bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering the expression system for Komagataella phaffii (Pichia pastoris): an attempt to develop a methanol-free expression system
Authors: Takagi Shinobu , Tsutsumi Noriko , Terui Yuji , Kong XiangYu , Yurimoto Hiroya , Sakai Yasuyoshi
Published: August 2019

The construction of a methanol-free expression system of Komagataella phaffii (Pichia pastoris) was attempted by engineering a strong methanol-inducible DAS1 promoter using Citrobacter braakii phytase production as a model case. Constitutive expression of KpTRM1, formerly PRM1—a positive transcription regulator for methanol-utilization (MUT) genes of K. phaffii,was demonstrated to produce phytase without addition of methanol, especially when a DAS1 promoter was used but not an AOX1 promoter. Another positive regulator, Mxr1p, did not have the same effect on the DAS1 promoter, while it was more effective than KpTrmp1 on the AOX1 promoter. Removing a potential upstream repression sequence (URS) and multiplying UAS1DAS1 in the DAS1 promoter significantly enhanced the yield of C. braakii phytase with methanol-feeding, which surpassed the native AOX1 promoter by 80%. However, multiplying UAS1DAS1 did not affect the yield of methanol-free expression by constitutive KpTrm1p. Another important region to enhance the effect of KpTrm1p under a methanol-free condition was identified in the DAS1 promoter, and was termed ESPDAS1. Nevertheless, methanol-free phytase production using an engineered DAS1 promoter outperformed phytase production with the GAP promoter by 25%. Difference in regulation by known transcription factors on the AOX1 promoter and the DAS1 promoter was also illustrated.
Missing in Analysis: Women in Foreign Policy–Making
Authors: Smith Karen E
Published: August 2019

Foreign policy analysis (FPA) opens the “black box” of the state and provides explanations of how and why foreign policy decisions are made, which puts individuals and groups (from committees to ministries) at the center of analysis. Yet the sex of the decision-maker and the gendered nature of the decision-making process have generally been left out of the picture. FPA has not addressed questions regarding the influence of women in foreign policy decision-making processes or the effects of gender norms on decision-making; indeed, FPA appears to be almost entirely gender-free. This article argues that “gendering” FPA is long overdue and that incorporating gender into FPA frameworks can provide a richer and more nuanced picture of foreign policy–making.
Evidence of Extensive Intraspecific Noncoding Reshuffling in a 169-kb Mitochondrial Genome of a Basidiomycetous Fungus
Authors: Lee Hsin-Han , Ke Huei-Mien , Lin Chan-Yi Ivy , Lee Tracy J , Chung Chia-Lin , Tsai Isheng J
Published: August 2019

Comparative genomics of fungal mitochondrial genomes (mitogenomes) have revealed a remarkable pattern of rearrangement between and within major phyla owing to horizontal gene transfer and recombination. The role of recombination was exemplified at a finer evolutionary time scale in basidiomycetes group of fungi as they display a diversity of mitochondrial DNA inheritance patterns. Here, we assembled mitogenomes of six species from the Hymenochaetales order of basidiomycetes and examined 59 mitogenomes from 2 genetic lineages of Phellinus noxius. Gene order is largely collinear, while intergene regions are major determinants of mitogenome size variation. Substantial sequence divergence was found in shared introns consistent with high horizontal gene transfer frequency observed in yeasts, but we also identified a rare case where an intron was retained in five species since speciation. In contrast to the hyperdiversity observed in nuclear genomes of Phellinus noxius, mitogenomes’ intraspecific polymorphisms at protein-coding sequences are extremely low. Phylogeny network based on introns revealed turnover as well as exchange of introns between two lineages. Strikingly, some strains harbor a mosaic origin of introns from both lineages. Analysis of intergenic sequence indicated substantial differences between and within lineages, and an expansion may be ongoing as a result of exchange between distal intergenes. These findings suggest that the evolution in mitochondrial DNAs is usually lineage specific but chimeric mitotypes are frequently observed, thus capturing the possible evolutionary processes shaping mitogenomes in a basidiomycete. The large mitogenome sizes reported in various basidiomycetes appear to be a result of interspecific reshuffling of intergenes.
Over 1000 genetic loci influencing blood pressure with multiple systems and tissues implicated
Authors: Cabrera Claudia P , Ng Fu Liang , Nicholls Hannah L , Gupta Ajay , Barnes Michael R , Munroe Patricia B , Caulfield Mark J
Published: August 2019

High blood pressure (BP) remains the major heritable and modifiable risk factor for cardiovascular disease. Persistent high BP, or hypertension, is a complex trait with both genetic and environmental interactions. Despite swift advances in genomics, translating new discoveries to further our understanding of the underlying molecular mechanisms remains a challenge. More than 500 loci implicated in the regulation of BP have been revealed by genome-wide association studies (GWAS) in 2018 alone, taking the total number of BP genetic loci to over 1000. Even with the large number of loci now associated to BP, the genetic variance explained by all loci together remains low (~5.7%). These genetic associations have elucidated mechanisms and pathways regulating BP, highlighting potential new therapeutic and drug repurposing targets. A large proportion of the BP loci were discovered and reported simultaneously by multiple research groups, creating a knowledge gap, where the reported loci to date have not been investigated in a harmonious way. Here, we review the BP-associated genetic variants reported across GWAS studies and investigate their potential impact on the biological systems using in silico enrichment analyses for pathways, tissues, gene ontology and genetic pleiotropy.
Optimizing Egg Recovery From Wild Northern Corn Rootworm Beetles (Coleoptera: Chrysomelidae)
Authors: Pereira Adriano E , Ludwick Dalton C , Barry Julie , Meinke Lance J , Moellenbeck Daniel J , Ellersieck Mark R , Reinders Jordan D , Geisert Ryan W , Hyte Keiran , Ernwall Amanda , Paddock Kyle J , Hibbard Bruce E
Published: August 2019

The northern corn rootworm, Diabrotica barberi Smith & Lawrence (Coleoptera: Chrysomelidae), is one of the most important insect pests in the U.S. Corn Belt. Efforts to obtain eggs from wild northern corn rootworm populations using techniques developed for other rootworm species have been unsuccessful due to lack of oviposition. In 2016, we evaluated four oviposition media in choice tests within each of three female densities in 30.5 × 30.5 × 30.5 cm BugDorm cages. The number of eggs laid per female was significantly affected by female density and the interaction of female density × oviposition media, but oviposition was relatively poor in all oviposition media (1.2 eggs per female when averaging the three female densities and all oviposition media). Single females were also evaluated in nonchoice assays in 6 cm × 6 cm × 8 cm clear plastic boxes and averaged up to 108 eggs per female depending on the oviposition media. In 2017, the cumulative number of eggs laid per female in boxes with one female was not significantly different from the number of eggs laid per female in boxes with 3 females. In 2018, the cumulative number of eggs laid per female was not significantly different between female densities of 1, 3, 5, or 10 females per box. Total egg production per box therefore increased as female density increased. More than 27,000 wild northern corn rootworm eggs were collected from just 190 females when collected relatively early in the field season. We now have an efficient and robust system for obtaining eggs from wild northern corn rootworm females.
A Codling Moth (Lepidoptera: Tortricidae) Kairomonal Lure Is Marginally Effective at Decreasing Fruit Damage in Apple Trees Outside of Orchard Settings
Authors: Jaffe Benjamin D , Landolt Peter J
Published: August 2019

Codling moth, Cydia pomonella (L.), is a significant pest of pome fruits and walnuts worldwide. Recently, a three-chemical kairomonal lure, comprised of pear ester, acetic acid, and n-butyl sulfide, was successfully used as an attractant in a mass-trapping scheme to reduce fruit damage in commercial apple orchards. In this study, we tested whether this same attractant could be used outside of an orchard setting to decrease fruit damage in isolated, unmanaged apple (Malus spp.) (Rosales: Rosaceae) trees. Traps containing the lures were placed in trees before the first codling moth flight and maintained throughout the summer. We found that while the traps statistically reduced the percent of apples damaged near the trap, the effect was smaller than expected and limited to areas near the trap. It is currently unclear, but site-specific effects (e.g., host type, apple density, codling moth source) may be important factors in the efficacy of management tools in these systems. While kairomone-based trapping could be a practical and feasible management tool in individual trees outside of orchards, more work needs to be done to understand the limitations of this method.
Resistance of Fruits From a Mandarin Cultivar to Feeding by Fork-Tailed Bush Katydids
Authors: Cass Bodil N , Grafton-Cardwell Elizabeth E , Rosenheim Jay A
Published: August 2019

Plants use a variety of mechanisms to defend against herbivore damage, each with different consequences for agricultural production. Crops relying on tolerance strategies may need different pest management approaches versus those relying on resistance strategies. Previous work suggested that densities of fork-tailed bush katydids (Scudderia furcata Brunner von Wattenwyl [Orthoptera: Tettigoniidae]) that generated substantial scarring on cultivars of sweet oranges (Citrus sinensis, (L.) Osbeck [Sapindales: Rutaceae]) produced only low levels of scarring on cultivars of Citrus reticulata Blanco mandarins. We used field experiments in representative cultivars of these species to test non-mutually exclusive hypotheses regarding the mechanisms underlying this observation: 1) katydids are averse to feeding on mandarin fruits, 2) damaged mandarin fruits preferentially abscise, 3) damaged mandarin fruit tissue recovers during development, and 4) katydid scars on mandarins have a different morphology that may result in misclassification. We found strong support for the first hypothesis, demonstrating that katydids reject opportunities to feed on C. reticulata fruit. Instead of chewing deep holes in the fruit, as was commonly observed for C. sinensis, the katydids only scratched the surface of the C. reticulata fruits. The hypotheses of preferential abscission of damaged fruits and of recovery of damaged tissue were not supported. The low incidence of damage to the mandarins prevented a comprehensive assessment of the scar morphology; however, at harvest, the superficial cuts in C. reticulata were not easily distinguishable from background damage. This indicates that in contrast to C. sinensis, C. reticulata has substantial natural resistance to fork-tailed bush katydids making them a non-pest in this crop.
Creativity at the Edge of Chaos: Theopoetics in a Blazing World
Authors: Walton Heather
Published: August 2019

Theopoetics is a diverse movement in which many contrasting understanding of poetics, and the sacred, are articulated. Although there is no essence or core to the theopoetic project, theopoetic practitioners appear willing to sustain a common space for conversation and their work displays a common celebration of creative ways for reimagining the divine. However, creativity itself is rarely interrogated within theopoetics. Nor is the ambiguity of creative making addressed. This article explores this significant but neglected topic in an attempt to generate further theopoetic reflection on the ambivalence of creativity in relation to both human and divine ‘making’. Starting with conversations between Richard Kearney and Catherine Keller, discussions are extended through an engagement with Siri Hustvedt’s works of art criticism and her novel The Blazing World. Through Husdtvedt’s representations of ‘the woman artist’ we are encouraged to move beyond hygienic understandings of creativity and acknowledge the ethical and theological ambiguity of this key concept within theopoetics.
Jets, bubbles, and heat pumps in galaxy clusters
Authors: Chen Yi-Hao , Heinz Sebastian , Enßlin Torsten A
Published: August 2019

Feedback from active galactic nucleus (AGN) jets has been proposed to counteract the catastrophic cooling in many galaxy clusters. However, it is still unclear which physical processes are acting to couple the energy from the bi-directional jets to the intra-cluster medium (ICM). We study the long-term evolution of rising bubbles that were inflated by AGN jets using magnetohydrodynamic simulations. In the wake of the rising bubbles, a significant amount of low-entropy gas is brought into contact with the hot cluster gas. We assess the energy budget of the uplifted gas and find it comparable to the total energy injected by the jets. Although our simulation does not include explicit thermal conduction, we find that, for reasonable assumptions about the conduction coefficient, the rate is fast enough that much of the uplifted gas may be thermalized before it sinks back to the core. Thus, we propose that the AGN can act like a geothermal heat pump to move low-entropy gas from the cluster core to the heat reservoir and will be able to heat the inner cluster more efficiently than would be possible by direct energy transfer from jets alone. We show that the maximum efficiency of this mechanism, i.e. the ratio between the conductive thermal energy and the work needed to lift the gas, ξmax, can exceed 100 per cent. While ξ < ξmax in realistic scenarios, AGN-induced thermal conduction has the potential to significantly increase the efficiency with which AGN can heat cool-core clusters and transform the bursty AGN activities into a smoother and enduring heating process.
The first maps of κd – the dust mass absorption coefficient – in nearby galaxies, with DustPedia
Authors: Clark C J R , De Vis P , Baes M , Bianchi S , Casasola V , Cassarà L P , Davies J I , Dobbels W , Lianou S , De Looze I , Evans R , Galametz M , Galliano F , Jones A P , Madden S C , Mosenkov A V , Verstocken S , Viaene S , Xilouris E M , Ysard N
Published: August 2019

The dust mass absorption coefficient, κd is the conversion function used to infer physical dust masses from observations of dust emission. However, it is notoriously poorly constrained, and it is highly uncertain how it varies, either between or within galaxies. Here we present the results of a proof-of-concept study, using the DustPedia data for two nearby face-on spiral galaxies M 74 (NGC 628) and M 83 (NGC 5236), to create the first ever maps of κd in galaxies. We determine κd using an empirical method that exploits the fact that the dust-to-metals ratio of the interstellar medium is constrained by direct measurements of the depletion of gas-phase metals. We apply this method pixel-by-pixel within M 74 and M 83, to create maps of κd. We also demonstrate a novel method of producing metallicity maps for galaxies with irregularly sampled measurements, using the machine learning technique of Gaussian process regression. We find strong evidence for significant variation in κd. We find values of κd at 500 $\mu$m spanning the range 0.11–0.25 ${\rm m^{2}\, kg^{-1}}$ in M 74, and 0.15–0.80 ${\rm m^{2}\, kg^{-1}}$ in M 83. Surprisingly, we find that κd shows a distinct inverse correlation with the local density of the interstellar medium. This inverse correlation is the opposite of what is predicted by standard dust models. However, we find this relationship to be robust against a large range of changes to our method – only the adoption of unphysical or highly unusual assumptions would be able to suppress it.
The role of insulin-like growth factor 2 receptor-mediated homeobox gene expression in human placental apoptosis, and its implications in idiopathic fetal growth restriction
Authors: Harris Lynda K , Pantham Priyadarshini , Yong Hannah E J , Pratt Anita , Borg Anthony J , Crocker Ian , Westwood Melissa , Aplin John , Kalionis Bill , Murthi Padma
Published: August 2019

Fetal growth restriction (FGR) is caused by poor placental development and function early in gestation. It is well known that placentas from women with FGR exhibit reduced cell growth, elevated levels of apoptosis and perturbed expression of the growth factors, cytokines and the homeobox gene family of transcription factors. Previous studies have reported that insulin-like growth factor-2 (IGF2) interacts with its receptor-2 (IGF2R) to regulate villous trophoblast survival and apoptosis. In this study, we hypothesized that human placental IGF2R-mediated homeobox gene expression is altered in FGR and contributes to abnormal trophoblast function. This study was designed to determine the association between IGF2R, homeobox gene expression and cell survival in pregnancies affected by FGR. Third trimester placentas were collected from FGR-affected pregnancies (n = 29) and gestation matched with control pregnancies (n = 30). Functional analyses were then performed in vitro using term placental explants (n = 4) and BeWo trophoblast cells. mRNA expression was determined by real-time PCR, while protein expression was examined by immunoblotting and immunohistochemistry. siRNA transfection was used to silence IGF2R expression in placental explants and the BeWo cell-line. cDNA arrays were used to screen for downstream targets of IGF2R, specifically homeobox gene transcription factors and apoptosis-related genes. Functional effects of silencing IGF2R were then verified by β-hCG ELISA, caspase activity assays and a real-time electrical cell-impedance assay for differentiation, apoptosis and cell growth potential, respectively. IGF2R expression was significantly decreased in placentas from pregnancies complicated by idiopathic FGR (P < 0.05 versus control). siRNA-mediated IGF2R knockdown in term placental explants and the trophoblast cell line BeWo resulted in altered expression of homeobox gene transcription factors, including increased expression of distal-less homeobox gene 5 (DLX5), and decreased expression of H2.0-Like Homeobox 1 (HLX) (P < 0.05 versus control). Knockdown of IGF2R transcription increased the expression and activity of caspase-6 and caspase-8 in placental explants, decreased BeWo proliferation and increased BeWo differentiation (all P < 0.05 compared to respective controls). This is the first study linking IGF2R placental expression with changes in the expression of homeobox genes that control cellular signalling pathways responsible for increased trophoblast cell apoptosis, which is a characteristic feature of FGR.
The Alphabet and its Legacy
Authors: Richey Madadh
Published: August 2019

The alphabet employed by the Phoenicians was the inheritor of a long tradition of alphabetic writing and was itself adapted for use throughout the Mediterranean basin by numerous populations speaking many languages. The present contribution traces the origins of the alphabet in Sinai and the Levant before discussing different alphabetic standardizations in Ugarit and Phoenician Tyre. The complex adaptation of the latter for representation of the Greek language is described in detail, then some brief attention is given to likely—Etruscan and other Italic alphabets—and possible (Iberian and Berber) descendants of the Phoenician alphabet. Finally, it is stressed that current research does not view the Phoenician and other alphabets as inherently simpler, more easily learned, or more democratic than other writing systems. The Phoenician alphabet remains, nevertheless, an impressive technological development worthy, especially by virtue of its generative power, of detailed study ranging from paleographic and orthographic specifications to social and political contextualization.
Social Equity in Public Administration: A Call to Action
Authors: Blessett Brandi , Dodge Jennifer , Edmond Beverly , Goerdel Holly T , Gooden Susan T , Headley Andrea M , Riccucci Norma M , Williams Brian N
Published: August 2019

This article presents a “Call to Action” Social Equity Manifesto developed at the Minnowbrook at 50 conference. The Social Equity Manifesto identifies several critical areas of emphasis that can help move toward the achievement of social equity in the research, teaching, and practice of public administration. Regarding research, we discuss the presence of social equity manuscripts in PAR, JPART, and ATP. Interestingly, the coverage of class inequality is low across all three journals. However, a clear research strength is the plurality of methodological and theoretical approaches. In terms of teaching, all of the NASPAA social equity award winning public affairs programs in the United States offer multiple courses that provide intentional coverage of social equity. With respect to practice in the United States, inequities exist across multiple policy areas. Programs and policies ranging from nondiscrimination to diversity management are discussed. In essence, exposing students to social equity perspectives within the context of public administration curricula can make PA graduates more responsive to the needs of all people.
ISO 4037:2019 VALIDATION OF RADIATION QUALITIES BY MEANS OF HALF-VALUE LAYER AND HP(10) DOSIMETRY
Authors: Bandalo V , Greiter M B , Brönner J , Hoedlmoser H
Published: August 2019

Radiation qualities were characterised and validated at the fully automated X-ray calibration facility of the Individual Monitoring Service at Helmholtz Zentrum München by using half-value layer and Hp(10) dosimetry approaches specified in the updated ISO 4037:2019 standard. As the ISO 4037 contains a somewhat vague description of the half-value layer procedure, we extended it to be more constrained and thus less subjective in its implementation. We specify both the measurement and data analysis steps performed in order to provide reproducible half-value layer results and compare the results with the Hp(10) dosimetry-based validation approach specified in the ISO 4037 as an alternative for field validation. Finally, we discuss the implications of our results and the extended procedure on validation and the recent changes to the ISO 4037.
APLNR is involved in ATRA‐induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K‐Akt‐mTOR signaling
Authors: Liu Yi , Liu Qingluan , Chen Shumin , Liu Yijun , Huang Yumei , Chen Pan , Li Xiayu , Gao Ge , Xu Keqian , Fan Songqing , Zeng Zhaoyang , Xiong Wei , Tan Ming , Li Guiyuan , Zhang Wenling
Published: August 2019

The apelin receptor (APLNR) is a GPCR involved in many pathophysiological processes; however, the correlation between APLNR expression and nasopharyngeal carcinoma (NPC) has not been reported. In this study, we used cDNA microarray data to determine APLNR expression levels in NPC tissues. We found that APLNR expression was reduced in NPC tissues compared with noncancerous nasopharyngeal epithelial tissues. Subsequently, a large‐scale sample of 1015 tissues was used to validate this discovery and explore the relationship between APLNR expression and prognosis of NPC. Expression levels of APLNR in NPC tissues were indeed down‐regulated. Furthermore, positive expression of APLNR in NPC predicted a better prognosis (disease‐free survival: P = 0.001; overall survival: P < 0.001). Moreover, ingenuity pathway analysis revealed that an indirect interaction existed between APLNR and retinoic acid (RA) in the cancer regulatory network. Consistently, after treatment with all‐trans‐RA (ATRA), we found that APLNR was significantly up‐regulated in NPC cell lines (5‐8F and HNE1), and proliferation of NPC cells was inhibited. Cell cycle arrest occurred in the G0/G1 phase. In contrast, knockdown of APLNR diminished ATRA‐induced growth inhibition of NPC cells. In addition, we surprisingly found that APLNR also played an important role in migration and invasion of NPC. Wound‐healing and Transwell assays revealed that APLNR overexpression led to reduced migratory and invasive properties in 2 NPC cell lines. Western blot results revealed that hallmarks of epithelial‐mesenchymal transition (EMT) were altered as well, suggesting that APLNR was capable of inhibiting EMT in NPC cells. Our study further demonstrated that low expression of APLNR promoted EMT in NPC cells by activating the PI3K‐protein kinase B‐mammalian target of rapamycin signaling pathway. Taken together, our data suggest that APLNR could potentially predict prognosis for patients with NPC and inhibit proliferation, migration, invasion, and EMT in nasopharyngeal cancer cells.—Liu, Y., Liu, Q., Chen, S., Liu, Y., Huang Y., Chen, P., Li, X., Gao, G., Xu, K., Fan, S., Zeng Z., Xiong W., Tan, M., Li, G., Zhang W. APLNR is involved in ATRA‐induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K‐Akt‐mTOR signaling. FASEB J. 33, 11959‐11972 (2019). www.fasebj.org
CD82 controls CpG‐dependent TLR9 signaling
Authors: Khan Nida S. , Lukason Daniel P. , Feliu Marianela , Ward Rebecca A. , Lord Allison K. , Reedy Jennifer L. , Ramirez‐Ortiz Zaida G. , Tam Jenny M. , Kasperkovitz Pia V. , Negoro Paige E. , Vyas Tammy D. , Xu Shuying , Brinkmann Melanie M. , Acharaya idu , Artavanis‐Tsakonas Katerina , Frickel Eva‐Maria , Becker Christine E. , Dagher Zeina , Kim You‐Me , Latz Eicke , Ploegh Hidde L. , Mansour Michael K. , Miranti Cindy K. , Levitz Stuart M. , Vyas Jatin M.
Published: August 2019

The tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, and aggregation. However, the mechanisms by which CD82 participates in innate immunity are unknown. We report that CD82 is a key regulator of TLR9 trafficking and signaling. TLR9 recognizes unmethylated cytosine‐phosphate‐guanine (CpG) motifs present in viral, bacterial, and fungal DNA. We demonstrate that TLR9 and CD82 associate in macrophages, which occurs in the endoplasmic reticulum (ER) and post‐ER. Moreover, CD82 is essential for TLR9‐dependent myddosome formation in response to CpG stimulation. Finally, CD82 modulates TLR9‐dependent NF‐αB nuclear translocation, which is critical for inflammatory cytokine production. To our knowledge, this is the first time a tetraspanin has been implicated as a key regulator of TLR signaling. Collectively, our study demonstrates that CD82 is a specific regulator of TLR9 signaling, which may be critical in cancer immunotherapy approaches and coordinating the innate immune response to pathogens.—Khan, N. S., Lukason, D. P., Feliu, M., Ward, R. A., Lord, A. K., Reedy, J. L., Ramirez‐Ortiz, Z. G., Tam, J. M., Kasperkovitz, P. V., Negoro, P. E., Vyas, T. D., Xu, S., Brinkmann, M. M., Acharaya, M., Artavanis‐Tsakonas, K., Frickel, E.‐M., Becker, C. E., Dagher, Z., Kim, Y.‐M., Latz, E., Ploegh, H. L., Mansour, M. K., Miranti, C. K., Levitz, S. M., Vyas, J. M. CD82 controls CpG‐dependent TLR9 signaling. FASEB J. 33, 12500–12514 (2019). www.fasebj.org
A Subgroup of Chronic Low Back Pain Patients With Central Sensitization
Authors: Aoyagi Kosaku , He Jianghua , Nicol Andrea L. , Clauw Daniel J. , Kluding Patricia M. , Jernigan Stephen , Sharma Neena K.
Published: August 2019

Background:

Our knowledge of central sensitization (CS) in chronic low back pain (CLBP) is limited. 2011 fibromyalgia criteria and severity scales (2011 FM survey) have been used to determine FM positive as a surrogate of CS. The major features of CS including widespread hyperalgesia and dysfunction of the descending inhibitory pathways can be identified by pressure pain threshold (PPT) and conditioned pain modulation (CPM) tests. The purpose of the study was to examine neurophysiological characteristics and psychosocial symptoms in a subgroup of FM-positive CLBP compared with FM-negative CLBP patients.

Methods:

A total of 46 participants with CLBP and 22 pain-free controls completed outcome measures of the 2011 FM survey, PPT and CPM tests, and psychosocial questionnaires. Differences between FM-positive and FM-negative CLBP participants on these measures and correlations were analyzed.

Results:

The 2011 FM survey identified 22 (48%) participants with CLBP as FM positive. FM-positive CLBP participants showed lower PPT values of the thumbnail (P=0.011) and lower back (P=0.003), lower CPM values of the thumbnail (P=0.002), and more severe pain catastrophizing, anxiety, and depression symptoms (P<0.05) than FM-negative CLBP participants. The 2011 FM scores were significantly correlated with the PPT and CPM values of the thumbnail and with psychosocial symptoms (P<0.001).

Discussion:

Our findings suggest a subgroup of CLBP patients exhibiting with signs and symptoms of CS. Associations between subjective and objective CS measures indicate that the 2011 FM survey can be utilized to identify the presence of CS in CLBP in clinical practice.
Lower circulating irisin in middle-aged and older adults with osteoporosis: a systematic review and meta-analysis
Authors: Zhou Kunyan , Qiao Xiaoyong , Cai Yitong , Li Ailin , Shan Dan
Published: August 2019

Objective:

Osteoporosis has imposed a heavy socioeconomic burden worldwide, especially in postmenopausal women. As a newly found protein, irisin has an important physiological role in bone metabolism. This meta-analysis intends to identify the association between circulating irisin levels and osteoporosis.

Methods:

This meta-analysis was conducted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline. A comprehensive search of five databases was performed from inception to January 2019. Studies with original date on middle-aged and older participants were included. Data were analyzed according to study characteristics and heterogeneity between studies. The quality of each study and the presence of publication bias were assessed by Newcastle-Ottawa score (NOS) and normal quantile plot.

Results:

Seven studies, with a total of 1,018 participants, conducted in four countries, were included. Six of them were identified as high-quality research. Five studies included postmenopausal women, and two studies included both men and women. Possible publication bias was found in the analysis of irisin and osteoporosis. Pooled analysis indicated decreased irisin levels in osteoporotic participants (mean difference −87.91, 95% CI, −92.56 to −83.25). Subgroup analysis revealed an even lower level of irisin in postmenopausal women and in participants with a history of fractures. Analysis on associations between irisin and femoral neck or lumbar spine bone mineral density showed a weak positive correlation.

Conclusions:

The findings of this analysis suggested that circulating irisin levels were decreased in middle-aged and older participants with osteoporosis. Irisin was positively correlated with bone mineral density.
Daily and bidirectional linkages between pain catastrophizing and spouse responses
Authors: Martire Lynn M. , Zhaoyang Ruixue , Marini Christina M. , Nah Suyoung , Darnall Beth D.
Published: August 2019

Pain catastrophizing has been shown to predict greater pain and less physical function in daily life for chronic pain sufferers, but its effects on close social partners have received much less attention. The overall purpose of this study was to examine the extent to which pain catastrophizing is an interpersonal coping strategy that is maladaptive for patients and their spouses. A total of 144 older knee osteoarthritis patients and their spouses completed baseline interviews and a 22-day diary assessment. Multilevel lagged models indicated that, on days when patients reported greater catastrophizing in the morning, their spouses experienced more negative affect throughout the day. In addition, a higher level of punishing responses from the spouse predicted greater pain catastrophizing the next morning, independent of patient pain and negative affect. Multilevel mediation models showed that patients' morning pain catastrophizing indirectly impacted spouses' negative affect and punishing responses through patients' own greater negative affect throughout the day. There was no evidence that spouses' empathic or solicitous responses either followed or preceded patients' catastrophizing. These findings suggest that cognitive-behavioral interventions that reduce pain catastrophizing should be modified for partnered patients to address dyadic interactions and the spouse's role in pain catastrophizing.
Time to Adjuvant Systemic Therapy Following Pancreatic Cancer Resection and Effect on Outcome
Authors: White Richard J. , Hasan Shaakir , Monga Dulabh , Finley Gene , Islam Mohammed , Schiffman Suzanne , Williams H. Kenneth , Kulkarni Abhijit , Thakkar Shyam , Kirichenko Alexander V. , Wegner Rodney E.
Published: August 2019

Objectives

The appropriate timing of chemotherapy following surgery for resectable pancreatic adenocarcinoma is controversial. Using the National Cancer Database we evaluated time to initiation of chemotherapy postresection and correlated with outcome.

Methods

We identified stage I-III pancreatic adenocarcinoma treated surgically with adjuvant chemoradiotherapy. Receiver operator curve analysis identified an interval of 66 days as the a priori value for largest discrepancy in outcome. Multivariable logistic regression analysis identified variables associated with increased time to chemotherapy postoperatively (>66 days). Propensity matching was performed to account for indication bias.

Results

In total, 6873 and 3348 patients received chemotherapy before and after the 66-day cutoff, respectively. Predictors of expedited chemotherapy included lower comorbidity, treatment outside a community program in an urban location, having insurance, white race, and treatment after 2009. Propensity-matched median survival was 21.8 months for all patients, and of these, 6462 were stage 1. Five-year survival was 20% in patients receiving chemotherapy within 66 days and 18% in those not (P= 0.0266). In stage 1 patients, 5-year survival was 23% versus 21% (P= 0.0116) in favor of expedited chemotherapy.

Conclusions

The present propensity-matched analysis showed a significant association with survival for earlier delivery of chemotherapy in the adjuvant setting.
Association Between Pancreatic Cystic Lesions and High-grade Intraepithelial Neoplasia and Aging
Authors: Matsuda Yoko , Kimura Wataru , Matsukawa Miho , Aida Junko , Takubo Kaiyo , Ishiwata Toshiyuki , Furukawa Toru , Mino-Kenudson Mari , Arai Tomio
Published: August 2019

Objectives

This study aimed to clarify clinicopathological features of pancreatic cysts.

Methods

Pancreata from 280 autopsies (median, 83 years; male, 146; female, 134) were sectioned every 5 mm. Cysts (<10 mm) were diagnosed as a simple cyst or low-grade, intermediate-grade, or high-grade dysplasia.

Results

We found 236 cysts in 93 patients (33.2%). The number and diameter of cysts increased according to the age. Of the 236 cysts, 9 (3.8%) were with high-grade dysplasia. Cysts with high-grade dysplasia arose in the pancreata of older patients with larger numbers of cysts. In contrast, 15 noncystic lesions with high-grade dysplasia were also detected. Hence, in total, 24 high-grade dysplastic lesions in 15 patients (5.4%) were noted. Of the 15 patients with high-grade dysplastic lesions, in 10 patients, the condition was accompanied by pancreatic cysts, whereas 5 patients did not have any cysts in the pancreas; therefore, patients with cyst showed higher incidence of high-grade dysplasia (10.8%; P = 0.0047) than patients without cyst (2.7%). All cysts with high-grade dysplasia were located in the branch duct of the pancreatic head/body, whereas 20% of noncystic lesions with high-grade dysplasia were located in the main pancreatic duct.

Conclusions

Cystic lesions with high-grade dysplasia may have different characteristics compared with noncystic high-grade dysplasia.
Examining gender differences in opioid, benzodiazepine, and antibiotic prescribing
Authors: Hamamsy Tymor , Tamang Suzanne , Lembke Anna
Published: August 2019

While gender differences have been explored across several areas of medicine, our study is the first to present a systematic comparison of drug prescribing behavior of male and female providers, including opioid, benzodiazepine, and antibiotic prescribing. Our work is of particular relevance to the current opioid crisis and other iatrogenic harms related to injudicious prescribing. Our objective is to explore prescribing differences between male and female providers across medical specialties and for different prescription drug categories in Medicare Part D. To this end, we performed a descriptive, retrospective study of 1.13 million medical providers who made drug claims to Medicare Part D in 2016, analyzing by gender, specialty, and drug category. We found that male providers across diverse specialties prescribe significantly more medications, including opioids, benzodiazepines, and antibiotics than female providers by volume, cost, and per patient. These observed gender differences in prescribing, while agnostic to the quality of care provided, nonetheless inform the design of prevention strategies that seek to reduce iatrogenic harms related to prescribing.
Depletion-of-susceptibles bias in influenza vaccine waning studies: how to ensure robust results
Authors: Lipsitch M. , Goldstein E. , Ray G.T. , Fireman B.
Published: August 2019

Vaccine effectiveness (VE) studies are subject to biases due to depletion of at-risk persons or of highly susceptible persons at different rates from different groups (depletion-of-susceptibles bias), a problem that can also lead to biased estimates of waning effectiveness, including spurious inference of waning when none exists. An alternative study design to identify waning is to study only vaccinated persons, and compare for each day the incidence in persons with earlier or later dates of vaccination. Prior studies suggested under what conditions this alternative would yield correct estimates of waning. Here we define the depletion-of-susceptibles process formally and show mathematically that for influenza vaccine waning studies, a randomized trial or corresponding observational study that compares incidence at a specific calendar time among individuals vaccinated at different times before the influenza season begins will not be vulnerable depletion-of-susceptibles bias in its inference of waning under the null hypothesis that none exists, and will – if waning does actually occur – underestimate the extent of waning. Such a design is thus robust in the sense that a finding of waning in that inference framework reflects actual waning of vaccine-induced immunity. We recommend such a design for future studies of waning, whether observational or randomized.
Childhood coordination and survival up to six decades later: extended follow-up of participants in the National Child Development Study
Authors: Batty G. David , Deary Ian J. , Hamer Mark , Ritchie Stuart J. , Bann David
Published: August 2019

Background

Poorer performance on standard tests of motor coordination in children has emerging links with sedentary behaviour, obesity, and functional capacity in later life. These observations are suggestive of an as-yet untested association of coordination with health outcomes.

Objective

To examine the association of performance on a series of psychomotor coordination tests in childhood with mortality up to six decades later.

Design, Setting, and Participants

The National Child Development Study (1958 birth cohort study) is a prospective cohort study based on a nationally representative sample of births from England, Scotland and Wales. A total of 17,415 individuals had their gross and fine motor psychomotor coordination assessed using nine tests at 11 and 16 years of age.

Main outcome and measure

All-cause mortality as ascertained from a vital status registry and survey records.

Results

Mortality surveillance between 7 and 58 years of age in an analytical sample of 17,336 men and women yielded 1,090 deaths. After adjustment for sex, higher scores on seven of the nine childhood coordination tests were associated with a lower risk of mortality in a stepwise manner. After further statistical control for early life socioeconomic, health, cognitive, and developmental factors, relations at conventional levels of statistical significance remains for three tests: ball catching at age 11 (hazard ratio; 95% confidence interval for 0-8 versus 10 catches: 1.56; 1.21, 2.01), match-picking at age 11 (>50 seconds versus 0-36: 1.33; 1.03, 1.70), and hopping at age 16 years (very unsteady versus very steady: 1.29; 1.02, 1.64).

Conclusion and Relevance

The apparent predictive utility of early life psychomotor coordination requires replication.

Key points

Question

What is the association of performance on a series of psychomotor coordination tests in childhood with mortality up to six decades later?

Findings

After taking into account multiple confounding factors, lower performance on three gross and fine motors skills tests in childhood were associated with a shorter survival over six decades.

Meaning

These findings require replication in other contexts and using complementary observational approaches.
Dopamine waves as a mechanism for spatiotemporal credit assignment
Authors: Hamid Arif A. , Frank Michael J. , Moore Christopher I.
Published: August 2019

Significant evidence supports the view that dopamine shapes reward-learning by encoding prediction errors. However, it is unknown whether dopamine decision-signals are tailored to the functional specialization of target regions. Here, we report a novel set of wave-like spatiotemporal activity-patterns in dopamine axons across the dorsal striatum. These waves switch between different activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. These specific motifs are associated with distinct task contexts: At reward delivery, dopamine signals rapidly resynchronize into propagating waves with opponent directions depending on instrumental task contingencies. Moreover, dopamine dynamics during reward pursuit signal the extent to which mice have instrumental control and interact with reward waves to predict future behavioral adjustments. Our results are consistent with a computational architecture in which striatal dopamine signals are sculpted by inference about instrumental controllability and provide evidence for a spatiotemporally “vectorized” role of dopamine in credit assignment.
Rethinking global carbon storage potential of trees. A comment on Bastin et al. 2019
Authors: Taylor Shawn D. , Marconi Sergio
Published: August 2019

Key Message

Bastin et al. 2019 used flawed assumptions in calculating the carbon storage of restored forests worldwide, resulting in a gross overestimate.

Context

Bastin et al. 2019 use two flawed assumptions: 1) that the area suitable for restoration does not contain any carbon currently, and 2) that soil organic carbon (SOC) from increased canopy cover will accumulate quickly enough to mitigate anthropogenic carbon emissions.

Aims

We re-evaluated the potential carbon storage worldwide using empirical relationships of tree cover and carbon.

Methods and Results

We use global datasets of tree cover, soil organic carbon, and above ground biomass to estimate the empirical relationships of tree cover and carbon stock storage. A more realistic range of global carbon storage potential is between 71.7 and 75.7 GtC globally, with a large uncertainty associated with SOC. This is less than half of the original 205 GtC estimate.

Conclusion

The potential global carbon storage of restored forests is much less than that estimated by Bastin et al. 2019. While we agree on the value of assessing global reforestation potential, we suggest caution in considering it the most effective strategy to mitigate anthropogenic emissions.
Mechanotransduction-dependent control of stereocilia dimensions and row identity in inner hair cells
Authors: Krey Jocelyn F. , Chatterjee Paroma , Dumont Rachel A. , Choi Dongseok , Bird Jonathan E. , Barr-Gillespie Peter G.
Published: August 2019

Actin-rich structures like stereocilia and microvilli are assembled with precise control of length, diameter, and relative spacing. We found that developmental widening of the second-tallest stereocilia rank (row 2) of mouse inner hair cells correlated with the appearance of mechanotransduction. Correspondingly, Tmc1KO/KO;Tmc2KO/KO or TmieKO/KO hair cells, which lack transduction, have significantly altered stereocilia lengths and diameters. EPS8 and the short splice isoform of MYO15A, identity markers for row 1 (tallest), lost their row exclusivity in transduction mutants, a result that was mimicked by block of transduction channels. Likewise, the heterodimeric capping protein subunit CAPZB and its partner TWF2 lost their row 2 tip localization in mutants, and GNAI3 failed to accumulate at row 1 tips. Redistribution of marker proteins was accompanied by increased variability in stereocilia height. Transduction channels thus specify and maintain row identity and control addition of new actin filaments to increase stereocilia diameter.
Adaptive Introgression Promotes Fast Adaptation In Oaks Marginal Populations
Authors: Goicoechea Pablo G , Guillardín Laura , Fernández-Ibarrodo Lierni , Valbuena-Carabaña Maria , González-Martínez Santiago C , Alía Ricardo , Kremer Antoine
Published: August 2019

Range shifts and species range limits are two fundamental, related processes in population and evolutionary genetics that have received much attention since a large impact of climate change in species’ distributions was predicted. In general, there is a broad consensus on the effects of abiotic interactions on range limits, but comprehensive evidence supporting/rejecting the impact of biotic interactions is lacking. Hybridization has long been recognized as a biotic interaction favoring marginal populations establishment and range expansion through transgressive segregation or adaptive introgression, but recently new roles have been claimed for hybridization, such as the trigger of adaptive radiations, or indirect effects on population sizes that would allow persistence until new mutations arises or the environment changes. In this work, we selected two Mediterranean oak species with ecological discrimination based on soil pH, and intensively sampled three interspecific pairs of marginal populations from taxon-extreme environments under heterogeneous climate conditions. We genotyped 110 EST-SSR markers evenly distributed across their genomes and applied a variety of population and landscape genetics models to validate candidate genes for local adaptation. Then, several introgression screens on shared candidates showed that the three inter-specific population pairs contain evidences of adaptive introgression and that events occur in both directions. Other significant findings from our work are: (i) Aproximate Bayesian Computation coupled to coalescent simulations supports small hybridization rates since recent secondary contact in two population pairs affected by Quaternary climatic oscillations but continuous old interspecific gene flow in the pair less affected by climate, (ii) introgression at loci involved in local adaptations leads to strong geographic structure of marginal oak populations when sampling is large enough, and (iii) sampling efforts can be targeted to reveal different components of populations structure. Finally, we review evidences that support our conclusions and discuss some evolutionary implications of adaptive introgression on range expansion.