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We revisit the study of string theory close to the Hagedorn temperature with the aim towards cosmological applications. We consider interactions of open and closed strings in a gas of Dp-branes, and/or one isolated Dp-brane, in an arbitrary number d of flat non-compact dimensions and general compact dimensions. Leading order string perturbation theory is used to obtain the basic interaction rates in a flat background, which are shown to be consistent with the random walk picture of highly excited strings that should apply in more general backgrounds. Using the random walk interpretation we infer the structure of more general semi-inclusive string scattering rates and then write down the corresponding Boltzmann equations describing ensembles of highly excited closed and open strings. We organise the interaction terms in Boltzmann equations so that detailed balance becomes manifest. We obtain the equilibrium solutions and show that they reduce to previously computed solutions for d = 0. We further study the behaviour of non-equilibrium fluctuations and find explicit analytic expressions for the equilibration rates (and for the number of open strings in d = 0). Potential implications for an early universe with strings at high temperatures are outlined. [ABSTRACT FROM AUTHOR]

We investigate the holographic complexity of CFTs compactified on a circle with a Wilson line, dual to magnetized solitons in AdS4 and AdS5. These theories have a confinement-deconfinement phase transition as a function of the Wilson line, and the complexity of formation acts as an order parameter for this transition. Through explicit calculation, we show that proposed complexity functionals based on volume and action obey a scaling relation with radius of the circle and further prove that a broad family of potential complexity functionals obeys this scaling behavior. As a result, we conjecture that the scaling law applies to the complexity of conformal field theories on a circle in more general circumstances. [ABSTRACT FROM AUTHOR]

Introduction and aims CYLD cutaneous syndrome (CCS) is an inherited hair follicle tumour syndrome where biallelic loss of function of the deubiquitinase enzyme CYLD gives rise to cylindroma skin tumours. The role of CYLD in skin biology is not well characterized but it is known to regulate several cell signalling pathways through deubiquitination of effector proteins. We aimed to determine how loss of CYLD function can lead to CCS skin tumour formation by studying the ubiquitome of CCS tumours and healthy skin. Methods Healthy skin (n = 5) and CCS tumour tissue (n = 5) were collected from flash frozen samples. Lysed homogenates were trypsin-digested and the resulting peptides underwent diglycine immunopurification for subsequent liquid chromatography–tandem mass spectrometry analysis on a Bruker Tims-TOF HT (Billerica, MA, USA) mass spectrometer. We utilized a data-independent acquisition method adapted for diglycine-containing peptides to generate mass spectrometry data. Peptide identification was performed by searching mass spectrometry data against an in silico neural network derived spectral library with diglycine modification. Results We identified 1273 ubiquitination sites across 649 proteins in CCS tumour and control samples. After performing t -tests (P < 0.05), we found 305 ubiquitination sites that were either unique to their respective condition or were differentially regulated. Analysis of ubiquitinated peptide sequences uncovered cell surface receptors with increased ubiquitination in CCS tumour samples including the insulin receptor, which had ubiquitination modifications at its kinase domain, suggesting increased insulin signalling in CCS tumours. Gene set enrichment analysis of CCS tumour ubiquitinated substrates revealed increased ubiquitination of secretory granules and extracellular exosomes, suggesting that loss of CYLD may disrupt regulation of protein secretion processes. Conclusions Our findings describe the ubiquitome of CCS keratinocytes, providing insights into how loss of CYLD function can affect biological processes in skin. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a Gram‐positive commensal that can also cause a variety of infections in humans. S. aureus virulence factor gene expression is under tight control by a complex regulatory network, which includes, sigma factors, sRNAs, and two‐component systems (TCS). Previous work in our laboratory demonstrated that overexpression of the sRNA tsr37 leads to an increase in bacterial aggregation. Here, we demonstrate that the clumping phenotype is dependent on a previously unannotated 88 amino acid protein encoded within the tsr37 sRNA transcript (which we named ScrA for S. aureusclumping regulator A). To investigate the mechanism of action of ScrA we performed proteomics and transcriptomics in a ScrA overexpressing strain and show that a number of surface adhesins are upregulated, while secreted proteases are downregulated. Results also showed upregulation of the SaeRS TCS, suggesting that ScrA is influencing SaeRS activity. Overexpression of ScrA in a saeR mutant abrogates the clumping phenotype confirming that ScrA functions via the Sae system. Finally, we identified the ArlRS TCS as a positive regulator of scrA expression. Collectively, our results show that ScrA is an activator of the SaeRS system and suggests that ScrA may act as an intermediary between the ArlRS and SaeRS systems. [ABSTRACT FROM AUTHOR]

We calculate the volume and action forms of holographic complexity for the gravitational collapse of scalar field matter in asymptotically anti-de Sitter spacetime, using numerical methods to reproduce the geometry responding to the oscillating field over multiple crossing times. Like the scalar field pulse, the volume complexity oscillates quasiperiodically before horizon formation. It also shows a scaling symmetry with the amplitude of the scalar field. The action complexity is also quasiperiodic with spikes of increasing amplitude. [ABSTRACT FROM AUTHOR]

Abstract: Hints of direct dark matter detection coming from the DAMA, CoGeNT experiments point toward light dark matter with isospin-violating and possibly inelastic couplings. However an array of astrophysical constraints are rapidly closing the window on light dark matter. We point out that if the relic density is determined by annihilation into invisible states, these constraints can be evaded. As an example we present a model of quasi-Dirac dark matter, interacting via two U(1) gauge bosons, one of which couples to baryon number and the other which kinetically mixes with the photon. Annihilation is primarily into “dark neutrinos” that do not mix with the SM, but which could provide an extra component of dark radiation. The model could soon be tested by several experiments searching for such light gauge bosons, and we predict that both could be detected. The model also requires a fourth generation of quarks, whose existence might increase the production cross section of Higgs bosons at the Tevatron and LHC. [Copyright &y& Elsevier]

We study the development of entropy fluctuations in brane inflation in a warped throat, including the brane–antibrane tachyon as the waterfall field. We find that there is a period at the end of inflation during which the entropy mode associated with the tachyon field increases exponentially. In turn, the induced entropy seeds a contribution to the curvature fluctuation on cosmological scales which grows rapidly and could exceed the primordial curvature perturbation. We identify parameter values for which in the absence of backreaction the induced curvature fluctuations are larger than the primordial adiabatic ones. In the specific model we study, however, backreaction limits the growth of the entropy fluctuations. We discuss situations in which backreaction effects are less constraining. The lesson of our investigation is that the study of the development of entropy fluctuations at the end of the period of inflation can lead to constraints on models of brane inflation and suggests that the curvaton mechanism may contribute significantly to the spectrum of cosmological perturbations. [ABSTRACT FROM AUTHOR]

We argue that many models of inflation in string theory require the usual ten-dimensional compactification geometry to be modified during inflation. Based on arguments from the four-dimensional effective theory, we propose a modified ten-dimensional geometry in which the four-dimensional effective theory is just consistent. We also discuss the implications of the light modes in reheating, following inflation. (Based on work in progress with Anupam Mazumdar and Robert Myers.) [ABSTRACT FROM AUTHOR]

One often neglected aspect of the host-pathogen interface is the presence of myriad glycoproteins and the carbohydrate glycans that they present. These are often the first point of contact for bacteria, with the oral cavity being rich in glycoprotein mucins within secretions such as saliva and crevicular fluid. Therefore, unsurprisingly, bacteria have evolved a myriad of enzymes (that one can consider virulence attributes) to access these glycans to allow attachment to host surfaces, which often results in modulation of host-cell behavior but also that bacteria harvest for nutritional purposes. This talk will summarise our recent work on the role of a range of novel CaZymes from periodontal pathogens in terms of their role in host-bacteria interactions and biofilm formation with potential routes to novel antimicrobials. It will also outline basic biochemical and structural biology work that has identified novel enzymes, lectin domains and biochemical activities that has lead to utilization of these seemingly obscure enzymes in bespoke, specialized biotechnological uses in biopharmaceutical protein analysis that we are currently investigating further. [ABSTRACT FROM AUTHOR]

Tannerella forsythia is a periodontal pathogen implicated in periodontitis. This gram-negative pathogen depends on exogenous peptidoglycan amino sugar N-acetylmuramic acid (NAM) for growth. In the biofilm state the bacterium can utilize sialic acid (Neu5Ac) instead of NAM to sustain its growth. Thus, the sialic acid utilization system of the bacterium plays a critical role in the growth and survival of the organism in the absence of NAM. We sought the function of a T. forsythia gene annotated as nanT coding for an inner-membrane sugar transporter located on a sialic acid utilization genetic cluster. To determine the function of this putative sialic acid transporter, an isogenic nanT- deletion mutant generated by allelic replacement strategy was evaluated for biofilm formation on NAM or Neu5Ac, and survival on KB epithelial cells. Moreover, since T. forsythia forms synergistic biofilms with Fusobacterium nucleatum , co-biofilm formation activity in mixed culture and sialic acid uptake in culture were also assessed. The data showed that the nanT -inactivated mutant of T. forsythia was attenuated in its ability to uptake sialic acid. The mutant formed weaker biofilms compared to the wild-type strain in the presence of sialic acid and as co-biofilms with F. nucleatum. Moreover, compared to the wild-type T. forsythia nanT -inactivated mutant showed reduced survival when incubated on KB epithelial cells. Taken together, the data presented here demonstrate that NanT-mediated sialic transportation is essential for sialic acid utilization during biofilm growth and survival of the organism on epithelial cells and implies sialic acid might be key for its survival both in subgingival biofilms and during infection of human epithelial cells in vivo . [ABSTRACT FROM AUTHOR]

Background: The role of extracorporeal membrane oxygenation (ECMO) for patients with refractory respiratory failure due to coronavirus 2019 (COVID‐19) is still unclear even now over a year into the pandemic. ECMO is becoming more commonplace even at smaller community hospitals. While the advantages of venovenous (VV) ECMO in acute respiratory distress syndrome (ARDS) from COVID‐19 have not been fully determined, we believe the benefits outweighed the risks in our patient population. Here we describe all patients who underwent VV ECMO at our center. Methods: All patients placed on ECMO at our center since the beginning of the pandemic, May 5, 2020, until February 20, 2021 were included in our study. All patients placed on ECMO during the time period described above were followed until discharge or death. The primary endpoint was in‐hospital death. Secondary outcomes included discharge disposition, that is, whether patients were sent to a long‐term acute care center (LTAC), inpatient rehabilitation, or went directly home. Results: A total of 41 patients were placed on VV ECMO for refractory acute respiratory failure. Survival to discharge, the primary end point, was 63.4% (26/41). Inpatient mortality was 36.6% (15/41). Conclusions: We show here that a successful high‐volume VV ECMO program for ARDS is achievable at even a medium‐size community hospital. We think our success can be replicated by most small‐ and medium‐size community hospitals with cardiothoracic surgery programs and intensivist teams. [ABSTRACT FROM AUTHOR]

Recently it has been argued that in Einstein gravity anti-de Sitter spacetime is unstable against the formation of black holes for a large class of arbitrarily small perturbations. We examine the effects of including a Gauss-Bonnet term. In five dimensions, spherically symmetric Einstein-Gauss-Bonnet gravity has two key features: Choptuik scaling exhibits a radius gap, and the mass function goes to a finite value as the horizon radius vanishes. These suggest that black holes will not form dynamically if the total mass-energy content of the spacetime is too small, thereby restoring the stability of anti-de Sitter spacetime in this context. We support this claim with numerical simulations and uncover a rich structure in horizon radii and formation times as a function of perturbation amplitude. [ABSTRACT FROM AUTHOR]

• Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) are prevalent in African pig and pork production systems. • The presence of antimicrobial, heavy metal resistance and virulence factor genes was noted. • The typical ST398 MRSA strains among pigs have been reported in Africa. • Other detected genotypes suggest an anthropogenic origin rather than zoonosis. To assess the emergence of livestock-associated Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) in the pig and pork production systems in Africa for the past two decades. PubMed and African Journals OnLine were searched for relevant primary studies from 2000 to 2019 using standardized key words. In total, 19 eligible articles were included in this review. The prevalence of S. aureus including MRSA ranged from 0% to 55% among live pigs and raw pork, and from 9.4% to 30.8% among pig farm and abattoir workers. Risk factors associated with S. aureus carriage among workers were: male gender, working in an abattoir, and medical-related occupation of a household member. S. aureus and MRSA from pigs and pork production systems in Africa are potentially pathogenic with diverse spa types and clonal complexes, with genes encoding antimicrobial resistance, heavy metal resistance, and virulence factors including secreted and enterotoxins, proteases and immune evasion cluster. The typical livestock-associated S. aureus CC398 and mecC genes were reported in two studies. Pigs are a potential source of the emerging livestock-associated S. aureus in Africa. Continued monitoring using a 'One Health' approach is recommended for effective infection prevention and control of these infections in Africa. [ABSTRACT FROM AUTHOR]

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that assist in protein folding around proline-peptide bonds, and they often possess chaperone activity. Staphylococcus aureus encodes three PPIases, i.e., PrsA, PpiB, and trigger factor (TF). Previous work by our group demonstrated a role for both PrsA and PpiB in S. aureus; however, TF remains largely unstudied. Here, we identify a role for TF in S. aureus biofilm formation and demonstrate cooperation between TF and the cytoplasmic PPIase PpiB. Mutation of the tig gene (encoding TF) led to reduced biofilm development in vitro but no significant attenuation of virulence in a mouse model of infection. To investigate whether TF possesses chaperone activity, we analyzed the ability of a tig mutant to survive acid and base stress. While there was no significant decrease for a tig mutant, a ppiB tig double mutant exhibited significant decreases in cell viability after acid and base challenges. We then demonstrated that a ppiB tig double mutant had exacerbated phenotypes in vitro and in vivo, compared to either single mutant. Finally, in vivo immunoprecipitation of epitope-tagged PpiB revealed that PpiB interacted with 4 times the number of proteins when TF was absent from the cell, suggesting that it may be compensating for the loss of TF. Interestingly, the only proteins found to interact with TF were TF itself, fibronectin-binding protein B (FnBPB), and the chaperone protein ClpB. Collectively, these results support the first phenotype for S. aureus TF and demonstrate a greater network of cooperation between chaperone proteins in Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Tannerella forsythia, a Gram-negative member of the Bacteroidetes has evolved to harvest and utilize sialic acid. The most common sialic acid in humans is a mono-Nacetylated version termed Neu5Ac (5-N-acetyl-neuraminic acid). Many bacteria are known to access sialic acid using sialidase enzymes. However, in humans a high proportion of sialic acid contains a second acetyl group attached via an O-group, i.e. chiefly O-acetylated Neu5,9Ac2 or Neu5,4Ac2. This diacetylated sialic acid is not cleaved efficiently by many sialidases and in order to access diacetylated sialic acid, some organisms produce sialate-O-acetylesterases that catalyse the removal of the second acetyl group. In the present study, we performed bioinformatic and biochemical characterization of a putative sialate-O-acetylesterase from T. forsythia (NanS), which contains two putative SGNH-hydrolase domains related to sialate-Oacetylesterases from a range of organisms. Purification of recombinant NanS revealed an esterase that has activity against Neu5,9Ac2 and its glycolyl form Neu5Gc,9Ac. Importantly, the enzyme did not remove acetyl groups positioned at the 4-O position (Neu5,4Ac2). In addition NanS can act upon complex N-glycans released from a glycoprotein [erythropoietin (EPO)], bovine submaxillary mucin and oral epithelial cell-bound glycans. When incubated with its cognate sialidase, NanS increased sialic acid release frommucin and oral epithelial cell surfaces, implying that this esterase improves sialic acid harvesting for this pathogen and potentially other members of the oral microbiome. In summary, we have characterized a novel sialate-O-acetylesterase that contributes to the sialobiology of this important human pathogen and has potential applications in the analysis of sialic acid diacetylation of biologics in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]