bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphology in Cognitive Grammar
Authors: Langacker Ronald W.
Published: January 2019

Basic morphological phenomena are examined from the standpoint of Cognitive Grammar, whose unified account of the many aspects of language structure allows the seamless integration of morphology with phonology, lexicon, and grammar. In this usage-based approach, structure resides in processing activity, being abstracted from usage events by the reinforcement of recurring patterns. The notion of a morpheme is viable when reconceptualized and formulated in these terms. Morphological structure is symbolic in nature, consisting in assemblies of form–meaning pairings. Among the more specific topics to be considered are the following: the nature of process morphemes; the stem/affix distinction; how this relates to compounding; morphological constructions; productivity (major vs. minor patterns); layering; phonotactic, phonological, and morphophonemic ‘rules’; and the emergence of morphological paradigms.
Paradigm Function Morphology
Authors: Stump Gregory
Published: January 2019

Paradigm Function Morphology is an inferential-realizational theory of morphology. This chapter explains the basic features of the theory, both in its earlier form (PFM1) and in its more recent form (PFM2). Because PFM2 draws an essential distinction between the morphosyntactic property set determining a word form’s syntax and semantics and the property set driving its morphological realization, it affords straightforward analyses of a range of noncanonical morphological phenomena, including defectiveness, syncretism, inflection classes, and deponency. The workings of PFM2 are demonstrated with a formal analysis of the conjugational system of Bena-bena (Gorokan, Papua New Guinea). Although PFM2 has been primarily developed as a model for inflectional systems, its logic is applicable in the domain of derivational morphology; it also affords the precise articulation of a realistic interface between a word’s morphology and its phonology, syntax, and semantics.
Self-Assembly of Embryonic and Two Extraembryonic Stem Cell Types Into Gastrulating Embryo-like Structures
Authors: Sozen Berna , Amadei Gianluca , Cox Andy , Wang Ran , Na Ellen , Czukiewska Sylwia , Chappell Lia , Voet Thierry , Michel Geert , Jing Naihe , Glover David M. , Zernicka-Goetz Magdalena
Published: January 2019

(Abstracted from Nature Cell Biology 2018;20:979–989)

Three stem cell types found in the natural embryo differentiate to become 3 distinct tissues: the embryonic tissue or epiblast, the trophectoderm, and the primitive endoderm. Signaling interactions between each of these tissue types are important for morphogenic pathways causing the cell rearrangements of gastrulation and establishing anterior and posterior identity.
Vision-related Quality of Life in Glaucoma Patients and its Correlations With Psychological Disturbances and Visual Function Indices
Authors: Wu Na , Kong Xiangmei , Gao Jian , Sun Xinghuai
Published: January 2019

Purpose:

The purpose of this study was to assess the vision-related quality of life (VR-QoL) in glaucoma patients and its correlations with psychological disturbances and visual function components.

Materials and Methods:

The 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and Hospital Anxiety and Depression Scale (HADS) questionnaires were administered to 428 Chinese glaucoma patients to evaluate their VR-QoL and anxiety and depression disorders, respectively. Sociodemographical and clinical factors were collected at the same time. Univariate analyses were used to investigate the associations between the variables and the VR-QoL. Multivariate linear regression analyses were used to identify the independent psychological and visual functional predictors of the VR-QoL. Standardized partial regression analyses were used to reveal the variables that mostly relevant to the VR-QoL.

Results:

The composite score (mean±SD) was 71.88±14.44 for NEI VFQ-25 and 13.17±6.56 for HADS. Visual function indices, including best-corrected visual acuity and mean deviation of both eyes in addition to psychological symptoms including anxiety and depression were both correlated with VR-QoL significantly, even after adjusting for sociodemographical and clinical factors. Standardized partial regression analyses further suggested that psychological disorders, especially anxiety rather than visual function components, were mostly relevant to VR-QoL.

Conclusions:

Deterioration of vision impairment and visual field defects in addition to increased recognition of psychological disturbances reduce the VR-QoL of glaucoma patients significantly. Alleviating psychological symptoms, especially anxiety, perhaps have a greater influence on the improvement of VR-QoL.
The Relationship Between Quantitative Pupillometry and Estimated Ganglion Cell Counts in Patients With Glaucoma
Authors: Chang Dolly S. , Arora Karun , Boland Michael V. , Friedman David S.
Published: January 2019

Purpose:

To assess the relationship between pupillary light reflex and estimated retinal ganglion cell (RGC) counts in patients with glaucoma.

Methods:

We recorded and analyzed pupil responses using an automated binocular pupillometer in 148 patients with glaucoma (mean age 67±11, 49% female) and 71 controls (age 60±9.6, 69% female) as part of a prospective clinical study. The amplitude of pupil constriction was calculated as the percentage change in pupil diameter between constriction onset and peak constriction in response to controlled stimuli. The magnitude of a relative afferent pupillary defect (RAPD) was defined as the log of the ratio of the amplitude between 2 eyes multiplied by 10. RGC counts were estimated using empirical formulas that combine estimates from both functional (eccentricity and sensitivity measured by standard automated perimetry) and structural (retinal nerve fiber layer thickness) tests. For analyses performed at the level of individual eyes, we used multilevel modeling to account for between-eye correlations within individuals.

Results:

Eyes with higher estimated RGC counts had a larger pupil response amplitude (z-score=8.24, P<0.001), shorter latency (z=−3.17, P=0.002), faster constriction velocity (z=6.64, P<0.001), shorter time to maximum constriction (z=−1.96, P=0.049), and longer time to maximum dilation (z=6.66, P<0.001). For every 0.3 log unit difference in RAPD score, there was an average decrease in estimated RGC count of 37,817 (P<0.001).

Conclusions:

There is a statistically significant association between estimated RGC count and pupillary response to stimuli. Quantitative pupillography may be useful in diagnosis and monitoring of optic neuropathies.
Risk of Primary Neuroendocrine Pancreatic Tumor After a First Primary Cancer
Authors: Kamath Geetanjali R. , Kim Michelle K. , Taioli Emanuela
Published: January 2019

Objective

This study aimed to describe the relative and excess risk of pancreatic neuroendocrine tumor (NET) at least 6 months after the first primary cancer (FPC) among the US population.

Methods

Surveillance, Epidemiology, and End-Results Program data were analyzed for patients diagnosed as having FPC from 2000 to 2015 (n = 4,008,092). Standardized incidence ratios, excess risk, and average time to diagnosis of a second primary pancreatic NET were reported by FPC site, stratified by sex and receipt of radiotherapy and chemotherapy.

Results

Risk of pancreatic NET was significantly higher after FPC at any site, any solid tumor (standardized incidence ratios, 1.3; 95% confidence interval, 1.2–1.5), pancreas, thymus, small intestine, liver, stomach, kidney, lung, and female breast. Excess incidence of pancreatic NET was highest among those with FPC (especially NET) of the pancreas, bladder, thymus, and female breast; those who received radiotherapy/chemotherapy for bladder, melanoma, and stomach cancers; and those who received chemotherapy for uterine, cervical, prostate, and other genital cancers. Time to diagnosis was shortest after pancreatic, liver, lung, and stomach cancer.

Conclusions

Cancer survivors have increased risk and excess incidence of primary pancreatic NET compared with the population, particularly for certain primary sites. High-risk patients should receive regular follow-up screenings, counseling to reduce carcinogen exposure, and lifestyle interventions.
Tocolysis: A Review of the Literature
Authors: Hanley Margaret , Sayres Lauren , Reiff Emily S. , Wood Amber , Grotegut Chad A. , Kuller Jeffrey A.
Published: January 2019

Importance

Preterm delivery represents an important cause of infant morbidity and mortality. Various tocolytics have been studied with the objective of stopping preterm labor, increasing gestational age at delivery, and preventing complications related to preterm birth.

Objective

This review aims to summarize the major classes of tocolytics and review the evidence regarding use of each.

Evidence Acquisition

A PubMed search of the following terms was performed to gather relevant data: “tocolytic,” “preterm labor,” “preterm delivery,” “PPROM,” “magnesium,” “indomethacin,” “nifedipine,” and “betamimetics.”

Results

The benefits and risks of nonsteroid anti-inflammatory drugs, calcium channel blockers, magnesium, and betamimetics are reviewed. Calcium channel blockers afford superior outcomes in terms of prolonging gestation and decreasing neonatal morbidity and mortality with the fewest adverse effects.

Conclusions and Relevance

Tocolytics, particularly calcium channel blockers, may provide benefit to pregnant women and their infants. Their use should be tailored to the particular clinical circumstances of the patient and used in conjunction with other management strategies (e.g., administration of corticosteroids for fetal lung maturation or magnesium for neuroprotection and transfer to a tertiary medical center). Further research and professional guidelines are needed on optimal use of these agents.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After participating in this activity, the provider should be better able to compare the major classes of tocolytics, including mechanisms of action; distinguish the role tocolytics play in preterm labor and appropriate clinical indication and course; and choose a tocolytic based on evidence regarding the potential benefits and risks.
Napsin A, Hepatocyte Nuclear Factor-1-Beta (HNF-1β), Estrogen and Progesterone Receptors Expression in Arias-Stella Reaction
Authors: Ip Philip P.C. , Wang Szu-Yen , Wong Oscar G.W. , Chow Kin-Long , Lee Horace Hok-Yeung , Cheung Annie N.Y. , Tse Ka-Yu
Published: January 2019

Background:

The Arias-Stella reaction (ASR) can mimic endometrial clear cell carcinoma (ECCC) in small biopsies, especially when drug or pregnancy history is unknown. A panel of immunohistochemical markers comprising napsin A, hepatocyte nuclear factor-1-beta (HNF-1β), estrogen and progesterone receptors (ER, PR) has been found useful in confirming a diagnosis of ECCC. However, the detailed characterization of how expression of this combination of markers in the ECCC mimics ASR has yet to be thoroughly evaluated.

Design:

The frequency and extent of napsin A, HNF-1β, ER, and PR expression in ASR were assessed in a large series. For napsin A, any cytoplasmic staining was considered positive while only nuclear staining was deemed to be positive for HNF-1β, ER, and PR. Immunohistochemical histoscores based on the intensity and extent of staining were calculated.

Results:

Forty cases were gestational and 10 were nongestational ASR. In 19 (38%), the reaction was extensive and involved >50% of the glands. A stromal decidual change was found in 31 (77.5%) of the gestational and 3 (30%) of the nongestational cases. Napsin A was positive in all gestational and 8 of 10 (80%) nongestational ASR. All ASR showed HNF-1β expression. ER expression was reduced in 37 (92.5%) and lost in 3 (7.5%) gestational ASR, and reduced in 9 (90%) and lost in 1 (10%) of nongestational ASR. None of the ASR in our series expressed PR.

Conclusions:

Naspin A and HNF-1β were frequently expressed in both gestational and nongestational ASR, and ER expression was usually either reduced or loss. Interpretation of these markers in small biopsies containing atypical clear cells should be made with caution.
Transplantation of Adipose-Derived Stem Cells Before Flap Expansion and After Expanded Flap Elevation Result in Different Effects
Authors: Wang Qianwen , Hou Shengchao , Wang Tailing , Guo Xin , Yu Hao , Wang Jiaqi
Published: January 2019

Background

Studies of using mesenchymal stem cells to assist skin and soft tissue expansion have shown that stem cells can improve expansion efficiency through promoting tissue regeneration. However, the issue that whether the flap viability is also improved is unknown.

Methods

Sixteen pigs were equally divided into 2 groups. A pair of 150 mL expanders was symmetrically inserted into each pig's dorsum. Group 1 received adipose-derived stem cells (ADSCs) injection before expansion, and group 2 received ADSCs grafting after flap elevation. After 4 weeks' expansion, a random flap measuring 2 cm × 16 cm was elevated along the long axis of each expanded flap on the pigs' back. Flap viability was measured at postoperative day 7. Histological analysis and cell tracking were performed. The expression of vascular endothelial growth factor was determined.

Results

The flap viability of the ADSCs-grafted expanded flap (75.5 ± 6.6%) was similar to the control (69.4 ± 8.4%) in group 1 (transplantation before expansion). However, in group 2 (transplantation after flap elevation), the ADSCs-grafted expanded flap had a higher flap viability (92.6 ± 5.7%) compared with control (66.2 ± 7.4%). Moreover, the ADSCs-grafted expanded flap in group 1 showed increased skin thickness, collagen content, cells proliferation, vascularization, and vascular endothelial growth factor expression. Cell tracking showed that the positively stained cell differentiating into an endotheliocyte could be seen in group 2.

Conclusions

Transplantation of ADSCs before tissue expansion does not improve flap viability but can promote tissue regeneration. Injection of ADSCs after flap elevation can increase the surviving rate of the expanded flap.
Treatment of Abdominal Surgical Wound Dehiscence With Bowel Exposure and Infection
Authors: Morinaga Keigo , Rikimaru Yukiko , Kiyokawa Kensuke
Published: January 2019

Abdominal surgical wound dehiscence with bowel exposure and infection carries a risk of intestinal fistula, making it extremely difficult to treat. The objective at this time is to heal such wounds safely and absolutely with using intrawound continuous negative pressure and irrigation treatment and artificial dermis. The subjects were 18 patients with abdominal wall dehiscence wounds with bowel exposure. Complications had already developed in 4 of the 18 cases of intestinal fistula. Subsequently, these 4 cases were treated with conservative treatment alone, whereas the other 14 were treated by split-thickness skin grafts. Intrawound continuous negative-pressure therapy has enabled the concomitant use of an artificial dermis inside the infected wound by maintaining irrigation of the wound. This method not only eliminated the danger of perforation from direct contact of the sponge with the bowel but also promoted the early proliferation of dermis-like tissue on the bowel surface, enabling safe and absolute healing.
A Test for the Clinical Evaluation of the Flexor Digitorum Superficialis of the Fifth Finger
Authors: Valdés-Flores Everardo , García-Álvarez Edgar , García-Pérez Mauricio M. , Castro-Govea Yanko , Santos-Ibarra Alejandro , Chacón-Martínez Hernán , Betancourt-Espericueta Lizbeth , Mecott Gabriel A.
Published: January 2019

Physical examination is essential in diagnosing tendinous lesions. This is particularly true of the flexor digitorum superficialis of the little finger (FDS5), which is functionally absent in approximately 30% of the population. The objective of our study was to determine the diagnostic value of 3 clinical tests commonly used to assess the function of this tendon.

Methods

Patients with wounds of the FDS5 were included in this study. Under local or regional anesthesia, 3 described clinical tests were performed to assess the function of the FDS5: (i) the classic test; (ii) Stein's modified test, and (iii) Mecott's modified test. We determined sensitivity, specificity, and predictive values of all such tests. The integrity of the tendon was assessed surgically. Correlation among blinded observers was also established.

Results

A total of 28 subjects with a mean age of 28 years (ranging from 5 to 56) participated in this study. The classic test obtained a sensitivity of 100% and a specificity of 72%; Stein's test resulted in a sensitivity of 83% and a specificity of 95%, whereas Mecott's test reached a sensitivity of 100% and a specificity of 95%.

Conclusions

Among the 3 tests described and used in our study, Mecott's modified test proved to be more sensitive and specific than the other two; therefore, we consider this to be the test that should be used in determining the integrity of the FDS5.
Nutritional Care for Patients With Esophageal Cancer
Authors: Hall Katrina A. , Spicer Maria T. , Ilich Jasminka Z. , Levenson Cathy W.
Published: January 2019

Esophageal cancer (EC) is frequently associated with gastrointestinal side effects that contribute to high rates of malnutrition. The objective of this review was to summarize the research on nutritional interventions during EC treatment and formulate recommendations for nutrition care. Recommendations include (1) nutritional assessment using screening tools, (2) dietitian-driven interventions using nutrition protocols, (3) immune-enhanced nutrition administered perioperatively, (4) parenteral nutrition administered concurrently with enteral nutrition and lipid emulsions containing omega-3 fatty acids, and (5) dietitian-driven nutrition therapy until intake meets nutritional goals. Patient outcomes are improved when dietitians plan and implement nutritional interventions throughout EC treatment.
Counseling Strategies to Improve Nutrition Care for Rural Appalachian Patients
Authors: Gutschall Melissa D. , Marchetti Jamie M. , Thompson Kyle L.
Published: January 2019

Culturally sensitive strategies are critical to help the rural Appalachian population prevent and manage chronic diseases. A multiple-methods approach examined specific nutrition strategies used by practitioners and community members (n = 61). Strategy subthemes were categorized into 4 themes from the previously established Rural Nutrition Care Model (1) access and resources (budgeting, planning, resources), (2) sociocultural influences (whole-family approach, simple messages, building rapport, avoiding assumptions), (3) traditional foods (gardening, cooking), and (4) health behaviors (small changes, prevention). Practitioners and patients had differing perspectives on the nutrition context of the rural population (P < .05), which provides a further rationale for the importance of culturally sensitive nutrition counseling strategies.
Dietary Calcium Intake and Physical Activity Levels Among Urban South Indian Type 2 Diabetic Patients
Authors: Raj Jeffrey Pradeep , Selvaraj Dhiraj Ravindran , Thomas John C.
Published: January 2019

Type 2 diabetes mellitus (T2DM) is an independent risk factor for osteoporosis. Data regarding dietary calcium intake (DCI) among T2DM patients in South India are limited. Thus, a cross-sectional study was conducted among 205 T2DM patients from 5 randomly chosen diabetes clinics across Erode city, Tamil Nadu. The mean DCI was 583.72 ± 32.23 mg per day, with 78.5% of patients consuming less than the recommended daily allowance. Low physical activity was noted in 45% of the participants. Other variables, low knowledge scores (adjusted odds ratio; 95% confidence interval) (4.65; 1.43-12.16), unemployment (2.76; 1.57-4.62), being elderly (2.05; 1.23-5.27), and female (1.59; 1.09-4.27), were significantly associated with low DCI.
Polyphasic classification of the gifted natural product producer Streptomyces roseifaciens sp. nov.
Authors: van der Aart Lizah T. , Nouioui Imen , Kloosterman Alexander , Igual José-Mariano , Willemse Joost , Goodfellow Michael , van Wezel Gilles P.
Published: January 2019

A polyphasic study was designed to establish the taxonomic status of a

Streptomyces

strain isolated from soil from the QinLing Mountains, Shaanxi Province, China, and found to be the source of known and new specialized metabolites. Strain MBT76T was found to have chemotaxonomic, cultural and morphological properties consistent with its classification in the genus

Streptomyces

. The strain formed a distinct branch in the Streptomyces16S rRNA gene tree and was closely related to the type strains of

Streptomyces hiroshimensis

and

Streptomyces
mobaraerensis. Multi-locus sequence analyses based on five conserved house-keeping gene alleles showed that strain MBT76T is closely related to the type strain of S. hiroshimensis, as was the case in analysis of a family of conserved proteins. The organism was also distinguished from

S. hiroshimensis

using cultural and phenotypic features. Average nucleotide identity and digital DNA–DNA hybridization values between the genomes of strain MBT76T and

S. hiroshimensis

DSM 40037T were 88.96 and 28.4±2.3%, respectively, which is in line with their assignment to different species. On the basis of this wealth of data it is proposed that strain MBT76T (=DSM 106196T=NCCB 100637T), be classified as a new species,

Streptomyces
roseifaciens sp. nov.
Detecting M/EEG modular brain states in rest and task
Authors: Kabbara A. , Khalil M. , O’Neill G. , Dujardin K. , El Traboulsi Y. , Wendling F. , Hassan M.
Published: January 2019

The human brain is a dynamic networked system that continually reconfigures its connectivity patterns over time. Thus, developing approaches able to adequately detect fast brain dynamics is critical. Of particular interest are the methods that analyze the modular structure of brain networks, i.e. the presence of clusters of regions that are densely inter-connected. In this paper, we propose a novel framework to identify fast modular states that dynamically fluctuate over time during rest and task. We validated our method using MEG data recorded during a finger movement task, identifying modular states linking somatosensory and primary motor regions. The algorithm was also validated on dense-EEG data recorded during picture naming task, revealing the sub-second transition between several modular states which relate to visual processing, semantic processing and language. Next, we validated our method on a dataset of resting state dense-EEG signals recorded from 124 patients with Parkinson’s disease and different cognitive phenotypes. Results disclosed brain modular states that differentiate cognitively intact patients, patients with moderate cognitive deficits and patients with severe cognitive deficits. Our new approach tracks the brain modular states, in healthy subjects and patients, on an adequate task-specific timescale.
Genomic approaches reveal an endemic sub-population of gray wolves in Southern China
Authors: Wang Guo-Dong , Zhang Ming , Wang Xuan , Yang Melinda A. , Cao Peng , Liu Feng , Lu Heng , Feng Xiaotian , Skoglund Pontus , Wang Lu , Fu Qiaomei , Zhang Ya-Ping
Published: January 2019

Despite being one of the most widely distributed terrestrial mammals, the history of gray wolves (Canis lupus) in China is not well understood as their habitats have been destroyed with growing economic development. Using six specimens from wolf skins in Chinese Natural History museums, we sequenced their genome using a modified ancient DNA procedure. Using whole genome sequence analysis, we showed that gray wolves from Southern China (SC) derive from a single lineage, distinct from gray wolves from the Tibetan Plateau (Canis lupus chanco) and Northern China, suggesting that SC gray wolves may form a distinct sub-population. Of SC gray wolves, one wolf from Zhejiang carries a genetic component from a canid that must have diverged earlier from other wolves than jackals did, perhaps through gene flow from a population related to or further diverged from wolves than the dhole, a species distributed in Southern China and Southeast Asia. This may indicate that interspecific gene flow likely played an important role in shaping the speciation patterns and population structure in the genus Canis. Our study is the first to survey museum genomes of gray wolves from Southern China, revealing the presence of an endemic population with ancient interspecific gene flow from a population related to the dhole, and highlighting how sequencing the paleogenome from museum specimens can help us to study extinct species.
The effect of pre-analytical conditions on blood metabolomics in epidemiological studies
Authors: Santos Ferreira Diana L , Maple Hannah J , Goodwin Matt , Brand Judith S , Yip Vikki , Min Josine L , Groom Alix , Lawlor Debbie A , Ring Susan
Published: January 2019

Background

Serum and plasma are commonly used biofluids for large-scale metabolomic-epidemiology studies. Their metabolomic profile is susceptible to changes due to variability in pre-analytical conditions and the impact of this is unclear.

Methods

Participant-matched EDTA-plasma and serum samples were collected from 37 non-fasting volunteers and profiled using a targeted nuclear magnetic resonance (NMR) metabolomics platform (N=151 traits). Metabolic concentrations were compared between reference (pre-storage: 4°C, 1.5h; post-storage: no sample preparation or NMR-analysis delays) and four, pre-storage, blood processing conditions, where samples were incubated at (i) 4°C, 24h; (ii) 4°C, 48h; (iii) 21°C, 24h; (iv) 21°C, 48h, before centrifugation; and two, post-storage, sample processing conditions in which samples (i) thawed overnight, then left for 24h before addition of sodium buffer followed by immediate NMR analysis; (ii) thawed overnight, addition of sodium buffer, then left for 24h before profiling. Linear regression models with random-intercepts were used to assess the impact of these six pre-analytical conditions on EDTA-plasma/serum metabolome.

Results

Fatty acids, beta-hydroxybutyrate, glycoprotein-acetyls and most lipid-related traits, in serum and plasma, were robust to the tested pre and post-storage conditions. Pre-storage conditions impacted concentrations of glycolysis metabolites, acetate, albumin and amino-acids by levels that could potentially bias research results (up to 1.4SD difference compared with reference). Post-storage conditions affected histidine, phenylalanine and LDL-particle-size, with differences up to 1.4SD.

Conclusions

Most metabolic traits are robust to the pre- and post-storage conditions tested here and that may commonly occur in large-scale cohorts. However, concentrations of glycolysis metabolites, and amino-acids may be compromised.

Key messages

In large scale epidemiological studies, blood processing delays, incubation at high temperature prior to long term storage, and NMR profiling delays after long term storage, may occur.

Concentrations of fatty acids, beta-hydroxybutyrate, glycoprotein acetyls and most lipid-related traits are robust to variations in pre-storage temperature and duration of incubation (4°C or 21°C for up to 48h prior to centrifugation) and post-storage sample handling (24h delay in sample preparation or NMR profiling).

Glycolytic metabolite concentrations are altered by pre-storage conditions and amino-acids, particularly histidine and phenylalanine, by both, pre and post-storage conditions.
Neofunctionalisation of basic helix loop helix proteins occurred when plants colonised the land
Authors: Bonnot Clémence , Hetherington Alexander J. , Champion Clément , Breuninger Holger , Kelly Steven , Dolan Liam
Published: January 2019

ROOT HAIR DEFECTIVE SIX-LIKE (RSL)genes control the development of structures – rhizoids, root hairs, gemmae, mucilage papillae – that develop from single cells at the surface of diverse groups of land plants. RSL proteins constitute a subclass (VIIIc) of the basic helix loop helix (bHLH) class VIII transcription factor family. We set out to determine if the function of RSL genes in the control of cell differentiation in land plants was inherited from streptophyte algal ancestor. The Charophyceae are a monophyletic class of streptophyte algae with tissue-like structures and rhizoids. We identified the single class VIII bHLH gene from the charophyceaen algaChara braunii(CbbHLHVIII). Phylogenetic analysis suggests that this protein is sister to the RSL (bHLH subclass VIIIc) proteins and together they constitute a monophyletic group. Expression of CbbHLHVIIIdoes not compensate for loss of the RSL function in either Marchantia polymorpha or Arabidopsis thaliana. Furthermore, CbbHLHVIII is expressed at sites of morphogenesis inC. braunii– the apices, nodes and gametangia – but not in rhizoids. This indicates thatC. brauniiclass VIII protein is functionally different from land plant RSL proteins; they control rhizoid development in land plants but not in the charophycean algae. These data are consistent with the hypothesis that RSL proteins and their function in the differentiation of cells at the plant surface evolved in the lineage leading to land plants after the divergence of the land plants andC. brauniifrom their last common ancestor. This may have occurred by neofunctionalisation at or before the colonisation of the land by streptophytes.
Seed Coat Pattern QTL and Development in Cowpea (Vigna unguiculata [L.] Walp.)
Authors: Herniter Ira A. , Lo Ryan , Muñoz-Amatriaín María , Lo Sassoum , Guo Yi-Ning , Huynh Bao-Lam , Lucas Mitchell , Jia Zhenyu , Roberts Philip A. , Lonardi Stefano , Close Timothy J.
Published: January 2019

The appearance of the seed is an important aspect of consumer preference for cowpea (Vigna unguiculata [L.] Walp.). Seed coat pattern in cowpea has been a subject of study for over a century. This study makes use of newly available resources, including mapping populations, a reference genome and additional genome assemblies, and a high-density single nucleotide polymorphism genotyping platform, to map various seed coat pattern traits to three loci, concurrent with the Color Factor (C), Watson (W), and Holstein (H) factors identified previously. Several gene models encoding proteins involved in regulating the later stages of the flavonoid biosynthesis pathway have been identified as candidate genes, including a basic helix-loop-helix gene (Vigun07g110700) for the C locus, a WD-repeat gene (Vigun09g139900) for the W locus and an E3 ubiquitin ligase gene (Vigun10g163900) for the H locus. A model of seed coat development, consisting of six distinct stages, is described to explain some of the observed pattern phenotypes.
False-positive neuroimaging: Undisclosed flexibility in testing spatial hypotheses allows presenting anything as a replicated finding
Authors: Hong YongWook , Yoo Yejong , Han Jihoon , Wager Tor D. , Woo Choong-Wan
Published: January 2019

Hypothesis testing in neuroimaging studies relies heavily on treating named anatomical regions (e.g., “the amygdala”) as unitary entities. Though data collection and analyses are conducted at the voxel level, inferences are often based on anatomical regions. The discrepancy between the unit of analysis and the unit of inference leads to ambiguity and flexibility in analyses that can create a false sense of reproducibility. For example, hypothesizing effects on “amygdala activity” does not provide a falsifiable and reproducible definition of precisely which voxels or which patterns of activation should be observed. Rather, it comprises a large number of unspecified sub-hypotheses, leaving room for flexible interpretation of findings, which we refer to as “model degrees of freedom.” From a survey of 135 functional Magnetic Resonance Imaging studies in which researchers claimed replications of previous findings, we found that 42.2% of the studies did not report any quantitative evidence for replication such as activation peaks. Only 14.1% of the papers used exact coordinate-based ora prioripattern-based models. Of the studies that reported peak information, 42.9% of the ‘replicated’ findings had peak coordinates more than 15 mm away from the ‘original’ findings, suggesting that different brain locations were activated, even when studies claimed to replicate prior results. To reduce the flexible and qualitative region-level tests in neuroimaging studies, we recommend adopting quantitative spatial models and tests to assess the spatial reproducibility of findings. Techniques reviewed here include permutation tests on peak distance, Bayesian MANOVA, anda priorimultivariate pattern-based models. These practices will help researchers to establish precise and falsifiable spatial hypotheses, promoting a cumulative science of neuroimaging.
A neuroprosthetic system to restore neuronal communication in modular networks
Authors: Buccelli S. , Bornat Y. , Colombi I. , Ambroise M. , Martines L. , Pasquale V. , Bisio M. , Tessadori J. , Nowak P. , Grassia F. , Averna A. , Tedesco M. , Bonifazi P. , Difato F. , Massobrio P. , Levi T. , Chiappalone M.
Published: January 2019

Recent advances in neurotechnology allow neurological impairments to be treated or reduced by brain machine interfaces and neuroprostheses. To develop energy-efficient and real-time capable devices, neuromorphic computing systems are envisaged as the core of next-generation ‘neurobiohybrid’ systems for brain repair. We demonstrate here the first exploitation of a neuromorphic prosthesis to restore bidirectional interactions between two neuronal populations, even when one is damaged or completely missing. We used in vitro modular cell cultures to mimic the mutual interaction between neuronal assemblies and created a focal lesion to functionally disconnect the two populations. Then, we employed our neuromorphic prosthesis for two specific applications with future clinical implications: bidirectional bridging to artificially reconnect two disconnected neuronal modules and hybrid bidirectional bridging to replace the activity of one module with a neuromorphic spiking neural network. Our neuroprosthetic system opens up new avenues for the development of novel bioelectrical therapeutics for human applications.
Mice carrying a humanizedFoxp2knock-in allele show region-specific shifts of striatal Foxp2 expression levels
Authors: Schreiweis C , Irinopoulou T , Vieth B , Laddada L , Oury F , Burguière E , Enard W , Groszer M
Published: January 2019

Genetic and clinical studies of speech and language disorders are providing starting points to unravel underlying neurobiological mechanisms. The gene encoding the transcription factorFOXP2has been the first example of a gene involved in the development and evolution of this human-specific trait. A number of autosomal-dominantFOXP2mutations are associated with developmental speech and language deficits indicating that gene dosage plays an important role in the disorder. Comparative genomics studies suggest that two human-specific amino acid substitutions in FOXP2 might have been positively selected during human evolution. A knock-in mouse model carrying these two amino acid changes in the endogenous mouseFoxp2gene(Foxp2hum/hum)shows profound changes in striatum-dependent behaviour and neurophysiology, supporting a functional role for these changes. However, how this affects Foxp2 expression patterns in different striatal regions and compartments has not been assessed. Here, we characterized Foxp2 protein expression patterns in adult striatal tissue inFoxp2hum/hummice. Consistent with prior reports in wildtype mice, we find that striatal neurons inFoxp2hum/hummice and wildtype littermates express Foxp2 in a range from low to high levels. However, we observe a shift towards more cells with higher Foxp2 expression levels inFoxp2hum/hummice, significantly depending on the striatal region and the compartment. As potential behavioural readout of these shifts in Foxp2 levels across striatal neurons, we employed a morphine sensitization assay. While we did not detect differences in morphine-induced hyperlocomotion during acute treatment, there was an attenuated hyperlocomotion plateau during sensitization inFoxp2hum/hummice. Taken together, these results suggest that the humanizedFoxp2allele in a mouse background is associated with a shift in striatal Foxp2 protein expression pattern.
CellSIUS provides sensitive and specific detection of rare cell populations from complex single cell RNA-seq data
Authors: Wegmann Rebekka , Neri Marilisa , Schuierer Sven , Bilican Bilada , Hartkopf Huyen , Nigsch Florian , Mapa Felipa , Waldt Annick , Cuttat Rachel , Salick Max R. , Raymond Joe , Kaykas Ajamete , Roma Guglielmo , Keller Caroline Gubser
Published: January 2019

Comprehensive benchmarking of computational methods for single-cell RNA sequencing (scRNA-seq) analysis is scarce. Using a modular workflow and a large dataset with known cell composition, we benchmarked feature selection and clustering methodologies for scRNA-seq data. Results highlighted a methodology gap for rare cell population identification for which we developed CellSIUS (Cell Subtype Identification from Upregulated gene Sets). CellSIUS outperformed existing approaches, enabled the identification of rare cell populations and, in contrast to other methods, simultaneously revealed transcriptomic signatures indicative of the rare cells’ function. We exemplified the use of our workflow and CellSIUS for the characterization of a human pluripotent cell 3D spheroid differentiation protocol recapitulating deep-layer corticogenesis in vitro. Results revealed lineage bifurcation between Cajal-Retzius cells and layer V/VI neurons as well as rare cell populations that differ by migratory, metabolic, or cell cycle status, including a choroid plexus neuroepithelial subgroup, revealing previously unrecognized complexity in human stem cell-derived cellular populations.
System analysis of cross-talk between nuclear receptors reveals an opposite regulation of the cell cycle by LXR and FXR in human HepaRG liver cells
Authors: Wigger Leonore , Casals-Casas Cristina , Baruchet Michaël , Trang Khanh B. , Pradervand Sylvain , Naldi Aurélien , Desvergne Béatrice
Published: January 2019

Transcriptional regulations exert a critical control of metabolic homeostasis. In particular, the nuclear receptors (NRs) are involved in regulating numerous pathways of the intermediate metabolism. The purpose of the present study was to explore in liver cells the interconnectedness between three of them, LXR, FXR, and PPARα, all three known to act on lipid and glucose metabolism, and also on inflammation. The human cell line HepaRG was selected for its best proximity to human primary hepatocytes. Global gene expression of differentiated HepaRG cells was assessed after 4 hours and 24 hours of exposure to GW3965 (LXR agonist), GW7647 (PPARα agonist), and GW4064 and CDCA (FXR synthetic and natural agonist, respectively). Our work revealed that, contrary to our expectations, NR specificity is largely present at the level of target genes, with a smaller than expected overlap of the set of genes targeted by the different NRs. It also highlighted the much broader activity of the synthetic FXR ligand compared to CDCA. More importantly, our results revealed that activation of FXR has a pro-proliferative effect and decreases polyploidy of hepatocytes, while LXR inhibits the cell cycle progression, inducing hepatocyte differentiation and a higher polyploidism. Conclusion: these results highlight the importance of analyzing the different NR activities in a context allowing a direct confrontation of each receptor outcome, and reveals the opposite role of FXR and LXR in hepatocyte cells division and maturation.
Community size affects the signals of ecological drift and niche selection on biodiversity
Authors: Siqueira Tadeu , Saito Victor S. , Bini Luis M. , Melo Adriano S. , Petsch Danielle K. , Landeiro Victor L. , Tolonen Kimmo T. , Jyrkänkallio-Mikkola Jenny , Soininen Janne , Heino Jani
Published: January 2019

Ecological drift can override the effects of deterministic niche selection on small populations and drive the assembly of small communities. We tested the hypothesis that smaller local communities are more dissimilar among each other because of ecological drift than larger communities, which are mainly structured by niche selection. We used a unique, comprehensive dataset on insect communities sampled identically in a total of 200 streams in climatically different regions (Brazil and Finland) that differ in community size by fivefold. Null models allowed us to estimate the magnitude to which beta diversity deviates from the expectation under a random assembly process while taking differences in species richness and relative abundance into account, i.e., beta deviation. Beta diversity of small tropical communities was consistently higher but closer to null expectations than β-diversity of large communities. However, although β-deviation and community size were strongly related in both regions, the direction of the relationship varied according to dissimilarity metrics. While incidence-based β-diversity was lower than expected (communities were less dissimilar than null expectations) and negatively related to community size in Brazil, abundance-based β-diversity was higher than expected (communities were more dissimilar than null expectations) and positively related to community size in both regions. We suggest that ecological drift drives variation in small communities by increasing the chances of species with low abundance and narrow distribution to occur within the metacommunity. Also, while weak niche selection and high dispersal rates likely reduced variation in community structure among large tropical streams, niche selection was likely sufficient to cause non-random variations in the relative abundances of genera among large communities in both regions. Habitat destruction, overexploitation, pollution, and reductions in connectivity have been reducing the size of biological communities. These environmental pressures will make smaller communities more vulnerable to novel conditions and render community dynamics more unpredictable, as random demographic processes should prevail under these conditions. Incorporation of community size into ecological models should provide conceptual, empirical and applied insights into a better understanding of the processes driving changes in biodiversity.
From Habitat Use to Social Behavior: Natural History of a Voiceless Poison Frog, Dendrobates tinctorius
Authors: Rojas Bibiana , Pašukonis Andrius
Published: January 2019

Descriptive studies of natural history have always been a source of knowledge on which experimental work and scientific progress rely. Poison frogs are a well-studied group of small Neotropical frogs with diverse parental behaviors, distinct calls, and bright colors that warn predators about their toxicity; and a showcase of advances in fundamental biology through natural history observations. The dyeing poison frog, Dendrobates tinctorius, is emblematic of the Guianas region, widespread in the pet-trade, and increasingly popular in research. This species shows several unusual behaviors, such as the lack of advertisement calls and the aggregation around tree-fall gaps, which remain poorly described and understood. Here, we summarize our observations from a natural population of D. tinctorius in French Guiana collected over various field trips between 2009 and 2017; our aim is to provide groundwork for future fundamental and applied research spanning parental care, animal dispersal, disease spread, habitat use in relation to color patterns, and intra specific communication, to name a few. We report sex differences in habitat use and the striking invasion of tree-fall gaps; describe their courtship and aggressive behaviors; document egg development and tadpole transport; and discuss how the knowledge generated by this study could set the grounds for further research on the behavior, ecology, and conservation of this species.
Sensitivity of single units in the LSO of decerebrate cat to sinusoidally amplitude modulated tones
Authors: Greene Nathaniel T. , Davis Kevin A.
Published: January 2019

Fluctuations in amplitude are a common component of behaviorally important sound stimuli. Amplitude modulation (AM) is encoded by the peripheral auditory system in the timing of discharge spikes, and, more centrally, in the discharge rate. The mechanism producing this transformation from a time- to rate-based code is not known, but recent modeling efforts have suggested a role for neurons with response characteristics consistent with cells in the lateral superior olive (LSO). The responses of single units in the LSO of unanesthetized decerebrate cat were recorded to monaural sinusoidally amplitude modulated (SAM) tones by systematically varying sound level and modulation frequency (fm), and are described in terms of synchronization to the envelope and average discharge rate as a function of fm. LSO units typically synchronize strongly to low fm, and discharge preferentially (i.e. more strongly) over a small range of fm in response to low level SAM tones. At higher sound levels synchronization decreases and response rate increases until most or all modulation in the response is lost. These results contrast with responses recorded in the barbiturate-anesthetized cat, which tend to respond to most low-frequency modulations, and are consistent with LSO as an intermediate processing stage between the peripheral temporal- and central rate-based code for AM sounds.
Diversity and function of fungi associated with the fungivorous millipede,Brachycybe lecontii
Authors: Macias Angie M. , Marek Paul E. , Morrissey Ember M. , Brewer Michael S. , Short Dylan P.G. , Stauder Cameron M. , Wickert Kristen L. , Berger Matthew C. , Metheny Amy M. , Stajich Jason E. , Boyce Greg , Rio Rita V. M. , Panaccione Daniel G. , Wong Victoria , Jones Tappey H. , Kasson Matt T.
Published: January 2019

Fungivorous millipedes (subterclass Colobognatha) likely represent some of the earliest known mycophagous terrestrial arthropods, yet their fungal partners remain elusive. Here we describe relationships between fungi and the fungivorous millipede,Brachycybe lecontii. Their fungal community is surprisingly diverse with 176 genera, 39 orders, and four phyla and includes several undescribed species. Of particular interest are twelve genera conserved across wood substrates and millipede clades that comprise the core fungal community ofB. lecontii.Wood decay fungi, long speculated to serve as the primary food source forBrachycybespecies, were absent from this core assemblage and proved lethal to millipedes in pathogenicity assays while entomopathogenic Hypocreales were more common in the core but had little effect on millipede health. This study represents the first survey of fungal communities associated with any colobognath millipede, and these results offer a glimpse into the complexity of millipede fungal communities.