Comparative genomics, antimicrobial resistance determinants, and pathogenicity of community-associated Staphylococcus aureus

Staphylococcus aureus is a major human pathogen and a global public health issue. It is considered an opportunistic pathogen as it asymptomatically colonizes its host, but can occasionally cause diseases that range in severity from relatively minor skin and soft tissue infections (SSTI) to life-threatening cases of pneumonia and endocarditis. There is a critical need to better understand mechanisms that lead to the evolution, resistance, and severity of S. aureus infections. Bacterial whole genome sequencing (WGS) techniques have offered new insights into S. aureus genomic populations and have the potential to predict antimicrobial resistance and infection severity. This study applied WGS 1) to describe the diversity and distribution of resistance mechanisms among community-associated S. aureus isolates, and 2) to identify S. aureus genetic signatures associated with SSTI isolates and derive a predictive risk model. WGS was performed on S. aureus isolates from patients within 14 primary care clinics in the South Texas Ambulatory Research Network from 2007 to 2015. The bacterial genomes were compared to a reference genome, FPR3757 (USA300 strain) to identify single nucleotide polymorphisms (SNPs). Phylogenetic analyses were conducted using concatenated SNP nucleotides in the core genomes. In the first study, the resistome was assembled by identifying antimicrobial resistance determinants related to the phenotypically derived antibiogram. The findings of this study identified that multidrug-resistant S. aureus isolates have emerged in the South Texas community; approximately one-third were multidrug-resistant. There was an increasing resistance pattern to fluoroquinolones. Furthermore, the genotype demonstrated to be highly predictive of antimicrobial resistance (very major error rate=0% and major error rate=1.4%). These findings highlight the genomic diversity of S. aureus strains in the South Texas community and demonstrate the utility of next generation sequencing to define the diversity and distribution of resistance mechanisms within S. aureus. Further work to explore antimicrobial selective pressures is needed. The second study utilized a bacterial genome-wide association study to identify specific variants associated with S. aureus pathogenicity. This study revealed the heterogeneity of S. aureus SSTI and nasal colonization isolates and identified potentially novel pathogenic mechanisms.Pharmac

Some new canonical forms for polynomials

We give some new canonical representations for forms over \cc. For example, a general binary quartic form can be written as the square of a quadratic form plus the fourth power of a linear form. A general cubic form in $(x_1,...,x_n)$ can be written uniquely as a sum of the cubes of linear forms $\ell_{ij}(x_i,...,x_j)$, $1 \le i \le j \le n$. A general ternary quartic form is the sum of the square of a quadratic form and three fourth powers of linear forms. The methods are classical and elementary.Comment: I have spoken about this material under the title "steampunk canonical forms". This is the final revised version which has been accepted by the Pacific Journal of Mathematics. Apart from the usual improvements which come after a thoughtful refereeing, Theorem 1.8 is ne

Have You Tried This? Field-Configuring Spaces and Implementing Moral Mandates

Organizational theorists and strategy scholars are both interested in how organizations deal with ambiguity, especially in relation to implementation. This chapter examines one source of ambiguity that organizations face, which is based on their efforts to implement moral mandates. These mandates, which are related to areas such as environmental sustainability and diversity, are inherently ambiguous, as they lack a shared understanding regarding their scope and associated practices. They are also often broad and systemic and may be unclearly aligned with an organization’s strategy. Due to these challenges, in this chapter, we theorize that collective action at the field level is necessary for organizations to advance and concretize moral mandates. We examine this theorizing through the case of the implementation of sustainability in higher education. We hypothesize and find support for the idea that when an organization’s members engage in collective action at the field level, those organizations have an increased likelihood of achieving sustainability implementation. To gain insight into this field-to-organization relationship, we qualitatively examine 18 years of conversations from an online forum to develop a process model of moral mandate implementation. We theorize that collective action functions as a field-configuring space, in which actors from a variety of organizations come together to (1) refine the scope of the mandate and (2) create an implementation repertoire that actors can draw on when seeking to bring sustainability to their own organizations.</p

EFFECTS OF PARTICLE SIZE AND FLUIDIZING VELOCITY ON THE CHARGE DENSITY OF ENTRAINED FINES

A previously-developed Faraday cup fluidized bed unit was modified to facilitate the in-situ monitoring of the transient entrainment rate and net charge of entrained fine powders. This enabled the determination of the transient charge density as a function of particle size and residence time of entrained fine particles. The results showed that the charge density increased significantly with increasing size of entrained fines, but was not very sensitive to the residence time and the fluidizing gas velocity for the finest entrained particles at gas velocities of 0.24 and 0.36 m/s. At Ug=0.48 m/s, the charge density of larger particles increased with increasing particle residence time

Deregulation of HDAC5 by Viral Interferon Regulatory Factor 3 Plays an Essential Role in Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphangiogenesis.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECs in vitro, its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy. Here, we report for the first time that viral interferon regulatory factor 3 (vIRF3) is readily detected in over 40% of KS lesions and that vIRF3 functions as a proangiogenic factor, inducing hypersprouting formation and abnormal growth in a LEC-specific manner. Mass spectrometry analysis revealed that vIRF3 interacted with histone deacetylase 5 (HDAC5), which is a signal-responsive regulator for vascular homeostasis. This interaction blocked the phosphorylation-dependent cytosolic translocation of HDAC5 and ultimately altered global gene expression in LECs but not in BECs. Consequently, vIRF3 robustly induced spindle morphology and hypersprouting formation of LECs but not BECs. Finally, KSHV infection led to the hypersprouting formation of LECs, whereas infection with a ΔvIRF3 mutant did not do so. Collectively, our data indicate that vIRF3 alters global gene expression and induces a hypersprouting formation in an HDAC5-binding-dependent and LEC-specific manner, ultimately contributing to KSHV-associated pathogenesis.IMPORTANCE Several lines of evidences indicate that KSHV infection of LECs induces pathological lymphangiogenesis and that the results resemble KS-like spindle morphology. However, the underlying molecular mechanism remains unclear. Here, we demonstrated that KSHV vIRF3 is readily detected in over 40% of various KS lesions and functions as a potent prolymphangiogenic factor by blocking the phosphorylation-dependent cytosolic translocation of HDAC5, which in turn modulates global gene expression in LECs. Consequently, vIRF3-HDAC5 interaction contributes to virus-induced lymphangiogenesis. The results of this study suggest that KSHV vIRF3 plays a crucial role in KSHV-induced malignancy

Genetic Determinants of Feline Leukemia Virus-Induced Multicentric Lymphomas

AbstractThree discrete forms of feline leukemia virus (FeLV)-associated lymphoma have been described clinically: (1) thymic, (2) alimentary, and (3) multicentric. The most common and best-characterized lymphomas are of T-cell origin, generally occurring in the thymus. These tumors typically contain mature T-cells, involve the activation of a distinctive set of proto-oncogenes, and contain FeLV proviruses whose long terminal repeat (LTR) sequences contain tandemly repeated enhancers. Previous studies of a small group of extrathymic, multicentric lymphomas implicated a different set of genetic determinants. The present study expands those observations by examining the lineage of origin, the involvement of proto-oncogenes, and the structure of LTR andenvgene sequences in a set of 11 natural, extrathymic lymphomas of the multicentric type. A pattern of genetic events associated with FeLV-positive multicentric lymphomas emerges from this analysis that is clearly distinct from the pattern associated with thymic lymphomas. The tumors do not contain T-cells or B-cells, as evidenced by the germ line organization of TCRβ and IgH loci. Proto-oncogenes strongly implicated in T-cell lymphomagenesis are not involved in these tumors. Rather, a distinct set of proto-oncogenes may be involved. Most striking is the repeated occurrence of an FeLV isolate whose LTR andenvgene bear unique sequence elements

Monitoring Observations of the Jupiter-Family Comet 17P/Holmes during 2014 Perihelion Passage

We performed a monitoring observation of a Jupiter-Family comet, 17P/Holmes, during its 2014 perihelion passage to investigate its secular change in activity. The comet has drawn the attention of astronomers since its historic outburst in 2007, and this occasion was its first perihelion passage since then. We analyzed the obtained data using aperture photometry package and derived the Afrho parameter, a proxy for the dust production rate. We found that Afrho showed asymmetric properties with respect to the perihelion passage: it increased moderately from 100 cm at the heliocentric distance r_h=2.6-3.1 AU to a maximal value of 185 cm at r_h = 2.2 AU (near the perihelion) during the inbound orbit, while dropping rapidly to 35 cm at r_h = 3.2 AU during the outbound orbit. We applied a model for characterizing dust production rates as a function of r_h and found that the fractional active area of the cometary nucleus had dropped from 20%-40% in 2008-2011 (around the aphelion) to 0.1%-0.3% in 2014-2015 (around the perihelion). This result suggests that a dust mantle would have developed rapidly in only one orbital revolution around the sun. Although a minor eruption was observed on UT 2015 January 26 at r_h = 3.0 AU, the areas excavated by the 2007 outburst would be covered with a layer of dust (<~ 10 cm depth) which would be enough to insulate the subsurface ice and to keep the nucleus in a state of low activity.Comment: 25 pages, 6 figures, 2 tables, ApJ accepted on December 29, 201

A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing