bluuebunny/crossref_metadata_2025 huggingface dataset:
Homeostatic state of microglia in a rat model of chronic sleep restriction
Authors: Hall Shannon , Deurveilher Samüel , Robertson George S , Semba Kazue
Published: May 2020

Chronic sleep restriction (CSR) negatively impacts brain functions. Whether microglia, the brain’s resident immune cells, play any role is unknown. We studied microglia responses to CSR using a rat model featuring slowly rotating wheels (3 h on/1 h off), which was previously shown to induce both homeostatic and adaptive responses in sleep and attention. Adult male rats were sleep restricted for 27 or 99 h. Control rats were housed in locked wheels. After 27 and/or 99 h of CSR, the number of cells immunoreactive for the microglia marker ionized calcium-binding adaptor molecule-1 (Iba1) and the density of Iba1 immunoreactivity were increased in 4/10 brain regions involved in sleep/wake regulation and cognition, including the prelimbic cortex, central amygdala, perifornical lateral hypothalamic area, and dorsal raphe nucleus. CSR neither induced mitosis in microglia (assessed with bromodeoxyuridine) nor impaired blood–brain barrier permeability (assessed with Evans Blue). Microglia appeared ramified in all treatment groups and, when examined quantitatively in the prelimbic cortex, their morphology was not affected by CSR. After 27 h, but not 99 h, of CSR, mRNA levels of the anti-inflammatory cytokine interleukin-10 were increased in the frontal cortex. Pro-inflammatory cytokine mRNA levels (tumor necrosis factor-α, interleukin-1β, and interleukin-6) were unchanged. Furthermore, cortical microglia were not immunoreactive for several pro- and anti-inflammatory markers tested, but were immunoreactive for the purinergic P2Y12 receptor. These results suggest that microglia respond to CSR while remaining in a physiological state and may contribute to the previously reported homeostatic and adaptive responses to CSR.
Strategies and Tools to Enhance Patient Safety: HROs, HEROs, and Safety Culture
Authors: Shea Kevin G.
Published: June 2020

Introduction:

The Institute of Medicine has defined multiple domains to improve safety, efficiency, and effectiveness of health care. High-Reliability Organizations (HROs) address these issues and promote safety/reliability at the highest level.

Methods:

HROs create a bottom-up, top-down culture that focuses upon continuous improvement by withholding blame on individuals yet requiring all members to be accountable for continuous improvement.

Results:

Supporting staff to speak up, identify, and engage on the path to perfect care and zero harm are elements of a safety culture. In addition to safety, HROs can also focus on effectiveness and efficiency. This may be accomplished by creating consistent care practices that reduce irrational variation, decrease complexity, and lower risk.

Discussion:

Developing a culture focused upon reliability, safety, and staff resilience is critical for HROs. HROs support and empower all staff to be vigilant and report concerns about any issue related to safety and support the development of a “Safety Culture.” HROs focus upon safety will be enhanced by an expanded focus upon effectiveness and efficiency to improve value. A focus on standard clinical practices and clinician integration into the supply chain will help organizations produce better value and be an essential tool to reduce complexity and risk within health care systems.
Curbing Burnout Hysteria With Self-Compassion: A Key to Physician Resilience
Authors: Sotile Wayne M. , Fallon Rebecca , Orlando Julia
Published: June 2020

Background:

Never before has physician suffering received as much attention in the peer-reviewed medical literature and popular media as now. The purpose of this paper is to propose that the manner in which these concerns are being addressed is further complicating physician and medical family well-being due to the perpetuation of work ambivalence.

Methods:

A search of the English literature was conducted using PubMed to identify papers addressing physician burnout and other forms of psychosocial suffering. In addition, a review of case records from the past 40 years of clinical experiences as counselors and life coaches to physicians and their life mates was conducted.

Results:

Reported levels of physician burnout and psychosocial morbidity have escalated over the past 10 years, as have clinically observed levels of work/life conflict expressed both by physicians and their spouses.

Discussion:

We contend that the contemporary rhetoric addressing physicians’ psychosocial experience is yielding the iatrogenic effect of promoting work ambivalence, which is a key building block in fostering physician burnout and its sequelae. We propose that curbing physician burnout requires a combination of empathy about the plight of physicians today, compassion that fuels workplace redesigns and family support, and self-compassion on the part of individual physicians.

Conclusions:

Both clinical experience and research suggest that physician well-being can be enhanced by coaching physicians to protect positive engagement in their work while practicing resilience-enhancing tactics and strategies.
TATTOO-ASSOCIATED CASES OF POSTERIOR SEGMENT UVEITIS WITH VOGT–KOYANAGI–HARADA DISEASE-LIKE FEATURES
Authors: Kesav Natasha P. , Kaplan Alexander J. , Hwang Christopher K. , Okeagu Chinwe , Sen H. Nida
Published: June 2020

Purpose:

To present two patients with treatment-naïve posterior segment uveitis with Vogt–Koyanagi–Harada-like features associated with tattoo-related inflammatory skin changes.

Methods:

Retrospective report of two cases.

Results:

Using clinical history and multimodal imaging, a diagnosis of posterior segment uveitis with Vogt–Koyanagi–Harada-like features was made in association with tattoo skin changes in both patients.

Conclusion:

Physicians should be aware that tattoo-associated posterior segment uveitis with Vogt–Koyanagi–Harada-like features can occur.
Three-Fourths of ICU Physical Therapists Report Use of Assistive Equipment and Technology in Practice: Results of an International Survey
Authors: Mayer Kirby P. , Carper Ramona A. , Henson Samantha C. , Clonce Emily A. , Christian Warren Jay , Seif Sherif M. , Pastva Amy M. , Needham Dale M. , Morris Peter E.
Published: June 2020

Introduction:

Patients surviving critical illness develop persistent functional mobility impairments that significantly impact their quality of life. Early rehabilitation interventions in the intensive care unit (ICU) may mitigate the sequelae of critical illness. However, implementation of such interventions is very low in clinical practice. Assistive rehabilitation equipment and technology, such as tilt beds and cycle ergometers, provide physical therapists (PTs) with strategies to complement functional mobility interventions.

Purpose:

To determine PTs' self-reported use of assistive rehabilitation equipment and technology in their clinical practices in the ICU and to describe the rationale for their use.

Methods:

An online survey (Qualtrics), with closed- and open-ended questions, was distributed to PTs working in the ICU, via e-mail through the Academy of Acute Care Physical Therapy “PTinICU” e-mail listserv and the online ICU Recovery Network and Twitter. Descriptive statistics were used to assess frequency and rationale for the use of specific equipment and technology.

Results:

PTs (n = 206, mean age 39.6 ± 9.7 years, 82% female) completed the survey (81% in the United States and 19% from 12 countries outside of the United States). Respondents (153/206, 74%) reported using at least one type of equipment or technology. The most commonly used were hospital tilt beds and tilt tables (n = 106, 51%), mobilization chairs (n = 80, 39%), standing frames (n= 66, 32%), cycle ergometers (n = 63, 31%), and exercise platforms (n = 36, 17%). The most common rationale for use was as a bridge to functional mobility (response ranging from 17% to 44% depending on the technology). The most common reason for not using equipment or technology was limited or no access (71%, 37/53). PTs from outside the United States (vs US-based PTs) reported greater use of equipment or technology (n = 206, 92% vs 70%, P = .001).

Conclusions:

Approximately 75% of PTs completing this survey report use of assistive rehabilitation equipment and technology in their ICU clinical practice, emphasizing the need for further research to understand the clinical approaches for use and the efficacy of such technology.
The Effect of Aging on the Electrically Evoked Compound Action Potential
Authors: Mussoi Bruna S. , Brown Carolyn J.
Published: June 2020

Objectives:

To examine the effect of aging on electrically evoked compound action potential (eCAP) growth functions and their relationship with speech recognition in noise in cochlear implant (CI) users.

Background:

Aging typically leads to difficulty understanding speech in background noise. Previous research has explored cognitive and central auditory mechanisms contributing to these age-related changes. However, it is likely that the peripheral auditory system may also play a role. One challenge is separating the effects of aging on cochlear structures from the effects of aging on the auditory nerve in humans. CI users provide a unique way to address this issue, as intracochlear electrical stimulation bypasses surviving hair cells and activates the auditory nerve directly. Studies in animal models suggest that age-related loss of spiral ganglion cells could lead to shallower eCAP growth functions and/or increased eCAP thresholds and potentially negatively impact speech recognition.

Methods:

Ten younger and 10 older postlingually deafened, adult CI recipients participated in this study. eCAP amplitude-intensity functions were recorded from a mid-array electrode and fit using linear functions. Speech recognition in noise was assessed using the Quick Speech-in-Noise (QuickSIN) test.

Results:

Older CI users had significantly shallower eCAP growth functions and higher eCAP thresholds than younger CI users. eCAP growth functions were not correlated with speech recognition in noise.

Conclusion:

Results of this study suggest that older adults may have poorer neural survival, resulting in higher eCAP thresholds and shallower eCAP growth functions. These findings expand our understanding of mechanisms underlying age-related changes in the peripheral auditory system.
Mental Health Care Utilization and Psychiatric Diagnoses in a Sample of Military Suicide Decedents and Living Matched Controls
Authors: Ryan Arthur T. , Ghahramanlou-Holloway Marjan , Wilcox Holly C. , Umhau John C. , Deuster Patricia A.
Published: June 2020

This article examines mental health care utilization and psychiatric diagnoses among US military personnel who died by suicide. We employed an existing electronic health record dataset including 800 US military suicide decedents and 800 matched controls. Suicide decedents were more likely to have received outpatient and inpatient mental health care and to have been diagnosed with depression, bipolar, and nonaffective psychotic disorders. Younger decedents and those in the US Marine Corps were less likely to receive MH care before suicide. Given that approximately half of the suicide decedents in our sample had no mental health care visits before their death, our study suggests the need for programs to increase treatment engagement by at-risk individuals. Such programs could address barriers to care such as stigma regarding mental illness and concerns that seeking mental health care would damage a service member's career.
HIV-1 induced changes in HLA-C∗03 : 04-presented peptide repertoires lead to reduced engagement of inhibitory natural killer cell receptors
Authors: Ziegler Maja C. , Nelde Annika , Weber Jeffrey K. , Schreitmüller Christian M. , Martrus Glòria , Huynh Tien , Bunders Madeleine J. , Lunemann Sebastian , Stevanovic Stefan , Zhou Ruhong , Altfeld Marcus
Published: June 2020

Objective:

Viral infections influence intracellular peptide repertoires available for presentation by HLA-I. Alterations in HLA-I/peptide complexes can modulate binding of killer immunoglobuline-like receptors (KIRs) and thereby the function of natural killer (NK) cells. Although multiple studies have provided evidence that HLA-I/KIR interactions play a role in HIV-1 disease progression, the consequence of HIV-1 infection for HLA-I/KIR interactions remain largely unknown.

Design:

We determined changes in HLA-I presented peptides resulting from HIV-1-infection of primary human CD4+ T cells and assessed the impact of changes in peptide repertoires on HLA-I/KIR interactions.

Methods:

Liquid chromatography-coupled tandem mass spectrometry to identify HLA-I presented peptides, cell-based in-vitro assays to evaluate functional consequences of alterations in immunopeptidome and atomistic molecular dynamics simulations to confirm experimental data.

Results:

A total of 583 peptides exclusively presented on HIV-1-infected cells were identified, of which only 0.2% represented HIV-1 derived peptides. Focusing on HLA-C∗03 : 04/KIR2DL3 interactions, we observed that HLA-C∗03 : 04-presented peptides derived from noninfected CD4+ T cells mediated stronger binding of inhibitory KIR2DL3 than peptides derived from HIV-1-infected cells. Furthermore, the most abundant peptide presented by HLA-C∗03 : 04 on noninfected CD4+ T cells (VIYPARISL) mediated the strongest KIR2DL3-binding, while the most abundant peptide presented on HIV-1-infected cells (YAIQATETL) did not mediate KIR2DL3-binding. Molecular dynamics simulations of HLA-C∗03 : 04/KIR2DL3 interactions in the context of these two peptides revealed that VIYPARISL significantly enhanced the HLA-C∗03 : 04/peptide contact area to KIR2DL3 compared with YAIQATETL.

Conclusion:

These data demonstrate that HIV-1 infection-induced changes in HLA-I-presented peptides can reduce engagement of inhibitory KIRs, providing a mechanism for enhanced activation of NK cells by virus-infected cells.
Is Thumb Proprioception Decreased in Patients With Trapeziometacarpal Joint Osteoarthritis?
Authors: Seok Hyun Sik , Lee Kyoung Hwan , Lee Yohan , Bae Kee Jeong , Kim Jihyeung , Gong Hyun Sik
Published: June 2020

Proprioception is thought to be essential for normal joint homeostasis, and its decreased function has been associated with an increased risk of joint diseases. However, only a few studies have been performed on the association between proprioceptive function in the trapeziometacarpal joint (TMCJ) and osteoarthritis. The purpose of this study was to compare TMCJ proprioceptive function in elderly women with radiographic TMCJ osteoarthritis relative to age-matched control women without osteoarthritis. We enrolled 19 women (mean age, 66 years) with symptomatic, radiographic Eaton and Littler grade 2, 3, and 4 TMCJ osteoarthritis and 19 age-matched control women without osteoarthritis. We evaluated thumb proprioception by using a joint-position reproduction test and compared the reposition error (RE) between the groups. We carried out a multivariate analysis for factors potentially associated with increased RE, such as age, body mass index, hand dominance, the presence of diabetes, pain level, and the presence of osteoarthritis. Also, a logistic regression analysis was performed for factors associated with the occurrence of TMCJ osteoarthritis. Patients with TMCJ osteoarthritis had greater RE than did the control patients in the joint-position reproduction test at 20°, 30°, and 40° of thumb palmar abduction. The multivariate analysis indicated that increased RE was associated with the presence of osteoarthritis, but not with the other factors assessed. The occurrence of TMCJ osteoarthritis was associated with increased RE at 20°, 30°, and 40° of thumb palmar abduction. This study showed that decreased proprioceptive function was associated with the presence of osteoarthritis in the TMCJ, although the causality remains unknown. Further studies on the role of proprioception in the pathogenesis of TMCJ osteoarthritis and the potential role of its training for disease prevention or treatment are required.
Digital Subtraction Angiography and Magnetic Resonance Imaging–Based Staging of Circulatory Obstruction in the Femoral Head During Osteonecrosis of the Femoral Head Development
Authors: Wang Benjie , Li Lu , Wang Yikai , Wang Zihua , Li Chuang , Fu Weimin , Qiu Xing , Zhao Dewei
Published: June 2020

Introduction

Nontraumatic osteonecrosis of the femoral head (NONFH) is a common and difficult disease in orthopedics. Magnetic resonance imaging (MRI) assessment of NONFH and bone marrow edema was combined with digital subtraction angiography (DSA) to evaluate the circulatory status of NONFH in different Association Research Circulation Osseous stages. Based on the circulatory obstruction status (venous stasis, arterial ischemia, and arterial occlusion), appropriate perioperative management was adopted to achieve hip joint preservation and effectively delay the time for total hip arthroplasty in young patients.

Methods

From January 2013 to March 2019, 41 orthopedic patients were evaluated for medical imaging. Sixty-one ONFH cases were enrolled. The inclusion criteria include: (1) Clear diagnosis of osteonecrosis of the femoral head. (2) No history of infection in the affected hip, no history of hip surgery, and no congenital hip diseases. The patients enrolled in this study were 8 women and 33 men between the ages of 19 and 64 years (mean, 39.25 ± 8.90 years). Preoperative X-ray, computed tomography, MRI, DSA, and histological data were taken.

Results

The combination of DSA and MRI can efficiently show blood supply changes in the femoral head of NONFH patients at different Association Research Circulation Osseous stages; and also can possibly reveal the causes and development of NONFH. Different stages of circulatory obstruction of the femoral head can be clearly distinguished and used to determine the required perioperative management, thus yielding successful surgical outcomes.

Conclusions

The existing classification systems do not fully reflect the progression of circulatory obstruction in ONFH. Each stage of NONFH development has its own characteristics circulatory obstruction. Early-stage NONFH displays characteristic venous stasis of the femoral head, whereas advanced stage NONFH is characterized by insufficient arterial blood supply to the femoral head. Corresponding NONFH treatment strategies should be considered based on their specific circulatory status. This work also provides guidance and recommendations for adopting corresponding femoral head preserving strategies for young patients in different NONFH circulatory status.
The importance of life history and population regulation for the evolution of social learning
Authors: Deffner Dominik , McElreath Richard
Published: May 2020

Social learning and life history interact in human adaptation, but nearly all models of the evolution of social learning omit age structure and population regulation. Further progress is hindered by a poor appreciation of how life history affects selection on learning. We discuss why life history and age structure are important for social learning and present an exemplary model of the evolution of social learning in which demographic properties of the population arise endogenously from assumptions aboutper capitavital rates and different forms of population regulation. We find that, counterintuitively, a stronger reliance on social learning is favoured in organisms characterized by ‘fast’ life histories with high mortality and fertility rates compared to ‘slower’ life histories typical of primates. Long lifespans make early investment in learning more profitable and increase the probability that the environment switches within generations. Both effects favour more individual learning. Additionally, under fertility regulation (as opposed to mortality regulation), more juveniles are born shortly after switches in the environment when many adults are not adapted, creating selection for more individual learning. To explain the empirical association between social learning and long life spans and to appreciate the implications for human evolution, we need further modelling frameworks allowing strategic learning and cumulative culture.

This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals’.
Behavioural variation and learning across the lifespan in wild white-faced capuchin monkeys
Authors: Perry Susan
Published: May 2020

Natural selection has evidently mediated many species characteristics relevant to the evolution of learning, including longevity, length of the juvenile period, social organization, timing of cognitive and motor development, and age-related shifts in behavioural propensities such as activity level, flexibility in problem-solving and motivation to seek new information. Longitudinal studies of wild populations can document such changes in behavioural propensities, providing critical information about the contexts in which learning strategies develop, in environments similar to those in which learning strategies evolved. The Lomas Barbudal Monkey Project provides developmental data for the white-faced capuchin,
Cebus capucinus
, a species that has converged with humans regarding many life-history and behavioural characteristics. In this dataset, focused primarily on learned aspects of foraging behaviour, younger capuchins are more active overall, more curious and opportunistic, and more prone to inventing new investigative and foraging-related behaviours. Younger individuals more often seek social information by watching other foragers (especially older foragers). Younger individuals are more creative, playful and inventive, and less neophobic, exhibiting a wider range of behaviours when engaged in extractive foraging. Whereas adults more often stick with old solutions, younger individuals often incorporate recently acquired experience (both social and asocial) when foraging.

This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals'.
The impact of learning opportunities on the development of learning and decision-making: an experiment with passerine birds
Authors: Rojas-Ferrer Isabel , Morand-Ferron Julie
Published: May 2020

Developmental context has been shown to influence learning abilities later in life, namely through experiments with nutritional and/or environmental constraints (i.e. lack of enrichment). However, little is known about the extent to which opportunities for learning affect the development of animal cognition, even though such opportunities are known to influence human cognitive development. We exposed young zebra finches (Taenopygia guttata) (n= 26) to one of three experimental conditions, i.e. an environment where (i) colour cues reliably predicted the presence of food (associative learning), (ii) a combination of two-colour cues reliably predicted the presence of food (conditional learning), or (iii) colour cues were non-informative (control). After conducting two different discrimination tasks, our results showed that experience with predictive cues can cause increased choice accuracy and decision-making speed. Our first learning task showed that individuals in the associative learning treatment outperformed the control treatment, while task 2 showed that individuals in the conditional learning treatment had shorter latencies when making choices compared with the control treatment. We found no support for a speed–accuracy trade-off. This dataset provides a rare longitudinal and experimental examination of the effect of predictive versus non-predictive cues during development on the cognition of adult animals.

This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals’.
The emergence of emotionally modern humans: implications for language and learning
Authors: Hrdy Sarah Blaffer , Burkart Judith M.
Published: May 2020

According to the Cooperative Breeding Hypothesis, apes with the life-history attributes of those in the line leading to the genusHomocould not have evolved unless male and female allomothers had begun to help mothers care for and provision offspring. As proposed elsewhere, the unusual way hominins reared their young generated novel phenotypes subsequently subjected to Darwinian social selection favouring those young apes best at monitoring the intentions, mental states and preferences of others and most motivated to attract and appeal to caretakers. Not only were youngsters acquiring information in social contexts different from those of other apes, but they would also have been emotionally and neurophysiologically different from them in ways that are relevant to how humans learn. Contingently delivered rewards to dependents who attracted and ingratiated themselves with allomothers shaped their behaviours and vocalizations and transformed the way developing youngsters learned from others and internalized their preferences.

This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals’.
The elaboration of exploratory play
Authors: Pelz Maddie , Kidd Celeste
Published: May 2020

We apply a new quantitative method for investigating how children's exploration changes across age in order to gain insight into how exploration unfolds over the course of a human life from a life-history perspective. In this study, different facets of exploratory play were quantified using a novel touchscreen environment across a large sample and wide age range of children in the USA (n= 105, ages = 1 year and 10 months to 12 years and 2 months). In contrast with previous theories that have suggested humans transition from more exploratory to less throughout maturation, we see children transition from less broadly exploratory as toddlers to more efficient and broad as adolescents. Our data cast doubt on the picture of human life history as involving a linear transition from more curious in early childhood to less curious with age. Instead, exploration appears to become more elaborate throughout human childhood.

This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals’.
Experimental evolutionary simulations of learning, memory and life history
Authors: Morgan Thomas J. H. , Suchow Jordan W. , Griffiths Thomas L.
Published: May 2020

Humans possess an unusual combination of traits, including our cognition, life history, demographics and geographical distribution. Many theories propose that these traits have coevolved. Such hypotheses have been explored both theoretically and empirically, with experiments examining whether human behaviour meets theoretical expectations. However, theory must make assumptions about the human mind, creating a potentially problematic gap between models and reality. Here, we employ a series of ‘experimental evolutionary simulations' to reduce this gap and to explore the coevolution of learning, memory and childhood. The approach combines aspects of theory and experiment by inserting human participants as agents within an evolutionary simulation. Across experiments, we find that human behaviour supports the coevolution of learning, memory and childhood, but that this is dampened by rapid environmental change. We conclude by discussing both the implications of these findings for theories of human evolution and the utility of experimental evolutionary simulations more generally.

This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals'.
Regulation of meiotic progression by Sertoli-cell androgen signaling
Authors: Larose Hailey , Kent Travis , Ma Qianyi , Shami Adrienne Niederriter , Harerimana Nadia , Li Jun Z. , Hammoud Saher Sue , Handel Mary Ann
Published: May 2020

Androgen receptor (AR) signaling in Sertoli cells is known to be important for germ-cell progression through meiosis, but the extent to which androgens indirectly regulates specific meiosis stages is not known. Here, we combine synchronization of spermatogenesis, cytological analyses and single-cell RNAseq (scRNAseq) in theSertolicellandrogenreceptorknockout (SCARKO) mutant and control mice, and demonstrate that SCARKO mutant spermatocytes exhibited normal expression and localization of key protein markers of meiotic prophase events, indicating that initiation of meiotic prophase is not androgen dependent. However, spermatocytes from SCARKO testes failed to acquire competence for the meiotic division phase. ScRNAseq analysis of wild type and SCARKO mutant testes revealed a molecular transcriptomic block in an early meiotic prophase state (leptotene/zygotene) in mutant germ cells, and identified several misregulated genes in SCARKO Sertoli cells, many of which have been previously implicated in male infertility. Together, our coordinated cytological and single-cell RNAseq analyses identified germ-cell intrinsic and extrinsic genes responsive to Sertoli-cell androgen signaling that promotes cellular states permissive for the meiotic division phase.
Genetically flexible but conserved: a new essential motif in the C-ter domain of HIV-1 group M integrases
Authors: Kanja Marine , Cappy Pierre , Levy Nicolas , Oladosu Oyndamola , Schmidt Sylvie , Rossolillo Paola , Winter Flore , Gasser Romain , Moog Christiane , Ruff Marc , Negroni Matteo , Lener Daniela
Published: May 2020

Using coevolution-network interference based on the comparison of two phylogenetically distantly related isolates, one from the main group M and the other from the minor group O of HIV-1, we identify, in the C-terminal domain (CTD) of integrase, a new functional motif constituted by four non-contiguous amino acids (N222K240N254K273). Mutating the lysines abolishes integration through decreased 3’-processing and inefficient nuclear import of reverse transcribed genomes. Solution of the crystal structures of wt and mutated CTDs shows that the motif generates a positive surface potential that is important for integration. The number of charges in the motif appears more crucial than their position within the motif. Indeed, the positions of the K could be permutated or additional K could be inserted in the motif, generally without affecting integrationper se. Despite this potential genetic flexibility, the NKNK arrangement is strictly conserved in natural sequences, indicative of an effective purifying selection exerted at steps other than integration. Accordingly, reverse transcription was reduced even in the mutants that retained wt integration levels, indicating that specifically the wt sequence is optimal for carrying out the multiple functions integrase exerts. We propose that the existence of several amino acids arrangements within the motif, with comparable efficiencies of integrationper se, might have constituted an asset for the acquisition of additional functions during viral evolution.

IMPORTANCE

Intensive studies on HIV-1 have revealed its extraordinary ability to adapt to environmental and immunological challenges, an ability that is also at the basis of antiviral treatments escape. Here, by deconvoluting the different roles of the viral integrase in the various steps of the infectious cycle, we report how the existence of alternative equally efficient structural arrangements for carrying out one function opens on the possibility of adapting to the optimisation of further functionalities exerted by the same protein. Such property provides an asset to increase the efficiency of the infectious process. On the other hand, though, the identification of this new motif provides a potential target for interfering simultaneously with multiple functions of the protein.
A control approach to the Covid-19 disease using a SEIHRD dynamical model
Authors: Pazos Fernando , Felicioni Flavia E.
Published: May 2020

The recent worldwide epidemic of Covid-19 disease, for which there is no vaccine or medications to prevent or cure it, led to the adoption of public health measures by governments and populations in most of the affected countries to avoid the contagion and its spread. These measures are known as nonpharmaceutical interventions (NPIs) and their implementation clearly produces social unrest as well as greatly affects the economy. Frequently, NPIs are implemented with an intensity quantified in an ad hoc manner. Control theory offers a worth-while tool for determining the optimal intensity of the NPIs in order to avoid the collapse of the healthcare system while keeping them as low as possible, yielding in a policymakers concrete guidance. We propose here the use of a simple proportional controller that is robust to large parametric uncertainties in the model used.
Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube
Authors: Dinh Huy Q. , Lin Xianzhi , Abbasi Forough , Nameki Robbin , Haro Marcela , Olingy Claire E. , Chang Heidi , Hernandez Lourdes , Gayther Simon A. , Wright Kelly N. , Aspuria Paul-Joseph , Karlan Beth Y. , Corona Rosario I. , Li Andrew , Rimel BJ , Siedhoff Matthew , Medeiros Fabiola , Lawrenson Kate
Published: May 2020

The human fallopian tube harbors the cell-of-origin for the majority of high-grade serous ‘ovarian’ cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We performed single-cell transcriptomic profiling in 12 primary fallopian specimens from 8 patients, analyzing around 53,000 individual cells to map the major immune, fibroblastic and epithelial cell types present in this organ. We identified 10 epithelial sub-populations, characterized by diverse transcriptional programs including SOX17 (enriched in secretory epithelial cells), TTF3 and RFX3 (enriched in ciliated cells) and NR2F2 (enriched in early, partially differentiated secretory cells). Based on transcriptional signatures, we reconstructed a trajectory whereby secretory cells differentiate into ciliated cellsviaa RUNX3highintermediate. Computational deconvolution of the cellular composition of advanced HGSCs based on epithelial subset signatures identified the ‘early secretory’ population as a likely precursor state for the majority of HGSCs. The signature of this rare population of cells comprised both epithelial (EPCAM, KRT) and mesenchymal (THY1,ACTA2) features, and was enriched in mesenchymal-type HGSCs (P = 6.7 × 10−27), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.
Lateral and longitudinal fish eDNA distribution in dynamic riverine habitats
Authors: Thalinger Bettina , Kirschner Dominik , Pütz Yannick , Moritz Christian , Schwarzenberger Richard , Wanzenböck Josef , Traugott Michael
Published: May 2020

Assessing the status and distribution of fish populations in rivers is essential for management and conservation efforts in these dynamic habitats. Currently, methods detecting environmental DNA (eDNA) are being established as an alternative and/or complementary approach to the traditional monitoring of fish species. In lotic systems, a sound understanding of hydrological conditions and their influence on the local target detection probability and DNA quantity is key for the interpretation of eDNA-based results. However, the effect of seasonal and diurnal changes in discharge and the comparability of semi-quantitative results between species remain hardly addressed. We conducted a cage experiment with four fish species (three salmonid and one cyprinid species) in a glacier-fed, fish-free river in Tyrol (Austria) during summer, fall, and winter discharge situations (i.e. 25-fold increase from winter to summer). Each season, water samples were obtained on three consecutive days at 13 locations downstream of the cages including lateral sampling every 1-2 m across the wetted width. Fish eDNA was quantified by species-specific endpoint PCR followed by capillary electrophoresis. Close to the cages, lateral eDNA distribution was heterogenous and mirrored cage placement within the stream. In addition to the diluting effect of increased discharge, longitudinal signal changes within the first 20 m were weakest at high discharge. For downstream locations with laterally homogenous eDNA distribution, the signals decreased significantly with increasing distance and discharge. Generally, the eDNA of the larger-bodied salmonid species was less frequently detected, and signal strengths were lower compared to the cyprinid species. This study exemplifies the importance of hydrological conditions for the interpretation of eDNA-based data across seasons. To control for heterogenous eDNA distribution and enable comparisons over time, sampling schemes in lotic habitats need to incorporate hydrological conditions and species traits.
Testing monotonic trends among multiple group means against a composite null
Authors: Hu Chenxiao , Sharpton Thomas , Jiang Duo
Published: May 2020

In biomedical applications, it is often of interest to test the alternative hypothesis that the means of three or more groups follow a strictly monotonic trend such asµ1> µ2> µ3against the null hypothesis that the group means are either equal or unequal but are not monotonic. This is useful, for example, for detecting biomarkers whose level in healthy, low-risk cancer and aggressive cancer subjects increases or decreases throughout the three groups. Various trend tests are available for testing monotonic alternatives. However, existing methods are designed for a highly restrictive null hypothesis where all group means are equal, which represents a special case of the null space in our problem. We demonstrate that these methods fail to control type I error when the group means may be unequal under the null. To test this broader null hypothesis, develop a greedy testing method which has an intuitive interpretation related to two-sample t tests. We show both theoretically and through simulations that the proposed method effectively controls type 1 error throughout the entire null space and achieves higher power than a naive implementation of multiple t-tests. We illustrate the greedy trend test method in real data to study microbial associations with parasite-related pathology in zebrafish.
Impacts of radiation on the bacterial and fungal microbiome of small mammals in the Chernobyl Exclusion Zone
Authors: Antwis Rachael E. , Beresford Nicholas A. , Jackson Joseph A. , Fawkes Ross , Barnett Catherine L. , Potter Elaine , Walker Lee , Gaschak Sergey , Wood Michael D.
Published: May 2020

Environmental impacts of the 1986 Chernobyl Nuclear Power Plant accident are much debated, but the effects of radiation on host microbiomes has received little attention to date. We present the first analysis of small mammal gut microbiome from the Chernobyl Exclusion Zone in relation to total absorbed dose rate and including caecum as well as faeces sample. The associations between microbiome communities and radiation exposure varied between host species. Associations between microbiome and radiation was different for analyses based on ambient versus total weighted absorbed dose rates. We found considerable variation between patterns for faecal and gut samples of bank voles, suggesting faecal samples are not an accurate indicator of gut composition. For bank vole guts, associations between radiation and bacterial community composition were robust against geographical and habitat variation. We found limited associations between radiation and fungal communities. Host physiological mechanisms or environmental factors may be driving these patterns.
Xylose Metabolism and the Effect of Oxidative Stress on Lipid and Carotenoid Production in Rhodotorula toruloides: Insights for Future Biorefinery
Authors: Pinheiro Marina Julio , Bonturi Nemailla , Belouah Isma , Miranda Everson Alves , Lahtvee Petri-Jaan
Published: May 2020

The use of cell factories to convert sugars from lignocellulosic biomass into chemicals in which oleochemicals and food additives, such as carotenoids, is essential for the shift towards sustainable processes. Rhodotorula toruloides is a yeast that naturally metabolises a wide range of substrates, including lignocellulosic hydrolysates, and converts them into lipids and carotenoids. In this study, xylose, the main component of hemicellulose, was used as the sole substrate for R. toruloides, and a detailed physiology characterisation combined with absolute proteomics and genome-scale metabolic models was carried out to understand the regulation of lipid and carotenoid production. To improve these productions, oxidative stress was induced by hydrogen peroxide and light irradiation and further enhanced by adaptive laboratory evolution. Based on the online measurements of growth and CO2 excretion, three distinct growth phases were identified during batch cultivations. The intracellular flux estimations correlated well with the measured protein levels and demonstrated improved NADPH regeneration, phosphoketolase activity and reduced beta-oxidation, correlating with increasing lipid yields. Light irradiation resulted in 70% higher carotenoid and 40% higher lipid yields. The presence of hydrogen peroxide did not affect the carotenoid yield but culminated in the highest lipid yield of 0.65 g/gDCW. The adapted strain showed improved fitness and 2.3-fold higher carotenoid yield than the parental strain. This work presented a holistic view of xylose conversion into microbial oil and carotenoids by R. toruloides for further cost-effective and renewable production of these molecules.
obaDIA: one-step biological analysis pipeline for data-independent acquisition and other quantitative proteomics data
Authors: Yan Jun , Zhai Hongning , Zhu Ling , Sa Sasha , Ding Xiaojun
Published: May 2020

Motivation

Data mining and data quality evaluation are indispensable constituents of quantitative proteomics, but few integrated tools available.

Results

We introduced obaDIA, a one-step pipeline to generate visualizable and comprehensive results for quantitative proteomics data. obaDIA supports fragment-level, peptide-level and protein-level abundance matrices from DIA technique, as well as protein-level abundance matrices from other quantitative proteomic techniques. The result contains abundance matrix statistics, differential expression analysis, protein functional annotation and enrichment analysis. Additionally, enrichment strategies which use total proteins or expressed proteins as background are optional, and HTML based interactive visualization for differentially expressed proteins in the KEGG pathway is offered, which helps biological significance mining. In short, obaDIA is an automatic tool for bioinformatics analysis for quantitative proteomics.

Availability

obaDIA is freely available fromhttps://github.com/yjthu/obaDIA.git.

Contact

dingxiaojun@e-omics.com
Recovery of Consciousness and Cognition after General Anesthesia in Humans
Authors: Mashour George A. , Palanca Ben J.A. , Basner Mathias , Li Duan , Wang Wei , Blain-Moraes Stefanie , Lin Nan , Maier Kaitlyn , Muench Maxwell , Tarnal Vijay , Vanini Giancarlo , Ochroch E. Andrew , Hogg Rosemary , Schwarz Marlon , Maybrier Hannah , Hardie Randall , Janke Ellen , Golmirzaie Goodarz , Picton Paul , McKinstry-Wu Andrew , Avidan Michael S. , Kelz Max B.
Published: May 2020

Understanding how consciousness and cognitive function return after a major perturbation is important clinically and neurobiologically. To address this question, we conducted a three-center study of 30 healthy humans receiving general anesthesia at clinically relevant doses for three hours. We administered a pre- and post-anesthetic battery of neurocognitive tests, recorded continuous electroencephalography to assess cortical dynamics, and monitored sleep-wake activity before and following anesthetic exposure. We hypothesized that cognitive reconstitution would be a process that evolved over time in the following sequence: attention, complex scanning and tracking, working memory, and executive function. Contrary to our hypothesis, executive function returned first and electroencephalographic analyses revealed that frontal cortical dynamics recovered faster than posterior cortical dynamics. Furthermore, actigraphy indicated normal sleep-wake patterns in the post-anesthetic period. These recovery patterns of higher cognitive function and arousal states suggest that the healthy human brain is resilient to the effects of deep general anesthesia.
Hippocampal subfield volumes across the healthy lifespan and the effects of MR sequence on estimates
Authors: Bussy Aurelie , Plitman Eric , Patel Raihaan , Tullo Stephanie , Salaciak Alyssa , Bedford Saashi A. , Farzin Sarah , Béland Marie-Lise , Valiquette Vanessa , Kazazian Christina , Tardif Christine , Devenyi Gabriel A. , Chakravarty Mallar
Published: May 2020

The hippocampus has been extensively studied in various neuropsychiatric disorders throughout the lifespan. However, inconsistent results have been reported with respect to which subfield volumes are most related to age. Here, we investigate whether these discrepancies may be explained by experimental design differences that exist between studies. Multiple datasets were used to collect 1690 magnetic resonance scans from healthy individuals aged 18-95 years old. Standard T1-weighted (T1w; MPRAGE sequence, 1 mm3voxels), high-resolution T2-weighted (T2w; SPACE sequence, 0.64 mm3voxels) and slab T2-weighted (Slab; 2D turbo spin echo, 0.4 x 0.4 x 2 mm3voxels) images were acquired. The MAGeT Brain algorithm was used for segmentation of the hippocampal grey matter (GM) subfields and peri-hippocampal white matter (WM) subregions. Linear mixed-effect models and Akaike information criterion were used to examine linear, second or third order natural splines relationship between hippocampal volumes and age. We demonstrated that stratum radiatum/lacunosum/moleculare and fornix subregions expressed the highest relative volumetric decrease, while the cornus ammonis 1 presented a relative volumetric preservation of its volume with age. We also found that volumes extracted from slab images were often underestimated and demonstrated different age-related relationships compared to volumes extracted from T1w and T2w images. The current work suggests that although T1w, T2w and slab derived subfield volumetric outputs are largely homologous, modality choice plays a meaningful role in the volumetric estimation of the hippocampal subfields.