bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation and evolution among geographic and seasonal eco-populations of soybean germplasm in Southern China
Authors: Zhang Zhipeng , Zeng Weiying , Cai Zhaoyan , Lai Zhenguang , Su Yanzhu , Xing Guangnan , Wang Wubin , Sun Zudong , Gai Junyi
Published: February 2019

Soybean (Glycine max (L.) Merrill) germplasm in Southern China is extremely diverse. In order to explore the differentiation and evolution among geographic sowing-seasonal ecotypes of the Southern China Soybean Germplasm Population (SCSGP), we tested a sample set of accessions comprising 359 of the spring-sowing (SP) ecotype and 341 of the summer–autumn-sowing (SA) ecotype for their flowering date and sensitivity to seasonal photo-thermal changes in Nanning, Guangxi, China. The sample set and another 175 wild annual accessions were genotyped with 60 representative simple sequence repeat (SSR) markers. The SCSGP is characterised by its geographic differentiation (four geo-regional ecotypes), especially its sowing-seasonal differentiation (SA and SP ecotypes), and their combinations (eight geo-seasonal eco-populations). The ecological differentiation coincided with genetic differentiation in terms of allele richness and genetic distance. Neighbour-joining clustering among accessions by using SSRs indicated SA varieties to be the primitive ecotype relative to SP. The SA ecotype of Eco-region III (SA-III) was the most primitive among the eight geo-seasonal eco-populations, from which evolved SA-IV, and then SA-VI and SA-V. The SP ecotype was mainly evolved from its older SA counterpart, starting from SP-III emerging from SA-III accompanied by its introduction to Eco-region IV and other boarder regions. The evolutionary relationship among the geo-seasonal eco-populations was validated further with the analysis of multi-population specific-present alleles, which supports the hypothesis of Southern China origin of cultivated soybeans.
Insights from the coalface: barriers to accessing medicines and pharmacy services for resettled refugees from Africa
Authors: Bellamy Kim , Ostini Remo , Martini Nataly , Kairuz Therese
Published: February 2019

Resettled refugees in Australia have been shown to exhibit a high prevalence of limited health literacy and are at greater risk of mismanaging their medication and not being able to access the healthcare services they need. The aim of the current study is to explore the barriers to accessing medicines and pharmacy services in Queensland, Australia, among resettled refugees from Africa; this research was conducted from the perspectives of healthcare professionals and people who help the refugees to resettle in their adopted country (resettlement workers). A ‘generic qualitative’ approach was used in this study. In-depth interviews were conducted among healthcare professionals (two GPs, nine pharmacists and three nurse practitioners) and resettlement workers. Participants were recruited via a purposive snowball sampling method in the cities of Brisbane and Townsville, Queensland, Australia. Twenty-four in-depth interviews were conducted; 14 with healthcare professionals. Three key themes emerged from the data: (1) Communication Barriers; (2) Navigating the Health System; and (3) Belief Systems and Culture. Perceptions of those ‘at the coalface’ – healthcare professionals and people who are responsible for assisting refugees to resettle in Australia – provide insight into the language and cultural challenges experienced by resettled refugees from Africa regarding access to the Australian health system, including medicines and pharmacy services.
Data visualization literacy: Definitions, conceptual frameworks, exercises, and assessments
Authors: Börner Katy , Bueckle Andreas , Ginda Michael
Published: February 2019

In the information age, the ability to read and construct data visualizations becomes as important as the ability to read and write text. However, while standard definitions and theoretical frameworks to teach and assess textual, mathematical, and visual literacy exist, current data visualization literacy (DVL) definitions and frameworks are not comprehensive enough to guide the design of DVL teaching and assessment. This paper introduces a data visualization literacy framework (DVL-FW) that was specifically developed to define, teach, and assess DVL. The holistic DVL-FW promotes both the reading and construction of data visualizations, a pairing analogous to that of both reading and writing in textual literacy and understanding and applying in mathematical literacy. Specifically, the DVL-FW defines a hierarchical typology of core concepts and details the process steps that are required to extract insights from data. Advancing the state of the art, the DVL-FW interlinks theoretical and procedural knowledge and showcases how both can be combined to design curricula and assessment measures for DVL. Earlier versions of the DVL-FW have been used to teach DVL to more than 8,500 residential and online students, and results from this effort have helped revise and validate the DVL-FW presented here.
Agency plus automation: Designing artificial intelligence into interactive systems
Authors: Heer Jeffrey
Published: February 2019

Much contemporary rhetoric regards the prospects and pitfalls of using artificial intelligence techniques to automate an increasing range of tasks, especially those once considered the purview of people alone. These accounts are often wildly optimistic, understating outstanding challenges while turning a blind eye to the human labor that undergirds and sustains ostensibly “automated” services. This long-standing focus on purely automated methods unnecessarily cedes a promising design space: one in which computational assistance augments and enriches, rather than replaces, people’s intellectual work. This tension between human agency and machine automation poses vital challenges for design and engineering. In this work, we consider the design of systems that enable rich, adaptive interaction between people and algorithms. We seek to balance the often-complementary strengths and weaknesses of each, while promoting human control and skillful action. We share case studies of interactive systems we have developed in three arenas—data wrangling, exploratory analysis, and natural language translation—that integrate proactive computational support into interactive systems. To improve outcomes and support learning by both people and machines, we describe the use of shared representations of tasks augmented with predictive models of human capabilities and actions. We conclude with a discussion of future prospects and scientific frontiers for intelligence augmentation research.
Hoping for optimality or designing for inclusion: Persistence, learning, and the social network of citizen science
Authors: Parrish Julia K. , Jones Timothy , Burgess Hillary K. , He Yurong , Fortson Lucy , Cavalier Darlene
Published: February 2019

The explosive growth in citizen science combined with a recalcitrance on the part of mainstream science to fully embrace this data collection technique demands a rigorous examination of the factors influencing data quality and project efficacy. Patterns of contributor effort and task performance have been well reviewed in online projects; however, studies of hands-on citizen science are lacking. We used a single hands-on, out-of-doors project—the Coastal Observation and Seabird Survey Team (COASST)—to quantitatively explore the relationships among participant effort, task performance, and social connectedness as a function of the demographic characteristics and interests of participants, placing these results in the context of a meta-analysis of 54 citizen science projects. Although online projects were typified by high (>90%) rates of one-off participation and low retention (<10%) past 1 y, regular COASST participants were highly likely to continue past their first survey (86%), with 54% active 1 y later. Project-wide, task performance was high (88% correct species identifications over the 31,450 carcasses and 163 species found). However, there were distinct demographic differences. Age, birding expertise, and previous citizen science experience had the greatest impact on participant persistence and performance, albeit occasionally in opposite directions. Gender and sociality were relatively inconsequential, although highly gregarious social types, i.e., “nexus people,” were extremely influential at recruiting others. Our findings suggest that hands-on citizen science can produce high-quality data especially if participants persist, and that understanding the demographic data of participation could be used to maximize data quality and breadth of participation across the larger societal landscape.
Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism
Authors: Kazuki Yasuhiro , Kobayashi Kaoru , Hirabayashi Masumi , Abe Satoshi , Kajitani Naoyo , Kazuki Kanako , Takehara Shoko , Takiguchi Masato , Satoh Daisuke , Kuze Jiro , Sakuma Tetsushi , Kaneko Takehito , Mashimo Tomoji , Osamura Minori , Hashimoto Mari , Wakatsuki Riko , Hirashima Rika , Fujiwara Ryoichi , Deguchi Tsuneo , Kurihara Atsushi , Tsukazaki Yasuko , Senda Naoto , Yamamoto Takashi , Scheer Nico , Oshimura Mitsuo
Published: February 2019

Significance

Genomically humanized animals overcoming species differences are invaluable for biomedical research. Although rats would be preferred over mice for several applications, generation of a humanized model is restricted to mice due to the difficulty of complex genetic manipulations in rats. In this study, we successfully generated humanized rats with megabase-sized gene clusters via combination of chromosome transfer using mouse artificial chromosome vector and genome editing technologies. In the humanized UGT2 and CYP3A transchromosomic rats described in this paper, the expression of the human genes, as well as the pharmacokinetics and metabolism of relevant probe substrates, accurately mimic the situation in humans. Thus, the advanced technologies can be used to generate fully humanized rats useful for biomedical research.
Interaction design of community-driven environmental projects (CDEPs): A case study from the Anacostia Watershed
Authors: Preece Jennifer , Pauw Daniel , Clegg Tamara
Published: February 2019

Water is becoming an increasingly precious resource across the world, but citizens can help ensure good-quality water by helping to manage their local watersheds. Local, place-based advocacy projects that are strongly grounded within their geographical area have the potential to inspire environmental change as citizens come together to collectively address environmental challenges in their own neighborhoods. However, less attention has been given to these small, intensely place-based local projects. Our research focuses on the interaction design of technology to support small, local, place-based “community-driven environmental projects” (CDEPs) for water management in the Anacostia River Watershed. Analysis of case study data collected over a 3-y period to identify the needs of CDEP members provides the basis for the interaction design of technology known as NatureNet to support CDEPs. From this research, six design insights for supporting CDEPs are suggested: (i) a shared common endeavor connected to the identity of the members, (ii) ways for newcomers and experienced participants to share a common space and function together effectively, (iii) support for different sources of knowledge, (iv) different modes of participation and ways for participants to express themselves, (v) different ways to express status through diverse opportunities, and (vi) support for porous and changing leadership roles. Taken together, the findings from our study suggest a preference for technology-lite, highly flexible software that supports the diverse needs of CDEP members.
Addressing the imagination gap through STEAMM+D and indigenous knowledge
Authors: Diamond Sara
Published: February 2019

Alex Manu describes an “imagination gap,” that is, “the gap between current capability and future possibility” [Manu A (2006)
The Imagination Challenge: Strategic Foresight and Innovation in the Global Economy
]. Merriam-Webster defines imagination as “the act of forming a mental image of something not present to the senses or never before wholly perceived in reality”; imagination combines “creative ability” and “resourcefulness” [Merriam-Webster (2018) Imagination.
Merriam-Webster Dictionary Online
. Available at
https://www.merriam-webster.com/dictionary/imagination
]. This paper considers two interdisciplinary fields in which distinct approaches have sought a solution to the “imagination gap” and have resulted in new research questions, methods, outcomes, and even philosophies. These are science, technology, engineering, arts, math, medicine, and design (STEAMM+D) and Indigenous research that establishes questions and methods from an integrated interdisciplinary worldview and the individual’s responsibilities toward community and land. By intertwining these approaches, it is possible for science and society to apply creative problem solving in addressing complex challenges, thereby fostering sustainable innovation.
Comparative 3D genome organization in apicomplexan parasites
Authors: Bunnik Evelien M. , Venkat Aarthi , Shao Jianlin , McGovern Kathryn E. , Batugedara Gayani , Worth Danielle , Prudhomme Jacques , Lapp Stacey A. , Andolina Chiara , Ross Leila S. , Lawres Lauren , Brady Declan , Sinnis Photini , Nosten Francois , Fidock David A. , Wilson Emma H. , Tewari Rita , Galinski Mary R. , Ben Mamoun Choukri , Ay Ferhat , Le Roch Karine G.
Published: February 2019

The positioning of chromosomes in the nucleus of a eukaryotic cell is highly organized and has a complex and dynamic relationship with gene expression. In the human malaria parasite
Plasmodium falciparum
, the clustering of a family of virulence genes correlates with their coordinated silencing and has a strong influence on the overall organization of the genome. To identify conserved and species-specific principles of genome organization, we performed Hi-C experiments and generated 3D genome models for five
Plasmodium
species and two related apicomplexan parasites.
Plasmodium
species mainly showed clustering of centromeres, telomeres, and virulence genes. In
P. falciparum
, the heterochromatic virulence gene cluster had a strong repressive effect on the surrounding nuclear space, while this was less pronounced in
Plasmodium vivax
and
Plasmodium berghei
, and absent in
Plasmodium yoelii
. In
Plasmodium knowlesi
, telomeres and virulence genes were more dispersed throughout the nucleus, but its 3D genome showed a strong correlation with gene expression. The
Babesia microti
genome showed a classical Rabl organization with colocalization of subtelomeric virulence genes, while the
Toxoplasma gondii
genome was dominated by clustering of the centromeres and lacked virulence gene clustering. Collectively, our results demonstrate that spatial genome organization in most
Plasmodium
species is constrained by the colocalization of virulence genes.
P. falciparum
and
P. knowlesi
, the only two
Plasmodium
species with gene families involved in antigenic variation, are unique in the effect of these genes on chromosome folding, indicating a potential link between genome organization and gene expression in more virulent pathogens.
Impacts of the Northwest Forest Plan on forest composition and bird populations
Authors: Phalan Benjamin T. , Northrup Joseph M. , Yang Zhiqiang , Deal Robert L. , Rousseau Josée S. , Spies Thomas A. , Betts Matthew G.
Published: February 2019

The Northwest Forest Plan (NWFP) initiated one of the most sweeping changes to forest management in the world, affecting 10 million hectares of federal land. The NWFP is a science-based plan incorporating monitoring and adaptive management and provides a unique opportunity to evaluate the influence of policy. We used >25 years of region-wide bird surveys, forest data, and land-ownership maps to test this policy’s effect on biodiversity. Clearcutting decreased rapidly, and we expected populations of older-forest–associated birds to stabilize on federal land, but to continue declining on private industrial lands where clearcutting continued. In contrast, we expected declines in early-seral–associated species on federal land because of reduced anthropogenic disturbance since the NWFP. Bayesian hierarchical models revealed that bird species’ population trends tracked changes in forest composition. However, against our expectations, declines of birds associated with older forests accelerated. These declines are partly explained by losses of older forests due to fire on federal land and continued clearcutting elsewhere. Indeed, the NWFP anticipated that reversing declines of older forests would take time. Overall, the early-seral ecosystem area was stable, but declined in two ecoregions—the Coast Range and Cascades—along with early-seral bird populations. Although the NWFP halted clearcutting on federal land, this has so far been insufficient to reverse declines in older-forest–associated bird populations. These findings underscore the importance of continuing to prioritize older forests under the NWFP and ensuring that the recently proposed creation of early-seral ecosystems does not impede the conservation and development of older-forest structure.
Mature vessel networks in engineered tissue promote graft–host anastomosis and prevent graft thrombosis
Authors: Ben-Shaul Shahar , Landau Shira , Merdler Uri , Levenberg Shulamit
Published: February 2019

Significance

Rapid graft revascularization, while critical for graft survival, is often not seen in current grafts due to poor basal vascularization. In the present work, we assessed the effect of engineered vessel network assembly and maturation in pre-vascularized constructs prior to implantation on the dynamics of graft integration and perfusion. Grafts bearing highly complex and mature vessel networks were rapidly invaded by host vasculature, which anastomosed with the engineered vessels, promoting their perfusion and reducing blood clot accumulation in the graft. The implantation of grafts with highly mature engineered vessels promises to improve graft integration with the host vasculature and its overall survival.
MGMT-activated DUB3 stabilizes MCL1 and drives chemoresistance in ovarian cancer
Authors: Wu Xiaowei , Luo Qingyu , Zhao Pengfei , Chang Wan , Wang Yating , Shu Tong , Ding Fang , Li Bin , Liu Zhihua
Published: February 2019

Significance

Ovarian cancer is the leading cause of death among gynecological malignancies and has a poor prognosis characterized by resistance to chemotherapy. MCL1 has been found to play an essential role in chemoresistance and could be a promising therapeutic target. However, designing specific inhibitors targeting MCL1 remains challenging. Here, we found that deubiquitinating enzyme 3 (DUB3) stabilizes MCL1 via deubiquitination. We identified that O6-methylguanine-DNA methyltransferase (MGMT) is a key activator of DUB3 transcription and that the MGMT inhibitor PaTrin-2 effectively suppresses ovarian cancer cells with elevated MGMT-DUB3-MCL1 expression. We further showed that histone deacetylase (HDAC) inhibitors could significantly activate MGMT/DUB3 expression to sensitize ovarian cancer cells to PaTrin-2, providing an ideal therapeutic option involving the combined treatment of HDACis and PaTrin-2 in ovarian cancer.
Second-generation IL-2 receptor-targeted diphtheria fusion toxin exhibits antitumor activity and synergy with anti–PD-1 in melanoma
Authors: Cheung Laurene S. , Fu Juan , Kumar Pankaj , Kumar Amit , Urbanowski Michael E. , Ihms Elizabeth A. , Parveen Sadiya , Bullen C. Korin , Patrick Garrett J. , Harrison Robert , Murphy John R. , Pardoll Drew M. , Bishai William R.
Published: February 2019

Significance

Regulatory T cells (Tregs) infiltrate tumors in various cancers and promote an immunosuppressive microenvironment that hinders antitumor immunity. Denileukin diftitox, a diphtheria-toxin–based fusion protein that depletes Tregs, was approved for the treatment of T cell malignancies, but its clinical use was limited due to the presence of protein aggregates and toxicity associated with vascular leakage. Here, we report the production of a second-generation IL-2 receptor-targeted, fully-folded, monomeric diphtheria fusion toxin and a V6A mutant variant that showed reduced vascular leak in vitro and reduced lethality in mice. In a mouse model of melanoma, we found a significant decrease in tumor growth associated with reduction in Tregs when the protein was tested as monotherapy or in combination with checkpoint blockade.
A glycyl radical enzyme enables hydrogen sulfide production by the human intestinal bacteriumBilophila wadsworthia
Authors: Peck Spencer C. , Denger Karin , Burrichter Anna , Irwin Stephania M. , Balskus Emily P. , Schleheck David
Published: February 2019

Significance

This paper describes a pathway for anaerobic bacterial metabolism of taurine (2-aminoethanesulfonate), an abundant substrate in the human intestinal microbiota, by the intestinal bacterium and opportunistic pathogen,Bilophila wadsworthia. This metabolism converts taurine to the toxic metabolite hydrogen sulfide (H2S), an activity associated with inflammatory bowel disease and colorectal cancer. A critical enzyme in this pathway is isethionate sulfite-lyase, a member of the glycyl radical enzyme family. This enzyme catalyzes a novel, radical-based C-S bond-cleavage reaction to convert isethionate (2-hydroxyethanesulfonate) to sulfite and acetaldehyde. This discovery improves our understanding of H2S production in the human body and may also offer new approaches for controlling intestinal H2S production andB. wadsworthiainfections.
Persistent metabolic youth in the aging female brain
Authors: Goyal Manu S. , Blazey Tyler M. , Su Yi , Couture Lars E. , Durbin Tony J. , Bateman Randall J. , Benzinger Tammie L.-S. , Morris John C. , Raichle Marcus E. , Vlassenko Andrei G.
Published: February 2019

Significance

Prior work has identified many sex differences in the brain, including during brain aging and in neurodegenerative diseases. Notably, many of these studies are performed by comparing age-matched females and males. Evolutionary theorists have predicted that females might have more youthful brains (neoteny) as compared with males, but until now findings in support of this theory have been limited to postmortem transcriptional analysis, some of which is contradictory. To test this hypothesis in vivo, we analyzed sex differences in a unique brain PET dataset in over 200 normal human adults across the adult life span. We find that in terms of brain metabolism, the adult female brain is on average a few years younger than the male brain.
Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes
Authors: Lee Mitchell B. , Dowsett Ian T. , Carr Daniel T. , Wasko Brian M. , Stanton Sarah G. , Chung Michael S. , Ghodsian Niloufar , Bode Anna , Kiflezghi Michael G. , Uppal Priya A. , Grayden Katherine A. , Elala Yordanos C. , Tang Thao T. , Tran Ngoc H. B. , Tran Thu H. B. , Diep Anh B. , Hope Michael , Promislow Daniel E. L. , Kennedy Scott R. , Kaeberlein Matt , Herr Alan J.
Published: February 2019

Significance

Mutations accumulate throughout life in every cell of the body. A long-standing question is to what extent these mutations contribute to aging. Age is the single greatest risk factor for cancer, a disease driven by random mutagenesis and selection for malignant phenotypes. We wondered whether cancer cells, being the most heavily mutagenized human cell, are short-lived due to mutagenesis. Single-cell measurements of replicative lifespan are not established for human cells. So, instead, we engineered diploid yeast to have cancer-associated defects that increase mutagenesis and then measured lifespan and mutation accumulation. Yeast cellular lifespan decreased as the total number of mutations increased to levels commonly found in human cancers, suggesting that the longevity of cancer cells may be inherently limited.
Resonant inelastic X-ray scattering determination of the electronic structure of oxyhemoglobin and its model complex
Authors: Yan James J. , Kroll Thomas , Baker Michael L. , Wilson Samuel A. , Decréau Richard , Lundberg Marcus , Sokaras Dimosthenis , Glatzel Pieter , Hedman Britt , Hodgson Keith O. , Solomon Edward I.
Published: February 2019

Significance

The electronic structure of the heme oxy-iron center in oxyhemoglobin and oxymyoglobin has been the subject of debate for decades. Various experimental and computational methods have been used to study this system, leading to conflicting conclusions. This study uses X-ray spectroscopy to directly probe the iron center in the highly delocalized oxyhemoglobin and its model compound to define the electronic structure and understand the differences between the protein and the model. This study settles a longstanding debate in bioinorganic chemistry and provides insight into heme iron–oxygen binding, the key first step in many biocatalytic processes.
Mesoscale modeling reveals formation of an epigenetically driven HOXC gene hub
Authors: Bascom Gavin D. , Myers Christopher G. , Schlick Tamar
Published: February 2019

Significance

The precise role of epigenetic factors in controlling chromatin structure is not well understood. Here, we use publicly available data to build and “fold” a nucleosome-resolution mesoscale model of the developmentally regulated HOXC gene locus that incorporates histone tail acetylation, linker histone binding, and nucleosome occupancy. We discover a spontaneous contact hub that bridges promoters and exon/intron junctions. Our work emphasizes how epigenetic factors are coordinated to influence chromatin architecture and opens the way for nucleosome resolution modeling of epigenetically regulated genes.
Local homogeneity of tonotopic organization in the primary auditory cortex of marmosets
Authors: Zeng Huan-huan , Huang Jun-feng , Chen Ming , Wen Yun-qing , Shen Zhi-ming , Poo Mu-ming
Published: February 2019

Significance

Marmoset is a New World monkey rich in social interaction and vocal communication. We used in vivo two-photon fluorescence calcium imaging of sound-evoked responses of large neuronal populations at single-neuron resolution in the primary auditory cortex (A1) of anesthetized marmosets. We found that the pure tone-evoked responses of marmoset A1 neurons are highly homogeneous in their frequency preference within local cortical regions, in sharp contrast to that found in rodents. Thus, there is species-specific local tonotopic organization in A1, which imposes distinct neural circuitry constraints for the cortical integration of auditory information.
DGAT1 inhibits retinol-dependent regulatory T cell formation and mediates autoimmune encephalomyelitis
Authors: Graham Kareem L. , Werner Bonnie J. , Moyer Kimberly M. , Patton Alycia K. , Krois Charles R. , Yoo Hong Sik , Tverskoy Maria , LaJevic Melissa , Napoli Joseph L. , Sobel Raymond A. , Zabel Brian A. , Butcher Eugene C.
Published: February 2019

The balance of effector versus regulatory T cells (Tregs) controls inflammation in numerous settings, including multiple sclerosis (MS). Here we show that memory phenotype CD4+T cells infiltrating the central nervous system during experimental autoimmune encephalomyelitis (EAE), a widely studied animal model of MS, expressed high levels of mRNA forDgat1encoding diacylglycerol-O-acyltransferase-1 (DGAT1), an enzyme that catalyzes triglyceride synthesis and retinyl ester formation. DGAT1 inhibition or deficiency attenuated EAE, with associated enhanced Treg frequency; and encephalitogenic, DGAT1−/−in vitro-polarized Th17 cells were poor inducers of EAE in adoptive recipients. DGAT1 acyltransferase activity sequesters retinol in ester form, preventing synthesis of retinoic acid, a cofactor for Treg generation. In cultures with T cell-depleted lymphoid tissues, retinol enhanced Treg induction from DGAT1−/−but not from WT T cells. The WT Treg induction defect was reversed by DGAT1 inhibition. These results demonstrate that DGAT1 suppresses retinol-dependent Treg formation and suggest its potential as a therapeutic target for autoimmune inflammation.
High-dimensional representation of texture in somatosensory cortex of primates
Authors: Lieber Justin D. , Bensmaia Sliman J.
Published: February 2019

Significance

The sense of touch affords a remarkable sensitivity to the microstructure of surfaces, affording us the ability to sense elements ranging in size from tens of nanometers to tens of millimeters. The hand sends signals about texture to the brain using three classes of nerve fibers through two neural codes: coarse features in spatial patterns of activation and fine features in precise temporal spiking patterns. In this study, we show that these nerve signals culminate in a complex, high-dimensional representation of texture in somatosensory cortex, whose structure can account for the structure of texture perception. This complexity arises from the neurons that act as idiosyncratic detectors of spatial and/or temporal motifs in the afferent input.
Convergent gene losses illuminate metabolic and physiological changes in herbivores and carnivores
Authors: Hecker Nikolai , Sharma Virag , Hiller Michael
Published: February 2019

Significance

Mammals repeatedly adapted to specialized diets, including plant-based diets for herbivores and meat- or insect-based diets for carnivores. Apart from consuming diets with different nutritional compositions, obligate herbivores and carnivores differ in other aspects, such as the time spent feeding, regularity of pancreatic juice secretion, exposure to toxic plant-derived compounds, and gut microbiome diversity. To better understand how diet-related changes evolved, we performed genome-wide screens for convergent gene losses that happened preferentially in herbivores or in carnivores. We discovered repeated losses of genes involved in fat digestion, pancreatic juice secretion, glucose homeostasis, appetite regulation, detoxification, and gut microbiome diversity. Our results reveal genomic changes associated with dietary specialization and illuminate metabolic and physiological changes in herbivorous and carnivorous mammals.
Hippocampal atrophy and intrinsic brain network dysfunction relate to alterations in mind wandering in neurodegeneration
Authors: O’Callaghan Claire , Shine James M. , Hodges John R. , Andrews-Hanna Jessica R. , Irish Muireann
Published: February 2019

Significance

Humans spend much of their waking life engaged in mind wandering. Underlying brain systems supporting this complex ability have been established in healthy individuals, yet it remains unclear how mind wandering is altered in neuropsychiatric populations. We reveal changes in the thought profiles elicited during periods of low cognitive demand in dementia, resulting in reduced mind wandering and an increased propensity toward stimulus-bound thought. These altered thought profiles were associated with structural and functional brain changes in the hippocampus, default, and frontoparietal networks, key regions implicated in internal mentation in healthy individuals. Our findings provide a unique clinical validation of current theoretical models of mind wandering and reveal a dimension of cognitive dysfunction that has received scant attention in dementia.
Genetically eliminating Purkinje neuron GABAergic neurotransmission increases their response gain to vestibular motion
Authors: Stay Trace L. , Laurens Jean , Sillitoe Roy V. , Angelaki Dora E.
Published: February 2019

Significance

One theory of cerebellar function proposes that it creates internal models for action planning, timing, and sensory processing. Purkinje neurons in the caudal vermis of macaques carry a model of gravitational and linear acceleration, and here we show that this computation is evolutionarily conserved and represented across multiple lobules of the rodent vermis. Further, we show that genetically blocking Purkinje neuron GABAergic output leaves this computational ability intact, but leads to increased response modulation amplitude. We conclude that Purkinje neuron feedback regulates gain control within the cerebellar circuit.
Zintl-phase Eu
2
ZnSb
2
: A promising thermoelectric material with ultralow thermal conductivity
Authors: Chen Chen , Xue Wenhua , Li Shan , Zhang Zongwei , Li Xiaofang , Wang Xinyu , Liu Yijie , Sui Jiehe , Liu Xingjun , Cao Feng , Ren Zhifeng , Chu Ching-Wu , Wang Yumei , Zhang Qian
Published: February 2019

Significance

Searching for compounds with intrinsic low lattice thermal conductivity has been proven a successful strategy for achieving high thermoelectric performance. Here we report a promising 2-1-2–type Eu
2
ZnSb
2
(
P
6
3
/
mmc
) Zintl-phase thermoelectric material. Its intrinsic crystal structure, together with its widely distributed plane defects, likely contribute to its effective phonon scattering, leading to ultralow thermal conductivity (∼0.41 W m
−1
⋅K
−1
at 300 K and ∼0.37 W m
−1
⋅K
−1
at 623 K), lower than that of most other Zintl compounds. By regulating the Zn deficiency, the maximum
ZT
value of Eu
2
Zn
0.98
Sb
2
reaches ∼1.0 at 823 K, which is quite respectable for p-type Zintl materials. This discovery provides a class of Zintl thermoelectric materials applicable in the medium-temperature range.
The
Mycobacterium tuberculosis
Pup-proteasome system regulates nitrate metabolism through an essential protein quality control pathway
Authors: Becker Samuel H. , Jastrab Jordan B. , Dhabaria Avantika , Chaton Catherine T. , Rush Jeffrey S. , Korotkov Konstantin V. , Ueberheide Beatrix , Darwin K. Heran
Published: February 2019

Significance

The proteasome is required for the full virulence of
Mycobacterium tuberculosis
. However, the extent of its role as a regulator of bacterial physiology remains unclear. In this work, we demonstrate a function of the proteasome system in maintaining the expression of essential chaperonin genes. This activity by the proteasome is required for
M. tuberculosis
to use nitrate as a nitrogen source. Furthermore, we identified a specific growth condition that robustly decreases the abundance of pupylated proteins. This observation strongly suggests the presence of a yet-to-be-determined mechanism of control over the Pup-proteasome system in
M. tuberculosis
that is induced in nitrate.
Chaperone-mediated autophagy is involved in the execution of ferroptosis
Authors: Wu Zheming , Geng Yang , Lu Xiaojuan , Shi Yuying , Wu Guowei , Zhang Mengmeng , Shan Bing , Pan Heling , Yuan Junying
Published: February 2019

Significance

This study reveals a common regulatory mechanism mediated by HSP90 that is shared by necroptosis and ferroptosis, two necrotic cell death mechanisms that have previously had no known mechanistic connections. Furthermore, this study demonstrates the involvement of chaperone-mediated autophagy in the execution of ferroptosis. Given the role of HSP90 as an important chaperone involved in major human maladies ranging from neurodegenerations to cancers, our work further implicates the roles of necroptosis and ferroptosis in human diseases.
Genome-wide colocalization of RNA–DNA interactions and fusion RNA pairs
Authors: Yan Zhangming , Huang Norman , Wu Weixin , Chen Weizhong , Jiang Yiqun , Chen Jingyao , Huang Xuerui , Wen Xingzhao , Xu Jie , Jin Qiushi , Zhang Kang , Chen Zhen , Chien Shu , Zhong Sheng
Published: February 2019

Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA–DNA interactions mapped in two normal, noncancerous cell types [using iMARGI, an enhanced version of the mapping of RNA–genome interactions (MARGI) assay]. Among the top 10 most significant RNA–DNA interactions in normal cells, 5 colocalized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA–DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA–DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA sequencing (RNA-seq). Thirty-seven of 42 fusion transcripts in the validation cohort were found to exhibit RNA–DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest an RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts.
Cyclin B3 promotes anaphase I onset in oocyte meiosis
Authors: Karasu Mehmet E. , Bouftas Nora , Keeney Scott , Wassmann Katja
Published: February 2019

Meiosis poses unique challenges because two rounds of chromosome segregation must be executed without intervening DNA replication. Mammalian cells express numerous temporally regulated cyclins, but how these proteins collaborate to control meiosis remains poorly understood. Here, we show that female mice genetically ablated for cyclin B3 are viable—indicating that the protein is dispensable for mitotic divisions—but are sterile. Mutant oocytes appear normal until metaphase I but then display a highly penetrant failure to transition to anaphase I. They arrest with hallmarks of defective anaphase-promoting complex/cyclosome (APC/C) activation, including no separase activity, high CDK1 activity, and high cyclin B1 and securin levels. Partial APC/C activation occurs, however, as exogenously expressed APC/C substrates can be degraded. Cyclin B3 forms active kinase complexes with CDK1, and meiotic progression requires cyclin B3–associated kinase activity. Cyclin B3 homologues from frog, zebrafish, and fruit fly rescue meiotic progression in cyclin B3–deficient mouse oocytes, indicating conservation of the biochemical properties and possibly cellular functions of this germline-critical cyclin.
Type I interferon induces CXCL13 to support ectopic germinal center formation
Authors: Denton Alice E. , Innocentin Silvia , Carr Edward J. , Bradford Barry M. , Lafouresse Fanny , Mabbott Neil A. , Mörbe Urs , Ludewig Burkhard , Groom Joanna R. , Good-Jacobson Kim L. , Linterman Michelle A.
Published: February 2019

Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection–induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here, we show that type I IFN produced after viral infection can induce CXCL13 expression in a phenotypically distinct population of lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal center formation. This identifies type I IFN as a novel inducer of CXCL13, which, in combination with other stimuli, can promote lung remodeling, converting a nonlymphoid tissue into one permissive to functional tertiary lymphoid structure formation.
SCAT5 vs. SCAT3 Symptom Reporting Differences and Convergent Validity in Collegiate Athletes
Authors: Asken Breton M , Houck Zachary M , Bauer Russell M , Clugston James R
Published: February 2019

Objective

The Sport Concussion Assessment Tool (SCAT), fifth Edition, Symptom Evaluation (S5SE) differs from previous versions by having examinees report trait (i.e. “typical” feelings) as opposed to state (i.e., “how you feel right now”) concussion-like symptoms at baseline. This study assessed differences among, and convergent validity of, scores on the S5SE, SCAT3 Symptom Evaluation (S3SE), and the Brief Symptom Inventory (BSI-18).

Methods

A total of 113 University of Florida varsity athletes completed symptom questionnaires on the same day in a counterbalanced administration. The final sample consisted of 94 participants (mean age ± SD = 18.4 ± 0.8 years, 57% male, 65% white) from 17 sports. We assessed convergent validity using Spearman rank-order correlations. Within-participant differences were analyzed with Wilcoxon Signed-Rank tests. We qualitatively described free-response answers to the S5SE question that asks, “if not feeling 100%, why?”.

Results

S5SE total severity score demonstrated adequate convergent validity with both the S3SE (rho = .407, p < .001) and BSI-18 (rho = .432, p < .001). Domain-specific analyses indicated variable convergent validity (rho < 0.4 to rho > 0.6). Severity scores did not differ between the S3SE and S5SE (p = .500), but 24.5% of participants reported S3SE > S5SE and 34.0% S5SE > S3SE. Three themes emerged from qualitative examination of reasons for “not feeling 100%”: (1) tiredness/sleep, (2) adjustment difficulties, and (3) academic/athletic stress.

Conclusions

Adequate convergent validity exists between SCAT5 and SCAT3 symptom severity in collegiate athletes. However, most examinees report different baseline symptom severity when asked to describe their trait (S5SE) versus state symptoms (S3SE). Clinicians should consider using the new SCAT5 Symptom Evaluation as a screening tool for identifying otherwise healthy or “undiagnosed” individuals who would benefit from targeted interventions.
No Linear Association Between Number of Concussions or Years Played and Cognitive Outcomes in Retired NFL Players
Authors: Fields Lindy , Didehbani Nyaz , Hart John , Cullum C Munro
Published: February 2019

Objective

The aim of the current study is to examine whether concussion history and years played are linearly associated with cognitive outcomes in retired National Football League (NFL) players.

Method

Thirty-five retired NFL players over the age of 50 who had sustained at least one concussion completed a clinical interview and brief neuropsychological battery. Correlational analyses were conducted between exposure variables [number of total concussions, concussions with loss of consciousness (LOC), and years played] and cognitive performance as characterized by cognitive composite scores based on performance on neuropsychological measures (attention/processing speed, language, memory, and overall composite scores).

Results

Correlational analyses corrected for multiple comparisons did not reveal any statistically significant correlations between exposure variables and cognitive outcomes.

Conclusions

We did not find a significant linear association between cognitive outcomes and either number of total concussions, concussions with LOC, or years played in the NFL. These findings do not support a dose–response relationship between sports-related exposure to head impacts and cognitive outcomes later in life. Rather, the findings suggest that cognitive difficulties experienced by some retired players later in life are not directly linearly associated with quantified exposure to head impacts sustained throughout a football career, but related to factors or combinations of factors that have yet to be elucidated.
Anatomical Map of the Facial Artery for Facial Reconstruction and Aesthetic Procedures
Authors: Koziej Mateusz , Trybus Marek , Hołda Mateusz , Polak Jakub , Wnuk Jakub , Brzegowy Paweł , Popiela Tadeusz , Walocha Jerzy , Chrapusta Anna
Published: February 2019

Background

The facial artery (FA) is the main blood vessel supplying the anterior face and an understanding of its anatomy is crucial in facial reconstruction and aesthetic procedures.

Objectives

The aim of this study was to assess the many anatomical features of the FA utilizing a multidimensional approach.

Methods

Head and neck computed tomographic angiographies of 131 patients (255 FAs) with good image quality were evaluated. The FA was classified according to its termination pattern, course, and location with reference to soft tissue/bone surrounding structures.

Results

In total, each branch was present as follows: the submental artery (44.8%), the inferior labial artery (60%), the superior labial artery (82.2%), the lateral nasal artery (25.1%), and the angular artery (42.5%). The most common FA course was the classic course, situated medially to the nasolabial fold (27.1%). In total 65.5% of the arteries were located medially to the nasolabial fold, and only 12.3% of them were totally situated lateral to the nasolabial fold. The median distance (with quartiles) from the inferior orbital rim reached the FA after the superior labial artery branched off in 50.2% of cases and was 36.6 mm (33.4; 43.3). The angle between the FA and the inferior border of the mandible was 49.8o (31.9; 72.4). The horizontal distances between the oral commissure and naris to the FA were 8.5 ± 4.0 mm and 12.1 ± 6.7 mm, respectively.

Conclusions

An anatomical map summarizing the major measurements and geometry of the FA was generated. The detailed anatomy and relative positioning of the FA should be considered to avoid any unexpected complications in plastic surgery.
How well do RNA-Seq differential gene expression tools perform in a complex eukaryote? A case study inArabidopsis thaliana
Authors: Froussios Kimon , Schurch Nick J , Mackinnon Katarzyna , Gierliński Marek , Duc Céline , Simpson Gordon G , Barton Geoffrey J
Published: February 2019

Motivation

RNA-seq experiments are usually carried out in three or fewer replicates. In order to work well with so few samples, differential gene expression (DGE) tools typically assume the form of the underlying gene expression distribution. In this paper, the statistical properties of gene expression from RNA-seq are investigated in the complex eukaryote, Arabidopsis thaliana, extending and generalizing the results of previous work in the simple eukaryote Saccharomyces cerevisiae.

Results

We show that, consistent with the results in S.cerevisiae, more gene expression measurements in A.thaliana are consistent with being drawn from an underlying negative binomial distribution than either a log-normal distribution or a normal distribution, and that the size and complexity of the A.thaliana transcriptome does not influence the false positive rate performance of nine widely used DGE tools tested here. We therefore recommend the use of DGE tools that are based on the negative binomial distribution.

Availability and implementation

The raw data for the 17 WT Arabidopsis thaliana datasets is available from the European Nucleotide Archive (E-MTAB-5446). The processed and aligned data can be visualized in context using IGB (Freese et al., 2016), or downloaded directly, using our publicly available IGB quickload server at https://compbio.lifesci.dundee.ac.uk/arabidopsisQuickload/public_quickload/ under ‘RNAseq>Froussios2019’. All scripts and commands are available from github at https://github.com/bartongroup/KF_arabidopsis-GRNA.

Supplementary information

Supplementary data are available at Bioinformatics online.
RiboD: a comprehensive database for prokaryotic riboswitches
Authors: Mukherjee Sumit , Das Mandal Sukhen , Gupta Nikita , Drory-Retwitzer Matan , Barash Danny , Sengupta Supratim
Published: February 2019

Riboswitches are cis-regulatory non-coding genomic segments that control the expression of downstream genes by undergoing conformational change upon ligand binding. We present a comprehensive database of prokaryotic riboswitches that allows the user to search for riboswitches using multiple criteria, extract information about riboswitch location and gene/operon it regulates. RiboD provides a very useful resource that can be utilized for the better understanding of riboswitch-based gene regulation in bacteria and archaea.

Availability and implementation

RiboD can be freely accessed on the web at http://ribod.iiserkol.ac.in/.