bluuebunny/crossref_metadata_2025 huggingface dataset:
Scale and direction of adaptive introgression between black cottonwood (Populus trichocarpa) and balsam poplar (P. balsamifera)
Authors: Suarez‐Gonzalez Adriana , Hefer Charles A. , Lexer Christian , Cronk Quentin C. B. , Douglas Carl J.
Published: March 2018

Introgression can introduce novel genetic variation at a faster rate than mutation alone and result in adaptive introgression when adaptive alleles are maintained in the recipient genome over time by natural selection. A previous study from our group demonstrated adaptive introgression fromPopulus balsamiferaintoP. trichocarpain a target genomic region. Here we expand our local ancestry analysis to the whole genome of both parents to provide a comprehensive view of introgression patterns and to identify additional candidate regions for adaptive introgression genomewide.Populus trichocarpais a large, fast‐growing tree of mild coastal regions of the Pacific Northwest, whereasP. balsamiferais a smaller stature tree of continental and boreal regions with intense winter cold. The species hybridize where they are parapatric. We detected asymmetric patterns of introgression across the whole genome of these two poplar species adapted to contrasting environments, with stronger introgression fromP. balsamiferatoP. trichocarpathan vice versa. AdmixedP. trichocarpaindividuals contained more genomic regions with unusually high levels of introgression (19 regions) and also the largest introgressed genome fragment (1.02 Mb) compared with admixedP. balsamifera(nine regions). Our analysis also revealed numerous candidate regions for adaptive introgression with strong signals of selection, notably related to disease resistance, and enriched for genes that may play crucial roles in survival and adaptation. Furthermore, we detected a potential overrepresentation of subtelomeric regions inP. balsamiferaintrogressed intoP. trichocarpaand possible protection of sex‐determining regions from interspecific gene flow.
Mitonuclear discordance in wolf spiders: Genomic evidence for species integrity and introgression
Authors: Ivanov Vladislav , Lee Kyung Min , Mutanen Marko
Published: March 2018

Systematists and taxonomists have benefited greatly from the emergence of molecular methods. Species identification has become straightforward through DNA barcoding and the rapid build‐up of massive DNA barcode reference libraries. In animals, mitonuclear discordance can significantly complicate the process of species identification and delimitation. The causes of mitonuclear discordance are either biological (e.g., introgression, incomplete lineage sorting, horizontal gene transfer androgenesis) or induced by operational factors (e.g., human error with specimen misidentification or incorrect species delimitation). Moreover, endosymbionts may play an important role in promoting fixation of mitochondrial genomes. Here, we study the mitonuclear discordance of wolf spiders species (Lycosidae) (independent cases from Alopecosa aculeata and Pardosa pullata groups) that share identical COI DNA barcodes. We approached the case utilizing double‐digest restriction site‐associated DNA sequencing (ddRADseq) to obtain and analyse genomic‐scale data. Our results suggest that the observed cases of mitonuclear discordance are not due to operational reasons but result from biological processes. Further analysis indicated introgression and that incomplete lineage sorting is unlikely to have been responsible for the observed discrepancy. Additional survey of endosymbionts provided ideas on further research and their role in shaping mitochondrial DNA distribution patterns. Thus, ddRADseq grants an efficient way to study the taxonomy of problematic groups with insight into underlying evolutionary processes.
Gene expression profiles of glucose toxicity‐exposed islet microvascular endothelial cells
Authors: Liu Mingming , Lu Wenbao , Hou Qunxing , Wang Bing , Sheng Youming , Wu Qingbin , Li Bingwei , Liu Xueting , Zhang Xiaoyan , Li Ailing , Zhang Honggang , Xiu Ruijuan
Published: March 2018

Objective

Islet microcirculation is mainly composed by IMECs. The aim of the study was to investigate the differences in gene expression profiles of IMECs upon glucose toxicity exposure and insulin treatment.

Methods

IMECs were treated with 5.6 mmol L−1 glucose, 35 mmol L−1 glucose, and 35 mmol L−1 glucose plus 10−8 mol L−1 insulin, respectively. Gene expression profiles were determined by microarray and verified by qPCR. GO terms and KEGG analysis were performed to assess the potential roles of differentially expressed genes. The interaction and expression tendency of differentially expressed genes were analyzed by Path‐Net algorithm.

Results

Compared with glucose toxicity‐exposed IMECs, 1574 mRNAs in control group and 2870 mRNAs in insulin‐treated IMECs were identified with differential expression, respectively. GO and KEGG pathway analysis revealed that these genes conferred roles in regulation of apoptosis, proliferation, migration, adhesion, and metabolic process etc. Additionally, MAPK signaling pathway and apoptosis were the dominant nodes in Path‐Net. IMECs survival and function pathways were significantly changed, and the expression tendency of genes from euglycemia and glucose toxicity exposure to insulin treatment was revealed and enriched in 7 patterns.

Conclusions

Our study provides a microcirculatory framework for gene expression profiles of glucose toxicity‐exposed IMECs.
RbpA and σB association regulates polyphosphate levels to modulate mycobacterial isoniazid‐tolerance
Authors: Wang Zhongwei , Cumming Bridgette M. , Mao Chunyou , Zhu Yan , Lu Pei , Steyn Adrie J.C. , Chen Shiyun , Hu Yangbo
Published: March 2018

To facilitate survival under drug stresses, a small population of Mycobacterium tuberculosis can tolerate bactericidal concentrations of drugs without genetic mutations. These drug‐tolerant mycobacteria can be induced by environmental stresses and contribute to recalcitrant infections. However, mechanisms underlying the development of drug‐tolerant mycobacteria remain obscure. Herein, we characterized a regulatory pathway which is important for the tolerance to isoniazid (INH) in Mycobacterium smegmatis. We found that the RNA polymerase binding protein RbpA associates with the stress response sigma factor σB, to activate the transcription of ppk1, the gene encoding polyphosphate kinase. Subsequently, intracellular levels of inorganic polyphosphate increase to promote INH‐tolerant mycobacteria. Interestingly, σB and ppk1 expression varied proportionately in mycobacterial populations and positively correlated with tolerance to INH in individual mycobacteria. Moreover, sigB and ppk1 transcription are both induced upon nutrient depletion, a condition that stimulates the formation of INH‐tolerant mycobacteria. Over‐expression of ppk1 in rbpA knockdown or sigB deleted strains successfully restored the number of INH‐tolerant mycobacteria under both normal growth and nutrient starved conditions. These data suggest that RbpA and σB regulate ppk1 expression to control drug tolerance both during the logarithmic growth phase and under the nutrition starved conditions.
Stable isotope analysis of fecal material provides insight into the diet of fin whales
Authors: Arregui Marina , Borrell Asunción , Víkingsson Gisli , Ólafsdóttir Droplaug , Aguilar Alex
Published: March 2018

In cetaceans, stable isotope analysis of tissues overcomes some of the potential biases encountered in studies of diet based on stomach content or fecal analysis. However, stable isotope ratios of tissues are only indicative of long‐term feeding and may be misleading when recent shifts in prey consumption have occurred. Stable isotope ratios of feces stand as a potential alternative source for resolving short‐term diet, but may be biased by digestive enzymes and bacteria. We investigate whether fecal stable isotope ratios of freshly dead fin whales are consistent with those of the main food found in their stomachs (krill) and with those of other potential prey. Results show that stable isotope ratios of krill remain unaltered after their transit along the digestive tract and, therefore, values in feces are reliable indicators of this prey consumption. In addition, the low isotope ratios of feces that visually appeared to contain only fish remains revealed a substantial contribution of krill in the digested food. This demonstrates that macroscopic gross fecal analysis may be misleading because less digestible components, like fish bones, may be overrepresented. We conclude that stable isotope ratios of feces contribute significant information to other techniques for short‐term diet reconstruction.
Xanthomonas arboricola pv. pruni, causal agent of bacterial spot of stone fruits and almond: its genomic and phenotypic characteristics in the X. arboricola species context
Authors: Garita‐Cambronero Jerson , Palacio‐Bielsa Ana , Cubero Jaime
Published: March 2018

Background

Xanthomonas arboricola pv. pruni (Xap) causes bacterial spot of stone fruits and almond, an important disease that may reduce the yield and vigour of the trees, as well as the marketability of affected fruits. Xap lies within the Xanthomonas genus, which has been intensively studied because of its strain specialization and host range complexity. Here, we summarize the recent advances in our understanding of the complexities of Xap, including studies of the molecular features that result after comparative phenotypic and genomic analyses, in order to obtain a clearer overview of the bacterial behaviour and infection mechanism in the context of the X. arboricola species.

Taxonomic status

Bacteria; Phylum Proteobacteria; Class Gammaproteobacteria; Order Xanthomonadales; Family Xanthomonadaceae; Genus Xanthomonas; Species X. arboricola; Pathovar pruni.

Host range and symptoms

Xap infects most Prunus species, including apricot, peach, nectarine, plum and almond, and occasionally cherry. Symptoms are found on leaves, fruits, twigs and branches or trunks. In severe infections, defoliation and fruit dropping may occur.

Distribution

Bacterial spot of stone fruits and almond is worldwide in distribution, with Xap being isolated in Africa, North and South America, Asia, Europe and Oceania. It is a common disease in geographical areas in which stone fruits and almonds are grown. Xap is listed as a quarantine organism in several areas of the world.

Genome

The genomes of six isolates from Xap have been publicly released. The genome consists of a single chromosome of around 5 000 000 bp with 65 mol% GC content and an extrachromosomal plasmid element of around 41 000 bp with 62 mol% GC content. Genomic comparative studies in X. arboricola have allowed the identification of putative virulence components associated with the infection process of bacterial spot of stone fruits and almond.

Disease control

Management of bacterial spot of stone fruits and almond is based on an integrated approach that comprises essential measures to avoid Xap introduction in a production zone, as well as the use of tolerant or resistant plant material and chemical treatments, mainly based on copper compounds. Management programmes also include the use of appropriate cultivation practices when the disease is already established. Finally, for the effective control of the disease, appropriate detection and characterization methods are needed for use in symptomatic or asymptomatic samples as a first approach for pathogen exclusion.

Useful websites

https://gd.eppo.int/taxon/XANTPR; http://www.cost.eu/COST_Actions/ca/CA16107; http://www.xanthomonas.org
Activation of PhoBR under phosphate‐rich conditions reduces the virulence of Xanthomonas oryzae pv. oryzae
Authors: Zheng Dehong , Xue Bingbing , Shao Yanan , Yu Haoquan , Yao Xiaoyan , Ruan Lifang
Published: March 2018

The two‐component signal transduction system PhoBR regulates the adaptation to phosphate limitation and the virulence of many animal bacterial pathogens. However, PhoBR in phytopathogens has rarely been investigated. In this study, we found that PhoBR in Xanthomonas oryzae pv. oryzae (Xoo), the pathogen of rice bacterial leaf blight, also regulates the adaptation to phosphate starvation. Unexpectedly, rice leaves infected by the phoBR‐deleted mutant and wild‐type PXO99A showed similar lesions, indicating that PhoBR is unnecessary for the virulence of Xoo. phoBR was found to be silenced during host infection, whereas artificially constitutive PhoBR expression attenuated virulence on host rice and growth in phosphate‐rich media. RNA‐sequencing (RNA‐seq) was then performed to investigate the global effect caused by constitutive PhoBR activation. RNA‐seq and further experiments revealed that the PhoBR regulon in Xoo comprised a wide range of genes. Nutrient transport and metabolism readjustments that resulted from PhoBR regulon activation may be responsible for growth attenuation. Our findings suggest that growth reduction regulated by PhoBR is a fitness cost of adaptation to phosphate starvation. PhoBR in Xoo is activated under phosphate‐limited conditions, which could exist in epiphytic and saprophytic surviving phases, and is strictly repressed within phosphate‐rich host plants to minimize fitness costs.
Wheat streak mosaic virus: a century old virus with rising importance worldwide
Authors: Singh Khushwant , Wegulo Stephen N. , Skoracka Anna , Kundu Jiban Kumar
Published: March 2018

Wheat streak mosaic virus (WSMV) causes wheat streak mosaic, a disease of cereals and grasses that threatens wheat production worldwide. It is a monopartite, positive‐sense, single‐stranded RNA virus and the type member of the genus Tritimovirus in the family Potyviridae. The only known vector is the wheat curl mite (WCM, Aceria tosichella), recently identified as a species complex of biotypes differing in virus transmission. Low rates of seed transmission have been reported. Infected plants are stunted and have a yellow mosaic of parallel discontinuous streaks on the leaves. In the autumn, WCMs move from WSMV‐infected volunteer wheat and other grass hosts to newly emerged wheat and transmit the virus which survives the winter within the plant, and the mites survive as eggs, larvae, nymphs or adults in the crown and leaf sheaths. In the spring/summer, the mites move from the maturing wheat crop to volunteer wheat and other grass hosts and transmit WSMV, and onto newly emerged wheat in the fall to which they transmit the virus, completing the disease cycle. WSMV detection is by enzyme‐linked immunosorbent assay (ELISA), reverse transcription‐polymerase chain reaction (RT‐PCR) or quantitative RT‐PCR (RT‐qPCR). Three types of WSMV are recognized: A (Mexico), B (Europe, Russia, Asia) and D (USA, Argentina, Brazil, Australia, Turkey, Canada). Resistance genes Wsm1, Wsm2 and Wsm3 have been identified. The most effective, Wsm2, has been introduced into several wheat cultivars. Mitigation of losses caused by WSMV will require enhanced knowledge of the biology of WCM biotypes and WSMV, new or improved virus detection techniques, the development of resistance through traditional and molecular breeding, and the adaptation of cultural management tactics to account for climate change.
Candida utilis fungaemia following endoscopic intervention on ureteral stent in a kidney transplant recipient: Case report and a review of the literature
Authors: Gaisne Raphaël , Jeddi Fakhri , Morio Florent , Le Clerc Quentin‐Côme , Hourmant Maryvonne , Blancho Gilles , Giral Magali , Cantarovich Diego , Dantal Jacques , Ville Simon
Published: March 2018

Infection due to species other than Candida albicans is increasing among solid organ transplant recipients. Candida utilis, commonly used in the food industry, is considered as a low‐virulence yeast. We report the first case of C. utilis fungaemia involving a solid organ transplant recipient. The infection was triggered by the withdrawal of a ureteral stent and was successfully treated with intravenous micafungin. We also propose a review of all reported cases of infection caused by C. utilis.
Molecular detection of fungi of public health importance in wild animals from Southern Brazil
Authors: Losnak Debora O. , Rocha Francielle R. , Almeida Barbara S. , Batista Keila Z. S. , Althoff Sérgio L. , Haupt Josiane , Ruiz Luciana S. , Anversa Laís , Lucheis Simone B. , Paiz Laís M. , Donalisio Maria Rita , Richini Pereira Virginia B.
Published: March 2018

Some animals have an important relationship with fungal infections, and searching for pathogens in animal samples may be an opportunity for eco‐epidemiological research. Since studies involving wildlife are generally restricted, using samples from road kills is an alternative. The aim of this study was to verify whether pathogenic fungi of public health importance occur in wildlife road kills from Santa Catarina State, Brazil. Organ samples (n = 1063) from 297 animals were analysed according to Polymerase Chain Reaction (PCR) using universal primers to detect fungi in general and, subsequently, using primers specific to Paracoccidioides brasiliensis, Histoplasma capsulatum and Cryptococcus spp. There were 102 samples positive for fungal species. Eight samples were positive for P. brasiliensis, three samples were positive for Cryptococcus spp. and one sample had coinfection by these two fungi. No sample was positive for Histoplasma spp. according to the molecular detection. Genetic sequencing allowed the identification of Fungal sp. in 89 samples, Cryptococcus neoformans in two samples and Aspergillus penicillioides in three samples. This study shows the importance of wild animals in the epidemiology of fungal infections and assists in the mapping of pathogen occurrence in a region that was not previously evaluated.
Antifungal treatment in haematological and oncological patients: Need for quality assessment in routine care
Authors: Lachenmayr Sarah J. , Berking Sophie , Horns Heidi , Strobach Dorothea , Ostermann Helmut , Berger Karin
Published: March 2018

Invasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18 years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy‐one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty‐four antifungals (20.0%) were co‐administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified.
Expression profile of pattern recognition receptors in skeletal muscle of SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients
Authors: Lehmann S. , Esch E. , Hartmann P. , Goswami A. , Nikolin S. , Weis J. , Beyer C. , Johann S.
Published: March 2018

Aims

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non‐neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis‐associated speck‐like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are early events in ALS, we hypothesized that PRRs might be abnormally expressed in muscle fibre degeneration.

Methods

Western blot analysis, real‐time PCR and immunohistochemistry were performed with muscle tissue from presymptomatic and early‐symptomatic male SOD1(G93A) mice and with muscle biopsies of control and sporadic ALS (sALS) patients. Analysed PRRs include nucleotide‐binding oligomerization domain‐like (NOD‐like) receptor protein 1 (NLRP1), NLR protein 3 (NLRP3), NLR family CARD domain‐containing 4 (NLRC4) and absent in melanoma 2. Additionally, expression levels of ASC, caspase 1, interleukin 1 beta (IL1β) and interleukin 18 (IL18) were evaluated.

Results

Expression of PRRs and ASC was detected in murine and human tissue. The PRR NLRC4, caspase 1 and IL1β were significantly elevated in denervated muscle of SOD1(G93A) mice and sALS patients. Furthermore, levels of caspase 1 and IL1β were already increased in presymptomatic animals.

Conclusion

Our findings suggest that increased inflammasome activation may be involved in skeletal muscle pathology in ALS. Furthermore, elevated levels of NLRC4, caspase 1 and IL1β reflect early changes in the skeletal muscle and may contribute to the denervation process.
A case of late‐onset Krabbe disease which showed subacute progression of spastic paresis with bilateral spinal cord lesions
Authors: Mitsutake Akihiko , Matsukawa Takashi , Ishiura Hiroyuki , Mitsui Jun , Taira Kenichiro , Tokushige Shin‐ichi , Iwata Atsushi , Terao Yasuo , Shimizu Jun , Sakai Norio , Tsuji Shoji
Published: March 2018

We report a 16‐year‐old boy with the late‐onset form of Krabbe disease. The patient had been free of neuromuscular diseases until he showed subacute progression of spastic paraparesis at age 15. There was no evident peripheral neuropathy. Magnetic resonance imaging (MRI) of the brain and the spinal cord showed T2‐weighted high‐intensity lesions along the bilateral pyramidal tract from the internal capsule to the lumbar cord. Bilateral pyramidal tract involvement raised the possibility of late‐onset Krabbe disease. A markedly reduced galactocerebrosidase activity and a homozygous known pathogenic mutation in the GALC gene confirmed the diagnosis. This case was unique in that the progression was subacute and the lesions from the cervical to the lumbar cord were clearly shown by MRI.
Egogram characteristics in Japanese patients with Parkinson's disease
Authors: Shinoda Tomomi , Nakashita Satoko , Hamada Mao , Hirono Kanako , Ito Mariko , Miyagi Tomo , Namihira Yukihiro , Tokashiki Takashi , Kashihara Kenichi , Nakashima Kenji , Maeda Tetsuya
Published: March 2018

Background

Personality has been investigated as a possible onset risk factor for Parkinson's disease (PD). Recently, personality has attracted increasing attention because certain non‐motor aspects may be associated with patients’ personality and deterioration of their quality of life. The Tokyo University Egogram version II (TEGII) is a reliable questionnaire for assessing personality in Japanese people, but few studies have reported personality assessments in Japanese PD patients.

Aim

To clarify the clinical utility of the TEGII for evaluating personality in Japanese PD.

Methods

Patients were consecutively enrolled in four medical centers throughout Japan, and their personality was evaluated using the TEGII. Personality is described in terms of five ego‐states: critical parent (CP), nurturing parent (NP), adult (A), free child (FC), and adapted child (AP). The scores for each ego‐state and the egogram patterns describe personality characteristics. We statistically analyzed our data and compared the results with standardized data from a Japanese cohort.

Results

We enrolled 133 PD patients. The mean scores ± SDs of the five ego‐states were CP: 11.4 ± 4.5, NP: 14.5 ± 4.2, A: 10.5 ± 4.8, FC: 11.1 ± 4.7, and AC: 9.5 ± 5.2. NP scores were significantly higher than the others (P < 0.001), and the NP dominant pattern (15.8%) was most frequent.

Conclusion

The NP dominant pattern, which illustrates a thoughtful, obliging and kind personality, is characteristic of Japanese PD patients. The TEGII is a simple clinical tool for evaluating personality in PD and can be used to evaluate changes in patients over time.
20 year trends in renal disease mortality in Ghana: A review of autopsies
Authors: Adjei David N , Adu Dwomoa , Quayson Solomon E , Kardaun Jan WPF , Erskine Isaac J , Lartey Isaac S , Agyemang Charles
Published: March 2018

Aim

Data on the changing levels in renal morbidity and mortality are scant globally. We sought to assess trends in renal disease mortality and attributable causes over a 20 year period in Ghana.

Methods

A retrospective analysis of 20 year autopsy records of the Pathology Departments of leading teaching hospitals in Ghana, (Korle‐Bu Teaching Hospital (KBTH) in Accra and Komfo Anokye Teaching Hospital (KATH) in Kumasi) from January 1994 to December 2013. Data comprising autopsies from in‐patients, community cases and coroners’ cases were used. We defined primary cause of death as death directly due to renal disease and secondary cause of death as death in which renal disease was a comorbid or contributing factor.

Results

Over the period, there were a total of 94 309 deaths, of which 5608 were attributed to renal disease (5.9/100). Mortality rate remained fairly the same from 1994 to 2009 (5.0%), but doubled from 2010 to 2013 (10.8%). Similar trends were observed among males and females during the same period. However, males had slightly higher mortality rates (6.6%; 95% CI: 46.1%–6.8%) compared to females (5.6%; 95% CI: 5.4%–5.8%; P = 0.271). The major leading attributable causes of renal disease death include end stage renal disease 45.0% and acute pyelonephritis accounting for 20.9% of the cases. Hypertensive heart disease accounted for 30.0% of all secondary cause of death while congestive heart disease and septicaemia accounted for 13.0% and 12.0%, respectively.

Conclusions

We observed marked increase in the renal disease mortality rate during the last few years predominantly driven by chronic and infectious related renal diseases as a main cause, and hypertensive heart disease and congestive heart failure as the main secondary causes. Measures geared towards prevention, treatment and managing such conditions may impact on the reduction of renal disease mortality rate among Ghanaian populations.
Renal regeneration after acute kidney injury
Authors: Coelho Silvia , Cabral Guadalupe , Lopes José A , Jacinto António
Published: March 2018

Summary at a Glance

This review focuses on the short and long term clinical risk factors that contribute to progression to chronic renal disease following acute insult. The probability of patient recovery, taking into consideration the aetiology of disease, and the cellular, molecular and immune response that determines tissue regeneration are discussed in detail.
Heart rate variability characteristics of patients with irritable bowel syndrome and associations with symptoms
Authors: Polster A. , Friberg P. , Gunterberg V. , Öhman L. , Le Nevé B. , Törnblom H. , Cvijovic M. , Simren M.
Published: March 2018

Background

Disturbed brain‐gut interactions are assumed to be of importance for symptom generation in patients with irritable bowel syndrome (IBS). The autonomic nervous system (ANS) is part of the bidirectional brain‐gut communication, but previous studies in IBS show diverging results. We aimed to identify subgroups of IBS patients with distinct ANS characteristics differentiating them from healthy controls (HC), and to study associations between ANS status and symptoms.

Methods

Heart rate variability (HRV) was measured in IBS patients and HC (Holter monitoring: supine and standing positions with controlled respiration and ambulatory 24‐hour period). Frequency (5 minutes, supine, standing) and time domains (24 hours, day, night) were analyzed. Validated questionnaires were used to measure gastrointestinal and psychological symptoms in patients. Patients and HC were compared on a univariate and multivariate level (principal component analysis [PCA] and orthogonal partial least squares discriminatory analysis (OPLS‐DA)).

Key Results

We analyzed 158 IBS patients (Rome III) and 39 HC. Patients differed significantly from HC in HRV parameters during daytime and in standing position. In the PCA, a majority of patients overlapped with HC, but the weighted means differed (P < .01). A subset of patients (n = 30; 19%) with an aberrant global HRV profile was identified through PCA and OPLS‐DA; these patients reported more severe symptoms of frequent (P < .05) and loose stools (P = .03), as well as urgency (P = .01).

Conclusions and Inferences

Altered ANS function was demonstrated in patients with IBS, and this might be of particular relevance for symptoms in a subset of the patients.
Radar plots: A novel modality for displaying disparate data on the efficacy of eluxadoline for the treatment of irritable bowel syndrome with diarrhea
Authors: Brenner D. M. , Dove L. S. , Andrae D. A. , Covington P. S. , Gutman C. , Chey W. D.
Published: March 2018

Background

Patients with irritable bowel syndrome with diarrhea (IBS‐D) experience a range of abdominal and bowel symptoms; successful management requires alleviation of this constellation of symptoms. Eluxadoline, a locally active mixed μ‐ and κ‐opioid receptor agonist and δ‐opioid receptor antagonist, is approved for the treatment of IBS‐D in adults based on the results of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation of diverse but interrelated efficacy endpoints.

Methods

Two double‐blind, placebo‐controlled, Phase 3 trials (IBS‐3001 and IBS‐3002) randomized patients meeting Rome III criteria for IBS‐D to twice‐daily eluxadoline 75 or 100 mg or placebo. Radar plots were prepared showing pooled Weeks 1‐26 response rates for the primary efficacy composite endpoint (simultaneous improvement in abdominal pain and stool consistency), stool consistency, abdominal pain, urgency‐free days, and adequate relief, and change from baseline to Week 26 in IBS‐D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and daily number of bowel movements.

Key Results

The studies enrolled 2428 patients. Eluxadoline increased Weeks 1‐26 responder proportions vs placebo for the composite endpoint, stool consistency, abdominal pain, urgency‐free days, and adequate relief. Changes from baseline to Week 26 in IBS‐D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and number of bowel movements were greater with eluxadoline vs placebo.

Conclusions and Inferences

Data presentation in radar plot format facilitates interpretation across multiple domains, demonstrating that eluxadoline treatment led to improvements vs placebo across 13 endpoints representing the range of symptoms experienced by patients with IBS‐D.
High temporal resolution gastric emptying breath tests in mice
Authors: Miller K. E. , Bajzer Ž. , Hein S. S. , Phillips J. E. , Syed S. , Wright A. M. , Cipriani G. , Gibbons S. J. , Szurszewski J. H. , Farrugia G. , Ordog T. , Linden D. R.
Published: March 2018

Background

Gastric emptying is a complex physiological process regulating the division of a meal into smaller partitions for the small intestine. Disrupted gastric emptying contributes to digestive disease, yet current measures may not reflect different mechanisms by which the process can be altered.

Methods

We have developed high temporal resolution solid and liquid gastric emptying breath tests in mice using [13C]‐octanoic acid and off axis‐ integrated cavity output spectroscopy (OA‐ICOS). Stretched gamma variate and 2‐component stretched gamma variate models fit measured breath excretion data.

Key Results

These assays detect acceleration and delay using pharmacological (7.5 mg/kg atropine) or physiological (nutrients, cold exposure stress, diabetes) manipulations and remain stable over time. High temporal resolution resolved complex excretion curves with 2 components, which was more prevalent in mice with delayed gastric emptying following streptozotocin‐induced diabetes. There were differences in the gastric emptying of Balb/c vs C57Bl6 mice, with slower gastric emptying and a greater occurrence of two‐phase gastric emptying curves in the latter strain. Gastric emptying of C57Bl6 could be accelerated by halving the meal size, but with no effect on the occurrence of two‐phase gastric emptying curves. A greater proportion of two‐phase gastric emptying was induced in Balb/c mice with the administration of PYY (8‐80 nmol) 60 min following meal ingestion.

Conclusions and Inferences

Collectively, these results demonstrate the utility of high temporal resolution gastric emptying assays. Two‐phase gastric emptying is more prevalent than previously reported, likely involves intestinal feedback, but contributes little to the overall rate of gastric emptying.
Different perception of chronic constipation between patients and gastroenterologists
Authors: Bellini M. , Gambaccini D. , Salvadori S. , Bocchini R. , Pucciani F. , Bove A. , Alduini P. , Battaglia E. , Bassotti G.
Published: March 2018

Background

There is a certain number of subjects that consider themselves to be constipated (self diagnosed constipation; SDC). The Rome Criteria separate FC from IBS‐C, but some SDC patients do not meet the Rome criteria (no Rome Constipation; NRC). Our aims were to evaluate the percentage of SDC subjects with a diagnosis of FC and IBS‐C and to compare demographic and clinical features, symptoms, and quality of life in the different SDC groups (FC, IBS‐C, NRC).

Methods

During a 2‐month period, 934 patients and 980 accompanying persons (AP) were asked to complete a survey. The presence of FC or IBS‐C was assessed. SDC subjects were invited to record the stool consistency (Bristol scale) and to fill in the Constipation Severity Index (CSI), obstructed defecation syndrome (ODS) and patient assessment of constipation‐quality of life (PAC‐QoL). The use of laxatives and enemas was evaluated.

Key Results

The probability of the ROME III criteria being present was higher in SDC compared with no‐SDC (OR 20.5). NRC was present in 13.5% of the SDC. In the patients’ group the agreement between a diagnosis of Rome III and SDC was good (K 0.62), whereas in the AP it was moderate (K 0.56). NRC showed lower mean values of ODS, CSI and PAC‐QoL, higher Bristol scale and a lower use of laxatives and enemas compared to IBS‐C and FC. No differences were found between IBS‐C and FC.

Conclusions and Inferences

The Rome III criteria identify subjects with a greater clinical impact, but separation of FC and IBS‐C does not seem justified.
Gastrointestinal dysmotility: A qualitative exploration of the journey from symptom onset to diagnosis
Authors: Twist K. , Ablett J. , Wearden A. , Paine P. , Vasant D. , Lal S. , Peters S.
Published: March 2018

Background

Gastrointestinal dysmotility (GID) covers a spectrum of disorders disrupting enteric neuromuscular co‐ordination which, when severe, causes intractable gastrointestinal symptoms and malnutrition and is a recognized cause of chronic intestinal failure. To date, no study has provided an in‐depth account of the experiences of patients with severe GID and their psychosocial needs. This study aimed to explore patients’ experiences from symptom onset and the process of seeking and receiving a diagnosis. It specifically explored the psychological effect of this process and the effect on relationships.

Methods

Participants (n = 20, mean age = 47.9, female n = 16, parenteral nutrition = 13) were recruited from a UK center with tertiary Neurogastroenterology and Intestinal Failure services. A qualitative exploratory design with semi‐structured in‐depth interviews was used. Data were analyzed using thematic analysis.

Key Results

Significant delays were experienced in obtaining a diagnosis. Participants reported having their mental health questioned and felt that they had to fight to prove their symptoms had a physical basis to access appropriate treatment. Although a diagnosis helped legitimize symptoms, the condition remained poorly understood by participants themselves, relatives, and health professionals. Participants discussed the impact that “feeling delegitimized” and the “lack of coherent understanding of GID” had on their relationships and mental health.

Conclusions & Inferences

The distressing experience of GID symptoms are compounded by a delay in validating symptoms and lack of coherent understanding. More knowledge of GID is needed by health professionals to speed up diagnosis and offer more coherent information. The psychological impact of a GID diagnosis should be acknowledged early to help facilitate adjustment.
Aphid (Myzus persicae) feeding on the parasitic plant dodder (Cuscuta australis) activates defense responses in both the parasite and soybean host
Authors: Zhuang Huifu , Li Juan , Song Juan , Hettenhausen Christian , Schuman Meredith C. , Sun Guiling , Zhang Cuiping , Li Jing , Song Dunlun , Wu Jianqiang
Published: March 2018

Dodders (Cuscuta spp.) are shoot holoparasites, whose haustoria penetrate host tissues to enable fusion between the parasite and host vascular systems, allowing Cuscuta to extract water, nutrients and other molecules from hosts. Aphids are piercing–sucking herbivores that use specialized stylets to feed on phloem sap. Aphids are known to feed on Cuscuta, but how Cuscuta and its host plant respond to aphids attacking the parasite was unknown.

Phytohormone quantification, transcriptomic analysis and bioassays were performed to determine the responses of Cuscuta australis and its soybean (Glycine max) hosts to the feeding of green peach aphid (GPA; Myzus persicae) on C. australis.

Decreased salicylic acid levels and 172 differentially expressed genes (DEGs) were found in GPA‐attacked C. australis, and the soybean hosts exhibited increased jasmonic acid contents and 1015 DEGs, including > 100 transcription factor genes. Importantly, GPA feeding on C. australis increased the resistance of the soybean host to subsequent feeding by the leafworm Spodoptera litura and soybean aphid Aphis glycines, resulting in 21% decreased leafworm mass and 41% reduced aphid survival rate.

These data strongly suggest that GPA feeding on Cuscuta induces a systemic signal, which is translocated to hosts and activates defense against herbivores.
Class C ARFs evolved before the origin of land plants and antagonize differentiation and developmental transitions in Marchantia polymorpha
Authors: Flores‐Sandoval Eduardo , Eklund D. Magnus , Hong Syuan‐Fei , Alvarez John P. , Fisher Tom J. , Lampugnani Edwin R. , Golz John F. , Vázquez‐Lobo Alejandra , Dierschke Tom , Lin Shih‐Shun , Bowman John L. 
Published: March 2018

A plethora of developmental and physiological processes in land plants is influenced by auxin, to a large extent via alterations in gene expression by AUXIN RESPONSE FACTORs (ARFs). The canonical auxin transcriptional response system is a land plant innovation, however, charophycean algae possess orthologues of at least some classes of ARF and AUXIN/INDOLE‐3‐ACETIC ACID (AUX/IAA) genes, suggesting that elements of the canonical land plant system existed in an ancestral alga.

We reconstructed the phylogenetic relationships between streptophyte ARF and AUX/IAA genes and functionally characterized the solitary class C ARF, MpARF3, in Marchantia polymorpha.

Phylogenetic analyses indicate that multiple ARF classes, including class C ARFs, existed in an ancestral alga. Loss‐ and gain‐of‐function MpARF3 alleles result in pleiotropic effects in the gametophyte, with MpARF3 inhibiting differentiation and developmental transitions in multiple stages of the life cycle. Although loss‐of‐function Mparf3 and Mpmir160 alleles respond to exogenous auxin treatments, strong miR‐resistant MpARF3 alleles are auxin‐insensitive, suggesting that class C ARFs act in a context‐dependent fashion.

We conclude that two modules independently evolved to regulate a pre‐existing ARF transcriptional network. Whereas the auxin‐TIR1‐AUX/IAA pathway evolved to repress class A/B ARF activity, miR160 evolved to repress class C ARFs in a dynamic fashion.
Plant stem cells and de novo organogenesis
Authors: Sang Ya Lin , Cheng Zhi Juan , Zhang Xian Sheng
Published: March 2018

Contents

Summary
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I.
Introduction
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II.
Regeneration‐initial cell: the origin of regeneration
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III.
Acquiring regeneration competency: the essential intermediate step for hormone‐induced regeneration
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IV.
Hormonal induction of stem cell regulators: the program for de novo establishment of apical meristems
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V.
Conclusions and perspectives
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Acknowledgements
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Author contributions
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References
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High cellular plasticity confers remarkable regeneration capacity to plants. Based on the activity of stem cells and their regulators, higher plants are capable of regenerating new individuals. De novo organogenesis exemplifies the regeneration of the whole plant body and is exploited widely in agriculture and biotechnology. In this Tansley insight article, we summarize recent advances that facilitate our understanding of the molecular mechanisms underlying de novo organogenesis. According to our current knowledge, this process can be divided into three steps, including activation of regeneration‐initial cells, acquisition of competency and de novo establishment of apical meristems. The functions of stem cells and their regulators are critical to de novo organogenesis, whereas auxin and cytokinin act as triggers and linkers between different steps.
Peeking at a plant through the holes in the wall – exploring the roles of plasmodesmata
Authors: Lu Kuan‐Ju , Danila Florence R. , Cho Yueh , Faulkner Christine
Published: March 2018

Plasmodesmata (PD) are membrane‐lined pores that connect neighbouring plant cells and allow molecular exchange via the symplast. Past studies have revealed the basic structure of PD, some of the transport mechanisms for molecules through PD, and a variety of physiological processes in which they function. Recently, with the help of newly developed technologies, several exciting new features of PD have been revealed. New PD structures were observed during early formation of PD and between phloem sieve elements and phloem pole pericycle cells in roots. Both observations challenge our current understanding of PD structure and function. Research into novel physiological responses, which are regulated by PD, indicates that we have not yet fully explored the potential contribution of PD to overall plant function. In this Viewpoint article, we summarize some of the recent advances in understanding the structure and function of PD and propose the challenges ahead for the community.
DNA is hypomethylated in circadian manifestations of bruxism
Authors: Oporto GH , Salazar LA
Published: March 2018

Objective

The aim of this study was to compare the global DNA methylation levels in patients under bruxism treatment and a control group.

Methods

Subjects undergoing bruxism treatment were classified in awake bruxism (42 patients), sleep bruxism (32 patients) and both conditions (42 patients). The control group included 42 individuals. A colorimetric assay (MethylFlash Methylated DNA 5‐mC Quantification Kit, Epigenetic Group Inc., NY, USA) was used to determine the global DNA methylation levels.

Results

Statistically significant differences were found in amounts of methylated DNA in all circadian manifestations of bruxism compared with a control group (sleep bruxism = 0.95% ± 2.02%; awake bruxism = 0.87% ± 2.1%; sleep and awake bruxism = 0.17% ± 0.25%; Control = 1.69% ± 1.6%; Kruskal–Wallis test [p = .0001] followed by Dunn’s test [p < .05]).

Conclusion

Patients undergoing bruxism treatment exhibited hypomethylated DNA levels when compared to control group. Our results suggest that DNA hypomethylation might be a novel aetiologic factor in bruxism aetiology. Further researches must be performed exploring the role of epigenetics modifications in circadian manifestations of bruxism.
Dentin dysplasia type I—A dental disease with genetic heterogeneity
Authors: Chen D , Li X , Lu F , Wang Y , Xiong F , Li Q
Published: March 2018

Hereditary dentin disorders include dentinogenesis imperfecta (DGI) and dentin dysplasia (DD), which are autosomal dominant diseases characterized by altered dentin structure such as abnormality in dentin mineralization and the absence of root dentin. Shields classifiedDGIinto three subgroups andDDinto two subtypes. Although they are all hereditary dentin diseases, they do not share the same causative genes. To date, the pathogenic genes ofDGItype I, which is considered a clinical manifestation of syndrome osteogenesis imperfecta, includeCOL1A1andCOL1A2. Mutations of theDSPPgene, which encodes the dentin sialophosphoprotein, a major non‐collagenous protein, are responsible for three isolated dentinal diseases:DGI‐II,DGI‐III, andDD‐II. However,DD‐I appears to be special in that researchers have found three pathogenicity genes―VPS4B,SSUH2, andSMOC2―in three affected families from different countries. It is believed thatDD‐I is a genetically heterogeneous disease and is distinguished from other types of dentin disorders. This review summarizes theDD‐I literature in the context of clinical appearances, radiographic characteristics, and functions of its pathogenic genes and aims to serve clinicians in further understanding and diagnosing this disease.
The role of unregulated care providers in Canada—A scoping review
Authors: Afzal Arsalan , Stolee Paul , Heckman George A. , Boscart Veronique M. , Sanyal Chiranjeev
Published: March 2018

Aims and objectives

This scoping review explored: (i) the role of unregulated care providers in the healthcare system; (ii) their potential role on interprofessional teams; (iii) the impact of unregulated care provider’s role on quality of care and patient safety; and (iv) education and employment standards.

Background

Unregulated care providers in Canada assist older adults with personal support and activities of daily living in a variety of care settings. As the care needs of an aging population become increasingly complex, the role of unregulated care providers in healthcare delivery has also evolved. Currently, many unregulated care providers are performing tasks previously performed by regulated health professionals, with potential implications for quality of care and patient safety. Information is fragmented on the role, education and employment standards of unregulated care providers.

Methods

A scoping review was conducted following the methods outlined by Arksey and O'Malley (International Journal of Social Research Methodology, 8, 2005, 19) and Levac, Colquhoun, and O'Brien (Implementation Science, 5, 2010, 69). An iterative search of published and grey literature was conducted from January 2000 to September 2016 using Medline, CINAHL, SCOPUS and Google. Inclusion and exclusion criteria were applied to identify relevant studies published in English.

Results

The search yielded 63 papers for review. Results highlight the evolving role of unregulated care providers, a lack of recognition and a lack of authority for unregulated care provider decision‐making in patient care. Unregulated care providers do not have a defined scope of practice. However, their role has evolved to include activities previously performed by regulated professionals. Variations in education and employment standards have implications for quality of care and patient safety.

Conclusions

Unregulated care providers are part of an important workforce in the long‐term care and community sectors in Canada. Their evolving role should be recognised and efforts made to leverage their experience on interprofessional teams and reduce variations in education and employment standards.

Implications for practice

This study highlights the evolving role of unregulated care providers in Canada and presents a set of recommendations for implementation at micro, meso, and macro policy levels.