bluuebunny/crossref_metadata_2025 huggingface dataset:
Native oligomerization determines the mode of action and biological activities of human cathelicidin LL-37
Authors: Xhindoli Daniela , Pacor Sabrina , Guida Filomena , Antcheva Nikolinka , Tossi Alessandro
Published: October 2013

LL-37 is a multifunctional component of innate immunity, with a membrane-directed antimicrobial activity and receptor-mediated pleiotropic effects on host cells. Sequence variations in its primate orthologues suggest that two types of functional features have evolved; human LL-37-like peptides form amphipathic helical structures and self-assemble under physiological conditions, whereas rhesus RL-37-like peptides only adopt this structure in the presence of bacterial membranes. The first type of peptide has a lower and more medium-sensitive antimicrobial activity than the second type, but an increased capacity to stimulate host cells. Oligomerization strongly affects the mode of interaction with biological membranes and, consequently, both cytotoxicity and receptor-mediated activities. In the present study we explored the effects of LL-37 self-association by using obligate disulfide-linked dimers with either parallel or antiparallel orientations. These had an increased propensity to form stacked helices in bulk solution and when in contact with either anionic or neutral model membranes. The antimicrobial activity against Gram-positive or Gram-negative bacteria, as well as the cytotoxic effects on host cells, strongly depended on the type of dimerization. To investigate the extent of native oligomerization we replaced Phe5 with the photoactive residue Bpa (p-benzoyl-L-phenylalanine), which, upon UV irradiation, enabled covalent cross-linking and allowed us to assess the extent of oligomerization in both physiological solution and in model membranes.
Stability of cerebral metabolism and substrate availability in humans during hypoxia and hyperoxia
Authors: Ainslie Philip N. , Shaw Andrew D. , Smith Kurt J. , Willie Christopher K. , Ikeda Keita , Graham Joseph , Macleod David B.
Published: October 2013

Characterization of the influence of oxygen availability on brain metabolism is an essential step toward a better understanding of brain energy homoeostasis and has obvious clinical implications. However, how brain metabolism depends on oxygen availability has not been clearly examined in humans. We therefore assessed the influence of oxygen on CBF (cerebral blood flow) and CMRO2 (cerebral metabolic rates for oxygen) and carbohydrates. PaO2 (arterial partial pressure of oxygen) was decreased for 15 min to ~60, ~44 and ~35 mmHg [to target a SaO2 (arterial oxygen saturation) of 90, 80 and 70% respectively], and elevated to ~320 and ~430 mmHg. Isocapnia was maintained during each trial. At the end of each stage, arterial–jugular venous differences and volumetric CBF were measured to directly calculate cerebral metabolic rates. During progressive hypoxaemia, elevations in CBF were correlated with the reductions in both SaO2 (R2=0.54, P<0.05) and CaO2 (arterial oxygen content) (R2=0.57, P<0.05). Despite markedly reduced CaO2, cerebral oxygen delivery was maintained by increased CBF. Cerebral metabolic rates for oxygen, glucose and lactate remained unaltered during progressive hypoxia. Consequently, cerebral glucose delivery was in excess of that required, and net lactate efflux increased slightly in severe hypoxia, as reflected by a small increase in jugular venous lactate. Progressive hyperoxia did not alter CBF, CaO2, substrate delivery or cerebral metabolism. In conclusion, marked elevations in CBF with progressive hypoxaemia and related reductions in CaO2 resulted in a well-maintained cerebral oxygen delivery. As such, cerebral metabolism is still supported almost exclusively by carbohydrate oxidation during severe levels of hypoxaemia.
Musical agency reduces perceived exertion during strenuous physical performance
Authors: Fritz Thomas Hans , Hardikar Samyogita , Demoucron Matthias , Niessen Margot , Demey Michiel , Giot Olivier , Li Yongming , Haynes John-Dylan , Villringer Arno , Leman Marc
Published: October 2013

Significance

Here we present a data set demonstrating that musical agency greatly decreases the perceived exertion during strenuous activity. We believe these findings are a major contribution to how we consider the role of music in the emergence of human societies. Furthermore, these findings are timely because they crucially help to understand the therapeutic power of music, a scientific field about to unfold. Although one would expect this workout with musical feedback (jymmin') to be a rather unconventional and dimensionally constrained (each instrument one-dimensionally regulates a musical signal) way to experience musical agency, the experience of the performers suggests an intimate entwinement of ecstatic pleasure and exertion during the performance.
ELL, a novel TFIIH partner, is involved in transcription restart after DNA repair
Authors: Mourgues Sophie , Gautier Violette , Lagarou Anna , Bordier Christine , Mourcet Amandine , Slingerland Joris , Kaddoum Lara , Coin Frédéric , Vermeulen Wim , Gonzales de Peredo Anne , Monsarrat Bernard , Mari Pierre-Olivier , Giglia-Mari Giuseppina
Published: October 2013

Significance

A variety of genotoxic agents cause DNA lesions which, when located on a transcribed gene, will block the RNA polymerase II and recruit DNA repair proteins, including the basal transcription factor IIH, to restore the genetic information via the pathway known as transcription-coupled repair. Once the repair process is completed, transcription is expected to restart to restore proper cellular functions. RNA polymerase II restart after DNA repair in higher eukaryotes has not been studied mechanistically. We have identified eleven-nineteen lysine-rich leukemia as specifically involved in transcription resumption after DNA repair and have been able to measure the effect of its absence on transcription and the dynamic behavior of RNA polymerase II during transcription-coupled repair.
ASPP2 suppresses squamous cell carcinoma via RelA/p65–mediated repression of p63
Authors: Tordella Luca , Koch Sofia , Salter Victoria , Pagotto Anna , Doondeea Jessica B. , Feller Stephan M. , Ratnayaka Indrika , Zhong Shan , Goldin Robert D. , Lozano Guillermina , McKeon Frank D. , Tavassoli Mahvash , Fritzsche Florian , Huber Gerhard F. , Rössle Matthias , Moch Holger , Lu Xin
Published: October 2013

Significance

Squamous cell carcinoma (SCC) is one of the most common human tumor types with high malignancy. Most SCC mouse models involve multiple genetic mutations. Here we present the
ASPP2
Δexon3/+
Balb/c mouse as a haploinsufficient SCC mouse model and identify ASPP2 as a suppressor of SCC and a potent repressor of p63 expression. The finding that ASPP2 represses p63 expression via NF-κB provides a molecular insight into how inflammatory signaling may affect SCC development. All these demonstrate that ASPP2 may serve as a molecular signature of SCC and the characterized
ASPP2
Δexon3/+
Balb/c mouse may provide a much-needed experimental model to extend our understanding of SCC as well as enable us to develop better strategies to treat SCC.
Crystal structures of an archaeal oligosaccharyltransferase provide insights into the catalytic cycle of N-linked protein glycosylation
Authors: Matsumoto Shunsuke , Shimada Atsushi , Nyirenda James , Igura Mayumi , Kawano Yoshiaki , Kohda Daisuke
Published: October 2013

Significance

Asparagine-linked glycosylation is one of the most ubiquitous posttranslational protein modifications in all kingdoms of life. A membrane enzyme, oligosaccharyltransferase (OST), catalyzes the transfer of sugar chains onto the asparagine residues of the Asn-X-Ser/Thr sequon in acceptor proteins. We determined the structures of an archaeal OST in two crystal forms. The comparison with the previous eubacterial OST structure revealed the structural conservation of the catalytic core and the membrane-spanning region. The archaeal and eubacterial OST structures probably correspond to different steps in the OST reaction cycle. The conversion between the structured and unstructured states of a characteristic loop in the membrane-spanning region is the structural basis for the dynamic recognition of the Asn residue in the sequon.
Reduced choice-related activity and correlated noise accompany perceptual deficits following unilateral vestibular lesion
Authors: Liu Sheng , Dickman J. David , Newlands Shawn D. , DeAngelis Gregory C. , Angelaki Dora E.
Published: October 2013

Significance

Correlations between single-neuron activity and perceptual decisions are used to probe functional links between sensory neurons and perception, but the roles of correlated noise and decoding strategy in shaping these correlations remain unclear. The peripheral vestibular system provides an ideal model system to explore these questions, due to interactions between afferent signals from the two sides of the brain. We made a unilateral lesion to the vestibular labyrinth and recorded from neurons in the contralateral vestibular and cerebellar nuclei. The lesion led to reduced neural sensitivity, reduced correlations with perceptual decisions, and less correlated noise among neurons. Simulations show that these changes could account for the effects of the lesion on behavior.
Tissue factor pathway inhibitor-alpha inhibits prothrombinase during the initiation of blood coagulation
Authors: Wood Jeremy P. , Bunce Matthew W. , Maroney Susan A. , Tracy Paula B. , Camire Rodney M. , Mast Alan E.
Published: October 2013

Significance

The generation of thrombin by prothrombinase, a complex composed of activated (a) factors X (FXa) and V (FVa), is a final step in blood coagulation. We demonstrate that tissue factor pathway inhibitor (TFPI) blocks thrombin generation by prothrombinase at physiologically relevant rates and concentrations, but only during the initiation of clot formation. TFPI mediates this inhibitory activity through two high-affinity interactions, one with FXa and one with FVa. This is the first description of an endogenous human protein that inhibits prothrombinase under physiological conditions and may prevent a full thrombotic response to subthreshold coagulant stimuli that otherwise could occlude blood vessels. It provides unique understanding of thrombotic disorders and has important implications for development of anti-TFPI agents to treat hemophilia.
PHYTOCHROME-DEPENDENT LATE-FLOWERING accelerates flowering through physical interactions with phytochrome B and CONSTANS
Authors: Endo Motomu , Tanigawa Yoshiyasu , Murakami Tadashi , Araki Takashi , Nagatani Akira
Published: October 2013

Significance

In plants, red light and blue light have antagonistic functions for the regulation of a flowering activator, CONSTANS (CO). Recently, direct regulation of CO by blue light photoreceptors has been reported. However, how red light regulates CO has remained unclear. In this paper, we identify a novel
PHYTOCHROME-DEPENDENT LATE-FLOWERING
(
PHL
) gene directly involved in red light photoreceptor phytochrome B (phyB) signaling. Furthermore, we reveal that PHL can bridge phyB and CO in a red light-dependent manner. These findings provide insight into the coordinated regulation of CO by red and blue photoreceptors in flowering regulation. Because PHL homologues are found in a wide variety of plant species, the mechanism we propose here appears to be universal to all flowering plants.
Differentiated kidney epithelial cells repair injured proximal tubule
Authors: Kusaba Tetsuro , Lalli Matthew , Kramann Rafael , Kobayashi Akio , Humphreys Benjamin D.
Published: October 2013

Significance

When epithelial cells in the proximal portion of the nephron are damaged they rapidly proliferate to repair the damage to the kidney. Whether a stem cell is responsible for this proliferative response or not is controversial. Although a scattered population of cells can be found in the human proximal tubule that seem to have stem-cell characteristics, they could also represent isolated damaged cells that have dedifferentiated and lost their epithelial characteristics. We resolve these conflicting models using genetic lineage analysis to demonstrate that fully differentiated proximal tubule cells not only proliferate after injury, but they also upregulate apparent stem-cell markers. This study shows that epithelial dedifferentiation is responsible for repair of mouse proximal tubule, rather than an adult stem-cell population.
Hemoglobin-derived porphyrins preserved in a Middle Eocene blood-engorged mosquito
Authors: Greenwalt Dale E. , Goreva Yulia S. , Siljeström Sandra M. , Rose Tim , Harbach Ralph E.
Published: October 2013

Significance

Fossils, in addition to documenting the existence of extinct species, can often provide information on the behavior of ancient organisms. The present study describes the fossil of a blood-engorged mosquito in oil shale from northwestern Montana. The existence of this rare specimen extends the existence of blood-feeding behavior in this family of insects 46 million years into the past. Heme, the oxygen-carrying group of hemoglobin in the host’s blood, was identified in the abdomen of the fossil mosquito by nondestructive mass-spectrometry analysis. Although large and fragile molecules such as DNA cannot survive fossilization, other complex organic molecules, in this case iron-stabilized heme, can survive intact and provide information relative to the mechanisms of the fossilization process.
Cytosolic reducing power preserves glutamate in retina
Authors: Du Jianhai , Cleghorn Whitney , Contreras Laura , Linton Jonathan D. , Chan Guy C.-K. , Chertov Andrei O. , Saheki Takeyori , Govindaraju Viren , Sadilek Martin , Satrústegui Jorgina , Hurley James B.
Published: October 2013

Significance

This report shows that the reducing power in the environment influences oxidation of glutamate in a neuronal tissue. Glutamate is a neurotransmitter, and it is especially important as a metabolite because it is required for synthesis of glutathione, other amino acids, and proteins. Glutamate also is a key intermediate in glutamine-dependent anaplerosis, now considered to be a principal source of citric acid cycle intermediates in cancer cells. Our analyses also show that the reducing power in the environmental can influence glutamate oxidation in cancer cells.
Crystal structure of a glucose/H
+
symporter and its mechanism of action
Authors: Iancu Cristina V. , Zamoon Jamillah , Woo Sang Bum , Aleshin Alexander , Choe Jun-yong
Published: October 2013

Significance

Glucose transporters mediate the exchange of glucose and related hexoses in living cells. In humans, these transporters (known as GLUT) are involved in several diseases, including cancer and diabetes. The glucose transporter from
Staphylococcus epidermidis
(GlcP
Se
) has high sequence homology to human GLUT, is specific for glucose, and is inhibited by human GLUT inhibitors. The crystal structure of GlcP
Se
, along with site-directed mutagenesis and transport-activity studies, provide insight into the mechanism of glucose transport.
Nitric oxide mediates local activity-dependent excitatory synapse development
Authors: Nikonenko Irina , Nikonenko Alexander , Mendez Pablo , Michurina Tatyana V. , Enikolopov Grigori , Muller Dominique
Published: October 2013

Significance

The development of brain networks is regulated through plasticity and activity-dependent mechanisms that control the continuous formation and pruning of spine synapses. However, the molecular events that contribute to these aspects of structural plasticity remain unclear. By assessing synapse development and spine dynamics in the rodent hippocampus, we find that activity-dependent spine formation is mediated by a postsynaptic signaling cascade implicating NO, cGMP, and vasodilator-stimulated phosphoprotein phosphorylation. Loss of this NO signaling mechanism interferes with the development of excitatory synapses and prevents structural adaptation of hippocampal excitatory synapses to environmental enrichment. These results provide a new understanding of the role played by NO in cognitive deficits and diseases, such as schizophrenia.
Observation of orientation-dependent electron transfer in molecule–surface collisions
Authors: Bartels Nils , Golibrzuch Kai , Bartels Christof , Chen Li , Auerbach Daniel J. , Wodtke Alec M. , Schäfer Tim
Published: October 2013

Significance

How molecules point in space—that is, their spatial orientation—determines how they interact with their environment. Exchange of energy, photons, and particles as well as chemical reactions are all elementary processes that depend on orientation. Electron transfer reactions are of particular interest because of their importance in a remarkably wide range of phenomena. In this work, we examine electron transfer reactions at surfaces, which control the change of oxidation state in surface chemistry, a critical factor explaining catalytic activity and selectivity. We report a strong orientation dependence for vibrational relaxation of a diatomic molecule colliding with a metal surface, an energy transfer process driven by electron transfer. These observations represent a challenge to modern theories of surface chemistry.
Crystal structure of
Bacillus subtilis
GabR, an autorepressor and transcriptional activator of
gabT
Authors: Edayathumangalam Raji , Wu Rui , Garcia Roman , Wang Yuguang , Wang Wei , Kreinbring Cheryl A. , Bach Alicia , Liao Jingling , Stone Todd A. , Terwilliger Thomas C. , Hoang Quyen Q. , Belitsky Boris R. , Petsko Gregory A. , Ringe Dagmar , Liu Dali
Published: October 2013

Significance

GabR is a member of the MocR/GabR subfamily of the GntR family of bacterial transcription regulators. It regulates the metabolism of γ-aminobutyric acid, an important nitrogen and carbon source in many bacteria. The crystal structures reported here show that this protein has evolved from the fusion of a type I aminotransferase and a winged helix-turn-helix DNA-binding protein to form a chimeric protein that adopts a dimeric head-to-tail configuration. The pyridoxal 5′-phosphate–binding regulatory domain of GabR is therefore an example of a coenzyme playing a role in transcription regulation rather than in enzymatic catalysis. Our structural and biochemical studies lay the mechanistic foundation for understanding the regulatory functions of the MocR/GabR subfamily of transcription regulators.
Attention is Required for Maintenance of Feature Binding in Visual Working Memory
Authors: Zokaei Nahid , Heider Maike , Husain Masud
Published: October 2013

Working memory and attention are intimately connected. However, understanding the relationship between the two is challenging. Currently, there is an important controversy about whether objects in working memory are maintained automatically or require resources that are also deployed for visual or auditory attention. Here we investigated the effects of loading attention resources on precision of visual working memory, specifically on correct maintenance of feature-bound objects, using a dual-task paradigm. Participants were presented with a memory array and were asked to remember either direction of motion of random dot kinematograms of different colour, or orientation of coloured bars. During the maintenance period, they performed a secondary visual or auditory task, with varying levels of load. Following a retention period, they adjusted a coloured probe to match either the motion direction or orientation of stimuli with the same colour in the memory array. This allowed us to examine the effects of an attention-demanding task performed during maintenance on precision of recall on the concurrent working memory task. Systematic increase in attention load during maintenance resulted in a significant decrease in overall working memory performance. Changes in overall performance were specifically accompanied by an increase in feature misbinding errors: erroneous reporting of nontarget motion or orientation. Thus in trials where attention resources were taxed, participants were more likely to respond with nontarget values rather than simply making random responses. Our findings suggest that resources used during attention-demanding visual or auditory tasks also contribute to maintaining feature-bound representations in visual working memory—but not necessarily other aspects of working memory.
A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation
Authors: Khatri Purvesh , Roedder Silke , Kimura Naoyuki , De Vusser Katrien , Morgan Alexander A. , Gong Yongquan , Fischbein Michael P. , Robbins Robert C. , Naesens Maarten , Butte Atul J. , Sarwal Minnie M.
Published: October 2013

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.
Pathogenic CD4+ T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes
Authors: Mohan James F. , Calderon Boris , Anderson Mark S. , Unanue Emil R.
Published: October 2013

In the nonobese diabetic mouse, a predominant component of the autoreactive CD4+ T cell repertoire is directed against the B:9-23 segment of the insulin B chain. Previous studies established that the majority of insulin-reactive T cells specifically recognize a weak peptide-MHC binding register within the B:9-23 segment, that to the 12–20 register. These T cells are uniquely stimulated when the B:9-23 peptide, but not the insulin protein, is offered to antigen presenting cells (APCs). Here, we report on a T cell receptor (TCR) transgenic mouse (8F10) that offers important new insights into the biology of these unconventional T cells. Many of the 8F10 CD4+ T cells escaped negative selection and were highly pathogenic. The T cells were directly recruited into islets of Langerhans, where they established contact with resident intra-islet APCs. Immunogenic insulin had to be presented in order for the T cells to localize and cause disease. These T cells bypassed an initial priming stage in the pancreatic lymph node thought to precede islet T cell entry. 8F10 T cells induced the production of antiinsulin antibodies and islets contained immunoglobulin (IgG) deposited on β cells and along the vessel walls.
The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow
Authors: Stadtmann Anika , Germena Giulia , Block Helena , Boras Mark , Rossaint Jan , Sundd Prithu , Lefort Craig , Fisher Charles I. , Buscher Konrad , Gelschefarth Bernadette , Urzainqui Ana , Gerke Volker , Ley Klaus , Zarbock Alexander
Published: October 2013

Neutrophils are recruited from the blood to sites of inflammation, where they contribute to immune defense but may also cause tissue damage. During inflammation, neutrophils roll along the microvascular endothelium before arresting and transmigrating. Arrest requires conformational activation of the integrin lymphocyte function–associated antigen 1 (LFA-1), which can be induced by selectin engagement. Here, we demonstrate that a subset of P-selectin glycoprotein ligand-1 (PSGL-1) molecules is constitutively associated with L-selectin. Although this association does not require the known lectin-like interaction between L-selectin and PSGL-1, the signaling output is dependent on this interaction and the cytoplasmic tail of L-selectin. The PSGL-1–L-selectin complex signals through Src family kinases, ITAM domain–containing adaptor proteins, and other kinases to ultimately result in LFA-1 activation. The PSGL-1–L-selectin complex–induced signaling effects on neutrophil slow rolling and recruitment in vivo demonstrate the functional importance of this pathway. We conclude that this is a signaling complex specialized for sensing adhesion under flow.
Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome
Authors: Fabbri Giulia , Khiabanian Hossein , Holmes Antony B. , Wang Jiguang , Messina Monica , Mullighan Charles G. , Pasqualucci Laura , Rabadan Raul , Dalla-Favera Riccardo
Published: October 2013

Richter syndrome (RS) derives from the rare transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly of the diffuse large B cell lymphoma (DLBCL) type. The molecular pathogenesis of RS is only partially understood. By combining whole-exome sequencing and copy-number analysis of 9 CLL-RS pairs and of an extended panel of 43 RS cases, we show that this aggressive disease typically arises from the predominant CLL clone by acquiring an average of ∼20 genetic lesions/case. RS lesions are heterogeneous in terms of load and spectrum among patients, and include those involved in CLL progression and chemorefractoriness (TP53 disruption and NOTCH1 activation) as well as some not previously implicated in CLL or RS pathogenesis. In particular, disruption of the CDKN2A/B cell cycle regulator is associated with ∼30% of RS cases. Finally, we report that the genomic landscape of RS is significantly different from that of de novo DLBCL, suggesting that they represent distinct disease entities. These results provide insights into RS pathogenesis, and identify dysregulated pathways of potential diagnostic and therapeutic relevance.
A point mutation in the human Slo1 channel that impairs its sensitivity to omega-3 docosahexaenoic acid
Authors: Hoshi Toshinori , Xu Rong , Hou Shangwei , Heinemann Stefan H. , Tian Yutao
Published: October 2013

Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA) at nanomolar concentrations reversibly activate human large-conductance Ca2+- and voltage-gated K+ (Slo1 BK) channels containing auxiliary β1 or β4 subunits in cell-free patches. Here we examined the action of DHA on the Slo1 channel without any auxiliary subunit and sought to elucidate the biophysical mechanism and the molecular determinants of the DHA sensitivity. Measurements of ionic currents through human Slo1 (hSlo1) channels reveal that the stimulatory effect of DHA does not require activation of the voltage or Ca2+ sensors. Unlike gating of the hSlo1 channel, that of the Drosophila melanogaster Slo1 (dSlo1) channel is unaltered by DHA. Our mutagenesis study based on the differential responses of human and dSlo1 channels to DHA pinpoints that Y318 near the cytoplasmic end of S6 in the hSlo1 channel is a critical determinant of the stimulatory action of DHA. The mutation Y318S in hSlo1, which replaces Y with S as found in dSlo1, greatly diminishes the channel’s response to DHA with a 22-carbon chain whether β1 or β4 is absent or present. However, the responses to α-linolenic acid, an omegea-3 fatty acid with an 18-carbon chain, and to arachidonic acid, an omega-6 fatty acid with a 20-carbon chain, remain unaffected by the mutation. Y318 in the S6 segment of hSlo1 is thus an important determinant of the electrophysiological response of the channel to DHA. Furthermore, the mutation Y318S may prove to be useful in dissecting out the complex lipid-mediated modulation of Slo1 BK channels.
The role of transmembrane channel–like proteins in the operation of hair cell mechanotransducer channels
Authors: Kim Kyunghee X. , Beurg Maryline , Hackney Carole M. , Furness David N. , Mahendrasingam Shanthini , Fettiplace Robert
Published: October 2013

Sound stimuli elicit movement of the stereocilia that make up the hair bundle of cochlear hair cells, putting tension on the tip links connecting the stereocilia and thereby opening mechanotransducer (MT) channels. Tmc1 and Tmc2, two members of the transmembrane channel–like family, are necessary for mechanotransduction. To assess their precise role, we recorded MT currents elicited by hair bundle deflections in mice with null mutations of Tmc1, Tmc2, or both. During the first postnatal week, we observed a normal MT current in hair cells lacking Tmc1 or Tmc2; however, in the absence of both isoforms, we recorded a large MT current that was phase-shifted 180°, being evoked by displacements of the hair bundle away from its tallest edge rather than toward it as in wild-type hair cells. The anomalous MT current in hair cells lacking Tmc1 and Tmc2 was blocked by FM1-43, dihydrostreptomycin, and extracellular Ca2+ at concentrations similar to those that blocked wild type. MT channels in the double knockouts carried Ca2+ with a lower permeability than wild-type or single mutants. The MT current in double knockouts persisted during exposure to submicromolar Ca2+, even though this treatment destroyed the tip links. We conclude that the Tmc isoforms do not themselves constitute the MT channel but are essential for targeting and interaction with the tip link. Changes in the MT conductance and Ca2+ permeability observed in the absence of Tmc1 mutants may stem from loss of interaction with protein partners in the transduction complex.
Melusin protects from cardiac rupture and improves functional remodelling after myocardial infarction
Authors: Unsöld Bernhard , Kaul Axel , Sbroggiò Mauro , Schubert Carola , Regitz-Zagrosek Vera , Brancaccio Mara , Damilano Federico , Hirsch Emilio , Van Bilsen Marc , Munts Chantal , Sipido Karin , Bito Virginie , Detre Elke , Wagner Nana Maria , Schäfer Katrin , Seidler Tim , Vogt Johannes , Neef Stefan , Bleckmann Annalen , Maier Lars S. , Balligand Jean Luc , Bouzin Caroline , Ventura-Clapier Renée , Garnier Anne , Eschenhagen Thomas , El-Armouche Ali , Knöll Ralph , Tarone Guido , Hasenfuß Gerd
Published: October 2013

Aims

Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach.

Methods and results

Mice overexpressing melusin in the heart (TG) and wild-type controls (WT) were subjected to permanent LAD ligation and both the acute response (Day 3) and subsequent remodelling (2 weeks) were examined. Mortality in wild-type mice was significant between Days 3 and 7, primarily due to cardiac rupture, but melusin's overexpression strongly reduced mortality (43.2% in wild-type vs. 27.3% in melusin-TG, P = 0.005). At Day 3 after MI, a time point preceding the mortality peak, TG hearts had increased heat shock protein 70 expression, increased ERK1/2 signalling, reduced cardiomyocyte hyper-contractility and inflammatory cell infiltrates, and increased matricellular protein expression in the infarcted area.

At 2 weeks after MI, melusin overexpression conferred a favourable adaptive remodelling characterized by reduced left ventricle dilatation and better preserved contractility in the presence of a comparable degree of hypertrophy. Adaptive remodelling in melusin TG mice was characterized by reduced apoptosis and fibrosis as well as increased cardiomyocyte contractility.

Conclusions

Consistent with its function as a chaperone protein, melusin overexpression exerts a dual protective action following MI reducing an array of maladaptive processes. In the early phase after MI, reduced inflammation and myocyte remodelling protect against cardiac rupture. Chronically, reduced myocyte loss and matrix remodelling, with preserved myocyte contractility, confer adaptive LV remodelling.
Selecting relative abundance proxies for BMSY and BMEY
Authors: Punt André E. , Smith Anthony D. M. , Smith David C. , Tuck Geoffrey N. , Klaer Neil L.
Published: October 2013

The objectives for many commercial fisheries include maximizing either yield or profit. Clearly specified management targets are a key element of effective fisheries management. Biomass targets are often specified for major commercial fisheries that are managed using quantitative stock assessments where biomass is calculated and tracked over time. BMSY, the biomass corresponding to Maximum Sustainable Yield, is often used as a target when maximizing yield is important, while BMEY is the biomass target to maximize profit. There are difficulties in estimating both quantities accurately, and this paper explores default proxies for each target biomass, expressed as biomass levels relative to carrying capacity, which are more easily estimated. Integration across a range of uncertainties about stock dynamics and the costs of fishing suggests that a proxy for BMSY in the range of 35–40% of carrying capacity minimizes the potential loss in yield compared with that which would arise if BMSY was known exactly, while a proxy for BMEY of 50–60% of carrying capacity minimizes the corresponding potential loss in profit. These estimates can be refined given stock-specific information regarding productivity (particularly the parameter which defines the resilience of recruitment to changes in spawning stock size) and costs and prices. It is more difficult to find a biomass level that achieves a high expected profit than a biomass level that achieves a high expected catch, because the former is sensitive to uncertainties related to costs and prices, as well as parameters which determine productivity.
Zunongwangia mangrovi sp. nov., isolated from mangrove (Avicennia marina) rhizosphere, and emended description of the genus Zunongwangia
Authors: Rameshkumar N. , Krishnan Ramya , Lang Elke , Matsumura Yuta , Sawabe Toko , Sawabe Tomoo
Published: October 2013

A Gram-stain-negative, strictly aerobic, slightly halophilic, non-motile and rod-shaped bacterial strain, designated P2E16T, was isolated from mangrove (Avicennia marina) rhizosphere, collected at Devipattinam mangroves, Tamil Nadu, India. Strain P2E16T grew optimally at pH 7.0–8.0, at 25–28 °C and in the presence of 2–3 % (w/v) NaCl. 16S rRNA gene analysis showed that strain P2E16T was phylogenetically closely related to the genus

Zunongwangia

, with

Zunongwangia profunda

SM-A87T as the closest related type strain (98.2 % 16S rRNA gene sequence similarity) and less than 93 % 16S rRNA gene sequence similarity to all other members of the family

Flavobacteriaceae

. Strain P2E16T contained MK-6 as the major respiratory quinone, phosphatidylethanolamine as the predominant polar lipid and iso-C15 : 0 (17.8 %), iso-C17 : 0 3-OH (15.1 %), C15 : 0 (12.8 %), iso-C17 : 1ω9c (9.8 %), iso-C15 : 1 G (9.0 %), and summed feature 3 (comprising C16 : 1ω7c and/or iso-C15 : 0 2-OH; 7.1 %) as the major fatty acids. The DNA G+C content was 34.3 mol%. Differential phenotypic properties, together with the phylogenetic distinctiveness and low DNA–DNA relatedness demonstrated that strain P2E16T was distinct from the type strain of

Zunongwangia profunda

. On the basis of these presented data, strain P2E16T is considered to represent a novel species of the genus

Zunongwangia

, for which the name Zunongwangia mangrovi sp. nov. is proposed. The type strain is P2E16T ( = DSM 24499T = LMG 26237T = KCTC 23496T). An emended description of the genus

Zunongwangia

is also provided.
Wickerhamomyces sylviae f.a., sp. nov., an ascomycetous yeast species isolated from migratory birds
Authors: Francesca Nicola , Carvalho Cláudia , Almeida Pedro Miguel , Sannino Ciro , Settanni Luca , Sampaio José Paulo , Moschetti Giancarlo
Published: October 2013

In the present work, we investigated the phylogenetic position and phenotypic characteristics of eight yeast isolates collected from migratory birds on the island of Ustica, Italy. A phylogenetic analysis based on the D1/D2 region of the large-subunit rRNA gene showed that all isolates clustered as a single separate lineage within the Wickerhamomyces clade. They exhibited distinct morphological and physiological characteristics and were clearly separated from their closest relatives, Wickerhamomyces lynferdii, Wickerhamomyces anomalus and Wickerhamomyces subpelliculosus, in blastn searches. On the basis of the isolation source, physiological features and molecular strain typing carried out with randomly amplified polymorphic DNA (RAPD)-PCR and minisatellite-primed (MSP)-PCR analysis, the isolates were identified as strains of the same species. The name Wickerhamomyces sylviae f.a., sp. nov. is proposed to accommodate these novel strains; the type strain is U88A2T ( = PYCC 6345T = CBS 12888T). The MycoBank number is MB 804762.
N,N′-Bis(2-aminobenzyl)ethane-1,2-diaminium dinitrate
Authors: Garza Rodríguez Luis Ángel , Elizondo Martínez Perla , Bernès Sylvain , Nájera Martínez Blanca , Pérez Rodríguez Nancy
Published: October 2013

In the title salt, C16H24N42+·2NO3−, both the cation and anion are placed in general positions, although the cation displays non-crystallographic inversion symmetry, with the aliphatic chain extended in an all-transconformation. The benzene rings are almost parallel, with a dihedral angle between their mean planes of 3.3 (6)°. The nitrate ions are placed in the vicinity of the protonated amine groups, forming efficient N—H...O inter-ion hydrogen bonds. Each nitrate ion in the asymmetric unit bridges two symmetry-related cations, forming anR44(18) ring, a common motif in organic ammonium nitrate salts. This results in the formation of chains along [010] with alternating cations and anions. The neutral amine groups are involved in slightly weaker N—H...O hydrogen bonds with the nitrate O atoms, and there are also a number of C—H...O hydrogen bonds present. The resulting supramolecular structure is based on a two-dimensional network extending in theabplane.
5,6-Dimethyl-1H-benzimidazol-3-ium nitrate
Authors: Liu Bao-Cheng , Zhu Shou-Jin , Liu Fa-Qian
Published: October 2013

The title salt, C9H11N2+·NO3−, features a planar cation (r.m.s. for 11 non-H atoms = 0.016 Å). In the crystal, N—H...O hydrogen bonds link nitrate and benzimidazole ions into a three-dimensional network.
Tris[4-bromo-2-(methyliminomethyl)phenolato-κ2N,O]cobalt(III)
Authors: Huang Qiu-Ping , Zhang Chun-Lian , Zhao Ru-Xia , Yang Li , Jiang Xi-Fu
Published: October 2013

In the title compound, [Co(C8H7BrNO)3], the CoIIIion is coordinated in a slightly distorted octahedral environment by three N atoms and three O atoms from three bidentate 4-bromo-2-(methyliminomethyl)phenolate ligands. The dihedral angles between the benzene rings are 82.6 (2), 57.1 (2) and 62.9 (2)°. In the crystal, molecules are linked by pairs of weak C—H...Br hydrogen bonds, forming inversion dimers.
2-Amino-6-chloro-N-methylbenzamide
Authors: Liang Yan-Hui , Mei Xiang-Dong , Li Yao-Fa , Pan Wen-Liang , Ning Jun
Published: October 2013

In the title compound, C8H9ClN2O, the dihedral angle between the benzene ring and the methylamide substituent is 68.39 (11)°. In the crystal, molecules are linked by N—H...O hydrogen bonds, forming layers parallel to theabplane.
Motivational interviewing and recovery: experiences of hope, meaning, and empowerment
Authors: Glassman Scott , Kottsieper Petra , Zuckoff Allan , A. Gosch Elizabeth
Published: October 2013

Purpose

– Non-participation in outpatient dual diagnosis services presents a challenge for providers assisting clients in their recovery. To better understand factors that facilitate participation, the purpose of this paper is to examine positive recovery states – hope, meaning, and empowerment – as they relate to motivational interviewing (MI) and service use.

Design/methodology/approach

– Six dually diagnosed adults completed four baseline assessments, four MI sessions, a post-MI tape-assisted recall interview, and one-month follow-up measures. Simulation modeling analysis of phone survey responses, comparisons of baseline and intervention phase data, and grounded theory analysis of interviews were conducted to determine MI's relationship to the dependent variables.

Findings

– MI was associated with modest improvement in levels of participation, hope, empowerment, and with greater change in life purpose. Key recovery themes were: positive sense of self, increased self-efficacy, and improved relationships. Feelings of safety and trust were tied to greater self-disclosure while more active emotions were more closely linked to the discussion of recovery progress.

Research limitations/implications

– The paper's finding are limited by small sample size and phone survey response sets.

Practical implications

– To better help dually diagnosed clients sustain treatment involvement, MI practitioners should pay special attention to recovery accomplishments, values, abilities, and self-esteem, while linking these attributes to service participation where appropriate and creating a safe, valuing atmosphere conducive to self-disclosure.

Originality/value

– This is the first paper to measure key recovery constructs within MI process, and to explore the role of positive emotions related to MI, recovery, and service participation.
Understanding communication channel choices in team knowledge sharing
Authors: Snyder Jason , Eng Lee-Partridge Joo
Published: October 2013

Purpose

– The goal of this paper is to develop and test a model that explains information and communication channel (ICC) choice for knowledge sharing in work teams.

Design/methodology/approach

– This paper reviews relevant literature in information and knowledge sharing and communication channel choices to develop the four-layered model. From the four-layered model, an online questionnaire was developed to look at the ICCs that participants have available to them, the ICCs they actually use when sharing information in teams, and their motivations for making their ICC choices.

Findings

– Although participants reported having access to a wide variety of ICCs, they tended to rely on face-to-face interactions, telephone and e-mail for sharing knowledge. In accordance with the four-layer model, participants reported that ICC choice was impacted by the type of knowledge being shared. In addition, ease of use, reliability, convenience, and the ability of the channel to document communications were all factors motivating ICC selection.

Research limitations/implications

– The layered model provides a framework for further research to investigate the factors at the outer layers of the four-layered model and the interaction among the layers in affecting ICC choices.

Practical implications

– The paper attempts to build a model that organizations can use as a guide to implementing strategies for information and knowledge sharing in teams.

Originality/value

– This paper develops and partially tests a model to understand communication choices and information sharing. It provides a framework to examine “traditional” communication choices in the midst of the uproar of the availability of Web 2.0 technologies.
Media coverage about organisations in critical situations
Authors: Korn Christine , Einwiller Sabine
Published: October 2013

Purpose

– This research aims to investigate how critical media coverage of an organisation affects its employees. The authors expect the effects to be similar to the way media coverage about an individual would affect this person, termed “reciprocal effects”.

Design/methodology/approach

– Drawing on a framework for the analysis of reciprocal effects of mass media by Kepplinger and qualitative interviews among employees of 14 different organisations undergoing a crisis, the authors develop an employee-model of reciprocal effects for the context of organisational crises.

Findings

– This qualitative research shows that employees are affected by media coverage on a critical issue about their employer. Mass media are an important source of information for employees in critical situations. The data indicate interpersonal conversations with colleagues are also important for obtaining information and coping with the situation. Employees show emotional reactions, such as helplessness or shame, and a tendency to defend their employer. The better employees feel informed by their organisation's internal communication, the better they know how to cope with the situation. The data indicate that the effects vary with the employees' level of organisational identification.

Practical implications

– The findings imply that open and constant internal communication with employees during a crisis fosters reactions that stabilise the organisation in critical situations.

Originality/value

– The study presented here is the first systematic analysis of the impact of media coverage of an organisation on its employees.
Factors associated with the publication of a CEO letter
Authors: Andreia Costa Graciete , Cristina Oliveira Lídia , Lima Rodrigues Lúcia , Craig Russell
Published: October 2013

Purpose

– In most European code-law oriented Latin countries, the publication of a CEO's letter to shareholders in a company's annual report is a fairly recent phenomenon. In this paper, the authors seek to determine the characteristics that explain why companies in one such country, i.e. Portugal, published a CEO letter.

Design/methodology/approach

– The paper's holistic theoretical framework draws on elements of agency theory, institutional theory and signalling theory. To understand the characteristics of Portuguese holding companies that published CEO letters, the authors used a logistic regression model to explore 266 observations over the years 2006-2011.

Findings

– The publication of a CEO letter becomes more likely if a firm is audited by a Big 4 accounting firm; has a higher level of profitability; and has a high number of foreign subsidiaries. Other findings are that finance companies are slightly more likely to publish a CEO letter than non-finance companies. The number of CEO letters increased to a peak in 2008, and then declined.

Practical implications

– The increasing number of companies now publishing a CEO letter raises the concern for regulatory authorities of whether the content of the CEO letter should be audited, since any numbers presented in the management report have to be audited in Portugal.

Originality/value

– To the best of the authors' knowledge this is the first empirical exploration of the characteristics that explain why companies publish a CEO letter. Mimetic and normative isomorphism is revealed to be a potentially important influence, since there is a tendency of companies audited by Big 4 accounting companies, and with foreign subsidiaries, to publish a CEO letter.