bluuebunny/crossref_metadata_2025 huggingface dataset:
Trade, transboundary impacts and the implementation of SDG 12
Authors: Amos Rob , Lydgate Emily
Published: July 2019

The 2015 Sustainable Development Goals (SDGs) were developed to ‘transform our world’. Yet critics argue that the concept of sustainable development serves to maintain an unsustainable status quo, or provide a positive gloss on a terminal conflict between its ‘pillars’: environmental protection, economic growth and social welfare. In this article, we examine this tension with respect to the implementation of SDG 12 in the European Union. SDG 12 calls for responsible consumption and production, which necessitates reconciling, or ‘decoupling’, economic growth and environmental degradation: the core of sustainable development. Initial examination reveals that the largest implementation gap is among high-consuming countries, including those of the EU, the focus of our article, who are failing to account for transboundary impacts of products consumed domestically. This shortcoming, facilitated by the flexibility of the SDG ‘global target, national action’ approach, undermines the achievement of other environmental SDGs relating to biodiversity and climate, among others. Yet, as compared to other EU approaches to addressing transboundary environmental harm from trade in existing Free Trade Agreements (FTAs) and Multilateral Environmental Agreements (MEAs), which we examine, the global focus and breadth of SDG 12 offers transformative potential. Ultimately, even if the three pillars of sustainable development are not ‘rebalanced’ toward environmental conservation, they can provide a construct for examining interactions and trade-offs between goals. Simply taking account of transboundary consumption, as SDG 12 indicators call for, would encourage more effective cooperation to help producing countries address environmental problems that result from production for export through impact assessment and enforcement.
Developmental regulation and lateralization of GABA receptors in the rat hippocampus
Authors: Khoshdel‐Sarkarizi Hoda , Hami Javad , Mohammadipour Abbas , Sadr‐Nabavi Ariane , Mahmoudi Mahmoud , Kheradmand Hamed , Peyvandi Mostafa , Nourmohammadi Esmail , Haghir Hossein
Published: July 2019

GABA is the chief inhibitory neurotransmitter in the adult brain. However, in the developing brain it acts as an excitatory transmitter causing depolarization. Thereby, activates calcium‐dependent processes that are crucial for brain development. Accordingly, GABA receptors have the great role in the brain development, especially in the area with persisting neurogenesis such as hippocampus. The present study investigated the development and lateralization of two important subunits of GABA receptors, GABAAα1 and GABAB1, in the developing rat hippocampus during the neurogenesis‐active period, at the first two postnatal weeks. Real‐time PCR, western blot and immunohistochemistry were used. We found that the mRNA and protein of these GABA receptor subunits have already been expressed at birth and significantly increased at postnatal day (P) 7, and also at P14. Also, regarding the optical densities of GABAAα1 and GABAB1 expressing hippocampal cells, we found a significant increase in the distribution pattern of these subunits in the all hippocampal subregions on day 14 after birth. The highest optical density of GABAAα1 was observed in the CA3, and GABAB1 in the CA2. Nevertheless, our results did not show a significant laterality differences in the expression of these subunits. Regarding the crucial role of GABA receptors in the hippocampus development; they probably have the same effects on development of the rat hippocampus on both sides.
Utility of serum ferritin and soluble interleukin-2 receptor as markers of disease activity in childhood systemic lupus erythematosus
Authors: Almutairi Nora , Aljaser Alwaleed , Almutairi Abdulaziz , Alshaikh Manal , Eldali Abdelmoneim , Al-Mayouf Sulaiman M.
Published: July 2019

Objective:

To assess the usefulness of serum ferritin and soluble interleukin-2 receptor (sIL-2r) levels as markers of disease activity in childhood systemic lupus erythematosus (cSLE) and their role in screen for subclinical macrophage activation syndrome (MAS).

Patients and methods:

This is a cross-sectional analysis of prospectively collected data. Consecutive children who met the Systemic Lupus International Collaborating Clinics (SLICC) criteria were enrolled between June 2015 and June 2017. All patients interviewed and assessed for disease activity using SLE disease activity index (SLEDAI). Biochemical and serological tests including markers of disease activity and MAS were measured by standard laboratory procedure.

Results:

A total of 31 (25 female; 6 male) consecutive cSLE patients with a mean age of 10.6 (±3.2) years were included. The most frequent manifestations were mucocutaneous and musculoskeletal (84%) followed by hematological (64.5%) then renal involvement (58%). Twenty-two patients had active disease (SLEDAI ≥ 4), with a mean of 9.8. Mean serum ferritin and sIL-2r were 555 (±1860) and 2789 (±1299) respectively. Both correlated significantly with leucocyte, platelet count, transferrin, C3 and SLEDAI
(p <
0.05). Additionally, sIL-2r had positive correlation with ANA, ds-DNA and C4. Both ferritin and sIL-2r had weak correlation with ESR, but no correlation with CRP. Twelve patients had a recent infection. However, they were comparable to patients without infection with regard to all clinical and laboratory features. Three patients had MAS proved by bone marrow aspiration.

Conclusion:

Measurement of serum ferritin and sIL-2r might help in assessing disease activity of cSLE. Both might be good screening markers for MAS in cSLE. A larger prospective study is required to allow more definitive conclusions.
Bone Mineral Density in Transgender Individuals After Gonadectomy and Long-Term Gender-Affirming Hormonal Treatment
Authors: Dobrolińska Magdalena , van der Tuuk Karin , Vink Patti , van den Berg Marjan , Schuringa Anke , Monroy-Gonzalez Andrea G. , García David Vállez , Schultz Willibrord C.M. Weijmar , Slart Riemer H.J.A.
Published: July 2019

Introduction

Establishing the influence of long-term, gender-affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender individuals is important to improve the therapeutic guidelines for these individuals.

Aim

To examine the effect of long-term HT and gonadectomy on BMD in transgender individuals.

Methods

68 transwomen and 43 transmen treated with HT who had undergone gonadectomy participated in this study. Dual-energy x-ray absorptiometry (DXA) scans were performed to measure BMD at the lumbar spine and total hip. Laboratory values related to sex hormones were collected within 3 months of performing the DXA scan and analyzed.

Main Outcome Measure

BMD and levels of sex hormones in transwomen and transmen.

Results

In transwomen, the mean BMD values at the lumbar spine and total hip at the first DXA scan were, respectively, 0.99 ± 0.15 g/cm2 (n = 68) and 0.94 ± 0.28 g/cm2 (n = 65). In transmen, the mean BMD values at the lumbar spine and total hip at the first DXA scan were, respectively, 1.08 ± 0.16 g/cm2 (n = 43) and 1.01 ± 0.18 g/cm2 (n = 43). A significant decrease in total hip BMD was found in both transwomen and transmen after 15 years of HT compared with 10 years of HT (P = .02).

Conclusion

In both transwomen and transmen, a decrease was observed in total hip bone mineral density after 15 years of HT compared to the first 10 years of HT.
Clinical impact of an antimicrobial stewardship program on high-risk pediatric patients
Authors: Goldman Jennifer L. , Newland Jason G. , Price Michael , Yu Diana , Lee Brian R.
Published: July 2019

Objective:

To evaluate the clinical impact of an antimicrobial stewardship program (ASP) on high-risk pediatric patients.

Design:

Retrospective cohort study.

Setting:

Free-standing pediatric hospital.

Patients:

This study included patients who received an ASP review between March 3, 2008, and March 2, 2017, and were considered high-risk, including patients receiving care by the neonatal intensive care (NICU), hematology/oncology (H/O), or pediatric intensive care (PICU) medical teams.

Methods:

The ASP recommendations included stopping antibiotics; modifying antibiotic type, dose, or duration; or obtaining an infectious diseases consultation. The outcomes evaluated in all high-risk patients with ASP recommendations were (1) hospital-acquired Clostridium difficile infection, (2) mortality, and (3) 30-day readmission. Subanalyses were conducted to evaluate hospital length of stay (LOS) and tracheitis treatment failure. Multivariable generalized linear models were performed to examine the relationship between ASP recommendations and each outcome after adjusting for clinical service and indication for treatment.

Results:

The ASP made 2,088 recommendations, and 50% of these recommendations were to stop antibiotics. Recommendation agreement occurred in 70% of these cases. Agreement with an ASP recommendation was not associated with higher odds of mortality or hospital readmission. Patients with a single ASP review and agreed upon recommendation had a shorter median LOS (10.2 days vs 13.2 days; P < .05). The ASP recommendations were not associated with high rates of tracheitis treatment failure.

Conclusions:

ASP recommendations do not result in worse clinical outcomes among high-risk pediatric patients. Most ASP recommendations are to stop or to narrow antimicrobial therapy. Further work is needed to enhance stewardship efforts in high-risk pediatric patients.
The response of glyphosate-resistant and glyphosate-susceptible biotypes of junglerice (Echinochloa colona) to mungbean interference
Authors: Mutti Navneet Kaur , Mahajan Gulshan , Jha Prashant , Chauhan Bhagirath S.
Published: July 2019

Glyphosate-resistant junglerice [Echinochloa colona(L.) Link] is a problematic weed in mungbean [Vigna radiata(L.) R. Wilczek] crops in Australia. Due to limited herbicide options in mungbean, there is an increased interest in developing integrated management strategies for the sustainable control ofE. colona. Pot experiments were conducted in a screenhouse in 2017 and 2018 by growingE. colonaplants (glyphosate-resistant [GR] and glyphosate-susceptible [GS] biotypes) alone (1 plant pot−1) and in competition with 4 and 8 mungbean plants pot−1. Both biotypes were developed from a single population using the clone method. The growth and seed production of both GR and GS biotypes were similar in response to mungbean competition. Averaged over biotypes, there was a reduction in the growth and seed production ofE. colonaas crop plants increased. Compared with the weed plants grown alone, crop interference reducedE. colonaheight by 17% to 19%, tiller numbers by 69% to 82%, total shoot biomass by 85% to 91%, and inflorescence numbers by 74% to 91%. WhenE. colonawas grown with 8 mungbean plants pot−1, leaf weight ratio increased by 42% compared with plants grown alone. Compared with weed plants grown alone, mungbean interference (4 and 8 plants pot−1) reduced weed seed production by 85% to 95%. These reductions were similar for both biotypes (GR and GS), suggesting that there was no fitness penalty associated with resistance. The results of this study suggest that mungbean interference can reduceE. colonagrowth and seed production, but it should not be considered as a stand-alone strategy to manageE. colonaand similar species in mungbean. These results also highlight the need for integrating crop competition with other management strategies to achieve complete and sustainable management of this weed.
Changes in the Thickness and Circulation of Multiyear Ice in the Beaufort Gyre Determined From Pseudo‐Lagrangian Methods from 2003–2015
Authors: Mahoney Andrew R. , Hutchings Jennifer K. , Eicken Hajo , Haas Christian
Published: July 2019

We combine Eulerian ice draft observations from moored ice‐profiling sonars with buoy‐ and satellite‐derived ice drift data to obtain Lagrangian observations of changes in the thickness distribution of sea ice circulating the Beaufort Sea. We examine repeat measurements of ice draft by identifying events where buoys or pseudobuoys made repeat overpasses within 30 km of ice‐profiling sonar‐equipped Beaufort Gyre Exploration Project moorings. Comparison of ice draft distributions from each overpass indicates that summertime melt rates are related to drift track, with more melt occurring in the southern Beaufort Sea than to the north. Additionally, we find that ice surviving summer in the Beaufort Sea since 2007 is similar in thickness to surrounding first‐year sea ice by the end of the following winter. These findings are supported by continuous ice thickness data from ice mass balance buoys. By examining “plumes” of pseudobuoys originating at each mooring location, we identify anomalous northward transport of ice in the southern Beaufort Sea in 2007 that likely contributed to the record‐breaking reduction in sea ice extent that year. We also find that repeat overpasses have been much rarer since 2007, due to reduced summertime sea ice extent in the Beaufort Gyre and possible changes in ice drift patterns. These changes contribute to diminished replenishment of multiyear sea ice volume in the Arctic.
Basement‐Cover Relationships and Their Along‐Strike Changes in the Linking Zone (Iberian Range, Spain): A Combined Structural and Gravimetric Study
Authors: Izquierdo‐Llavall E. , Ayala C. , Pueyo E. L. , Casas‐Sainz A. M. , Oliva‐Urcia B. , Rubio F. , Rodríguez‐Pintó A. , Rey‐Moral C. , Mediato J. F. , García‐Crespo J.
Published: July 2019

Contractional deformation in the transition between the Iberian and Catalan Coastal Ranges (Linking Zone) generated both thin‐skinned structures detached in low‐strength Triassic units and basement‐involved structures. To evaluate their extent and relative contribution to the overall structure, we carried out a study combining structural geology and gravimetry. New gravity data (938 stations) and density determinations (827 samples) were acquired and combined with previous existing databases to obtain Bouguer anomaly and residual Bouguer anomaly maps of the study area. Seven serial and balanced cross sections were built, their depth geometries being constrained through the 2.5‐D gravity modeling and the 3‐D gravity inversion that we accomplished. The residual Bouguer anomaly map shows a good correlation between basement antiforms and gravity highs whereas negative anomalies mostly correspond to (i) Meso‐Cenozoic synclines and (ii) Neogene‐Quaternary basins. Cross sections depict a southern, thick‐skinned domain where extensional, basement faults inherited from Late Jurassic‐Early Cretaceous times were inverted during the Cenozoic. To the north, we interpret the existence of both Triassic‐detached and basement‐involved deformation domains. The two deformation styles are vertically overlapped in the southernmost part of the Catalan Coastal Ranges but relay both across and along strike in the Eastern Iberian Range. These basement and cover relationships and their along‐strike variations are analyzed in terms of the interplay between structural inheritance, its obliquity to the shortening direction, and the continuity and effectiveness of Triassic décollements in the study area.
House Science Chair Questions Plan to Reduce Advisory Committees
Authors: Showstack Randy
Published: July 2019

Rep. Eddie Bernice Johnson calls on science agencies to provide information about their strategy for implementing the executive order eliminating one third of federal advisory committees.
EnKF Ionosphere and Thermosphere Data Assimilation Algorithm Through a Sparse Matrix Method
Authors: He Jianhui , Yue Xinan , Wang Wenbin , Wan Weixing
Published: July 2019

In this work, we constructed an ensemble Kalman filter (EnKF) ionosphere and thermosphere data assimilation system using the National Center for Atmospheric Research Thermosphere Ionosphere Electrodynamics General Circulation Model (NCAR‐TIEGCM) as the background model. We use a sparse matrix method to avoid significant matrix related calculation and storage. A series of observing system simulation experiments have been conducted to assess the performance of the system. The results show that the system optimizes ionosphere drivers efficiently by assimilating electron densities through their covariance. The short‐term forecast capability is enhanced significantly, and the effect of initial condition correction lasts for longer than 24 hr. To our knowledge, this is the first study to demonstrate that the EnKF‐based global ionosphere and thermosphere data assimilation can be conducted without using a supercomputer. This workstation‐based EnKF ionosphere and thermosphere data assimilation system benefits both scientific studies and near‐real‐time operation.
Influence of Recent Climate Shifts on the Relationship Between ENSO and Asian Monsoon Precipitation Oxygen Isotope Ratios
Authors: Cai Zhongyin , Tian Lide , Bowen Gabriel J.
Published: July 2019

Recent studies have revealed robust in‐phase relationships between El Niño–Southern Oscillation (ENSO) and Asian Monsoon precipitation δ18O values (i.e., warm ENSO events with high δ18O values), and this relationship has been used in an attempt to reconstruct past ENSO activity. However, whether this relationship holds in the past is unknown. Here we use precipitation δ18O data from Hong Kong (East Asia) and Bangkok (Southeast Asia) and an ice core δ18O record from Dasuopu glacier (South Asia) to examine the δ18O‐ENSO relationship across two recent climate shifts that occurred during the winters of 1976/1977 and 1988/1989. On an annual scale, the δ18O‐ENSO relationship is weak prior to 1977 and strongest after 1988. We show that the changing δ18O‐ENSO relationship mainly originates from changes in the dry season isotope/climate relationship (which is significant only after 1988), whereas the rainy season relationship is relatively stable. We confirm that, consistent with earlier work on the rainy season, the significant δ18O‐ENSO relationship in the dry season post‐1988 is associated with ENSO's influence on regional convection (Bay of Bengal to South China Sea region). We suggest the insignificant dry season relationship prior to 1989 is due to limited ENSO impacts on convection in the Bay of Bengal to South China Sea region, which is supported by the insignificant relationship between ENSO and vertical velocity at 500 hPa. These findings suggest that without additional constraints, systematic variability in isotope/climate relationships will lead to large uncertainties in ENSO reconstructions based on Asian Monsoon region δ18O data.
The inhibition of chloride intracellular channel 1 enhances Ca2+ and reactive oxygen species signaling in A549 human lung cancer cells
Authors: Lee Jae-Rin , Lee Jong-Yoon , Kim Hyun-Ji , Hahn Myong-Joon , Kang Jong-Sun , Cho Hana
Published: July 2019

Chloride intracellular channel 1 (CLIC1) is a promising therapeutic target in cancer due to its intrinsic characteristics; it is overexpressed in specific tumor types and its localization changes from cytosolic to surface membrane depending on activities and cell cycle progression. Ca2+ and reactive oxygen species (ROS) are critical signaling molecules that modulate diverse cellular functions, including cell death. In this study, we investigated the function of CLIC1 in Ca2+ and ROS signaling in A549 human lung cancer cells. Depletion of CLIC1 via shRNAs in A549 cells increased DNA double-strand breaks both under control conditions and under treatment with the putative anticancer agent chelerythrine, accompanied by a concomitant increase in the p-JNK level. CLIC1 knockdown greatly increased basal ROS levels, an effect prevented by BAPTA-AM, an intracellular calcium chelator. Intracellular Ca2+ measurements clearly showed that CLIC1 knockdown significantly increased chelerythrine-induced Ca2+ signaling as well as the basal Ca2+ level in A549 cells compared to these levels in control cells. Suppression of extracellular Ca2+ restored the basal Ca2+ level in CLIC1-knockdown A549 cells relative to that in control cells, implying that CLIC1 regulates [Ca2+]i through Ca2+ entry across the plasma membrane. Consistent with this finding, the L-type Ca2+ channel (LTCC) blocker nifedipine reduced the basal Ca2+ level in CLIC1 knockdown cells to that in control cells. Taken together, our results demonstrate that CLIC1 knockdown induces an increase in the intracellular Ca2+ level via LTCC, which then triggers excessive ROS production and consequent JNK activation. Thus, CLIC1 is a key regulator of Ca2+ signaling in the control of cancer cell survival.
Correction to: Role of the DNA damage response in prostate cancer formation, progression and treatment
Authors: Zhang Wenhao , van Gent Dik C. , Incrocci Luca , van Weerden Wytske M. , Nonnekens Julie
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Abundance and survival of microbial aerosols in the troposphere and stratosphere
Authors: Bryan N C , Christner B C , Guzik T G , Granger D J , Stewart M F
Published: July 2019

Bioaerosol transport in the atmosphere disperses microbial species between continents, affects human and plant health, and may influence hydrologic cycling. However, there have been few quantitative observations of bioaerosols at altitudes more than a few kilometers above the surface. Lack of data on bioaerosol distributions in the atmosphere has impeded efforts to assess the aerial dissemination of microbes and their vertical extent in the biosphere. In this study, a helium balloon payload system was used to sample microbial cells and dust particles in air masses as high as 38 km above sea level over three locations in the southwestern United States. The cell concentrations at altitudes between 3 and 29 km were highly similar (2–5 × 105 cells m−3) and approximately threefold lower than those observed in the convective boundary layer (CBL; 1 × 106 cells m−3), decreasing to 8 × 104 cells m−3 at 35–38 km. The detection of adenosine triphosphate (ATP) and recovery of bacteria possessing extreme tolerance to desiccation and shortwave ultraviolet radiation confirmed that certain microorganisms have the capacity to persist at lower altitudes of the stratosphere. Our data and related calculations provide constraints on the upper altitudinal boundary for microbial habitability in the biosphere.
In marine Bacteroidetes the bulk of glycan degradation during algae blooms is mediated by few clades using a restricted set of genes
Authors: Krüger Karen , Chafee Meghan , Ben Francis T , Glavina del Rio Tijana , Becher Dörte , Schweder Thomas , Amann Rudolf I , Teeling Hanno
Published: July 2019

We investigated Bacteroidetes during spring algae blooms in the southern North Sea in 2010–2012 using a time series of 38 deeply sequenced metagenomes. Initial partitioning yielded 6455 bins, from which we extracted 3101 metagenome-assembled genomes (MAGs) including 1286 Bacteroidetes MAGs covering ~120 mostly uncultivated species. We identified 13 dominant, recurrent Bacteroidetes clades carrying a restricted set of conserved polysaccharide utilization loci (PULs) that likely mediate the bulk of bacteroidetal algal polysaccharide degradation. The majority of PULs were predicted to target the diatom storage polysaccharide laminarin, alpha-glucans, alpha-mannose-rich substrates, and sulfated xylans. Metaproteomics at 14 selected points in time revealed expression of SusC-like proteins from PULs targeting all of these substrates. Analyses of abundant key players and their PUL repertoires over time furthermore suggested that fewer and simpler polysaccharides dominated early bloom stages, and that more complex polysaccharides became available as blooms progressed.
Synthesis, structures and magnetic properties of [(η9-C9H9)Ln(η8-C8H8)] super sandwich complexes
Authors: Münzfeld L. , Schoo C. , Bestgen S. , Moreno-Pineda E. , Köppe R. , Ruben M. , Roesky P. W.
Published: July 2019

Sandwich complexes are an indispensable part of organometallic chemistry, which is becoming increasingly important in the field of lanthanide-based single molecule magnets. Herein, a fundamental class of pure sandwich complexes, [(η9-C9H9)Ln(η8-C8H8)] (Ln=Nd, Sm, Dy, Er), is reported. These neutral and sandwiched lanthanide compounds exclusively contain fully π-coordinated coplanar eight and nine membered CH rings. The magnetic properties of these compounds are investigated, leading to the observation of slow relaxation of the magnetization, including open hysteresis loops up to 10 K for the Er(III) analogue. Fast relaxation of the magnetization is likewise observed near zero field, a highly important characteristic for quantum information processing schemes. Our synthetic strategy is straightforward and utilizes the reaction of [(η8-C8H8)LnI(thf)n] complexes with [K(C9H9)]. Although all compounds are fully characterized, structural details of the title compounds can also be deduced by Raman spectroscopy only.
Repeaterless quantum key distribution with efficient finite-key analysis overcoming the rate-distance limit
Authors: Maeda Kento , Sasaki Toshihiko , Koashi Masato
Published: July 2019

Quantum key distribution (QKD) over a point-to-point link enables us to benefit from a genuine quantum effect even with conventional optics tools such as lasers and photon detectors, but its capacity is limited to a linear scaling of the repeaterless bound. Recently, twin-field (TF) QKD was conjectured to beat the limit by using an untrusted central station conducting a single-photon interference detection. So far, the effort to prove the conjecture was confined to the infinite key limit which neglected the time and cost for monitoring an adversary’s act. Here we propose a variant of TF-type QKD protocol equipped with a simple methodology of monitoring to reduce its cost and provide an information-theoretic security proof applicable to finite communication time. We simulate the key rate to show that the protocol beats the linear bound in a reasonable running time of sending 1012 pulses, which positively solves the conjecture.
Chip-scale atomic diffractive optical elements
Authors: Stern Liron , Bopp Douglas G. , Schima Susan A. , Maurice Vincent N. , Kitching John E.
Published: July 2019

The efficient light–matter interaction and discrete level structure of atomic vapors made possible numerous seminal scientific achievements including time-keeping, extreme non-linear interactions, and strong coupling to electric and magnetic fields in quantum sensors. As such, atomic systems can be regarded as a highly resourceful quantum material platform. Recently, the field of thin optical elements with miniscule features has been extensively studied demonstrating an unprecedented ability to control photonic degrees of freedom. Hybridization of atoms with such thin optical devices may offer a material system enhancing the functionality of traditional vapor cells. Here, we demonstrate chip-scale, quantum diffractive optical elements which map atomic states to the spatial distribution of diffracted light. Two foundational diffractive elements, lamellar gratings and Fresnel lenses, are hybridized with atomic vapors demonstrating exceptionally strong frequency-dependent, non-linear and magneto-optic behaviors. Providing the design tools for chip-scale atomic diffractive optical elements develops a path for compact thin quantum-optical elements.
In vivo structural and functional assessment of optic nerve damage in neuromyelitis optica spectrum disorders and multiple sclerosis
Authors: Vabanesi Marco , Pisa Marco , Guerrieri Simone , Moiola Lucia , Radaelli Marta , Medaglini Stefania , Martinelli Vittorio , Comi Giancarlo , Leocani Letizia
Published: July 2019

Early detection of neuromyelitis optica spectrum disorders (NMOSD), especially after optic neuritis, a presenting manifestation commonly observed also in multiple sclerosis (MS), is crucial for timely treatment and prognosis. Integrated visual pathway assessment with optical coherence tomography (OCT) and visual evoked potentials (VEP) may help in this task, showing in vivo different pathophysiological backgrounds. We evaluated combined VEP and OCT in a cross-sectional, single-centre study assessing 50 consecutive NMOSD patients, 57 MS patients and 52 healthy controls. After optic neuritis, VEP were more frequently absent in NMOSD compared to MS; most NMOSD eyes with recordable VEP showed prolonged latency, but extreme latency delays were less common than in MS. OCT showed predominantly axonal involvement in NMOSD, with 88% eyes (95% CI: 69–97%) displaying retinal nerve fibre layer thickness <60 µm even after first optic neuritis episode. Accuracy of OCT was further enhanced by combination with VEP into a new Z-score derived OCT-VEP index, measuring prevalence of axonal damage or demyelination. Our results suggest that integrated optic nerve assessment may elucidate differences in optic neuritis pathophysiology; conduction slowing with relatively preserved nerve fibre layer suggests MS, while severe neuroaxonal loss after optic neuritis, often hindering VEP response, characterizes NMOSD.
Insights into the Microbiome of Breast Implants and Periprosthetic Tissue in Breast Implant-Associated Anaplastic Large Cell Lymphoma
Authors: Walker Jennifer N. , Hanson Blake M. , Pinkner Chloe L. , Simar Shelby R. , Pinkner Jerome S. , Parikh Rajiv , Clemens Mark W. , Hultgren Scott J. , Myckatyn Terence M.
Published: July 2019

Though rare, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a CD30+ T-cell lymphoma associated with textured breast implants, has adversely impacted our perception of the safety of breast implants. Its etiology unknown, one hypothesis suggests an initiating inflammatory stimulus, possibly infectious, triggers BIA-ALCL. We analyzed microbiota of breast, skin, implant and capsule in BIA-ALCL patients (n = 7), and controls via culturing methods, 16S rRNA microbiome sequencing, and immunohistochemistry. Alpha and beta diversity metrics and relative abundance of Gram-negative bacteria were calculated, and phylogenetic trees constructed. Staphylococcus spp., the most commonly cultured microbes, were identified in both the BIA-ALCL and contralateral control breast. The diversity of bacterial microbiota did not differ significantly between BIA-ALCL and controls for any material analyzed. Further, there were no significant differences in the relative abundance of Gram-negative bacteria between BIA-ALCL and control specimens. Heat maps suggested substantial diversity in the composition of the bacterial microbiota of the skin, breast, implant and capsule between patients with no clear trend to distinguish BIA-ALCL from controls. While we identified no consistent differences between patients with BIA-ALCL-affected and contralateral control breasts, this study provides insights into the composition of the breast microbiota in this population.
SREBP1-dependent de novo fatty acid synthesis gene expression is elevated in malignant melanoma and represents a cellular survival trait
Authors: Wu Su , Näär Anders M.
Published: July 2019

de novo fatty acid biosynthesis (DNFA) is a hallmark adaptation of many cancers that supports survival, proliferation, and metastasis. Here we elucidate previously unexplored aspects of transcription regulation and clinical relevance of DNFA in cancers. We show that elevated expression of DNFA genes is characteristic of many tumor types and correlates with poor prognosis, especially in melanomas. Elevated DNFA gene expression depends on the SREBP1 transcription factor in multiple melanoma cell lines. SREBP1 predominantly binds to the transcription start sites of DNFA genes, regulating their expression by recruiting RNA polymerase II to promoters for productive transcription elongation. We find that SREBP1-regulated DNFA represents a survival trait in melanoma cells, regardless of proliferative state and oncogenic mutation status. Indeed, malignant melanoma cells exhibit elevated DNFA gene expression after the BRAF/MEK signaling pathway is blocked (e.g. by BRAF inhibitors), and DNFA expression remains higher in melanoma cells resistant to vemurafenib treatment than in untreated cells. Accordingly, DNFA pathway inhibition, whether by direct targeting of SREBP1 with antisense oligonucleotides, or through combinatorial effects of multiple DNFA enzyme inhibitors, exerts potent cytotoxic effects on both BRAFi-sensitive and -resistant melanoma cells. Altogether, these results implicate SREBP1 and DNFA enzymes as enticing therapeutic targets in melanomas.
Dysfunctional EAT thickness may promote maladaptive heart remodeling in CVD patients through the ST2-IL33 system, directly related to EPAC protein expression
Authors: Vianello Elena , Dozio Elena , Bandera Francesco , Schmitz Gerd , Nebuloni Manuela , Longhi Erika , Tacchini Lorenza , Guazzi Marco , Corsi Romanelli Massimiliano Marco
Published: July 2019

Dysfunctional epicardial adipose tissue (EAT) secretome can influence the heart’s stretch response. However, the molecular mechanisms are still poorly understood. The aim of this study was to clarify how dysfunctional EAT promotes maladaptive heart remodeling in cardiovascular disease (CVD) through ST2 production associated with exchange protein directly activated by cAMP (EPAC) proteins. A series of 55 CVD males were enrolled and their EAT thickness, LV mass and volumes were measured by echocardiography. Blood, plasma and EAT biopsies were collected for molecular and proteomic assays. Taking EAT thickness as a continuous variable there was a direct correlation between the ST2 cardiac stretch mediator and EAT thickness (r = 0.54, p < 0.01) and an inverse relation between the ST2 gene and IL-33 expression (r −0.50, p < 0.01). In the CVD population EPAC2 expression directly correlated with the ST2 gene (r = 0.74, p < 0.0001) causing an ST2/IL-33 system local (p < 0.001) and systemic (sST2 = 57.33 ± 3.22 and IL-33 = 0.53 ± 017 pg/mL; p < 0.0001) protein imbalance associated with maladaptive remodeling. This indicated that dysfunctional EAT is a source of both EPAC and ST2 protein and an EPAC2 isoform seems involved in ST2 production in adipose tissue. Both EPAC2 and ST2 expression were directly related to maladaptive heart remodeling indices, suggesting EAT measurements could be useful in the early assessment of CVD complications.
High-throughput stability screening for detergent-solubilized membrane proteins
Authors: Kotov Vadim , Bartels Kim , Veith Katharina , Josts Inokentijs , Subhramanyam Udaya K. Tiruttani , Günther Christian , Labahn Jörg , Marlovits Thomas C. , Moraes Isabel , Tidow Henning , Löw Christian , Garcia-Alai Maria M.
Published: July 2019

Protein stability in detergent or membrane-like environments is the bottleneck for structural studies on integral membrane proteins (IMP). Irrespective of the method to study the structure of an IMP, detergent solubilization from the membrane is usually the first step in the workflow. Here, we establish a simple, high-throughput screening method to identify optimal detergent conditions for membrane protein stabilization. We apply differential scanning fluorimetry in combination with scattering upon thermal denaturation to study the unfolding of integral membrane proteins. Nine different prokaryotic and eukaryotic membrane proteins were used as test cases to benchmark our detergent screening method. Our results show that it is possible to measure the stability and solubility of IMPs by diluting them from their initial solubilization condition into different detergents. We were able to identify groups of detergents with characteristic stabilization and destabilization effects for selected targets. We further show that fos-choline and PEG family detergents may lead to membrane protein destabilization and unfolding. Finally, we determined thenmodynamic parameters that are important indicators of IMP stability. The described protocol allows the identification of conditions that are suitable for downstream handling of membrane proteins during purification.
Crustose lichens with lichenicolous fungi from Paleogene amber
Authors: Kaasalainen Ulla , Kukwa Martin , Rikkinen Jouko , Schmidt Alexander R.
Published: July 2019

Lichens, symbiotic consortia of lichen-forming fungi and their photosynthetic partners have long had an extremely poor fossil record. However, recently over 150 new lichens were identified from European Paleogene amber and here we analyse crustose lichens from the new material. Three fossil lichens belong to the extant genus Ochrolechia (Ochrolechiaceae, Lecanoromycetes) and one fossil has conidiomata similar to those produced by modern fungi of the order Arthoniales (Arthoniomycetes). Intriguingly, two fossil Ochrolechia specimens host lichenicolous fungi of the genus Lichenostigma (Lichenostigmatales, Arthoniomycetes). This confirms that both Ochrolechia and Lichenostigma already diversified in the Paleogene and demonstrates that also the specific association between the fungi had evolved by then. The new fossils provide a minimum age constraint for both genera at 34 million years (uppermost Eocene).
Children with Autism show Atypical Preference for Non-social Stimuli
Authors: Gale Catherine M. , Eikeseth Svein , Klintwall Lars
Published: July 2019

The present investigation describes three studies testing the hypothesis that children with Autism Spectrum Disorder (ASD) show an atypical preference for non-social stimuli. Preference for non-social and social stimuli was assessed using applications on a portable tablet computer. Twenty-eight children with ASD were matched on developmental age with the chronological age of 41 typically developing (TD) children. The non-social stimuli consisted of six different films of abstract moving geometric patterns. Social stimuli were six different films of the face of young adults (Study 1 and 3) or six films of different dogs’ faces (Study 2). When given a choice between the non-social and social stimuli, children with ASD preferred the non-social stimuli. When the human faces were replaced with dogs’ faces the participants with ASD continued to prefer the non-social stimuli. A high reinforcement value of non-social stimuli was also demonstrated when the non-social stimuli were presented alone, suggesting the preference for the non-social stimuli was not simply an avoidance of social stimuli. Whenever an infant prefers non-social stimuli over social stimuli, non-typical development in social communication and social interests may result, together with the development of high levels and frequently occurring stereotyped and repetitive behavior. These behaviors define Autism.
Impairment of the immune response after transcuticular introduction of the insect gonadoinhibitory and hemocytotoxic peptide Neb-colloostatin: A nanotech approach for pest control
Authors: Czarniewska Elżbieta , Nowicki Patryk , Kuczer Mariola , Schroeder Grzegorz
Published: July 2019

This article shows that nanodiamonds can transmigrate through the insect cuticle easily, and the doses used were not hemocytotoxic and did not cause inhibition of cellular and humoral immune responses in larvae, pupae and adults of Tenebrio molitor. The examination of the nanodiamond biodistribution in insect cells demonstrated the presence of nanodiamond aggregates mainly in hemocytes, where nanoparticles were efficiently collected as a result of phagocytosis. To a lesser extent, nanodiamond aggregates were also detected in fat body cells, while they were not observed in Malpighian tubule cells. We functionalized nanodiamonds with Neb-colloostatin, an insect hemocytotoxic and gonadoinhibitory peptide, and we showed that this conjugate passed through the insect cuticle into the hemolymph, where the peptide complexed with the nanodiamonds induced apoptosis of hemocytes, significantly decreased the number of hemocytes circulating in the hemolymph and inhibited cellular and humoral immune responses in all developmental stages of insects. The results indicate that it is possible to introduce a peptide that interferes with the immunity and reproduction of insects to the interior of the insect body by means of a nanocarrier. In the future, the results of these studies may contribute to the development of new pest control agents.
Sperm-borne miR-216b modulates cell proliferation during early embryo development via K-RAS
Authors: Alves Maíra Bianchi Rodrigues , de Arruda Rubens Paes , De Bem Tiago Henrique Camara , Florez-Rodriguez Shirley Andrea , Sá Filho Manoel Francisco de , Belleannée Clémence , Meirelles Flávio Vieira , da Silveira Juliano Coelho , Perecin Felipe , Celeghini Eneiva Carla Carvalho
Published: July 2019

Semen fertilizing potential is dependent upon the morphological, functional and molecular attributes of sperm. Sperm microRNAs (miRNAs) were recently shown to hold promise regarding their association with different fertility phenotypes. However, their role in fertility regulation remains to be determined. We postulated that sperm miRNAs might regulate early embryonic development. From this perspective, sperm quality and 380 sperm miRNAs were investigated in frozen–thawed semen from high (HF; 54.3 ± 1.0% pregnancy rate) and low (LF; 41.5 ± 2.3%) fertility bulls. Out of nine miRNAs that showed different levels in sperm cells, miR-216b was present at lower levels in HF sperm cells and zygotes. Among miR-216b target genes (K-RAS,BECN1andJUN),K-RAS, related to cell proliferation, revealed a higher level in HF two-cell embryos. First cleavage rate, blastocyst cell number and division number were also higher in HF. In addition, by using a model based on polyspermy embryos, we demonstrated an increase in miR-216b levels in zygotes associated with sperm cell entry. Our results shed light on a possible mechanism of paternal contribution involving sperm-borne miR-216b that modulates levels of miR-216b in zygotes andK-RASin two-cell embryos. This modulation might regulate early development by interfering with the first cleavage and blastocyst quality.
Establishment and equilibrium levels of deleterious mutations in large populations
Authors: Viljoen Johan W. , de Villiers J. Pieter , van Zyl Augustinus J. , Mezzavilla Massimo , Pepper Michael S.
Published: July 2019

Analytical and statistical stochastic approaches are used to model the dispersion of monogenic variants through large populations. These approaches are used to quantify the magnitude of the selective advantage of a monogenic heterozygous variant in the presence of a homozygous disadvantage. Dunbar’s results regarding the cognitive upper limit of the number of stable social relationships that humans can maintain are used to determine a realistic effective community size from which an individual can select mates. By envisaging human community structure as a network where social proximity rather than physical geography predominates, a significant simplification is achieved, implicitly accounting for the effects of migration and consanguinity, and with population structure and genetic drift becoming emergent features of the model. Effective community size has a dramatic effect on the probability of establishing beneficial alleles. It also affects the eventual equilibrium values that are reached in the case of variants conferring a heterozygous selective advantage, but a homozygous disadvantage, as in the case of cystic fibrosis and sickle cell disease. The magnitude of this selective advantage can then be estimated based on observed occurrence levels of a specific allele in a population, without requiring prior information regarding its phenotypic manifestation.
Increase of isoflavones in the aglycone form in soybeans by targeted crossings of cultivated breeding material
Authors: Miladinović Jegor , Đorđević Vuk , Balešević-Tubić Svetlana , Petrović Kristina , Ćeran Marina , Cvejić Jelena , Bursać Mira , Miladinović Dragana
Published: July 2019

Isoflavones are a group of phytoestrogens, naturally-occurring substances important for their role in human health. Legumes, particularly soybeans (Glycine max (L.) Merr.), are the richest source of isoflavones in human diet. Since there is not much current data on genetics of isoflavones in soybean, particularly in the aglycone form, elucidation of the mode of inheritance is necessary in order to design an efficient breeding strategy for the development of high-isoflavone soybean genotypes. Based on the isoflavone content in 23 samples of soybeans from four different maturity groups (00, 0, I and II), three crosses were made in order to determine the inheritance pattern and increase the content of total isoflavones and their aglycone form. Genotype with the lowest total isoflavone content (NS-L-146) was crossed with the low- (NS Zenit), medium (NS Maximus), and high- (NS Virtus) isoflavone genotypes. There were no significant differences in the total isoflavone content (TIF) between F2 populations, and there was no transgression among genotypes within the populations. Each genotype within all three populations had a higher TIF value than the lower parent (NS-L-146), while genotypes with a higher TIF value than the better parent were found only in the NS-L-146 × NS Zenit cross. However, significant differences in the aglycone ratio (ratio of aglycone to glycone form of isoflavones) were found between the populations. The highest aglycone ratio was found in the NS-L-146 × NS Maximus cross. The results indicate that the genetic improvement for the trait is possible.
Diversity of culture-independent bacteria and antimicrobial activity of culturable endophytic bacteria isolated from different Dendrobium stems
Authors: Wang Shan-Shan , Liu Jia-Meng , Sun Jing , Sun Yu-Feng , Liu Jia-Ni , Jia Ning , Fan Bei , Dai Xiao-Feng
Published: July 2019

Dendrobium is known for its pharmacological actions including anti-cancer effect, anti-fatigue effect, gastric ulcer protective effect, and so on. At present, only studies on endophytic fungi of Dendrobium affecting the metabolites of host plants have been reported, very little research has been done on endophytic bacteria. In this study, we have demonstrated the great diversity of endophytic bacteria in 6 Dendrobium samples from different origins and cultivars. According to the results of the culture-independent method, the endophytic bacterial community in Dendrobium stems showed obvious different in the 6 samples and was influenced by origin and cultivar. Some bacteria including Ralstonia, Comamonas and Lelliottia were first detected in Dendrobium in this study. Based on the culture-dependent method, a total of 165 cultivable endophytic bacteria isolates were isolated from the sterilized Dendrobium stems, and were classified into 43 species according to the 16S rRNA gene sequence analysis. Moreover, 14 of the 43 strains showed antimicrobial activity against phytopathogen using the Kirby-Bauer method. Strain NA-HTong-7 (Bacillus megaterium, 99.12%) showed the highest antimicrobial activity. This study was the first comprehensive study on endophytic bacteria of Dendrobium from different origins and cultivars, which provides new insights into the endophytic bacteria from Dendrobium.