bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion from mutualism to parasitism: a mutant of the ectomycorrhizal agaricomycete Tricholoma matsutake that induces stunting, wilting, and root degeneration in seedlings of its symbiotic partner, Pinus densiflora, in vitro
Authors: Murata Hitoshi , Nakano Shota , Yamanaka Takashi , Shimokawa Tomoko , Abe Tomoko , Ichida Hiroyuki , Hayashi Yoriko , Tahara Ko , Ohta Akira
Published: June 2019

Tricholoma matsutake is an ectomycorrhizal agaricomycete that produces matsutake mushrooms in association with conifers. Here, we isolated a pleiotropic mutant, designated as G1, following γ-ray irradiation of T. matsutake NBRC 33136. In addition to exhibiting increased cellulose- and amylose-degrading activities and altered mycelial morphology, G1 degenerated lateral roots and caused stunting or fatal wilting of seedlings of its symbiotic partner, Pinus densiflora, in vitro. A mutant, designated Ar 59, previously isolated after argon-ion beam irradiation, exhibited the same phenotypes as G1, but without its detrimental effects. Ar 59, like NBRC 33136, developed a Hartig net around healthy cortical cells that was composed of uniseriate hyphae. In G1-inoculated seedlings, the Hartig net was composed of heavily bundled hyphae penetrating the intercellular space, and it was accompanied by somewhat unusual forms of plant cortical cells. Sequences of rRNA gene-related markers, including four single nucleotide polymorphisms present within each strain, were 100% identical among NBRC 33136, G1, and Ar 59, indicating that they are mutants of the wild-type. Thus, γ-ray irradiation can convert the fungus from a beneficial to a harmful agent. These findings suggest the presence of an unknown mechanism in the fungal genome that can transform mutualism into parasitism.
Climate model bias correction for nonstationary conditions
Authors: Madani Mohammad , Chilkoti Vinod , Bolisetti Tirupati , Seth Rajesh
Published: June 2019

In most of the climate change impact assessment studies, climate model bias is considered to be stationary between the control and scenario periods. Few methods are found in the literature that addresses the issue of nonstationarity in correcting the bias. To overcome the shortcomings reported in these approaches, three new methods of bias correction (NBC_μ, NBC_σ, and NBC_bs) are presented. The methods are improvised versions of previous techniques relying on distribution mapping. The methods are tested using split sample approach over 50-year historical period for nine climate stations in Ontario, using six regional climate models. The average bias reduction improvement by new methods, in mean daily and monthly precipitation, was found to be 73.9%, 74.3%, and 77.4%, respectively, higher than that obtained by the previous methods (eQM 67.7% and CNCDFm_NP 64.1%). Thus, the methods are found to be more effective in accounting for nonstationarity in the model bias.
Stomatal opening and growth in tomato seedlings treated with different proportions of red and blue light
Authors: Yang Junwei , Liang Tingting , Liu Lu , Pan Tonghua , Zou Zhirong
Published: June 2019

Stomatal opening/closure plays a key role in balancing a plant’s need to conserve water, while still allowing for the exchange of photosynthetic and respiratory gasses with the atmosphere. Stomatal opening/closure can be induced by differences in light quality but a detailed knowledge of the role of light in stomatal regulation in tomato is limited. In this study, we evaluated red and blue light-dependent stomatal opening processes in tomato seedlings and explored the mechanisms involved using different light-quality treatments. After 10 h of darkness, tomato seedlings were subjected to the following five treatments: monochromatic red light (R), 33% blue (2R1B), 50% blue (1R1B), 67% blue (1R2B), and monochromatic blue light (B) at 200 μmol m−2s−1light intensity. The highest stomatal conductance recorded were for 1R1B. Stomatal aperture under 1R1B showed a 92.8% increase after 15 min and a 28.6% increase after 30 min compared with under R alone. Meanwhile, the study shows that the expressions of the plasma membrane H+-ATPase in the leaf were regulated by different proportions of blue light. The results show that the expressions of HA1 and HA4 increased under 1R1B and 1R2B after 15 min of exposure compared with under R alone. Under 1R1B, our results also show net photosynthesis increased compared with R and B after longer treatments, which may be related to chloroplast ultrastructure, and leaf dry weight increased compared with under 1R2B or B alone, but there were no differences under the R and 2R1B light treatments.
A case study in forensic soil examination from China
Authors: Guo Hongling , Wang Ping , Hu Can , Zhu Jun , Yang XueYing , Quan Yangke , Mei HongCheng , Li JinFeng
Published: June 2019

Soil examination can provide useful forensic information about the spatial location and human activities of a suspect. Soil is widely used in criminal investigations. In a case that occurred in the countryside of Jilin Province, in the NE of China, soil was found adhering to clothing on a body. Examination of plant debris in the soil using plant DNA barcoding technique found it to be ginseng root, which indicated that the soil might have come from a ginseng plantation. In the first instance, it helped in finding the place where the body was initially buried. Then a comparison was made between the soil recovered from the body and from the ginseng plantation. Composite analysis of minerals, pollen types and elements provided additional information to assist in making comparisons. Trace amounts of soil located on the body played an important role in locating the burial site and was regarded as the most valuable evidence in convicting the suspect of murder even without the suspect's DNA being available.
The forensic application of ground-penetrating radar, Tekoha Jevy indigenous village, Paraná, Brazil
Authors: Canata Rafael E. , Salvador Fábio A. S. , Borges Welitom R. , Ferreira Francisco J. F. , Seimetz Eduardo X. , Pinto Ivan , Barros Eduardo O.
Published: June 2019

Any archaeological site, according to the Brazilian Federal Constitution, is a patrimony of the Union; consequently, when crimes against this cultural patrimony occur, it becomes the responsibility of the Federal Police of Brazil. In 2013, there was a complaint to the Brazilian Federal Public Prosecutor's Office about the depredation of an archaeological site and forced withdrawal of the indigenous people because of the construction of a multimodal port in the city of Guaíra, in the state of Paraná, in southern Brazil. Thus, the Technical–Scientific Sector of the Federal Police Department, in partnership with Brazilian universities, used standard geophysical methods such as ground-penetrating radar (GPR) to investigate and locate buried archaeological targets. This paper discusses the results of 2D and 3D investigations in the Tekoha Jevy indigenous village, located in Guaíra County. In the field, 32 parallel sections of GPR data were acquired using 250 and 700 MHz shielded antennas. The results showed several anomalies, two of which were subjected to field checks using excavations, which revealed several artefacts such as ceramic fragments associated with ancient indigenous occupations on the banks of the Paraná River.
Mechanobiology of Macrophages: How Physical Factors Coregulate Macrophage Plasticity and Phagocytosis
Authors: Jain Nikhil , Moeller Jens , Vogel Viola
Published: June 2019

In addition to their early-recognized functions in host defense and the clearance of apoptotic cell debris, macrophages play vital roles in tissue development, homeostasis, and repair. If misregulated, they steer the progression of many inflammatory diseases. Much progress has been made in understanding the mechanisms underlying macrophage signaling, transcriptomics, and proteomics, under physiological and pathological conditions. Yet, the detailed mechanisms that tune circulating monocytes/macrophages and tissue-resident macrophage polarization, differentiation, specification, and their functional plasticity remain elusive. We review how physical factors affect macrophage phenotype and function, including how they hunt for particles and pathogens, as well as the implications for phagocytosis, autophagy, and polarization from proinflammatory to prohealing phenotype. We further discuss how this knowledge can be harnessed in regenerative medicine and for the design of new drugs and immune-modulatory drug delivery systems, biomaterials, and tissue scaffolds.
Digital Manufacturing for Microfluidics
Authors: Naderi Arman , Bhattacharjee Nirveek , Folch Albert
Published: June 2019

The microfluidics field is at a critical crossroads. The vast majority of microfluidic devices are presently manufactured using micromolding processes that work very well for a reduced set of biocompatible materials, but the time, cost, and design constraints of micromolding hinder the commercialization of many devices. As a result, the dissemination of microfluidic technology—and its impact on society—is in jeopardy. Digital manufacturing (DM) refers to a family of computer-centered processes that integrate digital three-dimensional (3D) designs, automated (additive or subtractive) fabrication, and device testing in order to increase fabrication efficiency. Importantly, DM enables the inexpensive realization of 3D designs that are impossible or very difficult to mold. The adoption of DM by microfluidic engineers has been slow, likely due to concerns over the resolution of the printers and the biocompatibility of the resins. In this article, we review and discuss the various printer types, resolution, biocompatibility issues, DM microfluidic designs, and the bright future ahead for this promising, fertile field.
Plant MIR156 regulates intestinal growth in mammals by targeting the Wnt/β-catenin pathway
Authors: Li Meng , Chen Ting , Wang Ran , Luo Jun-Yi , He Jia-Jian , Ye Rui-Song , Xie Mei-Ying , Xi Qian-Yun , Jiang Qing-Yan , Sun Jia-Jie , Zhang Yong-Liang
Published: June 2019

MicroRNAs (miRNAs) are important negative regulators of genes involved in physiological and pathological processes in plants and animals. Recent studies have shown that miRNAs might regulate gene expression among different species in a cross-kingdom manner. However, the specific roles of plant miRNAs in animals remain poorly understood and somewhat. Herein, we found that plant MIR156 regulates proliferation of intestinal cells both in vitro and in vivo. Continuous administration of a high plant miRNA diet or synthetic MIR156 elevated MIR156 levels and inhibited the Wnt/β-catenin signaling pathway in mouse intestine. Bioinformatics predictions and luciferase reporter assays indicated that MIR156 targets Wnt10b. In vitro, MIR156 suppressed proliferation by downregulating the Wnt10b protein and upregulating β-catenin phosphorylation in the porcine jejunum epithelial (IPEC-J2) cell line. Lithium chloride and an MIR156 inhibitor relieved this inhibition. This research is the first to demonstrate that plant MIR156 inhibits intestinal cell proliferation by targeting Wnt10b. More importantly, plant miRNAs may represent a new class of bioactive molecules that act as epigenetic regulators in humans and other animals.
A central core disease mutation in the Ca2+-binding site of skeletal muscle ryanodine receptor impairs single-channel regulation
Authors: Chirasani Venkat R. , Xu Le , Addis Hannah G. , Pasek Daniel A. , Dokholyan Nikolay V. , Meissner Gerhard , Yamaguchi Naohiro
Published: June 2019

Cryoelectron microscopy and mutational analyses have shown that type 1 ryanodine receptor (RyR1) amino acid residues RyR1-E3893, -E3967, and -T5001 are critical for Ca2+-mediated activation of skeletal muscle Ca2+ release channel. De novo missense mutation RyR1-Q3970K in the secondary binding sphere of Ca2+ was reported in association with central core disease (CCD) in a 2-yr-old boy. Here, we characterized recombinant RyR1-Q3970K mutant by cellular Ca2+ release measurements, single-channel recordings, and computational methods. Caffeine-induced Ca2+ release studies indicated that RyR1-Q3970K formed caffeine-sensitive, Ca2+-conducting channel in HEK293 cells. However, in single-channel recordings, RyR1-Q3970K displayed low Ca2+-dependent channel activity and greatly reduced activation by caffeine or ATP. A RyR1-Q3970E mutant corresponds to missense mutation RyR2-Q3925E associated with arrhythmogenic syndrome in cardiac muscle. RyR1-Q3970E also formed caffeine-induced Ca2+ release in HEK293 cells and exhibited low activity in the presence of the activating ligand Ca2+ but, in contrast to RyR1-Q3970K, was activated by ATP and caffeine in single-channel recordings. Computational analyses suggested distinct structural rearrangements in the secondary binding sphere of Ca2+ of the two mutants, whereas the interaction of Ca2+ with directly interacting RyR1 amino acid residues Glu3893, Glu3967, and Thr5001 was only minimally affected. We conclude that RyR1-Q3970 has a critical role in Ca2+-dependent activation of RyR1 and that a missense RyR1-Q3970K mutant may give rise to myopathy in skeletal muscle.
Transitional human alveolar type II epithelial cells suppress extracellular matrix and growth factor gene expression in lung fibroblasts
Authors: Correll Kelly A. , Edeen Karen E. , Zemans Rachel L. , Redente Elizabeth F. , Serban Karina A. , Curran-Everett Douglas , Edelman Benjamin L. , Mikels-Vigdal Amanda , Mason Robert J.
Published: June 2019

Epithelial-fibroblast interactions are thought to be very important in the adult lung in response to injury, but the specifics of these interactions are not well defined. We developed coculture systems to define the interactions of adult human alveolar epithelial cells with lung fibroblasts. Alveolar type II cells cultured on floating collagen gels reduced the expression of type 1 collagen (COL1A1) and α-smooth muscle actin (ACTA2) in fibroblasts. They also reduced fibroblast expression of hepatocyte growth factor (HGF), fibroblast growth factor 7 (FGF7, KGF), and FGF10. When type II cells were cultured at an air-liquid interface to maintain high levels of surfactant protein expression, this inhibitory activity was lost. When type II cells were cultured on collagen-coated tissue culture wells to reduce surfactant protein expression further and increase the expression of some type I cell markers, the epithelial cells suppressed transforming growth factor-β (TGF-β)-stimulated ACTA2 and connective tissue growth factor (CTGF) expression in lung fibroblasts. Our results suggest that transitional alveolar type II cells and likely type I cells but not fully differentiated type II cells inhibit matrix and growth factor expression in fibroblasts. These cells express markers of both type II cells and type I cells. This is probably a normal homeostatic mechanism to inhibit the fibrotic response in the resolution phase of wound healing. Defining how transitional type II cells convert activated fibroblasts into a quiescent state and inhibit the effects of TGF-β may provide another approach to limiting the development of fibrosis after alveolar injury.
Renal nerves and leukocyte infiltration in the kidney during salt-sensitive hypertension
Authors: Alsheikh Ammar J. , Lund Hayley , Dasinger John Henry , Abais-Battad Justine M. , Fehrenbach Daniel J. , Mattson David L.
Published: June 2019

Based on previous studies suggesting a role of renal nerves in renal inflammation, the present studies were performed to test the hypothesis that renal nerves mediate renal damage in Dahl salt-sensitive (SS) hypertension by increasing renal leukocyte infiltration. Experiments were performed in Dahl SS rats with bilateral renal denervation (RDN) and bilateral sham operation ( n = 10 or 11 per group) and with unilateral RDN and contralateral sham operation ( n = 10). After denervation, rats were switched from a low-salt 0.4% NaCl (LS) diet to a high-salt 4% NaCl (HS) diet and maintained on HS diet for 21 days. Bilateral RDN reduced the magnitude of hypertension assessed by radiotelemetry in Dahl SS rats compared with sham-operated rats (mean arterial pressure 140.9 ±4.8 mmHg and 159.7 ± 3.5 mmHg, respectively) and reduced proteinuria at day 21 of HS diet. However, assessment of renal leukocyte infiltration demonstrated no significant effect of bilateral RDN on the number of infiltrating leukocytes (RDN 3.6 ± 0.5 × 106 vs. sham operated 4.3 ± 0.3 × 106 CD45+ cells) or any of the subsets examined by flow cytometry. The unilateral RDN experiment showed no effect of RDN on the renal infiltration of leukocytes (RDN 6.5 ± 0.9 × 106 vs. sham operated 6.1 ± 1.1 × 106 CD45+ cells/kidney) or renal damage in RDN vs. sham-operated kidney after 21 days of HS diet. This work investigated the relationship between renal nerves and renal inflammation during Dahl SS hypertension. Contrary to our hypothesis, the results of this work suggest that immune cell infiltration in the kidney of Dahl SS rats is not mediated by the renal nerves.
Claudin-19 mediates the effects of NO on the paracellular pathway in thick ascending limbs
Authors: Monzon Casandra M. , Garvin Jeffrey L.
Published: June 2019

Claudins are a family of tight junction proteins that provide size and charge selectivity to solutes traversing the paracellular space. Thick ascending limbs (TALs) express numerous claudins, including claudin-19. Nitric oxide (NO), via cGMP, reduces dilution potentials in perfused TALs, a measure of paracellular permeability, but the role of claudin-19 is unknown. We hypothesized that claudin-19 mediates the effects of NO/cGMP on the paracellular pathway in TALs via increases in plasma membrane expression of this protein. We measured the effect of the NO donor spermine NONOate (SPM) on dilution potentials with and without blocking antibodies and plasma membrane expression of claudin-19. During the control period, the dilution potential was −18.2 ± 1.8 mV. After treatment with 200 μmol/l SPM, it was −14.7 ± 2.0 mV ( P < 0.04). In the presence of claudin-19 antibody, the dilution potential was −12.7 ± 2.1 mV. After SPM, it was −12.9 ± 2.4 mV, not significantly different. Claudin-19 antibody alone had no effect on dilution potentials. In the presence of Tamm-Horsfall protein antibody, SPM reduced the dilution potential from −9.7 ± 1.0 to −6.3 ± 1.1 mV ( P < 0.006). Dibutyryl-cGMP (500 µmol/l) reduced the dilution potential from −19.6 ± 2.6 to −17.2 ± 2.3 mV ( P < 0.002). Dibutyryl-cGMP increased expression of claudin-19 in the plasma membrane from 29.9 ± 3.8% to 65.9 ± 10.1% of total ( P < 0.011) but did not change total expression. We conclude that claudin-19 mediates the effects of the NO/cGMP signaling cascade on the paracellular pathway.
Effect of renal tubule-specific knockdown of the Na+/H+exchanger NHE3 in Akita diabetic mice
Authors: Onishi Akira , Fu Yiling , Darshi Manjula , Crespo-Masip Maria , Huang Winnie , Song Panai , Patel Rohit , Kim Young Chul , Nespoux Josselin , Freeman Brent , Soleimani Manoocher , Thomson Scott , Sharma Kumar , Vallon Volker
Published: June 2019

Na+/H+exchanger isoform 3 (NHE3) contributes to Na+/bicarbonate reabsorption and ammonium secretion in early proximal tubules. To determine its role in the diabetic kidney, type 1 diabetic Akita mice with tubular NHE3 knockdown [Pax8-Cre; NHE3-knockout (KO) mice] were generated. NHE3-KO mice had higher urine pH, more bicarbonaturia, and compensating increases in renal mRNA expression for genes associated with generation of ammonium, bicarbonate, and glucose (phosphoenolpyruvate carboxykinase) in proximal tubules and H+and ammonia secretion and glycolysis in distal tubules. This left blood pH and bicarbonate unaffected in nondiabetic and diabetic NHE3-KO versus wild-type mice but was associated with renal upregulation of proinflammatory markers. Higher renal phosphoenolpyruvate carboxykinase expression in NHE3-KO mice was associated with lower Na+-glucose cotransporter (SGLT)2 and higher SGLT1 expression, indicating a downward tubular shift in Na+and glucose reabsorption. NHE3-KO was associated with lesser kidney weight and glomerular filtration rate (GFR) independent of diabetes and prevented diabetes-associated albuminuria. NHE3-KO, however, did not attenuate hyperglycemia or prevent diabetes from increasing kidney weight and GFR. Higher renal gluconeogenesis may explain similar hyperglycemia despite lower SGLT2 expression and higher glucosuria in diabetic NHE3-KO versus wild-type mice; stronger SGLT1 engagement could have affected kidney weight and GFR responses. Chronic kidney disease in humans is associated with reduced urinary excretion of metabolites of branched-chain amino acids and the tricarboxylic acid cycle, a pattern mimicked in diabetic wild-type mice. This pattern was reversed in nondiabetic NHE3-KO mice, possibly reflecting branched-chain amino acids use for ammoniagenesis and tricarboxylic acid cycle upregulation to support formation of ammonia, bicarbonate, and glucose in proximal tubule. NHE3-KO, however, did not prevent the diabetes-induced urinary downregulation in these metabolites.
Temporal and spatial dynamics of spinal sensorimotor processing in an intersegmental cutaneous nociceptive reflex
Authors: White Jason M. , Lee Hyun Joon , Malone Patrick , DeWeerth Stephen P. , Tansey Keith E.
Published: June 2019

The cutaneus trunci muscle (CTM) reflex produces a skin “shrug” in response to pinch on a rat’s back through a three-part neural circuit: 1) A-fiber and C-fiber afferents in segmental dorsal cutaneous nerves (DCNs) from lumbar to cervical levels, 2) ascending propriospinal interneurons, and 3) the CTM motoneuron pool located at the cervicothoracic junction. We recorded neurograms from a CTM nerve branch in response to electrical stimulation. The pulse trains were delivered at multiple DCNs (T6–L1), on both sides of the midline, at two stimulus strengths (0.5 or 5 mA, to activate Aδ fibers or Aδ and C fibers, respectively) and four stimulation frequencies (1, 2, 5, or 10 Hz) for 20 s. We quantified both the temporal dynamics (i.e., latency, sensitization, habituation, and frequency dependence) and the spatial dynamics (spinal level) of the reflex. The evoked responses were time-windowed into Early, Mid, Late, and Ongoing phases, of which the Mid phase, between the Early (Aδ fiber mediated) and Late (C fiber mediated) phases, has not been previously identified. All phases of the response varied with stimulus strength, frequency, history, and DCN level/side stimulated. In addition, we observed nociceptive characteristics like C fiber-mediated sensitization (wind-up) and habituation. Finally, the range of latencies in the ipsilateral responses were not very large rostrocaudally, suggesting a myelinated neural path within the ipsilateral spinal cord for at least the A fiber-mediated Early-phase response. Overall, these results demonstrate that the CTM reflex shares the temporal dynamics in other nociceptive reflexes and exhibits spatial (segmental and lateral) dynamics not seen in those reflexes.

NEW & NOTEWORTHY We have physiologically studied an intersegmental reflex exploring detailed temporal, stimulus strength-based, stimulation history-dependent, lateral and segmental quantification of the reflex responses to cutaneous nociceptive stimulations. We found several physiological features in this reflex pathway, e.g., wind-up, latency changes, and somatotopic differences. These physiological observations allow us to understand how the anatomy of this reflex may be organized. We have also identified a new phase of this reflex, termed the “mid” response.
Contributions of optostatic and optokinetic cues to the perception of vertical
Authors: Niehof Nynke , Perdreau Florian , Koppen Mathieu , Medendorp W. Pieter
Published: June 2019

While it has been well established that optostatic and optokinetic cues contribute to the perception of vertical, it is unclear how the brain processes their combined presence with the nonvisual vestibular cues. Using a psychometric approach, we examined the percept of vertical in human participants ( n = 17) with their body and head upright, presented with a visual frame tilted at one of eight orientations (between ±45°, steps of 11.25°) or no frame, surrounded by an optokinetic roll-stimulus (velocity =  ±30°/s or stationary). Both cues demonstrate relatively independent biases on vertical perception, with a sinusoidal modulation by frame orientation of ~4° and a general shift of ~1–2° in the rotation direction of the optic flow. Variability was unaffected by frame orientation but was higher with than without optokinetic rotation. An optimal-observer model in which vestibular, optostatic, and optokinetic cues provide independent sources to vertical perception was unable to explain these data. In contrast, a model in which the optokinetic signal biases the internal representation of gravity, which is then optimally integrated with the optostatic cue, provided a good account, at the individual participant level. We conclude that optostatic and optokinetic cues interact differently with vestibular cues in the neural computations for vertical perception.

NEW & NOTEWORTHY Static and dynamic visual cues are known to bias the percept of vertical, but how they interact with vestibular cues remains to be established. Guided by an optimal-observer model, the present results suggest that optokinetic information is combined with vestibular information into a single, vestibular-optokinetic estimate, which is integrated with an optostatically derived estimate of vertical.
Repetitive doublet firing in human motoneurons: evidence for interaction between common synaptic drive and plateau potential in natural motor control
Authors: Kudina Lydia P. , Andreeva Regina E.
Published: June 2019

The firing behavior of spinal motoneurons (MNs) is a result of processing synaptic inputs by MN membrane properties, including plateau potentials, fundamentally explored in animals. However, there is much less data about a plateau potential role in human motor control. We explored human MN repetitive doublet firing during gentle isometric voluntary muscle contractions with the aim of revealing possible evidence for interaction between plateau potentials and common synaptic drive known as an important determinant of MN pool firing behavior. Single-motor unit (MU) repetitive firing of trapezius and triceps brachii was analyzed. Subjects were asked to recruit MUs capable of firing repetitive doublets. The analysis of interspike intervals (ISIs) of background firing of simultaneously recorded MUs showed that beyond doublet series ISIs varied, often in unison with significant correlation coefficients, demonstrating common synaptic drive. During doublet series, MUs showed persistent doublet ISIs (typically 4–7 ms) and a tendency to increase the number of doublets in series throughout the experiment. This was consistent with involvement of MN plateau potentials resulting in persistent delayed depolarization (underlying each doublet) and warm-up effect. Common synaptic drive “started” doublet series; probably both mechanisms controlled postdoublet ISIs. However, convincing effects of plateau potentials on MU firing behavior during single firing were not found. Thus our results suggest a plateau potential role in specifying the essential firing pattern, doubling, of some MUs rather than its effect on firing behavior of the MN pool, on the whole, during voluntary muscle contractions in humans.

NEW & NOTEWORTHY Properties of human motoneuron repetitive doublet firing were explored during voluntary muscle contractions. It was shown for the first time that these properties seem to be consistent with properties of both plateau potentials, resulting in persistent delayed depolarization (underlying each doublet) and common synaptic drive, starting this unusual firing; both mechanisms could probably control postdoublet intervals. A convincing effect of plateau potentials on motoneuron single-spike firing, despite doublet firing, was not found.
Evidence-Based Practice: Improving the Quality of Perinatal Care
Authors: Soll Roger F. , McGuire William
Published: June 2019

Background: For clinical research findings to improve the quality of care and outcomes for newborn infants and their families, they need to be implemented in policy and adopted in practice. Methods: We describe the principles of effective dissemination and implementation of research findings and highlight examples of collaborative quality improvement strategies to ensure that guidelines, protocols, policies and practices reflect research-informed evidence. Results: Passive dissemination of research findings is generally ineffective in driving change. Implementation strategies that use multi-faceted approaches acting on different barriers to change are better at driving improvements in the quality of care practices. These initiatives are increasingly embedded within regional, national and international networks of neonatal care centres that collaborate in conducting research, implementing its findings and auditing its uptake. Examples of successful network-based collaborative quality improvement programmes include efforts to increase use of evidence-based strategies to prevent hospital-acquired bloodstream infections, optimise surfactant replacement for preterm infants, reduce the incidence of bronchopulmonary dysplasia, improve antibiotic stewardship and promote the use of human milk to prevent necrotising enterocolitis in very-low-birth-weight infants. Conclusions: Effective dissemination and implementation are essential for research evidence to improve quality of care and outcomes for newborn infants and their families. Multifaceted initiatives within network-based collaborative quality improvement programmes facilitate continuous audit and benchmarking cycles to ensure equity of access to evidence-based care practices.
Rapid and Efficient Differentiation of Rodent Neural Stem Cells into Oligodendrocyte Progenitor Cells
Authors: Li Shen , Zheng Jiao , Chai Linlin , Lin Mengsi , Zeng Ruocheng , Lu Jianhong , Bian Jing
Published: June 2019

Oligodendrocyte progenitor cells (OPCs) may have beneficial effects in cell replacement therapy of neurodegenerative disease owing to their unique capability to differentiate into myelinogenic oligodendrocytes (OLs) in response to extrinsic signals. Therefore, it is of significance to establish an effective differentiation methodology to generate highly pure OPCs and OLs from some easily accessible stem cell sources. To achieve this goal, in this study, we present a rapid and efficient protocol for oligodendroglial lineage differentiation from mouse neural stem cells (NSCs), rat NSCs, or mouse embryonic stem cell-derived neuroepithelial stem cells. In a defined culture medium containing Smoothened Agonist, basic fibroblast growth factor, and platelet-derived growth factor-AA, OPCs could be generated from the above stem cells over a time course of 4–6 days, achieving a cell purity as high as ∼90%. In particular, these derived OPCs showed high expandability and could further differentiate into myelin basic protein-positive OLs within 3 days or alternatively into glial fibrillary acidic protein-positive astrocytes within 7 days. Furthermore, transplantation of rodent NSC-derived OPCs into injured spinal cord indicated that it is a feasible strategy to treat spinal cord injury. Our results suggest a differentiation strategy for robust production of OPCs and OLs from rodent stem cells, which could provide an abundant OPC source for spinal cord injury.
Pharmacokinetics of Benzylpenicillin (Penicillin G) during Prolonged Intermittent Renal Replacement Therapy
Authors: Cheng Vesa , Rawlins Matthew , Chang Tim , Fox Emma , Dyer John , Allen Chris , Litton Edward , Page Michael M. , Hoad Kirsten , Roberts Jason A.
Published: June 2019

Prolonged intermittent renal replacement therapy (PIRRT) is an increasingly adopted method of renal replacement in critically ill patients. Like continuous renal replacement therapy, PIRRT can alter the pharmacokinetics (PK) of many drugs. In this setting, dosing data for antibiotics like benzylpenicillin are lacking. In order to enable clinicians to prescribe benzylpenicillin safely and effectively, knowledge of the effects of PIRRT on the plasma PK of benzylpenicillin is required. Herein, we describe the PK of benzylpenicillin in 2 critically ill patients on PIRRT for the treatment of penicillin-susceptible Staphylococcus aureus bacteremia complicated by infective endocarditis. Blood samples were taken for each patient taken over dosing periods during PIRRT and off PIRRT. Two-compartment PK models described significant differences in the mean clearance of benzylpenicillin with and without PIRRT (6.61 vs. 3.04 L/h respectively). We would suggest a benzylpenicillin dose of 1,800 mg (3 million units) every 6-h during PIRRT therapy as sufficient to attain PK/pharmacodynamic target.
To Better Understand the Link between Psychopathy and Antisocial Behavior: Moderation by Dispositional Mindfulness
Authors: Bronchain Jonathan , Monié Benoit , Becquié Sophie , Chabrol Henri , Raynal Patrick
Published: June 2019

Background: Dispositional mindfulness deficits and psychopathic personality traits have been shown to be closely associated and independent predictors of antisocial behaviors (AB) in young adults. However, the interaction effects of these 2 factors have not yet been explored. The aim of this study was to examine the contribution of dispositional mindfulness and psychopathic traits to ABs in a college student sample. Methods: Participants were 1,572 students from different French universities who completed self-report questionnaires. Regression analyses were conducted in order to test a moderation model between psychopathic traits and AB. Results: Moderation analyses revealed that dispositional mindfulness interacted with psychopathic personality traits in predicting AB. In males with high levels of dispositional mindfulness, as psychopathic traits increased, AB increased less than in males with low levels of dispositional mindfulness. Conclusions: The present study suggests possible implications for prevention and treatment of AB among non-clinical young adults with relatively high psychopathic traits.
Stent Retriever Thrombectomy Potentially Increases the Recanalization Rate, Improves Clinical Outcome, and Decreases Mortality in Acute Basilar Occlusion: A Systematic Review and Meta-Analysis
Authors: Shu Liang , Salehi Ravesh Mona , Jansen Olav , Jensen-Kondering Ulf
Published: June 2019

Background: Acute basilar artery occlusion (BAO) is a devastating condition if untreated. The optimal treatment strategy, however, is unknown. Historically, interventional approaches have been favored over intravenous thrombolysis (IVT), although this is not supported by good evidence. The aim of this systematic review and meta-analysis was to summarize and compare the results for treatment modalities of BAO, namely, IVT and interventional stent retriever thrombectomy (SRT). Methods: Studies on IVT and SRT in BAO were systematically searched. Successful recanalization (TICI ≥2b), favorable clinical outcome (modified Rankin Scale score ≤2), mortality, and the rate of symptomatic intracranial hemorrhage (SICH) were the target parameters. Only studies with ≥15 patients were included. IVT prior to SRT was allowed. Studies were excluded (1) if >1 thrombectomy device was used in >50% of the patients and (2) when data on outcome or treatment could not be parsed (e.g. registries). Odds ratios (ORs) were calculated using Mantel-Haenszel risk ratio estimation. Results are given as OR and the 95% confidence interval (95% CI). The χ2 test was used to compare the outcome parameters clinical outcome, recanalization, mortality, and SICH. Results: A total of 17 studies (4 on IVT and 13 on SRT) with a total of 672 patients (IVT, n = 314; SRT, n = 358) were identified. Cumulatively, we found a highly significantly improved clinical outcome (43 vs. 31%, p = 0.004, OR [95% CI] = 1.66 [1.21, 2.76]), increased recanalization rate (88 vs. 60%, p < 0.00001, OR [95% CI] = 3.99 [2.73, 5.84]), and decreased mortality (26 vs. 41%, p = 0.0004, OR [95% CI] = 1.86 [1.33, 2.61]), as well as an equal rate of SICH (5 vs. 7%, p = 0.15, OR [95% CI] = 1.68 [0.82, 3.43]), in patients treated with SRT compared to those treated with IVT alone. Conclusions: The data from this meta-analysis suggest a possible superiority of SRT over IVT, pending positive results of randomized controlled trials. According to international recommendations, patients with BAO should preferentially be treated with SRT; if no contraindications exist, IVT should not be withheld.
The Promise of Selecting Individuals from the Extremes of Exposure in the Analysis of Gene-Physical Activity Interactions
Authors: Osazuwa-Peters Oyomoare L. , Schwander Karen , Waken R.J. , de las Fuentes Lisa , Kilpeläinen Tuomas O. , Loos Ruth J.F. , Racette Susan B. , Sung Yun Ju , Rao D.C.
Published: June 2019

Background: Dichotomization using the lower quartile as cutoff is commonly used for harmonizing heterogeneous physical activity (PA) measures across studies. However, this may create misclassification and hinder discovery of new loci. Objectives: This study aimed to evaluate the performance of selecting individuals from the extremes of the exposure (SIEE) as an alternative approach to reduce such misclassification. Method: For systolic and diastolic blood pressure in the Framingham Heart Study, we performed a genome-wide association study with gene-PA interaction analysis using three PA variables derived by SIEE and two other dichotomization approaches. We compared number of loci detected and overlap with loci found using a quantitative PA variable. In addition, we performed simulation studies to assess bias, false discovery rates (FDR), and power under synergistic/antagonistic genetic effects in exposure groups and in the presence/absence of measurement error. Results: In the empirical analysis, SIEE’s performance was neither the best nor the worst. In most simulation scenarios, SIEE was consistently outperformed in terms of FDR and power. Particularly, in a scenario characterized by antagonistic effects and measurement error, SIEE had the least bias and highest power. Conclusion: SIEE’s promise appears limited to detecting loci with antagonistic effects. Further studies are needed to evaluate SIEE’s full advantage.
Socioeconomic Inequalities in the Rise of Adult Obesity: A Time-Trend Analysis of National Examination Data from Germany, 1990–2011
Authors: Hoebel Jens , Kuntz Benjamin , Kroll Lars E. , Schienkiewitz Anja , Finger Jonas D. , Lange Cornelia , Lampert Thomas
Published: June 2019

Objective: Despite extensive study of the obesity epidemic, research on whether obesity has risen faster in lower or in higher socioeconomic groups is inconsistent. This study examined secular trends in obesity prevalence by socioeconomic position and the resulting obesity inequalities in the German adult population. Methods: Data were drawn from three national examination surveys conducted in 1990–1992, 1997–1999 and 2008–2011 (n = 18,541; age range: 25–69 years). Obesity was defined by a body mass index ≥30 kg/m2 using standardised measurements of body height and weight. Education and equivalised household disposable income were used as indicators of socioeconomic position. Time trends in socioeconomic inequalities in obesity were examined using linear probability and log-binomial regression models. Results: In each survey period, the highest socioeconomic groups had the lowest prevalence of obesity. The low and medium socioeconomic groups showed increases in obesity prevalence, whereas no such trend was observed in the high socioeconomic groups. Absolute inequalities in obesity by income increased by an average of 0.53 percentage points per year (95% confidence interval [CI] 0.01–1.05, p = 0.047) among men and 0.47 percentage points per year (95% CI 0.05–0.90, p = 0.029) among women. Absolute inequalities in obesity by education increased on average by 0.64 percentage points per year (95% CI 0.19–1.08, p = 0.005) among women but not among men (0.33 percentage points, 95% CI –0.27 to 0.92, p = 0.283). Conclusions: These findings suggest a widening obesity gap between the top and the bottom of the socioeconomic spectrum. This has the potential to have adverse consequences for population health and health inequalities in coming decades. Interventions that are effective in preventing and reducing obesity in socially disadvantaged groups are needed.
Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy
Authors: Donaldson Malcolm , Kriström Berit  , Ankarberg-Lindgren Carina , Verlinde Siska , van Alfen-van der Velden Janiëlle , Gawlik Aneta , van Gelder Marleen M.H.J. , Sas Theo ,   on behalf of the European Society for Paediatric Endocrinology Turner Syndrome Working Group
Published: June 2019

Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17β-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17β-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions.
Histological Evidence of Diabetic Kidney Disease Precede Clinical Diagnosis
Authors: Comai Giorgia , Malvi Deborah , Angeletti Andrea , Vasuri Francesco , Valente Sabrina , Ambrosi Francesca , Capelli Irene , Ravaioli Matteo , Pasquinelli Gianandrea , D’Errico Antonietta , Fornoni Alessia , La Manna Gaetano
Published: June 2019

Background: In the absence of a histological diagnosis, persistent albuminuria is globally accepted as the main diagnostic criteria for diabetic kidney disease (DKD). Methods: In the present retrospective study, we evaluated data from an Italian cohort of 42 deceased diabetic donors (mainly with type 2 diabetes). Using the kidney biopsies obtained at the time of donation to evaluate single or double allocation based on Karpinski score, we determined the prevalence of histological lesions attributable to diabetes. Results: All 42 donors presented with proteinuria in the normal range and an estimated glomerular filtration rate (eGFR) (chronic kidney disease [CKD]-EPI) >60 mL/min/1.73 m2. A kidney biopsy was available for 36 patients; of these, one was not interpretable and 32 showed histopathological lesions consistent with DKD and encompassing all histological classes. Thus, we found a relatively high proportion of histologically proven DKD that had been clinically undiagnosed, as none of the patient had significant proteinuria and eGFR <60 mL/min/1.73 m2. Conclusions: The data we present here support the need to implement routine kidney biopsies in normoalbuminuric diabetic subjects in the early stages of CKD. Such strategy may help to improve risk stratification in diabetic patients and guide therapeutic decisions during the early stages of the disease.
Multiple Stakeholder Views on Data Sharing in a Biobank in an Integrated Healthcare Delivery System: Implications for Biobank Governance
Authors: Tai Caroline G. , Harris-Wai Julie , Schaefer Catherine , Liljestrand Petra , Somkin Carol P.
Published: June 2019

Background: Beginning in 2005, researchers at Kaiser Permanente Northern California (KPNC) Division of Research developed the Research Program on Genes, Environment, and Health (RPGEH), a research resource of linked biospecimens, health surveys, and electronic health records on more than 200,000 adult KPNC members. This study examined multiple stakeholders’ values and preferences regarding protection of participants’ privacy and wide sharing of participant data by RPGEH. Methods: We conducted 45 semi-structured interviews in person or via phone and two focus groups with seven stakeholder groups, including RPGEH participants and decliners who are KPNC members, KPNC research scientists, external scientists, leadership, Human Subjects Research Protection Program staff, and RPGEH Community Advisory Panel members. Results: Three major themes emerged related to: (1) perceived individual and social harms associated with data sharing; (2) concerns to address when governing access to RPGEH data; and (3) impact of a blurred boundary between research and clinical care in the context of biobanking. Conclusions: The study results were considered in the development of RPGEH data governance and motivated the inclusion of KPNC Community Advisory Panel members and ELSI experts on committees that evaluate data access proposals. Our findings can help inform other biobanks going through similar processes developing data sharing and access policies.
Tophaceous Gout of the Middle Ear: Case Reports and Review of the Literature
Authors: Saliba Joe , Sakano Hitomi , Friedman Rick A. , Harris Jeffrey P.
Published: June 2019

Tophaceous gout of the middle ear is a rare occurrence that presents as a granular white-colored mass. It is frequently misdiagnosed as cholesteatoma or tympanosclerosis in patients who otherwise may not manifest any clinical or biochemical signs of gout. While uncommon, it can lead to clinically significant disease such as conductive hearing loss. The present report describes 2 cases of middle ear gouty tophi initially mistaken for another entity. Both patients underwent surgery, and the diagnosis of gout was revealed after final histopathological analysis. A review of the literature is also presented.