also experience a heightened sense of control—a psychological factor known to have powerful stress-buffering effects—leadership should be associated with reduced stress levels. Using unique samples of real leaders, including military officers and government officials, we found that, compared with nonleaders, leaders had lower levels of the stress hormone cortisol and lower reports of anxiety (study 1). In study 2, leaders holding more powerful positions exhibited lower cortisol levels and less anxiety than leaders holding less powerful positions, a relationship explained significantly by their greater sense of control. Altogether, these findings reveal a clear relationship between leadership and stress, with leadership level being inversely related to stress.
3D imaging and mechanical modeling of helical buckling in
Medicago truncatula
plant roots
Authors: Silverberg Jesse L. , Noar Roslyn D. , Packer Michael S. , Harrison Maria J. , Henley Christopher L. , Cohen Itai , Gerbode Sharon J.
Published: September 2012

We study the primary root growth of wild-type Medicago truncatula plants in heterogeneous environments using 3D time-lapse imaging. The growth medium is a transparent hydrogel consisting of a stiff lower layer and a compliant upper layer. We find that the roots deform into a helical shape just above the gel layer interface before penetrating into the lower layer. This geometry is interpreted as a combination of growth-induced mechanical buckling modulated by the growth medium and a simultaneous twisting near the root tip. We study the helical morphology as the modulus of the upper gel layer is varied and demonstrate that the size of the deformation varies with gel stiffness as expected by a mathematical model based on the theory of buckled rods. Moreover, we show that plant-to-plant variations can be accounted for by biomechanically plausible values of the model parameters.
HIV-1 Gag protein can sense the cholesterol and acyl chain environment in model membranes
Authors: Dick Robert A. , Goh Shih Lin , Feigenson Gerald W. , Vogt Volker M.
Published: September 2012

Membrane binding of the HIV-1 group-specific antigen (Gag) structural protein, a critical step in viral assembly at the plasma membrane, is mediated by the myristoylated, highly basic matrix (MA) domain, which interacts with negatively charged lipids in the inner leaflet. According to a popular model, virus particles bud from membrane rafts, microdomains enriched in cholesterol and high-melting phospholipids with higher order than found outside rafts. How Gag might recognize membrane rafts, if they exist in the inner leaflet, is unknown. Using a liposome flotation assay with proteins translated in vitro, we investigated whether Gag can sense the composition of the hydrophobic part of the bilayer, by fixing lipid head group composition and varying hydrophobic properties. In liposomes composed solely of phosphatidylserine and phosphatidylcholine, and with the same overall membrane negative charge, Gag strongly preferred lipids with both acyl chains unsaturated over those with only one chain unsaturated. Adding cholesterol increased Gag binding and led to closer packing of phospholipids. However, higher membrane order, as measured by electron spin resonance, was not correlated with increased Gag binding. Gag proteins from two other retroviruses gave similar results. These liposome binding preferences were qualitatively recapitulated by purified myristoylated HIV-1 MA. Phosphatidylinositol 4,5-bisphosphate and cholesterol enhanced binding in an additive manner. Taken together, these results show that Gag is sensitive both to the acyl chains of phosphatidylserine and to cholesterol concentration and other details of the membrane environment. These observations may help explain how retroviruses acquire a raft-like lipid composition.
Long range order and two-fluid behavior in heavy electron materials
Authors: Shirer Kent R. , Shockley Abigail C. , Dioguardi Adam P. , Crocker John , Lin Ching H. , apRoberts-Warren Nicholas , Nisson David M. , Klavins Peter , Cooley Jason C. , Yang Yi-feng , Curro Nicholas J.
Published: September 2012

The heavy electron Kondo liquid is an emergent state of condensed matter that displays universal behavior independent of material details. Properties of the heavy electron liquid are best probed by NMR Knight shift measurements, which provide a direct measure of the behavior of the heavy electron liquid that emerges below the Kondo lattice coherence temperature as the lattice of local moments hybridizes with the background conduction electrons. Because the transfer of spectral weight between the localized and itinerant electronic degrees of freedom is gradual, the Kondo liquid typically coexists with the local moment component until the material orders at low temperatures. The two-fluid formula captures this behavior in a broad range of materials in the paramagnetic state. In order to investigate two-fluid behavior and the onset and physical origin of different long range ordered ground states in heavy electron materials, we have extended Knight shift measurements to URu
2
Si
2
, CeIrIn
5
, and CeRhIn
5
. In CeRhIn
5
we find that the antiferromagnetic order is preceded by a relocalization of the Kondo liquid, providing independent evidence for a local moment origin of antiferromagnetism. In URu
2
Si
2
the hidden order is shown to emerge directly from the Kondo liquid and so is not associated with local moment physics. Our results imply that the nature of the ground state is strongly coupled with the hybridization in the Kondo lattice in agreement with phase diagram proposed by Yang and Pines.
Emergent states in heavy-electron materials
Authors: Yang Yi-feng , Pines David
Published: September 2012

We obtain the conditions necessary for the emergence of various low-temperature ordered states (local-moment antiferromagnetism, unconventional superconductivity, quantum criticality, and Landau Fermi liquid behavior) in Kondo lattice materials by extending the two-fluid phenomenological theory of heavy-electron behavior to incorporate the concept of hybridization effectiveness. We use this expanded framework to present a new phase diagram and consistent physical explanation and quantitative description of measured emergent behaviors such as the pressure variation of the onset of local-moment antiferromagnetic ordering at
T

N

, the magnitude of the ordered moment, the growth of superconductivity within that ordered state, the location of a quantum critical point, and of a delocalization line in the pressure/temperature phase diagram at which local moments have disappeared and the heavy-electron Fermi surface has grown to its maximum size. We apply our model to CeRhIn
5
and a number of other heavy-electron materials and find good agreement with experiment.
Cyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates penile erection
Authors: Hurt K. Joseph , Sezen Sena F. , Lagoda Gwen F. , Musicki Biljana , Rameau Gerald A. , Snyder Solomon H. , Burnett Arthur L.
Published: September 2012

Nitric oxide (NO) generated by neuronal NO synthase (nNOS) initiates penile erection, but has not been thought to participate in the sustained erection required for normal sexual performance. We now show that cAMP-dependent phosphorylation of nNOS mediates erectile physiology, including sustained erection. nNOS is phosphorylated by cAMP-dependent protein kinase (PKA) at serine(S)1412. Electrical stimulation of the penile innervation increases S1412 phosphorylation that is blocked by PKA inhibitors but not by PI3-kinase/Akt inhibitors. Stimulation of cAMP formation by forskolin also activates nNOS phosphorylation. Sustained penile erection elicited by either intracavernous forskolin injection, or augmented by forskolin during cavernous nerve electrical stimulation, is prevented by the NOS inhibitorl-NAME or in nNOS-deleted mice. Thus, nNOS mediates both initiation and maintenance of penile erection, implying unique approaches for treating erectile dysfunction.
Enhanced production of early lineages of monocytic and granulocytic cells in mice with colitis
Authors: Trottier Mark D. , Irwin Regina , Li Yihang , McCabe Laura R. , Fraker Pamela J.
Published: September 2012

The bone marrow (BM) is a large, highly active, and responsive tissue. Interestingly, little is known about the impact of colitis on hematopoietic functions. Using dextran sodium sulfate (DSS) to induce colitis in mice, we identified significant changes in the BM. Specifically, cells of the monocytic and granulocytic lineages increased nearly 60% and 80%, respectively. This change would support and promote the large infiltration of the gut with neutrophils and monocytes that are the primary cause of inflammation and tissue damage during colitis. Conversely, the early lineages of B and T cells declined in the marrow and thymus with particularly large losses observed among pre-B and pre-T cells with heightened levels of apoptosis noted among CD4
+
CD8
+
thymocytes from DSS-treated mice. Also noteworthy was the 40% decline in cells of the erythrocytic lineages in the marrow of colitis mice, which undoubtedly contributed to the anemia observed in these mice. The peripheral blood reflected the marrow changes as demonstrated by a 2.6-fold increase in neutrophils, a 60% increase in monocytes, and a decline in the lymphocyte population. Thus, colitis changed the BM in profound ways that parallel the general outcomes of colitis including infiltration of the gut with monocytes and neutrophils, inflammation, and anemia. The data provide important understandings of the full impact of colitis that may lead to unique treatments and therapies.
bHLH-PAS heterodimer of methoprene-tolerant and Cycle mediates circadian expression of juvenile hormone-induced mosquito genes
Authors: Shin Sang Woon , Zou Zhen , Saha Tusar T. , Raikhel Alexander S.
Published: September 2012

Juvenile hormone (JH) governs a great diversity of processes in insect development and reproduction. It plays a critical role in controlling the gonadotrophic cycles of female mosquitoes by preparing tissues for blood digestion and egg development. Here, we show that in femaleAedes aegyptimosquitoes JH III control of gene expression is mediated by a heterodimer of two bHLH-PAS proteins—the JH receptor methoprene-tolerant (MET) and Cycle (CYC, AAEL002049). We identifiedAedesCYC as a MET-interacting protein using yeast two-hybrid screening. Binding of CYC and MET required the presence of JH III. In newly eclosed female mosquitoes, the expression of two JH-responsive genes,Kr-h1andHairy, was dependent on both the ratio of light to dark periods and JH III. Their expression was compromised by in vivo RNA interference (RNAi) depletions ofCYC,MET, and the steroid receptor coactivatorSRC/FISC. Moreover, JH III was not effective in induction ofKr-h1andHairygene expression in vitro in fat bodies of female mosquitoes with RNAi-depletedCYC,METorSRC/FISC.A sequence containing an E-box–like motif from theAedes Kr-h1gene promoter specifically interacted with a protein complex, which included MET and CYC from the female mosquito fat body nuclear extract. These results indicate that a MET/CYC heterodimer mediates JH III activation ofKr-h1andHairygenes in the context of light-dependent circadian regulation in female mosquitoes during posteclosion development. This study provides an important insight into the understanding of the molecular basis of JH action.
Impairment of O-antigen production confers resistance to grazing in a model amoeba–cyanobacterium predator–prey system
Authors: Simkovsky Ryan , Daniels Emy F. , Tang Karen , Huynh Stacey C. , Golden Susan S. , Brahamsha Bianca
Published: September 2012

The grazing activity of predators on photosynthetic organisms is a major mechanism of mortality and population restructuring in natural environments. Grazing is also one of the primary difficulties in growing cyanobacteria and other microalgae in large, open ponds for the production of biofuels, as contaminants destroy valuable biomass and prevent stable, continuous production of biofuel crops. To address this problem, we have isolated a heterolobosean amoeba, HGG1, that grazes upon unicellular and filamentous freshwater cyanobacterial species. We have established a model predator–prey system using this amoeba andSynechococcus elongatusPCC 7942. Application of amoebae to a library of mutants ofS. elongatusled to the identification of a grazer-resistant knockout mutant of thewzmABC O-antigen transporter gene, SynPCC7942_1126. Mutations in three other genes involved in O-antigen synthesis and transport also prevented the expression of O-antigen and conferred resistance to HGG1. Complementation of these rough mutants returned O-antigen expression and susceptibility to amoebae. Rough mutants are easily identifiable by appearance, are capable of autoflocculation, and do not display growth defects under standard laboratory growth conditions, all of which are desired traits for a biofuel production strain. Thus, preventing the production of O-antigen is a pathway for producing resistance to grazing by certain amoebae.
Biogenesis of the mitochondrial Hsp70 chaperone
Authors: Blamowska Marta , Neupert Walter , Hell Kai
Published: September 2012

Chaperones mediate protein folding and prevent deleterious protein aggregation in the cell. However, little is known about the biogenesis of chaperones themselves. In this study, we report on the biogenesis of the yeast mitochondrial Hsp70 (mtHsp70) chaperone, which is essential for the functionality of mitochondria. We show in vivo and in organello that mtHsp70 rapidly folds after its import into mitochondria, with its ATPase domain and peptide-binding domain (PBD) adopting their structures independently of each other. Importantly, folding of the ATPase domain but not of the PBD was severely affected in the absence of the Hsp70 escort protein, Hep1. We reconstituted the folding of mtHsp70, demonstrating that Hep1 and ATP/ADP were required and sufficient for its de novo folding. Our data show that Hep1 bound to a folding intermediate of mtHsp70. Binding of an adenine nucleotide triggered release of Hep1 and folding of the intermediate into native mtHsp70. Thus, Hep1 acts as a specialized chaperone mediating the de novo folding of an Hsp70 chaperone.
Structural basis of the junctional anchorage of the cerebral cavernous malformations complex
Authors: Gingras Alexandre R. , Liu Jian J. , Ginsberg Mark H.
Published: September 2012

The products of genes that cause cerebral cavernous malformations (CCM1/KRIT1, CCM2, and CCM3) physically interact. CCM1/KRIT1 links this complex to endothelial cell (EC) junctions and maintains junctional integrity in part by inhibiting RhoA. Heart of glass (HEG1), a transmembrane protein, associates with KRIT1. In this paper, we show that the KRIT1 band 4.1, ezrin, radixin, and moesin (FERM) domain bound the HEG1 C terminus (Kd = 1.2 µM) and solved the structure of this assembly. The KRIT1 F1 and F3 subdomain interface formed a hydrophobic groove that binds HEG1(Tyr1,380-Phe1,381), thus defining a new mode of FERM domain–membrane protein interaction. This structure enabled design of KRIT1(L717,721A), which exhibited a >100-fold reduction in HEG1 affinity. Although well folded and expressed, KRIT1(L717,721A) failed to target to EC junctions or complement the effects of KRIT1 depletion on zebrafish cardiovascular development or Rho kinase activation in EC. These data establish that this novel FERM–membrane protein interaction anchors CCM1/KRIT1 at EC junctions to support cardiovascular development.
The Cbp3–Cbp6 complex coordinates cytochrome b synthesis with bc1 complex assembly in yeast mitochondria
Authors: Gruschke Steffi , Römpler Katharina , Hildenbeutel Markus , Kehrein Kirsten , Kühl Inge , Bonnefoy Nathalie , Ott Martin
Published: September 2012

Respiratory chain complexes in mitochondria are assembled from subunits derived from two genetic systems. For example, the bc1 complex consists of nine nuclear encoded subunits and the mitochondrially encoded subunit cytochrome b. We recently showed that the Cbp3–Cbp6 complex has a dual function for biogenesis of cytochrome b: it is both required for efficient synthesis of cytochrome b and for protection of the newly synthesized protein from proteolysis. Here, we report that Cbp3–Cbp6 also coordinates cytochrome b synthesis with bc1 complex assembly. We show that newly synthesized cytochrome b assembled through a series of four assembly intermediates. Blocking assembly at early and intermediate steps resulted in sequestration of Cbp3–Cbp6 in a cytochrome b–containing complex, thereby making Cbp3–Cbp6 unavailable for cytochrome b synthesis and thus reducing overall cytochrome b levels. This feedback loop regulates protein synthesis at the inner mitochondrial membrane by directly monitoring the efficiency of bc1 complex assembly.
Tryptophan hydroxylase-1 regulates immune tolerance and inflammation
Authors: Nowak Elizabeth C. , de Vries Victor C. , Wasiuk Anna , Ahonen Cory , Bennett Kathryn A. , Le Mercier Isabelle , Ha Dae-Gon , Noelle Randolph J.
Published: September 2012

Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control inflammatory responses and immune tolerance. Here we report the novel finding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a potent regulator of immunity. In models of skin allograft tolerance, tumor growth, and experimental autoimmune encephalomyelitis, Tph-1 deficiency breaks allograft tolerance, induces tumor remission, and intensifies neuroinflammation, respectively. All of these effects of Tph-1 deficiency are independent of its downstream product serotonin. Because mast cells (MCs) appear to be the major source of Tph-1 and restoration of Tph-1 in the MC compartment in vivo compensates for the defect, these experiments introduce a fundamentally new mechanism of MC-mediated immune suppression that broadly impacts multiple arms of immunity.
An Amino Acid Substitution Inhibits Specialist Herbivore Production of an Antagonist Effector and Recovers Insect-Induced Plant Defenses
Authors: Schmelz Eric A. , Huffaker Alisa , Carroll Mark J. , Alborn Hans T. , Ali Jared G. , Teal Peter E.A.
Published: September 2012

Plants respond to insect herbivory through the production of biochemicals that function as either direct defenses or indirect defenses via the attraction of natural enemies. While attack by closely related insect pests can result in distinctive levels of induced plant defenses, precise biochemical mechanisms responsible for differing responses remain largely unknown. Cowpea (Vigna unguiculata) responds to Fall armyworm (Spodoptera frugiperda) herbivory through the detection of fragments of chloroplastic ATP synthase γ-subunit proteins, termed inceptin-related peptides, present in larval oral secretions (OS). In contrast to generalists like Fall armyworm, OS of the legume-specializing velvetbean caterpillar (VBC; Anticarsia gemmatalis) do not elicit ethylene production and demonstrate significantly lower induced volatile emission in direct herbivory comparisons. Unlike all other Lepidoptera OS examined, which preferentially contain inceptin (Vu-In; +ICDINGVCVDA−), VBC  OS contain predominantly a C-terminal truncated peptide, Vu-In−A (+ICDINGVCVD−). Vu-In−A is both inactive and functions as a potent naturally occurring antagonist of Vu-In-induced responses. To block antagonist production, amino acid substitutions at the C terminus were screened for differences in VBC gut proteolysis. A valine-substituted peptide (Vu-InƊV; +ICDINGVCVDV−) retaining full elicitor activity was found to accumulate in VBC  OS. Compared with the native polypeptide, VBC that previously ingested 500 pmol of the valine-modified chloroplastic ATP synthase γ-subunit precursor elicited significantly stronger plant responses in herbivory assays. We demonstrate that a specialist herbivore minimizes the activation of defenses by converting an elicitor into an antagonist effector and identify an amino acid substitution that recovers these induced plant defenses to a level observed with generalist herbivores.
Transferring corporate knowledge via succession planning: analysis and solutions – Part 2
Authors: Appelbaum Steven H. , Benyo Christina , Gunkel Heidi , Ramadan Said , Sakkal Fadi , Wolff Damian
Published: September 2012

Purpose

The focus of the paper is a large, national, publicly traded company. As a large number of its workforce consists of “baby boomers”, 50 percent of its employees will be of retirement age within the next five years. Having acknowledged the company's concerns about efficiency of new employees and the loss of morale in senior employees, this two‐part article sets out to provide motivational tools for management and to suggest solutions to restructure and reorganize in a way to prevent the inevitable – i.e. the loss of corporate knowledge – via succession planning.

Design/methodology/approach

A survey and individual interviews were conducted within the company to measure current job satisfaction and company culture as well as how the different generations of employees view each other and themselves. Employees were also questioned about their legacy in the organization and their thoughts about transferring corporate knowledge from one generation to another. This is a two‐part article. Part 1 covers the background to the case under investigation, a review of relevant literature and the hypotheses to test the problem to be studied and solved. Part 2 describes the methodology and data related to demographics, the testing of the hypotheses and conclusions and recommendations.

Findings

The study found a correlation between job satisfaction and effective communication and a negative correlation between pre‐retirees and their lack of motivation as they approach retirement. Also, it was found that senior employees possess a willingness to share and transfer knowledge to younger generations.

Research limitations/implications

The article relies on limited survey and interview data of one particular regional department within a large organization. Certain demographic questions were omitted to preserve confidentiality. The selected department and interview subjects were chosen by the organization and therefore the occurrence of sampling error is possible.

Practical implications

This study monitored the impact that recent retirees will have on the remaining staff of a company. The act of effective succession planning is of paramount importance since the “baby boomer” generation is comprised of 76 million North Americans and the threat of the loss of corporate knowledge will inevitably increase as the population ages. The article offers recommendations as to how an organization can better manage the impact of a large number of retirees on the remaining workforce and what it can do to maximize efficiency.

Originality/value

The article offers practical solutions for dealing with the impact of retiring baby boomers and identifies models for a proactive approach in dealing with an issue that will affect the North American economy within the next five years.
The music of leadership
Authors: Cook Peter , Howitt John
Published: September 2012

Purpose

In an attempt to rethink business after the worst recession for many decades, it is vital to rethink leadership and the sorts of HR strategies that will help companies thrive and survive in ways that are genuinely sustainable. This paper aims to explore three musical genres and their connections and contrasts with leadership.

Design/methodology/approach

Through literature reviews informed by qualitative and action research, the paper reviews three musical paradigms and connects them with leadership practices.

Findings

In an ever‐complex world, leadership needs to convey complex concepts simply and concisely. It also needs to value diverse talents in ways that go beyond the usual definitions of diversity.

Research limitations/implications

Qualitative/action research inevitably needs to be backed up by more formal research into the topic. This paper offers an agenda for action and further qualitative/quantitative research.

Practical implications

Great leaders also have personal mastery, whilst also being able to tune in to the world around them. These are skills that can be learned/enhanced through experiential learning in the main.

Social implications

Great leaders make complexity compellingly clear. They do this through providing sufficient structure to enable people to be their best. Music is the analogy of choice for making complex communications clear and there is much more to understand in this area.

Originality/value

Much effort has been expended on examining the parallels between business leadership and sports. Relatively little effort has been spent on music, which offers unique insights into the questions of diversity and teamwork in the context of high performance.
Effective and efficient mobile learning: issues and tips for developers
Authors: Little Bob
Published: September 2012

Purpose

This paper's aim is to outline trends and recent developments in the design, developments and use of mobile learning.

Design/methodology/approach

The paper uses interviews with key players in the mobile learning development sector, along with complementary research.

Findings

It is found that: mobile learning is developing fast – not just in terms of applications but also in terms of its philosophy and standards; mobile learning can offer great value to learners because it can connect employees to the knowledge and expertise they need, when and where they need it; and new standards, authoring tools and authoring approaches to mobile learning are developing.

Practical implications

Merely transferring classroom based training to “e”, and especially mobile, learning does not really work. New technology, techniques and interoperable standards need to be – and are being – developed for mobile learning.

Originality/value

No comparable articles exist.
“Become what you are!”
Authors: Duke Alan , Boulanger Daniel
Published: September 2012

Purpose

This article's aim is to demonstrate the pertinence and success of Michelin's worldwide talent and career management model, the purpose of which is to allow all employees to realise their full potential, or “become what they are”.

Design/methodology/approach

The article is an inside account of principles, career management methods, development programmes and measurement tools by two former international career managers with Michelin – one English, one French – responsible for policy design and application, career development for senior management, and identification and development of tomorrow's leaders worldwide. A comparative table demonstrates the stark differences between a “become what you are” and a “do what you know” approach.

Findings

In a corporate culture based on respect for people, successful development of employee potential requires a three‐way partnership between employee, line manager and an independent career manager who is ultimately responsible for appointments. Managers do not own their people and individual development takes precedence over short‐term operational needs. The model results in cohesiveness, loyalty and business success.

Research implications/limitations

This is a case study of one career management model as related by two seasoned professionals responsible for making it work worldwide.

Practical implications

The model can be applied in any national culture and across organisational barriers or “silos”. It is transferable wholly or partially to other organisations, both private and public.

Social implications

The result is an improved working atmosphere where employees are generally content to get on with the job and let someone else, calmly and impartially, plan their futures. This person is known, is independent from line management, and has the authority to act.

Originality/value

This is not a new theory, but a view from within of a highly successful career management model that has stood the test of time and can be applied universally.
Connecting across continents: collaborative learning in a Web 2.0 world
Authors: Davis Kate , Hallam Gillian , Henry Katya , Davis Wendy , Fairbairn Kysira , Heidelberger Ellen
Published: September 2012

Purpose

The article aims to review a university course, offered to students in both Australia and Germany, to encourage them to learn about designing, implementing, marketing and evaluating information programs and services in order to build active and engaged communities. The concepts and processes of Web 2.0 technologies come together in the learning activities, with students establishing their own personal learning networks (PLNs).

Design/methodology/approach

The case study examines the principles of learning and teaching that underpin the course and presents the students' own experiences of the challenges they faced as they explored the interactive, participative and collaborative dimensions of the web.

Findings

The online format of the course and the philosophy of learning through play provided students with a safe and supportive environment for them to move outside of their comfort zones, to be creative, to experiment and to develop their professional personas. Reflection on learning was a key component that stressed the value of reflective practice in assisting library and information science (LIS) professionals to adapt confidently to the rapidly changing work environment.

Originality/value

This study provides insights into the opportunities for LIS courses to work across geographical boundaries, to allow students to critically appraise library practice in different contexts and to become active participants in wider professional networks.
Mobile augmented reality applications for library services
Authors: Hahn Jim
Published: September 2012

Purpose

The purpose of this paper is to introduce mobile augmented reality applications for library uses and next generation library services.

Design/methodology/approach

Examples are drawn from museum and archives informatics, computer science applied research, and computer vision research as well as original research and development work from the Undergraduate Library at the University of Illinois.

Findings

Mobile augmented reality uses include augmenting physical book stacks browsing, library navigation, optical character recognition, facial recognition, and building identification mobile software for compelling library experiences.

Originality/value

The paper suggests uses of mobile augmented reality applications in library settings and models a demonstration prototype interface.
Management versus repetitive tasks – avoiding “working for the weekend”
Authors: Thomas Janelle R. , Holley Robert P.
Published: September 2012

Purpose

In this paper the authors aim to examine ways to motivate staff whose job assignments include repetitive library tasks such as shelving, copy cataloguing, circulation, and other similar functions.

Design/methodology/approach

The authors review the appropriate management literature and build upon the extensive management experience of the second author.

Findings

Ways to increase employee motivation including enriching the work experience, effective communication, appropriate incentives, and treating each employee as an individual. Sharing tasks among staff and maintaining an ergonomic workspace are also important. Library automation and eliminating unneeded tasks can reduce repetitive tasks but can also lead to a reduction in staff.

Practical implications

The paper provides practical steps for managers to take to keep staff motivated when faced with repetitive tasks.

Originality/value

This paper summarizes the management literature on this topic to provide practical guidance for library managers.
Using predictive analytics in the library
Authors: Massis Bruce E.
Published: September 2012

Purpose

The purpose of this column is to introduce predictive analytics and its potential for use in the library.

Design/methodology/approach

The paper uses a literature review and commentary on this topic that has been addressed by theoreticians, researchers and practitioners.

Findings

Today, there are numerous commercial data‐analysis software tools that can assist the library in its organizational planning efforts. Most prominently in the basic areas of staffing, budgets, collections, services and facilities, predictive analytics can be used to help develop an overall plan of financial and programmatic development for the library.

Originality/value

The value in addressing this issue is to suggest that libraries might consider use of data‐analysis software to support their budget and planning processes.