bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of free access to swimming pools on children’s participation in swimming. A comparative regression discontinuity study
Authors: Higgerson J , Halliday E , Ortiz-Nunez A , Barr B
Published: April 2018

Objective

Investigating the extent to which providing children with free swimming access during school holidays increased participation in swimming and whether this effect differed according to the socioeconomic deprivation of the neighbourhoods in which children lived.

Setting

A highly disadvantaged local authority (LA) in North West England.

Intervention

Provision of children with free swimming during the summer holidays.

Outcome measures

Number of children swimming, and the number of swims, per 100 population in 2014.

Design

Comparative regression discontinuity investigating the extent to which participation rates amongst children aged 5–15 were greater in the intervention LA compared to a similar control LA. We estimated the differential effect of the intervention across five groups, defined by quintiles of area deprivation.

Results

Free swimming during the summer holidays was associated with an additional 6% of children swimming (95% CI: 4–9%) and an additional 33 swims per 100 children per year (95% CI: 21–44). The effects were greatest in areas with intermediate levels of deprivation (quintiles 3 and 4) within this deprived LA.

Conclusion

Providing free facilities for children in disadvantaged areas is likely to increase swimming participation and may help reduce inequalities in physical activity.
Molecular Characterization and Identification of Stubby Root Nematode Species From Multiple States in the United States
Authors: Huang Danqiong , Yan Guiping , Gudmestad Neil , Whitworth Jonathan , Frost Kenneth , Brown Charles , Ye Weimin , Agudelo Paula , Crow William
Published: April 2018

Stubby root nematodes (SRN) are important plant parasites infecting many crops and widely distributed in many regions of the United States. SRN transmit Tobacco rattle virus, which causes potato corky ringspot disease, thereby having a significant economic impact on the potato industry. In 2015 to 2017, 184 soil samples and 16 nematode suspensions from North Dakota, Minnesota, Idaho, Oregon, Washington, South Carolina, North Carolina, and Florida were assayed for the presence of SRN. SRN were found in 106 soil samples with population densities of 10 to 320 SRN per 200 g of soil and in eight of the nematode suspensions. Sequencing of ribosomal DNA (rDNA) or species-specific polymerase chain reaction assays revealed the presence of four SRN species, including Paratrichodorus allius, P. minor, P. porosus, and Trichodorus obtusus. Accordingly, their rDNA sequences were characterized by analyzing D2-D3 of 28S rDNA, 18S rDNA, and internal transcribed spacer (ITS) rDNA obtained in this study and retrieved from GenBank. Both intra- and interspecies variations were higher in ITS rDNA than 18S rDNA and D2-D3 of 28S rDNA. Based on phylogenetic analysis, the four SRN species formed a monophyletic group, with P. allius more closely related to P. porosus than P. minor and T. obtusus. Indel variation of ITS2 rDNA was present in P. allius populations from the same geographic regions. This study documented the occurrence of SRN species across multiple states. The intra- and interspecies genetic diversity of rDNA in this study will provide more information for understanding the evolutionary relationships of SRN and will be valuable for future studies of SRN species identification and management.
Outcomes of Adoptive Cell Transfer With Tumor-infiltrating Lymphocytes for Metastatic Melanoma Patients With and Without Brain Metastases
Authors: Mehta Gautam U. , Malekzadeh Parisa , Shelton Thomas , White Donald E. , Butman John A. , Yang James C. , Kammula Udai S. , Goff Stephanie L. , Rosenberg Steven A. , Sherry Richard M.
Published: April 2018

Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous melanoma, the efficacy of this therapy for brain metastases is unclear. Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain metastases, were analyzed. Treatment consisted of preparative chemotherapy, autologous TIL infusion, and high-dose interleukin-2. Treatment outcomes, sites of initial tumor progression, and overall survival were analyzed. Among 144 total patients, 15 patients with treated and 18 patients with untreated brain metastases were identified. Intracranial objective responses (OR) occurred in 28% patients with untreated brain metastases. The systemic OR rates for patients with M1c disease without identified brain disease, treated brain disease, and untreated brain disease, and were 49%, 33% and 33%, respectively, of which 59%, 20% and 16% were durable at last follow-up. The site of untreated brain disease was the most likely site of initial tumor progression (61%) in patients with untreated brain metastases. Overall, we found that ACT with TIL can eliminate small melanoma brain metastases. However, following TIL therapy these patients frequently progress in the brain at a site of untreated brain disease. Patients with treated or untreated brain disease are less likely to achieve durable systemic ORs following TIL therapy compared with M1c disease and no history of brain disease. Melanoma brain metastases likely require local therapy despite the systemic effect of ACT.
Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma
Authors: Larbcharoensub Noppadol , Mahaprom Komkrit , Jiarpinitnun Chuleeporn , Trachu Narumol , Tubthong Nattha , Pattaranutaporn Poompis , Sirachainan Ekaphop , Ngamphaiboon Nuttapong
Published: April 2018

Objectives:

Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients.

Materials and Methods:

Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated.

Results:

A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival.

Conclusions:

Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored.
Downregulation of adenosine and adenosine A1 receptor contributes to neuropathic pain in resiniferatoxin neuropathy
Authors: Kan Hung-Wei , Chang Chin-Hong , Lin Chih-Lung , Lee Yi-Chen , Hsieh Sung-Tsang , Hsieh Yu-Lin
Published: April 2018

The neurochemical effects of adenosine signaling in small-fiber neuropathy leading to neuropathic pain are yet to be explored in a direct manner. This study examined this system at the level of ligand (through the ectonucleotidase activity of prostatic acid phosphatase [PAP]) and adenosine A1 receptors (A1Rs) in resiniferatoxin (RTX) neuropathy, a peripheral neurodegenerative disorder that specifically affects nociceptive nerves expressing transient receptor potential vanilloid type 1 (TRPV1). We conducted immunohistochemistry on dorsal root ganglion (DRG) neurons, high-performance liquid chromatography for functional assays, and pharmacological interventions to alter PAP and A1Rs in mice with RTX neuropathy. In DRG of RTX neuropathy, PAP(+) neurons were reduced compared with vehicle-treated mice (P = 0.002). Functionally, PAP ectonucleotidase activity was consequently reduced (ie, the content of adenosine in DRG, P = 0.012). PAP(+) neuronal density was correlated with the degree of mechanical allodynia, which was reversed by intrathecal (i.t.) lumbar puncture injection of recombinant PAP with a dose-dependent effect. Furthermore, A1Rs were downregulated (P = 0.002), and this downregulation was colocalized with the TRPV1 receptor (31.0% ± 2.8%). Mechanical allodynia was attenuated in a dose-dependent response by i.t. injection of the A1R ligand, adenosine; however, no analgesia was evident when an exogenous adenosine was blocked by A1R antagonist. This study demonstrated dual mechanisms of neuropathic pain in TRPV1-induced neuropathy, involving a reduced adenosine system at both the ligand (adenosine) and receptor (A1Rs) levels.
Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation
Authors: Omer Endashaw , Kedar Archana , Nagarajarao Harsha S. , Nikitina Yana , Vedanarayanan Vetta , Subramony Charu , Lahr Christopher J. , Abell Thomas L.
Published: April 2018

Background and Aims:

Cajal cells serve as the pacemaker cells of the gastrointestinal tract and regulates peristalsis. On the baisis of that fact, it has been hypothesized that a decrease in Cajal cells can lead to gastroparesis and other motility issues. Treatment with medications has a limited efficacy and most resort to gastric electrical stimulation (GES) devices for symptomatic relief. We believe that the number of Cajal cells present is directly proportional to symptomatic relief with GES.

Materials and Methods:

Twenty-three (white female) subjects were recruited from the gastric motility clinic University of Mississipi for this study with the criteria of drug refractory gastropersis. Symptoms were measured using Likert scale and gastric emptying times were measured pre-GES and post-GES. Serosal electrogram measurements were recorded during surgical placement of permanent electrical stimulator under various modes. Cajal cell count scoring via immunohistochemistry were performed during the implantaion of the GES.

Results:

The data were grouped in 2 categories based on the Cajal cells that is ≥2.00 and <2.00. Subjects with higher Cajal cells reported a statiscially improvement in gastroperesis symptoms. Significant differences were also noted in the first hour gastric emptying study. The mean group difference is 17.5 (95% confidence interval, 1.41-33.58; P=0.035). Serosal amplitude differences were noted being significantly higher in the group with ≥2 cajal cells.

Conclusions:

Electrograms obtained after GES demonstrates immediate improvement in gastric electrical activity and gastroparesis symptoms in patients with relatively higher Cajal cell counts when compared with patients with extensive loss of Cajal cells.
Primary Mammary Analog Secretory Carcinoma (MASC) of the Vulva With ETV6-NTRK3 Fusion: A Case Report
Authors: Nguyen Jane K. , Bridge Julia A. , Joshi Chandrika , McKenney Jesse K.
Published: April 2018

Mammary analog secretory carcinoma is a primary salivary gland neoplasm with histologic, immunophenotypic, and molecular features identical to those of secretory carcinoma of the breast. Similar neoplasms have now been reported to occur in various nonmammary sites including the parotid gland, submandibular gland, sinuses, lip, skin, thyroid gland, and lung. We report, to our knowledge, the first example of a primary vulvar neoplasm with pathologic features identical to secretory carcinoma of the breast and anETV6-NTRK3fusion.
Developments in the Transition From Animal Use to Simulation-Based Biomedical Education
Authors: Pawlowski John B. , Feinstein David M. , Gala Shalin G.
Published: April 2018

Summary Statement

There has been a significant shift from the use of animals in biomedical training exercises toward simulation-based education methods. The transition has been driven by technological advances, empirical evidence of improved student outcomes, cost-effectiveness, and a growing concern for the welfare of animals. These factors have spurred policy changes worldwide in how medical and science curricula are delivered. We detail how some of these policy changes evolved and comment on the future direction of simulation-based education and its implications for healthcare providers, instructors, and the general public.
Surgical Telementoring Without Encumbrance
Authors: Rojas-Muñoz Edgar , Cabrera Maria Eugenia , Andersen Daniel , Popescu Voicu , Marley Sherri , Mullis Brian , Zarzaur Ben , Wachs Juan
Published: April 2018

Objective:

This study investigates the benefits of a surgical telementoring system based on an augmented reality head-mounted display (ARHMD) that overlays surgical instructions directly onto the surgeon's view of the operating field, without workspace obstruction.

Summary Background Data:

In conventional telestrator-based telementoring, the surgeon views annotations of the surgical field by shifting focus to a nearby monitor, which substantially increases cognitive load. As an alternative, tablets have been used between the surgeon and the patient to display instructions; however, tablets impose additional obstructions of surgeon's motions.

Methods:

Twenty medical students performed anatomical marking (Task1) and abdominal incision (Task2) on a patient simulator, in 1 of 2 telementoring conditions: ARHMD and telestrator. The dependent variables were placement error, number of focus shifts, and completion time. Furthermore, workspace efficiency was quantified as the number and duration of potential surgeon-tablet collisions avoided by the ARHMD.

Results:

The ARHMD condition yielded smaller placement errors (Task1: 45%, P < 0.001; Task2: 14%, P = 0.01), fewer focus shifts (Task1: 93%, P < 0.001; Task2: 88%, P = 0.0039), and longer completion times (Task1: 31%, P < 0.001; Task2: 24%, P = 0.013). Furthermore, the ARHMD avoided potential tablet collisions (4.8 for 3.2 seconds in Task1; 3.8 for 1.3 seconds in Task2).

Conclusion:

The ARHMD system promises to improve accuracy and to eliminate focus shifts in surgical telementoring. Because ARHMD participants were able to refine their execution of instructions, task completion time increased. Unlike a tablet system, the ARHMD does not require modifying natural motions to avoid collisions.
Association of Preoperative Anticholinergic Medication Exposure With Postoperative Healthcare Resource Use and Outcomes
Authors: McIsaac Daniel I. , Wong Coralie A. , Diep Deric , van Walraven Carl
Published: April 2018

Objective:

The aim of this study was to measure the association of preoperative anticholinergic exposure with length of stay (LOS) and other outcomes in older people having elective noncardiac surgery.

Summary Background Data:

Anticholinergic medications are associated with adverse events in nonsurgical populations; the association of anticholinergic medications with outcomes in elective surgery patients is poorly described.

Methods:

We conducted a retrospective, population-based cohort study using linked administrative data in Ontario, Canada. We identified all people >65 years old, from 2003 to 2014, having major, elective noncardiac surgery. Anticholinergic medication exposure was quantified using the Anticholinergic Risk Scale (ARS). Multilevel, multivariable modeling measured the adjusted association of ARS with LOS (primary outcome), institutional discharge, readmissions, costs, and survival (secondary outcomes).

Results:

Of 245,410 individuals, 71,569 had anticholinergic exposure (ARS 1–2, 15.6%; ARS ≥3, 13.6%). Median LOS was 5 days (interquartile range 3–7). Using proportional hazards analysis to model time to discharge, adjusting for in-hospital death as a competing risk, and surgical risk, demographic characteristics, and comorbidities, higher ARS scores were associated with longer LOS [smaller hazard ratios (HRs) mean longer LOS; ARS 1–2: adjusted HR 0.94, 95% confidence interval (CI), 0.93–0.95, P < 0.0001; ARS ≥3: adjusted HR 0.93, 95% CI, 0.91–0.95, P < 0.0001]. Similar associations were observed for all secondary outcomes.

Conclusions:

Increasing ARS scores were associated with increased LOS, decreased survival, higher rates of institutional discharge and readmission, and higher costs of care. Perioperative interventional research to reduce the anticholinergic exposure in older surgical patients is likely warranted.
Derivation and Validation of a Generalizable Preoperative Frailty Index Using Population-based Health Administrative Data
Authors: McIsaac Daniel I. , Wong Coralie A. , Huang Allen , Moloo Husein , van Walraven Carl
Published: April 2018

Objective:

To develop and validate a preoperative frailty index (pFI) for use in population-based health administrative (HA) data.

Summary Background Data:

Frailty is a robust predictor of adverse postoperative outcomes. Population-level frailty measures used in surgical studies have significant methodological limitations. Frailty indices (FIs) are a well-defined approach to measuring frailty with well-described methods for development and evaluation. An appropriate preoperative FI in HA data has not been derived or evaluated.

Methods:

Retrospective cohort study using linked HA data in Canada. We identified people >65 years (2002–2015) who had major elective or emergency surgery. Standardized methods were used to construct a 30-variable pFI. Unadjusted and multilevel, multivariable adjusted models were used to measure the association of the pFI with 1-year mortality and institutional discharge. Elective patients were the derivation cohort, emergency patients were the validation cohort. Prespecified sensitivity analyses were performed.

Results:

We identified 415,704 elective, and 95,581 emergency patients. The elective 1-year mortality rate was 4.7%. Thirty percent of population-level deaths occurred in people with frailty. Every 0.1-unit increase in the pFI was associated with a 2.20-fold increase in the adjusted odds of mortality (95% CI 2.15–2.26; c-statistic 0.81), and a 1.70-fold increase in institutional discharge (95% CI 1.59–1.80; c-statistic 0.71). pFI performance was similar in emergency patients, and was robust to changes in index composition.

Conclusions:

A preoperative FI derived from HA data is a robust method to measure frailty in elective and emergency patients. Generalizable FIs should be considered a standard approach to population-level study of surgical frailty.
Effects of Different Levels of Intra-Abdominal Pressure on the Postoperative Hepatic Function of Patients Undergoing Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis
Authors: Cheng Zheng-Jun , Wang Yun-Bing , Chen Long , Gong Jian-Ping , Zhang Wei
Published: April 2018

Objective:

The aim of this meta-analysis is to compare the differences in postoperative markers of the hepatic function under different intra-abdominal pressures in laparoscopic cholecystectomy (LC).

Methods:

Several databases were searched for control studies, and then the weighted data were pooled with random-effect models.

Results:

A total of 11 studies involving 865 patients were included. The meta-analysis reveals that the level of the aspartate aminotransferase and alanine transaminase of the low-pressure group has a lower postoperative increase than the moderate-pressure group (P<0.001). The level of the aspartate aminotransferase and alanine transaminase of the moderate-pressure group has a lower postoperative increase than the high-pressure group (P<0.001). Totally, the effect of lower pressure LC on postoperative hepatic functions is less significant than that of the higher one. Potential subgroup analysis does not modify these results.

Conclusions:

The recommended pressure in LC is suggested to be lower so as to result in a better surgical safety, especially for special populations.
Trans-generational immunization in the acrobat ant
Crematogaster scutellaris
Authors: Bordoni Adele , Dapporto Leonardo , Tatini Irene , Celli Martina , Bercigli Manuel , Ressurrección Barrufet Serena , Perito Brunella , Turillazzi Stefano
Published: April 2018

Trans-generational immunization is defined as the transmission of an enhanced resistance to a pathogen from parents to offspring. By using the host–parasite system of the ant
Crematogaster scutellaris
and the entomopathogenic fungus
Metarhizium anisopliae
, we describe this phenomenon for the first time in ants. We exposed four groups of hibernating queens to different treatments (i) a non-lethal dose of live conidiospores in Triton, (ii) a dose of heat-killed conidiospores in Triton, (iii) a control Triton solution, and (iv) a naive control. We exposed their first workers to a high dose of conidiospores and measured mortality rates
.
Workers produced by queens exposed to live conidiospores survived longer than those belonging to the other groups, while exposure to Triton and dead spores had no effect. Starved workers showed a significantly higher mortality. The treatments did not influence queen mortality, nor the number of offspring they produced at the emergence of the first worker, showing no evidence of immunization costs—at least for these parameters in the first year of colony development. We propose that trans-generational immunization represents an important component of social immunity that could affect colony success, particularly during the critical phase of claustral foundation.
Inheritance patterns of plumage coloration in common buzzards
Buteo buteo
do not support a one-locus two-allele model
Authors: Kappers Elena Frederika , de Vries Christiaan , Alberda Anneke , Forstmeier Wolfgang , Both Christiaan , Kempenaers Bart
Published: April 2018

Balancing selection is a major mechanism to maintain colour polymorphisms over evolutionary time. In common buzzards, variation in plumage colour was reportedly maintained by a heterozygote advantage: heterozygote intermediates had higher fitness than homozygote light and dark morphs. Here, we challenge one of the basic premises of the heterozygote advantage hypothesis, by testing whether plumage colour variation in common buzzards follows a one-locus two-allele inheritance model. Using a long-term population study with 202 families, we show that colour variation in buzzards is highly heritable. However, we find no support for a simple Mendelian one-locus two-allele model of inheritance. Our results rather suggest that buzzard plumage colour should be considered a quantitative polygenic trait. As a consequence, it is unlikely that the proposed heterozygote advantage is the mechanism that maintains this genetic variation. We hypothesize that plumage colour effects on fitness might depend on the environment, but this remains to be tested.
Life-history trade-offs: are they linked to personality in a precocial mammal (
Cavia aperea
)?
Authors: Guenther Anja
Published: April 2018

Life-history trade-offs are predicted to contribute to the maintenance of personality variation. Individuals with ‘fast’ lifestyles should develop faster, reproduce earlier and exhibit more risky behaviours. Evidence for such predicted links, however, remains equivocal. Here, I test how growth rate, timing of maturation, litter size and maternal effort correlate with exploration, boldness, fearlessness, docility and escape latency. I found several links that were predicted by recent theory while others were against theoretical predictions, e.g. fast-growing individuals were more fearful. Thus, while I found personality to be integrated with life history, I cannot fully support recent hypotheses aiming to explain such behaviour–life-history associations.
Heterogeneous ceramide distributions alter spatially resolved growth of
Staphylococcus aureus
on human stratum corneum
Authors: Cleary Joseph M. , Lipsky Zachary W. , Kim Minyoung , Marques Cláudia N. H. , German Guy K.
Published: April 2018

Contemporary studies have revealed dramatic changes in the diversity of bacterial microbiota between healthy and diseased skin. However, the prevailing use of swabs to extract the microorganisms has meant that only population ‘snapshots’ are obtained, and all spatially resolved information of bacterial growth is lost. Here we report on the temporospatial growth of
Staphylococcus aureus
on the surface of the human stratum corneum (SC); the outermost layer of skin. This bacterial species dominates bacterial populations on skin with atopic dermatitis (AD). We first establish that the distribution of ceramides naturally present in the SC is heterogeneous, and correlates with the tissue's structural topography. This distribution subsequently impacts the growth of bacterial biofilms. In the SC retaining healthy ceramide concentrations, biofilms exhibit no spatial preference for growth. By contrast, a depletion of ceramides consistent with reductions known to occur with AD enables
S. aureus
to use the patterned network of topographical canyons as a conduit for growth. The ability of ceramides to govern bacterial growth is confirmed using a topographical skin canyon analogue coated with the ceramide subcomponent
d
-sphingosine. Our work appears to explain the causal link between ceramide depletion and increased
S. aureus
populations that is observed in AD. It may also provide insight into disease transmission as well as improving pre-operative skin cleansing techniques.
Counteracting estimation bias and social influence to improve the wisdom of crowds
Authors: Kao Albert B. , Berdahl Andrew M. , Hartnett Andrew T. , Lutz Matthew J. , Bak-Coleman Joseph B. , Ioannou Christos C. , Giam Xingli , Couzin Iain D.
Published: April 2018

Aggregating multiple non-expert opinions into a collective estimate can improve accuracy across many contexts. However, two sources of error can diminish collective wisdom: individual estimation biases and information sharing between individuals. Here, we measure individual biases and social influence rules in multiple experiments involving hundreds of individuals performing a classic numerosity estimation task. We first investigate how existing aggregation methods, such as calculating the arithmetic mean or the median, are influenced by these sources of error. We show that the mean tends to overestimate, and the median underestimate, the true value for a wide range of numerosities. Quantifying estimation bias, and mapping individual bias to collective bias, allows us to develop and validate three new aggregation measures that effectively counter sources of collective estimation error. In addition, we present results from a further experiment that quantifies the social influence rules that individuals employ when incorporating personal estimates with social information. We show that the corrected mean is remarkably robust to social influence, retaining high accuracy in the presence or absence of social influence, across numerosities and across different methods for averaging social information. Using knowledge of estimation biases and social influence rules may therefore be an inexpensive and general strategy to improve the wisdom of crowds.
Single cardiac ventricular myosins are autonomous motors
Authors: Wang Yihua , Yuan Chen-Ching , Kazmierczak Katarzyna , Szczesna-Cordary Danuta , Burghardt Thomas P.
Published: April 2018

Myosin transduces ATP free energy into mechanical work in muscle. Cardiac muscle has dynamically wide-ranging power demands on the motor as the muscle changes modes in a heartbeat from relaxation, via auxotonic shortening, to isometric contraction. The cardiac power output modulation mechanism is explored
in vitro
by assessing single cardiac myosin step-size selection versus load. Transgenic mice express human ventricular essential light chain (ELC) in wild- type (WT), or hypertrophic cardiomyopathy-linked mutant forms, A57G or E143K, in a background of mouse α-cardiac myosin heavy chain. Ensemble motility and single myosin mechanical characteristics are consistent with an A57G that impairs ELC N-terminus actin binding and an E143K that impairs lever-arm stability, while both species down-shift average step-size with increasing load. Cardiac myosin
in vivo
down-shifts velocity/force ratio with increasing load by changed unitary step-size selections. Here, the loaded
in vitro
single myosin assay indicates quantitative complementarity with the
in vivo
mechanism. Both have two embedded regulatory transitions, one inhibiting ADP release and a second novel mechanism inhibiting actin detachment via strain on the actin-bound ELC N-terminus. Competing regulators filter unitary step-size selection to control force-velocity modulation without myosin integration into muscle. Cardiac myosin is muscle in a molecule.
Biofilm inhibition and pathogenicity attenuation in bacteria by
Proteus mirabilis
Authors: Yu Shichen , Zhu Xiaoshan , Zhou Jin , Cai Zhonghua
Published: April 2018

Biofilms play an important role in the antibiotic resistance of encased bacteria, and biofilm formation is regulated by quorum sensing (QS). Inhibiting the QS system may, therefore, degrade the integrity of a biofilm and expose the bacterial pathogens within it to the deleterious effects of molecules such as antibiotics. Moreover, the use of QS inhibitors (QSIs) may provide a novel approach for treating bacterial infections of aquacultures. In the present study, the bacterium
Proteus mirabilis
was identified as a potential producer of QSIs. Varying concentrations (0.1–1.1%) of filtrates prepared from the culture of
P. mirabilis
inhibited biofilm formation by the pathogens
Pseudomonas aeruginosa
,
Vibrio harveyi
and
Staphylococcus aureus
by as much as 58.9%, 41.5% and 41.9%, respectively. These filtrates as well as the crude aqueous extracts prepared from them increased the sensitivities of pathogens to the inhibitory effects of kanamycin. The filtrates also showed pathogenicity attenuation potential in
P. aeruginosa
by decreasing the production of virulence factors. Moreover, the filtrates did not influence the planktonic growth of these pathogens. The results indicate that
P. mirabilis
may act as a non-specific (or broad-spectrum) inhibitor of biofilm formation that will help control infectious diseases that adversely affect the aquaculture industry.
Poor neuro-motor tuning of the human larynx: a comparison of sung and whistled pitch imitation
Authors: Belyk Michel , Johnson Joseph F. , Kotz Sonja A.
Published: April 2018

Vocal imitation is a hallmark of human communication that underlies the capacity to learn to speak and sing. Even so, poor vocal imitation abilities are surprisingly common in the general population and even expert vocalists cannot match the precision of a musical instrument. Although humans have evolved a greater degree of control over the laryngeal muscles that govern voice production, this ability may be underdeveloped compared with control over the articulatory muscles, such as the tongue and lips, volitional control of which emerged earlier in primate evolution. Human participants imitated simple melodies by either singing (i.e. producing pitch with the larynx) or whistling (i.e. producing pitch with the lips and tongue). Sung notes were systematically biased towards each individual's habitual pitch, which we hypothesize may act to conserve muscular effort. Furthermore, while participants who sung more precisely also whistled more precisely, sung imitations were less precise than whistled imitations. The laryngeal muscles that control voice production are under less precise control than the oral muscles that are involved in whistling. This imprecision may be due to the relatively recent evolution of volitional laryngeal-motor control in humans, which may be tuned just well enough for the coarse modulation of vocal-pitch in speech.
Porous polymer coatings on metal microneedles for enhanced drug delivery
Authors: Ullah Asad , Kim Chul Min , Kim Gyu Man
Published: April 2018

We present a simple method to coat microneedles (MNs) uniformly with a porous polymer (PLGA) that can deliver drugs at high rates. Stainless steel (SS) MNs of high mechanical strength were coated with a thin porous polymer layer to enhance their delivery rates. Additionally, to improve the interfacial adhesion between the polymer and MNs, the MN surface was modified by plasma treatment followed by dip coating with polyethyleneimine, a polymer with repeating amine units. The average failure load (the minimum force sufficient for detaching the polymer layer from the surface of SS) recorded for the modified surface coating was 25 N, whereas it was 2.2 N for the non-modified surface. Calcein dye was successfully delivered into porcine skin to a depth of 750 µm by the porous polymer-coated MNs, demonstrating that the developed MNs can pierce skin easily without deformation of MNs; additional skin penetration tests confirmed this finding. For visual comparison, rhodamine B dye was delivered using porous-coated and non-coated MNs in gelatin gel which showed that delivery with porous-coated MNs penetrate deeper when compared with non-coated MNs. Finally, lidocaine and rhodamine B dye were delivered in phosphate-buffered saline (PBS) medium by porous polymer-coated and non-coated MNs. For rhodamine B, drug delivery with the porous-coated MNs was five times higher than that with the non-coated MNs, whereas 25 times more lidocaine was delivered by the porous-coated MNs compared with the non-coated MNs.
Membrane-assisted extraction of monoterpenes: from
in silico
solvent screening towards biotechnological process application
Authors: Janoschek L. , Grozdev L. , Berensmeier S.
Published: April 2018

This work focuses on the process development of membrane-assisted solvent extraction of hydrophobic compounds such as monoterpenes. Beginning with the choice of suitable solvents, quantum chemical calculations with the simulation tool COSMO-RS were carried out to predict the partition coefficient (log
P
) of (S)-(+)-carvone and terpinen-4-ol in various solvent–water systems and validated afterwards with experimental data. COSMO-RS results show good prediction accuracy for non-polar solvents such as n-hexane, ethyl acetate and n-heptane even in the presence of salts and glycerol in an aqueous medium. Based on the high log
P
value, n-heptane was chosen for the extraction of (S)-(+)-carvone in a lab-scale hollow-fibre membrane contactor. Two operation modes are investigated where experimental and theoretical mass transfer values, based on their related partition coefficients, were compared. In addition, the process is evaluated in terms of extraction efficiency and overall product recovery, and its biotechnological application potential is discussed. Our work demonstrates that the combination of
in silico
prediction by COSMO-RS with membrane-assisted extraction is a promising approach for the recovery of hydrophobic compounds from aqueous solutions.
The rise and fall of an ancient Adélie penguin ‘supercolony’ at Cape Adare, Antarctica
Authors: Emslie Steven D. , McKenzie Ashley , Patterson William P.
Published: April 2018

We report new discoveries and radiocarbon dates on active and abandoned Adélie penguin (
Pygoscelis adeliae
) colonies at Cape Adare, Antarctica. This colony, first established at approximately 2000 BP (calendar years before present, i.e. 1950), is currently the largest for this species with approximately 338 000 breeding pairs, most located on low-lying Ridley Beach. We hypothesize that this colony first formed after fast ice began blocking open-water access by breeding penguins to the Scott Coast in the southern Ross Sea during a cooling period also at approximately 2000 BP. Our results suggest that the new colony at Cape Adare continued to grow, expanding to a large upper terrace above Ridley Beach, until it exceeded approximately 500 000 breeding pairs (a ‘supercolony’) by approximately 1200 BP. The high marine productivity associated with the Ross Sea polynya and continental shelf break supported this growth, but the colony collapsed to its present size for unknown reasons after approximately 1200 BP. Ridley Beach will probably be abandoned in the near future due to rising sea level in this region. We predict that penguins will retreat to higher elevations at Cape Adare and that the Scott Coast will be reoccupied by breeding penguins as fast ice continues to dissipate earlier each summer, restoring open-water access to beaches there.
Nest size is predicted by female identity and the local environment in the blue tit (
Cyanistes caeruleus
), but is not related to the nest size of the genetic or foster mother
Authors: O'Neill Louis G. , Parker Timothy H. , Griffith Simon C.
Published: April 2018

The potential for animals to respond to changing climates has sparked interest in intraspecific variation in avian nest structure since this may influence nest microclimate and protect eggs and offspring from inclement weather. However, there have been relatively few large-scale attempts to examine variation in nests or the determinates of individual variation in nest structure within populations. Using a set of mostly pre-registered analyses, we studied potential predictors of variation in the size of a large sample (803) of blue tit (
Cyanistes caeruleus
) nests across three breeding seasons at Wytham Woods, UK. While our pre-registered analyses found that individual females built very similar nests across years, there was no evidence in follow-up (
post hoc
) analyses that their nest size correlated to that of their genetic mother or, in a cross-fostering experiment, to the nest where they were reared. In further pre-registered analyses, spatial environmental variability explained nest size variability at relatively broad spatial scales, and especially strongly at the scale of individual nest boxes. Our study indicates that nest structure is a characteristic of individuals, but is not strongly heritable, indicating that it will not respond rapidly to selection. Explaining the within-individual and within-location repeatability we observed requires further study.
Categorizing experience-based foraging plasticity in mites: age dependency, primacy effects and memory persistence
Authors: Schausberger Peter , Davaasambuu Undarmaa , Saussure Stéphanie , Christiansen Inga C.
Published: April 2018

Behavioural plasticity can be categorized into activational (also termed contextual) and developmental plasticity. Activational plasticity allows immediate contextual behavioural changes, whereas developmental plasticity is characterized by time-lagged changes based on memory of previous experiences (learning). Behavioural plasticity tends to decline with age but whether this holds true for both plasticity categories and the effects of first-in-life experiences is poorly understood. We tackled this issue by assessing the foraging plasticity of plant-inhabiting predatory mites,
Amblyseius swirskii
, on thrips and spider mites following age-dependent prey experience, i.e. after hatching or after reaching maturity. Juvenile and young adult predator females were alternately presented thrips and spider mites, for establishing 1st and 2nd prey-in-life experiences, and tested, as gravid females, for their foraging plasticity when offered both prey species. Prey experience by juvenile predators resulted in clear learning effects, which were evident in likelier and earlier attacks on familiar prey, and higher proportional inclusion of familiar prey in total diet. First prey-in-life experience by juvenile but not adult predators resulted in primacy effects regarding attack latency. Prey experience by adult predators resulted mainly in prey-unspecific physiological changes, with easy-to-grasp spider mites providing higher net energy gains than difficult-to-grasp thrips. Prey experience by juvenile, but not adult, predators was adaptive, which was evident in a negative correlation between attack latencies and egg production. Overall, our study provides key evidence that similar experiences by juvenile and adult predators, including first-in-life experiences, may be associated with different types of behavioural plasticity, i.e. developmental and activational plasticity.
A new large squalodelphinid (Cetacea, Odontoceti) from Peru sheds light on the Early Miocene platanistoid disparity and ecology
Authors: Bianucci Giovanni , Bosio Giulia , Malinverno Elisa , de Muizon Christian , Villa Igor M. , Urbina Mario , Lambert Olivier
Published: April 2018

The South Asian river dolphin (
Platanista gangetica
) is the only extant survivor of the large clade Platanistoidea, having a well-diversified fossil record from the Late Oligocene to the Middle Miocene. Based on a partial skeleton collected from the Chilcatay Formation (Chilcatay Fm; southern coast of Peru), we report here a new squalodelphinid genus and species,
Macrosqualodelphis ukupachai
. A volcanic ash layer, sampled near the fossil, yielded the
40
Ar/
39
Ar age of 18.78 ± 0.08 Ma (Burdigalian, Early Miocene). The phylogenetic analysis places
Macrosqualodelphis
as the earliest branching squalodelphinid. Combined with several cranial and dental features, the large body size (estimated body length of 3.5 m) of this odontocete suggests that it consumed larger prey than the other members of its family. Together with
Huaridelphis raimondii
and
Notocetus vanbenedeni
, both also found in the Chilcatay Fm, this new squalodelphinid further demonstrates the peculiar local diversity of the family along the southeastern Pacific coast, possibly related to their partition into different dietary niches. At a wider geographical scale, the morphological and ecological diversity of squalodelphinids confirms the major role played by platanistoids during the Early Miocene radiation of crown odontocetes.
Phylogeography of hydrothermal vent stalked barnacles: a new species fills a gap in the Indian Ocean ‘dispersal corridor’ hypothesis
Authors: Watanabe Hiromi Kayama , Chen Chong , Marie Daniel P. , Takai Ken , Fujikura Katsunori , Chan Benny K. K.
Published: April 2018

Phylogeography of animals provides clues to processes governing their evolution and diversification. The Indian Ocean has been hypothesized as a ‘dispersal corridor’ connecting hydrothermal vent fauna of Atlantic and Pacific oceans. Stalked barnacles of the family Eolepadidae are common associates of deep-sea vents in Southern, Pacific and Indian oceans, and the family is an ideal group for testing this hypothesis. Here, we describe
Neolepas marisindica
sp. nov. from the Indian Ocean, distinguished from
N. zevinae
and
N. rapanuii
by having a tridentoid mandible in which the second tooth lacks small elongated teeth. Morphological variations suggest that environmental differences result in phenotypic plasticity in the capitulum and scales on the peduncle in eolepadids. We suggest that diagnostic characters in Eolepadidae should be based mainly on more reliable arthropodal characters and DNA barcoding, while the plate arrangement should be used carefully with their intraspecific variation in mind. We show morphologically that
Neolepas
specimens collected from the South West Indian Ridge, the South East Indian Ridge and the Central Indian Ridge belong to the new species. Molecular phylogeny and fossil evidence indicated that
Neolepas
migrated from the southern Pacific to the Indian Ocean through the Southern Ocean, providing key evidence against the ‘dispersal corridor’ hypothesis. Exploration of the South East Indian Ridge is urgently required to understand vent biogeography in the Indian Ocean.
Machine learning methods for locating re-entrant drivers from electrograms in a model of atrial fibrillation
Authors: McGillivray Max Falkenberg , Cheng William , Peters Nicholas S. , Christensen Kim
Published: April 2018

Mapping resolution has recently been identified as a key limitation in successfully locating the drivers of atrial fibrillation (AF). Using a simple cellular automata model of AF, we demonstrate a method by which re-entrant drivers can be located quickly and accurately using a collection of indirect electrogram measurements. The method proposed employs simple, out-of-the-box machine learning algorithms to correlate characteristic electrogram gradients with the displacement of an electrogram recording from a re-entrant driver. Such a method is less sensitive to local fluctuations in electrical activity. As a result, the method successfully locates 95.4% of drivers in tissues containing a single driver, and 95.1% (92.6%) for the first (second) driver in tissues containing two drivers of AF. Additionally, we demonstrate how the technique can be applied to tissues with an arbitrary number of drivers. In its current form, the techniques presented are not refined enough for a clinical setting. However, the methods proposed offer a promising path for future investigations aimed at improving targeted ablation for AF.
A new archaic baleen whale
Toipahautea waitaki
(early Late Oligocene, New Zealand) and the origins of crown Mysticeti
Authors: Tsai Cheng-Hsiu , Fordyce R. Ewan
Published: April 2018

A new genus and species of extinct baleen whale
†
Toipahautea waitaki
(Late Oligocene, New Zealand) is based on a skull and associated bones, from the lower Kokoamu Greensand, about 27.5 Ma (local upper Whaingaroan Stage, early Chattian). The upper jaw includes a thin, elongate and apparently toothless maxilla, with evidence of arterial supply for baleen. Open sutures with the premaxilla suggest a flexible (kinetic) upper jaw. The blowhole is well forward. The mandible is bowed laterally and slightly dorsally; unlike the Eomysticetidae, there are no mandibular alveoli, and the coronoid process is tapered and curved laterally. Jaw structure is consistent with baleen-assisted gulp-feeding. The age of early Chattian makes
†
Toipahautea
a very early, if not the oldest named, toothless and baleen-bearing mysticete, suggesting that the full transition from toothed to baleen-bearing probably occurred in the Early Oligocene. Late Oligocene mysticetes vary considerably in jaw form and kinesis, tooth form and function, and development of baleen, implying a wide range of raptorial, suctorial and filter-feeding behaviour. More study may elucidate the function of jaws, teeth and baleen in terms of opportunist/generalist feeding, as in modern gray whales, versus specialized feeding. We here propose that early mysticetes, when transitioned from toothed to baleen-bearing, were generalists and opportunists instead of specializing in any forms of feeding strategies. In addition, two different phylogenetic analyses placed
†
Toipahautea
either in a polytomy including crown Mysticeti, or immediately basal to the crown, and above †Eomysticetidae in both cases. Because the
†
Toipahautea waitaki
holotype is an immature individual, it may plot more basally in phylogeny than its true position.