scholarly journals A Critical Region in the FlaA Flagellin Facilitates Filament Formation of theVibrio choleraeFlagellum

2018 ◽  
Vol 200 (15) ◽  
Author(s):  
Mylea A. Echazarreta ◽  
Johnathan L. Kepple ◽  
Li-Hua Yen ◽  
Yue Chen ◽  
Karl E. Klose
Keyword(s):  
Diarrheal Disease ◽  
Critical Role ◽  
The Other ◽  
Class Iii ◽  
Content Type ◽  
Important Region ◽  
Filament Structure ◽  
Flagellar Filament ◽  
Necessary And Sufficient ◽  
Class Iv

ABSTRACTVibrio choleraeis a Gram-negative bacterium with a monotrichous flagellum that causes the human disease cholera. Flagellum-mediated motility is an integral part of the bacterial life cycle inside the host and in the aquatic environment. TheV. choleraeflagellar filament is composed of five flagellin subunits (FlaA, FlaB, FlaC, FlaD, and FlaE); however, only FlaA is necessary and sufficient for filament synthesis.flaAis transcribed from a class III flagellar promoter, whereas the other four flagellins are transcribed from class IV promoters. However, expressingflaAfrom a class IV promoter still facilitated motility in a strain that was otherwise lacking all five flagellins (ΔflaA-E). Furthermore, FlaA fromV. parahaemolyticus(FlaAVP; 77% identity) supported motility of theV. choleraeΔflaA-Estrain, whereas FlaA fromV. vulnificus(FlaAVV; 75% identity) did not, indicating that FlaA amino acid sequence is responsible for its critical role in flagellar synthesis. Chimeric proteins composed of different domains of FlaAVCand FlaD or FlaAVVrevealed that the N-terminal D1domain (D1N) contains an important region required for FlaA function. Further analyses of chimeric FlaAVC-FlaD proteins identified a lysine residue present at position 145 of the other flagellins but absent from FlaAVCthat can prevent monofilament formation. Moreover, the D1Nregion of amino acids 87 to 153 of FlaAVVinserted into FlaAVCallows monofilament formation but not motility, apparently due to the lack of filament curvature. These results identify residues within the D1Ndomain that allow FlaAVCto fold into a functional filament structure and suggest that FlaAVCassists correct folding of the other flagellins.IMPORTANCEV. choleraecauses the severe diarrheal disease cholera. Its ability to swim is mediated by rotation of a polar flagellum, and this motility is integral to its ability to cause disease and persist in the environment. The current studies illuminate how one specific flagellin (FlaA) within a multiflagellin structure mediates formation of the flagellar filament, thus allowingV. choleraeto swim. This knowledge can lead to safer vaccines and potential therapeutics to inhibit cholera.

scholarly journals The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence inStaphylococcus aureus

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Rachel L. Zapf ◽  
Richard E. Wiemels ◽  
Rebecca A. Keogh ◽  
Donald L. Holzschu ◽  
Kayla M. Howell ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Small Rna ◽  
Hemolytic Activity ◽  
Interaction Analysis ◽  
Critical Role ◽  
Content Type ◽  
Fold Reduction ◽  
Novel Target ◽  
Rna Interaction ◽  
Necessary And Sufficient

ABSTRACTSmall RNAs (sRNAs) remain an understudied class of regulatory molecules in bacteria in general and in Gram-positive bacteria in particular. In the major human pathogenStaphylococcus aureus, hundreds of sRNAs have been identified; however, only a few have been characterized in detail. In this study, we investigate the role of the sRNA Teg41 inS. aureusvirulence. We demonstrate that Teg41, an sRNA divergently transcribed from the locus that encodes the cytolytic alpha phenol-soluble modulin (αPSM) peptides, plays a critical role in αPSM production. Overproduction of Teg41 leads to an increase in αPSM levels and a corresponding increase in hemolytic activity fromS. aureuscells and cell-free culture supernatants. To identify regions of Teg41 important for its function, we performed anin silicoRNA-RNA interaction analysis which predicted an interaction between the 3′ end of Teg41 and the αPSM transcript. Deleting a 24-nucleotide region from theS. aureusgenome, corresponding to the 3′ end of Teg41, led to a 10-fold reduction in αPSM-dependent hemolytic activity and attenuation of virulence in a murine abscess model of infection. Restoration of hemolytic activity in the Teg41Δ3′ strain was possible by expressing full-length Teg41 intrans. Restoration of hemolytic activity was also possible by expressing the 3′ end of Teg41, suggesting that this region of Teg41 is necessary and sufficient for αPSM-dependent hemolysis. Our results show that Teg41 is positively influencing αPSM production, demonstrating for the first time regulation of the αPSM peptides by an sRNA inS. aureus.IMPORTANCEThe alpha phenol-soluble modulins (αPSMs) are among the most potent toxins produced byStaphylococcus aureus. Their biological role during infection has been studied in detail; however, the way they are produced by the bacterial cell is not well understood. In this work, we identify a small RNA molecule called Teg41 that plays an important role in αPSM production byS. aureus. Teg41 positively influences αPSM production. The importance of Teg41 is highlighted by the fact that a strain containing a deletion in the 3′ end of Teg41 produces significantly less αPSMs and is attenuated for virulence in a mouse abscess model of infection. As the search for new therapeutic strategies to combatS. aureusinfection proceeds, Teg41 may represent a novel target.

scholarly journals Surgical Treatment of Patients with Lennox-Gastaut Syndrome Phenotype

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Shi-Yong Liu ◽  
Ning An ◽  
Xiang Fang ◽  
Prabhdeep Singh ◽  
Joseph Oommen ◽  
...  
Keyword(s):  
Intelligence Quotient ◽  
Seizure Control ◽  
Brain Mri ◽  
Class Ii ◽  
The Other ◽  
Imaging Findings ◽  
Class Iii ◽  
Intellectual Outcome ◽  
Generalized Epilepsy ◽  
Class Iv

Lennox-Gastaut syndrome (LGS) is a devastating and refractory generalized epilepsy affecting children and adolescents. In this study we report the results of resective surgery in 18 patients with LGS phenotype who underwent single-lobe/lesionectomy or multilobe resection plus multiple subpial transection and/or callosotomy. After surgery, seven patients became completely seizure-free (Engel Class I) and five almost seizure-free (Engel Class II). Additional four had significant seizure control (Engel Class III), and two had no change in seizure frequency (Engel Class IV). Of the 4 patients without any lesion on brain MRI, 2 ended with Engel Class II, 1 with III and the other with IV in Engels’ classification. Mean intelligence quotient (IQ) increased from 56.1 ± 8.1 (mean ± SD) before operation to 67.4 ± 8.2 (mean ± SD) after operation, a significant improvement (P=0.001). Results also indicated that the younger the patient at surgery, or the shorter the interval between onset of seizure and resective operation, the better the intellectual outcome. Our data suggest that resective epilepsy surgery can be successful in patients with LGS phenotype as long as the EEG shows dominance of discharges in one hemisphere and corresponding ipsilateral imaging findings, even with contralateral ictal discharges.

Multiple subpial transections: outcome and complications in 20 patients who did not undergo resection

2002 ◽  
Vol 97 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Johannes Schramm ◽  
Ales F. Aliashkevich ◽  
Thomas Grunwald
Keyword(s):  
Mr Imaging ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Content Type ◽  
Surgical Methods ◽  
Over Time ◽  
Class Iv ◽  
Fine Print

Object. The authors describe patient characteristics, surgical methods, complications, and outcome over time in a cohort of patients who underwent multiple subpial transection (MST) without concomitant cortical resection. Methods. Twenty consecutive patients in whom drug-resistant epilepsy had been diagnosed a mean of 16 ± 9 years earlier (mean ± standard deviation [SD]) were treated with MST without cortical resection. The mean follow-up period was 49.3 ± 18.3 months (mean ± SD, median 58 months). At 12 months of follow up, two of the 20 patients were Engel Class I, one was Class II, six were Class III, and 11 were Class IV. At latest follow up, one patient was Engel Class I, one was Class II, seven were Class III, and 11 were Class IV. According to an alternative five-tiered classification system, two outcomes were excellent, seven were good, one was fair, nine were poor, and one was worse. Outcome was found to be better in patients with no lesions observed on magnetic resonance (MR) imaging, and worse in those with large MST areas. Outcome had a tendency to change (this occurred in 13 of 20 cases). Five patients (25%) improved and seven (35%) deteriorated in Engel outcome class, and in one (5%) both developments occurred over time. Most outcome class changes occurred before the end of the 2nd year (nine), and four were observed in the 5th year. There where seven transient neurological deficits and four surgical complications. There was no permanent significant morbidity, and there were no deaths. Conclusions. Forty-five percent of patients achieved a worthwhile improvement after pure MST, if Engel outcome Class III is deemed a worthwhile improvement. The alternative five-tiered classification resulted in 50% with worthwhile improvement (excellent, good, or fair outcome), 45% with poor, and 5% with worse outcome. Lesions that are detectable on MR imaging, and large MST areas are predictive of worse results. Significant intraoperative problems may arise, but this happens infrequently. There is a notable rate of transient morbidity but the rate of permanent morbidity is not significant.

scholarly journals Multiple Flagellin Proteins Have Distinct and Synergistic Roles inAgrobacterium tumefaciensMotility

2018 ◽  
Vol 200 (23) ◽  
Author(s):  
Bitan Mohari ◽  
Melene A. Thompson ◽  
Jonathan C. Trinidad ◽  
Sima Setayeshgar ◽  
Clay Fuqua
Keyword(s):  
Escherichia Coli ◽  
Agrobacterium Tumefaciens ◽  
Basal Body ◽  
Mutational Analysis ◽  
The Other ◽  
Model Systems ◽  
Helical Conformation ◽  
Content Type ◽  
Suppressor Mutations ◽  
Flagellar Filament

ABSTRACTRotary flagella propel bacteria through liquid and across semisolid environments. Flagella are composed of the basal body that constitutes the motor for rotation, the curved hook that connects to the basal body, and the flagellar filament that propels the cell. Flagellar filaments can be composed of a single flagellin protein, such as inEscherichia coli, or made up of multiple flagellins, such as inAgrobacterium tumefaciens. The four distinct flagellins FlaA, FlaB, FlaC, and FlaD produced by wild-typeA. tumefaciensare not redundant in function but have specific properties. FlaA and FlaB are much more abundant than FlaC and FlaD and are readily observable in mature flagellar filaments, when either FlaA or FlaB is fluorescently labeled. Cells producing FlaA with any one of the other three flagellins can generate functional filaments and thus are motile, but FlaA alone cannot constitute a functional filament. InflaAmutants that manifest swimming deficiencies, there are multiple ways by which these mutations can be phenotypically suppressed. These suppressor mutations primarily occur within or upstream of theflaBflagellin gene or in the transcription factorsciPregulating flagellin expression. The helical conformation of the flagellar filament appears to require a key asparagine residue present in FlaA and absent in other flagellins. However, FlaB can be spontaneously mutated to render helical flagella in the absence of FlaA, reflecting their overall similarity and perhaps the subtle differences in the specific functions they have evolved to fulfill.IMPORTANCEFlagellins are abundant bacterial proteins comprising the flagellar filaments that propel bacterial movement. Several members of the alphaproteobacterial group express multiple flagellins, in contrast to model systems, such as withEscherichia coli, which has one type of flagellin. The plant pathogenAgrobacterium tumefacienshas four flagellins, the abundant and readily detected FlaA and FlaB, and lower levels of FlaC and FlaD. Mutational analysis reveals that FlaA requires at least one of the other flagellins to function, asflaAmutants produce nonhelical flagella and cannot swim efficiently. Suppressor mutations can rescue this swimming defect through mutations in the remaining flagellins, including structural changes imparting helical shape to the flagella, and putative regulators. Our findings shed light on how multiple flagellins contribute to motility.

Does Global Justice Require More than Just Global Institutions?

2016 ◽  
Vol 3 (1) ◽  
pp. 19-31
Author(s):  
Kok-Chor Tan
Keyword(s):  
Global Justice ◽  
The Other ◽  
Global Institutions ◽  
Institutional Approach ◽  
The One ◽  
Necessary And Sufficient ◽  
Strong Reading

The ‘institutional approach’ to justice holds that persons’ responsibility of justice is primarily to support, maintain, and comply with the rules of just institutions. Within the rules of just institutions, so long as their actions do not undermine these background institutions, individuals have no further responsibilities of justice. But what does the institutional approach say in the non-ideal context where just institutions are absent, such as in the global case? One reading of the institutional approach, in this case, is that our duties are primarily to create just institutions, and that when we are doing our part in this respect, we may legitimately pursue other personal or associational ends. This ‘strong’ reading of our institutional duty takes it to be both a necessary and sufficient duty of justice of individuals that they do their part to establish just arrangements. But how plausible is this? On the one hand this requirement seems overly inflexible; on the other it seems overly lax. I clarify the motivation and context of this reading of the institutional duty, and suggest that it need not be as implausible as it seems.

Posterior approach for cervical intramedullary arteriovenous malformation with diffuse-type nidus

1999 ◽  
Vol 91 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Kenji Ohata ◽  
Toshihiro Takami ◽  
Alaa El-Naggar ◽  
Michiharu Morino ◽  
Akimasa Nishio ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Poor Prognosis ◽  
Posterior Approach ◽  
The Other ◽  
Anterior Spinal Artery ◽  
Neural Element ◽  
Feeding Artery ◽  
Diffuse Type ◽  
Content Type ◽  
Fine Print

✓ The treatment of spinal intramedullary arteriovenous malformations (AVMs) with a diffuse-type nidus that contains a neural element poses different challenges compared with a glomus-type nidus. The surgical elimination of such lesions involves the risk of spinal cord ischemia that results from coagulation of the feeding artery that, at the same time, supplies cord parenchyma. However, based on evaluation of the risks involved in performing embolization, together with the frequent occurrence of reperfusion, which necessitates frequent reembolization, the authors consider surgery to be a one-stage solution to a disease that otherwise has a very poor prognosis. Magnetic resonance (MR) imaging revealed diffuse-type intramedullary AVMs in the cervical spinal cords of three patients who subsequently underwent surgery via the posterior approach. The AVM was supplied by the anterior spinal artery in one case and by both the anterior and posterior spinal arteries in the other two cases. In all three cases, a posterior median myelotomy was performed up to the vicinity of the anterior median fissure that divided the spinal cord together with the nidus, and the feeding artery was coagulated and severed at its origin from the anterior spinal artery. In the two cases in which the posterior spinal artery fed the AVM, the feeding artery was coagulated on the dorsal surface of the spinal cord. Neurological outcome improved in one patient and deteriorated slightly to mildly in the other two patients. Postoperative angiography demonstrated complete disappearance of the AVM in all cases. Because of the extremely poor prognosis of patients with spinal intramedullary AVMs, this surgical technique for the treatment of diffuse-type AVMs provides acceptable operative outcome. Surgical intervention should be considered when managing a patient with a diffuse-type intramedullary AVM in the cervical spinal cord.

Interest rate option hedging portfolios without bank account

2019 ◽  
Vol 37 (1) ◽  
pp. 134-142
Author(s):  
Alberto Bueno-Guerrero
Keyword(s):  
Design Methodology ◽  
Contingent Claim ◽  
Necessary And Sufficient Condition ◽  
Barrier Option ◽  
Bank Account ◽  
Content Type ◽  
Option Hedging ◽  
Hedging Portfolio ◽  
Necessary And Sufficient ◽  
First Time

Purpose This paper aims to study the conditions for the hedging portfolio of any contingent claim on bonds to have no bank account part. Design/methodology/approach Hedging and Malliavin calculus techniques recently developed under a stochastic string framework are applied. Findings A necessary and sufficient condition for the hedging portfolio to have no bank account part is found. This condition is applied to a barrier option, and an example of a contingent claim whose hedging portfolio has a bank account part different from zero is provided. Originality/value To the best of the authors’ knowledge, this is the first time that this issue has been addressed in the literature.

Islamic hedging for pilgrimage funds: case of Indonesia

2019 ◽  
Vol 11 (3) ◽  
pp. 328-341
Author(s):  
Rifki Ismal ◽  
Nurul Izzati Septiana
Keyword(s):  
Exchange Rate ◽  
The Other ◽  
Exchange Rate Risk ◽  
Content Type ◽  
Other Hand ◽  
Rate Risk ◽  
Risk Identify ◽  
Hajj Season ◽  
The Right ◽  
Very High

Purpose The demand for Saudi Arabian real (SAR) is very high in the pilgrimage (hajj) season while the authority, unfortunately, does not hedge the hajj funds. As such, the hajj funds are potentially exposed to exchange rate risk, which can impact the value of hajj funds and generate extra cost to the pilgrims. The purpose of this paper is to conduct simulations of Islamic hedging for pilgrimage funds to: mitigate and minimize exchange rate risk, identify and recommend the ideal time, amount and tenors of Islamic hedging for hajj funds, estimate cost saving by pursuing Islamic hedging and propose technical and general recommendations for the authority. Design/methodology/approach Forward transaction mechanism is adopted to compute Islamic forward between SAR and Rupiah (Indonesian currency) or IDR. Findings – based on simulations, the paper finds that: the longer the Islamic hedging tenors, the better is the result of Islamic hedging, the decreasing of IDR/USD is the right time to hedge the hajj funds and, on the other hand, the IDR/SAR appreciation is not the right time to hedge the hajj funds. Findings Based on simulations, the paper finds that: the longer the Islamic hedging tenors, the better is the result of Islamic hedging, the decreasing of IDR/USD is the right time to hedge the hajj funds and, on the other hand, the IDR/SAR appreciation is not the right time to hedge the hajj funds. Research limitations/implications The research suggests the authority to (and not to) hedge the hajj fund, depending on economic conditions and market indicators. Even though the assessment is for the Indonesian case, other countries maintaining hajj funds might also learn from this paper. Originality/value To the best of author’s knowledge, this is the first paper in Indonesia that attempts to simulate the optimal hedging of hajj funds.

Relief of facial pain after combined removal of precentral and postcentral cortex

1971 ◽  
Vol 34 (4) ◽  
pp. 537-543 ◽  
Author(s):  
Richard A. Lende ◽  
Wolff M. Kirsch ◽  
Ralph Druckman
Keyword(s):  
Facial Pain ◽  
The Other ◽  
Precentral Gyrus ◽  
Nerve Section ◽  
Content Type ◽  
Burning Pain ◽  
Cortical Localization ◽  
The Brain ◽  
Fine Print ◽  
Frontal Lobotomy

✓ Cortical removals which included precentral and postcentral facial representations resulted in relief of facial pain in two patients. Because of known failures following only postcentral (SmI) ablations, these operations were designed to eliminate also the cutaneous afferent projection to the precentral gyrus (MsI) and the second somatic sensory area (SmII). In one case burning pain developed after a stroke involving the brain stem and was not improved by total fifth nerve section; prompt relief followed corticectomy and lasted until death from heart disease 20 months later. In the other case persistent steady pain that developed after fifth rhizotomy for trigeminal neuralgia proved refractory to frontal lobotomy; relief after corticectomy was immediate and has lasted 14 months. Cortical localization was established by stimulation under local anesthesia. Each removal extended up to the border of the arm representation and down to the upper border of the insula. Such a resection necessarily included SmII, and in one case responses presumably from SmII were obtained before removal. The suggestions of Biemond (1956) and Poggio and Mountcastle (1960) that SmII might be concerned with pain sensibility may be pertinent in these cases.

scholarly journals Spo0A Suppresses sin Locus Expression in Clostridioides difficile

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Babita Adhikari Dhungel ◽  
Revathi Govind
Keyword(s):  
Diarrheal Disease ◽  
Toxin Production ◽  
The United States ◽  
Upstream Region ◽  
Pcr Analysis ◽  
Bacterial Cells ◽  
Master Regulator ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Clostridioides difficile is the leading cause of nosocomial infection and is the causative agent of antibiotic-associated diarrhea. The severity of the disease is directly associated with toxin production, and spores are responsible for the transmission and persistence of the organism. Previously, we characterized sin locus regulators SinR and SinR′ (we renamed it SinI), where SinR is the regulator of toxin production and sporulation. The SinI regulator acts as its antagonist. In Bacillus subtilis, Spo0A, the master regulator of sporulation, controls SinR by regulating the expression of its antagonist, sinI. However, the role of Spo0A in the expression of sinR and sinI in C. difficile had not yet been reported. In this study, we tested spo0A mutants in three different C. difficile strains, R20291, UK1, and JIR8094, to understand the role of Spo0A in sin locus expression. Western blot analysis revealed that spo0A mutants had increased SinR levels. Quantitative reverse transcription-PCR (qRT-PCR) analysis of its expression further supported these data. By carrying out genetic and biochemical assays, we show that Spo0A can bind to the upstream region of this locus to regulates its expression. This study provides vital information that Spo0A regulates the sin locus, which controls critical pathogenic traits such as sporulation, toxin production, and motility in C. difficile. IMPORTANCE Clostridioides difficile is the leading cause of antibiotic-associated diarrheal disease in the United States. During infection, C. difficile spores germinate, and the vegetative bacterial cells produce toxins that damage host tissue. In C. difficile, the sin locus is known to regulate both sporulation and toxin production. In this study, we show that Spo0A, the master regulator of sporulation, controls sin locus expression. Results from our study suggest that Spo0A directly regulates the expression of this locus by binding to its upstream DNA region. This observation adds new detail to the gene regulatory network that connects sporulation and toxin production in this pathogen.

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