bluuebunny/crossref_metadata_2025 huggingface dataset:
P-355 Thin endometrium is associated to higher risk of having a displaced window of implantation (WOI)
Authors: Valbuena Perilla D , Castellón J A , Gómez M , García I , Simón C , Ruiz-Alonso M
Published: June 2023

Study question

Is thin endometrium (<6 mm) associated to an abnormal receptivity status?

Summary answer

Thin endometrium (<6 mm) is significantly associated with a displaced WOI.

What is known already

The measurement of endometrial thickness by 2D vaginal ultrasound (US) is a routine practice in Assisted Reproduction Techniques (ART). Thin endometrium (<6 mm) is associated with poor reproductive outcome; however, the potential reason is unknown.

Study design, size, duration

Retrospective cohorts study including 25,888 patients in which endometrial lining was measured by 2D US the day before progesterone supplementation in HRT cycles for frozen embryo transfers and Endometrial Receptivity Analysis (ERA) was performed after 5 days of progesterone administration.

Endometrial thickness was classified as < 6 mm, 6-12 mm, or > 12 mm; ERA results were considered as receptive or displaced WOI (Pre-receptive, post-receptive, proliferative, and late-receptive) that needs a personalized embryo transfer (pET).

Participants/materials, setting, methods

Endometrial thickness was measured from one endometrial layer to the other on a longitudinal transvaginal scan at the site of maximum thickness evidenced by 2D US. For ERA analysis, RNA was extracted and sequenced by NGS. Then, the ERA computational predictor obtained the diagnosis as standard or displaced WOI.

Main results and the role of chance

RA results reveal that women with thin endometrium (<6mm) present significantly higher incidence of displaced WOI (47.49%) than 6-12mm (38.20%) (p = 0.0038), and >12mm (39.75%) (p = 0.026). No other differences were found.

*Significant different against other two groups.

Global Chi-square test for association P = 0.002.

Limitations, reasons for caution

This is a retrospective study, having innate limitations of its nature.

Wider implications of the findings

Thin endometrium (<6mm) is associated to a higher displaced WOI compared to normal lining or hypertrophic endometrium. Normal endometrial thickness (6-12 mm) considered as “receptive” does not preclude a transcriptomic receptivity status in 38.20% of the cases. This finding should be considered when embryo transfer is planned.

Trial registration number

Not applicable
P-384 Advanced paternal age: a mapping of the ethical issues
Authors: Couture V
Published: June 2023

Study question

What are the ethical issues raised by advanced paternal age?

Summary answer

Advanced paternal age is an ethically challenging phenomenon at the intersection of perinatal ethics, public health ethics, research ethics and policymaking.

What is known already

Although there is no clear indication on when begins advanced paternal age (APA), there is a tendency to consider 40 years old and over as a turning point in male reproduction. APA is now associated with several risks for male fertility, miscarriages, future child health and psychological development. Clinicians, scientists, social science researchers and ethicists have pointed several ethical issues raised by APA. For the moment, the scope of this discussion has not been fully assessed in a systematic way.

Study design, size, duration

To support a comprehensive evaluation of APA, we propose a mapping of the ethical issues of APA.

Participants/materials, setting, methods

First, we conducted a systematic literature review to identify ethical issues pointed by researchers and clinicians. Second, this first list of issues was discussed by a panel of experts (N = 23) through a web survey. The results from both data collections were triangulated by qualitative analysis into an integrated list of issues.

Main results and the role of chance

Six groups of issues emerged from data analysis. The first group relates to issues associated with the family project. In other words, how to balance the risks of APA with the benefits of the family project. The second group looks at the issues for healthcare professionals, i.e., how to support the family project while respecting the professional duty to protect their patients’ wellbeing. The third group refers to the gender justice issues and how APA generates inequities between gendered reproductive roles. The fourth group covers the public health dimension of APA and the justification to create intervention to respond to a collective and potentially intergenerational phenomenon. The fifth group is concerned about ways to develop sound and fair policies to respond to the challenges of APA. The sixth group encompasses research ethics issues on how to respectfully develop the field of research on APA.

Limitations, reasons for caution

APA is a burgeoning field of research, and it faces two principal limitations: (1) there is no clear understanding of the molecular mechanism of APA effect, and (2) data on the psychosocial dimension of APA is scarce. For these reasons, the ethical reflection is still speculative.

Wider implications of the findings

These findings offer a roadmap for future research on the ethics of APA. They provide a comprehensive understanding of issues that can be discussed during preconception counselling. At last, they suggest indications for the development of public health interventions or policies dedicated to address the most challenging aspects of APA.

Trial registration number

not applicable
P-487 Preimplantation genetic testing for aneuploidy for recurrent pregnancy loss: a systematic review and meta-analysis
Authors: Zhao S
Published: June 2023

Study question

Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live rate of recurrent pregnancy loss(RPL)?

Summary answer

PGT-A can improve the live birth rate and reduce the rate of miscarriages in women with RPL following in vitro fertilization-embryo transfer (IVF-ET).

What is known already

PGT-A has been widely used in women with RPL over the past decade. However, there is no consensus supporting this approach to the management of RPL.

Study design, size, duration

Systematic review and meta-analysis according to PRISMA guidelines. The research population was focused on RPL women. The intervention was PGT-A. The comparator was IVF/ICSI without PGT-A or expectant management. The primary outcome was the live birth rate per woman, and the secondary outcomes were the miscarriage rate and clinical pregnancy rate.

Participants/materials, setting, methods

PubMed, EMBASE, The Cochrane Library, and trial registers were searched for studies on PGT-A and RPL up to October 2022. There were no limitations regarding the year of publication or duration of follow-up but to the English language. The primary outcome was the live birth rate per woman, and the secondary outcomes were the miscarriage rate and clinical pregnancy rate.

Main results and the role of chance

Out of 1466 search results, 9 studies (including one RCT, one prospective pilot study, and seven retrospective cohort studies) were included in the review. Seven of these studies compared the live birth rate of RPL with PGT-A versus without PGT-A following in vitro fertilization-embryo transfer (IVF-ET). PGT-A signiﬁcantly increased live birth rate (odds ratio(OR): 2.07; 95% conﬁdence interval: 1.88 to 2.27) and lowered miscarriage rate (OR: 0.21; 95% conﬁdence interval: 0.13 to 0.34). However, PGT-A did not improve the clinical pregnancy rate. In two studies comparing the live birth rate/ongoing pregnancy of RPL with PGT-A versus expectant management, the result shows that PGT-A did not improve the live birth rate (OR: 1.11; 95% conﬁdence interval: 0.74 to 1.67).

Limitations, reasons for caution

Limitations include the retrospective design and heterogeneity of studies included, limiting comparison and pooling of data. Some studies have limited sample sizes. The data collected in the database could not exclude anatomic or chromosomal abnormalities in women with RPL.

Wider implications of the findings

PGT-A can improve the live birth rate and reduce the rate of miscarriages in women with RPL following IVF-ET. However, there is no evidence of a beneficial effect of PGT-A if compared with expectant management. It is important to evaluate carefully the application of PGT-A in clinical practice.

Trial registration number

not applicable
P-541 Does the IVF embryo remain at the site of deposition in successful IVF cycles?
Authors: Vasquez Carlon D , Rouleau J P , Costa M , Hernández J , Naftolin F N , Palumbo A
Published: June 2023

Study question

Does the placement of the IVF embryo differ from the implantation site?

Summary answer

At five weeks the implanted embryo has not moved in the lateral plane of the endometrial cavity but is slightly lower in the vertical plane.

What is known already

We previously showed that vertical placement of embryos approximately 9 mm from the fundus and equidistant from the tubal ostia has the highest implantation rate. Whether the embryo migrates from the point where the droplet is deposited before implantation is controversial. We used 3D ultrasound to compare the point of placement with the location of the gestational sac (GS) at 5 weeks gestational age (GA).

Study design, size, duration

Prospective analysis of 292 transfers of single egg donation blastocysts (2018-2020) and 139 resultant pregnancies in which the position of the GS in the coronal plane at 5 weeks was compared to that of the embryo flash immediately post transfer. A Voluson 6 with a 4D RAB4-8 transabdominal probe imaged the embryo transfer and a 4D RIC-5-9 transvaginal probe imaged the pregnancy scan (GE Healthcare, Austria).

Participants/materials, setting, methods

Consecutive patients with a normal uterine cavity undergoing egg donation in a single private IVF Center. Embryo transfers were performed under 2D US guidance using a soft Wallace Catheter. A 3D volume of the uterus was acquired immediately post-transfer. A second 3D scan was performed at 5 weeks GA. Distances of the embryo flash and the center of GS from the fundus, ostia and internal cervical os (ICO) were recorded and compared using SPSS.

Main results and the role of chance

Of 292 transfer procedures, 139 pregnancies who had the first ultrasound in our Center were included and analysed. The mean distance between the embryo flash and the uterine fundus was significantly less than the distance between the center of the GS and the uterine fundus [(9,49±3,03 vs 11,02±3,9 mm respectively (p < 0,05)]. The mean distances between the embryo flash and the right and left ostium were 16,66 ± 4,96 and 16,69 ± 4,61 mm respectively, with no significant differences from the same distances taken from the center of the GS.

Limitations, reasons for caution

As the image is of the embryo flash and not the embryo, this might have been misleading.

Wider implications of the findings

These findings extend and support the proposal of an optimal point of embryo placement for pregnancy. The apparent vertical difference in the implantation of the embryo could be due to uterine growth or it could be consequence of uterine peristalsis. This bears further study.

Trial registration number

not applicable
P-622 Age-specific reference intervals for anti-müllerian hormone in Mexico: A population-based study. implications for Latin America
Authors: Rodriguez-Purata J , Gingold J , Alonso-de-Mendieta M , Gomez-Cuesta M J , Cervantes-Bravo E
Published: June 2023

Study question

To determine the age-specific normal range of antimullerian hormone (AMH) levels in a female Latin American population.

Summary answer

Age-related nomograms for general population for the 3rd-97th percentiles were produced. These nomograms could provide a reference guide for clinicians to consult women with infertility.

What is known already

The variation of AMH levels among different races and ethnicities has been well documented (Seifer et al., 2009). Despite the wide use of AMH measurements in clinical assessment of ovarian reserve, a population-based estimate for its reference range in Latin America is not available.

Study design, size, duration

A longitudinal, observational, retrospective, real-world study was carried out, including all AMH measurements performed from January 2017 to December 2018 at a large clinical laboratory network in the Mexico City area, encompassing 35 locations. A total of 6444 AMH measurements were included.

Participants/materials, setting, methods

AMH was assayed using either the cobas or ELISA methodologies. All AMH measurements from women 25-45 years were included. The Kolmogorov-Smirnov test was used to confirm that AMH levels between patients assayed with cobas were comparable to those assayed with ELISA at every age.

Main results and the role of chance

In total, 6444 measurements were identified and available for analysis. Age-related normograms for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles of AMH were produced. The overall rate of AMH decline accelerated after 40 years of age. In women 25-30 years, 11.4% (63/554) had an AMH <1.0ng/mL. In women 30-35 years, 18.6% (276/1484) had an AMH <1.0ng/mL. In women 35-40 yeras, 35.8% (830/2319) had an AMH <1.0ng/mL. In women 40-45 years, 58.0% (1120/1932) had an AMH <1.0ng/mL.

Limitations, reasons for caution

The lack of medical history for patients precluded identification and exclusión of patients with iatrogenically abnormal AMH levels (e.g. due to oophorectomy). Patients undergoing measurement of AMH were primarily referred through fertility clinics, limiting the potential for extrapolation to the general population.

Wider implications of the findings

The study reports age-specific AMH levels drawn from a large sample of women around Mexico City. The study includes the largest dataset to date. Latin American patients considering fertility preservation should be aware of the high prevalence of diminished ovarian reserve in this large cohort, including among women 35-39.

Trial registration number

Not Applicable
Activation of the Mu-Delta Opioid Receptor Heteromers Blocks Morphine Rewarding Effects
Authors: Requana Aradas Ariadna , Djaboub Youssra , McCort-Tranchepain Isabelle , Hajasova Zuzana , Clémenceau Loïc , Canestrelli Corinne , Mann Anika , Schulz Stefan , Delaval Angélique , Acher Francine , Massotte Dominique , Noble Florence , Marie Nicolas
Published: June 2023

Background

Evidence has accumulated demonstrating the existence of opioid receptor heteromers, and recent data suggest that targeting these heteromers could reduce opioid side effects while retaining therapeutic effects. Indeed, CYM51010 characterized as a MOR (mu opioid receptor)/DOR (delta opioid receptor) heteromer–preferring agonist promoted antinociception comparable with morphine but with less tolerance. In the perspective of developing these new classes of pharmacological agents, data on their putative side effects are mandatory.

Methods

Therefore, in this study, we investigated the effects of CYM51010 in different models related to drug addiction in mice, including behavioral sensitization, conditioned place preference and withdrawal.

Results

We found that, like morphine, CYM51010 promoted acute locomotor activity as well as psychomotor sensitization and rewarding effect. However, it induced less physical dependence than morphine. We also investigated the ability of CYM51010 to modulate some morphine-induced behavior. Whereas CYM51010 was unable to block morphine-induced physical dependence, it blocked reinstatement of an extinguished morphine induced-conditioned place preference.

Conclusions

Altogether, our results reveal that targeting MOR-DOR heteromers could represent a promising strategy to block morphine reward.
What is a Lattice W-Algebra?
Authors: Izosimov Anton , Beffa Gloria Marí
Published: June 2023

We employ the Poisson-Lie group of pseudo-difference operators to define lattice analogs of classical $W_{m}$-algebras. We then show that the so-constructed algebras coincide with the ones given by discrete Drinfeld–Sokolov-type reduction.
Antibody to Plasmodium falciparum Variant Surface Antigens, var Gene Transcription, and ABO Blood Group in Children With Severe or Uncomplicated Malaria
Authors: Barua Priyanka , Duffy Michael F , Manning Laurens , Laman Moses , Davis Timothy M E , Mueller Ivo , Haghiri Ali , Simpson Julie A , Beeson James G , Rogerson Stephen J
Published: June 2023

Background

Antibodies to variant surface antigens (VSAs) such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) may vary with malaria severity. The influence of ABO blood group on antibody development is not understood.

Methods

Immunoglobulin G antibodies to VSAs in Papua New Guinean children with severe (n = 41) or uncomplicated (n = 30) malaria were measured by flow cytometry using homologous P falciparum isolates. Isolates were incubated with ABO-matched homologous and heterologous acute and convalescent plasma. RNA was used to assess var gene transcription.

Results

Antibodies to homologous, but not heterologous, isolates were boosted in convalescence. The relationship between antibody and severity varied by blood group. Antibodies to VSAs were similar in severe and uncomplicated malaria at presentation, higher in severe than uncomplicated malaria in convalescence, and higher in children with blood group O than other children. Six var gene transcripts best distinguished severe from uncomplicated malaria, including UpsA and 2 CIDRα1 domains.

Conclusions

ABO blood group may influence antibody acquisition to VSAs and susceptibility to severe malaria. Children in Papua New Guinea showed little evidence of acquisition of cross-reactive antibodies following malaria. Var gene transcripts in Papua New Guinean children with severe malaria were similar to those reported from Africa.
Rilmazafone: A designer benzodiazepine pro-drug involved in fatal intoxications
Authors: Kronstrand Robert , Roman Markus , Johansson Anna , Wu Xiongyu , Green Henrik , Truver Michael T
Published: June 2023

Rilmazafone is a pro-drug that can be prescribed in Japan to treat insomnia. Rilmazafone metabolizes into active compounds by a ring closure resulting in a triazolo benzodiazepine structure similar to alprazolam. In mid-2022, the National Board of Forensic Medicine in Sweden were requested to investigate two separate deaths with the suspected use of pagoclone. Packages labeled “Pagoclone” were found at each scene that was suspected to contain rilmazafone based on website information. During screening by high resolution mass spectrometry, rilmazafone metabolites were presumptively identified. Due to the lack of reference material for the active metabolites, the metabolites were synthesized in house and quantification of the compounds identified in the two autopsy cases was prompted. In Case 1, femoral blood concentrations of 7.9, 65 and 170 ng/g of the metabolites rilmazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included the medications haloperidol, alimemazine, fluoxetine, olanzapine and acetaminophen. In Case 2, femoral blood concentrations of 1.7, 1.4 and 70 ng/g of rimazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included loperamide, alimemazine and pregabalin. The intake of rilmazafone was determined as the cause of death in Case 1 and contributed in the Case 2.
Hot Earth or Young Venus? A nearby transiting rocky planet mystery
Authors: Kaltenegger L , Payne R C , Lin Z , Kasting J , Delrez L
Published: June 2023

Venus and Earth provide astonishingly different views of the evolution of a rocky planet, raising the question of why these two rocky worlds evolved so differently. The recently discovered transiting Super-Earth LP 890-9c (TOI-4306c, SPECULOOS-2c) is a key to the question. It circles a nearby M6V star in 8.46 d. LP890-9c receives similar flux as modern Earth, which puts it very close to the inner edge of the Habitable Zone (HZ), where models differ strongly in their prediction of how long rocky planets can hold onto their water. We model the atmosphere of a hot LP890-9c at the inner edge of the HZ, where the planet could sustain several very different environments. The resulting transmission spectra differ considerably between a hot, wet exo-Earth, a steamy planet caught in a runaway greenhouse, and an exo-Venus. Distinguishing these scenarios from the planet’s spectra will provide critical new insights into the evolution of hot terrestrial planets into exo-Venus. Our model and spectra are available online as a tool to plan observations. They show that observing LP890-9c can provide key insights into the evolution of a rocky planet at the inner edge of the HZ as well as the long-term future of Earth.
Clinical features of newly diagnosed systemic lupus erythematosus after SARS-CoV-2 vaccination
Authors: Moriyama Masayori , Noda Kentaro , Ito Haruyasu , Matsushita Takayuki , Kurosaka Daitaro
Published: June 2023

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes damage to multiple organs. Various factors, including vaccination, have been associated with SLE development. Vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in 2020, and there are a few reports on the exacerbation of SLE after SARS-CoV-2 vaccination. The influence of SARS-CoV-2 vaccination on SLE development remains unclear. We present the case of a 53-year-old man who developed peritonitis and was subsequently diagnosed with SLE on Day 9 after receiving a third dose of the messenger ribonucleic acid-1273 SARS-CoV-2 vaccine. This case and previous reports have shown that patients who developed SLE after SARS-CoV-2 vaccination are more likely to develop it within 2 weeks of vaccination, especially when they have a higher rate of immunological abnormalities or a family history of autoimmune diseases. Furthermore, these features suggest that type I interferon is involved in the pathogenesis of SLE after SARS-CoV-2 vaccination.
Development of “Baby, Me, & NRT”: A Behavioral Intervention to Improve the Effectiveness of Nicotine Replacement Therapy in Pregnancy
Authors: McDaid Lisa , Emery Joanne , Thomson Ross , Coleman Tim , Cooper Sue , Dickinson Anne , Kinahan-Goodwin Darren , Phillips Lucy , Naughton Felix
Published: June 2023

Background

The effectiveness of Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy is limited by inconsistent and incorrect use. This paper describes the development process for “Baby, Me, & NRT”, a novel pregnancy-specific intervention aimed at enhancing adherence to NRT.

Methods

An integrated approach to intervention development was used, combining evidence, theory, stakeholders’ feedback, and tailoring principles. The process involved six iterative steps: (1) synthesizing relevant published evidence and guidance, (2) collecting primary qualitative data on barriers and facilitators to NRT adherence along with potential intervention design features, (3) identifying relevant behavioral theories and mapping the evidence against these, (4) prioritizing behavioral determinants identified in steps 1 and 2, generating intervention objectives, and identifying behavior change techniques which target the prioritized determinants, (5) consulting with stakeholders on intervention components, key content and tailoring features, and (6) producing a prototype intervention along with implementation guidance.

Results

The prototype intervention comprises of a multi-component, 1-month cessation programme, which includes six enhanced behavioral support sessions delivered by a trained advisor, tailored text messages, a website, and an illustrated booklet. It promotes the uptake of high-dose and combination NRT, emphasizes the importance of adherence, addresses motivation to use NRT, proactively helps problem solve NRT use issues, and provides guidance on preventing and managing smoking lapses.

Conclusion

The development process generated an evidence- and theory-guided intervention, designed with stakeholder input, aimed at improving NRT effectiveness for smoking cessation in pregnancy. The prototype intervention has since been optimized and is being evaluated in a randomized controlled trial.
Erwinia amylovora Type III Secretion System Inhibitors Reduce Fire Blight Infection Under Field Conditions
Authors: Yuan Xiaochen , Sundin George W. , Zeng Quan , Johnson Kenneth B. , Cox Kerik D. , Yu Manda , Huang Jian , Yang Ching-Hong
Published: June 2023

Fire blight, caused by Erwinia amylovora, is an economically important disease in apples and pears worldwide. This pathogen relies on the type III secretion system (T3SS) to cause disease. Compounds that inhibit the function of the T3SS (T3SS inhibitors) have emerged as alternative strategies for bacterial plant disease management, as they block bacterial virulence without affecting growth, unlike traditional antibiotics. In this study, we investigated the mode of action of a T3SS inhibitor named TS108, a plant phenolic acid derivative, in E. amylovora. We showed that adding TS108 to an in vitro culture of E. amylovora repressed the expression of several T3SS regulon genes, including the master regulator gene hrpL. Further studies demonstrated that TS108 negatively regulates CsrB, a global regulatory small RNA, at the posttranscriptional level, resulting in a repression of hrpS, which encodes a key activator of hrpL. Additionally, TS108 has no impact on the expression of T3SS in Dickeya dadantii or Pseudomonas aeruginosa, suggesting that its inhibition of the E. amylovora T3SS is likely species specific. To better evaluate the performance of T3SS inhibitors in fire blight management, we conducted five independent field experiments in four states (Michigan, New York, Oregon, and Connecticut) from 2015 to 2022 and observed reductions in blossom blight incidence as high as 96.7% compared with untreated trees. In summary, the T3SS inhibitors exhibited good efficacy against fire blight.
Genome Sequence Resource of Burkholderia gladioli KRS027: A Strain with Antifungal Activity Against Plant Pathogens
Authors: Wang Dan , Zhang Dan-Dan , Li Ran , Zhu He , Song Jian , Kong Zhi-Qiang , Dai Xiao-Feng , Han Dongfei , Chen Jie-Yin
Published: June 2023

Some species of Burkholderia have been studied extensively for their ability to control plant diseases and promote plant growth. Burkholderia gladioli KRS027 is a strain isolated from the rhizosphere soil of a healthy plant in a pathogen-infested cotton field in Xinjiang, China, which had an inhibitory ability against various plant-pathogenic fungi. To understand its biocontrol mechanism, we assembled a high-quality genome of KRS027 using the PacBio-HiFiReads. The KRS027 genome contained two circular DNA chromosomes and one plasmid, of which Chr1 contained 4,187,756 bp with 67.95% GC content, Chr2 had 3,892,275 bp with 68.56% GC content, and the plasmid comprised 177,327 bp with 61.11% GC content. Moreover, the genome contains 20 secondary metabolite biosynthesis gene clusters involving polyketides (PKS), nonribosomal peptides (NRPS), hybrid NRPS/PKS, and terpene. The genes involved in biosynthesis of phytotoxins, such as toxoflavin, rhizotoxin, and bongkrekic acid, were not detected. The high-quality genome resource of strain KRS027 will provide a molecular basis for further research on its biocontrol mechanisms.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Pseudomonas solani sp. nov. isolated from the rhizosphere of eggplant in Japan
Authors: Sawada Hiroyuki , Takeuchi Kasumi , Someya Nobutaka , Morohoshi Tomohiro , Satou Mamoru
Published: June 2023

The search for bacteria that can be used as biocontrol agents to control crop diseases yielded a promising candidate, Sm006T, which was isolated from the rhizosphere of eggplant (Solanum melongena) growing in a field in Aichi Prefecture, Japan, in 2006. The cells were Gram-stain-negative, aerobic, non-spore-forming, rod-shaped and motile with one polar flagellum. The results of homology searches and phylogenetic analyses based on the 16S rRNA gene sequence indicated that Sm006T represents a member of the genus

Pseudomonas

. The genomic DNA G+C content was 66.3 mol% and the major cellular fatty acids (more than 5 % of the total fatty acids) were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C12 : 0. Phylogenetic analyses using the rpoD gene sequence and phylogenomic analysis of the whole genome sequence revealed that Sm006T represents a member of the

Pseudomonas resinovorans

group; however, its phylogenetic position does not match that of any known species of the genus

Pseudomonas

. The average nucleotide identity and digital DNA–DNA hybridisation values between the strain and closely related species were lower than the thresholds for prokaryotic species delineation (95–96 and 70 %, respectively), with the highest values observed for

Pseudomonas tohonis

TUM18999T (92.05 and 46.3 %, respectively). Phenotypic characteristics, cellular fatty acid composition and possession of 2,4-diacetylphloroglucinol biosynthetic gene cluster could be used to differentiate the strain from its closest relatives. The phenotypic, chemotaxonomic and genotypic data obtained during this study indicated that Sm006T represents a novel species of the genus

Pseudomonas

, for which we propose the name Pseudomonas solani sp. nov., with Sm006T (= MAFF 212523T = ICMP 24689T) as the type strain.
Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging
Authors: Poudel Sher Bahadur , Frikha-Benayed Dorra , Ruff Ryan R. , Yildirim Gozde , Dixit Manisha , Korstanje Ron , Robinson Laura , Miller Richard A. , Harrison David E. , Strong John R. , Schaffler Mitchell B. , Yakar Shoshana
Published: June 2023

Declines in mitochondrial content and impaired cytochrome c oxidase activity (complex IV) can result in reduced energy metabolism and increased levels of oxidants. Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both in vitro and in vivo settings. Mitoquinone (MitoQ) is a selective antioxidant that specifically targets mitochondria and effectively reduces the accumulation of reactive oxygen species (ROS) within cells.

To investigate the effect of acute and long-term administration of MB on skeletal morphology, we administered MB to aged (18 months old) female C57BL/J6 mice, as well as to adult male and female mice with a genetically diverse background (UM-HET3). Additionally, we used MitoQ as an alternative approach to target mitochondrial oxidative stress during aging in adult female and male UM-HET3 mice.

Although we observed some beneficial effects of MB and MitoQ in vitro, the administration of these compounds in vivo did not alter the progression of age-induced bone loss. Specifically, treating 18-month-old female mice with MB for 6 or 12 months did not have an effect on age-related bone loss. Similarly, long-term treatment with MB from 7 to 22 months or with MitoQ from 4 to 22 months of age did not affect the morphology of cortical bone at the mid-diaphysis of the femur, trabecular bone at the distal-metaphysis of the femur, or trabecular bone at the lumbar vertebra-5 (L5) in UM-HET3 mice.

Based on our findings, it appears that long-term treatment with MB or MitoQ alone, as a means to reduce skeletal oxidative stress, is insufficient to inhibit age-associated bone loss. This supports the notion that interventions solely with antioxidants may not provide adequate protection against skeletal aging.
Hybrid machine-learning framework for volumetric segmentation and quantification of vacuoles in individual unlabeled yeast cells using holotomography
Authors: Lee Moosung , Kunzi Marina , Neurohr Gabriel , Lee Sung Sik , Park Yongkeun
Published: June 2023

The precise, quantitative evaluation of intracellular organelles in three-dimensional (3D) imaging data poses a significant challenge due to the inherent constraints of traditional microscopy techniques, the requirements of the use of exogenous labeling agents, and existing computational methods. To counter these challenges, we present a hybrid machine-learning framework exploiting correlative imaging of 3D quantitative phase imaging with 3D fluorescence imaging of labeled cells. The algorithm, which synergistically integrates a random-forest classifier with a deep neural network, is trained using the correlative imaging data set, and the trained network is then applied to 3D quantitative phase imaging of unlabeled cell data. We applied this method to unlabeled live budding yeast cells. The results revealed precise segmentation of vacuoles inside individual yeast cells, and also provided quantitative evaluations of biophysical parameters, including volumes, concentration, and dry masses of automatically segmented vacuoles.
Absolute calibration of ribosome profiling assesses the dynamics of ribosomal flux on transcripts
Authors: Tomuro Kotaro , Mito Mari , Toh Hirotaka , Kawamoto Naohiro , Miyake Takahito , Chow Siu Yu A. , Doi Masao , Ikeuchi Yoshiho , Shichino Yuichi , Iwasaki Shintaro
Published: June 2023

Ribosome profiling, which is based on deep sequencing of ribosome footprints, has served as a powerful tool for elucidating the regulatory mechanism of protein synthesis. However, the current method has substantial issues: contamination by rRNAs and the lack of appropriate methods to determine overall ribosome numbers in transcripts. Here, we overcame these hurdles through the development of “Ribo-FilterOut”, which is based on the separation of footprints from ribosome subunits by ultrafiltration, and “Ribo-Calibration”, which relies on external spike-ins of stoichiometrically defined mRNA-ribosome complexes. A combination of these approaches measures the absolute number of ribosomes on a transcript, the translation initiation rate, and the overall number of translation events before its decay, all in a genome-wide manner. Moreover, our method revealed the allocation of ribosomes under heat shock stress, during aging, and across cell types. Our strategy transforms ribosome profiling technique from relative to absolute quantification of translation.
The F pilus serves as a conduit for the DNA during conjugation between physically distant bacteria
Authors: Goldlust Kelly , Ducret Adrien , Halte Manuel , Dedieu-Berne Annick , Erhardt Marc , Lesterlin Christian
Published: June 2023

Horizontal transfer of F-like plasmids by bacterial conjugation is responsible for disseminating antibiotic resistance and virulence determinants among pathogenic Enterobacteriaceae species, a growing health concern worldwide. Central to this process is the conjugative F pilus, a long extracellular filamentous polymer that extends from the surface of plasmid donor cells, allowing it to probe the environment and make contact with the recipient cell. It is well established the F pilus can retract to bring mating pair cells in tight contact before DNA transfer. However, whether DNA transfer can occur through the extended pilus has been a subject of active debate. In this study, we use live-cell microscopy to show that the F pilus can indeed serve as a conduit for the DNA during transfer between physically distant cells. Our findings enable us to propose a new model for conjugation that revises our understanding of the DNA transport mechanism and the dissemination of drug resistance in complex bacterial communities.

One-Sentence Summary:

Plasmid DNA passes through the F pilus during conjugational transfer between physically distant bacteria.
Characterization of Tigurilysin, a Novel Human CD59-Specific Cholesterol-Dependent Cytolysin, Reveals a Role for Host Specificity in Augmenting Toxin Activity
Authors: Shahi Ifrah , Dongas Sophia A. , Ilmain Juliana K. , Torres Victor J. , Ratner Adam J.
Published: June 2023

Cholesterol dependent cytolysins (CDCs) are a large family of pore forming toxins, produced by numerous gram-positive pathogens. CDCs depend on host membrane cholesterol for pore formation; some CDCs also require surface associated human CD59 (hCD59) for binding, conferring specificity for human cells. We purified a recombinant version of a putative CDC encoded in the genome ofStreptococcus oralis subsp. tigurinus, tigurilysin (TGY), and used CRISPR/Cas9 to construct hCD59 knockout (KO) HeLa and JEG-3 cell lines. Cell viability assays with TGY on WT and hCD59 KO cells showed that TGY is a hCD59-dependent CDC. Two variants of TGY exist amongS. oralis subsp. tigurinusgenomes, only one of which is functional. We discovered that a single amino acid change between these two TGY variants determines its activity. Flow cytometry and oligomerization western blots revealed that the single amino acid difference between the two TGY isoforms disrupts host cell binding and oligomerization. Furthermore, experiments with hCD59 KO cells and cholesterol depleted cells demonstrated that TGY is fully dependent on both hCD59 and cholesterol for activity, unlike other known hCD59-dependent CDCs. Using full-length CDCs and toxin constructs differing only in the binding domain, we determined that having hCD59-dependence leads to increased lysis efficiency, conferring a potential advantage to organisms producing hCD59-dependent CDCs.

IMPORTANCE

Cholesterol dependent cytolysins (CDCs) are produced by a variety of disease-causing bacteria, and may play a significant role in pathogenesis. Understanding CDC mechanisms of action provides useful information for developing anti-virulence strategies against bacteria that utilize CDCs and other pore-forming toxins in pathogenesis. This study describes for the first time a novel human-specific CDC with an atypical pore forming mechanism compared to known CDCs. In addition, this study demonstrates that human-specificity potentially confers increased lytic efficiency to CDCs. These data provide a possible explanation for the selective advantage of developing hCD59-dependency in CDCs and the consequent host restriction.
Optimisation of a DNA extraction protocol for improving the bacterial and fungal classification based on Nanopore sequencing
Authors: Thu May Soe , Sawaswong Vorthorn , Chanchaem Prangwalai , Klomkliew Pavit , Campbell Barry J. , Hirankarn Nattiya , Fothergill Joanne L. , Payungporn Sunchai
Published: June 2023

Ribosomal RNA gene amplicon sequencing is commonly used to evaluate microbiome profiles in health and disease and document the impact of interventional treatments. Long-read nanopore sequencing is attractive since it can provide greater classification at the species level. However, optimised protocols to target marker genes for bacterial and fungal profiling are needed. To achieve an increased taxonomic resolution, we developed extraction and long-amplicon PCR-based approaches using Nanopore sequencing. Three sample lysis conditions were applied to a mock microbial community, including known bacterial and fungal species; the 96 MagBead DNA lysis buffer (ML) alone, incorporating bead-beating (MLB) or bead-beating plus MetaPolyzyme enzymatic treatment (MLBE). Profiling of bacterial comparison, MLB had more statistically different bacterial phyla and genera than the others. For fungal profiling, MLB had a significant increase of Ascomycota and a decline of Basidiomycota, subsequently failing to detectMalasseziaandCryptococcus. Also, the principal coordinates analysis (PCoA) plot by the Bray-Curtis index showed a significant difference among groups for bacterial (p =0.033) and fungal (p =0.012) profiles. Overall, the microbial profiling and diversity analysis revealed that ML and MLBE have more similarity than MLB for both bacteria and fungi, therefore, bead-beating is not recommended for long-read amplicon sequencing. However, ML alone was suggested as an optimal approach considering DNA yield, classification, reagent cost and hands-on time. This could be an initial proof-of-concept study for simultaneous human microbiome and mycobiome studies.
Crystal structure of dihydrofolate reductase from the emerging pathogenic fungus Candida auris
Authors: Kirkman Tim , Sketcher Alice , de Morais Barroso Vinicius , Ishida Kelly , Tosin Manuela , Dias Marcio Vinicius Bertacine
Published: June 2023

Candida auris has emerged as a global health problem with a dramatic spread by nosocomial transmission and a high mortality rate. Antifungal therapy for C. auris infections is currently limited due to widespread resistance to fluconazole and amphotericin B and increasing resistance to the front-line drug echinocandin. Therefore, new treatments are urgently required to combat this pathogen. Dihydrofolate reductase (DHFR) has been validated as a potential drug target for Candida species, although no structure of the C. auris enzyme (CauDHFR) has been reported. Here, crystal structures of CauDHFR are reported as an apoenzyme, as a holoenzyme and in two ternary complexes with pyrimethamine and cycloguanil, which are common antifolates, at near-atomic resolution. Preliminary biochemical and biophysical assays and antifungal susceptibility testing with a variety of classical antifolates were also performed, highlighting the enzyme-inhibition rates and the inhibition of yeast growth. These structural and functional data might provide the basis for a novel drug-discovery campaign against this global threat.
The generalized nonlocal fractal calculus: an efficient tool for fractal circuit analysis
Authors: Banchuin Rawid
Published: June 2023

Purpose

The purpose of this paper is to propose a novel nonlocal fractal calculus scheme dedicated to the analysis of fractal electrical circuit, namely, the generalized nonlocal fractal calculus.

Design/methodology/approach

For being generalized, an arbitrary kernel function has been adopted. The condition on order has been derived so that it is not related to the γ-dimension of the fractal set. The fractal Laplace transforms of our operators have been derived.

Findings

Unlike the traditional power law kernel-based nonlocal fractal calculus operators, ours are generalized, consistent with the local fractal derivative and use higher degree of freedom. As intended, the proposed nonlocal fractal calculus is applicable to any kind of fractal electrical circuit. Thus, it has been found to be a more efficient tool for the fractal electrical circuit analysis than any previous fractal set dedicated calculus scheme.

Originality/value

A fractal calculus scheme that is more efficient for the fractal electrical circuit analysis than any previous ones has been proposed in this work.
Authentic brand positioning or woke washing? LGBTQI+ consumer perceptions of brand activism
Authors: Tressoldi Cassiano , Espartel Lélis Balestrin , Rohden Simoni F.
Published: June 2023

Purpose

The lesbian, gay, bisexual, transgender, queer, intersex and others (LGBTQI+) movement has been the focus of companies that seek to win over consumers by supporting diversity. Any positioning, however, that is not perceived as being consistent and genuine can harm the brand's image. Through a queer theoretical perspective, the authors explore perceptions of LGBTQI+ consumers regarding brand activism.

Design/methodology/approach

Qualitative research was carried out that involved interviewing Brazilian consumers who are part of the LGBTQI+ community.

Findings

Aspects of the identity of these individuals draw closer to those brands that share the same values the individuals have. Brand activism is perceived positively in terms of the brand's representativeness and social impact. When activism is perceived as inauthentic, activism generates a backlash and consumers begin to boycott brands as the consumers associate positioning with woke-washing practices.

Originality/value

The results indicate that to adopt an activist stance with regard to the LGBTQI+ public, brands need to be consistent in the brands' communication and advertising and in brands' organizational culture and diversity. This research provides important indicators for brands that genuinely want to support the LGBTQI+ community and is the first to use queer theory to analyze brand activism.
Fostering college aspirations: engaging English teachers in students’ future pathways
Authors: Richards Dasmen , Lawson Amber , Nicol Jaime , Woodcock Benjamin K. , Pritchett Taria , Julien David
Published: June 2023

Purpose

This essay is for the Community Voices feature of the special issue titled “The Role of English Teaching and Teachers in Supporting Youths’ University Futures and Literacies.” This paper aims to provide various recommendations for English teachers and teacher educators who are invested in fostering the college aspirations of students.

Design/methodology/approach

This essay is for the Community Voices feature of the special issue titled “The Role of English Teaching and Teachers in Supporting Youths' University Futures and Literacies.” A group of six educators convene to develop recommendations for English teachers and teachers educators that can be helpful when engaging with students regarding their college aspirations.

Findings

This essay is for the Community Voices feature of the special issue titled “The Role of English Teaching and Teachers in Supporting Youths’ University Futures and Literacies.” We provide nine recommendations for English teachers and teachers educators to support students' college access and readiness.

Originality/value

This essay is for the Community Voices feature of the special issue titled “The Role of English Teaching and Teachers in Supporting Youths’ University Futures and Literacies.” This paper generates new insights to further develop college readiness and access within English classrooms.
Numerical and experimental study of natural convection heat transfer on flat and corrugated plates
Authors: Verdério Júnior Sílvio Aparecido , Coelho Pedro J. , Scalon Vicente Luiz , del Rio Oliveira Santiago
Published: June 2023

Purpose

The purpose of this study is to numerically and experimentally investigate the natural convection heat transfer in flat plates and plates with square, trapezoidal and triangular corrugations.

Design/methodology/approach

This work is an extension of the previous studies by Verderio et al. (2021a, 2021b, 2021c, 2021d, 2022a). An experimental apparatus was built to measure the plates’ temperatures during the natural convection cooling process. Several physical parameters were evaluated through the experimental methodology. Free and open-source computational tools were used to simulate the experimental conditions and to quantitatively and qualitatively evaluate the thermal plume characteristics over the plates.

Findings

The numerical results were experimentally validated with reasonable accuracy in the range of studied

RaLP for the different plates. Empirical correlations of

Nu¯LPexp=f(RaLP),

h¯conv=f(RaLP) and

Nu¯LPexp⋅(A/AP)=f(RaLP), with good accuracy and statistical representativeness, were obtained for the studied geometries. The convective thermal efficiency of corrugated plates (Δη), as a function of

RaLP, was also experimentally studied quantitatively. In agreement with the findings of Oosthuizen and Garrett (2001), the experimental and numerical results proved that the increase in the heat exchange area of the corrugations has a greater influence on the convective exchange and the thermal efficiency than the disturbances caused in the flow (which reduce

h¯conv). The plate with trapezoidal corrugations presented the highest convective thermal efficiency, followed by the plates with square and triangular corrugations. It was also proved that the thermal efficiency of corrugated plates increases with

RaLP.

Practical implications

The results demonstrate that corrugated surfaces have greater thermal efficiency than flat plates in heating and/or cooling systems by natural convection. This way, corrugated plates can reduce the dependence on auxiliary forced convection systems, with application in technological areas and Industry 4.0.

Originality/value

The empirical correlations obtained for the corrected Nusselt number and thermal efficiency for the corrugated plate geometries studied are original and unpublished, as well as the experimental validation of the developed three-dimensional numerical code.