bluuebunny/crossref_metadata_2025 huggingface dataset:
CALMODULIN-LIKE-38 and PEP1 RECEPTOR 2 integrate nitrate and brassinosteroid signals to regulate root growth
Authors: Song Xiaoyun , Li Jianfu , Lyu Mengli , Kong Xiuzhen , Hu Shi , Song Qingwei , Zuo Kaijing
Published: July 2021

Plants exhibit remarkable developmental plasticity, enabling them to adapt to adverse environmental conditions such as low nitrogen (N) in the soil. Brassinosteroids (BRs) promote root foraging for nutrients under mild N deficiency, but the crosstalk between the BR- and N-signaling pathways in the regulation of root growth remains largely unknown. Here, we show that CALMODULIN-LIKE-38 (CML38), a calmodulin-like protein, specifically interacts with the PEP1 RECEPTOR 2 (PEPR2), and negatively regulates root elongation in Arabidopsis (Arabidopsis thaliana) in response to low nitrate (LN). CML38 and PEPR2 are transcriptionally induced by treatments of exogenous nitrate and BR. Compared with Col-0, the single mutants cml38 and pepr2 and the double mutant cml38 pepr2 displayed enhanced primary root growth and produced more lateral roots under LN. This is consistent with their higher nitrate absorption abilities, and their stronger expression of nitrate assimilation genes. Furthermore, CML38 and PEPR2 regulate common downstream genes related to BR signaling, and they have positive roles in BR signaling. Low N facilitated BR signal transmission in Col-0 and CML38- or PEPR2-overexpressing plants, but not in the cml38 and pepr2 mutants. Taken together, our results illustrate a mechanism by which CML38 interacts with PEPR2 to integrate LN and BR signals for coordinating root development to prevent quick depletion of N resources in Arabidopsis.
Metalloid transporters and their regulation in plants
Authors: Yamaji Naoki , Ma Jian Feng
Published: July 2021

Transport of metalloids including B, Si, and As is mediated by a combination of channels and efflux transporters in plants, which are strictly regulated in response to environmental changes.
Reproductive Health for Conflict-Affected Displaced Women in Nigeria: An Intersectionality-Based Critical Ethnography Study
Authors: Amodu Oluwakemi C , Salami Bukola O , Richter Magdalena S
Published: July 2021

Nigeria is a significant contributor to the global forcibly displaced population. The majority of this displacement is related to Boko Haram and herdsmen attacks in Northern Nigeria. A growing body of research has started to investigate issues surrounding protection concerns for the internally displaced who have been uprooted by these uprisings and attacks. Importantly, research is also starting to engage with issues of sexual violence and unwanted pregnancies associated with the conflict and displacement. This article aims to develop this work further by examining intersecting factors shaping the reproductive health experiences of women internally displaced by the Boko Haram and Herdsmen crisis in Northern Nigeria. To this end, a critical ethnography study involving in-depth interviews with 29 internally displaced women and five service providers in Northern Nigeria was completed between May 2019 to September 2019. Three major intersected subjects pertaining to women’s reproductive health access were observed. These were: (1) normative perceptions and the prevalence of urogenital infections; (2) decisions made on birthplaces and number of births; (3) income and accessibility to care. The findings illustrate the interrelated economic and sociocultural factors that constrain access to reproductive health for internally displaced women.
Promissory ethical regimes: publics and public goods in genome editing for human health
Authors: Wienroth Matthias , Scully Jackie Leach
Published: July 2021

This paper analyses promissory discourse for genome editing and human health in the UK, attending to the articulation of public goods and their beneficiary publics. Focusing on promissory reasoning about an emerging technology field as anticipatory and ethical considerations as integral to such debates, the notion of ethical regime as a mode of governance is applied to the concept of promissory regime. By analyzing key documents and interviews with opinion leaders—thus focusing on the discursive dimension—an enabling promissory ethical regime for genome editing and its contestation are identified. This regime posits scientific knowledge production now, and improved treatment or prevention of hereditary diseases later, as key goods of genome editing for human health and as a sociotechnical project worthy of support. Specific publics are created as beneficiaries. These publics and goods play out as ethical rationales for the promissory governance of the emerging field of human genome editing.
The acute effects of aerobic exercise on sleep in patients with unipolar depression: a randomized controlled trial
Authors: Brupbacher Gavin , Zander-Schellenberg Thea , Straus Doris , Porschke Hildburg , Infanger Denis , Gerber Markus , von Känel Roland , Schmidt-Trucksäss Arno
Published: July 2021

Study Objectives

Insomnia increases the risk of negative disease trajectory, relapse, and suicide in patients with depression. We aimed at investigating the effects of a single bout of aerobic exercise, performed after 02:00 pm, on the subsequent night’s sleep in patients with depression.

Methods

The study was designed as a two-arm parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. Patients between 18 and 65 years of age with a primary diagnosis of unipolar depression were included. The intervention was a single 30-minute bout of moderate aerobic exercise. The control group sat and read for 30 minutes. The primary outcome was sleep efficiency measured by polysomnography. Secondary outcomes were other polysomnographic variables, subjective sleep quality, daytime sleepiness, mood states, and adverse events.

Results

Ninety-two patients were randomized to the exercise (N = 46) or control group (N = 46). There were no clinically relevant differences at baseline. Intent-to-treat analysis ANCOVA of follow-up sleep efficiency, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = −0.93, p = 0.59). There was no evidence for significant differences between both groups in any other objective or subjective sleep outcomes, daytime sleepiness, or adverse events. The intervention had an immediate positive effect on mood states, including depressiveness (β = −0.40, p = 0.003).

Conclusions

This is the first trial to study the effects of a single bout of aerobic exercise on sleep in patients with depression to the best of our knowledge. Aerobic exercise had no effect on sleep efficiency but had a strong beneficial effect on mood and did not increase adverse outcomes. These results add to the growing body of evidence that, contrary to sleep hygiene recommendations, exercise after 02:00 pm is not detrimental for sleep.

Clinical Trial Registration

Clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03673397. Protocol registered on September 17, 2018.
Building capacity from within: qualitative evaluation of a training program aimed at upskilling healthcare workers in delivering an evidence-based implementation approach
Authors: Morrow April , Chan Priscilla , Tiernan Gabriella , Steinberg Julia , Debono Deborah , Wolfenden Luke , Tucker Katherine M , Hogden Emily , Taylor Natalie
Published: July 2021

Translating evidence into complex health systems is an ongoing challenge. Building the capacity of healthcare workers in behavioral and implementation science methods may facilitate the use of evidence-based implementation approaches, leading to sustainable and effective translation. The aim was to describe the development, contents and evaluation of a training workshop aimed at upskilling hospital-embedded staff to deliver an evidence-based implementation approach. The Hide and Seek Project (HaSP) is a cluster randomized controlled trial testing two implementation approaches for improving hereditary cancer referral at eight Australian hospitals. Healthcare workers were recruited as “Implementation Leads” and trained via a one-day workshop—TRAining in evideNce-baSed ImpLementATion for hEalth (TRANSLATE). The purpose of TRANSLATE was to upskill Implementation Leads in the delivery of HaSP, as well as implementation science methods more broadly. Implementation Leads participated in semi-structured evaluation interviews, which were analyzed using inductive thematic analysis. Nine Implementation Leads from various professional backgrounds completed the training. Four key themes were identified: (i) training day reactions, (ii) learning, (iii) implementation barriers and facilitators, and (iv) building health system capacity for implementation. Participants reported high levels of satisfaction, and anticipated that the knowledge and skills may be useful in the future. We describe a novel training program focused on the delivery of evidence-based implementation within health systems. Guided by insights from this study, methods to deliver the training on a larger scale and across different contexts are being explored. The prolonged impact of TRANSLATE will be further evaluated at trial completion.

Trial registration: ANZCTR, ACTRN12618001072202. Registered on June 27, 2018
Analysis of the insecticide resistance mechanism in Anopheles culicifacies sensu lato from a malaria-endemic state in India
Authors: Kareemi Tazeen I , Mishra Ashok K , Chand Sunil K , Nirankar Jitendra K , Vishwakarma Anup K , Tiwari Archana , Bharti Praveen K
Published: July 2021

Background

Understanding the dynamics and mechanisms of insecticide resistance in malaria vectors is crucial for vector control activities. The present study investigates the level of insecticide resistance in Anopheles culicifacies and explores the role of two main mechanisms in conferring resistance target site insensitivity and metabolic resistance.

Methods

A. culicifacies mosquitoes were collected and the voltage-gated sodium channel (VGSC) gene was amplified and sequenced to analyse the knockdown resistance (kdr) mutations. Further, a non-experimental homology model was generated to investigate the effect of kdr mutations on the conformation of protein. Metabolic resistance was determined using bioassay-based resistant and susceptible mosquitoes and the expression levels of the genes CYP6Z1 and GSTe2 were compared between the two groups.

Results

Sequence analysis of the VGSC gene revealed the presence of L1014F (n=48 [17%]), L1014S and V1010L (n=5 [1.7%]) mutations in the study area. In gene expression studies, a significant upregulation of CYP6Z1 in deltamethrin-resistant (fold change 243.62; p=0.02) mosquitoes and that of GSTe2 in dichlorodiphenyltrichloroethane (fold change 403.45; p=0.01) and alpha-cypemethrin resistant (fold change 217.51; p=0.0005) mosquitoes was observed.

Conclusions

The study revealed that expression of the genes (CYP6Z1 and GSTe2) conferring metabolic resistance play a key role in insecticide resistance in A. culicifacies populations in central India. However, mutations L101F, L10104S and V10101L also have a role to some extent in spreading resistance.

GeneBank accession numbers: MW559058, MW559059 and MW559060

Cover Image: Workflow of Chimera–Modeller interface. In the top window of Chimera's multi-align viewer the sequence alignment of VGSC proteins of human (pdb id_6AGF), cockroach (pdb id 5XOM) and A. culicifacies (ACT176122.1) is shown. The dialog box in the middle is of the comparative modelling tool of Modeller. The A. culicifacies sequence is designated as the target while human and cockroach sequences are templates. Upon selection of the template sequences in the dialog box, the structures of the respective proteins are displayed in the Chimera window. As the run is completed, the results are displayed in the form of a list of models with their scores in a table.
Liver Dysfunction Associated With In-Hospital Mortality in Adult Extracorporeal Membrane Oxygenation Support
Authors: Dobrilovic Nikola , March Robert , Yin Kanhua , Lateef Omar , Alimohamed Mazahir , Bak Erica , Delibasic Maja , Karlson Karl , Edwards Niloo , Raman Jaishankar
Published: July 2021

OBJECTIVES:

Extracorporeal membrane oxygenator support is a powerful clinical tool that is currently enjoying a resurgence in popularity. Wider use of extracorporeal membrane oxygenator support is limited by its significant risk profile and extreme consumption of resources. This study examines the role of markers of liver dysfunction in predicting outcomes of adult patients requiring extracorporeal membrane oxygenator support.

DESIGN:

Retrospective review.

SETTING:

Large extracorporeal membrane oxygenator center, Chicago, IL.

PATIENTS:

This study reports a single institution experience examining all adult patients for whom extracorporeal membrane oxygenator support was used over an 8-year period. Data were collected regarding patient demographics, details of extracorporeal membrane oxygenator support provided, laboratory data, and outcomes. Trends in liver function were examined for their ability to predict survival.

INTERVENTION:

Extracorporeal membrane oxygenator support, critical care.

MEASUREMENTS AND MAIN RESULTS:

Mean age was 50 years (range, 19–82 yr). There were 86 male patients (56.6%) and 66 female patients (43.4%). Indications for initiation of extracorporeal membrane oxygenator support included cardiac 76 patients (50.0%), respiratory 48 patients (31.6%), extracorporeal cardiopulmonary resuscitation 21 patients (13.3%), and combined cardiac/respiratory seven patients (4.6%). Mean duration of extracorporeal membrane oxygenator support was 17 days (range 1–223 d) or median 8 days (interquartile range, 4–17 d). Overall, in-hospital mortality was 56% (86/152). Forty-five percent of adult patients (68/152) surpassed at least one of the following established liver dysfunction thresholds: total bilirubin greater than 15 mg/dL, aspartate aminotransferase greater than 20× upper limit of normal, and alanine aminotransferase greater than 20× upper limit of normal. The multivariable logistic analysis yielded three significant findings associated with in-hospital mortality: highest total bilirubin greater than 15 (adjusted odds ratio = 4.40; 95% CI, 1.19–21.87; p = 0.04), age (adjusted odds ratio = 1.03; 95% CI, 1.00–1.05; p = 0.04), and highest lactate (adjusted odds ratio = 1.15; 95% CI, 1.06–1.26; p = 0.002).

CONCLUSIONS:

Increases in age, highest total bilirubin, and lactate all correlated with in-hospital mortality in multivariable analysis of patients requiring extracorporeal membrane oxygenator support.
OPTICAL COHERENCE TOMOGRAPHIC PATTERNS OF POSTERIOR SEGMENT STICKY HEAVY SILICONE OIL
Authors: Zewar Ahmed N. , Lochhead Jonathan
Published: July 2021

Purpose:

To describe unique optical coherence tomography observations of adherent preretinal heavy silicone oil after removal.

Methods:

Retrospective observational review of files and optical coherence tomography scans of patients who had pars plana vitrectomy with heavy silicone oil. We investigated the possible precipitating preoperative and intraoperative factors and the association with postoperative epiretinal membrane and cystoid macular edema.

Results:

Forty-one eyes from 39 patients were involved. Two characteristic sticky silicone oil structures were identified in 33 patients (80%): variably reflective macrodroplets (bubbles) and hyperreflective microdroplets (dots). The main contributing variable was the tamponade duration. Other notable associations included postoperative epiretinal membrane and cystoid macular edema formation. Surgical interventions including heavy liquid did not show a strong predilection to their development. We reported two novel findings of sticky prefoveal macrodroplets in five patients and intravitreal macrodroplets and microdroplets casting shadows on the underlying retina in four patients.

Conclusion:

This study confirms previously reported optical coherence tomography observations of sticky emulsified silicone oil remnants after removal. This is the first report of two distinctly different optical coherence tomography appearances after heavy silicone oil removal. The variability in size and reflectivity may be attributed to the amount and nature of the induced inflammatory reaction.
FLUID-BASED VISUAL PROGNOSTICATION IN TYPE 3 MACULAR NEOVASCULARIZATION-FLIP-3 STUDY
Authors: Sharma Ashish , Cheung CHUI MING GEMMY , Arias-Barquet Luis , Ozdek Sengul , Parachuri Nikulaa , Kumar Nilesh , Hilely Assaf , Zur Dinah , Loewenstein Anat , Vella Giovanna , Bandello Francesco , Querques Giuseppe
Published: July 2021

Purpose:

To analyze the effect of fluid on visual acuity in cases of Type 3 macular neovascularization.

Methods:

This multicentric, retrospective cohort study included eyes with treatment-naïve Type 3 macular neovascularization. Analysis of fluid in different compartments was performed. Group A included eyes with isolated intraretinal fluid, whereas Group B included eyes with intraretinal fluid in conjunction with subretinal fluid and/or sub retinal pigment epithelial fluid.

Results:

Eyes in Group A (31, 55.3%) had better best-corrected visual acuity of 20/50 snellen equivalent (0.42 ± 0.31 logarithm of the minimum angle of resolution) at baseline and 20/50 snellen equivalent (0.40 ± 0.28 logarithm of the minimum angle of resolution) at complete resolution compared with Group B with visual acuity of 20/80 snellen equivalent (0.64 ± 0.35 logarithm of the minimum angle of resolution) (P = 0.0181) at baseline and 20/100 snellen equivalent (0.70 ± 0.40 logarithm of the minimum angle of resolution) (P = 0.0021) at complete resolution. Subfoveal atrophy was more in Group B (82.6% 19/23) at complete resolution in comparison to Group A (16/31, 51.6%). Eyes in Group B needed more anti–vascular endothelial growth factor injections (10.3 ± 9.0) for complete resolution compared with Group A (5.7 ± 4.8).

Conclusion:

Intraretinal fluid may be associated with good visual acuity in Type 3 macular neovascularization in contrast to other forms of neovascular age related macular degeneration. Furthermore, intraretinal fluid in isolation may need fewer injections and could probably be associated with less subfoveal atrophy.
Corneal Endothelial Changes in Patients With Primary Congenital Glaucoma
Authors: Tamçelik Nevbahar , Batu Oto Bilge , Mergen Burak , Kiliçarslan Oğuzhan , Gönen Busenur , Arici Ceyhun
Published: July 2021

Précis:

Specular microscopic parameters were found to be decreased in patients with primary congenital glaucoma (PCG). Patients with PCG and Haab striae had lower endothelial cell density (ECD) and central corneal thickness (CCT) than those without Haab striae did. The type of surgery (viscogoniotomy, viscotrabeculotomy, or combined viscotrabeculotomy and trabeculectomy) did not affect specular microscopic parameters.

Purpose:

The purpose of this study was to compare specular microscopic parameters such as corneal ECD, coefficient of variation (CV), hexagonal cell percentage (HEX), and CCT between patients with PCG and healthy controls; to determine the predictive ability of Haab striae for endothelial cell changes PCG by comparing patients with and without Haab striae; and to investigate if the type of surgery used to treat glaucoma (viscogoniotomy, viscotrabeculotomy, or combined viscotrabeculotomy and trabeculectomy) affects specular microscopic parameters.

Methods:

A cross-sectional specular microscopic analysis of patients with PCG and healthy controls was performed. One hundred eyes of 62 patients with PCG with and without Haab striae and 101 eyes of 101 healthy controls were enrolled in this study. Specular microscopic parameters, including ECD, HEX, CV, and CCT, of all subjects were evaluated.

Results:

Patients with PCG showed significantly lower ECD and CCT than healthy controls did. Those with Haab striae had lower ECD and CCT but no differences in age, HEX, and CV compared with those without Haab striae. ECD, CV, HEX, or CCT did not significantly differ among patients treated with the 3 different types of surgery.

Conclusions:

Prolonged exposure to elevated intraocular pressure during prenatal and/or early postnatal life results in structural changes in immature infant corneas. Specular microscopic parameters differed significantly between healthy controls and patients with PCG. The type of surgery had no effect on these parameters. Among patients with PCG, those with Haab striae had isolated corneal endothelial cell loss without morphologic changes within the endothelium.
Changes to Corneal Topography and Biometrics After PRESERFLO Microshunt Surgery for Glaucoma
Authors: Ibarz Barberá Marta , Morales-Fernandez Laura , Gómez de Liaño Rosario , Tañá Rivero Pedro , Teus Miguel A.
Published: July 2021

Precis:

Glaucoma surgery with PRESERFLO Microshunt shows mild and transient changes in the corneal astigmatism, corneal elevation and biometrics in the early postoperative period. Posterior corneal elevation (PCE) tends to be higher in primary open angle glaucoma (POAG).

Purpose:

The aim was to determine the changes in the corneal keratometry, astigmatism and elevation, refraction, axial length (AL) and anterior chamber depth and volume after the implantation of the PRESERFLO Microshunt in patients with POAG in the early postoperative period.

Patients and Methods:

Patients diagnosed with POAG who underwent an ab externo (polystyrene-block-isobutylene-block-styrene) microshunt implantation were recruited. The central corneal thickness, the intraocular pressure (IOP), best-corrected visual acuity, refraction, biometrics, and corneal topography with a Scheimpflug topographer were analyzed preoperatively and 24 hours, 1 week, 1 month, and 3 months after surgery.

Results:

A total of 30 eyes of 29 patients were included. In 24 eyes the device was implanted as a stand-alone procedure and in 6 eyes it was combined with cataract surgery. The results were analyzed separately. The IOP decreased from 21.8±5.2 and 16.5±1.5 mm Hg at baseline to 10.9±1.8 and 10.1±1.1 mm Hg at 3 months in the noncombined and combined groups (P<0.01). The anterior surface astigmatism, posterior surface astigmatism, and total corneal astigmatism increased in each group 0.4±0.3/0.2±1.0 D, 0.08±0.1/0.03±0.1 D and 0.4±0.3/0.2±0.9 D, respectively, at 3 months. The anterior corneal elevation and PCE (ACE max, ACE min, PCE max) increased in the first week (P=0.01) with no significant changes at 3 months in the noncombined group. The changes observed in the combined group were not significant. The AL decreased to 0.13±0.23 and 0.2±0.07 mm in each group (P=0.01). There was a significant correlation between the IOP and the maximum elevation of the posterior surface of the cornea at the preoperative examination (r=0.93, P=0.02).

Conclusions:

The PRESERFLO Microshunt implant for glaucoma surgery induces mild and transient changes in corneal astigmatism, AL and anterior chamber depth in the early postoperative period.
Effects of Corneal Biomechanical Properties on Rebound Tonometry (Icare200) and Applanation Tonometry (Perkins) Readings in Patients With Primary Congenital Glaucoma
Authors: Morales-Fernandez Laura , Saenz-Frances Federico , Pérez-García Pilar , Garcia-Feijoo Julian , Garcia-Saenz Sofia , Gómez de Liaño Rosario , Martinez-de-la-Casa Jose M.
Published: July 2021

Objective:

The aim was to assess the influence of corneal biomechanics on intraocular pressure (IOP) measurements made with the Icare200 (IC200) rebound tonometer and the Perkins handheld applanation tonometer in patients with primary congenital glaucoma (PCG).

Materials and Methods:

A total of 40 PCG patients and 40 healthy controls, age, and sex-matched, were recruited. IOP was measured with the Ocular Response Analyzer (IOPc, IOPg), IC200 and Perkins. The variables age, IOP, corneal hysteresis (CH), corneal resistance factor (CRF), central corneal thickness (CCT), best-corrected visual acuity, spherical equivalent, medications, and glaucoma surgeries were recorded for each subject. Univariate and multivariate analysis were used to detect effects of variables on IOP measurements.

Results:

Mean CCT was 545.65±71.88 μm in PCG versus 558.78±27.58 μm in controls (P=0.284). CH and CRF were significantly lower in PCG group than in control group: mean CH 8.11±1.69 versus 11.15±1.63 mm Hg (P<0.001), and mean CRF 9.27±2.35 versus 10.71±1.75 mm Hg (P=0.002). Mean differences between IOP IC200-Perkins were 0.79±0.53 mm Hg in PCG versus 0.80±0.23 mm Hg in controls (P<0.001) and mean differences IC200-IOPc were −0.89±5.15 mm Hg in PCG (P<0.001) versus 1.60±3.03 mm Hg in controls (all P<0.009). Through multivariate analysis, CRF showed positive association and CH negative association with IOP measured with Perkins or IC200 in both subject groups. No association was detected for CCT, age, or sex.

Conclusion:

CH and CRF were identified as the main factors interfering with IOP measurements made with both tonometers in patients with PCG and healthy controls.
Fruitful collaborations: the Taylor White project in the Blacker Wood Natural History Collection
Authors: Williams Lauren
Published: July 2021

As part of a themed print issue of
Notes and Records
dedicated to a research project surrounding the eighteenth-century Taylor White collection of animal paintings, this article provides context by describing the initial acquisition of the collection, and by situating it within the larger Blacker Wood Natural History Collection held at McGill University Library. Highlights of the Blacker Wood Collection are discussed, along with the collection's founder, Dr Casey Wood. The second part of the article provides a brief examination of the movement, in some academic administrative circles, towards the ‘de-professionalization’ of librarian work within academic libraries, and offers an outline of the specialized skills that librarians bring to the description, analysis and preservation of special collections. The Taylor White Project is then offered as an example of research collaborations between scholars and librarians; a description of the advantages of embedding a scholar within specific library collections to work with, rather than replace, a librarian is provided. The author suggests this strategy as one potential answer to the question of ‘de-professionalization’, to move away from divisive discussions towards a more symbiotic relationship between scholars and librarians.
Electric field control of magnetism
Authors: Ramesh Ramamoorthy , Manipatruni Sasikanth
Published: July 2021

Electric field control of magnetism is an extremely exciting area of research, from both a fundamental science and an applications perspective and has the potential to revolutionize the world of computing. To realize this will require numerous further innovations, both in the fundamental science arena as well as translating these scientific discoveries into real applications. Thus, this article will attempt to bridge the gap between condensed matter physics and the actual manifestations of the physical concepts into applications. We have attempted to paint a broad-stroke picture of the field, from the macroscale all the way down to the fundamentals of spin–orbit coupling that is a key enabler of the physics discussed. We hope it will help spur more translational research within the broad materials physics community. Needless to say, this article is written on behalf of a large number of colleagues, collaborators and researchers in the field of complex oxides as well as current and former students and postdocs who continue to pursue cutting-edge research in this field.
Human sickness detection is not dependent on cultural experience
Authors: Arshamian Artin , Sundelin Tina , Wnuk Ewelina , O'Meara Carolyn , Burenhult Niclas , Rodriguez Gabriela Garrido , Lekander Mats , Olsson Mats J. , Lasselin Julie , Axelsson John , Majid Asifa
Published: July 2021

Animals across phyla can detect early cues of infection in conspecifics, thereby reducing the risk of contamination. It is unknown, however, if humans can detect cues of sickness in people belonging to communities with whom they have limited or no experience. To test this, we presented Western faces photographed 2 h after the experimental induction of an acute immune response to one Western and five non-Western communities, including small-scale hunter–gatherer and large urban-dwelling communities. All communities could detect sick individuals. There were group differences in performance but Western participants, who observed faces from their own community, were not systematically better than all non-Western participants. At odds with the common belief that sickness detection of an out-group member should be biased to err on the side of caution, the majority of non-Western communities were unbiased. Our results show that subtle cues of a general immune response are recognized across cultures and may aid in detecting infectious threats.
Euzebya pacifica sp. nov., a novel member of the class Nitriliruptoria
Authors: Jian Shu-Ling , Xu Lin , Meng Fan-Xu , Sun Cong , Xu Xue-Wei
Published: July 2021

A Gram-stain-positive, aerobic, chemo-organotrophic, rod-shaped, non-spore-forming strain, which produced convex, circular, pink-pigmented colonies, designated as DY32-46T, was isolated from seawater collected from the Pacific Ocean. DY32-46T was found to grow at 20–40 °C (optimum, 30–35 °C), pH 6.0–8.0 (optimum, pH 6.5) and with 0–5 % (w/v) NaCl (optimum, 1–2 %). The results of chemotaxonomic analysis indicated that the respiratory quinone of DY32-46T was MK-9(H4), and major fatty acids (>10 %) were C17 : 1
ω8c, summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c), C16 : 0 and C15 : 1
ω6c. The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophospholipid, three unidentified glycolipids, three unidentified phospholipids, one unidentified phosphoglycolipid and five unidentified lipids. The DNA G+C content of DY32-46T was 70.6 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences and genomic data indicated that DY32-46T should be assigned to the genus

Euzebya

. ANI and in silico DNA–DNA hybridization values between strain DY32-46T and type strains of

Euzebya

species were 73.1–87.2 % and 20.2–32.4 %, respectively. Different phenotypic properties, together with genetic distinctiveness, demonstrated that strain DY32-46T was clearly distinct from recognized species of the genus

Euzebya

. Therefore, DY32-46T represents a novel species within the genus

Euzebya

, for which the name Euzebya pacifica sp. nov is proposed. The type strain is DY32-46T (=MCCC 1K03476T=KCTC 49091T).
Mode of Presentation and Outcomes of COVID-19 Cases in a Tertiary Hospital in Nigeria
Authors: Raji Yakubu Egigogo , Waziri Bala , Hussaini Sadiq Aliyu , Ja’agi Ahmad Idris , Alhaji Umar Isah , Aliyu Abdulmalik M. , Muhammad Abdullahi , Garba Adama Saidu
Published: July 2021

Coronavirus disease 2019 (COVID-19) has spread across the globe with its consequent human and economic challenges. To achieve effective control of the pandemic, efforts need to be holistic and global. Understanding patients’ demographics and clinical characteristics will assist in the control of the infection. However, there is a paucity of studies on the clinical presentation of COVID-19 patients from Nigeria and indeed Africa. Thus, this retrospective case series evaluated the medical records of COVID-19 patients admitted in a tertiary hospital in Nigeria. Patients’ demographics, and other clinical variables were assessed and presented. Data of 14 patients with complete records were included in the study. Most of the patients (78.6%) were males and the mean age of the study participants is 63.5 years (SD; 11.5). The commonest presenting symptoms were fever (93%), cough (71.4%), and dyspnoea (57.1%). At presentation, 13 patients had coexisting diseases while 8 (57.0%) patients had moderate disease and the remaining 6 (43.0%) had severe cases. After management, 1 patient died, two were referred and 11 recovered and were discharged alive. Thus, this study has identified advanced age, male gender, and comorbidity as increased risk factors for hospitalisation. The patient survival outcome in this study was also good.
Indications that Stockholm has reached herd immunity, given limited restrictions, against several variants of SARS-CoV-2
Authors: Carlsson Marcus , Söderberg-Nauclér Cecilia
Published: July 2021

“When COVID-19 cases go up, public compliance with restrictions is poor, when cases go down, public compliance is good.” In this article, we question this explanation and show that relatively low levels of sero-prevalence helps to keep cases down. In other words, the herd-immunity threshold appears to be much lower than previously thought. We construct a mathematical model taking pre-immunity, antibody waning and more infectious variants of concern into consideration, thereby providing a theoretical framework in which the cases in Stockholm county can be fully predicted without relying on neither oscillations in restrictions (and public compliance thereof) nor vaccination roll-out. We also show that it is very difficult to match the data from Stockholm without including pre-immunity, or, which turns out to be equivalent, great variations in susceptibility.
A note on variable susceptibility, the herd-immunity threshold and modeling of infectious diseases
Authors: Carlsson Marcus , Wittsten Jens , Söderberg-Nauclér Cecilia
Published: July 2021

The unfolding of the COVID-19 pandemic has been very difficult to predict using mathematical models for infectious diseases. While it has been demonstrated that variations in susceptibility have a damping effect on key quantities such as the incidence peak, the herd-immunity threshold and the final size of the pandemic, this complex phenomenon is almost impossible to measure or quantify, and it remains unclear how to incorporate it for modeling and prediction.

In this work we show that, from a modeling perspective, variability in susceptibility on an individual level is equivalent with a fraction θ of the population having an “artificial” sterilizing immunity. Given that this new parameter θ can be estimated, we also derive formulas for R0, the herd-immunity threshold and the final size of the pandemic. In the particular case of SARS-CoV-2, there is by now undoubtedly variable susceptibility due to waning immunity from both vaccines and previous infections, and our findings may be used to greatly simplify models. If such variations were also present prior to the first wave, as indicated by a number of studies, these findings can help explain why the magnitude of the initial waves of SARS-CoV-2 was relatively low, compared to what one may have expected based on standard models.
Dysregulated myogenesis and autophagy in genetically induced pulmonary emphysema
Authors: Balnis Joseph , Drake Lisa A. , Singer Diane V. , Vincent Catherine E. , Korponay Tanner C. , D’Armiento Jeanine , Lee Chun Geun , Elias Jack A. , Singer Harold A. , Jaitovich Ariel
Published: July 2021

Patients with chronic obstructive pulmonary disease (COPD)-pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced muscle mass and force-generation capacity, which are influenced by fibers integrity. Myogenesis, which is muscle turnover driven by progenitor cells such as satellite cells, contributes to the maintenance of muscle integrity in the context of organ development and injury-repair cycles. Injurious events crucially occur in COPD patients’ skeletal muscles in the setting of exacerbations and infections which lead to acute decompensations for limited periods of time after which, patients typically fail to recover the baseline status they had before the acute event. Autophagy, which is dysregulated in muscles from COPD patients, is a key regulator of satellite cells activation and myogenesis, yet very little research has so far investigated the mechanistic role of autophagy dysregulation in COPD muscles. Using a genetically inducible murine model of COPD-driven muscle dysfunction and confirmed with a second genetic animal model, we found a significant myogenic dysfunction associated with a reduced proliferative capacity of freshly isolated satellite cells. Transplantation experiments followed by lineage tracing suggest that an intrinsic defect in satellite cells, and not in the COPD environment, plays a dominant role in the observed myogenic dysfunction. RNA sequencing analysis of freshly isolated satellite cells suggests dysregulation of transcripts associated with control of cell cycle and autophagy, which is confirmed by a direct observation of COPD mice satellite cells fluorescent-tracked autophagosome formation. Moreover, spermidine-induced autophagy stimulation leads to improved satellite cells autophagosome turnover, replication rate and myogenesis. Our data suggests that pulmonary emphysema causes a disrupted myogenesis, which could be improved with stimulation of autophagy and satellite cells activation, leading to an attenuated muscle dysfunction in this context.
De novo synthesized polyunsaturated fatty acids operate as both host immunomodulators and nutrients for Mycobacterium tuberculosis
Authors: Laval Thomas , Pedró-Cos Laura , Malaga Wladimir , Guenin-Macé Laure , Pawlik Alexandre , Mayau Véronique , Yahia-Cherbal Hanane , Frigui Wafa , Bertrand-Michel Justine , Guilhot Christophe , Demangel Caroline
Published: July 2021

Successful control of Mycobacterium tuberculosis (Mtb) infection by macrophages relies on immunometabolic reprogramming, where the role of fatty acids (FAs) remains poorly understood. Recent studies unraveled Mtb’s capacity to acquire saturated and monounsaturated FAs via the Mce1 importer. However, upon activation macrophages produce polyunsaturated FAs (PUFAs), mammal-specific FAs mediating the generation of key immunomodulatory eicosanoids. Here, we asked whether de novo synthesis of PUFAs is modulated in Mtb-infected macrophages and benefits host or pathogen. Quantitative lipidomics revealed that Mtb infection activates the early PUFA biosynthetic pathway for production of eicosanoids. While PUFA synthesis blockade significantly impaired the inflammatory and antimicrobial responses of infected macrophages, it had no effect on Mtb growth in vivo. Using a click-chemistry approach, we found that Mtb efficiently imports PUFAs of the ω6 subset via Mce1 in axenic culture, including the eicosanoid precursor arachidonic acid (AA). Notably, Mtb preferentially internalized AA over all other FAs within infected macrophages, but here Mtb’s import of AA was largely Mce1-independent and correlated with elevated AA uptake by host cells. Together, these findings reveal AA as a major FA substrate for intracellular Mtb. They suggest that Mtb’s hijacking of host-derived AA may counteract its stimulatory effect on anti-mycobacterial immune responses.
Thioredoxin reductase controls the capacity of peroxiredoxins to limit mitochondrial H2O2release
Authors: Hoehne Michaela Nicole , Jacobs Lianne J.H.C. , Lapacz Kim Jasmin , Murschall Lena Maria , Marker Teresa , Morgan Bruce , Fricker Mark , Belousov Vsevolod V. , Riemer Jan
Published: July 2021

H2O2performs central roles in signaling at physiological levels, while at elevated levels it causes molecular damage. Mitochondria are major producers of H2O2, which has been implied in regulating diverse processes inside and outside the organelle. However, it still remains unclear whether and how mitochondria in intact cells release H2O2. Here we employed the genetically encoded high-affinity H2O2sensor HyPer7 in mammalian tissue culture cells to investigate different modes of mitochondrial H2O2release. We found substantial heterogeneity of HyPer7 dynamics between individual cells, and observed H2O2released from mitochondria directly at the surface of the organelle and in the bulk cytosol, but not in the nucleus nor on the plasma membrane, pointing to steep gradients emanating from mitochondria. These gradients are controlled by cytosolic peroxiredoxins that act redundantly and are present with a substantial reserve capacity. Furthermore, dynamic adaptation of cytosolic thioredoxin reductase levels during metabolic changes results in improved H2O2handling and explains previously observed cell-to-cell differences. Thus, our data indicate that H2O2-mediated signaling likely occurs close to mitochondria during specific metabolic conditions.

HIGHLIGHTS

Mitochondrial H2O2can be detected in the cytosol in intact human cells

Mitochondrial H2O2gradients are steep and controlled by peroxiredoxins 1 and 2

Peroxiredoxins 1 and 2 complement for each other

Peroxiredoxins 1 and 2 are present with a substantial reserve capacity

Metabolism-induced changes of reducing processes control peroxiredoxin activity
Myosin-driven Nucleation of Actin Filaments Drives Stereocilia Development Critical for Hearing
Authors: Moreland Zane G. , Jiang Fangfang , Aguilar Carlos , Barzik Melanie , Gong Rui , Shams Arik , Faaborg-Andersen Christian , Werth Jesse C. , Harley Randall , Sutton Daniel C. , Cole Stacey M. , Parker Andrew , Morse Susan , Wilson Elizabeth , Takagi Yasuharu , Sellers James R. , Brown Steve D.M. , Friedman Thomas B. , Alushin Gregory M. , Bowl Michael R. , Bird Jonathan E.
Published: July 2021

The assembly and maintenance of actin-based mechanosensitive stereocilia in the cochlea is critical for lifelong hearing. Myosin-15 (MYO15) is hypothesized to modulate stereocilia height by trafficking actin regulatory proteins to their tip compartments, where actin polymerization must be precisely controlled during development. We identified a mutation (p.D1647G) in the MYO15 motor-domain that initially maintained trafficking, but caused progressive hearing loss by stunting stereocilia growth, revealing an additional function for MYO15. Consistent with its maintenance of tip traffickingin vivo, purified p.D1647G MYO15 modestly reduced actin-stimulated ATPase activityin vitro. Using ensemble and single-filament fluorescencein vitroassays, we demonstrated that wild-type MYO15 directly accelerated actin filament polymerization by driving nucleation, whilst p.D1647G MYO15 blocked this activity. Collectively, our studies suggest direct actin nucleation by MYO15 at the stereocilia tip is necessary for elongationin vivo, and that this is a primary mechanism disrupted in DFNB3 hereditary human hearing loss.
Identification of general acid catalyst for the ATPase activity of Lynch syndrome-related MutL homologs
Authors: Fukui Kenji , Fujii Yuki , Yano Takato
Published: July 2021

Mutations of mismatch repair MutL homologs are causative of a hereditary cancer, Lynch syndrome. Investigation of MutL facilitates genetic diagnoses essential for cancer risk managements and therapies. We characterized MutL homologs from human and a hyperthermophile, Aquifex aeolicus, (aqMutL) to reveal the catalytic mechanism for the ATPase activity. Although existence of a general acid catalyst had not been conceived in the mechanism, analysis of the pH dependence of the aqMutL ATPase activity revealed that the reaction is accelerated by general acid-base catalysis. Analyses of mutant aqMutLs showed that Lys79 is the general acid, and the corresponding residues were confirmed to be critical for activities of human homologs, on the basis of which a catalytic mechanism for MutL ATPase is proposed. These and other results described here would contribute to evaluating the pathogenicity of Lynch syndrome-associated missense mutations.
Cation-chloride cotransporters, Na/K pump, and channels in cell water and ions regulation: in silico and experimental studies of the U937 cells under stopping the pump and during RVD
Authors: Yurinskaya Valentina E. , Vereninov Alexey A.
Published: July 2021

Cation-coupled chloride cotransporters play a key role in generating the Cl‾ electrochemical gradient on the cell membrane which is important for regulation of many cellular processes. However, the cooperation of transporters and channels of the plasma membrane in holding the ionic homeostasis of the whole cell remains poorly characterized because of the lack of a suitable tool for its computation. Our software successfully predicted in real-time changes in the ion homeostasis of U937 cells after stopping the Na/K pump, but so far considered the model with only NC cotransporter. Here the model with all main types of cotransporters is used in computation of the rearrangements of ionic homeostasis due to stopping the pump and associated with the regulatory volume decrease (RVD) of cells swollen in hypoosmolar medium. The parameters obtained for the real U937 cells are used. Successful prediction of changes in ion homeostasis in real-time after stopping the pump using the model with all major cotransporters indicates that the model is reliable. Using this model for analysis RVD showed that there is a “physical” RVD, associated with the time-dependent changes in electrochemical ion gradients, but not with alteration of channels and transporters of the plasma membrane that should be considered in studies of truly active regulatory processes mediated by the intracellular signaling network. The developed software can be useful for calculation of the balance of the partial unidirectional fluxes of monovalent ions across the cell membrane of various cells under various conditions.
Longitudinal in vivo changes in radial peripapillary capillaries and optic nerve head structure in non-human primates with early experimental glaucoma
Authors: Musial Gwen , Adhikari Suman , Mirhajianmoghadam Hanieh , Queener Hope M. , Schill Alexander W. , Patel Nimesh B. , Porter Jason
Published: July 2021

Purpose

There is conflicting evidence as to whether a loss of radial peripapillary capillaries (RPCs) precedes neuronal loss in glaucoma. We examined the time-course of in vivo changes in RPCs, optic nerve head (ONH) structure, and retinal nerve fiber layer thickness (RNFLT) in experimental glaucoma (EG).

Methods

Spectral domain optical coherence tomography images were acquired before and approximately every 2 weeks after inducing unilateral EG in 9 rhesus monkeys to quantify mean anterior lamina cribrosa surface depth (ALCSD), minimum rim width (MRW), and RNFLT. Perfused RPC density was measured from adaptive optics scanning laser ophthalmoscope images acquired on the temporal half of the ONH. The time of first significant change was quantified as when values fell and remained outside of the 95% confidence interval established from control eyes.

Results

Mean ALCSD and/or MRW were the first parameters to change in 8 EG eyes. RPC density changed first in the 9th. At their first points of change, mean ALCSD posteriorly deformed by 100.2 ± 101.2 μm, MRW thinned by 82.3 ± 65.9 μm, RNFLT decreased by 25 ± 14 μm, and RPC density decreased by 4.5 ± 2.1%. RPC density decreased before RNFL thinning in 5 EG eyes. RNFLT decreased before RPC density decreased in 2 EG eyes, while 2 EG eyes had simultaneous changes.

Conclusions

In most EG eyes, RPC density decreased before (or simultaneous with) a change in RNFLT, suggesting that vascular factors may play a role in axonal loss in some eyes in early glaucoma.