bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Psychoanamnese
Authors: Müller H.V.
Published: June 2017

Die Patienten sind in 4 Gruppen aufzugliedern, und zwar in die der somatisch Kranken, in die der psycho-somatisch Kranken, die der Kranken mit larvierten Depressionen und die der psychopathischen (besser persönlichkeitsgestörten) Patienten. Die Gruppe 1 benötigt keine Psychoanamne-se, während die 2. und 3. Gruppe die für eine Aufnahme der Psychoanamnese dankbarsten Fälle enthält. Besonders schwierig ist die Erhebung der Psychoanamnese bei den Patienten der Gruppe 4; aber auch hier sind die Resultate recht gut. Die Psychoanamnese hat in der heutigen klinischen Medizin einen hohen Stellenwert, wird aber z.T. wegen eigener Unzulänglichkeit und Zeitnot zu wenig ausgeübt. Die hauptsächliche Bedeutung der Psychoanamnese in der klinischen Medizin liegt darin, daß der beratende Arzt durch eine Steuerung des Gesprächs eine umfassende Exploration und offene Selbstdarstellung des Patienten erreicht. Besonders dadurch, daß er viele nicht mehr in seinem Bewußtsein vorhandenen Fakten neu erlebt, erkennt der Patient leichter die Zusammenhänge zwischen seinen Erlebnissen und seinen psychischen Reaktionen, aber auch, und das ist vor allem anderen wichtig, die engen Beziehungen zwischen Psyche und Soma. In der Homöopathie hat die Psychoanamnese eine noch größere Bedeutung als in der klinischen Medizin. Denn neben der Aufdeckung der Beziehungen Erlebnis: psychische Reaktion: somatische Erkrankung spielt der Arzt eine vorherrschende Rolle. Er soll nicht nur den Patienten steuern, sondern durch die Psychoanamnese Informationen gewinnen, um mit ziemlicher Sicherheit das betreffende Simile zu finden. Nur durch die Psychoanamnese können viele Krankheitsbilder geklärt und die betreffenden Persönlichkeiten einwandfrei erkannt werden, weshalb diese Methode gerade in der Homöopathie eine vorrangige Stellung einnimmt.
Belladonna und die Reinigung der Arzneimittellehre
Authors: Keller Georg v.
Published: June 2017

Hauptvertreter der kritisch wissenschaftlichen Homöopathie war Richard Hughes (1836-1902). Er glaubte, mit einer gereinigten Arzneimittellehre die Homöopathie zum Allgemeingut aller Ärzte machen zu können. Er wollte zu diesem Zwecke gerade die Symptome aus der Materia medica entfernen, auf die es dem Praktiker bei der Mittelwahl besonders ankommt: die nicht meßbaren reinen Empfindungen und die phantasievollen Symptome, die häufig bei Hochpotenzprüfungen sich herausgestellt haben und die Hahnemann in seinem späteren Leben an seinen Patienten beobachtet hatte. Daß diese gereinigte Arzneimittellehre für die praktische Arbeit ungeeignet wäre, versucht der Verfasser am Beispiel von Belladonna aufzuzeigen.
Calcium carbonicum Hahnemanni
Authors: Illing Kurt-Hermann
Published: June 2017

Es wird über die erfolgreiche Behandlung von 6 Patienten mit Calcium carbonicum Hahnemanni berichtet. Im einzelnen handelt es sich um ein Ekzem bei einem 5jährigen Mädchen, um ein Asthma bronchiale bei einem 6jährigen Mädchen, eine rezidivierende Bronchitis bei einem 3jährigen Mädchen, um eine Enuresis bei einem 7jährigen Jungen, klimakterische Störungen und Fluor albus bei einer 45jährigen Patientin und um eine Neurofibromatose bei einem 3jährigen Mädchen.
Homöopathische Behandlung von Kindern mit Down Syndrom
Authors: Storm W.
Published: June 2017

Neben einigen vorwiegend "schulmedizinisch" zu behandelnden medizinischen Komplikationen wird das Leben vieler Kinder mit Down Syndrom durch zahlreiche Alltagsprobleme bestimmt, die zu häufigen Arztbesuchen zwingen. Es sind dies zwar meist keine lebensbedrohlichen Komplikationen, dennoch die Lebensqualität wesentlich mitbestimmende Erkrankungen. Anhand von sechs Fallbeispielen wird die erfolgreiche Anwendung homöopathischer Heilmittel bei Kindern mit Down Syndrom dargestellt.
Low-temperature absorption spectra and electron structure of HoFe3(BO3)4 single crystal
Authors: Malakhovskii A. V. , Gnatchenko S. L. , Kachur I. S. , Piryatinskaya V. G. , Gudim I. A.
Published: June 2017

Polarized absorption spectra of HoFe3(BO3)4 single crystal in the range of 8500–24 500 cm−1 were studied as a function of temperature beginning from 2 K. The ground and excited electron states of Ho3+ were identified. The abrupt changes of the spectra at the reorientation phase transition at 4.7 K were observed. The exchange splitting of some excited states were revealed and measured. They changed at the reorientation phase transition. Several vibronic transitions were observed. The splitting of absorption lines corresponding to the C2 local symmetry of the Ho ion was not observed. Moreover, spectra of some absorption bands correspond to splitting in the cubic crystal field. There are some absorption lines, whose polarization cannot be explained both in D3 and C2 local symmetries. Some lines appear or disappear as a result of the transition from the easy axis to the easy plane state of the crystal. All these observations testify to the substantial changes of the local magnetic and structural properties in the excited states of the Ho3+ ion and to the strong influence of the magnetic moments orientation on the polarization of the electron transitions.
Singular optics of spin waves in a two-sublattice antiferromagnet with uniaxial magnetic anisotropy
Authors: Gorobets Yu. I. , Gorobets O. Yu.
Published: June 2017

Based on exact 3D solutions of the Landau-Lifshitz equations in a two-sublattice antiferromagnet with uniaxial magnetic anisotropy, the existence of nonlinear spin waves with singular points on the wavefront is predicted. These waves are spin-wave analogs of optical singularities.
Features of the magnetic state of ensembles of nanoparticles of substituted manganites: Experiment and model calculations
Authors: Polishchuk D. M. , Tykhonenko-Polishchuk Yu. O. , Solopan S. O. , Bodnaruk A. V. , Kulyk M. M. , Tovstolytkin A. I. , Pogorily A. M.
Published: June 2017

The magnetic characteristics of ensembles of La0.6Sm0.1Sr0.3MnO3 nanoparticles measured at different temperatures are analyzed quantitatively. The field and temperature dependences of the magnetization of the ensemble are calculated on the basis of this analysis. The calculations indicate that the spread in the parameters of the nanoparticles has a decisive influence on the key magnetic parameters of the ensemble: coercitive force, residual magnetization, and blocking temperature. It is shown that complete agreement between the experimental and calculated dependences is possible only if it is assumed that two different regions contribute to the total magnetic signal: anisotropic strong magnetic and isotropic weak magnetic regions. The effect of temperature on the behavior of the two types of regions is determined. It is concluded that the analytic procedure proposed here can be used to characterize the properties of other systems of magnetic nanoparticles, and can also be extended to the analysis and prediction of the results of magnetodynamic measurements.
Outcome of Low-Intensity Pulsed Ultrasound (LIPUS) for Opening Wedge High Tibial Osteotomy
Authors: Saito Ryusuke , Nagase Tsuyoshi , Tateishi Tomohiko , Shimizu Sadanori , Kato Takuya , Nakagawa Teruhiko , Tsutiya Masamitsu
Published: June 2017

Objective:

Opening Wedge High Tibial Osteotomy (OWHTO) for knee osteoarthritis and for osteonecrosis has reported good results. Use of low intensity pulsed ultrasound (LIPUS) after OWHTO had become an option for the treatment of OWHTO since April 2016. The purpose of this study was to examine whether LIPUS has an accelerating effect on synostosis after OWHTO.

Materials and Methods:

The control subjects were 24 patients with a total of 26 knees (9 male with knees and 15 female with 17 knees treated) treated with OWHTO only. OWHTO was performed from April 2015 to March 2016 (non-LIPUS control group). The average age of the patients was 61 years. The test subjects were 25 patients with a total of 27 knees (8 male with 9 knees and 17 female with 18 knees treated) treated with OWHTO and LIPUS. OWHTO was performed from April 2016 until the present. LIPUS was started after the surgery (LIPUS + group). The average age was 64.6 years. FTA, ROM, intraoperative open angle, and the time to bone union were examined.

Results:

There was no difference between the 2 groups in FTA, ROM, and open angle. Synostosis was obtained in 18 knees in the control group (no LIPUS) with an average duration of 8.4 months. The LIPUS + group had a short observation period with none of the patients experiencing bone union.

Discussion:

The synostosis promoting effect of LIPUS is expected. In this study, there were no bone union cases because of the short observation period. It is necessary to extend the follow-up period, and clarify the utility of LIPUS.
Assessing and Communicating the Value of Biomedical Research: Results From a Pilot Study
Authors: Guthrie Susan , Krapels Joachim , Adams Alexandra , Alberti Philip , Bonham Ann , Garrod Bryn , Esmond Sarah , Scott Caitlin , Cochrane Gavin , Wooding Steven
Published: June 2017

Purpose

Assessing the impact of research requires an approach that is sensitive both to the context of the research and the perspective of the stakeholders trying to understand its benefits. Here, the authors report on a pilot that applied such an approach to research conducted at the Collaborative Center for Health Equity (CCHE) of the University of Wisconsin School of Medicine and Public Health.

Method

The pilot assessed the academic impact of CCHE’s work; the networks between CCHE and community partners; and the reach of CCHE’s programs, including an attempt to estimate return on investment (ROI). Data included bibliometrics, findings from a stakeholder survey and in-depth interviews, and financial figures.

Results

The pilot illustrated how CCHE programs increase the capacity of community partners to advocate for their communities and engage with researchers to ensure that research benefits the community. The results illustrate the reach of CCHE’s programs into the community. The authors produced an estimate of the ROI for one CCHE program targeting childhood obesity, and values ranged from negative to positive.

Conclusions

The authors experienced challenges using novel assessment techniques at a small scale including the lack of comparator groups and the scarcity of cost data for estimating ROI. This pilot demonstrated the value of research from a variety of perspectives—from academic to community. It illustrates how metrics beyond grant income and publications can capture the outputs of an academic health center in a way that may better align with the aims of the center and stakeholders.
The Professionalism and Integrity in Research Program: Description and Preliminary Outcomes
Authors: DuBois James M. , Chibnall John T. , Tait Raymond , Vander Wal Jillon S.
Published: June 2017

Violations of rules and regulations in research can cause significant problems for human participants, animal subjects, data integrity, institutions, and investigators. The Professionalism and Integrity in Research Program (PI Program) provides remediation training that addresses the root causes of violations of rules and regulations in research. Through assessments, a three-day workshop, and follow-up coaching calls, the PI Program teaches evidence-based decision-making strategies designed to help researchers to compensate for bias, uncertainty, and work-related stress, and foster the skills needed to oversee research projects in today’s complex regulatory environments. Across its first three years (2013–2015), the program trained 39 researchers from 24 different institutions in the United States. Participant evaluations of the program’s faculty and workshop content were highly positive (4.7–4.8 and 4.5–4.6, respectively, on a 5-point scale). Preliminary program outcome assessment using validated measures of professional decision making and cognitive distortions in a pre- and postworkshop design indicated significant improvements. A follow-up survey of participants found statistically significant increases in a variety of target behaviors, including training research staff members to foster compliance and research quality, using standard operating procedures to support compliance and research integrity, performing self-audits of research operations, reducing job stressors, actively overseeing the work of the research team, and seeking help when experiencing uncertainty. Assessment of the PI Program was conducted with modest sample sizes, yet evaluation, outcome assessment, and self-reported survey data provided statistically significant evidence of effectiveness in achieving program goals.
Extubation Success Prediction in a Multicentric Cohort of Patients with Severe Brain Injury
Authors: Asehnoune Karim , Seguin Philippe , Lasocki Sigismond , Roquilly Antoine , Delater Adrien , Gros Antoine , Denou Florian , Mahé Pierre-Joachim , Nesseler Nicolas , Demeure-dit-Latte Dominique , Launey Yoann , Lakhal Karim , Rozec Bertrand , Mallédant Yannick , Sébille Véronique , Jaber Samir , Le Thuaut Aurélie , Feuillet Fanny , Cinotti Raphaël ,   ATLANREA group
Published: June 2017

Background

Patients with brain injury are at high risk of extubation failure.

Methods

We conducted a prospective observational cohort study in four intensive care units of three university hospitals. The aim of the study was to create a score that could predict extubation success in patients with brain injury.

Results

A total of 437 consecutive patients with brain injury were included, and 338 patients (77.3%) displayed successful extubation. In the multivariate analysis, four features were associated with success the day of extubation: age less than 40 yr, visual pursuit, swallowing attempts, and a Glasgow coma score greater than 10. In the score, each item counted as one. A score of 3 or greater was associated with 90% extubation success. The area under the receiver–operator curve was 0.75 (95% CI, 0.69 to 0.81). After internal validation by bootstrap, the area under the receiver–operator curve was 0.73 (95% CI, 0.68 to 0.79). Extubation success was significantly associated with shorter duration of mechanical ventilation (11 [95% CI, 5 to 17 days] vs. 22 days [95% CI, 13 to 29 days]; P < 0.0001), shorter intensive care unit length of stay (15 [95% CI, 9 to 23 days] vs. 27 days [95% CI, 21 to 36 days]; P < 0.0001), and lower in-intensive care unit mortality (4 [1.2%] vs. 11 [11.1%]; P < 0.0001).

Conclusions

Our score exploring both airway functions and neurologic status may increase the probability of successful extubation in patients with severe brain injury.
Hydrogen Peroxide Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors
Authors: Sugiyama Daisuke , Kang Sinyoung , Arpey Nicholas , Arunakul Preeyaphan , Usachev Yuriy M. , Brennan Timothy J.
Published: June 2017

Background

H2O2 has a variety of actions in skin wounds but has been rarely studied in deep muscle tissue. Based on response to the transient receptor potential ankyrin 1 antagonists after plantar incision, we hypothesized that H2O2 exerts nociceptive effects via the transient receptor potential ankyrin 1 in muscle.

Methods

Nociceptive behaviors in rats (n = 269) and mice (n = 16) were evaluated after various concentrations and volumes of H2O2 were injected into the gastrocnemius muscle or subcutaneous tissue. The effects of H2O2 on in vivo spinal dorsal horn neuronal activity and lumbar dorsal root ganglia neurons in vitro were evaluated from 26 rats and 6 mice.

Results

Intramuscular (mean ± SD: 1,436 ± 513 s) but not subcutaneous (40 ± 58 s) injection of H2O2 (100 mM, 0.6 ml) increased nociceptive time. Conditioned place aversion was evident after intramuscular (–143 ± 81 s) but not subcutaneous (–2 ± 111 s) injection of H2O2. These H2O2-induced behaviors were blocked by transient receptor potential ankyrin 1 antagonists. Intramuscular injection of H2O2 caused sustained in vivo activity of dorsal horn neurons, and H2O2 activated a subset of dorsal root ganglia neurons in vitro. Capsaicin nerve block decreased guarding after plantar incision and reduced nociceptive time after intramuscular H2O2. Nociceptive time after intramuscular H2O2 in transient receptor potential ankyrin 1 knockout mice was shorter (173 ± 156 s) compared with wild-type mice (931 ± 629 s).

Conclusions

The greater response of muscle tissue to H2O2 may help explain why incision that includes deep muscle but not skin incision alone produces spontaneous activity in nociceptive pathways.
PREDICTORS OF ONE-YEAR VISUAL OUTCOMES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Kodjikian Laurent , Decullier Evelyne , Souied Eric H. , Roux Adeline , Aulagner Gilles , Huot Laure ,   for the GEFAL Study Group
Published: June 2017

Purpose:

To determine predictors of best-corrected visual acuity (BCVA) outcomes 1 year after ranibizumab or bevacizumab treatment for neovascular age-related macular degeneration, within the French Study Group Avastin versus Lucentis for neovascular age-related macular degeneration (GEFAL).

Methods:

Patients aged ≥50 years presenting subfoveal neovascular age-related macular degeneration were randomized to receive ranibizumab or bevacizumab (3 monthly intravitreal injections followed by an as-needed regimen). The main outcome measures were BCVA and its change from baseline at 1 year. Variables with a P value <0.20 in the univariate model and/or which were clinically relevant were included in the multivariate analysis.

Results:

The following baseline factors were associated with a lower BCVA score at 1 year and with less improvement in BCVA (multivariate analysis): intraretinal fluid, thickness of central subfield macular ≤277 μm, predominantly classic choroidal neovascularization, and total area of choroidal neovascularization (all P ≤ 0.01). Pigment epithelium detachment and high baseline BCVA were associated with less improvement in BCVA (P = 0.03, P = 0.05, respectively). Patients who met retreatment criteria but did not receive the corresponding injection had significantly poorer outcomes (only tested in the univariate analysis).

Conclusion:

This study confirms the predictors of BCVA score at 1 year posttreatment; the presence of intraretinal fluid was associated with a poor prognosis.
TEMPORAL THINNING IN SICKLE CELL RETINOPATHY IS ASSOCIATED WITH DIMINISHED PERFUSION ON OCTA AND DENSE SCOTOMA ON MICROPERIMETERY
Authors: Sambhav Kumar , Grover Sandeep , Chalam Kakarla V.
Published: June 2017

Purpose:

To establish correlation between the structural compromise (capillary loss and hypoperfusion on optical coherence tomography [optical coherence tomography angiography]) with perimacular functional impairment noted on microperimetry.

Methods:

Retrospective case series. Clinical records and multimodal imaging findings of patients presenting with sickle cell disease were reviewed.

Results:

Three eyes of three patients (two men) were included in the study with a visual acuity of 20/20 and no sickle cell retinopathy. Images using optical coherence tomography angiography (AngioVue OCT angiography system; Optovue, Inc, Fremont, CA) were obtained along with spectral domain optical coherence tomography, fluorescein angiography, and microperimetry (MP-1). Spectral domain optical coherence tomography revealed selective loss of inner retinal layers with thinning of the retina. Optical coherence tomography angiography revealed compromise of both superficial and deep capillaries in the area of temporal thinning expressed on spectral domain optical coherence tomography. MP-1 demonstrated focal increase in threshold (decreased sensitivity) correlating with the perfusion defects on optical coherence tomography angiography. Fluorescein angiography did not show any substantial perfusion compromise.

Conclusion:

Optical coherence tomography angiography may reflect the extent of functional compromise even before it being evident on fluorescein angiography. The area vascular compromise was larger in the deep plexus compared with the superficial plexus. The area of complete loss of retinal sensitivity corresponds to loss of vasculature in both the superficial and deep plexuses, whereas the area of decreased sensitivities corresponds to compromise only in the deep plexus.
Is a time symmetric interpretation of quantum theory possible without retrocausality?
Authors: Leifer Matthew S. , Pusey Matthew F.
Published: June 2017

Huw Price has proposed an argument that suggests a time symmetric ontology for quantum theory must necessarily be retrocausal, i.e. it must involve influences that travel backwards in time. One of Price's assumptions is that the quantum state is a state of reality. However, one of the reasons for exploring retrocausality is that it offers the potential for evading the consequences of no-go theorems, including recent proofs of the reality of the quantum state. Here, we show that this assumption can be replaced by a different assumption, called
λ
-mediation, that plausibly holds independently of the status of the quantum state. We also reformulate the other assumptions behind the argument to place them in a more general framework and pin down the notion of time symmetry involved more precisely. We show that our assumptions imply a timelike analogue of Bell's local causality criterion and, in doing so, give a new interpretation of timelike violations of Bell inequalities. Namely, they show the impossibility of a (non-retrocausal) time symmetric ontology.
Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution
Authors: Warnock Rachel C. M. , Yang Ziheng , Donoghue Philip C. J.
Published: June 2017

Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions.
Acute peaks of testosterone suppress paternal care: evidence from individual hormonal reaction norms
Authors: Goymann Wolfgang , Flores Dávila Pamela
Published: June 2017

A long-standing tenet of evolutionary endocrinology states that testosterone mediates the life-history trade-off between mating and paternal care. However, the support for a role of testosterone in suppressing paternal care is mixed: implantation studies in birds suggest that high-level testosterone implants suppress paternal care, but circulating levels of testosterone and paternal care are typically not correlated. Because any trade-off in real life must be realized with hormone levels that are within an individual's reaction norm, it is crucial to show that natural changes in the hormone can modulate behaviour. Here, we used GnRH-injections to alter testosterone levels of free-living male black redstarts within each individual's hormonal reaction norm: individuals experiencing a short-term peak in testosterone resumed feeding their offspring later and showed a stronger suppression of offspring-feeding behaviour than control males. For the first time, this study demonstrated that short-term peaks in testosterone within the hormonal reaction norm of individuals can suppress paternal behaviour. Our findings reconcile previous seemingly contradictive effects that testosterone implants had on paternal care and the absence of correlations between circulating testosterone levels and paternal care, and demonstrate that the differential production of testosterone within the hormonal reaction norm of single individuals can indeed function as a mechanism to mediate a potential trade-off between mating and parenting. On a broader note, our results suggest that natural and short peaks in testosterone can elicit adaptive behavioural changes.
Seeds integrate biological information about conspecific and allospecific neighbours
Authors: Yamawo Akira , Mukai Hiromi
Published: June 2017

Numerous organisms integrate information from multiple sources and express adaptive behaviours, but how they do so at different developmental stages remains to be identified. Seeds, which are the embryonic stage of plants, need to make decisions about the timing of emergence in response to environmental cues related to survival. We investigated the timing of emergence of
Plantago asiatica
(Plantaginaceae) seed while manipulating the presence of
Trifolium repens
seed and the relatedness of neighbouring
P. asiatica
seed. The relatedness of neighbouring
P. asiatica
seed and the presence of seeds of
T. repens
did not on their own influence the timing of
P. asiatica
emergence. However, when encountering a
T. repens
seed, a
P. asiatica
seed emerged faster in the presence of a sibling seed than in the presence of a non-sibling seed. Water extracts of seeds gave the same result. We show that
P. asiatica
seeds integrate information about the relatedness of neighbouring
P. asiatica
seeds and the presence of seeds of a different species via water-soluble chemicals and adjust their emergence behaviour in response. These findings suggest the presence of kin-dependent interspecific interactions.
Breaking out of the comfort zone: El Niño-Southern Oscillation as a driver of trophic flows in a benthic consumer of the Humboldt Current ecosystem
Authors: Riascos José M. , Solís Marco A. , Pacheco Aldo S. , Ballesteros Manuel
Published: June 2017

The trophic flow of a species is considered a characteristic trait reflecting its trophic position and function in the ecosystem and its interaction with the environment. However, climate patterns are changing and we ignore how patterns of trophic flow are being affected. In the Humboldt Current ecosystem, arguably one of the most productive marine systems, El Niño-Southern Oscillation is the main source of interannual and longer-term variability. To assess the effect of this variability on trophic flow we built a 16-year series of mass-specific somatic production rate (P/B) of the Peruvian scallop (
Argopecten purpuratus
), a species belonging to a former tropical fauna that thrived in this cold ecosystem. A strong increase of the P/B ratio of this species was observed during nutrient-poor, warmer water conditions typical of El Niño, owing to the massive recruitment of fast-growing juvenile scallops. Trophic ecology theory predicts that when primary production is nutrient limited, the trophic flow of organisms occupying low trophic levels should be constrained (bottom-up control). For former tropical fauna thriving in cold, productive upwelling coastal zones, a short time of low food conditions but warm waters during El Niño could be sufficient to waken their ancestral biological features and display massive proliferations.
Hierarchical complexity and the size limits of life
Authors: Heim Noel A. , Payne Jonathan L. , Finnegan Seth , Knope Matthew L. , Kowalewski Michał , Lyons S. Kathleen , McShea Daniel W. , Novack-Gottshall Philip M. , Smith Felisa A. , Wang Steve C.
Published: June 2017

Over the past 3.8 billion years, the maximum size of life has increased by approximately 18 orders of magnitude. Much of this increase is associated with two major evolutionary innovations: the evolution of eukaryotes from prokaryotic cells approximately 1.9 billion years ago (Ga), and multicellular life diversifying from unicellular ancestors approximately 0.6 Ga. However, the quantitative relationship between organismal size and structural complexity remains poorly documented. We assessed this relationship using a comprehensive dataset that includes organismal size and level of biological complexity for 11 172 extant genera. We find that the distributions of sizes within complexity levels are unimodal, whereas the aggregate distribution is multimodal. Moreover, both the mean size and the range of size occupied increases with each additional level of complexity. Increases in size range are non-symmetric: the maximum organismal size increases more than the minimum. The majority of the observed increase in organismal size over the history of life on the Earth is accounted for by two discrete jumps in complexity rather than evolutionary trends within levels of complexity. Our results provide quantitative support for an evolutionary expansion away from a minimal size constraint and suggest a fundamental rescaling of the constraints on minimal and maximal size as biological complexity increases.
A urine-dependent human urothelial organoid offers a promising alternative to rodent models of infection
Authors: Horsley Harry , Dharmasena Dhanuson , Malone-Lee James , Rohn Jennifer L.
Published: June 2017

Murine models describe a defined host/pathogen interaction for urinary tract infection, but human cell studies are scant. Although recent human urothelial organoid models are promising, none demonstrate long-term tolerance to urine, the natural substrate of the tissue and of the uropathogens that live there. We developed a novel human organoid from progenitor cells which demonstrates key structural hallmarks and biomarkers of the urothelium. After three weeks of transwell culture with 100% urine at the apical interface, the organoid stratified into multiple layers. The apical surface differentiated into enlarged and flattened umbrella-like cells bearing characteristic tight junctions, structures resembling asymmetric unit membrane plaques, and a glycosaminoglycan layer. The apical cells also expressed apical cytokeratin-20, a spatial feature of the mammalian urothelium. Urine itself was necessary for full development, and undifferentiated cells were urine-tolerant despite the lack of membrane plaques and a glycosaminoglycan layer. Infection withEnterococcus faecalisrevealed the expected invasive outcome, including urothelial sloughing and the formation of intracellular colonies similar to those previously observed in patient cells. This new biomimetic model could help illuminate invasive behaviours of uropathogens, and serve as a reproducible test bed for disease formation, treatment and resolution in patients.
Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer
Authors: Wittkowski Knut M. , Dadurian Christina , Seybold Martin P. , Kim Han Sang , Hoshino Ayuko , Lyden David
Published: June 2017

Most breast cancer deaths are caused by metastasis and treatment options beyond radiation and cytotoxic drugs, which have severe side effects, and hormonal treatments, which are or become ineffective for many patients, are urgently needed. This study reanalyzed existing data from three genome-wide association studies (GWAS) using a novel computational biostatistics approach (muGWAS), which had been validated in studies of 600–2000 subjects in epilepsy and autism. MuGWAS jointly analyzes several neighboring single nucleotide polymorphisms while incorporating knowledge about genetics of heritable diseases into the statistical method and about GWAS into the rules for determining adaptive genome-wide significance.

Results from three independent GWAS of 1000–2000 subjects each, which were made available under the National Institute of Health’s “Up For A Challenge” (U4C) project, not only confirmed cell-cycle control and receptor/AKT signaling, but, for the first time in breast cancer GWAS, also consistently identified many genes involved in endo-/exocytosis (EEC), most of which had already been observed in functional and expression studies of breast cancer. In particular, the findings include genes that translocate (ATP8A1, ATP8B1, ANO4, ABCA1) and metabolize (AGPAT3, AGPAT4, DGKQ, LPPR1) phospholipids entering the phosphatidylinositol cycle, which controls EEC. These novel findings suggest scavenging phospholipids via alpha-cyclodextrins (αCD) as a novel intervention to control local spread of cancer, packaging of exosomes (which prepare distant microenvironment for organ-specific metastases), and endocytosis of β1 integrins (which are required for spread of metastatic phenotype and mesenchymal migration of tumor cells).

Beta-cyclodextrins (βCD) have already been shown to be effective inin vitroand animal studies of breast cancer, but exhibits cholesterol-related ototoxicity. The smaller αCDs also scavenges phospholipids, but cannot fit cholesterol. Anin-vitrostudy presented here confirms hydroxypropyl (HP)-αCD to be twice as effective as HPβCD against migration of human cells of both receptor negative and estrogen-receptor positive breast cancer.

If the previous successful animal studies with βCDs are replicated with the safer and more effective αCDs, clinical trials of adjuvant treatment with αCDs are warranted. Ultimately, all breast cancer are expected to benefit from treatment with HPαCD, but women with triplenegative breast cancer (TNBC) will benefit most, because they have fewer treatment options and their cancer advances more aggressively.
MicroED Structures from Micrometer Thick Protein Crystals
Authors: Martynowycz Michael W. , Glynn Calina , Miao Jennifer , Jason de la Cruz M. , Hattne Johan , Shi Dan , Cascio Duilio , Rodriguez Jose , Gonen Tamir
Published: June 2017

Theoretical calculations suggest that crystals exceeding 100 nm thickness are excluded by dynamical scattering from successful structure determination using microcrystal electron diffraction (MicroED). These calculations are at odds with experimental results where MicroED structures have been determined from significantly thicker crystals. Here we systematically evaluate the influence of thickness on the accuracy of MicroED intensities and the ability to determine structures from protein crystals one micrometer thick. To do so, we compareab initiostructures of a human prion protein segment determined from thin crystals to those determined from crystals up to one micrometer thick. We also compare molecular replacement solutions from crystals of varying thickness for a larger globular protein, proteinase K. Our results indicate that structures can be reliably determined from crystals at least an order of magnitude thicker than previously suggested by simulation, opening the possibility for an even broader range of MicroED experiments.

Atomic resolution protein structures can be determined by MicroED from crystals that surpass the theoretical maximum thickness limit by an order of magnitude.
Gelsolin regulates proliferation, apoptosis and invasion in NK/T-cell lymphoma cells through the PI3K/Akt signaling pathway
Authors: Guo Yanwei , Zhang Hongqiao , Xing Xin , Wang Lijuan , Zhang Jian , Yan Lin , Zheng Xiaoke , Zhang Mingzhi
Published: June 2017

The expression of gelsolin (GSN) is abnormal in many cancers, including extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). However, the biological function of GSN and its mechanism in NKTCL remain unclear. We found GSN overexpression significantly suppressed cell proliferation, colony formationand invasion and promoted apoptosis of YTS cells. Moreover, the upregulation of GSN significantly decreased the protein levels of PI3K and p-AKT. Interestingly, blocking the PI3K/AKT signaling pathway significantly inhibited cell proliferation and invasion and promoted apoptosis of YTS cells. In conclusion, our findings indicate that GSN can suppress cell proliferation and invasion and promote apoptosis of YTS cells, which is likely to be mediated at least partially through inhibition of the PI3K/AKT signaling pathway.
Lis1 has two opposing modes of regulating cytoplasmic dynein
Authors: DeSantis Morgan E. , Cianfrocco Michael A. , Htet Zaw Min , Tran Phuoc Tien , Reck-Peterson Samara L. , Leschziner Andres E.
Published: June 2017

Regulation is central to the functional versatility of cytoplasmic dynein, a motor involved in intracellular transport, cell division, and neurodevelopment. Previous work established that Lis1, a conserved and ubiquitous regulator of dynein, binds to its motor domain and induces a tight microtubule-binding state in dynein. The work we present here—a combination of biochemistry, single-molecule assays, cryo-electron microscopy and in vivo experiments—led to the surprising discovery that Lis1 has two opposing modes of regulating dynein, being capable of inducing both low and high affinity for the microtubule. We show that these opposing modes depend on the stoichiometry of Lis1 binding to dynein and that this stoichiometry is regulated by the nucleotide state of dynein’s AAA3 domain. We present data on the in vitro and in vivo consequences of abolishing the novel Lis1-induced weak microtubule-binding state in dynein and propose a new model for the regulation of dynein by Lis1.
Spontaneous Phase Separation of Cocultured Cell MixturesIn vitro
Authors: Hadjiantoniou Sebastian V. , Leblanc-Latour Maxime , Ignacio Maxime , Lefevbre Cory S. , Slater Gary W. , Pelling Andrew E.
Published: June 2017

During Embryogenesis, cells undergo constant organizational remodelling. Biochemical and biophysical guidance cues act in tandem to guide migration and morphogenesis into distinct cellular patterns. It has been shown that various cell types will express different configurations of cellular adhesion molecules known as cadherins and integrins. Coculturedin vitroexperiments have focused on revealing the extensive genetic expression profiles that modulate embryogenesis whilst overlooking the physical cell-cell and cell-substrate interactions that influence organization. We demonstrate that NIH3T3 and MDCK cells undergo a spontaneous phase separation when coculturedin vitroand that this phenomenon occurs through purely physical binding energies. A Monte Carlo simulation model of a mixture of cells with different cell-cell and cell-substrate binding energies reveals that the spontaneous phase separation occurs due to the minimization of interfacial free energy within the system. Cell-cell and cell-substrate binding plays a critical role in cell organization and is capable of phase separating different populations of cells in vitro.
Assembly ofFrancisella novicidaCpf1 endonuclease in complex with guide RNA and target DNA
Authors: Alcón Pablo , Montoya Guillermo , Stella Stefano
Published: June 2017

Bacteria and archaea use the CRISPR–Cas system as an adaptive response against infection by foreign nucleic acids. Owing to its remarkable flexibility, this mechanism has been harnessed and adopted as a powerful tool for genome editing. The CRISPR–Cas system includes two classes that are subdivided into six types and 19 subtypes according to conservation of thecasgene and loci organization. Recently, a new protein with endonuclease activity belonging to class 2 type V has been identified. This endonuclease, termed Cpf1, in complex with a single CRISPR RNA (crRNA) is able to recognize and cleave a target DNA preceded by a 5′-TTN-3′ protospacer-adjacent motif (PAM) complementary to the RNA guide. To obtain structural insight into the inner workings of Cpf1, the crystallization of an active complex containing the full extent of the crRNA and a 31-nucleotide dsDNA target was attempted. The gene encoding Cpf1 fromFrancisella novicidawas cloned, overexpressed and purified. The crRNA was transcribed and purifiedin vitro. Finally, the ternary FnCpf1–crRNA–DNA complex was assembled and purified by preparative electrophoresis before crystallization. Crystals belonging to space groupC2221, with unit-cell parametersa= 85.2,b= 137.6,c= 320.5 Å, were obtained and subjected to preliminary diffraction experiments.
Structure of bovine cytochromecoxidase crystallized at a neutral pH using a fluorinated detergent
Authors: Luo Fangjia , Shinzawa-Itoh Kyoko , Hagimoto Kaede , Shimada Atsuhiro , Shimada Satoru , Yamashita Eiki , Yoshikawa Shinya , Tsukihara Tomitake
Published: June 2017

Cytochromecoxidase (CcO) couples proton pumping to O2reduction. Its enzymatic activity depends sensitively on pH over a wide range. However, owing to difficulty in crystallizing this protein, X-ray structure analyses of bovine CcO aimed at understanding its reaction mechanism have been conducted using crystals prepared at pH 5.7, which is significantly lower than that in the cell. Here, oxidized CcO at pH 7.3 was crystallized using a fluorinated octyl-maltoside derivative, and the structure was determined at 1.77 Å resolution. No structural differences between crystals obtained at the neutral pH and the acidic pH were detected within the molecules. On the other hand, some differences in intermolecular interactions were detected between the two types of crystal. The influence of pH on the molecular surface is likely to contribute to the pH dependency of the aerobic oxidation of ferrocytochromec.
Corporate governance model in Thai state-owned enterprises: structural equation modelling approach
Authors: Khongmalai Orapan , Distanont Anyanitha
Published: June 2017

Purpose

Corporate governance (CG) is a mechanism for directing, administering and controlling organisations. CG has become a vital component in driving efficient operation of state-owned enterprises (SOEs). The purpose of this paper is to examine the relationship between CG practices and the performance of Thai SOEs.

Design/methodology/approach

This research is quantitative in nature; data were collected through a questionnaire, which was distributed to a sample of 1,140 respondents from 38 Thai SOEs. Structural equation modelling was used for data analysis.

Findings

The results indicate that the board of directors has a direct negative influence on the performance of Thai SOEs. However, management systems play a significant role in mediating the relationship between boards of directors and the performance of Thai SOEs. Additionally, corporate governance practices should be implemented not only at the board-of-director level but also at all levels of operation throughout the organisation.

Practical implications

To develop effective boards of directors, SOEs should be pushed to develop the appropriate strategic management systems (i.e. risk management, internal controls, internal audits, human resource management and information technology). These systems allow boards of directors to access and use important information that will help guide the business process, which leads to performance improvement in SOEs.

Originality/value

This empirical study investigates the relationships between CG practices and the performance of SOEs in the context of developing countries.
Factors affecting the audit process and social theories
Authors: Mahdavi Gholamhossein , Daryaei Abbas Ali
Published: June 2017

Purpose

The purpose of this paper is to apply the concept of social theories to explain auditors’ attitude toward balance time between marketing activities and auditing responsibilities.

Design/methodology/approach

Data were collected through a survey, from which a measure of auditor’s view on the importance of marketing was identified and regressed against balance between audit time and marketing activities. In addition, a measure of balanced attitude of auditors toward the time of the audit and marketing activities was identified and regressed against attitude toward the importance of corporate governance mechanisms.

Findings

The results obtained from the hypothesis test indicated that the audit fee can be a decisive factor in the status of auditors to carry out their function in the social structure which is limited to the stakeholders. The balance time between auditing and marketing is of the same importance to all auditors. Furthermore, entrepreneur auditors find the present corporate governance good for the prosperity and creativity of the forces within the auditing firms. As a result, entrepreneur auditors are very effective in corporate governance mechanisms.

Originality/value

The most significant contribution of the present study is the development of auditing literature to better understand and analyze the behavior of auditors.
In search of sustainable legitimacy of private firms in China
Authors: Liang Xin , Xiu Lin , Wu Sibin , Zhang Shujuan
Published: June 2017

Purpose

Private firms in China are like the third child in a family, constantly struggling to establish their position in an environment favoring their state-owned and collective siblings. The purpose of this paper is to discover some long-term-oriented legitimacy building strategies for private firms in China.

Design/methodology/approach

This paper examines the effect of both internal and external institutional factors on long-term legitimacy for private enterprises. The authors integrate stakeholder perspective and institutional theory to provide a framework of building sustainable legitimacy.

Findings

The authors’ framework delineates that a private company can build sustainable legitimacy through catering long-term legitimacy conferring to constituents such as customers, social responsibility and patriotism in the external institutional environment.

Practical implications

The authors’ framework further indicates how private firms could leverage internal institutional environment through developing appropriate mission, culture, leadership and human resources practices in conformity to the demands of constituents for gaining long-term legitimacy.

Originality/value

This paper is the first to address the short-term nature of legitimacy building strategies proposed in the past literature. In addition, it is also the first attempt to explore the multiplicity in legitimacy in China in search of long-term legitimacy building approaches.
Optimization of the reefed parachute using genetic algorithm
Authors: Yang Xue , Yu Li , Zhao Xiao-Shun
Published: June 2017

Purpose

The purpose of this paper is to find optimal reef parameters to minimize the maximum instantaneous opening load for a reefed parachute with geometry and environmental parameters given in the model.

Design/methodology/approach

The dynamic model Drop Test Vehicle Simulation (DTVSim) is used to model the inflation and descent of the reefed parachute system. It is solved by the fourth-order Runge–Kutta method, and the opening load values are thereby obtained. A parallel genetic algorithm (GA) code is developed to optimize the reefed parachute. A penalty scheme is used to have the maximum dynamic pressure restricted within a certain range.

Findings

The simulation results from DTVSim fit well with experimental data from drop tests, showing that the simulator has high accuracy. The one-stage and two-stage reefed parachute systems are optimized by GA and their maximum opening loads are decreased by 43 and 25 per cent, respectively. With the optimal reef parameters, two of the peaks in the opening load curve are almost equal. The velocity, loiter time and flight path angle of the parachute system all change, but these changes have no negative effect on the parachute’s operational performance.

Originality/value

An optimization method for reefed parachute design is proposed for the first time. This methodology can be used in the preliminary design phase for a reefed parachute system and significantly improve design efficiency.