scholarly journals The Rate of Osmotic Downshock Determines the Survival Probability of Bacterial Mechanosensitive Channel Mutants

2014 ◽  
Vol 197 (1) ◽  
pp. 231-237 ◽  
Author(s):  
Maja Bialecka-Fornal ◽  
Heun Jin Lee ◽  
Rob Phillips
Keyword(s):  
Environmental Changes ◽  
Cultured Cells ◽  
Osmotic Shock ◽  
Survival Rates ◽  
Content Type ◽  
Prevailing Paradigm ◽  
Osmotic Change ◽  
Limited Effectiveness ◽  
Sense And Respond ◽  
Changes Over Time

Mechanosensitive (MS) channels allow cells to sense and respond to environmental changes. In bacteria, these channels are believed to protect against an osmotic shock. The physiological function of these channels has been characterized primarily by a standardized assay, where aliquots of batch-cultured cells are rapidly pipetted into a hypotonic medium. Under this method, it has been inferred many types of MS channels (MscS homologs inEscherichia coli) demonstrate limited effectiveness against shock, typically rescuing less than 10% of the cells when expressed at native levels. We introduce a single-cell-based assay which allows us to control how fast the osmolarity changes, over time scales ranging from a fraction of a second to several minutes. We find that the protection provided by MS channels depends strongly on the rate of osmotic change, revealing that, under a slow enough osmotic drop, MscS homologs can lead to survival rates comparable to those found in wild-type strains. Further, after the osmotic downshift, we observe multiple death phenotypes, which are inconsistent with the prevailing paradigm of how cells lyse. Both of these findings require a reevaluation of our basic understanding of the physiology of MS channels.

The impact of executives’ perceptions of environmental threats and organizational slack on innovation strategies

2016 ◽  
Vol 7 (2) ◽  
pp. 216-230 ◽  
Author(s):  
Chengyuan Wang ◽  
Biao Luo ◽  
Yong Liu ◽  
Zhengyun Wei
Keyword(s):  
Cognitive Theory ◽  
Environmental Changes ◽  
Ordinary Least Squares ◽  
Organizational Slack ◽  
Least Squares Regression ◽  
Content Type ◽  
Environmental Threats ◽  
Innovation Strategies ◽  
The Impact ◽  
The Relationship

Purpose The paper aims to study the relationship between executives’ perceptions of environmental threats and innovation strategies and investigate the moderating effect of contextual factor (i.e. organizational slack) on such relations. It proposes a dualistic relationship between executives’ perceptions of environmental threats and innovation strategies, in which different perceptions of environmental threats will lead to corresponding innovation strategies, and dyadic organizational slack can promote such processes. Design/methodology/approach The paper is based on a survey with 163 valid questionnaires, which were all completed by executives. Hierarchical ordinary least-squares regression analysis is used to test the hypotheses proposed in this paper. Findings The paper provides empirical insights about that executives tend to choose exploratory innovation when they perceive environmental changes as likely loss threats, yet adopt exploitative innovation when perceiving control-reducing threats. Furthermore, unabsorbed slack (e.g. financial redundancy) positively moderates both relationships, while absorbed slack (e.g. operational redundancy) merely positively influences the relationship between the perception of control-reducing threats and exploitative innovation. Originality/value The paper bridges the gap between organizational innovation and cognitive theory by proposing a dualistic relationship between executives’ perceptions of environmental threats and innovation strategies. The paper further enriches innovation studies by jointly considering both subjective and objective influence factors of innovation and argues that organizational slack can moderate such dualistic relationship.

scholarly journals Effects of Tedizolid Phosphate on Survival Outcomes and Suppression of Production of Staphylococcal Toxins in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Vien T. M. Le ◽  
Hoan N. Le ◽  
Marcos Gabriel Pinheiro ◽  
Kenneth J. Hahn ◽  
Mary L. Dinh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Production ◽  
Protective Efficacy ◽  
Survival Rates ◽  
Rabbit Model ◽  
Rank Test ◽  
Necrotizing Pneumonia ◽  
Time Curve ◽  
Content Type

ABSTRACT The protective efficacy of tedizolid phosphate, a novel oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, and saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. Tedizolid phosphate was administered to rabbits at 6 mg/kg of body weight intravenously twice daily, which yielded values of the 24-h area under the concentration-time curve approximating those found in humans. The overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily (P = 0.66 by the log-rank test versus the results obtained with tedizolid phosphate). These survival rates were significantly greater than the survival rates of 17% for rabbits treated with 30 mg/kg vancomycin twice daily (P = 0.003) and 17% for rabbits treated with saline (P = 0.002). The bacterial count in the lungs of rabbits treated with tedizolid phosphate was significantly decreased compared to that in the lungs of rabbits treated with saline, although it was not significantly different from that in the lungs of rabbits treated with vancomycin or linezolid. The in vivo bacterial production of alpha-toxin and Panton-Valentine leukocidin, two key S. aureus-secreted toxins that play critical roles in the pathogenesis of necrotizing pneumonia, in the lungs of rabbits treated with tedizolid phosphate and linezolid was significantly inhibited compared to that in the lungs of rabbits treated with vancomycin or saline. Taken together, these results indicate that tedizolid phosphate is superior to vancomycin for the treatment of S. aureus necrotizing pneumonia because it inhibits the bacterial production of lung-damaging toxins at the site of infection.

scholarly journals Osmoadaptation Strategy of the Most Halophilic Fungus, Wallemia ichthyophaga, Growing Optimally at Salinities above 15% NaCl

2013 ◽  
Vol 80 (1) ◽  
pp. 247-256 ◽  
Author(s):  
Janja Zajc ◽  
Tina Kogej ◽  
Erwin A. Galinski ◽  
José Ramos ◽  
Nina Gunde-Cimerman
Keyword(s):  
Biomass Production ◽  
Osmotic Shock ◽  
Model Organism ◽  
Salinity Range ◽  
Growth Media ◽  
Optimal Salinity ◽  
Content Type ◽  
Batch Cultures ◽  
Specific Growth Rates ◽  
Optimum Salinity

ABSTRACTWallemia ichthyophagais a fungus from the ancient basidiomycetous genusWallemia(Wallemiales, Wallemiomycetes) that grows only at salinities between 10% (wt/vol) NaCl and saturated NaCl solution. This obligate halophily is unique among fungi. The main goal of this study was to determine the optimal salinity range for growth of the halophilicW. ichthyophagaand to unravel its osmoadaptation strategy. Our results showed that growth on solid growth media was extremely slow and resulted in small colonies. On the other hand, in the liquid batch cultures, the specific growth rates ofW. ichthyophagawere higher, and the biomass production increased with increasing salinities. The optimum salinity range for growth ofW. ichthyophagawas between 15 and 20% (wt/vol) NaCl. At 10% NaCl, the biomass production and the growth rate were by far the lowest among all tested salinities. Furthermore, the cell wall content in the dry biomass was extremely high at salinities above 10%. Our results also showed that glycerol was the major osmotically regulated solute, since its accumulation increased with salinity and was diminished by hypo-osmotic shock. Besides glycerol, smaller amounts of arabitol and trace amounts of mannitol were also detected. In addition,W. ichthyophagamaintained relatively small intracellular amounts of potassium and sodium at constant salinities, but during hyperosmotic shock, the amounts of both cations increased significantly. Given our results and the recent availability of the genome sequence,W. ichthyophagashould become well established as a novel model organism for studies of halophily in eukaryotes.

Dealing with surprise attacks: decomposing ERM as a dynamic capability to handle crises

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Vishnu Chandar Venkatesh ◽  
Meeta Dasgupta ◽  
Anupama Prashar ◽  
Torben Juul Andersen
Keyword(s):  
Empirical Evidence ◽  
Small And Medium Enterprises ◽  
Survival Rates ◽  
Dynamic Capability ◽  
Expert Interviews ◽  
Content Type ◽  
Intelligence Gathering ◽  
Enterprise Risk ◽  
Medium Enterprises ◽  
Alliance Building

PurposeTurbulent hypercompetitive market conditions make small and medium enterprises (SMEs) vulnerable to abrupt crises caused by unexpected competitor moves. In these situations, enterprise risk management (ERM) can serve as a dynamic capability (DC) to overcome the impending crisis and improve SMEs' survival rates. To explore this capacity, which has only been vaguely addressed in prior research, we conduct an exploratory, abductive study to update the extant (ERM and DC) literature with empirical evidence from expert interviews.Design/methodology/approachWe conduct an exploratory, abductive study using empirical evidence from expert interviews.FindingsOur findings reveal ERM as a second-order DC in the micro-foundational components of competitive intelligence gathering, alliance building and integrative capabilities. We find that competitive intensity and government policy moderate the effects of these foundational capabilities. Finally, our study proposes a survivability model that provides new valuable knowledge of ERM as a DC for SMEs to deal with competition-driven crises.Originality/valueThis research survivability model shows how ERM as DC can facilitate the survivability of SMEs against competitive surprises. Although restricted to crises arising out of competitive surprises, this study provides valuable knowledge to the literature on what type of DCs are useful for specific situations. The study findings not only extended Teece's (2007) DCs framework to competitive crises but also placed it within a hierarchy of capabilities. The research findings indicate that an ERM culture in SMEs promote the growth and development of sensing, seizing and reconfiguring capabilities, vital for tiding competitive crises.

scholarly journals TREM-1 Promotes Survival during Klebsiella pneumoniae Liver Abscess in Mice

2014 ◽  
Vol 82 (3) ◽  
pp. 1335-1342 ◽  
Author(s):  
Yi-Tsung Lin ◽  
Kai-Yu Tseng ◽  
Yi-Chen Yeh ◽  
Fu-Chen Yang ◽  
Chang-Phone Fung ◽  
...  
Keyword(s):  
Small Intestine ◽  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Survival Rates ◽  
Bacterial Clearance ◽  
Mesenteric Lymph Nodes ◽  
Content Type ◽  
Cytokine Levels ◽  
Peptide Expression ◽  
Antimicrobial Peptide Expression

ABSTRACTKlebsiella pneumoniaeliver abscess (KPLA) is prevalent in East Asia. Liver abscess can develop after translocation ofK. pneumoniaefrom a patient's bowel into the liver via the portal circulation. TREM-1 (triggeringreceptorexpressed onmyeloid cells1) amplifies inflammatory signaling during infection, but its role in KPLA is poorly understood. We used an animal study to characterize the role of TREM-1 in KPLA. We compared survival rates, bacterial burdens in tissues, inflammatory cytokine levels, and histology findings between wild-type andTrem-1knockout (KO) mice after oral inoculation of capsular type K1K. pneumoniae. Translocation ofK. pneumoniaeto mesenteric lymph nodes and liver was examined, and intestinal permeability, antimicrobial peptide expression, and the clearance ofK. pneumoniaein the small intestine were determined. In the absence of TREM-1, KPLA model mice showed increasedK. pneumoniaedissemination, enhanced liver and systemic inflammation, and reduced survival. Impaired bacterial clearance in the small intestine causes enhancedK. pneumoniaetranslocation, which rendersTrem-1KO mice more susceptible toK. pneumoniaeoral infection. In conclusion, TREM-1-mediated bacterial clearance in the small intestine is an important immune response againstK. pneumoniae. TREM-1 deficiency enhancesK. pneumoniaetranslocation in the small intestine and increases mortality rates in mice with KPLA.

Vertical translocation: the enigma of the disappearing atlantodens interval in patients with myelopathy and rheumatoid arthritis. Part I. Clinical, radiological, and neuropathological features

1997 ◽  
Vol 87 (6) ◽  
pp. 856-862 ◽  
Author(s):  
Adrian T. H. Casey ◽  
H. Alan Crockard ◽  
Jennian F. Geddes ◽  
John Stevens
Keyword(s):  
Cervical Myelopathy ◽  
Survival Rates ◽  
Cord Compression ◽  
Atlantoaxial Subluxation ◽  
Lateral Mass ◽  
Progressive Decrease ◽  
Content Type ◽  
Statistical Comparison ◽  
High Cervical ◽  
Fine Print

✓ This statistical comparison between patients with cervical myelopathy secondary to horizontal atlantoaxial subluxation and those with vertical translocation is designed to elucidate the mechanisms responsible for cranial settling and the effect of translocation on the development of spinal cord compression. In a 10-year study of a cohort of 256 patients, 186 suffered from myelopathy and 116 (62%) of these exhibited vertical translocation according to the Redlund-Johnell criteria. Vertical translocation occurred after a significantly longer period of disease than atlantoaxial subluxation (p < 0.001). Translocation was characterized clinically by a high cervical myelopathy with features of a cruciate paralysis present in 35% of individuals compared with 26% who exhibited horizontal atlantoaxial subluxation (p = 0.29), but there was a surprising paucity of cranial nerve problems. The patients with vertical translocation had a greater degree of neurological disability (p = 0.002) and poorer survival rates (p = 0.04). Radiologically, vertical translocation was secondary to lateral mass collapse and associated with a progressive decrease in the atlantodens interval ([ADI], r = 0.4; p < 0.001) and pannus (p = 0.003). Thirty percent of patients exhibited an ADI of less than 5 mm. This phenomenon has been termed pseudostabilization. The authors' studies emphasize that the ADI (frequently featured in the literature) is totally unreliable as an indicator of neuraxial compromise in the presence of vertical translocation.

The US brewing industry, strategic windows and survival

2014 ◽  
Vol 20 (4) ◽  
pp. 434-458 ◽  
Author(s):  
Lynn A. Walter ◽  
Linda F. Edelman ◽  
Keneth J. Hatten
Keyword(s):  
Dynamic Capabilities ◽  
Survival Rates ◽  
Second Phase ◽  
Brewing Industry ◽  
Content Type ◽  
Operational Capabilities ◽  
Select Group ◽  
The Us ◽  
The Usa

Purpose – This paper aims to investigate how dynamic capabilities enabled survival in a select group of brewers, during one of the lengthiest and most severe industry consolidations in history. In doing so, we advance Abell’s (1978) theory of strategic windows through integration with the resource-based view of the firm. Design/methodology/approach – Using a mixed method approach, we first apply case study methods to develop hypotheses around the timing and level of operational capability required for survival. In the second phase, we test these hypothesized estimations on the USA Brewing population. Findings – Indicate that brewers which had advanced distribution and manufacturing operational capabilities before the strategic window of opportunity closed had higher survival rates. Practical implications – This study reinforces the importance of making timely strategic investments in capabilities. Originality/value – The integration of strategic window and capability theories advances our understanding of the roles that capabilities and time play in determining firm survival.

scholarly journals Knowledge representation for missing persons investigations

2017 ◽  
Vol 19 (1/2) ◽  
pp. 138-150
Author(s):  
Mark Taylor ◽  
Denis Reilly
Keyword(s):  
Knowledge Representation ◽  
Design Methodology ◽  
Situation Calculus ◽  
Content Type ◽  
Missing Persons ◽  
State Changes ◽  
Changes Over Time ◽  
Investigation Process ◽  
Practical Implications ◽  
Over Time

Purpose This paper aims to present the application of situation calculus for knowledge representation in missing persons investigations. Design/methodology/approach The development of a knowledge representation model for the missing persons investigation process based upon situation calculus, with a demonstration of the use of the model for a missing persons example case. Findings Situation calculus is valuable for knowledge representation for missing persons investigations, as such investigations have state changes over time, and due to the complexity of the differing investigation activities applicable to different situations, can be difficult to represent using simpler approaches such as tables or flowcharts. Research limitations/implications Situation calculus modelling for missing persons investigations adds formalism to the process beyond that which can be afforded by the current use of text, tables or flowcharts. The additional formalism is useful in dealing with the uncertainty present in such investigations. Practical implications The implications are a simplification of the application of the current police guidelines, and thoroughness in the application of such guidelines for missing persons investigations via situation calculus modelling. Social implications This paper supports the management of missing person investigations, by using the most critical variables in a missing persons investigation to determine relevant investigation and search activities applicable to the circumstances of a given case. Originality/value The novelty of the knowledge representation approach is the application of situation calculus via state and action vectors and a matrix of fluents to the process of missing persons investigations.

scholarly journals In VitroandIn VivoAntimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

2012 ◽  
Vol 56 (11) ◽  
pp. 5961-5970 ◽  
Author(s):  
Luísa C. S. Antunes ◽  
Francesco Imperi ◽  
Fabrizia Minandri ◽  
Paolo Visca
Keyword(s):  
Human Serum ◽  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Therapeutic Potential ◽  
Survival Rates ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Gallium Nitrate ◽  
Content Type ◽  
Bacterial Physiology

ABSTRACTMultidrug-resistantAcinetobacter baumanniiposes a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumanniichemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO3)3, the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58A. baumanniistrains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO3)3delayed the entry ofA. baumanniiinto the exponential phase and drastically reduced bacterial growth rates. Ga(NO3)3activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO3)3also protectedGalleria mellonellalarvae from lethalA. baumanniiinfection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO3)3inhibited the growth in human serum of 76% of the multidrug-resistantA. baumanniiisolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment ofA. baumanniibloodstream infections. Ga(NO3)3also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistantA. baumannii.

Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2

2003 ◽  
Vol 99 (3) ◽  
pp. 480-483 ◽  
Author(s):  
Goro Otsuka ◽  
Kiyoshi Saito ◽  
Tetsuya Nagatani ◽  
Jun Yoshida
Keyword(s):  
Symptom Onset ◽  
Survival Rates ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Content Type ◽  
Fine Print

Object. Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. Methods. From among 283 patients with neurofibromatosis who had been registered in a nationwide study in Japan between 1986 and 1987, 74 patients with bilateral vestibular schwannomas were analyzed. The mean duration of follow up after diagnosis was 121 months (range 2–287 months). Results of a Kaplan—Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis (< 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival. Conclusions. This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

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