bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration
Authors: Simkin Jennifer , Sammarco Mimi C. , Dawson Lindsay A. , Tucker Catherine , Taylor Louis J. , Van Meter Keith , Muneoka Ken
Published: March 2015

Mammalian digit regeneration progresses through consistent stages: histolysis, inflammation, epidermal closure, blastema formation, and finally redifferentiation. What we do not yet know is how each stage can affect others. Questions of stage timing, tissue interactions, and microenvironmental states are becoming increasingly important as we look toward solutions for whole limb regeneration. This study focuses on the timing of epidermal closure which, in mammals, is delayed compared to more regenerative animals like the axolotl. We use a standard wound closure device, Dermabond (2‐octyl cyanoacrylate), to induce earlier epidermal closure, and we evaluate the effect of fast epidermal closure on histolysis, blastema formation, and redifferentiation. We find that fast epidermal closure is reliant upon a hypoxic microenvironment. Additionally, early epidermal closure eliminates the histolysis stage and results in a regenerate that more closely replicates the amputated structure. We show that tools like Dermabond and oxygen are able to independently influence the various stages of regeneration enabling us to uncouple histolysis, wound closure, and other regenerative events. With this study, we start to understand how each stage of mammalian digit regeneration is controlled.
Bayesian sequential monitoring design for two‐arm randomized clinical trials with noncompliance
Authors: Shen Weining , Ning Jing , Yuan Ying
Published: March 2015

In early‐phase clinical trials, interim monitoring is commonly conducted based on the estimated intent‐to‐treat effect, which is subject to bias in the presence of noncompliance. To address this issue, we propose a Bayesian sequential monitoring trial design based on the estimation of the causal effect using a principal stratification approach. The proposed design simultaneously considers efficacy and toxicity outcomes and utilizes covariates to predict a patient's potential compliance behavior and identify the causal effects. Based on accumulating data, we continuously update the posterior estimates of the causal treatment effects and adaptively make the go/no‐go decision for the trial. Numerical results show that the proposed method has desirable operating characteristics and addresses the issue of noncompliance. Copyright © 2015 John Wiley & Sons, Ltd.
Word Detectives
Authors: Goodwin Amanda P. , Perkins Jennifer
Published: March 2015

This study describes an intervention that uses morphology to support word learning within comprehension instruction of content‐specific texts. The intervention is detailed such that the morphological understandings used to support word choice and word learning activities are clear and can be replicated by researchers and educators. Six main components that contributed to the intervention's success were identified including teaching students about comprehension strategies; teaching students about morphological problem‐solving (i.e., word‐solving); having students read and code use of strategies within text; sharing of main understandings on a visual; reinforcing learning through games; and including closure that reviewed and applied learning to different academic domains. This learning was fit within research‐based comprehension strategy instruction and also within the Common Core Standards movement. Implications for instruction and research are shared.
Considering Community Psychology Competencies: A Love Letter to Budding Scholar‐Activists Who Wonder if They Have What It Takes
Authors: Langhout Regina Day
Published: March 2015

Recently, community psychologists have re‐vamped a set of 18 competencies considered important for how we practice community psychology. Three competencies are: (1) ethical, reflexive practice, (2) community inclusion and partnership, and (3) community education, information dissemination, and building public awareness. This paper will outline lessons I—a white working class woman academic—learned about my competency development through my research collaborations, using the lens of affective politics. I describe three lessons, from school‐based research sites (elementary schools serving working class students of color and one elite liberal arts school serving wealthy white students). The first lesson, from an elementary school, concerns ethical, reflective practice. I discuss understanding my affect as a barometer of my ability to conduct research from a place of solidarity. The second lesson, which centers community inclusion and partnership, illustrates how I learned about the importance of “before the beginning” conversations concerning social justice and conflict when working in elementary schools. The third lesson concerns community education, information dissemination, and building public awareness. This lesson, from a college, taught me that I could stand up and speak out against classism in the face of my career trajectory being threatened. With these lessons, I flesh out key aspects of community practice competencies.
Dietary Fenofibrate Reduces Hepatic Lipid Deposition by Regulating Lipid Metabolism in Yellow Catfish Pelteobagrus fulvidraco Exposed to Waterborne Zn
Authors: Zheng Jia‐Lang , Luo Zhi , Hu Wei , Pan Ya‐Xiong , Zhuo Mei‐Qing
Published: March 2015

Fenofibrate is known to possess lipid‐lowering effects by regulation of gene transcription involved in lipid metabolism. Waterborne Zn exposure induces lipid deposition in yellow catfish Pelteobagrus fulvidraco. Thus, the present working hypothesis is that dietary fenofibrate addition will reduce hepatic lipids in yellow catfish exposed to waterborne Zn. To this end, juvenile yellow catfish were exposed to 0.04 (control), 0.35 mg/L waterborne Zn, 0.15 % dietary fenofibrate, and 0.35 mg Zn/l + 0.15 % dietary fenofibrate for 8 weeks. Growth performance, lipid deposition and metabolism in the liver were determined. Dietary fenofibrate promoted growth performance and reduced hepatic lipid content of yellow catfish exposed to waterborne Zn. However, these effects did not appear in fish in normal water. The lipid‐lowering effect of fenofibrate on fish exposed to waterborne Zn was associated with increased lipolysis, as indicated by increased CPT I activities and expression of lipolytic genes PPARα, CPT IA, ATGL and HSL, and with reduced lipogenesis as indicated by reduced activities of G6PD, 6PGD, ME and ICDH. Dietary fenofibrate significantly increased mRNA levels of FAS, LPL and ACCα, but reduced mRNA levels of ACCβ and PPARγ in fish exposed to waterborne Zn. Pearson correlations between transcriptional factors expression, and activities and expression of several enzymes were observed, indicating that changes at the molecular and enzymatic levels may underlie the patterns of lipid metabolism and accordingly affect hepatic fat storage. Taken together, our results suggest that the lipid‐lowering effect of fenofibrate was attributed, in part, to the down‐regulation of lipogenesis and up‐regulation of fatty acid oxidation.
Failing to Master Divinity: How Institutional Type, Financial Debt, Community Acceptance, and Gender Affect Seminary Graduates’ Career Choices
Authors: Ferguson Todd W.
Published: March 2015

Seminaries, as both educational and religious organizations, have the goal of training religious leaders. In this article, I analyze the factors associated with the breakdown of this process, i.e. when a seminarian does not want to be in a religious career. I offer four reasons for this breakdown: institutional type, financial strain, community acceptance, and gender. Drawing on recent survey data of 3015 American and Canadian seminarians graduating with the Master of Divinity degree from 136 seminaries from the Association of Theological Schools, I interpret results from multilevel logistic regressions testing five hypotheses. I find that Master of Divinity graduates who attend a university-affiliated seminary are less likely to want to be in a religious career, while those who feel more accepted within the seminary community are more likely. Educational debt has no effect. Most importantly, gender has profound effects on the choice to enter a religious career.
Protective effect of antioxidants on DNA damage in leukocytes from X‐linked adrenoleukodystrophy patients
Authors: Marchetti Desirèe P. , Donida Bruna , da Rosa Helen T. , Manini Paula R. , Moura Dinara J. , Saffi Jenifer , Deon Marion , Mescka Caroline P. , Coelho Daniella M. , Jardim Laura B. , Vargas Carmen R.
Published: March 2015

Toxic metabolites accumulation and oxidative stress have been associated to the pathophysiology of X‐linked adrenoleukodystrophy (X‐ALD), an inborn error of peroxisome metabolism. Parameters of oxidative damage to proteins and lipids in X‐ALD patients were already described in literature; however, DNA injuries were not studied yet. Considering that, the aims were to investigate DNA damage by comet assay in heterozygotes and symptomatic X‐ALD patients, to look for associations between DNA damage and lipid peroxidation as measured by urinary 15‐F2t‐isoprostane; and to evaluate the in vitro effect of N‐acetyl‐l‐cysteine (NAC), trolox (TRO) and rosuvastatin (RSV) on DNA damage in leukocytes from symptomatic patients. Symptomatic patients presented higher DNA damage levels than those found in heterozygotes and controls; heterozygotes and controls showed similar results. In order to investigate the in vitro antioxidant effect on DNA damage, whole blood cells from symptomatic patients were incubated with NAC (1 and 2.5 mM), TRO (25 and 75 μM) and RSV (0.5, 2 and 5 μM) before DNA damage analysis. NAC, TRO and RSV, at all tested concentrations, were all capable to reduce DNA damage in symptomatic X‐ALD patients until control levels. Finally, DNA damage correlated with urinary isoprostanes and plasmatic levels of TBA‐RS and DCFH‐DA, allowing to hypothesize that DNA damage might be induced by lipid peroxidation in symptomatic patients. The present work yields experimental evidence that NAC, TRO and RSV reduce the in vitro DNA injury in symptomatic X‐ALD patients, what may suggest that the administration of these antioxidants might be considered as an adjuvant therapy for X‐ALD.
Application of mobile phones in epilepsy care
Authors: Ranganathan Lakshmi , Aadhimoolam Chinnadurai Somasundaram , Samivel Balasubramanian , Kesavamurthy Bhanu , Mehndiratta Man Mohan
Published: March 2015

Objectives To evaluate the applications of mobile phones in the day to day care of epileptic patients as a diagnostic, prognostic and therapeutic tool.

Methods Detailed search of various mobile applications in the field of epileptology was made in MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, LILACS and corresponding developer websites of mobile applications were also looked into regarding their technical specifications and user friendliness.

Results A plethora of apps are available across various mobile platforms especially Android, iOS and Windows. Careful selection and application of such apps by both the healthcare providers, the epileptic patients and their caregivers with proper understanding of their potential benefits as well as limitations will result in better diagnosis, prognosis and treatment of epilepsy.

Conclusion The field of medicine is rapidly inculcating advanced cutting edge technologies for better diagnosis of diseases and better targeted therapy to such diseases. Hi tech electronic gadgets, in particular, are now becoming part and parcel of patient care in many specialties. The advent of the modern portable computers has revolutionised almost every specialty. The field of mobile technology is advancing with a break neck pace, with increase in mobile subscribers, advanced handsets practically like digital personal assistants with advanced capabilities. The possibilities of using such rapidly evolving mobile technology in the field of medicine are endless. This article explores such possibilities in the field of epileptology after analysing the current and existing applications of mobile phones in care of the epileptic patients worldwide.
A case of paroxysmal nocturnal dystonia responsive to cyproheptadine: Is it almost always epileptic?
Authors: Sayadnasiri Mohammad
Published: March 2015

Nocturnal Paroxysmal Dystonia (NPD) is characterized by abnormal dyskinetic movements occur mostly during non-REM sleep. From introducing NPD in early 1980s, most authors have been in favour of an epileptic origin for these sleep-related episodes. Clinical characteristics of NPD including abrupt hypermotor behaviours, automatisms and vocalizations, abnormal EEG findings in some patients and therapeutic response to anti-epileptic drugs persuade clinicians to accept NPD as sleep-related epilepsy with frontal lobe origin but it seems this conclusion may not be true in all cases. We present a young adult patient with refractory NPD who responded to antihistamine cyproheptadine and propose an alternative theory to describe NPD according to the basal ganglia dysregulation. So, in such patients, other therapeutic approach should be reasonably sought.
Pharmacognostic, physicochemical and phytochemical investigation of Bacopa monnieri L. stem and its anticonvulsant potential in laboratory animals
Authors: Mishra Amrita , Mishra Arun , PrakashTiwari Om , Jha Shivesh
Published: March 2015

Aim The aim of present work was to study the pharmacognostic standardization, physicochemical, phytochemical and pharmacological evaluation of the stem of Bacopa monnieri L.

Method Standard method was followed for pharmacognostic, physicochemical, and phytochemical study. For quantitative analysis, HPTLC technique was employed. Maximal electroconvulsive shock (MES) and pentylenetetrazole (PTZ) method was used for anticonvulsant evaluation.

Result Microscopic study of the stem showed presence of epidermis and cortex having large intercellular spaces. The oval shaped starch grains were present in cells of cortex and endodermis. Total ash (5.98%), water-soluble ash (4.91%), acid-insoluble ash (3.96%), water soluble extractive (15.31%) and ethanol soluble extractive (6.74%) values were evaluated for physicochemical evaluations. Quantitative estimation of Bacoside A (marker compound) by HPTLC technique was performed. The linearity (100–600 ng), the % recovery (97.81% w/w) were estimated. The Bacoside A in the alcoholic extract was found to be higher than that of the other extracts. The proposed HPTLC method was found to be simple and accurate. The anticonvulsant activities of all the extracts were evaluated by MES and PTZ models in mice.

Conclusion The least anticonvulsant potential was recorded for acetone extract in dose of 100 mg/kg and maximum anticonvulsant action was recorded for ethanolic extract in dose of 300 mg/kg.
Genetic polymorphisms of CYP2C19 and IL1B have no influence on esomeprazole treatment for mild erosive esophagitis
Authors: Hsu Wen‐Hung , Kuo Fu‐Chen , Hu Huang‐Ming , Hsu Ping‐I , Wu Deng‐Chyang , Kuo Chao‐Hung
Published: March 2015

Interleukin (IL)‐1β is a potent inhibitor of gastric acid secretion and its genetic polymorphism is linked to the severity of reflux esophagitis. Proton‐pump inhibitor (PPI) metabolized by P450 2C19 (CYP2C19) is the chief medication in reflux esophagitis treatment. The CYP2C19 genotype may influence the therapeutic effect of PPI for reflux esophagitis. From November 2009 to June 2012, 184 patients were enrolled in this study with endoscopy examination, 8 weeks of esomeprazole treatment, and 20 weeks of follow‐up with questionnaire. These patients also received endoscopy examination after 20 weeks. Blood was collected for genetic polymorphism analysis with polymerase chain reaction. After 8 weeks of treatment with esomeprazole, all of these 184 patients had achieved complete symptom relief. However, in the following 12 weeks, 58.70% (108/184) complained of symptom relapse, 45.65% (84/184) patients had persistent esophageal erosion verified by endoscopy, and in total, 76.09% (140/184) patients had treatment failure at the end of 20 weeks. There were no influences between the genetic polymorphisms of CYP2C19 and IL1B to treatment failure (p = 0.896). Therefore, prolonging PPI treatment and further lifestyle modification might be warranted for symptomatic mild esophagitis. There were no relationships between IL‐1β and CYP2C19 in the treatment effect in mild reflux esophagitis.
Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma
Authors: Wu Chun‐Chieh , Lin Zu‐Yau , Kuoc Chao‐Hung , Chuang Wan‐Long
Published: March 2015

Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH) were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment). Our results showed that colchicine caused significantly dose‐dependent antiproliferative effects on both cell lines (all p < 0.0001). Nude mouse (BALB/c‐nu) experiments showed that the increased tumor volume ratios in colchicine‐treated mice were significantly lower than control mice started from the 11th day of treatment (p = 0.0167). The tumor growth rates in colchicine‐treated mice after 14 days of treatment were significantly lower than in control mice (0.147 ± 0.004/d vs. 0.274 ± 0.003/d, p = 0.0015). In addition to the well‐known direct colchicine–tubulin interaction as a common anticancer mechanism of colchicine, microarray and quantitative reverse transcriptase‐polymerase chain reaction showed that the antiproliferative effects of both 2 ng/mL and 6 ng/mL colchicine on C14/KMUH cells could be partially explained by downregulations of both HSD11B2 and MT‐COI. There was no effect of colchicine on MT‐COI expression in C51/KMUH cells, however, 6 ng/mL colchicine also downregulated HSD11B2 in this cell line. In conclusion, clinically acceptable colchicine concentrations can inhibit the proliferation of human cholangiocarcinoma cells. This drug has good potential for the palliative treatment of cholangiocarcinoma due to its low cost and our long‐standing prescription experience.
Predicting the Risk for Hospital-Onset Clostridium difficile Infection (HO-CDI) at the Time of Inpatient Admission: HO-CDI Risk Score
Authors: Tabak Ying P. , Johannes Richard S. , Sun Xiaowu , Nunez Carlos M. , McDonald L. Clifford
Published: March 2015

OBJECTIVE

To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission

DESIGN

Retrospective data analysis

SETTING

Six US acute care hospitals

PATIENTS

Adult inpatients

METHODS

We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations.

RESULTS

Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76–0.81) with good calibration. Among 79% of patients with risk scores of 0–7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001).

CONCLUSION

Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.

Infect Control Hosp Epidemiol 2015;00(0):1–7
Direct numerical simulation of transition in a sharp cone boundary layer at Mach 6: fundamental breakdown
Authors: Sivasubramanian Jayahar , Fasel Hermann F.
Published: March 2015

Direct numerical simulations (DNS) were performed to investigate the laminar–turbulent transition in a boundary layer on a sharp cone with an isothermal wall at Mach 6 and at zero angle of attack. The motivation for this research is to make a contribution towards understanding the nonlinear stages of transition and the final breakdown to turbulence in hypersonic boundary layers. In particular, the role of second-mode fundamental resonance, or (K-type) breakdown, is investigated using high-resolution ‘controlled’ transition simulations. The simulations were carried out for the laboratory conditions of the hypersonic transition experiments conducted at Purdue University. First, several low-resolution simulations were carried out to explore the parameter space for fundamental resonance in order to identify the cases that result in strong nonlinear interactions. Subsequently, based on the results from this study, a set of highly resolved simulations that proceed deep into the turbulent breakdown region have been performed. The nonlinear interactions observed during the breakdown process are discussed in detail in this paper. A detailed description of the flow structures that arise due to these nonlinear interactions is provided and an analysis of the skin friction and heat transfer development during the breakdown is presented. The controlled transition simulations clearly demonstrate that fundamental breakdown may indeed be a viable path to complete breakdown to turbulence in hypersonic cone boundary layers at Mach 6.
A framework for studying the effect of compliant surfaces on wall turbulence
Authors: Luhar M. , Sharma A. S. , McKeon B. J.
Published: March 2015

This paper extends the resolvent formulation proposed by McKeon & Sharma (J. Fluid Mech., vol. 658, 2010, pp. 336–382) to consider turbulence–compliant wall interactions. Under this formulation, the turbulent velocity field is expressed as a linear superposition of propagating modes, identified via a gain-based decomposition of the Navier–Stokes equations. Compliant surfaces, modelled as a complex wall admittance linking pressure and velocity, affect the gain and structure of these modes. With minimal computation, this framework accurately predicts the emergence of the quasi-two-dimensional propagating waves observed in recent direct numerical simulations. Further, the analysis also enables the rational design of compliant surfaces, with properties optimized to suppress flow structures energetic in wall turbulence. It is shown that walls with unphysical negative damping are required to interact favourably with modes resembling the energetic near-wall cycle, which could explain why previous studies have met with limited success. Positive-damping walls are effective for modes resembling the so-called very-large-scale motions, indicating that compliant surfaces may be better suited for application at higher Reynolds number. Unfortunately, walls that suppress structures energetic in natural turbulence are also predicted to have detrimental effects elsewhere in spectral space. Consistent with previous experiments and simulations, slow-moving spanwise-constant structures are particularly susceptible to further amplification. Mitigating these adverse effects will be central to the development of compliant coatings that have a net positive influence on the flow.
Salinity transfer in bounded double diffusive convection
Authors: Yang Yantao , van der Poel Erwin P. , Ostilla-Mónico Rodolfo , Sun Chao , Verzicco Roberto , Grossmann Siegfried , Lohse Detlef
Published: March 2015

The double diffusive convection between two parallel plates is numerically studied for a series of parameters. The flow is driven by the salinity difference and stabilised by the thermal field. Our simulations are directly compared with experiments by Hage & Tilgner (Phys. Fluids, vol. 22, 2010, 076603) for several sets of parameters and reasonable agreement is found. This, in particular, holds for the salinity flux and its dependence on the salinity Rayleigh number. Salt fingers are present in all simulations and extend through the entire height. The thermal Rayleigh number seems to have a minor influence on the salinity flux but affects the Reynolds number and the morphology of the flow. In addition to the numerical calculation, we apply the Grossmann–Lohse theory for Rayleigh–Bénard flow to the present problem without introducing any new coefficients. The theory successfully predicts the salinity flux both with respect to the scaling and even with respect to the absolute value for the numerical and experimental results.
On the benefits of being redundant: low compositional fidelity of diatom death assemblages does not hamper the preservation of environmental gradients in shallow lakes
Authors: Hassan Gabriela S.
Published: March 2015

Comparisons between death assemblages and their source living communities are among the most common actualistic methods of evaluating the preservation of compositional and environmental information in fossil assemblages. Although live-dead studies have commonly focused on marine mollusks, the potential of diatoms to preserve ecological information in continental settings has been overlooked. Thus, little is known about the nature and magnitude of the taphonomic biases affecting live-dead agreement of diatom assemblages, despite their extensive application as modern and fossil bioindicators in paleoecological and paleoenvironmental reconstructions. In this study, I analyzed three live-dead data sets in order to evaluate the compositional and environmental fidelity exhibited by diatom death assemblages in shallow lakes. I find that diatom death assemblages (DAs) do differ significantly in their taxonomic composition from living assemblages (LAs), mainly as a consequence of (1) differences in the temporal resolution between time-averaged DAs and non-averaged LAs, and (2) differential preservation of diatom taxa related to the intrinsic properties of their valves. Despite compositional dissimilarities, DAs were able to capture the same environmental gradients as LAs, with high significance. This decoupling between live-dead agreement in community composition and community response to gradients can be related to the existence of at least two mutually exclusive subsets of species that significantly captured compositional dissimilarities based on the full set of the species in the three lakes. This functional redundancy implies that the between-sample relationships of living assemblages can be significantly preserved by DAs even if some taxa are removed by taphonomic processes. The preservation of environmental gradients thus does not require good preservation of all living taxa. Structural redundancy compensates for the loss of compositional fidelity caused by postmortem processes in the diatom data set.
A morphospace of planktonic marine diatoms. I. Two views of disparity through time
Authors: Kotrc Benjamin , Knoll Andrew H.
Published: March 2015

Both molecular clocks and the first appearances of major groups in the fossil record suggest that most of the range of diatom morphologies observed today had evolved by the end of the Cretaceous Period. Despite this, a canonical reading of the Cenozoic fossil record suggests a dramatic rise in taxonomic diversity that can be interpreted as an explosion of morphological variety. We investigated this apparent discrepancy by using a discrete-character-based, empirical diatom morphospace, resolved by molecular phylogeny and by fossil occurrences through time. The morphospace shows little correspondence to phylogeny and little Cenozoic change in disparity as measured by mean pairwise distance. There is, however, an increase in the total volume of morphospace occupied. Although the increase in occupied volume through time ostensibly supports a conclusion of increasing morphological variety, sampling biases and other data suggest an underlying stationary pattern more consistent with molecular clock data.
Exploring photosymbiotic ecology of planktic foraminifers from chamber-by-chamber isotopic history of individual foraminifers
Authors: Takagi Haruka , Moriya Kazuyoshi , Ishimura Toyoho , Suzuki Atsushi , Kawahata Hodaka , Hirano Hiromichi
Published: March 2015

Evolution of photosymbiotic ecology is an important adaptation for planktic foraminifers that enhances the ecological advantage of living in oligotrophic oceans. Therefore, detecting photosymbiotic ecology in fossil species is one of the keys to understanding the paleobiodiversity dynamics of planktic foraminifers. Because foraminiferal tests record the ontogenetic history of ecological information in geochemical signatures, analyzing individual geochemical profiles with growth can reveal a species’ ecology. This study examined chamber-by-chamber stable isotopes (δ13C and δ18O) of foraminiferal individuals to identify photosymbiotic signals. We observed an ontogenetic δ13C increase of up to 2.4‰, accompanied by relatively stable, negative δ18O, in the symbiotic species Globigerinoides conglobatus and Globigerinoides sacculifer. In contrast, δ13C and δ18O showed significant positive correlation during ontogeny in the asymbiotic species Globorotalia truncatulinoides. These two ecological groups produce contrasting isotopic profiles, thereby allowing us to use our ontogenetic isotopic analyses of individual specimens to identify algal photosymbiosis in fossil foraminifers. The chamber-by-chamber isotope analyses with individual ontogeny have great advantages in analyzing rare species because only one individual is required to describe ontogenetic isotopic history. In addition to photosymbiotic identification, our methods hold great potential to provide new insight into species paleoecological studies such as the ontogenetic history of calcification depth.
Breaking the mold: using biomechanical experiments to assess the life orientation of dorsibiconvex brachiopods
Authors: Barclay Kristina M. , Schneider Chris L. , Leighton Lindsey R.
Published: March 2015

Understanding the life orientation of fossil organisms, such as brachiopods, is not only important for understanding the biology of the organism in question, but it also can be used to interpret paleoecological information about the assemblages from which the specimens were derived. The dorsibiconvex brachiopod morphology is particularly common, especially among the Order Atrypida, yet there have been few independent, biomechanical studies to assess the life orientation of these brachiopods. In this study, we assess potential orientations of two end-member morphologies of a dorsibiconvex brachiopod, Pseudoatrypa lineata, from the Mid–Late Devonian of North America by placing realistic models in a flume.

Using materials with the specific gravity of calcium carbonate, we modeled two well-preserved Pseudoatrypa lineata from the Waterways Formation (Givetian–Frasnian, Alberta, Canada) to represent the original shell. The hydrodynamic stability of the models was assessed by placing the models in a recirculating flume in one of three initial orientations: (1) anterior commissure upstream, (2) umbo upstream, and (3) lateral (specimen perpendicular to flow), each with the dorsal and ventral valve topmost. The entire process was conducted both on a Plexiglas substrate and on well-sorted, mediumgrained sand. All scenarios were repeated five times for a total of sixty trials per specimen (120 total).

Flume trials indicate that neither brachiopod had a true hydrodynamically stable orientation.

Reorientations occurred at low velocities (~0.2 m/s), with transport occurring soon after (~0.3 m/s).

Assuming that a juvenile, pedunculate, dorsibiconvex brachiopod would initially have been oriented with its ventral valve topmost, our results suggest two outcomes: the brachiopods either (1) were attached via pedicles throughout their lives or (2) lived in quiet, undisturbed waters. Given the abundance of dorsibiconvex brachiopods in observed high-energy environments, our results indicate it is more conservative to assume dorsibiconvex brachiopods retained pedicles throughout their lives.
Residents’ Self-Reported Quality of Life in Long-Term Care Facilities in Canada
Authors: Kehyayan Vahe , Hirdes John P. , Tyas Suzanne L. , Stolee Paul
Published: March 2015

La qualité de vie (QV) dont bénéficient les résidents des centres d'hébergement de soins de longue durée (SLD) est un résultat important des soins. Cette étude descriptive transversale a examiné la qualité de vie auto-declarée de résidents des établissements de SLD au Canada, tout en utilisant l'auto-évaluation interRAI Nursing Home Quality of Life Survey. Un objectif secondaire était de tester les propriétés pschométriques de l'instrument. Les tests psychométriques de l'instrument ont soutenu sa fiabilité et la validité de sa convergence et de son contenu pour l'évaluation de QV des résidents. Les résultats ont montré que les résidents ont évalués positivement plusieurs aspects de leur vie, comme d'avoir la vie privée lors des visites (76,9%) et l'honnêteté du personnel en traitant avec eux (73,6%). Les résidents ont accordé des taux inférieures à d'autres aspects, comme l'autonomie, la liaison entre le personnel et les résidents, et les relations personnelles. Les résultats suggèrent des lacunes importantes entre les philosophies de soins dans les établissements et leur traduction dans un environnement de soins ou les soins sont vraiment dirigés aux résidents. En outre, les résultats ont des implications potentielles pour la planification de soins aux résidents, la programmation de l'installation, le développement de la politique sociale et de la recherche future.
Utilitarianism, Multiplicity and Liberalism
Authors: SEBO JEFF
Published: March 2015

I argue that utilitarianism requires us to tolerate intrapersonal disagreement for the same reasons that it requires us to tolerate interpersonal disagreement. I begin by arguing that multiplicity has the same costs and benefits as multiculturalism: It causes conflict, but it also allows us to perform experiments in living, adopt a division of labour, compartmentalize harm and learn from ourselves. I then argue that, in light of these costs and benefits, utilitarianism requires us to adopt a liberal system of individual self-government, according to which we should not try to impose a unified set of beliefs and values on ourselves. Finally, I argue that we should apply this policy of liberal toleration to intrapersonal disagreement about utilitarianism too. If we want to maximize utility, then we should tolerate inner conflict not only about how to maximize utility but also about whether we should be maximizing utility in the first place.
Trx1/TrxR1 system regulates post‐selected DP thymocytes survival by modulating ASK1‐JNK/p38 MAPK activities
Authors: Jin Rong , Gao Yuhan , Zhang Shusong , Teng Fei , Xu Xi , Aili Abudureyimujiang , Wang Yuqing , Sun Xiuyuan , Pang Xuewen , Ge Qing , Zhang Yu
Published: March 2015

A key process in the development of T lymphocyte in the thymus is T‐cell receptor (TCR) selection. It is controlled by complex signaling pathways that contain redox‐sensitive molecules. However, the redox status early after TCR selection and how redox regulators promote the survival of post‐selected DP thymocytes has not been directly addressed. The present study demonstrated that the transition from pre‐ to post‐selected double‐positive (DP) stages was accompanied with an increase of reactive oxygen species (ROS) and a transient surge in the expression of a variety of redox regulators. Among them, the thioredoxin (Trx)1/thioredoxin reductase (TrxR)1 system was found to be critically involved in the regulation of cell survival of DP thymocytes, especially that of post‐selected CD69+ subset, as its inhibition caused a specific reduction of these cells both in vitro and in vivo, most likely owing to increased apoptosis. Suppression of the glutathione‐dependent redox system, on the other hand, showed no obvious impact. Biochemically, treatment of DP thymcoytes with TrxR1 inhibitor alone or in conjunction with anti‐CD3 resulted in enhanced phosphorylation of redox‐sensitive ASK‐1, JNK and p38 MAPK, and upregulated expression of Bim. Taken together, the data presented here suggest that the timely upregulation of Trx1/TrxR1 and the active control of intracellular redox status is critical for the survival of thymocytes during and short after positive selection.
Clostridium difficile heterogeneously impacts intestinal community architecture but drives stable metabolome responses
Authors: Rojo David , Gosalbes María J , Ferrari Rafaela , Pérez-Cobas Ana E , Hernández Ester , Oltra Rosa , Buesa Javier , Latorre Amparo , Barbas Coral , Ferrer Manuel , Moya Andrés
Published: March 2015

Clostridium difficile-associated diarrhoea (CDAD) is caused by C. difficile toxins A and B and represents a serious emerging health problem. Yet, its progression and functional consequences are unclear. We hypothesised that C. difficile can drive major measurable metabolic changes in the gut microbiota and that a relationship with the production or absence of toxins may be established. We tested this hypothesis by performing metabolic profiling on the gut microbiota of patients with C. difficile that produced (n=6) or did not produce (n=4) toxins and on non-colonised control patients (n=6), all of whom were experiencing diarrhoea. We report a statistically significant separation (P-value <0.05) among the three groups, regardless of patient characteristics, duration of the disease, antibiotic therapy and medical history. This classification is associated with differences in the production of distinct molecules with presumptive global importance in the gut environment, disease progression and inflammation. Moreover, although severe impaired metabolite production and biological deficits were associated with the carriage of C. difficile that did not produce toxins, only previously unrecognised selective features, namely, choline- and acetylputrescine-deficient gut environments, characterised the carriage of toxin-producing C. difficile. Additional results showed that the changes induced by C. difficile become marked at the highest level of the functional hierarchy, namely the metabolic activity exemplified by the gut microbial metabolome regardless of heterogeneities that commonly appear below the functional level (gut bacterial composition). We discuss possible explanations for this effect and suggest that the changes imposed by CDAD are much more defined and predictable than previously thought.
Description of quantum coherence in thermodynamic processes requires constraints beyond free energy
Authors: Lostaglio Matteo , Jennings David , Rudolph Terry
Published: March 2015

Recent studies have developed fundamental limitations on nanoscale thermodynamics, in terms of a set of independent free energy relations. Here we show that free energy relations cannot properly describe quantum coherence in thermodynamic processes. By casting time-asymmetry as a quantifiable, fundamental resource of a quantum state, we arrive at an additional, independent set of thermodynamic constraints that naturally extend the existing ones. These asymmetry relations reveal that the traditional Szilárd engine argument does not extend automatically to quantum coherences, but instead only relational coherences in a multipartite scenario can contribute to thermodynamic work. We find that coherence transformations are always irreversible. Our results also reveal additional structural parallels between thermodynamics and the theory of entanglement.
The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment
Authors: Cotney Justin , Muhle Rebecca A. , Sanders Stephan J. , Liu Li , Willsey A. Jeremy , Niu Wei , Liu Wenzhong , Klei Lambertus , Lei Jing , Yin Jun , Reilly Steven K. , Tebbenkamp Andrew T. , Bichsel Candace , Pletikos Mihovil , Sestan Nenad , Roeder Kathryn , State Matthew W. , Devlin Bernie , Noonan James P.
Published: March 2015

Recent studies implicate chromatin modifiers in autism spectrum disorder (ASD) through the identification of recurrent de novo loss of function mutations in affected individuals. ASD risk genes are co-expressed in human midfetal cortex, suggesting that ASD risk genes converge in specific regulatory networks during neurodevelopment. To elucidate such networks, we identify genes targeted by CHD8, a chromodomain helicase strongly associated with ASD, in human midfetal brain, human neural stem cells (hNSCs) and embryonic mouse cortex. CHD8 targets are strongly enriched for other ASD risk genes in both human and mouse neurodevelopment, and converge in ASD-associated co-expression networks in human midfetal cortex. CHD8 knockdown in hNSCs results in dysregulation of ASD risk genes directly targeted by CHD8. Integration of CHD8-binding data into ASD risk models improves detection of risk genes. These results suggest loss of CHD8 contributes to ASD by perturbing an ancient gene regulatory network during human brain development.
Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp3 carbons
Authors: Wu Xuesong , Yang Ke , Zhao Yan , Sun Hao , Li Guigen , Ge Haibo
Published: March 2015

Cobalt-catalysed sp2 C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process. In comparison, much less efforts have been devoted to the sp3 carbons. Here we report the cobalt-catalysed site-selective dehydrogenative cyclization of aliphatic amides via a C–H bond functionalization process on unactivated sp3 carbons with the assistance of a bidentate directing group. This method provides a straightforward synthesis of monocyclic and spiro β- or γ-lactams with good to excellent stereoselectivity and functional group tolerance. In addition, a new procedure has been developed to selectively remove the directing group, which enables the synthesis of free β- or γ-lactam compounds. Furthermore, the first cobalt-catalysed intermolecular dehydrogenative amination of unactivated sp3 carbons is also realized.
Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia
Authors: Buchner Maike , Park Eugene , Geng Huimin , Klemm Lars , Flach Johanna , Passegué Emmanuelle , Schjerven Hilde , Melnick Ari , Paietta Elisabeth , Kopanja Dragana , Raychaudhuri Pradip , Müschen Markus
Published: March 2015

Despite recent advances in the cure rate of acute lymphoblastic leukaemia (ALL), the prognosis for patients with relapsed ALL remains poor. Here we identify FOXM1 as a candidate responsible for an aggressive clinical course. We show that FOXM1 levels peak at the pre-B-cell receptor checkpoint but are dispensable for normal B-cell development. Compared with normal B-cell populations, FOXM1 levels are 2- to 60-fold higher in ALL cells and are predictive of poor outcome in ALL patients. FOXM1 is negatively regulated by FOXO3A, supports cell survival, drug resistance, colony formation and proliferation in vitro, and promotes leukemogenesis in vivo. Two complementary approaches of pharmacological FOXM1 inhibition—(i) FOXM1 transcriptional inactivation using the thiazole antibiotic thiostrepton and (ii) an FOXM1 inhibiting ARF-derived peptide—recapitulate the findings of genetic FOXM1 deletion. Taken together, our data identify FOXM1 as a novel therapeutic target, and demonstrate feasibility of FOXM1 inhibition in ALL.
Neutral particle mass spectrometry with nanomechanical systems
Authors: Sage Eric , Brenac Ariel , Alava Thomas , Morel Robert , Dupré Cécilia , Hanay Mehmet Selim , Roukes Michael L. , Duraffourg Laurent , Masselon Christophe , Hentz Sébastien
Published: March 2015

Current approaches to mass spectrometry (MS) require ionization of the analytes of interest. For high-mass species, the resulting charge state distribution can be complex and difficult to interpret correctly. Here, using a setup comprising both conventional time-of-flight MS (TOF-MS) and nano-electromechanical systems-based MS (NEMS-MS) in situ, we show directly that NEMS-MS analysis is insensitive to charge state: the spectrum consists of a single peak whatever the species’ charge state, making it significantly clearer than existing MS analysis. In subsequent tests, all the charged particles are electrostatically removed from the beam, and unlike TOF-MS, NEMS-MS can still measure masses. This demonstrates the possibility to measure mass spectra for neutral particles. Thus, it is possible to envisage MS-based studies of analytes that are incompatible with current ionization techniques and the way is now open for the development of cutting-edge system architectures with unique analytical capability.
Supramolecular synergy in the boundary lubrication of synovial joints
Authors: Seror Jasmine , Zhu Linyi , Goldberg Ronit , Day Anthony J. , Klein Jacob
Published: March 2015

Hyaluronan, lubricin and phospholipids, molecules ubiquitous in synovial joints, such as hips and knees, have separately been invoked as the lubricants responsible for the remarkable lubrication of articular cartilage; but alone, these molecules cannot explain the extremely low friction at the high pressures of such joints. We find that surface-anchored hyaluronan molecules complex synergistically with phosphatidylcholine lipids present in joints to form a boundary lubricating layer, which, with coefficient of friction μ≈0.001 at pressures to over 100 atm, has a frictional behaviour resembling that of articular cartilage in the major joints. Our findings point to a scenario where each of the molecules has a different role but must act together with the others: hyaluronan, anchored at the outer surface of articular cartilage by lubricin molecules, complexes with joint phosphatidylcholines to provide the extreme lubrication of synovial joints via the hydration–lubrication mechanism.
Meta-analyses of gene methylation and smoking behavior in non-small cell lung cancer patients
Authors: Huang Tao , Chen Xiaoying , Hong Qingxiao , Deng Zaichun , Ma Hongying , Xin Yanfei , Fang Yong , Ye Huadan , Wang Rujie , Zhang Cheng , Ye Meng , Duan Shiwei
Published: March 2015

Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were likely to be potentially useful biomarkers in the early diagnosis of NSCLC.