bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineralogical Constraints on the Magma Mixing Beneath the Iheya Graben, an Active Back-Arc Spreading Centre of the Okinawa Trough
Authors: Zhang Yu-Xiang , Zeng Zhi-Gang , Gaetani Glenn , Zhang Le , Lai Zhi-Qing
Published: October 2020

The Iheya Graben is a back-arc spreading centre in the middle part of the Okinawa Trough. It is also located in the centre of an anomalous volcanic zone (volcanic arc migration phenomenon, or VAMP) and is characterized by bimodal volcanism, unusually high heat flow and active hydrothermal circulation. The subvolcanic magma plumbing system and the magmatic processes related to the formation of rare erupted intermediate lavas in this area remain uncertain. In this study, we conducted systematic mineralogical analyses (in situ major element, trace element and Sr isotopes) and whole rock geochemical analyses (major element, trace element and Sr–Nd isotopes) on an andesite (T5-2; type C andesite) and a rhyolite (C11; type 2 rhyolite), and present evidence for magma mixing in the origins of these lavas. Andesite T5-2 contains a mafic mineral assemblage and a silicic mineral assemblage, which are derived from a basaltic melt and a type 2 rhyolitic melt, respectively. A 4:6 mixture of basalt and type 2 rhyolite from the Iheya Graben reproduces the whole-rock major element, trace element, and Sr–Nd isotope compositions of T5-2. Rhyolite C11 contains a group of disequilibrium minerals that crystallized from a less evolved rhyolitic melt with relatively more enriched Sr–Nd isotope compositions, suggesting mixing of this melt with a more evolved and isotopically more depleted rhyolitic melt. This mixing process could produce a series of rhyolitic melts with a negative correlation between SiO2 concentrations and 87Sr/86Sr ratios (or a positive correlation for 143Nd/144Nd ratios), which are recorded by the whole group of type 2 rhyolites. The results from mineral-based thermobarometers suggest that the premixing storage temperatures of the basaltic and rhyolitic melts are ∼1100 °C and 870–900 °C, respectively. The hybrid andesitic melt has temperatures of ∼950 to ∼980 °C. The magma storage pressures are not well constrained, ranging from ∼400 MPa to ∼100 MPa. We show that magma mixing plays a significant role in the origins of diverse volcanism in the middle Okinawa Trough; more specifically, two of the three types of andesites (types B and C) and one of the two types of rhyolites (type 2) are associated with magma mixing. We thus propose a complex magma plumbing system with multichamber magma storage and frequent magma mixing beneath the Iheya Graben.
Academic entrepreneurship and attentional discrepancy among key stakeholders: Evidence from research universities in Korea
Authors: Kang Dong-In , Kang In-Je , Kim Yeong-Ju , Nguyen Chi Mai , Choung Jae-Yong
Published: October 2020

While understandings on the institutional environment and individual motivations have been at the center of describing the antecedents of academic entrepreneurship, findings from this research trigger skepticism in the currently dominant perspective. By building on the traditional institutional theory with insights from the stakeholders and attention-based perspectives, it is possible to postulate that reaching multiple stakeholders’ needs is essential in maximizing the effectiveness of a collective entrepreneurial process. We argue that aligning selective interests, or attentions, among key stakeholders is a critical factor that promotes academic entrepreneurship. Quantitative and qualitative investigations on Korean research universities confirm that involved stakeholders are subject to severe discrepancy in how they place attentional prioritizations in technology, formal institution, and informal institution capabilities. In spite of favorable national and university incentives, the different degrees of misaligned interests among key players prove to hold heavy repercussions in the collective planning and execution of academic entrepreneurship.
Early Life Exposure to Environmental Contaminants (BDE-47, TBBPA, and BPS) Produced Persistent Alterations in Fecal Microbiome in Adult Male Mice
Authors: Gomez Matthew V , Dutta Moumita , Suvorov Alexander , Shi Xiaojian , Gu Haiwei , Mani Sridhar , Yue Cui Julia
Published: October 2020

The gut microbiome is a pivotal player in toxicological responses. We investigated the effects of maternal exposure to 3 human health-relevant toxicants (BDE-47, tetrabromobisphenol [TBBPA], and bisphenol S [BPS]) on the composition and metabolite levels (bile acids [BAs] and short-chain fatty acids [SCFAs]) of the gut microbiome in adult pups. CD-1 mouse dams were orally exposed to vehicle (corn oil, 10 ml/kg), BDE-47 (0.2 mg/kg), TBBPA (0.2 mg/kg), or BPS (0.2 mg/kg) once daily from gestational day 8 to the end of lactation (postnatal day 21). 16S rRNA sequencing and targeted metabolomics were performed in feces of 20-week-old adult male pups (n = 14 − 23/group). Host gene expression and BA levels were quantified in liver. BPS had the most prominent effect on the beta-diversity of the fecal microbiome compared with TBPPA and BDE-47 (QIIME). Seventy-three taxa were persistently altered by at least 1 chemical, and 12 taxa were commonly regulated by all chemicals (most of which were from the Clostridia class and were decreased). The most distinct microbial biomarkers were S24-7 for BDE-47, Rikenellaceae for TBBPA, and Lactobacillus for BPS (LefSe). The community-wide contributions to the shift in microbial pathways were predicted using FishTaco. Consistent with FishTaco predictions, BDE-47 persistently increased fecal and hepatic BAs within the 12α hydroxylation pathway, corresponding to an up-regulation with the hepatic BA-synthetic enzyme Cyp7a1. Fecal BAs were also persistently up-regulated by TBBPA and BPS (liquid chromatography-mass spectrometry). TBBPA increased propionic acid and succinate, whereas BPS decreased acetic acid (gas chromatography-mass spectrometry). There was a general trend in the hepatic down-regulation of proinflammatory cytokines and the oxidative stress sensor target gene (Nqo1), and a decrease in G6Pdx (the deficiency of which leads to dyslipidemia). In conclusion, maternal exposure to these toxicants persistently modified the gut-liver axis, which may produce an immune-suppressive and dyslipidemia-prone signature later in life.
Comprehensive In Silico Evaluation of Accessory Rod Position, Rod Material and Diameter, Use of Cross-connectors, and Anterior Column Support in a Pedicle Subtraction Osteotomy Model
Authors: Jazini Ehsan , Gelb Daniel E. , Tareen Jarid , Ludwig Steven C. , Harris Jonathan A. , Amin Dhara B. , Wang Wenhai , Van Horn Margaret R. , Patel Pavan D. , Mirabile Belin A. , Bucklen Brandon S.
Published: October 2020

Study Design.

In silico finite element study.

Objective.

The aim of this study was to evaluate effects of six construct factors on rod and screw strain at the lumbosacral junction in an in silico pedicle subtraction osteotomy (PSO) model: traditional inline and alternative Ames-Deviren-Gupta (ADG) multi-rod techniques, number of accessory rods (three-rod vs. four-rod), rod material (cobalt-chrome [CoCr] or stainless steel [SS] vs. titanium [Ti]), rod diameter (5.5 vs. 6.35 mm), and use of cross-connectors (CC), or anterior column support (ACS).

Summary of Background Data.

Implant failure and pseudoarthrosis at the lumbosacral junction following PSO are frequently reported. Clinicians may modulate reconstructs with multiple rods, rod position, rod material, and diameter, and with CC or ACS to reduce mechanical demand. An evaluation of these features’ effects on rod and screw strains is lacking.

Methods.

A finite element model (T12–S1) with intervertebral discs and ligaments was created and validated with cadaveric motion data. Lumbosacral rod and screw strain data were collected for 96 constructs across all six construct factors and normalized to the Ti 2-Rod control.

Results.

The inline technique resulted in 12.5% to 51.3% more rod strain and decreased screw strain (88.3% to 95%) compared to ADG at the lumbosacral junction. An asymmetrical strain distribution was observed in the three-rod inline technique in comparison to four-rod, which was more evenly distributed. Regardless of construct features, rod strain was significantly decreased by rod material (CoCr > SS > Ti), and increasing rod diameter from 5.5 mm to 6.35 mm reduced strain by 9.9% to 22.1%. ACS resulted in significant reduction of rod (37.8%–59.8%) and screw strains (23.2%–65.8%).

Conclusion.

Increasing rod diameter, using CoCr rods, and ACS were the most effective methods in reducing rod strain at the lumbosacral junction. The inline technique decreased screw strain and increased rod strain compared to ADG.

Level of Evidence: N/A.
Hangman’s Fracture
Authors: Turtle Joel , Kantor Adam , Spina Nicholas T. , France John C. , Lawrence Brandon D.
Published: October 2020

Study Design:

Review article.

Objective:

A review and update of the treatment of Hangman’s fractures including the indications for both nonoperative and operative treatment of typical and atypical fractures.

Summary of Background Data:

Hangman’s fractures are the second most common fracture pattern of the C2 vertebrae following odontoid fractures. Many of the stable extension type I and II fractures can be treated with external immobilization, whereas the predominant flexion type IIa and III fractures require surgical stabilization.

Methods:

A review of the literature.

Results:

The clinical and radiographic outcomes of the treatment of Hangman’s fractures lend a good overall prognosis when the correct diagnosis is made. The nonoperative treatment of stable type I and II fractures with external immobilization leads to excellent long-term outcomes as does the operative treatment of the unstable type IIa and III fractures.

Conclusions:

Hangman’s fractures can be classified as stable (type I and most II) or unstable (type IIa and III) and the optimal treatment depends upon this distinction. Stable injuries do well with rigid immobilization and rarely require operative intervention. In contrast, unstable injuries do poorly if treated nonoperatively but do well with surgical intervention. When treating atypical Hangman’s variants, great vigilance and close clinical observation is paramount if nonoperative treatment is indicated given the potential for neurological compression in this fracture pattern. Properly identifying and treating these injuries represents an opportunity for the spine surgeon to optimize patient outcomes.
Regional Anesthesia for Spine Surgery
Authors: Garg Bhavuk , Ahuja Kaustubh , Khanna Puneet , Sharan Alok D.
Published: October 2020

Recent advancements in spine surgery anesthesia techniques and pain management has led to a paradigm shift from conventional open spinal procedures to minimally invasive spine surgeries performed on an outpatient basis. Spinal anesthesia and epidural anesthesia alone or in combination with spinal are common regional anesthesia modalities used in spine surgeries. New modalities of regional analgesia have emerged recently including erector spinae and thoracolumbar interfascial plane block, aimed at decreasing perioperative pain and enhancing early recovery in patients undergoing spine surgery. In this narrative review we discuss the characteristics of regional anesthesia including its types, indications, contraindications, benefits, and potential complications along with new modalities of regional analgesia.
Safety and efficacy of electrochemotherapy in a series of patients with nonmetastasized primary or recurrent anorectal malignant melanoma
Authors: Farricha Victor , Quaglino Pietro , Brizio Matteo , de Terlizzi Francesca , Bartolo Joana , Carvalhal Sara , Caracò Corrado , Di Monta Gianluca
Published: October 2020

Anorectal malignant melanoma (AMM) is a rare malignant tumor. Surgery remains the gold standard but new adjuvant treatments to allow local sphincter-saving are warranted. Electrochemotherapy (ECT) is an alternative to surgery in selected cohorts of patients. To evaluate safety and efficacy of ECT in a retrospective series of patients with primary or recurrent AMM in terms of local disease control, local progression free and overall survival. Seven primary and one recurrent AMM underwent ECT. Patients were followed at 1 and 2 months and at the longest available follow-up with clinical examination and/or ultrasound. One month after ECT 6/8 (75%) patients showed complete response, 1/8 partial response (12.5%) and 1/8 stable disease (12.5%), confirmed at 2 months. Bleeding stopped in all patients, and pain was absent or mild/moderate in all patients. No serious adverse events were observed. At 1 year of follow-up seven out of eight patients were alive (87.5%), four were disease-free and three were alive with disease. At the longest available follow-up (mean 4.9 ± 2.0 years) five out of eight (62.5%) of patients were still alive. Our study showed that ECT is well tolerated and effective in the treatment of patients with anal melanoma with good local control of disease.
Association between polymorphisms in the vitamin D receptor and susceptibility to multiple sclerosis
Authors: Cancela Díez Bárbara , Pérez-Ramírez Cristina , Maldonado-Montoro María del Mar , Carrasco-Campos María Isabel , Sánchez Martín Almudena , Pineda Lancheros Laura Elena , Martínez-Martínez Fernando , Calleja-Hernández Miguel Ángel , Ramírez-Tortosa María Carmen , Jiménez-Morales Alberto
Published: October 2020

Objectives

Multiple sclerosis (MS) is a neurodegenerative chronic inflammatory. Mutations in the vitamin D receptor (VDR) gene can substantially affect serum vitamin D levels or alter its functionality, and can consequently increase susceptibility to developing MS. The objective of this study was to evaluate the association between polymorphisms in the VDR gene and risk of MS in a (Spanish) Caucasian population.

Patients and methods

We conducted a retrospective case-control study comprising 209 patients with relapsing-remitting multiple sclerosis (RRMS) and 836 controls of Caucasian origin from southern Spain. The ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms were determined by allelic discrimination real-time PCR using TaqMan probes.

Results

The recessive logical regression model, adjusted for age and sex, revealed that the TT genotype for VDR FokI (rs2228570) polymorphism was associated with higher risk of MS (P = 0.0150; OR = 1.82; 95% CI = 1.12–2.94; TT vs. CT + CC). No association between the other polymorphisms and development of MS was found in any of the models analyzed. The haplotype analysis, adjusted for age, smoking, and sex, did not find any statistically significant association between the haplotypes analyzed and risk of MS.

Conclusions

The VDR FokI (rs2228570) polymorphism was significantly associated with developing MS. We found no influence of the ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms on the risk of developing MS in our patients.
Age-Related Changes in Astigmatism and Potential Causes
Authors: Namba Hiroyuki , Sugano Akira , Murakami Takanori , Utsunomiya Hiroshi , Nishitsuka Koichi , Ishizawa Kenichi , Kayama Takamasa , Yamashita Hidetoshi
Published: October 2020

Astigmatism causes deterioration of the retinal image and affects vision quality. Maintenance and improvement of visual function requires an understanding of the prevalence, age-related changes, and mechanisms of astigmatism. In this article, we discuss the findings of studies that investigated astigmatism. Some of these studies showed that the prevalence of high degrees of astigmatism in childhood typically decreases with emmetropization. With-the-rule astigmatism occurs most commonly in young adults. With age, the prevalence of astigmatism increases, and the axis shifts from a predominance of with-the-rule astigmatism to a predominance of against-the-rule astigmatism. This age-related change is caused by alterations in corneal curvature. Although the cause of this change is not fully understood, alterations in the position and tension of the eyelid, corneal stromal collagen fibrils, Descemet membrane, and extraocular muscles may influence the shape of the cornea. Furthermore, genetic factors may contribute to the development of astigmatism. Technological advances in ophthalmology are expected to improve our understanding of the etiology of astigmatism and enable the maintenance of quality of vision.
Novel approaches in uterus transplantation
Authors: Brännström Mats , Kvarnström Niclas , Dahm-Kähler Pernilla
Published: October 2020

Purpose of review

Uterus transplantation (UTx) is the first existing infertility treatment for women with no uterus and for women with a present nonfunctional uterus, which is unable to carry a pregnancy. This type of transplantation is a novel addition within the field of vascularized composite allografts and is the first ephemeral kind of transplantation, with the graft intended for only a restricted number of years, until the desired numbers of children have been born and with subsequent graft removal. The proof-of-concept of UTx, as an infertility treatment for women with uterine factor infertility, came with the report of the first live birth after UTx, occurring in Sweden in 2014. This UTx live birth has been followed by around 30 births, taking place in four continents. Despite the initial clinical success, UTx should still be regarded as an experimental procedure, at a developmental phase. The clinical UTx activities at several centers around the globe take place within scientific clinical trials and aim to advance UTx further. This review describes certain developmental areas around UTx. These relate to surgery, donor selection, assisted reproduction, and inclusion of new recipient groups.

Recent findings

Successful UTx procedures, with live births, have been reported both after live and deceased donor transplantation. There exist developments in the areas of robotic surgery for live donor hysterectomy, of alternate vascular connections to the graft, modifications of inclusion criteria/investigations of donors, assisted reproduction in conjunction with UTx, as well as discussions concerning expanding the pool of eligible recipients.

Uterus transplantation has repeatedly proven to be a feasible infertility treatment for women with absolute uterine factor infertility. Ongoing studies aim to increase safety and efficiency of the procedure as well as to better define suitable donors and recipients.
Novel Approach of Mandibular Distraction to Avoid Tracheostomy in KAT6B-related Gene Disorders
Authors: Bacos Jonathan , Maduekwe Uma , Janes Lindsay , Gosain Arun K.
Published: October 2020

Previously, severe upper airway obstruction in patients with retrognathia and glossoptosis has been managed with tracheostomy. However, tracheostomy is associated with significant morbidity. In recent years, mandibular distraction has become an alternative management strategy in infants, but these applications have been limited to patient populations with retrognathia and glossoptosis. The authors present 2 unique cases of patients with KAT6B-related gene disorders, who present with a paradox of tongue-based airway obstruction in the absence of retrognathia. In both cases mandibular distraction osteogenesis with an obliquely oriented vector was successfully performed and both children avoided the need for tracheostomy.
Tailoring Research Recruitment for Acute Care Settings
Authors: Friz Amanda M. , Benson Clark , Mullen Shannon , Block Laura , Gilmore-Bykovskyi Andrea
Published: October 2020

Background:

There is a pressing need to increase enrollment and representation in Alzheimer’s disease and related dementia (ADRD) research. Current recruitment approaches focus largely on clinic and community settings, with minimal engagement of acute care environments despite their broad use across diverse populations. The objectives of this study were to examine views, preferences, and recommendations regarding acute care–based ADRD research recruitment among persons with dementia and their caregivers.

Methods:

The authors conducted semistructured interviews with recently hospitalized persons with dementia (N=3) and family caregivers (N=28). Interviews were analyzed using thematic analysis.

Findings:

All participants endorsed acute care as an appropriate time for recruitment into ADRD research studies and identified important elements of an appropriately tailored recruitment approach and an interpersonally effective research staff. Participants emphasized that this approach should consider the acute care context with respect to participant situation, uncertainty, and timing. Participant suggestions informed the design of a 5-step process to guide ADRD research recruitment in the context of acute care.

Discussion:

Findings provide valuable insights from people with dementia and their caregivers regarding opportunities for research engagement surrounding acute care and can inform expanded recruitment in these settings.
Uncovering biomarkers during therapeutic neuromodulation with PARRM: Period-based Artifact Reconstruction and Removal Method
Authors: Dastin-van Rijn Evan M. , Provenza Nicole R. , Calvert Jonathan S. , Gilron Ro’ee , Allawala Anusha B. , Darie Radu , Syed Sohail , Matteson Evan , Vogt Gregory S. , Avendano-Ortega Michelle , Vasquez Ana C. , Ramakrishnan Nithya , Oswalt Denise N. , Bijanki Kelly R. , Wilt Robert , Starr Philip A. , Sheth Sameer A. , Goodman Wayne K. , Harrison Matthew T. , Borton David A.
Published: October 2020

Advances in device development have enabled concurrent stimulation and recording at adjacent locations in the central nervous system. However, stimulation artifacts obscure the sensed underlying neural activity. Here, we developed a novel method, termed Period-based Artifact Reconstruction and Removal Method (PARRM), to remove stimulation artifacts from neural recordings by leveraging the exact period of stimulation to construct and subtract a high-fidelity template of the artifact. Benchtop saline experiments, computational simulations, five uniquein vivoparadigms across animal and human studies, and an obscured movement biomarker were used for validation. Performance was found to exceed that of state-of-the-art filters in recovering complex signals without introducing contamination. PARRM has several advantages: it is 1) superior in signal recovery; 2) easily adaptable to several neurostimulation paradigms; and 3) low-complexity for future on-device implementation. Real-time artifact removal via PARRM will enable unbiased exploration and detection of neural biomarkers to enhance efficacy of closed-loop therapies.

Online, real-time artifact removal via PARRM will enable unbiased exploration of neural biomarkers previously obscured by stimulation artifact.
The Power of Social Information in Ant-Colony House-Hunting: A Computational Modeling Approach
Authors: Zhao Jiajia , Lynch Nancy , Pratt Stephen C.
Published: October 2020

The decentralized cognition of animal groups is both a challenging biological problem and a potential basis for bio-inspired design. The understanding of these systems and their application can benefit from modeling and analysis of the underlying algorithms. In this study, we define a modeling framework that can be used to formally represent all components of such algorithms. As an example application of the framework, we adapt to it the much-studied house-hunting algorithm used by emigrating colonies ofTemnothoraxants to reach consensus on a new nest. We provide a Python simulator that encodes accurate individual behavior rules and produces simulated behaviors consistent with empirical observations, on both the individual and group levels. Critically, through multiple simulated experiments, our results highlight the value of individual sensitivity to site population in ensuring consensus. With the help of this social information, our model successfully reproduces experimental results showing the high cognitive capacity of colonies and their rational time investment during decision-making, and also predicts the pros and cons of social information with regard to the colonies’ ability to avoid and repair splits. Additionally, we use the model to make new predictions about several unstudied aspects of emigration behavior. Our results indicate a more complex relationship between individual behavior and the speed/accuracy trade-off than previously appreciated. The model proved relatively weak at resolving colony divisions among multiple sites, suggesting either limits to the ants’ ability to reach consensus, or an aspect of their behavior not captured in our model. It is our hope that these insights and predictions can inspire further research from both the biology and computer science community.
Human USP18 is regulated by miRNAsviathe 3’UTR, a sequence duplicated in lincRNA genes residing in chr22q11.21
Authors: Rubino Erminia , Cruciani Melania , Tchitchek Nicolas , Le Tortorec Anna , Rolland Antoine D. , Veli Önay , Vallet Leslie , Gaggi Giulia , Michel Frédérique , Dejucq-Rainsford Nathalie , Pellegrini Sandra
Published: October 2020

Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of interferon-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here we explored post-transcriptional regulation of USP18 by microRNAs (miRNAs) and identified four miRNAs (miR-24-3p, miR-191-5p, miR-423-5pandmiR-532-3p) that efficiently targetUSP18through binding to the 3’UTR. Among these, three miRNAs are particularly enriched in circulating monocytes which exhibit low baselineUSP18. Intriguingly, theUSP183’UTR sequence is duplicated in human and chimpanzee genomes. In human, we found several copies of the 3’UTR that are embedded in long intergenic non-coding (linc) RNA genes residing in chr22q11.21 and exhibiting a tissue-specific expression pattern. Interestingly, one of these lincRNAs (here namedlinc-UR-B1) is uniquely and highly expressed in testis. RNA-seq data analyses from testicular cell subsets revealed a positive correlation betweenlinc-UR-B1andUSP18expression in spermatocytes and spermatids. Overall, our findings uncover a set of miRNAs and lincRNAs, which may be part of a network evolved to fine-tune baseline USP18, particularly in cell types where IFN responsiveness needs to be tightly controlled.

SIGNIFICANT STATEMENT

USP18 is a non-redundant negative feedback regulator of type I IFN signaling and a key determinant of cell responsiveness to IFN. How baseline USP18 is set in different human cell types is ill defined. We identified three microRNAs that restrain USP18 level notably in primary monocytes through binding the 3’UTR. We found several copies of the USP18 3’UTR embedded in long intergenic non-coding (linc) RNAs which reside in a complex region of human chromosome 22. These lincRNAs are expressed in a tissue-specific manner. We describe one lincRNA expressed only in testis, and most notably in germ cells. Correlative analyses suggest that microRNAs and lincRNAs may form a network controlling baseline USP18 and IFN responsiveness.
Computation of single-cell metabolite distributions using mixture models
Authors: Tonn Mona K. , Thomas Philipp , Barahona Mauricio , Oyarzún Diego A.
Published: October 2020

Metabolic heterogeneity is widely recognised as the next challenge in our understanding of non-genetic variation. A growing body of evidence suggests that metabolic heterogeneity may result from the inherent stochasticity of intracellular events. However, metabolism has been traditionally viewed as a purely deterministic process, on the basis that highly abundant metabolites tend to filter out stochastic phenomena. Here we bridge this gap with a general method for prediction of metabolite distributions across single cells. By exploiting the separation of time scales between enzyme expression and enzyme kinetics, our method produces estimates for metabolite distributions without the lengthy stochastic simulations that would be typically required for large metabolic models. The metabolite distributions take the form of Gaussian mixture models that are directly computable from single-cell expression data and standard deterministic models for metabolic pathways. The proposed mixture models provide a systematic method to predict the impact of biochemical parameters on metabolite distributions. Our method lays the groundwork for identifying the molecular processes that shape metabolic heterogeneity and its functional implications in disease.
The Poisson-lognormal model as a versatile framework for the joint analysis of species abundances
Authors: Chiquet Julien , Mariadassou Mahendra , Robin Stéphane
Published: October 2020

Joint Species Abundance Models (JSDM) provide a general multivariate framework to study the joint abundances of all species from a community. JSDM account for both structuring factors (environmental characteristics or gradients, such as habitat type or nutrient availability) and potential interactions between the species (competition, mutualism, parasitism, etc.), which is instrumental in disentangling meaningful ecological interactions from mere statistical associations.

Modeling the dependency between the species is challenging because of the count-valued nature of abundance data and most JSDM rely on Gaussian latent layer to encode the dependencies between species in a covariance matrix. The multivariate Poisson-lognormal (PLN) model is one such model, which can be viewed as a multivariate mixed Poisson regression model. The inference of such models raises both statistical and computational issues, many of which were solved in recent contributions using variational techniques and convex optimization.

The PLN model turns out to be a versatile framework, within which a variety of analyses can be performed, including multivariate sample comparison, clustering of sites or samples, dimension reduction (ordination) for visualization purposes, or inference of interaction networks. This paper presents the general PLN framework and illustrates its use on a series a typical experimental datasets. All the models and methods are implemented in theRpackagePLNmodels, available fromcran.r-project.org.
Mild traumatic brain injury induces transient, sequential increases in proliferation, neuroblasts/immature neurons, and cell survival: a time course study in the male mouse dentate gyrus
Authors: Clark LR , Yun S , Acquah NK , Kumar PL , Metheny HE , Paixao RCC , Cohen AS , Eisch AJ
Published: October 2020

Mild traumatic brain injuries (mTBIs) are prevalent worldwide. mTBIs can impair hippocampal-based functions such as memory and cause network hyperexcitability of the dentate gyrus (DG), a key entry point to hippocampal circuitry. One candidate for mediating mTBI-induced hippocampal cognitive and physiological dysfunction is injury-induced changes in the process of DG neurogenesis. There are conflicting results on how TBI impacts the process of DG neurogenesis; this is not surprising given that both the neurogenesis process and the post-injury period are dynamic, and that the quantification of neurogenesis varies widely in the literature. Even within the minority of TBI studies focusing specifically on mild injuries, there is disagreement about if and how mTBI changes the process of DG neurogenesis. Here we utilized a clinically-relevant rodent model of mTBI (lateral fluid percussion injury, LFPI), gold-standard markers and quantification of the neurogenesis process, and three time points post-injury to generate a comprehensive picture of how mTBI affects adult hippocampal DG neurogenesis. Male C57BL/6J mice (6-8 weeks old) received either sham surgery or mTBI via LFPI. Proliferating cells, neuroblasts/immature neurons, and surviving cells were quantified via stereology in DG subregions (subgranular zone [SGZ], outer granule cell layer [oGCL], molecular layer, and hilus) at short-term (3 days post-injury, dpi), intermediate (7 dpi), and long-term (31 dpi) time points. The data suggest this model of mTBI induces transient, sequential increases in ipsilateral SGZ/GCL proliferating cells, neuroblasts/immature neurons, and surviving cells which are suggestive of mTBI-induced neurogenesis. In contrast to these ipsilateral hemisphere findings, measures in the contralateral hemisphere were not increased in key neurogenic DG subregions after LFPI. Our work in this mTBI model is in line with most literature on other and more severe models of TBI in showing TBI stimulates the process of DG neurogenesis. However, as our DG data in mTBI provide temporal, subregional, and neurogenesis-stage resolution, these data are important to consider in regard to the functional importance of TBI-induction of the neurogenesis process and future work assessing the potential of replacing and/or repairing DG neurons in the brain after TBI.
Robust switches in thalamic network activity require a timescale separation between sodium and T-type calcium channel activations
Authors: Jacquerie Kathleen , Drion Guillaume
Published: October 2020

Switches in brain states, synaptic plasticity and neuromodulation are fundamental processes in our brain that take place concomitantly across several spatial and timescales. All these processes target neuron intrinsic properties and connectivity to achieve specific physiological goals, raising the question of how they can operate without interfering with each other. Here, we highlight the central importance of a timescale separation in the activation of sodium and T-type calcium channels to sustain robust switches in brain states in thalamic neurons that are compatible with synaptic plasticity and neuromodulation. We quantify the role of this timescale separation by comparing the robustness of rhythms of six published conductance-based models at the cellular, circuit and network levels. We show that robust rhythm generation requires a T-type calcium channel activation whose kinetics are situated between sodium channel activation and T-type calcium channel inactivation in all models despite their quantitative differences.
A fluorescent sensor for spatiotemporally resolved endocannabinoid dynamicsin vitroandin vivo
Authors: Dong Ao , He Kaikai , Dudok Barna , Farrell Jordan S , Guan Wuqiang , Liput Daniel J , Puhl Henry L , Cai Ruyi , Duan Jiali , Albarran Eddy , Ding Jun , Lovinger David M , Li Bo , Soltesz Ivan , Li Yulong
Published: October 2020

Endocannabinoids (eCBs) are retrograde neuromodulators that play an important role in a wide range of physiological processes; however, the release andin vivodynamics of eCBs remain largely unknown, due in part to a lack of suitable probes capable of detecting eCBs with sufficient spatiotemporal resolution. Here, we developed a new eCB sensor called GRABeCB2.0. This genetically encoded sensor consists of the human CB1 cannabinoid receptor fused to circular-permutated EGFP, providing cell membrane trafficking, second-resolution kinetics, high specificity for eCBs, and a robust fluorescence response at physiological eCB concentrations. Using the GRABeCB2.0sensor, we monitored evoked changes in eCB dynamics in both cultured neurons and acute brain slices. Interestingly, in cultured neurons we also observed spontaneous compartmental eCB transients that spanned a distance of approximately 11 μm, suggesting constrained, localized eCB signaling. Moreover, by expressing GRABeCB2.0in the mouse brain, we readily observed foot shock-elicited and running-triggered eCB transients in the basolateral amygdala and hippocampus, respectively. Lastly, we used GRABeCB2.0in a mouse seizure model and observed a spreading wave of eCB release that followed a Ca2+wave through the hippocampus. Thus, GRABeCB2.0is a robust new probe for measuring the dynamics of eCB release under both physiological and pathological conditions.
TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42in HMC3 cells
Authors: Akhter Rumana , Shao Yvonne , Formica Shane , Khrestian Maria , Bekris Lynn M.
Published: October 2020

Alzheimer’s disease (AD) is characterized by the accumulation in the brain of extracellular amyloid β (Aβ) plaques as well as intraneuronal inclusions (neurofibrillary tangles) consisting of total tau and phosphorylated tau. Also present are dystrophic neurites, loss of synapses, neuronal death, and gliosis. AD genetic studies have highlighted the importance of inflammation in this disease by identifying several risk associated immune response genes, including TREM2. TREM2 has been strongly implicated in basic microglia function including, phagocytosis, apoptosis, and the inflammatory response to Aβ in mouse brain and primary cells. These studies show that microglia are key players in the response to Aβ and in the accumulation of AD pathology. However, details are still missing about which apoptotic or inflammatory factors rely on TREM2 in their response to Aβ, especially in human cell lines. Given these previous findings our hypothesis is that TREM2 influences the response to Aβ toxicity by enhancing phagocytosis and inhibiting both the BCL-2 family of apoptotic proteins and pro-inflammatory cytokines. Aβ42treatment of the human microglial cell line, HMC3 cells, was performed and TREM2 was overexpressed or silenced and the phagocytosis, apoptosis and inflammatory response were evaluated. Results indicate that a robust phagocytic response to Aβ after 24 hours requires TREM2 in HMC3 cells. Also, TREM2 inhibits Aβ induced apoptosis by activating the Mcl-1/Bim complex. TREM2 is involved in activation of IP-10, MIP-1a, and IL-8, while it inhibits FGF-2, VEGF and GRO. Taken together, TREM2 plays a role in enhancing the microglial functional response to Aβ toxicity in HMC3 cells. This novel information suggests that therapeutic strategies that seek to activate TREM2 may not only enhance phagocytosis, but it may also inhibit beneficial inflammatory factors, emphasizing the need to define TREM2-related inflammatory activity in not only mouse models of AD, but also in human AD.
Atypical molecular basis for drug resistance to mitochondrial function inhibitors inPlasmodium falciparum
Authors: Painter Heather J. , Morrisey Joanne M. , Mather Michael W. , Orchard Lindsey M. , Luck Cuyler , Smilkstein Martin J. , Riscoe Michael K. , Vaidya Akhil B. , Llinás Manuel
Published: October 2020

The continued emergence of drug-resistantPlasmodium falciparumparasites hinders global attempts to eradicate malaria, emphasizing the need to identify new antimalarial drugs. Attractive targets for chemotherapeutic intervention are the cytochrome (cyt)bc1complex, which is an essential component of the mitochondrial electron transport chain (mtETC) necessary for ubiquinone recycling and mitochondrially localized dihydroorotate dehydrogenase (DHODH) critical forde novopyrimidine synthesis. Despite the essentiality of this complex, resistance to a novel acridone class of compounds targeting cytbc1was readily attained, resulting in a parasite strain (SB1-A6) that was pan-resistant to both mtETC and DHODH inhibitors. Here we describe the molecular mechanism behind the resistance of the SB1-A6 parasite line which lacks the common cytbc1point mutations characteristic of resistance to mtETC inhibitors. Using Illumina whole-genome sequencing, we have identified both a copy number variation (∼2x) and a single-nucleotide polymorphism (C276F) associated withpfdhodhin SB1-A6. We have characterized the role of both genetic lesions by mimicking the copy number variation via episomal expression ofpfdhodhand introducing the identified SNP using CRISPR/Cas9 and assessed their contributions to drug resistance. Although both of these genetic polymorphisms have been previously identified as contributing to both DSM-1 (1) and atovaquone resistance (2, 3), SB1-A6 represents a unique genotype in which both alterations are present in a single line, suggesting that the combination contributes to the pan-resistant phenotype. This novel mechanism of resistance to mtETC inhibition has critical implications for the development of future drugs targeting thebc1complex orde novopyrimidine synthesis that could help guide future anti-malarial combination therapies and reduce the rapid development of drug resistance in the field.
Attractive internuclear force drives the collective behavior of nuclear arrays inDrosophilaembryos
Authors: Wu Xiaoxuan , Kong Kakit , Xiao Wenlei , Liu Feng
Published: October 2020

The emerging collective behaviors during embryogenesis play an important role in precise and reproducible morphogenesis. An important question in the study of collective behavior is what rule underlies the emerging pattern. Here we use theDrosophilaembryo as a test tube to study this question. We focus on the nuclear array without membrane separation on the embryo periphery from the nuclear cycle (NC) 11 to NC14. After live imaging with light sheet microscopy, we extract the nuclear trajectory, speed, and internuclear distance with an automatic nuclear tracing method. We find that the nuclear speed shows a period of standing waves along the anterior-posterior (AP) axis after each metaphase as the nuclei collectively migrate towards the embryo poles and partially move back. And the maximum nuclear speed dampens by 38% in the second half of the standing wave. Moreover, the nuclear density is 35% higher in the middle than the pole region of the embryo during the S phase of NC11-NC14. To find mechanical rules controlling the collective motion and packing patterns of the nuclear array, we use the deep neural network (DNN) to learn the force field from data. We find two potential strong nuclear-age-dependent force fields, i.e., the repulsive or attractive force field. Simulations with the particle-based model indicate that only if the net internuclear force is attractive and increases with distance, the pseudo-synchronous mitotic wave in a nuclear array with lower nuclear density in embryo poles can drive the collective motion with the damped standing wave of the nuclear speed, and the collective nuclear motion, in turn, maintains the non-uniform nuclear density.
Surveillance of densoviruses and mesomycetozoans inhabiting grossly normal tissues of three New Zealand asteroid species
Authors: Hewson Ian , Sewell Mary A.
Published: October 2020

Asteroid wasting events and mass mortality have occurred for over a century. We currently lack a fundamental understanding of the microbial ecology of asteroid disease, with disease investigations hindered by sparse information about the microorganisms associated with grossly normal specimens. We surveilled viruses and protists associated with grossly normal specimens of three asteroid species (Patiriella regularis, Stichaster australis, Coscinasterias muricata) on the North Island, New Zealand, using metagenomes prepared from virus and ribosome-sized material. We discovered several densovirus-like genome fragments in our RNA and DNA metagenomic libraries. Subsequent survey of their prevalence within populations by quantitative PCR (qPCR) demonstrated their occurrence in only a few (13 %) specimens (n = 36). Survey of large and small subunit rRNAs in metagenomes revealed the presence of a mesomycete (most closely matchingIchthyosporeasp.). Survey of large subunit prevalence and load by qPCR revealed that it is widely detectable (80%) and present predominately in body wall tissues across all 3 species of asteroid. Our results raise interesting questions about the roles of these microbiome constituents in host ecology and pathogenesis under changing ocean conditions.
A colony-level optimization model provides a potential mechanism for the evolution of novel castes in eusocial ant colonies
Authors: Nag Suryadeepto , Bhat Ananda Shikhara
Published: October 2020

Ant species often have multiple morphologically distinct ‘castes’ within a single colony. Given that most of these castes are involved in non-reproductive tasks, and since such individuals thus never reproduce, the question of how ant castes can evolve is a non-trivial one. Over the years, several models have been proposed in order to explain the evolution of castes in ant colonies. Here, we attempt to answer this question using an economics-based approach, developing an optimization model that implements adaptation and selection at the colony level. We argue that due to the nature of ant colonies, selection is shifted to the group level, and, due to this, individual ants are sheltered from negative selection. We show that our framework can explain the evolution of novel castes in ant colonies, and discuss the novelty of our model with regard to previous models that have been proposed. We also show that our model is consistent with several empirical observations of ant colonies.
Phylogeny, classification, and character evolution of tribe Citharexyleae (Verbenaceae)
Authors: Frost Laura A. , O’Leary Nataly , Lagomarsino Laura P. , Tank David C. , Olmstead Richard G.
Published: October 2020

Premise of the study

Tribe Citharexyleae comprises three genera:Baillonia, Citharexylum, andRehdera. While there is good support for these genera as a clade, relationships between genera remain unresolved due to low sampling of the largest genus,Citharexylum. A molecular phylogenetic approach was taken to resolve intergeneric relationships in Citharexyleae and infrageneric relationships inCitharexylum.

Methods

Seven chloroplast regions, two nuclear ribosomal spacers, and six low-copy nuclear loci were analyzed for 64 species of Citharexyleae. Phylogenetic analyses were conducted using maximum likelihood, Bayesian inference, and Bayesian multi-species coalescent approaches. Habit, presence/absence of thorns, inflorescence architecture, flower color, fruit color, and geography were examined to identify diagnostic characters for clades withinCitharexylum.

Key results

Intergeneric relationships resolvedRehderaas sister toCitharexylumandBaillonianested withinCitharexylum. Two species,C. oleinumandC. tetramerum, fell outside of Citharexyleae close to tribe Duranteae. There is strong support for seven clades withinCitharexylum, each characterized by a unique combination of geography, fruit color/maturation, and inflorescence architecture.

Conclusions

Bailloniais included inCitharexylum; Rehderais retained as a distinct genus. A subgeneric classification forCitharexylumis proposed.
Alteration of gut microbiota with a broad-spectrum antibiotic does not impair maternal care in the European earwig
Authors: Van Meyel Sophie , Devers Séverine , Dupont Simon , Dedeine Franck , Meunier Joël
Published: October 2020

Abstract

The microbes residing within the gut of an animal host often increase their own fitness by modifying their host’s physiological, reproductive, and behavioural functions. Whereas recent studies suggest that they may also shape host sociality and therefore have critical effects on animal social evolution, the impact of the gut microbiota on maternal care remains unexplored. This is surprising, as this behaviour is widespread among animals, often determines the fitness of both juveniles and parents, and is essential in the evolution of complex animal societies. Here, we tested whether life-long alterations of the gut microbiota with rifampicin - a broad-spectrum antibiotic - impair pre- and post-hatching maternal care in the European earwig. Our results first confirm that rifampicin altered the mothers’ gut microbial communities and indicate that the composition of the gut microbiota differs before and after egg care. Contrary to our predictions, however, the rifampicin-induced alterations of the gut microbiota did not modify pre- or post-hatching care. Independent of maternal care, rifampicin increased the females’ feces production and resulted in lighter eggs and juveniles. By contrast, rifampicin altered none of the other 21 physiological, reproductive and longevity traits measured over the 300 days of a female’s lifetime. Overall, these findings reveal that altering the gut microbiota with a large spectrum antibiotic such as rifampicin does not necessarily affect host sociality. They also emphasize that not all animals have evolved a co-dependence with their microbiota and call for caution when generalizing the central role of gut microbes in host biology.