bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Affecting Microbial Contamination on the Back Surface of Worn Soft Contact Lenses
Authors: Tan Jacqueline , Siddireddy Jaya Sowjanya , Wong Katherine , Shen Qing , Vijay Ajay Kumar , Stapleton Fiona
Published: May 2021

SIGNIFICANCE

The results of this study demonstrate that Smart Touch Technology packaging, which is designed to reduce and simplify contact lens handling before insertion, is effective in reducing the frequency of bacterial contamination of the back surface of contact lenses after short-term wear.

PURPOSE

The purpose of this study was to investigate the effect of lens packaging type, chelating agent, and finger contamination on microbial contamination on the back surface of worn soft contact lenses.

METHODS

Twenty-five subjects completed each contralateral lens wear comparison in this randomized study: Smart Touch Technology versus conventional blister packaging for (1) silicone hydrogel lenses with ethylenediaminetetraacetic acid (EDTA) and (2) hydrogel lenses without EDTA in the packaging, and (3) silicone hydrogel lenses without EDTA versus hydrogel lenses with EDTA both in Smart Touch Technology packaging. Participants washed hands, underwent finger swabs, and inserted the lenses. After 45 minutes, lenses were removed aseptically and the posterior lens surfaces cultured.

RESULTS

Thirty-eight subjects (average age, 30.9 ± 12.5 years) participated in this study. Overall, the level of back surface contamination was low for both lens materials, ranging from 0 to 43 colony-forming unit (CFU)/lens for the silicone hydrogel and 0 to 17 CFU/lens for the hydrogel lenses. The proportion of lenses with zero back surface contamination ranged from 16 to 64% for silicone hydrogel lenses and 28 to 64% for hydrogel lenses. Contact lenses from conventional packaging containing EDTA had 3.38 times increased risk (95% confidence interval [CI], 1.02 to 11.11; P = .05) of contamination being present compared with lenses from Smart Touch packaging with EDTA. Contact lenses from conventional packaging without EDTA had 3.4 times increased risk (95% CI, 1.02 to 11.36; P = .05) of contamination being present compared with Smart Touch packaging without EDTA, and silicone hydrogel lenses had a 6.28 times increased risk (95% CI, 1.65 to 23.81; P = .007) of contamination being present compared with hydrogels. The median (interquartile range) number of bacteria isolated from fingers used to perform lens insertion after handwashing but before lens insertion was not significantly different between the silicone hydrogel and hydrogel lenses (63.7 [204.2] vs. 59 [84.5], P = .09). Finger contamination was not significantly associated with lens contamination in the presence or absence of EDTA.

CONCLUSIONS

Smart Touch Technology packaging was effective in reducing the proportion of contaminated lenses. Although silicone hydrogel lenses were more likely to be contaminated, the presence of EDTA ameliorated this effect. Finger contamination was not associated with lens contamination.
Safety of Routine Pedicle Division during Delayed Breast Augmentation following Free Flap Breast Reconstruction
Authors: Rose Jessica F. , Doval Andres F. , Zavlin Dmitry , Ellsworth Warren A. , Echo Anthony , Spiegel Aldona J.
Published: May 2021

Background:

Autologous free flap breast reconstruction is a common reconstructive procedure, with the ability to produce a natural breast shape and a long history of success. Despite its benefits, there are special situations in which patients lack sufficient donor-site tissue to achieve adequate breast size and projection. With this study, the authors describe their institutional experience of delayed implant augmentation after autologous breast reconstruction with a particular focus on pedicle division as a technique to improve aesthetic results.

Methods:

A retrospective chart review of patients that underwent free flap autologous breast reconstruction with delayed implant augmentation was conducted over a 13-year period. Flaps were divided into a control group without pedicle division and a divided pedicle group. Groups were compared in terms of demographics, clinical and surgical characteristics, implant details, and postoperative implant and flap complications.

Results:

No significant differences in terms of age, body mass index, comorbidities, radiation therapy, or surgical indications were noted. The most common reason for delayed implant augmentation after autologous breast reconstruction was change in breast size and breast asymmetry. In terms of implant and flap complications, we found no significant differences between the control and divided pedicle groups after delayed implant augmentation.

Conclusions:

From the authors’ institutional experience, pedicle division in delayed breast augmentation with implants after free flap breast reconstruction can be safety performed in selected cases. This technique can be a powerful tool for plastic surgeons to improve the final aesthetic appearance of the reconstructed breast.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
The Association between Away Rotations and Rank Order in the Integrated Plastic Surgery Match
Authors: Sergesketter Amanda R. , Glener Adam D. , Shammas Ronnie L. , Nguyen Vu T. , Ko Jason H. , Lifchez Scott D. , Momoh Adeyiza O. , Marcus Jeffrey R. , Hollenbeck Scott T. , Phillips Brett T.
Published: May 2021

Background:

Given the competition in the integrated plastic surgery Match, away rotations are ubiquitous among plastic surgery applicants to differentiate their applications. This study aimed to characterize how performing an away rotation affects rank order and Match outcomes for integrated plastic surgery programs.

Methods:

An online survey was designed and distributed to the top 25 integrated plastic surgery programs in the United States as determined by Doximity. Programs were polled about away rotation structure, position of rotators on their 2018 to 2019 rank list, and composition of current resident classes.

Results:

Twenty-five programs completed the survey (response rate, 100 percent). On average, programs interviewed 34.9 applicants (range, 22 to 50 applicants) and ranked 32.8 applicants (range, 10 to 50 applicants). Most “ranked-to-match” positions were occupied by home students or away rotators (60.9 percent). Rank order of home students, away rotators, and nonrotators varied significantly (p < 0.001), with median rank order of home students [5 (interquartile range, 1 to 9)] and rotators [14 (interquartile range, 6 to 27)] higher than nonrotators [17 (interquartile range, 10 to 29)]. Rank orders of away rotators tended to follow a bimodal distribution. Furthermore, 64.4 percent of integrated residents were either a home student or away rotator at their matched integrated program, with 20 percent of residency programs composed of greater than 70 percent of away rotators/home students across postgraduate years 1 through 6 classes.

Conclusions:

For integrated plastic surgery programs, the majority of ranked-to-match students on rank lists and current residents were either home students or away rotators at their respective program. Performing well on an away rotation appears to confer significant benefit to the applicant applying in the integrated plastic surgery Match.
Differences in HIV clinical outcomes amongst heterosexuals in the United Kingdom by ethnicity
Authors: Dhairyawan Rageshri , Okhai Hajra , Hill Teresa , Sabin Caroline A.
Published: May 2021

Objective:

We investigated differences in clinical outcomes in heterosexual participants, by ethnicity in the UK Collaborative HIV Cohort Study from 2000 to 2017.

Design:

Cohort analysis.

Methods:

Logistic/proportional hazard regression assessed ethnic group differences in CD4+ cell count at presentation, engagement-in-care, combination antiretroviral therapy (cART) initiation, viral suppression and rebound.

Results:

Of 12 302 participants [median age: 37 (interquartile range: 31–44) years, 52.5% women, total follow-up: 85 846 person-years], 64.4% were black African, 19.1% white, 6.3% black Caribbean, 3.6% black other, 3.3% South Asian/other Asian and 3.4% other/mixed. CD4+ cell count at presentation amongst participants from non-white groups were lower than the white group. Participants were engaged-in-care for 79.6% of follow-up time; however, black and other/mixed groups were less likely to be engaged-in-care than the white group (adjusted odds ratios vs. white: black African: 0.70 (95% confidence interval (CI) 0.63–0.79], black Caribbean: 0.74 (0.63–0.88), other/mixed: 0.78 (0.62–0.98), black other: 0.81 (0.64–1.02)). Of 8867 who started cART, 79.1% achieved viral suppression, with no differences by ethnicity in cART initiation or viral suppression. Viral rebound (22.2%) was more common in the black other [1.95 (1.37–2.77)], black African [1.85 (1.52–2.24)], black Caribbean [1.73 (1.28–2.33)], South Asian/other Asian [1.35 (0.90–2.03)] and other/mixed [1.09 (0.69–1.71)] groups than in white participants.

Conclusion:

Heterosexual people from black, Asian and minority ethnic (BAME) groups presented with lower CD4+ cell counts, spent less time engaged-in-care and were more likely to experience viral rebound than white people. Work to understand and address these differences is needed.
The Early (2009–2017) Experience With Robot-assisted Cholecystectomy in New York State
Authors: Hoffman Aaron B. , Myneni Ajay A. , Towle-Miller Lorin M. , Karim Syed A. , Train Arianne T. , Burstein Matthew , Schwaitzberg Steven D. , Noyes Katia
Published: May 2021

Objective:

The aim of this study was to examine real-life patterns of care and patient outcomes associated with robot-assisted cholecystectomy (RAC) in New York State (NYS).

Background:

Although robotic assistance may offer some technological advantages, RACs are associated with higher procedural costs and longer operating times compared to traditional laparoscopic cholecystectomies (LCs). Evidence on long-term patient outcomes after RAC from large population-based datasets remains limited and inconsistent.

Methods:

Using NYS inpatient and ambulatory surgery data from the Statewide Planning and Research Cooperative System (2009–2017), we conducted bivariate and multivariate analyses to examine patterns of utilization, complications, and secondary procedures following cholecystectomies.

Results:

Among 299,306 minimally invasive cholecystectomies performed in NYS between 2009 and 2017, one thousand one hundred eighteen (0.4%) were robot-assisted. Compared to those undergoing LC, RAC patients were older, travelled further for surgery, and were more likely to have public insurance and preoperative comorbidities. RAC versus LC patients were more significantly likely to have conversions to open procedure (4.9% vs 2.8%), bile duct injuries (1.3% vs 0.4%), and major reconstructive interventions (0.6% vs 0.1%), longer median length of stay (3 vs 1 day), readmissions (7.3% vs 4.4%), and higher 12-month post-index surgery hospital charges (P < 0.01 for all estimates). Other postoperative complications decreased over time for LC but remained unchanged for RAC patients.

Conclusions:

Patients receiving RAC in NYS experienced higher rates of complications compared to LC patients. Addressing patient-, surgeon-, and system-level factors associated with intra/postoperative complications and applying recently promulgated safe cholecystectomy strategies coupled with advanced imaging modalities like fluorescence cholangiography to RAC may improve patient outcomes.
Esophagogastrostomy With Fundoplication Versus Double-tract Reconstruction After Laparoscopic Proximal Gastrectomy for Gastric Cancer
Authors: Tominaga Shinta , Ojima Toshiyasu , Nakamura Masaki , Katsuda Masahiro , Hayata Keiji , Kitadani Junya , Takeuchi Akihiro , Motobayashi Hideki , Nakai Tomoki , Yamaue Hiroki
Published: May 2021

Purpose:

We investigated that double-tract reconstruction (DTR) may be more beneficial than esophagogastrostomy (EG) with fundoplication in terms of nutritional outcomes, focusing on loss of body weight.

Materials and Methods:

This study included 56 consecutive patients with early gastric cancer in the upper third of the stomach who received laparoscopic proximal gastrectomy, 39 underwent EG. In the 17 patients requiring resection of the abdominal esophagus or where the size of the remnant stomach was 50% or less, we performed DTR.

Results:

There was no significant difference in the rate of body weight change at 6 or 12 months, or in biochemical markers (hemoglobin, total protein, and albumin) at 12 months. However, 8 patients in the EG group had extreme body weight loss (≥20%) within 12 months. Conversely, in the DTR group, no patients had any extreme body weight loss.

Conclusion:

DTR is useful after laparoscopic proximal gastrectomy, especially in terms of preventing extreme body weight loss.
Traumatic posterior anal injury requiring a sphincteroplasty without diversion: a case report
Authors: Weledji Elroy P. , Ntonwetape Ngwane
Published: May 2021

Introduction and importance:

The anal sphincters may be divided by direct anal trauma or by severe pelvic injuries. Clinical assessment of traumatic anal injury may suffice in determining the sphincter defect in resource-limited settings where endoanal ultrasonography is not available. As long as about half the sphincter ring remains active there is a good chance of restoring satisfactory fecal continence following an overlapping sphincteroplasty.

Case presentation:

A 25-year-old heterosexual African man was admitted as an emergency following gunshots to the abdomen and pelvis. He underwent small bowel resection, and a delayed repair of a discrete 50% posterior anal sphincter complex injury (grade 3b) without a diverting stoma.

Clinical discussion:

The case presented the successful repair of a discrete posterior anal sphincter damage from a gunshot that was not total but sufficient to cause appreciable loss of anorectal control. The preoperative clinical assessment correlated well with the intraoperative assessment of the sphincter injury. Following an overlapping sphincteroplasty, the patient maintained continence at 1-year follow-up.

Conclusion:

In resource-limited settings, preoperative clinical assessment may correlate well with the intraoperative assessment of anal sphincter injury and, thus allow a safe and efficacious repair.
Update on neuroimaging in brain tumours
Authors: Smits Marion
Published: May 2021

Purpose of review

To highlight some of the recent advances in magnetic resonance imaging (MRI), in terms of acquisition, analysis, and interpretation for primary diagnosis, treatment planning, and surveillance of patients with a brain tumour.

Recent findings

The rapidly emerging field of radiomics associates large numbers of imaging features with clinical characteristics. In the context of glioma, attempts are made to correlate such imaging features with the tumour genotype, using so-called radiogenomics. The T2-fluid attenuated inversion recovery (FLAIR) mismatch sign is an easy to apply imaging feature for identifying isocitrate dehydrogenase-mutant 1p/19q intact glioma with very high specificity.

For treatment planning, resting state functional MRI (fMRI) may become as powerful as task-based fMRI. Functional ultrasound has shown the potential to identify functionally active cortex during surgery.

For tumour response assessment automated techniques have been developed. Multiple new guidelines have become available, including those for adult and paediatric glioma and for leptomeningeal metastases, as well as on brain metastasis and perfusion imaging.

Neuroimaging plays a central role but still often falls short on essential questions. Advanced imaging acquisition and analysis techniques hold great promise for answering such questions, and are expected to change the role of neuroimaging for patient management substantially in the near future.
Update on neuroimaging in non-Alzheimer's disease dementia: a focus on the Lewy body disease spectrum
Authors: Scamarcia Pietro G. , Agosta Federica , Caso Francesca , Filippi Massimo
Published: May 2021

Purpose of review

An accurate differential diagnosis between Alzheimer's disease (AD) and non-AD dementia is of paramount importance to study disease mechanisms, define prognosis, and select patients for disease-specific treatments. The purpose of the present review is to describe the most recent neuroimaging studies in Lewy body disease spectrum (LBDS), focusing on differences with AD.

Recent findings

Different neuroimaging methods are used to investigate patterns of alterations, which can be helpful to distinguish LBDS from AD. Positron emission tomography radiotracers and advanced MRI structural and functional methods discriminate these two conditions with increasing accuracy. Prodromal disease stages can be identified, allowing an increasingly earlier diagnosis.

Neuroimaging biomarkers can aid in obtaining the best diagnostic accuracy in LBDS. Despite the main role of neuroimaging in clinical setting is to exclude secondary causes of dementia, structural and metabolic imaging techniques give an essential help to study in-vivo pathophysiological mechanisms of diseases. The importance of neuroimaging in LBDS is given by the increasing number of imaging biomarker developed and studied in the last years.
Resuming In-Person Classes under COVID-19: Evaluating Assigned Seating Protocols in Limiting Contacts at Postsecondary Institutions
Authors: Daly-Grafstein Daniel , Daly Patricia , Gustafson Reka
Published: May 2021

In order to limit the spread of COVID-19, Canadian postsecondary institutions are offering the majority of classes online for the 2020-21 academic year. The goal of Canada’s public health pandemic response is to reduce severe illness and mortality from COVID-19 while minimizing social disruption. To achieve this goal, post secondary institutions need practical tools to limit COVID-19 spread and facilitate contact tracing while returning students to in-person instruction. In this paper, we explore the impact of assigned seating for students attending in-person classes in reducing potential contacts. We conduct a variety of seating simulations using student enrollment data and measure the number of potential contacts under each scenario. We find that assigning seats to students significantly reduces the expected number of contacts relative to random seating, making the return to in-person classes more feasible under these scenarios.
Spatial and regional directory of tropicalAuriculariamushrooms in Southwest, Nigeria
Authors: Ekun Victor S. , Adenipekun Clementina O. , Ojuederie Omena B. , Etaware Peter M.
Published: May 2021

Bioremediation of wastelands and dumpsites in Africa is fast declining due to reduced mushroom populations. In the past, the forest of Africa was teaming with mushrooms, but nowadays; mushrooms are severely exploited, resulting in gradual drift to extinction. Mushrooms have the tendency to degrade recalcitrant wastes and absorb heavy metals (Bio-accumulation). Unless concerted efforts are made to rejuvenate or rescue the surviving mushroom population, Africa will one day be overshadowed by wastes. The mushroom diversity in Southwest, Nigeria was determined by both morphological and molecular markers, 14 primers (OPB-11, OPB-12, OPB-15, OPB-20, OPB-21, OPH-3, OPH-5, OPH-10, OPH-15, OPT-1, OPT-5, OPT-7, OPT-10 and OPT-19) produced polymorphism with the test samples under electrophoresis gel (PCR and RAPD). Using standard morphological markers,Auricularia auriculawas found to be evenly distributed across 8 locations in Ekiti and Osun, 6 locations in Ogun, 5 locations in Oyo and 4 locations in Lagos. There was none identified in Ondo.Auricularia polytrichawas found in abundance in all the locations in Ondo. Lagos only had 3 out of its outline Stations graced with the presence ofA. polytricha, whereas, Ogun, Ekiti, Osun and Oyo had no records ofA. polytricha. From the genetic dissimilarity chart, 6 clusters of mushroom, sub-characterized into 3 distinct species (Auricularia polytricha,A. auriculaand an unrelatedAuriculariaoutlier species) and 5 cultivars were obtained in the region of Southwest, Nigeria. The population of all theAuriculariamushrooms currently present in Southwest, Nigeria was effectively captioned (Location, type and identity) by this research.
SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity
Authors: Joyce M. Gordon , Chen Wei-Hung , Sankhala Rajeshwer S. , Hajduczki Agnes , Thomas Paul V. , Choe Misook , Chang William , Peterson Caroline E. , Martinez Elizabeth , Morrison Elaine B. , Smith Clayton , Ahmed Aslaa , Wieczorek Lindsay , Anderson Alexander , Chen Rita E. , Case James Brett , Li Yifan , Oertel Therese , Rosado Lorean , Ganesh Akshaya , Whalen Connor , Carmen Joshua M. , Mendez-Rivera Letzibeth , Karch Christopher , Gohain Neelakshi , Villar Zuzana , McCurdy David , Beck Zoltan , Kim Jiae , Shrivastava Shikha , Jobe Ousman , Dussupt Vincent , Molnar Sebastian , Tran Ursula , Kannadka Chandrika B. , Zemil Michelle , Khanh Htet , Wu Weimin , Cole Matthew A. , Duso Debra K. , Kummer Larry W. , Lang Tricia J. , Muncil Shania E. , Currier Jeffrey R. , Krebs Shelly J. , Polonis Victoria R. , Rajan Saravanan , McTamney Patrick M. , Esser Mark T. , Reiley William W. , Rolland Morgane , de Val Natalia , Diamond Michael S. , Gromowski Gregory D. , Matyas Gary R. , Rao Mangala , Michael Nelson L. , Modjarrad Kayvon
Published: May 2021

The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferritin nanoparticle (SpFN) vaccine elicited neutralizing titers more than 20-fold higher than convalescent donor serum, following a single immunization, while RBD-Ferritin nanoparticle (RFN) immunogens elicited similar responses after two immunizations. Passive transfer of IgG purified from SpFN- or RFN-immunized mice protected K18-hACE2 transgenic mice from a lethal SARS-CoV-2 virus challenge. Furthermore, SpFN- and RFN-immunization elicited ACE2 blocking activity and neutralizing ID50 antibody titers >2,000 against SARS-CoV-1, along with high magnitude neutralizing titers against major VoC. These results provide design strategies for pan-coronavirus vaccine development.

HIGHLIGHTS

Iterative structure-based design of four Spike-domain Ferritin nanoparticle classes of immunogens

SpFN-ALFQ and RFN-ALFQ immunization elicits potent neutralizing activity against SARS-CoV-2, variants of concern, and SARS-CoV-1

Passively transferred IgG from immunized C57BL/6 mice protects K18-hACE2 mice from lethal SARS-CoV-2 challenge
High-Stability Polyimide-based Flexible Electrodes with IrOxto Interface the Mouse Vagus Nerve
Authors: Sun Tao , Falcone Jessica , Crosfield Christine , Lopez Maria Fernanda , Peragine Joanne , Modi Romil , Sharma Rohit , Baker Brian , Anderson Gavin , Savani Shubh , Li Chunyan , Chang Eric H. , Sohal Harbaljit , Rieth Loren
Published: May 2021

Objective

We developed robust and cost-effective cuffFlexelectrodes to facilitate bioelectronic medicine research in mouse models. They utilize polyimide (PI) as a dielectric insulation and iridium oxide (IrOx) for the electrodes, and are designed to interface small autonomic and somatic nerves (e.g. mouse vagus nerve).

Approach

Flexelectrodes were made using micro-fabrication technology, and innovative integration processes were developed to enable reliable acute and chronic vagus nerve interfaces. The electrochemical properties ofFlexelectrodes were characterized. Moreover, accelerated aging at 57 °C and stimulation-stability (Stim-Stab) testing (109pulses at ∼ 1.59 mC/cm2/phase) were performed to evaluate the lifetime of the PI encapsulation and IrOxelectrodes, respectively.Flexelectrodes efficacy was demonstrated by stimulating the mouse vagus nerve (∼100 µm) and measuring heart and respiratory rate changes as biomarkers.

Results

Cost effective and robust lead and connector integration strategies were demonstrated, including small helical leads that improved the lead elongation by > 7x. PI encapsulation had stable impedance spectra for at least 336 days for interdigitated electrodes. Stim-Stab testing using an aggressive paradigm and rigorous optical and electrical characterization, revealed that half of electrodes showed less than minor damage at the endpoints. A trend of decreasing respiratory rate with stimulation current reached statistical significance at 500 µA, demonstrating efficacy forFlexelectrodes.

Significance

Flexelectrodes offer demonstrated efficacy, low impedance (443 ± 32 Ω at 103Hz), excellent bench test stability, and cost-effective fabrication. Acute devices are easy to integrate, and mechanically robust chronic devices will be investigatedin vivoin future studies. These characteristics make the electrodes well-positioned to advance bioelectronics medicine research by 1) enabling reliable studies with statistically relevant populations of acute mouse models, and 2) offering the potential for a technology that can be used in chronic studies, which scales to very small nerves.
Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity
Authors: Gilchrist James J , Makino Seiko , Naranbhai Vivek , Lau Evelyn , Danielli Sara , Hameiri-Bowen Dan , Lee Wanseon , Ng Esther , Whalley Justin , Knight Julian C , Fairfax Benjamin P
Published: May 2021

Natural Killer (NK) cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect NK gene expression is poorly understood. We performed expression quantitative trait locus (eQTL) mapping of negatively selected NK cells from a population of healthy Europeans (n=245). We find a significant subset of genes demonstrate eQTL specific to NK cells and these are highly informative of human disease, in particular autoimmunity. An NK cell transcriptome-wide association study (TWAS) across five common autoimmune diseases identified further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor (KIR) Region, GNLY and MC1R. Our findings provide new insights into the unique biology of NK cells, demonstrating markedly different eQTL from other immune cells, with implications for disease mechanisms.
Frequent paternal mitochondrial inheritance and rapid haplotype frequency shifts in copepod hybrids
Authors: Lee Jeeyun , Willett Christopher S.
Published: May 2021

Mitochondria are assumed to be maternally inherited in most animal species, and this foundational concept has fostered advances in phylogenetics, conservation, and population genetics. Like other animals, mitochondria were thought to be solely maternally inherited in the marine copepodTigriopus californicus, which has served as a useful model for studying mitonuclear interactions, hybrid breakdown, and environmental tolerance. However, we present PCR, Sanger sequencing, and Illumina Nextera sequencing evidence that extensive paternal mitochondrial DNA (mtDNA) transmission is occurring in inter-population hybrids ofT. californicus. PCR on four types of crosses between three populations (total sample size of 376 F1 individuals) with 20% genome-wide mitochondrial divergence showed 2% to 59% of F1 hybrids with both paternal and maternal mtDNA, where low and high paternal leakage values were found in different cross directions of the same population pairs. Sequencing methods further verified nucleotide similarities between F1 mtDNA and paternal mtDNA sequences. Interestingly, the paternal mtDNA in F1s from some crosses inherited haplotypes that were uncommon in the paternal population. Compared to some previous research on paternal leakage, we employed more rigorous methods to rule out contamination and false detection of paternal mtDNA due to non-functional nuclear mitochondrial DNA fragments. Our results raise the potential that other animal systems thought to only inherit maternal mitochondria may also have paternal leakage, which would then affect the interpretation of past and future population genetics or phylogenetic studies that rely on mitochondria as uniparental markers.
A broadly active fucosyltransferase LmjFUT1 whose mitochondrial localization and catalytic activity is essential in the parasitic protozoan Leishmania
Authors: Guo Hongjie , Damerow Sebastian , Penha Luciana , Menzies Stefanie , Polanco Gloria , Zegzouti Hicham , Ferguson Michael A. J. , Beverley Stephen M.
Published: May 2021

Glycoconjugates play major roles in the infectious cycle of the trypanosomatid parasite Leishmania. While GDP-Fucose synthesis is essential (Guo et al 2017), fucosylated glycoconjugates have not been reported in Leishmania major. Four predicted fucosyltransferases appear conventionally targeted to the secretory pathway; SCA1/2 play a role in side-chain modifications of lipophosphoglycan, while gene deletion studies here showed that FUT2 and SCAL were not essential. Unlike most eukaryotic glycosyltransferases, the predicted α 1-2 fucosyltransferase encoded by FUT1 localized to the mitochondrion. A quantitative ‘plasmid segregation’ assay, expressing FUT1 from the multicopy episomal pXNG vector in a chromosomal null Δfut1- background, established that FUT1 is essential. Similarly “plasmid shuffling” confirmed that both enzymatic activity and mitochondrial localization were required for viability, comparing import-blocked or catalytically inactive enzymes respectively. Enzymatic assays of tagged proteins expressed in vivo or of purified recombinant FUT1 showed it had a broad fucosyltransferase activity including glycan and peptide substrates. Unexpectedly a single rare Δfut1-s segregant (Δfut1s) was obtained in rich media, which showed severe growth defects accompanied by mitochondrial dysfunction and loss, all of which were restored upon FUT1 re-expression. Thus, FUT1 along with the similar Trypanosoma brucei enzyme TbFUT1 (Bandini et al 2021) joins the eukaryotic O-GlcNAc transferase isoform as one of the few glycosyltransferases acting within the mitochondrion. Trypanosomatid mitochondrial FUT1s may offer a facile system for probing mitochondrial glycosylation in a simple setting and their essentiality renders it an attractive target for chemotherapy of these serious human pathogens.

Significance Statement

Abundant surface glycoconjugates play key roles in the infectious cycle of protozoan parasites including Leishmania. Through defining biosynthetic pathways we identified a fucosyltransferase FUT1 that was localized to the parasite mitochondrion, an atypical compartment for glycosyltransferases. FUT1 was essential for normal growth, requiring both mitochondrial localization and enzymatic activity. Loss of FUT1 in a unique segregant showed extensive mitochondrial defects. Enzymatic tests showed FUT1 could fucosylate glycan and peptide substrates in vitro, although as yet the native substrate is unknown. Trypanosomatid mitochondrial FUT1s may offer a facile system in the future for probing mitochondrial glycosylation in a setting uncomplicated by multiple isoforms targeted to diverse compartments, and its essentiality renders it an attractive target for chemotherapy of these deadly parasites.
Binding mechanism underlying FIH-1 suppression caused by the N-terminal disordered region of Mint3
Authors: Ten Tensho , Nagatoishi Satoru , Hoshino Masaru , Nakayama Yoshiki , Seiki Motoharu , Sakamoto Takeharu , Tsumoto Kouhei
Published: May 2021

Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which makes investigation of this interaction challenging. Therefore, we adopted a physicochemical approach that combined thermodynamic studies with structural analyses in solution, to clarify the binding mechanism. First, using a combination of CD, NMR, and hydrogen/deuterium exchange mass spectrometry (HDX-MS), we confirmed that the N-terminal half, which is the interacting part of Mint3, is mostly disordered. Next, using isothermal titration calorimetry (ITC), we revealed that the interaction of Mint3 and FIH-1 produces an enormous change in enthalpy and entropy. The profile is consistent with the model that the flexibility of disordered Mint3 is drastically reduced upon binding to FIH-1. Moreover, we performed a series of ITC experiments with several types of truncated Mint3s, an effective approach since the interacting part of Mint3 is disordered, and identified 78-88 as a novel core site for binding to FIH-1. The truncation study of Mint3 also revealed the thermodynamic contribution of each part to the interaction, where one contributes to the affinity (ΔG), while the other only affects enthalpy (ΔH), by forming non-covalent bonds. This insight can serve as a foothold for further investigation of IDRs and drug development for cancer therapy.
Evolution towards increasing complexity through functional diversification in a protocell model of the RNA world
Authors: Roy Suvam , Sengupta Supratim
Published: May 2021

The encapsulation of genetic material inside compartments together with the creation and sustenance of functionally diverse internal components are likely to have been key steps in the formation of ‘live’, replicating protocells in an RNA world. Several experiments have shown that RNA encapsulated inside lipid vesicles can lead to vesicular growth and division through physical processes alone. Replication of RNA inside such vesicles can produce a large number of RNA strands. Yet, the impact of such replication processes on the emergence of the first ribozymes inside such protocells and on the subsequent evolution of the protocell population remains an open question. In this paper, we present a model for the evolution of protocells with functionally diverse ribozymes. Distinct ribozymes can be created with small probabilities during the error-prone RNA replication process via the rolling circle mechanism. We identify the conditions that can synergistically enhance the number of different ribozymes inside a protocell and allow functionally diverse protocells containing multiple ribozymes to dominate the population. Our work demonstrates the existence of an effective pathway towards increasing complexity of protocells that might have eventually led to the origin of life in an RNA world.
Mind blanking is a distinct mental state linked to a recurrent brain profile of globally positive connectivity during ongoing mentation
Authors: Mortaheb Sepehr , Van Calster Laurens , Raimondo Federico , Klados Manousos A. , Boulakis Paradeisios Alexandros , Georgoula Kleio , Majerus Steve , Van De Ville Dimitri , Demertzi Athena
Published: May 2021

Mind blanking (MB) is a waking state during which we do not report any mental content, challenging the view of a constantly thought-oriented brain. Here, we comprehensively characterize the MB’s neurobehavioral profile with the aim to delineate its role during ongoing mentation. Using fMRI experience-sampling, we show that MB is reported less frequently, faster, and with low transitional dynamics among other mental states, pointing to its role as a transient mental relay. Regarding its neural underpinnings, we observe higher global signal amplitude during MB reports, indicating a distinct physiological substrate. Using the time-varying functional connectome MB reports get classified with high accuracy, suggesting that MB has a unique neural composition. Indeed, a pattern of globally positive-phase coherence shows the highest similarity to the connectivity patterns associated with MB reports. We observe that this pattern’s rigid signal architecture hinders content reportability due to the brain’s inability to differentiate signals in an informative way. Collectively, we show that MB has a unique neurobehavioural profile, indicating that non-reportable mental events can happen during wakefulness. Our results add to the characterization of spontaneous mentation and pave the way for more mechanistic investigations of MB’s phenomenology.

Significance Statement

The human mind is generally assumed to be thought-oriented. Mind blanking (MB) challenges this stance because it appears as if we are derived of any particular mental content to report. We here show that, during spontaneous thinking, MB is a mental state that happens by default, it has a unique behavioural profile, and it is of a rigid neural architecture that does not permit the formulation of reportable contents. Our work essentially proposes that non-reportable mental events can happen during wakefulness, and challenges the view of the mind as a constant thought-oriented operator.
Variation in susceptibility among three Caribbean coral species and their algal symbionts indicates the threatened staghorn coral,Acropora cervicornis, is particularly susceptible to elevated nutrients and heat stress
Authors: Palacio-Castro Ana M. , Dennison Caroline E. , Rosales Stephanie M. , Baker Andrew C.
Published: May 2021

Coral cover is declining worldwide due to multiple interacting threats. We compared the effects of elevated nutrients and temperature on three Caribbean corals:Acropora cervicornis, Orbicella faveolata, andSiderastrea siderea. Colonies hosting different algal types were exposed to either ambient nutrients (A), elevated NH4(N), or elevated NH4+ PO4(N+P) at control temperatures (26 °C) for > 2 months, followed by a 3-week thermal challenge (31.5 °C).A. cervicornishostedSymbiodinium (S. fitti)and was highly susceptible to the combination of elevated nutrients and temperature. During heat stress,A. cervicornispre-exposed to elevated nutrients experienced 84%-100% mortality and photochemical efficiency (Fv/Fm) declines of 41-50%. In comparison, no mortality and lowerFv/Fmdeclines (11-20%) occurred inA. cervicornisthat were heat-stressed but not pre-exposed to nutrients.O. faveolataandS. siderearesponse to heat stress was determined by their algal symbiont community and was not affected by nutrients.O. faveolatapredominantly hostedDurusdinium trenchiiorBreviolum, but only corals hostingBreviolumwere susceptible to heat, experiencing 100% mortality, regardless of nutrient treatment.S. sidereacolonies predominantly hostedCladocopiumC1 (C. goreaui),CladocopiumC3,D. trenchii, or variable proportions ofCladocopiumC1 andD. trenchii. This species was resilient to elevated nutrients and temperature, with no significant mortality in any of the treatments. However, during heat stress,S. sidereahostingCladocopiumC3 suffered higher reductions inFv/Fm(41-56%) compared toS. sidereahostingCladocopiumC1 andD. trenchii(17-26% and 10-16%, respectively). These differences in holobiont susceptibility to elevated nutrients and heat may help explain historical declines inA. cervicornisstarting decades earlier than other Caribbean corals. Our results suggest that tackling only warming temperatures may be insufficient to ensure the continued persistence of Caribbean corals, especiallyA. cervicornis. Reducing nutrient inputs to reefs may also be necessary for these iconic coral species to survive.
Information transfer in mammalian glycan-based communication
Authors: Fuchsberger Felix F. , Kim Dongyoon , Baranova Natalia , Kagelmacher Marten , Wawrzinek Robert , Rademacher Christoph
Published: May 2021

Glycan-binding proteins, so-called lectins, are exposed on mammalian cell surfaces and decipher the information encoded within glycans translating it into biochemical signal transduction pathways in the cell. These glycan-lectin communication pathways are complex and difficult to analyse. However, quantitative data with single cell resolution provides means to disentangle the associated signalling cascades. We chose C-Type lectin receptors (CLRs) expressed on immune cells as a model system to study their capacity to transmit information encoded in glycans of incoming particles. Lectin receptor NFκB-reporter cell lines expressing DC-SIGN, MCL, dectin-1, dectin-2, and mincle, as well as TNFαR and TLR-1&2 in monocytic cell lines were characterized by comparing their efficiency to transmit glycan-encoded information. The information content was measured by following NFκB dependent GFP expression. While most receptors did transmit information to NFκB efficiently, we found dectin-2 to be an inefficient signalling receptor. Yet upon closer analysis we show that the sensitivity of the dectin-2 signal transduction pathway (EC50) can be enhanced by overexpression of its co-receptor FcRγ, while its transmitted information cannot. In this context, we expanded our investigation towards the integration of multiple signal transduction pathways, which is crucial during pathogen recognition. We show how lectin receptors using a similar signal transduction pathway (dectin-1 and dectin-2) are being integrated; by striking a compromise between the lectins. By using dectin-2 and other lectins as example we demonstrate how cellular heterogeneity and the receptor itself determine the efficiency and therefore outcome of the signal transduction pathways.
mSWI/SNF interacts with the ribosome and its inhibition/mutations alter translation and sensitize to mTOR/PI3K inhibitors
Authors: Ulicna Livia , Kimmey Samuel C. , Weber Christopher M. , Allard Grace M. , Bedall Sean C. , Crabtree Gerald R. , Bean Gregory R. , Van Rechem Capucine
Published: May 2021

The chromatin remodelers mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) subunits are mutated, deleted or amplified in more than 40% of cancers. Understanding their functions in normal cells and the consequences of cancer’s alterations will lead to path toward new targeted therapies. Canonically, mSWI/SNF complexes regulate the structure of chromatin, however they likely have additional functions which could be relevant in carcinogenesis. Here, we highlight the substantial alteration of mSWI/SNF subunits expression in both the nucleus and cytoplasm in breast cancer cases. We demonstrate mSWI/SNF cytoplasmic localization and interaction with the translation initiation machinery. Short-term inhibition and depletion of specific subunits alter protein synthesis, implicating a direct role for these factors in translation. Inhibition and depletion of specific subunits increase sensitivity to mTOR-PI3K inhibitors, suggesting a potential therapeutic opportunity for diseases harboring mutations in these complexes. Indeed,SMARCA4pathogenic mutations decrease protein synthesis. Furthermore, taking advantage of the DepMap studies, we demonstrate cancer cells harboring mutations of specific mSWI/SNF subunits exhibit a genetic dependency on translation factors and are particularly sensitive to translation pathway inhibitors. In conclusion, we report an unexpected cytoplasmic role for mSWI/SNF in protein synthesis, suggesting potential new therapeutic opportunities for patients afflicted by cancers demonstrating alterations in its subunits.

Statement of significance

This study establishes direct functions for mSWI/SNF in protein synthesis. mSWI/SNF inhibition, depletion and cancer mutations alter translation and increase sensitivity to translation pathway inhibitors, illustrating the potential for new therapeutic strategies.
Tensor P-Spline Smoothing for Spatial Analysis of Plant Breeding Trials
Authors: Piepho Hans-Peter , Boer Martin P. , Williams Emlyn R.
Published: May 2021

Large agricultural field trials may display irregular spatial trends that cannot be fully captured by a purely randomization-based analysis. For this reason, paralleling the development of analysis-of-variance procedures for randomized field trials, there is a long history of spatial modelling for field trials, starting with the early work of Papadakis on nearest neighbour analysis, which can be cast in terms of first or second differences among neighbouring plot values. This kind of spatial modelling is amenable to a natural extension using P-splines, as has been demonstrated in recent publications in the field. Here, we consider the P-spline framework, focussing on model options that are easy to implement in linear mixed model packages. Two examples serve to illustrate and evaluate the methods. A key conclusion is that first differences are rather competitive with second differences. A further key observation is that second differences require special attention regarding the representation of the null space of the smooth terms for spatial interaction, and that an unstructured variance-covariance structure is required to ensure invariance to translation and rotation of eigenvectors associated with that null space. We develop a strategy that permits fitting this model with ease, but the approach is more demanding than that needed for fitting models using first differences. Hence, even though in other areas second differences are very commonly used in the application of P-splines, our main conclusion is that with field trials first differences have advantages for routine use.
RevGadgets: an R Package for visualizing Bayesian phylogenetic analyses from RevBayes
Authors: Tribble Carrie M. , Freyman William A. , Landis Michael J. , Lim Jun Ying , Barido-Sottani Joëlle , Kopperud Bjørn Tore , Höhna Sebastian , May Michael R.
Published: May 2021

Statistical phylogenetic methods are the foundation for a wide range of evolutionary and epidemiological studies. However, as these methods grow increasingly complex, users often encounter significant challenges with summarizing, visualizing, and communicating their key results.

We presentRevGadgets, anRpackage for creating publication-quality figures from the results of a large variety of phylogenetic analyses performed inRevBayes(and other phylogenetic software packages).

We demonstrate how to useRevGadgetsthrough a set of vignettes that cover the most common use cases that researchers will encounter.

RevGadgetsis an open-source, extensible package that will continue to evolve in parallel withRevBayes, helping researchers to make sense of and communicate the results of a diverse array of analyses.

[Bayesian phylogenetics, data visualization, R, RevBayes]