bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo assembly of the Mongolian gerbil genome and transcriptome
Authors: Cheng Shifeng , Fu Yuan , Zhang Yaolei , Xian Wenfei , Wang Hongli , Grothe Benedict , Liu Xin , Xu Xun , Klug Achim , McCullagh Elizabeth A
Published: January 2019

BACKGROUND

The Mongolian gerbil (Meriones unguiculatus) has historically been used as a model organism for the auditory and visual systems, stroke/ischemia, epilepsy and aging related research since 1935 when laboratory gerbils were separated from their wild counterparts. In this study we report genome sequencing, assembly, and annotation further supported by transcriptome data from 27 different tissues samples.

FINDINGS

The genome was assembled using Illumina HiSeq 2000 and resulted in a final genome size of 2.54 Gbp with contig and scaffold N50 values of 31.4 Kbp and 500.0 Kbp, respectively. Based on the k-mer estimated genome size of 2.48 Gbp, the assembly appears to be complete. The genome annotation was supported by transcriptome data that identified 36 019 predicted protein-coding genes across 27 tissue samples. A BUSCO search of 3023 mammalian groups resulted in 86% of curated single copy orthologs present among predicted genes, indicating a high level of completeness of the genome.

CONCLUSIONS

We report a de novo assembly of the Mongolian gerbil genome that was further enhanced by annotation of transcriptome data from several tissues. Sequencing of this genome increases the utility of the gerbil as a model organism, opening the availability of now widely used genetic tools.
KLF4 protein stability regulated by interaction with pluripotency transcription factors overrides transcriptional control
Authors: Dhaliwal Navroop K , Abatti Luis E , Mitchell Jennifer A
Published: January 2019

Embryonic stem (ES) cells are regulated by a network of transcription factors which maintain the pluripotent state. Differentiation relies on downregulation of pluripotency transcription factors disrupting this network. While investigating transcriptional regulation of the pluripotency transcription factorKlf4, we observed homozygous deletion of distal enhancers caused 17 fold decrease inKlf4transcript but surprisingly decreased protein levels by less than 2 fold indicating post-transcriptional control of KLF4 protein overrides transcriptional control. The lack of sensitivity of KLF4 to transcription is due to high protein stability (half-life >24hr). This stability is context dependent and disrupted during differentiation, evidenced by a shift to a half-life of <2hr. KLF4 protein stability is maintained through interaction with other pluripotency transcription factors (NANOG, SOX2 and STAT3) that together facilitate association of KLF4 with RNA polymerase II. In addition, the KLF4 DNA binding and transactivation domains are required for optimal KLF4 protein stability. Post-translational modification of KLF4 destabilizes the protein as cells exit the pluripotent state and mutations that prevent this destabilization also prevent differentiation. These data indicate the core pluripotency transcription factors are integrated by post-translational mechanisms to maintain the pluripotent state, and identify mutations that increase KLF4 protein stability while maintaining transcription factor function.
Vibrotactile perception in the sole of the foot in people with normal glucose tolerance and type 2 diabetes
Authors: Peterson Magnus , Pingel Ronnie , Rolandsson Olov , Dahlin Lars B.
Published: January 2019

Aim

To evaluate vibrotactile perception thresholds in people with normal glucose tolerance (NGT) and type 2 diabetes (T2DM) in relation to other sensory tests.

Methods

Nerve function was evaluated in 36 and 42 participants with NGT and T2DM, respectively [mean age 70.0 (1.2) years; males n=40, females n=38]. The mean duration of T2DM was 12.3 (7.3) years. Vibration perception thresholds were measured at four frequencies (8, 16, 32 and 125 Hz) bilaterally on the sole of the foot at first and fifth metatarsal heads using Multifrequency vibrametry and compared to vibration perception thresholds using Biothesiometer (128 Hz) bilaterally (medial malleolus and distal dorsal bony surface of great toes), touch sensation with Semmes-Weinstein monofilament bilaterally (10 g) at three sites on the sole of foot (distal great toe and 1st and 5th metatarsal heads), electrophysiology (amplitude and conduction velocity of sural nerve; right side) and thermal sensory testing (i.e. small diameter nerve fibers; method of limits using Thermotest®).

Results

Vibration perception and temperature thresholds in the foot and sural nerve function were different between the NGT and T2DM categories. Measuring vibration perception thresholds at lower frequencies with Multifrequency vibrametry, compared to Biothesiometer, both provided similar correlations to the amplitude of the sural nerve. Temperature thresholds did also correlate with vibration perception thresholds and with sural nerve function. Only 4/42 participants with T2DM showed pathology by monofilament test, none with NGT.

Conclusions

Vibration perception thresholds have a fair correlation to amplitude of the sural nerve, even when measured at a non-tactile surface. Thus in the present study, measuring vibration perception threshold at a tactile surface does not seem to provide any clear advantage over the traditional way of measuring vibration perception on the medial malleolus. In people with T2DM, both large and small diameter nerve fibers seem to be affected.
Arbuscular Mycorrhizal Fungus (AMF) and reduction of arsenic uptake in lentil crops
Authors: Alam Mohammad Zahangeer , Hoque Md. Anamul , McGee Rebecca , Carpenter-Boggs Lynne
Published: January 2019

Arsenic (As) is a carcinogenic and hazardous substance that poses a serious risk to human health. Physiological studies have shown that growth of lentil crop have been impaired due to arsenic toxicity, and is transportable into human food chains. Our research focused on the transportation of As in lentil crops and its mitigation using Arbuscular Mycorrhizal Fungus (AMF). Shoot length, fresh and dry weight of shoot and root were found comparatively higher in 5 and 15 mgkg-1 arsenic treated lentil seedlings than in a 100 mgkg-1 As concentrated soil. As accumulation in lentil’s pods of BARI Mashur 1 were found higher than others; but As uptake in root and shoot were increased significantly in all BARI released lentil genotypes. Biomass growth of lentil was found higher in AMF treated soils in compare to non-AMF. AMF effectively reduced the arsenic uptake in root and shoot at 8 and 45 mgkg-1 As concentrated soils compared. As free lentil seeds are significantly important for human consumption through mitigation of As accumulation in lentil roots shoots and pods. AMF shows great potential in providing As free lentil seeds throughout the world.
How many days are needed to estimate accelerometry-assessed physical activity during pregnancy? Methodological analyses based on a cohort study using wrist-worn accelerometer
Authors: da Silva Shana Ginar , Evenson Kelly R , Ekelund Ulf , da Silva Inácio Crochemore Mohsam , Domingues Marlos Rodrigues , da Silva Bruna Gonçalves Cordeiro , de Almeida Mendes Márcio , Cruz Glória Isabel Niño , Hallal Pedro Curi
Published: January 2019

Background

Objective methods to measure physical activity (PA) can lead to better cross-cultural comparisons, monitoring temporal PA trends, and measuring the effect of interventions. However, when applying this technology in field-work, the accelerometer data processing is prone to methodological issues. One of the most challenging issues relates to standardizing total wear time to provide reliable data across participants. It is generally accepted that at least 4 complete days of accelerometer wear represent a week for adults. It is not known if this same assumption holds true for pregnant women.

Aim

We assessed the optimal number of days needed to obtain reliable estimates of overall PA and moderate-to-vigorous physical activity (MVPA) during pregnancy using a raw triaxial wrist-worn accelerometer.

Methods

Cross-sectional analyses were carried out in the antenatal wave of the 2015 Pelotas (Brazil) Birth Cohort Study. Participants wore the wrist ActiGraph wGT3X-BT accelerometer for seven consecutive days. The daily average acceleration, which indicates overall PA, was measured as milli-g (mg), and time spent in MVPA (minutes/day) was analyzed in 5-minute bouts. ANOVA and Kruskal-Wallis tests were used to compare variability across days of the week. Bland-Altman plots and Spearman-Brown Prophecy Formula were applied to determine the reliability coefficient associated with one to seven days of measurement. Analyses were stratified by sociodemographic factors and nutritional status.

Results

Among 2,082 pregnant women who wore the accelerometer for seven complete days, overall and MVPA were lower on Sundays compared to other days of the week. Reliability of >=0.80 to evaluate overall PA was reached with at least three monitoring days, whereas six days were needed to estimate reliable measures of MVPA.

Conclusions

Our findings indicate that the usual approach obtaining one week of accelerometry in adults is also appropriate for pregnant women, particularly to obtain differences on weekend days and reliably estimate MVPA.
Maternal antibodies provide strain-specific protection against infection with the Lyme disease pathogen in a wild rodent
Authors: Gomez-Chamorro Andrea , Heinrich Vanina , Sarr Anouk , Roethlisberger Owen , Genné Dolores , Jacquet Maxime , Voordouw Maarten J.
Published: January 2019

The vertebrate immune system can produce antibodies that protect the host against pathogens. Females can transmit antibodies to their offspring, which provide short-term protection against infection. The tick-borne bacteriumBorrelia afzeliicauses Lyme disease in Europe and consists of multiple strains that cycle between the tick vector (Ixodes ricinus) and vertebrate hosts such as the bank vole (Myodes glareolus). We used a controlled experiment to show that infected female bank voles transmit protective antibodies to their offspring that are specific for the strain ofB. afzelii. To test the specificity of protection, the offspring were challenged with either the same strain to which the mothers had been exposed or a different strain. The maternal antibodies protected the offspring against the same strain, but not against the different strain. The offspring from the uninfected control mothers were equally susceptible to both strains. Our study shows that maternal antibodies provide strong but highly strain-specific protection againstB. afzeliiin an important rodent reservoir host. The transmission of maternal antibodies may have important consequences for the epidemiology of multiple-strain pathogens in nature.

Author Summary

Many pathogens that cause infectious disease consist of multiple strains. In vertebrate hosts, the immune system can generate antibodies that are highly specific for different pathogen strains. Mothers can transmit these antibodies to their offspring and thereby protect them from infectious disease. To date, few studies have investigated whether this transgenerational transfer of protective antibodies is important for pathogens that cycle in wild animal populations. The tick-borne spirochete bacteriumBorrelia afzeliicauses Lyme disease in Europe and cycles betweenIxodesticks and wild rodent hosts, such as the bank vole (Myodes glareolus). The purpose of our study was to test whether female bank voles infected withB. afzeliitransmit antibodies to their offspring that protect them from an infected tick bite. Our study found that infected mothers do transmit antibodies, but the offspring were only protected against the strain ofB. afzeliito which their mothers had been exposed and not to a different strain (i.e. protection was highly strain-specific). The broader implications of our study is that the transfer of protective antibodies between generations in the vertebrate host population could be important for organizing the community of pathogen strains that circulate in nature.
Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
Authors: Henríquez-Olguin Carlos , Knudsen Jonas R. , Raun Steffen H. , Li Zhencheng , Dalbram Emilie , Treebak Jonas T. , Sylow Lykke , Holmdahl Rikard , Richter Erik A. , Jaimovich Enrique , Jensen Thomas E.
Published: January 2019

Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source regulating glucose transport capacity during moderate-intensity exercise.
Motion perception in the common marmoset
Authors: Cloherty Shaun L. , Yates Jacob L. , Graf Dina , DeAngelis Gregory C. , Mitchell Jude F.
Published: January 2019

Visual motion processing is a well-established model system for studying neural population codes in primates. The common marmoset, a small new world primate, offers unparalleled opportunities to probe these population codes in key motion processing areas, such as cortical areas MT and MST, because these areas are accessible for imaging and recording at the cortical surface. However, little is currently known about the perceptual abilities of the marmoset. Here, we introduce a paradigm for studying motion perception in the marmoset and compare their psychophysical performance to human observers. We trained two marmosets to perform a motion estimation task in which they provided an analog report of their perceived direction of motion with an eye movement to a ring that surrounded the motion stimulus. Marmosets and humans exhibited similar trade-offs in speed vs. accuracy: errors were larger and reaction times were longer as the strength of the motion signal was reduced. Reverse correlation on the temporal fluctuations in motion direction revealed that both species exhibited short integration windows, however, marmosets had substantially less non-decision time than humans. Our results provide the first quantification of motion perception in the marmoset and demonstrate several advantages to using analog estimation tasks.
Mechanistic Analyses of Supercoiling Behaviors of DNA in Nucleosomes and Chromatins
Authors: Zhang Hao , Li Tianhu
Published: January 2019

Besides those in 146-base pair nucleosome core particle DNA, supercoils have been known to be present in 10-base pair arm DNA segments and naked linker DNA segments. The interacting patterns among histone octamers, histone H1, 10-base pair arm DNA segments and linker DNA have, however, not yet been elucidated. In the current report, we examine correlations among constituents of nucleosomes from the mechanistic perspectives and present molecular pathways for elucidating supercoiling behaviors of their component DNA sequences. It is our hope that our new analyses could serve as incentives to further clarify correlations between histones and DNA in the dynamic structures of chromatins in the future.
Predictive markers for Parkinson’s disease using deep neural nets on neuromelanin sensitive MRI
Authors: Shinde Sumeet , Prasad Shweta , Saboo Yash , Kaushick Rishabh , Saini Jitender , Pal Pramod Kumar , Ingalhalikar Madhura
Published: January 2019

Neuromelanin sensitive magnetic resonance imaging (NMS-MRI) has been crucial in identifying abnormalities in the substantia nigra pars compacta (SNc) in Parkinson’s disease (PD). PD is characterized by loss of dopaminergic neurons in SNc and current techniques employ estimation of contrast ratios of the SNc visualized on NMS-MRI to discern PD patients from the healthy controls. However, the extraction of these features is time-consuming and laborious and moreover provides lower prediction accuracies. Furthermore, these do not account for patterns of subtle changes in PD in the SNc. To mitigate this, our work establishes a computer-based analysis technique based on convolutional neural networks (CNNs) to create prognostic and diagnostic biomarkers of PD from NMS-MRI. The technique not only performs with a superior cross-validation accuracy (83.7%) as well as testing accuracy (80%) as compared to contrast ratio-based classification (52.7% cross-validation and 56.5% testing accuracy) and radiomics based classifier (81.1% cross-validation and 60.3% testing accuracy); but also locates the most discriminative regions on the neuromelanin contrast images. These discriminative activations demonstrate that the left SNc plays a key role in the classification in comparison to the right SNc, and are in agreement with the concept of asymmetry in PD. Overall, the proposed technique has the potential to support radiological diagnosis of PD while facilitating deeper understanding into the abnormalities in SNc.
Selective targeting of unipolar brush cell subtypes by cerebellar mossy fibers
Authors: Balmer Timothy S. , Trussell Laurence O.
Published: January 2019

In vestibular cerebellum, primary afferents carry signals from single vestibular end organs, whereas secondary afferents from vestibular nucleus carry integrated signals. Selective targeting of distinct mossy fibers to postsynaptic cells determines how the cerebellum processes vestibular signals. We focused on vestibular projections to ON and OFF classes of unipolar brush cells (UBCs), which transform single mossy fiber signals into long-lasting excitation or inhibition respectively, and impact the activity of ensembles of granule cells. To determine whether these contacts are indeed selective, connectivity was traced back from UBC to specific ganglion cell, hair cell and vestibular organ subtypes. We show that a specialized subset of primary afferents contacts ON UBCs, but not OFF UBCs, while secondary afferents contact both subtypes. Striking anatomical differences were observed between primary and secondary afferents, their synapses, and the UBCs they contact. Thus, each class of UBC functions to transform specific signals through distinct anatomical pathways.
Sequence learning is driven by improvements in motor planning
Authors: Ariani Giacomo , Diedrichsen Jörn
Published: January 2019

The ability to perform complex sequences of movements quickly and accurately is critical for many motor skills. While training improves performance in a large variety of motor-sequence tasks, the precise mechanisms behind such improvements are poorly understood. Here we investigated the contribution of single-action selection, sequence pre-planning, online planning, and motor execution to performance in a discrete sequence production (DSP) task. Five visually-presented numbers cued a sequence of five finger presses, which had to be executed as quickly and accurately as possible. To study how sequence planning influenced sequence production, we manipulated the amount of time that participants were given to prepare each sequence by using a forced-response paradigm. Over 4 days, participants were trained on 10 sequences and tested on 80 novel sequences. Our results revealed that participants became faster in selecting individual finger presses. They also preplanned 3-4 sequence items into the future, and the speed of pre-planning improved for trained, but not for untrained, sequences. Because pre-planning capacity remained limited, the remaining sequence elements had to be planned online during sequence execution, a process that also improved with sequence-specific training. Overall, our results support the view that motor sequence learning effects are best characterized by improvements in planning processes that occur both before and concurrently with motor execution.

New & Noteworthy

Complex skills often require the production of sequential movements. While practice improves performance, it remains unclear how these improvements are achieved. Our findings show that learning effects in a sequence production task can be attributed to an enhanced ability to plan upcoming movements. These results shed new light on planning processes in the context of movement sequences, and have important implications for our understanding of the neural mechanisms that underlie skill acquisition.
An integrated microfluidic platform for quantifying drug permeation across biomimetic vesicle membranes
Authors: Schaich Michael , Cama Jehangir , Nahas Kareem Al , Sobota Diana , Jahnke Kevin , Deshpande Siddharth , Dekker Cees , Keyser Ulrich F.
Published: January 2019

The low membrane permeability of candidate drug molecules is a major challenge in drug development and insufficient permeability is one reason for the failure of antibiotic treatment against bacteria. Quantifying drug transport across specific pathways in living systems is challenging since one typically lacks knowledge of the exact lipidome and proteome of the individual cells under investigation. Here, we quantify drug permeability across biomimetic liposome membranes, with comprehensive control over membrane composition. We integrate the microfluidic octanol-assisted liposome assembly platform with an optofluidic transport assay to create a complete microfluidic total analysis system for quantifying drug permeability. Our system enables us to form liposomes with charged lipids mimicking the negative charge of bacterial membranes at physiological salt and pH levels, which proved difficult with previous liposome formation techniques. Furthermore, the microfluidic technique yields an order of magnitude more liposomes per experiment than previous assays. We demonstrate the feasibility of the assay by determining the permeability coefficient of norfloxacin across biomimetic liposomes.
A gold standard method for human cell quantification after xenotransplantation
Authors: Bensalah Mona , Klein Pierre , Riederer Ingo , Chaouch Soraya , Muraine Laura , Savino Wilson , Butler-Browne Gillian , Trollet Capucine , Mouly Vincent , Bigot Anne , Negroni Elisa
Published: January 2019

Xenotransplantation of human cells into immunodeficient mouse models is a very powerful tool and an essential step for the pre-clinical evaluation of therapeutic cell-and gene-based strategies. Here we describe an optimized protocol combining immunofluorescence and real-time quantitative PCR to both quantify and visualize the fate and localization of human myogenic cells after injection in regenerating muscles of immunodeficient mice. Whereas real-time quantitative PCR-based method provides an accurate quantification of human cells, it does not document their specific localization. The addition of an immunofluorescence approach using human-specific antibodies recognizing engrafted human cells gives information on the localization of the human cells within the host muscle fibres, in the stem cell niche or in the interstitial space.

These two combined approaches offer an accurate evaluation of human engraftment including cell number and localization and should provide a gold standard to compare results obtained either using different types of human stem cells or comparing healthy and pathological muscle stem cells between different research laboratories worldwide.
3D spatial organization and network-guided comparison of mutation profiles in Glioblastoma reveals similarities across patients
Authors: Dincer Cansu , Kaya Tugba , Keskin Ozlem , Gursoy Attila , Tuncbag Nurcan
Published: January 2019

Mutation profiles of Glioblastoma (GBM) tumors are very heterogeneous which is the main challenge in the interpretation of the effects of mutations in disease. Additionally, the impact of the mutations is not uniform across the proteins and protein-protein interactions. The pathway level representation of the mutations is very limited. In this work, we approach these challenges through a systems level perspective in which we analyze how the mutations in GBM tumors are distributed in protein structures/interfaces and how they are organized at the network level. Our results show that out of 14644 mutations, 4392 have structural information and ~13% of them form spatial patches. Despite a small portion of all mutations, 3D patches partially decrease the heterogeneity across the patients. Hub proteins adapt multiple patches of mutations usually with a very large one and connects mutations in multiple binding sites through the core of the protein. We reconstructed patient specific networks for 290 GBM tumors. Network-guided analysis of mutations completes the interaction components that mutated proteins potentially affect, and groups the patients according to the reconstructed networks. As a result, we found 4 tumor clusters that overcome the heterogeneity in mutation profiles, and reveal predominant pathways in each group. Additionally, the network-based similarity analysis shows that each group of patients carries a set of signature 3D mutation patches. We believe that this study provides another perspective to the analysis of mutation effects and a good training towards the network-guided precision medicine.

Author Summary

Glioblastoma (GBM) is the most aggressive brain tumor type with a 15 months of survival on average. The mutation distribution of the GBM patients is very heterogeneous and standard treatments fail to consider the inter-tumor heterogeneity. In our study, we follow a systems level approach that integrates mutation profiles with protein-protein interaction networks. We hypothesized that although the mutations are heterogeneous, the mutations that are close in 3D of the same protein may affect the protein function similarly and this information can be used to get meaningful relation between disease state and mutations. Therefore, we spatially grouped these mutations as “patches” and reconstructed patient specific protein interaction networks. When we cluster these networks based on their pathway similarities, we found four patient groups in GBM. Then, the comparison of groups revealed overrepresentation of 3D patches. This finding can be used for patient specific therapy.
Instantaneous polarized light imaging reveals activity dependent structural changes of dendrites in mouse hippocampal slices
Authors: Koike-Tani Maki , Tominaga Takashi , Oldenbourg Rudolf , Tani Tomomi
Published: January 2019

Intrinsic Optical Signal (IOS) imaging has been widely used to map patterns of brain activityin vivoin a label-free manner. Traditional IOS refers to changes in light transmission, absorption, and scattering, which have been correlated with neuronal swelling and volume changes in the observed tissue. Here we use polarized light for IOS imaging to monitor structural changes of cellular and sub-cellular architectures of neurons due to their synaptic activity in isolated brain slices. In order to reveal fast spatio-temporal changes of birefringence associated with neuronal activity, we developed the instantaneous PolScope. The instantaneous PolScope records changes in transmission, birefringence, and slow axis orientation in tissue at high spatial and temporal resolution using a single camera exposure. These capabilities enabled us to correlate polarization-sensitive IOS with traditional IOS on the same preparations. We detected reproducible spatio-temporal changes in both IOSs at the stratum radiatum in mouse hippocampal slices evoked by Schaffer collateral stimulation in the CA1 area. Upon stimulation, changes in traditional IOS signals were broadly similar across the area, while birefringence imaging revealed local variations not seen in traditional IOS. Locations with high resting birefringence produced larger stimulation-evoked birefringence changes than those with low resting birefringence. Local application of glutamate to the synaptic region in CA1 induced increase in both transmittance and birefringence signals. Blocking synaptic transmission with CNQX and D-APV (inhibitors of AMPA-and NMDA-type ionotropic glutamate receptors, respectively) reduced the peak amplitude of the optical signals. Changes in both IOSs were enhanced by an inhibitor of the membranous glutamate transporter, DL-TBOA. Our results indicate that birefringence imaging can monitor structural alterations of dendrites subjected to excitatory synaptic transmission also associated with neuronal activity in the brain.
MicroRNAs reinforce repression of PRC2 transcriptional targets independently and through a feed-forward regulatory network
Authors: Shivram Haridha , Le Steven V. , Iyer Vishwanath R.
Published: January 2019

Gene expression can be regulated at multiple levels, but it is not known if and how there is broad coordination between regulation at the transcriptional and post-transcriptional levels. Transcription factors and chromatin regulate gene expression transcriptionally, whereas microRNAs (miRNAs) are small regulatory RNAs that function post-transcriptionally. Systematically identifying the post-transcriptional targets of miRNAs and the mechanism of transcriptional regulation of the same targets can shed light on regulatory networks connecting transcriptional and post-transcriptional control. We used individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) for the RNA-induced silencing complex (RISC) component AGO2 and global miRNA depletion to identify genes directly targeted by miRNAs. We found that Polycomb repressive complex 2 (PRC2) and its associated histone mark, H3K27me3, is enriched at hundreds of miRNA-repressed genes. We show that these genes are directly repressed by PRC2 and constitute a significant proportion of direct PRC2 targets. For just over half of the genes corepressed by PRC2 and miRNAs, PRC2 promotes their miRNA-mediated repression by increasing expression of the miRNAs that are likely to target them. miRNAs also repress the remainder of the PRC2 target genes, but independently of PRC2. Thus, miRNAs post-transcriptionally reinforce silencing of PRC2-repressed genes that are inefficiently repressed at the level of chromatin, by either forming a feed-forward regulatory network with PRC2 or repressing them independently of PRC2.
Benchmarking the triple-A supply chain: orchestrating agility, adaptability, and alignment
Authors: Feizabadi Javad , Maloni Michael , Gligor David
Published: January 2019

Purpose

Limited research examines the triple-A supply chain of agility, adaptability and alignment. The purpose of this paper is to draw on extant literature under the lens of resource orchestration theory to develop a comprehensive framework of antecedents and consequences of triple-A supply chains, allowing both scholars and practitioners to benchmark and prioritize triple-A capabilities.

Design/methodology/approach

A systematic literature review focusing on four supply chain journals is conducted to integrate the distinct bodies of knowledge on supply chain agility, adaptability and alignment.

Findings

The integration of this literature identifies common and distinct antecedents and consequences of each, developing a comprehensive model of triple-A supply chains as well as proposing opportunities for further study.

Originality/value

Limited studies to date have an integrated agility, adaptability and alignment, thus lacking a comprehensive framework of triple-A supply chains. Managers can use the findings to determine actions needed to deploy triple-A capabilities and better understand the resulting potential benefits.
A comparative study of HR involvement in strategic decision-making in China and Australia
Authors: Zhao Shuming , Sheehan Cathy , De Cieri Helen , Cooper Brian
Published: January 2019

Purpose

The purpose of this paper is to address gaps in the knowledge about human resource (HR) professional involvement in strategic decision-making in China compared with that in Australia.

Design/methodology/approach

First, the authors compare the strategic involvement of Chinese and Australian HR professionals. Second, based on the upper echelon theory, the authors compare the impact of chief executive officer (CEO) and top management team (TMT) between both countries on HR involvement in strategic decision-making. Data were collected from matched pairs of HR and TMT executives in China (n= 168) and in Australia (n= 102).

Findings

Results indicate a difference, despite of no statistical significance, in HR involvement in strategic decision-making between Chinese and Australian samples. TMT behavioural integration was positively related to HR involvement in strategic decision-making in a collectivistic culture (i.e. in China), but not in an individualistic culture (i.e. in Australia). However, CEO support for HRM was positively related to HR involvement in strategic decision-making in Australia, whereas it is not related in China.

Originality/value

The paper conducts a comparative study and practical, and research implications are discussed at the end.
Endemic and cosmopolitan fungal taxa exhibit differential abundances in total and active communities of Antarctic soils
Authors: Cox Filipa , Newsham Kevin K. , Robinson Clare H.
Published: January 2019

Our understanding of the diversity and community dynamics of soil fungi has increased greatly through the use of DNA‐based identification. Community characterization of metabolically active communities via RNA sequencing has previously revealed differences between ‘active’ and ‘total’ fungal communities, which may be influenced by the persistence of DNA from nonactive components. However, it is not known how fungal traits influence their prevalence in these contrasting community profiles. In this study, we coextracted DNA and RNA from soil collected from three Antarctic islands to test for differences between total and active soil fungal communities. By matching these geographically isolated fungi against a global dataset of soil fungi, we show that widely dispersed taxa are often more abundant in the total community, whilst taxa restricted to Antarctica are more likely to have higher abundance in the active community. In addition, we find that active communities have lower richness, and show a reduction in the abundance of the most dominant fungi, whilst there are consistent differences in the abundances of certain taxonomic groups between the total and active communities. These results suggest that the views of soil fungal communities offered by DNA‐ and RNA‐based characterization differ in predictable ways.
Effects of habitat fragmentation on the functional diversity of insects in Thousand Island Lake, China
Authors: Tu Tian‐Hao , Wang Ji‐Rui , Gu Jian‐Qiang , Li Tian‐Qi , Lv Kun , Zhou Guo‐Xin , Xu Zhi‐Hong
Published: January 2019

Due to habitat fragmentation, the loss of species diversity has been extensively studied. On the contrary, the effects of habitat fragmentation on functional diversity is still poorly understood. In the Thousand Island Lake, we conducted studies of insect functional diversity on a set of 29 isolated islands. We used 10 functional diversity indices from three aspects (functional richness, functional evenness and functional divergence) to respectively describe functional diversity of insects on sample islands.

We found the following results: (i) The functional indices selected could reflect the functional diversity of sample islands and it is further proved that in general, three components of functional diversity were independent of each other; (ii) Sample islands could be divided into two categories, island JSD and the remaining islands; (iii) Functional richness increased with island area and shape index, but had no significant correlation with isolation. Likewise, both functional evenness and functional divergence had no significant correlation with island attributes. The conclusion to emphasize from our research is that: (i) habitat fragmentation reduced the biological functional diversity to some extent, further demonstrating the importance of habitat continuity in biodiversity protection; and (ii) for functional diversity protection of insects in a fragmented landscape, an island which has high approximate shape index values of at least hundred hectare magnitude order has a critical promoting effect.
Pictorial review of Morel‐Lavallée lesions
Authors: Hussein Karim , White Benjamin , Sampson Matthew , Gupta Sunil
Published: January 2019

A Morel‐Lavallée lesion is a post‐traumatic soft tissue degloving injury which presents as a haemolymphatic mass or collection. Morel‐Lavallée lesions are the result of direct trauma or shearing forces abruptly separating skin and subcutaneous tissue from underlying fascia causing disruption of perforating vessels and nerves, creating a potential space that may fill with blood, lymph and debris forming a collection. Morel‐Lavallée lesions usually occur adjacent to osseous protuberances, most commonly along the greater trochanter. Early diagnosis and management is essential to prevent complications. We present this pictorial review to highlight the imaging characteristics of Morel‐Lavallée lesions across imaging modalities to improve recognition, early diagnosis and management.
Changes in Pain Score Associated With Clinically Meaningful Outcomes in Children With Acute Pain
Authors: Tsze Daniel S. , Hirschfeld Gerrit , von Baeyer Carl L. , Suarez Leonor E. , Dayan Peter S.
Published: January 2019

Background

Identifying changes in pain score associated with clinically meaningful outcomes is necessary when using self‐report measures to assess pain in children. We aimed to determine the changes in pain score associated with a minimum clinically significant difference (MCSD), ideal clinically significant difference (ICSD), and patient‐perceived adequate analgesia (PPAA) and to evaluate for differences based on initial pain intensity and patient characteristics.

Methods

This was a cross‐sectional study of children 6 to 17 and 4 to 17 years old who were assessed using the Verbal Numerical Rating Scale (VNRS) and Faces Pain Scale–Revised (FPS‐R), respectively. Children qualitatively described any endorsed change in pain score; those who received an analgesic were asked if they wanted additional analgesics to decrease their pain intensity. We used a receiver operating characteristic curve–based methodology to identify changes in pain score associated with “a little less” and “much less” pain (MCSD and ICSD, respectively) and patients declining additional analgesics because of adequate analgesia (PPAA).

Results

We enrolled 431 children with painful conditions. For the VNRS, raw change and percent reductions in pain scores associated with MCSD, ICSD, and PPAA were 2/10 and 20%, 3/10 and 44%, and 2/10 and 29%, respectively, and for the FPS‐R, 2/10 and 33%, 4/10 and 60%, and 4/10 and 40%, respectively. Raw change in pain scores increased with increasing initial pain intensity, but percent reductions remained stable. There were no significant differences based on patient characteristics such as age, sex, and race/ethnicity.

Conclusion

Our findings provide patient‐centered outcomes in children that are suitable for designing trials and are generalizable across patient characteristics.
Bionic hand as artificial organ: Current status and future perspectives
Authors: Aman Martin , Sporer Matthias E. , Gstoettner Clemens , Prahm Cosima , Hofer Christian , Mayr Winfried , Farina Dario , Aszmann Oskar C.
Published: January 2019

Even though the hand comprises only 1% of our body weight, about 30% of our central nervous systems (CNS) capacity is related to its control. The loss of a hand thus presents not only the loss of the most important tool allowing us to interact with our environment, but also leaves a dramatic sensory‐motor deficit that challenges our CNS. Reconstruction of hand function is therefore not only an essential part of restoring body integrity and functional wholeness but also closes the loop of our neural circuits diminishing phantom sensation and neural pain. If biology fails to restore meaningful function, today we can resort to complex mechatronic replacement that have functional capabilities that in some respects even outperform biological alternatives, such as hand transplantation. As with replantation and transplantations, the challenge of bionic replacement is connecting the target with the CNS to achieve natural and intuitive control. In recent years, we have developed a number of strategies to improve neural interfacing, signal extraction, interpretation and stable mechanical attachment that are important parts of our current research. This work gives an overview of recent advances in bionic reconstruction, surgical refinements over technological interfacing, skeletal fixation, and modern rehabilitation tools that allow quick integration of prosthetic replacement.
Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes
Authors: Li Jia , Gordon Stuart C. , Rupp Loralee B. , Zhang Talan , Trudeau Sheri , Holmberg Scott D. , Moorman Anne C. , Spradling Philip R. , Teshale Eyasu H. , Boscarino Joseph A. , Schmidt Mark A. , Daida Yihe G. , Lu Mei ,   the CHeCS Investigators
Published: January 2019

Background

The role of hepatitis C (HCV) eradication on the long‐term complications of type 2 diabetes mellitus remains incompletely studied.

Aim

To investigate whether antiviral treatment impacted risk of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS).

Methods

We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine‐Gray subdistribution hazard ratio [sHR]), with death as a competing event.

Results

Among 1395 HCV‐infected patients with type 2 diabetes, 723 (52%) were treated with either interferon‐based or direct‐acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end‐stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA‐treated patients and interferon‐treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause‐specific hazards, exclusion of patients with on‐treatment retinopathy, and treatment status as a time‐varying covariate.

Conclusion

Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.
Consensus statements on the management of clinically localized prostate cancer from the Hong Kong Urological Association and the Hong Kong Society of Uro‐Oncology
Authors: Ma Wai‐Kit , Poon Darren Ming‐Chun , Chan Chi‐Kwok , Chan Tim‐Wai , Cheung Foon‐Yiu , Ho Lap‐Yin , Lee Eric Ka‐Chai , Leung Angus Kwong‐Chuen , Leung Simon Yiu‐Lam , So Hing‐Shing , Tam Po‐Chor , Kwong Philip Wai‐Kay
Published: January 2019

Objective

To formulate consensus statements to facilitate physician management strategies for patients with clinically localized prostate cancer (PCa) in Hong Kong by jointly convening a panel of 12 experts from the two local professional organizations representing PCa specialists, who had previously established consensus statements on the management of metastatic PCa for the locality.

Methods

Through a series of meetings, the panellists discussed their clinical experience and the published evidence regarding various areas of the management of localized PCa, then drafted consensus statements. At the final meeting, each drafted statement was voted on by every panellist based on its practicability of recommendation in the locality.

Results

A total of 76 consensus statements were ultimately accepted and established by panel voting.

Conclusion

Derived from the recent evidence and major overseas guidelines, along with local clinical experience and practicability, the consensus statements were aimed to serve as a practical reference for physicians in Hong Kong for the management of localized PCa.
Fire‐sensitive species dominate seed rain after fire suppression: Implications for plant community diversity and woody encroachment in the Cerrado
Authors: Mariano Vanessa , Rebolo Isabele F. , Christianini Alexander V.
Published: January 2019

Woody encroachment is becoming common in tropical savannas. We studied natural seed rain and performed seed addition experiments in a Brazilian savanna that had not been burned for several decades. We found greater abundance of fire‐sensitive species in the seed rain, likely contributing to woody encroachment. Flexible fire management policies that allow for natural and prescribed fires may be required to maintain savanna diversity.
“I'm not what I used to be”: A qualitative study exploring how young people experience being diagnosed with a chronic illness
Authors: Kirk Susan , Hinton Denise
Published: January 2019

Background

Childhood long‐term conditions are usually diagnosed in infancy or early childhood. Little is known about the particular experiences and needs of young people who receive a chronic illness diagnosis during adolescence or late childhood. This paper will examine this experience in relation to multiple sclerosis (MS), which is increasingly being diagnosed before adulthood.

Aims

To explore how young people experience an MS diagnosis.

Methods

Qualitative study using a grounded theory approach. In‐depth interviews were conducted with 21 young people diagnosed with MS. Participants were recruited through health service and voluntary sector organizations in the United Kingdom.

Results

Young people's pre‐illness normality was disrupted by the diagnosis of a chronic illness (MS). Participants experienced their body as changed physically, cognitively, and emotionally and as changeable due to symptom unpredictability. This influenced how participants perceived and presented their identity, disrupted their relationships, and altered their future biography. Young people developed strategies to manage their condition and identities in order to incorporate MS into their current and future lives, which required continual illness and identity work in response to changing symptoms, social contexts, and relationships.

Conclusions

Although young peoples' experience of living with chronic illness has been widely explored, the aftermath of diagnosis has been underresearched from their perspective. This study contributes to this knowledge gap by illuminating how young people experience a chronic illness diagnosis and negotiate the resulting changes to their identity, relationships, and future. The findings suggest that young people need preparation and support in disclosing their diagnosis to others. Professionals supporting young people with long‐term conditions need to work closely with specialist mental health services to ensure that they receive appropriate emotional support. Schools have an important role in ensuring young people with long‐term conditions achieve their academic potential and receive appropriate careers advice.