bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of a Stand-Alone Online Learning Module for Cellular Respiration Instruction
Authors: Goff Eric E. , Reindl Katie M. , Johnson Christina , McClean Phillip , Offerdahl Erika G. , Schroeder Noah L. , White Alan R.
Published: June 2018

With the recent rise of alternative instructional methodologies such as flipped classrooms and active learning, many core concepts are being introduced outside of the classroom prior to scheduled class meeting times. One popular means for external concept introduction in many undergraduate biology courses is the use of stand-alone online learning modules. Using a group of four large introductory biology course sections, we investigate the use of a stand-alone online learning module developed using animations from Virtual Cell Animation Collection as a resource for the introduction of cellular respiration concepts outside of the classroom. Results from four sections of introductory biology (
n
= 629) randomized to treatments show that students who interacted with the stand-alone online learning module had significantly higher normalized gain scores on a cellular respiration assessment than students who only attended a traditional lecture as a means of concept introduction (
p
< 0.001,
d
= 0.59). These findings suggest a superior ability to convey certain introductory cellular respiration topics in a stand-alone manner outside of the classroom than in a more traditional lecture-based classroom setting.
Microbiology Education and Infection Control Competency: Offering a New Perspective
Authors: Cox Jennifer L. , Simpson Maree Donna
Published: June 2018

Healthcare-associated infections (HAIs) have become a significant and costly problem for healthcare institutions worldwide. Despite the crucial role of infection prevention and control (IC) procedures, there is a substantial body of evidence to indicate that IC knowledge and practices of health professional graduates is, however, sub-optimal. This paper presents a discussion of the critical role microbiology plays in infection control education and practice, arguing that without an ability to apply microbiology knowledge to IC decision-making, there is an inherent risk of incorrect application of IC practices and thus a risk to patient (and nurse) safety. The authors propose a re-conceptualization of infection control competency, using nursing as an exemplar profession, to reflect practice that is not based on simple memorization of protocols but rather on a sound understanding of microbiology and informed decision-making. The proposal for re-conceptualizing the definition and assessment of IC competence, if adopted, would potentially enhance students’ understanding and synthesis of microbiology knowledge and help build students’ capacity to apply that knowledge to practice.
How Undergraduate Science Students Use Learning Objectives to Study
Authors: Osueke Bethany , Mekonnen Birook , Stanton Julie Dangremond
Published: June 2018

Learning objectives communicate the knowledge and skills that instructors intend for students to acquire in a course. Student performance can be enhanced when learning objectives align with instruction and assessment. We understand how instructors should use learning objectives, but we know less about how students should use them. We investigated students’ use and perceptions of learning objectives in an undergraduate science course at a public research university. In this exploratory study, students (
n
= 185) completed two open-ended assignments regarding learning objectives and we analyzed the content of their answers. We found that students used learning objectives in ways that reflected the recommendations of past and present instructors, suggesting that students are receptive to instruction on how to use learning objectives. Students generally found learning objectives to be useful because the objectives helped them to narrow their focus and organize their studying, suggesting that students may need additional help from instructors in order to self-direct their learning. Students who chose not to use learning objectives often found other resources, such as case studies covered in class, to be more helpful for their learning. Some of these students recognized that the concepts included in case studies and learning objectives overlapped, pointing to a benefit of alignment between instructional activities and learning objectives. These qualitative results provide the data necessary for designing a quantitative instrument to test the extent to which students’ use of learning objectives affects their performance.
Claw Waving for Sex: An Inquiry-Based Lab to Teach Sexual Dimorphism and Behavior in Fiddler Crabs
Authors: Angra Aakanksha , Weigel Emily , Onstine Alison
Published: June 2018

We designed a three-week guided inquiry-based lab for non-biology majors revolving around the ideas of sexual dimorphism, selection, and behavior, using fiddler crabs (Uca pugilator) as a model. Specifically, students worked in small teams to design experiments, collect data, and present findings in a short oral presentation. Students gained exposure to scientific skills, including designing an ethogram, understanding the purpose of inter-observer reliability, graphing, statistics, and oral communication.
Simulation of MICROBACT Strip Assay Using Colored Liquids to Demonstrate Identification of Unknown Gram-Negative Organisms in Undergraduate Laboratory
Authors: Khan Latifa B. , Swift Simon , Kamal Tania , Read Hannah M.
Published: June 2018

Identification of unknown microorganisms to the species level is an important component of a microbiology course. Modern technologies such as matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing offer a rapid species level identification when compared to conventional phenotype-based methods, however they rely on a well-established taxonomy database and phenotypic assays can still play an important role in species determination. Another major limitation is the up-front cost of purchasing these modern specialized instruments and the requirement of skilled personnel to operate specialized equipment and software, which makes them unsuitable to use in the undergraduate teaching laboratory. Commercial biochemical identification systems such as the Oxoid Microbact™ GNB 12A/12E/24E kit is used for the identification of Enterobacteriaceae and other Gram negative bacteria in clinical and veterinary diagnostic laboratories, and food industries for disease control and treatment. In this article, we describe a method of reliably simulating this Microbact™ strip assay using artificial color liquids (which are affordable and easy to source) for the demonstration of phenotypic characterization of unknown Gram negative organisms while providing a safe teaching environment as no bacteria are used, familiarizing students with the concept of using Microbact™ 12A kit to identify a range of unknown Gram negative organisms.
Psychological perspective on compassion in modern healthcare settings
Authors: Rydon-Grange Michelle
Published: June 2018

Compassionate care is a foundation of the National Health Service (NHS). However, several high-profile inquiries into healthcare failures in the NHS suggest compassion is often absent in our hospitals. Ensuing policies mandate healthcare professionals to ‘show more compassion’ but, as the psychological evidence-base indicates, this instruction neglects the complexity of this social emotion. This paper applies the psychological research on compassion to modern healthcare settings with the aim of creating a better understanding of the pathways leading to uncompassionate care. A review of the empirical evidence suggests a range of psychological factors modulate compassion. In particular, the psychological literature indicates the human compassion system is adaptive, highly attuned to its environment. As such, a healthcare professional’s ability to experience and display compassionate behaviour will be, in part, determined by the environment in which they practise; that is, aspects of the organisational environment will either facilitate or inhibit compassion. This paper argues that the typical organisational set-up of a modern healthcare setting seriously undermines compassionate care. Organisational features frequently associated with uncompassionate care include the understaffing of hospital wards, excessive working shift patterns and the dogged focus on achieving service efficiencies—each has been identified as contributing to the alarming breakdown of compassionate care at the centre of several healthcare failings. Policies focusing on culture change in the NHS neglect the growing psychological evidence base on compassion, but by applying a psychological understanding of compassion to healthcare settings, we can begin to adequately understand and address the real causes of uncompassionate care.
A millennium-long perspective on high-elevation pine recruitment in the Spanish central Pyrenees
Authors: Sangüesa-Barreda Gabriel , Camarero J. Julio , Esper Jan , Galván J. Diego , Büntgen Ulf
Published: June 2018

Long-term fluctuations in forest recruitment, at time scales well beyond the life-span of individual trees, can be related to climate changes. The underlying climatic drivers are, however, often understudied. Here, we present the recruitment history of a high-elevation mountain pine (Pinus uncinata Ram.) forest in the Spanish central Pyrenees throughout the last millennium. A total of 1108 ring-width series translated into a continuous chronology from 924 to 2014 CE, which allowed estimated germination dates of 470 trees to be compared against decadal-scale temperature variability. High recruitment intensity mainly coincided with relatively warm periods in the early 14th, 15th, 19th, and 20th centuries, whereas cold phases during the mid-17th, early 18th, and mid-19th centuries overlapped with generally low recruitment rates. In revealing the importance of prolonged warm conditions for high-elevation pine recruitment in the Pyrenees, this study suggests increased densification and even possible upward migration of tree-line ecotones under predicted global warming.
Pea-protein alginate encapsulation adversely affects development of clinical signs of Citrobacter rodentium-induced colitis in mice treated with probiotics
Authors: Varankovich Natallia , Grigoryan Alexander , Brown Kirsty , Inglis G. Douglas , Uwiera Richard R.E. , Nickerson Michael T. , Korber Darren R.
Published: June 2018

The efficacy of two strains of Lactobacillus probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0052) immobilized in microcapsules composed of pea protein isolate (PPI) and alginate microcapsules was assessed using a mouse model of Citrobacter rodentium-induced colitis. Accordingly, 4-week-old mice were fed diets supplemented with freeze-dried probiotics (group P), probiotic-containing microcapsules (group PE) (lyophilized PPI–alginate microcapsules containing probiotics), or PPI–alginate microcapsules containing no probiotics (group E). Half of the mice (controls, groups P, PE, and E) received C. rodentium by gavage 2 weeks after initiation of feeding. Daily monitoring of disease symptoms (abnormal behavior, diarrhea, etc.) and body weights was undertaken. Histopathological changes in colonic and cecal tissues, cytokine expression levels, and pathogen and probiotic densities in feces were examined, and the microbial communities of the distal colon mucosa were characterized by 16S rRNA sequencing. Infection with C. rodentium led to marked progression of infectious colitis, as revealed by symptomatic and histopathological data, changes in cytokine expression, and alteration of composition of mucosal communities. Probiotics led to changes in most of the disease markers but did not have a significant impact on cytokine profiles in infected animals. On the basis of cytokine expression analyses and histopathological data, it was evident that encapsulation materials (pea protein and calcium alginate) contributed to inflammation and worsened a set of symptoms in the cecum. These results suggest that even though food ingredients may be generally recognized as safe, they may in fact contribute to the development of an inflammatory response in certain animal disease models.
Arrayvolution: using microphone arrays to study bats in the field
Authors: Koblitz Jens C.
Published: June 2018

Some parameters of echolocation signals can be studied using a single receiver. However, studying parameters such as source level, echolocation beam shape, and direction of signal emission require the use of multireceiver arrays. Acoustic localization allows for determination of the position of bats at the time of signal emission. When multiple animals are present, calls can be assigned to individuals based on their location. This combination makes large multireceiver arrays a powerful tool in bioacoustics research. Here, an overview of different array configurations used to record bats in the field is presented. In some studies, the absolute position of bats and not only relative to the array is crucial. Combining acoustic localizations from a source with geo-referenced receivers allows for determining geo-referenced movements of bats. Current applications of arrays aim to improve acoustic monitoring of bats and study anthropogenic impact.
Genome ofSerratianematodiphilaMB307 offers unique insights into its diverse traits
Authors: Basharat Zarrin , Tanveer Faouzia , Yasmin Azra , Shinwari Zabta Khan , He Tongtong , Tong Yigang
Published: June 2018

A pigment-producing species of Serratia was isolated from the rhizosphere of a heavy metal resistant Cannabis sativa plant growing in effluent-affected soil of Hattar Industrial Estate, Haripur, Pakistan. Here, we report the genome sequence of this bacterium, which has been identified as Serratia nematodiphila on the basis of whole genome comparison using the OrthoANI classification scheme. The bacterium exhibited diverse traits, including plant growth promotion, antimicrobial, bioremediation, and pollutant tolerance capabilities including metal tolerance, azo dye degradation, ibuprofen degradation, etc. Plant growth-promoting exoenzyme production as well as phosphate solubilisation properties were observed. Genes for phosphate solubilisation, siderophore production, and chitin destruction were identified in addition to other industrially important enzymes like nitrilase and lipase. Secondary metabolite producing apparatus for high value chemicals in the whole genome was also analysed. The number of antibiotic resistance genes was then profiled in silico, through a match with Antibiotic Resistant Gene and CAR database. This is the first report of a S. nematodiphila genome from a polluted environment. This could significantly contribute to the understanding of pollution tolerance, antibiotic resistance, association with nematodes, production of bio-pesticide, and their role in plant growth promotion.
Genome-wide identification of the AP2/ERF transcription factor family in pepper (Capsicum annuumL.)
Authors: Jin Jing-Hao , Wang Min , Zhang Huai-Xia , Khan Abid , Wei Ai-Min , Luo De-Xu , Gong Zhen-Hui
Published: June 2018

The AP2/ERF family is one of the largest transcription factor families in the plant kingdom. AP2/ERF genes contributing to various processes including plant growth, development, and response to various stresses have been identified. In this study, 175 putative AP2/ERF genes were identified in the latest pepper genome database and classified into AP2, RAV, ERF, and Soloist subfamilies. Their chromosomal localization, gene structure, conserved motif, cis-acting elements within the promoter region, and subcellular locations were analyzed. Transient expression of CaAP2/ERF proteins in tobacco revealed that CaAP2/ERF064, CaAP2/ERF109, and CaAP2/ERF127 were located in the nucleus, while CaAP2/ERF171 was located in the nucleus and cytoplasm. Most of the CaAP2/ERF genes contained cis-elements within their promoter regions that responded to various stresses (HSE, LTR, MBS, Box-W1/W-box, and TC-rich repeats) and phytohormones (ABRE, CGTCA-motif, and TCA-element). Furthermore, RNA-seq analysis revealed that CaAP2/ERF genes showed differential expression profiles in various tissues as well as under biotic stresses. Moreover, qRT-PCR analysis of eight selected CaAP2/ERF genes also showed differential expression patterns in response to infection with Phytophthora capsici (HX-9) and in response to phytohormones (SA, MeJA, and ETH). This study will provide basic insights for further studies of the CaAP2/ERF genes involved in the interaction between pepper and P. capsici.
A PTAS for Scheduling Unrelated Machines of Few Different Types
Authors: Gehrke Jan Clemens , Jansen Klaus , Kraft Stefan E. J. , Schikowski Jakob
Published: June 2018

Scheduling on Unrelated Machines is a classical optimization problem where [Formula: see text] jobs have to be distributed to [Formula: see text] machines. Each of the jobs [Formula: see text] has on machine [Formula: see text] a processing time [Formula: see text]. The goal is to minimize the makespan, i.e., the maximum completion time of the longest-running machine. Unless [Formula: see text], this problem does not allow for a polynomial-time approximation algorithm with a ratio better than [Formula: see text]. A natural scenario is however that many machines are of the same type, like a CPU and GPU cluster: for each of the [Formula: see text] machine types, the machines [Formula: see text] of the same type [Formula: see text] satisfy [Formula: see text] for all jobs [Formula: see text]. For the case where the number [Formula: see text] of machine types is constant, this paper presents an approximation scheme, i.e., an algorithm of approximation ratio [Formula: see text] for [Formula: see text], with an improved running time only single exponential in [Formula: see text].
Dynamic RLE-Compressed Edit Distance Tables Under General Weighted Cost Functions
Authors: Hyyrö Heikki , Inenaga Shunsuke
Published: June 2018

Kim and Park [A dynamic edit distance table, J. Disc. Algo., 2:302–312, 2004] proposed a method (KP) based on a “dynamic edit distance table” that allows one to efficiently maintain unit cost edit distance information between two strings [Formula: see text] of length [Formula: see text] and [Formula: see text] of length [Formula: see text] when the strings can be modified by single-character edits to their left or right ends. This type of computation is useful e.g. in cyclic string comparison. KP uses linear time, [Formula: see text], to update the distance representation after each single edit. Recently Hyyrö et al. [Incremental string comparison, J. Disc. Algo., 34:2-17, 2015] presented an efficient method for maintaining the dynamic edit distance table under general weighted edit distance, running in [Formula: see text] time per single edit, where [Formula: see text] is the maximum weight of the cost function. The work noted that the [Formula: see text] space requirement, and not the running time, may be the main bottleneck in using the dynamic edit distance table. In this paper we take the first steps towards reducing the space usage of the dynamic edit distance table by RLE compressing [Formula: see text] and [Formula: see text]. Let [Formula: see text] and [Formula: see text] be the lengths of RLE compressed versions of [Formula: see text] and [Formula: see text], respectively. We propose how to store the dynamic edit distance table using [Formula: see text] space while maintaining the same time complexity as the previous methods for uncompressed strings.
Grover’s Search with Faults on Some Marked Elements
Authors: Kravchenko Dmitry , Nahimovs Nikolajs , Rivosh Alexander
Published: June 2018

Grover’s algorithm is a quantum query algorithm solving the unstructured search problem of size [Formula: see text] using [Formula: see text] queries. It provides a significant speed-up over any classical algorithm [3].

The running time of the algorithm, however, is very sensitive to errors in queries. Multiple authors have analysed the algorithm using different models of query errors and showed the loss of quantum speed-up [2, 6].

We study the behavior of Grover’s algorithm in the model where the search space contains both faulty and non-faulty marked elements. We show that in this setting it is indeed possible to find one of marked elements in [Formula: see text] queries.

We also analyze the limiting behavior of the algorithm for a large number of steps and show the existence and the structure of a limiting state [Formula: see text].
Quantum Walks on Two-Dimensional Grids with Multiple Marked Locations
Authors: Nahimovs Nikolajs , Rivosh Alexander
Published: June 2018

The running time of a quantum walk search algorithm depends on both the structure of the search space (graph) and the configuration (the placement and the number) of marked locations. While the first dependence has been studied in a number of papers, the second dependence remains mostly unstudied.

We study search by quantum walks on the two-dimensional grid using the algorithm of Ambainis, Kempe and Rivosh [3]. The original paper analyses one and two marked locations only. We move beyond two marked locations and study the behaviour of the algorithm for several configurations of multiple marked locations.

In this paper, we prove two results showing the importance of how the marked locations are arranged. First, we present two placements of [Formula: see text] marked locations for which the number of steps of the algorithm differs by a factor of [Formula: see text]. Second, we present two configurations of [Formula: see text] and [Formula: see text] marked locations having the same number of steps and probability of finding a marked location.
Deformations of weak ℚ-Fano 3-folds
Authors: sano Taro
Published: June 2018

We prove that a weak [Formula: see text]-Fano [Formula: see text]-fold with terminal singularities has unobstructed deformations. By using this result and computing some invariants of a terminal singularity, we provide two results on global deformation of a weak [Formula: see text]-Fano [Formula: see text]-fold. We also treat a stacky proof of the unobstructedness of deformations of a [Formula: see text]-Fano [Formula: see text]-fold.
Biholomorphisms between Hartogs domains over homogeneous Siegel domains
Authors: Seo Aeryeong
Published: June 2018

In this paper, we characterize the Hartogs domains over homogeneous Siegel domains of type II and explicitly describe their automorphism groups. Moreover, we prove that any proper holomorphic map between equidimensional Hartogs domains over homogeneous Siegel domains of type II is a biholomorphism.
Conduction-band nonparabolicity effect on refractive index and phase match in asymmetric quantum wells pumped by two infrared beams
Authors: Cao Xiaolong , Che Yongli , Yao Jianquan
Published: June 2018

An asymmetric quantum well (AQW) system that is pumped by two infrared beams is designed to generate terahertz (THz) waves. The refractive index and phase mismatch associated with the intersubband transition of the AQW structure are calculated and analyzed for both present and absent conduction band nonparabolicity. The calculated results reveal that, for increasing wavelengths, the refractive index of the AQW for the short-wavelength pump beam varies more than 0.83 and undergoes a 0.204 [Formula: see text]m redshift, when the conduction band nonparabolicity is considered. The variation of the refractive index of the AQW with the long-wavelength pump beam, changes from 0.225 to 0.316 after considering the conduction-band nonparabolicity. In addition, no redshift is observed. Whether the refractive index of one pump beam with its specific wavelength increases is determined mainly by the linear terms. However, for increasing the other pump wavelengths, the refractive index of one pump beam mainly depends on the nonlinear terms. Subband energy-levels and dipole transition matrix elements show noticeable changes due to conduction-band nonparabolicity, which change the refractive index. Phase matching can be achieved by adjusting the wavelength of the two pump beams. However, both phase mismatch and coverage increase when the conduction band nonparabolicity is considered.
Particle picture representation of the non-symmetric Rosenblatt process and Hermite processes of any order
Authors: Treszczotko Łukasz
Published: June 2018

We provide a particle picture representation for the non-symmetric Rosenblatt process and for Hermite processes of any order, extending the result of Bojdecki, Gorostiza and Talarczyk in [4]. We show that these processes can be obtained as limits of certain functionals of a system of particles evolving according to symmetric stable Lévy motions. In the case of [Formula: see text]-Hermite processes the corresponding functional involves [Formula: see text]-intersection local time of symmetric stable Lévy processes.
Backward stochastic differential equations with unbounded generators
Authors: Gashi Bujar , Li Jiajie
Published: June 2018

In this paper, we consider two classes of backward stochastic differential equations (BSDEs). First, under a Lipschitz-type condition on the generator of the equation, which can also be unbounded, we give sufficient conditions for the existence of a unique solution pair. The method of proof is that of Picard iterations and the resulting conditions are new. We also prove a comparison theorem. Second, under the linear growth and continuity assumptions on the possibly unbounded generator, we prove the existence of the solution pair. This class of equations is more general than the existing ones.
Some properties of g-frames in Banach spaces
Authors: Khosravi Amir , Banyarani Jamaleh Sohrabi
Published: June 2018

In this paper, we introduce and study woven approximate Schauder g-frames. We show that for any two approximate Schauder g-frames, each weaving is an approximate Schauder g-frame if and only if there is a uniform constant [Formula: see text] such that every weaving is a C-approximate Schauder g-frame, and we obtain some perturbation results for approximate Schauder g-frames. Finally, some results have been found for weaving approximate Schauder g-frames.
An integrated framework for identification of effective and synergistic anti-cancer drug combinations
Authors: Sharma Aman , Rani Rinkle
Published: June 2018

Combination drug therapy is considered a better treatment option for various diseases, such as cancer, HIV, hypertension, and infections as compared to targeted drug therapies. Combination or synergism helps to overcome drug resistance, reduction in drug toxicity and dosage. Considering the complexity and heterogeneity among cancer types, drug combination provides promising treatment strategy. Increase in drug combination data raises a challenge for developing a computational approach that can effectively predict drugs synergism. There is a need to model the combination drug screening data to predict new synergistic drug combinations for successful cancer treatment. In such a scenario, machine learning approaches can be used to alleviate the process of drugs synergy prediction. Experimental data from a single-agent or multi-agent drug screens provides feature data for model training. On the contrary, identification of effective drug combination using clinical trials is a time consuming and resource intensive task. This paper attempts to address the aforementioned challenges by developing a computational approach to effectively predict drug synergy. Single-drug efficacy is used for predicting drug synergism. Our approach obviates the need to understand the underlying drug mechanism to predict drug combination synergy. For this purpose, nine machine learning algorithms are trained. It is observed that the Random forest models, in comparison to other models, have shown significant performance. The [Formula: see text]-fold cross-validation is performed to evaluate the robustness of the best predictive model. The proposed approach is applied to mutant-BRAF melanoma and further validated using melanoma cell-lines from AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge dataset.
Junction Riemann problem for one-dimensional shallow water equations with bottom discontinuities and channels width variations
Authors: Elshobaki Mohamed , Valiani Alessandro , Caleffi Valerio
Published: June 2018

We investigate the solution of the nonlinear junction Riemann problem for the one-dimensional shallow water equations (SWEs) in a simple star network made of three rectangular channels. We consider possible bottom discontinuities between the channels and possible differences in the channels width. In the literature, the solution of the Riemann problem at the junction is investigated for the symmetric case without bottom steps and channels width variations. Here, the solution is extended to a more general situation such that neither the equality of the channels width nor the symmetry of the flow are assumed in the downstream channels. The analysis is performed under sub-criticality conditions and the results are summarized in a main theorem, while a series of numerical examples are presented and support our conclusions.
Loess slide susceptibility assessment using frequency ratio model and artificial neural network
Authors: Qiu Haijun , Cui Peng , Regmi Amar Deep , Hu Sheng , Hao Junqing
Published: June 2018

Landslide susceptibility assessment is essential for disaster management. The aim of this study is to select a reliable and accurate model for loess slide susceptibility assessment. We use a frequency ratio model and artificial neural network to develop loess slide susceptibility maps. We analysed the relationships between loess slide frequency and conditioning factors including elevation, slope gradient, aspect, profile curvature, thickness of loess, rainfall, topographic wetness index, valley depth, distance to rivers and land use. We developed a landslide inventory consisting of 223 loess slides by the interpretation of remote sensing images from earlier published or unpublished reports and from intensive field surveys. From these 223 loess slides, 178 (80%) were selected for training the models and the remaining 45 (20%) slides were used for validating the developed models. The validation was carried out by using receiver operating characteristic (ROC) curves. From the analysis, it is seen that both the frequency ratio model and artificial neural network performed equally well, although the frequency ratio method is much easier to apply. The loess slide susceptibility maps can be used for land use planning and risk mitigation in loess terrain.
Marine Environmental Epigenetics
Authors: Eirin-Lopez Jose M. , Putnam Hollie M.
Published: June 2018

Marine organisms’ persistence hinges on the capacity for acclimatization and adaptation to the myriad of interacting environmental stressors associated with global climate change. In this context, epigenetics—mechanisms that facilitate phenotypic variation through genotype–environment interactions—are of great interest ecologically and evolutionarily. Our comprehensive review of marine environmental epigenetics guides our recommendations of four key areas for future research: the dynamics of wash-in and wash-out of epigenetic effects, the mechanistic understanding of the interplay of different epigenetic marks and the interaction with the microbiome, the capacity for and mechanisms of transgenerational epigenetic inheritance, and the evolutionary implications of the interaction of genetic and epigenetic features. Emerging insights in marine environmental epigenetics can be applied to critical issues such as aquaculture, biomonitoring, and biological invasions, thereby improving our ability to explain and predict the responses of marine taxa to global climate change.
New roles of aldosterone and mineralocorticoid receptors in cardiovascular disease: translational and sex-specific effects
Authors: Davel Ana Paula , Jaffe Iris Z. , Tostes Rita C. , Jaisser Frederic , Belin de Chantemèle Eric J.
Published: June 2018

Recent advances in the field of mineralocorticoid receptor (MR) and its ligand aldosterone expanded the role of this hormone and its receptor far beyond their initial function as a regulator of Na+ and K+ homeostasis in epithelial cells. The symposium “New Roles of Aldosterone and Mineralocorticoid Receptors in Cardiovascular Disease: Translational and Sex-Specific Effects” presented at the 38th World Congress of the International Union of Physiological Sciences (Rio de Janeiro, Brazil) highlighted the contribution of extrarenal MRs to cardiovascular disease. This symposium showcased how MRs expressed in endothelial, vascular smooth muscle, and immune cells plays a critical role in the development of vascular disease associated with aging, obesity, and chronic aldosterone stimulation and demonstrated that MR antagonism prevents the acute renal dysfunction and tubular injury induced by ischemia-reperfusion injury. It was also shown that the adipocyte-derived hormone leptin is a new direct regulator of aldosterone secretion and that leptin-mediated aldosterone production is a major contributor to obesity-associated hypertension in women. Sex differences in the role of aldosterone and of endothelial MR in the cardiovascular outcomes of obesity were highlighted. This review summarizes these important emerging concepts regarding the contribution of aldosterone and cell-specific MR to cardiovascular disease in male and female subjects and further supports sex-specific benefits of MR antagonist drugs to be tested in additional populations.
Genetics of guanylyl cyclase pathways in the cochlea and their influence on hearing
Authors: Fitzakerley Janet L. , Trachte George J.
Published: June 2018

Although hearing loss is the most common sensory deficit in Western societies, there are no successful pharmacological treatments for this disorder. Recent experiments have demonstrated that manipulation of intracellular cyclic guanosine monophosphate (cGMP) concentrations can have both beneficial and harmful effects on hearing. In this review, we will examine the role of cGMP as a key second messenger involved in many aspects of cochlear function and discuss the known functions of downstream effectors of cGMP in sound processing. The nitric oxide-stimulated soluble guanylyl cyclase system (sGC) and the two natriuretic peptide-stimulated particulate GCs (pGCs) will be more extensively covered because they have been studied most thoroughly. The cochlear GC systems are attractive targets for medical interventions that improve hearing while simultaneously representing an under investigated source of sensorineural hearing loss.
Aortic Angulation Does Not Impact Outcomes in Self-Expandable or Balloon-Expandable Transcatheter Aortic Valve Replacement
Authors: Elmously Adham , Gray Katherine D. , Truong Quynh A. , Burshtein Aaron , Wong S. Chiu , de Biasi Andreas R. , Worku Berhane , Salemi Arash
Published: June 2018

Objectives: The role of aortic angulation in attenuating procedural success in balloon-expandable (BE) and self-expandable (SE) transcatheter aortic valve replacement (TAVR) has been controversial. Methods: We retrospectively assessed patients undergoing SE and BE TAVR who had an aortic angle measured on multidetector computed tomography at a single tertiary referral center. The primary outcome was device success, measured per the Valve Academic Research Consortium-2 criteria. Clinical outcomes at 30 days (including mortality) were also assessed. Results: A total of 251 patients were identified; 182 patients received a BE valve and 69 patients an SE valve. The median aortic angle was 46.8° (range 24.4–70°) in the BE group and 43.3° (range 20–71°) in the SE group. In multivariate logistic regression analysis, aortic angulation did not affect device success. Mortality at 30 days and 12 months and postprocedural clinical outcomes were similarly not associated with aortic angulation. Conclusion: In this cohort of patients undergoing BE and SE TAVR over a wide range of aortic angles, we found no associations between angle and device success or any other clinical metrics. Increased aortic angulation does not adversely affect outcomes in BE or SE TAVR.
A Case of Uterine Carcinosarcoma Detected Simultaneously with Breast and Colon Cancer (Triple Primary Malignant Tumor)
Authors: Lee Eunhyun , Ji Yong-Il
Published: June 2018

Uterine carcinosarcoma, also known as malignant mixed Mullerian tumor of the uterus, is rare and rarely diagnosed simultaneously with cancers in other organs. We report a case of a 63-year-old woman who was simultaneously diagnosed with uterine carcinosarcoma, breast cancer, and colon cancer.
Depression and Smoking Augment the Production of Circulating Autoantibodies against Glycated HSA in Rheumatoid Arthritis Patients
Authors: Alouffi Sultan , Sherwani Subuhi , Al-Mogbel Mohammed S. , Sherwani Mohammad Khalid A. , Ali Khan Mohd Wajid
Published: June 2018

Background: Depression and smoking contribute to the prognosis of autoimmune rheumatoid arthritis (RA). Advanced glycation end products (AGEs) are also detected in RA patients. This study correlates RA in patients with various levels of depression and a history of smoking through the detection of antibodies against AGEs of proteins. Methods: Sixty RA subjects were selected and divided into 4 groups based on their levels of depression and smoking habits. The division was as follows: group I consisted of RA patients classified as depressed (RA-D); group II consisted of RA patients with a history of smoking (RA-S); group III consisted of RA patients suffering from depression who were also smokers (RA-DS); and group IV consisted of patients with RA alone (RA-A), i.e., not depressed and non-smokers. In vitro human serum albumin (HSA) was modified by glucose, and the modifications were studied by biochemical and biophysical techniques. Glycated (G)-HSA was used as an antigen, and autoantibodies against G-HSA (G-HSA-Abs) were screened in serum samples of different groups of RA subjects. Oxidative stress levels in all patients and healthy individuals were analyzed by protein-bound carbonyl content estimations. Results: Significant biochemical and biophysical changes were detected in G-HSA when compared to native (N)-HSA. All patients and control subjects were screened for circulating G-HSA-Abs and N-HSA-Abs. From the cohort of different samples, serum autoantibodies from RA-DS showed a high recognition of G-HSA-Abs titres compared to RA-D or RA-S. RA-A exhibited the least binding of circulating G-HSA-Abs of all the groups. The oxidative stress marker, the carbonyl content also exhibited highest levels in RA-DS, followed by RA-D and RA-S. Band shift assay showed the highest titres of immunoglobulin G in the serum samples of RA-DS. Conclusions: Smoking and concomitant depression in RA subjects may lead to enhanced oxidative stress levels responsible for the gradual formation and/or exposing of cryptic epitopes on HSA that induce the production of G-HSA-Abs. Hence, we postulate that by reducing depression and corresponding oxidative stress, it may be possible to control or limit the severity of the precipitation of RA disease activity and improve prognosis.
A Partial Response at Week 4 Can Predict Subsequent Outcome during Lamotrigine Augmentation Therapy in Treatment-Resistant Depressive Disorder: A Preliminary Study
Authors: Nagai Goyo , Mihara Kazuo , Kagawa Shoko , Nakamura Akifumi , Suzuki Takeshi , Nemoto Kenji , Kondo Tsuyoshi
Published: June 2018

Background/Aims: The present study prospectively examined whether or not a partial response at week 4 predicts subsequent response at week 8 during lamotrigine augmentation therapy in 51 (16 males and 35 females) inpatients with treatment-resistant depressive disorder using an open-study design. Methods: The subjects were 51 depressed patients who had already shown insufficient response to at least 3 psychotropics including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 19), bipolar I disorder (n = 9), and bipolar II disorder (n = 23). The final doses of lamotrigine were 100 mg/day for 29 subjects who were not taking valproate and 75 mg/day for 22 subjects taking valproate. Depressive symptoms were evaluated by the Montgomery-Åsberg Depression Rating Scale (MADRS) before the start of lamotrigine and then at week 4, and finally after the 8th week of treatment. Results: A significant linear relationship was found between percent improvements in MADRS scores at weeks 4 and 8 (r = 0.492, y = 0.438x + 30.223, R2 = 0.226, p < 0.001). The receiver operating characteristics analysis indicated that a percent improvement of 16% or greater at week 4 was significantly (p < 0.01) predictive of response (50% or more reduction in the MADRS score). The patients were significantly divided by the cut-off point into the responders and the nonresponders (18/26 vs. 1/25, p < 0.001). Conclusion: The present study suggests that a partial response at week 4 can predict subsequent outcome at week 8 during lamotrigine augmentation therapy in patients with treatment-resistant depressive disorder, and that the absence of a partial improvement at week 4 is highly predictive of nonresponse.
Effect of Bisphenol A Glycol Methacrylate on Virulent Properties of Streptococcus mutans UA159
Authors: Kim Kyungsun , An Jung-Sub , Lim Bum-Soon , Ahn Sug-Joon
Published: June 2018

Bisphenol A glycidyl methacrylate (bis-GMA), which is released into the oral environment by dental composites through incomplete polymerization, hydrolysis, and mechanical degradation, can significantly influence oral ecology around resin-based materials. The purpose of this study was to investigate how bis-GMA changes the virulence properties of Streptococcus mutans, a major cariogenic bacterium in humans. The results show that bis-GMA not only inhibited the planktonic growth of cells in medium containing glucose, fructose, or mannose, but also reduced the viability of S. mutans. However, the presence of bis-GMA increased sugar transport and intracellular polysaccharide accumulation in S. mutans, thereby increasing the potential of cell persistence. In addition, bis-GMA could enhance S. mutans’s adhesion to hard surfaces and glucan synthesis, which could contribute to biofilm formation. Although free bis-GMA made cells vulnerable to acidic stress, it also provided increased resistance to hydrogen peroxide, which might confer an advantage in competition with other oral microorganisms during the early stage of biofilm development. Interestingly, the presence of bis-GMA did not change the ability of S. mutans to interact with saliva. The results suggest that leachable bis-GMA could contribute to biofilm-related secondary dental caries at the marginal interface between resin-based materials and teeth by altering the virulent properties of S. mutans, although bis-GMA reduced the planktonic growth and viability of S. mutans.
Remodeling of the Corneal Epithelial Scaffold for Treatment of Persistent Epithelial Defects in Diabetic Keratopathy
Authors: Ohta Manami , Morita Yukiko , Yamada Naoyuki , Nishida Teruo , Morishige Naoyuki
Published: June 2018

Background: To develop a strategy based on surgical removal of a degenerated corneal epithelial scaffold for treatment of persistent epithelial defects (PEDs) in diabetic keratopathy. Case Presentation: Three diabetic patients with PEDs were initially treated with eyedrops containing the fibronectin-based peptide PHSRN (Pro-His-Ser-Arg-Asn) or both the substance P-derived peptide FGLM-NH2 and the insulin-like growth factor-1-derived peptide SSSR. A degenerated Bowman’s layer or calcified lesion thought to be responsible for incomplete healing was surgically removed after confirmation of reactivity to the peptide eyedrops. All three patients achieved complete epithelial wound closure after surgery. Two cases treated by phototherapeutic keratectomy or lamellar keratoplasty did not show PED recurrence during 6 or 36 months of follow-up, respectively. One case treated by mechanical removal of a degenerated Bowman’s layer manifested recurrence after 1 month, but resurfacing of the defect was again achieved after repeat surgery. Conclusion: We propose a new strategy for treatment of diabetic PEDs based on surgical remodeling of the corneal epithelial scaffold for patients who respond to peptide eyedrops but fail to achieve wound closure.
Leser-Trélat Sign Presenting in a Patient with Relapsing Mycosis Fungoides
Authors: Alsaif Fahad , Alkhayal Fares Abdulmajed , Aldahash Rawan , Alhumaidi Ahmed
Published: June 2018

The Leser-Trélat sign is a rare sign of some malignant tumors and is characterized by the sudden appearance of seborrheic keratosis in association with an underlying malignancy. We describe a 60-year-old Saudi man with mycosis fungoides (MF) who developed numerous, rapidly growing, seborrheic keratoses on his face and back. To the best of our knowledge, this is the first reported case of MF with the Leser-Trélat sign from Saudi Arabia.
Cell Death Pathways Drive Necroinflammation during Acute Kidney Injury
Authors: von Mässenhausen Anne , Tonnus Wulf , Linkermann Andreas
Published: June 2018

Renal tubules represent an intercellular unit and function as a syncytium. When acute tubular necrosis was first visualized to occur through a process of synchronized regulated necrosis (SRN) in handpicked primary renal tubules, it became obvious that SRN actually promotes nephron loss. This realization adds to our current understanding of acute kidney injury (AKI)-chronic kidney disease (CKD) transition and argues for the prevention of AKI episodes to prevent CKD progression. Because SRN is triggered by necroptosis and executed by ferroptosis, 2 recently identified signaling pathways of regulated necrosis, a combination therapy employing necrostatins and ferrostatins may be beneficial for protection against nephron loss. Clinical trials in AKI and during the process of kidney transplantation are now required to prevent SRN. Additionally, necrotic cell death drives autoimmunity and necroinflammation and therefore represents a therapeutic target even for the prevention of antibody-mediated rejection of allografts years after the transplantation process.
Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Qin Chuan , Guo Yun , Yang De-Gang , Yang Ming-Liang , Du Liang-Jie , Li Jian-Jun
Published: June 2018

Background/Aims: Spinal cord injury (SCI) has long been a subject of great interest in a wide range of scientific fields. Several attempts have been made to demonstrate motor function improvement in rats with SCI after transplantation of induced pluripotent stem cells (iPSC). This systematic review and meta-analysis was designed to summarize the effects of iPSC on locomotor recovery in rat models of SCI. Methods: We searched the publications in the PubMed, Medline, Science Citation Index, Cochrane Library, CNKI, and Wan-fang databases and the China Biology Medicine disc. Results were analyzed by Review Manager 5.3.0. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Six randomized controlled preclinical trials covering eight comparisons and including 212 rats were selected. The subgroup analyses were based on the following items: different SCI models, cell counts, iPSC sources, iPSC differentiations and transplantation methods. The pooled results indicated that iPSC transplantation significantly improved locomotor recovery of rats after SCI by sustaining beneficial effects, especially in the subgroups of contusion, moderate cell counts (5×105), source of human fetal lung fibroblasts, iPSC-neural precursors and intraspinal injection. Conclusion: Our meta-analysis of the effects of iPSC transplantation on locomotor function in SCI models is, to our knowledge, the first meta-analysis in this field. We conclude that iPSC transplantation improves locomotor recovery in rats with SCI, implicating this strategy as an effective therapy. However, more studies are required to validate our conclusions.