Propionibacterium acnes bacteriophages display limited genetic diversity and broad killing activity against bacterial skin isolates.

UnlabelledInvestigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.ImportancePropionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne

Smectic ordering in liquid crystal - aerosil dispersions II. Scaling analysis

Liquid crystals offer many unique opportunities to study various phase transitions with continuous symmetry in the presence of quenched random disorder (QRD). The QRD arises from the presence of porous solids in the form of a random gel network. Experimental and theoretical work support the view that for fixed (static) inclusions, quasi-long-range smectic order is destroyed for arbitrarily small volume fractions of the solid. However, the presence of porous solids indicates that finite-size effects could play some role in limiting long-range order. In an earlier work, the nematic - smectic-A transition region of octylcyanobiphenyl (8CB) and silica aerosils was investigated calorimetrically. A detailed x-ray study of this system is presented in the preceding Paper I, which indicates that pseudo-critical scaling behavior is observed. In the present paper, the role of finite-size scaling and two-scale universality aspects of the 8CB+aerosil system are presented and the dependence of the QRD strength on the aerosil density is discussed.Comment: 14 pages, 10 figures, 1 table. Companion paper to "Smectic ordering in liquid crystal - aerosil dispersions I. X-ray scattering" by R.L. Leheny, S. Park, R.J. Birgeneau, J.-L. Gallani, C.W. Garland, and G.S. Iannacchion

Atom Interferometers

Interference with atomic and molecular matter waves is a rich branch of atomic physics and quantum optics. It started with atom diffraction from crystal surfaces and the separated oscillatory fields technique used in atomic clocks. Atom interferometry is now reaching maturity as a powerful art with many applications in modern science. In this review we first describe the basic tools for coherent atom optics including diffraction by nanostructures and laser light, three-grating interferometers, and double wells on AtomChips. Then we review scientific advances in a broad range of fields that have resulted from the application of atom interferometers. These are grouped in three categories: (1) fundamental quantum science, (2) precision metrology and (3) atomic and molecular physics. Although some experiments with Bose Einstein condensates are included, the focus of the review is on linear matter wave optics, i.e. phenomena where each single atom interferes with itself.Comment: submitted to Reviews of Modern Physic

Near-Peer Emergency Medicine for Medical Students in Port-au-Prince, Haiti: An Example of Rethinking Global Health Interventions in Developing Countries

Background: During a 3-year time frame, a partnership between medical trainees in Haiti and the United States was forged with the objective of implementing an emergency response skills curriculum at a medical school in Port-au-Prince. The effort sought to assess the validity of a near-peer, bidirectional, cross-cultural teaching format as both a global health experience for medical students and as an effective component of improving medical education and emergency response infrastructure in developing countries such as Haiti. Method: Medical students and emergency medicine (EM) residents from a North American medical school designed and taught a module on emergency response skills in PAP and certified medical students in basic cardiac life support (BLS) over 2 consecutive years. Five-point Likert scale self-efficacy (SE) surveys and multiple-choice fund of knowledge (FOK) assessments were distributed pre- and postmodule each year and analyzed with paired 't'tests and longitudinal follow-up of the first cohort. Narrative evaluations from participants were collected to gather feedback for improving the module. Findings: Challenges included bridging language barriers, maintaining continuity between cohorts, and adapting to unexpected schedule changes. Overall, 115 students were certified in BLS with significant postcurriculum improvements in SE scores (2.75 ± 0.93 in 2013 and 2.82 ± 1.06 in 2014; 'P' < 0.001) and FOK scores (22% ± 15% in 2013 and 41% ± 16% in 2014; 'P' < 0.001). Of 24 Haitian students surveyed at 1-year follow-up from the 2013 cohort, 7 (29.3%) reported using taught skills in real-life situations since completing the module. The US group was invited to repeat the project for a third year. Conclusions: Near-peer, cross-cultural academic exchange is an effective method of medical student–centered emergency training in Haiti. Limitations such as successfully implementing sustainability measures, addressing cultural differences, and coordinating between groups persist. This scalable, reproducible, and mutually beneficial collaboration between North American and Haitian medical trainees is a valid conduit for building Haiti's emergency response infrastructure and promoting global health

Mesofluidic Devices for DNA-Programmed Combinatorial Chemistry

Hybrid combinatorial chemistry strategies that use DNA as an information-carrying medium are proving to be powerful tools for molecular discovery. In order to extend these efforts, we present a highly parallel format for DNA-programmed chemical library synthesis. The new format uses a standard microwell plate footprint and is compatible with commercially available automation technology. It can accommodate a wide variety of combinatorial synthetic schemes with up to 384 different building blocks per chemical step. We demonstrate that fluidic routing of DNA populations in the highly parallel format occurs with excellent specificity, and that chemistry on DNA arrayed into 384 well plates proceeds robustly, two requirements for the high-fidelity translation and efficient in vitro evolution of small molecules

ESRRA-C11orf20 Is a Recurrent Gene Fusion in Serous Ovarian Carcinoma

Many ovarian cancers have a chromosomal rearrangement that fuses two neighboring genes, ESRRA and c11orf20. Similar rearrangements may be common, important features of cancer genomes that have largely escaped detection

A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress–disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental healt

Attosecond Delays in X-ray Molecular Ionization

The photoelectric effect is not truly instantaneous, but exhibits attosecond delays that can reveal complex molecular dynamics. Sub-femtosecond duration light pulses provide the requisite tools to resolve the dynamics of photoionization. Accordingly, the past decade has produced a large volume of work on photoionization delays following single photon absorption of an extreme ultraviolet (XUV) photon. However, the measurement of time-resolved core-level photoionization remained out of reach. The required x-ray photon energies needed for core-level photoionization were not available with attosecond tabletop sources. We have now measured the x-ray photoemission delay of core-level electrons, and here report unexpectedly large delays, ranging up to 700 attoseconds in NO near the oxygen K-shell threshold. These measurements exploit attosecond soft x-ray pulses from a free-electron laser (XFEL) to scan across the entire region near the K-shell threshold. Furthermore, we find the delay spectrum is richly modulated, suggesting several contributions including transient trapping of the photoelectron due to shape resonances, collisions with the Auger-Meitner electron that is emitted in the rapid non-radiative relaxation of the molecule, and multi-electron scattering effects. The results demonstrate how x-ray attosecond experiments, supported by comprehensive theoretical modelling, can unravel the complex correlated dynamics of core-level photoionization

Complete genomic sequences of Propionibacterium freudenreichii phages from Swiss cheese reveal greater diversity than Cutibacterium (formerly Propionibacterium) acnes phages

Background:A remarkable exception to the large genetic diversity often observed for bacteriophages infecting aspecific bacterial host was found for the Cutibacterium acnes (formerly Propionibacterium acnes) phages, which are highly homogeneous. Phages infecting the related species, which is also a member of the Propionibacteriaceae family, Propionibacterium freudenreichii , a bacterium used in production of Swiss-type cheeses, have also been described and are common contaminants of the cheese manufacturing process. However, little is known about their genetic composition and diversity.Results:We obtained seven independently isolated bacteriophages that infect P. freudenreichii from Swiss-typecheese samples, and determined their complete genome sequences. These data revealed that all seven phage isolates are of similar genomic length and GC% content, but their genomes are highly diverse, including genes encoding the capsid, tape measure, and tail proteins. In contrast to C. acnes phages, all P. freudenreichii phage genomes encode a putative integrase protein, suggesting they are capable of lysogenic growth. This is supported by the finding of related prophages in some P. freudenreichii strains. The seven phages could further be distinguished as belonging to two distinct genomic types, or ‘ clusters ’ , based on nucleotide sequences, and host range analyses conducted on a collection of P. freudenreichii strains show a higher degree of host specificity than is observed for the C. acnes phages.Conclusions:Overall, our data demonstrate P. freudenreichii bacteriophages are distinct from C. acnes phages, asevidenced by their higher genetic diversity, potential for lysogenic growth, and more restricted host ranges. This suggests substantial differences in the evolution of these related species from the Propionibacteriaceae family and their phages, which is potentially related to their distinct environmental niches