bluuebunny/crossref_metadata_2025 huggingface dataset:
Robustness and applicability of functional genomics tools on scRNA-seq data
Authors: Holland Christian H. , Tanevski Jovan , Gleixner Jan , Kumar Manu P. , Mereu Elisabetta , Perales-Patón Javier , Joughin Brian A. , Stegle Oliver , Lauffenburger Douglas A. , Heyn Holger , Szalai Bence , Saez-Rodriguez Julio
Published: September 2019

Many tools have been developed to extract functional and mechanistic insight from bulk transcriptome profiling data. With the advent of single-cell RNA sequencing (scRNA-seq), it is in principle possible to do such an analysis for single cells. However, scRNA-seq data has characteristics such as drop-out events, low library sizes and a comparatively large number of samples/cells. It is thus not clear if functional genomics tools established for bulk sequencing can be applied to scRNA-seq in a meaningful way. To address this question, we performed benchmark studies on in silico and in vitro single-cell RNA-seq data. We included the bulk-RNA tools PROGENy, GO enrichment and DoRothEA that estimate pathway and transcription factor (TF) activities, respectively, and compared them against the tools AUCell and metaVIPER, designed for scRNA-seq. For the in silico study we simulated single cells from TF/pathway perturbation bulk RNA-seq experiments. Our simulation strategy guarantees that the information of the original perturbation is preserved while resembling the characteristics of scRNA-seq data. We complemented the in silico data with in vitro scRNA-seq data upon CRISPR-mediated knock-out. Our benchmarks on both the simulated and real data revealed comparable performance to the original bulk data. Additionally, we showed that the TF and pathway activities preserve cell-type specific variability by analysing a mixture sample sequenced with 13 scRNA-seq different protocols. Our analyses suggest that bulk functional genomics tools can be applied to scRNA-seq data, outperforming dedicated single cell tools. Furthermore we provide a benchmark for further methods development by the community.
The Imposition of Value on Odor: Transient and Persistent Representations of Odor Value in Prefrontal Cortex
Authors: Wang Peter Y. , Boboila Cristian , Shamash Philip , Wu Zheng , Stein Nicole P , Abbott L.F. , Axel Richard
Published: August 2019

The representation of odor in olfactory cortex (piriform) is distributive and unstructured and can only be afforded behavioral significance upon learning. We performed 2-photon imaging to examine the representation of odors in piriform and in two downstream stations, the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), as mice learned olfactory associations. In piriform we observed minor changes in neural activity unrelated to learning. In OFC, 30% of the neurons acquired robust responses to conditioned stimuli (CS+) after learning, and these responses were gated by context and internal state. The representation in OFC, however, diminished after learning and persistent representations of CS+ and CS− odors emerged in mPFC. Optogenetic silencing indicates that these two brain structures function sequentially to consolidate the learning of appetitive associations. These data demonstrate the transformation of a representation of odor identity in piriform into transient and persistent representations of value in the prefrontal cortex.
The Developmental Transcriptome ofAe. albopictus,a Major Worldwide Human Disease Vector
Authors: Gamez Stephanie , Antoshechkin Igor , Mendez-Sanchez Stelia C. , Akbari Omar S.
Published: September 2019

Aedes albopictusmosquitoes are important vectors for a number of human pathogens including the Zika, dengue, and chikungunya viruses. Capable of displacingAedes aegyptipopulations, it adapts to cooler environments which increases its geographical range and transmission potential. There are limited control strategies forAedes albopictusmosquitoes which is likely attributed to the lack of comprehensive biological studies on this emerging vector. To fill this void, here using RNAseq we characterizedAedes albopictusmRNA expression profiles at 47 distinct time points throughout development providing the first high-resolution comprehensive view of the developmental transcriptome of this worldwide human disease vector. This enabled us to identify several patterns of shared gene expression among tissues as well as sex-specific expression patterns. Moreover, to illuminate the similarities and differences betweenAedes aegypti, a related human disease vector, we performed a comparative analysis using the two developmental transcriptomes. We identify life stages were the two species exhibited significant differential expression among orthologs. These findings provide insights into the similarities and differences betweenAedes albopictusandAedes aegyptimosquito biology. In summary, the results generated from this study should form the basis for future investigations on the biology ofAedes albopictusmosquitoes and provide a goldmine resource for the development of transgene-based vector control strategies.
Methods for broad-scale plant phenology assessments using citizen scientists’ photographs
Authors: Barve Vijay V. , Brenskelle Laura , Li Daijiang , Stucky Brian J. , Barve Narayani V. , Hantak Maggie M. , McLean Bryan S. , Paluh Daniel J. , Oswald Jessica A. , Belitz Michael , Folk Ryan , Guralnick Robert
Published: September 2019

Broad-scale plant flowering phenology data has predominantly come from geographically and taxonomically restricted monitoring networks. However, platforms such as iNaturalist, where citizen scientists upload photographs and curate identifications, provide a promising new source of data. Here we develop a general set of best practices for scoring iNaturalist digital records supporting downstream re-use in phenology studies. We focus on a case study group, Yucca, because it has showy flowers and is well documented on iNaturalist. Additionally, drivers of Yucca phenology are not well-understood despite need for Yucca to synchronize flowering with obligate moth pollinators. Finally, evidence of anomalous flowering events have been recently reported, but the extent of those events is unknown. We use best-practices approach to annotate nearly 9,000 Yucca iNaturalist records, and compare the spatiotemporal coverage of this dataset with other broad-scale monitoring resources. Our findings demonstrate that iNaturalist provides unique phenology information, including delineation of extents of unusual flowering events. We also determine if unusual early flowering events impact later, typical flowering periods. Finally, we adapt a plant phenology global knowledge-store to integrate iNaturalist annotation results, supporting broadest reuse. Our approach has application to other plant groups, leveraging rapidly increasing data resources from iNaturalist to study phenology.
Identification of the main glutamine and glutamate transporters inStaphylococcus aureusand their impact on c-di-AMP production
Authors: Zeden Merve S. , Kviatkovski Igor , Schuster Christopher F. , Thomas Vinai C. , Fey Paul D. , Gründling Angelika
Published: September 2019

AStaphylococcus aureusstrain deleted for the c-di-AMP cyclase genedacAis unable to survive in rich medium unless it acquires compensatory mutations. Previously identified mutations were inopuD, encoding the main glycine-betaine transporter, andalsT, encoding a predicted amino acid transporter. Here, we show that inactivation of OpuD restores the cell size of adacAmutant to near wild-type size, while inactivation of AlsT does not, suggesting two different mechanisms for the growth rescue. AlsT was identified as an efficient glutamine transporter, indicating that preventing glutamine uptake in rich medium rescues the growth of theS. aureus dacAmutant. In addition, GltS was identified as a glutamine transporter. By performing growth curves with WT,alsTandgltSmutant strains in defined medium supplemented with ammonium, glutamine or glutamate, we revealed that ammonium and glutamine, but not glutamate promote the growth ofS. aureus. This suggests that besides ammonium also glutamine can serve as a nitrogen source under these conditions. Ammonium and uptake of glutamine via AlsT inhibited c-di-AMP production, while glutamate uptake had no effect. These findings provide, besides the previously reported link between potassium and osmolyte uptake, a connection between nitrogen metabolism and c-di-AMP signalling inS. aureus.

Graphical abstract
Cdc42 promotes Bgs1 recruitment for septum synthesis and glucanase localization for cell separation during cytokinesis in fission yeast
Authors: Onwubiko Udo N. , Robinson Julie , Mustaf Rose Albu , Das Maitreyi E.
Published: September 2019

Cytokinesis in fission yeast involves actomyosin ring constriction concurrent to septum synthesis followed by septum digestion resulting in cell separation. A recent report indicates that endocytosis is required for septum synthesis and cell separation. The conserved GTPase Cdc42 is required for membrane trafficking and promotes endocytosis. Cdc42 is activated by Guanine nucleotide exchange factors (GEFs). Cdc42 GEFs have been shown to promote timely initiation of septum synthesis and proper septum morphology. Here we show that Cdc42 promotes the recruitment of the major primary septum synthesizing enzyme Bgs1 and consequent ring constriction. Cdc42 is also required for proper localization of the septum digesting glucanases at the division site. Thus, Cdc42 is required to promote multiple steps during cytokinesis.
A G1 sizer mechanism coordinates growth and division in the mouse epidermis
Authors: Xie Shicong , Skotheim Jan M.
Published: September 2019

Cell size homeostasis is often achieved by coupling cell cycle progression to cell growth. Studies of cell size homeostasis in single-celled bacteria and yeast have observed several distinct phenomena. Growth can be coupled to division through a range of mechanisms, including a ‘sizer’, wherein cells of varying birth size divide at similar final sizes [1–3], and an ‘adder’, wherein cells increase in size a fixed amount per cell cycle [4–6]. Importantly, intermediate control mechanisms are observed, and even the same organism can exhibit distinct control phenomena depending on growth conditions [2,7,8]. While studying unicellular organisms in laboratory conditions may give insight into their growth control in the wild, this is less apparent for studies of mammalian cells growing outside the organism. Sizer, adder, and intermediate mechanisms have been observedin vitro[9–12], but it is unclear how these diverse size homeostasis phenomena relate to mammalian cell proliferationin vivo. To address this gap, we analyzed time-lapse images of the mouse epidermis taken over one week during normal tissue turnover [13]. We quantified the 3D volume growth and cell cycle progression of single cells within the mouse skin. In dividing epidermal stem cells, we found that cell growth is coupled to division through a sizer mechanism operating largely in the G1 phase. Thus, while the majority of tissue culture studies to-date identified adder mechanisms, our analysis demonstrates that sizer mechanisms are importantin vivoand highlights the need to determine their underlying molecular origin.
AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture
Authors: Zheng Dongqing , Sussman Jonathan H. , Jeon Matthew P. , Parrish Sydney T. , Delfarah Alireza , Graham Nicholas A.
Published: September 2019

Oncogenes can generate metabolic vulnerabilities in cancer cells. Here, we tested how AKT and MYC affect the ability of cells to shift between respiration and glycolysis. Using immortalized mammary epithelial cells, we discovered that constitutively active AKT but not MYC induced cell death in galactose culture, where cells must rely on oxidative phosphorylation for energy generation. However, the negative effects of AKT were short-lived, and AKT-expressing cells recommenced growth after ~15 days in galactose. To identify the mechanisms regulating AKT-mediated cell death, we used metabolomics and found that AKT cells dying in galactose upregulated glutathione metabolism. Next, using proteomics, we discovered that AKT-expressing cells dying in galactose upregulated nonsense-mediated mRNA decay, a marker of sensitivity to oxidative stress. We therefore measured levels of reactive oxygen species (ROS) and discovered that galactose induced ROS in cells expressing AKT but not MYC. Additionally, ROS were required for the galactose-induced death of AKT-expressing cells. We then tested whether these findings could be replicated in breast cancer cell lines with constitutively active AKT signaling. Indeed, we found that galactose induced rapid cell death in breast cancer cell lines and that ROS were required for galactose-induced cell death. Together, our results demonstrate that AKT but not MYC induces a metabolic vulnerability in cancer cells, namely the restricted flexibility to use oxidative phosphorylation.

Implications

The discovery that AKT but not MYC restricts the ability to utilize oxidative phosphorylation highlights that therapeutics targeting tumor metabolism must be tailored to the individual genetic profile of tumors.
Sympatric wren-warblers partition acoustic signal space and song perch height
Authors: Chitnis Shivam S. , Rajan Samyuktha , Krishnan Anand
Published: September 2019

By evolving divergent acoustic signals, sympatric assemblages of animals may minimize potentially costly masking interference. Acoustic signal space may be multidimensional, with coexisting species also vocalizing from different regions of physical space. Here, we demonstrate acoustic signal space partitioning in four sympatric species of wren-warbler (Cisticolidae, Prinia), in an Indian dry deciduous scrub habitat. We find that the breeding songs of wren-warblers are divergent from each other in multivariate parameter space, with only minimal interspecific overlap. Partitioning of signal space exerts constraints on the intraspecific diversity of acoustic signals, and each species exhibits different strategies to overcome these constraints. Two species partition intraspecific signal space into multiple note types, whereas a third exhibits intraspecific variation in repetition rate, thus supporting song diversity within a constrained acoustic space. Finally, we find that the four species also partition song perch heights, thus exhibiting separation along multiple axes of acoustic signal space. We hypothesize that divergent song perch heights may be driven by competition for higher singing perches or other ecological factors rather than signal propagation. Acoustic signal partitioning along multiple axes may therefore, we propose, arise from a combination of diverse ecological processes.
De‐aliased and de‐noise Cadzow filtering for seismic data reconstruction
Authors: Huang Weilin , Feng Deshan , Chen Yangkang
Published: August 2019

Cadzow filtering is currently considered as one of the most effective approaches for seismic data reconstruction. The basic version of Cadzow filtering first reorders each frequency slice of the seismic data (to be reconstructed) to a block Hankel/Toeplitz matrix, and then implements a rank‐reduction operator, that is truncated singular value decomposition, to the Hankel/Toeplitz matrix. However, basic Cadzow filtering cannot deal with the problem of recovering regularly missing data (up‐sampling) in the case of strongly aliased energy, because the regularly missing data will mix with signals in the singular spectrum. To solve this problem, it has been proposed to precondition the reconstruction of high‐frequency components using information from the low‐frequency components which are less aliased. In this paper, we further extend the de‐aliased Cadzow filtering approach to reconstruct regularly sampled seismic traces from the noisy observed data by modifying the reinserting operation, in which the high‐frequency components are projected onto the sub‐space spanned by several singular vectors of the low‐frequency components. At each iteration, the filtered data are weighted to the original data as a feedback. The weighting factor is related to the background noise level and changes with iteration. The feasibility of the proposed technique is validated via two‐dimensional, three‐dimensional and five‐dimensional synthetic data examples, as well as two‐dimensional post‐stack and three‐dimensional pre‐stack field data examples. The results demonstrate that the proposed technique can effectively interpolate regularly sampled data and is robust in noisy environments.
Simple study designs in ecology produce inaccurate estimates of biodiversity responses
Authors: Christie Alec P. , Amano Tatsuya , Martin Philip A. , Shackelford Gorm E. , Simmons Benno I. , Sutherland William J.
Published: August 2019

Monitoring the impacts of anthropogenic threats and interventions to mitigate these threats is key to understanding how to best conserve biodiversity. Ecologists use many different study designs to monitor such impacts. Simpler designs lacking controls (e.g. Before–After (BA) and After) or pre‐impact data (e.g. Control–Impact (CI)) are considered to be less robust than more complex designs (e.g. Before–After Control‐Impact (BACI) or Randomized Controlled Trials (RCTs)). However, we lack quantitative estimates of how much less accurate simpler study designs are in ecology. Understanding this could help prioritize research and weight studies by their design's accuracy in meta‐analysis and evidence assessment.

We compared how accurately five study designs estimated the true effect of a simulated environmental impact that caused a step‐change response in a population's density. We derived empirical estimates of several simulation parameters from 47 ecological datasets to ensure our simulations were realistic. We measured design performance by determining the percentage of simulations where: (a) the true effect fell within the 95% Confidence Intervals of effect size estimates, and (b) each design correctly estimated the true effect's direction and magnitude. We also considered how sample size affected their performance.

We demonstrated that BACI designs performed: 1.3–1.8 times better than RCTs; 2.9–4.2 times versus BA; 3.2–4.6 times versus CI; and 7.1–10.1 times versus After designs (depending on sample size), when correctly estimating true effect's direction and magnitude to within ±30%. Although BACI designs suffered from low power at small sample sizes, they outperformed other designs for almost all performance measures. Increasing sample size improved BACI design accuracy, but only increased the precision of simpler designs around biased estimates.

Synthesis and applications. We suggest that more investment in more robust designs is needed in ecology since inferences from simpler designs, even with large sample sizes may be misleading. Facilitating this requires longer‐term funding and stronger research–practice partnerships. We also propose ‘accuracy weights’ and demonstrate how they can weight studies in three recent meta‐analyses by accounting for study design and sample size. We hope these help decision‐makers and meta‐analysts better account for study design when assessing evidence.
Conservation translocations: a review of common difficulties and promising directions
Authors: Berger‐Tal O. , Blumstein D. T. , Swaisgood R. R.
Published: August 2019

Translocations are a common conservation and management strategy, but despite their popularity, translocations are a high‐cost endeavor with a history of failures. It is therefore imperative to maximize their success by learning from our collective experience. The Global Re‐introduction Perspectives Series is a collection of conservation translocation case studies, generated by the IUCN’s Conservation Translocation Specialist Group, and presented in a structured format with an emphasis on practical information. All 293 animal translocation case studies to date include a section in which the authors list the difficulties they have faced during the translocation project, with over 1200 difficulties described so far. We reviewed all difficulties reported in the series to get insights into the common perceived difficulties faced by wildlife managers during animal translocations. The most reported‐upon problems had to do with animal behavior, followed by monitoring difficulties, lack of funding, quality of release habitat, lack of baseline knowledge and lack of public support. We scrutinized each of these difficulties to highlight future research directions that are most likely to improve translocation success, and put a special emphasis on difficulties stemming from animal behavior, and on solutions that may alleviate these problems and improve conservation translocation success world‐wide.
Mandibular fractures and dental injuries sustained during baseball and softball over 14 years in a Japanese population: A retrospective multicentre study
Authors: Nogami Shinnosuke , Yamauchi Kensuke , Bottini Gian Battista , Morishima Hiromitsu , Sai Yuko , Otake Yoshio , Higuchi Keisuke , Kumagai Masahiro , Gaggl Alexander , Takahashi Tetsu
Published: August 2019

Background/Aim

Active participation in sports is a risk factor for maxillofacial fractures. The aim of this retrospective multicentre study was to survey and evaluate the characteristics of mandibular fractures, and dental injuries that occurred during the practice of baseball and softball in Sendai, Japan.

Material and Methods

The records of 454 patients with maxillofacial fractures from three departments of Oral and Maxillofacial Surgery across a period 14 years were analysed. Fifty‐one patients with 56 mandible fractures and dental injuries that occurred playing baseball or softball were included in this multicenter retrospective study. Patients were divided according to age, gender, sites of fractures, mechanism of fractures and treatment methods.

Results

There were 42 males and nine females, with a male‐to‐female ratio of 4.7:1.0. The mean age was 19.9 years old (range: 13‐47 years old). As for the site, body of the mandible fractures prevailed, followed by the condyle, symphysis and angle. Fractures were mostly caused by the impact of a ball (42; 82.4%), followed by collisions with another player (5; 9.8%) and direct strike of a bat (4; 7.8%). All patients with mandibular fractures were treated with open reduction and internal fixation, except for six patients with condylar head fractures who were managed conservatively.

Conclusions

The impact of a thrown ball against the batter's mandible can cause a condylar fracture when playing baseball and softball.
An agglutination test for fast and specific detection of Erwinia psidii
Authors: Montoya‐Estrada Claudia N. , Silva Patrick F. , Costa Camila R. , Oliveira Leandro L. , Guimarães Lúcio M.S. , Badel Jorge L. , Alfenas Acelino C.
Published: August 2019

Dieback and wilt, caused by Erwinia psidii (Ep), is one of the most important emergent diseases of Eucalyptus spp. in Brazil. Currently, pathogen detection relies on isolation of bacteria from infected plant tissue and either identification based on morphological, physiological and biochemical tests or DNA amplification using the polymerase chain reaction (PCR), which in many cases is laborious and cumbersome. Considering the need for a simpler and more rapid, yet reliable, method for detecting the pathogen, we obtained a polyclonal antibody (anti‐Ep) and developed an agglutination test for specific detection of E. psidii. The antiserum was produced against the E. psidii strain LPF534 and tested against 101 E. psidii isolates from Eucalyptus spp.; three E. psidii isolates from Psidium guajava; 23 Ralstonia solanacearum and 18 Xanthomonas axonopodis isolates pathogenic to Eucalyptus spp.; and seven endophytic isolates from Eucalyptus spp., three of which are phylogenetically related to the genus Erwinia. Results of direct ELISA indicated that a concentration as low as 3.5 µg/ml of the anti‐Ep antibody was able to detect the E. psidii antigen and that the antibody did not cross‐reacted with other bacteria pathogenic and non‐pathogenic to Eucalyptus spp. In the agglutination test, the anti‐Ep antibody showed positive reaction with all strains of E. psidii tested whereas cross‐reaction with none of the strains that belong to other taxonomic groups was observed. The agglutination test showed a detection limit of 105 colony‐forming units (CFU)/ml, and its specificity was the same as that obtained by PCR amplification using E. psidii‐specific primers. These results demonstrate that the agglutination test developed here is a useful tool for specific, fast and inexpensive detection of E. psidii although only operational on pure bacterial suspensions and not yet directly from infected tissues.
Toward evidence‐based severity assessment in rat models with repeated seizures: II. Chemical post–status epilepticus model
Authors: Koska Ines , van Dijk Roelof Maarten , Seiffert Isabel , Di Liberto Valentina , Möller Christina , Palme Rupert , Hellweg Rainer , Potschka Heidrun
Published: August 2019

Objective

Considering the complexity of neuronal circuits and their epilepsy‐associated alterations, epilepsy models cannot be completely replaced by in vitro experimental approaches. Decisions about ethical approval of in vivo studies require a thorough weighing of the animal's burden and the benefit regarding the expected gain in knowledge.

Methods

Based on combined behavioral, biochemical, and physiological analyses, we assessed the impact on animal well‐being and condition in different phases of the pilocarpine post–status epilepticus (SE) model in rats.

Results

As a consequence of SE, increased levels of impairment were evident in the early postinsult phase and late chronic phase, whereas only mild impairment was observed in the interim phase. Parameters that stood out as sensitive indicators of animal distress include burrowing, which proved to be affected throughout all experimental phases, saccharin preference, fecal corticosterone metabolites, heart rate, and heart rate variability.

Significance

The cumulative burden with temporary but not long‐lasting phases of more pronounced impairment suggests a classification of severe as a basis for laboratory‐specific prospective and retrospective evaluation. Among the parameters analyzed, burrowing behavior and saccharin preference stand out as candidate parameters that seem to be well suited to obtain information about animal distress in epileptogenesis models.
Shifts in the skin microbiome associated with diaper dermatitis and emollient treatment amongst infants and toddlers in China
Authors: Zheng Yumei , Wang Qian , Ma Laiji , Chen Yuanyuan , Gao Ying , Zhang Gaolei , Cui Shumei , Liang Haiyun , Song Liya , He Congfen
Published: August 2019

Background

The microbiological basis of diaper dermatitis has not been clearly elucidated; however, a better understanding of microbial colonization may be vital for developing appropriate therapies.

Methods

Using 16S‐rRNA gene sequencing technology, we characterized and compared the bacterial communities obtained from the buttock skin sites of children with diaper dermatitis and from healthy controls. Bacterial diversity in the buttock lesion area and subsequent recovery after emollient treatment have been discussed herein.

Results

In buttock skin of children with or without diaper dermatitis, Staphylococcus and Anaerococcus were predominant in the total skin microbiome. Compared with the healthy group, the overall skin bacterial richness and diversity were higher in children with diaper dermatitis, with the abundance of Proteobacteria being significantly higher. In the diaper dermatitis group, the richness of Enterococcus, Erwinia and Pseudomonas was significantly higher, and the levels of Clostridium and Actinomyces were significantly lower than those in healthy children. Richness of Staphylococcus aureus was significantly higher in the diaper dermatitis group, whereas that of Staphylococcus epidermidis and Bifidobacterium longum was lower. Staphylococcus epidermidis and Staphylococcus haemolyticus, the dominant species found in buttock skin, were observed to recover earlier after the disease had improved through emollient treatment.

Conclusion

Staphylococcus epidermidis, as skin probiotic bacterium, and B longum, Clostridium butyricum and Lactobacillus ruminis, which are intestinal probiotic bacteria, are significantly decreased in diaper dermatitis lesions. These changes in the buttock skin microflora indicate an imbalance in the microflora and suggest that the intestinal microflora may be undergoing dynamic changes. The results of this study suggest that probiotic bacterial supplementation may be useful in the treatment and prevention of diaper dermatitis.
The role of Rsv1 in the transcriptional regulation of genes involved in sugar metabolism for long‐term survival
Authors: Kim Eun‐Jung , Cho Yong‐Joon , Chung Woo‐Hyun , Roe Jung‐Hye
Published: August 2019

Glucose limitation is a major stress condition that cells must respond to by altering their metabolism to ensure survival. Rsv1 is a zinc finger protein previously shown to be required for survival during stationary phase. In this study, we present a novel mechanism regulated by Rsv1 in the fission yeast Schizosaccharomyces pombe that is involved in altering glucose metabolic flux. We found that rsv1 gene expression is induced by Rst2 and Atf1, two transcription factors regulated by the cAMP‐dependent protein kinase (PKA) pathway and the mitogen‐activated protein kinase (MAPK) cascade, respectively. The downstream target genes of Rsv1 were identified by genome‐wide ChIP sequencing of Rsv1‐bound DNA sites and RNA sequencing analysis of Rsv1‐dependent transcripts that were differentially expressed under glucose starvation. Rsv1 directly regulated the expression of at least 21 genes that mostly encode transporters and proteins related to sugar metabolism. Among these, gcd1, which encodes glucose dehydrogenase in the gluconate shunt for the pentose phosphate pathway, was most remarkably repressed by Rsv1. The defect in survival of Δrsv1 mutant under glucose starvation condition was mitigated by additional deletion of a gcd1, idn1, or a gene for a putative lactonase (SPCC16c4.10), suggesting the critical importance of downregulating the gluconate shunt and pentose phosphate pathway for long‐term survival. These results show an intricate response to glucose starvation: increasing the synthesis of a transcription factor via two signal transduction pathways, which sheds light on the importance of remodeling a metabolic circuit to secure glucose for cell survival.
Peri‐Incisional Botulinum Toxin Therapy for Treatment of Intractable Head Pain After Lateral Skull Base Surgery: A Case Series
Authors: Dang Sabina , Shinn Justin R. , Sowder Justin , Ries William Russell , Stephan Scott J.
Published: August 2019

Objective

The objective of this case series was to describe botulinum toxin therapy as a novel treatment of intractable head pain following lateral skull base surgery.

Background

Intractable headaches following lateral skull base surgery are described in 23%‐75% of patients and can significantly impact quality of life. Currently, the etiology of the headaches is unclear and treatment options are limited. Botulinum toxin is indicated for a multitude of functional and cosmetic reasons, including chronic migraine, and has been further described in treatment of various postsurgical pain syndromes.

Methods

In this case series, 4 patients underwent subcutaneous peri‐incisional injections of botulinum toxin for intractable headache and head pain syndromes. Three patients had undergone lateral skull base surgery and the fourth patient had undergone a temporoparietal fascial flap harvest. Average injection dose ranged from 20 to 60 units with an average duration of effect ranging from 2 weeks to 4 months.

Results

All patients experienced significant relief of chronic head pain and returned for additional peri‐incisional botulinum toxin injections, suggesting meaningful patient‐perceived value.

Conclusions

Botulinum toxin therapy may represent a novel treatment for intractable head pain following lateral skull base surgery and temporoparietal fascial flap harvest. This study represents a small case series and, although 100% of the patients who were treated significantly improved, future inquiry is necessary to confirm these findings.
Serum Vitamin B12 and Methylmalonic Acid Status in Migraineurs: A Case‐Control Study
Authors: Togha Mansoureh , Razeghi Jahromi Soodeh , Ghorbani Zeinab , Martami Fahimeh , Seifishahpar Maryam
Published: August 2019

Background

Although the exact pathophysiological mechanistic pathways that result in the initiation of migraine attacks remain unclear, there are some proposed mechanisms including neurogenic inflammation, trigeminovascular system activation, vascular dysfunction, and augmented release of nitric oxide (NO) and homocysteine (Hcy). Vitamin B12 is thought to be involved in important pathways that seem to be related to the pathogenesis of migraine including scavenging against NO and prevention of hyperhomocysteinemia. Therefore, the aim of the current study was to evaluate the serum vitamin B12 and methylmalonic acid (MMA) status in a group of migraine patients compared to healthy controls.

Methods

After the recruitment of cases and controls, demographic data and migraine characteristics (including the number of headache days, severity of headaches, and duration of each attack in hours) were recorded. Serum vitamin B12 and MMA levels were measured using the enzyme‐linked immunosorbent assay technique.

Results

Seventy migraine patients and 70 healthy subjects were enrolled in this case control study. The serum levels of B12 were found to be significantly lower in migraine patients than in healthy subjects (512 ± 300 vs 667 ± 351 pg/mL, P = .007); whereas migraineurs had higher levels of MMA than controls (1.39 [0.59,4.01] vs 1.01 [0.49,1.45] µg/dL, P = .027). In the fully adjusted multiple regression model, those in the highest vs the lowest serum B12 quartile had 80% decrease in the odds of having migraine ([OR = 0.20, 95% CI = 0.05‐0.73], [P for trend = .008]); while, patients in the highest quartile of MMA had more than 5 times increased risk of having migraine ([OR = 5.44, 95% CI = 1.49‐19.87] [P for trend = .002]). There was no association between serum B12 and MMA levels and headache characteristics.

Conclusion

Taken together, these findings suggest that participants with lower vitamin B12 and higher MMA levels that considered as lower functional activity of B12 had higher odds of migraine.
Enhancement of Curie temperature and photoluminescent properties of Nd2Mo2O7, Ho2Mo2O7, and Gd2Mo2O7
Authors: Öztürk Esra , Kalem Volkan , Karacaoglu Erkul
Published: August 2019

For Nd1.90Er0.10Mo2O7, Ho1.90Er0.10Mo2O7, and Gd1.98Eu0.02Mo2O7 nominal compositions, oxide compounds were prepared by solid‐state reaction method. X‐ray diffraction measurements show that molybdenum oxides formed cubic phase except for Nd1.90Er0.10Mo2O7. Scanning electron microscopy was used to observe their microstructure and elemental analysis. The photoluminescence properties of the materials, the excitation and emission spectra and the decay curve, were investigated using photoluminescence spectrophotometer. Dielectric and piezoelectric properties of the ptoluminescent materials, the dielectric constant, dielectric loss, piezoelectric constant, and Curie temperature, were measured for electrical characterization. Nd1.90Er0.10Mo2O7, Ho1.90Er0.10Mo2O7, and Gd1.98Eu0.02Mo2O7 materials show both photoluminescence and piezoelectric properties.
Improved phosphate‐based glass fiber performance achieved through acid etch/polydopamine treatment
Authors: Parsons Andrew J. , Felfel Reda M. , Wadge Matthew D. , Grant David M.
Published: August 2019

Phosphate‐based glass fibers (PGF) are of interest as reinforcements for degradable implants, but have seen limited application due to their rapid loss of strength when subjected to aqueous conditions. Previous studies have utilized heat treatments to improve longer term strength retention at a significant cost to initial strength. In this study, acid etching is used to recover the initial fiber strength after heat treatment and a subsequent coating of polydopamine is applied to provide longer term retention of this recovered strength. After an initial loss of strength after heat treatment (1135 ‐> 509 MPa), an optimized combination of acid treatment and polydopamine coating was able to recover to approximately 85% of the initial strength (969 MPa). The result was significant in comparison to acid treatment (647 MPa) or coating (688 MPa) alone. The combined acid/coating treatment was demonstrated to maintain fiber properties for at least 14 days, although the amount of polydopamine coating was observed to decrease over this period. The approach reported here is of importance as it offers the required step change in degradation performance that is needed for PGF‐reinforced degradable composites.
LDK378 inhibits the recruitment of myeloid‐derived suppressor cells to spleen via the p38–GRK2–CCR2 pathway in mice with sepsis
Authors: Hu Jie , Zhang Wenqin , Liu Yanjuan , Yang Yang , Tan Chuyi , Wei Xue , Wang Yufang , Tan Sipin , Liu Meidong , Liu Ke , Liu Ying , Zhang Huali , Xiao Xianzhong
Published: August 2019

Myeloid‐derived suppressor cells (MDSCs) are functionally immunosuppressive cells that are persistently increased in abundance and associated with adverse clinical outcomes in sepsis. Here, we investigated the therapeutic potential of an anaplastic lymphoma kinase inhibitor, LDK378, in cecal ligation and puncture (CLP)‐induced polymicrobial sepsis and examined its effects on the recruitment of MDSCs. LDK378 significantly improved the survival of CLP‐induced polymicrobial septic mice, which was paralleled by reduced organ injury, decreased release of inflammatory cytokines and decreased recruitment of MDSCs to the spleen. Importantly, LDK378 inhibited the migration of MDSCs to the spleen by blocking the CLP‐mediated upregulation of CC chemokine receptor 2 (CCR2), a chemokine receptor critical for the recruitment of MDSCs. Mechanistically, LDK378 treatment blocked the CLP‐induced CCR2 upregulation of MDSCs via partially inhibiting the phosphorylation of p38 and G‐protein‐coupled receptor kinase‐2 (GRK2) in bone marrow MDSCs of septic mice. Furthermore, in vitro experiments also showed that lipopolysaccharide (LPS)‐induced migration of MDSCs was similarly owing to the activation of GRK2 and upregulation of CCR2 by LPS, whereas the treatment with LDK378 partially blocked the LPS‐induced phosphorylation of p38 and GRK2 and decreased the expression of CCR2 on the cell surface, therefore leading to the suppression of MDSC migration. Together, these findings unravel a novel function of LDK378 in the host response to infection and suggest that LDK378 could be a potential therapeutic agent for sepsis.

See also: News and Commentary by Patil
Epidemiologic evaluation of calcium oxalate urolithiasis in dogs in the United States: 2010‐2015
Authors: Hunprasit Vachira , Schreiner Pamela J. , Bender Jeffrey B. , Lulich Jody P.
Published: August 2019

Background

Positive health implications of early recognition of calcium oxalate (CaOx) urolithiasis include increased opportunity for nonsurgical removal, early dietary modification to minimize urolith growth, early removal to avoid urinary obstruction, and early recognition of genetic and metabolic diseases before they contribute to additional morbidity.

Objectives

To identify high‐ and low‐risk dog breeds for CaOx uroliths and to determine the relationship of age and sex to the development of CaOx uroliths.

Animals

Calcium oxalate urolith submissions between 2010 and 2015.

Methods

A comparative cross‐sectional study was conducted to identify high‐ and low‐risk breeds for CaOx uroliths by comparing cases to multiple comparison groups. At‐risk breeds were identified if odds ratios were significant (Pvalue <.05) across all comparison groups.

Results

Of 258 898 urolith submissions, 124 285 were CaOx. Calcium oxalate was identified in 212 breeds. Twelve breeds were identified as high‐risk breeds, and 14 breeds were identified as low‐risk breeds. All high‐risk breeds were small dog breeds, and all low‐risk breeds were medium to large dog breeds. Overall, the mean age ± standard deviation of the first CaOx urolith was 8.4 ± 2.8 years.

Conclusions and Clinical Importance

To achieve the health benefits of preclinical evaluation, breeds at high risk for CaOx urolithiasis should be screened at 5 to 6 years of age, which is 2 to 3 years before likely development of clinical urolithiasis.
Disentangling the effects of plea discount and potential trial sentence on decisions to plead guilty
Authors: Schneider Ryan A. , Zottoli Tina M.
Published: August 2019

Background

Most criminal convictions are a result of guilty pleas. Concerns have been raised that large differentials between plea and potential trial sentences can be coercive to some defendants, especially when the threat of potential trial sentence is very large. The limited research, to date, suggests that the likelihood of pleading guilty goes up with increasing size of potential trial sentence. However, existing studies have failed to separate the effects of trial sentence and plea discount; as a result, in almost all studies, large potential trial sentences are paired with large discounts and small trial sentences with small discounts, making it difficult to know how the threat of trial sentence actually affects defendant decisions.

Method

In this study, we examined the effects of guilt, magnitude of potential trial sentence (5 years and 25 years), and size of plea discount (20%, 50%, and 75%) in a fully crossed, between‐subjects design, with acceptance of plea offer as the dependent variable.

Results

We found that potential trial sentence and plea discount had independent and opposite effects on plea decisions, with discount carrying the most weight. Specifically, participants accepted more plea offers in higher relative to lower discount conditions and when potential trial sentence was 5 years rather than 25 years. The pattern of effects was similar for participants in guilty and innocent conditions.

Implications

Our results run somewhat counter to conventional wisdom on how discount and potential trial sentence affect plea decisions and suggest that, given similar discounts, the likelihood for pleading guilty may be higher for defendants facing less serious charges that carry less severe sentences. We discuss the policy and research implications of these data.
Independent genetic control of drought resistance, recovery, and growth of Eucalyptus globulus seedlings
Authors: Ammitzboll Hans , Vaillancourt René E. , Potts Brad M. , Harrison Peter A. , Brodribb Tim , Sussmilch Frances C. , Freeman Jules S.
Published: August 2019

Drought is a major stress impacting forest ecosystems worldwide. We utilized quantitative trait loci (QTL) analysis to study the genetic basis of variation in (a) drought resistance and recovery and (b) candidate traits that may be associated with this variation in the forest tree Eucalyptus globulus. QTL analysis was performed using a large outcrossed F2 mapping population from which 300 trees were phenotyped based on the mean performance of their open‐pollinated F3 progeny. Progenies were grown in a glasshouse in a randomized complete block design. A subset of seedlings was subjected to a drought treatment after which they were rewatered and scored for damage and growth postdrought. Nondroughted seedlings were assessed for growth traits as well as lignotuber size and resprouting following severe damage to the main stem. QTL were detected for most traits. Importantly, independent QTL were detected for (a) drought damage and plant size, (b) drought damage and growth recovery, and (c) lignotuber size and resprouting capacity. Such independence argues that trade‐offs are unlikely to be a major limitation to the response to selection and at the early life history stage studied; there are opportunities to improve resilience to drought without adverse effects on productivity.
Age‐dependent loss of seed viability is associated with increased lipid oxidation and hydrolysis
Authors: Wiebach Janine , Nagel Manuela , Börner Andreas , Altmann Thomas , Riewe David
Published: August 2019

The accumulation of reactive oxygen species has been associated with a loss of seed viability. Therefore, we have investigated the germination ability of a range of seed stocks, including two wheat collections and one barley collection that had been dry‐aged for 5–40 years. Metabolite profiling analysis revealed that the accumulation of glycerol was negatively correlated with the ability to germinate in all seed sets. Furthermore, lipid degradation products such as glycerol phosphates and galactose were accumulated in some seed sets. A quantitative analysis of nonoxidized and oxidized lipids was performed in the wheat seed set that showed the greatest variation in germination. This analysis revealed that the levels of fully acylated and nonoxidized storage lipids like triacylglycerols and structural lipids like phospho‐ and galactolipids were decreasing. Moreover, the abundance of oxidized variants and hydrolysed products such as mono‐/diacylglycerols, lysophospholipids, and fatty acids accumulated as viability decreased. The proportional formation of oxidized and nonoxidized fatty acids provides evidence for an enzymatic hydrolysis of specifically oxidized lipids in dry seeds. The results link reactive oxygen species with lipid oxidation, structural damage, and death in long‐term aged seeds.
Severe hypernatremia and transient azotemia in a cat following inadvertent intravenous administration of a commercial polyethylene glycol solution
Authors: Hoehne Sabrina N. , Kohen Casey J. , Puschner Birgit , Gennity Ingrid , Hagley Simon P. , Farrell Kate S. , Unger Karin , Cagle Laura A. , Jandrey Karl E.
Published: August 2019

Objective

To describe the clinical signs, clinicopathologic abnormalities, treatment, and outcome after IV administration of polyethylene glycol 3350 (PEG3350) in a cat.

Case Summary

A cat was inadvertently administered 6 g/kg of PEG3350 in electrolyte solution, IV, resulting in severe hypernatremia (203 mmol/L), diffuse encephalopathy, hemolysis, and moderate azotemia. The hemolysis and acute kidney injury observed immediately following PEG3350 administration resolved with supportive care. Administration of IV and oral electrolyte‐free water slowly corrected the hypernatremia and the neurologic signs subsequently improved. Complete resolution of clinical signs was documented one month following hospital discharge. The PEG3350 concentrations in serum, plasma, and urine samples confirmed toxic exposure to PEG3350. Efficacy of treatment was evident by decreasing concentrations of PEG3350 in serum after the first 24 hours of treatment. Renal elimination of PEG3350 was significant and PEG3350 was still detected in the urine 17 days after exposure.

New Information Provided

This is the first report to describe the clinical signs and clinicopathologic abnormalities in a cat intoxicated with IV PEG3350. Potential pathophysiologic mechanisms are discussed, and the successful supportive medical treatment is outlined.