bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative contribution of climate change and human activities to vegetation degradation and restoration in North Xinjiang, China
Authors: Yang Hongfei , Yao Liang , Wang Youbao , Li Jianlong
Published: June 2017

Climate change and human activities are the two primary driving factors in the vegetation degradation process, and the assessment of their relative roles in vegetation degradation is important to understand the driving mechanisms of vegetation degradation. In this study, net primary productivity (NPP) was selected as an indicator to distinguish the relative roles of climate change and human activities in vegetation degradation and restoration from 2001 to 2010 in North Xinjiang, China. The potential NPP and the human appropriation of NPP were served as the indicator of the effects of climate change and human activities in vegetation degradation and restoration. The results showed that human activities were the dominant factor that induced vegetation degradation, accounts for 55% (153 720 km2) of the total degradation, whereas 25% (69 336 km2) of the total degradation resulted from climate change; the combination of human activities and climate change was the cause in 20% (55 429 km2) of the total degradation. In contrast, 61% (66 927 km2) of the total vegetation restoration was dominated by human activities and 29% (31 553 km2) was caused by climate change; the areas of vegetation restoration caused by the combination of human activities and climate change were 10 551 km2 (10%). The relative roles of the two factors possessed great spatial heterogeneity in five vegetation types. Climate dominated degradation expansion and human activities dominated vegetation restoration in forest. Both the degradation and restoration were dominated by human activities in grassland. In desert, degradation was dominated by human activities and vegetation restoration by climate. In cropland and crop/natural vegetation mosaic, degradation was dominated by both human activities and climate change and restoration was dominated by human activities. These results demonstrated that human activities played a demonstrably positive role in vegetation restoration, and ecological restoration projects were effective on mitigating vegetation degradation and also promoting restoration in the southern areas of North Xinjiang.
Evolution of nonspectral rhodopsin function at high altitudes
Authors: Castiglione Gianni M. , Hauser Frances E. , Liao Brian S. , Lujan Nathan K. , Van Nynatten Alexander , Morrow James M. , Schott Ryan K. , Bhattacharyya Nihar , Dungan Sarah Z. , Chang Belinda S. W.
Published: June 2017

Significance

Protein evolution in response to different environments has long been of interest to both evolutionary biologists and biochemists. High-altitude specialist catfishes in the Andes mountains offer an opportunity to examine the molecular adaptations accompanying adaptation to cold environments. Rhodopsins and other visual pigments form the first step in vision and have long been a model system for studying the molecular basis of sensory adaptations; however, many of these studies have focused solely on spectral shifts. Recent studies suggest that other aspects of function are as important for visual performance. We demonstrate that high-altitude amino acid variants significantly accelerate RH1 kinetics. These results suggest that the activity–stability trade-off characterized in cold-adapted enzymes also affects adaptation of signaling proteins through similar molecular mechanisms.
Togetherness or othering?
Authors: Taylor Charlotte
Published: June 2017

This chapter addresses the theme of othering by reporting on preliminary work from a European project aimed at building a dictionary of migration discourse keywords. The chapter investigates the use of the terms COMMUNITY and comunità in two British and Italian newspapers (Guardian, Times, Repubblica, Corriere della Sera) using corpus-assisted discourse analysis. In the first stage, it shows how these terms are interpreted as keywords of migration discourse. In the second, it examines the evaluative weighting of these lexical items. Contrary to previous work (e.g. Williams, 1983; Gallissot, 2007), it is shown here that the terms COMMUNITY and comunità are actually used as part of a pattern of othering, when employed in the context of migration discourse.
The European “stranger” in Le Monde’s headline discourse
Authors: Le Élisabeth
Published: June 2017

Using systemic functional grammar, a qualitative/quantitative, top-down/bottom-up, three-pronged approach of Le Monde’s print and online headline discourse on “Europe” during 2014 revealed the existence of three groups of “Other Europeans”: non-EU member states, “visible” because of their political, economic or strategic weight, “quasi-invisible” States who joined the EU in 2004 or later, and non-EU members, invisible for their lack of political, economic or strategic weight. These various degrees of visibility, combined with the foregrounding of the European Union, point to the construction of “strangers within”, whose quasi-invisibility and quality of “neither foe nor friend” may result in them being perceived as potentially “dangerous”.
Profiling of new Europeans in the British conservative press
Authors: Szymańska Jolanta
Published: June 2017

This chapter presents an exploratory analysis of discursive strategies through which Europe and Europeans are represented, focusing on how their images are profiled in the texts of the British conservative newspaper Daily Telegraph, a quality newspaper ranked as one of the three most widely read in the UK throughout the 2000s. We explore articles retrieved from the Internet version of the Daily Telegraph
from the 1st of May, 2004 to the 1st of May, 2009, aiming to establish the patterns of distribution of the words “EU”, “Europe” or “European”, and discover possible othering techniques that do not overtly transgress the rules of political correctness. Such covert profiling, among other factors, can hardly be underestimated as a determinant in the process of opinion forming and decision making among the general public, the effects of which have been revealed in time, as witnessed during the Brexit referendum. Cognitive images can be projected and, in the process of repetition, legitimized through language use. Thus, when a given lexical patterning appears regularly, it acquires the potential of shaping particular perceptions of objects and ideas. Both quantitative and interpretative analyses of the corpus amounting to 550,000 words have revealed a range of subtle othering techniques through which the concept of Europeans has been significantly and consistently profiled.
Discursive legitimation of criminalization and victimization of sub-Saharan immigrants in Spanish El País and ABC newspapers
Authors: Martínez Lirola María
Published: June 2017

This chapter analyses some visual characteristics used to criminalize and victimize sub-Saharan immigrants in a sample from the Spanish press. It contributes to the debate on the discursive construction of “the other”, in this case, the sub-Saharan immigrant, in the quality Spanish press. The corpus consists of all the news items published on sub-Saharan immigrants in the digital editions of the two most popular Spanish newspapers, El País and ABC, from 1 January 2012 to 1 January 2015. Visual grammar (Kress and van Leeuwen, 2006) and the model proposed by van Leeuwen (1996, 2008) for the analysis of the representation of social actors is used to deconstruct the main visual strategies used by the Spanish press to criminalize and victimize immigrants in order to reinforce the us–them dichotomy and to legitimize the representation of sub-Saharan immigrants as “the others”. The main findings of the study show how immigrants are represented as criminals and victims, which does not favour their integration but contributes to the highlighting of racist attitudes and discrimination.
Negotiating an identity
Authors: Molek-Kozakowska Katarzyna
Published: June 2017

The chapter investigates the mediated entextualizations of the identities of Polish immigrants to the UK in the period of post-crisis politics and economic reforms. The media discourse studied is collected from MojaWyspa.co.uk (MyIsland), one of the largest Polish-language online hubs designed for the substantial Polish community living on the British Isles. The study shows which discursive strategies of othering are employed to delimit the Polish immigrants’ collective identity, which self/other-presentation techniques are used, and how this group identity is legitimized argumentatively. It examines the linguistic realizations of self/other reference, active/passive and positive/negative predication strategies, topoi and argumentative schema for self-legitimization and various framing devices, as well as the mitigation of the sense of identity crisis through temporality. It reveals the diversity of Polish immigrants’ self-presentation techniques and proves the Polish migrant identity to be in the process of renegotiation.
Monument as semiotic landscape
Authors: Huebner Thom , Phoocharoensil Supakorn
Published: June 2017

As semiotic spaces, monuments convey messages through multiple information design modes, including language, materiality and
emplacement. As research on semiotic landscape has pointed out (e.g., Shohamy and Waksman
2009, Abousnnouga and Machin 2010, Train
2016), these messages are often contested in nature and convey competing discourses inherent in the spaces they occupy.
This paper explores those competing discourses manifested in a monument dedicated to the 1976 student protest and violent
suppression of it by the Thai military and right-wing paramilitary groups. Working within a production of space framework (Lefebvre 1991) and drawing on insights from the grammar of visual design (Kress and van Leeuwen 2006) and nexus analysis (Scollon and Scollon 2004), the paper attempts to show how these contested discourses are reflected in the monument’s
historiography as conceived, in its physical appearance and emplacement, and as it is experienced today. The analysis is based on
photographic data of the monument and its immediate physical context, published accounts of the events of October 6, and
interviews with survivors, commemoration planners, and the monument’s designer.
Erecting fascism: Nation, identity, and space in Trieste in the first half of the twentieth century
Authors: Klabjan Borut
Published: June 2017

This article discusses the transformation of the urban space after World War I in the former Habsburg port city of Trieste. It reveals the key role played by the newly annexed northeastern Adriatic borderland in the national symbolism of postwar Italy, and it indicates how slogans and notions of Italian nationalism, irredentism, and fascism intertwined and became embodied in the local cultural landscape. The analysis is mostly concentrated on the era between the two world wars, but the aim of the article is to interpret the interwar years as part of longer term historical developments in the region rather than a break in its history. Looking at how monuments, buildings, and spatial planning in general functioned as ideological and national marking, and how this helped to shape the nation in a multi-ethnic town, this article seeks to contribute to a better understanding of changes as well as continuities in the modern history of south-central Europe. It argues that even if the cityscape had undergone drastic changes in its aesthetics after World War I, its ideological language was rooted in prewar nationalism and continued to support the local urban palimpsest in the Cold War.
Expression and purification of swine RAG2 in E. coli for production of porcine RAG2 polyclonal antibodies
Authors: Jin Yu-Bei , Yang Wen-Tao , Huang Ke-Yan , Chen Hong-Liang , Shonyela Seria-Masole , Liu Jing , Liu Qiong , Feng Bo , Zhou You , Zhi Shu-Li , Jiang Yan-Long , Wang Jian-Zhong , Huang Hai-Bin , Shi Chun-Wei , Yang Gui-Lian , Wang Chun-Feng
Published: June 2017

Recombination activating gene 2 (RAG2) is necessary for immature B cell differentiation. Antibodies to human and rabbit RAG2 are currently commercially available, but antibodies to swine RAG remain unavailable to date. In this study, the swine RAG2 genes sequence was synthesized and then cloned into a pET-28a vector. The recombinant fusion protein was successfully expressed in E. coli, purified through nickel column chromatography, and further digested with Tobacco Etch Virus protease. The cleaved protein was purified by molecular-exclusion chromatography and named pRAG2. We used pRAG2 to immunize rabbits, collected the serum and purified rabbit anti-pRAG2 polyclonal antibodies. The rabbit anti-pRAG2 polyclonal antibodies were tested via immunofluorescence on eukaryotic cells overexpressing pRAG2 and also able to recognize pig natural RAG2 and human RAG2 protein in western blotting. These results indicated that the prepared rabbit anti-pRAG2 polyclonal antibodies may serve as a tool to detect immature B cell differentiation of swine.
Time course analyses of orthographic and phonological priming effects in developing readers
Authors: Zeguers Maaike HT , Huizenga HM , van der Molen MW , Snellings P
Published: June 2017

It has been assumed that fluent reading requires efficient integration of orthographic and phonological codes. However, it is thus far unclear how this integration process develops when children learn to become fluent readers. Therefore, we used masked priming to investigate time courses of orthographic and phonological code activation in children at incremental levels of reading development (second, fourth and sixth grade). The first study used targets with small phonological differences between phonological and orthographic primes, which are typical in transparent orthographies. The second study manipulated the strength of the phonological difference between prime and target to clarify whether phonological difference influences phonological priming effects. Results in both studies showed that orthographic priming effects became facilitative at increasingly short durations during reading development, but phonological priming was absent. These results are taken to suggest that development of reading fluency is accompanied by increased automatization of orthographic representations. The absence of phonological priming suggests that developing readers cannot yet activate phonological codes automatically.
Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage
Authors: Burger Kaspar , Schlackow Margarita , Potts Martin , Hester Svenja , Mohammed Shabaz , Gullerova Monika
Published: June 2017

The endoribonuclease Dicer is a key component of the human RNA interference pathway and is known for its role in cytoplasmic microRNA production. Recent findings suggest that noncanonical Dicer generates small noncoding RNA to mediate the DNA damage response (DDR). Here, we show that human Dicer is phosphorylated in the platform–Piwi/Argonaute/Zwille–connector helix cassette (S1016) upon induction of DNA damage. Phosphorylated Dicer (p-Dicer) accumulates in the nucleus and is recruited to DNA double-strand breaks. We further demonstrate that turnover of damage-induced nuclear, double-stranded (ds) RNA requires additional phosphorylation of carboxy-terminal Dicer residues (S1728 and S1852). DNA damage-induced nuclear Dicer accumulation is conserved in mammals. Dicer depletion causes endogenous DNA damage and delays the DDR by impaired recruitment of repair factors MDC1 and 53BP1. Collectively, we place Dicer within the context of the DDR by demonstrating a DNA damage-inducible phosphoswitch that causes localized processing of nuclear dsRNA by p-Dicer to promote DNA repair.
The glycolytic enzyme phosphofructokinase-1 assembles into filaments
Authors: Webb Bradley A. , Dosey Anne M. , Wittmann Torsten , Kollman Justin M. , Barber Diane L.
Published: June 2017

Despite abundant knowledge of the regulation and biochemistry of glycolytic enzymes, we have limited understanding on how they are spatially organized in the cell. Emerging evidence indicates that nonglycolytic metabolic enzymes regulating diverse pathways can assemble into polymers. We now show tetramer- and substrate-dependent filament assembly by phosphofructokinase-1 (PFK1), which is considered the “gatekeeper” of glycolysis because it catalyzes the step committing glucose to breakdown. Recombinant liver PFK1 (PFKL) isoform, but not platelet PFK1 (PFKP) or muscle PFK1 (PFKM) isoforms, assembles into filaments. Negative-stain electron micrographs reveal that filaments are apolar and made of stacked tetramers oriented with exposed catalytic sites positioned along the edge of the polymer. Electron micrographs and biochemical data with a PFKL/PFKP chimera indicate that the PFKL regulatory domain mediates filament assembly. Quantified live-cell imaging shows dynamic properties of localized PFKL puncta that are enriched at the plasma membrane. These findings reveal a new behavior of a key glycolytic enzyme with insights on spatial organization and isoform-specific glucose metabolism in cells.
Evidence for a possible bimodal distribution of the nodal distances of the extreme trans-Neptunian objects: Avoiding a trans-Plutonian planet or just plain bias?
Authors: de la Fuente Marcos C. , de la Fuente Marcos R.
Published: June 2017

It is a well-known fact that the presence of a massive perturber interacting with a population of minor bodies following very eccentric orbits can strongly affect the distribution of their nodal distances. The details of this process have been explored numerically and its outcome confirmed observationally in the case of Jupiter, where a bimodal distribution of nodal distances of comets has been found. Here, we show evidence for a possible bimodal distribution of the nodal distances of the extreme trans-Neptunian objects (ETNOs) in the form of a previously unnoticed correlation between nodal distance and orbital inclination. This proposed correlation is unlikely to be the result of observational bias as data for both large semimajor axis Centaurs and comets fit well into the pattern found for the ETNOs, and all these populations are subjected to similar background perturbations when moving well away from the influence of the giant planets. The correlation found is better understood if these objects tend to avoid a putative planet with semimajor axis in the range of 300–400 au.
Cyclophilins: Less Studied Proteins with Critical Roles in Pathogenesis
Authors: Singh Khushwant , Winter Mark , Zouhar Miloslav , Ryšánek Pavel
Published: June 2017

Cyclophilins (EC 5.2.1.8) belong to a subgroup of proteins known as immunophilins, which also include FK506-binding proteins and parvulins. Members of the immunophilins have two main characteristic properties: (i) peptidyl-prolyl cis-trans isomerase activity and (ii) the ability to bind immunosuppressant molecules of fungal origin. Cyclophilins are some of the most conserved proteins present in eukaryotes and prokaryotes, and they have been implicated in diverse cellular processes and responses to multiple biotic and abiotic stresses. Cyclophilins have been exploited in humans and plants extensively, but they have only recently received attention in regard to phytopathogens. In Phellinus sulphurascens and species of the genus Leptosphaeria and Phytophthora, high expression of cyclophilins was found to be related to infection. Moreover, recent studies of cyclophilins in certain phytopathogens, such as Magnaporthe oryzae, Botrytis cinerea, Cryphonectria parasitica, and Puccinia triticina, demonstrated their roles as a pathogenicity factors. In addition to pathogenicity, cyclophilins have high affinity for the immunosuppressive drug cyclosporin A, which is a potent antifungal agent. Although cyclophilins are highly conserved in phytopathogens, because they have been less studied, their role remains largely unknown. In this review, we provide detailed information on the cyclophilins in several phytopathogens, including fungi and oomycetes, as well as their role in suppressing plant immunity.
Systemic Aminoglycosides-Induced Vestibulotoxicity in Humans
Authors: Van Hecke Ruth , Van Rompaey Vincent , Wuyts Floris L. , Leyssens Laura , Maes Leen
Published: June 2017

Objectives:

This systematic review aimed to investigate the prevalence and characteristics of vestibular adverse effects of aminoglycoside (AG) therapy in humans and to analyze objective vestibular tests for the detection of AG-induced vestibulotoxicity.

Design:

PubMed, Cochrane Database, Web of Science, and reference lists of all included studies were screened by two independent researchers. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Studies were included according to preset inclusion criteria and reported outcomes of studies evaluating vestibular function using one or more objective vestibular function tests in adults and children after systemic AG administration. The methodological quality of each study was assessed using the quality assessment tool for quantitative studies. Interrater reliability was established using Cohen’s Kappa.

Results:

Twenty-seven studies were included, with the vast majority showing AG-induced vestibulotoxic side effects, ranging from 0 to 60%. Most studies reported AG-induced abnormalities by caloric and rotatory testing, whereas only a few studies reported using video Head Impulse test and vestibular evoked myogenic potential testing.

Conclusions:

Because type I hair cells (particularly of the semicircular canals) are more susceptible to ototoxicity, video Head Impulse test and vestibular evoked myogenic potential testing seem more promising for the early detection of vestibulotoxicity than caloric and rotatory testing. Prospective studies using an extensive vestibular test battery are needed to further characterize the impact of AGs on the different vestibular end organs and to identify the most sensitive vestibular technique for the early detection of vestibulotoxicity.
Bilateral tibial shaft fractures: a multicenter analysis
Authors: Cui Shari , Bauer Jennifer M. , Mir Hassan , Cannada Lisa K.
Published: June 2017

Background:

Bilateral tibial shaft fractures represent high-energy trauma. While treatment and complications of bilateral femoral fractures are well defined, there is limited literature on bilateral tibial shaft fractures. We present a multicenter study on bilateral tibial shaft fractures, analyzing the most commonly associated injuries and complications.

Methods:

A retrospective review was performed to identify all patients with bilateral tibial shaft fractures treated during a 5-year period. Demographics, injury measures, treatments, and complications were collected. Categories were evaluated and ranked based on frequency of occurrence.

Results:

Approximately 2000 tibial shaft fractures were treated during a 5-year period, of which 68 patients (19 females, 49 males) had sufficient records for inclusion. The average age was 39 yr (range 15-83 yr). There were 80 open fractures in 55 patients. Other musculoskeletal trauma and chest trauma were the two most common associated injuries (followed by face, head, and abdominal trauma). Two patients had definitive casting, 67 patients (129 tibias) were surgically treated, and four patients required amputation on arrival. Fourteen patients developed nonunions, 13 had compartment syndrome, and 34 were affected by nonsurgical complications. Thirty-one patients required subsequent surgery to promote healing. There were six mortalities.

Conclusions:

We present the largest group of patients with bilateral tibial fractures and show a high rate of open fractures, severe systemic injuries, and frequent complications. Orthopaedic surgeons must balance early surgical treatment with the presence of associated injuries and educate patients regarding complications and the possibility of subsequent surgeries to promote healing of these serious injuries.
Unilateral Internal Mammary Recipient Vessels for Bilateral DIEP Flap Breast Reconstruction
Authors: Lee Jeffrey H. , Varon David E. , Halvorson Eric G.
Published: June 2017

The deep inferior epigastric perforator flap has become increasingly popular for breast reconstruction with the most common recipient vessels being the internal mammary artery and vein. In certain cases, however, these recipient vessels are inadequate due to an absent or diminutive vein. Moreover, patients at high risk for future coronary artery disease may sacrifice the best conduit for coronary revascularization if the internal mammary recipients are used. Alternative recipient vessels, including the thoracodorsal, thoracoacromial, external jugular, and cephalic vessels have significant limitations. In this report, we describe a novel technique using unilateral internal mammary recipient vessels for bilateral free flap breast reconstruction. Two cases are presented that represent distinct indications for this technique: (1) absence or inadequacy of unilateral recipient vessels and (2) preservation of the left internal mammary system for future bypass in patients at high risk for coronary artery disease.
Clozapine Use in a Cohort of First-Episode Psychosis
Authors: Doyle Roisin , Behan Caragh , O'Keeffe Donal , Masterson Sarah , Kinsella Anthony , Kelly Aine , Sheridan Ann , Keating Dolores , Hynes Caroline , Madigan Kevin , Lawlor Elizabeth , Clarke Mary
Published: June 2017

Purpose/Background

For approximately one third of individuals treated for psychosis or schizophrenia, antipsychotic medications will have little or no therapeutic benefit. Clozapine remains the sole medication approved for treatment-resistant schizophrenia, and studies have demonstrated its superior efficacy in reducing psychotic symptoms.

Methods/Procedures

Data were collected from the medical records of people who originally presented with a first-episode psychosis between 1995 and 1999 (N = 171). Data were obtained from first presentation up to December 31, 2013 or until the patient was discharged or transferred. Information on service use and physical health was gathered using a data collection template designed specifically for this audit.

Findings/Results

Twenty-eight (16.3%) of the cohort were prescribed clozapine. Data were available for 24 individuals. Of this clozapine subsample, the mean age at baseline was 23.11 (SD = 4.58); 82.14% (n = 23) were male; and 82.14% (n = 23) had a baseline diagnosis of schizophrenia. The mean time to first trial of clozapine was 6.7 years. The mean number of antipsychotics prescribed before clozapine trial was 4.85. After the initiation of clozapine, the mean number of hospital admissions reduced from 6.04 per year to 0.88 per year.

Implications/Conclusions

Nearly 1 in 5 of the original cohort was considered to have a suboptimal response to trials of antipsychotic medication. The use of clozapine for treatment-resistant schizophrenia is underutilized, and better understanding of the barriers to prescribing clozapine is necessary given the implications for patient's quality of life and hospital admission rates. Physical health data further emphasizes the importance of physical health monitoring in this vulnerable population.
Early Cutaneous Signs of Neurofibromatosis Type 1
Authors: Sirvaitis Skirmante , Sirvaitis Ringaile , Perusek Thomas , Garcia-Zuazaga Jorge
Published: June 2017

Purpose

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a multisystem disease with cutaneous symptoms occurring from birth to adulthood. It is a disorder with multiple malformations and tumors involving the skin, nervous system, and skeleton. The purpose of this report is to provide dermatology nurse practitioners with an unusual case involving axillary freckling as well as evidence-based guidance for the diagnosis and management of cutaneous NF1 symptoms.

Relevance

NF1 affects approximately 1 in 3,500 people. There is an equal incidence in men and women as well as in all races and ethnic groups. Most of the time, patients initially present to a primary care provider; however, patients may also present to a dermatology practice. It is indispensable for dermatology nurse practitioners to recognize early manifestations of this disorder so that the patient may be referred to seek specialized care and decrease the chance of disease complications.

Essential Points

This report provides a case of NF1 as well as background, pathophysiology, diagnostic criteria, differential diagnoses, prognosis, and treatment of cutaneous manifestations of this disease.
Oxygen–Flow–Pressure Targets for Resuscitation in Critical Hemodynamic Therapy
Authors: He Huaiwu , Long Yun , Zhou Xiang , Wang Xiaoting , Zhang Hongmin , Chai Wenzhao , Cui Na , Wang Hao , Liu Dawei
Published: June 2017

Far from traditional “vital signs,” the field of hemodynamic monitoring (HM) is rapidly developing. However, it is also easy to misunderstand hemodynamic therapy as merely HM and some concrete bundles or guidelines for circulation support. Here, we describe the concept of “critical hemodynamic therapy” and clarify the concepts of the “therapeutic target” and “therapeutic endpoint” in clinical practice. Three main targets (oxygen delivery, blood flow, perfusion pressure) for resuscitation are reviewed in critically ill patients according to the sepsis guidelines and hemodynamic consensus. ScvO2 at least 70% has not been recommended as a directed target for initial resuscitation, and the directed target of mean arterial pressure (MAP) still is 65 mmHg. Moreover, the individual MAP target is underlined, and using flow-dependent monitoring to guide fluid infusion is recommended. The flow-directed target for fluid infusion might be a priority, but it remains controversial in resuscitation. The interpretation of these targets is necessary for adequate resuscitation and the correction of tissue hypoxia. The incoherence phenomenon of resuscitation (macrocirculation and microcirculation, tissue perfusion, and cellular oxygen utilization) is gaining increased attention, and early identification of these incoherences might be helpful to reduce the risk of over-resuscitation.
Ultrasonographic Evaluation of the Urethral Rhabdosphincter Morphology in Female Patients With Urodynamic Stress Incontinence
Authors: Zacharakis Dimitrios , Grigoriadis Themos , Pitsouni Eleni , Domali Ekaterini , Protopapas Athanasios , Athanasiou Stavros
Published: June 2017

Objectives

During the last 2 decades, ultrasonography has been proposed for the morphologic evaluation of the urethral rhabdosphincter. The aims of this study were to evaluate the feasibility of a simple sonographic technique for the assessment of the urethral rhabdosphincter morphology by using a 2-dimensional (2D) transvaginal transducer and to evaluate any associations between the sonographic parameters of rhabdosphincter morphology with the presence of urodynamic stress incontinence (USI).

Methods

This was a prospective study of women who underwent urodynamic studies and an introital 2D ultrasonography and divided in 2 groups based on the presence or absence of USI. Measurements included rhabdosphincter thickness at the 3-o’clock (right) and 9-o’clock (left) positions and the rhabdosphincter outer (Π) and inner circumference (π). Based on these values, the mean thickness of the rhabdosphincter (R + L / 2), the rhabdosphincter differential perimeter (Π − π), and area (A − α) were also calculated.

Results

Statistical analysis showed that women with a rhabdosphincter area of less than 0.65 cm2, mean thickness of less than 0.24 cm, and differential perimeter of less than 1.08 cm had 3.98, 5.67, and 5.41 times greater odds for USI, respectively. Receiver operating characteristic curve analysis results showed that the optimal cutoff values for the prediction of USI from rhabdosphincter thickness, differential perimeter. and surface area were 0.24 cm (79.6% sensitivity, 63.4% specificity), 1.08 cm (70.8% sensitivity and 69.1% specificity), and 0.65 cm2 (71.9% sensitivity, 57.1% specificity), respectively.

Conclusions

Introital ultrasonography with a 2D transvaginal probe allowed the visualization of the urethral rhabdosphincter morphology in greater than 90% of the cases. Sonographic measurements showed that patients with USI had a thinner urethral rhabdosphincter than did women with a normal sphincteric mechanism.
A novel mathematical method for disclosing oscillations in gene transcription: a comparative study
Authors: Antoulas Athanasios C. , Zhu Bokai , Zhang Qiang , York Brian , O'Malley Bert W. , Dacso Clifford
Published: June 2017

Circadian rhythmicity, the 24-hour cycle responsive to light and dark, is determined by periodic oscillations in gene transcription. This phenomenon has broad ramifications in physiologic function. Recent work has disclosed more cycles in gene transcription, and to the uncovering of these we apply a novel signal processing methodology known as the pencil method and compare it to conventional parametric, nonparametric, and statistical methods. Methods: In order to assess periodicity of gene expression over time, we analyzed a database derived from livers of mice entrained to a 12-hour light/12-hour dark cycle. We also analyzed artificially generated signals to identify differences between the pencil decomposition and other alternative methods. Results: The pencil decomposition revealed hitherto-unsuspected oscillations in gene transcription with 12-hour periodicity. The pencil method was robust in detecting the 24-hour circadian cycle that was known to exist, as well as confirming the existence of shorter-period oscillations. A key consequence of this approach is that orthogonality of the different oscillatory components can be demonstrated. thus indicating a biological independence of these oscillations, that has been subsequently confirmed empirically by knocking out the gene responsible for the 24-hour clock. Conclusion: System identification techniques can be applied to biological systems and can uncover important characteristics that may elude visual inspection of the data. Significance: The pencil method provides new insights on the essence of gene expression and discloses a wide variety of oscillations in addition to the well-studied circadian pattern. This insight opens the door to the study of novel mechanisms by which oscillatory gene expression signals exert their regulatory effect on cells to influence human diseases.
Correction of copy number induced false positives in CRISPR screens
Authors: de Weck Antoine , Golji Javad , Jones Mike , Korn Joshua , Billy Eric , McDonald E. Robert , Schmelzle Tobias , Bitter Hans , Kauffmann Audrey
Published: June 2017

Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function screens. However, a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons, since the entire amplified region can exhibit lethal scores. These false-positive hits can either be discarded from further analysis, which in cancer models can represent a significant number of hits, or methods can be developed to rescue the true-positives within amplified regions. We propose two methods to rescue true positive hits in amplified regions by correcting for this copy number artefact. The Local Drop Out (LDO) method uses the relative lethality scores within genomic regions to assess true essentiality and does not require additional orthogonal data (e.g. copy number value). LDO is meant to be used in screens covering a dense region of the genome (e.g. a whole chromosome or the whole genome). The General Additive Model (GAM) method models the screening data as a function of the known copy number values and removes the systematic effect from the measured lethality. GAM does not require the same density as LDO, but does require prior knowledge of the copy number values. Both methods have been developed with single sample experiments in mind so that the correction can be applied even in smaller screens. Here we demonstrate the efficacy of both methods at removing the copy number effect and rescuing hits from some of the amplified regions. We estimate a 70-80% decrease of false positive hits in regions of high copy number with either method.
Online, Interactive Tutorials Provide Effective Instruction in Science Process Skills
Authors: Kramer Maxwell , Olson Dalay , Walker J.D.
Published: June 2017

Explicit emphasis on teaching science process skills leads to both gains in the skills themselves and, strikingly, deeper understanding of content. Here, we created and tested a series of online, interactive tutorials with the goal of helping undergraduate students develop science process skills. We designed the tutorials in accordance with evidence-based multimedia design principles and student feedback from usability testing. We then tested the efficacy of the tutorials in an introductory undergraduate biology class. Based on a multivariate ordinary least squares regression model, students that received the tutorials are predicted to score 0.824 points higher on a 15 point science process skill assessment than their peers that received traditional textbook instruction on the same topic. This moderate but significant impact indicates that well designed online tutorials can be more effective than traditional ways of teaching science process skills to undergraduate students. We also found trends that suggest the tutorials are especially effective for non-native English speaking students. However, due to a limited sample size, we were unable to confirm that these trends occurred due to more than just variation in the sampled student group.
The grayling genome reveals selection on gene expression regulation after whole genome duplication
Authors: Varadharajan Srinidhi , Sandve Simen R. , Gillard Gareth B. , Tørresen Ole K. , Mulugeta Teshome D. , Hvidsten Torgeir R. , Lien Sigbjørn , Vøllestad Leif Asbjørn , Jentoft Sissel , Nederbragt Alexander J. , Jakobsen Kjetill S.
Published: June 2017

Whole genome duplication (WGD) has been a major evolutionary driver of increased genomic complexity in vertebrates. One such event occurred in the salmonid family ~80 million years ago (Ss4R) giving rise to a plethora of structural and regulatory duplicate-driven divergence, making salmonids an exemplary system to investigate the evolutionary consequences of WGD. Here, we present a draft genome assembly of European grayling(Thymallus thymallus)and use this in a comparative framework to study evolution of gene regulation following WGD. Among the Ss4R duplicates identified in European grayling and Atlantic salmon(Salmo salar), one third reflect non-neutral tissue expression evolution, with strong purifying selection, maintained over ~50 million years. Of these, the majority reflect conserved tissue regulation under strong selective constraints related to brain and neural-related functions, as well as higher-order protein-protein interactions. A small subset of the duplicates has evolved tissue regulatory expression divergence in a common ancestor, which have been subsequently conserved in both lineages, suggestive of adaptive divergence following WGD. These candidates for adaptive tissue expression divergence have elevated rates of protein coding- and promoter-sequence evolution and are enriched for immune- and lipid metabolism ontology terms. Lastly, lineage-specific duplicate divergence points towards underlying differences in adaptive pressures on expression regulation in the non-anadromous grayling versus the anadromous Atlantic salmon.

Our findings enhance our understanding of the role of WGD in genome evolution and highlights cases of regulatory divergence of Ss4R duplicates, possibly related to a niche shift in early salmonid evolution.
Mapping-free variant calling using haplotype reconstruction from k-mer frequencies
Authors: Audano Peter , Ravishankar Shashidhar , Vannberg Fredrik
Published: June 2017

1

Motivation

The standard protocol for detecting variation in DNA is to map millions of short sequence reads to a known reference and find loci that differ. While this approach works well, it cannot be applied where the sample contains dense variants or is too distant from known references.De novoassembly or hybrid methods can recover genomic variation, but the cost of computation is often much higher. We developed a novel k-mer algorithm and software implementation, Kestrel, capable of characterizing densely-packed SNPs and large indels without mapping, assembly, or de Bruijn graphs.

Results

When applied to mosaic penicillin binding protein (PBP) genes inStreptococcus pneumoniae,we found near perfect concordance with assembled contigs at a fraction of the CPU time. Multilocus sequence typing (MLST) with this approach was able to bypassde novoassemblies. Kestrel has a very low false-positive rate when calling variants over the whole genome, but limitations of a purely k-mer based approach affect sensitivity.

Availability

Source code and documentation for a Java implementation of Kestrel can be found athttps://github.com/paudano/kestrel. All test code for this publication is located athttps://github.com/paudano/kescases.

Contact

paudano@gatech.edu,fredrik.vannberg@biology.gatech.edu
Low-complexity domains adhere by reversible amyloid-like interactions between kinked β-sheets
Authors: Hughes Michael P. , Sawaya Michael R. , Goldschmidt Lukasz , Rodriguez Jose A. , Cascio Duilio , Gonen Tamir , Eisenberg David S.
Published: June 2017

Control of metabolism by compartmentation is a widespread feature of higher cells. Recent studies have focused on dynamic intracellular bodies such as stress granules, P-bodies, nucleoli, and metabolic puncta. These bodies appear as separate phases, some containing reversible, amyloid-like fibrils formed by interactions of low-complexity protein domains. Here we report five atomic structures of segments of low-complexity domains from granule-forming proteins, one determined to 1.1 Å resolution by micro-electron diffraction. Four of these interacting protein segments show common characteristics, all in contrast to pathogenic amyloid: kinked peptide backbones, small surface areas of interaction, and predominate attractions between aromatic side-chains. By computationally threading the human proteome on three of our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such reversible interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, keratins, and cornified envelope proteins, consistent with the capacity of cells to form a wide variety of dynamic intracellular bodies.

One Sentence Summary

Atomic structures show transient membraneless organelles of cells formed by a new type of protein interaction akin to pathogenic amyloid fibrils.
Genomic variations in paired normal controls for lung adenocarcinomas
Authors: Qu Li-Wei , Zhou Bo , Wang Gui-Zhen , Chen Ying , Zhou Guang-Biao
Published: June 2017

Somatic genomic mutations in lung adenocarcinomas (LUADs) have been extensively dissected, but whether the counterpart normal lung tissues that are exposed to ambient air or tobacco smoke as the tumor tissues do, harbor genomic variations, remains unclear. Here, the genome of normal lung tissues and paired tumors of 11 patients with LUAD were sequenced, the genome sequences of counterpart normal controls (CNCs) and tumor tissues of 513 patients were downloaded from TCGA database and analyzed. In the initial screening, genomic alterations were identified in the “normal” lung tissues and verified by Sanger capillary sequencing. In CNCs of TCGA datasets, a mean of 0.2721 exonic variations/Mb and 5.2885 altered genes per sample were uncovered. The C:G→T:A transitions, a signature of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes in CNCs. 16 genes had a variant rate of more than 2%, and CNC variations inMUC5B,ZXDB,PLIN4,CCDC144NL,CNTNAP3B, andCCDC180were associated with poor prognosis whereas alterations inCHD3andKRTAP5-5were associated with favorable clinical outcome of the patients. This study identified the genomic alterations in CNC samples of LUADs, and further highlighted the DNA damage effect of tobacco on lung epithelial cells.
Genome reconstruction and characterisation of extensively drug-resistant bacterial pathogens through direct metagenomic sequencing of human faeces
Authors: Mu Andre , Kwong Jason C. , Isles Nicole S. , Gonçalves da Silva Anders , Schultz Mark B. , Ballard Susan A. , Carter Glen P. , Williamson Deborah A. , Seemann Torsten , Stinear Timothy P. , Howden Benjamin P.
Published: June 2017

Whole-genome sequencing of microbial pathogens is revolutionising modern approaches to outbreaks of infectious diseases and is reliant upon organism culture. Culture-independent methods have shown promise in identifying pathogens, but high level reconstruction of microbial genomes from microbiologically complex samples for more in-depth analyses remains a challenge. Here, using metagenomic sequencing of a human faecal sample and analysis by tetranucleotide frequency profiling projected onto emergent self-organising maps, we were able to reconstruct the underlying populations of two extensively-drug resistant pathogens,Klebsiella pneumoniaecarbapenemase (KPC)-producingKlebsiella pneumoniaeand vancomycin-resistantEnterococcus faecium.From these genomes, we were able to ascertain molecular typing results, such as MLST, and identify highly discriminatory mutations in the metagenome to distinguish closely related strains. These proof-of-principle results demonstrate the utility of clinical sample metagenomics to recover sequences of important drug-resistant bacteria and application of the approach in outbreak investigations, independent of the need to culture the organisms.
UFBoot2: Improving the Ultrafast Bootstrap Approximation
Authors: Hoang Diep Thi , Chernomor Olga , Haeseler Arndt von , Minh Bui Quang , Vinh Le Sy
Published: June 2017

The standard bootstrap (SBS), despite being computationally intensive, is widely used in maximum likelihood phylogenetic analyses. We recently proposed the ultrafast bootstrap approximation (UFBoot) to reduce computing time while achieving more unbiased branch supports than SBS under mild model violations. UFBoot has been steadily adopted as an efficient alternative to SBS and other bootstrap approaches.

Here, we present UFBoot2, which substantially accelerates UFBoot and reduces the risk of overestimating branch supports due to polytomies or severe model violations. Additionally, UFBoot2 provides suitable bootstrap resampling strategies for phylogenomic data. UFBoot2 is 778 and 8.4 times (median) faster than SBS and RAxML rapid bootstrap on tested datasets, respectively. UFBoot2 is implemented in the IQ-TREE software package version 1.6 and freely available athttp://www.iqtree.org.
Design, synthesis, crystal structure andin vitrocytotoxic properties of a novel Schiff base derived from indole and biphenyl
Authors: Bu Fan-Zhi , Tan Xue-Jie , Xing Dian-Xiang , Wang Chao
Published: June 2017

A novel and potentially active dihydroorotate dehydrogenase (DHODH) inhibitor, namely 3-({(E)-[(E)-1-(biphenyl-4-yl)ethylidene]hydrazinylidene}methyl)-1H-indole (BEHI) acetonitrile disolvate, C23H19N3·2CH3CN, has been designed and synthesized. The structure of BEHI was characterized by elemental analysis, Q-TOF (quadrupole time-of-flight) MS, NMR, UV–Vis and single-crystal X-ray diffraction. The antitumour activity of the target molecule was evaluated by the MTT method. Results indicated that BEHI exhibited rather potent cytotoxic activity against human A549 (IC50= 20.5 µM) and mouse breast 4T1(IC50= 18.5 µM) cancer cell lines. Meanwhile, to rationalize its potencies in the target, BEHI was docked into DHODH and the interactions with the active site residues were analyzed. Single-crystal structure analysis indicated that hydrogen bonds are present only between BEHI and acetonitrile solvent molecules in the asymmetric unit. The interplay of weak π–π stacking and weak C(N)—H...π interactions between neighbouring BEHI molecules play crucial roles in the formation of the final supramolecular frameworks.