bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetic population structureand drug resistanceof Mycobacterium tuberculosis complex in the Volta Region of Ghana
Authors: Ameke Selassie , Asare Prince , Aboagye Sammy Yaw , Otchere Isaac Darko , Osei-Wusu Stephen , Yeboah-Manu Dorothy , Asante-Poku Adwoa 
Published: August 2020

AbstractContextAvailable molecular epidemiological data from recent studies suggest significant genetic variation between the different phylogenetic lineages ofMycobacterium tuberculosiscomplex (MTBC) and the MTBC lineages might have adapted to different human populationsAimThis study sought to determine the phylogenetic population structure of clinical MTBC isolates from the Volta Region of Ghana.MethodsThe MTBC isolates obtained from collected sputum samples were characterized by standard methods. Non-tuberculous mycobacterial isolates were characterized by amplification of the heat shock protein 65 (hsp65) gene and sequencing. The drug susceptibility profiles of the MTBCs determined using GenoType MTBDRplusResultsOne hundred and seventeen (117, 93.6%) out of 125 mycobacterial positive isolates were characterized as members of the MTBC of whichM. tuberculosissensu stricto (MTBss) andM. africanum(Maf) were respectively 94 (80.3%) and 23 (19.7%). In all, 39 distinct spoligotype patterns were obtained; 26 for MTBss and 13 for Maf lineages. Spoligotyping identified 89 (76.04 %) Lineage 4, 16 (13.7 %) Lineage 5, 7 (6.0%) Lineage 6, 3 (2.6%) Lineage 2, 1(0.9%) Lineage 3 and 1 (0.9%) Lineage 1. Among the Lineage 4 isolates, 62/89 (69.7%) belonged to Cameroon sub-lineage, 13 (14.6%) Ghana, 8 (9.0%) Haarlem, 2 (2.2%) LAM, 1 (1.1%) Uganda I, 1 (1.1%) X and the remaining two were orphan. Significant localization of Maf was found within the Ho municipality (n=13, 29.5%) compared to the more cosmopolitan Ketu-South/Aflao (n=3, 8.3%) (p-value= 0.017). Eight (8) non-tuberculous mycobacteria were characterized asM. abscessus(7) andM. fortuitum(1)ConclusionWe confirmed the importance ofM. africanumlineages as a cause of TB in the Volta region of Ghana.Key MessageThe phylogenetic population structure obtained agrees with previously described prevalence ofM. tuberculosiscomplex phylogenetic lineages from other regions of Ghana. It also confirms the stable prevalence ofM.africanum as an important human TB causing pathogen in Ghana.
Hypoxia-induced miR-92a regulates p53 signalling pathway and apoptosis by targeting calcium-sensing receptor in Genetically Improved Farmed Tilapia (Oreochromis niloticus)
Authors: Qiang Jun , He Jie , Tao Yi-Fan , Bao Jin-Wen , Zhu Jun-Hao , Xu Pao 
Published: August 2020

AbstractmiR-92a miRNAs are immune molecules that regulate apoptosis (programmed cell death) during the immune response. Apoptosis helps to maintain the dynamic balance in tissues of fish under hypoxia stress. The aim of this study was to explore the role and potential mechanisms of miR-92a in the liver of tilapia under hypoxia stress. We first confirmed thatCaSR(encoding a calcium-sensing receptor) is a target gene of miR-92a in genetically improved farmed tilapia (GIFT) using luciferase reporter gene assays. In GIFT under hypoxia stress, miR-92a was up-regulated andCaSRwas down-regulated in a time-dependent manner. Knocked-downCaSRexpression led to inhibited expression ofp53,TP53INP1andcaspase-3/8, reduced the proportion of apoptotic hepatocytes, and decreased the activity of calcium ions induced by hypoxia in hepatocytes. GIFT injected in the tail vein with an miR-92a agomir showed up-regulation of miR-92a and down-regulation ofCaSR,p53,TP53INP1, andcaspase-3/8genes in the liver, resulting in lower serum alanine aminotransferase and aspartate aminotransferase activities under hypoxia stress. These findings suggest that stimulation of miR-92a interferes with hypoxia-induced apoptosis in hepatocytes of GIFT by targetingCaSR, thereby alleviating liver damage. These results provide new insights into the adaptation mechanisms of GIFT to hypoxia stress.
Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma
Authors: Muhammad Sakri Muhammad Shahidan , Abdul Rahman Wan Faiziah Wan , Al-Astani Tengku Din Tengku Ahmad Damitri , Jaafar Hasnan , Gopalan Vinod 
Published: August 2020

AbstractAngiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1, and Flt-4, have been found to play an essential role in regulating angiogenesis. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4, and rapamycin+platelet factor-4. The tumors were subsequently subjected to immunohistological protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semi-quantitative scoring method, while the mRNA expression levels were analyzed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4 treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent anti-angiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.
A comparison of several media types and basic techniques used to assess outdoor airborne fungi in Melbourne, Australia
Authors: Black Wesley D 
Published: August 2020

AbstractDespite the recent increase in interest in indoor air quality regarding mould, there is no single widely accepted standard media for the detection of airborne fungi, nor verification of many commonly used techniques. Commonly used media including malt-extract agar (MEA), Sabouraud dextrose agar (Sab, SDA, SabCG), potato dextrose agar (PDA) with and without antibiotics chloramphenicol & gentamycin (CG) were compared for their suitability in detecting a range of common airborne fungi by collecting 150 L outdoor air on a number of different days and seasons via an Anderson 400-hole sampler in suburban Melbourne, Australia. There was relatively little variation in mean numbers of colony forming units (CFU) and types of fungi recovered between MEA, PDA, SabCG media groups relative to variation within each group. There was a significant difference between SabCG, Dichloran-18% glycerol (DG18) and V8® Original juice agar media, however. Antibiotics reliably prevented the growth of bacteria that typically interfered with the growth and appearance of fungal colonies. There was no significant evidence for a growth enhancing factor from potato, mineral supplements or various vegetable juices. Differing glucose concentrations had modest effects, showing a vague ideal at 2%-4% with peptone. Sanitisation/sterilisation of the aluminium Andersen 400-hole sampler top-plate by flame is possible, but not strictly required nor advisable. The use of SabCG as a standard medium was generally supported.
Parental genome unification is highly erroneous in mammalian embryos
Authors: Cavazza Tommaso , Politi Antonio Z , Aldag Patrick , Baker Clara , Elder Kay , Blayney Martyn , Lucas-Hahn Andrea , Niemann Heiner , Schuh Melina 
Published: August 2020

AbstractThe vast majority of human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but the origin of this remains elusive. Using bovine embryos as a model for human embryos, we identify an error-prone mechanism of parental genome unification which often results in aneuploidy. Surprisingly, genome unification initiates hours before breakdown of the two pronuclei that encapsulate the parental genomes. While still within intact pronuclei, the parental genomes polarize towards each other, in a process driven by centrosomes, dynein, and microtubules. The maternal and paternal chromosomes eventually cluster at the pronuclear interface, in direct proximity to each other. Parental genome clustering often fails however, leading to massive chromosome segregation errors, incompatible with healthy embryo development. Nucleoli, which associate with chromatin, also cluster at the pronuclear interface in human zygotes. Defects in nucleolar clustering correlate with failure in human embryo development, suggesting a conserved mechanism.
Hydroxylation of antitubercular drug candidate, SQ109, by mycobacterial cytochrome P450
Authors: Bukhdruker Sergey , Varaksa Tatsiana , Grabovec Irina , Marin Egor , Shabunya Polina , Kadukova Maria , Grudinin Sergei , Kavaleuski Anton , Gusach Anastasiia , Gilep Andrei , Borshchevskiy Valentin , Strushkevich Natallia 
Published: August 2020

AbstractSpreading of the multidrug-resistant (MDR) strains of the deadliest pathogenMycobacterium tuberculosis(Mtb) generates the need for new effective drugs. SQ109 showed activity against resistant Mtb and already advanced to Phase II/III clinical trials. Fast SQ109 degradation is attributed to the human liver Cytochrome P450s (CYPs). However, no information is available about interactions of the drug with Mtb CYPs. Here, we show that Mtb CYP124, previously assigned as a methyl-branched lipid monooxygenase, binds and hydroxylates SQ109in vitro. A 1.25 Å-resolution crystal structure of the CYP124–SQ109 complex unambiguously shows two conformations of the drug, both positioned for hydroxylation of the ω-methyl group in the trans position. The hydroxylated SQ109 presumably forms stabilizing H-bonds with its target, the Mycobacterial membrane protein Large 3 (MmpL3). We anticipate that Mtb CYPs could function as analogs of drug-metabolizing human CYPs affecting pharmacokinetics and pharmacodynamics of antitubercular (anti-TB) drugs.
Developing and Deploying a Scalable Computing Platform to Support MOOC Education in Clinical Data Science
Authors: Mayer David , Russell Seth , Wilson Melissa P. , Kahn Michael G. , Wiley Laura K. 
Published: August 2020

AbstractOne of the challenges of teaching applied data science courses is managing individual students’ local computing environment. This is especially challenging when teaching massively open online courses (MOOCs) where students come from across the globe and have a variety of access to and types of computing systems. There are additional challenges with using sensitive health information for clinical data science education. Here we describe the development and performance of a computing platform developed to support a series of MOOCs in clinical data science. This platform was designed to restrict and log all access to health datasets while also being scalable, accessible, secure, privacy preserving, and easy to access. Over the 19 months the platform has been live it has supported the computation of more than 2300 students from 101 countries.
Draft Genome Sequences of Nine Japanese Strains of the Kiwifruit Bacterial Canker Pathogen,Pseudomonas syringaepv. actinidiae Biovar 3
Authors: Fujikawa Takashi , Sawada Hiroyuki 
Published: August 2020

AbstractPseudomonas syringaepv. actinidiae is the pathogen that causes kiwifruit bacterial canker and is categorized into several groups (biovars). In Japan, biovar 3, known as the pandemic group, was first discovered in 2014. Here, we sequenced the genomes of nine Japanese biovar 3 strains.
A glycoengineered antigen exploiting a conserved proteinO-glycosylation pathway in theBurkholderiagenus for diagnosis of glanders infections
Authors: Wang Guanbo , Glaser Lena , Scott Nichollas E. , Mohamed Yasmine Fathy , Ingram Rebecca , Laroucau Karine , Valvano Miguel A. 
Published: August 2020

ABSTRACTWe recently described a proteinO-glycosylation pathway conserved in all species of theBurkholderiagenus that results in synthesis and incorporation of a trisaccharide glycan to membrane-exported proteins. Here, we exploited this system to construct and evaluate a diagnostic tool for glanders.Burkholderia mallei, the causative agent of glanders, is a highly infectious and fatal zoonotic pathogen that mainly infects horses, mules, donkeys and occasionally humans. A highly sensitive and specific diagnostic tool is crucial for the control, elimination and eradication ofB. malleiinfections. We constructed plasmids carrying synthetic genes encoding a modified, previously unannotatedBurkholderiaglycoprotein containing three glycosylation sequons fused to the cholera toxin B-subunit. The resulting proteins were glycosylated in theB. cenocepaciaK56-2 parental strain, but not in glycosylation-deficient mutants, as determined by SDS-PAGE and fluorescent lectin blots. One of these glycoproteins was used as an antigen in ELISA and western blots to screen a panel of serum samples collected from glanders-infected and healthy horses previously investigated by complement fixation test and indirect ELISA based on a semi-purified fraction ofB. mallei. We show that ELISA and western blot assays based on our glycoprotein antigen provide 100 % specificity, with a sensitivity greater than 88%. The glycoprotein antigen was recognized by serum samples collected from patients infected withB. pseudomallei, B. mallei, B. multivoransandB. cenocepacia. Our results indicate that proteinO-glycosylation inBurkholderiacan be exploited as a biomarker for diagnosis ofBurkholderia-associated infections.IMPORTANCEGlanders is a severe zoonotic disease caused by the Gram-negative bacteriumBurkholderia mallei, which affects horses, mules and donkeys, as well as humans.B. malleiis also considered a category B biothreat agent. Due to insufficient pathognomonic symptoms in the early stages of glanders, diagnosis can be difficult. Complement fixation is the most accurate and reliable serological test prescribed by the World Organization for Animal Health; however, this test has a considerable number of false-positive results. We have recently described a conserved proteinO-glycosylation pathway present in all species of theBurkholderiagenus; we also demonstrated thatBurkholderia-infected humans develop anti-glycan antibodies. Here, we exploited this system to construct and evaluate a synthetic glycoengineered protein antigen as a diagnostic tool for glanders. Our results show 100 % specificity in the detection of antibodies from infected horses, indicating that proteinO-glycosylation inBurkholderiacan be exploited as a biomarker for diagnosis ofBurkholderia-associated infections.
Functional correlation of H3K9me2 and nuclear compartment formation
Authors: Fukuda Kei , Shimura Chikako , Miura Hisashi , Tanigawa Akie , Suzuki Takehiro , Dohmae Naoshi , Hiratani Ichiro , Shinkai Yoichi 
Published: August 2020

AbstractBackgroundHistone H3 lysine 9 dimethylation (H3K9me2) is a highly conserved silencing epigenetic mark. Chromatin marked with H3K9me2 forms large domains in mammalian cells and correlates well with lamina-associated domains and the B compartment. However, the role of H3K9me2 in 3-dimensional (3D) genome organization remains unclear.ResultsWe investigated the genome-wide H3K9me2 distribution, the transcriptome and 3D genome organization in mouse embryonic stem cells (mESCs) upon the inhibition or depletion of H3K9 methyltransferases (MTases) G9a/GLP, SETDB1, and SUV39H1/2. We found that H3K9me2 is regulated by these five MTases; however, H3K9me2 and transcription in the A and B compartments were largely regulated by different sets of the MTases: H3K9me2 in the A compartments were mainly regulated by G9a/GLP and SETDB1, while H3K9me2 in the B compartments were regulated by all five H3K9 MTases. Furthermore, decreased H3K9me2 correlated with the changes to the more active compartmental state that accompanied transcriptional activation.ConclusionOur data showed that H3K9me2 domain formation is functionally linked to 3D genome organization.
The Steinhoff signals: The role of responsible investing for asset managers
Authors: Haasbroek Hendrik Jacobus , Bick Geoff , Giamporcaro Stephanie 
Published: August 2020

Subject area of the teaching case:
The case can be used in the subject areas of finance and in particular investments, corporate governance, ESG, or responsible investments. It is suitable for students from all financial backgrounds, from a novice in the financial markets to an expert in finance. It is, however, expected that the class should have a sound fundamental grounding in financial analysis and valuations. The purpose of this case is to prepare students for future investments they would make in whatever capacity – whether in private or listed companies – and to prepare them for future roles on boards of directors. The examples of real-life events in this case study are used to prepare students for future similar situations in which they might find themselves.

Student level:
This teaching case is aimed at postgraduate students pursuing an MBA or a specialist Masters in a finance programme. This case can be used as a master class in corporate governance, investments, or responsible investments. This case is also suited for an executive education class in management. It is particularly relevant to a module that focusses on investments, corporate governance, ESG, or responsible investments.

Brief overview of the teaching case:
The case study chronicles meetings held on 8 November 2017 at a fictional South African asset manager, Active Investment Management (AIM). These meetings discuss the firm's investment in JSE-listed Steinhoff International Holdings. The case deals with the questions that active fund managers need to address when balancing financial analysis; environmental, social, and governance (ESG) analysis; portfolio management; and the need to comply with their fiduciary duty to clients. It also looks at the need for responsible investing in decision-making.

Expected learning outcomes:

The understanding of the assessment around the complexities of asset management when it comes to responsible investment.
To determine why institutional investors should apply responsible investment principles when making investment decisions.
An understanding of the evaluation of the unique roles of the three pillars of corporate governance, namely asset managers, auditors, and the board of directors.
The ability to assess how to integrate financial analysis and ESG principles in making investment recommendations.
Group foraging in carnivorous plants: Carnivorous plant Drosera makinoi (Droseraceae) is more effective at trapping larger prey in large groups
Authors: Tagawa Kazuki , Watanabe Mikio 
Published: August 2020

AbstractSome predatory animals, represented by large carnivores, forage in groups and benefit from this behavior. We tested the hypothesis that carnivorous plants also benefit from group foraging to improve the efficiency of trapping large prey using Drosera makinoi (Droseraceae). As a result of our field observations, it was found that larger neighboring D. makinoi density yields a greater number of large preys (≥3 mm) and total prey biomass per plant. Results showed that a total of 43.4% of the events to trap large prey was achieved by two trap leaves belonging to two neighboring D. makinoi plants. Our results proved that group foraging in D. makinoi enables them to trap large prey.
On the “merger paradox” in price competition with asymmetric product differentiation
Authors: Toshimitsu Tsuyoshi , Nakajima Tetsuya 
Published: August 2020

AbstractBy assuming asymmetric product differentiation, we consider the “merger paradox” in price competition (or the incentive to collude in prices). We investigate whether the emergence of the merger paradox depends on the degree of product differentiation between firms. In particular, unlike Deneckere and Davidson (1985), we demonstrate that if the degree of product differentiation between the insider and outsider is sufficiently small, then they are strategic substitutes, and thus, the merger paradox arises in price competition.
Look back at text or rely on memory? Efficacy of reading comprehension strategies in good and poor oral comprehenders
Authors: Tobia Valentina , Bonifacci Paola 
Published: August 2020

BackgroundReading comprehension is a multifactorial process, but one of its features has been relatively under‐investigated: it is the strategy used when answering reading comprehension questions. In order to find the correct answer, children can either respond to questions about a text relying on their text memory or look back at the written text. This study analyses (i) which strategy, memory or look‐back is more frequently adopted in primary school children according to grade level and type of text (expository vs narrative) and (ii) the preferred (most frequently used) and more efficient (higher number of correct responses) strategy for poor oral comprehenders. Poor oral comprehenders were selected for having adequate nonword decoding skills but impaired oral comprehension, compared with good oral comprehenders.MethodsThe total sample comprised 1,417 primary school children. A standardised test assessing reading and comprehension of oral and written language was administered.ResultsIn the comparison among children attending different grades, older children showed a more frequent use of the look‐back strategy for the expository text, whereas no age‐related difference emerged for the narrative text. Poor oral comprehenders (n = 88) showed a different pattern, compared with matched good oral comprehenders (n = 88), for both preference and efficiency of strategies. Despite having a globally poorer performance in reading comprehension, poor oral comprehenders were more accurate than good oral comprehenders when using the look‐back strategy.ConclusionsThe complex pattern of results obtained reinforces the idea that intervention strategies should be personalised based on individual characteristics and specific for the type of task and text.
‘It's Only Leftist Women Who Talk that Damn Nonsense About Women Being at a Disadvantage’: Eugenia Charles's Gender Politics in Dominica
Authors: Umoren Imaobong 
Published: August 2020

ABSTRACTBorn in 1919 in Dominica and educated in Grenada, Canada and Britain, Eugenia Charles became the islands first female barrister, head of a political party and in 1980, Prime Minister. With political views on the right of the spectrum, her close alliances and friendships with Margaret Thatcher and Ronald Reagan as well as her own defiant personality, Charles gained the title of ‘Iron Lady of the Caribbean’. This moniker, however, obscures more than it reveals, especially when it relates to Charles's gender politics. This article examines her speeches, interviews and policies and argues that a politics of contradiction and ambivalence characterised Charles's gender politics. This ambivalence partly explains the resilience of andocentric masculinist ideologies present in Caribbean political structures. Moreover, it demonstrates the continuity of ‘first‐wave’ Caribbean feminism in the late twentieth century and the pragmatism of women in politics.