bluuebunny/crossref_metadata_2025 huggingface dataset:
An amplicon panel for high-throughput and low-cost genotyping of Pacific oyster
Authors: Sutherland Ben J G , Thompson Neil F , Surry Liam B , Gujjula Krishna Reddy , Carrasco Claudio D , Chadaram Srinivas , Lunda Spencer L , Langdon Christopher J , Chan Amy M , Suttle Curtis A , Green Timothy J
Published: June 2024

Maintaining genetic diversity in cultured shellfish can be challenging due to high variance in individual reproductive success, founder effects, and rapid genetic drift, but is important to retain adaptive potential and avoid inbreeding depression. To support broodstock management and selective breeding in cultured Pacific oysters (Crassostrea (Magallana) gigas), we developed an amplicon panel targeting 592 genomic regions and SNP variants with an average of 50 amplicons per chromosome. Target SNPs were selected based on elevated observed heterozygosity or differentiation in Pacific oyster populations in British Columbia, Canada. The use of the panel for parentage applications was evaluated using multiple generations of oysters from a breeding program on Vancouver Island, Canada (n = 181) and families selected for Ostreid herpesvirus-1 resistance from the Molluscan Broodstock Program in Oregon, USA (n = 136). Population characterization was evaluated using wild, naturalized, farmed, or hatchery oysters sampled throughout the Northern Hemisphere (n = 189). Technical replicates showed high genotype concordance (97.5%; n = 68 replicates). Parentage analysis found suspected pedigree and sample handling errors, demonstrating the panel's value for quality control in breeding programs. Suspected null alleles were identified and found to be largely population dependent, suggesting population-specific variation impacting target amplification. Null alleles were identified using existing data without the need for pedigree information, and once they were removed, assignment rates increased to 93.0 and 86.0% of possible assignments in the two breeding program datasets. A pipeline for analyzing the amplicon sequence data from sequencer output, amplitools, is also provided.
Dogs and their genes: what ever will they think of next?
Authors: Ostrander Elaine A
Published: June 2024

The Edward Novitski Prize recognizes creativity and intellectual ingenuity in the solution of problems in genetics research. The prize honors scientific experimental work—either a single experimental accomplishment or a body of work.

Ostrander is recognized for work developing the domestic dog as an experimental system for solving fundamental biological problems and identifying genetic sequences of relevance to human health and disease. Including work on disease and behavioral health, Ostrander has shown a dedication to creative methods for understanding canine genetics and the value of translating research organisms to human genetics.
Genome size and chromosome number are critical metrics for accurate genome assembly assessment in Eukaryota
Authors: Hjelmen Carl E
Published: June 2024

The number of genome assemblies has rapidly increased in recent history, with NCBI databases reaching over 41,000 eukaryotic genome assemblies across about 2,300 species. Increases in read length and improvements in assembly algorithms have led to increased contiguity and larger genome assemblies. While this number of assemblies is impressive, only about a third of these assemblies have corresponding genome size estimations for their respective species on publicly available databases. In this paper, genome assemblies are assessed regarding their total size compared to their respective publicly available genome size estimations. These deviations in size are assessed related to genome size, kingdom, sequencing platform, and standard assembly metrics, such as N50 and BUSCO values. A large proportion of assemblies deviate from their estimated genome size by more than 10%, with increasing deviations in size with increased genome size, suggesting nonprotein coding and structural DNA may be to blame. Modest differences in performance of sequencing platforms are noted as well. While standard metrics of genome assessment are more likely to indicate an assembly approaching the estimated genome size, much of the variation in this deviation in size is not explained with these raw metrics. A new, proportional N50 metric is proposed, in which N50 values are made relative to the average chromosome size of each species. This new metric has a stronger relationship with complete genome assemblies and, due to its proportional nature, allows for a more direct comparison across assemblies for genomes with variation in sizes and architectures.
The maternal protein NLRP5 stabilizes UHRF1 in the cytoplasm: implication for the pathogenesis of multilocus imprinting disturbance
Authors: Unoki Motoko , Uemura Shuhei , Fujimoto Akihiro , Sasaki Hiroyuki
Published: June 2024

We have recently discovered that the so-called subcortical maternal complex (SCMC) proteins composing of cytoplasmic lattices are destabilized in Uhrf1 knockout murine fully grown oocytes (FGOs). Here we report that human UHRF1 interacts with human NLRP5 and OOEP, which are core components of the SCMC. Moreover, NLRP5 and OOEP interact with DPPA3, which is an essential factor for exporting UHRF1 from the nucleus to the cytoplasm in oocytes. We identify that NLRP5, not OOEP, stabilizes UHRF1 protein in the cytoplasm utilizing specifically engineered cell lines mimicking UHRF1 status in oocytes and preimplantation embryos. Further, UHRF1 is destabilized both in the cytoplasm and nucleus of Nlrp5 knockout murine FGOs. Since pathogenic variants of the SCMC components frequently cause multilocus imprinting disturbance and UHRF1 is essential for maintaining CpG methylation of imprinting control regions during preimplantation development, our results suggest possible pathogenesis behind the disease, which has been a long-standing mystery.
Modeling Fertilization Outcome in a Changing World
Authors: Chan Kit Yu Karen , KO Wing Ho
Published: June 2024

Synopsis

Marine organisms have complex life histories. For broadcast spawners, successful continuation of the population requires their small gametes to make contact in the water column for sufficiently long periods for fertilization to occur. Anthropogenic climate change has been shown to impact fertilization success in various marine invertebrates, including sea urchins, which are key grazers in their habitats. Gamete performance of both sexes declined when exposed to elevated temperatures and/or pCO2 levels. Examples of reduced performance included slower sperm swimming speed and thinning egg jelly coat. However, such responses to climate change stress were not uniform between individuals. Such variations could serve as the basis for selection. Fertilization kinetics have long been modeled as a particle collision process. Here, we present a modified fertilization kinetics model that incorporates individual variations in performance in a more environmentally relevant regime, and which the performance of groups with different traits can be separately tracked in a mixture. Numerical simulations highlight that fertilization outcomes are influenced by changes in gamete traits as they age in sea water and the presence of competition groups (multiple dams or sires). These results highlight the importance of considering multiple individuals and at multiple time points during in vivo assays. We also applied our model to show that interspecific variation in climate stress vulnerabilities elevates the risk of hybridization. By making a numerical model open-source, we aim to help us better understand the fate of organisms in the face of climate change by enabling the community to consider the mean and variance of the response to capture adaptive potential.
Resistance towards and biotransformation of a Pseudomonas-produced secondary metabolite during community invasion
Authors: Hansen Morten L , Dénes Zsófia , Jarmusch Scott A , Wibowo Mario , Lozano-Andrade Carlos N , Kovács Ákos T , Strube Mikael L , Andersen Aaron J C , Jelsbak Lars
Published: June 2024

The role of antagonistic secondary metabolites produced by Pseudomonas protegens in suppression of soil-borne phytopathogens has been clearly documented. However, their contribution to the ability of P. protegens to establish in soil and rhizosphere microbiomes remains less clear. Here, we use a four-species synthetic community (SynCom) in which individual members are sensitive towards key P. protegens antimicrobial metabolites (DAPG, pyoluteorin, and orfamide A) to determine how antibiotic production contributes to P. protegens community invasion and to identify community traits that counteract the antimicrobial effects. We show that P. protegens readily invades and alters the SynCom composition over time, and that P. protegens establishment requires production of DAPG and pyoluteorin. An orfamide A-deficient mutant of P. protegens invades the community as efficiently as wildtype, and both cause similar perturbations to community composition. Here, we identify the microbial interactions underlying the absence of an orfamide A mediated impact on the otherwise antibiotic-sensitive SynCom member, and show that the cyclic lipopeptide is inactivated and degraded by the combined action of Rhodococcus globerulus D757 and Stenotrophomonas indicatrix D763. Altogether, the demonstration that the synthetic community constrains P. protegens invasion by detoxifying its antibiotics may provide a mechanistic explanation to inconsistencies in biocontrol effectiveness in situ.
In vitro activity of ozenoxacin against Staphylococcus aureus and Streptococcus pyogenes clinical isolates recovered in a worldwide multicentre study (2020–2022)
Authors: García-Castillo María , Hernández-García Marta , Correa Adriana , Coppi Marco , Griener Thomas , Fritsche Thomas , Pitart Cristina , Sampaio Jorge , Seifert Harald , Wake Karen , Wootton Mandy , Vila Jordi , Cantón Rafael
Published: June 2024

Objectives

We performed a multicentre study (2020–2022) to compare the in vitro activity of ozenoxacin and comparator agents against Staphylococcus aureus and Streptococcus pyogenes clinical isolates from skin and soft-tissue infections (SSTI).

Methods

A total of 1725 isolates (1454 S. aureus and 271 S. pyogenes) were collected in 10 centres from eight countries between January 2020 and December 2022. Antimicrobial susceptibility testing was determined (microdilution-SENSITITRE). Results were interpreted following European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 (clinical breakpoints, ECOFF) and CLSI criteria.

Results

Ozenoxacin exhibited high in vitro activity against S. aureus (MIC50/90 = 0.002/0.12 mg/L) and S. pyogenes (MIC50/90 = 0.015/0.03 mg/L), inhibiting 99% of the isolates at MIC ≤ 0.5 mg/L and at MIC ≤ 0.06, respectively. The most active comparators against S. aureus were retapamulin (MIC90 = 0.12 mg/L), fusidic acid (MIC90 = 0.25 mg/L) and mupirocin (MIC90 = 0.5 mg/L); and against S. pyogenes were retapamulin (MIC90 = 0.03 mg/L), clindamycin (MIC90 = 0.12 mg/L) and mupirocin (MIC90 = 0.25 mg/L). Ciprofloxacin and methicillin resistant rates for S. aureus were 31.3% (455/1454) and 41% (598/1454), respectively. Additionally, 62% (373/598) of the MRSA were also ciprofloxacin non-susceptible, whereas only 10% (23/271) of the MSSA were ciprofloxacin resistant. Ozenoxacin was more active against ciprofloxacin-susceptible S. aureus than against ciprofloxacin-resistant isolates, and showed a slightly higher MIC in MRSA isolates than in MSSA. However, ozenoxacin activity was comparable in both ciprofloxacin-resistant MSSA and MRSA subsets. On the other hand, ozenoxacin had similar activity in ciprofloxacin-susceptible and resistant S. pyogenes isolates.

Conclusions

Ozenoxacin is a potent antimicrobial agent of topic use against Gram-positive bacteria causing SSTI, including MRSA isolates non-susceptible to ciprofloxacin.
Two-phase biomarker studies for disease progression with multiple registries
Authors: Mao Fangya , Cook Richard J
Published: June 2024

We consider the design and analysis of two-phase studies of the association between an expensive biomarker and disease progression when phase I data are obtained by pooling registries having different outcome-dependent recruitment schemes. We utilize two analysis methods, namely maximum-likelihood and inverse probability weighting (IPW), to handle missing covariates arising from a two-phase design. In the likelihood framework, we derive a class of residual-dependent designs for phase II sub-sampling from an observed data likelihood accounting for the phase I sampling plans used by the different registries. In the IPW approach, we derive and evaluate optimal stratified designs that approximate Neyman allocation. Simulation studies and an application to a motivating example demonstrate the finite sample improvements from the proposed designs over simple random sampling and standard stratified sampling schemes.
(421) SYSTEMATIC REVIEW OF PROSTATIC AND PELVIC IMAGING PARAMETERS TO PREDICT POST RADICAL PROSTATECTOMY ERECTILE DYSFUNCTION
Authors: Al-Mitwalli Dr Abdullah , Wani Dr Mudassir , Lee Dr Wai Gin , Tandogdu Dr Zafer , Ralph Prof David
Published: June 2024

Objectives

With surgery for prostate cancer there remains significant long-term post operative sequalae; these are, urinary incontinence and erectile dysfunction (ED). Certain mpMRI parameters such as membranous-urethral-length, have been shown to correlate with post-operative recovery of urinary continence. We are carrying out a comprehensive systematic review to identify imaging parameters that predict the recovery of erectile function after laparoscopic or robotic prostatectomy.

Methods

A systematic search was performed including Pubmed, Embase and Cochrane reviews from January 2000 up to August 2022. A protocol of this study was registered preliminarily in the International Prospective Register of Systematic Reviews (PROSPERO; Registrations ID CRD 42022359557). The review considered studies utilising an imaging parameter or technique obtained by any form of imaging modality and in any operative phase to correlate with validated erectile function assessment after robotic or laparoscopic radical prostatectomy.

Results

A total of 8 studies met our inclusion criteria. We categorised the studies based on the imaging modality into three groups: MRI (n=4), diffusion tensor imaging (DTI) (n=2) and intraoperative ultrasonography (n=2). Parameters with significant correlation to erectile function identified on pre-operative MRI were dynamic contrast enhancement of prostatic tissue and area of neurovascular bundle (NVB). The number of periprostatic nerve fibres on DTI had significant correlation erectile function post-operatively. Ultrasonography studies identified used pulsatile arterial flow and the number of visible blood vessels on simultaneous transrectal ultrasound during laparoscopic prostatectomy and also ultrasound doppler used as a laparoscopic probe to identify arterial flow intra-operatively.

Conclusions

Our systematic review revealed possible imaging parameters of anatomical and functional features that could be linked out erectile function after minimally invasive radical prostatectomy. Small sample studies, lack of heterogeneity makes pooling of results challenging. More research is needed to establish these parameters to predict and mitigate risk of erectile function post prostatectomy.

Conflicts of Interest

None.
(352) THE METABOLIC ROLE OF PROLACTIN: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Corona Dr Giovanni , Rastrelli Prof Giulia , Comeglio Dr Paolo , Guaraldi Dr Federica , Mezzatenta Dr Diego , Sforza Dr Alessandra , Vignozzi Prof Linda , Maggi Prof Mario
Published: June 2024

Objectives

Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been poorly investigated. The aim of the study is to systematically review and analyze data from clinical studies focusing on the metabolic consequences of abnormally high prolactin levels (HPRL) and low prolactin levels (LPRL).

Methods

A comprehensive systematic review was performed using Medline, Embase and Cochrane search. In particular, two separate literature searches (one for HPRL and one for LPRL) until 31 March 2022 for published English-language articles were performed.

Results

17 studies were included in the analysis of HPRL. When compared to controls, patients with HPRL showed worse body composition. Moreover, higher total (12.55 [1.59-23.52] mg/dL p=0.02) and low-density lipoprotein (LDL)-cholesterol (13.40 [4.07-22.74] mg/dL p<0.001) as well as higher triglyceride levels (20.99 [9.36-32.63] mg/dL p<0.001) were observed in patients with HPRL. Finally, when glucose profile was analyzed, subjects with HPRL were characterized by higher HOMA index and insulin levels. Dopamino-agonist therapy resulted in an improvement of total (-19.26 [-25.22;-13.29] mg/dL p<0.001) and LDL cholesterol (-18.84[-24.44;-13.24] p<0.001) as well as triglyceride levels, fasting glycaemia and HOMA index.

12 cross-sectional and 3 longitudinal studies were included in the analysis of LPRL. Subjects included in cross-sectional studies, and with LPRL, showed worse lipid profiles and higher fasting glucose when compared to controls. The age-adjusted probability of diabetes was increased in subjects with LPRL (OR=1.60[1.43;1.79] p<0.001. Similar risk was observed when longitudinal studies were considered (OR=1.30[1.11;1.52] p<0.001 for LPRL vs. controls).

Conclusions

Pathological PRL elevation, but also its reduction, impairs metabolism and body composition in both genders, increasing the risk of diabetes. Patients with hypoprolactinemia, because of endogenous or iatrogenic conditions, deserve, as those with hyperprolactinemia, careful metabolic assessment.

Conflicts of Interest

The authors declare no conflict of interest.
(1012) PAIN DURING RECEPTIVE ANAL SEX: IS IT A NOVEL SEXUAL DYSFUNCTION?
Authors: Giola Dr Massimo
Published: June 2024

Objectives

Anodyspareunia, or pain during receptive anal intercourse, has been introduced in the medical and sexological literature in 1998 by S. Rosser, but 25 years later it remains unacknowledged as a novel sexual dysfunction. Although pain during anal sex is not universal and in fact affects a minority of people engaging in receptive anal intercourse, it is reported by a significant proportion of gay, bisexual, and other men who have sex with men (GBM) and cisgender heterosexual women. It is imperative to re-consider the nature and role of anodyspareunia as a barrier to achieve full sexual satisfaction and as a cause of ill sexual health.

Methods

A systematic literature review from 1998 to 2023 was conducted, identifying 11 peer-reviewed papers (8 original studies and 3 previous reviews), plus 7 non-peer reviewed self-help books giving useful insights.

Results

The 8 original studies found a prevalence of anodyspareunia ranging from 5.5 to 14% of GBM, from 15.4 to 23% of GBM following treatment for prostate cancer; in the one and only study among women a prevalence of 8.7% was demonstrated. The risk factors for anodyspareunia in the literature can be grouped under three main categories, ie performance anxiety, sexual inexperience, and internalised homophobia. The self-help books propose some psychosexual techniques that warrant further investigations in clinical trials. The role of poppers, identified as a protective factor in some studies, remains to be defined, due to the lack of pharmaceutical grade preparations.

Conclusions

Anodyspareunia emerges from the available literature as a novel sexual dysfunction, and although several aspects need further research it apperas to fulfill the criteria and the definition accepted for all the other sexual dysfunctions. Advocacy work by scientific societies such as ESSM is needed to legitimise anodyspareunia and include it in future editions of standards and guidelines.

Conflicts of Interest

None.
(224) EVALUATION OF ONLINE ADAPTATION OF EDUCATION PROGRAM ON TRANS-INCLUSIVE HEALTHCARE AND GENDER AFFIRMATION FOR MEDICAL PROFESSIONALS IN BOSNIA AND HERZEGOVINA VIA REGIONAL EXPERTS' COOPERATION
Authors: Hasanbegović Delila , Zegura Prof Iva , Dušek Tina , Kojović Vladimir , Vlahović Erin ,   ON behalf of Sarajevo Open Centre
Published: June 2024

Objectives

Sarajevo Open Centre- SOC and a number of medical/mental health experts from Bosnia and Herzegovina, Croatia, and Serbia created an online, video lecture for E-medikacija, BiH online platform for additional education and professional development of MDs (medical doctors). The topic of the education session is Medical Aspects of Trans-Inclusive Health Care/Gender Affirmation. The education is a result of the cooperation between the Federation BiH Medical Chamber, Sarajevo Open Centre (SOC), and medical experts from the region who have extensive expertise working with transgender, intersex, and gender-diverse persons. The need for the education of MDs and mental health professionals in BIH is observed every day when trans persons seek inclusive and specific health care in BiH health institutions/medical facilities, and since BiH does not have educated medical personnel to lead and monitor the process of gender affirmation process, such as MD's, psychologists, endocrinologists, gynecologists, urologists, pediatricians, plastic and reconstructive surgeons, this educations program was essential.

Methods

The education program for medical workers was adapted to an online version to include a wide range of medical workers and to bridge obstacles of on-site education such as distance, costs, and avoiding attendance because of stigma. Participants fulfilled the online evaluation form and knowledge test. The completed and verified allowed them to get credits to extend their seven-year medical license.

Results

Out of 2854 registered users, 667 medical professionals visited the webpage where the education was uploaded. 173 users attended the online education in comparison to 7 when it was held onsite. 167 users successfully passed the knowledge test.

Conclusions

86% of attendants are very satisfied with the online education program and consider it to improve their knowledge and professional competencies in working with transgender clients. They express their willingness to further participate in educational and collaborative activities with SOC.

Conflicts of Interest

No.
Non-thermal radiation from dual jet interactions in supermassive black hole binaries
Authors: Gutiérrez Eduardo M , Combi Luciano , Romero Gustavo E , Campanelli Manuela
Published: June 2024

Supermassive black hole binaries (SMBHBs) are natural by-products of galaxy mergers and are expected to be powerful multimessenger sources. They can be powered by the accretion of matter and then radiate across the electromagnetic spectrum, much like normal active galactic nuclei (AGNs). Current electromagnetic observatories have a good chance of detecting and identifying these systems in the near future. However, precise observational indicators are needed to distinguish individual AGNs from SMBHBs. In this paper, we propose a novel electromagnetic signature from SMBHBs: non-thermal emission produced by the interaction between the jets ejected by the black holes. We study close SMBHBs, which accrete matter from a circumbinary disc and the mini-discs formed around each hole. Each black hole ejects a magnetically dominated jet in the direction of its spin through the Blandford–Znajek mechanism. We argue that in such a situation, the interaction between the jets can trigger strong magnetic reconnection events, where particles are accelerated and emit non-thermal radiation. Depending on whether the jets are aligned or misaligned, this radiation can have different periodicities. We model the evolution of the particles accelerated during the dual jet interaction and calculate their radiative output, obtaining spectra and providing estimates for the variability time-scales. We finally discuss how this emission compares with that of normal AGNs.
One-sided H α excess before the first pericentre passage in galaxy pairs
Authors: Chung Jiwon , Lee Joon Hyeop , Jeong Hyunjin
Published: June 2024

We present novel insights into the interplay between tidal forces and star formation in interacting galaxies before their first pericentre passage. We investigate seven close pair galaxies devoid of visible tidal disturbances, such as tails, bridges, and shells. Using integral field spectroscopy data of extended Calar Alto Legacy Integral Field Area, we unveil a previously unreported phenomenon: H $\alpha$ emission, a proxy for recent star formation, exhibits a significant enhancement in regions facing the companion galaxy, reaching up to 1.9 times higher flux compared to opposite directions. Notably, fainter companions within pairs display a more pronounced one-sided H $\alpha$ excess, exceeding the typical range observed in isolated galaxies with 2$\sigma$ confidence level. Furthermore, the observed H $\alpha$ excess in fainter companion galaxies exhibits a heightened prominence at the outer galactic regions. These findings suggest that tidal forces generated before the first pericentre passage exert a stronger influence on fainter galaxies due to their shallower potential wells by their brighter companions. This unveils a more intricate interplay between gravitational interactions and star formation history within interacting galaxies than previously understood, highlighting the need further to explore the early stages of interaction in galaxy evolution.
Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter
Authors: Hutchens Steven , Melkote Ashvini , Jursa Thomas , Shawlot William , Trasande Leonardo , Smith Donald R , Mukhopadhyay Somshuvra
Published: June 2024

Elevated manganese (Mn) accumulates in the brain and induces neurotoxicity. SLC30A10 is an Mn efflux transporter that controls body Mn levels. We previously reported that full-body Slc30a10 knockout mice (1) recapitulate the body Mn retention phenotype of humans with loss-of-function SLC30A10 mutations and (2) unexpectedly develop hypothyroidism induced by Mn accumulation in the thyroid, which reduces intra-thyroid thyroxine. Subsequent analyses of National Health and Nutrition Examination Survey data identified an association between serum Mn and subclinical thyroid changes. The emergence of thyroid deficits as a feature of Mn toxicity suggests that changes in thyroid function may be an underappreciated, but critical, modulator of Mn-induced disease. To better understand the relationship between thyroid function and Mn toxicity, here we further defined the mechanism of Mn-induced hypothyroidism using mouse and rat models. Slc30a10 knockout mice exhibited a profound deficit in thyroid iodine levels that occurred contemporaneously with increases in thyroid Mn levels and preceded the onset of overt hypothyroidism. Wild-type Mn-exposed mice also exhibited increased thyroid Mn levels, an inverse correlation between thyroid Mn and iodine levels, and subclinical hypothyroidism. In contrast, thyroid iodine levels were unaltered in newly generated Slc30a10 knockout rats despite an increase in thyroid Mn levels, and the knockout rats were euthyroid. Thus, Mn-induced thyroid dysfunction in genetic or Mn exposure-induced mouse models occurs due to a reduction in thyroid iodine subsequent to an increase in thyroid Mn levels. Moreover, rat and mouse thyroids have differential sensitivities to Mn, which may impact the manifestations of Mn-induced disease in these routinely used animal models.
Eukaryotic AlaX provides multiple checkpoints for quality and quantity of aminoacyl-tRNAs in translation
Authors: Li Zi-Han , Zhou Xiao-Long
Published: June 2024

Translational fidelity relies critically on correct aminoacyl-tRNA supply. The trans-editing factor AlaX predominantly hydrolyzes Ser-tRNAAla, functioning as a third sieve of alanyl-tRNA synthetase (AlaRS). Despite extensive studies in bacteria and archaea, the mechanism of trans-editing in mammals remains largely unknown. Here, we show that human AlaX (hAlaX), which is exclusively distributed in the cytoplasm, is an active trans-editing factor with strict Ser-specificity. In vitro, both hAlaX and yeast AlaX (ScAlaX) were capable of hydrolyzing nearly all Ser-mischarged cytoplasmic and mitochondrial tRNAs; and robustly edited cognate Ser-charged cytoplasmic and mitochondrial tRNASers. In vivo or cell-based studies revealed that loss of ScAlaX or hAlaX readily induced Ala- and Thr-to-Ser misincorporation. Overexpression of hAlaX impeded the decoding efficiency of consecutive Ser codons, implying its regulatory role in Ser codon decoding. Remarkably, yeast cells with ScAlaX deletion responded differently to translation inhibitor treatment, with a gain in geneticin resistance, but sensitivity to cycloheximide, both of which were rescued by editing-capable ScAlaX, alanyl- or threonyl-tRNA synthetase. Altogether, our results demonstrated the previously undescribed editing peculiarities of eukaryotic AlaXs, which provide multiple checkpoints to maintain the speed and fidelity of genetic decoding.
Apollon: a deoxyribozyme that generates a yellow product
Authors: Volek Martin , Kurfürst Jaroslav , Kožíšek Milan , Srb Pavel , Veverka Václav , Curtis Edward A
Published: June 2024

Colorimetric assays in which the color of a solution changes in the presence of an input provide a simple and inexpensive way to monitor experimental readouts. In this study we used in vitro selection to identify a self-phosphorylating kinase deoxyribozyme that produces a colorimetric signal by converting the colorless substrate pNPP into the yellow product pNP. The minimized catalytic core, sequence requirements, secondary structure, and buffer requirements of this deoxyribozyme, which we named Apollon, were characterized using a variety of techniques including reselection experiments, high-throughput sequencing, comparative analysis, biochemical activity assays, and NMR. A bimolecular version of Apollon catalyzed multiple turnover phosphorylation and amplified the colorimetric signal. Engineered versions of Apollon could detect oligonucleotides with specific sequences as well as several different types of nucleases in homogenous assays that can be performed in a single tube without the need for washes or purifications. We anticipate that Apollon will be particularly useful to reduce costs in high-throughput screens and for applications in which specialized equipment is not available.
Formation of left-handed helices by C2′-fluorinated nucleic acids under physiological salt conditions
Authors: El-Khoury Roberto , Cabrero Cristina , Movilla Santiago , Kaur Harneesh , Friedland David , Domínguez Arnau , Thorpe James D , Roman Morgane , Orozco Modesto , González Carlos , Damha Masad J
Published: June 2024

Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2′F-araC and 2′F-riboG, induce the formation of the Z-form under low ionic strength. We show that oligomers entirely made of these two nucleosides exclusively produce left-handed duplexes that bind to the Zα domain of ADAR1. The effect of the two nucleotides is so dramatic that Z-form duplexes are the only species observed in 10 mM sodium phosphate buffer and neutral pH, and no B-form is observed at any temperature. Hence, in contrast to other studies reporting formation of Z/B-form equilibria by a preference for purine glycosidic angles in syn, our NMR and computational work revealed that sequential 2′F…H2N and intramolecular 3′H…N3′ interactions stabilize the left-handed helix. The equilibrium between B- and Z- forms is slow in the 19F NMR time scale (≥ms), and each conformation exhibited unprecedented chemical shift differences in the 19F signals. This observation led to a reliable estimation of the relative population of B and Z species and enabled us to monitor B–Z transitions under different conditions. The unique features of 2′F-modified DNA should thus be a valuable addition to existing techniques for specific detection of new Z-binding proteins and ligands.
Multi-transcriptomics identifies targets of the endoribonuclease DNE1 and highlights its coordination with decapping
Authors: Pouclet Aude , Pflieger David , Merret Rémy , Carpentier Marie-Christine , Schiaffini Marlene , Zuber Hélène , Gagliardi Dominique , Garcia Damien
Published: June 2024

Decapping is a crucial step in mRNA degradation in eucaryotes and requires the formation of a holoenzyme complex between the decapping enzyme DECAPPING 2 (DCP2) and the decapping enhancer DCP1. In Arabidopsis (Arabidopsis thaliana), DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1) is a direct protein partner of DCP1. The function of both DNE1 and decapping is necessary to maintain phyllotaxis, the regularity of organ emergence in the apex. In this study, we combined in vivo mRNA editing, RNA degradome sequencing, transcriptomics, and small RNA-omics to identify targets of DNE1 and study how DNE1 and DCP2 cooperate in controlling mRNA fate. Our data reveal that DNE1 mainly contacts and cleaves mRNAs in the coding sequence and has sequence cleavage preferences. DNE1 targets are also degraded through decapping, and both RNA degradation pathways influence the production of mRNA-derived small interfering RNAs. Finally, we detected mRNA features enriched in DNE1 targets including RNA G-quadruplexes and translated upstream open reading frames. Combining these four complementary high-throughput sequencing strategies greatly expands the range of DNE1 targets and allowed us to build a conceptual framework describing the influence of DNE1 and decapping on mRNA fate. These data will be crucial to unveil the specificity of DNE1 action and understand its importance for developmental patterning.
Alterations in the rate of fertility, egg viability, and hatch parameters of adult geese exposed to different breeding methods
Authors: Akinbola Elizabeth T , Ewuola  Emmanuel O
Published: June 2024

In a 10-wk study, alterations in the rate of fertility, egg viability, and hatch parameters of adult geese exposed to different breeding methods were investigated. Twenty-four matured geese (4.0 ± 0.45 average weight) were randomly divided into three groups (TNM—natural mating group, TIM—artificial insemination group, TNI—natural mating and insemination group) of two replicates with four geese per replicate in a completely randomized design. Fresh semen collected from six ganders (5.2 ± 0.69 average weight) was pooled and used to inseminate the geese in TIM and TN1 at 0.2Ml at insemination times. The geese in TNM and TNI were allowed to mate naturally. Insemination and mating was done at 3 d interval and eggs from each treatment were collected daily. Incubation of eggs was done weekly, candling and transfer to hatcher were done on day 27 and goslings hatched out on day 30. Fertility, early embryo mortality (EEM), mid embryo mortality (MEM), late embryo mortality (LEM), hatch of fertile eggs (HOF), and hatch of set eggs (HOS) were obtained and analyzed using descriptive statistics and ANOVA and means separated using least significant difference test. Geese in TNI had significantly higher fertility (93.33 ± 10.97%) than TNM (59.67 ± 31.29%) and TIM (83.60 ± 17.14%). The EEM was higher in TIM than in the two other groups while the HOF and HOS were higher in TNM and TNI than in TIM. This study suggests that in comparison with TIM, higher fertility, hatchability, and lower embryo mortality can be obtained when geese are inseminated and naturally mated simultaneously.
Acute exposure to dihydroxyacetone promotes genotoxicity and chromosomal instability in lung, cardiac, and liver cell models
Authors: Hernandez Arlet , Hedlich-Dwyer Jenna , Hussain Saddam , Levi Hailey , Sonavane Manoj , Suzuki Tetsuya , Kamiya Hiroyuki , Gassman Natalie R
Published: June 2024

Inhalation exposures to dihydroxyacetone (DHA) occur through spray tanning and e-cigarette aerosols. Several studies in skin models have demonstrated that millimolar doses of DHA are cytotoxic, yet the genotoxicity was unclear. We examined the genotoxicity of DHA in cell models relevant to inhalation exposures. Human bronchial epithelial cells BEAS-2B, lung carcinoma cells A549, cardiomyocyte Ac16, and hepatocellular carcinoma HepG3 were exposed to DHA, and low millimolar doses of DHA were cytotoxic. IC90 DHA doses induced cell cycle arrest in all cells except the Ac16. We examined DHA’s genotoxicity using strand break markers, DNA adduct detection by Repair Assisted Damage Detection (RADD), metaphase spreads, and a forward mutation assay for mutagenesis. Similar to results for skin, DHA did not induce significant levels of strand breaks. However, RADD revealed DNA adducts were induced 24 h after DHA exposure, with BEAS-2B and Ac16 showing oxidative lesions and A549 and HepG3 showing crosslink-type lesions. Yet, only low levels of reactive oxygen species or advanced glycation end products were detected after DHA exposure. Metaphase spreads revealed significant increases in chromosomal aberrations in the BEAS-2B and HepG3 with corresponding changes in ploidy. Finally, we confirmed the mutagenesis observed using the supF reporter plasmid. DHA increased the mutation frequency, consistent with methylmethane sulfonate, a mutagen and clastogen. These data demonstrate DHA is a clastogen, inducing cell-specific genotoxicity and chromosomal instability. The specific genotoxicity measured in the BEAS-2B in this study suggests that inhalation exposures pose health risks to vapers, requiring further investigation.
Acute particulate hexavalent chromium exposure induces DNA double-strand breaks and activates homologous recombination repair in rat lung tissue
Authors: Lu Haiyan , Wise Sandra S , Speer Rachel M , Croom-Perez Tayler J , Toyoda Jennifer H , Meaza Idoia , Williams Aggie , Wise John Pierce , Kouokam J Calvin , Young Wise Jamie , Hoyle Gary W , Zhu Cairong , Ali Abdul-Mehdi , Wise John Pierce
Published: June 2024

Hexavalent chromium [Cr(VI)] is an established human lung carcinogen, but the carcinogenesis mechanism is poorly understood. Chromosome instability, a hallmark of lung cancer, is considered a major driver of Cr(VI)-induced lung cancer. Unrepaired DNA double-strand breaks are the underlying cause, and homologous recombination repair is the primary mechanism preventing Cr(VI)-induced DNA breaks from causing chromosome instability. Cell culture studies show acute Cr(VI) exposure causes DNA double-strand breaks and increases homologous recombination repair activity. However, the ability of Cr(VI)-induced DNA breaks and repair impact has only been reported in cell culture studies. Therefore, we investigated whether acute Cr(VI) exposure could induce breaks and homologous recombination repair in rat lungs. Male and female Wistar rats were acutely exposed to either zinc chromate particles in a saline solution or saline alone by oropharyngeal aspiration. This exposure route resulted in increased Cr levels in each lobe of the lung. We found Cr(VI) induced DNA double-strand breaks in a concentration-dependent manner, with females being more susceptible than males, and induced homologous recombination repair at similar levels in both sexes. Thus, these data show this driving mechanism discovered in cell culture indeed translates to lung tissue in vivo.
New insights about the antidepressant-like effects of riparin A in a chronic murine model of depression
Authors: Prinholato da Silva Cássio , Oliveira Denise Dias , Benincasa Bruno Iglesias , Barbar Bruna , Perri Raphaela Gonçalves Barros , Fachin Ana Lúcia , Falconi-Sobrinho Luiz Luciano , Beleboni Rene Oliveira
Published: June 2024

Riparin A is a synthetic form of natural riparins. Acute scale studies that take into consideration the structure–activity relationship have shown preliminary evidence of antidepressant and anxiolytic effects of riparin A, similar to that already known for other riparins. However, for better pharmacological characterization of this new compound, further studies are required. The aim of this work was to evaluate the effect of chronic treatment with riparin A (10 mg/kg; intraperitoneally) on depressive-like behavior in the forced swimming test and tail suspension test, as well as the reduction of anhedonia in the sucrose preference test, and on anxiety-like behavior in the open field and elevated plus maze apparatus, triggered in rats previously subjected to unpredictable chronic mild stress by 4 weeks. In addition, a pentobarbital-induced sleep time test was also used. Riparin A reduced the duration of immobility in both the forced swimming test and tail suspension test, as well as attenuated the anhedonia in the sucrose preference test. Furthermore, riparin A appears to produce anxiolytic effects in rats exposed to an open field and elevated plus maze, while increasing the alertness/vigilance in rats submitted to pentobarbital-induced sleep time test, without altering their locomotor integrity. Our results suggest that chronic riparin A appears to be a potential pharmacological target for new studies on the control of depression- and anxiety-like behaviors in stressed rats.
Surgical Management of Hidradenitis Suppurativa
Authors: Krajewski Aleksandra , Alsayed Ahmed , Capek Allison , Casey Kathleen , Chandawarkar Rajiv
Published: June 2024

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory disease of the skin, characterized by recurrent draining sinuses and abscesses, predominantly in skin folds carrying terminal hairs and apocrine glands. Treatment for this debilitating disease has been medical management with antibiotics and immune modulators. With the advent of better reconstructive surgical techniques, the role of surgery in the treatment of HS has expanded, from being a last resort to a modality that is deployed earlier. Larger defects can be more easily reconstructed, allowing for a more radical excision of diseased areas. Locoregional flaps, perforator flaps, and propeller flaps that use the fasciocutaneous tissue allow reconstruction of defects with similar tissue, and provide better cosmetic and functional outcomes. They are easy to execute and can be performed even in resource-poor settings with concurrent use of immune modulators and postoperative antibiotics. Hidradenitis can be successfully treated with surgery in early stages as well as severe disease, due to the advances in understanding disease behavior, multidisciplinary care, and advanced reconstructive techniques. Coupled with a multidisciplinary care team, surgery offers a durable, lasting cure for HS, significantly reducing disease morbidity.
Waist Reduction through Conversion from False to Floating Ribs
Authors: Manzaneda Raúl M. , Adrianzen Gerardo A.
Published: June 2024

Background:

Waist reduction by ultrasound-guided monocortical fracture (RibXcar), usually performed on floating ribs, may show limitations when performed on false ribs (9 and 10) because of the stress force exerted on the anterior fixation point (cartilage union to sternum). Hence, we introduced a procedure for conversion from false to floating ribs to improve the final result of the treatment of false ribs through a rib treatment scheme.

Methods:

Forty-nine female patients undergoing rib surgery were recruited. Waist measurements and angular variations were compared between two groups of patients, the first (26 patients) consisting of patients who underwent RibXcar with conversion surgery (ribs 9 and 10) and the second (23 patients) consisting of patients who underwent RibXcar without conversion surgery (ribs 9 and 10).

Results:

The waist measurements taken after 6 months showed a mean decrease of 8.70 cm in the group where only RibXcar was performed, whereas a statistically significant mean reduction of 17.04 cm was observed in the group where RibXcar was performed with rib conversion surgery.

Conclusions:

The false-to-floating-rib conversion technique combined with RibXcar demonstrated more reduction in waist circumference and a more efficient rib angulation compared with RibXcar alone.
Operability of the Southampton Hand Assessment Procedure (SHAP) Tasks Using Voluntary Closing and Voluntary Opening Body-Powered Prosthesis Simulator
Authors: Nishizaka Chika , Mano Hiroshi , Shibata Teruki , Noguchi Satoko , Kobayashi Mio , Haga Nobuhiko , Ohnishi Kengo , Fujiwara Sayaka
Published: June 2024

Introduction

Body-powered prostheses are still essential in practice. There are two types of mechanisms to manipulate body-powered prostheses: voluntary closing (VC) and voluntary opening (VO). However, there are no studies investigating which is better suited for what type of movement in daily life.

Materials and Methods

The participants were eight right-handed, able-bodied adults. They were divided into two groups: a VC-to-VO group, in which the VC type was practiced first and then the VO type, and a VO-to-VC group, in which they practiced in the opposite order. VC/VO-type terminal device (EquiluxTM) was attached to a body-powered prosthesis simulator for the left hand, and the Southampton Hand Assessment Procedure (SHAP) tasks were practiced repeatedly. We compared the VC type and VO type for the number of practices to reach a plateau, Index of Functionality (IOF) score, the six prehensile pattern scores, and the time required for the 26 SHAP tasks. Scores were also compared before and after practice. In addition, changes in IOF and scores for each of the six patterns with proficiency were compared between VC type and VO type.

Results

Significant improvements were observed with manipulation practice for both types of devices. The mean SHAP scores at the plateau were 82.6 for VO type and 92.0 for VC type, with VC type significantly higher than VO type. In the six prehensile pattern scores, only two patterns, Tripod and Power, showed significant differences. When comparing the time required, Food Cutting task was an exception and significantly faster in the VC type, while there were no significant differences for the other tasks.

Conclusions

It was suggested that the VC type is more suitable for tasks requiring grip strength.

Clinical Relevance

We believe that this research will improve the daily lives of individuals with upper-limb amputation.
De Hoogstraat Xperience Prosthesis Transhumeral: An Innovative Test Prosthesis
Authors: de Backer-Bes Femke , Lange Maaike , Brouwers Michael , van Wijk Iris
Published: June 2024

Introduction

To choose a suitable prosthesis, clients need to experience both the weight and the control of a prosthesis. A few years ago, De Hoogstraat Rehabilitation Center developed the Xperience Prosthesis for children and adults with a transradial congenital or acquired limb deficiency. Because of the positive effects, we developed a reusable test prosthesis for the transhumeral level. Xperience Prosthesis Transhumeral is an innovative test prosthesis and an essential tool in managing expectations when providing clients with a suitable upper-limb prosthesis.

Xperience Prosthesis Transhumeral is a 3D-printed, reusable adjustable socket system with a passive elbow unit and the possibility to fit and experience myoelectric, static, and passive terminal devices.

Conclusions

Xperience Prosthesis Transhumeral is a practical and easy-to-handle tool for professionals. For clients, this tool is a unique way to experience the weight, function, and control of a prosthesis before making a final choice.

Clinical Relevance

Using Xperience Prosthesis Transhumeral in an expert rehabilitation center for upper-limb clients guides professionals to choose the right prosthesis with the client.