bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreas preservation: clinical practice and future developments
Authors: Branchereau Julien , Hunter James , Friend Peter , Ploeg Rutger
Published: July 2020

Purpose of review

To summarize recently published studies of preservation strategies including machine perfusion in pancreas transplantation.

Recent findings

The shortage of conventional donors is leading units to use extended criteria donors (ECDs) and donors after cardiac death (DCD). Static cold storage (SCS) is still the standard method of preservation for pancreases and University of Wisconsin remains the gold standard preservation solution. In experimental studies, oxygen delivered during preservation reduced tissue injury and improved islet cell yield and function. Hypothermic machine perfusion of discarded human pancreases has been shown to improve adenosine triphosphate levels without adversely effect histology and oedema compared with SCS. Normothermic machine perfusion of discarded human organs has so far been challenging and led to increasing injury, rather than preservation. There are currently no clinical studies in pancreas transplant with the exception of a small number of pancreases being transplanted following normothermic regional perfusion.

The storm of new organ preservation methods is now being more widely studied in the pancreas, with some promising results. These new strategies have the potential to allow expansion of the donor pool and greater utilization of ECD and DCD organs.
Update on Nocardia infections in solid-organ transplantation
Authors: Saullo Jennifer L. , Miller Rachel A.
Published: July 2020

Purpose of review

Nocardia is a ubiquitous pathogen associated with life-threatening opportunistic infections. Organ transplant recipients are uniquely predisposed to Nocardia infections due to their iatrogenic cell-mediated immune deficit necessary to maintain allograft function. This review aims to address recent updates in the epidemiology, clinical presentation, diagnostics, treatment, and outcomes of Nocardia infections in solid-organ transplant recipients.

Recent findings

The incidence of Nocardia infection depends on multiple patient and environmental factors. Among transplant recipients, lung recipients are most commonly affected. Species identification and antimicrobial susceptibility testing are critical for optimizing therapy as substantial variation occurs among and within Nocardia spp. This has been increasingly accomplished through advances in molecular methods leading to improved accuracy and wider accessibility to testing. There are emerging data applying novel therapeutics and short course therapy that may offer alternative management approaches for transplant associated nocardiosis to minimize drug toxicity and intolerance.

Further prospective, multicenter studies are needed to better characterize the epidemiology of Nocardia in transplant recipients, as well as evaluate the impact of diagnostic advancements and new treatment strategies.
Electrodiagnostic Testing of Entrapment Neuropathies: A Review of Existing Guidelines
Authors: Pugdahl Kirsten , Tankisi Hatice , Fuglsang-Frederiksen Anders
Published: July 2020

Entrapment neuropathies cover a wide range of isolated nerve injuries along the course of the upper and lower extremity nerves. Electrodiagnostic (EDX) testing is usually an essential part of the evaluation of entrapment neuropathies, and examinations for the most common entrapment neuropathies, carpal tunnel syndrome and ulnar neuropathy at the elbow, constitute a significant part of the daily work in EDX laboratories. Despite this, guidelines for EDX testing are generally sparse or do not exist for entrapment neuropathies, whereas a wide variety of different techniques are available to the clinical neurophysiologist. This study reviews the existing, more or less, detailed EDX criteria or practice parameters that are suggested by consensus groups in peer-reviewed journals for the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow, common peroneal (fibular) neuropathy at the fibular head, and tibial neuropathy at the tarsal tunnel. It is concluded that future research is needed to develop and refine EDX guidelines in entrapment neuropathies.
Three alternative proposals to emend the Rules of the International Code of Nomenclature of Prokaryotes to resolve the status of the Cyanobacteria in the prokaryotic nomenclature
Authors: Oren Aharon
Published: July 2020

Three alternative proposals to emend the Rules of the International Code of Nomenclature of Prokaryotes are presented to resolve the status of the

Cyanobacteria

in the prokaryotic nomenclature. Two were earlier published (Oren and Garrity, Int J Syst Evol Microbiol 2014;64 : 309–310; Pinevich, Int J Syst Evol Microbiol 2015;65 : 1070–1074). The third proposal is based on reciprocation of Article 45.1 of the International Code of Nomenclature for algae, fungi, and plants. According to Article 13b of the Statutes of the International Committee on Systematics of Prokaryotes, a decision on these proposals must be reached within 11 months from the date of this publication.
The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites
Authors: Xu Feifei , Jiménez-González Alejandro , Einarsson Elin , Ástvaldsson Ásgeir , Peirasmaki Dimitra , Eckmann Lars , Andersson Jan O. , Svärd Staffan G. , Jerlström-Hultqvist Jon
Published: July 2020

Diplomonad parasites of the genus Giardia have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic Giardia species, Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for other Giardia species. Comparative data would be particularly valuable for Giardia muris, which colonizes mice and is commonly used as a prototypic in vivo model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of G. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. G. muris and G. intestinalis share many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different to G. intestinalis, G. muris maintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from the G. muris genome suggest significant metabolic differences to G. intestinalis. Additionally, G. muris encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the Giardia genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the Giardia genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host–pathogen interaction in the G. muris–mouse pathosystem.
Hidden introductions of freshwater red algae via the aquarium trade exposed by DNA barcodes
Authors: Zhan Shing Hei , Hsieh Tsai-Yin , Yeh Lan-Wei , Kuo Ting-Chun , Suda Shoichiro , Liu Shao-Lun
Published: July 2020

The global aquarium trade can introduce alien freshwater invaders, potentially impacting local aquatic ecosystems and their biodiversity. The role of the aquarium trade in spreading freshwater red macroalgae that hitchhike on ornamental aquatic plants and animals is unassessed. We investigated this human-mediated phenomenon via a broad biodiversity survey and genetic analysis of freshwater red algae in the field and aquarium shops in East Asia. UsingrbcL-based DNA barcoding, we surveyed 125 samples from 46 field sites and 88 samples from 53 aquarium shops (213 samples in total) mostly across Taiwan – a key hub in the global aquarium trade – as well as in Hong Kong, Okinawa (Japan), the Philippines, and Thailand. We augmented ourrbcL sequences with GenBankrbcL sequences that represent 40 additional countries globally. We found 26 molecular operational taxonomic units (mOTUs) in Taiwan, some of which are cryptic. Phylogeographical analysis revealed three potential introduced mOTUs in Taiwan, which exhibit no local genetic variation in Taiwan and are distributed across continents. Also, we posit that some presumably endangered freshwater red algae may be preserved in aquaria, an unintentionalex situconservation site for these organisms that are vulnerable to water pollution from anthropogenic disturbances. Collectively, these data suggest that freshwater red algae have been hitchhiking and dispersed via the aquarium trade, an important and overlooked mechanism of introduction of these organisms across the globe.
Assessing the Relationship between Serum IGF-1 and BMI by Age in the Long Life Family Study
Authors: Sherlala Rehab A. , Kammerer Candace M. , Kuipers Allison L. , Wojczynski Mary K. , Ukraintseva Svetlana V. , Feitosa Mary F. , Mengel-From Jonas , Zmuda Joseph M. , Minster Ryan L.
Published: July 2020

Background

Serum levels of insulin-like growth factor 1 (IGF-1) and body mass index (BMI) are both associated with susceptibility to age-related diseases. Reports on the correlation between them have been conflicting, with both positive to negative correlations reported. However, the age ranges of the participants varied widely among these studies.

Methods

Using data on 4,241 participants (aged 24–110) from the Long Life Family Study, we investigated the relationship between IGF-1 and BMI by age groups using regression analysis.

Results

When stratified by age quartile, the correlation between IGF-1 and BMI varied: in the 1st quartile (Q1, 24 y–58 y) the correlation was negative (r = −0.1, P = 0.0008); in Q2 (59 y– 66 y) it was negative (r = −0.035) but non-significant; in Q3 (67 y–86 y) it was positive (r = 0.045) but non-significant; and in Q4 (87 y–110 y) the correlation was positive (r = 0.14, P < 0.0001). This pattern did not differ by sex. We observed a similar age-related pattern between IGF-1 and BMI among participants in the third National Health and Nutritional Examination Survey.

Conclusions

Our results, that the relationship between IGF-1 and BMI differs by age, may explain some of the inconsistency in reports about their relationship and encourage additional studies to understand the mechanisms underlying it.
Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19
Authors: Komissarov Alexey , Molodtsov Ivan , Ivanova Oxana , Maryukhnich Elena , Kudryavtseva Svetlana , Mazus Alexey , Nikonov Evgeniy , Vasilieva Elena
Published: July 2020

Due to the constantly growing numbers of COVID-19 infections and death cases attempts were undertaken to find drugs with anti SARS-CoV-2 activity among ones already approved for other pathologies. In the framework of such attempts, in a number of in vitro, as well as in vivo, models it was shown that hydroxychloroquine (HCQ) has an effect against SARS-CoV-2. While there was not enough clinical data to support the use of HCQ, several countries including Russia have included HCQ in treatment protocols for infected patients and for prophylactic. Here, we evaluated the SARS-CoV-2 RNA in nasopharynx swabs from infected patients in mild conditions and compared the viral RNA load dynamics between patients receiving HCQ and control group without antiviral pharmacological therapy. We found statistically significant relationship between maximal RNA quantity and patients’ deteriorating medical conditions, as well as confirmed the arterial hypertension to be a risk factor for people with COVID-19. However, we showed that HCQ therapy neither shortened the viral shedding period nor reduced the virus RNA load.
Quantitative Epithermal Neutron Activation Analysis of Seven Micro Elements in Breast Milk of Lactating Mothers from the Central region of Ghana
Authors: Aboh Irene Korkoi , Vowotor Michael K. , Druye Andrews Adjei
Published: July 2020

Background

Epithermal instrumental neutron activation analysis (EINAA) technique is used for the determination and estimation of the concentration levels of micronutrients such as Sodium (Na), Magnesium (Mg), Potassium (K), Calcium (Ca), Manganese (Mn), Copper (Cu) and Iodine (I) in breastmilk.

Aim

To examine the concentration of seven micro elements in the breastmilk of lactating mother who were exclusively breastfeeding.

Methods

This study employed quantitative experimental research where 27 lactating mothers voluntarily participated in the study from two health facilities in the Cape Coast Metropolitan area. Data was collected over a period of four weeks. A three millimetre (3mm) thick of flexible boron was used to cut off thermal neutrons in order to assess epithermal neutrons. This was done to create an activation energy which examines the amount of the 7 micro nutrients in the breastmilk. The standard reference materials used were the International Atomic Energy Agency (IAEA)-336; IAEA-407, IAEA-350 and National Institute of Standard and Technology (NIST) USA SRM 1577b. The Relative standardization method was used in the quantification of the elements.

Results

The study achieved about 94.7% accuracy. The estimated health risk calculated showed that the concentrations of chlorine (Cl) and iodine (I) were high in the order I > Cl with all very far above the maximum Upper Limit (UL) of the daily Recommended Dietary Allowance (RDA) for all life stages except for children below 8 years.

Conclusion

Mn is found in very high quantities in the diet consumed by the parents of babies. These children could be exposed to metabolic disorders or unexplained diseases in future without knowing their origin.
The Phase Shift Correlation function uncovers periodic Ulcerative Colitis microbiome relationships without temporal sampling
Authors: Brown Robert E. , Arlova Alena , Gillevet Patrick M.
Published: July 2020

Correlation analysis is a fundamental technique to determine potential relationships within biological processes. However, many biological processes have been shown to function in a periodic manner. When modeling correlations, the fluctuations that are associated with periodicity cause significant issues. We have implemented a Phase Shift Correlation (PSC) algorithm, with a corresponding value PSCrho, to address the periodicity and phase variance associated with features that vary with the same frequency -- but are phase shifted. The phase shift could well indicate causality with one feature’s quantitative change leading to the change in the other feature.

We applied the PSC algorithm to Ulcerative Colitis (UC) microbiome data and compared the resulting feature relationships with the equivalent Spearman correlation function results. PSC located many instances of higher phase shifted correlations, where the corresponding Pearson correlation was low.
Profiling the intratumoral immune landscapes of primary and syngeneic Kras-driven sarcoma mouse models
Authors: Gutierrez Wade R. , Scherer Amanda , McGivney Gavin R. , Knepper-Adrian Vickie , Laverty Emily A. , Roughton Grace , Dodd Rebecca D.
Published: July 2020

The introduction of immunotherapy has revolutionized cancer treatment and fueled interest in the immune cell composition of preclinical tumor models. Both genetically-engineered mouse models and syngeneic cell transplant approaches use immunocompetent mice to study mechanisms driving immunotherapy response and resistance. Due to their rapid and reproducible nature, there has been an expanded interest in developing new syngeneic tools from established primary tumor models. However, there are few analyses directly comparing the immune profiles of primary models with their derived syngeneic counterparts. Here we report comprehensive immunophenotyping of primary tumors from two well-established sarcoma models and four syngeneic allografts derived from these models. We observed that cell lines derived from the same type of genetically engineered primary tumor form allografts with significantly different levels of immune infiltration and intratumoral immune cell composition. Most notable are the differences in the T cell compartment of the syngeneic models, including CD4+ T cell, CD8+ T cell, and regulatory T cell populations – each of which have well-documented roles in tumor response to immunotherapy. Our findings highlight the importance of thorough characterization of syngeneic models prior to their use in preclinical studies in order to maintain scientific rigor and to increase the translatability of findings from bench to bedside.
Trantrace: a reliable, traceable, and collaborative solution to streamline the translation of emerging biomedical resources
Authors: Su Min , Wang Zhaohong , Li Mengyu , Ye Weixing , Chen Peter , Huang Mo , He Zili , Xia Chaoran , Cui Jie , Liu Rui , Wang Congmao
Published: July 2020

Background

Precision medicine is gaining popularity in routine health care, which heavily relies on the interpretation of emerging biomedical databases and professional guidelines. Translation of those biomedical materials, that is crucial to deliver research discovery to health interventions in non-native English-speaking countries, remains a large amount of work for biomedical practitioners.

Results

We presented an application called Trantrace to facilitate the routine of large-scale long-running translation. Especially for the case that many people joined multiple translation projects, it has a rigorous task division and cooperation process: assignment, translation, review, release, and iteration. Trantrace empowers users to build own projects with different permissions, version control all the translation operation without specific skills, and further improve the translation efficiency through real-time task management tools.

Conclusions

By providing a working platform for collaborative translation and enabling long-time version correction, the Trantrace contributes towards the creation of a multilingual biomedical knowledge commons, which would be a valuable aid for personalized therapies. The source code is freely accessible athttps://github.com/sgi-drylab/trantrace.
iMDA-BN: Identification of miRNA-Disease Associations based on the Biological Network and Graph Embedding Algorithm
Authors: Zheng Kai , You Zhu-Hong , Wang Lei
Published: July 2020

Benefiting from advances in high-throughput experimental techniques, important regulatory roles of miRNAs, lncRNAs, and proteins, as well as biological property information, are gradually being complemented. As the key data support to promote biomedical research, domain knowledge such as intermolecular relationships that are increasingly revealed by molecular genome-wide analysis is often used to guide the discovery of potential associations. However, the method of performing network representation learning from the perspective of the global biological network is scarce. These methods cover a very limited type of molecular associations and are therefore not suitable for more comprehensive analysis of molecular network representation information. In this study, we propose a computational model based on the Biological network for predicting potential associations between miRNAs and diseases called iMDA-BN. The iMDA-BN has three significant advantages: I) It uses a new method to describe disease and miRNA characteristics which analyzes node representation information for disease and miRNA from the perspective of biological networks. II) It can predict unproven associations even if miRNAs and diseases do not appear in the biological network. III) Accurate description of miRNA characteristics from biological properties based on high-throughput sequence information. The iMDA-BN predictor achieves an AUC of 0.9145 and an accuracy of 84.49% on the miRNA-disease association baseline dataset, and it can also achieve an AUC of 0.8765 and an accuracy of 80.96% when predicting unknown diseases and miRNAs in the biological network. Compared to existing miRNA-disease association prediction methods, iMDA-BN has higher accuracy and the advantage of predicting unknown associations. In addition, 45, 49, and 49 of the top 50 miRNA-disease associations with the highest predicted scores were confirmed in the case studies, respectively.
Targeting the ubiquitin-proteasome system in a pancreatic cancer subtype with hyperactive MYC
Authors: Lankes K , Hassan Z , Doffo MJ , Schneeweis C , Lier S , Öllinger R , Rad R , Krämer OH , Keller U , Saur D , Reichert M. , Schneider G , Wirth M
Published: July 2020

Purpose

The myelocytomatosis oncogene (MYC) is an important driver in a subtype of pancreatic ductal adenocarcinoma (PDAC). However, MYC remains a challenging therapeutic target, therefore identifying druggable synthetic lethal interactions in MYC-active PDAC may lead to novel precise therapies.

Methods

Cluster analysis using direct MYC target genes was used to identify PDAC with active MYC. We profiled the transcriptome of established human cell lines, murine primary PDAC cell lines and also accessed public available repositories for transcriptomic profiling. Networks active in MYC hyperactive subtypes were analyzed by gene set enrichment analysis. An unbiased pharmacological drug screen with FDA-approved anti-cancer drugs was conducted to define MYC-associated vulnerabilities, which were validated by analysis of drug response repositories and genetic gain- and loss-of-function experiments.

Results

In an unbiased pharmacological drug screen with FDA-approved anti-cancer drugs we detected that the proteasome inhibitor bortezomib triggers a MYC-associated vulnerability. By integrating publicly available data sets we found the unfolded protein response as a signature connected to MYC. Furthermore, the increased sensitivity of MYC hyperactive PDACs to bortezomib was validated in genetically modified PDAC cells.

Conclusions

In sum, we provide evidence that perturbing the ubiquitin proteasome system might be an option to target MYC hyperactive PDAC cells and our data provide the rationale to further develop precise targeting of the ubiquitin-proteasome system as a subtype-specific therapeutic approach.
HYPERGLYCEMIA-INDUCED MIR-467 DRIVES TUMOR INFLAMMATION AND GROWTH IN BREAST CANCER
Authors: Gajeton Jasmine , Krukovets Irene , Muppala Santoshi , Verbovetskiy Dmitriy , Zhang Jessica , Stenina-Adognravi Olga
Published: July 2020

Tumor microenvironment contains the parenchyma, blood vessels, and infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs affect the developing tumor and drive cancer inflammation.

Hyperglycemic patients have a higher risk of developing breast cancer (BC). We have identified a novel miRNA-dependent pathway activated by hyperglycemia that promotes BC angiogenesis and inflammation supporting BC growth. miR-467 is upregulated in endothelial cells (EC), macrophages, BC cells, and in BC tumors. A target of miR-467, thrombospondin-1 (TSP-1), inhibits angiogenesis and promotes resolution of inflammation. Systemic injections of a miR-467 antagonist in mouse models of hyperglycemia resulted in decreased BC growth (P<.001). Tumors from hyperglycemic mice had a 2-fold increase in macrophage accumulation compared to normoglycemic controls (P<.001), and TAM infiltration was prevented by the miR-467 antagonist (P<.001). BC specimens from hyperglycemic patients had increased miR-467 levels, increased angiogenesis, decreased levels of TSP-1, and increased TAM infiltration in malignant breast tissue in hyperglycemic vs normoglycemic patients (2.17-fold,P=.002) and even in normal breast tissue from hyperglycemic patients (2.18-fold inc.,P=.04). In malignant BC tissue, miR-467 levels were upregulated 258-fold in hyperglycemic patients compared to normoglycemic patients (P<.001) and increased 56-fold in adjacent normal tissue (P=.008).

Our results suggest that miR-467 accelerates tumor growth by inducing angiogenesis and promoting the recruitment of TAMs to drive hyperglycemia-induced cancer inflammation.
The Small GTPase OsRac1 forms two distinct immune receptor complexes containing the PRR OsCERK1 and the NLR Pit
Authors: Akamatsu Akira , Fujiwara Masayuki , Hamada Satoshi , Wakabayashi Megumi , Yao Ai , Wang Qiong , Kosami Ken-ichi , Dang Thu Thi , Kaneko-Kawano Takako , Shimamoto Ko , Kawano Yoji
Published: July 2020

Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and Leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. In this study, using biochemical and bioimaging approaches, we reveal that OsRac1 formed two distinct receptor complexes with OsCERK1 and with Pit. Supporting this result, OsCERK1 and Pit utilized different transport systems for anchorage to the plasma membrane. Activation of OsCERK1 and Pit led to OsRac1 activation and, concomitantly, OsRac1 shifted from a small to a large protein complex fraction. We also found that the chaperone Hsp90 contributed to the proper transport of Pit to the plasma membrane and the immune induction of Pit. These findings illuminate how the PRR OsCERK1 and the NLR Pit orchestrate rice immunity through the small GTPase OsRac1.
Characterization of Bacterial Isolates in Vermicompost Produced from a Mixture of Cow dung, Straw, Neem leaf and Vegetable Wastes
Authors: Satpathy Jyotismita , Saha Mirkashim H. , Mishra Aditya S. , Mishra Sujit K.
Published: July 2020

Vermicomposting is a non-thermophilic biological oxidation process of composting where certain species of earthworm are used to enhance the process of conversion of organic waste to compost. Earthworm helps in influencing the growth of certain microbial species, and also improves the physical and chemical properties of the soil. The microbial population present in vermicompost play an important role in increasing the productivity of crop as well as maintain the structural stability of the soil. Different types of bacteria found in vermicompost and is depends on the environmental condition and the raw materials used in vermicomposting. Owing to this, a study was carried out to identify the bacteria exist in vermicompost produced from cow dungs, straw, neem leafs and vegetable wastes. The phenotypic studies such as colony morphology, microscopic studies, and biochemical characterization have identified eight bacterial species namelyActinomyces israelli, Azotobacter, Micrococus luteus, Bacillus cereus, Bacillus subtillis, Pseudomonas aeruginosa, Enterobacterin the vermicompost. All these bacteria were present in the gut ofEesenia Foetidaand found beneficial for the soil and crop plants.
Activation of prodynorphin neurons in the dorsomedial hypothalamus inhibits food intake and promotes positive valence
Authors: Imoto Daigo , Yamamoto Izumi , Matsunaga Hirokazu , Yonekura Toya , Lee Ming-Liang , Kato Kan X , Yamasaki Takeshi , Otsuguro Ken-ichi , Horiuchi Motohiro , Iijima Norifumi , Kimura Kazuhiro , Toda Chitoku
Published: July 2020

The regulation of food intake is one of the major research areas in the study of metabolic syndromes such as obesity. Gene targeting studies have clarified the roles of hypothalamic neurons in feeding behaviour. However, our understanding of neural function under physiological conditions is still limited. Immediate early genes, such as activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), are useful markers of neuronal activity. Here, we investigated the role of Arc/Arg3.1 gene-expressing neurons in the hypothalamus after refeeding using the targeted recombination in active populations method. We identified refeeding-responsive prodynorphin/cholecystokinin neurons in the dorsomedial hypothalamus that project to the paraventricular hypothalamic nucleus. Chemogenetic activation of these neurons decreased food intake and promoted positive valence. Our findings provide insight into the role of newly identified hedonic neurons in the process of feeding-induced satiety.
Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses
Authors: Kolmus Krzysztof , Erdenebat Purevsuren , Stewig Blair , Szymańska Ewelina , Goryca Krzysztof , Derezińska-Wołek Edyta , Szumera-Ciećkiewicz Anna , Brewińska-Olchowik Marta , Piwocka Katarzyna , Prochorec-Sobieszek Monika , Mikula Michał , Miączyńska Marta
Published: July 2020

Molecular details of how endocytosis contributes to oncogenesis remain elusive. Ourin silicoanalysis of colorectal cancer (CRC) patients revealed stage-dependent alterations in the expression of 113 endocytosis-related genes. Among them transcription of the Endosomal Sorting Complex Required for Transport (ESCRT)-I componentVPS37Bwas decreased in the advanced stages of CRC. Expression of other ESCRT-I core subunits remained unchanged in the investigated dataset. We analyzed an independent cohort of CRC patients showing also reducedVPS37AmRNA and protein abundance. Transcriptomic profiling of CRC cells revealed non-redundant functions of Vps37 proteins. Knockdown ofVPS37AandVPS37Btriggered p21-mediated inhibition of cell proliferation and sterile inflammatory response driven by the Nuclear Factor (NF)-κB transcription factor and associated with mitogen-activated protein kinase signaling. Co-silencing ofVPS37Cfurther potentiated activation of these independently induced processes. The type and magnitude of transcriptional alterations correlated with the differential ESCRT-I stability upon individual and concurrent Vps37 depletion. Our study provides novel insights into cancer cell biology by describing cellular stress responses that are associated with ESCRT-I destabilization, which might occur in CRC patients.

SUMMARY STATEMENT

Endosomal Sorting Complex Required for Transport (ESCRT)-I destabilization upon concurrent depletion of Vps37 proteins is linked to the activation of sterile inflammatory response and cell growth inhibition.
The impact of allometry on vomer shape and its implications for the taxonomy and cranial kinesis of crown-group birds
Authors: Plateau Olivia , Foth Christian
Published: July 2020

Crown birds are subdivided into two main groups, Palaeognathae and Neognathae, that can be distinguished, among other means, by the organization of the bones in their pterygoidpalatine complex (PPC). Shape variation of the vomer, which is the most anterior part of the PPC, was recently analysed with help of geometric morphometrics to discover morphological differences between palaeognath and neognath birds. Based on this study, the vomer was identified as sufficient to distinguish the two main groups (and even some inclusive neognath groups) and their cranial kinetic system. As there are notable size differences between the skulls of Palaeognathae and Neognathae, we here investigate the impact of allometry on vomeral shape and its implication for taxonomic classification by re-analysing the data of the previous study. Different types of multivariate statistical analyses reveal that taxonomic identification based on vomeral shape is strongly impaired by allometry, as the error of correct identification is high when shape data is corrected for size. This finding is evidenced by a great overlap between palaeognath and neognath subclades in morphospace. Correct taxonomic identification is further impeded by the convergent presence of a flattened vomeral morphotype in multiple neognath subclades. As the evolution of cranial kinesis has been linked to vomeral shape in the original study, the correlation between shape and size of the vomer across different bird groups found in the present study questions this conclusion. In fact, cranial kinesis in crown birds results from the loss of the jugal-postorbital bar in the temporal region and ectopterygoid in the PPC and the combination of a mobilized quadratezygomatic arch complex and a flexible PPC. Therefore, we can conclude that vomer shape itself is not a suitable proxy for exploring the evolution of cranial kinesis in crown birds and their ancestors. In contrast, the evolution of cranial kinesis needs to be viewed in context of the braincase, quadrate-zygomatic arch and the whole pterygoid-palatine complex.
Potential anti-adipogenic activity ofCalligonum comosumcuminaldehyde on mouse 3T3-preadipocytes
Authors: Mohammad Mohammad G , El-Serafi Ahmed , Madkour Mohamed I. , Alhabshi Abeer , Wadea Ansar , Jabal Rola Abu , Divyasree P , Soliman Sameh S.M.
Published: July 2020

Obesity is a medical condition associated with serious medical and psycho-social consequences and an augmented body fat mass. Several compounds were suggested to counteract obesity and fat accumulation with variable degrees of success. Searching for a safe and effective anti-adipogenic substance, we found that cuminaldehyde-rich essential oil extracted fromCalligonum comosumpotentially mediate activities. The results showed thatC. comosumessential oil and its major component cuminaldehyde, selectively caused significant reduction in the viability of 3T3-L1 cells when compared to fibroblasts. Furthermore, cuminaldehyde caused significant reduction in the lipid content, glucose uptake and levels of both triglycerides and cholesterol in adipocytes. Moreover, the formation of 3D-adipocyte pellets in the presence of cuminaldeyde was affected. Adipocytes matured in the presence of cuminaldehyde have significant reduction in the expression of adipocyte-specific transcripts, CAAT-enhancer binding protein alpha (CEBPa) and Peroxisome proliferator-activated receptor gamma (PPARg). Taken together, these results demonstrate a potential inhibitory role of cuminaldehyde extracted fromC. comosumoil on lipid accumulation. Consequently, cuminaldeyde can be considered as a new potential anti-adipogenic agent for prevention and treatment of obesity.
How far are we in the rapid prediction of drug resistance caused by kinase mutations?
Authors: Erguven Mehmet , Karakulak Tülay , Diril M. Kasim , Karaca Ezgi
Published: July 2020

Protein kinases regulate various cell signaling events in a diverse range of species through phosphorylation. The phosphorylation occurs upon transferring the terminal phosphate of an ATP molecule to a designated target residue. Due to the central role of protein kinases in proliferative pathways, point mutations occurring within or in the vicinity of ATP binding pocket can render the enzyme overactive, leading to cancer. Combatting such mutation-induced effects with the available drugs has been a challenge, since these mutations usually happen to be drug resistant. Therefore, the functional study of naturally and/or artificially occurring kinase mutations have been at the center of attention in diverse biology-related disciplines. Unfortunately, rapid experimental exploration of the impact of such mutations remains to be a challenge due to technical and economical limitations. Therefore, the availability of kinase-ligand binding affinity prediction tools is of great importance. Within this context, we have tested six state-of-the-art web-based affinity predictors (DSX-ONLINE, KDEEP, HADDOCK2.2, PDBePISA, Pose&Rank, and PRODIGY-LIG) in assessing the impact of kinase mutations with their ligand interactions. This assessment is performed on our structure-based protein kinase mutation benchmark, BINDKIN. BINDKIN contains 23 wild type-mutant pairs of kinase-small molecule complexes, together with their corresponding binding affinity data (in the form of IC50, Kd, and Ki). The web-server performances over BINDKIN show that the raw server predictions fail to produce good correlations with the experimental data. However, when we start looking in to the direction of change (whether a mutation improves/worsens the binding), we observe that over Kidata, DSX-ONLINE achieves a Pearson’s R correlation coefficient of 0.97. When we used homology models instead of crystal structures, this correlation drops to 0.45. These results highlight that there is still room to improve the available web-based predictors to estimate the impact of protein kinase point mutations. We present our BINDKIN benchmark and all the related results online for the sake of aiding such improvement efforts. Our files can be reached athttps://github.com/CSB-KaracaLab/BINDKIN
Azetidin-2-ones: structures of antimitotic compounds based on the 1-(3,4,5-trimethoxyphenyl)azetidin-2-one core
Authors: Twamley Brendan , O'Boyle Niamh M. , Meegan Mary J.
Published: July 2020

A series of related substituted 1-(3,4,5-trimethoxyphenyl)azetidin-2-ones have been characterized: 3-(4-fluorophenyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C25H24FNO5 (1), 3-(furan-2-yl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C23H23NO6 (2), 4-(4-methoxyphenyl)-3-(naphthalen-1-yl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C29H27NO5 (3), 3-(3,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C27H29NO7 (4) and 4,4-bis(4-methoxyphenyl)-3-phenyl-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C32H31NO6 (5). All of the compounds are racemic. The lactam and 3,4,5-trimethoxyphenyl rings are approximately co-planar and the orientation of the lactam and the 4-methoxyphenyl substituent is approximately orthogonal. The chiral centres, although eclipsed by geometry, have torsion angles ranging from −7.27 to 13.08° for the 3 position, and −8.69 to 13.76° for the 4 position of the β-lactam. The structures display intramolecular C—H...O bonding between the 3,4,5-trimethoxyphenyl ring and the lactam ketone. Further C—H...O interactions are observed and form either an opposing methoxy `buckle' to join two molecules together or a cyclic dimer.
The crystal structures of salts of N-(4-fluorophenyl)piperazine with four aromatic carboxylic acids and with picric acid
Authors: Harish Chinthal Chayanna , Yathirajan Hemmige S. , Kavitha Channappa N. , Foro Sabine , Glidewell Christopher
Published: July 2020

The structures are reported for five salts formed by reactions between N-(4-fluorophenyl)piperazine and aromatic acids. In 4-(4-fluorophenyl)piperazin-1-ium 2-fluorobenzoate monohydrate, C10H14FN2
+·C7H4FO2
−·H2O, (I), the components are linked by a combination of N—H...O and O—H...O hydrogen bonds to form a chain of alternating R
4
6(12) and R
6
6(16) rings. The ionic components of 4-(4-fluorophenyl)piperazin-1-ium 2-bromobenzoate 0.353-hydrate, C10H14FN2
+·C7H4BrO2
−·0.353H2O, (II), are linked by N—H...O hydrogen bonds to form a centrosymmetric four-ion aggregate containing an R
4
4(12) motif, and these aggregates are linked into a molecular ladder by a single C—H...π(arene) hydrogen bond. 4-(4-Fluorophenyl)piperazin-1-ium 2-iodobenzoate, C10H14FN2
+·C7H4IO2
−, (III), crystallizes with Z′ = 2 in space group P\overline{1}: the four independent ions are linked by N—H...O hydrogen bonds to form a non-centrosymmetric aggregate again containing an R
4
4(12) motif, and aggregates of this type are linked into a ribbon by a combination of C—H...O and C—H...π(arene) hydrogen bonds. The anion in 4-(4-fluorophenyl)piperazin-1-ium 2,4,6-trinitrophenolate, C10H14FN2
+·C6H2N3O7
−, (IV), shows clear evidence of extensive electronic delocalization from the phenolate O atom into the adjacent ring. The ions are linked by a combination of two-centre N—H...O and three-centre N—H...(O)2 hydrogen bonds to form centrosymmetric four-ion aggregates containing three types of ring. The ions in 4-(4-fluorophenyl)piperazin-1-ium 3,5-dinitrobenzoate, C10H14FN2
+·C7H3N2O6
−, (V), are again linked by N—H...O hydrogen bonds to form centrosymmetric R
4
4(12) aggregates, which are themselves linked by a C—H...π(arene) hydrogen bond to form sheets, the stacking of which leads to the formation of narrow channels, containing disordered and/or mobile solvent entities. Comparisons are made with some related structures.
Crystal structure, Hirshfeld surface analysis and DFT studies of 2-[(2-hydroxy-5-methylbenzylidene)amino]benzonitrile
Authors: Faizi Md. Serajul Haque , Cinar Emine Berrin , Aydin Alev Sema , Agar Erbil , Dege Necmi , Mashrai Ashraf
Published: July 2020

The title compound, C15H12N2O, was synthesized by condensation reaction of 2-hydroxy-5-methylbenzaldehyde and 2-aminobenzonitrile, and crystallizes in the orthorhombic space group Pbca. The phenol ring is inclined to the benzonitrile ring by 25.65 (3)°. The configuration about the C=N bond is E, stabilized by a strong intramolecular O—H...N hydrogen bond that forms an S(6) ring motif. In the crystal, C—H...O and C—H...N interactions lead to the formation of sheets perpendicular to the a axis. C—H...π interactions, forming polymeric chains along the a-axis direction, connect these sheets into a three-dimensional network. A Hirshfeld surface analysis indicates that the most important contributions for the packing arrangement are from H...H and C...H/H...C interactions. The density functional theory (DFT) optimized structure at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined molecular structure and the HOMO–LUMO energy gap is given.
Autism identification across ethnic groups: a narrative review
Authors: Tromans Samuel , Chester Verity , Gemegah Eli , Roberts Kristian , Morgan Zoe , Yao Guiqing Lily , Brugha Traolach
Published: July 2020

Purpose

The purpose of the paper is to review autism identification across different ethnic groups. Diagnosis of autism may be missed or delayed in certain ethnic groups, leading to such groups being underserved relative to their needs. This can result in members of such groups being effectively denied essential avenues of support that can substantially improve the quality of life of autistic persons as well as those whom care for them.

Design/methodology/approach

A literature search for articles reporting autism identification across ethnic groups was undertaken. Data are compared, with a special focus on possible explanations for any inter-group variation.

Findings

Autism identification appears to be generally lower in minority ethnic groups relative to the majority population. Individuals presenting with autism from minority groups appear to have more severe forms of the condition.

Originality/value

There are a multitude of potential explanations for inter-ethnicity variation in autism identification, including health care-related factors, broader environmental influences, cultural factors and possible biological differences. Implications for clinical practice and public health include a need to look at means of ensuring equitable access to relevant autism diagnostic and support services across ethnic groups. Further work is required to better understand the belief systems that operate within specific ethnic groups, how this may potentially impact upon autism identification and measures to address the concerns of such groups.
Expressivity in children with autism and Williams syndrome
Authors: Lai Philip To
Published: July 2020

Purpose

The purpose of this study is to investigate the social and affective aspects of communication in school-age children with HFA and school-age children with WS using a micro-analytic approach. Social communication is important for success at home, school, work and in the community. Lacking the ability to effectively process and convey information can lead to deficits in social communication. Individuals with high functioning autism (HFA) and individuals with Williams syndrome (WS) often have significant impairments in social communication that impact their relationships with others. Currently, little is known about how school-age children use and integrate verbal and non-verbal behaviors in the context of a social interaction.

Design/methodology/approach

A micro-analytic coding scheme was devised to reveal which channels children use to convey information. Language, eye gaze behaviors and facial expressions of the child were coded during this dyadic social interaction. These behaviors were coded throughout the entire interview, as well as when the child was the speaker and when the child was the listener.

Findings

Language results continue to pose problems for the HFA and WS groups compared to their typically developing (TD) peers. For non-verbal communicative behaviors, a qualitative difference in the use of eye gaze was found between the HFA and WS groups. For facial expression, the WS and TD groups produced more facial expressions than the HFA group.

Research limitations/implications

No differences were observed in the HFA group when playing different roles in a conversation, suggesting they are not as sensitive to the social rules of a conversation as their peers. Insights from this study add knowledge toward understanding social-communicative development in school-age children.

Originality/value

In this study, two non-verbal behaviors will be assessed in multiple contexts: the entire biographical interview, when the child is the speaker and when the child is the listener. These social and expressive measures give an indication of how expressive school-age children are and provide information on their attention, affective state and communication skills when conversing with an adult. Insights from this study will add knowledge toward understanding social-communicative development in school-age children.
Examining team performance: the role of psychological contracts and engagement among co-workers
Authors: Schreuder Frits , Schalk René , Batistič Sasa
Published: July 2020

Purpose

The aim of this study was to investigate the role of shared psychological contract beliefs between colleagues in a work team, in team in-role performance and extra-role behaviours.

Design/methodology/approach

Employees and team managers of 113 work teams answered questions about their working environment and relationships with experiences and perceptions. The data were used in CFA and structural modelling.

Findings

The results indicated that evaluations of co-worker psychological contracts in work teams are significantly associated with team in-role performance and extra-role behaviours through work engagement.

Practical implications

Employees with perceived contract fulfilment not only contribute more to their team but also change their expectations of what a team should offer. Managers should be informed that these new and enhanced expectations have repercussions for existing HRM practices.

Originality/value

Laulié and Tekleab (2016) have suggested that perceptions of psychological contract fulfilment shared by team members may act as a motivational driver for team performance, team attitudes and behaviours. This study is one of the first applications of this proposition in a mediation model and empirically tested for non-hierarchical co-worker relationships.
Should the cost of capital, used in connection with goodwill impairment testing, vary across countries?
Authors: Salameh Elie
Published: July 2020

Learning outcomes

Through the discussion of this case, students will have better understanding of the conceptual stakes related to accounting treatment for goodwill and factors determining goodwill impairment testing. The case also discusses the determination of the cost of capital and the impact of taking into account certain factors related to country risk for determining the discount rate in an international framework.

Case overview/synopsis

Greenfields Company continues to expand through acquisitions in emerging markets. The company aims to overcome the complexity of measuring goodwill subsequent to the initial recognition. The case was written to illustrate challenges of estimating the appropriate discount rate to be used in the goodwill impairment testing as investments in emerging countries give rise to many discount rate measurement problems such as the availability of statistical data and the risk assessment to be considered.

Complexity academic level

The case can be used at undergraduate or postgraduate level and it requires fundamental knowledge in accounting and corporate finance.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 1: Accounting and Finance.