Wild, asexual, vertebrate hybrids have many characteristics that make them good model systems for studying how genomes evolve and epigenetic modifications influence animal physiology. In particular, ...the formation of asexual hybrid lineages is a form of reproductive incompatibility, but we know little about the genetic and genomic mechanisms by which this mode of reproductive isolation proceeds in animals. Asexual lineages also provide researchers with the ability to produce genetically identical individuals, enabling the study of autonomous epigenetic modifications without the confounds of genetic variation. Here, we briefly review the cellular and molecular mechanisms leading to asexual reproduction in vertebrates and the known genetic and epigenetic consequences of the loss of sex. We then specifically discuss what is known about asexual lineages of Fundulus diaphanus x F. heteroclitus to highlight gaps in our knowledge of the biology of these clones. Our preliminary studies of F. diaphanus and F. heteroclitus karyotypes from Porter's Lake (Nova Scotia, Canada) agree with data from other populations, suggesting a conserved interspecific chromosomal arrangement. In addition, genetic analyses suggest that: (a) the same major clonal lineage (Clone A) of F. diaphanus x F. heteroclitus has remained dominant over the past decade, (b) some minor clones have also persisted, (c) new clones may have recently formed, and iv) wild clones still mainly descend from F. diaphanus ♀ x F. heteroclitus ♂ crosses (96% in 2017–2018). These data suggest that clone formation may be a relatively rare, but continuous process, and there are persistent environmental or genetic factors causing a bias in cross direction. We end by describing our current research on the genomic causes and consequences of a transition to asexuality and the potential physiological consequences of epigenetic variation.
Natural polymers, based on proteins or polysaccharides, have attracted increasing interest in recent years due to their broad potential uses in biomedicine. The chemical stability, structural ...versatility, biocompatibility and high availability of these materials lend them to diverse applications in areas such as tissue engineering, drug delivery and wound healing. Biomaterials purified from animal or plant sources have also been engineered to improve their structural properties or promote interactions with surrounding cells and tissues for improved in vivo performance, leading to novel applications as implantable devices, in controlled drug release and as surface coatings. This review describes biomaterials derived from and inspired by natural proteins and polysaccharides and highlights their promise across diverse biomedical fields. We outline current therapeutic applications of these nature-based materials and consider expected future developments in identifying and utilising innovative biomaterials in new biomedical applications.
The molecular mechanisms underlying the stress response are poorly described in crustaceans. This includes the snow crab (Chionoecetes opilio), a commercially important stenotherm species distributed ...throughout the northern hemisphere. A better understanding of the stress response in C. opilio is desperately needed for commercial and conservation purposes. The purpose of this study was to investigate the transcriptional and metabolomic response of C. opilio exposed to stressors. Crabs were randomly assigned to 24 or 72 h treatment groups where they were exposed to conditions simulating live transport (handling and air exposure). A control group was kept in cold (2 °C) and well‑oxygenated saltwater. The hepatopancreas of the crabs was sampled to perform RNA-sequencing and high-performance chemical isotope labeling metabolomics. Differential gene expression analyses showed that classic crustaceans' stress markers, such as crustacean hyperglycemic hormones and heat shock proteins, were overexpressed in response to stressors. Tyrosine decarboxylase was also up-regulated in stressed crabs, suggesting an implication of the catecholamines tyramine and octopamine in the stress response. Deregulated metabolites revealed that low oxygen was an important trigger in the stress response as intermediate metabolites of the tricarboxylic acid cycle (TCA) accumulated. Lactate, which accumulated unevenly between crabs could potentially be used to predict mortality. This study provides new information on how stressors affect crustaceans and provides a basis for the development of stress markers in C. opilio.
Display omitted
•Crustacean hyperglycemic hormone and HSPs are overexpressed in stressed snow crabs.•Tyramine and octopamine are likely involved in the stress response.•Amino acids might be an important energy source for crabs during stress.•This study provides a basis for the development of stress markers in snow crabs.•The simulated transport conditions generated a stress response that shares a lot with the hypoxia response.
To compare the clinical features and resuscitative measures of children with Kawasaki disease shock syndrome vs septic shock.
In this retrospective case-control study, children with Kawasaki disease ...shock syndrome admitted to the intensive care unit from 2007 to 2017 were identified and compared with age-matched controls with septic shock. We studied 9 children with Kawasaki disease shock syndrome and 18 children with septic shock. Clinical characteristics were abstracted and between-group differences were compared.
Compared with septic shock controls, children with Kawasaki disease shock syndrome were less likely to have an underlying comorbid illness (1/9 11% vs 11/18 61%; P = .02) and were more likely to have at least 1 of the 5 classic diagnostic signs of Kawasaki disease at presentation (9/9 100% vs 0/18 0%; P < .001), a longer duration of illness before admission (9 days IQR, 7-14 days vs 3 days IQR, 1-5 days; P = .004), and a lower platelet count at presentation (140 IQR 73, 167) vs 258 IQR, 137-334; P = .02). Among patients who underwent echocardiography, abnormalities such as ventricular dysfunction, valvulitis, and coronary artery dilation were more common in the Kawasaki disease shock syndrome cohort (5/9 56% vs 0/7 0%; P = .03). There were no differences in volume of fluid resuscitation, vasoactive-inotropic scores, duration of inotropic therapy, or biochemical markers of illness severity (other than platelet count) between the matched groups.
A longer duration of illness before admission, lack of any significant underlying medical comorbidities, a lower platelet count, echocardiographic abnormalities, and the presence of classic diagnostic signs of Kawasaki disease at presentation may be useful early features to differentiate Kawasaki disease shock syndrome from septic shock.
The current standard of care in the neoadjuvant setting for high-risk HER2-positive (HER2 +) breast cancer is to combine systemic chemotherapy with dual HER2 blockade, trastuzumab and pertuzumab. ...Targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer. To improve treatment-associated toxicity, chemotherapy-sparing approaches are currently being investigated. Trastuzumab deruxtecan (T-DXd) is an HER2-directed antibody-drug-conjugate (ADC) with promising results in the metastatic setting for HER2-positive breast cancer. The SHAMROCK study investigates neoadjuvant T-DXd in early stage HER2-positive breast cancer, using pathological complete response (pCR) rate as the primary endpoint.
This is a phase II open-label, single arm, adaptive multi-centre trial of T-DXd in the neoadjuvant setting in stage 2-3 HER2-positive breast cancer. Eligible patients will receive 5.4 mg/kg of T-DXd intravenously every 3 weeks for up to 6 cycles. A repeat biopsy will performed after 2 cycles for the RNA disruption index (RDI) score assessment. According to their likelihood of pCR, as determined by the RDI score, patients will either undergo 4 or 6 cycles of T-DXd prior to imaging. Patients with imaging complete response (iCR) after either 4 or 6 cycles will proceed to surgery. Patients who do not achieve iCR will either undergo further systemic therapy or proceed to surgery.
The SHAMROCK study is a chemotherapy-sparing approach to curative intent treatment, investigating neoadjuvant T-DXd. We hypothesise that neoadjuvant T-DXd will have a high pCR rate and be associated low toxicity in early stage HER2-positive breast cancer.
EudraCT Number: 2022-002485-32; ClinicalTrials.gov identifier: NCT05710666; Cancer Trials Ireland study number: CTRIAL-IE 22-01.
During the postpartum period, fathers may be at risk of increased stress and loneliness, which may be offset or buffered by the provision of social support. This study aimed to explore fathers' ...postpartum experiences of loneliness, perceived stress, and social support. A constructivist grounded theory approach was used to inform study design and analysis. Semistructured interviews were conducted to collect data from 12 fathers, living in the Republic of Ireland, who had an infant aged 6 months or younger. A grounded theory entitled "support for the supporter," describing fathers' experiences with social support, and loneliness during the postpartum period, was derived. Participants described experiencing increased financial pressure and having difficulty balancing the role of "breadwinner" with fatherhood. Participants described feeling excluded from maternity care and lacked avenues for information within the Irish health care system. Participants linked their experiences of loneliness to the lack of social support in the postpartum period. This study offers a novel insight into Irish fathers' experiences with maternity care during the COVID-19 pandemic. This study is the first to qualitatively explore paternal postpartum loneliness and provides a good foundation for future research and intervention in this area. Findings suggest that it would be wise to promote social support from other experienced fathers, friends, family, and from partners to reduce paternal postpartum loneliness.
A flaperon belonging to Malaysian Airlines flight MH370 washed ashore on Réunion Island covered with the barnacle Lepas anatifera in July 2015, more than a year after the plane's disappearance. Here, ...we report the first high‐precision δ18Ocalcite versus temperature relationship for L. anatifera reared under laboratory conditions to unlock clues to the flaperon's drift path and origin. Using this experimental relationship and known growth rates for L. anatifera, we also demonstrate a new method for (a) converting δ18O data for one of the MH370 barnacles into a dated time series of sea surface temperatures (SSTs) experienced during the last part of the flaperon's drift and (b) identifying best fits between the observed flaperon SST time series and 50,000 SST histories generated from a particle‐tracking simulation. Our new method identifies a flaperon drift path far south of a previous isotope‐based reconstruction. We conclude with specific recommendations for using our method to continue the search for MH370 and other applications.
Plain Language Summary
More than 8 years ago, on 8 March 2014, Malaysia Airlines Flight 370 departed from Kuala Lumpur, never to be seen again despite a 4‐year extensive search using sonar imaging technology, submersible vehicles, drift models, and other high‐tech methods. Pieces of plane debris were found across the Indian Ocean, with some confirmed to be of the missing plane. One of the MH370 flaperons, a part of the aircraft's wing, beached on Réunion Island with several generations of stalked barnacles attached to its surface, later identified as Lepas anatifera. At least some of the barnacles were attached and growing shortly after the crash. This study contributes the first experimentally derived equation relating oxygen isotope values of stalked barnacle L. anatifera shells to sea surface temperature during shell formation. We demonstrate how applying the new temperature‐δ18O relationship to published data from small L. anatifera shells collected from the MH370 flaperon, combined with a novel particle‐tracking simulation method, can be used to reconstruct the latter part of the flaperon drift path before beaching. This same method could be applied to the largest, oldest barnacles collected from the same debris to provide important information about the debris drift origin and location of the missing plane.
Key Points
First experimentally derived sea surface temperature‐δ18Oshell equation for the stalked barnacle, Lepas anatifera
New numerical modeling method for reconstructing debris drift paths and origins from barnacle δ18Oshell data
First application of these new tools to barnacle δ18Oshell data from missing flight MH370 to produce a partial drift reconstruction
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children. Currently, there is no RSV vaccine or universally accessible antiviral treatment ...available. Addressing the urgent need for new antiviral agents, we have investigated the capacity of a non-coding single-stranded oligonucleotide (ssON) to inhibit RSV infection. By utilizing a GFP-expressing RSV, we demonstrate that the ssON significantly reduced the proportion of RSV infected A549 cells (lung epithelial cells). Furthermore, we show that ssON's antiviral activity was length dependent and that both RNA and DNA of this class of oligonucleotides have antiviral activity. We reveal that ssON inhibited RSV infection by competing with the virus for binding to the cellular receptor nucleolin
. Additionally, using a recombinant RSV that expresses luciferase we show that ssON effectively blocked RSV infection in mice. Treatment with ssON
resulted in the upregulation of RSV-induced interferon stimulated genes (ISGs) such as
,
,
, and
This study highlights the possibility of using oligonucleotides as therapeutic agents against RSV infection. We demonstrate that the mechanism of action of ssON is the inhibition of viral entry
, likely through the binding of the receptor, nucleolin and that ssON treatment against RSV infection
additionally results in the upregulation of ISGs.
Medical Education 2011: 45: 183–191
Objectives To help reduce pressure on faculty staff, medical students have been used as raters in objective structured clinical examinations (OSCEs). There are ...few studies regarding their ability to complete checklists and global rating scales, and a paucity of data on their ability to provide feedback to junior colleagues. The objectives of this study were: (i) to compare expert faculty examiner (FE) and student‐examiner (SE) assessment of students’ (candidates’) performances on a formative OSCE; (ii) to assess SE feedback provided to candidates, and (iii) to seek opinion regarding acceptability from all participants.
Methods Year 2 medical students (candidates, n = 66) participated in a nine‐station formative OSCE. Year 4 students (n = 27) acted as SEs and teaching doctors (n = 27) served as FEs. In each station, SEs and FEs independently scored the candidates using checklists and global rating scales. The SEs provided feedback to candidates after each encounter. The FEs evaluated SEs on the feedback provided using a standardised rating scale (1 = strongly disagree, 5 = strongly agree) for several categories, according to whether the feedback was: balanced; specific; accurate; appropriate; professional, and similar to feedback the FE would have provided. All participants completed questionnaires exploring perceptions and acceptability.
Results There was a high correlation on the checklist items between raters on each station, ranging from 0.56 to 0.86. Correlations on the global rating for each station ranged from 0.23 to 0.78. Faculty examiners rated SE feedback highly, with mean scores ranging from 4.02 to 4.44 for all categories. There was a high degree of acceptability on the part of candidates and examiners.
Conclusions Student‐examiners appear to be a viable alternative to FEs in a formative OSCE in terms of their ability to both complete checklists and provide feedback.
Abstract
The inshore commercial squids, Loligo vulgaris and L. forbesii, co-occur in the ecoregions of Celtic Seas and Greater North Sea but the spatio-temporal structure of their spawning ranges is ...poorly understood. To help solve the problem, data sets collected during the last 30 years by British, German, French, and Irish scientists, as well as observations from multinational Citizen Science, were combined. Spawning grounds of L. forbesii were found to form an external semi-circle around the spawning grounds of L. vulgaris, with the latter being centred on the English Channel and southernmost North Sea. The nursery grounds of both species appear to coincide with the respective spawning grounds, though L. forbesii makes much wider use of the North Sea. Seasonally, the position of the spawning grounds of both species is driven by the local temperature regime, although this is possibly subject to interannual variability. Spawning of both species begins around November and gradually progresses eastward following favourable currents and increasing water temperatures. Spawning in both species is mostly over by July, though some egg masses persist until August–November. Nursery grounds follow the same seasonal shift from west to east, at least in L. forbesii.
PDF
