bluuebunny/crossref_metadata_2025 huggingface dataset:
Author Profiling and Related Applications
Authors: Oakes Michael
Published: January 2019

Author profiling is the analysis of people’s writing in an attempt to find out which classes they belong to, such as gender, age group or native language. Many of the techniques for author profiling are derived from the related task of Author Identification, so we will look at this topic first. Author identification is the task of finding out who is most likely to have written a disputed document, and there are a number of computational approaches to this. The three main subtasks are the compilation of corpora of texts known to be written by the candidate authors, the selection of linguistic features to represent those texts, and statistics for discriminating between those features which are most indicative of a particular author’s writing style. Plagiarism is the unacknowledged use of another author’s original work, and we will look at software for its detection. The chapter will cover the types of text obfuscation strategies used by plagiarists, commercial plagiarism detection software and its shortcomings, and recent research systems. Strategies have been developed for both external plagiarism detection (where the original source is searched for in a large document collection) and intrinsic plagiarism detection (where the source text is not available, necessitating a search for inconsistencies within the suspicious document). The specific problems of plagiarism by translation of an original in another language, and the unauthorized copying of sections of computer code, are described. Evaluation forums and publicly available test data sets are covered for each of the main topics of this chapter.
Morphology in Lexical-Functional Grammar and Head-driven Phrase Structure Grammar
Authors: Sadler Louisa , Nordlinger Rachel
Published: January 2019

Lexical-Functional Grammar (LFG) and Head-Driven Phrase Structure Grammar (HPSG) are both lexicalist, non-transformational, constraint-based grammatical frameworks. While they differ in many respects, they share a number of fundamental principles relevant to morphological theory and analysis, which guide the overall architecture of the grammar. The two frameworks also share a common commitment to being fully explicit and implementable, with strong links to computational implementations. This chapter provides an overview of the general approaches to morphology and the morphology-syntax interface taken by researchers working within these frameworks, illustrating the relevant aspects of each framework through discussion of morphological phenomena such as multiple exponence, auxiliaries, case stacking, morphotactics and clitics.
Morphological Theory and Diachronic Change
Authors: Hüning Matthias
Published: January 2019

Variation and change are essential for any human language, but at the same time they form a challenge for theoretical models of grammar. This chapter discusses some notions and phenomena encountered in word-formation change that should be relevant to any morphological theory. It focuses on the notion of reanalysis and on phenomena related to this notion. In its second half, the chapter focuses on the notion of productivity and on the view that every change in word-formation has to be seen as a change in productivity. It is claimed that theoretical models will need to become more attentive to usage-based perspectives in order to integrate the dynamics of language and language change. The examples used for illustration purposes in this chapter are taken from Dutch, German, and English.
Theoretical Issues in Word Formation
Authors: Lieber Rochelle
Published: January 2019

This chapter surveys a number of frameworks and theoretical issues in the analysis of derivation and compounding that have occupied morphologists over the last six decades, and begins to assess what has been achieved over this period. Topics include the formal nature of word formation, the relevant units of analysis, the form of morphological rules and processes, the relationship of morphological theory to syntax and phonology, and the theoretical treatment of lexical semantics. The chapter also explores a variety of narrower issues such as bracketing paradoxes, headedness, the question of affix ordering, and the nature of derivational paradigms.
Morphological Theory and Psycholinguistics
Authors: Gagné Christina L. , Spalding Thomas
Published: January 2019

This chapter reviews psycholinguistic theories and experimental work relating to morphologically complex words. It presents five general theoretical approaches to the processing of complex words, followed by four areas of experimental work that have been used to test these theories. The theories differ in the extent to which constituent morphemes are explicitly represented and used in processing. Indeed, they range from an approach in which there are only orthographic and semantic representations (i.e. no separate word or morpheme representations) to an approach in which the whole word and all possible constituents are represented and activated. In general, the experimental work supports the idea that the processing of complex words makes use of the morphological constituents of the words. However, the details of such processing are not yet clear.
Endangered Tenderness
Authors: Fisk Charles
Published: January 2019

At a lecture in 1984 about the figure of the alienated Fremdling in Schubert’s Winterreise song cycle, I understood more clearly than ever before why Franz Schubert was the composer with whom I had most identified as I struggled with my own homosexuality. In a flash, the term Fremdling came to identify a figure who haunted not only Schubert’s songs, but also much of his instrumental music—a queer, existentially imperiled figure whose expressions of tenderness were so often overshadowed by ominous or disquieting musical elements. Frederic Chopin is another composer whose music has strongly resonated with my own experience of sexual and affective dysphoria, not only in the longer pieces, in which the promise of emotional fulfillment is either denied or ambiguous, but also in the melancholy nostalgia of many of the shorter pieces, especially in those with ambiguously evocative, duetlike textures.
Transgender Passing Guides and the Vocal Performance of Gender and Sexuality
Authors: Pennington Stephan
Published: January 2019

There has been a consistent interest in how people perform gender vocally. An under-utilized source of insight into the vocal presentation of self can be found in the passing guides transgender people circulate amongst themselves that analyze how cisgender people perform gender through the voice. This chapter uses transgender passing guides, feminist sociolinguistics, and vocal pedagogy literature to present a consolidated set of tools to analyze the construction of normative gender vocal performance. After presenting these tools, the chapter then uses them to analyze the musical performances of cisgender artists trying to pass as a different gender, cisgender queer artists twisting those vocal norms in order to make themselves audible as queer, and cisgender artists trying to pass as their own gender.
Construction of thermostable cellobiohydrolase I from the fungus Talaromyces cellulolyticus by protein engineering
Authors: Nakabayashi Makoto , Kamachi Saori , Malle Dominggus , Yanamoto Toshiaki , Kishishita Seiichiro , Fujii Tatsuya , Inoue Hiroyuki , Ishikawa Kazuhiko
Published: January 2019

Fungus-derived GH-7 family cellobiohydrolase I (CBHI, EC 3.2.1.91) is one of the most important industrial enzymes for cellulosic biomass saccharification. Talaromyces cellulolyticus is well known as a mesophilic fungus producing a high amount of CBHI. Thermostability enhances the economic value of enzymes by making them more robust. However, CBHI has proven difficult to engineer, a fact that stems in part from its low expression in heterozygous hosts and its complex structure. Here, we report the successful improvement of the thermostability of CBHI from T. cellulolyticus using our homologous expression system and protein engineering method. We examined the key structures that seem to contribute to its thermostability using the 3D structural information of CBHI. Some parts of the structure of the Talaromyces emersonii CBHI were grafted into T. cellulolyticus CBHI and thermostable mutant CBHIs were constructed. The thermostability was primarily because of the improvement in the loop structures, and the positive effects of the mutations for thermostability were additive. By combing the mutations, the constructed thermophilic CBHI exhibits high hydrolytic activity toward crystalline cellulose with an optimum temperature at over 70°C. In addition, the strategy can be applied to the construction of the other thermostable CBHIs.
Prevalence and determinants of metabolic syndrome in Spanish salaried workers: evidence from 15 614 men and women
Authors: Matilla-Santander Nuria , Espinola Marina , Cartanyà-Hueso Àurea , Lidón-Moyano Cristina , González-Marrón Adrián , Martín-Sánchez Juan Carlos , Cainzos-Achirica Miguel , Martínez Sánchez Jose M
Published: January 2019

Objective

To describe the prevalence of Spanish workers with Metabolic Syndrome (MetS) and those at risk of developing MetS in 2015.

Methods

Cross-sectional study of workers (n = 15 614). We used a modified definition of the NCEP:ATPIII criteria for MetS (we used body mass index (BMI) above 28.8 kg/m2 instead of the waist circumference criterion). We calculated the prevalence of MetS (having at least three components) and of being at risk of MetS (having one or two components). We calculated adjusted odds ratios (aOR) of MetS according to socio-economic and workplace characteristics.

Results

The proportions of workers with and at risk of MetS were 7.1 and 31.9%, respectively. The most prevalent criterion was having a BMI > 28.8 kg/m2 (24.1%) in men and cHDL < 40 mg/dl in women (12.9%). There were significant associations between MetS and men (aOR compared to women = 3.73, CI 95%: 3.19; 4.36); age (higher among oldest, aOR = 5.75, CI 95%: 4.37;7.56); and social class (higher among lower social class, aOR = 2.03, CI 95%: 1.65;2.48).

Conclusion

Reducing any of the five MetS components, while taking into account the differences found by socio-economic and workplace characteristics, should be one priority for reducing MetS prevalence.
Social Cognition, Language, and Social Behavior in 7-Year-Old Children at Familial High-Risk of Developing Schizophrenia or Bipolar Disorder: The Danish High Risk and Resilience Study VIA 7—A Population-Based Cohort Study
Authors: Christiani Camilla Jerlang , Jepsen Jens R M , Thorup Anne , Hemager Nicoline , Ellersgaard Ditte , Spang Katrine S , Burton Birgitte K , Gregersen Maja , Søndergaard Anne , Greve Aja N , Gantriis Ditte L , Poulsen Gry , Uddin Md Jamal , Seidman Larry J , Mors Ole , Plessen Kerstin J , Nordentoft Merete
Published: January 2019

Objective

To characterize social cognition, language, and social behavior as potentially shared vulnerability markers in children at familial high-risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP).

Methods

The Danish High-Risk and Resilience Study VIA7 is a multisite population-based cohort of 522 7-year-old children extracted from the Danish registries. The population-based controls were matched to the FHR-SZ children on age, sex, and municipality. The FHR-BP group followed same inclusion criteria. Data were collected blinded to familial high-risk status. Outcomes were social cognition, language, and social behavior.

Results

The analysis included 202 FHR-SZ children (girls: 46%), 120 FHR-BP children (girls: 46.7%), and 200 controls (girls: 46.5%). FHR-SZ children displayed significant deficits in language (receptive: d = −0.27, P = .006; pragmatic: d = −0.51, P < .001), social responsiveness (d = −0.54, P < .001), and adaptive social functioning (d = −0.47, P < .001) compared to controls after Bonferroni correction. Compared to FHR-BP children, FHR-SZ children performed significantly poorer on adaptive social functioning (d = −0.29, P = .007) after Bonferroni correction. FHR-BP and FHR-SZ children showed no significant social cognitive impairments compared to controls after Bonferroni correction.

Conclusion

Language, social responsiveness, and adaptive social functioning deficits seem associated with FHR-SZ but not FHR-BP in this developmental phase. The pattern of results suggests adaptive social functioning impairments may not be shared between FHR-BP and FHR-SZ in this developmental phase and thus not reflective of the shared risk factors for schizophrenia and bipolar disorder.
Posterior Thoracolumbar Instrumented Fusion for Burst Fractures
Authors: Ituarte Felipe , Wiegers Nicholas W. , Ruppar Todd , Goldstein Christina , Nourbakhsh Ali
Published: January 2019

Study Design:

This was a meta-analysis study.

Objective:

To compare different posterior spine fixation methods for burst fracture fixation.

Summary of Background Data:

This study was performed to elucidate if the current body of literature supports one posterior spinal fusion fixation method for burst fracture to minimize the rate of implant failure and progression of posttraumatic kyphosis.

Materials and Methods:

An extensive electronic search was conducted using PubMed for pertinent articles. The articles were examined against the inclusion and exclusion criteria. Data pertaining to kyphosis angle, Frankel score, vertebral level, blood loss, operation time, hospital stay, postoperative bracing, instrument failure, complications, and follow-up were collected. A random effects model was chosen due to variation among the individual studies’ patient populations and surgical methods.

Results:

A total of 23 publications were eventually deemed eligible according to the criteria and included into this study. The group with 2 levels above and 1 below with intermediate screws had the greatest maintenance of spine kyphosis and lowest implant failure at final follow-up (P<0.001). There was no difference between the periods of hospital stay (P=0.788) and blood loss (P=0.154) among different tiers.

Conclusions:

A fixation method consisting of 2 levels above and 1 below with intermediate screws for the thoracolumbar burst fractures showed the highest correction of kyphosis angle both at immediate and final follow-up and also the lowest implant failure at final follow-up.
Clinical Characteristics of Basal Cell Carcinoma in African Americans: A 10-Year Retrospective Review at a Single Academic Institution
Authors: Gupta Rishu , Gordon Shayna L. , Council M. Laurin , Hurst Eva A.
Published: January 2019

BACKGROUND

Basal cell carcinoma (BCC) is an uncommon diagnosis in African Americans, and as a result, there is a limited amount of data available.

OBJECTIVE

We sought to describe the clinical characteristics of BCC in African Americans treated with Mohs micrographic surgery (MMS).

METHODS

We performed a retrospective case series in an ambulatory referral center at a single academic institution from 2007 to 2017 to characterize BCCs in African Americans treated with MMS.

RESULTS

A total of 17 patients, who identified as black or African American, with 18 BCCs were included for analysis. Patients were predominantly female (82%) with a mean age at diagnosis of 61 years. Seventy-eight percent of tumors were located in the head and neck region with 50% of BCCs located in high-risk areas. The average preoperative and postoperative defect size was 1.78 and 5.90 cm2, respectively, with a mean number of 2.2 Mohs stages required for tumor clearance. One patient had Gorlin syndrome.

CONCLUSION

The presented retrospective review adds to limited available reported studies regarding BCC in African Americans to potentially aid in early recognition of these tumors.
Implementing Our Microsurgical Breast Reconstruction Enhanced Recovery after Surgery Pathway: Consensus Obstacles and Recommendations
Authors: Stone Jill P. , Siotos Charalampos , Sarmiento Samuel , Temple-Oberle Claire , Aliu Oluseyi , Cooney Damon S. , Broderick Kristen P. , Sacks Justin M. , Manahan Michele A. , Rosson Gedge D.
Published: January 2019

Enhanced recovery after surgery pathways are well established in other surgical specialties but are relatively new in plastic surgery. These guidelines focus on improving patient care by incorporating evidence-based recommendations. Length of stay is shorter, and overall hospital costs are lower without compromising patient satisfaction. When care is standardized, ambiguity is removed and physician acceptance is improved. Yet, implementation can be challenging on an institutional level. The Johns Hopkins microsurgical breast reconstruction team identified areas of dogmatic dissonance during 3 focus groups to formalize an enhanced recovery pathway for microsurgical breast reconstruction. Six microsurgeons used nominal group technique to reach consensus. Four discussion points were identified: multidisciplinary buy-in, venous thromboembolism (VTE) chemophylaxis, early feeding, and dietary restrictions. Evidence-based recommendations and our enhanced recovery after surgery protocol are provided.
Cellular Dynamics in Early Healing of Mouse Tympanic Membranes
Authors: Chari Divya A. , Frumm Stacey M. , Akil Omar , Tward Aaron D.
Published: January 2019

Aim:

To better elucidate the cellular dynamics by which perforations in the tympanic membrane (TM) are healed.

Background:

Under normal conditions, epidermal cells are born and then migrate radially outward from the malleus in the TM. It is unknown what the relative contribution of newly proliferated cells from different lineages is in the healing of TM perforations.

Methods:

Thirty-six female mice were used in this study. Ethynyl deoxyuridine, a thymidine analogue that labels newly proliferated cells, was injected intraperitoneally into each mouse and then subsequently supplied in the drinking water. Acute perforations were performed on the right TM and the left TM served as the control and remained intact. The animals were sacrificed at six time points between 2 hours and 6 days. We stained for proliferative, epithelial, mesenchymal markers, and ethynyl deoxyuridine and analyzed the distribution of cells.

Results:

In control TMs, newly proliferated cells were detected around the malleus handle and then migrated radially outward. Perforated TMs had a significantly higher number of newly proliferated cells throughout the tympanic membrane with a marked proliferative response of epithelial, mesenchymal, and mucosal cells in the region of the malleus and perforation. The majority of cells in the healed perforation were newly proliferated. In the anterior TM opposite the perforation, an increased turnover of keratinocytes was noted, but not mesenchymal cells.

Conclusions:

Perforation of the TM alters the cellular dynamics throughout the entire TM, rather than simply adjacent to the perforation. This argues for long distance signaling occurring in the perforated TM.
Clinical and Physiologic Predictors and Postoperative Outcomes of Near Dehiscence Syndrome
Authors: Baxter Michael , McCorkle Colin , Trevino Guajardo Carolina , Zuniga Maria Geraldine , Carter Alex M. , Della Santina Charles C. , Minor Lloyd B. , Carey John P. , Ward Bryan K.
Published: January 2019

Objective:

To identify predictors of near dehiscence (ND) or thin rather than dehiscent bone overlying the superior semicircular canal in patients with signs and symptoms suggestive of superior semicircular canal dehiscence syndrome (SCDS), as well as postoperative outcomes.

Study Design:

Retrospective case-control study.

Setting:

Tertiary referral center.

Patients:

All 288 patients who underwent middle cranial fossa approach for repair of SCDS (1998–2018) were reviewed for cases of ND. Demographics, symptoms, and clinical signs including nystagmus, ocular vestibular-evoked myogenic potential (oVEMP) amplitude, cervical vestibular-evoked myogenic potential (cVEMP) thresholds, and low-frequency air-bone gap were compared before and after surgery.

Main Outcome Measure:

Presence of preoperative ND and postoperative symptoms and physiologic measures.

Results:

Seventeen cases of ND (16 patients, 17 ears) and 34 cases (34 ears) of frank SCDS were identified. ND cases differed from frank dehiscence cases in that they were less likely to have nystagmus in response to ear canal pressure or loud sounds, OR = 0.05 (95% CI 0.01–0.25) and Valsalva, OR = 0.08 (0.01–0.67), smaller peak-to-peak oVEMP amplitudes, OR = 0.84 (0.75–0.95), and higher cVEMP thresholds, OR = 1.21 (1.07–1.37). Patients with ND had similar symptoms to those with frank SCDS before surgery, and after surgery had outcomes similar to patients with frank SCDS.

Conclusions:

In patients with symptoms consistent with SCDS, predictors of ND include absence of nystagmus in response to pressure/loud sounds, greater cVEMP thresholds, and smaller oVEMP amplitudes. We propose ND is on a spectrum of dehiscence that partially accounts for the diversity of clinical presentations of patients with SCDS.
Adequacy of bystander actions in unconscious patients: an audit study in the Ghent region (Belgium)
Authors: Lamote Ines , Calle Paul , Lyphout Cathelijne , Van de Voorde Patrick
Published: January 2019

Objective

Early recognition and appropriate bystander response has proven effect on the outcome of many critically ill patients, including those in cardiac arrest. We wanted to audit prehospital bystander response in our region and identify areas for improvement.

Patients and methods

We prospectively collected data, including Emergency Medical Services dispatch center audio files, on all patients with a decreased level of consciousness presenting to the Ghent University Hospital prehospital emergency care unit (n = 151). Three trained emergency physicians reviewed the bystander responses, both before and after dispatcher advice was given. Suboptimal actions (SAs) were only withheld if there was 100% consensus.

Results

SAs were recognized in 54 (38%) of the 142 cases, and most often related to delayed (n = 35) or inaccurate (n = 12) alerting of the dispatch center. In seven cases, the aid given was considered suboptimal in itself. Importantly, in 21 (25.9%) of the 81 cases where a clear advice was given by the dispatcher, this advice was ignored. In 12 cases, a general practitioner was present at scene. We recognized SAs in 80% of these cases (8/10; insufficient information, n = 2). Cardiopulmonary resuscitation was started in only 29 (43.3%) of the 67 cases of cardiac arrest where dispatcher-assisted cardiopulmonary resuscitation was indicated at the moment of first Emergency Medical Services call.

Conclusion

We audited bystander response for unconscious patients in our region and found a high degree of suboptimal actions. These results should inform policy makers and healthcare professionals and force them to urgently reflect on how to improve the first parts of the chain of survival.
Facial Emotion Recognition Abilities in Women Experiencing Eating Disorders
Authors: Wyssen Andrea , Lao Junpeng , Rodger Helen , Humbel Nadine , Lennertz Julia , Schuck Kathrin , Isenschmid Bettina , Milos Gabriella , Trier Stephan , Whinyates Katherina , Assion Hans-Jörg , Ueberberg Bianca , Müller Judith , Klauke Benedikt , Teismann Tobias , Margraf Jürgen , Juckel Georg , Kossmann Christian , Schneider Silvia , Caldara Roberto , Munsch Simone
Published: January 2019

Objective

Impairments in facial emotion recognition are an underlying factor of deficits in emotion regulation and interpersonal difficulties in mental disorders and are evident in eating disorders (EDs).

Methods

We used a computerized psychophysical paradigm to manipulate parametrically the quantity of signal in facial expressions of emotion (QUEST threshold seeking algorithm). This was used to measure emotion recognition in 308 adult women (anorexia nervosa [n= 61], bulimia nervosa [n= 58], healthy controls [n= 130], and mixed mental disorders [mixed,n= 59]). The M (SD) age was 22.84 (3.90) years. The aims were to establish recognition thresholds defining how much information a person needs to recognize a facial emotion expression and to identify deficits in EDs compared with healthy and clinical controls. The stimuli included six basic emotion expressions (fear, anger, disgust, happiness, sadness, surprise), plus a neutral expression.

Results

Happiness was discriminated at the lowest, fear at the highest threshold by all groups. There were no differences regarding thresholds between groups, except for the mixed and the bulimia nervosa group with respect to the expression of disgust (F(3,302) = 5.97,p= .001, η2= .056). Emotional clarity, ED pathology, and depressive symptoms did not predict performance (R2Change≤ .010,F(1,305) ≤ 5.74,p≥ .079). The confusion matrix did not reveal specific biases in either group.

Conclusions

Overall, within-subject effects were as expected, whereas between-subject effects were marginal and psychopathology did not influence emotion recognition. Facial emotion recognition abilities in women experiencing EDs compared with women experiencing mixed mental disorders and healthy controls were similar. Although basic facial emotion recognition processes seems to be intact, dysfunctional aspects such as misinterpretation might be important in emotion regulation problems.

Clinical Trial Registration Number: DRKS-ID: DRKS00005709.
Soil Bacterial and Fungal Response to Wildfires in the Canadian Boreal Forest Across a Burn Severity Gradient
Authors: Whitman Thea , Whitman Ellen , Woolet Jamie , Flannigan Mike D , Thompson Dan K , Parisien Marc-Andre
Published: January 2019

Global fire regimes are changing, with increases in wildfire frequency and severity expected for many North American forests over the next 100 years. Fires can result in dramatic changes to C stocks and can restructure plant and microbial communities, which can have long-lasting effects on ecosystem functions. We investigated wildfire effects on soil microbial communities (bacteria and fungi) in an extreme fire season in the northwestern Canadian boreal forest, using field surveys, remote sensing, and high-throughput amplicon sequencing. We found that fire occurrence, along with vegetation community, moisture regime, pH, total carbon, and soil texture are all significant predictors of soil microbial community composition. Communities become increasingly dissimilar with increasingly severe burns, and the burn severity index (an index of the fractional area of consumed organic soils and exposed mineral soils) best predicted total bacterial community composition, while burned/unburned was the best predictor for fungi. Globally abundant taxa were identified as significant positive fire responders, including the bacteria Massilia sp. (64x more abundant with fire) and Arthrobacter sp. (35x), and the fungi Penicillium sp. (22x) and Fusicladium sp. (12x) Bacterial and fungal co-occurrence network modules were characterized by fire responsiveness as well as pH and moisture regime. Building on the efforts of previous studies, our results identify specific fire-responsive microbial taxa and suggest that accounting for burn severity improves our understanding of their response to fires, with potentially important implications for ecosystem functions.
Diversity patterns in parasite populations capable for persistence and reinfection with a view towards thehuman cytomegalovirus
Authors: Pokalyuk Cornelia , Görzer Irene
Published: January 2019

Many parasites like thecytomegalovirus, HIVandEscherichia coliare capable to persist in and reinfect its host. The evolutionary advantage (if so) of these complicated mechanisms have not been quantitatively analyzed so far. Here we take a first step by investigating a host-parasite model for which these mechanisms are driving the evolution of the parasite population. We consider two variants of the model. In one variant parasite reproduction is directed by balancing selection, in the other variant parasite reproduction is neutral. In the former scenario reinfection and persistence have been shown to sustain the maintenance of diversity in the parasite population in certain parameter regimes (Pokalyuk and Wakolbinger, 2018). Here we analyse the diversity patterns in the latter, neutral scenario. We evaluate the biological relevance of both model variants with respect to thehuman cytomegalovirus(HCMV), an ancient herpesvirus that is carried by a substantial fraction of mankind and manages to maintain a high diversity in its coding regions.
Visual-olfactory integration in the human disease vector mosquito,Aedes aegypti
Authors: Vinauger Clément , Breugel Floris Van , Locke Lauren T. , Tobin Kennedy K.S. , Dickinson Michael H. , Fairhall Adrienne , Akbari Omar S. , Riffell Jeffrey A.
Published: January 2019

Mosquitoes rely on the integration of multiple sensory cues, including olfactory, visual, and thermal stimuli, to detect, identify and locate their hosts [1–4]. Although we increasingly know more about the role of chemosensory behaviours in mediating mosquito-host interactions [1], the role of visual cues remains comparatively less studied [3], and how the combination of olfactory and visual information is integrated in the mosquito brain remains unknown. In the present study, we used a tethered-flight LED arena, which allowed for quantitative control over the stimuli, to show that CO2exposure affects target-tracking responses, but not responses to large-field visual stimuli. In addition, we show that CO2modulates behavioural responses to visual objects in a time-dependent manner. To gain insight into the neural basis of this olfactory and visual coupling, we conducted two-photon microscopy experiments in a new GCaMP6s-expressing mosquito line. Imaging revealed that the majority of ROIs in the lobula region of the optic lobe exhibited strong responses to small-field stimuli, but showed little response to a large-field stimulus. Approximately 20% of the neurons we imaged were modulated when an attractive odour preceded the visual stimulus; these same neurons also elicited a small response when the odour was presented alone. By contrast, imaging in the antennal lobe revealed no modulation when visual stimuli were presented before or after the olfactory stimulus. Together, our results are the first to reveal the dynamics of olfactory modulation in visually evoked behaviours of mosquitoes, and suggest that coupling between these sensory systems is asymmetrical and time-dependent.
Detecting convergent adaptive amino acid evolution
Authors: Rey Carine , Lanore Vincent , Veber Philippe , Guéguen Laurent , Lartillot Nicolas , Sémon Marie , Boussau Bastien
Published: January 2019

In evolutionary genomics, researchers have taken an interest in identifying in the genomes substitutions that subtend convergent phenotypic adaptations. This is a difficult question to address, because genomes contain billions of sites, many of which have substituted in the lineages where the adaptations took place, and yet are not linked to them. Those extra substitutions may be linked to other adaptations, may be neutral, or may be linked to mutational biases. Furthermore, one can think of various ways of defining substitutions of interest, and various methods that match those definitions have been used, resulting in different sets of candidate substitutions. In this manuscript we first clarify how adaptation to convergent phenotypic evolution can manifest itself in coding sequences. Second, we review methods that have been proposed to detect convergent adaptive evolution in coding sequences and expose the assumptions that underlie them. Finally, we examine their power on simulations of convergent changes, including in the presence of a confounding factor.
Time- and size-resolved bacterial aerosol dynamics in highly polluted air: new clues for haze formation mechanism
Authors: Zhang Ting , Li Xinyue , Wang Minfei , Chen Haoxuan , Yao Maosheng
Published: January 2019

Aerosol chemistry is often studied without considering microbial involvements. Here, we have applied a high-volume (1 m3/min) aerosol sampler and the Micro-Orifice Uniform Deposit Impactor (NanoMoudi) along with molecular and microscopic methods to investigate time-and size-resolved bacterial aerosol dynamics in air. Under high particulate matter (PM) polluted episodes, bacterial aerosols were detected to have a viability up to 50-70% in the 0.56-1 μm size range, at which elevated levels of SO42−, NO3− and NH4+ were concurrently observed. Engineered or acclimated for both pharmaceuticals and wastewater treatment, bacteria such as Psychrobacter spp., Massilia spp., Acinetobacter lwoffii, Exiguobacterium aurantiacum, and Bacillus megaterium were shown to have experienced massive abundance shifts in polluted air on early mornings and late afternoons, on which were previously reported to witness rapid new particle formation events. For example, Acinetobacter spp. were shown to account for > 96% abundance at a corresponding PM2.5 level of 208 ng/m3. The bacterial aerosol changes corresponded to the observed PM2.5 mass peak shift from 3.2-5.6 μm to the high viability size range of 0.56-1μm. Additionally, it is interesting that elevated levels of soluble Na, Ca, Mg, K, Al, Fe and P elements that are required for bacterial growth were observed to co-occur with those significant bacterial aerosol structure shifts in the air. For particular time-resolved PM2.5 pollution episodes, Acinetobacter and Massilia were shown to alternate in dominating the time-resolved aerosol community structures. The results from a HYSPLIT trajectory model simulation suggested that the role by air mass transport in affecting the observed bacterial aerosol dynamics could be minor. As an evidence, we found that Acinetobacter, Psychrobacter, Exiguobacterium, and Bacillus genera were emitted into the air with a level of > 3000 CFU/m3 from a pharmaceutical plant. In addition, high level of VOCs up to 15,030 ppbv, mainly Acetone (61%) and Acetaldehyde (11%), were also detected in the air inside the plant. All the data including size-resolved viability and time-resolved bacterial aerosol dynamics together with their growth conditions detected in the air suggested that airborne bacteria in the size range of 0.56- 1μm could have played important roles for haze formation in Beijing. The results about time- and size-resolved bacterial aerosol dynamics from this work provide a fresh understanding of aerosol chemistry especially in highly polluted air. It is hoped that these findings could lend a support in future cost-effective air pollution control practices.
Pancreatic tumor organoids for modeling in vivo drug response and discovering clinically-actionable biomarkers
Authors: Huang Ling , Bockorny Bruno , Paul Indranil , Akshinthala Dipikaa , Gandarilla Omar , Bose Arindam , Sanchez-Gonzalez Veronica , Rouse Emily E , Lehoux Sylvain D. , Pandell Nicole , Clohessy John G. , Grossman Joseph , Gonzalez Raul , Pino Sofia Perea Del , Daaboul George , Sawhney Mandeep S. , Freedman Steven D. , Cummings Richard D , Emili Andrew , Muthuswamy Lakshmi B , Hidalgo Manuel , Muthuswamy Senthil K
Published: January 2019

Patient-derived models are transforming translational cancer research. It is not clear if the emergence of patient-derived organoid (PDO) models can extend the utility of the widely used patient-derived xenograft (PDX). In addition, the utility of PDO models for serum biomarker discovery is not known. Here, we demonstrate that PDO models recapitulate the genomics, cell biology, glycomics and drug responses observed in PDX models. Furthermore, we demonstrate the applicability of PDO models for identification of N-glycans that are enriched in the glycome of pancreatic ductal adenocarcinoma (PDAC). Surprisingly, among all the glycans observed in PDX and PDOs, a core set of 57 N-glycans represent 50-94% of the relative abundance of all N-glycans detected, suggesting that only a subset of glycans dominate the cell surface landscape in PDAC. In addition, we outline a tumor organoid-based pipeline to identify surface proteins in extracellular vesicles (EV) from media supernatant of PDO cultures. When combined with the affinity-based validation platform, the EV surface proteins discovered in PDOs are effective in differentiating patients with PDAC from those with benign pancreatitis in the clinic, identifying PDO as powerful discovery platform for serum biomarkers. Thus, PDOs extend the utility of the archival collections of PDX models for translational research and function as a powerful platform for identification of clinically-actionable biomarkers in patients blood.

Significance statement

Tumor organoids extend the utility of PDX models as platforms for investigating drug response, glycosylation changes and function as new platforms for discovering blood-based biomarkers
CRISPR interference-based platform for multimodal genetic screens in human iPSC-derived neurons
Authors: Tian Ruilin , Gachechiladze Mariam A. , Ludwig Connor H. , Laurie Matthew T. , Hong Jason Y. , Nathaniel Diane , Prabhu Anika V. , Fernandopulle Michael S. , Patel Rajan , Abshari Mehrnoosh , Ward Michael E. , Kampmann Martin
Published: January 2019

CRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based screens were conducted in cancer cell lines, rather than healthy, differentiated cells. Here, we describe a CRISPR interference (CRISPRi)-based platform for genetic screens in human neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous genes in such neurons, and present results from three complementary genetic screens. First, a survival-based screen revealed neuron-specific essential genes and genes that improved neuronal survival upon knockdown. Second, a screen with a single-cell transcriptomic readout uncovered several examples of genes whose knockdown had strikingly cell-type specific consequences. Third, a longitudinal imaging screen detected distinct consequences of gene knockdown on neuronal morphology. Our results highlight the power of unbiased genetic screens in iPSC-derived differentiated cell types and provide a platform for systematic interrogation of normal and disease states of neurons.
A rabbit monoclonal antibody against the antiviral and cancer genomic DNA mutating enzyme APOBEC3B
Authors: Brown William L. , Law Emily K. , Carpenter Michael A. , Argyris Prokopios P. , Levin-Klein Rena , Ranum Alison N. , Molan Amy M. , Forster Colleen L. , Anderson Brett D. , Lackey Lela , Harris Reuben S.
Published: January 2019

The DNA cytosine deaminase APOBEC3B (A3B) is normally an antiviral factor in the innate immune response. However, A3B has been implicated in cancer mutagenesis, particularly in solid tumors of the bladder, breast, cervix, head/neck, and lung. Here, we report data on the generation and characterization of a rabbit monoclonal antibody (mAb) for human A3B through a series of immunoblot, immunofluorescence microscopy, and immunohistochemistry experiments. Positive results indicate that one mAb, 5210-87-13, will be useful for fundamental research in virology and cancer biology and that immunohistochemical quantification of A3B enzyme levels may constitute a clinical biomarker for tumor evolvability and differential treatment.
Active site plasticity and possible modes of chemical inhibition of the human DNA deaminase APOBEC3B
Authors: Shi Ke , Demir Özlem , Carpenter Michael A. , Banerjee Surajit , Harki Daniel A. , E. Amaro Rommie , Harris Reuben S. , Aihara Hideki
Published: January 2019

The single-stranded DNA cytosine deaminase APOBEC3B (A3B) functions in innate immunity against viruses, but is also strongly implicated in eliciting mutations in cancer genomes. Because of the critical role of A3B in promoting virus and tumor evolution, small molecule inhibitors are desirable. However, there is no reported structure for any of the APOBEC3-family enzymes in complex with a small molecule bound in the active site, which hampers the development of small molecules targeting A3B. Here we report high-resolution structures of an active A3B catalytic domain chimera with loop 7 residues exchanged with those from the corresponding region of APOBEC3G (A3G). The structures reveal novel open conformations lacking the catalytically essential zinc ion, with the highly conserved active site residues extensively rearranged. These inactive conformations are stabilized by 2-pyrimidone or an iodide ion bound in the active site. Molecular dynamics simulations corroborate the remarkable plasticity of the engineered active site and identify key interactions that stabilize the native A3B active site. These data provide insights into A3B active site dynamics and suggest possible modes of its inhibition by small molecules, which would aid in rational design of selective A3B inhibitors for constraining virus and tumor evolution.
Computing Hubs in the Hippocampus and Cortex
Authors: Clawson Wesley , Vicente Ana F. , Bernard Christophe , Battaglia Demian , Quilichini Pascale P
Published: January 2019

Neural computation, which relies on the active storage and sharing of information, occurs within large neuron networks in the highly dynamic context of varying brain states. Whether such functions are performed by specific subsets of neurons and whether they occur in specific dynamical regimes remain poorly understood. Using high density recordings in the hippocampus, medial entorhinal and medial prefrontal cortex of the rat, we identify computing microstates, or discreet epochs, in which specific computing hub neurons perform well defined storage and sharing operations in a brain state-dependent manner. We retrieve a multiplicity of distinct computing microstates within each global brain state, such as REM and nonREM sleep. Half of recorded neurons act as computing hubs in at least one microstate, suggesting that functional roles are not firmly hardwired but dynamically reassigned at the second timescale. We identify sequences of microstates whose temporal organization is dynamic and stands between order and disorder. We propose that global brain states constrain the language of neuronal computations by regulating the syntactic complexity of these microstate sequences.
Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production
Authors: Yuan Lin , Zhang Xun , Yang Ming , Zou Yizhou , Xiang Yang , Qu Xiangping , Liu Huijun , Du Xizi , Wang Leyuan , Wu Shuangyan , Wu Mengping , Qin Ling , Qin Qingwu , Qin Xiaoqun , Liu Chi
Published: January 2019

Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin β4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. Specific ITGB4 deficiency in AECs induces exaggerated Th2 responses, severe allergen-induced airway inflammation and airway hyperresponsiveness (AHR) in mouse model of allergic asthma. However, the underlying mechanisms remain unexplored. In this study, we determine the role of ITGB4 of AECs in the regulation of Th2 response and in the induction of asthma and identify the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated Th2 cells infiltration, inflammation and AHR and higher production of CCL17 in HDM treated mice. ITGB4-regulated CCL17 production in AECs was regulated by EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 by antibody inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated that ITGB4 of AECs negatively regulates the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway.
CHCHD4 regulates a proliferation-EMT switch in tumour cells, through respiratory complex I mediated metabolism
Authors: Thomas Luke W. , Esposito Cinzia , Stephen Jenna M. , Costa Ana S. H. , Frezza Christian , Blacker Thomas S. , Szabadkai Gyorgy , Ashcroft Margaret
Published: January 2019

BACKGROUND

Mitochondrial metabolism involves oxidative phosphorylation (OXPHOS) via the respiratory chain and is required for the maintenance of tumour cell proliferation and regulation of epithelial–mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study we interrogate the role of CHCHD4-regulated respiratory chain activity and metabolism in tumour cell proliferation and EMT-related phenotypes.

RESULTS

We show that CHCHD4 is essential for the proliferation of tumour cells irrespective of their aetiology. In human tumours, elevated CHCHD4 expression is correlated with a mitochondrial OXPHOS gene signature and with a proliferative gene signature associated with the mTORC1 signalling pathway. Elevated CHCHD4 increases tumour cell proliferation, in a manner that is dependent on complex I (CI) activity, glutamine consumption and mTORC1 activation. CHCHD4 expression is inversely correlated with EMT gene expression both in vitro and in vivo. Finally, we show CHCHD4 regulates the intracellular distribution of the EMT marker vimentin, in a CI-mediated manner.

CONCLUSIONS

CHCHD4 regulates tumour cell proliferation and metastatic (EMT-related) phenotypes through its control of CI-mediated mitochondrial metabolism.
Bacterioplankton dynamics driven by inter-annual variation in phytoplankton spring bloom communities in the Baltic Sea
Authors: Camarena-Gómez María Teresa , Ruiz-González Clara , Piiparinen Jonna , Lipsewers Tobias , Sobrino Cristina , Logares Ramiro , Spilling Kristian
Published: January 2019

In the Baltic Sea, climate change has caused shifts in the phytoplankton spring bloom communities with co-occurrence of diatoms and dinoflagellates. Such changes likely affect the composition and function of associated bacterioplankton, key members of the carbon cycling, although the actual effects are unknown. To understand how changes in phytoplankton impact on bacterioplankton composition and function, we analysed bacterioplankton communities and their production during different phases of the spring bloom in four consecutive years across the Baltic Sea, and related them to environmental variables. Phytoplankton communities varied largely in composition, modifying the taxonomic structure and richness of the associated bacterioplankton assemblages. In presence of certain diatoms (Achnanthes taeniata, Skeletonema costatum and Chaetoceros spp.), bacterial production and diversity were high and with more relative abundance of Flavobacteriia, Gammaproteobacteria and Betaproteobacteria. This bacterial community structure correlated positively with high diatom biomass and with high bacterial production rates. In contrast, during dinoflagellate-dominated blooms or when the diatom Thalassiosira baltica was abundant, both bacterial production rates and diversity were low, with bacterial communities dominated by SAR11 and Rhodobacteraceae. Our results demonstrate that, changes in the phytoplankton spring bloom will have profound consequences on bacterial community structure and their role in carbon cycling.