bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction
Authors: Foblets Marie-Claire , Goodale Mark , Sapignoli Maria , Zenker Olaf
Published: October 2021

This chapter provides background information about the aims, objectives, and genesis of the Oxford Handbook of Law and Anthropology as a project of the Law & Anthropology Department, Max Planck Institute of Social Anthropology, Halle, Germany. The volume is structured around five thematic parts: Part I: Global Perspectives on Law and Anthropology; Part II: Recurring Themes in Law and Anthropology; Part III: Anthropology in Law and Legal Practice; Part IV: Anthropology at the Limits of Law; and Part V: Current Directions in Law and Anthropology. The introduction briefly presents each of these parts, sketching out common themes, major debates, and points of intersection and tension in the dynamic interaction of the disciplines of law and anthropology.
Russian Legal Anthropology
Authors: Stammler Florian , Ivanova Aytalina , Donahoe Brian
Published: October 2021

This chapter traces the development of legal anthropology in Russia from imperial times to the present. The authors suggest an innovative research agenda based on thorough consideration of Russia’s long history of legal ethnography, a strong applied orientation, and interdisciplinary cooperation between legal scholars and anthropologists, which ideally would start from the conception of a research project and would include joint fieldwork. They provide a brief overview of the different types of studies of law and society in Russia that claim the name ‘legal anthropology’ (iuridicheskaia antropologiia, antropologiia pravo), but which in fact come out of different disciplines; have different approaches, aims, and orientations; and are not in conversation with one another. On the basis of their fieldwork, the authors identify two contrasting types of societies that exist among the Indigenous peoples of Russia: non-state societies (on the example of the Nenets in the Yamal-Nenets Autonomous Okrug) and almost-state societies (on the basis of the Sakha in the Republic of Sakha (Yakutia)). The examples illustrate why, in one society, non-state legal activity is pragmatically geared towards ‘getting things done’ and solving internal questions, while in the other there is a quest to contribute to legislative processes on a more general, countrywide level. Doing so also means mapping the cultural diversity of the current social life of legal systems that coexist within one state. This has both scholarly and practical value and can lead to wider recognition of legal anthropology as a unified field within and beyond academic scholarship.
Emotion, Affect, and Law
Authors: Clarke Kamari Maxine
Published: October 2021

This chapter introduces perspectives within an emerging anthropology of emotion, affect, and the law, which traces how embodied emotional responses are mobilized socially and politically to reinforce the moral legitimacy of particular legalistic and technocratic solutions to the problem of violence in Africa. Taking the particular case of Dominic Ongwen, a convicted commander of the Ugandan Lord’s Resistance Army who was brought before the International Criminal Court for a range of crimes against humanity, we see the beginning of a trend to demonstrate methodologically an interrelationship between micro processes and macro and historical processes. This happens through a study of the emotive and affective processes that go into the making of individual ‘perpetrators’. But we also see that part of that process involves the necessary connection to the longue durée that makes such racial depictions immediately believable. Through an examination of both the psychosocial and complex historical and political conditions that underscore inter-generational trauma in postcolonial contexts, we see how the intersection of emotion, affects, and law has played out in the study of law and anthropology.
Greek Festivals in the Roman Era
Authors: Newby Zahra
Published: October 2021

Greek festival culture expanded in the period of the Roman empire, through the establishment of Greek-style festivals in Rome under Nero and Domitian, by their influence on the western provinces (Italy, Gaul and N. Africa), and through their continued vitality in the East. This was a period when control of festivals lay firmly in imperial hands and the headquarters of the athletic synod were moved to Rome. At the same time, Greek writers such as Pausanias suggest the enduring centrality of Olympia as the Panhellenic site par excellence, and new festival foundations were a popular form of Greek civic euergetism. This study explores the place that festivals played in the negotiations between Greek identity and Roman power, questioning whether the establishment of a new periodos challenged the traditional supremacy of Olympia, Delphi, Isthmia and Nemea, or rather reflected the emergence of an empire-wide culture based in part on the diffusion of Greek cultural values.
Local Festivals
Authors: Nijf Onno van
Published: October 2021

The chapter will draw attention to the importance of some 500 known Greek agonistic festivals for local identity politics and for the networking of cities in the first three centuries ce. The chapter will establish the role of such festivals as ‘civic rituals’. They will be studied against a diachronic and comparative background focusing on the role of public ritual and ceremony as a feature of political culture in the pre-modern world. The study relies on documentary sources to shed light on issues such as organization, planning and financing. Finally the religious dimensions will be explored, both in the context of traditional civic cult, but also with special attention for their link with the imperial cult.
Etruscan Events
Authors: Thuillier Jean-Paul
Published: October 2021

Sports are a well-represented motif in Etruscan iconography since the Orientalizing Period, with a predilection for horse racing and boxing bouts performed to music. Contrary to current opinion, Etruscan sport shows strong originality in comparison with a so-called Greek model on many points, such as technical aspects of chariot-racing, the status of athletes, the presence of women in public space; its influence on Roman ludi has been considerable. Beside funerary games organized in a gentilician or clan-based framework, the Etruscans also were acquainted with sacred games, in particular the Pan-Etruscan games in which the members of the League of Twelve Cities competed in the sanctuary of Voltumna at Orvieto.
Games in the Republic
Authors: Futrell Alison
Published: October 2021

From its earliest days, Roman spectacle served a range of social and political ends; even as these shared experiences solidified group identity and channelled public emotions toward positive ends, organizers, performers, and attendees also claimed these events as opportunities to advance individual ambitions, to press for greater access to public resources, and to assert the legitimacy of various narratives about Roman identity and power. Evidence for theatrical events is of particular interest, because of the intense verbal component in these shows. Elite leaders organized spectacle space to secure preferred messaging, to spotlight elite social dominance, and to restrict popular capacity to divert such venues toward the support of other class goals. Utilizing ritual habits of group expression, however, organized sub-elites in the audience worked to seize control of dramatic scripts, redirecting the stage narrative to refocus and challenge contemporary political discourse and reclaiming architectural messaging to undermine elite intentions.
Gymnasium and Bath
Authors: Fagan Garrett G.
Published: October 2021

In the Greco-Roman Mediterranean, gymnasiums and baths served complex social functions. More than simply places to cleanse the body or engage in exercise, these became venues for public spectacle, a purpose suggested by the design features and artistic decoration that went into the construction of these spaces. By the first and second centuries ce, in the Roman world spaces dedicated to exercise were fully integrated into multipurpose bathing venues. In their developed forms, the gymnasia and the baths were both places to view and display the body and to sustain ideological discourse focusing on youthful and dynamic physicality.
Serine/threonine kinase inhibition as antifibrotic therapy: transforming growth factor-β and Rho kinase inhibitors
Authors: Mendoza Fabian A , Jimenez Sergio A
Published: October 2021

Serine/threonine kinases mediate the phosphorylation of intracellular protein targets, transferring a phosphorus group from an adenosine triphosphate molecule to the specific amino acid residues within the target proteins. Serine/threonine kinases regulate multiple key cellular functions. From this large group of kinases, TGF-β through serine/threonine activity of its receptors and Rho kinase (ROCK) play an important role in the development and maintenance of fibrosis in various human diseases, including SSc. In recent years, multiple drugs targeting and inhibiting these kinases have been developed, opening the possibility of becoming potential antifibrotic agents of clinical value for treating fibrotic diseases. This review analyses the contribution of TGF-β and ROCK-mediated serine/threonine kinase molecular pathways to the development and maintenance of pathological fibrosis and the potential clinical use of their inhibition.
Effect of preformed foot orthoses in reducing pain in children with juvenile idiopathic arthritis: a multicentre randomized clinical trial
Authors: Fellas Antoni , Singh-Grewal Davinder , Chaitow Jeffrey , Santos Derek , Clapham Matthew , Coda Andrea
Published: October 2021

Objectives

The aim of this study is to investigate the effect of customized preformed foot orthoses on pain, quality of life, swollen and tender lower joints and foot and ankle disability in children with JIA.

Methods

Parallel group design. Children diagnosed with JIA were recruited from the three children’s hospitals in New South Wales, Australia. Participants were randomly assigned to a control group receiving a standard flat innersole (sham) with no corrective modifications. The trial group were prescribed a preformed device that was customized based on biomechanical assessments. Pain was the primary outcome and was followed up to 12 months post intervention. Secondary outcomes include quality of life, foot and ankle disability and swollen and tender joints. A linear mixed model was used to assess the impact of the intervention at each time point.

Results

Sixty-six participants were recruited. Child-reported pain was reduced statistically and clinically significant at 4 weeks and 3 months post intervention in favour of the trial group. Statistical significance was not reached at 6 and 12-month follow-ups. Quality of life and foot and ankle disability were not statistically significant at any follow-up; however, tender midfoot and ankle joints were significantly reduced 6 months post intervention.

Conclusion

Results of this clinical trial indicate customized preformed foot orthoses can be effective in reducing pain and tender joints in children with JIA exhibiting foot and ankle symptoms. Long-term efficacy of foot orthoses remains unclear. Overall, the trial intervention was safe, inexpensive and well tolerated by paediatric patients.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR): 12616001082493.
A Call to (Caring) Arms: A Response to The Care Manifesto: The Politics of Interdependence
Authors: Brennan Deborah
Published: October 2021

The Care Manifesto: The Politics of Interdependence calls for the reorganization of personal relationships, communities, economies, and institutions around the principle of care. Arguing that carelessness is endemic to modern societies, the authors offer numerous practical ideas for action and policy to counter this lack of care. The Manifesto has many strengths and is likely to inform, motivate and energise its readers. Given the broad ambition of the authors, it is disappointing however that they barely glance beyond Europe, the UK and the USA. In taking such a narrow perspective, they miss whole worlds of scholarship, analysis and practical examples. The lack of acknowledgment of feminist social policy is another remarkable omission. Despite its limits, The Care Manifesto conveys a profound sense of urgency about the economic, social, and ecological perils facing the world while suggesting constructive and practical alternatives so that readers are not left feeling pessimistic and powerless. It calls for a new politics based around care and a new ideal of citizenship that recognises multiple sites ranging from the personal to the planetary.
Assessing and Promoting Independence in Young Adults with Autism Spectrum Disorder
Authors: Cheak-Zamora Nancy , Tait Andrew , Coleman Ann
Published: October 2021

Objective:

Quality of life, independence, and employment outcomes are poor for young adults with autism spectrum disorder (YA-ASD). This study explored the desires and experiences of YA-ASD as they transition into adulthood.

Methods:

Fifteen YA-ASD, age 18 to 25 years, were recruited from autism spectrum disorder centers, participant registries, and social media advertising. Interested individuals completed a survey and individual interview. Semistructured interview guides included questions about transition experiences, current independence, and future goals. Interview transcripts were analyzed using thematic analysis.

Results:

The desire of young adults with autism spectrum disorder for independence was shown within 4 themes. YA-ASD described their vision of adulthood along with their need for improved skills in driving, living independently, and decision-making.

Conclusion:

The findings indicate YA-ASD desire to be independent but lack the specific support services to get there.
Effects of coronavirus disease-2019 on voice: our experience of laryngeal complications following mechanical ventilation in severe coronavirus disease-2019 pneumonitis and review of current literature
Authors: Watson Natalie A. , Karagama Yakubu , Burnay Victoria , Boztepe Selda , Warner Susan , Chevretton Elfy B.
Published: October 2021

Purpose of review

Dysphonia has been described as a major symptom of coronavirus disease-2019 (COVID-19). A literature review examining this topic was undertaken and is presented here, combined with insights from our experience in managing patients with laryngeal complications following mechanical ventilation for severe COVID-19 pneumonitis.

Recent findings

Naunheim et al. reported that patients who are most at risk of needing intubation with COVID-19 disease are those with patient-specific risk factors and these are at an increased risk for subsequent laryngotracheal injury following intubation (1). In our cohort of 105 patients referred with laryngological symptoms postintubation for COVID-19 pneumonitis, 40% presented as urgent reviews, of which almost half had severe postintubation complications requiring surgery. Perceptual voice ratings and patient-reported voice ratings varied widely, but there was no significant change in voice scores postoperatively. The reflux symptom index (RSI) scores did improve significantly (p = 0.0266). The need for surgery was associated with the presence of comorbidities for instance hypertension, diabetes and obesity in our cohort. This is in support of reported association of comorbidity as a risk factor for intubation and subsequent development of postintubation airway complications.

Dysphonia following COVID-19 infection may have multiple causes. Literature reports demonstrate intubation injury, sensory neuropathy, and postviral neuropathy are associated with voice changes. Our personal experience has confirmed postintubation injury markedly affects glottic function with resultant dysphonia attributable to scar formation, posterior glottic stenosis, granulation and subglottic stenosis. Frequent surgical intervention is required for airway patency and may have short-term further deleterious effects on phonation, although in our cohort this is not statistically significant analysing Grade, Roughness, Breathiness, Asthenia, Strain, Voice Handicap Index-10 or Airway, Voice, Swallow scores. Maximal antireflux medications and advice statistically improved RSI scores postoperatively.
Anthropology in the PICU: Addressing the Local Worlds of Families in an Otherwise Foreign Land
Authors: Peeler Katherine R.
Published: October 2021

Critical illness is a scary, and often previously unknown, experience for children and their families. To best assist pediatric critically ill patients and their caregivers, it is imperative to understand their local worlds outside of the PICU and what matters to them most. Anthropology, and its ethnographic lens and mode of inquiry, is an underutilized aspect of multidisciplinary care and research in pediatric critical care but has much to offer as exemplified herein.
Strain Echocardiography and Myocardial Dysfunction in Critically Ill Children With Multisystem Inflammatory Syndrome Unrecognized by Conventional Echocardiography: A Retrospective Cohort Analysis
Authors: Basu Sonali , Kim Esther J. , Sharron Matthew P. , Austin Ashley , Pollack Murray M. , Harahsheh Ashraf S. , Dham Niti
Published: October 2021

OBJECTIVES:

Multisystem inflammatory syndrome in children is a newly defined complication of severe acute respiratory syndrome coronavirus 2 infection that can result in cardiogenic shock in the pediatric population. Early detection of cardiac dysfunction is imperative in directing therapy and identifying patients at highest risk for deterioration. This study compares the strengths of conventional and strain echocardiography in identifying cardiac dysfunction in critically ill children with multisystem inflammatory syndrome in children and their association with ICU therapeutic needs and clinical outcomes.

DESIGN:

Retrospective, observational cohort study.

SETTING:

A large, quaternary care PICU.

PATIENTS:

Sixty-five pediatric patients admitted to the PICU with the diagnosis of multisystem inflammatory syndrome in children from March 2020 to March 2021.

INTERVENTIONS:

Global longitudinal strain four chamber was measured retrospectively by strain echocardiography and compared with conventional echocardiography. Cardiac dysfunction was defined by left ventricular ejection fraction less than 55% and global longitudinal strain four chamber greater than or equal to –17.2%. Clinical variables examined included cardiac biomarkers, immune therapies, and ICU interventions and outcomes.

MEASUREMENTS AND MAIN RESULTS:

Twenty-four patients (37%) had abnormal left ventricular ejection fraction and 56 (86%) had abnormal global longitudinal strain four chamber. Between patients with normal and abnormal left ventricular ejection fraction, we failed to identify a difference in cardiac biomarker levels, vasoactive use, respiratory support needs, or ICU length of stay. Global longitudinal strain four chamber was associated with maximum cardiac biomarker levels. Abnormal global longitudinal strain four chamber was associated with greater odds of any vasoactive use (odds ratio, 5.8; 95% CI, 1.3–25.3; z-statistic, 2.3; p = 0.021). The number of days of vasoactive infusion was correlated with global longitudinal strain four chamber (r = 0.400; 95% CI, 2.4–3.9; p < 0.001). Children with abnormal strain had longer ICU length of stay (4.5 d vs 2 d; p = 0.014).

CONCLUSIONS:

Our findings suggest strain echocardiography can detect abnormalities in cardiac function in multisystem inflammatory syndrome in children patients unrecognized by conventional echocardiography. These abnormalities are associated with increased use of intensive care therapies. Evaluation of these patients with strain echocardiography may better identify those with myocardial dysfunction and need for more intensive therapy.
Comparing Incision Choices in Immediate Microvascular Breast Reconstruction after Nipple-Sparing Mastectomy: Unique Considerations to Optimize Outcomes
Authors: Salibian Ara A. , Bekisz Jonathan M. , Frey Jordan D. , Thanik Vishal D. , Levine Jamie P. , Karp Nolan S. , Choi Mihye
Published: October 2021

Background:

Incision planning is a critical factor in nipple-sparing mastectomy outcomes. Evidence on optimal incision patterns in patients undergoing nipple-sparing mastectomy and immediate microvascular breast reconstruction is lacking in the literature.

Methods:

A single-institution retrospective review was performed of consecutive patients undergoing nipple-sparing mastectomy and immediate microvascular autologous reconstruction from 2007 to 2019. Outcomes—including major mastectomy flap necrosis, full nipple-areola complex necrosis, and any major ischemic complication of the skin envelope—were compared among incision types. Multivariable logistic regression identified factors associated with major ischemic complication.

Results:

Two hundred seventy-nine reconstructions (163 patients) were identified, primarily using internal mammary recipient vessels (98.9 percent). Vertical incisions were used in 139 cases; inframammary, in 53; lateral radial, in 51; and inverted-T, in 35. Thirty-two cases (11.5 percent) had major mastectomy flap necrosis, 11 (3.9 percent) had full nipple-areola complex necrosis, and 38 (13.6 percent) had any major ischemic complication. Inframammary incisions had higher rates of major ischemic complication (25 percent) than vertical (5.8 percent; p < 0.001) and lateral radial (7.8 percent; p = 0.032) incisions. Inverted-T incisions also had higher rates of major ischemic complication (36.1 percent) than both vertical (p < 0.001) and lateral radial (p = 0.002) incisions. Inframammary incisions (OR, 4.382; p = 0.002), inverted-T incisions (OR, 3.952; p = 0.011), and mastectomy weight (OR, 1.003; p < 0.001) were independently associated with an increased risk of major ischemic complication. Inframammary incisions with major ischemic complication demonstrated significantly higher body mass index, mastectomy weight, and flap weight compared to those without.

Conclusions:

Inframammary and inverted-T incisions are associated with a higher risk of major ischemic skin envelope complications after nipple-sparing mastectomy and immediate microvascular breast reconstruction. Radial incisions can be considered to optimize recipient vessel exposure without compromising perfusion.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
From Salvage to Prevention: A Single-Surgeon Experience with Acellular Dermal Matrix and Infection in Prepectoral Breast Reconstruction
Authors: Powers Jeremy M. , Reuter Muñoz Katherine D. , Parkerson Jamie , Nigro Lauren C. , Blanchet Nadia P.
Published: October 2021

Background:

Increasing amounts of acellular dermal matrix are being used with the adoption of prepectoral breast reconstruction. Postoperative infection remains a challenge in breast reconstruction, and the contribution of acellular dermal matrix type, processing, and sterility assurance level to risk of complications in prepectoral reconstruction is not well studied.

Methods:

The authors performed a retrospective review of patients who underwent immediate prepectoral breast reconstruction from February of 2017 to July of 2020. Because of an increase in the rate of infection, the drain protocol was changed and acellular dermal matrix type was switched from AlloDerm (sterility assurance level, 10−3) to DermACELL (sterility assurance level, 10−6) in January of 2019. Demographic and surgical variables were collected, in addition to details regarding development and management of infection.

Results:

Despite higher rates of direct-to-implant reconstruction and bilateral procedures and increased implant volumes, the rate of infection was significantly lower in patients who received DermACELL instead of AlloDerm [two of 38 (5.3 percent) versus 11 of 41 (26.8 percent); p = 0.014]. Drain duration was slightly longer in the DermACELL group, consistent with the change in drain protocol. Baseline demographic and clinical characteristics remained similar between the two groups.

Conclusions:

With increased reliance on large amounts of acellular dermal matrix for prepectoral breast reconstruction, it directly follows that the properties of acellular dermal matrix with respect to incorporation, sterility, and implant support are that much more important to consider. There have been few studies comparing different types of acellular dermal matrix in prepectoral breast reconstruction, and further research is required to determine the contribution of acellular dermal matrix type and processing techniques to development of postoperative infection.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
New evidence for managing Gram-negative bloodstream infections
Authors: Nutman Amir , Tellapragada Chaitanya , Giske Christian G. , Yahav Dafna
Published: October 2021

Purpose of review

Gram-negative bloodstream infections (GNBSI) are common and carry considerable mortality. Treatment is complicated by increasing antimicrobial resistance, posing a challenge for timely appropriate antibiotics and limiting the choices of effective definitive therapy. The present review aims to summarize recent studies addressing the management of GNBSI.

Recent findings

New rapid diagnostic tests (RDT) for pathogen identification and antibiotic susceptibility are associated with improved antimicrobial stewardship and reduced length of stay. No mortality benefit or patient-related outcomes are reported. Data regarding the use of new beta-lactam beta-lactamase inhibitors (BLBLIs) for treating multidrug resistance Gram-negative bacteria is supportive, though questions regarding combinations, optimal dosing, mode of administration, and resistance emergence remain to be clarified. Current data regarding cefiderocol necessitates further studies in order to support its use in GNBSI. Shortened (≤7 days) duration of therapy and early oral step down for GNBSI are supported by the literature. The role of repeated blood cultures should be further defined.

RDTs should be implemented to improve antibiotic stewardship. Clinical implications on patient-related outcomes should be evaluated. New BLBLIs show promise in the treatment of GNBSI. Additional data are needed regarding the use of cefiderocol. Antibiotic therapy should be shortened and early oral step down should be considered.
Feature-based gating of cortical information transmission
Authors: Ray Sonia Baloni , Kaping Daniel , Treue Stefan
Published: October 2021

In highly developed visual systems, spatial- and feature-based attentional modulation interact to prioritize relevant information and suppress irrelevant details. We investigated the specific role and integration of these two attentional mechanisms in visual cortical area MST of rhesus monkeys. We show that spatial attention acts as a gate for information processing by providing unimpeded high-gain pass-through processing for all sensory information from attended visual locations. Feature-based attentional enhancement does not only show the known dependency on a match between the attended feature and a given cell’s selectivity, but surprisingly is restricted to those features for which a given cell contributes to perception. This necessitates a refinement of the feature-similarity gain model of attention and documents highly optimized attentional gating of sensory information for cortical processing. This gating is shaped by neuronal sensory preferences, behavioral relevance, and the causal link to perception of neurons that process this visual input.
Mouse model and human patient data suggest critical roles for Pten and p53 in suppressing POLE mutant tumor development
Authors: Park Vivian S. , Sun Meijuan J.S. , Frey Wesley D. , Williams Leonard G. , Hodel Karl P. , Strauss Juliet D. , Wellens Sydney J. , Jackson James G. , Pursell Zachary F.
Published: October 2021

Mutations in the exonuclease domain of POLE are associated with tumors harboring very high mutation burdens. The mechanisms linking this significant mutation accumulation and tumor development remain poorly understood. Pole+/P286R;Trp53+/− mice showed accelerated cancer mortality compared to Pole+/P286R;Trp53+/+ mice. Cells from Pole+/P286R mice showed increased p53 activation, and subsequent loss of p53 permitted rapid growth, implicating canonical p53 loss of heterozygosity in POLE mutant tumor growth. Somewhat surprisingly, however, p53 status had no effect on tumor mutation burden or single base substitution signatures in POLE mutant tumors from mice or humans. Pten has important roles in maintaining genome stability. We find that PTEN mutations are highly enriched in human POLE mutant tumors, including many in POLE signature contexts. One such signature mutation, PTEN-F341V, was previously shown in a mouse model to specifically decrease nuclear Pten and lead to increased DNA damage. We found tumors in Pole+/P286R mice that spontaneously acquired PtenF341V mutations and were associated with significantly reduced nuclear Pten and elevated DNA damage. Taken together with recent published work, our results support the idea that POLE-mediated hypermutagenesis is necessary, but not entirely sufficient, for tumorigenesis. Disabling surveillance of nuclear DNA damage is a likely sufficient factor.
A curated collection of Klebsiella metabolic models reveals variable substrate usage and gene essentiality
Authors: Hawkey Jane , Vezina Ben , Monk Jonathan M. , Judd Louise M. , Harshegyi Taylor , López-Fernández Sebastián , Rodrigues Carla , Brisse Sylvain , Holt Kathryn E. , Wyres Kelly L.
Published: October 2021

The Klebsiella pneumoniae species complex (KpSC) is a set of seven Klebsiella taxa which are found in a variety of niches, and are an important cause of opportunistic healthcare-associated infections in humans. Due to increasing rates of multi-drug resistance within the KpSC, there is a growing interest in better understanding the biology and metabolism of these organisms to inform novel control strategies. We collated 37 sequenced KpSC isolates isolated from a variety of niches, representing all seven taxa. We generated strain-specific genome scale metabolic models (GEMs) for all 37 isolates and simulated growth phenotypes on 511 distinct carbon, nitrogen, sulphur and phosphorus substrates. Models were curated and their accuracy assessed using matched phenotypic growth data for 94 substrates (median accuracy of 96%). We explored species-specific growth capabilities and examined the impact of all possible single gene deletions on growth in 145 core carbon substrates. These analyses revealed multiple strain-specific differences, within and between species and highlight the importance of selecting a diverse range of strains when exploring KpSC metabolism. This diverse set of highly accurate GEMs could be used to inform novel drug design, enhance genomic analyses, and identify novel virulence and resistance determinants. We envisage that these 37 curated strain-specific GEMs, covering all seven taxa of the KpSC, provide a valuable resource to the Klebsiella research community.
Markerless Video Analysis of Spontaneous Bodily Movements in 4-Month-Old Infants Predicts Autism-like Behavior in 18-Month-Olds
Authors: Doi Hirokazu , Iijima Naoya , Furui Akira , Soh Zu , Shinohara Kazuyuki , Iriguchi Mayuko , Shimatani Koji , Tsuji Toshio
Published: October 2021

Early intervention is now considered the core treatment strategy for autism spectrum disorders (ASD). Thus, it is of significant clinical importance to establish a screening tool for the early detection of ASD in infants. To achieve this goal, in a longitudinal design, we analysed spontaneous bodily movements of 4-month-old infants and assessed their ASD-like behaviours at 18 months of age. Infants at high risk for ASD at 18 months of age exhibited less rhythmic and weaker bodily movement patterns at 4 months of age than low-risk infants. When the observed bodily movement patterns were submitted to a machine learning-based analysis, linear and non-linear classifiers successfully predicted ASD-like behaviour at 18 months of age based on the bodily movement patterns at 4 months of age, at the level acceptable for practical use. This suggests the utility of the proposed method for the early screening of infants at risk for ASD.
Mechanism of optimal time-course COVID-19 vaccine prioritization based on non-Markovian steady-state prediction
Authors: Feng Mi , Tian Liang , Zhou Changsong
Published: October 2021

Vaccination is essential for controlling the coronavirus disease (COVID-19) pandemic. An effective time-course strategy for the allocation of COVID-19 vaccines is crucial given that the global vaccine supply will still be limited in some countries/regions in the near future and that mutant strains have emerged and will continue to spread worldwide. Both asymptomatic and symptomatic transmission have played major roles in the COVID-19 pandemic, which can only be properly described as a typical non-Markovian process. However, the prioritization of vaccines in the non-Markovian framework still lacks sufficient research, and the underlying mechanism of the time-course vaccine allocation optimization has not yet been uncovered. In this paper, based on an age-stratified compartmental model calibrated through clinical and epidemiological data, we propose optimal vaccination strategies (OVS) through steady-state prediction in the non-Markovian framework. This OVS outperforms other empirical vaccine prioritization approaches in minimizing cumulative infections, cumulative deaths, or years of life lost caused by the pandemic. We found that there exists a fast decline in the prevention efficiency of vaccination if vaccines are solely administered to a selected age group, which indicates that the widely adopted strategy to continuously vaccinate high-risk group is not optimal. Through mathematical analysis of the model, we reveal that dynamic vaccine allocations to combinations of different age groups is necessary to achieve optimal vaccine prioritization. Our work not only provides meaningful references for vaccination in countries currently lacking vaccines and for vaccine allocation strategies to prevent mutant strains in the future, but also reveals the mechanism of dynamic vaccine allocation optimization, forming a theoretical and modelling framework empirically applicable to the optimal time-course prioritization.
Somatic mutation detection: a critical evaluation through simulations and reanalyses in oaks
Authors: Schmitt Sylvain , Leroy Thibault , Heuertz Myriam , Tysklind Niklas
Published: October 2021

Abstract

Mutation, the source of genetic diversity, is the raw material of evolution; however, the mutation process remains understudied, especially in plants. Using both a simulation and reanalysis framework, we set out to explore and demonstrate the improved performance of variant callers developed for cancer research compared to single nucleotide polymorphism (SNP) callers in detecting de novo somatic mutations.

In anin silicoexperiment, we generated Illumina-like sequence reads spiked with simulated mutations at different allelic fractions to compare the performance of seven commonly-used variant callers to recall them. More empirically, we then reanalyzed two of the largest datasets available for plants, both developed for identifying within-individual variation in long-lived pedunculate oaks.

Based on thein silicoexperiment, variant callers developed for cancer research outperform SNP callers regarding plant mutation recall and precision, especially at low allele frequency. Such variants at low allelic fractions are typically expected for within-individual de novo plant mutations, which initially appear in single cells. Reanalysis of published oak data with Strelka2, the best-performing caller based on our simulations, identified up to 3.4x more candidate somatic mutations than reported in the original studies.

Our results advocate the use of cancer research callers to boost de novo mutation research in plants, and to reconcile empirical reports with theoretical expectations.

This version of the article has been peer-reviewed and recommended byPeer Community in Genomicshttps://doi.org/10.24072/pci.genomics.100024
Phage-encoded ribosomal protein S21 expression is linked to late stage phage replication
Authors: Chen Lin-Xing , Jaffe Alexander L. , Borges Adair L. , Penev Petar I. , Nelson Tara Colenbrander , Warren Lesley A. , Banfield Jillian F.
Published: October 2021

The ribosomal protein S21 (bS21) gene has been detected in diverse viruses with a large range of genome sizes, yet its in situ expression and potential significance have not been investigated. Here, we report five closely related clades of bacteriophages (phages) represented by 47 genomes (8 curated to completion and up to 331 kbp in length) that encode a bS21 gene. The bS21 gene is on the reverse strand within a conserved region that encodes the large terminase, major capsid protein, prohead protease, portal vertex proteins and some hypothetical proteins. These phages are predicted to infect Bacteroidetes species that inhabit a range of depths in freshwater lakes. Transcriptionally active bS21-encoding phages were sampled in the late-stage of replication, when core structural genes, bS21 and a neighboring gene of unknown function were highly expressed. Thus, our analyses suggest that bS21, which is involved in translation initiation, substitutes into the Bacteroidetes ribosomes and selects for phage transcripts during the late-stage replication when large-scale phage protein production is required for assembly of phage particles.
Astrocytes derived from ASD patients alter behavior and destabilize neuronal activity through aberrant Ca2+signaling
Authors: Allen Megan , Huang Ben S. , Notaras Michael J. , Lodhi Aiman , Alonso Estibaliz Barrio , Wolujewicz Paul , Witztum Jonathan , Longo Francesco , Chen Maoshan , Greening David , Klann Eric , Elizabeth Ross M. , Liston Conor , Colak Dilek
Published: October 2021

The cellular mechanisms of Autism Spectrum Disorder (ASD) are poorly understood. Cumulative evidence suggests that abnormal synapse function underlies many features of this disease. Astrocytes play in several key neuronal processes, including the formation of synapses and the modulation of synaptic plasticity. Astrocyte abnormalities have also been identified in the postmortem brain tissue of ASD patients. However, it remains unclear whether astrocyte pathology plays a mechanistic role in ASD, as opposed to a compensatory response. To address this, we strategically combined stem cell culturing with transplantation techniques to determine disease specific properties inherent to patient derived astrocytes. We demonstrate that ASD astrocytes induce repetitive behavior as well as impair memory and long-term potentiation when transplanted into the healthy mouse brain. Thesein vivophenotypes were accompanied by reduced neuronal network activity and spine density caused by ASD astrocytes in hippocampal neuronsin vitro. Transplanted ASD astrocytes also exhibit exaggerated Ca2+fluctuations in chimeric brains. Genetic modulation of evoked Ca2+responses in ASD astrocytes modulates behavior and neuronal activity deficits. Thus, we determine that ASD patient astrocytes are sufficient to induce repetitive behavior as well as cognitive deficit, suggesting a previously unrecognized primary role for astrocytes in ASD.
Factorbook: an Updated Catalog of Transcription Factor Motifs and Candidate Regulatory Motif Sites
Authors: Pratt Henry E. , Andrews Gregory R. , Phalke Nishigandha , Purcaro Michael J. , van der Velde Arjan , Moore Jill E. , Weng Zhiping
Published: October 2021

The human genome contains roughly 1,600 transcription factors (TFs) (1), DNA-binding proteins recognizing characteristic sequence motifs to exert regulatory effects on gene expression. The binding specificities of these factors have been profiled bothin vitro, using techniques such as HT-SELEX (2), andin vivo, using techniques including ChIP-seq (3, 4). We previously developed Factorbook, a TF-centric database of annotations, motifs, and integrative analyses based on ChIP-seq data from Phase II of the ENCODE Project. Here we present an update to Factorbook which significantly expands the breadth of cell type and TF coverage. The update includes an expanded motif catalog derived from thousands of ENCODE Phase II and III ChIP-seq experiments and HT-SELEX experiments; this motif catalog is integrated with the ENCODE registry of candidate cis-regulatory elements to annotate a comprehensive collection of genome-wide candidate TF binding sites. The database also offers novel tools for applying the motif models within machine learning frameworks and using these models for integrative analysis, including annotation of variants and disease and trait heritability. We will continue to expand the resource as ENCODE Phase IV data are released.
Effects of background food on alternative grain uptake and zinc phosphide efficacy in wild house mice
Authors: Henry Steve , Brown Peter R. , Van de Weyer Nikki , Robinson Freya , Hinds Lyn A.
Published: October 2021

BACKGROUND

House mice (Mus musculus) cause significant, ongoing losses to grain crops in Australia, particularly during mouse plagues. Zinc phosphide (ZnP) coated grain is used for control, but with variable success. In a laboratory setting, we tested if mice would (1) switch from consumption of one grain type to another when presented with an alternative, and (2) consume ZnP-treated grains when presented as a choice with a different grain.

RESULTS

Mice readily switched from their background grain to an alternative grain, preferring cereals (wheat or barley) over lentils. Mice readily consumed ZnP-coated barley grains. Their mortality rate was significantly higher (86%, n=30) in the presence of a less-favoured grain (lentils) compared to their mortality rate (47%, n=29; and 53%, n=30) in the presence of a more-favoured grain (wheat and barley, respectively). Mice died between 4-112 h (median = 18 h) after consuming one or more toxic grains. Independent analysis of ZnP-coated grains showed variable toxin loading indicating that consumption of a single grain would not guarantee intake of a lethal dose. There was also a strong and rapid behavioural aversion if mice did not consume a lethal dose on the first night.

CONCLUSIONS

The registered dose rate of 25 g ZnP/kg wheat; ∼ 1 mg ZnP/grain in Australia needs to be re-evaluated to determine what factors may be contributing to variation in efficacy. Further field research is also required to understand the complex association between ZnP dose, and quantity and quality of background food on efficacy of ZnP baits.
Exhausted mature dendritic cells exhibit a slower and less persistent random motility but retain chemotaxis against CCL19
Authors: Choi Yongjun , Sunkara Vijaya , Lee Yeojin , Cho Yoon-Kyoung
Published: October 2021

Dendritic cells (DCs), which are immune sentinels in the peripheral tissues, play a number of roles, including patrolling for pathogens, internalising antigens, transporting antigens to the lymph nodes (LNs), interacting with T cells, and secreting cytokines. The well-coordinated migration of DCs under various immunological or inflammatory conditions is therefore essential to ensure an effective immune response. Upon maturation, DCs migrate faster and more persistently than immature DCs (iDCs), which is believed to facilitate CCR7-dependent chemotaxis. It has been reported that lipopolysaccharide-activated DCs produce IL-12 only transiently, and become resistant to further stimulation through exhaustion. However, little is known about the influence of DC exhaustion on cellular motility. Here, we studied the cellular migration of exhausted DCs in tissue-mimicked confined environments. We found that the speed of exhausted matured DCs (xmDCs) decreased significantly compared to active matured DCs (amDCs) and iDCs. In contrast, the speed fluctuation increased compared to that of amDCs and was similar to that of iDCs. In addition, the diffusivity of the xmDCs was significantly lower than that of the amDCs, which implies that DC exhaustion reduces the space exploration ability. Interestingly, CCR7-dependent chemotaxis against CCL19 in xmDCs was not considerably different from that observed in amDCs. Taken together, we report a unique intrinsic cell migration behavior of xmDCs, which exhibit a slower, less persistent, and less diffusive random motility, which results in the DCs remaining at the site of infection, although a well-preserved CCR7-dependent chemotactic motility is maintained.
Belemnite phylogeny and decline during the mid-Cretaceous
Authors: Stevens Kevin
Published: October 2021

Belemnites are common fossil coleoid cephalopods of the Mesozoic. They began to diversify in the Triassic-Early Jurassic and maintained this diversity until the early Early Cretaceous. During the mid-Cretaceous, they declined in diversity and distribution, being restricted to only the Boreal and Austral Realm since the Turonian. Here, I present the first cladistic analysis of belemnite phylogeny, spanning taxa representative of the whole diversity and stratigraphic range of the group. This analysis shows that the usually applied subdivision of all belemnites into “Belemnitina” and “Belemnopseina” is not supported. A newly identified clade, the Pseudoalveolata, is suggested here. Pseudoalveolate belemnites represent the last remaining belemnites after the Aptian. Oceanic anoxia and warming are likely the main cause of the mid-Cretaceous belemnite decline, resulting in the Aptian-Albian dominance of the warm-adapted pseudoalveolate genusNeohibolites. The rise of teleost fish diversity during the mid-Cretaceous is discussed and its relevance for belemnite evolution. Some teleosts (e.g.,Enchodus) might have taken over the mesopredator niches left by belemnites during the mid-Cretaceous, being better adapted to warming seas. Belemnites were not able to recover their earlier widespread distribution and diversity and the last remaining, disjunctly distributed families, the northern Belemnitellidae and southern Dimitobelidae, became extinct at the K/Pg-boundary.
C9orf72-derived poly-GA DPRs undergo endocytic uptake in iNPC-derived astrocytes and spread to motor neurons
Authors: Marchi Paolo M. , Marrone Lara , Brasseur Laurent , Bousset Luc , Webster Christopher P. , Destro Marco , Smith Emma F. , Walther Christa G. , Alfred Victor , Marroccella Raffaele , Robinson Darren , Shaw Allan C. , Wan Lai Mei , Grierson Andrew J. , Ebbens Stephen J. , De Vos Kurt J. , Hautbergue Guillaume M. , Ferraiuolo Laura , Melki Ronald , Azzouz Mimoun
Published: October 2021

Dipeptide repeat proteins (DPRs) are aggregation-prone polypeptides encoded by the pathogenic G4C2 repeat expansion in the C9orf72 gene, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). In this study, we focus on the role of poly-GA DPRs in disease spread. We demonstrate that recombinant poly-GA oligomers can directly convert into solid-like aggregates and form characteristic &[beta]-sheet fibrils in vitro. To dissect the process of cell-to-cell DPR transmission, we closely follow the fate of poly-GA DPRs in either their oligomeric or fibrillized form after administration in the cell culture medium. We observe that poly-GA DPRs are taken up via dynamin-dependent and - independent endocytosis, eventually converging at the lysosomal compartment and leading to axonal swellings in neurons. We then use a co-culture system to demonstrate astrocyte-to- motor neuron DPR propagation, showing that astrocytes may internalise and release aberrant peptides in disease pathogenesis. Overall, our results shed light on the mechanisms of poly- GA cellular uptake and cell-to-cell propagation, suggesting lysosomal impairment as a possible feature underlying the cellular pathogenicity of these DPR species.