bluuebunny/crossref_metadata_2025 huggingface dataset:
Assisting Rapid Soft-Tissue Expansion with Adipose-Derived Stem Cells: An Experimental Study in a Pig Model
Authors: Wang Qianwen , Zhou Lu , Wang Tailing , Guo Xin , Yu Hao , Wang Jiaqi
Published: October 2018

Background:

Rapid tissue expansion has been attempted, aiming at shortening the period of conventional expansion. However, it has scarcely been clinically applied because of its drawbacks such as low expansion efficiency and tissue destruction. Adipose-derived stem cell transplantation is a promising therapeutic method in regenerative medicine. However, its effects on rapid expansion remain poorly understood.

Methods:

Twenty-four expanders were implanted in the dorsum of 12 pigs. Rapid expansion persisted for 1 week with 20 ml of saline daily. The increased area of the expanded skin was measured. Histologic and ultrastructural analysis and cell tracking were performed. The expression of vascular endothelial growth factor, fibroblast growth factor-2, and epidermal growth factor was also determined.

Results:

The increased area of adipose-derived stem cell–grafted expanded skin (0.91 ± 0.06 cm2) was significantly more than the non–adipose-derived stem cell–treated control (0.51 ± 0.05 cm2) (p < 0.01). Enhanced tissue regeneration in the adipose-derived stem cell–grafted expanded skin was evidenced by increased skin thickness, proliferating cells, extracellular matrix, and vascularization (113 ± 19/mm2 versus control 59 ± 14/mm2) (all p < 0.05). Higher expression of vascular endothelial growth factor and epidermal growth factor was observed in the adipose-derived stem cell–transplanted expanded skin (p < 0.01 and p < 0.05, respectively), whereas the expression of fibroblast growth factor-2 was higher in the non–adipose-derived stem cell–treated control (p < 0.05). Transmission electron microscopy showed that a high density of collagen fibers could be seen in the adipose-derived stem cell–treated expanded skin. Cell tracking showed that the positively stained cells could be seen.

Conclusion:

For rapid tissue expansion, adipose-derived stem cell transplantation may limit tissue destruction and improve the expansion efficiency by promoting tissue regeneration.
Brief Report: Age-Disparate Relationships and HIV Prevalence Among Never Married Women in Rakai, Uganda
Authors: Mwinnyaa George , Gray Ronald H. , Grabowski Mary K. , Ssekasanvu Joseph , Ndyanabo Anthony , Ssekubugu Robert , Kagaayi Joseph , Kigozi Godfrey , Nakigozi Gertrude , Serwadda David M. , Laeyendecker Oliver ,   on behalf of the Rakai Community Cohort Study
Published: October 2018

Background:

Age-disparate relationships are associated with increased HIV prevalence. We determined whether the frequency of age-disparate relationships in never married women changed over time and whether they are associated with HIV prevalence in Rakai, Uganda.

Methods:

A total of 10,061 never married women, aged 15–49 years, in the Rakai Community Cohort Study provided information on the age of their male sexual partners from 1997 to 2013. Logistic regression was used to assess trends in age-disparate relationships (≥5 years) between never married women and their male partners. Log-binomial regression was used to estimate adjusted prevalence ratios (adjPR) of HIV prevalence associated with age-disparate relationships.

Results:

Two thousand nine hundred ninety-nine women (30%) had a male partner ≥5 years older, which remained stable over time. The prevalence of HIV among women in age-disparate relationships was 14%, 10% for women in relationships with men 0–4 years older (adjPR 1.36, 95% confidence interval: 1.22 to 1.53) not controlling women's age; however, after age adjustment, the impact of age-disparate relationships on HIV prevalence was attenuated. Age-disparate relationships were associated with increased HIV prevalence among women aged 15–17 years (adjPR 1.83, 95% confidence interval: 1.10 to 3.17), but not in other age groups.

Conclusions:

The frequency of age-disparate relationships among never married women was unchanged over a 15-year period in Rakai, Uganda. Age-disparate relationships were associated with increased HIV prevalence among adolescents aged 15–17 years, but not older women.
Nasal Stenosis Treated With a Composite Skin Graft
Authors: Kim Seon Tae , Jung Joo Hyun , Woo Joo Hyun , Cha Heung Eog , Chang Jin Soon , Kang Il Gyu
Published: October 2018

A 58-year-old female patient was presented, who complained about breathing and aesthetic difficulties due to external nasal valve obstruction and nasal deformity that developed after nasal trauma surgery. Nasal stenosis recurs easily after surgery, especially if internal nasal stenosis is not adequately managed. Nasal stenosis in this case was well treated using a composite skin graft.
Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees
Authors: Dumanian Gregory A. , Potter Benjamin K. , Mioton Lauren M. , Ko Jason H. , Cheesborough Jennifer E. , Souza Jason M. , Ertl William J. , Tintle Scott M. , Nanos George P. , Valerio Ian L. , Kuiken Todd A. , Apkarian A. Vania , Porter Kyle , Jordan Sumanas W.
Published: October 2018

Objective:

To compare targeted muscle reinnervation (TMR) to “standard treatment” of neuroma excision and burying into muscle for postamputation pain.

Summary Background Data:

To date, no intervention is consistently effective for neuroma-related residual limb or phantom limb pain (PLP). TMR is a nerve transfer procedure developed for prosthesis control, incidentally found to improve postamputation pain.

Methods:

A prospective, randomized clinical trial was conducted. 28 amputees with chronic pain were assigned to standard treatment or TMR. Primary outcome was change between pre- and postoperative numerical rating scale (NRS, 0–10) pain scores for residual limb pain and PLP at 1 year. Secondary outcomes included NRS for all patients at final follow-up, PROMIS pain scales, neuroma size, and patient function.

Results:

In intention-to-treat analysis, changes in PLP scores at 1 year were 3.2 versus −0.2 (difference 3.4, adjusted confidence interval (aCI) −0.1 to 6.9, adjusted P = 0.06) for TMR and standard treatment, respectively. Changes in residual limb pain scores were 2.9 versus 0.9 (difference 1.9, aCI −0.5 to 4.4, P = 0.15). In longitudinal mixed model analysis, difference in change scores for PLP was significantly greater in the TMR group compared with standard treatment [mean (aCI) = 3.5 (0.6, 6.3), P = 0.03]. Reduction in residual limb pain was favorable for TMR (P = 0.10). At longest follow-up, including 3 crossover patients, results favored TMR over standard treatment.

Conclusions:

In this first surgical RCT for the treatment of postamputation pain in major limb amputees, TMR improved PLP and trended toward improved residual limb pain compared with conventional neurectomy.

Trial Registration:

NCT 02205385 at ClinicalTrials.gov.
Changes in exhaled 13CO2/12CO2 breath delta value as an early indicator of infection in intensive care unit patients
Authors: O'Rourke Ann P. , Buckman Sara A. , Evans David C. , Kerwin Andrew J. , Breunig Emily A. , Bütz Daniel E.
Published: October 2018

BACKGROUND

We have developed a new, noninvasive predictive marker for onset of infection in surgical intensive care unit (ICU) patients. The exhaled 13CO2/12CO2 ratio, or breath delta value (BDV), has been shown to be an early marker for infection in a proof of concept human study and in animal models of bacterial peritonitis. In these studies, the BDV changes during onset and progression of infection, and these changes precede physiological changes associated with infection. Earlier diagnosis and treatment will significantly reduce morbidity, mortality, hospitalization costs, and length of stay. The objective of this prospective, observational, multicenter study was to determine the predictive value of the BDV as an early diagnostic marker of infection.

METHODS

Critically ill adults after trauma or acute care surgery with an expected length of stay longer than 5 days were enrolled. The BDV was obtained every 4 hours for 7 days and correlated to clinical infection diagnosis, serum C-reactive protein, and procalcitonin levels. Clinical infection diagnosis was made by an independent endpoint committee. This trial was registered at the US National Institutes of Health (ClinicalTrials.gov) NCT02327130.

RESULTS

Groups were demographically similar (n = 20). Clinical infection diagnosis was confirmed on day 3.9 ± 0.63. Clinical suspicion of infection (defined by SIRS criteria and/or new antibiotic therapy) was on day 2.1 ± 0.5 in all infected patients. However, 5 (56%) of 9 noninfected subjects also met clinical suspicion criteria. The BDV significantly increased by 1‰ to 1.7‰ on day 2.1 after enrollment (p < 0.05) in subjects who developed infections, while it remained at baseline (± 0.5‰) for subjects without infections.

CONCLUSION

A BDV greater than 1.4‰ accurately differentiates subjects who develop infections from those who do not and predicts the presence of infection up to 48 hours before clinical confirmation. The BDV may predict the onset of infection and aid in distinguishing SIRS from infection, which could prompt earlier diagnosis, earlier appropriate treatment, and improve outcomes.

LEVEL OF EVIDENCE

Diagnostic test, level III.
Point-of-Care Ultrasound for Skin and Soft Tissue Infections
Authors: Comer Amanda B.
Published: October 2018

Skin and soft tissue infections are a common complaint seen in the emergency setting, with diagnosis traditionally made by history and physical examination alone. Cellulitis and cutaneous abscesses are often misdiagnosed. Because cellulitis and cutaneous abscesses can appear similar in presentation, they are often misdiagnosed and thus treated inappropriately. To improve accuracy of diagnosis and thus treatment, evidence now supports the use of point-of-care ultrasound for diagnosis of skin and soft tissue infections. This article reviews the difference in the 2 most common skin and soft tissue infections and discusses implications for point-of-care ultrasound in the emergency care setting to aid in diagnosis.
The Impact of Paratonia on Fine and Gross Motor Function in Older Adults With Mild and Moderate Dementia
Authors: Van Deun Bieke , Van Den Noortgate Nele , Van Bladel Anke , Palmans Tanneke , Cambier Dirk
Published: October 2018

Background:

Dementia is associated with impairment in gait, balance, and fine motor function. Paratonia, a form of hypertonia, is often present in severe dementia. However, little is known about muscle tone in early dementia, and the eventual relation between muscle tone abnormalities and changes in fine and gross motor function.

Methods:

Three groups of participants were included in the study: healthy controls (n=60), participants with mild dementia (MiD) (n=31), and participants with moderate dementia (n=31). Measurements of fine motricity (Purdue pegboard test), balance and gait (Dynaport Hybrid), the presence of paratonia (PAI), and muscle tone measurements (MyotonPRO) were performed.

Results:

Paratonia was present in 42% of participants with MiD and in 58% of participants with moderate dementia. Participants with paratonia had lower Purdue Pegboard scores (P<0.001), lower balance coordination in semitandem stance (P<0.001), lower walking speed at a fast pace (P=0.001), and lower step regularity at normal (P=0.025) and fast (P<0.001) pace.

Conclusions:

Paratonia is already present in participants with MiD and is associated with a decline in both fine and gross motor performance. Early detection of paratonia might be helpful to detect persons at higher risk of motor deterioration and falls.
Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins
Authors: Ali Ibraheem , Ruiz Diego Garrido , Ni Zuyao , Johnson Jeffrey R. , Zhang Heng , Li Pao-Chen , Khalid Mir , Conrad Ryan J. , Guo Xinghua , Min Jinrong , Greenblatt Jack , Jacobson Matthew , Krogan Nevan J. , Ott Melanie
Published: October 2018

Post-translational modifications of the RNA polymerase II C-terminal domain (CTD) coordinate the transcription cycle. Crosstalk between different modifications is poorly understood. Here, we show how acetylation of lysine residues at position 7 of characteristic heptad repeats (K7ac)—only found in higher eukaryotes—regulates phosphorylation of serines at position 5 (S5p), a conserved mark of polymerases initiating transcription. We identified the regulator of pre-mRNA domain-containing (RPRD) proteins as reader proteins of K7ac. K7ac enhanced CTD peptide binding to the CTD-interacting domain (CID) of RPRD1A and RPRD1B proteins in isothermal calorimetry and molecular modeling experiments. Deacetylase inhibitors increased K7ac- and decreased S5-phosphorylated polymerases, consistent with acetylation-dependent S5 dephosphorylation by an RPRD-associated S5 phosphatase. Consistent with this model, RPRD1B knockdown increased S5p, but enhanced K7ac, indicating RPRD proteins recruit K7 deacetylases, including HDAC1. We also report auto-regulatory crosstalk between K7ac and S5p via RPRD proteins and their interactions with acetyl- and phospho-eraser proteins.
High residual prevalence of vaccine-serotypeStreptococcus pneumoniaecarriage after introduction of a pneumococcal conjugate vaccine in Malawi: a prospective serial cross-sectional study
Authors: Swarthout Todd D. , Fronterre Claudio , Lourenço José , Obolski Uri , Gori Andrea , Bar-Zeev Naor , Everett Dean , Kamng’ona Arox W. , Mwalukomo Thandie S. , Mataya Andrew A. , Mwansambo Charles , Banda Marjory , Gupta Sunetra , Diggle Peter , French Neil , Heyderman Robert S.
Published: October 2018

Background

There are concerns that pneumococcal conjugate vaccines (PCV) in sub-Saharan Africa sub-optimally interrupt vaccine-serotype (VT) carriage and transmission, thus limiting vaccine-induced direct and indirect protection. We assessed carriage in vaccinated children and unvaccinated populations targeted for indirect protection, between 4 and 7 years after Malawi’s November 2011 introduction of PCV13 using a 3+0 schedule.

Methods

We conducted sequential prospective nasopharyngeal carriage surveys between 2015 and 2018 among healthy PCV-vaccinated and PCV-unvaccinated children, and HIV-infected adults. VT and NVT carriage risk by age was analysed by non-linear regression.

Results

Among PCV-vaccinated children, there was a 24% relative reduction in carriage, from a mean 21.1% to 16.1%; 45% reduction among older PCV-unvaccinated children, from 27.5% to 15.2%; 41.4% reduction among adults, from 15.2% to 8.9%. Using carriage data from children 3.6 to 10 years of age, VT carriage probability declined with age, with a similar prevalence half-life among PCV-vaccinated (3.34 years) and PCV-unvaccinated (3.26 years) children.

Conclusion

Compared to high-income settings, the 3+0 schedule in Malawi has led to a sub-optimal reduction in pneumococcal carriage prevalence. This is likely due to recolonisation of vaccinated children with waning vaccine-induced immunity, resulting in insufficient indirect protection of unvaccinated populations. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns is required.
Protein aggregation capture on microparticles enables multi-purpose proteomics sample preparation
Authors: Batth Tanveer S. , Tollenaere Maxim A.X. , Rüther Patrick L. , Gonzalez-Franquesa Alba , Prabhakar Bhargav S. , Bekker-Jensen Simon , Deshmukh Atul S. , Olsen Jesper V.
Published: October 2018

Universal proteomics sample preparation is challenging due to the high heterogeneity of biological samples. Here we describe a novel mechanism that exploits the inherent instability of denatured proteins for non-specific immobilization on microparticles by protein aggregation capture. To demonstrate the general applicability of this mechanism, we analyzed phosphoproteomes, tissue proteomes, and interaction proteomes as well as dilute secretomes. The findings presents a practical, sensitive and cost-effective proteomics sample preparation method.
Elevated expression of LGR5 and WNT signalling factors in neuroblastoma cells with acquired drug resistance
Authors: Myssina Svetlana , Clark-Corrigall John , Michaelis Martin , Cinatl Jindrich , Ahmed Shafiq U. , Carr-Wilkinson Jane
Published: October 2018

Neuroblastoma (NB) is the most common paediatric solid cancer with high fatality, relapses and acquired resistance to drug therapy. The clinical challenge NB poses requires new therapeutic approaches to improve survival rates.

The WNT signalling pathway is crucial in embryonic development but has also been reported to be dysregulated in glioblastoma, ovarian, breast and colorectal cancer. LGR5 is a receptor which potentiates the WNT/β-catenin signalling pathway, hence contributing to cancer stem cell proliferation and self-renewal. LGR5 has been reported to promote both development and survival of colorectal cancer and glioblastomas.

Our previous study illustrated that LGR5 is associated with aggressiveness in NB cell lines established at different stages of treatment. Following these findings, we investigated whether LGR5 is involved in acquired drug resistance via the WNT pathway in NB cell lines.

Cell lines in this study have an acquired drug resistance to vincristine (VCR) or doxorubicin (DOX).

In this study, we showed LGR5-LRP6 cooperation with enhanced expression of both proteins in SHSY5YrVCR, IMR32rDOX, IMR5rVCR and IMR5rDOX NB cell lines compared to paired parental cells. We also found elevated expression of β-catenin in cell lines with acquired drug resistance is indicative of β-catenin-dependent WNT signalling.

This study warrants further investigation into the role of the WNT signalling pathway in acquired drug resistance.
An Accessible Continuous-Culture Turbidostat for Pooled Analysis of Complex Libraries
Authors: McGeachy Anna M. , Meacham Zuriah A. , Ingolia Nicholas T.
Published: October 2018

We present an accessible, robust continuous-culture turbidostat system that enables biologists to generate and phenotypically analyze highly complex libraries in yeast and bacteria. Our system has many applications in genomics and systems biology; here, we demonstrate three of these uses. We first measure how the growth rate of budding yeast responds to limiting nitrogen at steady state and in a dynamically varying environment. We also demonstrate the direct selection of a diverse, genome-scale protein fusion library in liquid culture. Finally, we perform a comprehensive mutational analysis of the essential gene RPL28 in budding yeast, mapping sequence constraints on its wild-type function and delineating the binding site of the drug cycloheximide through resistance mutations. Our system can be constructed and operated with no specialized skills or equipment and applied to study genome-wide mutant pools and diverse libraries of sequence variants under well-defined growth conditions.
The Swiss Primary Ciliary Dyskinesia registry: objectives, methods and first results
Authors: Myrofora Goutaki , Marc Eich , Halbeisen Florian S. , Juerg Barben , Carmen Casaulta , Christian Clarenbach , Hafen Gaudenz , Philipp Latzin , Nicolas Regamey , Romain Lazor , Stefan Tschanz , Maura Zanolari , Elisabeth Maurer , Claudia Kuehni E. ,   Swiss PCD Registry (CH-PCD) Working Group
Published: October 2018

Primary Ciliary Dyskinesia (PCD) is a rare hereditary, multi-organ disease caused by defects in ciliary structure and function. It results in a wide range of clinical manifestations, most commonly in the upper and lower airways. Central data collection in national and international registries is essential to studying the epidemiology of rare diseases and filling in gaps in knowledge of diseases such as PCD. For this reason, the Swiss Primary Ciliary Dyskinesia Registry (CH-PCD) was founded in 2013 as a collaborative project between epidemiologists and adult and paediatric pulmonologists.

The registry records patients of any age, suffering from PCD, who are treated and resident in Switzerland. It collects information from patients identified through physicians, diagnostic facilities, and patient organisations. The registry dataset contains data on diagnostic evaluations, lung function, microbiology and imaging, symptoms, treatments, and hospitalizations.

By May 2018, CH-PCD has contacted 566 physicians of different specialties and identified 134 patients with PCD. At present this number represents an overall 1 in 63,000 prevalence of people diagnosed with PCD in Switzerland. Prevalence differs by age and region; it is highest in children and adults younger than 30 years, and in Espace Mittelland. The median age of patients in the registry is 25 years (range 5-73), and 49 patients have a definite PCD diagnosis based on recent international guidelines. Data from CH-PCD are contributed to international collaborative studies and the registry facilitates patient identification for nested studies.

CH-PCD has proven to be a valuable research tool that already has highlighted weaknesses in PCD clinical practice in Switzerland. Development of centralised diagnostic and management centres and adherence to international guidelines are needed to improve diagnosis and management—particularly for adult PCD patients.
The CRUNCH model does not account for load-dependent changes in visuospatial working memory in older adults: Evidence for the file-drawer problem in neuroimaging
Authors: Jamadar Sharna D
Published: October 2018

Numerous neuroimaging studies have shown that older adults tend to activate the brain to a greater extent than younger adults during the performance of a task. This is typically interpreted as evidence for cognitive compensation. The Compensation-Related Utilisation of Neural Circuits Hypothesis (CRUNCH) model is a highly influential model of compensation, and states that increased functional magnetic resonance imaging (fMRI) activity in older adults compared to younger adults should reverse at higher levels of task difficulty. We tested the CRUNCH model using a visuospatial working memory paradigm, and found that fMRI activity in older vs. younger adults was in the opposite direction to that predicted by the model. Given that the CRUNCH model is the predominant model of compensation, this result was surprising. We followed up our results with a systematic review of the CRUNCH in healthy ageing literature using p-curve analysis. We find evidence for selective reporting, or the ‘file-drawer’ problem, in the cognitive compensation literature. Further experimental work is required to validate the CRUNCH model in cognitive ageing.

Abbreviations

CRUNCH: compensation-related utilisation of neural circuits hypothesis; fMRI: functional magnetic resonance imaging

Highlights

-

CRUNCH is the leading model of cognitive compensation in ageing

-

We find fMRI activity in old vs. young adults in opposite direction predicted by CRUNCH

-

We report quantitative evidence of selective reporting in CRUNCH literature
Sparse Coding with a Somato-Dendritic Rule
Authors: Drix Damien , Hafner Verena V. , Schmuker Michael
Published: October 2018

Cortical neurons are silent most of the time. This sparse activity is energy efficient, and the resulting neural code has favourable properties for associative learning. Most neural models of sparse coding use some form of homeostasis to ensure that each neuron fires infrequently. But homeostatic plasticity acting on a fast timescale may not be biologically plausible, and could lead to catastrophic forgetting in embodied agents that learn continuously. We set out to explore whether inhibitory plasticity could play that role instead, regulating both the population sparseness and the average firing rates. We put the idea to the test in a hybrid network where rate-based dendritic compartments integrate the feedforward input, while spiking somas compete through recurrent inhibition. A somato-dendritic learning rule allows somatic inhibition to modulate nonlinear Hebbian learning in the dendrites. Trained on MNIST digits and natural images, the network discovers independent components that form a sparse encoding of the input and support linear decoding. These findings con-firm that intrinsic plasticity is not strictly required for regulating sparseness: inhibitory plasticity can have the same effect, although that mechanism comes with its own stability-plasticity dilemma. Going beyond point neuron models, the network illustrates how a learning rule can make use of dendrites and compartmentalised inputs; it also suggests a functional interpretation for clustered somatic inhibition in cortical neurons.
HERV-K HML-2 transcription in diverse cancers is related with cancer stem cell and epithelial-mesenchymal transition markers
Authors: Lin Audrey T. , Santander Cindy G. , Nascimento Fabricia F. , Marchi Emanuele , Karamitros Timokratis , Katzourakis Aris , Magiorkinis Gkikas
Published: October 2018

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the youngest lineage in the human genome, have intact open reading frames, some encoding for accessory genes called np9 and rec that interact with oncogenic pathways. Many studies have established that ERVs are transiently expressed in both stem cells and cancer, resulting in aberrant self-renewal and uncontrolled proliferation. np9 and rec expression are significantly correlated with a range of cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) biomarkers, including cellular receptors, transcription factors, and histone modifiers. Surprisingly, these ERV genes are negatively correlated with genes known to promote pluripotency in embryonic stem cell lines, such as Oct4. These results indicate that HERV-K (HML-2) is part of the transcriptional landscape responsible for cancer cells undergoing the phenotypic switch that characterises EMT. The discovery of np9 and rec’s correlation with CSC and EMT biomarkers suggest a yet undescribed role affecting the transitional CSC-like state in EMT and the shift towards cancer malignancy.

Importance

In this study, we find that human endogenous retrovirus HERV-K (HML-2)-encoded genes np9 and rec are correlated with the expression of many biomarkers associated with cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT). There has been a significant effort to develop novel treatments targeting CSC and EMT-specific signalling pathways and cell surface markers. This research describes HERV-K (HML-2) as interacting or being part of the regulatory network that make up reversible cell state switching in EMT. Our findings suggest these specific HERVs may be good candidate biomarkers in identifying the transitional CSC-like states that are present during the progression of EMT and cancer metastasis.
Different macroevolutionary routes to becoming a biodiversity hotspot
Authors: Igea J. , Tanentzap A. J.
Published: October 2018

Why is species diversity so unevenly distributed across different regions on Earth? Regional differences in biodiversity may stem from differences in rates of speciation and dispersal and colonization times, but these hypotheses have rarely been tested simultaneously at a global scale. Here we uncovered the routes that generated hotpots of mammal and bird biodiversity by analyzing the tempo and mode of diversification and dispersal within major biogeographic realms. Hotspots in tropical realms had higher rates of speciation whereas those in temperate realms received more immigrant species from their surrounding regions. We also found that hotspots had higher spatial complexity and energy availability, providing a link between the environment and macroevolutionary history. Our study highlights how assessing differences in macroevolutionary history can help to explain why biodiversity varies so much worldwide.
Spontaneous intake and long-term effects of essential oils after a negative postnatal experience in chicks
Authors: Guilloteau Laurence A. , Collin Anne , Koch Alexia , Leterrier Christine
Published: October 2018

The postnatal period is critical for broiler chicks as they are exposed to, possibly stressful, environmental changes in the hatchery and during transportation to the rearing houses. The ability of broiler chicks to spontaneously drink essential oils (EO) to mitigate the effects of a negative postnatal experience was tested. Chicks were either immediately placed in the rearing facility (C group), or subjected to a 24h-delay period before their placement (D group), mimicking the possible transportation delay in commercial conditions.

In experiment 1, each group had access to either water only or to water and one EO (cardamom, marjoram or verbena) from D1 to D13. The verbena EO intake was higher in the D group than in the C group from D1 to D6 and the cardamom EO intake was lower in the D group than in the C group from D6 to D13.

In experiment 2, half of the groups had access to water only and the other half was offered water and the 3 EO simultaneously. The EO were not differently chosen by chicks between D and C groups except a lower cardamom EO intake was observed in the D group than in the C group from D6 to D12. The delayed placement of the D group reduced chicken growth until 34 days of age and temporarily increased the feed conversion ratio, but did not affect their welfare or the prevalence of health disorders. The EO intake did not allow the chicks in the D group to overcome the growth reduction, but did overcome the reduction in Pectoralis major muscle yield. In conclusion, chicks are able to make spontaneous choices regarding EO intake according to their postnatal experience when EO are presented individually, but in our experimental design, they were not when EO were simultaneously presented. The EO intake only partially mitigated the decrease in chicken performance after the negative postnatal experience.
Cingulate dependent social risk assessment in rats
Authors: Han Yingying , Bruls Rune , Thomas Rajat Mani , Pentaraki Vasiliki , Jelinek Naomi , Heinemans Mirjam , Bassez Iege , Verschooren Sam , Pruis Illanah , Lierde Thijs Van , Carrillo Nathaly , Gazzola Valeria , Carrillo Maria , Keysers Christian
Published: October 2018

Social transmission of distress has been conceived of as a one-way phenomenon in which an observer catches the emotions of another. Here we use a paradigm in which an observer rat witnesses another receive electro-shocks. Bayesian model comparison and Granger causality argue against this one-way vision in favor of bidirectional information transfer: how the observer reacts to the demonstrator’s distress influences the behavior of the demonstrator. Intriguingly, this was true to a similar extent across highly familiar and entirely unfamiliar rats. Injecting muscimol in the anterior cingulate of observers reduced freezing in the observers and in the demonstrators receiving the shocks. That rats share the distress of unfamiliar strains is at odds with evolutionary thinking that empathy should be biased towards close individuals. Using simulations, we support the complementary notion that distress transmission could be selected to more efficiently detect dangers in a group.
Impact of mutation rate and selection at linked sites on fine-scale DNA variation across the homininae genome
Authors: Castellano David , Eyre-Walker Adam , Munch Kasper
Published: October 2018

DNA diversity varies across the genome of many species. Variation in diversity across a genome might arise for one of three reasons; regional variation in the mutation rate, selection and biased gene conversion. We show that both non-coding and non-synonymous diversity are correlated to a measure of the mutation rate, the recombination rate and the density of conserved sequences in 50KB windows across the genomes of humans and non-human homininae. We show these patterns persist even when we restrict our analysis to GC-conservative mutations, demonstrating that the patterns are not driven by biased gene conversion. The positive correlation between diversity and our measure of the mutation rate seems to be largely a direct consequence of regions with higher mutation rates having more diversity. However, the positive correlation with recombination rate and the negative correlation with the density of conserved sequences suggests that selection at linked sites affect levels of diversity. This is supported by the observation that the ratio of the number of non-synonymous to non-coding polymorphisms is negatively correlated to a measure of the effective population size across the genome. Furthermore, we find evidence that these genomic variables are better predictors of non-coding diversity in large homininae populations than in small populations, after accounting for statistical power. This is consistent with genetic drift decreasing the impact of selection at linked sites in small populations. In conclusion, our comparative analyses describe for the first time how recombination rate, gene density, mutation rate and genetic drift interact to produce the patterns of DNA diversity that we observe along and between homininae genomes.
Cortical subnetworks encode context of visual stimulus
Authors: Hamm Jordan P. , Shymkiv Yuriy , Han Shuting , Yang Weijian , Yuste Rafael
Published: October 2018

Cortical processing of sensory events is significantly influenced by context. For instance, a repetitive or redundant visual stimulus elicits attenuated cortical responses, but if the same stimulus is unexpected or “deviant”, responses are augmented. This contextual modulation of sensory processing is likely a fundamental function of neural circuits, yet an understanding of how it is computed is still missing. Using holographic two-photon calcium imaging in awake animals, here we identify three distinct, spatially intermixed ensembles of neurons in mouse primary visual cortex which differentially respond to the same stimulus under separate contexts, including a subnetwork which selectively responds to deviant events. These non-overlapping ensembles are distributed across layers 2-5, though deviance detection is more common in superficial layers. Contextual preferences likely arise locally since they are not present in bottom up inputs from the thalamus or top-down inputs from prefrontal cortex. The functional parcellation of cortical circuits into independent ensembles that encode stimulus context provides a circuit basis underlying cortically based perception of novel or redundant stimuli, a key deficit in many psychiatric disorders.

One Sentence Summary

Visual cortex represents deviant and redundant stimuli with separate subnetworks.
Abnormal LTR retrotransposons formed by the recombination outside the host genome
Authors: Zeng Fanchun , Sun Zhongyi
Published: October 2018

Long terminal repeat (LTR) retrotransposons are the dominant feature of higher plant genomes, which have a similar life cycle with retrovirus. Previous studies cannot account for all observed complex LTR retrotransposon patterns. In this study, we first identified 63 complex LTR retrotransposons in rice genome, and most of complex elements harbored flanking target-site duplications (TSDs). But these complex elements in which outermost LTRs had not the most highly homologous can’t be explained. We propose a new model that the homologous recombination of two new different normal LTR retrotransposon elements in the same family can occur before their integration to the rice genome. The model can explain at least fourteen complex retrotransposons formations. We also find that normal LTR retrotransposons can swap their LTRs to generate abnormal LTR retrotransposons in which LTRs are different because of homologous recombination before their integration to the genome.
ADHD: relation between cognitive characteristics and DAT1 / DRD4 dopamine polymorphisms
Authors: Cristina Pinto María , Enrique Ávila Jorge , María Polanco Angela , Antonio Vásquez Rafael , Humberto Arboleda
Published: October 2018

Attention deficit hyperactivity disorder (ADHD) is a clinical and diagnostic heterogeneous picture. This study analysed the association of functional polymorphisms in DAT1 VNTR 3’ UTR and DRD4 VNTR Exon III candidate genes, and the neuropsychological characterisation of attention and executive functions of a group of children with ADHD vs. controls. 32 patients and 51 controls were selected. The DAT1 10-repeat allele appeared more frequently in the two groups (cases: 0.93/control: 0.82), showing an OR: 2.5 (IC 95%: 0.684-9.133; p: 0.158). In DRD4, the 4-repeat allele shows the highest occurrence (cases: 0.62/controls: 0.60). None of the markers presented a significant association after a direct analysis, but the DRD4 7-repeat marker showed a positive risk when performing a Bayesian logistic analysis (coefficient: −1.69; OR: 5.39 CI 95%: 1.167-40.97). On the other hand, when considering association with cognitive performance, a positive risk for processing speed and attention tasks was identified.
Demethylmenaquinone methyl transferase is a membrane domain-associated protein essential for menaquinone homeostasis in Mycobacterium smegmatis
Authors: Puffal Julia , A. Mayfield Jacob , Moody D. Branch , S. Morita Yasu
Published: October 2018

The intracellular membrane domain (IMD) in mycobacteria is a spatially distinct region of the plasma membrane with diverse functions. Previous comparative proteomic analysis of the IMD suggested that menaquinone biosynthetic enzymes are associated with this domain. In the present study, we determined the subcellular site of these enzymes using sucrose density gradient fractionation. We found that the last two enzymes, the methyltransferase MenG, and the reductase MenJ, are associated with the IMD. MenA, the prenyltransferase that mediates the first membrane-associated step of the menaquinone biosynthesis, is associated with the conventional plasma membrane. For MenG, we additionally showed the polar enrichment of the fluorescent protein fusion colocalizing with an IMD marker protein in situ. To start dissecting the roles of IMD-associated enzymes, we further tested the physiological significance of MenG. The deletion of menG at the endogenous genomic loci was possible only when an extra copy of the gene was present, indicating that it is an essential gene in M. smegmatis. Using a tetracycline-inducible switch, we achieved gradual and partial depletion of MenG over three consecutive 24 hour subcultures. This partial MenG depletion resulted in progressive slowing of growth, which corroborated the observation that menG is an essential gene. Upon MenG depletion, there was a significant accumulation of MenG substrate, demethylmenaquinone, even though the cellular level of menaquinone, the reaction product, was unaffected. Furthermore, the growth retardation was coincided with a lower oxygen consumption rate and ATP accumulation. These results imply a previously unappreciated role of MenG in regulating menaquinone homeostasis within the complex spatial organization of mycobacterial plasma membrane.
Divergent selection causes whole genome differentiation without physical linkage among the targets in Spodoptera frugiperda (Noctuidae)
Authors: Nam Kiwoong , Nhim Sandra , Robin Stéphanie , Bretaudeau Anthony , Nègre Nicolas , d’Alençon Emmanuelle
Published: October 2018

The process of speciation involves whole genome differentiation by overcoming gene flow between diverging populations. We have ample knowledge which evolutionary forces may cause genomic differentiation, and several speciation models have been proposed to explain the transition from genetic to genomic differentiation. However, it is still unclear what are critical conditions enabling genomic differentiation in nature. The Fall armyworm, Spodoptera frugiperda, is observed as two sympatric strains that have different host-plant ranges, suggesting the possibility of ecological divergent selection. In our previous study, we observed that these two strains show genetic differentiation across the whole genome with an unprecedentedly low extent, suggesting the possibility that whole genome sequences started to be differentiated between the strains. In this study, we analyzed whole genome sequences from these two strains from Mississippi to identify critical evolutionary factors for genomic differentiation. The genomic Fst is low (0.017) while 91.3% of 10kb windows have Fst greater than 0, suggesting genome-wide differentiation with a low extent. We identified nearly 400 outliers of genetic differentiation between strains, and found that physical linkage among these outliers is not a primary cause of genomic differentiation. Fst is not significantly correlated with gene density, a proxy for the strength of selection, suggesting that a genomic reduction in migration rate dominates the extent of local genetic differentiation. Our analyses reveal that divergent selection alone is sufficient to generate genomic differentiation, and any following diversifying factors may increase the level of genetic differentiation between diverging strains in the process of speciation.
Alcohol consumption is associated with widespread changes in blood DNA methylation: analysis of cross-sectional and longitudinal data
Authors: Dugué Pierre-Antoine , Wilson Rory , Lehne Benjamin , Jayasekara Harindra , Wang Xiaochuan , Jung Chol-Hee , Joo JiHoon E , Makalic Enes , Schmidt Daniel F , Baglietto Laura , Severi Gianluca , Gieger Christian , Ladwig Karl-Heinz , Peters Annette , Kooner Jaspal S , Southey Melissa C , English Dallas R , Waldenberger Melanie , Chambers John C , Giles Graham G , Milne Roger L
Published: October 2018

Background:

DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart.

Methods:

Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined using baseline peripheral blood samples from 5,606 adult Melbourne Collaborative Cohort Study (MCCS) participants. For a subset of 1,088 of them, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. Independent data from the LOLIPOP (N=4,042) and KORA (N=1,662) cohorts were used to replicate associations discovered in the MCCS.

Results:

Cross-sectional analyses identified 1,414 CpGs associated with alcohol intake at P<10-7, 1,243 of which had not been reported previously. Of these 1,243 novel associations, 1,078 were replicated (P<0.05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated (P<0.05) 403 of 518 associations that had been reported previously. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1,414 CpGs, 530 were differentially methylated (P<0.05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1,414 cross-sectional associations.

Conclusion:

Our study indicates that, for middle-aged and older adults, alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with changes in alcohol consumption.
A model of ganglion axon pathways accounts for percepts elicited by retinal implants
Authors: Beyeler Michael , Nanduri Devyani , Weiland James D. , Rokem Ariel , Boynton Geoffrey M. , Fine Ione
Published: October 2018

Retinal prostheses, now implanted in over 250 patients worldwide, electrically stimulate surviving cells in order to evoke neuronal responses that are interpreted by the brain as visual percepts (‘phosphenes’). However, instead of seeing focal spots of light, current implant users perceive highly distorted phosphenes that vary in shape both across subjects and electrodes. We characterized these distortions by asking users of the Argus retinal prosthesis system (Second Sight Medical Products) to draw elicited percepts on a touchscreen. We found that phosphene shape could be accurately predicted by simulating the topographic organization of nerve fiber bundles in each subject’s retina. Our model shows that activation of ganglion axons contributes to a rich repertoire of phosphene shapes, successfully replicating percepts ranging from ‘blobs’ to oriented ‘streaks’ and ‘wedges’ depending on electrode location. This work provides a first step towards future devices that incorporate stimulation strategies tailored to each individual patient’s retinal neurophysiology.

One Sentence Summary

We show that the perceptual experience of retinal implant users can be accurately predicted using a computational model that simulates the topographic organization of each individual patient’s retinal ganglion axon pathways.
Bacterial T6SS Effector EvpP Inhibits Neutrophil Recruitment via Jnk-Caspy Inflammasome SignalingIn vivo
Authors: Tan Jinchao , Yang Dahai , Wang Zhuang , Zheng Xin , Zhang Yuanxing , Liu Qin
Published: October 2018

The type VI secretion system (T6SS) comprises dynamic complex bacterial contractile nanomachines and is used by many bacteria to inhibit or kill other prokaryotic or eukaryotic cells. Previous studies have revealed that T6SS is constitutively active in response to various stimuli, or fires effectors into host cells during infection. It has been proposed that the T6SS effector EvpP inEdwardsiella piscicidacan inhibit NLRP3 inflammasome activation via the Ca2+-dependent JNK pathways. Here, we developed anin vivoinfection model by microinjecting bacteria into the tail vein muscle of 3-day-post-fertilized zebrafish larvae, and found that both macrophages and neutrophils are essential for bacterial clearance. Further study revealed that EvpP plays a critical role in promoting the pathogenesis ofE. piscicidavia inhibiting the phosphorylation of Jnk signaling to reduce the expression ofcxcl8a,mmp13andIL-1β in vivo.Subsequently, by utilizingTg(mpo:eGFP+/+) zebrafish larvae forE. piscicidainfection, we found that the EvpP-inhibited Jnk-caspy inflammasome signaling axis significantly suppressed the recruitment of neutrophils to infection sites, and thecaspy‐ orIL-1β-MO knockdown larvae were more susceptible to infection and failed to restrict bacterial colonizationin vivo.

IMPORTANCE

Innate immunity is regulated by phagocytic cells and is critical for host control of bacterial infection. In many bacteria, T6SSs can affect bacterial virulence in certain environments, but little is known about the mechanisms underlying T6SS regulation of innate immune responses during infectionin vivo. Here, we investigated the role of anE. piscicidaT6SS effector EvpP in manipulating the reaction of neutrophilsin vivo.We show that EvpP inhibits the activation of Jnk-caspy inflammasome pathway in zebrafish larvae, and reveal that macrophages are essential for neutrophil recruitmentin vivo. This interaction improves our understanding about the complex and contextual role of a bacterial T6SS effector in modulating the action of myeloid cells during infection, and offers new insights into the warfare between bacterial weapons and host immunological surveillance.