bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological outcomes of debriefing healthcare providers who experience expected and unexpected patient death in clinical or simulation experiences: A scoping review
Authors: Harder Nicole , Lemoine Jocelyne , Harwood Rae
Published: October 2019

Aims and objectives

To synthesise and map the literature on the psychological outcomes reported following debriefing of healthcare providers who experience expected and unexpected patient death in either clinical practice or simulation setting.

Background

Patient death occurs in both the clinical and simulation environments and can result in psychological stress in healthcare providers and students. While debriefing following patient death has demonstrated the ability to promote positive psychological outcomes, addressing the psychological or emotional stress of the event is inconsistently addressed.

Design

A scoping review was conducted using the Arksey and O'Malley framework.

Method

The Cochrane Library, MEDLINE, CINAHL, PsycINFO, JBI and Scopus databases were searched with English language constraints and no limit on publication date. The Scoping Reviews (PRISMA‐ScR) Checklist was used (Annals of Internal Medicine, 2018, 169, 467) (see Appendix S1).

Results

Eighteen articles (16 research papers and 2 review papers) met the inclusion criteria. Of the 16 research papers, 9 reported on debriefing models in the simulation environment and 7 in the clinical setting. The types of debriefing models found in the simulation setting tended to focus on healthcare providers' learning, while those in the clinical setting typically focused on healthcare providers' emotional reactions and resulted in positive psychological effects.

Conclusion

Debriefing has the potential to positively affect psychological outcomes of healthcare providers who experience patient death. The type of debriefing that is selected is a key component to achieving these positive outcomes.

Relevance to Clinical Practice

This scoping review identified the debriefing frameworks used in both simulation and clinical environments following patient death events, and any associated psychological outcomes. There is a need for debriefing to occur after each death in either environment; however, there is a lack of evidence‐based debriefing frameworks that can be used in both the clinical and simulation environments to promote positive psychological outcomes.
Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway
Authors: Ruan Hao , Lv Ziwei , Liu Shuaishuai , Zhang Liang , Huang Kai , Gao Shaoyan , Gan Wenhua , Liu Xiaowei , Zhang Shanshan , Helian Kaiyue , Li Xiaohe , Zhou Honggang , Yang Cheng
Published: October 2019

Objectives

Anlotinib hydrochloride (AL3818) is a novel multitarget tyrosine kinase inhibitor which has the same targets as nintedanib, an effective drug has been approved for the treatment of idiopathic pulmonary fibrosis. Here, we examined whether anlotinib could also attenuate bleomycin-induced pulmonary fibrosis in mice and explored the antifibrosis mechanism.

Methods

We have evaluated the effect of anlotinib on bleomycin-induced pulmonary fibrosis in mice. Inflammatory cytokines in alveolar lavage fluid including IL-1β, IL-4, IL-6 and TNF-α were determined by ELISA. Biomarkers of oxidative stress were measured by corresponding kit. Histopathologic examination was analysed by H&E staining and immunohistochemistry. In vitro, we investigated whether anlotinib inhibited TGFβ/Smad3 and non-Smad pathways by luciferase assay or Western blotting. We also evaluated whether anlotinib inhibited TGF-β1-induced epithelial–mesenchymal transition (EMT) and promoted myofibroblast apoptosis in order to explore the possible molecular mechanism.

Key findings

The results indicated that anlotinib treatment remarkably attenuated inflammation, oxidative stress and pulmonary fibrosis in mouse lungs. Anlotinib could inhibit the TGF-β1 signalling pathway. Additionally, anlotinib not only profoundly inhibited TGF-β1-induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and promoted the apoptosis in fibroblasts.

Conclusions

In summary, the results suggest that anlotinib-mediated suppression of pulmonary fibrosis is related to the inhibition of TGF-β1 signalling pathway.
Evaluation of the inflammatory response to two intra‐articular hyaluronic acid formulations in normal equine joints
Authors: Johnston Georgina C. A. , Wood Kelly A. , Jackson Karen V. , Perkins Nigel R. , Zedler Steven T.
Published: October 2019

Intra‐articular (IA) hyaluronic acid (HA) is commonly used to treat equine arthritis. Inflammatory response or “joint flare” is a recognized potential side effect. However, the incidence and severity of inflammation following IA HA injection in horses is not well documented. This study compared the effects of two IA HA formulations of different molecular weight (MW) and a saline control on clinical signs and synovial fluid markers of inflammation in normal equine joints. Eight adult horses each had three healthy fetlock joints randomly assigned to treatment with either 1.4 mega Dalton HA, 0.8 mega Dalton HA or saline control once weekly for three weeks. Clinical evaluation and synovial fluid analysis were performed by blinded assessors. Outcomes of interest were lameness score, joint effusion score and synovial fluid white cell count and differential, total protein, viscosity and serum amyloid A. Joints injected with HA developed significant mild‐to‐moderate inflammatory responses often associated with lameness and joint effusion compared with saline control joints. The higher MW HA formulation elicited a significantly greater inflammatory response than the lower MW HA after the first injection. In HA injected joints, viscosity remained poor for the entire study. Both IA HA formulations in this study induced an inflammatory response in healthy equine joints. This may have implications for the use of HA in equine joints. The findings in this study are limited to the two HA formulations used. Further investigation of different HA formulations and the use of HA in normal and arthritic equine joints is warranted.
Can interspecies affairs in the dark lead to evolutionary innovation?
Authors: Wilkins Laetitia G. E.
Published: October 2019

Evolutionary adaptation is the adjustment of species to a new or changing environment. Engaging in mutualistic microbial symbioses has been put forward as a key trait that promotes the differential, evolutionary success of many animal and plant lineages (McFall‐Ngai, 2008). Microbial mutualists allow these organisms to occupy new ecological niches where they could not have persisted on their own or would have been constrained by competitors. Vertical transmission of beneficial microbial symbionts from parents to the offspring is expected to link the adaptive association between a given host and microbe, and it can lead to coevolution and sometimes even cospeciation (Fisher, Henry, Cornwallis, Kiers, & West, 2017). Vertical transmission also causes bottlenecks that strongly reduce the effective population size and genetic diversity of the symbiont population. Moreover, vertically transmitted symbionts are assumed to have fewer opportunities to exchange genes with relatives in the environment. In a “From the Cover” article in this issue of Molecular Ecology, Breusing, Johnson, Vrijenhoek, and Young (2019) investigated whether hybridization among different host species could lead to interspecies exchange of otherwise strictly vertically transmitted symbionts. Hybridization of divergent lineages can potentially cause intrinsic and extrinsic incompatibilities, swamp rare alleles, and lead to population extinctions. In some cases, however, it might also create novel trait combinations that lead to evolutionary innovation (Marques, Meier, & Seehausen, 2019). Breusing et al. (2019) linked the concept of hybridization to symbiont transmission, and their findings have significant implications for the study of evolution of vertically transmitted symbionts and their hosts.
In vivo imaging of hemodynamic redistribution and arteriogenesis across microvascular network
Authors: Sun Naidi , Ning Bo , Bruce Anthony C. , Cao Rui , Seaman Scott A. , Wang Tianxiong , Fritsche‐Danielson Regina , Carlsson Leif G. , Peirce Shayn M. , Hu Song
Published: October 2019

Objective

Arteriogenesis is an important mechanism that contributes to restoration of oxygen supply in chronically ischemic tissues, but remains incompletely understood due to technical limitations. This study presents a novel approach for comprehensive assessment of the remodeling pattern in a complex microvascular network containing multiple collateral microvessels.

Methods

We have developed a hardware‐software integrated platform for quantitative, longitudinal, and label‐free imaging of network‐wide hemodynamic changes and arteriogenesis at the single‐vessel level. By ligating feeding arteries in the mouse ear, we induced network‐wide hemodynamic redistribution and localized arteriogenesis. The utility of this technology was demonstrated by studying the influence of obesity on microvascular arteriogenesis.

Results

Simultaneously monitoring the remodeling of competing collateral arterioles revealed a new, inverse relationship between initial vascular resistance and extent of arteriogenesis. Obese mice exhibited similar remodeling responses to lean mice through the first week, including diameter increase and flow upregulation in collateral arterioles. However, these gains were subsequently lost in obese mice.

Conclusions

Capable of label‐free, comprehensive, and dynamic quantification of structural and functional changes in the microvascular network in vivo, this platform opens up new opportunities to study the mechanisms of microvascular arteriogenesis, its implications in diseases, and approaches to pharmacologically rectify microvascular dysfunction.
Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes
Authors: Kim Ji Young , Kim Jihee , Ahn Yuri , Lee Eun Jung , Hwang Shinwon , Almurayshid Abdurrahman , Park Keedon , Chung Hwa‐Jee , Kim Heung Jae , Lee Si‐Hyung , Lee Myung‐Shik , Oh Sang Ho
Published: October 2019

Autophagy regulates cellular turnover by disassembling unnecessary or dysfunctional constituents. Recent studies demonstrated that autophagy and its regulators play a wide variety of roles in melanocyte biology. Activation of autophagy is known to induce melanogenesis and regulate melanosome biogenesis in melanocytes. Also, autophagy induction was reported to regulate physiologic skin color via melanosome degradation, although the downstream effectors are not yet clarified. To determine the role of autophagy as a melanosome degradation machinery, we administered several autophagy inducers in human keratinocytes and melanocytes. Our results showed that the synthetic autophagy inducer PTPD‐12 stimulated autophagic flux in human melanocytes and in keratinocytes containing transferred melanosomes. Increased autophagic flux led to melanosome degradation without affecting the expression of MITF. Furthermore, the color of cell pellets of both melanocytes and keratinocytes was visibly lightened. Inhibition of autophagic flux by chloroquine resulted in marked attenuation of PTPD‐12‐induced melanosome degradation, whereas the expression of melanogenesis pathway genes and proteins remained unaffected. Taken together, our results suggest that the modulation of autophagy can contribute to the regulation of melanocyte biology and skin pigmentation.
High‐energy visible light at ambient doses and intensities induces oxidative stress of skin—Protective effects of the antioxidant and Nrf2 inducer Licochalcone A in vitro and in vivo
Authors: Mann Tobias , Eggers Kerstin , Rippke Frank , Tesch Mirko , Buerger Anette , Darvin Maxim E. , Schanzer Sabine , Meinke Martina C. , Lademann Jürgen , Kolbe Ludger
Published: October 2019

Background

Solar radiation causes skin damage through the generation of reactive oxygen species (ROS). While UV filters effectively reduce UV‐induced ROS, they cannot prevent VIS‐induced (400‐760 nm) oxidative stress. Therefore, potent antioxidants are needed as additives to sunscreen products.

Methods

We investigated VIS‐induced ROS formation and the photoprotective effects of the Nrf2 inducer Licochalcone A (LicA).

Results

Visible spectrum of 400‐500 nm dose‐dependently induced ROS in cultured human fibroblasts at doses equivalent to 1 hour of sunshine on a sunny summer day (150 J/cm2). A pretreatment for 24 hours with 1 µmol/L LicA reduced ROS formation to the level of unirradiated cells while UV filters alone were ineffective, even at SPF50+. In vivo, topical treatment with a LicA‐containing SPF50 + formulation significantly prevented the depletion of intradermal carotenoids by VIS irradiation while SPF50 + control did not protect.

Conclusion

LicA may be a useful additive antioxidant for sunscreens.
The Feeling of Bodily Ownership
Authors: Bradley Adam
Published: October 2019

In certain startling neurological and psychiatric conditions, what is ordinarily most intimate and familiar to us—our own body—can feel alien. For instance, in cases of somatoparaphrenia subjects misattribute their body parts to others, while in cases of depersonalization subjects feel estranged from their bodies. These ownership disorders thus appear to consist in a loss of any feeling of bodily ownership, the felt sense we have of our bodies as our own. Against this interpretation of ownership disorders, I defend Sufficiency, the thesis that every experience of bodily awareness suffices for a feeling of bodily ownership. Since Sufficiency conflicts with a face‐value interpretation of these ownership disorders, the burden is on me to explain away the apparent tension. To do so, I identify and correct what I believe to be the fundamental mistake in the extant literature on the feeling of bodily ownership, namely the tendency to treat the notion of a feeling of bodily ownership as a single psychological construct. Instead, I distinguish the feeling of minimal ownership, the first‐personal character of bodily awareness, from the feeling of affective ownership, the distinctive type of felt concern we have for our bodies. I motivate this distinction by raising the disownership puzzle, the fact that subjects suffering from ownership disorders display an ambiguous set of symptoms, arguing the distinction I draw between minimal and affective ownership is just what is required to resolve the puzzle.
Studying Emotions in Security and Diplomacy: Where We Are Now and Challenges Ahead
Authors: Pace Michelle , Bilgic Ali
Published: October 2019

The core objective of this special issue has been to shed light on emotions as (1) frames that shape interpersonal diplomatic relations, (2) as key tools that are used as part of the statecraft's toolbox, and (3) as formative/productive dynamics with real effects on human beings—that, in turn, often construct and maintain conflicts. It is therefore pertinent that we interrogate the political psychology of individual, collective, mass, and communal emotions and how these are often (mis)used in diplomacy and security narratives to legitimize politicians' decisions and practices. This concluding article provides a state of the art account of the study of emotions in International Relations (IR), sums up the main findings from all special issue contributions and constructively explores potential challenges ahead for the study of emotions in IR, especially in security and diplomacy studies. It concludes with an appeal for the development of a multiperspective approach—that is, one that combines social sciences, natural sciences, and humanities—for a nuanced study of the role of emotional work in state, diplomatic as well as security narratives and practices. This approach will in turn require methodological pluralism in how we go about, as reflexive researchers, our emotional research.
The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium
Authors: Harville Emily W. , Mishra Gita D. , Yeung Edwina , Mumford Sunni L. , Schisterman Enrique F. , Jukic Anne Marie , Hatch Elizabeth E. , Mikkelsen Ellen M. , Jiang Hong , Ehrenthal Deborah B. , Porucznik Christina A. , Stanford Joseph B. , Wen Shi‐Wu , Harvey Alysha , Symons Downs Danielle , Yajnik Chittaranjan , Santillan Donna , Santillan Mark , McElrath Thomas F. , Woo Jessica G. , Urbina Elaine M. , Chavarro Jorge E. , Sotres‐Alvarez Daniela , Bazzano Lydia , Zhang Jun , Steiner Anne , Gunderson Erica P. , Wise Lauren A.
Published: October 2019

Background

Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature.

Objectives

The consortium will investigate the effects of preconception exposures on four sets of outcomes: (1) fertility and miscarriage; (2) pregnancy‐related conditions; (3) perinatal and child health; and (4) adult health outcomes.

Population

A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation.

Design

The included studies are a mix of studies following women or couples intending to conceive, general‐health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages.

Methods

Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors.

Preliminary results

Twenty‐three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general‐population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data.

Conclusions

The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.
Effect of season and superstimulatory treatment on in vivo and in vitro embryo production in wood bison (Bison bison athabascae)
Authors: Palomino Jesus Manuel , Mastromonaco Gabriela F. , Cervantes Miriam P. , Mapletoft Reuben J. , Anzar Muhammad , Adams Gregg P.
Published: October 2019

Two experiments were done using a two‐by‐two design to determine the effects of season and superstimulatory protocol on embryo production in wood bison. In Experiment 1 (in vivo‐derived embryos), ovarian superstimulation was induced in female bison during the ovulatory and anovulatory seasons with either two or three doses of FSH given every‐other‐day (FSH × 2 vs. FSH × 3, respectively). Bison were given hCG to induce ovulation, inseminated 12 and 24 hr after hCG, and embryos were collected 8 days after hCG (n = 10 bison/group). In Experiment 2 (in vitro embryo production), ovarian superstimulation was induced in female bison during the ovulatory and anovulatory seasons with two doses of FSH, and in vivo maturation of the cumulus–oocyte complexes (COC) was induced with hCG at either 48 or 72 hr after the last dose of FSH. COC were collected 34 hr after hCG, and expanded COC were used for in vitro fertilization and culture. In Experiment 1, the number of follicles ≥9 mm, the proportion of follicles that ovulated, the number of CL, and the total number of ova/embryos collected did not differ between seasons or treatment groups, but the number of transferable embryos was greater (p < .05) in the ovulatory season. In Experiment 2, no differences were detected between seasons or treatment groups for any end point. The number of transferable embryos produced per bison was greatest (p < .05) using in vitro fertilization and was unaffected by season (1.5 ± 0.2 and 1.1 ± 0.3 during anovulatory and ovulatory seasons, respectively), in contrast to in vivo embryo production which was affected by season (0.1 ± 0.01 and 0.7 ± 0.2 during anovulatory and ovulatory seasons, respectively). Results demonstrate that transferable embryos can be produced throughout the year in wood bison by both in vivo and in vitro techniques, but the efficiency of embryo production of in vivo‐derived embryos is significantly lower during the anovulatory season.
‘At some point it has been enough’ ‐ Processes of perceived failure of citizens’ initiatives
Authors: Meerstra‐de Haan Erzsi , Meier Sabine , Bulder Elles , Haartsen Tialda
Published: October 2019

Citizens’ initiatives are believed to be a suitable alternative approach to service provision, especially in rural areas where services are under pressure because of depopulation and decentralisation measures of the state. To date, research has mainly focused on best practices and successful examples of these initiatives. However, understanding failure is equally important in order to learn more about the processes citizens’ initiatives go through, the chances of success and to develop tools for the support needed. This article focuses on the perception of initiators of citizens’ initiatives on failure. Within the relevant body of literature, six obstacles to the success of citizens’ initiatives stand out. In order to understand the processes of failure in more detail, we investigated three case studies on failed citizens’ initiatives in the Northern Netherlands. The following aspects seem to be of vital importance to whether or not a citizens’ initiative fails: 1) how governments and (semi‐) governmental organisations interact with the citizens’ initiative; 2) how people are able to balance the different needs for senses of ownership and responsibility; and 3) how participants are able to balance personal investments. Finally, the interviewed initiators justify failure as a discrepancy of scale caused by different scopes of actions of local and regional governments and housing corporations at the regional level, and citizens’ initiatives, at the local level. To overcome this discrepancy, citizens’ initiatives require tailor‐made and context‐specific support.
Hair cell maturation is differentially regulated along the tonotopic axis of the mammalian cochlea
Authors: Jeng Jing‐Yi , Ceriani Federico , Hendry Aenea , Johnson Stuart L. , Yen Piece , Simmons Dwayne D. , Kros Corné J. , Marcotti Walter
Published: October 2019

Key points

Outer hair cells (OHCs) enhance the sensitivity and the frequency tuning of the mammalian cochlea.

Similar to the primary sensory receptor, the inner hair cells (IHCs), the mature functional characteristics of OHCs are acquired before hearing onset.

We found that OHCs, like IHCs, fire spontaneous Ca2+‐induced action potentials (APs) during immature stages of development, which are driven by CaV1.3 Ca2+ channels.

We also showed that the development of low‐ and high‐frequency hair cells is differentially regulated during pre‐hearing stages, with the former cells being more strongly dependent on experience‐independent Ca2+ action potential activity.

Sound amplification within the mammalian cochlea depends upon specialized hair cells, the outer hair cells (OHCs), which possess both sensory and motile capabilities. In various altricial rodents, OHCs become functionally competent from around postnatal day 7 (P7), before the primary sensory inner hair cells (IHCs), which become competent at about the onset of hearing (P12). The mechanisms responsible for the maturation of OHCs and their synaptic specialization remain poorly understood. We report that spontaneous Ca2+ activity in the immature cochlea, which is generated by CaV1.3 Ca2+ channels, differentially regulates the maturation of hair cells along the cochlea. Under near‐physiological recording conditions we found that, similar to IHCs, immature OHCs elicited spontaneous Ca2+ action potentials (APs), but only during the first few postnatal days. Genetic ablation of these APs in vivo, using CaV1.3−/− mice, prevented the normal developmental acquisition of mature‐like basolateral membrane currents in low‐frequency (apical) hair cells, such as IK,n (carried by KCNQ4 channels), ISK2 and IACh (α9α10nAChRs) in OHCs and IK,n and IK,f (BK channels) in IHCs. Electromotility and prestin expression in OHCs were normal in CaV1.3−/− mice. The maturation of high‐frequency (basal) hair cells was also affected in CaV1.3−/− mice, but to a much lesser extent than apical cells. However, a characteristic feature in CaV1.3−/− mice was the reduced hair cell size irrespective of their cochlear location. We conclude that the development of low‐ and high‐frequency hair cells is differentially regulated during development, with apical cells being more strongly dependent on experience‐independent Ca2+ APs.
Laminar Heat Transfer of Gas-Liquid Segmented Flows in Circular Ducts With Constant Wall Temperature
Authors: Alrbee K. , Muzychka Y. S. , Duan X.
Published: October 2019

Laminar heat transfer of gas-liquid Taylor flow in circular tubes is considered. Previous studies have found that introducing a gas phase into a flow stream of a liquid phase significantly increases the heat transfer rate. Other studies considered the effect of slug length on heat transfer rates. The present study’s aim is to demonstrate heat transfer enhancement due to the shortening of liquid slug lengths in a segmented flow and to further validate a model previously developed by the second author. An experimental setup was assembled using mini scale horizontal tube in which the two phase fluid flow is heated under constant wall temperature. New experimental data for gas-liquid Taylor flow in mini scale were carefully obtained using 1 cSt silicone oil which was segmented by air. The experiments were performed with a liquid fraction maintained constant at 0.5 and Reynolds numbers from 50 to 320. In the present work, it is shown that for constant wall temperature, the dimensionless mean wall flux and Nusselt number have been increased by a factor of two at the upper limit of laminar flow which was considered with ReD = 320, when the slug aspect ratio LS/D equal to 10. On other hand the enhancement becomes three times at the same limit of flow when slug aspect ratio has reduced to 1.25 which almost approaches the tube diameter.
Numerical Study on Gas-Yield Power-Law Fluid in T-Junction Minichannel
Authors: Ihmoudah Abdalsalam , Awad Mohamed M. , Rahman Aziz , Butt Stephen D.
Published: October 2019

In this study, a computational examination of Taylor bubbles was performed for gas/non-Newtonian fluid two-phase flows developed in a minichannel T-junction mixer with a hydraulic diameter of 1 mm. The investigations employed three separate aqueous xanthan gum solutions at concentrations of 0.05, 0.1 and 0.15 w/w, which are referred to as non-Newtonian (yield power-law) fluids. The effective concentration of the xanthan gum solutions and superficial velocity of the inlet liquid phase on the length, velocity, and shape of the Taylor bubbles was studied using the ANSYS FLUENT 19 software package. The simulation results show an increase in bubble velocity with increasing film thickness, particularly in solutions of higher viscosity XG-0.15%. Furthermore, bubble lengths decreased as the xanthan gum concentrations increased, but bubble shapes underwent alterations when the concentrations increased. Another interesting result of the tests shows that when the liquid inlet velocity increases, bubble lengths decrease during lower liquid superficial velocity, whereas during higher velocities, they change only slightly after increases in concentration. Finally, with increasing XG concentration, the liquid film thickness around the bubble increased. The results show good agreement with correlations after modifying a capillary number (Ca*) for non-Newtonian liquids in all cases.
TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection
Authors: de Marcken Marine , Dhaliwal Khushwant , Danielsen Ann Caroline , Gautron Anne Sophie , Dominguez-Villar Margarita
Published: October 2019

Differences in TLR7 and TLR8 signaling program virus-specific responses of human monocytes to infection.
iRhom2 inhibits bile duct obstruction–induced liver fibrosis
Authors: Sundaram Balamurugan , Behnke Kristina , Belancic Andrea , Al-Salihi Mazin A. , Thabet Yasser , Polz Robin , Pellegrino Rossella , Zhuang Yuan , Shinde Prashant V. , Xu Haifeng C. , Vasilevska Jelena , Longerich Thomas , Herebian Diran , Mayatepek Ertan , Bock Hans H. , May Petra , Kordes Claus , Aghaeepour Nima , Mak Tak W. , Keitel Verena , Häussinger Dieter , Scheller Jürgen , Pandyra Aleksandra A. , Lang Karl S. , Lang Philipp A.
Published: October 2019

iRhom2 reduces hepatic stellate cell activation and liver fibrosis after bile duct ligation.
Inflammation induces stem cell quiescence
Authors: VanHook Annalisa M.
Published: October 2019

Chronic inflammation causes olfactory stem cells to become quiescent and secrete immunomodulatory cytokines.
Comparative Genomics of Rumen
Butyrivibrio
spp. Uncovers a Continuum of Polysaccharide-Degrading Capabilities
Authors: Palevich Nikola , Kelly William J. , Leahy Sinead C. , Denman Stuart , Altermann Eric , Rakonjac Jasna , Attwood Graeme T.
Published: October 2019

Feeding a global population of 8 billion people and climate change are the primary challenges facing agriculture today. Ruminant livestock are important food-producing animals, and maximizing their productivity requires an understanding of their digestive systems and the roles played by rumen microbes in plant polysaccharide degradation. Members of the genera
Butyrivibrio
and
Pseudobutyrivibrio
are a phylogenetically diverse group of bacteria and are commonly found in the rumen, where they are a substantial source of polysaccharide-degrading enzymes for the depolymerization of lignocellulosic material. Our findings have highlighted the immense enzymatic machinery of
Butyrivibrio
and
Pseudobutyrivibrio
species for the degradation of plant fiber, suggesting that these bacteria occupy similar niches but apply different degradation strategies in order to coexist in the competitive rumen environment.
Tuberculosis Vaccine Development: Progress in Clinical Evaluation
Authors: Sable Suraj B. , Posey James E. , Scriba Thomas J.
Published: October 2019

Tuberculosis (TB) is the leading killer among all infectious diseases worldwide despite extensive use of the
Mycobacterium bovis
bacille Calmette-Guérin (BCG) vaccine. A safer and more effective vaccine than BCG is urgently required. More than a dozen TB vaccine candidates are under active evaluation in clinical trials aimed to prevent infection, disease, and recurrence.
The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence
Authors: Chandrasekar Aswath P. , Cummins Nathan W. , Badley Andrew D.
Published: October 2019

Advances in HIV-1 therapy have transformed the once fatal infection into a manageable, chronic condition, yet the search for a widely applicable approach to cure remains elusive. The ineffectiveness of antiretroviral therapy (ART) in reducing the size of the HIV-1 latent reservoir has prompted investigation into the mechanisms of HIV-1 latency and immune escape.
Reconstruction of Dispersal Patterns of Hypervirulent Meningococcal Strains of Serogroup C:cc11 by Phylogenomic Time Trees
Authors: Lo Presti Alessandra , Neri Arianna , Fazio Cecilia , Vacca Paola , Ambrosio Luigina , Grazian Clara , Liseo Brunero , Rezza Giovanni , Maiden Martin Christopher James , Stefanelli Paola
Published: October 2019

Neisseria meningitidis
is one of the few commensal bacteria that can even cause large epidemics of invasive meningococcal disease (IMD).
N. meningitis
serogroup C belonging to the hypervirulent clonal complex 11 (cc11) represents an important public health threat worldwide. We reconstructed the dispersal patterns of hypervirulent meningococcal strains of serogroup C:cc11 by phylogenomic time trees.
Molecular Imaging: a Novel Tool To Visualize Pathogenesis of Infections
In Situ
Authors: Gordon Oren , Ruiz-Bedoya Camilo A. , Ordonez Alvaro A. , Tucker Elizabeth W. , Jain Sanjay K.
Published: October 2019

Molecular imaging is an emerging technology that enables the noninvasive visualization, characterization, and quantification of molecular events within living subjects. Positron emission tomography (PET) is a clinically available molecular imaging tool with significant potential to study pathogenesis of infections in humans.
Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease
Authors: Burggraaf Maroeska J. , Speer Alexander , Meijers Aniek S. , Ummels Roy , van der Sar Astrid M. , Korotkov Konstantin V. , Bitter Wilbert , Kuijl Coenraad
Published: October 2019

Aspartic proteases are common in eukaryotes and retroviruses but are relatively rare among bacteria (N. D. Rawlings and A. Bateman, BMC Genomics 10:437, 2009,
https://doi.org/10.1186/1471-2164-10-437
). In contrast to eukaryotic aspartic proteases, bacterial aspartic proteases are generally located in the cytoplasm. We have identified a surface-associated mycobacterial aspartic protease, PecA, which cleaves itself and many other type VII secretion substrates of the PE_PGRS family. PecA is present in most pathogenic mycobacterial species, including
M. tuberculosis
. In addition, pathogenicity of
M. marinum
is reduced in the
ΔpecA
mutant, indicating that PecA contributes to virulence.
Maintenance of Sympatric and Allopatric Populations in Free-Living Terrestrial Bacteria
Authors: Chase Alexander B. , Arevalo Philip , Brodie Eoin L. , Polz Martin F. , Karaoz Ulas , Martiny Jennifer B. H.
Published: October 2019

Due to the promiscuous exchange of genetic material and asexual reproduction, delineating microbial species (and, by extension, populations) remains challenging. Because of this, the vast majority of microbial studies assessing population structure often compare divergent strains from disparate environments under varied selective pressures. Here, we investigated the population structure within a single bacterial ecotype, a unit equivalent to a eukaryotic species, defined as highly clustered genotypic and phenotypic strains with the same ecological niche. Using a combination of genomic and computational analyses, we assessed the phylogenetic structure, extent of recombination, and flexible gene content of this genomic diversity to infer patterns of gene flow. To our knowledge, this study is the first to do so for a dominant soil bacterium. Our results indicate that bacterial soil populations, similarly to those in other environments, are structured by gene flow discontinuities and exhibit distributional patterns consistent with both isolation by distance and isolation by environment. Thus, both dispersal limitation and local environments contribute to the divergence among closely related soil bacteria as observed in macroorganisms.
Crystal Structure of African Swine Fever Virus dUTPase Reveals a Potential Drug Target
Authors: Li Changyao , Chai Yan , Song Hao , Weng Changjiang , Qi Jianxun , Sun Yeping , Gao George F.
Published: October 2019

African swine fever virus (ASFV), an
Asfivirus
affecting pigs and wild boars with up to 100% case fatality rate, is currently rampaging throughout China and some other countries in Asia. There is an urgent need to develop therapeutic and preventive reagents against the virus. Our crystallographic and biochemical studies reveal that ASFV E165R is a member of trimeric dUTP nucleotidohydrolase (dUTPase) family that catalyzes the hydrolysis of dUTP into dUMP. Our apo-E165R and E165R-dUMP structures reveal the constitutive residues and the configuration of the active center of this enzyme in rich detail and give evidence that the active center of E165R is very similar to that of dUTPases from
Plasmodium falciparum
and
Mycobacterium tuberculosis
, which have already been used as targets for designing drugs. Therefore, our high-resolution structures of E165R provide useful structural information for chemotherapeutic drug design.
Validating DNA Extraction Protocols for Bentonite Clay
Authors: Engel Katja , Coyotzi Sara , Vachon Melody A. , McKelvie Jennifer R. , Neufeld Josh D.
Published: October 2019

Extraction of microbial DNA from MX-80 bentonite is challenging due to low biomass and adsorption of nucleic acid molecules to the charged clay matrix. Blocking agents improve DNA recovery, but their impact on microbial community profiles from low-biomass samples has not been characterized well. In this study, we evaluated the effect of casein and phosphate as blocking agents for quantitative recovery of nucleic acids from MX-80 bentonite. Our data justify a simplified framework for analyzing microbial community DNA associated with swelling MX-80 bentonite samples within the context of a deep geological repository for used nuclear fuel. This study is among the first to demonstrate successful extraction of DNA from Wyoming MX-80 bentonite.
Maternal Humoral Immune Responses Do Not Predict Postnatal HIV-1 Transmission Risk in Antiretroviral-Treated Mothers from the IMPAACT PROMISE Study
Authors: Hompe Eliza D. , Jacobson Denise L. , Eudailey Joshua A. , Butler Kevin , Edwards Whitney , Pollara Justin , Brummel Sean S. , Fouda Genevieve G. , Chinula Lameck , Kamanga Melvin , Kinikar Aarti , Moodley Dhayendre , Owor Maxensia , Fowler Mary Glenn , Permar Sallie R.
Published: October 2019

Each year, >150,000 infants become newly infected with HIV-1 through MTCT despite ART, with up to 42% of infections occurring during breastfeeding. Several factors contribute to continued pediatric infections, including ART nonadherence, the emergence of drug-resistant HIV strains, acute infection during breastfeeding, and poor access to ART in resource-limited areas. A better understanding of the maternal humoral immune responses that provide protection against postnatal transmission in the setting of ART is critical to guide the design of maternal vaccine strategies to further eliminate postnatal HIV transmission. In this study, we found that in women treated with antiretrovirals during pregnancy, there was a positive correlation between plasma viral load and breast milk and plasma IgA responses; however, conclusions regarding odds of MTCT risk were limited by the small sample size. These findings will inform future studies to investigate maternal immune interventions that can synergize with ART to eliminate MTCT during breastfeeding.
IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae
Authors: Kubota Hiroaki , Suzuki Yasunori , Okuno Rumi , Uchitani Yumi , Ariyoshi Tsukasa , Takemura Nobuyuki , Mihara Fuminori , Mezaki Kazuhisa , Ohmagari Norio , Matsui Mari , Suzuki Satowa , Sekizuka Tsuyoshi , Kuroda Makoto , Yokoyama Keiko , Sadamasu Kenji
Published: October 2019

IMP-type metallo-β-lactamases comprise one group of the “Big 5” carbapenemases. Here, a novel
bla
IMP-68
gene encoding IMP-68 (harboring a Ser262Gly point mutant of IMP-11) was discovered from meropenem-resistant but imipenem-susceptible
Klebsiella pneumoniae
TA6363. The Ser262Gly substitution was previously identified as important for substrate specificity according to a study of other IMP variants, including IMP-6. We confirmed that IMP-68 exhibited weaker imipenem-hydrolyzing activity than that for other carbapenems, demonstrating that the antimicrobial susceptibility profile of TA6363 originated from IMP-68 substrate specificity, with this likely to affect treatment strategies using antibacterial agents in clinical settings. Notably, the carbapenem resistance conferred by IMP-68 was undetectable based on the MIC of imipenem as a carbapenem representative, which demonstrates a comparable antimicrobial susceptibility profile to IMP-6-producing
Enterobacteriaceae
that previously spread in Japan due to lack of awareness of its existence.
Sediment routing from shelf to basin floor in the Quaternary Golo System of Eastern Corsica, France, western Mediterranean Sea
Authors: Sweet Michael L. , Gaillot Gwladys T. , Jouet Gwenael , Rittenour Tammy M. , Toucanne Samuel , Marsset Tania , Blum Michael D.
Published: October 2019

How and when sediment moves from shallow marine to deep-water environments is an important and poorly understood control on basin-scale sediment dispersal patterns, the evolution of continental margins, and hydrocarbon exploration in deep-water basins. The Golo River (Eastern Corsica, France), its delta, canyons, and fans provide a unique opportunity to study sediment routing from source to sink in a relatively compact depositional system. We studied this system using an array of high-frequency seismic data, multi-beam bathymetry, and five cores for lithology and age control.

Movement of sediment to deep water was controlled by interactions between the Golo River, the Golo Delta, and shelf-penetrating submarine canyons. Sediment moved to deep water when lobes of the Golo Delta prograded to the heads of these canyons, or when the Golo River itself flowed directly into one of them. Sand accumulated in canyons, deep-water channels, and submarine fans during glacial periods of low sea level, while mud was deposited throughout the slope, in the relatively short reach of leveed-confined channels, and in the mud-rich fringes around the sandy fans. During interglacial periods of high sea level, the basin was blanketed by mud-rich deposits up to 10 m thick interbedded with distinctive carbonate-rich sediments. Deposition rates in the basin ranged from 0.07 m/ka to 0.59 m/ka over the last 450 ka. Mud deposition rates remained relatively constant at ∼0.16 m/ka during all time periods, while sand deposition only happened during glacial periods of low sea level with an average rate of 0.24 m/ka.

In addition to sea-level controls on sediment delivery, avulsions of the Golo River and its deltaic lobes preferentially routed sediment down either the North or South Golo canyons. Thus, while the larger, sequence-scale architecture of the basin is controlled by allogenic sea level forcing, millennial-scale autogenic processes operating on the shelf and in deep water shaped the distribution of sand and mud, and the internal geometry of the deltas and submarine fans that they fed. While some aspects of the Golo system are characteristic of steep, tectonically active margins, others such as the nature of connections between rivers and shelf-penetrating submarine canyons are observed in most margins with active submarine fans regardless of their tectonic setting.
Separating multiple episodes of partial melting in polyorogenic crust: An example from the Haiyangsuo complex, northern Sulu belt, eastern China
Authors: Feng Peng , Wang Lu , Brown Michael , Wang Songjie , Li Xiawen
Published: October 2019

The exotic Haiyangsuo complex is structurally part of the Sulu belt but its contact relationship with surrounding Sulu gneisses is unexposed and therefore unknown, making its affinity uncertain. It comprises gneisses with in-source leucosomes that host minor metabasite bodies; both are cut by leucogranite dikes. In this study, we determine the timing and petrogenesis of leucosomes and leucogranites and assess the tectonic affinity of the complex based on data from gneisses and metabasites. Most zircon from gneisses and leucosomes has oscillatory-zoned cores with CL-bright overgrowth rims, but some has CL-dark cores or mantles between cores and rims. CL-dark and bright zircon yield weighted mean ages of ca. 1817–1812 Ma. CL-dark zircon has flat heavy rare earth element (HREE) patterns and crystallization temperatures of 829–875 °C, suggesting metamorphic growth, whereas rims have steep HREE patterns but a similar range of crystallization temperatures, suggesting growth from anatectic melt; εHf (t = 1813 Ma) of –18.3 to –10.8 indicates a North China Craton source. Magmatic zircon from metabasites yields ages of ca. 825 Ma, similar to those of scattered metabasite occurrences in the North China Craton. Paleoproterozoic zircon cores were scavenged during magma ascent. By contrast, zircon cores from the leucogranites yield concordant dates of 776–701 Ma, consistent with protolith ages in the Sulu belt, whereas overgrowth mantles and rims yield weighted mean ages of ca. 220 Ma and 162 Ma, respectively. Both mantles and rims host multiphase solid inclusions, representing former melt, suggesting anatexis and crystallization of zircon first during initial decompression and then during orogenic collapse of the Sulu belt; whole-rock Nd and Sr isotope compositions implicate the Sulu belt gneisses as the source of these melts. Our interpretation of these data is that the Haiyangsuo complex has an early geologic history similar to the Jiaobei terrane from the southeastern part of the North China Craton and was incorporated into the Sulu belt during Triassic collision of the Yangtze and North China Cratons. The two stages of melting relate to Upper Triassic early exhumation and Upper Jurassic late-stage orogenic collapse, during which the leucogranite magma was derived from a source similar to one elsewhere in the Sulu belt such as the subducted Yangtze Craton and not the North China Craton. This shows that during continental collisions, crust from the upper plate may be dragged into the subduction channel, deformed, and subsequently exhumed in association with partial melting of the crust.
Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy in India (THIN study): a randomised controlled trial
Authors: Aker Karoline , Støen Ragnhild , Eikenes Live , Martinez-Biarge Miriam , Nakken Ingeborg , Håberg Asta Kristine , Gibikote Sridhar , Thomas Niranjan
Published: October 2019

Objective

To evaluate the neuroprotective effect of therapeutic hypothermia (TH) induced by phase changing material (PCM) on MRI biomarkers in infants with hypoxic-ischaemic encephalopathy (HIE) in a low-resource setting.

Design

Open-label randomised controlled trial.

Setting

One neonatal intensive care unit in a tertiary care centre in India.

Patients

50 term/near-term infants admitted within 5 hours after birth with predefined physiological criteria and signs of moderate/severe HIE.

Interventions

Standard care (n=25) or standard care plus 72 hours of hypothermia (33.5°C±0.5°C, n=25) induced by PCM.

Main outcome measures

Primary outcome was fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC) on neonatal diffusion tensor imaging analysed according to intention to treat.

Results

Primary outcome was available for 22 infants (44%, 11 in each group). Diffusion tensor imaging showed significantly higher FA in the cooled than the non-cooled infants in left PLIC and several white matter tracts. After adjusting for sex, birth weight and gestational age, the mean difference in PLIC FA between groups was 0.026 (95% CI 0.004 to 0.048, p=0.023). Conventional MRI was available for 46 infants and demonstrated significantly less moderate/severe abnormalities in the cooled (n=2, 9%) than in the non-cooled (n=10, 43%) infants. There was no difference in adverse events between groups.

Conclusions

This study confirmed that TH induced by PCM reduced brain injury detected on MRI in infants with moderate HIE in a neonatal intensive care unit in India. Future research should focus on optimal supportive treatment during hypothermia rather than looking at efficacy of TH in low-resource settings.

Trial registration number

CTRI/2013/05/003693.