bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat-shock inducible CRISPR/Cas9 system generates heritable mutations in rice
Authors: Nandy Soumen , Pathak Bhuvan , Zhao Shan , Srivastava Vibha
Published: September 2018

Transient expression of CRISPR/Cas9 is an effective approach for limiting its activities and improving its precision in genome editing. Here, we describe the heat-shock inducible CRISPR/Cas9 system for controlled genome editing, and demonstrate its efficiency in the model crop, rice. Using a soybean heat-shock protein gene promoter and the rice U3 promoter to express Cas9 and sgRNA, respectively, we developed the heat-shock (HS) inducible CRISPR/Cas9 system, and tested its efficacy in targeted mutagenesis. Two loci were targeted by transforming rice with HS-CRISPR/Cas9 vectors, and the presence of targeted mutations was determined before and after the HS treatment. We found only a low rate of targeted mutagenesis before HS, but an increased rate of mutagenesis after HS treatment among the transgenic lines. Specifically, only ∼11% of transformants showed characteristic insertions-deletions at the ambient room temperature, but a higher percentage (∼45%) of callus lines developed mutations after a few days of HS treatment. Analysis of regenerated plants harboring HS-CRISPR/Cas9 revealed that targeted mutagenesis was suppressed in the plants but induced by HS, which was detectable by Sanger sequencing after several weeks of HS treatments. Most importantly, the HS-induced mutations were transmitted to the progeny at a high rate, generating monoallelic and biallelic mutant lines that independently segregated from Cas9. Taken together, this work shows that HS-CRISPR/Cas9 is a controlled and reasonably efficient platform for genome editing, and therefore, a promising tool for limiting genome-wide off-target effects and improving the precision of genome editing.

Significance Statement

A method for the temporal control on gene editing based on the use of heat-shock induced expression of CRISPR/Cas9 is described, which was efficient in producing heritable mutations in the rice genome. We assume this method will be useful for targeting essential genes and improving the precision of CRISPR/Cas9.
Quantitative multi-locus metabarcoding and waggle dance interpretation reveal honey bee spring foraging patterns in Midwest agroecosystems
Authors: Richardson Rodney T. , Curtis Hailey R. , Matcham Emma G. , Hua-Lin Chia , Suresh Sreelakshmi , Sponsler Douglas B. , Hearon Luke E. , Johnson Reed M.
Published: September 2018

We explored the pollen foraging behavior of honey bee colonies situated in the corn and soybean dominated agroecosystems of central Ohio over a month-long period using both pollen metabarcoding and waggle dance inference of spatial foraging patterns. For molecular pollen analysis we developed simple and cost-effective laboratory and bioinformatics methods. Targeting four plant barcode loci (ITS2, rbcL, trnL and trnH), we implemented metabarcoding library preparation and dual-indexing protocols designed to minimize amplification biases and index mis-tagging events. We constructed comprehensive, curated reference databases for hierarchical taxonomic classification of metabarcoding data and used these databases to train the Metaxa2 DNA sequence classifier. Comparisons between morphological and molecular palynology provide strong support for the quantitative potential of multi-locus metabarcoding. Results revealed consistent foraging habits between locations and show clear trends in the phenological progression of honey bee spring foraging in these agricultural areas. Our data suggest that three key taxa, woody Rosaceae such as pome fruits and hawthorns, Salix, and Trifolium provided the majority of pollen nutrition during the study. Spatially, these foraging patterns were associated with a significant preference for forests and tree lines relative to crop fields and herbaceous land cover.
Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats
Authors: Javadi-Paydar Mehrak , Kerr Tony M. , Harvey Eric L. , Cole Maury , Taffe Michael A.
Published: September 2018

Background

Electronic nicotine delivery systems (ENDS, e-cigarettes) are increasingly used for the self-administration of nicotine by various human populations, including previously nonsmoking adolescents. Studies in preclinical models are necessary to evaluate health impacts of ENDS including the development of nicotine addiction, effects of ENDS vehicles, flavorants and co-administered psychoactive substances such as ∆9-tetrahydrocannabinol (THC). This study was conducted to validate a rat model useful for the study of nicotine effects delivered by inhalation of vapor created by ENDS.

Methods

Male Sprague-Dawley rats (N=8) were prepared with radiotelemetry devices for the reporting of temperature and activity. Experiments subjected rats to inhalation of vapor generated by an electronic nicotine delivery system (ENDS) adapted for rodents. Inhalation conditions included vapor generated by the propylene glycol (PG) vehicle, Nicotine (1, 10, 30 mg/mL in the PG) and THC (12.5, 25 mg/mL).

Results

Nicotine inhalation increased spontaneous locomotion and decreased body temperature of rats. Pretreatment with the nicotinic cholinergic receptor antagonist mecamylamine (2 mg/kg, i.p.) prevented stimulant effects of nicotine vapor inhalation and attenuated the hypothermic response. Combined inhalation of nicotine and THC resulted in apparently independent effects which were either additive (hypothermia) or opposed (activity).

Conclusions

These studies provide evidence that ENDS delivery of nicotine via inhalation results in nicotine-typical effects on spontaneous locomotion and thermoregulation in male rats. Effects were blocked by a nicotinic antagonist, demonstrating mechanistic specificity. This system will therefore support additional studies of the contribution of atomizer/wick design, vehicle constituents and/or flavorants to the effects of nicotine administered by ENDS.
Co-option and Detoxification of a Phage Lysin for Housekeeping Function
Authors: Randich Amelia M. , Kysela David T. , Morlot Cécile , Brun Yves V.
Published: September 2018

Temperate phages constitute a potentially beneficial genetic reservoir for bacterial innovation despite being selfish entities encoding an infection cycle inherently at odds with bacterial fitness. These phages integrate their genomes into the bacterial host during infection, donating new, but deleterious, genetic material: the phage genome encodes toxic genes, such as lysins, that kill the bacterium during the phage infection cycle. Remarkably, some bacteria have exploited the destructive properties of phage genes for their own benefit by co-opting them as toxins for functions related to bacterial warfare, virulence, and secretion. However, do toxic phage genes ever become raw material for functional innovation? Here we report on a toxic phage gene whose product has lost its toxicity and has become a domain of a core cellular factor, SpmX, throughout the bacterial order Caulobacterales. Using a combination of phylogenetics, bioinformatics, structural biology, cell biology, and biochemistry, we have investigated the origin and function of SpmX and determined that its occurrence is the result of the detoxification of a phage peptidoglycan hydrolase gene. We show that the retained, attenuated activity of the phage-derived domain plays an important role in proper cell morphology and developmental regulation in representatives of this large bacterial clade. To our knowledge, this is the first observation of phage gene domestication in which a toxic phage gene has been co-opted for a housekeeping function.
Natural variation in the roles of C. elegans autophagy components during microsporidia infection
Authors: Balla Keir M. , Lažetić Vladimir , Troemel Emily
Published: September 2018

Natural genetic variation can determine the outcome of an infection, and often reflects the co-evolutionary battle between hosts and pathogens. We previously found that a natural variant of the nematode Caenorhabditis elegans from Hawaii (HW) has increased resistance against natural microsporidian pathogens in the Nematocida genus, when compared to the standard laboratory strain of N2. In particular, HW animals can clear infection, while N2 animals cannot. In addition, HW animals have lower levels of intracellular colonization of Nematocida compared to N2. Here we investigate how this natural variation in resistance relates to autophagy. We found that there is much better targeting of autophagy-related machinery to parasites under conditions where they are cleared. In particular, ubiquitin targeting to Nematocida cells correlates very well with their subsequent clearance in terms of timing, host strain and age, as well as Nematocida species. Furthermore, clearance correlates with targeting of the LGG-2/LC3 autophagy protein to parasite cells, with HW animals having much more efficient targeting of LGG-2 to parasite cells than N2 animals. Surprisingly, however, we found that lgg-2 is not required to clear infection. Instead we found that loss of lgg-2 leads to increased intracellular colonization in the HW background, although interestingly, it does not affect colonization in the N2 background. Altogether our results suggest that there is natural genetic variation in an lgg-2-dependent process that regulates intracellular levels of microsporidia at a very early stage of infection prior to clearance.
Stochastic Simulation to Visualize Gene Expression and Error Correction in Living Cells
Authors: Chen Kevin Y. , Zuckerman Daniel M. , Nelson Philip C.
Published: September 2018

Stochastic simulation can make the molecular processes of cellular control more vivid than the traditional differential-equation approach by generating typical system histories instead of just statistical measures such as the mean and variance of a population. Simple simulations are now easy for students to construct from scratch, that is, without recourse to black-box packages. In some cases, their results can also be compared directly to single-molecule experimental data. After introducing the stochastic simulation algorithm, this article gives two case studies, involving gene expression and error correction, respectively. Code samples and resulting animations showing results are given in the online supplement.
Active protein neddylation or ubiquitylation is dispensable for stress granule dynamics
Authors: Markmiller Sebastian , Fulzele Amit , Higgins Reneé , Yeo Gene W. , Bennett Eric J
Published: September 2018

Many protein homeostasis stressors induce the formation of membraneless cytoplasmic stress granules (SGs) that contain large assemblies of repressed mRNAs and associated RNA binding proteins. Similar stressors have been shown to globally alter the function of the ubiquitin proteasome system (UPS) resulting in the accumulation of ubiquitylated proteins. Previous studies have demonstrated that ubiquitin and specific UPS components co-localize with SGs and that reducing the abundance or activity of ubiquitin pathway proteins can inhibit SG formation. These studies suggest that SG dynamics and composition may be regulated by ubiquitylation of SG resident proteins. Using ubiquitin-specific proteomic approaches, we demonstrate that many proteins, including some SG proteins are dynamically ubiquitylated upon SG-inducing sodium arsenite treatment. We utilized potent and selective inhibitors of the ubiquitin activating enzyme (UAE) or the NEDD8 activating enzyme (NAE) to directly test if active protein ubiquitylation or neddylation was required for SG dynamics. Using ubiquitin-site specific proteomics, we establish that UAE inhibition results in the rapid loss of nearly all protein ubiquitylation regardless of ubiquitin chain type. Addition of UAE or NAE inhibitors to cells did not alter arsenite-induced SG formation or dissolution. While we confirmed that ubiquitin co-localizes with both sodium arsenite and thapsigargin-induced SGs, antibodies that recognize all forms of ubiquitin more strongly co-localize with SGs compared to antibodies that preferentially recognize polyubiquitin or specific polyubiquitin-linkages. Interestingly, ubiquitin itself co-localizes with SGs in a UAE independent manner suggesting that the ubiquitin present within SGs is likely unconjugated ubiquitin. Our findings clearly demonstrate that active protein ubiquitylation or neddylation is not required for SG dynamics. These results suggest that ubiquitin-binding SG proteins may recruit free ubiquitin into SGs to modulate SG protein interactions.
Gut microbial compositions mirror caste-specific diets in a major lineage of eusocial insects
Authors: Otani Saria , Zhukova Mariya , Koné N’golo Abdoulaye , da Costa Rafael Rodrigues , Mikaelyan Aram , Sapountzis Panagiotis , Poulsen Michael
Published: September 2018

Eusocial insects owe their ecological success to the division of labour and processes within colonies often rely on the presence of specific microbial symbionts, but associations between microbial community compositions and castes with different tasks and diets within colonies remain largely unexplored. Fungus-growing termites evolved to use fungi to externally degrade plant material, complemented by specific and complex gut microbiotas. Here we explore to which extent division of labour and dietary differences within fungus-growing termite castes are linked to gut bacterial community structure. Using amplicon sequencing, we characterise community compositions in sterile (worker and soldier) and reproductive (queen and king) termites and combine this with gut enzyme, microscopy, andin situanalyses to further elucidate sterile caste-specific microbiota compositions. Gut bacterial communities are structured primarily according to termite caste and genus. In contrast to the observed rich and diverse sterile caste microbiotas, royal pair microbiotas are extremely skewed and dominated by few bacterial taxa, reflecting the specialised dietary intake and unique, reproduction-centred lifestyle of the queen and king.
Rat bone marrow derived mesenchymal stem cells differentiate to germ cell like cells
Authors: Kumar Kuldeep , Das Kinsuk , Madhusoodan AP , Kumar Ajay , Singh Purnima , Mondal Tanmay , Bag Sadhan
Published: September 2018

Summary Statement

Thein vitrodifferentiation of rMSCs provides an excellent model for studying cell commitment and their potential in stem cell technology. We have demonstrated that rat bone marrow derived MSCs are able to differentiate into germ-line cellsin vitrowhich has an enormous scope in the advancement of fertility research. In future, this technique can be utilized in different domestic animal species for propagation of elite germ plasm.

Germ cells undergo distinctive male or female pathways to produce spermatozoa or oocyte respectively essential for sexual reproduction. Mesenchymal stem cells (MSCs) have the capacity of trans-differentiation to form the multiple lineages of cells of mesoderm, endoderm, and ectoderm origin. Herein, MSCs were isolated from rat bone marrow and characterized by their morphological features, expression of surface markers by immunophenotyping and molecular biology tools as well as self renewal and differentiation capability. Thereafter, by inducing these cells with retinoic acid we could able to show that bone marrow derived MSCs are able to trans-differentiate into male germ cell-like cells which were further characterized by the expressions of germ cell specific markers. Thisin vitrostudy for the generation of germ-like cells suggests that bone marrow MSCs can be a potential source of germ cells that could be a sustainable source of sperm / oocyte production for potential therapeutic applications in future. Moreover, this technique can be applied in different domestic animal species for propagation of elite germ plasm.
Visualizing ATP-dependent substrate-processing dynamics of the human 26S proteasome at near-atomic resolution
Authors: Dong Yuanchen , Zhang Shuwen , Wu Zhaolong , Li Xuemei , Wang Wei Li , Zhu Yanan , Stoilova-McPhie Svetla , Lu Ying , Finley Daniel , Mao Youdong
Published: September 2018

The proteasome is an ATP-dependent 2.5-megadalton machine responsible for ubiquitylated protein degradation in all eukaryotic cells. Here we present cryo-EM structures of the substrate-engaged human 26S proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during polyubiquitylated protein degradation. These structures visualize a continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to processive substrate translocation, during which ATP hydrolysis sequentially navigate through all six ATPase subunits. Three principle modes of coordinated ATP hydrolysis are observed, featuring hydrolytic events in two oppositely positioned ATPases, in two consecutive ATPases, and in one ATPase at a time. They regulate deubiquitylation, translocation initiation and processive unfolding of substrates, respectively. A collective power stroke in the ATPase motor is generated by synchronized ATP binding and ADP release in the substrate-engaging and disengaging ATPases, respectively. It is amplified largely in the substrate-disengaging ATPase, and propagated unidirectionally by coordinated ATP hydrolysis in the third consecutive ATPase.
Neural responses to natural and model-matched stimuli reveal distinct computations in primary and non-primary auditory cortex
Authors: Norman-Haignere Sam V. , McDermott Josh H.
Published: September 2018

A central goal of sensory neuroscience is to construct models that can explain neural responses to complex, natural stimuli. As a consequence, sensory models are often tested by comparing neural responses to natural stimuli with model responses to those stimuli. One challenge is that distinct model features are often correlated across natural stimuli, and thus model features can predict neural responses even if they do not in fact drive them. Here we propose a simple alternative for testing a sensory model: we synthesize stimuli that yield the same model response as a natural stimulus, and test whether the natural and “model-matched” stimulus elicit the same neural response. We used this approach to test whether a common model of auditory cortex – in which spectrogram-like peripheral input is processed by linear spectrotemporal filters – can explain fMRI responses in humans to natural sounds. Prior studies have that shown that this model has good predictive power throughout auditory cortex, but this finding could reflect stimulus-driven correlations. We observed that fMRI voxel responses to natural and model-matched stimuli were nearly equivalent in primary auditory cortex, but that non-primary regions showed highly divergent responses to the two sound sets, suggesting that neurons in non-primary regions extract higher-order properties not made explicit by traditional models. This dissociation between primary and non-primary regions was not clear from model predictions due to the influence of stimulus-driven response correlations. Our methodology enables stronger tests of sensory models and could be broadly applied in other domains.

Author Summary

Modeling neural responses to natural stimuli is a core goal of sensory neuroscience. Here we propose a new approach for testing sensory models: we synthesize a “model-matched” stimulus that yields the same model response as a natural stimulus, and test whether it produces the same neural response. We used model-matching to test whether a standard model of auditory cortex can explain human cortical responses measured with fMRI. Model-matched stimuli produced nearly equivalent voxel responses in primary auditory cortex, but highly divergent responses in non-primary regions. This dissociation was not evident using more standard approaches for model testing, and suggests that non-primary regions compute higher-order stimulus properties not captured by traditional models. The methodology could be broadly applied in other domains.
Synthetic genome defenses against selfish DNA elements stabilize engineered bacteria against evolutionary failure
Authors: Geng Peng , Leonard Sean P. , Mishler Dennis M. , Barrick Jeffrey E.
Published: September 2018

Mobile genetic elements drive evolution by disrupting genes and rearranging genomes. Eukaryotes have evolved epigenetic mechanisms, including DNA methylation and RNA interference, that silence mobile elements and thereby preserve the integrity of their genomes. We created an artificial reprogrammable epigenetic system based on CRISPR interference to give engineered bacteria a similar line of defense against transposons and other selfish elements in their genomes. We demonstrate that this CRISPR interference against mobile elements (CRISPRi-ME) approach can be used to simultaneously repress two different transposon families in Escherichia coli, thereby increasing the evolutionary stability of costly protein expression. We further show that silencing a transposon in Acinetobacter baylyi ADP1 reduces mutation rates by a factor of five, nearly as much as deleting all copies of this element from its genome. By deploying CRISPRi-ME on a broad-host-range vector we have created a generalizable platform for stabilizing the genomes of engineered bacterial cells for applications in metabolic engineering and synthetic biology.

Significance

Engineered cells often cease to function or lose productivity when mutations arise in their genomes. Mobile DNA elements, such as transposons, are major sources of these inactivating mutations. Eukaryotic genomes have evolved flexible epigenetic defenses against mobile DNA that help them to maintain genome integrity, but bacteria do not possess comparable silencing systems. We developed a synthetic control system based on CRISPR interference that can be used to give bacterial cells a reprogrammable line of defense against selfish DNA elements in their genomes. We show that this system effectively represses multicopy transposons and multiple families of transposons. Limiting selfish DNA proliferation within a genome in this way improves the reliability of genetically engineered functions in replicating bacterial cell populations.
Evolutionary analyses of base-pairing interactions in DNA and RNA secondary structures
Authors: Golden Michael , Murrell Ben , Pybus Oliver G. , Martin Darren , Hein Jotun
Published: September 2018

Pairs of nucleotides within functional nucleic acid secondary structures often display evidence of coevolution that is consistent with the maintenance of base-pairing. Here we introduce a sequence evolution model, MESSI, that infers coevolution associated with base-paired sites in DNA or RNA sequence alignments. MESSI can estimate coevolution whilst accounting for an unknown secondary structure. MESSI can also use GPU parallelism to increase computational speed. We used MESSI to infer coevolution associated with GC, AU (AT in DNA), GU (GT in DNA) pairs in non-coding RNA alignments, and in single-stranded RNA and DNA virus alignments. Estimates of GU pair coevolution were found to be higher at base-paired sites in single-stranded RNA viruses and non-coding RNAs than estimates of GT pair coevolution in single-stranded DNA viruses, suggesting that GT pairs do not stabilise DNA secondary structures to the same extent that GU pairs do in RNA. Additionally, MESSI estimates the degrees of coevolution at individual base-paired sites in an alignment. These estimates were computed for a SHAPE-MaP-determined HIV-1 NL4-3 RNA secondary structure and two corresponding alignments. We found that estimates of coevolution were more strongly correlated with experimentally-determined SHAPE-MaP pairing scores than three non-evolutionary measures of base-pairing covariation. To assist researchers in prioritising substructures with potential functionality, MESSI automatically ranks substructures by degrees of coevolution at base-paired sites within them. Such a ranking was created for an HIV-1 subtype B alignment, revealing an excess of top-ranking substructures that have been previously identified as having structure-related functional importance, amongst several uncharacterised top-ranking substructures.
Successful outcome of early ambulation after extensive skin grafting in extramammary Paget's disease
Authors: Maeda Takuya , Yoshino Koji , Nagai Kojiro , Oaku Satoe , Kato Megumi , Hata Hiroo
Published: September 2018

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that mainly affects the senior population. There is a relatively high risk of postoperative complications from surgery in the senior population, such as disuse syndrome, deep vein thrombosis and postoperative delirium. To prevent such postoperative complications, early ambulation is recommended. However, EMPD often requires extensive skin grafting because of the need for a large resection margin. To avoid skin graft failure, many institutions require that patients have several days of postoperative bedrest. For these reasons, there has been no consensus on standard postoperative rest for EMPD. In this study, we defined 20 patients who walked from the day after surgery as an “early ambulation group” and 23 patients with 5 days postoperative bedrest as a “control group”. We evaluated the skin graft survival, postoperative complications and the duration of hospitalization for both groups. Skin graft survival and complications related to the surgical wounds (infection and hemorrhage) in the early ambulation group were found to be comparable with those in the control group. Of note, the other complications (aspiration pneumonia, ileus, delirium, orthostatic hypotension and insomnia) were less frequent (P < 0.001) and the duration of postoperative hospitalization was shorter (P = 0.013) in the early ambulation group than in the control group. Our study suggests that early ambulation after surgery for EMPD does not impair skin graft survival but reduces postoperative complications and the duration of hospitalization.
Quantifying wildlife watchers’ preferences to investigate the overlap between recreational and conservation value of natural areas
Authors: Mancini Francesca , Coghill George M. , Lusseau David
Published: September 2018

Nature‐based recreation substantially benefits human wellbeing, for example, by improving physical and mental health. However, recreation can also have severe ecological impacts. The recreational value of landscapes and natural areas is often used to generate support for public spending in conservation. However, we still don't know whether nature‐based recreationists place greater recreational value on natural areas that have high conservation value compared to other green spaces.

Here, we determine which attributes of nature‐based tourism provide recreational services. We used pictures of wildlife posted on Flickr to quantify wildlife watching activities in Scotland. We then determined the environmental variables key to attracting wildlife watchers to a destination, such as protected areas (PAs), the perceived naturalness, and the presence of different types of infrastructure.

Infrastructure best predicts the intensity of wildlife watching activities in Scotland, while areas of high natural value are rarely used. PAs are weak attractors of wildlife watchers, with PAs designated to protect threatened habitats or species having low recreational value. In accessible and highly visited areas, higher biodiversity increases the intensity of wildlife watching activities.

Synthesis and applications. Areas of high natural and conservation value and areas of high recreational value do not tend to overlap. Recreational ecosystem services are mainly provided by the wider countryside and highly transformed landscapes, as opposed to wild ecosystems and protected areas designated to protect environmental features of high conservation value. These results question the synergy between the goals of recreation and those of conservation and the use of recreation as a justification for economic investment in conservation. During wildlife watching activities most people experience an urbanised, highly transformed nature; it is important to determine how this human‐dominated nature can influence support for conservation of wild and remote areas.
Onmang Þæt – Incipient Grammaticalisation in Old and Middle English
Authors: Nykiel Jerzy
Published: September 2018

This paper examines the development and use of the temporal subordinatoronmang þæt. The development of the subordinator is seen as a special case of grammaticalisation, i.e. incipient grammaticalisation.Onmang þætarises through the incorporation of the prepositional phraseonmang+ demonstrative into the subordinator structure and in this respectonmang þætresembles the grammaticalisation of otherOEsubordinators. The grammaticalisation ofonmang þætis however arrested in earlyME, as the paper shows using a generative approach. I interpret this turn in the grammaticalisation of the subordinator as indicative of incipient grammaticalisation and I further use this observation as an avenue to identifying other features concomitant with incipient grammaticalisation. What I suggest is that incipient grammaticalisation should be associated with low frequency, minimal erosion, lack of fusion, and, finally, specialisation. I tentatively argue that options reduced via specialisation, as is the case withonmang þæt, may be the ones that qualify as cases of incipient grammaticalisation. Importantly, what follows is that incipient grammaticalisation as discussed in this study is not to be taken as referring to the early stages of grammaticalisation as such but to the grammaticalisation of infrequent structures available for a longer period of time.
Does social capital pay off? The case of small business resilience after Hurricane Katrina
Authors: Torres Ariana P. , Marshall Maria I. , Sydnor Sandra
Published: September 2018

This article uses objective and subjective measures of small business resilience and multiple categories of social capital pay‐offs to answer two main questions. Does social capital pay off after a natural disaster; and if it does, what type of social capital has the greatest impact on small business resilience? The pay‐off from bridging social capital—receiving support from the community—is what drives both objective and subjective resilience post‐Katrina. The results also show linking capital—support from institutions—can improve economic resilience. Our results provide evidence social capital is a key asset for long‐term resilience for small businesses. Business owners with links to the community and institutions—with more social capital—will be better off when facing a natural disaster.
International labour standards and decent work: a critical analysis of Thailand's experiences, with suggestions for theory, policy, practice and research
Authors: Suttawet Chokchai , Bamber Greg J
Published: September 2018

The International Labour Organization (ILO) promotes labour standards and decent work to counter a global ‘race to the bottom’ in terms of job regulation. By analysing Thailand's experiences, we consider three questions: 1) How might we characterize Thai capitalism?; 2) What are Thailand's labour market contexts for human resource management and industrial relations?; and 3) What is Thailand's situation regarding decent work and how is it related to politics, ILO labour standards and labour law? We identify two Thai labour‐market contexts: state‐owned and private enterprises where there is unionization (Type A); and public services/smaller enterprises/informal work where unionization is negligible (Type B). We find implementation of decent work is patchy. We suggest that Thailand reforms its tripartite agency to promote decent work and improve human resource management. These steps are more likely to be more effective and sustained under a parliamentary democracy than under a military junta. Our analysis has relevance also for other economies.
Guidelines and considerations for designing field experiments simulating precipitation extremes in forest ecosystems
Authors: Asbjornsen Heidi , Campbell John L. , Jennings Katie A. , Vadeboncoeur Matthew A. , McIntire Cameron , Templer Pamela H. , Phillips Richard P. , Bauerle Taryn L. , Dietze Michael C. , Frey Serita D. , Groffman Peter M. , Guerrieri Rosella , Hanson Paul J. , Kelsey Eric P. , Knapp Alan K. , McDowell Nathan G. , Meir Patrick , Novick Kimberly A. , Ollinger Scott V. , Pockman Will T. , Schaberg Paul G. , Wullschleger Stan D. , Smith Melinda D. , Rustad Lindsey E.
Published: September 2018

Precipitation regimes are changing in response to climate change, yet understanding of how forest ecosystems respond to extreme droughts and pluvials remains incomplete. As future precipitation extremes will likely fall outside the range of historical variability, precipitation manipulation experiments (PMEs) are critical to advancing knowledge about potential ecosystem responses. However, fewPMEs have been conducted in forests compared to short‐statured ecosystems, and forestPMEs have unique design requirements and constraints. Moreover, past forestPMEs have lacked coordination, limiting cross‐site comparisons. Here, we review and synthesize approaches, challenges, and opportunities for conductingPMEs in forests, with the goal of guiding design decisions, while maximizing the potential for coordination.

We reviewed 63 forestPMEs at 70 sites world‐wide. Workshops, meetings, and communications with experimentalists were used to generate and build consensus around approaches for addressing the key challenges and enhancing coordination.

Past forestPMEs employed a variety of study designs related to treatment level, replication, plot and infrastructure characteristics, and measurement approaches. Important considerations for establishing new forestPMEs include: selecting appropriate treatment levels to reach ecological thresholds; balancing cost, logistical complexity, and effectiveness in infrastructure design; and preventing unintended water subsidies. Response variables in forestPMEs were organized into three broad tiers reflecting increasing complexity and resource intensiveness, with the first tier representing a recommended core set of common measurements.

Differences in site conditions combined with unique research questions of experimentalists necessitate careful adaptation of guidelines for forestPMEs to balance local objectives with coordination among experiments. We advocate adoption of a common framework for coordinating forestPMEdesign to enhance cross‐site comparability and advance fundamental knowledge about the response and sensitivity of diverse forest ecosystems to precipitation extremes.
PyPHLAWD: A python tool for phylogenetic dataset construction
Authors: Smith Stephen A. , Walker Joseph F.
Published: September 2018

Comprehensive phylogenetic trees are essential for many ecological and evolutionary studies. Researchers may use existing trees or construct their own. In order to infer new trees, researchers often rely on programmes that construct datasets from publicly available molecular data.

Here, we present PyPHLAWD, a phylogenetically guided tool written in python that creates molecular datasets for building trees. PyPHLAWD constructs clusters (putative orthologs) that may be used for downstream analyses and provides users with a set of easy to interpret results. PyPHLAWD can conduct both baited (analyses that require the identification of gene regions a priori) and clustering analyses (analyses that do not require a priori identification of gene regions).

PyPHLAWD is extensible, flexible, open source, and available at https://github.com/FePhyFoFum/PyPHLAWD, with a detailed website outlining instructions and functionality at https://fephyfofum.github.io/PyPHLAWD/.

The utility of PyPHLAWD is highlighted here with an example workflow for the plant clade Dipsacales and may be applied to any clade with publicly available data on GenBank.
Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis
Authors: Okhuijsen‐Pfeifer C. , Huijsman E. A. H. , Hasan A. , Sommer I. E. C. , Leucht S. , Kahn R. S. , Luykx J. J.
Published: September 2018

Objective

No consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.

Methods

Articles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.

Results

Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).

Conclusion

The few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.
Carotid Artery Calcification on Orthopantomograms (CACO Study) – is it indicative of carotid stenosis?
Authors: Constantine S , Roach D , Liberali S , Kiermeier A , Sarkar P , Jannes J , Sambrook P , Anderson P , Beltrame J
Published: September 2018

It is unclear whether incidental carotid artery calcification (CAC) on radiographs has a defined relationship to clinically significant carotid artery stenosis, and therefore risk of stroke. The primary objective of this study was to ascertain the relationship between dental radiograph detected carotid calcification and carotid artery stenoses ≥50% on carotid duplex ultrasound. We carried out an observational study of patients undergoing routine dental orthopantomogram (OPG) examinations. Consecutive patients with CAC on OPG were prospectively matched to those without CAC based on age and gender. Ultrasound of the carotid arteries was performed to determine the presence of stenosis (≥50%) in either vessel. Of 5780 consecutive OPG examinations with suitable images for analysis, CAC was detected in 10.8%. A total of 233 patients underwent carotid ultrasound (130 with and 103 without CAC on OPG). The prevalence of a clinically significant (≥50%) carotid stenosis on ultrasound was 15.4% (20/130) in those with CAC and 5.8% (6/103) for those without CAC on OPG. Incidental CAC detected on routine OPG requires both radiological reporting and clinical follow‐up since 1 in 7 patients will have a clinically significant carotid artery stenosis as compared with 1 in 20 patients who do not have CAC.

Trial Registration: Australian and New Zealand Clinical Trials Registry website (U1111‐1148‐1066). http://www.ANZCTR.org.au/ACTRN12613001038785.aspx
Diagnosis and management of NSAID‐Exacerbated Respiratory Disease (N‐ERD)—a EAACI position paper
Authors: Kowalski Marek L. , Agache Ioana , Bavbek Sevim , Bakirtas Arzu , Blanca Miguel , Bochenek Grażyna , Bonini Matteo , Heffler Enrico , Klimek Ludger , Laidlaw Tanya M. , Mullol Joaquim , Niżankowska‐Mogilnicka Ewa , Park Hae‐Sim , Sanak Marek , Sanchez‐Borges Mario , Sanchez‐Garcia Silvia , Scadding Glenis , Taniguchi Masami , Torres Maria J. , White Andrew A. , Wardzyńska Aleksandra
Published: September 2018

NSAID‐exacerbated respiratory disease (N‐ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence‐based recommendations for the diagnosis and management of N‐ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N‐ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N‐ERD. Recommendations for the most effective management of a patient with N‐ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub‐phenotypes and emerging sub‐endotypes of N‐ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N‐ERD and unmet needs, which should be addressed in the future.
The Ovicaprine Mystique: Livestock Commodification in Postindustrial Lesotho
Authors: Hoag Colin
Published: September 2018

Economic anthropologists often look to goods that resist commodification to understand how culture determines what can be exchanged and on what terms. Livestock in Africa have served as prominent examples of such “recalcitrant commodities.” In this article, I argue that goods that do not resist commodification—what I call “clean‐break commodities”—also illuminate the culture of the economy. Drawing on fifteen months of fieldwork in Lesotho, I contrast the reticence to sell cattle in African societies, long the focus of anthropologists as well as experts in conservation and development, with the prodigious sale of sheep and goats (i.e., ovicaprids). Narrow focus on charismatic cattle cultures obscures both the historically shifting commodification of ovicaprids and the economic dreamworlds in which they become enrolled. Ovicaprid cultures morphed over time as rural Basotho navigated their country's structural transitions in the regional political economy—from recently colonized ethnostate to labor reserve for South African mining industries and to defunct labor reserve. Just as the resistance of cattle to commodification described by James Ferguson as the “bovine mystique” opened a window into social life in the labor reserve, the facile commodification of ovicaprids that I call the “ovicaprine mystique” does the same throughout Lesotho's history. [bovine mystique, livestock, commodification, postindustry, sub‐Saharan Africa]
RMI and ROMA are equally effective in discriminating between benign and malignant gynecological tumors: A prospective population‐based study
Authors: Liest Ann‐Lisbeth , Omran Ahmed Shaker , Mikiver Rasmus , Rosenberg Per , Uppugunduri Srinivas
Published: September 2018

Introduction

Our primary objective was to test the hypothesis that human epididymal protein 4 (HE4) and risk of ovarian malignancy index outperform the CA 125 and risk of malignancy index tests in categorizing a pelvic mass into high or low risk of malignancy in a Swedish population. Furthermore, cut‐off values needed to be defined for HE4 and ROMA in premenopausal and postmenopausal women prior to their introduction to clinical practice. A third objective was to investigate the correlation between HE4 levels in serum and urine.

Material and methods

Women with a pelvic mass scheduled for surgery were recruited from nine hospitals in south‐east Sweden. Preoperative blood samples were taken for analyzing CA125 and HE4 as well as urine samples for analyzing HE4.

Results

We enrolled a total of 901 women, of whom 784 were evaluable. In the premenopausal and postmenopausal groups, no significant differences were found for sensitivity, positive and negative predictive value, either for RMI vs ROMA or for CA125 vs HE4 using a fixed specificity of 75%. Cut‐off values indicating malignancy were established for HE4 and ROMA in premenopausal and postmenopausal women. We found no correlation between HE4 concentration in serum and urine.

Conclusions

We could not confirm that ROMA had diagnostic superiority over RMI in categorizing women with a pelvic mass into low‐risk or high‐risk groups for malignancy in a Swedish population. We have defined cut‐off values for HE4 and ROMA. The lack of correlation between serum and urine HE4 obviates the introduction of urine HE4 analysis in clinical diagnostics.
The human yolk sac size reflects involvement in embryonic and fetal growth regulation
Authors: Odland Karlsen Henriette , Johnsen Synnøve L. , Rasmussen Svein , Trae Gro , Reistad Hilde M. T. , Kiserud Torvid
Published: September 2018

Introduction

The human yolk sac provides the embryo with stem cells, nutrients, and gas exchange. We hypothesized that more maternal resources, reflected in body size and body composition, would condition a a larger yolk sac, ensuring resources for the growing embryo. Thus, we aimed to determine the relation between maternal size in early pregnancy and yolk sac size.

Material and methods

This subsidiary study was embedded in the multinational World Health Organization fetal growth project that included healthy women with a body mass index of 18‐30, reliable information of their regular last menstrual period and singleton pregnancies. Yolk sac diameter, crown‐rump length, and maternal height, weight, body mass index, and body composition were assessed before 13 weeks of gestation, and the fetal biometry was repeated during the pregnancy.

Results

Of 140 participants, 122 with a successful yolk sac measurement were entered in the present analysis. Maternal weight was negatively associated with the yolk sac diameter (P = 0.007) and so was maternal height (P = 0.011), fat mass (P = 0.037), and lean body mass (P = 0.018), but not body mass index (P = 0.121). Significant effects were predominantly due to the female embryos and could be traced at 24 weeks of gestation. That is, a small yolk sac : crown‐rump length ratio in early pregnancy was associated with a high fetal abdominal circumference (P < 0.001) and estimated fetal weight (P = 0.001).

Conclusions

The human yolk sac is involved in the regulation of embryonic growth, but contrary to our hypothesis, the yolk sac has a compensatory capacity, being larger when the mothers are smaller; and the effect can be traced on fetal size at 24 weeks of gestation.
Optic nerve head blood flow regulation during changes in arterial blood pressure in patients with primary open‐angle glaucoma
Authors: Bata Ahmed M. , Fondi Klemens , Witkowska Katarzyna J. , Werkmeister René M. , Hommer Anton , Vass Clemens , Resch Hemma , Schmidl Doreen , Popa‐Cherecheanu Alina , Chua Jacqueline , Garhöfer Gerhard , Schmetterer Leopold
Published: September 2018

Purpose

Abnormal autoregulation of optic nerve head blood flow (ONHBF) has been postulated to play an important role in primary open‐angle glaucoma (POAG). We used laser Doppler flowmetry (LDF) to estimate quantitatively the ONHBF and compared ONHBF autoregulation between glaucoma patients and healthy controls during isometric exercise.

Methods

Forty patients with POAG and 40 healthy age‐ and sex‐matched subjects underwent three periods of isometric exercise, each consisting of 2 min of handgripping. Optic nerve head blood flow (ONHBF) was measured continuously using LDF. Systemic blood pressure, intraocular pressure and ocular perfusion pressure were assessed in all participants.

Results

Isometric exercise was associated with an increase in ocular perfusion pressure during all handgripping periods in both groups (p < 0.001). However, there was no change in ONHBF in either group. Three of the glaucoma patients and two of the healthy subjects showed a consistent 10% decrease in blood flow during isometric exercise, in spite of an increase in their blood pressure. This difference between groups was not significant (p = 0.61). Four other glaucoma subjects showed a consistent increase in blood flow of more than 10% during isometric exercise, whereas this was not seen in healthy subjects (p = 0.035).

Conclusion

This study suggests that abnormal ONHBF autoregulation is more often seen in patients with POAG than healthy control subjects. The relationship to the glaucoma disease process is currently unknown and requires further investigation.