bluuebunny/crossref_metadata_2025 huggingface dataset:
SILVERRUSH. IV. Lyα luminosity functions at z = 5.7 and 6.6 studied with ∼1300 Lyα emitters on the 14–21 deg2 sky
Authors: Konno Akira , Ouchi Masami , Shibuya Takatoshi , Ono Yoshiaki , Shimasaku Kazuhiro , Taniguchi Yoshiaki , Nagao Tohru , Kobayashi Masakazu A R , Kajisawa Masaru , Kashikawa Nobunari , Inoue Akio K , Oguri Masamune , Furusawa Hisanori , Goto Tomotsugu , Harikane Yuichi , Higuchi Ryo , Komiyama Yutaka , Kusakabe Haruka , Miyazaki Satoshi , Nakajima Kimihiko , Wang Shiang-Yu
Published: October 2017

We present the Lyα luminosity functions (LFs) at z = 5.7 and 6.6 derived from a new large sample of 1266 Lyα emitters (LAEs) identified in total areas of 14 and 21 deg2, respectively, based on the early narrowband data of the Subaru/Hyper Suprime-Cam survey. Together with careful Monte Carlo simulations that account for the incompleteness of the LAE selection and the flux estimate systematics in the narrowband imaging, we have determined the Lyα LFs with unprecedentedly small statistical and systematic uncertainties in a wide Lyα luminosity range of 1042.8–43.8 erg s−1. We obtain best-fit Schechter parameters of $L^{*}_{\mathrm{Ly}\alpha } = 1.6^{+2.2}_{-0.6} \ (1.7^{+0.3}_{-0.7}) \times 10^{43}\:\mathrm{erg}\:\mathrm{s}^{-1}$, $\phi ^{*}_{\mathrm{Ly}\alpha } = 0.85^{+1.87}_{-0.77} \ (0.47^{+1.44}_{-0.44}) \times 10^{-4}\:\mathrm{Mpc}^{-3}$, and $\alpha = -2.6^{+0.6}_{-0.4} \ (-2.5^{+0.5}_{-0.5})$ at z = 5.7 (6.6). We confirm that our best-estimate Lyα LFs are consistent with the majority of the previous studies, but find that our Lyα LFs do not agree with the high number densities of LAEs recently claimed by Matthee/Santos et al.’s studies that may overcorrect the incompleteness and the flux systematics. Our Lyα LFs at z = 5.7 and 6.6 show an indication that the faint-end slope is very steep (α ≃ −2.5), although it is also possible that the bright-end LF results are enhanced by systematic effects such as the contribution from AGNs, blended merging galaxies, and/or large ionized bubbles around bright LAEs. Comparing our Lyα LF measurements with four independent reionization models, we estimate the neutral hydrogen fraction of the intergalactic medium to be $x_\mathrm{H\,{\small I}} = 0.3 \pm 0.2$ at z = 6.6, which is consistent with the small Thomson scattering optical depth obtained by Planck 2016.
A Phytophthora palmivora Extracellular Cystatin-Like Protease Inhibitor Targets Papain to Contribute to Virulence on Papaya
Authors: Gumtow Rebecca , Wu Dongliang , Uchida Janice , Tian Miaoying
Published: October 2017

Papaya fruits, stems, and leaves are rich in papain, a cysteine protease that has been shown to mediate plant defense against pathogens and insects. Yet the oomycete Phytophthora palmivora is a destructive pathogen that infects all parts of papaya plants, suggesting that it has evolved cysteine protease inhibitors to inhibit papain to enable successful infection. Out of five putative extracellular cystatin-like cysteine protease inhibitors (PpalEPICs) from P. palmivora transcriptomic sequence data, PpalEPIC8 appeared to be unique to P. palmivora and was highly induced during infection of papaya. Purified recombinant PpalEPIC8 strongly inhibited papain enzyme activity, suggesting that it is a functional cysteine protease inhibitor. Homozygous PpalEPIC8 mutants were generated using CRISPR/Cas9-mediated gene editing via Agrobacterium-mediated transformation (AMT). Increased papain sensitivity of in-vitro growth and reduced pathogenicity during infection of papaya fruits were observed for the mutants compared with the wild-type strain, suggesting that PpalEPIC8, indeed, plays a role in P. palmivora virulence by inhibiting papain. This study provided genetic evidence demonstrating that plant-pathogenic oomycetes secrete cystatins as important weapons to invade plants. It also established an effective gene-editing system for P. palmivora by the combined use of CRISPR/Cas9 and AMT, which is expected to be applicable to other oomycetes.
A history of US Army PAs
Authors: Chalupa Robyn L. , Marble W. Sanders
Published: October 2017

The US military has a long tradition of using physician assistants (PAs). The Army began using PAs in 1971 in an effort to supplement the physicians and surgeons in the medical corps. As their numbers grew, PAs gradually replaced general medical officers assigned to battalions. Later, specialty positions developed in aviation medicine, orthopedics, and emergency medicine. The need for a PA serving as an adviser in the major commands slowly developed at all levels of leadership. In 2015, the Army removed limitations on female PAs assigned to combat units. PAs lead in tactical and clinical settings, filling command roles, senior clinical positions, and administrative leadership roles.
A Multilevel Analysis of Professional Conflicts in Health Care Teams: Insight for Future Training
Authors: Bochatay Naike , Bajwa Nadia M. , Cullati Stéphane , Muller-Juge Virginie , Blondon Katherine S. , Junod Perron Noëlle , Maître Fabienne , Chopard Pierre , Vu Nu Viet , Kim Sara , Savoldelli Georges L. , Hudelson Patricia , Nendaz Mathieu R.
Published: October 2017

Purpose

Without a proper understanding of conflict between health care professionals, designing effective conflict management training programs for trainees that reflect the complexity of the clinical working environment is difficult. To better inform the development of conflict management training, this study sought to explore health care professionals’ experiences of conflicts and their characteristics.

Method

Between 2014 and early 2016, 82 semistructured interviews were conducted with health care professionals directly involved in first-line patient care in four departments of the University Hospitals of Geneva. These professionals included residents, fellows, certified nursing assistants, nurses, and nurse supervisors. All interviews were transcribed verbatim, and conventional content analysis was used to derive conflict characteristics.

Results

Six conflict sources were identified. Among these sources, disagreements on patient care tended to be the primary trigger of conflict, whereas sources related to communication contributed to conflict escalation without directly triggering conflict. A framework of workplace conflict that integrates its multidimensional and cyclical nature was subsequently developed. This framework suggests that conflict consequences and responses are interrelated, and might generate further tensions that could affect health care professionals, teams, and organizations, as well as patient care. Findings also indicated that supervisors’ responses to contentious situations often failed to meet health care professionals’ expectations.

Conclusions

Understanding conflicts between health care professionals involves several interrelated dimensions, such as sources, consequences, and responses to conflict. There is a need to strengthen health care professionals’ ability to identify and respond to conflict and to further develop conflict management programs for clinical supervisors.
Study Behaviors and USMLE Step 1 Performance: Implications of a Student Self-Directed Parallel Curriculum
Authors: Burk-Rafel Jesse , Santen Sally A. , Purkiss Joel
Published: October 2017

Purpose

To determine medical students’ study behaviors when preparing for the United States Medical Licensing Examination (USMLE) Step 1, and how these behaviors are associated with Step 1 scores when controlling for likely covariates.

Method

The authors distributed a study-behaviors survey in 2014 and 2015 at their institution to two cohorts of medical students who had recently taken Step 1. Demographic and academic data were linked to responses. Descriptive statistics, bivariate correlations, and multiple linear regression analyses were performed.

Results

Of 332 medical students, 274 (82.5%) participated. Most students (n = 211; 77.0%) began studying for Step 1 during their preclinical curriculum, increasing their intensity during a protected study period during which they averaged 11.0 hours studying per day (standard deviation [SD] 2.1) over a period of 35.3 days (SD 6.2). Students used numerous third-party resources, including reading an exam-specific 700-page review book on average 2.1 times (SD 0.8) and completing an average of 3,597 practice multiple-choice questions (SD 1,611). Initiating study prior to the designated study period, increased review book usage, and attempting more practice questions were all associated with higher Step 1 scores, even when controlling for Medical College Admission Test scores, preclinical exam performance, and self-identified score goal (adjusted R
2 = 0.56, P < .001).

Conclusions

Medical students at one public institution engaged in a self-directed, “parallel” Step 1 curriculum using third-party study resources. Several study behaviors were associated with improved USMLE Step 1 performance, informing both institutional- and student-directed preparation for this high-stakes exam.
Dilemmas of Representation: Patient Engagement in Health Professions Education
Authors: Rowland Paula , Kumagai Arno K.
Published: October 2017

The role of the patient in bedside teaching has long been a matter of consideration in health professions education. Recent iterations of patient engagement include patients as storytellers, members of curriculum planning committees, guest lecturers, and health mentors. While these forms of patient engagement are reported to have many benefits for learners, educators, and the patients themselves, there is concern that such programs may not be representative of the diversity of patients that health care professionals will encounter throughout their careers. This problem of representation has vexed not only educators but also sociologists and political scientists studying patients’ and the public’s involvement in arenas such as health services research, policy, and organizational design.

In this Perspective, the authors build on these sociological and political science approaches to expand our understanding of the problem of representation in patient engage-ment. In doing so, the authors’ reconfiguration of the problem sheds new light on the dilemma of representation. They argue for an understanding of representation that not only is inclusive of who is being represented but that also takes seriously what is being represented, how, and why. This argument has implications for educators, learners, administrators, and patient participants.
The “Glocalization” of Medical School Accreditation: Case Studies From Taiwan, South Korea, and Japan
Authors: Ho Ming-Jung , Abbas Joan , Ahn Ducksun , Lai Chi-Wan , Nara Nobuo , Shaw Kevin
Published: October 2017

Purpose

In an age of globalized medical education, medical school accreditation has been hailed as an approach to external quality assurance. However, accreditation standards can vary widely across national contexts. To achieve recognition by the World Federation for Medical Education (WFME), national accrediting bodies must develop standards suitable for both local contexts and international recognition. This study framed this issue in terms of “glocalization” and aimed to shine light on this complicated multistakeholder process by exploring accreditation in Taiwan, South Korea, and Japan.

Method

This study employed a comparative case-study design, examining the national standards that three accreditation bodies in East Asia developed using international reference standards. In 2015–2016, the authors conducted document analysis of the English versions of the standards to identify the differences between the national and international reference standards as well as how and why external standards were adapted.

Results

Each country’s accreditation body sought to balance local needs with global demands. Each used external standards as a template (e.g., Liaison Committee on Medical Education, General Medical Council, or WFME standards) and either revised (Taiwan, South Korea) or annotated (Japan) the standards to fit the local context. Four categories of differences emerged to account for how and why national standards departed from external references: structural, regulatory, developmental, and aspirational.

Conclusions

These countries’ glocalization of medical accreditation standards serve as examples for others seeking to bring their accreditation practices in line with global standards while ensuring that local values and societal needs are given adequate consideration.
Hospital-based Patient-specific Templates for Total Knee Arthroplasty: A Proof of Concept Clinical Study
Authors: Hafez Mahmoud A. , Hamza Hosamuddin , Nabeel Ahmed
Published: October 2017

Introduction:

All available patient-specific instruments or patient-specific templates (PSTs) are controlled by implant companies. Most of these companies outsource some of the steps of the PST such as imaging, preoperative planning, manufacturing of PST, and packing/sterilization. This is a proof of concept clinical study on the hospital-based PST system for total knee arthroplasty (TKA).

Methods:

A total number of 257 TKA procedures were performed on the basis of a new concept of hospital-based PSTs. All 5 steps of the PST [ie, imaging (computed tomographic scanning), planning, PST production, packing/sterilization, and surgery] were performed by the hospital. All cases included in this work are documented in the Egyptian Community Arthroplasty Register.

Results:

All cases had their surgeries performed without resorting to conventional intramedullary guides. Computed tomography–based imaging was easy and affordable. Planning was controlled by the surgeon. Polyamide nylon was the best available material and it was autoclavable. Desktop 3-dimensional printers were able to produce PSTs made of nylon, but it was difficult and time consuming. Industrial printers were superior in quality to desktop printers but more expensive. The whole process could be performed in as short a duration as 3 working days.

Conclusions:

Hospital-based PST was feasible and it was facilitated by the introduction of desktop 3-dimensional printers. This technique was less expensive and more time saving than commercially available PSTs as well as the conventional TKA.
Epithelial Erosions and Refractive Results After Single-Step Transepithelial Photorefractive Keratectomy and Alcohol-Assisted Photorefractive Keratectomy in Myopic Eyes: A Comparative Evaluation Over 12 Months
Authors: Fattah Maamoun A. , Antonios Rafic , Arba Mosquera Sam , Abiad Bachir , Awwad Shady T.
Published: October 2017

Purpose:

To evaluate the epithelial erosion incidence and refractive results in myopic eyes undergoing single-step transepithelial photorefractive keratectomy (TransPRK) compared with alcohol-assisted photorefractive keratectomy (PRK).

Methods:

This was a retrospective nonrandomized comparative study conducted at the American University of Beirut Medical Center. A total of 189 eyes that had undergone single-step transepithelial PRK (TransPRK) were compared with 189 matched eyes that had undergone alcohol-assisted PRK over a follow-up of 1 year. The incidence and symptoms of epithelial erosion were evaluated in both treatment groups using a post hoc questionnaire administered to patients selected in the study. Visual and refractive outcomes, including vector analysis of astigmatism, and corneal higher-order aberrations were also compared at 1-year postoperatively.

Results:

Baseline characteristics were similar between 2 groups (P > 0.05). A slight difference was detected at 12-month follow-up in the refractive cylinder (P = 0.02) and difference vector (P = 0.01) between eyes that had undergone TransPRK versus alcohol-assisted PRK. All other visual and refractive outcomes were similar at 12-month follow-up between both groups. Of note, 9.9% of patients with alcohol-assisted PRK (10/101) reported to the clinic because of tearing and stabbing sensation within 1 week after contact lens removal as opposed to 1% (1/100) of the TransPRK group (P = 0.0097). Subclinical recurrent epithelial erosion symptoms occurred more frequently in alcohol-assisted PRK: soreness to touch, sharp pains, and eyelid sticking occurred in 26.0% versus 6.6%, 32.5% versus 7.9%, and 26.0% versus 6.6% among the patients who were treated with alcohol-assisted PRK versus those who were treated with TransPRK, respectively (P ≤ 0.002).

Conclusions:

Single-step TransPRK for myopic eyes yields refractive results similar to those of alcohol-assisted PRK but shows a lesser incidence of early postoperative epithelial erosions and subsequent subclinical recurrent erosions.
Lenalidomide-Associated Thyroid-Related Eyelid Retraction
Authors: Slean Geraldine R. , Silkiss Rona Z.
Published: October 2017

Several antineoplastic treatments have been responsible for thyroid dysfunction and thyroid eye disease. Min, Vaidya, and Becker (2011) reported a case of euthyroid Graves orbitopathy after treatment with ipilimumab with the patient displaying proptosis and myositis in the setting of normal thyroid function tests and elevated thyroid antibodies. The authors report a case of a 76-year-old woman who developed right upper lid retraction and proptosis after 2.5 years of treatment with lenalidomide for multiple myeloma. Thyroid function tests were normal: thyroid-stimulating hormone 0.808 mIU/mL, total T3 102 ng/dL, free T4 1.48 ng/dL. Thyroid antibodies were elevated: thyrotropin receptor antibody 2.26 IU/L, thyroglobulin antibody 1043.1 IU/mL, and thyroid peroxidase antibody 38 IU/mL. A nuclear medicine thyroid scan was normal. Given the possible thyroid effects from lenalidomide, patients who receive this medication should be periodically evaluated for thyroid dysfunction and thyroid eye disease.
Current opinions in office-based rhinology
Authors: Unsal Aykut A. , Gregory Naomi , Rosenstein Kenneth
Published: October 2017

Purpose of review

The care of rhinologic patients has undergone a remarkable transformation in recent years. With the advent of endoscopic sinus surgery and high-tech image-guided computer systems, the surgical care of patients with benign sinonasal disease has successfully transitioned from the main hospital operating room to the outpatient ambulatory surgical center. Currently, there is yet another movement underway, in an attempt to care for these patients in the office setting.

Recent findings

As the medical device sector continues to innovate at rapid speed, new technologies such as the radiofrequency ablator, microdebrider, balloon sinus dilator, and steroid-eluting stent have propelled the care of rhinologic patients into the clinic setting.

In conjunction with an overall increased attention toward cost and time savings, the push to modernize instrumentation is now enabling the otolaryngologist to keep both the medical and surgical treatment of rhinologic patients, particularly those with chronic disease, within the office setting.
Exploring Acuity-Adaptable Care in a Rural Hospital
Authors: Sosebee Tonya , Potter Robert , Gilbert Valarie , Newcomb Patricia , Hampton Michelle
Published: October 2017

OBJECTIVE

The objective of this study is to assess benefits of the acuity-adaptable (AA) care model in rural hospitals.

BACKGROUND

The AA model aims to provide care in the same space from admission to discharge regardless of acuity. Evidence is lacking to support claims that AA care will improve patient safety, increase nurse productivity, and improve patient/staff satisfaction in rural hospitals.

METHODS

Patients admitted to a rural intensive care unit (ICU) were allocated to an AA group or an ICU group. Patients in the AA group remained in the ICU room through discharge. Patients in the ICU group transferred out of ICU when acuity permitted. Patient anxiety, depression, and perception of emotional care were measured. Staff responses were assessed qualitatively.

RESULTS

Acuity-adaptable patients reported significantly more anxiety and less perceived emotional care than ICU patients. Intensive care unit nurses resisted caring for less acute patients.

CONCLUSION

Disadvantages may outweigh benefits of AA care delivery in the rural ICU.
Anchoring like octopus: biologically inspired soft artificial sucker
Authors: Sareh Sina , Althoefer Kaspar , Li Min , Noh Yohan , Tramacere Francesca , Sareh Pooya , Mazzolai Barbara , Kovac Mirko
Published: October 2017

This paper presents a robotic anchoring module, a sensorized mechanism for attachment to the environment that can be integrated into robots to enable or enhance various functions such as robot mobility, remaining on location or its ability to manipulate objects. The body of the anchoring module consists of two portions with a mechanical stiffness transition from hard to soft. The hard portion is capable of containing vacuum pressure used for actuation while the soft portion is highly conformable to create a seal to contact surfaces. The module is integrated with a single sensory unit which exploits a fibre-optic sensing principle to seamlessly measure proximity and tactile information for use in robot motion planning as well as measuring the state of firmness of its anchor. In an experiment, a variable set of physical loads representing the weights of potential robot bodies were attached to the module and its ability to maintain the anchor was quantified under constant and variable vacuum pressure signals. The experiment shows the effectiveness of the module in quantifying the state of firmness of the anchor and discriminating between different amounts of physical loads attached to it. The proposed anchoring module can enable many industrial and medical applications where attachment to environment is of crucial importance for robot control.
Enamel crystallite strength and wear: nanoscale responses of teeth to chewing loads
Authors: Xia Jing , Tian Z. Ryan , Hua Licheng , Chen Lei , Zhou Zhongrong , Qian Linmao , Ungar Peter S.
Published: October 2017

The nanoscale responses of teeth to chewing loads are poorly understood. This has contributed to debate concerning the aetiology of enamel wear and resistance to fracture. Here we develop a new model for reactions of individual hydroxyapatite nanofibres to varying loads and directions of force. Hydroxyapatite nanofibres, or crystallites, composed of chains of bonded nanospheres, are the fundamental building blocks of enamel. This study indicates that these nanofibres respond to contact pressure in three distinct ways depending on force magnitude and direction: (i) plucking (nanosphere loss when the strength of the bonding protein ‘glue’ is exceeded), (ii) plastic deformation (compression to gradually bend nanofibres and squeeze the protein layer), and (iii) fragmentation (nanofibres fracture when the strength of H-bonds that bind smaller nanoparticles into nanospheres is exceeded). Critical contact pressure to initiate plucking is the lowest, followed by plastic deformation, and then fragmentation. Further, lower contact pressures are required for a response with shear forces applied perpendicular to the long axes of crystallites than with crushing forces parallel to them alone. These nanoscale responses are explained as a function of the interfacial nanochemical bonding between and within individual crystallites. In other words, nanochemistry plays a critical role in the responses of enamel to varying chewing loads.
Gene delivery ability of polyethylenimine and polyethylene glycol dual-functionalized nanographene oxide in 11 different cell lines
Authors: Wu Liping , Xie Jinshan , Li Tan , Mai Zihao , Wang Lu , Wang Xiaoping , Chen Tongsheng
Published: October 2017

We recently developed a polyethylenimine (PEI) and polyethylene glycol (PEG) dual-functionalized reduced graphene oxide (GO) (PEG−nrGO−PEI, RGPP) for high-efficient gene delivery in HepG2 and Hela cell lines. To evaluate the feasibility and applicability of RGPP as a gene delivery carrier, we here assessed the transfection efficiency of RGPP on gene plasmids and siRNA in 11 different cell lines. Commercial polyalkyleneimine cation transfection reagent (TR) was used as comparison. In HepG2 cells, RGPP exhibited much stronger delivery ability for siRNA and large size plasmids than TR. For green fluorescent protein (GFP) plasmid, RGPP showed about 47.1% of transfection efficiency in primary rabbit articular chondrocytes, and about 27% of transfection efficiency in both SH-SY5Y and A549 cell lines. RGPP exhibited about 37.2% of GFP plasmid transfection efficiency in EMT6 cells and about 26.0% of GFP plasmid transfection efficiency in LO2 cells, but induced about 33% of cytotoxicity in both cell lines. In 4T1 and H9C2 cell lines, RGPP had less than 10% of GFP plasmid transfection efficiency. Collectively, RGPP is a potential nano-carrier for high-efficiency gene delivery, and needs to be further optimized for different cell lines.
The optimization of fermentation conditions for producing cellulase of
Bacillus amyloliquefaciens
and its application to goose feed
Authors: Ye Miao , Sun Linghong , Yang Ru , Wang Zaigui , Qi KeZong
Published: October 2017

The proper culture conditions for producing cellulase of
Bacillus amyloliquefaciens
S1, isolated from the cecum of goose was optimized by single-factor experiment combined with orthogonal test. The properties of the cellulase were investigated by DNS method. The appropriate doses of
B. amyloliquefaciens
S1 were obtained by adding them to goose feed. It indicated that the suitable culture conditions of producing cellulase were the culture temperature of 37°C, the initial pH of 7.0, the incubation time of 72 h and the loaded liquid volume of 75 ml per 250 ml. The effects of each factor on producing cellulase by
B. amyloliquefaciens
S1 were as follows: initial pH > incubation time = culture temperature > loaded liquid volume. The optimum reaction temperature and pH were 50°C and 7.0, respectively. This enzyme is a kind of neutral cellulase that possesses resistance to heat and acidity. It showed high activity to absorbent cotton, soya bean meal and filter paper. By adding different doses of
B. amyloliquefaciens
S1 to the goose feed, it was found that the egg production, average egg weight, fertilization rate and the hatching rate were promoted both in experiment 1 (1.5 g kg
−1
) and experiment 2 (3 g kg
−1
). Also the difference of egg production, fertilization rate and hatching rate between experiment 1 and control group was obvious (
p
 < 0.05), and the average egg weight was significantly increased in experiment 2 (
p
 < 0.05).
On three-dimensional misorientation spaces
Authors: Krakow Robert , Bennett Robbie J. , Johnstone Duncan N. , Vukmanovic Zoja , Solano-Alvarez Wilberth , Lainé Steven J. , Einsle Joshua F. , Midgley Paul A. , Rae Catherine M. F. , Hielscher Ralf
Published: October 2017

Determining the local orientation of crystals in engineering and geological materials has become routine with the advent of modern crystallographic mapping techniques. These techniques enable many thousands of orientation measurements to be made, directing attention towards how such orientation data are best studied. Here, we provide a guide to the visualization of misorientation data in three-dimensional vector spaces, reduced by crystal symmetry, to reveal crystallographic orientation relationships. Domains for all point group symmetries are presented and an analysis methodology is developed and applied to identify crystallographic relationships, indicated by clusters in the misorientation space, in examples from materials science and geology. This analysis aids the determination of active deformation mechanisms and evaluation of cluster centres and spread enables more accurate description of transformation processes supporting arguments regarding provenance.
A pronounced uterine pro-inflammatory response at parturition is an ancient feature in mammals
Authors: Hansen Victoria L. , Faber Lauren S. , Salehpoor Ali A. , Miller Robert D.
Published: October 2017

Regulating maternal immunity is necessary for successful human pregnancy. Whether this is needed in mammals with less invasive placentation is subject to debate. Indeed, the short gestation times in marsupials have been hypothesized to be due to a lack of immune regulation during pregnancy. Alternatively, the maternal marsupial immune system may be unstimulated in the absence of a highly invasive placenta. Transcripts encoding pro-inflammatory cytokines were found to be overrepresented in the whole uterine transcriptome at terminal pregnancy in the opossum,
Monodelphis domestica
. To investigate this further, immune gene transcripts were quantified throughout opossum gestation. Transcripts encoding pro-inflammatory cytokines remained relatively low during pre- and peri-attachment pregnancy stages. Levels dramatically increased late in gestation, peaking within 12 h prior to parturition. These results mirror the spike of inflammation seen at eutherian parturition but not at attachment or implantation. Our results are consistent with the role of pro-inflammatory cytokines at parturition being an ancient and conserved birth mechanism in therian mammals.
How we perceive our own retina
Authors: Kirschfeld Kuno
Published: October 2017

Ever since the days of René Descartes, in the seventeenth century, the search for the relationship between subjective perception and neural activity has been an ongoing challenge. In neuroscience, an approach to the problem via the visual system has produced a paradigm using perceptual suppression, changing with time. Cortical areas in which the neural activity was modulated in temporal correlation with this percept could be traced. Although these areas may lead directly to perception, such temporal correlation of neural activity does not suffice as ultimate proof that they actually do so. In this article, I will use a different method to show that, for the perception of our own retina, any brain area leading directly to this perception also needs to represent the retina without distortion. Furthermore, I will demonstrate that the phenomenon of size constancy must be realized in this area.
Multimodal cell tracking from systemic administration to tumour growth by combining gold nanorods and reporter genes
Authors: Comenge Joan , Sharkey Jack , Fragueiro Oihane , Wilm Bettina , Brust Mathias , Murray Patricia , Lévy Raphaël , Plagge Antonius
Published: October 2017

Understanding the fate of exogenous cells after implantation is important for clinical applications. Preclinical studies allow imaging of cell location and survival. Labelling with nanoparticles enables high sensitivity detection, but cell division and cell death cause signal dilution and false positives. By contrast, genetic reporter signals are amplified by cell division. Here we characterise lentivirus-based bi-cistronic reporter gene vectors and silica-coated gold nanorods (GNRs) as synergistic tools for cell labelling and tracking. Co-expression of the bioluminescence reporter luciferase and the optoacoustic reporter near-infrared fluorescent protein iRFP720 enabled cell tracking over time in mice. Multispectral optoacoustic tomography (MSOT) showed immediate biodistribution of GNR-labelled cells after intracardiac injection and successive clearance of GNRs (day 1-15) with high resolution, while optoacoustic iRFP720 detection indicated tumour growth (day 10-40). This multimodal cell tracking approach could be applied widely for cancer and regenerative medicine research to monitor short- and long-term biodistribution, tumour formation and metastasis.
Barriers to Integration of Bioinformatics into Undergraduate Life Sciences Education
Authors: Williams Jason J. , Drew Jennifer C. , Galindo-Gonzalez Sebastian , Robic Srebrenka , Dinsdale Elizabeth , Morgan William , Triplett Eric W. , Burnette James , Donovan Samuel , Elgin Sarah , Fowlks Edison R. , Goodman Anya L. , Grandgenett Nealy F. , Goller Carlos , Hauser Charles , Jungck John R. , Newman Jeffrey D. , Pearson William , Ryder Elizabeth , Wilson Sayres Melissa A. , Sierk Michael , Smith Todd , Tosado-Acevedo Rafael , Tapprich William , Tobin Tammy C. , Toro Arlín , Welch Lonnie , Wright Robin , Ebenbach David , McWilliams Mindy , Rosenwald Anne G. , Pauley Mark A.
Published: October 2017

Bioinformatics, a discipline that combines aspects of biology, statistics, and computer science, is increasingly important for biological research. However, bioinformatics instruction is rarely integrated into life sciences curricula at the undergraduate level. To understand why, the Network for Integrating Bioinformatics into Life Sciences Education (NIBLSE, “nibbles”) recently undertook an extensive survey of life sciences faculty in the United States. The survey responses to open-ended questions about barriers to integration were subjected to keyword analysis. The barrier most frequently reported by the ~1,260 respondents was lack of faculty training. Faculty at associate’s-granting institutions report the least training in bioinformatics and the least integration of bioinformatics into their teaching. Faculty from underrepresented minority groups (URMs) in STEM reported training barriers at a higher rate than others, although the number of URM respondents was small. Interestingly, the cohort of faculty with the most recently awarded PhD degrees reported the most training but were teaching bioinformatics at a lower rate than faculty who earned their degrees in previous decades. Other barriers reported included lack of student interest in bioinformatics; lack of student preparation in mathematics, statistics, and computer science; already overly full curricula; and limited access to resources, including hardware, software, and vetted teaching materials. The results of the survey, the largest to date on bioinformatics education, will guide efforts to further integrate bioinformatics instruction into undergraduate life sciences education.
Jak-Stat pathway induces Drosophila follicle elongation by a gradient of apical contractility
Authors: Alégot Hervé , Pouchin Pierre , Bardot Olivier , Mirouse Vincent
Published: October 2017

Tissue elongation and its control by spatiotemporal signals is a major developmental question. Currently, it is thought thatDrosophilaovarian follicular epithelium elongation requires the planar polarization of the basal domain cytoskeleton and of the extra-cellular matrix, associated with a dynamic process of rotation around the anteroposterior axis. Here we show, by careful kinetic analysis offat2mutants, that neither basal planar polarization nor rotation is required during a first phase of follicle elongation. Conversely, a JAK-STAT signaling gradient from each follicle pole orients early elongation. JAK-STAT controls apical pulsatile contractions, and Myosin II activity inhibition affects both pulses and early elongation. Early elongation is associated with apical constriction at the poles and oriented cell rearrangements, but without any visible planar cell polarization of the apical domain. Thus, a morphogen gradient can trigger tissue elongation via a control of cell pulsing and without planar cell polarity requirement.

Impact Statement

Follicle elongation does not rely solely on the basal side of the cells but also requires a mechanism integrating a developmental cue with a morphogenetic process involving their apical domain.
Estimating barriers to gene flow from distorted isolation by distance patterns
Authors: Ringbauer Harald , Kolesnikov Alexander , Field David , Barton Nicholas H.
Published: October 2017

In continuous populations with local migration, nearby pairs of individuals have on average more similar genotypes than geographically well separated pairs. A barrier to gene flow distorts this classical pattern of isolation by distance. Genetic similarity is decreased for sample pairs on different sides of the barrier and increased for pairs on the same side near the barrier. Here, we introduce an inference scheme that utilizes this signal to detect and estimate the strength of a linear barrier to gene flow in two-dimensions. We use a diffusion approximation to model the effects of a barrier on the geographical spread of ancestry backwards in time. This approach allows us to calculate the chance of recent coalescence and probability of identity by descent. We introduce an inference scheme that fits these theoretical results to the geographical covariance structure of bialleleic genetic markers. It can estimate the strength of the barrier as well as several demographic parameters. We investigate the power of our inference scheme to detect barriers by applying it to a wide range of simulated data. We also showcase an example application to aAntirrhinum majus(snapdragon) flower color hybrid zone, where we do not detect any signal of a strong genome wide barrier to gene flow.
Mast Cells in the Developing Brain Determine Adult Sexual Behavior
Authors: Lenz Kathryn M. , Pickett Lindsay A. , Wright Christopher L. , Davis Katherine T. , Galan Anabel , McCarthy Margaret M.
Published: October 2017

Sex differences in brain and behavior are programmed during development by gonadal hormones. We found that the immune system-derived mast cell is a primary target for the masculinizing hormone, estradiol. Male rats had more mast cells in the preoptic area (POA), a brain region essential for male copulatory behavior, during the critical period for sexual differentiation. Activating mast cells in females masculinized POA neuronal and microglial morphology and adult sex behavior, and inhibiting mast cells in males blunted masculinization. Estradiol increased mast cell number and caused mast cells to release histamine, which stimulated microglia to release prostaglandins and thereby induced male-typical synaptic patterning. Inducing an allergic reaction in pregnant dams increased mast cell number in the brains of female fetuses and masculinized neuronal and microglia morphology and adult copulatory behavior. These findings identify a novel non-neuronal origin of brain sex differences and non-steroidal source of variability in brain feminization.
The effect of stimulation interval on plasticity following repeated blocks of intermittent theta burst stimulation
Authors: Tse Nga Yan , Goldsworthy Mitchell R. , Ridding Michael C. , Coxon James P. , Fitzgerald Paul B. , Fornito Alex , Rogasch Nigel
Published: October 2017

Introduction

Theta burst stimulation (TBS) is a non-invasive brain stimulation paradigm capable of influencing cortical circuits in humans by inducing neural plasticity. Applying spaced blocks of TBS can affect both the direction and magnitude of plasticity, but the impact of interval duration on these interactions following intermittent TBS (iTBS) is unclear.

Objectives

To assess the effect of interval duration on plasticity magnitude/direction following spaced iTBS.

Methods

15 healthy participants received three different iTBS conditions on separate days: single iTBS; spaced iTBS with a 5 minute interval (iTBS-5); and spaced iTBS with a 15 minute interval (iTBS-15). Changes in cortical excitability and short-interval cortical inhibition (SICI) resulting from iTBS were assessed via motor-evoked potentials (MEPs) measured from the first dorsal interosseus muscle before and up to 60 mins following stimulation.

Results

iTBS-15 increased MEP amplitude up to 60 mins post stimulation, whereas iTBS-5 decreased MEP amplitude. In contrast, MEP amplitude was not altered by single iTBS. Despite the significant effect of iTBS-15 on MEP amplitude at the group level, there was still considerable inter-individual variability, with only 53% of individuals meeting response criteria. Modulation of SICI did not differ between conditions.

Conclusions

The interval duration between spaced iTBS plays an important role in determining the direction of plasticity on excitatory, but not inhibitory circuits in human motor cortex. While iTBS-15 can increase the magnitude of facilitation in some individuals compared to single iTBS, this approach still suffers from high inter-individual variability.
Inflammatory cellular response to mechanical ventilation in elastase-induced experimental emphysema: role of pre-existing alveolar macrophages infiltration
Authors: Rouze Anahita , Voiriot Guillaume , Guivarch Elise , Roux Françoise , Tran Van Nhieu Jeanne , Isabey Daniel , Brochard Laurent , Maitre Bernard , Mekontso-Dessap Armand , Boczkowski Jorge
Published: October 2017

Background

An excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstructive pulmonary disease (COPD) patients submitted to invasive mechanical ventilation. The aim of this study was to evaluate the response to normal tidal volume (Vt) mechanical ventilation in a murine model of pulmonary emphysema, which represents the alveolar component of COPD. In this model, two time points associated with different levels of lung inflammation but similar lung destruction, were analyzed.

Methods

C57BL/6 mice received a tracheal instillation of 5 IU of porcine pancreatic elastase (Elastase mice) or the same volume of saline (Saline mice). Fourteen (D14) and 21 (D21) days after instillation, mice were anesthetized, intubated, and either mechanically ventilated (MV) with a normal Vt (8 mL/kg) or maintained on spontaneous ventilation (SV) during two hours. We analyzed respiratory mechanics, emphysema degree (mean chord length by lung histological analysis), and lung inflammation (bronchoalveolar lavage (BAL) cellularity, proportion and activation of total lung inflammatory cells by flow cytometry).

Results

As compared with Saline mice, Elastase mice showed a similarly increased mean chord length and pulmonary compliance at D14 and D21, while BAL cellularity was comparable between groups. Lung mechanics was similarly altered during mechanical ventilation in Elastase and Saline mice. Activated alveolar macrophages CD11bmid were present in lung parenchyma in both Elastase SV mice and Elastase MV mice at D14 but were absent at D21 and in Saline mice, indicating an inflammatory state with elastase at D14 only. At D14, Elastase MV mice showed a significant increase in percentage of neutrophils concomitant with a decrease in percentage of alveolar macrophages in total lung, as compared with Elastase SV mice. Furthermore, alveolar macrophages of Elastase MV mice at D14 overexpressed Gr1, and monocytes showed a trend to overexpression of CD62L, compared with Elastase SV mice.

Conclusions

In an elastase-induced model of pulmonary emphysema, normal Vt mechanical ventilation produced an increase in the proportion of pulmonary neutrophils, and an activation of alveolar macrophages and pulmonary monocytes. This response was observed only when the emphysema model showed an underlying inflammation (D14), reflected by the presence of activated alveolar macrophages CD11bmid.
Enhanced Astrocyte Responses are Driven by a Genetic Risk Allele Associated with Multiple Sclerosis
Authors: Ponath Gerald , Lincoln Matthew R. , Dahlawi Somiah , Mubarak Mayyan , Sumida Tomokazu , Airas Laura , Zhang Shun , Isitan Cigdem , Nguyen Thanh D. , Raine Cedric S. , Hafler David A. , Pitt David
Published: October 2017

Epigenetic annotation studies of genetic risk variants for multiple sclerosis (MS) implicate dysfunctional lymphocytes in MS susceptibility; however, the role of central nervous system (CNS) cells remains unclear. We investigated the effect of the risk variant, rs7665090G, located near NFKB1, on astrocytes. We demonstrated that chromatin is accessible at the risk locus, a prerequisite for its impact on astroglial function. The risk variant was associated with increased NF-κB signaling and target gene expression driving lymphocyte recruitment in cultured human astrocytes and astrocytes within MS lesions, and with increased lesional lymphocytic infiltrates. In MS patients, the risk genotype was associated with increased lesion volumes on MRI. Thus, we established that the rs7665090G variant perturbs astrocyte function resulting in increased CNS access for peripheral immune cells. MS may thus result from variant-driven dysregulation of the peripheral immune system and the CNS, where perturbed CNS cell function aids in establishing local autoimmune inflammation.

One Sentence Summary

The NF-κB relevant multiple sclerosis risk variant, rs7665090G, drives astrocyte responses that promote lesion formation.
Do adolescents take more risks? Not when facing a novel uncertain situation
Authors: Noémi Éltető , Karolina Janacsek , Andrea Kóbor , Ádám Takács , Eszter Tóth-Fáber , Dezso Németh
Published: October 2017

In real-life decision-making, sub-optimal risk-taking seems characteristic of adolescents. Such behavior increases the chance of serious negative, and at times, irreversible outcomes for this population (e.g., road traffic accidents, addictions). We are still lacking conclusive evidence, however, for an inverted U-shaped developmental trajectory for risk-taking. This raises the question whether adolescents are really more risk-prone or when facing a novel risky situation, they behave just as children and adults do. To answer this question, we used the Balloon Analogue Risk Task (BART) to assess the risky decision making of 188 individuals ranging in age from 7 to 30. The BART provided useful data for characterizing multiple aspects of risk-taking. Surprisingly, we found that adolescents were not more inclined to take risks than children or young adults. Participants in all age groups were able to adapt their learning processes to the probabilistic environment and improve their performance during the sequential risky choice. There were no age-related differences in risk-taking at any stage of the task. Likewise, neither negative feedback reactivity nor overall task performance distinguished adolescents from the younger and older age groups. Our findings prompt 1) methodological considerations about the validity of the BART and 2) theoretical debate whether the amount of experience on its own may account for age-related changes in real-life risk-taking, since risk-taking in a novel and uncertain situation was invariant across developmental stages.
SEACOIN 2.0 – an interactive mining and visualization tool for information retrieval, summarization, and knowledge discovery
Authors: Uppal Karan , Lee Eva K.
Published: October 2017

Motivation

The rapidly increasing size of biomedical databases such as MEDLINE requires the use of intelligent data mining methods for information extraction and summarization. Existing biomedical text-mining tools have limited capabilities for inferring topological and network relationships between biomedical terms. Very often too much is returned during summarization leading to information overload.

Results

We present herein SEACOIN 2.0, an interactive knowledge discovery and hypothesis generation tool for biomedical literature.SEACOIN generates k-ary relational networks of biomedical terms using a novel term ranking scheme to facilitate efficient information retrieval, summarization, and visual data exploration. Summarization is presented via multiple dynamic visualization panels. We evaluate the system performance in information retrieval and features extraction using the BioCreative 2013 Track 3 learning corpus. An average F-measure of 94% was achieved for document retrieval and an average precision of 88% was achieved for identification of top co-occurrence terms. The system allows interactive mining of complex implicit and explicit relationships among biomedical entities (genes, chemicals, diseases/disorders, mutations, etc.) and provides a framework for hypothesis generation. It also improves our understanding of various biological processes and disease mechanisms.

Contact

eva.lee@gatech.edu