bluuebunny/crossref_metadata_2025 huggingface dataset:
Looking beyond the D.U.S.T. – building resilient rangeland communities
Authors: Kelly Dana , Phelps David
Published: April 2019

The role of towns and small business is poorly understood, yet towns are vital for the long-term viability of communities in rural and remote Australia. This case study in the central western region of Queensland (CWQ) examines the impacts of drought on rural towns and how to build a resilient regional community and alleviate hardship. Evidence was collected during drought from town businesses through surveys, interviews and a public meeting in 2017. Towns in CWQ are especially exposed to the risks of drought, as approximately half of the businesses are directly linked to agriculture. Townspeople are major contributors to social cohesion and resilience in rural and regional communities, which are often service and maintenance centres of nationally important infrastructure such as roads for inter-state freight transport and tourism. Drought and declining grazier incomes have led to reduced spending in towns. Populations have dropped sharply, as itinerant agricultural workers leave the region. The complex economic and social flow-on impacts of drought have resulted in lower socioeconomic resilience. The majority of community members interviewed expressed a desire to build secure livelihoods, which echoes other research where existing and new rangelands livelihoods are seen as contributing to the success of the nation, a common global desire. Local organisations in CWQ display innovative business and community strategies. Future actions need to support and build on these initiatives. A framework with the acronym D.U.S.T. has been developed, with associated actions aimed at building resilience in these communities. D.U.S.T. is appropriate for this often-dusty region, and stands for: D. Decide to act; U. Understand the context; S. Support and develop local capacities and institutions; and T. Transform regional governance. The key for decision-makers is to work with local people who understand the contextual complexity and local needs. Actions need to be based on principles of adaptability, equity and inclusiveness, and working with the whole of the community. Building on existing collaborations and innovations as well as transforming governance and secure funding arrangements are needed. Lessons from the communities in CWQ may help other rural and remote regions build resilience to cope with the unpredictable financial, social and environmental future.
Role for the shoot apical meristem in the specification of juvenile leaf identity inArabidopsis
Authors: Fouracre Jim P. , Poethig R. Scott
Published: April 2019

Significance

Developmental transitions during shoot development in plants are regulated by factors originating outside and within the shoot apical meristem (SAM). The best-known example of this is the vegetative-to-reproductive transition, which is initiated by a leaf-derived signal that transforms the vegetative SAM into a developmentally stable inflorescence meristem. Although the juvenile-to-adult vegetative transition (vegetative phase change) is also thought to be regulated by factors exogenous and internal to the SAM, how this process is coordinated spatially remains unknown. Here we demonstrate that the SAM specifies leaf identity early in development, but that leaves become more important determinants of shoot identity as the shoot ages. We also reveal a role for the plant aging pathway in the regulation of meristem size.
A qualitative inquiry of video learning by Chinese L2 learners
Authors: Huang Ting , Lammers Jayne C.
Published: April 2019

Previous research in Chinese L2 learning has shown that video learning is an effective way to engage students, especially for learning social realities such as cultural values (e.g., dating practices). Chinese L2 learners commonly have experience with learning social realities from videos, including textbook videos, television dramas, music clips and talk shows Using the lens of internalization, this qualitative study provides a detailed interpretation of what video offered its Chinese L2 participants and what challenges the participants experienced learning about social realities. This article discusses three focused cases with 12 interviews, 30 observations, 3 clip-elicitation conversations, and documents (including memos and field notes). Use of a three-phase Constant Comparative Method (CCM) revealed that the learning processes of Chinese L2 learners displayed similarities and differences. Participants had distinctive trajectories in their learning of social realities. Implications for Chinese L2 research and education are discussed.
Register in Systemic Functional Linguistics*
Authors: Matthiessen Christian M. I. M.
Published: April 2019

Christian M. I. M. Matthiessen elaborates on the Systemic Functional Linguistics (SFL) approach to register in this contribution to the inaugural issue ofRegister Studies.He is Chair Professor of the Department of English at the Hong Kong Polytechnic University, where he pursues a scholarly agenda that includes developing the theory of Systemic Functional Linguistics and applying it to text and discourse analysis, functional grammar, issues related to language evolution and typology, and comprehensive descriptive models of register. Throughout his career, Matthiessen has made major contributions to SFL theories and methods. Among his major works isLexicogrammatical Cartography: English Systems(1995, International Language Sciences Publishers). More than any other scholar, Matthiessen has expounded on Halliday’s early ideas on register and applied SFL theory to describing models of register variation. He remains an active researcher in the area of register studies which includes his registerial cartography – the comprehensive and systematic description of the registers in a language. Matthiessen’s work has left an indelible mark on the theory and systematic study of patterns of register in language use.
Afterword
Authors: Finegan Edward
Published: April 2019

Edward Finegan, Professor Emeritus of Linguistics and Law at the University of Southern California, provides this afterword to synthesize and provide commentary on the six articles in this issue. He has been involved with research on register for more than 30 years, publishing a large number of empirical studies on register and the bookSociolinguistic Perspectives on Register(Biber & Finegan 1994, Oxford University Press). He is also co-author on theLongman Grammar of Spoken and Written English(Biber, Johansson, Leech, Conrad, & Finegan 1999, Longman), the first comprehensive reference grammar to systematically account for register. He is currently involved in research on the relationship between register variation and social dialect variation. In addition to his research on register, Finegan has made tremendous contributions in the areas of general linguistics, language variation in the U.S., and language attitudes toward correctness, publishing widely-used textbooks in all three areas. He has also been an influential figure in the application of linguistics in legal proceedings, acting as expert witness in many legal cases, particularly those related to defamation and trademark. He currently serves as the Editor of the journalDictionaries: The Journal of the Dictionary Society of North America.
Castanea Mill.
Authors: Savill P.
Published: April 2019

This chapter discusses the origin and introduction; climatic and site requirements, and other silvicultural characteristics; shake; diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; timber and uses; area and yield; and place of sweet chestnut (Castanea sativa) in British forestry.
Cryptomeria D. Don.
Authors: Savill P.
Published: April 2019

This chapter describes the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; timber and uses; and place of Japanese red cedar (Cryptomeria japonica) in British forestry.
Fraxinus L.
Authors: Savill P.
Published: April 2019

This chapter describes the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; provenance, improved seed and breeding; area, yield and rotation length; timber; and place of ash (Fraxinus excelsior) in British forestry. The chapter also explores possible alternatives to ash in a changing climate.
Ostrya Scop.
Authors: Savill P.
Published: April 2019

This chapter describes the origin and introduction; climatic and site requirements, and silviculture; pests and diseases; provenance, seed production and nursery conditions; pests and diseases; and timber properties and utilization of hop-hornbeams (Ostrya sp.) in British forestry.
Picea A. Dietr.
Authors: Savill P.
Published: April 2019

This chapter describes the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; genetic and provenance; area, yield and rotations; timber and uses; Christmas trees; habitat and ecology; yield and timber; and place of spruces (Picea abies, P. omorika, P. orientalis, and P. sitchensis) in British forestry.
Pinus L.
Authors: Savill P.
Published: April 2019

This chapter describes the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; area and yield; timber and uses; and place of pines (Pinus contorta, P. muricata, P. nigra, P. nigra subsp. nigra, P. nigra susbp. salzamanni, P. peuce, P. radiata, P. strobus, and P. sylvestris) in British forestry.
Pseudotsuga Carr.
Authors: Savill P.
Published: April 2019

This chapter discusses the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; area and yield; timber; and place of Douglas fir (Pseudotsuga menziesii) in British forestry.
Pterocarya Nutt. ex Moq.
Authors: Savill P.
Published: April 2019

This chapter discusses the climatic and site requirements, and silviculture; provenance, seed production and nursery practice; pests and diseases; timber properties and utilization; and place of Pterocarya fraxinifolia in British forestry.
Taxus L.
Authors: Savill P.
Published: April 2019

This chapter describes the origin; climatic and site requirements, and other silvicultural characteristics; diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; yew as a poisonous tree; growth and yield; timber and uses; and place of yew (Taxus baccata) in British forestry.
Thuja L.
Authors: Savill P.
Published: April 2019

This chapter discusses the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; yield; timber and uses; and place of western red cedar (Thuja plicata) in British forestry.
Tsuga Carrière.
Authors: Savill P.
Published: April 2019

This chapter discusses the origin and introduction; climatic and site requirements, and other silvicultural characteristics; diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; timber and uses; and place of western hemlock (Tsuga heterophylla) in British forestry.
Extreme weather events in early summer 2018 connected by a recurrent hemispheric wave-7 pattern
Authors: Kornhuber Kai , Osprey Scott , Coumou Dim , Petri Stefan , Petoukhov Vladimir , Rahmstorf Stefan , Gray Lesley
Published: April 2019

The summer of 2018 witnessed a number of extreme weather events such as heatwaves in North America, Western Europe and the Caspian Sea region, and rainfall extremes in South-East Europe and Japan that occurred near-simultaneously. Here we show that some of these extremes were connected by an amplified hemisphere-wide wavenumber 7 circulation pattern. We show that this pattern constitutes an important teleconnection in Northern Hemisphere summer associated with prolonged and above-normal temperatures in North America, Western Europe and the Caspian Sea region. This pattern was also observed during the European heatwaves of 2003, 2006 and 2015 among others. We show that the occurrence of this wave 7 pattern has increased over recent decades.
Aging Vs. Hypertension: An Autopsy Study of Sclerotic Renal Histopathological Lesions in Adults With Normal Renal Function
Authors: Okabayashi Yusuke , Tsuboi Nobuo , Kanzaki Go , Sasaki Takaya , Haruhara Kotaro , Koike Kentaro , Takahashi Hiroyuki , Ikegami Masahiro , Shimizu Akira , Yokoo Takashi
Published: April 2019

BACKGROUND AND AIMS

Arterial hypertension and glomerular ischemia coexist in elderly patients with hypertension. Thus, 2 conflicting therapeutic purposes, i.e., reduction of pressure overload and maintenance of renal arterial perfusion, must be considered in elderly patients with hypertension. This study examined this issue from the perspective of renal histopathology.

METHODS

Adult autopsied kidneys without apparent renal disease were analyzed for histopathological features that might be related to aging or hypertension. Mean glomerular volume (GV), global glomerulosclerosis (GGS), arteriosclerotic lesions (AL), arteriolar hyalinosis (AH), and interstitial fibrosis/tubular atrophy (IF/TA) were evaluated.

RESULTS

This study included 59 Japanese autopsy patients, of whom 28 (47%) were hypertensive. Overall, GGS, IF/TA, and AL, but not GV or AH, tended to increase with aging. Multivariate analysis revealed that age, but not hypertension, was an independent factor associated with GGS, IF/TA, and AL. In contrast, hypertension was independently associated with GV. AH was not associated with age or hypertension in this autopsy series. Of note, in the late elderly group (≥75 years), GGS was significantly lower in hypertensives than in normotensives. No such trend was found in the non-elderly (<65 years) or early elderly groups (65–74 years).

CONCLUSIONS

Normal aging has a major impact on the development of renal sclerotic lesions compared to hypertension in adults with no apparent renal disease. Hypertension may play a role in maintaining downstream glomerular perfusion in the aging kidney.
Flirting with danger: predation risk interacts with male condition to influence sexual display
Authors: de Moraes Pedro Z , Diniz Pedro , Fernandez-Juricic Esteban , Macedo Regina H
Published: April 2019

Sexual signaling coevolves with the sensory systems of intended receivers; however, predators may be unintended receivers of sexual signals. Conspicuous aerial displays in some species may place males at high risk of predation from eavesdropping predators. There are three different hypotheses to explain how signaling males can deal with increased predation risk: (1) males invest in survival by decreasing signal conspicuousness; (2) males invest in reproduction by increasing signal conspicuousness; and (3) male response is condition-dependent according to his residual reproductive value. Here, we used blue-black grassquits (Volatinia jacarina) to test these hypotheses, asking whether males modify leap displays under different levels of predation risk. Grassquit males develop an iridescent nuptial plumage and spend considerable time emitting a multimodal signal: while leaping from a perch, males clap their wings above their heads and emit a high-pitched short song. We exposed males to predator and nonpredator playbacks while video recording their displays. We found interactions between predation risk and 2 male condition variables (ectoparasite infestation and proportion of nuptial plumage coverage) that influenced display behavior. Less parasitized males and those with higher proportion of nuptial plumage showed no change in display behavior, while more parasitized males and those with lower proportion of nuptial plumage increased the vigor of displays under predation risk. In other words, males with low residual reproductive value increased reproductive effort when there was a high risk of extrinsic death. Our study provides some empirical support for the terminal investment hypothesis.
Morphological diversity of wild rabbit populations: implications for archaeology and palaeontology
Authors: Pelletier Maxime
Published: April 2019

Morphometric characteristics of the European rabbit (Oryctolagus cuniculus) are regularly used in archaeological and palaeontological studies to explore aspects of prehistoric human hunting behaviour, to reconstruct past environments or to define new species. However, the variability of these characteristics is still both poorly understood and under-documented due to a lack of population-level data that are essential for reliably interpreting the fossil record of this species. Here we address the morphometric diversity of wild rabbits in seven current populations from south-western Europe. Size variations in different skeletal parts were analysed to explore the potential impact of sexual dimorphism. A geometric morphometric analysis of the third lower premolar (p3) – a tooth commonly used to distinguish leporid species – was used to evaluate the relative effects of size, phylogeny, geographical location and climate on shape variation. The results show a negligible impact of sexual dimorphism, contradicting previous studies. We also demonstrate geography and climate to be the main factors driving variation in p3 shape, potentially calling into question criteria typically used to identify rabbit species. These results are valuable not only for palaeobiologists studying the taxonomy and the evolutionary history of the leporid family but also for archaeologists interested in the socio-economic and behavioural aspects of Palaeolithic human groups.
Changes in clinical indicators related to the transition from dialysis to kidney transplantation—data from the ERA-EDTA Registry
Authors: Tantiyavarong Pichaya , Kramer Anneke , Heaf James G , Finne Patrik , Åsberg Anders , Cases Aleix , Caskey Fergus J , Massy Ziad A , Jager Kitty J , Noordzij Marlies
Published: April 2019

Background

Kidney transplantation should improve abnormalities that are common during dialysis treatment, like anaemia and mineral and bone disorder. However, its impact is incompletely understood. We therefore aimed to assess changes in clinical indicators after the transition from chronic dialysis to kidney transplantation.

Methods

We used European Renal Association–European Dialysis and Transplant Association Registry data and included adult dialysis patients for whom data on clinical indicators before and after transplantation (2005–15) were available. Linear mixed models were used to quantify the effect of transplantation and of time after transplantation for each indicator.

Results

In total, 16 312 patients were included. The mean age at transplantation was 50.1 (standard deviation 14.2) years, 62.9% were male and 70.2% were on haemodialysis before transplantation. Total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides increased right after transplantation but decreased thereafter. All other indicators normalized or approached the target range soon after transplantation and these improvements were sustained for the first 4 years of follow-up. In patients with higher estimated glomerular filtration rate (eGFR) levels (30–60 and >60 mL/min/1.73 m2), the improvement of haemoglobin, ferritin, ionized calcium, phosphate, parathyroid hormone, HDL cholesterol, triglycerides, albumin and C-reactive protein levels was more pronounced than in patients with a lower eGFR (<30 mL/min/1.73 m2).

Conclusions

Except for total cholesterol, LDL cholesterol and triglycerides, all clinical indicators improved after transplantation. These improvements were related to eGFR. Nevertheless, values remained out of range in a considerable proportion of patients and anaemia and hyperparathyroidism were still common problems. Further research is needed to understand the complex relationship between eGFR and the different clinical indicators.
Coronary artery bypass confers intermediate-term survival benefit over percutaneous coronary intervention with new-generation stents in real-world patients with multivessel coronary artery disease, including left main disease: a retrospective analysis of 6383 patients
Authors: Panoulas Vasileios F , Ilsley Charles J , Kalogeras Konstantinos , Khan Habib , Monteagudo Vela Maria , Dalby Miles , Kabir Tito , Smith Robert D , Mason Mark , Grocott-Mason Richard , Cummings Ian , Lüscher Thomas F , Raja Shahzad G
Published: April 2019

OBJECTIVES

The intermediate-term all-cause mortality rate of real-world patients with multivessel disease (MVD) treated with percutaneous coronary intervention (PCI) with new-generation drug-eluting stents or coronary artery bypass grafting (CABG) remains unknown. We sought to compare the intermediate-term all-cause mortality rates of real-world patients with MVD including left main stem disease, treated with CABG or PCI.

METHODS

All consecutive all-comer patients with MVD undergoing CABG or PCI with second/third generation drug-eluting stents from 2007 to 2015 in Harefield Hospital, UK were included in this study. The revascularization modality was based on heart team discussions. Primary outcome was all-cause mortality. Mean follow-up of the study was 3.3 years. Cox regression analysis and propensity matching were used.

RESULTS

Of 6383 patients with MVD, 4230 underwent CABG, whereas 2153 had PCI with new-generation stents. In the CABG group, the mean age was 66.4 ± 10 years, whereas in the PCI group it was 65.3 ± 12.1 years (P < 0.001). Fewer female patients with MVD were treated with CABG than were treated with PCI (18.5% vs 20.5%; P = 0.026). There was a higher 5-year estimated survival rate among patients having CABG (88% vs 78.3%; Plog-rank < 0.001). The adjusted hazard ratio (HR) for PCI over CABG was 1.74 [95% confidence interval (CI) 1.41–2.16; P < 0.001]. A total of 653 patients having CABG and 653 having PCI were included in the propensity-matched groups. At mean follow-up, PCI was associated with a higher adjusted HR for all-cause mortality (2.18, 95% CI 1.54–3.1; P < 0.001).

CONCLUSIONS

In this contemporary cohort of real-world patients with MVD, CABG was associated with increased intermediate-term survival compared to PCI with new-generation drug-eluting stents.
Immunogenicity and Efficacy of a Measles Virus-Vectored Chikungunya Vaccine in Nonhuman Primates
Authors: Rossi Shannan L , Comer Jason E , Wang Eryu , Azar Sasha R , Lawrence William S , Plante Jessica A , Ramsauer Katrin , Schrauf Sabrina , Weaver Scott C
Published: April 2019

Background

Chikungunya virus (CHIKV) infection can result in chikungunya fever (CHIKF), a self-limited acute febrile illness that can progress to chronic arthralgic sequelae in a large percentage of patients. A new measles virus-vectored vaccine was developed to prevent CHIKF, and we tested it for immunogenicity and efficacy in a nonhuman primate model.

Methods

Nine cynomolgus macaques were immunized and boosted with the measles virus-vectored chikungunya vaccine or sham-vaccinated. Sera were taken at multiple times during the vaccination phase to assess antibody responses against CHIKV. Macaques were challenged with a dose of CHIKV previously shown to cause fever and viremia, and core body temperature, viremia, and blood cell and chemistry panels were monitored.

Results

The vaccine was well tolerated in all macaques, and all seroconverted (high neutralizing antibody [PRNT80 titers, 40–640] and enzyme-linked immunosorbent assay titers) after the boost. Furthermore, the vaccinated primates were protected against viremia, fever, elevated white blood cell counts, and CHIKF-associated cytokine changes after challenge with the virulent La Reunión CHIKV strain.

Conclusions

These results further document the immunogenicity and efficacy of a measles-vectored chikungunya vaccine that shows promise in Phase I–II clinical trials. These findings are critical to human health because no vaccine to combat CHIKF is yet licensed.
The Laminin Interactome: A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization
Authors: Su Yu-Ching , Mattsson Emma , Singh Birendra , Jalalvand Farshid , Murphy Timothy F , Riesbeck Kristian
Published: April 2019

Laminin is a well-defined component of the airway basement membrane (BM). Efficient binding of laminin via multiple interactions is important for nontypeable Haemophilus influenzae (NTHi) colonization in the airway mucosa. In this study, we identified elongation factor thermo-unstable (EF-Tu), l-lactate dehydrogenase (LDH), protein D (PD), and peptidoglycan-associated lipoprotein P6 as novel laminin-binding proteins (Lbps) of NTHi. In parallel with other well-studied Lbps (protein 4 [P4], protein E [PE], protein F [PF], and Haemophilus adhesion and penetration protein [Hap]), EF-Tu, LDH, PD, and P6 exhibited interactions with laminin, and mediated NTHi laminin-dependent adherence to pulmonary epithelial cell lines. More importantly, the NTHi laminin interactome consisting of the well-studied and novel Lbps recognized laminin LG domains from the subunit α chains of laminin-111 and -332, the latter isoform of which is the main laminin in the airway BM. The NTHi interactome mainly targeted multiple heparin-binding domains of laminin. In conclusion, the NTHi interactome exhibited a high plasticity of interactions with different laminin isoforms via multiple heparin-binding sites.
High-throughput multimodal automated phenotyping (MAP) with application to PheWAS
Authors: Liao Katherine P , Sun Jiehuan , Cai Tianrun A , Link Nicholas , Hong Chuan , Huang Jie , Huffman Jennifer E , Gronsbell Jessica , Zhang Yichi , Ho Yuk-Lam , Castro Victor , Gainer Vivian , Murphy Shawn N , O’Donnell Christopher J , Gaziano J Michael , Cho Kelly , Szolovits Peter , Kohane Isaac S , Yu Sheng , Cai Tianxi
Published: April 2019

Objective

Electronic health records linked with biorepositories are a powerful platform for translational studies. A major bottleneck exists in the ability to phenotype patients accurately and efficiently. The objective of this study was to develop an automated high-throughput phenotyping method integrating International Classification of Diseases (ICD) codes and narrative data extracted using natural language processing (NLP).

Materials and Methods

We developed a mapping method for automatically identifying relevant ICD and NLP concepts for a specific phenotype leveraging the Unified Medical Language System. Along with health care utilization, aggregated ICD and NLP counts were jointly analyzed by fitting an ensemble of latent mixture models. The multimodal automated phenotyping (MAP) algorithm yields a predicted probability of phenotype for each patient and a threshold for classifying participants with phenotype yes/no. The algorithm was validated using labeled data for 16 phenotypes from a biorepository and further tested in an independent cohort phenome-wide association studies (PheWAS) for 2 single nucleotide polymorphisms with known associations.

Results

The MAP algorithm achieved higher or similar AUC and F-scores compared to the ICD code across all 16 phenotypes. The features assembled via the automated approach had comparable accuracy to those assembled via manual curation (AUCMAP 0.943, AUCmanual 0.941). The PheWAS results suggest that the MAP approach detected previously validated associations with higher power when compared to the standard PheWAS method based on ICD codes.

Conclusion

The MAP approach increased the accuracy of phenotype definition while maintaining scalability, thereby facilitating use in studies requiring large-scale phenotyping, such as PheWAS.
Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis
Authors: Li Jing-Yi , Liu Yi-Feng , Xu Hai-Yan , Zhang Jun-Yu , Lv Ping-Ping , Liu Miao-E , Ying Yan-Yun , Qian Ye-Qing , Li Kun , Li Cheng , Huang Yun , Xu Gu-Feng , Ding Guo-Lian , Mao Yu-Chan , Xu Chen-Ming , Liu Xin-Mei , Sheng Jian-Zhong , Zhang Dan , Huang He-Feng
Published: April 2019

Basonuclin (BNC1) is expressed primarily in proliferative keratinocytes and gametogenic cells. However, its roles in spermatogenesis and testicular aging were not clear. Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree. In this study, we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging. Genome-wide expression profiling and direct binding studies (by chromatin immunoprecipitation sequencing) with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10 (Klhl10), testis expressed 14 (Tex14), and spermatogenesis and centriole associated 1 (Spatc1). Moreover, biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like (TAF7L), a germ cell-specific paralogue of the transcription factor IID subunit TAF7, both in vitro and in testis, suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis. The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex, thus, disturbing expression of related genes and leading to testicular premature aging. Similarly, expressions of BNC1, TAF7L, Y-box-binding protein 2 (YBX2), outer dense fiber of sperm tails 1 (ODF1), and glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) were significantly decreased in the testis of men with non-obstructive azoospermia. The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.
Limits to Compensatory Mutations: Insights from Temperature-Sensitive Alleles
Authors: Tomala Katarzyna , Zrebiec Piotr , Hartl Daniel L
Published: April 2019

Previous experiments with temperature-sensitive mutants of the yeast enzyme orotidine 5′-phosphate decarboxylase (encoded in gene URA3) yielded the unexpected result that reversion occurs only through exact reversal of the original mutation (Jakubowska A, Korona R. 2009. Lack of evolutionary conservation at positions important for thermal stability in the yeast ODCase protein. Mol Biol Evol. 26(7):1431–1434.). We recreated a set of these mutations in which the codon had two nucleotide substitutions, making exact reversion much less likely. We screened these double mutants for reversion and obtained a number of compensatory mutations occurring at alternative sites in the molecule. None of these compensatory mutations fully restored protein performance. The mechanism of partial compensation is consistent with a model in which protein stabilization is additive, as the same secondary mutations can compensate different primary alternations. The distance between primary and compensatory residues precludes direct interaction between the sites. Instead, most of the compensatory mutants were clustered in proximity to the catalytic center. All of the second-site compensatory substitutions occurred at relatively conserved sites, and the amino acid replacements were to residues found at these sites in a multispecies alignment of the protein. Based on the estimated distribution of changes in Gibbs free energy among a large number of amino acid replacements, we estimate that, for most proteins, the probability that a second-site mutation would have a sufficiently large stabilizing effect to offset a temperature-sensitive mutation in the order of 10−4 or less. Hence compensation is likely to take place only for slightly destabilizing mutations because highly stabilizing mutations are exceeding rare.
DrugComb: an integrative cancer drug combination data portal
Authors: Zagidullin Bulat , Aldahdooh Jehad , Zheng Shuyu , Wang Wenyu , Wang Yinyin , Saad Joseph , Malyutina Alina , Jafari Mohieddin , Tanoli Ziaurrehman , Pessia Alberto , Tang Jing
Published: April 2019

Drug combination therapy has the potential to enhance efficacy, reduce dose-dependent toxicity and prevent the emergence of drug resistance. However, discovery of synergistic and effective drug combinations has been a laborious and often serendipitous process. In recent years, identification of combination therapies has been accelerated due to the advances in high-throughput drug screening, but informatics approaches for systems-level data management and analysis are needed. To contribute toward this goal, we created an open-access data portal called DrugComb (https://drugcomb.fimm.fi) where the results of drug combination screening studies are accumulated, standardized and harmonized. Through the data portal, we provided a web server to analyze and visualize users’ own drug combination screening data. The users can also effectively participate a crowdsourcing data curation effect by depositing their data at DrugComb. To initiate the data repository, we collected 437 932 drug combinations tested on a variety of cancer cell lines. We showed that linear regression approaches, when considering chemical fingerprints as predictors, have the potential to achieve high accuracy of predicting the sensitivity of drug combinations. All the data and informatics tools are freely available in DrugComb to enable a more efficient utilization of data resources for future drug combination discovery.
Endoscopic Transnasal Trans-Sphenoidal Approach for Pituitary Adenomas: A Comparison to the Microscopic Approach Cohort by Propensity Score Analysis
Authors: Castaño-Leon Ana M , Paredes Igor , Munarriz Pablo M , Jiménez-Roldán Luis , Hilario Amaya , Calatayud Maria , Hernandez-Lain Aurelio , Garcia Ester , Garcia Alfredo , Lagares Alfonso , Alén Jose F
Published: April 2019

BACKGROUND

Despite some evidence for the adoption of endoscopic transnasal trans-sphenoidal surgery (ETSS) for pituitary adenomas, the advantages of this technique over the traditional approach have not been robustly confirmed.

OBJECTIVE

To compare ETSS with the microscopic sublabial trans-septal trans-sphenoidal surgery (MTSS) for pituitary adenomas.

METHODS

We retrospectively reviewed 2 cohorts of ETSS and MTSS performed at our institution from 1995 to 2017. Patient characteristics, surgical data, and outcomes were recorded prospectively. We performed a univariate and multivariable analysis to determine the best surgical approach. To improve the quality of the results, we matched the distribution of patient characteristics between groups by propensity score (PS) method.

RESULTS

A total of 187 procedures (90 MTSS, 97 ETSS) were reviewed. We found better results in the ETSS group in terms of gross total resection (P = .002) and hormone-excess secretion control (P = .014). There was also a lower incidence of cerebrospinal fluid leakage (P = .039), transitory diabetes insipidus (P = .028), and postoperative hypopituitarism (P = .045), as well as a shorter hospital length of stay (P < .001). After PS matching, we confirmed by multivariable logistic regression analysis an increased odds ratio of gross total resection for the ETSS (3.910; 95% CI 1.720-8.889; P = .001).

CONCLUSION

By PS method, our results suggest that the ETSS provides advantages over the traditional MTSS approach for tumor resection. Better control of secreting tumors and a lower rate of most complications also support the selection of the ETSS approach for the treatment of pituitary adenomas.
Influenza Antiviral Prescribing Practices and the Influence of Rapid Testing Among Primary Care Providers in the US, 2009–2016
Authors: Fowlkes Ashley L , Steffens Andrea , Reed Carrie , Temte Jonathan L , Campbell Angela P ,   Influenza Incidence Surveillance Project Working Group, Rubino Heather , Heberlein-Larson Lea , Barlow Shari , Reisdorf Erik , Di Lonardo Steve , Martin Karen , Lynfield Ruth , Strain Anna , Boxrud Dave , Baber Jill , Feist Michele , McHugh Lisa , Green Nicole , Selzer Christine , Ledbetter Johnathan , Lojo Jose , Oni Oluwakemi , Thomas Ann , Boulton Rachelle , Kurkjian Katie , Toney Denise , Kelly Sean T , Hamilton Janet , Schroeder Monica
Published: April 2019

Background

Early influenza antiviral treatment within 2 days of illness onset can reduce illness severity and duration. Reliance on low sensitivity rapid influenza diagnostic tests (RIDTs) to guide antiviral prescribing has been reported. We describe antiviral prescribing practices among primary care providers from a large surveillance network in the United States.

Methods

From 2009–2016, a network of 36 to 68 outpatient clinics per year collected respiratory specimens and clinical data for patients with influenza-like illness (ILI). Specimens were tested for influenza using polymerase chain reaction (PCR). We used multivariable logistic regression to assess factors influencing antiviral prescribing.

Results

Among 13 540 patients with ILI, 2766 (20%) were prescribed antivirals. In age groups recommended to receive empiric antiviral treatment for suspected influenza, 11% of children <2 years and 23% of adults ≥65 years received a prescription. Among 3681 patients with a positive PCR test for influenza, 40% tested negative by RIDT. In multivariable analysis, prescription receipt was strongly associated with a positive RIDT (adjusted odds ratio [aOR] 12, 95% CI 11–14) and symptom onset ≤2 days before visit (aOR 4.3, 95% CI 3.8–4.9). Antiviral prescribing was also more frequent among pediatric and private family practice clinics compared with community health centers (aOR 1.9, 95% CI 1.6–2.2, and 1.3, 95% CI 1.1–1.5, respectively).

Conclusion

Primary care providers were more likely to prescribe antivirals to patients with a positive RIDT, but antivirals were prescribed infrequently even to patients in high-risk age groups. Understanding patient and provider characteristics associated with antiviral prescribing is important for communicating treatment recommendations.
Formalism of a harmonic oscillator in the future-included complex action theory
Authors: Nagao Keiichi , Nielsen Holger Bech
Published: April 2019

In a special representation of complex action theory that we call “future-included,” we study a harmonic oscillator model defined with a non-normal Hamiltonian $\hat{H}$, in which a mass $m$ and an angular frequency $\omega$ are taken to be complex numbers. In order for the model to be sensible some restrictions on $m$ and $\omega$ are required. We draw a phase diagram in the plane of the arguments of $m$ and $\omega$, according to which the model is classified into several types. In addition, we formulate two pairs of annihilation and creation operators, two series of eigenstates of the Hamiltonians $\hat{H}$ and $\hat{H}^\dagger$, and coherent states. They are normalized in a modified inner product $I_Q$, with respect to which the Hamiltonian $\hat{H}$ becomes normal. Furthermore, applying to the model the maximization principle that we previously proposed, we obtain an effective theory described by a Hamiltonian that is $Q$-Hermitian, i.e. Hermitian with respect to the modified inner product $I_Q$. The generic solution to the model is found to be the “ground” state. Finally we discuss what the solution implies.
Justice Anthony Kennedy’s Federalism and the Limits of State Sovereignty
Authors: Colucci Frank J
Published: April 2019

This article analyzes Justice Anthony M. Kennedy’s commitment to protecting state sovereignty. In contrast to scholars who view Kennedy’s behavior as merely pragmatic or centrist, this article focuses on principles and tensions underlying his liberty-based approach to federalism. From his early career in Sacramento through three decades on the U.S. Supreme Court, Kennedy sought to restore a federalism he considered essential to personal and political liberty but increasingly “endangered.” His opinions extended beyond the constitutional text to protect traditional areas of state concern, state treasuries, and local political decision making against increasing federal control. However, Kennedy subordinated state sovereignty when it interfered with the federal government’s direct relationship to citizens, promoted economic protectionism, and violated his expansive conceptions of constitutional liberty and human dignity. The article concludes by situating Kennedy’s distinctive conception of federalism within the larger Rehnquist and Roberts Courts.
Vitamin D and UV exposure in construction workers—a randomized control trial using text messaging to promote positive behaviours
Authors: Lansdown T C , Cowan S , Nioi A , Cowie H , Wendelboe-Nelson C , Rashid S , Ritchie P , Cherrie J W
Published: April 2019

Background

The aim of this study was to determine whether a text messaging intervention (supported by a smartphone application) would be effective in the promotion of sun-safe behaviours. Both excessive and insufficient exposure to ultra-violet (UV) radiation were considered.

Methods

A randomized control crossover trial was conducted. 112 participants from nine sites in the United Kingdom contributed to the study. There were three intervention waves, two in winter (Vitamin D-focussed) and one in summer (UV exposure-focussed). Stages of Change, Standard Erythemal (UV) Dose and assayed blood samples (Vitamin D) were employed to evaluate the effectiveness throughout the 21-day data collection periods.

Results

The intervention was effective in promoting positive progression in Stages of Change for Vitamin D; and this in turn was predictive of increased Vitamin D levels in participants. More limited positive findings were found with respect to UV exposure. Overall, for those in the Intervention, Vitamin D levels were significantly predicted to increase during both of the winter data collection waves.

Conclusions

Interventions of this type are recommended to promote healthy Vitamin-D levels in construction workers.
How rhythms of the sleeping brain tune memory and synaptic plasticity
Authors: Puentes-Mestril Carlos , Roach James , Niethard Niels , Zochowski Michal , Aton Sara J
Published: April 2019

Decades of neurobehavioral research has linked sleep-associated rhythms in various brain areas to improvements in cognitive performance. However, it remains unclear what synaptic changes might underlie sleep-dependent declarative memory consolidation and procedural task improvement, and why these same changes appear not to occur across a similar interval of wake. Here we describe recent research on how one specific feature of sleep—network rhythms characteristic of rapid eye movement and non-rapid eye movement—could drive synaptic strengthening or weakening in specific brain circuits. We provide an overview of how these rhythms could affect synaptic plasticity individually and in concert. We also present an overarching hypothesis for how all network rhythms occurring across the sleeping brain could aid in encoding new information in neural circuits.
Implementing Equal Pay Policy: Clash Between Gender Equality and Corporatism
Authors: Saari Milja , Kantola Johanna , Koskinen Sandberg Paula
Published: April 2019

More often than not gender equality policies are good on paper but fall foul of politicized implementation processes. The reasons behind this are becoming a key area of investigation for feminist scholarship on the implementation of gender policies. This article analyzes the barriers to implementing gender equality policies in a corporatist regime. Focusing on the 2007 nurses’ industrial action in Finland, the article considers the case of “Nancy the Nurse,” which aimed at negotiating higher wages for nurses. Our findings suggest that the corporatist regime effectively prevented the implementation of gender equality policy, thus upholding the status quo and maintaining current wage relativities.
Nodulation Induces Systemic Resistance of Medicago truncatula and Pisum sativum Against Erysiphe pisi and Primes for Powdery Mildew-Triggered Salicylic Acid Accumulation
Authors: Smigielski Lara , Laubach Eva-Maria , Pesch Lina , Glock Joanna Marie Leyva , Albrecht Frank , Slusarenko Alan , Panstruga Ralph , Kuhn Hannah
Published: April 2019

Plants encounter beneficial and detrimental microorganisms both above- and belowground and the health status of the plant depends on the composition of this pan-microbiome. Beneficial microorganisms contribute to plant nutrition or systemically or locally protect plants against pathogens, thus facilitating adaptation to a variety of environments. Induced systemic resistance, caused by root-associated microbes, manifests as aboveground resistance against necrotrophic pathogens and is mediated by jasmonic acid/ethylene-dependent signaling. By contrast, systemic acquired resistance relies on salicylic acid (SA) signaling and confers resistance against secondary infection by (hemi)biotrophic pathogens. To investigate whether symbiotic rhizobia that are ubiquitously found in natural ecosystems are able to modulate resistance against biotrophs, we tested the impact of preestablished nodulation of Medicago truncatula and pea (Pisum sativum) plants against infection by the powdery mildew fungus Erysiphe pisi. We found that root symbiosis interfered with fungal penetration of M. truncatula and reduced asexual spore formation on pea leaves independently of symbiotic nitrogen fixation. Improved resistance of nodulated plants correlated with elevated levels of free SA and SA-dependent marker gene expression upon powdery mildew infection. Our results suggest that nodulation primes the plants systemically for E. pisi-triggered SA accumulation and defense gene expression, resulting in increased resistance.
Prevalence of Soil-borne Diseases in Kalanchoe blossfeldiana Reveals a Complex of Pathogenic and Opportunistic Fungi
Authors: Madriz-Ordeñana Kenneth , Jørgensen Hans Jørgen Lyngs , Balan Andreea , Sørensen Daniel Madriz , Nielsen Kai Lønne , Thordal-Christensen Hans
Published: April 2019

Greenhouse cultivation of ornamentals is subjected to a high incidence of soil-borne fungal pathogens. In Kalanchoe, these pathogens are responsible for root and stem rot, and for infection of the vascular tissue. Well-known soil-borne pathogens are believed to cause these diseases. Yet, a systematized survey of these pathogens is lacking for Kalanchoe produced commercially. Here, we studied the occurrence of soil-borne fungal pathogens associated with cultivation of Kalanchoe in Denmark and production of cuttings and stock plants in greenhouse facilities located in Turkey and Vietnam. Molecular identification of pathogens complemented mycological identification and pathogenicity testing of the soil-borne fungal pathogens. This study revealed that the fungi Corynespora cassiicola, Thielaviopsis basicola, Fusarium solani, and F. oxysporum are the most prevalent pathogens associated with root and stem rotting and wilt of Kalanchoe under the conditions studied. Furthermore, the study showed that some of the pathogens are part of an infection complex comprising both primary and opportunistic fungal species. The fact that some of the pathogens were present in some regions, while absent in others, suggests how they move between greenhouse facilities on infected plant material. This study generated important information about the soil-borne fungal complex affecting Kalanchoe, which is useful for a better understanding of the biology of the disease and for designing control strategies.