bluuebunny/crossref_metadata_2025 huggingface dataset:
Is self-reported short sleep duration associated with obesity? A systematic review and meta-analysis of cohort studies
Authors: Guimarães Kisian Costa , Silva Catarina Mendes , Latorraca Carolina de Oliveira Cruz , Oliveira Ricardo de Ávila , Crispim Cibele Aparecida
Published: July 2021

Context

A possible association between self-reported short sleep duration and risk of obesity has been studied.

Objective

To analyze the association between sleep duration and obesity.

Methods

The LILACS, Medline, Central, Embase, and OpenGrey databases were searched from inception until July 2020. Two authors screened the studies independently according to the PECO strategy, as follows: participants: > 18 years old; exposure: short sleep duration; control: regular sleep; outcome: obesity). Only cohort studies were included. A total of 3286 studies were retrieved with the search strategy, but only 36 were included. Disagreements were resolved by a third author. The quality of studies was assessed with Newcastle-Ottawa Quality Assessment Form for Cohort Studies. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation.

Results

Thirty-six studies were included, and 22 contributed quantitative data. Most of the studies (n = 27) assessed sleep by self-report. The meta-analysis showed a significant association between self-reported short sleep and development of obesity, and the chances of developing obesity increased when self-reported sleep duration decreased.

Conclusions

Self-reported short sleep was significantly associated with a higher incidence of obesity, with moderate quality of evidence.

Systematic Review Registration

PROSPERO registration no. CRD42019130143.
Fish protein hydrolysates as a health-promoting ingredient—recent update
Authors: Nirmal Nilesh P , Santivarangkna Chalat , Benjakul Soottawat , Maqsood Sajid
Published: July 2021

Dietary habits and lifestyle-related diseases indicate that food has a direct impact on individual health. Hence, a diet containing essential nutrients is important for healthy living. Fish and fish products are important in diets worldwide because of their nutritional value, especially their easily digestible proteins with essential amino acids. Similarly, fish protein hydrolysate (FPH) obtained from fish muscle and by-products has been reported to exhibit various biological activities and to have functional properties, which make FPH a suitable nutraceutical candidate. This review focuses on the health-promoting ability of FPH in terms of skin health, bone and cartilage health, blood lipid profile, and body-weight management studied in rats and human model systems. The absorption and bioavailability of FPH in humans is discussed, and challenges and obstacles of FPH as a functional food ingredient are outlined.
IRONMAN tunes responses to iron deficiency in concert with environmental pH
Authors: Gautam Chandan Kumar , Tsai Huei-Hsuan , Schmidt Wolfgang
Published: July 2021

Iron (Fe) is an essential mineral element that governs the composition of natural plant communities and limits crop yield in agricultural ecosystems due to its extremely low availability in most soils, particularly at alkaline pH. To extract sufficient Fe from the soil under such conditions, some plants, including Arabidopsis (Arabidopsis thaliana), secrete Fe-mobilizing phenylpropanoids, which mobilize sparingly soluble Fe hydroxides by reduction and chelation. We show here that ectopic expression of the peptides IRONMAN (IMA1) and IMA2 improves growth on calcareous soil by inducing biosynthesis and secretion of the catecholic coumarin 7,8-dihydroxy-6-methoxycoumarin (fraxetin) via increased expression of MYB72 and SCOPOLETIN 8-HYDROXYLASE, a response that is strictly dependent on elevated environmental pH (pHe). By contrast, transcription of the cytochrome P450 family protein CYP82C4, catalyzing the subsequent hydroxylation of fraxetin to sideretin, which forms less stable complexes with iron, was strongly repressed under such conditions. We concluded that IMA peptides regulate processes supporting Fe uptake at both acidic and elevated pH by controlling gene expression upstream of or in concert with a putative pHe signal, adapting the plant to prevailing edaphic conditions. This regulatory pattern confers tolerance to calcareous soils by extending the pH range in which Fe can be efficiently absorbed from the soil. Our results further suggest that pHe calibrates the activities of components of the Fe deficiency response, accentuating processes that are most efficient under the prevailing conditions. Altering the expression of IMA peptides provides a route for generating plants adapted to calcareous soils.
Proton and calcium pumping P-type ATPases and their regulation of plant responses to the environment
Authors: Fuglsang Anja T , Palmgren Michael
Published: July 2021

Plant plasma membrane H+-ATPases and Ca2+-ATPases maintain low cytoplasmic concentrations of H+ and Ca2+, respectively, and are essential for plant growth and development. These low concentrations allow plasma membrane H+-ATPases to function as electrogenic voltage stats, and Ca2+-ATPases as “off” mechanisms in Ca2+-based signal transduction. Although these pumps are autoregulated by cytoplasmic concentrations of H+ and Ca2+, respectively, they are also subject to exquisite regulation in response to biotic and abiotic events in the environment. A common paradigm for both types of pumps is the presence of terminal regulatory (R) domains that function as autoinhibitors that can be neutralized by multiple means, including phosphorylation. A picture is emerging in which some of the phosphosites in these R domains appear to be highly, nearly constantly phosphorylated, whereas others seem to be subject to dynamic phosphorylation. Thus, some sites might function as major switches, whereas others might simply reduce activity. Here, we provide an overview of the relevant transport systems and discuss recent advances that address their relation to external stimuli and physiological adaptations.
CYCLIC NUCLEOTIDE-GATED ION CHANNEL 2 modulates auxin homeostasis and signaling
Authors: Chakraborty Sonhita , Toyota Masatsugu , Moeder Wolfgang , Chin Kimberley , Fortuna Alex , Champigny Marc , Vanneste Steffen , Gilroy Simon , Beeckman Tom , Nambara Eiji , Yoshioka Keiko
Published: July 2021

Cyclic nucleotide-gated ion channels (CNGCs) have been firmly established as Ca2+-conducting ion channels that regulate a wide variety of physiological responses in plants. CNGC2 has been implicated in plant immunity and Ca2+ signaling due to the autoimmune phenotypes exhibited by null mutants of CNGC2 in Arabidopsis thaliana. However, cngc2 mutants display additional phenotypes that are unique among autoimmune mutants, suggesting that CNGC2 has functions beyond defense and generates distinct Ca2+ signals in response to different triggers. In this study, we found that cngc2 mutants showed reduced gravitropism, consistent with a defect in auxin signaling. This was mirrored in the diminished auxin response detected by the auxin reporters DR5::GUS and DII-VENUS and in a strongly impaired auxin-induced Ca2+ response. Moreover, the cngc2 mutant exhibits higher levels of the endogenous auxin indole-3-acetic acid, indicating that excess auxin in the cngc2 mutant causes its pleiotropic phenotypes. These auxin signaling defects and the autoimmunity syndrome of the cngc2 mutant could be suppressed by loss-of-function mutations in the auxin biosynthesis gene YUCCA6 (YUC6), as determined by identification of the cngc2 suppressor mutant repressor of cngc2 (rdd1) as an allele of YUC6. A loss-of-function mutation in the upstream auxin biosynthesis gene TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA1, WEAK ETHYLENE INSENSITIVE8) also suppressed the cngc2 phenotypes, further supporting the tight relationship between CNGC2 and the TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS–YUCCA -dependent auxin biosynthesis pathway. Taking these results together, we propose that the Ca2+ signal generated by CNGC2 is a part of the negative feedback regulation of auxin homeostasis in which CNGC2 balances cellular auxin perception by influencing auxin biosynthesis.
Between mutuality, autonomy and domination: rethinking digital platforms as contested relational structures
Authors: Schüßler Elke , Attwood-Charles Will , Kirchner Stefan , Schor Juliet B
Published: July 2021

This Special Issue advances a new understanding of digital platforms as dynamic and relational. An archetypal transaction platform, we argue, is comprised of three canonical social relationships which exist in tension with each other. The first is mutuality—the practices of sharing and reciprocity which animated the early days of the ‘sharing economy’. The second is autonomy—representing the desire for freedom and independence attracting many earners to platforms. The third is domination—the exercise of power and control which drives many platform owners and managers. As we argue below, these three social relationships are present in varying degrees on all platforms. By conceptualizing platforms as contested relational structures, we aim to bridge prior attempts to classify ‘what platforms are’ with diverse empirical studies of ‘what platforms do’ in different contexts. In our view, platforms can do different things at the same time because they are different things at the same time.
How Do Statutes ‘Speak’ in Recent Technology Advancement Cases?
Authors: Leung Samuel Yee Ching
Published: July 2021

The focus of this article is the well-known statutory construction principle ‘a statute is always speaking’. This principle has a long history and has been applied in numerous cases. It has always been said that social changes are rapid, and the judges may need to give an ‘updated’ reading to a statute because legislative drafters just did not (and could not) foresee everything. However, as time goes by, the ways in which the courts apply this principle do not seem to be exactly the same. Also, the range of factors that the courts will consider seems to be expanding as the case law shows. In particular, in the 21st century, the need to use this principle is reinforced in technology advancement cases due to the unprecedented speed of technological improvements. Illustrative examples are therefore needed to provide certainty and predictability to the application of the principle. This article aims to accomplish this task. It will scrutinize three types of technology advancement cases to understand how the principle has been applied in recent years in technology context.
Saving Face While (Not) Talking about Race: How Undergraduates Inhabit Racialized Structures at an Elite and Predominantly White College
Authors: Nelson Ingrid A , Graham Hannah J , Rudin Natalie L
Published: July 2021

Through a qualitative case study of an elite, predominantly White, liberal arts college, we find that the unmarked Whiteness of core organizational structures and practices socialized undergraduates to normalize segregation while commodifying diversity. Analysis of publicly available documents (webpages, student newspaper, speeches) and student interviews (n=57) revealed that individuals’ attitudes were filtered through organizational structures. When students spoke about race, they tended to use two scripts: diversity script and/or naturalization of segregation script. Yet these culturally legitimated scripts were decoupled from organizational practices. Even though most students claimed to value diversity for its learning potential, many students believed social segregation was “natural,” and either “opted out” of conversations about race or “opted in” to conversations within homogeneous friend groups to maintain respectability within tightly-knit, well-resourced campus networks. The decoupling of structures, scripts, and behaviors motivated undergraduates of all races to adopt White, elite norms for (not) talking about race, which we dub “civilized diversity discourse.” Drawing on racialized organizations theory, we argue that the unmarked Whiteness of organizational structures—as well as the college’s size and status—shaped students’ scripts and behaviors in ways that ensure the enactment and entrenchment of racial ignorance and structural White supremacy.
Parenchyma underlies the interspecific variation of xylem hydraulics and carbon storage across 15 woody species on a subtropical island in Japan
Authors: Kawai Kiyosada , Minagi Kanji , Nakamura Tomomi , Saiki Shin-Taro , Yazaki Kenichi , Ishida Atsushi
Published: July 2021

Parenchyma is an important component of the secondary xylem. It has multiple functions and its fraction is known to vary substantially across angiosperm species. However, the physiological significance of this variation is not yet fully understood. Here, we examined how different types of parenchyma (ray parenchyma [RP], axial parenchyma [AP] and AP in direct contact with vessels [APV]) are coordinated with three essential xylem functions: water conduction, storage of non-structural carbohydrate (NSC) and mechanical support. Using branch sapwood of 15 co-occurring drought-adapted woody species from the subtropical Bonin Islands, Japan, we quantified 10 xylem anatomical traits and examined their linkages to hydraulic properties, storage of soluble sugars and starch and sapwood density. The fractions of APV and AP in the xylem transverse sections were positively correlated with the percentage loss of conductivity in the native condition, whereas that of RP was negatively correlated with the maximum conductivity across species. Axial and ray parenchyma fractions were positively associated with concentrations of starch and NSC. The fraction of parenchyma was independent of sapwood density, regardless of parenchyma type. We also identified a negative relationship between hydraulic conductivity and NSC storage and sapwood density, mirroring the negative relationship between the fractions of parenchyma and vessels. These results suggest that parenchyma fraction underlies species variation in xylem hydraulic and carbon use strategies, wherein xylem with a high fraction of AP may adopt an embolism repair strategy through an increased starch storage with low cavitation resistance.
Clinical and Laboratory Diagnosis of Cryptosporidiosis among Children with Acute Gastroenteritis at a Tertiary Hospital, Cairo, Egypt
Authors: Wahed Mohammad Ashraf Abdel , Shehab Yasmine Elsayed Abdelrahman , Abou-Seri Hanan Mahmoud , Awad Yosra Mohamed Mohsen
Published: July 2021

Background

Most studies on gastroenteritis have focused on viral and bacterial infections, while gastroenteritis where intestinal protozoan parasites may have played a role has not been well studied. This study was therefore, designed to assess the frequency and several potential risk factors for Cryptosporidium infection among children suffering from acute gastroenteritis and presented to a tertiary hospital in Cairo, Egypt. Effectiveness of modified Ziehl–Neelsen (MZN) and nested polymerase chain reaction (nPCR) for Cryptosporidium detection were evaluated as well.

Methods

A cross-sectional study was performed during the period from July 2018 to December 2018, where 100 human diarrheic stool samples were collected from children aged 3 months up to 12 years old presented to Ain Shams University Pediatrics Hospital, Cairo, Egypt with acute gastroenteritis. Demographic and clinical data were obtained from the participants. Initial parasite screening was done using the MZN staining method, and microscopically examined for Cryptosporidium infection, while genotyping was based on molecular diagnostic assays using nPCR and sequencing for selected samples.

Results

The overall frequency of Cryptosporidium infection was 5% using light microscopy, while 19% of samples were positive by nPCR. Cryptosporidium hominis was the only detected genotype. Clinical picture among cases were not significant in comparison to patients with other causes of gastroenteritis.

Conclusion

Cryptosporidium infection is more common below 5 years of age; however, clinical data are not enough for suspicion of infection. Nucleic acid-based methods are more sensitive and specific despite the high cost in developing countries. However, real estimation of Cryptosporidium disease burden is of an outmost importance to achieve prevention and detection of the Cryptosporidium species genetic diversity.

Lay summary

Cryptosporidium is a protozoan, which causes gastroenteritis in humans. It is most common below 5 years of age; however, diarrhea and vomiting characteristics are not different from other causes of gastroenteritis. General diagnostic methods are inadequate for detection of these infections. Nested polymerase chain reaction (nPCR) and sequencing are accurate methods for pathogen detection and species verification. Our study included 100 Egyptian children with acute gastroenteritis. The overall frequency of Cryptosporidium infection was 5% using light microscopy, while 19% of samples were positive by nPCR. The clinical picture of the children presenting with this disease was not significantly different from those presenting with gastroenteritis due to other causes. This emphasizes the importance of proper diagnosis to know the true burden of the disease.
Applicant Preferences for Virtual Interviews: Insights from the 2020–21 Integrated Plastic Surgery Application Cycle
Authors: Hemal Kshipra , Sarac Benjamin A. , Boyd Carter J. , Runyan Christopher M. , Gosman Amanda A. , Janis Jeffrey E.
Published: July 2021

Background:

The COVID-19 pandemic created an unprecedented residency application cycle that required the use of virtual interviews. The inaugural class of applicants participating in virtual interviews were surveyed concerning their preferences and suggestions for future application cycles.

Methods:

A survey was distributed to 349 individuals who applied for an integrated plastic surgery residency position at three institutions during the 2020–21 application cycle. Responses were analyzed to determine the most popular attributes of virtual interviews.

Results:

Response rate was 44%. Eighty-six percent of applicants valued having time to consider their interview offers before scheduling; however, nearly one-third felt the instructions provided by programs lacked clarity and did not abide by the American Council of Academic Plastic Surgeons guidelines. Eighty-two percent of applicants valued having a preinterview social, and most preferred smaller breakout rooms organized by themes. A short interview day (less than three hours) was associated with less applicant familiarity with the program, its people, and its location when compared with medium (three to seven hours) and long (more than seven hours) interview days (P < 0.001 for all). Eighty percent of applicants preferred an interview day where they were placed into interview rooms by a program coordinator.

Conclusions:

The virtual interview format can be optimized in many ways to benefit both applicants and programs. The data presented in this article provide suggestions for future iterations of virtual interviews.
The Application of Hypnosis in Obstetrics
Authors: Babbar Shilpa , Oyarzabal Alejandro J.
Published: July 2021

Hypnosis, the induction of a naturally relaxed state of mind and body, is most commonly practiced by pregnant women in preparation for the childbirth experience. A literature review was performed to assess the effects of hypnosis before, during and after pregnancy. The majority of data is extracted from case series and low-quality studies thereby limiting the acceptability of hypnosis for various pregnancy related conditions. A few well-designed studies show that self-hypnosis may be beneficial for mitigating labor pain and fear of childbirth. Women can safely pursue hypnotherapy during pregnancy; however, high quality trials are needed to demonstrate its complete efficacy.
Adverse events associated with femtosecond laser–assisted cataract surgery reported to the MAUDE database
Authors: Koenig Lisa R. , Duong Andrew T. , Yuan Melissa , Van Tassel Sarah H.
Published: July 2021

Purpose:

To report real-world complications associated with femtosecond laser–assisted cataract surgery (FLACS).

Setting:

Deidentified database.

Design:

Retrospective review.

Methods:

The U.S. Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database was culled for adverse events involving ophthalmic femtosecond laser during cataract surgery from January 2010 to January 2020. Reports in which the narrative description was inadequate to determine the nature of the complication were excluded. Each report was reviewed for complications, which were subsequently assigned to a complication category as determined by these authors. The number of events per year was determined and compared.

Results:

Between January 2010 and January 2020, the MAUDE database search yielded 2927 reports involving femtosecond laser, of which 1927 met inclusion criteria and were included for analysis. These reports revealed 2704 complications: 1115 capsule tears (41.2%), 329 of which required vitrectomy, 372 instances of suction loss, 321 other capsulotomy-related complications, and 432 corneal or incisional complications. Rare complications included 54 reports of miosis, 16 reports of endophthalmitis, and 4 reports of toxic anterior segment syndrome. The number of events in the MAUDE database increased year over year between 2011 and 2017, peaking in 2017 at 303 events.

Conclusions:

By drawing on real-world data in the MAUDE database, this study identified the complications of greatest importance in clinical practice. Surgeons should be aware of the spectrum of possible complications to best prepare for all potential outcomes and to effectively counsel patients.
Suboptimal Dosing of β-Blockers in Chronic Heart Failure
Authors: McGinlay Melanie , Straw Sam , Byrom-Goulthorp Rowenna , Relton Samuel D. , Gierula John , Cubbon Richard M. , Kearney Mark T. , Witte Klaus K.
Published: July 2021

Background

The evidence base for the benefits of β-blockers in heart failure with reduced ejection fraction (HFrEF) suggests that higher doses are associated with better outcomes.

Objectives

The aim of this study was to report the proportion of patients receiving optimized doses of β-blockers, outcomes, and factors associated with suboptimal dosing.

Methods

This was a prospective cohort study of 390 patients with HFrEF undergoing clinical and echocardiography assessment at baseline and at 1 year.

Results

Two hundred thirty-seven patients (61%) were receiving optimized doses (≥5-mg/d bisoprolol equivalent), 72 (18%) could not be up-titrated (because of heart rate < 60 beats/min or systolic blood pressure <100 mm Hg), and the remaining 81 (21%) should have been. Survival was similarly reduced in those who could not and should have been receiving 5 mg/d or greater, and patient factors did not explain the failure to attain optimized dosing.

Conclusions

Many patients with HFrEF are not receiving optimal dosing of β-blockers, and in around half, there was no clear contraindication in terms of heart rate or blood pressure.
Ketorolac Is Safe and Associated With Lower Rate of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children With Pancreatic Duct Manipulation
Authors: Mark Jacob A. , Kramer Robert E.
Published: July 2021

Objectives:

Use of non-steroidal anti-inflammatory drugs (NSAIDs) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prevention in pediatrics is not well studied. Because of difficulty in accurately dosing indomethacin suppositories in pediatric patients, our center has used intravenous ketorolac for PEP prevention and present data on its safety and associated PEP rates.

Methods:

Prospective monitoring of PEP for all patients who underwent ERCP at a pediatric tertiary care center from July 2010 to June 2018. Retrospective review of patient and procedural factors and severity of PEP. Routine use of ketorolac for PEP prevention began in 2014.

Results:

Two hundred and ninety-eight ERCPs were analyzed. One hundred and sixty-six patients received intraprocedural ketorolac and 132 did not. One patient had post-ERCP bleeding and bleeding rates were not significantly different between ketorolac and non-ketorolac groups (0.6% vs 0%, P = 1). Overall rates of PEP were not significantly different between the ketorolac and no ketorolac group (9% vs 13%, P = 0.29); however, for high-risk pediatric patients with injection of contrast into and/or cannulation of the pancreatic duct, the rates of PEP were significantly lower for patients who received ketorolac (11% vs 25%, P = 0.035).

Conclusions:

Pediatric patients undergoing ERCP with manipulation of the pancreatic duct are high risk for PEP, and ketorolac was associated with a lower rate of PEP in these patients. Ketorolac was well tolerated without a higher rate of bleeding after ERCP. These results are the first to provide evidence showing an association with intraprocedural NSAID use and lower rates of PEP in select pediatric patients.
First Performance Evaluation of an Artificial Intelligence-Based Computer-Aided Detection System for Pulmonary Nodule Evaluation in Dual-Source Photon-Counting Detector CT at Different Low-Dose Levels
Authors: Jungblut Lisa , Blüthgen Christian , Polacin Malgorzata , Messerli Michael , Schmidt Bernhard , Euler Andre , Alkadhi Hatem , Frauenfelder Thomas , Martini Katharina
Published: July 2021

Objective

The aim of this study was to evaluate the image quality (IQ) and performance of an artificial intelligence (AI)-based computer-aided detection (CAD) system in photon-counting detector computed tomography (PCD-CT) for pulmonary nodule evaluation at different low-dose levels.

Materials and Methods

An anthropomorphic chest-phantom containing 14 pulmonary nodules of different sizes (range, 3–12 mm) was imaged on a PCD-CT and on a conventional energy-integrating detector CT (EID-CT). Scans were performed with each of the 3 vendor-specific scanning modes (QuantumPlus [Q+], Quantum [Q], and High Resolution [HR]) at decreasing matched radiation dose levels (volume computed tomography dose index ranging from 1.79 to 0.31 mGy) by adapting IQ levels from 30 to 5. Image noise was measured manually in the chest wall at 8 different locations. Subjective IQ was evaluated by 2 readers in consensus. Nodule detection and volumetry were performed using a commercially available AI-CAD system.

Results

Subjective IQ was superior in PCD-CT compared with EID-CT (P < 0.001), and objective image noise was similar in the Q+ and Q-mode (P > 0.05) and superior in the HR-mode (PCD 55.8 ± 11.7 HU vs EID 74.8 ± 5.4 HU; P = 0.01). High resolution showed the lowest image noise values among PCD modes (P = 0.01). Overall, the AI-CAD system delivered comparable results for lung nodule detection and volumetry between PCD- and dose-matched EID-CT (P = 0.08–1.00), with a mean sensitivity of 95% for PCD-CT and of 86% for dose-matched EID-CT in the lowest evaluated dose level (IQ5). Q+ and Q-mode showed higher false-positive rates than EID-CT at lower-dose levels (IQ10 and IQ5). The HR-mode showed a sensitivity of 100% with a false-positive rate of 1 even at the lowest evaluated dose level (IQ5; CDTIvol, 0.41 mGy).

Conclusions

Photon-counting detector CT was superior to dose-matched EID-CT in subjective IQ while showing comparable to lower objective image noise. Fully automatized AI-aided nodule detection and volumetry are feasible in PCD-CT, but attention has to be paid to false-positive findings.
Multiple sex chromosomes in teleost fishes from a cytogenetic perspective: state of the art and future challenges
Authors: Sember Alexandr , Nguyen Petr , Perez Manolo F. , Altmanová Marie , Ráb Petr , Cioffi Marcelo de Bello
Published: July 2021

Despite decades of cytogenetic and genomic research of dynamic sex chromosome evolution in teleost fishes, multiple sex chromosomes have been largely neglected. In this review, we compiled available data on teleost multiple sex chromosomes, identified major trends in their evolution and suggest further trajectories in their investigation. In a compiled dataset of 440 verified records of fish sex chromosomes, we counted 75 multiple sex chromosome systems with 60 estimated independent origins. We showed that male-heterogametic systems created by Y-autosome fusion predominate and that multiple sex chromosomes are over-represented in the order Perciformes. We documented a striking difference in patterns of differentiation of sex chromosomes between male and female heterogamety and hypothesize that faster W sex chromosome differentiation may constrain sex chromosome turnover in female-heterogametic systems. We also found no significant association between the mechanism of multiple sex chromosome formation and percentage of uni-armed chromosomes in teleost karyotypes. Last but not least, we hypothesized that interaction between fish populations, which differ in their sex chromosomes, can drive the evolution of multiple sex chromosomes in fishes. This underlines the importance of broader inter-population sampling in studies of fish sex chromosomes.

This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Thermosensitive sex chromosome dosage compensation in ZZ/ZW softshell turtles,Apalone spinifera
Authors: Bista Basanta , Wu Zhiqiang , Literman Robert , Valenzuela Nicole
Published: July 2021

Sex chromosome dosage compensation (SCDC) overcomes gene-dose imbalances that disturb transcriptional networks, as when ZW females or XY males are hemizygous for Z/X genes. Mounting data from non-model organisms reveal diverse SCDC mechanisms, yet their evolution remains obscure, because most informative lineages with variable sex chromosomes are unstudied. Here, we discovered SCDC in turtles and an unprecedented thermosensitive SCDC in eukaryotes. We contrasted RNA-seq expression of Z-genes, their autosomal orthologues, and control autosomal genes inApalone spinifera(ZZ/ZW) andChrysemys pictaturtles with temperature-dependent sex determination (TSD) (proxy for ancestral expression). This approach disentangled chromosomal context effects on Z-linked and autosomal expression, from lineage effects owing to selection or drift. EmbryonicApaloneSCDC is tissue- and age-dependent, regulated gene-by-gene, complete in females via Z-upregulation in both sexes (Type IV) but partial and environmentally plastic via Z-downregulation in males (accentuated at colder temperature), present in female hatchlings and a weakly suggestive in adult liver (Type I). Results indicate that embryonic SCDC evolved with/after sex chromosomes inApalone's family Tryonichidae, while co-opting Z-gene upregulation present in the TSD ancestor. Notably,Apalone's SCDC resembles pygmy snake's, and differs from the full-SCDC ofAnolislizards who share homologous sex chromosomes (XY), advancing our understanding of how XX/XY and ZZ/ZW systems compensate gene-dose imbalance.

This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Do male and female heterogamety really differ in expression regulation? Lack of global dosage balance in pygopodid geckos
Authors: Rovatsos Michail , Gamble Tony , Nielsen Stuart V. , Georges Arthur , Ezaz Tariq , Kratochvíl Lukáš
Published: July 2021

Differentiation of sex chromosomes is thought to have evolved with cessation of recombination and subsequent loss of genes from the degenerated partner (Y and W) of sex chromosomes, which in turn leads to imbalance of gene dosage between sexes. Based on work with traditional model species, theory suggests that unequal gene copy numbers lead to the evolution of mechanisms to counter this imbalance. Dosage compensation, or at least achieving dosage balance in expression of sex-linked genes between sexes, has largely been documented in lineages with male heterogamety (XX/XY sex determination), while ZZ/ZW systems are assumed to be usually associated with the lack of chromosome-wide gene dose regulatory mechanisms. Here, we document that although the pygopodid geckos evolved male heterogamety with a degenerated Y chromosome 32–72 Ma, one species in particular, Burton's legless lizard (Lialis burtonis), does not possess dosage balance in the expression of genes in its X-specific region. We summarize studies on gene dose regulatory mechanisms in animals and conclude that there is in them no significant dichotomy between male and female heterogamety. We speculate that gene dose regulatory mechanisms are likely to be related to the general mechanisms of sex determination instead of type of heterogamety.

This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Sex chromosomes in meiotic, hemiclonal, clonal and polyploid hybrid vertebrates: along the ‘extended speciation continuum'
Authors: Stöck Matthias , Dedukh Dmitrij , Reifová Radka , Lamatsch Dunja K. , Starostová Zuzana , Janko Karel
Published: July 2021

We review knowledge about the roles of sex chromosomes in vertebrate hybridization and speciation, exploring a gradient of divergences with increasing reproductive isolation (speciation continuum). Under early divergence, well-differentiated sex chromosomes in meiotic hybrids may cause Haldane-effects and introgress less easily than autosomes. Undifferentiated sex chromosomes are more susceptible to introgression and form multiple (or new) sex chromosome systems with hardly predictable dominance hierarchies. Under increased divergence, most vertebrates reach complete intrinsic reproductive isolation. Slightly earlier, some hybrids (linked in ‘the extended speciation continuum') exhibit aberrant gametogenesis, leading towards female clonality. This facilitates the evolution of various allodiploid and allopolyploid clonal (‘asexual’) hybrid vertebrates, where ‘asexuality' might be a form of intrinsic reproductive isolation. A comprehensive list of ‘asexual' hybrid vertebrates shows that they all evolved from parents with divergences that were greater than at the intraspecific level (K2P-distances of greater than 5–22% based on mtDNA). These ‘asexual' taxa inherited genetic sex determination by mostly undifferentiated sex chromosomes. Among the few known sex-determining systems in hybrid ‘asexuals', female heterogamety (ZW) occurred about twice as often as male heterogamety (XY). We hypothesize that pre-/meiotic aberrations in all-female ZW-hybrids present Haldane-effects promoting their evolution. Understanding the preconditions to produce various clonal or meiotic allopolyploids appears crucial for insights into the evolution of sex, ‘asexuality' and polyploidy.

This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Interaction between sex-determining genes from two species: clues fromXenopushybrids
Authors: Roco Álvaro S. , Ruiz-García Adrián , Bullejos Mónica
Published: July 2021

Hybrids provide an interesting model to study the evolution of sex-determining genes and sex chromosome systems as they offer the opportunity to see how independently evolving sex-determining pathways interactin vivo. In this context, the genusXenopusrepresents a stimulating model, since species with non-homologous sex chromosomes and different sex-determining genes have been identified. In addition, the possibility of interspecies breeding is favoured in this group, which arose by alloploidization events, with species ploidy ranging from 2n= 2x= 20 inX. tropicalis(the only diploid representative of the genus) to 2n= 12x= 108 inX. ruwenzoriensis. To study how two sex-determining genes interactin vivo,X. laevis×X. tropicalis hybrids were produced. Gonadal differentiation in these hybrids revealed that thedm-wgene is dominant overX. tropicalismale-determining sex chromosomes (Y or Z), even though the Y chromosome is dominant inX. tropicalis(Y > W>Z). In the absence of thedm-wgene (the Z chromosome fromX. laevisis present), the W chromosome fromX. tropicalisis able to trigger ovarian development. Testicular differentiation will take place in the absence of W chromosomes from any of the parental species. The dominance/recessivity relationships between these sex-determining loci in the context of either parental genome remains unknown.

This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Sex chromosome evolution from a heteromorphic to a homomorphic system by inter-population hybridization in a frog
Authors: Ogata Mitsuaki , Suzuki Kazuo , Yuasa Yoshiaki , Miura Ikuo
Published: July 2021

Sex chromosomes generally evolve from a homomorphic to heteromorphic state. Once a heteromorphic system is established, the sex chromosome system may remain stable for an extended period. Here, we show the opposite case of sex chromosome evolution from a heteromorphic to a homomorphic system in the Japanese frog
Glandirana rugosa.
One geographic group, Neo-ZW, has ZZ-ZW type heteromorphic sex chromosomes. We found that its western edge populations, which are geographically close to another West-Japan group with homomorphic sex chromosomes of XX-XY type, showed homozygous genotypes of sex-linked genes in both sexes. Karyologically, no heteromorphic sex chromosomes were identified. Sex-reversal experiments revealed that the males were heterogametic in sex determination. In addition, we identified another similar population around at the southwestern edge of the Neo-ZW group in the Kii Peninsula: the frogs had homomorphic sex chromosomes under male heterogamety, while shared mitochondrial haplotypes with the XY group, which is located in the east and bears heteromorphic sex chromosomes. In conclusion, our study revealed that the heteromorphic sex chromosome systems independently reversed back to or turned over to a homomorphic system around each of the western and southwestern edges of the Neo-ZW group through hybridization with the West-Japan group bearing homomorphic sex chromosomes.

This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Sex-biased gene expression and recent sex chromosome turnover
Authors: Lichilín Nicolás , El Taher Athimed , Böhne Astrid
Published: July 2021

Cichlids are well known for their propensity to radiate generating arrays of morphologically and ecologically diverse species in short evolutionary time. Following this rapid evolutionary pace, cichlids show high rates of sex chromosome turnover. We here studied the evolution of sex-biased gene (SBG) expression in 14 recently diverged taxa of the Lake Tanganyika Tropheini cichlids, which show different XY sex chromosomes. Across species, sex chromosome sequence divergence predates divergence in expression between the sexes. Only one sex chromosome, the oldest, showed signs of demasculinization in gene expression and potentially contribution to the resolution of sexual conflict. SBGs in general showed high rates of turnovers and evolved mostly under drift. Sexual selection did not shape the rapid evolutionary changes of SBGs. Male-biased genes evolved faster than female-biased genes, which seem to be under more phylogenetic constraint. We found a relationship between the degree of sex bias and sequence evolution driven by sequence differences among the sexes. Consistent with other species, strong sex bias towards sex-limited expression contributes to resolving sexual conflict in cichlids.

This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
The avian W chromosome is a refugium for endogenous retroviruses with likely effects on female-biased mutational load and genetic incompatibilities
Authors: Peona Valentina , Palacios-Gimenez Octavio M. , Blommaert Julie , Liu Jing , Haryoko Tri , Jønsson Knud A. , Irestedt Martin , Zhou Qi , Jern Patric , Suh Alexander
Published: July 2021

It is a broadly observed pattern that the non-recombining regions of sex-limited chromosomes (Y and W) accumulate more repeats than the rest of the genome, even in species like birds with a low genome-wide repeat content. Here, we show that in birds with highly heteromorphic sex chromosomes, the W chromosome has a transposable element (TE) density of greater than 55% compared to the genome-wide density of less than 10%, and contains over half of all full-length (thus potentially active) endogenous retroviruses (ERVs) of the entire genome. Using RNA-seq and protein mass spectrometry data, we were able to detect signatures of female-specific ERV expression. We hypothesize that the avian W chromosome acts as a refugium for active ERVs, probably leading to female-biased mutational load that may influence female physiology similar to the ‘toxic-Y’ effect inDrosophilamales. Furthermore, Haldane's rule predicts that the heterogametic sex has reduced fertility in hybrids. We propose that the excess of W-linked active ERVs over the rest of the genome may be an additional explanatory variable for Haldane's rule, with consequences for genetic incompatibilities between species through TE/repressor mismatches in hybrids. Together, our results suggest that the sequence content of female-specific W chromosomes can have effects far beyond sex determination and gene dosage.

This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Characterization of A Novel Autoimmune Encephalitis Associated Antibody against CRMP2
Authors: Xu Kaibiao , Wang Dongmei , He Yan , Wang Shengnan , Liu Guanghui , Pan Yue , Jiang Haishan , Peng Yu , Xiao Fenliang , Huang Yihua , Wang Qiqi , Wu Yongming , Pan Suyue , Hu Yafang
Published: July 2021

Objective

Autoimmune encephalitis (AE) is a large category disorder urging antibody characterization. The aim was to identify a novel AE related autoantibody targeting an intracellular synaptic protein.

Methods

Suspected AE patients had negative conventional antibodies screening but strong immunolabel signals on rat brain sections with the serum and cerebrospinal fluid (CSF) samples were considered burdening unkown antibody. Immunoprecipitation from the rat brain protein lysate followed by mass spectrometry analysis was used to identify the targeting antigen. Western blotting and/or cell-based assay (CBA) with antigen-overexpressing HEK293T cells were used for antibody specificity, epitope and IgG subtype determination. Patients with similar immunostaining pattern on rat brain sections were retrospectively screened for the antibody.

Results

The antibody against collapsin response mediator protein 2 (CRMP2), a synaptic protein involved in axon guidance, was identified in a patient with suspected AE. The patient samples reactivated with HEK293T cell overexpressed CRMP2, rather than CRMP1, 3, 4, and 5. The patient samples mainly stained neuronal cytoplasm of the cortex, hippocampus and cerebellum Purkinje cells. This reactivity was eliminated by pre-immunoabsorption with CRMP2-overexpressing HEK293T cells. CRMP2 truncation experiments indicated that 536 amino acids at C-terminus was necessary for the epitope. Subtype analysis showed that anti-CRMP2 antibody was IgG4. Moreover, screening from 19 suspected AE patients led to identification of anti-CRMP2 antibody in another patient with a diagnosis of encephalomyelitis. The two patients responded to immunotherapy.

Conclusions

This study discovered a novel anti-CRMP2 antibody associated with AE. Testing of the antibody might be promising for AE diagnosis and treatment.
A Wastewater-Based Epidemic Model for SARS-CoV-2 with Application to Three Canadian Cities
Authors: Nourbakhsh Shokoofeh , Fazil Aamir , Li Michael , Mangat Chand S. , Peterson Shelley W. , Daigle Jade , Langner Stacie , Shurgold Jayson , D’Aoust Patrick , Delatolla Robert , Mercier Elizabeth , Pang Xiaoli , Lee Bonita E. , Stuart Rebecca , Wijayasri Shinthuja , Champredon David
Published: July 2021

1

The COVID-19 pandemic has stimulated wastewater-based surveillance, allowing public health to track the epidemic by monitoring the concentration of the genetic fingerprints of SARS-CoV-2 shed in wastewater by infected individuals. Wastewater-based surveillance for COVID-19 is still in its infancy. In particular, the quantitative link between clinical cases observed through traditional surveillance and the signals from viral concentrations in wastewater is still developing and hampers interpretation of the data and actionable public-health decisions.

We present a modelling framework that includes both SARS-CoV-2 transmission at the population level and the fate of SARS-CoV-2 RNA particles in the sewage system after faecal shedding by infected persons in the population.

Using our mechanistic representation of the combined clinical/wastewater system, we perform exploratory simulations to quantify the effect of surveillance effectiveness, public-health interventions and vaccination on the discordance between clinical and wastewater signals. We also apply our model to surveillance data from three Canadian cities to provide wastewater-informed estimates for the actual prevalence, the effective reproduction number and incidence forecasts. We find that wastewater-based surveillance, paired with this model, can complement clinical surveillance by supporting the estimation of key epidemiological metrics and hence better triangulate the state of an epidemic using this alternative data source.
Characterization of SARS-CoV-2 Genetic Material in Wastewater
Authors: Robinson Carolyn A , Hsieh Hsin-Yeh , Hsu Shu-Yu , Wang Yang , Salcedo Braxton T , Klutts Jessica , Zemmer Sally , Belenchia Anthony , Reynolds Melissa , Semkiw Elizabeth , Foley Trevor , Wan XiuFeng , Wieberg Chris G. , Wenzel Jeff , Lin Chung-Ho , Johnson Marc C
Published: July 2021

SARS-CoV-2 genetic material has been detected in raw wastewater around the world throughout the COVID-19 pandemic and has served as a useful tool for monitoring community levels of SARS-CoV-2 infections. SARS-CoV-2 genetic material is highly detectable in a patient’s feces and the household wastewater for several days before and after a positive COVID-19 qPCR test from throat or sputum samples. Here, we characterize genetic material collected from raw wastewater samples and determine recovery efficiency during a concentration process. We find that pasteurization of raw wastewater samples did not reduce SARS-CoV-2 signal if RNA is extracted immediately after pasteurization. On the contrary, we find that signal decreased by approximately half when RNA was extracted 24-36 hours post-pasteurization and ∼90% when freeze-thawed prior to concentration. As a matrix control, we use an engineered enveloped RNA virus. Surprisingly, after concentration, the recovery of SARS-CoV-2 signal is consistently higher than the recovery of the control virus leading us to question the nature of the SARS-CoV-2 genetic material detected in wastewater. We see no significant difference in signal after different 24-hour temperature changes; however, treatment with detergent decreases signal ∼100-fold. Furthermore, the density of the samples is comparable to enveloped retrovirus particles, yet, interestingly, when raw wastewater samples were used to inoculate cells, no cytopathic effects were seen indicating that wastewater samples do not contain infectious SARS-CoV-2. Together, this suggests that wastewater contains fully intact enveloped particles.