bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating interaction networks into the determination of functionally related hit genes in genomic experiments with Markov random fields
Authors: Robinson Sean , Nevalainen Jaakko , Pinna Guillaume , Campalans Anna , Radicella J Pablo , Guyon Laurent
Published: April 2017

Motivation

Incorporating gene interaction data into the identification of ‘hit’ genes in genomic experiments is a well-established approach leveraging the ‘guilt by association’ assumption to obtain a network based hit list of functionally related genes. We aim to develop a method to allow for multivariate gene scores and multiple hit labels in order to extend the analysis of genomic screening data within such an approach.

Results

We propose a Markov random field-based method to achieve our aim and show that the particular advantages of our method compared with those currently used lead to new insights in previously analysed data as well as for our own motivating data. Our method additionally achieves the best performance in an independent simulation experiment. The real data applications we consider comprise of a survival analysis and differential expression experiment and a cell-based RNA interference functional screen.

Availability and implementation

We provide all of the data and code related to the results in the paper.

Supplementary information

Supplementary data are available at Bioinformatics online.
Age of Migration Differentials in Life Expectancy With Cognitive Impairment: 20-Year Findings From the Hispanic-EPESE
Authors: Garcia Marc A , Saenz Joseph L , Downer Brian , Chiu Chi-Tsun , Rote Sunshine , Wong Rebeca
Published: April 2017

Background and Objectives

To examine differences in life expectancy with cognitive impairment among older Mexican adults according to nativity (U.S.-born/foreign-born) and among immigrants, age of migration to the United States.

Research Design and Methods

This study employs 20 years of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly to estimate the proportion of life spent cognitively healthy and cognitively impaired prior to death among older Mexican adults residing in the southwestern United States. We combine age-specific mortality rates with age-specific prevalence of cognitive impairment, defined as a Mini-Mental Status Exam score of less than 21 points to calculate Sullivan-based life table models with and without cognitive impairment in later life.

Results

Foreign-born Mexican immigrants have longer total life expectancy and comparable cognitive healthy life expectancy regardless of gender compared to U.S.-born Mexican-Americans. However, the foreign-born spend a greater number of years after age 65 with cognitive impairment relative to their U.S.-born counterparts. Furthermore, we document an advantage in life expectancy with cognitive impairment and proportion of years after age 65 cognitively healthy among mid-life immigrant men and women relative to early- and late-life migrants.

Discussion and Implications

The relationship between nativity, age of migration, and life expectancy with cognitive impairment means that the foreign-born are in more need of support and time-intensive care in late life. This issue merits special attention to develop appropriate and targeted screening efforts that reduce cognitive decline for diverse subgroups of older Mexican-origin adults as they age.
Hybrid de novo genome assembly of the Chinese herbal fleabane Erigeron breviscapus
Authors: Yang Jing , Zhang Guanghui , Zhang Jing , Liu Hui , Chen Wei , Wang Xiao , Li Yahe , Dong Yang , Yang Shengchao
Published: April 2017

Background: The plants in the Erigeron genus of the Compositae (Asteraceae) family are commonly called fleabanes, possibly due to the belief that certain chemicals in these plants repel fleas. In the traditional Chinese medicine, Erigeron breviscapus, which is native to China, was widely used in the treatment of cerebrovascular disease. A handful of bioactive compounds, including scutellarin, 3,5-dicaffeoylquinic acid, and 3,4-dicaffeoylquinic acid, have been isolated from the plant. With the purpose of finding novel medicinal compounds and understanding their biosynthetic pathways, we propose to sequence the genome of E. breviscapus. Findings: We assembled the highly heterozygous E. breviscapus genome using a combination of PacBio single-molecular real-time sequencing and next-generation sequencing methods on the Illumina HiSeq platform. The final draft genome is approximately 1.2 Gb, with contig and scaffold N50 sizes of 18.8 kb and 31.5 kb, respectively. Further analyses predicted 37 504 protein-coding genes in the E. breviscapus genome and 8172 shared gene families among Compositae species. Conclusions: The E. breviscapus genome provides a valuable resource for the investigation of novel bioactive compounds in this Chinese herb.
Solid Papillary Breast Carcinomas Resembling the Tall Cell Variant of Papillary Thyroid Neoplasms
Authors: Foschini Maria P. , Asioli Sofia , Foreid Susan , Cserni Gabor , Ellis Ian O. , Eusebi Vincenzo , Rosai Juan
Published: April 2017

Thirteen cases of invasive solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (BPTC) are reported here. Some cases had long-term follow-up. BPTC is a special type of primary breast neoplasm showing a triple-negative profile but low aggressive potential. Knowledge on BPTC is still scanty; therefore, the aim of the present paper was to report on the features of an additional 13 cases. All the patients were female individuals, and the mean age at presentation was 62.6 years; nodule sizes ranged from 0.6 to 2.5 cm (average, 1.6 cm). All the cases were characterized on histology by papillary, follicular as well as solid structures. The cells were columnar, eosinophilic mostly with granular cytoplasms, rich in mitochondria, with the features of oncocytes in no fewer than 7 cases. Estrogen and progesterone receptors as well as HER2 were consistently negative. The Ki67 proliferative index was low. Markers consistent with thyroid origin, such as TTF1 and thyroglobulin, were negative. Five cases stained for mammoglobin and GATA 3 were positive. All cases proved to be invasive and 2 cases each experienced metastases to 1 lymph node (axillary and intramammary). One case of the latter had a local recurrence. Nevertheless, all the patients are alive, free of disease 24 to 132 months after surgery, of which 8 are without further treatment The present series confirms that BPTC is a primary breast tumor of low malignant potential.
Kidney Biopsy Yield
Authors: Sekulic Miroslav , Crary Gretchen S.
Published: April 2017

Kidney biopsies are conducted under varying scenarios, presenting variables that could potentially influence yield and adequacy of tissue collected. We retrospectively reviewed 636 native and allograft kidney biopsies, and compared tissue collected between differing practitioners performing the biopsy (nephrologists or radiologists), imaging modalities for guidance (ultrasound or computed tomography), gauge needle used (18 or 16 G), and between on-site evaluators of biopsy adequacy conducted at the time of biopsy (general pathologists, renal pathologists, nephrologists). For radiologists using ultrasound guidance and 18 G needles, those using on-site evaluation of adequacy collected more glomeruli and glomeruli per length of tissue core than those not using on-site evaluation. Radiologists not using on-site evaluation but who used a larger bore needle (16 vs. 18 G) could generally collect comparable tissue as other biopsy performers who used on-site evaluation. Radiologists performing ultrasound-guided biopsies with 18 G needles without on-site evaluation consistently provided poorer tissue yield and had a higher rate of providing insufficient tissue so that a diagnosis could not be rendered. Nephrologists collected less total length of tissue cores, glomeruli, and arteries per case (whether performing the biopsy and/or performing on-site adequacy) compared with other groups using on-site evaluation, however, providing comparable density of glomeruli and arteries. Complication rates did not differ between compared groups using 18 G needles. It is our observation that the various conditions by which a kidney biopsy is obtained influences the yield of tissue collected and the subsequent ability for a pathologist to effectively provide a diagnosis.
An Unanticipated Complication of Atopic Dermatitis
Authors: MacGillivray Megan E. , Fiorillo Loretta
Published: April 2017

An infant with a history of atopic dermatitis presented to the emergency department on 5 occasions with flulike symptoms. Eventually, this child presented with signs of infection and increased intracranial pressure: fever, bulging anterior fontanel, and leukocytosis. A computed tomography scan identified a large frontal lobe brain abscess. The abscess was surgically drained; culture was positive for Staphylococcus aureus. The initial source of the infected brain abscess was explored. Ultimately, it was thought to be secondary to impetiginized atopic dermatitis, an unusual but serious consequence of a common skin condition.
The Evaluation of Trauma Care
Authors: Bal Alkan , Cooper Michael , Lee Amanda , Anil Murat , Hennes Halim
Published: April 2017

Objective

The purpose of the study is to compare the outcomes of pediatric trauma patients with motor vehicle crashes (MVCs) and motor vehicle versus pedestrian crashes (MPCs) at a level 1 pediatric trauma center in the United States and a pediatric trauma center in Turkey.

Methods

The medical records of all pediatric MVC and MPC subjects presenting to the emergency departments (EDs) of a level 3 hospital in Turkey (Izmir Tepecik Training and Research Hospital [ITTRH]) and a level 1 pediatric trauma center in the United States (Children's Medical Center Dallas [CMCD]) over a 1-year period were reviewed. Data that were collected include patient demographics, prehospital report (mechanism of injury, mode of transportation), injury severity score (ISS), abbreviated injury scale score, Glasgow Coma Scale score, ED length of stay, ED interventions, ED and hospital disposition, and mortality. Patients with moderate (ISS, 5–15) and severe (ISS, >15) trauma scores were included in the study.

Results

One hundred six patient charts from the ITTRH and 125 patient charts from the CMCD with moderate and severe ISS due to MVCs and MPCs were reviewed. Most of the patients were pedestrians (86%) in the ITTRH group and passengers (60%) in the CMCD group. The percentage of patients transferred by ambulance (ground or air) to the CMCD and the ITTRH was 97.9% and 85%, respectively. Fifteen percent of ITTRH patients and 2.1% of CMCD patients arrived by private vehicle. Emergency department arrival ISS and Glasgow Coma Scale were similar between the 2 hospitals (P > 0.05). The overall mortality rate in the study population was 8.8% (11/125) at the CMCD and 4.7% (5/106) at the ITTRH. (P = 0.223). Blood product utilization was significantly higher in the CMCD group compared with the ITTRH group (P = 0.005). The use of hypertonic saline/mannitol/hyperventilation in patients with significant head trauma and increased intracranial pressure was higher in the ITTRH group (P = 0.000).

Conclusions

This is the first study that compared pediatric trauma care and outcome at a level 1 pediatric trauma center in the United States and a pediatric hospital in Turkey. Our findings highlight the opportunities to improve pediatric trauma care in Turkey. Specifically, there is a need for national trauma registries, enhanced trauma education, and standardized trauma patient care protocols. In addition, efforts should be directed toward improving prehospital care through better integration within the health care system and physician participation in educating prehospital providers. Data and organized trauma care will be instrumental in system-wide improvement and developing appropriate injury-prevention strategies.
Complexities of Consent
Authors: Dreisinger Naomi , Zapolsky Nathan
Published: April 2017

Informed consent is a communicative process of sharing information with patients, which helps assure their understanding of the information provided and asks for their permission to proceed. Informed consent allows a patient or a patient's family to use his or her own value system to determine the need for a particular procedure or test. Asking a patient for permission to treat requires the provider to respect the patient's autonomy through allowing him or her to be an active part of the decision-making process. Consent in the pediatric emergency department can be a complex process. Parental consent is generally required for medical evaluation and treatment of pediatric patients, but in the pediatric emergency department, there are exceptions to this rule. If the provider determines that a parent's refusal of consent places the child at risk of harm, then consent is not necessary. By using the concepts of Emergency Medical Treatment and Active Labor Act, in emergent situations, consent may not be necessary. Finally, adolescents are often deeply concerned about privacy—their acceptance of appropriate care is often based on this promise of confidentiality. In the emergency department, adolescents can therefore be treated for issues relating to reproductive care without parental consent. It is important for the emergency department physician to understand the rules surrounding the care of pediatric patients to avoid compromising their privacy and ultimately their well-being and medical care.
Performance of Virological Testing for Early Infant Diagnosis: A Systematic Review
Authors: Mallampati Divya , Ford Nathan , Hanaford Alisse , Sugandhi Nandita , Penazzato Martina
Published: April 2017

Background:

Improved access to both maternal antiretroviral therapy and infant prophylaxis may have an impact on the performance of virological assays for diagnosis of HIV infection in infants. This systematic review was performed to assess the diagnostic accuracy of virological testing at birth as well as the performance of virological testing on dried blood spots at 6 weeks among HIV- and antiretroviral (ARV)-exposed infants.

Methods:

A systematic review was performed for studies published between January 1, 2009 and January 30, 2015. The search strategy included studies related to HIV, nucleic acid amplification tests, and newborns/infants and queried PubMed, Embase, the Cochrane Library, LILACS as well as several conference proceedings. Two independent reviewers collected studies and extracted data. The final analysis includes summary estimates of the sensitivities and specificities of the virological assays assessed. The GRADE approach was used to assess the overall quality of evidence and Quality Assessment of Diagnostic Accuracy Studies was used to evaluate the risk of bias in the studies.

Results:

A total of 2243 records were screened with a final selection of 5 manuscripts. To assess the test characteristics of virological testing at birth, 2 studies were used to calculate a pooled sensitivity of 69.3% (95% confidence interval: 61.1 to 77.4) and a specificity of 99.9% (98.6–100%). The quality of evidence to support the sensitivity of assays at birth was low, whereas the quality of evidence for the specificity of such tests was intermediate-high. In terms of the performance of virological testing on dried blood spots for HIV- and ARV-exposed infants, 3 studies were used to calculate a pooled sensitivity of 99.4% (98.3–100.00%) and specificity of 99.6% (99.1–100.00%). The quality of evidence for both outcomes was low.

Conclusion:

The performance of polymerase chain reaction at birth demonstrates low sensitivity and high specificity, reflecting the difficulty of detecting intrapartum infections at birth and transmission dynamics. In addition, there is no evidence to suggest poor performance of virological testing on dried blood spots for ARV-exposed infants. Overall, given the very limited and low-quality evidence, further research is needed to assess the accuracy of polymerase chain reaction at different time points and in the context of more effective prevention of mother-to-child transmission interventions.
Interrelations of Epicardial Fat Volume, Left Ventricular T1-Relaxation Times and Myocardial Strain in Hypertensive Patients
Authors: Homsi Rami , Kuetting Daniel , Sprinkart Alois , Steinfeld Nina , Meier-Schroers Michael , Luetkens Julian , Nadal Jennifer , Dabir Darius , Fischer Stefan , Gieseke Juergen , Schild Hans , Thomas Daniel
Published: April 2017

Purpose:

This cardiac magnetic resonance study was performed to assess myocardial fibrosis by evaluating T1-relaxation time (T1), to measure left ventricular (LV) strain, and to determine epicardial fat volume (EFV) in hypertensive patients with no history of cardiovascular (CV) events and to relate the results to the presence of coronary atherosclerotic artery disease (CAD) in these patients.

Materials and Methods:

A total of 123 subjects were examined at 1.5 T. Of them, 98 were hypertensive patients (58 men; mean age, 62.9±10.7 y; body mass index, 29.0±5.6 kg/m2) and 25 were controls without CV risk factors or disease (13 men; 60.1±10.7 y; 28.1±5.4 kg/m2). All patients had a well-treated blood pressure. In the hypertensive group, 56 patients had no CAD, whereas 42 patients had CAD. T1 was assessed by a modified Look-Locker inversion recovery sequence. Longitudinal and circumferential peak systolic strain (LS; CS) was determined with dedicated cardiac magnetic resonance software (feature tracking). EFV (normalized to the body surface area) was assessed by a 3D Dixon sequence.

Results:

T1 (ms) and EFV (mL/m2) were higher and CS and LS (%) were lower in hypertensive patients compared with those in nonhypertensive controls (P<0.05), independent of the presence of CAD (controls: T1=967.2±16.9, LS=−25.2±4.6, CS=−28.7±5.0, EFV=58.2±21.1; hypertensive patients overall: T1=991.3±45.5, LS=−21.0±4.5, CS=−25.0±5.9, EFV=71.1±25.3; hypertensive patients without CAD: T1=991.6±48.4, LS=−21.0±4.7, CS=−24.6±6.3, EFV=71.3±26.6; hypertensive patients with CAD: T1=986.7±39.2, LS=−21.1±4.3, CS=−25.5±5.4, EFV=70.9±23.6). There were no significant differences between hypertensive patients with and those without CAD and between patients grouped according to the number of vessels affected (0-vessel disease, 1-vessel disease, 2-vessel disease, or 3-vessel disease).

Conclusions:

Hypertension is associated with signs of myocardial fibrosis and an impaired LV contractility despite a normal LV ejection fraction, as well as with an increased EFV. However, CAD, in the absence of previous pathologies with consecutive myocardial ischemic damage, did not additionally affect these parameters.
Computed Tomography Angiographic Assessment of Acute Chest Pain
Authors: Miller Matthew M. , Ridge Carole A. , Litmanovich Diana E.
Published: April 2017

Acute chest pain is a leading cause of Emergency Department visits. Computed tomography angiography plays a vital diagnostic role in such cases, but there are several common challenges associated with the imaging of acute chest pain, which, if unrecognized, can lead to an inconclusive or incorrect diagnosis. These imaging challenges fall broadly into 3 categories: (1) image acquisition, (2) image interpretation (including physiological and pathologic mimics), and (3) result communication. The aims of this review are to describe and illustrate the most common challenges in the imaging of acute chest pain and to provide solutions that will facilitate accurate diagnosis of the causes of acute chest pain in the emergency setting.
Invasive Candida Infections in Liver Transplant Recipients: Clinical Features and Risk Factors for Mortality
Authors: Bassetti Matteo , Peghin Maddalena , Carnelutti Alessia , Righi Elda , Merelli Maria , Ansaldi Filippo , Trucchi Cecilia , Alicino Cristiano , Sartor Assunta , Wauters Joost , Lagrou Katrien , Tascini Carlo , Menichetti Francesco , Mesini Alessio , De Rosa Francesco G. , Lagunes Leonel , Rello Jordi , Colombo Arnaldo L. , Vena Antonio , Munoz Patricia , Tumbarello Mario , Sganga Gabriele , Martin-Loeches Ignacio , Viscoli Claudio
Published: April 2017

Background

Invasive fungal infections remain a leading cause of morbidity and mortality among liver transplant recipients (LTRs). In this patient population, invasive Candida infections (ICIs) account for the large majority of cases. To date, only small studies and case-series analysing clinical presentation and risk factors for mortality in LTRs with ICIs are available.

Methods

We performed a retrospective multicenter multinational study in 10 centers in Europe and Brazil. All consecutive LTRs developing ICIs during the period January 2011 to December 2013 were included in the study.

Results

A total of 42 LTRs were included. Median age was 52.5 years, and 78.6% of patients were men. Viral hepatitis was the most common cause for liver transplantation (42.9%). Candidemia represented the majority of cases (24, 57.1%), followed by intra-abdominal candidiasis (18, 42.9%). Overall 30-day mortality was 23.8%, with higher mortality in patients with candidemia compared with intra-abdominal candidiasis (37.5% vs 5.6%, P = 0.02). Multivariate analysis showed candidemia to be a risk factor associated with mortality among LTRs presenting ICIs (odds ratio, 11.86; 95% confidence interval, 1.5-280; P = 0.01). Candida albicans represented the most common isolate (59.5%). High rates of antifungal resistances were found, with 16.7% and 4.8% of isolates displaying resistance to azoles and caspofungin, respectively.

Conclusions

Our study confirms the occurrence of high mortality rates in LTRs developing ICIs. Mortality rates varied according to the type of infection, with candidemia representing a risk factor for mortality. The high rates of antifungal resistance should be considered in the choice of the empiric antifungal regimen.
Remotely distinguishing and mapping endogenic water on the Moon
Authors: Klima Rachel L. , Petro Noah E.
Published: April 2017

Water and/or hydroxyl detected remotely on the lunar surface originates from several sources: (i) comets and other exogenous debris; (ii) solar-wind implantation; (iii) the lunar interior. While each of these sources is interesting in its own right, distinguishing among them is critical for testing hypotheses for the origin and evolution of the Moon and our Solar System. Existing spacecraft observations are not of high enough spectral resolution to uniquely characterize the bonding energies of the hydroxyl molecules that have been detected. Nevertheless, the spatial distribution and associations of H, OH
−
or H
2
O with specific lunar lithologies provide some insight into the origin of lunar hydrous materials. The global distribution of OH
−
/H
2
O as detected using infrared spectroscopic measurements from orbit is here examined, with particular focus on regional geological features that exhibit OH
−
/H
2
O absorption band strengths that differ from their immediate surroundings.

This article is part of the themed issue ‘The origin, history and role of water in the evolution of the inner Solar System’.
Biologics-associated Risks for Incident Skin and Soft Tissue Infections in Psoriasis Patients: Results from Propensity Score-Stratified Survival Analysis
Authors: Liu Su-Hsun , Hsieh Tsung-Han , Chen Leslie Y , Huang Yhu-Chering , Huang Yu-Huei
Published: April 2017

Background

How biologics affect psoriasis patients’ risks for SSTIs in a pragmatic clinical setting remains unclear.

Methods

In a cohort of adult psoriasis outpatients (aged 20 years or older) who visited the Dermatology Clinic in 2010-2015, we compared incident SSTI risks between patients using biologics (users) versus nonbiologics (nonusers). We also estimated SSTI risks in biologics-associated time-periods relative to nonbiologics only in users. We applied random effects Cox proportional hazard models with propensity score-stratification to account for differential baseline hazards.

Results

Over a median follow-up of 2.8 years (interquartile range: 1.5, 4.3), 172 of 922 patients ever received biologics (18.7%); 233 SSTI incidents occurred during 2518.3 person-years, with an overall incidence of 9.3/100 person-years (95% confidence interval [CI]: 8.1, 10.6). In univariate analysis, users showed an 89% lower risk for SSTIs than nonusers (hazard ratio [HR]: 0.11, 95%CI: 0.05, 0.26); the association persisted in a multivariable model (adjusted HR: 0.26, 95%CI: 0.12, 0.58). Among biologics users, biologics-exposed time-periods were associated with a nonsignificant 21% increased risk (adjusted HR: 1.21, 95%CI: 0.41, 3.59).

Conclusions

Despite of adjusting for the underlying risk profiles, risk comparisons between biologics users and nonusers remained confounded by treatment selection. By comparing time-periods being exposed versus unexposed to biologics among users, the current analysis did not find evidence for an increased SSTI risk that was associated with biologics use in psoriasis patients.
Experience-dependent plasticity in accessory olfactory bulb interneurons following male-male social interaction
Authors: Cansler Hillary L. , Maksimova Marina A. , Meeks Julian P.
Published: April 2017

Chemosensory information processing in the mouse accessory olfactory system (AOS) guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC-interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit. Here, we describe targeted electrophysiological studies of AOB inhibitory internal granule cells (IGCs), many of which upregulate the immediate-early geneArcafter male-male social experience. Following the resident-intruder paradigm,Arc-expressing IGCs in acute AOB slices from resident males displayed stronger excitation than non-expressing neighbors when sensory inputs are stimulated. The increased excitability ofArc-expressing IGCs was not correlated with changes in the strength or number of excitatory synapses with MCs, but was instead associated with increased intrinsic excitability and decreased HCN channel-mediated IHcurrents. Consistent with increased inhibition by IGCs, MCs responded to sensory input stimulation with decreased depolarization and spiking following resident-intruder encounters. These results reveal that non-mating behaviors drive AOB inhibitory plasticity, and indicate that increased MC inhibition involves intrinsic excitability changes inArc-expressing interneurons.

Significance Statement

The accessory olfactory bulb (AOB) is a site of experience-dependent plasticity between excitatory mitral cells (MCs) and inhibitory internal granule cells (IGCs), but the physiological mechanisms and behavioral conditions driving this plasticity remain unclear. Here, we report studies of AOB neuronal plasticity following male-male social chemosensory encounters. We show that the plasticity-associated immediate-early geneArcis selectively expressed in IGCs from resident males following the resident-intruder assay. After behavior,Arc-expressing IGCs are more strongly excited by sensory input stimulation and MC activation is suppressed.Arc-expressing IGCs do not show increased excitatory synaptic drive, but instead show increased intrinsic excitability. These data indicate that MC-IGC plasticity is induced after male-male social chemosensory encounters, resulting in enhanced MC suppression byArc-expressing IGCs.
Transcript isoform differences across human tissues are predominantly driven by alternative start and termination sites of transcription
Authors: Reyes Alejandro , Huber Wolfgang
Published: April 2017

Most human genes have multiple transcription start and polyadenylation sites, as well as alternatively spliced exons. Although such transcript isoform diversity contributes to the differentiation between cell types, the importance of contributions from the different isoform generating processes is unclear. To address this question, we used 798 samples from the Genotype-Tissue Expression (GTEx) to investigate cell type dependent differences in exon usage of over 18,000 protein-coding genes in 23 cell types. We found tissue-dependent isoform usage in about half of expressed genes. Overall, tissue-dependent splicing accounted only for a minority of tissue-dependent exon usage, most of which was consistent with alternative transcription start and termination sites. We verified this result on a second, independent dataset, Cap Analysis of Gene Expression (CAGE) data from the FANTOM consortium, which confirmed widespread tissue-dependent usage of alternative transcription start sites. Our analysis identifies transcription start and termination sites as the principal drivers of isoform diversity across tissues. Moreover, our results indicate that most tissue-dependent splicing involves untranslated exons and therefore may not have consequences at the proteome level.
Learning the high-dimensional immunogenomic features that predict public and private antibody repertoires
Authors: Greiff Victor , Weber Cédric R. , Palme Johannes , Bodenhofer Ulrich , Miho Enkelejda , Menzel Ulrike , Reddy Sai T.
Published: April 2017

Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which are defined as antibody or T-cell receptor (TCR) clonal sequences shared across individuals. As of yet, it has remained unclear whether public clones possess predictable sequence features that separate them from private clones, which are believed to be generated largely stochastically. This knowledge gap represents a lack of insight into the shaping of immune repertoire diversity. Leveraging a machine learning approach capable of capturing the high-dimensional compositional information of each clonal sequence (defined by the complementarity determining region 3, CDR3), we detected predictive public- and private-clone-specific immunogenomic differences concentrated in the CDR3’s N1-D-N2 region, which allowed the prediction of public and private status with 80% accuracy in both humans and mice. Our results unexpectedly demonstrate that not only public but also private clones possess predictable high-dimensional immunogenomic features. Our support vector machine model could be trained effectively on large published datasets (3 million clonal sequences) and was sufficiently robust for public clone prediction across studies prepared with different library preparation and high-throughput sequencing protocols. In summary, we have uncovered the existence of high-dimensional immunogenomic rules that shape immune repertoire diversity in a predictable fashion. Our approach may pave the way towards the construction of a comprehensive atlas of public clones in immune repertoires, which may have applications in rational vaccine design and immunotherapeutics.
A macrophage response toMycobacterium lepraephenolic glycolipid initiates nerve damage in leprosy
Authors: Madigan Cressida A. , Cambier C.J. , Kelly-Scumpia Kindra M. , Scumpia Philip O. , Cheng Tan-Yun , Zailaa Joseph , Bloom Barry R. , Moody D. Branch , Smale Steven T. , Sagasti Alvaro , Modlin Robert L. , Ramakrishnan Lalita
Published: April 2017

Mycobacterium lepraecauses leprosy, and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interactions of theM. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia, and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events ofM. leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated byM. lepraebut by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected withM. marinumexpressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages toM. lepraePGL-1 in initiating nerve damage in leprosy.
TGH: Trans-Generational Hormesis and the Inheritance of Aging Resistance
Authors: Fang Ng Li , Suresh Jahnavi , Chaithanya Krishna , Linfan Xiao , Tan Tuan Zea , Gruber Jan , Tolwinski Nicholas S.
Published: April 2017

Animals respond to dietary changes by adapting their metabolism to available nutrients through insulin and insulin-like growth factor signalling. Restricting calorie intake generally extends life and health span, butDrosophilafed non-ideal sugars such as galactose are stressed and have shorter life spans. Here, we report that although these flies have shorter life spans, their offspring show significant life extension if switched to a normal sugar (glucose) diet. We define this as TGH or trans-generational hormesis, a beneficial effect that comes from a mild stress. We trace the effects to changes in stress responses in parents, ROS production, effects on lipid metabolism, and changes in chromatin and gene expression. We find that this mechanism is similar to what happens to the long livedIndymutants on normal food, but surprisingly find thatIndyis required for life span extension for galactose fed flies.Indymutant flies grown on galactose do not live longer as do their siblings grown on glucose, rather overexpression of Indy rescues lifespan for galactose reared flies. We define a process where sugar metabolism can generate epigenetic changes that are inherited by offspring, providing a mechanism for how transgenerational nutrient sensitivities are passed on.
Enzymes and Substrates Are Balanced at Minimal Combined Mass Concentrationin vivo
Authors: Dourado Hugo , Maurino Veronica G. , Lercher Martin J.
Published: April 2017

A fundamental problem in biology is how cells organize their resource investment. Cellular metabolism, for example, typically involves hundreds of enzymes and metabolites, but it is unclear according to which principles their concentrations are set. Reasoning that natural selection will drive cells towards achieving a given physiological state at minimal cost, we derive a general equation that predicts the concentration of a metabolite from the concentration of the most abundant and costly enzyme consuming it. Simulations of cellular growth as well as experimental data demonstrate that costs are approximately proportional to molecular masses. For effectively irreversible reactions, the cell maximizes its metabolic efficiency by investing equally into substrate and unbound enzyme molecules. Without fitting any free parameters, the resulting model predictsin vivosubstrate concentrations from enzyme concentrations and substrate affinities with high accuracy across data fromE. coliand diverse eukaryotes (R2=0.79, geometric mean fold-error 1.74). The corresponding organizing principle – the minimization of the summed mass concentrations of solutes – may facilitate reducing the complexity of kinetic models and will contribute to the design of more efficient synthetic cellular systems.
A model for autonomous and non-autonomous effects of the Hippo pathway inDrosophila
Authors: Gou Jia , Lin Lin , Othmer Hans G.
Published: April 2017

While significant progress has been made toward understanding morphogen-mediated patterning in development from both the experimental and the theoretical side, the control of size and shape of tissues and organs is poorly understood. Both involve adjustment of the scale of gene expression to the size of the system, but how growth and patterning are coupled to produce scale invariance and how molecular-level information is translated into organ- and organism-level functioning is one of the most difficult problems in biology. The Hippo pathway, which controls cell proliferation and apoptosis inDrosophilaand mammalian cells, contains a core kinase mechanism that affects control of the cell cycle and growth. Studies involving over- and under-expression of components in the morphogen and Hippo pathways inDrosophilareveal conditions that lead to over- or undergrowth. Herein we develop a mathematical model that incorporates the current understanding of the Hippo signal transduction network and which can explain qualitatively both the observations on whole-disc manipulations and the results arising from mutant clones. We find that a number of non-intuitive experimental results can be explained by subtle changes in the balances between inputs to the Hippo pathway. Since signal transduction and growth control pathways are highly conserved across species, much of what is learned aboutDrosophilaapplies in higher organisms, and may have direct relevance to tumor dynamics in mammalian systems.
Does motivation matter? The influence of the agency perspective on temporary agency workers
Authors: Chen Pei-Chen , Wang Ming-Chao , Fang Shih-Chieh
Published: April 2017

Purpose

Based on agency perspective on temporary agency workers, the purpose of this paper is to explore the relationship between firms’ agency problems and agency cost on agency workers; moreover, intrinsic motivation and extrinsic motivation are considered in seeking to understand how they moderate this relationship.

Design/methodology/approach

Using the Hsinchu Science Park directory of corporate affiliations as a sample frame, the authors adopted a paired questionnaire which included two parts in order to consider the possible problem of common method variances. The first part is completed by the manager of the firms and the second part is completed by his/her temporary agency workers. Finally, 94 firms completed questionnaires, providing a total sample of 94 R&D managers and 458 temporary agency workers. The rate of participation was 31.65 percent.

Findings

Using a questionnaire survey of 94 high-tech firms, from which a total of 94 R&D managers and 458 temporary agency workers participated, the results show that firms’ agency problems have a positive influence on the agency cost of monitoring temporary agency workers. In addition, while this relationship is negatively moderated by extrinsic motivation, intrinsic motivation has a non-significant moderating effect.

Originality/value

The managers of firms should consider not only the short-term flexibility of employing temporary agency workers, but also the long-term cultivation of promoting great agency workers. This could maximize the efficiency of the interaction between intrinsic motivation and extrinsic motivation. Of course, the firms should think about how to reduce the agency problems created by goal conflict, information asymmetry and risk sharing with temporary agency workers, because this could also provide a chance for the firms to decrease agency costs spent on monitoring.
Team-member exchange, voice behavior, and creative work involvement
Authors: Shih Hsi-An , Wijaya Nikodemus Hans Setiadi
Published: April 2017

Purpose

The purpose of this paper is to conceptualize the links among team-member exchange (TMX), voice behavior, and creative work involvement.

Design/methodology/approach

A total of 260 employees were participants in this study. All were alumni of a Business School in Indonesia. Data were gathered at two time points four months apart. Hierarchical regression and bootstrapping analyses were conducted to find the effects of TMX on voice behavior and creative work involvement.

Findings

Results from the analyses showed positive effects of TMX on both voice behavior and creative work involvement. A positive effect of voice behavior on creative work involvement was found. The results also exhibited a partial mediating effect of voice behavior on the relationship between TMX and creative work involvement.

Practical implications

The findings point to the importance of maintaining TMX quality in work teams for enhancing employee voice and creativity. Organizations may need to develop members’ reciprocal relationship skill in teams and maintain the roles of team leaders to develop the quality of TMX. It is also suggested that the practice of self-management teams may enhance the quality of TMX and voice behavior of employees.

Originality/value

This paper offers new insight on how levels of TMX may impact on members’ voice behavior and creative work involvement. Longitudinal data may provide a more accurate prediction of the links among TMX, voice behavior, and creative work involvement.
Antecedents of social media usage and performance benefits in small- and medium-sized enterprises (SMEs)
Authors: Odoom Raphael , Anning-Dorson Thomas , Acheampong George
Published: April 2017

Purpose

Despite the blossoming nature of social media marketing, the nuances and implications among small- and medium-sized enterprises (SMEs) appear to be under-researched in literature. The purpose of this paper is to progress knowledge and offer extended understanding of the motivations and performance benefits of social media accrued by SMEs with an empirical study from an emerging economy.

Design/methodology/approach

Based on past research, the study hypothesizes that interactivity, compatibility and cost effectiveness are motivations germane to social media usage, which consequently offer performance benefits. Data from 210 SMEs (having Facebook and/or Twitter accounts) are employed to investigate the proposed conceptual model using structural equation modeling with sub-group analysis.

Findings

Finding from this study demonstrate that the interdependencies of social media motivations, as well as effects of social media usage are positive but erratic across product-based and service-based SMEs. Moreover, SMEs who offer physical products are more likely to employ social media based on cost-effective motives while service SMEs are more likely to consider interactivity as a key motivation. Additionally, findings from the study data suggest that in a tale of two sites, Facebook proved to edge Twitter in terms of engendering performance benefits among SME users.

Originality/value

The findings provide evidence to issues of potential research and managerial interest, offering insightful implications to the academic and practitioner communities. Evidently, irrespective of some usage bottlenecks, SMEs in emerging markets appears to be reaping enhanced social media benefits by deploying their marketing campaigns via multiple platforms.
Master data management and its organizational implementation
Authors: Vilminko-Heikkinen Riikka , Pekkola Samuli
Published: April 2017

Purpose

Master data management (MDM) aims to improve the value of an organization’s most important data, such as customer data, by bridging the silos between organizational units and information systems. However, incorporating data management practices into an organization is not a simple task. The purpose of this paper is to provide a new understanding of the challenges in establishing and developing the MDM function within an organization.

Design/methodology/approach

This papers report an ethnographic study within a municipality. The data were collected from two consecutive MDM development projects over the time period of 32 months by observing MDM-related activities and interviewing appropriate actors. Observations, interviews, and impressions were documented to a diary that was later qualitatively analyzed. Various project documentation were also used.

Findings

In total 15 challenges were identified. Seven of these were not identified earlier in the literature. New challenges included legislation-driven challenges, mutual understanding of master data domains, and the level of granularity for those domains. Eight issues, such as data owner and data definitions, were MDM specific, others being more generic. All of the issues were identified as preconditions or as affecting factors for the others. Three of the issues were identified as pivotal. The issues emphasize strong alignment between the complex concept of MDM and the organization adopting it.

Research limitations/implications

This research was based on a single qualitative case study, and caution should be exercised with regard to generalizations. The findings increase understanding about the complex organizational phenomena. The study offers public sector and private sector practitioners insights of the organizational issues that establishing a MDM function can encounter.

Originality/value

The issues discovered in the research shed light on the strong alignment between the complex concept of MDM and the organization. The results of this study assist researchers in their endeavor to understand the organizational aspects of MDM, and to build theoretical models, frameworks, practices, and explanations.
Business growth through intentional and non-intentional network processes
Authors: Rennemo Øystein , Widding Lars Øystein , Bogren Maria
Published: April 2017

Purpose

The purpose of this paper is to examine business growth and explore the “growth mode” among 24 women entrepreneurs participating in a Nordic research, development and networking programme.

Design/methodology/approach

A longitudinal design made it possible to follow entrepreneurial growth as an unfolding and emerging research process with a methodology inductive in nature and driven by empirical findings. The analysis is structured following established procedures for inductive, theory-building research, using guidelines for constant comparison techniques and working recursively between the data and the emerging theory.

Findings

Two processes were found important to understand the women entrepreneurs’ growth mode. The first is interpreted as intentionally driven and relates to the women’s achievement of expanding their knowledge reservoir; the other is non-intentionally driven and a result of uncontrolled network responses. The latter unfolded as a movement towards a preferable macro-actor status for some of the entrepreneurs.

Practical implications

The study calls attention to relevant knowledge preferable to entrepreneurs who face challenges when trying to grow their businesses. The political implications of this study relate to the importance of awareness among governmental organizations and municipal business advisers regarding the effects of entrepreneurial networking.

Originality/value

This study provides an empirically rigorous insight into the processes of entrepreneurial growth. The findings led the authors to develop a conceptual model for business growth, which contributes to the recent stream of literature on how new businesses are growing.