bluuebunny/crossref_metadata_2025 huggingface dataset:
A Mixed-Effects Model of Associations Between Interleukin-6 and Hippocampal Volume
Authors: Harrell Erin R , Bui Chuong , Newman Sharlene D ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: October 2021

Previous studies report hippocampal volume loss can help predict conversion from normative aging to mild cognitive impairment to dementia. Additionally, a growing literature indicates that stress-related allostatic load may increase disease vulnerability. The current study examined the relationship between stress-related cytokines (ie, interleukin-6 [IL-6]), cognition as measured by Mini-Mental State Examination (MMSE) scores, and hippocampal volume. Mixed models were employed to examine both within- (across time) and between-subject effects of IL-6 and hippocampal volume on MMSE score among 566 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The within-subject analysis found left hippocampal volume significantly (p = .009) predicted MMSE score. Between-subject analysis found the effect of IL-6 on MMSE was moderated by right hippocampal volume (p = .001). These results replicate previous findings and also extend prior work demonstrating stress-related cytokines may play a role in Alzheimer’s disease progression.
Tres desafíos de legitimidad del Sistema Interamericano de Derechos HumanosThree legitimacy challenges to the Inter-American System of Human Rights
Authors: Bernal Carlos
Published: October 2021

This article analyses three core challenges that hinder the legitimacy of the Inter-American System of Human Rights. They relate to the Inter-American standards, the observance of due process, and the nature and proportionality of compensatory remedies. The analysis accounts for challenges, and outlines a proposal for overcoming them as well.
Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells
Authors: Jagoda Evelyn , Xue James R , Reilly Steven K , Dannemann Michael , Racimo Fernando , Huerta-Sanchez Emilia , Sankararaman Sriram , Kelso Janet , Pagani Luca , Sabeti Pardis C , Capellini Terence D
Published: October 2021

Although some variation introgressed from Neanderthals has undergone selective sweeps, little is known about its functional significance. We used a Massively Parallel Reporter Assay (MPRA) to assay 5,353 high-frequency introgressed variants for their ability to modulate the gene expression within 170 bp of endogenous sequence. We identified 2,548 variants in active putative cis-regulatory elements (CREs) and 292 expression-modulating variants (emVars). These emVars are predicted to alter the binding motifs of important immune transcription factors, are enriched for associations with neutrophil and white blood cell count, and are associated with the expression of genes that function in innate immune pathways including inflammatory response and antiviral defense. We combined the MPRA data with other data sets to identify strong candidates to be driver variants of positive selection including an emVar that may contribute to protection against severe COVID-19 response. We endogenously deleted two CREs containing expression-modulation variants linked to immune function, rs11624425 and rs80317430, identifying their primary genic targets as ELMSAN1, and PAN2 and STAT2, respectively, three genes differentially expressed during influenza infection. Overall, we present the first database of experimentally identified expression-modulating Neanderthal-introgressed alleles contributing to potential immune response in modern humans.
3DSNP 2.0: update and expansion of the noncoding genomic variant annotation database
Authors: Quan Cheng , Ping Jie , Lu Hao , Zhou Gangqiao , Lu Yiming
Published: October 2021

The rapid development of single-molecule long-read sequencing (LRS) and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) technologies presents both challenges and opportunities for the annotation of noncoding variants. Here, we updated 3DSNP, a comprehensive database for human noncoding variant annotation, to expand its applications to structural variation (SV) and to implement variant annotation down to single-cell resolution. The updates of 3DSNP include (i) annotation of 108 317 SVs from a full spectrum of functions, especially their potential effects on three-dimensional chromatin structures, (ii) evaluation of the accessible chromatin peaks flanking the variants across 126 cell types/subtypes in 15 human fetal tissues and 54 cell types/subtypes in 25 human adult tissues by integrating scATAC-seq data and (iii) expansion of Hi-C data to 49 human cell types. In summary, this version is a significant and comprehensive improvement over the previous version. The 3DSNP v2.0 database is freely available at https://omic.tech/3dsnpv2/.
piRBase: integrating piRNA annotation in all aspects
Authors: Wang Jiajia , Shi Yirong , Zhou Honghong , Zhang Peng , Song Tingrui , Ying Zhiye , Yu Haopeng , Li Yanyan , Zhao Yi , Zeng Xiaoxi , He Shunmin , Chen Runsheng
Published: October 2021

Piwi-interacting RNAs are a type of small noncoding RNA that have various functions. piRBase is a manually curated resource focused on assisting piRNA functional analysis. piRBase release v3.0 is committed to providing more comprehensive piRNA related information. The latest release covers >181 million unique piRNA sequences, including 440 datasets from 44 species. More disease-related piRNAs and piRNA targets have been collected and displayed. The regulatory relationships between piRNAs and targets have been visualized. In addition to the reuse and expansion of the content in the previous version, the latest version has additional new content, including gold standard piRNA sets, piRNA clusters, piRNA variants, splicing-junction piRNAs, and piRNA expression data. In addition, the entire web interface has been redesigned to provide a better experience for users. piRBase release v3.0 is free to access, browse, search, and download at http://bigdata.ibp.ac.cn/piRBase.
SPIRE—a software tool for bicontinuous phase recognition: application for plastid cubic membranes
Authors: Hain Tobias M , Bykowski Michał , Saba Matthias , Evans Myfanwy E , Schröder-Turk Gerd E , Kowalewska Łucja
Published: October 2021

Bicontinuous membranes in cell organelles epitomize nature’s ability to create complex functional nanostructures. Like their synthetic counterparts, these membranes are characterized by continuous membrane sheets draped onto topologically complex saddle-shaped surfaces with a periodic network-like structure. Their structure sizes, (around 50–500 nm), and fluid nature make transmission electron microscopy (TEM) the analysis method of choice to decipher their nanostructural features. Here we present a tool, Surface Projection Image Recognition Environment (SPIRE), to identify bicontinuous structures from TEM sections through interactive identification by comparison to mathematical “nodal surface” models. The prolamellar body (PLB) of plant etioplasts is a bicontinuous membrane structure with a key physiological role in chloroplast biogenesis. However, the determination of its spatial structural features has been held back by the lack of tools enabling the identification and quantitative analysis of symmetric membrane conformations. Using our SPIRE tool, we achieved a robust identification of the bicontinuous diamond surface as the dominant PLB geometry in angiosperm etioplasts in contrast to earlier long-standing assertions in the literature. Our data also provide insights into membrane storage capacities of PLBs with different volume proportions and hint at the limited role of a plastid ribosome localization directly inside the PLB grid for its proper functioning. This represents an important step in understanding their as yet elusive structure–function relationship.
Single-cell genomics in plants: current state, future directions, and hurdles to overcome
Authors: Cuperus Josh T
Published: October 2021

Single-cell genomics has the potential to revolutionize the study of plant development and tissue-specific responses to environmental stimuli by revealing heretofore unknown players and gene regulatory processes. Here, I focus on the current state of single-cell genomics in plants, emerging technologies and applications, in addition to outlining possible future directions for experiments. I describe approaches to enable cheaper and larger experiments and technologies to measure multiple types of molecules to better model and understand cell types and their different states and trajectories throughout development. Lastly, I discuss the inherent limitations of single-cell studies and the technological hurdles that need to be overcome to widely apply single-cell genomics in crops to generate the greatest possible knowledge gain.
qGL3/OsPPKL1 induces phosphorylation of 14-3-3 protein OsGF14b to inhibit OsBZR1 function in brassinosteroid signaling
Authors: Gao Xiuying , Zhang Jiaqi , Cai Guang , Du Huaying , Li Jianbo , Wang Ruqin , Wang Yuji , Yin Jing , Zhang Wencai , Zhang Hongsheng , Huang Ji
Published: October 2021

Brassinosteroids (BRs) play essential roles in regulating plant growth and development, however, gaps still remain in our understanding of the BR signaling network. We previously cloned a grain length quantitative trait locus qGL3, encoding a rice (Oryza sativa L.) protein phosphatase with Kelch-like repeat domain (OsPPKL1), that negatively regulates grain length and BR signaling. To further explore the BR signaling network, we performed phosphoproteomic analysis to screen qGL3-regulated downstream components. We selected a 14-3-3 protein OsGF14b from the phosphoproteomic data for further analysis. qGL3 promoted the phosphorylation of OsGF14b and induced the interaction intensity between OsGF14b and OsBZR1. In addition, phosphorylation of OsGF14b played an important role in regulating nucleocytoplasmic shuttling of OsBZR1. The serine acids (Ser258Ser259) residues of OsGF14b play an essential role in BR-mediated responses and plant development. Genetic and molecular analyses indicated that OsGF14b functions as a negative regulator in BR signaling and represses the transcriptional activation activity of OsBZR1. Collectively, these results demonstrate that qGL3 induces the phosphorylation of OsGF14b, which modulates nucleocytoplasmic shuttling and transcriptional activation activity of OsBZR1, to eventually negatively regulate BR signaling and grain length in rice.
COVID-19 outcomes among pregnant and nonpregnant women at reproductive age in Egypt
Authors: BahaaEldin Hala , El Sood Hanaa Abu , Samy Sahar , Khader Yousef , AbdelFatah Mohamad , Hassany Mohamed , Afifi Salma , Eid Alaa
Published: October 2021

Background

To describe demographic, clinical and epidemiological characteristics of pregnant and nonpregnant women with confirmed COVID-19 at reproductive age and determine risk factors of COVID-19 severe outcomes during pregnancy.

Methods

A retrospective study for females aged 18–49 with confirmed COVID-19 by RT-PCR in Egypt, February–July 2020. Data were obtained from Egypt National Surveillance, bivariate and multivariate analysis for demographic and clinical characteristics and outcomes of COVID-19 between pregnant and nonpregnant women including ICU admission, need for ventilator and death was performed.

Results

A total of 23 095 females were identified, with mean (SD) age of 35.1 (8.1) year. Of those, 408 (1.8%) were pregnant, with mean (SD) age of 29.3 (8.1) years. Compared to nonpregnant, pregnant patients were more likely to be admitted to hospital (OR = 1.7 CI = 1.4–2.1), ICU (OR = 2.4, CI = 1.3–4.3), need ventilator (OR = 3.9, CI = 2.1–7.4) and have severe outcome (OR = 3.0, CI = 1.9–4.7). Factors associated with severe outcome included: pregnancy, age > 30 years, underlying medical conditions, and living in rural areas.

Conclusion

Pregnant women with COVID-19 are at higher risk of severe symptoms and outcome including ICU admission, requiring ventilator and death. To reduce risk of severe outcome, counseling about for seeking medical care and health education about COVID-19 preventive measures should be performed.
Shaping the Future of Social Work Practice in Healthcare: Addressing COVID-19 Needs through Integrated Primary Care
Authors: Dennelly Lauren , Sousa Cindy , Roberts Kate
Published: October 2021

COVID-19 has illustrated the urgency of promoting integrated healthcare as the model of the future, with social workers not only supporting the physical and mental health of providers and patients, but also leading efforts to transform systems, policies, and social work education. Primary care, where the role of social workers is continuing to grow, is a central location for integrating the treatment of medical, social, and behavioral problems. In these settings, social workers can take the lead to meet community needs, assist in public health efforts, and bolster the frontline medical workforce. The following article reflects upon what we as social workers have learned a year into the global pandemic and how we can apply this knowledge to shaping the future of social work in primary care. Authors consider how the multiple medical and psychosocial needs of patients affected by COVID-19 are addressed in primary care through three core functions of social work: providing behavioral healthcare, coordinating care, and undertaking population health-based interventions. Article ends with a discussion about how social work can respond to the urgent task of transforming health within the context of social work practice, policy, and education for the next generation of healthcare social workers.
A CRISPR/Cas9 method facilitates efficient oligo-mediated gene editing in Debaryomyces hansenii
Authors: Strucko Tomas , Andersen Niklas L , Mahler Mikkel R , Martínez José L , Mortensen Uffe H
Published: October 2021

Halophilic and osmotolerant yeast Debaryomyces hansenii has a high potential for cell factory applications due to its resistance to harsh environmental factors and compatibility with a wide substrate range. However, currently available genetic techniques do not allow the full potential of D. hansenii as a cell factory to be harnessed. Moreover, most of the currently available tools rely on the use of auxotrophic markers that are not suitable in wild-type prototrophic strains. In addition, the preferred non-homologous end-joining (NHEJ) DNA damage repair mechanism poses further challenges when precise gene targeting is required. In this study, we present a novel plasmid-based CRISPRCUG/Cas9 method for easy and efficient gene editing of the prototrophic strains of D. hansenii. Our toolset design is based on a dominant marker and facilitates quick assembly of the vectors expressing Cas9 and single or multiple single-guide RNAs (sgRNAs) that provide the possibility for multiplex gene engineering even in prototrophic strains. Moreover, we have constructed NHEJ-deficient D. hansenii that enable our CRISPRCUG/Cas9 tools to support the highly efficient introduction of point mutations and single/double gene deletions. Importantly, we also demonstrate that 90-nt single-stranded DNA oligonucleotides are sufficient for direct repair of DNA breaks induced by sgRNA-Cas9, resulting in precise edits reaching 100% efficiencies. In conclusion, tools developed in this study will greatly advance basic and applied research in D. hansenii. In addition, we envision that our tools can be rapidly adapted for gene editing of other non-conventional yeast species including the ones belonging to the CUG clade.
Dose–response genotoxicity of triclosan in mice: an estimate of acceptable daily intake based on organ toxicity
Authors: Cao Yiyi , Xi Jing , You Xinyue , Liu Weiying , Luan Yang
Published: October 2021

Triclosan (TCS) is widely used and it bioaccumulates in humans. We found that TCS induced DNA damage in TK6 cell in our previous work. Herein, we performed a pilot assay of the TK6 cell/TK gene (TK+/−) mutation assay without metabolic activation for 24 h and found that TCS significantly induced mutation frequency. We further investigated the dose–response toxicity and genotoxicity of TCS. We combined the newly developed Pig-a gene mutation assay with bone marrow micronucleus (MN) test in a 19-day short-term study. ICR mice were administered orally with TCS at six dose levels from 0 to1000 mg/kg/day. We quantitatively assessed the dose–response relationships for the Pig-a assay, MN test, and organ coefficient data for possible points of departure (PoDs) by estimating the benchmark dose using PROAST software. We did not observe elevated Pig-a mutant frequency or MN frequency in TCS-treated mice. But a dose-dependent and statistically significant increase in liver organ coefficient data was observed. The PoD and acceptable daily intake based on organ toxicity were further developed and no greater than 1.82 and 0.00182 mg/kg/day, respectively, indicating that the toxicity of TCS may has been underestimated in previous studies and greater attention should be paid to low-level TCS exposure.
The Moderating Effect of Treatment Engagement on Fear-avoidance Beliefs in People With Chronic Low Back Pain
Authors: Marshall Paul W. , Morrison Natalie M.V. , Mifsud Annaleise , Gibbs Mitchell , Khan Naseeb , Meade Tanya
Published: October 2021

Objectives:

The fear-avoidance model (FAM) is used to explain pain-related disability and design targeted interventions for people with chronic low back pain. While treatment engagement is critical, it is unknown how treatment moderates the FAM.

Methods:

This study examined whether pathways within the FAM were moderated by treatment engagement in 508 people with chronic low back pain. Measures of disability, pain, fear, catastrophizing, anxiety, depression, and self-efficacy were collected through self-report, and descriptors of treatment engaged within the last month (physical activity type, medication, allied and medical health practitioner). Moderated mediation analyses were performed to examine the conditional effect of treatment engagement on fear-avoidance pathways.

Results:

The conditional effect of anxiety on disability was only significant for people who did not report any treatment engagement in the last month (B=1.03, 95% confidence interval: 0.53-1.53, P<0.001). The effect of depression increased for people reporting more different types of treatment in the last month (1 level of treatment increase, B=0.27, 95% confidence interval: 0.05-0.50, P=0.019). Conversely, greater treatment engagement had a positive influence on the mediating effect of self-efficacy. That is, the effect of pain on efficacy reduced with greater treatment engagement, with a concomitant increased effect of self-efficacy on disability.

Discussion:

Clinicians should explore the history and rationale behind patient treatment seeking behavior to ensure this is not reinforcing the negative effects of depressive symptoms on pain-related disability.
Perioperative Intravenous Lidocaine Infusion on Postoperative Recovery in Patients Undergoing Arthroscopic Rotator Cuff Repair Under General Anesthesia
Authors: Kim Seon Ju , Choi Yong Seon , Chun Yong Min , Kim Hye Jin , Han Chunggu , Shin Seokyung
Published: October 2021

Objective:

Arthroscopic rotator cuff repair (ARCR) is known to cause severe postoperative pain that may interfere with recovery. Intravenous (IV) lidocaine has analgesic, anti-inflammatory, and antihyperalgesic effects, and is being used in various types of surgeries. However, the effect of IV lidocaine in ARCR is not well-known.

Materials and Methods:

Ninety patients undergoing ARCR were randomly allocated to receive IV lidocaine (1.5 mg/kg bolus of 1% lidocaine after anesthesia induction followed by a continuous infusion of 2 mg/kg/h up to 1 h after surgery) or an equal volume of saline. In both groups, an IV patient-controlled analgesia (PCA) device was used that contained fentanyl 10 µg/mL, infused at 1 mL/h with a 1 mL bolus dose. The primary outcome was fentanyl requirements given via IV PCA during the first 24 hours after surgery. Perioperative pain scores and functional recovery were assessed as secondary outcomes.

Results:

The amount of fentanyl administered via IV PCA up to 24 hours after surgery was significantly lower in the lidocaine group compared with the control group (329 [256.2 to 428.3] vs. 394.5 [287.0 to 473.0], P=0.037). The number of PCA bolus attempts were lower in the lidocaine group without statistical significance. There were no differences in postoperative pain scores or functional shoulder scores between the 2 groups.

Discussion:

IV lidocaine appears to be helpful in reducing opioid requirements during the acute postoperative period in patients undergoing ARCR. IV lidocaine may be a viable option as a component of multimodal analgesia in ARCR when regional analgesia is not possible.
The Influence of Hypercapnia and Atmospheric Pressure on the Pao 2/Fio 2 Ratio—Pathophysiologic Considerations, a Case Series, and Introduction of a Clinical Tool*
Authors: Gilissen Vincent J. H. S. , Koning Mark V. , Klimek Markus
Published: October 2021

OBJECTIVES:

The ratio between Pao
2 and Fio
2 is used as a marker for impaired oxygenation and acute respiratory distress syndrome classification. However, any discrepancy between Fio
2 and o
2 fraction in the alveolus affects the Pao
2/Fio
2 ratio. Correcting the Pao
2/Fio
2 ratios using the alveolar gas equation may result in an improved reflection of the pulmonary situation. This study investigates the difference between standard and corrected Pao
2/Fio
2 in magnitude, its correlation with the mortality of acute respiratory distress syndrome classification, and trends over time.

DESIGN:

A register and a retrospective study combined with the development of a mathematical model to determine the difference between standard and corrected Pao
2/Fio
2 ratio for various levels of Paco
2 and atmospheric pressure.

SETTING:

ICU in a secondary hospital in The Netherlands.

PATIENTS:

Patients admitted to the ICU for pneumonia or acute respiratory distress syndrome. Register cohort: January 1, 2010, till March 1, 2020 (n = 1008). Retrospective cohort: March 1, 2020, till June 1, 2020 (n = 34).

MEASUREMENTS AND MAIN RESULTS:

The register was used to determine the 7-day ICU mortality per acute respiratory distress syndrome classification based on the standard and corrected Pao
2/Fio
2 ratio. The retrospective dataset correlated the Paco
2 with Pao
2/Fio
2 ratio over time in patients with assumed stable oxygenation. The model demonstrated an increased difference between the standard and corrected Pao
2/Fio
2 ratios by a lower Fio
2 and atmospheric pressure and higher Pao
2 and Paco
2. Reclassification of severe acute respiratory distress syndrome resulted in an increase in mortality from 28.1% for standard Pao
2/Fio
2 to 30.6% for corrected Pao
2/Fio
2 ratios. Acute Physiology and Chronic Health Evaluation scores correlated better with 7-day ICU-mortality when corrected Pao
2/Fio
2 ratio was used for classification. For patients with Fio
2 less than 50% (n = 55), change in Paco
2 correlated with change in Pao
2/Fio
2 ratio (r = –0.388; p = 0.003).

INTERVENTIONS:

A corrected Pao
2/Fio
2 ratio was calculated.

CONCLUSIONS:

Correcting the Pao
2/Fio
2 ratio for the alveolar gas equation predominantly affects patients with high ratios between Pao
2 and Fio
2 and Paco
2 and at low atmospheric pressure. Using the corrected Pao
2/Fio
2 ratio for acute respiratory distress syndrome classification results in improved correlation with the 7-day ICU mortality and increases generalization among acute respiratory distress syndrome studies. The authors provide a free, web-based tool.
Application of Human Adipose-Derived Stem cells for Bone Regeneration of the Skull in Humans
Authors: Torres-Guzman Ricardo A. , Huayllani Maria T. , Avila Francisco R. , Maita Karla , Zubair Abba C. , Quinones-Hinojosa Alfredo , Sarabia-Estrada Rachel , Forte Antonio J.
Published: October 2021

Background:

Archeological archives report cranioplasty as 1 of the oldest surgical procedures; however, it was not until the last century that true advances have been made. Alternative approaches are necessary to achieve optimal closure of the defect with fewer adverse effects. We aim to evaluate the use of human adipose-derived stem cells (hADSCs) alone or seeded in scaffolds as the main treatment for cranial bone defects and to assess human patient outcomes.

Methods:

A systematic review was performed by querying PubMed, Ovid MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature databases with the MeSH terms: “adipose-derived stem cells,” “cranial bone defect,” “stromal vascular factor,” “fat grafting,” as well as synonyms in combinations determined by our search strategy. We included human models that used hADSCs as primary therapy. We excluded studies in languages other than English.

Results:

One hundred ninety-four studies were identified after removal of duplicates. Four articles that used hADSCs as the main therapy to treat calvarial defects in humans were included. One article applied the cell therapy alone, and 3 used β-tricalcium phosphate granules as a scaffold to seed the hADSCs.

Conclusions:

Bone regeneration was reached in a short and intermediate period using autologous hADSCs in humans with no major adverse effects in all 4 articles included. A long-term follow-up study (6 years) exhibited late infections and reabsorption of the β-tricalcium phosphate scaffold seeded with hADSCs.
Digital Volumetric Monitoring of Palate Growth in Children With Cleft Lip and Palate
Authors: Ambrosio Eloá Cristina Passucci , Fusco Nathália dos Santos , Carrara Cleide Felício Carvalho , Bergamo Mariel Tavares , Lourenço Neto Natalino , Cruvinel Thiago , Rios Daniela , Almeida Ana Lucia Pompeia Fraga , Soares Simone , Machado Maria Aparecida Andrade Moreira , Oliveira Thais Marchini
Published: October 2021

This study aimed to evaluate longitudinally the volume of the dental arches in children with unilateral cleft lip and palate before and after the rehabilitative plastic surgeries. This is a longitudinal retrospective study was composed by 102 digitized dental casts of children with unilateral complete cleft lip (G1) and cleft lip and palate (G2). The palate volume was evaluated at 3 periods: preoperative (T1), postoperative 1 (T2), and postoperative 2 (T3). The intra- and inter-examiner reliability was analyzed by Wilcoxon test/Dahlberg formula and interclass correlation coefficient, respectively. The intragroup comparison was analyzed by Wilcoxon test and Friedman test followed by post-hoc Dunn test. Mann–Whitney test was applied for the intergroup comparison (α = 5%). G1 had a significant growth at T2 (P = 0.031). G2 demonstrated a positive development at T2, but decreased at T3 (P = 0.003). The intergroup analysis revealed that G2 showed a greater volume at T1 and T2 (P < 0.0001 and P = 0.0024, respectively). T2-T1 exhibited no statistically significant difference (P = 0.262). In conclusion, there was a volumetric increase in the dental arches after cheiloplasty followed by a reduction after palatoplasty. Further investigations are necessary to validate the preliminary results of the present study.
Infection dynamics in ecosystems: on the interaction between red and grey squirrels, pox virus, pine martens and trees
Authors: Roberts M. G. , Heesterbeek J. A. P.
Published: October 2021

Ecological and epidemiological processes and interactions influence each other, positively and negatively, directly and indirectly. The invasion potential of pathogens is influenced by the ecosystem context of their host species’ populations. This extends to the capacity of (multiple) host species to maintain their (common) pathogen and the way pathogen dynamics are influenced by changes in ecosystem composition. This paper exemplifies these interactions and consequences in a study of red and grey squirrel dynamics in the UK. Differences and changes in background habitat and trophic levels above and below the squirrel species lead to different dynamic behaviour in many subtle ways. The range of outcomes of the different interactions shows that one has to be careful when drawing conclusions about the mechanisms and processes involved in explaining observed phenomena concerning pathogens in their natural environment. The dynamic behaviour also shows that planning interventions, for example for conservation purposes, benefits from understanding the complexity of interactions beyond the particular pathogen and its threatened host species.
The cerebellar anatomy of red junglefowl and white leghorn chickens: insights into the effects of domestication on the cerebellum
Authors: Racicot Kelsey J. , Popic Christina , Cunha Felipe , Wright Dominic , Henriksen Rie , Iwaniuk Andrew N.
Published: October 2021

Domestication is the process by which wild organisms become adapted for human use. Many phenotypic changes are associated with animal domestication, including decreases in brain and brain region sizes. In contrast with this general pattern, the chicken has a larger cerebellum compared with the wild red junglefowl, but what neuroanatomical changes are responsible for this difference have yet to be investigated. Here, we quantified cell layer volumes, neuron numbers and neuron sizes in the cerebella of chickens and junglefowl. Chickens have larger, more folded cerebella with more and larger granule cells than junglefowl, but neuron numbers and cerebellar folding were proportional to cerebellum size. However, chickens do have relatively larger granule cell layer volumes and relatively larger granule cells than junglefowl. Thus, the chicken cerebellum can be considered a scaled-up version of the junglefowl cerebellum, but with enlarged granule cells. The combination of scaling neuron number and disproportionate enlargement of cell bodies partially supports a recent theory that domestication does not affect neuronal density within brain regions. Whether the neuroanatomical changes we observed are typical of domestication or not requires similar quantitative analyses in other domesticated species and across multiple brain regions.
Translational control in neurovascular brain development
Authors: Chalkiadaki Kleanthi , Statoulla Elpida , Markou Maria , Bellou Sofia , Bagli Eleni , Fotsis Theodore , Murphy Carol , Gkogkas Christos G.
Published: October 2021

The human brain carries out complex tasks and higher functions and is crucial for organismal survival, as it senses both intrinsic and extrinsic environments. Proper brain development relies on the orchestrated development of different precursor cells, which will give rise to the plethora of mature brain cell-types. Within this process, neuronal cells develop closely to and in coordination with vascular cells (endothelial cells (ECs), pericytes) in a bilateral communication process that relies on neuronal activity, attractive or repulsive guidance cues for both cell types and on tight-regulation of gene expression. Translational control is a master regulator of the gene-expression pathway and in particular for neuronal and ECs, it can be localized in developmentally relevant (axon growth cone, endothelial tip cell) and mature compartments (synapses, axons). Herein, we will review mechanisms of translational control relevant to brain development in neurons and ECs in health and disease.
A second peirosaurid crocodyliform from the Mid-Cretaceous Kem Kem Group of Morocco and the diversity of Gondwanan notosuchians outside South America
Authors: Nicholl Cecily S. C. , Hunt Eloise S. E. , Ouarhache Driss , Mannion Philip D.
Published: October 2021

Notosuchians are an extinct clade of terrestrial crocodyliforms with a particularly rich record in the late Early to Late Cretaceous (approx. 130–66 Ma) of Gondwana. Although much of this diversity comes from South America, Africa and Indo-Madagascar have also yielded numerous notosuchian remains. Three notosuchian species are currently recognized from the early Late Cretaceous (approx. 100 Ma) Kem Kem Group of Morocco, including the peirosauridHamadasuchus rebouli. Here, we describe two new specimens that demonstrate the presence of at least a fourth notosuchian species in this fauna.Antaeusuchus taouzensisn. gen. n. sp. is incorporated into one of the largest notosuchian-focused character-taxon matrices yet to be compiled, comprising 443 characters scored for 63 notosuchian species, with an increased sampling of African and peirosaurid species. Parsimony analyses run under equal and extended implied weighting consistently recoverAntaeusuchusas a peirosaurid notosuchian, supported by the presence of two distinct waves on the dorsal dentary surface, a surangular which laterally overlaps the dentary above the mandibular fenestra, and a relatively broad mandibular symphysis. Within Peirosauridae,Antaeusuchusis recovered as the sister taxon ofHamadasuchus. However, it differs fromHamadasuchuswith respect to several features, including the ornamentation of the lateral surface of the mandible, the angle of divergence of the mandibular rami, the texture of tooth enamel and the shape of the teeth, supporting their generic distinction. We present a critical reappraisal of the non-South American Gondwanan notosuchian record, which spans the Middle Jurassic–late Eocene. This review, as well as our phylogenetic analyses, indicate the existence of at least three approximately contemporaneous peirosaurid lineages within the Kem Kem Group, alongside other notosuchians, and support the peirosaurid affinities of the ‘trematochampsid’Miadanasuchus oblitafrom the Maastrichtian of Madagascar. Furthermore, the Cretaceous record demonstrates the presence of multiple lineages of approximately contemporaneous notosuchians in several African and Madagascan faunas, and supports previous suggestions regarding an undocumented pre-Aptian radiation of Notosuchia. By contrast, the post-Cretaceous record is depauperate, comprising rare occurrences of sebecosuchians in north Africa prior to their extirpation.
Mitigating the externality of diseases of poverty through health aid
Authors: Jnawali Kamal , Tyshenko Michael G. , Oraby Tamer
Published: October 2021

Externality exists in healthcare when an individual benefits from others being healthy as it reduces the probability of getting sick from illness. Healthy workers are considered to be the more productive labourers leading to a country’s positive economic growth over time. Several research studies have modelled disease transmission and its economic impact on a single country in isolation. We developed a two-country disease-economy model that explores disease transmission and cross-border infection of disease for its impacts. The model includes aspects of a worsening and rapid transmission of disease juxtaposed by positive impacts to the economy from tourism. We found that high friction affects the gross domestic product (GDP) of the lower-income country more than the higher-income country. Health aid from one country to another can substantially help grow the GDP of both countries due to the positive externality of disease reduction. Disease has less impact to both economies if the relative cost of treatment over an alternative (e.g. vaccination) is lower than the baseline value. Providing medical supplies to another country, adopting moderate friction between the countries, and finding treatments with lower costs result in the best scenario to preserve the GDP of both countries.
Density-dependent effects on reproductive output in a capital breeding carnivore, the northern elephant seal (Mirounga angustirostris)
Authors: Holser Rachel R. , Crocker Daniel E. , Robinson Patrick W. , Condit Richard , Costa Daniel P.
Published: October 2021

All organisms face resource limitations that will ultimately restrict population growth, but the controlling mechanisms vary across ecosystems, taxa, and reproductive strategies. Using four decades of data, we examine how variation in the environment and population density affect reproductive outcomes in a capital-breeding carnivore, the northern elephant seal (Mirounga angustirostris). This species provides a unique opportunity to examine the relative importance of resource acquisition and density-dependence on breeding success. Capital breeders accrue resources over large temporal and spatial scales for use during an abbreviated reproductive period. This strategy may have evolved, in part, to confer resilience to short-term environmental variability. We observed density-dependent effects on weaning mass, and maternal age (experience) was more important than oceanographic conditions or maternal mass in determining offspring weaning mass. Together these findings show that the mechanisms controlling reproductive output are conserved across terrestrial and marine systems and vary with population dynamics, an important consideration when assessing the effect of extrinsic changes, such as climate change, on a population.
The moment of tooth: rate, fate and pattern of Pacific lingcod dentition revealed by pulse-chase
Authors: Carr E. M. , Summers A. P. , Cohen K. E.
Published: October 2021

Tooth replacement rates of polyphyodont cartilaginous and bony fishes are hard to determine because of a lack of obvious patterning and maintaining specimens long enough to observe replacement. Pulse-chase is a fluorescent technique that differentially colours developing mineralized tissue. We presentin situtooth replacement rate and position data for the oral and pharyngeal detentions ofOphiodon elongatus(Pacific lingcod). We assessed over 10 000 teeth, in 20 fish, and found a daily replacement rate of about two teeth (3.6% of the dentition). The average tooth is in the dental battery for 27 days. The replacement was higher in the lower pharyngeal jaw (LPJ). We found no difference between replacement rates of feeding and non-feeding fish, suggesting feeding was not a driver of tooth replacement. Lingcod teeth have both a size and location fate; smaller teeth at one spot will not grow into larger teeth, even if a large tooth nearby is lost. We also found increased rates of replacement at the posterior of the LPJ relative to the anterior. We propose that lingcod teeth do not migrate in the jaw as they develop; their teeth are fated in size and location, erupting in their functional position.
New Middle Eocene proboscidean from Togo illuminates the early evolution of the elephantiform-like dental pattern
Authors: Hautier Lionel , Tabuce Rodolphe , Mourlam Mickaël J. , Kassegne Koffi Evenyon , Amoudji Yawovi Zikpi , Orliac Maëva , Quillévéré Frédéric , Charruault Anne-Lise , Johnson Ampah Kodjo Christophe , Guinot Guillaume
Published: October 2021

Africa has played a pivotal role in the evolution of early proboscideans (elephants and their extinct relatives), yet vast temporal and geographical zones remain uncharted on the continent. A long hiatus encompassing most of the Eocene (Ypresian to the Early Priabonian, around 13 Myr timespan) considerably hampers our understanding of the early evolutionary history of the group. It is notably the case with the origin of its most successful members, the Elephantiformes, i.e. all elephant-like proboscideans most closely related to modern elephants. Here, we describe a proboscidean lower molar discovered in Lutetian phosphate deposits from Togo, and name a new genus and species,Dagbatitherium tassyi. We show thatDagbatitheriumdisplays several elephantiform dental characteristics such as a three-layered Schmelzmuster, the presence of a mesoconid, transversely enlarged buccal cusps and the individualization of a third lophid closely appressed to a minute distal cingulid.Dagbatitheriumrepresents a stem Elephantiformes, pushing back the origin of the group by about 10 Myr, i.e. a third of its currently known evolutionary history. More importantly,Dagbatitheriumpotentially unlocks the puzzle of the origin of the unique elephantiform tooth crown organization by bridging a critical temporal and morphological gap between early bunodont incipiently bilophodont proboscidean taxa and more derived elephantiforms.
M protein of subacute sclerosing panencephalitis virus, synergistically with the F protein, plays a crucial role in viral neuropathogenicity
Authors: Satoh Yuto , Higuchi Kurara , Nishikawa Daichi , Wakimoto Hiroshi , Konami Miho , Sakamoto Kento , Kitagawa Yoshinori , Gotoh Bin , Jiang Da-Peng , Hotta Hak , Itoh Masae
Published: October 2021

Subacute sclerosing panencephalitis (SSPE) is a rare fatal neurodegenerative disease caused by a measles virus (MV) variant, SSPE virus, that accumulates mutations during long-term persistent infection of the central nervous system (CNS). Clusters of mutations identified around the matrix (M) protein in many SSPE viruses suppress productive infectious particle release and accelerate cell–cell fusion, which are features of SSPE viruses. It was reported, however, that these defects of M protein function might not be correlated directly with promotion of neurovirulence, although they might enable establishment of persistent infection. Neuropathogenicity is closely related to the character of the viral fusion (F) protein, and amino acid substitution(s) in the F protein of some SSPE viruses confers F protein hyperfusogenicity, facilitating viral propagation in the CNS through cell–cell fusion and leading to neurovirulence. The F protein of an SSPE virus Kobe-1 strain, however, displayed only moderately enhanced fusion activity and required additional mutations in the M protein for neuropathogenicity in mice. We demonstrated here the mechanism for the M protein of the Kobe-1 strain supporting the fusion activity of the F protein and cooperatively inducing neurovirulence, even though each protein, independently, has no effect on virulence. The occurrence of SSPE has been estimated recently as one in several thousand in children who acquired measles under the age of 5 years, markedly higher than reported previously. The probability of a specific mutation (or mutations) occurring in the F protein conferring hyperfusogenicity and neuropathogenicity might not be sufficient to explain the high frequency of SSPE. The induction of neurovirulence by M protein synergistically with moderately fusogenic F protein could account for the high frequency of SSPE.
Covid-19 Epidemic Prediction in France : the Multimodal Case
Authors: Quadrat J.-P.
Published: October 2021

In two previous papers we have proposed models to estimate the Covid-19 epidemic when the number of daily positive cases has a bell shaped form that we call a mode. We have observed that each Covid variant produces this type of epidemic shape at a different moment, resulting in a multimodal epidemic shape. We will show in this document that each mode can still be estimated with models described in the two previous papers provides we replace the cumulated number of positive cases y by the cumulated number of positive cases reduced by a parameter P to be estimated. Therefore denoting z the logarithm of y −P, z follows approximately the differential equation ż = b −azr where a, b, r have also to be estimated from the observed data. We will show the obtained predictions on the four French modes April, November 2020, May and September 2021. The comparison between the prediction obtained before the containment decisions made by the French government and the observed data afterwards suggests the inefficiency of the epidemic lockdowns.
Child mental and behavioral health services during the COVID-19 pandemic: Trends and implications for service outcomes during telehealth expansion
Authors: Riley Elizabeth N. , Cordell Kate D. , Shimshock Stephen M. , Lyons John S. , Vsevolozhskaya Olga A.
Published: October 2021

Transportation to/from care is a significant barrier to healthcare access and utilization. The novel coronavirus pandemic prompted a widespread expansion of telehealth service delivery throughout much of 2020. We used propensity score matching to generate two comparison groups of children served in a large public mental and behavioral health system between (1) April-December 2019 (pre-pandemic; n=2,794), and (2) between April-December 2020 (during the COVID-19 pandemic, n=2,794), followed by longitudinal linear mixed-effects modelling to explore the relationship between caregiver transportation needs and child-level outcomes. Our analyses indicated a statistically significant association between the resolution of caregiver’s transportation needs and children’s clinical improvement in the 2019 (pre-pandemic) sample; there was no such association found in the 2020 (pandemic) sample. Our findings suggest that the use of telehealth may mitigate the effect of caregiver transportation needs on child-level clinical outcomes.
Reversing the miRNA -5p/-3p stoichiometry reveals physiological roles and targets of miR-140 miRNAs
Authors: Cameron Young , Melissa Caffrey , Janton Christopher , Kobayashi Tatsuya
Published: October 2021

The chondrocyte specific miR-140 miRNAs are necessary for normal endochondral bone growth in mice. miR-140 deficiency causes dwarfism and craniofacial deformity. However, the physiologically important targets of miR-140 miRNAs are still unclear. The miR-140 gene (Mir140) encodes three chondrocyte-specific microRNAs, miR-140-5p, derived from the 5’ strand of primary miR-140, and miR140-3p.1 and -3p.2, derived from the 3’ strand of primary miR-140. miR-140-3p miRNAs are ten times more abundant than miR-140-5p likely due to the non-preferential loading of miR-140-5p to Argonaute proteins. To differentiate the role of miR-140-5p and -3p miRNAs in endochondral bone development, two distinct mouse models, miR140-C>T, in which the first nucleotide of miR-140-5p was altered from cytosine to uridine, and miR140-CG, where the first two nucleotides of miR-140-3p were changed to cytosine and guanine, were created. These changes are expected to alter Argonaute protein loading preference of -5p and -3p to increase -5p loading and decrease -3p loading without changing the function of miR140-5p. These models presented a mild delay in epiphyseal development with delayed chondrocyte maturation. Using RNA-sequencing analysis of the two models, direct targets of miR140-5p, including Wnt11, were identified. Disruption of the predicted miR140-5p binding site in the 3’ untranslated region of Wnt11 was shown to increase Wnt11 mRNA expression and caused a modest acceleration of epiphyseal development. These results show that the relative abundance of miRNA-5p and -3p can be altered by changing the first nucleotide of miRNAs in vivo, and this method can be useful to identify physiologically important miRNA targets.
A molecular framework for proximal secondary vein branching in the Arabidopsis thaliana embryo
Authors: Kastanaki Elizabeth , Blanco-Touriñán Noel , Sarazin Alexis , Sturchler Alessandra , Gujas Bojan , Rodriguez-Villalon Antia
Published: October 2021

The establishment of a closed vascular network in foliar organs is achieved through the coordinated specification of newly recruited procambial cells, their proliferation and elongation. An important, yet poorly understood component of this process, is secondary vein branching; a mechanism employed in Arabidopsis thaliana cotyledons to extend vascular tissues throughout the organ’s surface by secondary vein formation.

To investigate the underlying molecular mechanism in vein branching, we analyzed at a single-cell level the discontinuous vein network of cotyledon vascular pattern 2 (cvp2) cvp2-like 1 (cvl1). Utilizing live-cell imaging and genetic approaches we uncovered two distinct branching mechanisms during embryogenesis.

Similar to wild type, distal veins in cvp2 cvl1 embryos emerged from the bifurcation of cell files contained in the midvein. However, the branching events giving rise to proximal veins are absent in this mutant. Restoration of proximal branching in cvp2 cvl1 cotyledons could be achieved by increasing OCTOPUS dosage as well as by silencing of RECEPTOR LIKE PROTEIN KINASE 2 (RPK2) expression. The RPK2-mediated restriction of proximal branching is auxin and CLE-independent.

Our work defines a genetic network conferring plasticity to Arabidopsis embryos to adapt the spatial configuration of vascular tissues to organ growth.