bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies
Authors: Peng Guangdun , Tam Patrick P. L. , Jing Naihe 
Published: August 2017

Abstract
Establishment of progenitor cell populations and lineage diversity during embryogenesis and the differentiation of pluripotent stem cells is a fascinating and intricate biological process. Conceptually, an understanding of this developmental process provides a framework to integrate stem-cell pluripotency, cell competence and differentiating potential with the activity of extrinsic and intrinsic molecular determinants. The recent advent of enabling technologies of high-resolution transcriptome analysis at the cellular, population and spatial levels proffers the capability of gaining deeper insights into the attributes of the gene regulatory network and molecular signaling in lineage specification and differentiation. In this review, we provide a snapshot of the emerging enabling genomic technologies that contribute to the study of development and stem-cell biology.
Nutritional and smoking advice recalled by patients attending a UK age-related macular degeneration clinic
Authors: Bott Deborah , Huntjens Byki , Binns Alison 
Published: August 2017

Abstract

Background
Age-related macular degeneration (AMD) is responsible for half of registered visual impairment in the UK. The Royal College of Ophthalmologists recommends providing guidance to people with AMD regarding smoking, diet, and nutritional supplements. The aim of this study was to investigate lifestyle advice recalled by patients with neovascular AMD (nAMD).

Methods
The study took place at a UK hospital outpatients’ clinic. Eligible patients with unilateral nAMD were presented with a survey about lifestyle advice provision.

Results
Of 248 respondents, only 39.9% remembered receiving advice regarding diet at the hospital. Only 24.2% of respondents recalled receiving advice regarding nutritional supplements, and only 19.8% of respondents started taking daily supplements as a result of their AMD. The most prevalent reason for not taking supplements amongst those advised to do so was lack of understanding of how it would help their eyes. Nearly 13% of the sample reported currently smoking, 53.1% of which reported that they were advised to stop smoking when diagnosed with AMD.

Conclusion
The findings suggest that it would be beneficial to review the provision of lifestyle advice to patients attending AMD outpatients’ clinics, and to consider whether advice is being provided in an optimal format for later recall.
Chloroplast thioredoxin systems: prospects for improving photosynthesis
Authors: Nikkanen Lauri , Toivola Jouni , Diaz Manuel Guinea , Rintamäki Eevi 
Published: August 2017

Thioredoxins (TRXs) are protein oxidoreductases that control the structure and function of cellular proteins by cleavage of a disulphide bond between the side chains of two cysteine residues. Oxidized thioredoxins are reactivated by thioredoxin reductases (TR) and a TR-dependent reduction of TRXs is called a thioredoxin system. Thiol-based redox regulation is an especially important mechanism to control chloroplast proteins involved in biogenesis, in regulation of light harvesting and distribution of light energy between photosystems, in photosynthetic carbon fixation and other biosynthetic pathways, and in stress responses of plants. Of the two plant plastid thioredoxin systems, the ferredoxin-dependent system relays reducing equivalents from photosystem I via ferredoxin and ferredoxin-thioredoxin reductase (FTR) to chloroplast proteins, while NADPH-dependent thioredoxin reductase (NTRC) forms a complete thioredoxin system including both reductase and thioredoxin domains in a single polypeptide. Chloroplast thioredoxins transmit environmental light signals to biochemical reactions, which allows fine tuning of photosynthetic processes in response to changing environmental conditions. In this paper we focus on the recent reports on specificity and networking of chloroplast thioredoxin systems and evaluate the prospect of improving photosynthetic performance by modifying the activity of thiol regulators in plants.
This article is part of the themed issue ‘Enhancing photosynthesis in crop plants: targets for improvement'.
The Novel Monocomponent FAD-dependent Monooxygenase HpaM Catalyzes the 2-Decarboxylative Hydroxylation of 5-Hydroxypicolinic Acid inAlcaligenes faecalisJQ135
Authors: Qiu Jiguo , Liu Bin , Zhao Lingling , Zhang Yanting , Cheng Dan , Yan Xin , Jiang Jiandong , Hong Qing , He Jian 
Published: August 2017

Abstract5-hydroxypicolinic acid (5HPA) is a natural pyridine derivative that can be microbially degraded. However, the physiological, biochemical, and genetic foundation of the microbial catabolism of 5HPA remains unknown. In this study, a gene clusterhpa(which is involved in degradation of 5HPA inAlcaligenes faecalisJQ135) was cloned and HpaM was identified as a novel monocomponent FAD-dependent monooxygenase. HpaM shared a sequence only 31% similarity with the most related protein 6-hydroxynicotinate 3-monooxygenase (NicC) ofPseudomonas putidaKT2440.hpaMwas heterologously expressed inE. coliBL21(DE3), and the recombinant HpaM was purified via Ni-affinity chromatography. HpaM catalyzed the 2-decarboxylative hydroxylation of 5-HPA, thus generating 2,5-dihydroxypyridine (2,5-DPH). Monooxygenase activity was only detected in the presence of FAD and NADH, but not of FMN and NADPH. The apparentKmvalues of HpaM toward 5HPA and NADH were 45.4 μ and 37.8 μ, respectively. Results of gene deletion and complementation showed thathpaMwas essential for 5HPA degradation inAlcaligenes faecalisJQ135.ImportancePyridine derivatives are ubiquitous in nature and important chemical materials that are currently widely used in agriculture, pharmaceutical, and chemical industries. Thus, the microbial degradation and transformation mechanisms of pyridine derivatives received considerable attention. Decarboxylative hydroxylation was an important degradation process in pyridine derivatives, and previously reported decarboxylative hydroxylations happened in the C3 of the pyridine ring. In this study, we cloned the gene clusterhpa, which is responsible for 5HPA degradation inAlcaligenes faecalisJQ135, thus identifying a novel monocomponent FAD-dependent monooxygenase HpaM. Unlike 3-decarboxylative monooxygenases, HpaM catalyzed decarboxylative hydroxylation in the C2 of the pyridine ring in 5-hydroxypicolinic acid. These findings deepen our understanding of the molecular mechanism of microbial degradation of pyridine derivatives. Furthermore, HpaM offers potential for applications to transform useful pyridine derivatives.
Revealing unidentified heterogeneity in different epithelial cancers using heterocellular subtype classification
Authors: Poudel Pawan , Nyamundanda Gift , Ragulan Chanthirika , Lawlor Rita T. , Das Kakoli , Tan Patrick , Scarpa Aldo , Sadanandam Anguraj 
Published: August 2017

AbstractCancers are currently diagnosed, categorised, and treated based on their tissue of origin. However, how different cellular compartments of tissues (e.g., epithelial, immune and stem cells) are similar across cancer types is unknown. Here we used colorectal cancer subtypes and their signatures representing different colonic crypt cell types as surrogates to classify different epithelial cancers into five heterotypic cellular (heterocellular) subtypes. The stem-like and inflammatory heterocellular subtypes are ubiquitous across epithelial cancers so capture intrinsic, tissue-independent properties. Conversely, well-differentiated/specialized goblet-like/enterocyte heterocellular subtypes differ across cancer types due to their colorectum-specific genes. The transit-amplifying heterocellular subtype shows a dynamic range of cellular differentiation with shared common pathways (Wnt, FGFR) in certain cancer types. Importantly, this approach revealed previously unrecognised heterogeneity in pancreatic, breast, microsatellite-instability enriched andKRASmutation-dependent cancers. Immune cell-type differences are common and useful for patient stratification for immunotherapy. This unique approach identifies cell type-dependent but tissue-independent heterogeneity in different cancers for precision medicine.
A retrieved context model of the emotional modulation of memory
Authors: Talmi Deborah , Lohnas Lynn J. , Daw Nathaniel D. 
Published: August 2017

AbstractEmotion enhances episodic memory, an effect thought to be an adaptation to prioritise the memories that best serve evolutionary fitness. But viewing this effect largely in terms of prioritising what to encode or consolidate neglects broader rational considerations about what sorts of associations should be formed at encoding, and which should be retrieved later. Although neurobiological investigations have provided many mechanistic clues about how emotional arousal modulates item memory, these effects have not been wholly integrated with the cognitive and computational neuroscience of memory more generally.Here we apply the Context Maintenance and Retrieval Model (CMR, Polyn, Norman & Kahana, 2009) to this problem by extending it to describe the way people may represent and process emotional information. A number of ways to operationalise the effect of emotion were tested. The winning emotional CMR (eCMR) model reconceptualises emotional memory effects as arising from the modulation of a process by which memories become bound to ever-changing temporal and emotional contexts. eCMR provides a good qualitative fit for the emotional list-composition effect and the emotional oddball effect, illuminating how these effects are jointly determined by the interplay of encoding and retrieval processes. eCMR explains the increased advantage of emotional memories in delayed memory tests through the limited ability of retrieval to reinstate the temporal context of encoding.By leveraging the rich tradition of temporal context models, eCMR helps integrate existing effects of emotion and provides a powerful tool to test mechanisms by which emotion affects memory in a broad range of paradigms.
Real-time genomic and epidemiological investigation of a multi-institution outbreak of KPC-producing Enterobacteriaceae: a translational study
Authors: Kwong JC , Lane C , Romanes F , Gonçalves da Silva A , Easton M , Cronin K , Waters MJ , Tomita T , Stevens K , Schultz MB , Baines SL , Sherry NL , Carter G , Mu A , Sait M , Ballard SA , Seemann T , Stinear TP , Howden BP 
Published: August 2017

ABSTRACTBackgroundUntil recently, KPC-producing Enterobacteriaceae were rarely identified in Australia. Following an increase in the number of incident cases across the state of Victoria, we undertook a real-time combined genomic and epidemiological investigation. The scope of this study included identifying risk factors and routes of transmission, and investigating the utility of genomics to enhance traditional field epidemiology for informing management of established widespread outbreaks.Methods and FindingsAll KPC-producing Enterobacteriaceae isolates referred to the state reference laboratory from 2012 onwards were included. Whole-genome sequencing (WGS) was performed in parallel with a detailed descriptive epidemiological investigation of each case, using Illumina sequencing on each isolate. This was complemented with PacBio long-read sequencing on selected isolates to establish high-quality reference sequences and interrogate characteristics of KPC-encoding plasmids. Initial investigations indicated the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates (K. pneumoniae92%) identified from 35 different locations across metropolitan and rural Victoria between 2012-2015. Initial combined analyses of the epidemiological and genomic data resolved the outbreak into distinct nosocomial transmission networks, and identified healthcare facilities at the epicentre of KPC transmission. New cases were assigned to transmission networks in real-time, allowing focussed infection control efforts. PacBio sequencing confirmed a secondary transmission network arising from inter-species plasmid transmission. Insights from Bayesian transmission inference and analyses of within-host diversity informed the development of state-wide public health and infection control guidelines, including interventions such as an intensive approach to screening contacts following new case detection to minimise unrecognised colonisation.ConclusionsA real-time combined epidemiological and genomic investigation proved critical to identifying and defining multiple transmission networks of KPC Enterobacteriaceae, while data from either investigation alone were inconclusive. The investigation was fundamental to informing infection control measures in real-time and the development of state-wide public health guidelines on carbapenemase producing Enterobacteriaceae management.
A network modeling approach to elucidate drug resistance mechanisms and predict combinatorial drug treatments in breast cancer
Authors: Zañudo Jorge G. T. , Albert Réka 
Published: August 2017

AbstractBackgroundMechanistic models of within-cell signal transduction networks can explain how these networks integrate internal and external inputs to give rise to the appropriate cellular response. These models can be fruitfully used in cancer cells, whose aberrant decision-making regarding their survival or death, proliferation or quiescence can be connected to errors in the state of nodes or edges of the signal transduction network.ResultsHere we present a comprehensive network, and discrete dynamic model, of signal transduction in breast cancer based on the literature of ER+, HER2+, and PIK3CA-mutant breast cancers. The network model recapitulates known resistance mechanisms to PI3K inhibitors and suggests other possibilities for resistance. The model also reveals known and novel combinatorial interventions that are more effective than PI3K inhibition alone.ConclusionsThe use of a logic-based, discrete dynamic model enables the identification of results that are mainly due to the organization of the signaling network, and those that also depend on the kinetics of individual events. Network-based models such as this will play an increasing role in the rational design of high-order therapeutic combinations.
A nutrient-dependent division antagonist is regulated post-translationally by the Clp proteases inBacillus subtilis
Authors: Hill Norbert S. , Zuke Jason D. , Buske P. J. , Chien An-Chun , Levin Petra Anne 
Published: August 2017

ABSTRACTChanges in nutrient availability have dramatic and well-defined impacts on both transcription and translation in bacterial cells. At the same time, the role of post-translational control in adaptation to nutrient-poor environments is poorly understood. Here we report a role for the bacterial Clp proteases in degradation of the division inhibitor UgtP during growth in nutrient-poor medium. Under nutrient-rich conditions, interactions with its substrate UDP-glucose promote interactions between UgtP and the tubulin-like cell division protein FtsZ inBacillus subtilis, inhibiting maturation of the cytokinetic ring and increasing cell size. In nutrient-poor medium, reductions in UDP-glucose availability favor UgtP oligomerization, sequestering it from FtsZ and allowing division to occur at a smaller cell mass. Intriguingly, in nutrient-poor conditions UgtP levels are reduced ∼ 3-fold independent of UDP-glucose, suggesting an additional layer of regulation.B. subtiliscells cultured under different nutrient conditions indicate that UgtP accumulation is controlled through a nutrient-dependent post-translational mechanism dependent on the Clp proteases. Notably, all threeB. subtilisClp chaperones appeared able to target UgtP for degradation during growth in nutrient-poor conditions. Together these findings highlight conditional proteolysis as a mechanism for bacterial adaptation to a rapidly changing nutritional landscape.
The effect of sequence mismatches on binding affinity and endonuclease activity are decoupled throughout the Cas9 binding site
Authors: Zhang Liyang , Rube H. Tomas , Bussemaker Harmen J. , Pufall Miles A. 
Published: August 2017

ABSTRACTThe CRISPR-Cas9 system is a powerful genomic tool. Although targeted to complementary genomic sequences by a guide RNA (gRNA), Cas9 tolerates gRNA:DNA mismatches and cleaves off-target sites. How mismatches quantitatively affect Cas9 binding and cutting is not understood. UsingSelexGLMto construct a comprehensive model for DNA-binding specificity, we observed that 13-bp of complementarity in the PAM-proximal DNA contributes to affinity. We then adaptedSpec-seqand developedSEAM-seqto systematically compare the impact of gRNA:DNA mismatches on affinity and endonuclease activity, respectively. Though most often coupled, these simple and accessible experiments identified sometimes opposing effects for mismatches on DNA-binding and cutting. In the PAM-distal region mismatches decreased activity but not affinity, whereas in the PAM-proximal region some reduced-affinity mismatches enhanced activity. This mismatch-activation was particularly evident where the gRNA:DNA duplex bends. We developed integrative models from these measurements that estimate catalytic efficiency and can be used to predict off-target cleavage.
The helicase domain of Polθ counteracts RPA to promote alt-NHEJ
Authors: Mateos-Gomez Pedro A. , Kent Tatiana , Kashkina Ekaterina , Pomerantz Richard T , Sfeir Agnel 
Published: August 2017

AbstractMammalian polymerase theta (Polθ; encoded byPOLQ) is a unique multifunctional enzyme that promotes error-prone DNA repair by alternative-NHEJ (alt-NHEJ). Here we perform structure-function analyses and report that, in addition to the polymerase domain, the helicase activity plays a central role during Polθ–mediated double-stranded break (DSB) repair. Our results show that Polθ–helicase promotes chromosomal translocations by alt-NHEJ in mouse embryonic stem cells. In addition, the helicase activity suppresses CRISPR/Cas9 mediated gene targeting by homologous recombination (HR).In vitroexperiments reveal that Polθ–helicase displaces RPA to facilitate the annealing of complementary DNA during alt-NHEJ. Consistent with an antagonistic role for RPA during alt-NHEJ, we show that the inhibition of RPA1 subunit enhances end-joining and suppresses recombination at telomeres. Taken together, our results reveal that the balance between HR and alt-NHEJ is regulated by opposing activities of Polθ and RPA, providing critical insight into the mechanism that control DSB repair pathway choice in mammalian cells.
“One country, two systems” after the Umbrella movement: problems and prospects
Authors: Cheung Chor-yung 
Published: August 2017

Purpose
The purpose of this paper is to assess critically the political challenges facing Hong Kong’s “one country, two systems” policy following the Umbrella Movement and to evaluate the territory’s democratic and autonomous future.

Design/methodology/approach
A critical, contextual, and analytical approach has been adopted to evaluate the problems and prospects for post-Umbrella Movement Hong Kong.

Findings
The contradictions embedded in the “one country, two systems” policy have become apparent since the Umbrella Movement arose and Hong Kong’s political and democratic future is as problematic as its prospects are uncertain, though the possibility of some rapprochement between Hong Kong and Beijing should not be ruled out completely.

Research limitations/implications
The critical evaluation offered by this paper is no scientific prediction. Social scientific analysis of this kind is suggestive rather than definitive. The informed discussion offered by this paper will help readers to better understand the strengths and weaknesses inherent in Beijing’s “one country, two systems” policy and the tortuous process of democratization in Hong Kong. The conclusion drawn in the paper points to a possible way out of the political impasse that is facing post-Umbrella Movement Hong Kong.

Originality/value
This paper is a pioneering study of the most important political conflict between Beijing and Hong Kong since 1997, the conclusion of which may have important political and policy implications for both China and Hong Kong.
Integrating Indigenous enterprises into the Australian construction industry
Authors: Denny-Smith George , Loosemore Martin 
Published: August 2017

Purpose
The purpose of this paper is to explore the barriers to entry for Indigenous businesses into the Australian construction industry.

Design/methodology/approach
A national survey was conducted with 33 Indigenous businesses operating in the Australian construction industry.

Findings
The findings show that Indigenous enterprises face similar challenges to many small non-Indigenous enterprises wishing to enter the industry. These include adjusting to unique construction industry cultures and practices, breaking into existing business networks and building social capital and being under-cut by industry incumbents and competitors when tendering for projects. These barriers are similar to those faced by other non-Indigenous social enterprises, although Indigenous enterprises do appear to experience relatively greater difficulty in starting-up their businesses and in securing sufficient capital, finance and assistance to enable them to scale-up and tender for normal work packages at a competitive price.

Research limitations/implications
The results are limited to Australian Indigenous businesses. The survey does not allow a comparison of non-Indigenous and Indigenous businesses, although comparison of results with existing non-Indigenous research into small to medium-sized firms in construction does allow some tentative insights. These need to be explored further.

Practical implications
These results indicate that there are significant barriers to be addressed within the Australian construction industry if government indigenous procurement policies are to achieve their stated aims of increasing the number of Indigenous firms in the industry. The results also have important implications for Indigenous businesses and for non-Indigenous firms operating in the Australian construction industry.

Social implications
This is an important gap in knowledge to address if countries like Australia are to redress the significant inequalities in income and health suffered by Indigenous populations.

Originality/value
In countries like Australia, with significant Indigenous populations, governments are seeking to address persistent disadvantage by using new social procurement initiatives to create quasi construction markets for Indigenous enterprises to participate in the construction industry. While there is an emerging body of research into the barriers facing mainstream small to medium-sized enterprises and, to a lesser extent, social enterprises in construction, the barriers to entry facing Indigenous construction enterprises have been largely ignored.