bluuebunny/crossref_metadata_2025 huggingface dataset:
Lytic bacteriophage vB_KmiS-Kmi2C disrupts biofilms formed by members of the Klebsiella oxytoca complex, and represents a novel virus family and genus
Authors: Newberry Fiona , Shibu Preetha , Smith-Zaitlik Thomas , Eladawy Mohamed , McCartney Anne L , Hoyles Lesley , Negus David
Published: April 2023

Aims

This study aimed to characterize the lytic phage vB_KmiS-Kmi2C, isolated from sewage water on a GES-positive strain of Klebsiella michiganensis.

Methods and Results

Comparative phylogenetic and network-based analyses were used to characterize the genome of phage vB_KmiS-Kmi2C (circular genome of 42 234 bp predicted to encode 55 genes), demonstrating it shared little similarity with other known phages. The phage was lytic on clinical strains of K. oxytoca (n = 2) and K. michiganensis (n = 4), and was found to both prevent biofilm formation and disrupt established biofilms produced by these strains.

Conclusions

We have identified a phage capable of killing clinically relevant members of the K. oxytoca complex (KoC). The phage represents a novel virus family (proposed name Dilsviridae) and genus (proposed name Dilsvirus).
More than algorithms: an analysis of safety events involving ML-enabled medical devices reported to the FDA
Authors: Lyell David , Wang Ying , Coiera Enrico , Magrabi Farah
Published: April 2023

Objective

To examine the real-world safety problems involving machine learning (ML)-enabled medical devices.

Materials and Methods

We analyzed 266 safety events involving approved ML medical devices reported to the US FDA’s MAUDE program between 2015 and October 2021. Events were reviewed against an existing framework for safety problems with Health IT to identify whether a reported problem was due to the ML device (device problem) or its use, and key contributors to the problem. Consequences of events were also classified.

Results

Events described hazards with potential to harm (66%), actual harm (16%), consequences for healthcare delivery (9%), near misses that would have led to harm if not for intervention (4%), no harm or consequences (3%), and complaints (2%). While most events involved device problems (93%), use problems (7%) were 4 times more likely to harm (relative risk 4.2; 95% CI 2.5–7). Problems with data input to ML devices were the top contributor to events (82%).

Discussion

Much of what is known about ML safety comes from case studies and the theoretical limitations of ML. We contribute a systematic analysis of ML safety problems captured as part of the FDA’s routine post-market surveillance. Most problems involved devices and concerned the acquisition of data for processing by algorithms. However, problems with the use of devices were more likely to harm.

Conclusions

Safety problems with ML devices involve more than algorithms, highlighting the need for a whole-of-system approach to safe implementation with a special focus on how users interact with devices.
Our epistemic dependence on others: Nyāya and Buddhist accounts of testimony as a source of knowledge
Authors: Picascia Rosanna
Published: April 2023

This paper argues that philosophical debates between Nyāya and Buddhists on the nature and acquisition of testimonial knowledge present contrasting images of the role played by the epistemic agent in the knowing process. According to Nyāya, an individual can acquire testimonial knowledge automatically—and with little epistemic work—from a trustworthy speaker’s say-so. On the other hand, Buddhist epistemologists, who claim that testimonial knowledge is a species of inferential knowledge, argue that, in order to acquire knowledge from a speaker’s statements, an epistemic agent must possess non-testimonial evidence for the reliability of the testimony in question. This disagreement regarding the division of epistemic labour in testimonial exchanges demonstrates how differently Nyāya and Buddhist philosophers view the prevalence and practical importance of testimonial knowledge. For Nyāya, the ubiquity and easy acquisition of testimonial knowledge help explain the success of our daily actions. However, for Buddhist epistemologists, despite the regularity with which we successfully act based on what others tell us, testimonial knowledge is, in fact, less common, and more difficult to acquire, than we might think.
Ensemble species distribution modeling ofCulex tarsalis(Diptera: Culicidae) in the continental United States
Authors: Rhodes Charlotte G , Chaves Luis F , Bergmann Luke R , Hamer Gabriel L
Published: April 2023

West Nile virus (WNV) is the primary mosquito-borne disease in the United States and has had case reports every year since its introduction in 1999. As such, it is critical that we characterize the distribution of WNV vectors. Estimates of Culex tarsalis Coquillett species distribution, a major WNV vector, are scarce. We used ensemble distribution modeling to estimate habitat suitability for this species across the contiguous United States by consolidating presence data from four publicly available mosquito trapping data servers. The central plains region and much of the western US were estimated to have high habitat suitability. We identified multiple metrics of temperature and precipitation to be important in predicting the occurrence of Cx. tarsalis in a given geographic area. Furthermore, we observed habitat suitability for Cx. tarsalis to be significantly higher in areas with a high incidence of West Nile neuroinvasive disease compared to areas with low WN disease incidence, suggesting that Cx. tarsalis is present in regions with a high incidence of disease.
The Scourges: Why Abortion Is Even More Morally Serious than Miscarriage
Authors: Miller Calum
Published: April 2023

Several recent papers have suggested that the pro-life view entails a radical, implausible thesis: that miscarriage is the biggest public health crisis in the history of our species and requires radical diversion of funds to combat. In this paper, I clarify the extent of the problem, showing that the number of miscarriages about which we can do anything morally significant is plausibly much lower than previously thought, then describing some of the work already being done on this topic. I then briefly survey a range of reasons why abortion might be thought more serious and more worthy of prevention than miscarriage. Finally, I lay out my central argument: that reflection on the wrongness of killing reveals that the norms for ending life and failing to save life are different, in such a way that could justify the prioritization of anti-abortion advocacy over anti-miscarriage efforts. Such an account can also respond to similar problems posed to the pro-lifer, such as the question of whom to save in a “burning lab” type scenario.
Predicting the potential value of the new discharge medicines service in England
Authors: Thayer Nick , Mackridge Adam John , White Simon
Published: April 2023

Objectives

In 2021, community pharmacies in England were commissioned to support patients post-discharge through the discharge medicines service (DMS). Past studies described the benefit of DMS in avoiding readmissions. This study aimed to estimate the impact of DMS in this respect, projecting the maximal benefit if all areas mirrored the most active region.

Methods

A retrospective observational study, including modelling, using DMS claims data from March 2021 to February 2022, obtained from the NHS Business Services Authority (data from all community pharmacies in England for patients discharged where hospital clinicians referred them to community pharmacy). The impact of DMS on reducing readmission during this period was estimated using previous study data and estimated maximal benefit from full implementation of the service across England.

Key findings

In the study period 65 634 completed DMS claims were made. Claims at Integrated Care System (ICS) area level varied from 509/10 000 admissions to <1/10 000 admissions. Combining data from past studies provides a relative risk ratio of 0.756 (95% CI 0.678 to 0.843) for 90 day readmission (DMS versus normal care). DMS is estimated to have resulted in 8393 (95% CI 7061 to 9564) fewer readmissions after 30 days reducing to 5869 (95% CI 3774 to 7740) after 90 days. If all-ICS areas were as active as the highest performing area, DMS would avoid estimated >29 000 readmissions at 90 days each year.

Conclusions

DMS has significant potential to reduce readmissions. DMS implementation is currently variable and full implementation across all-ICS areas could increase the benefits five-fold.
Chrysin and its nanoliposome ameliorated non-alcoholic steatohepatitis via inhibiting TLR4 signalling pathway
Authors: Liu Hao , Jiang Ningman , Kuang Ge , Gong Xia , Hu Jun , Liu Jin , Yin Xinru , Wu Shengwang , Wan Jingyuan
Published: April 2023

Objectives

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease histologically characterized by liver steatosis, hepatocellular injury, inflammation and fibrosis, resulting in cirrhosis and hepatocellular carcinoma, but effective measures and obvious pathogenesis for NASH remain elusive. Chrysin (CH) has been reported to have anti-inflammatory effects but shows lower bioavailability.

Methods

In this study, a chrysin nanoliposome (CH-NL) was first prepared and characterized. Then, we used the methionine–choline-deficient (MCD) diet to induce a mouse model of NASH. Finally, the effects of CH and CH-NL on NASH were evaluated in the liver of NASH mice.

Key findings

The results showed that CH or CH-NL significantly reduced the accumulation of lipids in hepatocytes, alleviated liver injury, decreased the generation of radical oxygen species, and attenuated the accumulation of collagen fibre in the liver of NASH mice. In addition, CH and its nano-liposomes markedly inhibited the production of inflammatory cytokines and inflammatory cell infiltration in the liver of NASH mice. Further studies found that CH-NL and CH-NL downregulated the MCD diet-induced activation of Toll-like receptor 4 (TLR4) signalling pathway in the liver of mice.

Conclusions

CH and its nanoliposome alleviated MCD diet-induced NASH in mice, which might be through inhibiting TLR4 signalling pathway.
Symptomatic scrotal-inguino-retroperitoneal lymphocele in a kidney transplant patient—to drain but how to drain?
Authors: Ng Hung Shin Brian , Tan Samuel X , Griffin Anthony , Kanagarajah Vijay , Tan Ailin
Published: April 2023

Scrotal-inguino-retroperitoneal (SIR) lymphocele is a rare complication following kidney transplant. This entity is characterized by a tract originating in the retroperitoneal space, through the inguinal canal and scrotum following lymph hydrodissection. Systematic review investigating SIR lymphocele yielded cases with open fenestration of the sac into the peritoneum as treatment. We described a case report of a male in his 60s with a functioning kidney transplant and SIR lymphocele, which was successfully managed in the short term with percutaneous drainage of the collection. However, the collection recurred and computed tomography scan showed a multiloculated collection that prompted surgical management. Intraoperatively, the encapsulated fluid-filled tract was excised and a drain was placed, which was removed 48 h later. The patient wore a hernia belt for 6 weeks as support. He had no recurrence of his lymphocele following serial reviews for 9 months now.
Terminating a common envelope jets supernova impostor event with a super-Eddington blue supergiant
Authors: Cohen Tamar , Soker Noam
Published: April 2023

We conducted one-dimensional stellar evolutionary numerical simulations to build blue supergiant stellar models with a very low-envelope mass and a super-Eddington luminosity of 107L⊙ that mimic the last phase of a common envelope evolution (CEE) where a neutron star (NS) accretes mass from the envelope and launches jets that power the system. Common envelope jets supernovae (CEJSNe) are CEE transient events where an NS spirals-in inside the envelope and then the core of a red supergiant (RSG) star accretes mass and launches jets that power the transient event. In case the NS (or black hole) does not enter the core of the RSG, the event is a CEJSN-impostor. We propose that in some cases a CEJSN-impostor event might end with such a phase of a blue supergiant lasting for several years to few tens of years. The radius of the blue supergiant is about tens to few hundreds’ solar radii. We use a simple prescription to deposit the jets’ energy into the envelope. We find that the expected accretion rate of envelope mass onto the NS at the end of the CEE allows the power of the jets to be as we assume, 107L⊙. Such a low-mass envelope might be the end of the RSG envelope or a rebuilt envelope from mass fallback. Our study of a blue supergiant at the termination of a CEJSN-impostor event adds to the rich variety of transients that CEJSNe and CEJSN-impostors might form.
Fuzzy Aquarius: evolution of a Milky-way like system in the Fuzzy Dark Matter scenario
Authors: Nori Matteo , Macciò Andrea V , Baldi Marco
Published: April 2023

We present the first high-resolution zoom-in simulation of a Milky-way-like halo extracted from the Aquarius Project in the Fuzzy Dark Matter (FDM) framework. We use the N-body code AX-GADGET, based on a particle-oriented solution of the Schrödinger–Poisson equations, able to detail the complexity of structure formation while keeping track of the quantum effects in FDM. The halo shows a cored density profile, with a core size of several kpc for an FDM mass of mχ = 2.5h × 10−22 eV/c2. A flattening is observed also in the velocity profile, representing a distinct feature of FDM dynamics. We provide a quantitative analysis of the impact of fuzziness on subhaloes in terms of abundance, mass, distance, and velocity distribution functions, and their evolution with redshift. Very interestingly, we show that all collapsed structures, despite showing a flat density profile at z = 0, do not reach the solitonic ground state at the time of formation: on the contrary, they asymptotically converge to it on a time-scale that depends on their mass and formation history. This implies that current limits on FDM mass – obtained by applying simple scaling relations to observed galaxies – should be taken with extreme care, since single objects can significantly deviate from the expected asymptotic behaviour during their evolution.
A kinetic-scale magnetic hole in the magnetopause reconnection separatrix region
Authors: Li Zhi , Zhang Mao
Published: April 2023

Magnetic holes are ubiquitous in Earth’s magnetosphere plasma system. Understanding their formation mechanisms and influence to background plasma is crucial for insight into energy conversion in near-earth space environments. Here, we present unambiguous evidence that a kinetic-scale magnetic hole occurs in the separatrix region of asymmetry reconnection at the Earth’s magnetopause, implying that the connection between magnetic holes and reconnection should be more extensive. By taking advantage of high-resolution measurements, we show that electrons along the separatrix region are trapped and significantly thermalized by magnetic hole. Observations suggest that separatrix region with significant shear flow can provide favourable conditions for stable magnetic holes, which can further continuously generate high-energy electrons.
Star cluster formation and survival in the first galaxies
Authors: Garcia Fred Angelo Batan , Ricotti Massimo , Sugimura Kazuyuki , Park Jongwon
Published: April 2023

Using radiation-hydrodynamic cosmological simulations, we present a detailed (0.1 pc resolution), physically motivated portrait of a typical-mass dwarf galaxy before the epoch of reionization, resolving the formation, and evolution of star clusters into individual 10 M⊙ star particles. In the rest-frame ultraviolet, the galaxy has an irregular morphology with no bulge or disc, dominated by light emitted from numerous, compact, and gravitationally-bound star clusters. This is especially interesting in light of recent James Webb Space Telescope observations that − aided by the magnifying power of gravitational lenses – have imaged, at parsec-scale resolution, individual young star clusters forming in similar galaxies at z> 6. Because of their low metallicities and high temperatures, star-forming gas clouds in this galaxy have densities ∼100 times higher than typical giant molecular clouds; hence, their expected star formation efficiencies (SFEs) are high enough (around 10 − 70 per cent) to produce a sizeable population of potential globular cluster progenitors, but typically smaller (a few 100 − 2 ×104M⊙, half-mass radii of up to 3 pc) and of lower metallicities (10−3.5– 10−2.5 Z⊙). The initial mass function of the star-forming clouds is log-normal, whereas the bound star cluster mass function is a power-law with a slope that depends mainly on SFE but also on the temporal proximity to a major starburst. We find slopes between −0.5 and −2.5 depending on the assumed sub-grid SFE. Star formation is self-regulated on galactic scales; however, the multimodal metallicity distribution of the star clusters and the fraction of stars locked into surviving bound star clusters depends on SFE.
Kinetic simulations of the filamentation instability in pair plasmas
Authors: Iwamoto Masanori , Sobacchi Emanuele , Sironi Lorenzo
Published: April 2023

The non-linear interaction between electromagnetic waves and plasmas attracts significant attention in astrophysics because it can affect the propagation of Fast Radio Bursts (FRBs) – luminous millisecond-duration pulses detected at radio frequency. The filamentation instability (FI) – a type of non-linear wave–plasma interaction – is considered to be dominant near FRB sources, and its non-linear development may also affect the inferred dispersion measure of FRBs. In this paper, we carry out fully kinetic particle-in-cell simulations of the FI in unmagnetized pair plasmas. Our simulations show that the FI generates transverse density filaments, and that the electromagnetic wave propagates in near vacuum between them, as in a waveguide. The density filaments keep merging until force balance between the wave ponderomotive force and the plasma pressure gradient is established. We estimate the merging time-scale and discuss the implications of filament merging for FRB observations.
Reaction dynamics of C(3P) + Si2(X $^{3}\Sigma ^-_g$ ) → Si(3P) + SiC(X 3Π) on a global CHIPR potential energy surface of the ground state Si2C(X 1A1)
Authors: Li Ximing , Qin Zhi , Chen Guangan , Liu Linhua
Published: April 2023

The dynamics of C(3P) + Si2(X $^{3}\Sigma ^-_g$ ) → Si(3P) + SiC(X 3Π) on its ground state Si2C(X 1A1) are of great significance in carbon-rich interstellar chemistry. Using the combined-hyperbolic-inverse-power-representation method, we construct the first global potential energy surface (PES) for the electronic ground state Si2C(X 1A1) based on a total of 4080 ab initio energy points, which are obtained at the Davidson-corrected internally contracted multireference configuration interaction level of theory. The topographical features of the newly constructed PES are examined in detail and show good agreement with previous theoretical and experimental studies. Finally, we investigate the C(3P) + Si2(X $^{3}\Sigma ^-_g$ ) → Si(3P) + SiC(X 3Π) reaction using the quasi-classical trajectory and time-dependent wave packet calculations, yielding reasonable integral cross sections and rate constants, which are expected to be useful for astrochemical modelling in carbon-rich interstellar environments.
Bright X-ray pulsars as sources of MeV neutrinos in the sky
Authors: Asthana Aman , Mushtukov Alexander A , Dobrynina Alexandra A , Ognev Igor S
Published: April 2023

High-mass accretion rate on to strongly magnetized neutron stars results in the appearance of accretion columns supported by the radiation pressure and confined by the strong magnetic field of a star. At mass accretion rates above $\sim 10^{19}\, {\rm g\, s^{-1}}$ , accretion columns are expected to be advective. Under such conditions, a noticeable part of the total energy release can be carried away by neutrinos of a MeV energy range. Relying on a simple model of the neutrino luminosity of accreting strongly magnetized neutron stars, we estimate the neutrino energy fluxes expected from six ULX pulsars known up to date and three brightest Be X-ray transits hosting magnetized neutron stars. Despite the large neutrino luminosity expected in ULX pulsars, the neutrino energy flux from the Be X-ray transients of our Galaxy, Small Magellanic Cloud (SMC), and Large Magellanic Cloud is dominant. However, the neutrino flux from the brightest X-ray transients is estimated to be below the isotropic background by two orders of magnitude at least, which makes impossible direct registration of neutrino emission from accreting strongly magnetized neutron stars nowadays.
An occupational health survey of the UK’s mortuary workforce
Authors: Estrin-Serlui T , Bailey D , Osborn M
Published: April 2023

Background

Mortuaries are predominantly staffed by anatomical pathology technologists (APTs) and pathologists, and the work they undertake carries implicit health risk due to its nature. Until now there has not been a nationwide assessment of the occupational health of these essential workers in the UK.

Aims

To assess the current occupational health status and needs of the mortuary workforce in the UK.

Methods

We created a bespoke, brief online survey which was approved by the professional bodies representing APTs and pathologists in the UK. The survey was disseminated electronically using these organizations’ targeted mailing lists.

Results

Two hundred and thirty participants completed the survey, comprising 108 (47%) APTs and 122 (53%) pathologists. Most (89%) respondents reported that they have suffered from occupational health issues, the largest subcategory being musculoskeletal problems (77%). Almost half (48%) of APTs and around one-quarter (26%) of pathologists who responded have taken time off work in the last year because of occupational health problems, with almost one-fifth (19%) of the APTs having taken at least 4 weeks off.

Conclusions

A significant number of workhours are lost per year to sick leave resulting from occupational health problems. Respondents’ comments highlight issues in workspaces, rest facilities and staffing, and variability in working conditions across the country. We suggest that future workforce planning should prioritize good occupational health, with nationwide improvements in mortuary design.
Communication About Complementary and Alternative Medicine When Patients Decline Conventional Cancer Treatment: Patients’ and Physicians’ Experiences
Authors: Wode Kathrin , Sharp Lena , Fransson Per , Nordberg Johanna Hök
Published: April 2023

Background

Complementary and alternative medicine (CAM) is a broad set of nonconventional practices used alongside or instead of conventional treatment: The latter poses obvious risks related to cancer prognosis. Patient-physician dialogue about CAM is crucial for patient safety and mutual trust. Little is known about communication in the rare situations when patients decline recommended cancer treatment and consider using CAM. The objective of this study was to explore patients’ and physicians’ experiences from situations when patients decline recommended cancer treatment and consider using CAM.

Materials and Methods

Semi-structured interviews were carried out with 7 CAM-using cancer patients who had declined some or all conventional treatment as well as 10 physicians from oncology and palliative care. Framework analysis was used.

Results

Regarding treatment choices, there was a dissonance between physicians’ focus on medical reasoning and patients’ expression of complex values. Physicians’ difficulty in understanding patients’ treatment decline was exacerbated when patients considered using CAM, impairing communication even further. Inequalities in roles resulting in power struggles risked pushing both parties toward extreme and inflexible standpoints. Despite these challenges regarding treatment choices and hierarchical roles, both parties considered open and respectful communication as crucial.

Conclusions

This study highlights the difficulty of shared decision-making in practice when patients’ and physicians’ views on treatment decisions deviate in clinically challenging situations. Our results point to a need to address the complexity of these situations, pay attention to patients’ values, and improve knowledge among physicians about CAM.
Association Between Lymphopenia and Survival Outcomes in Esophageal Carcinoma Patients Receiving Combined Immunotherapy and Chemoradiotherapy
Authors: Cheng Xingyuan , Chen Baoqing , Wang Sifen , Zhang Jun , Zhu Jinhan , Liu Mengzhong , Liu Shiliang , Xi Mian
Published: April 2023

Background

To investigate the association between absolute lymphocyte count (ALC) nadir and survival outcomes in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy (CRT) combined with anti-PD-1 immunotherapy, as well as to explore clinical characteristics and dosimetric parameters that affect ALC nadir during CRT.

Patients and Methods

Patients with ESCC (n = 602) who underwent definitive CRT were analyzed, of whom 166 received combined anti-PD-1 immunotherapy and CRT. Changes in ALC and survival were compared between patients with and without immunotherapy. Propensity score matching (PSM) was performed to minimize the effects of confounding factors. Low ALC was defined as nadir of <0.33 × 103 cells/μL during CRT (top tertile). Univariate and multivariate logistic regression were used to identify predictors of low ALC nadir.

Results

Patients with immunotherapy had significantly higher ALC in the first 3 weeks during CRT and higher ALC nadir than those without. Overall survival was more favorable in patients with immunotherapy both before and after PSM. After a median follow-up of 12.1 months, patients with low ALC during CRT had a worse progression-free survival (PFS) (P = .026). In multivariate analysis, low ALC remained a significant prognostic factor for PFS. Planning target volume (PTV) and heart V5 were revealed to be independent predictors of low ALC.

Conclusions

The addition of anti-PD-1 immunotherapy to definitive CRT could mitigate the decline of ALC during radiotherapy and might prolong survival. Low ALC nadir was correlated to worse PFS, larger PTV, and higher heart V5 in patients receiving combined immunotherapy and CRT.
A Divergent Clade KAI2 Protein in the Root Parasitic Plant Orobanche minor Is a Highly Sensitive Strigolactone Receptor and Is Involved in the Perception of Sesquiterpene Lactones
Authors: Takei Saori , Uchiyama Yuta , Bürger Marco , Suzuki Taiki , Okabe Shoma , Chory Joanne , Seto Yoshiya
Published: April 2023

Strigolactones (SLs) were initially discovered as germination inducers for root parasitic plants. In 2015, three groups independently reported the characterization of the SL receptor in the root parasitic plant Striga hermonthica, which causes significant damage to crop production, particularly in sub-Saharan Africa. The characterized receptors belong to HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE2 (HTL/KAI2), which is a member of the α/β-hydrolase protein superfamily. In non-parasitic plants, HTL/KAI2 perceives the smoke-derived germination inducer karrikin and a yet-unidentified endogenous ligand. However, root parasitic plants evolved a specific clade of HTL/KAI2 that has diverged from the KAI2 clade of non-parasitic plants. The S. hermonthica SL receptors are included in this specific clade, which is called KAI2 divergent (KAI2d). Orobanche minor is an obligate root holoparasitic plant that grows completely dependent on the host for water and nutrients because of a lack of photosynthetic ability. Previous phylogenetic analysis of KAI2 proteins in O. minor has demonstrated the presence of at least five KAI2d clade genes. Here, we report that KAI2d3 and KAI2d4 in O. minor have the ability to act as the SL receptors. They directly interact with SLs in vitro, and when expressed in Arabidopsis, they rescue thermo-inhibited germination in response to the synthetic SL analog GR24. In particular, KAI2d3 showed high sensitivity to GR24 when expressed in Arabidopsis, suggesting that this receptor enables highly sensitive SL recognition in O. minor. Furthermore, we provide evidence that these KAI2d receptors are involved in the perception of sesquiterpene lactones, non-strigolactone-type germination inducers.
Variability of tintinnid ciliate communities with water masses in the western Pacific Ocean
Authors: Li Haibo , Wang Chaofeng , Zhao Li , Dong Yi , Zhao Yuan , Zhang Wuchang
Published: April 2023

Tintinnids play a pivotal role in the marine plankton ecosystem and are model organisms in plankton studies. However, the biogeographic distribution type and community variation of tintinnids from coastal to open waters in the western Pacific have never been studied before. In the present study, 42 surface tintinnid samples were collected from coastal water to the western Pacific warm pool. A total of 84 tintinnid species were identified. The Kuroshio intrusion has obvious influence on tintinnid distribution and community structure. Fifty-two tintinnid species with relatively high occurrence frequency were classified into neritic, transitional, Kuroshio, warm-pool and cosmopolitan species. We verified the existence of tintinnid transitional species and community in Mixed Water between Neritic and Kuroshio Waters (KW). Tintinnid species richness, abundance, Shannon-Wiener index and Pielou index were higher in the KW than in the Warm-pool Water. The community complexity and stability was highest in the KW. Our findings provide a profound understanding of planktonic biogeography and community variation from nearshore to open waters in tropical and subtropical oceans.
RNA degradome analysis reveals DNE1 endoribonuclease is required for the turnover of diverse mRNA substrates in Arabidopsis
Authors: Nagarajan Vinay K , Stuart Catherine J , DiBattista Anna T , Accerbi Monica , Caplan Jeffrey L , Green Pamela J
Published: April 2023

In plants, cytoplasmic mRNA decay is critical for posttranscriptionally controlling gene expression and for maintaining cellular RNA homeostasis. Arabidopsis DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1) is a cytoplasmic mRNA decay factor that interacts with proteins involved in mRNA decapping and nonsense-mediated mRNA decay (NMD). There is limited information on the functional role of DNE1 in RNA turnover, and the identities of its endogenous targets are unknown. In this study, we utilized RNA degradome approaches to globally investigate DNE1 substrates. Monophosphorylated 5′ ends, produced by DNE1, should accumulate in mutants lacking the cytoplasmic exoribonuclease XRN4, but be absent from DNE1 and XRN4 double mutants. In seedlings, we identified over 200 such transcripts, most of which reflect cleavage within coding regions. While most DNE1 targets were NMD-insensitive, some were upstream ORF (uORF)-containing and NMD-sensitive transcripts, indicating that this endoribonuclease is required for turnover of a diverse set of mRNAs. Transgenic plants expressing DNE1 cDNA with an active-site mutation in the endoribonuclease domain abolished the in planta cleavage of transcripts, demonstrating that DNE1 endoribonuclease activity is required for cleavage. Our work provides key insights into the identity of DNE1 substrates and enhances our understanding of DNE1-mediated mRNA decay.
Biosynthesis of polyprenylated xanthones in Hypericum perforatum roots involves 4-prenyltransferase
Authors: Sayed Hesham M B , Nassar Sara , Kaufholdt David , Beerhues Ludger , Liu Benye , El-Awaad Islam
Published: April 2023

Polyprenylated xanthones are natural products with a multitude of biological and pharmacological activities. However, their biosynthetic pathway is not completely understood. In this study, metabolic profiling revealed the presence of 4-prenylated 1,3,5,6-tetrahydroxyxanthone derivatives in St. John's wort (Hypericum perforatum) root extracts. Transcriptomic data mining led to the detection of 5 variants of xanthone 4-prenyltransferase (HpPT4px) comprising 4 long variants (HpPT4px-v1 to HpPT4px-v4) and 1 short variant (HpPT4px-sh). The full-length sequences of all 5 variants were cloned and heterologously expressed in yeast (Saccharomyces cerevisiae). Microsomes containing HpPT4px-v2, HpPT4px-v4, and HpPT4px-sh catalyzed the addition of a prenyl group at the C-4 position of 1,3,5,6-tetrahydroxyxanthone; 1,3,5-trihydroxyxanthone; and 1,3,7-trihydroxyxanthone, whereas microsomes harboring HpPT4px-v1 and HpPT4px-v3 additionally accepted 1,3,6,7-tetrahydroxyxanthone. HpPT4px-v1 produced in Nicotiana benthamiana displayed the same activity as in yeast, while HpPT4px-sh was inactive. The kinetic parameters of HpPT4px-v1 and HpPT4px-sh chosen as representative variants indicated 1,3,5,6-tetrahydroxyxanthone as the preferred acceptor substrate, rationalizing that HpPT4px catalyzes the first prenylation step in the biosynthesis of polyprenylated xanthones in H. perforatum. Dimethylallyl pyrophosphate was the exclusive prenyl donor. Expression of the HpPT4px transcripts was highest in roots and leaves, raising the question of product translocation. C-terminal yellow fluorescent protein fusion of HpPT4px-v1 localized to the envelope of chloroplasts in N. benthamiana leaves, whereas short, truncated, and masked signal peptides led to the disruption of plastidial localization. These findings pave the way for a better understanding of the prenylation of xanthones in plants and the identification of additional xanthone-specific prenyltransferases.
DNA methylation signatures of duplicate gene evolution in angiosperms
Authors: Kenchanmane Raju Sunil K , Ledford Marshall , Niederhuth Chad E
Published: April 2023

Gene duplication is a source of evolutionary novelty. DNA methylation may play a role in the evolution of duplicate genes (paralogs) through its association with gene expression. While this relationship has been examined to varying extents in a few individual species, the generalizability of these results at either a broad phylogenetic scale with species of differing duplication histories or across a population remains unknown. We applied a comparative epigenomic approach to 43 angiosperm species across the phylogeny and a population of 928 Arabidopsis (Arabidopsis thaliana) accessions, examining the association of DNA methylation with paralog evolution. Genic DNA methylation was differentially associated with duplication type, the age of duplication, sequence evolution, and gene expression. Whole-genome duplicates were typically enriched for CG-only gene body methylated or unmethylated genes, while single-gene duplications were typically enriched for non-CG methylated or unmethylated genes. Non-CG methylation, in particular, was a characteristic of more recent single-gene duplicates. Core angiosperm gene families were differentiated into those which preferentially retain paralogs and “duplication-resistant” families, which convergently reverted to singletons following duplication. Duplication-resistant families that still have paralogous copies were, uncharacteristically for core angiosperm genes, enriched for non-CG methylation. Non-CG methylated paralogs had higher rates of sequence evolution, higher frequency of presence–absence variation, and more limited expression. This suggests that silencing by non-CG methylation may be important to maintaining dosage following duplication and be a precursor to fractionation. Our results indicate that genic methylation marks differing evolutionary trajectories and fates between paralogous genes and have a role in maintaining dosage following duplication.
Uptake of glucose from the rhizosphere, mediated by apple MdHT1.2, regulates carbohydrate allocation
Authors: Tian Xiaocheng , Zou Hui , Xiao Qian , Xin Haijun , Zhu Lingcheng , Li Yuxing , Ma Baiquan , Cui Ningbo , Ruan Yong-Ling , Ma Fengwang , Li Mingjun
Published: April 2023

Plant roots can absorb sugars from the rhizosphere, which reduces the consumption of carbon derived from photosynthesis. However, the underlying mechanisms that roots use to control sugar absorption from soil are poorly understood. Here, we identified an apple (Malus × domestica Borkh.) hexose transporter, MdHT1.2, that functions on the root epidermis to absorb glucose (Glc) from the rhizosphere. Based on RNA-seq data, MdHT1.2 showed the highest expression level among 29 MdHT genes in apple roots. Biochemical analyses demonstrated that MdHT1.2 was mainly expressed in the epidermal cells of fine roots, and its protein was located on the plasma membrane. The roots of transgenic apple and Solanum lycopersicum lines overexpressing MdHT1.2 had an increased capability to absorb Glc when fed with [13C]-labeled Glc or 2-NBDG, whereas silencing MdHT1.2 in apple showed the opposite results. Further studies established that MdHT1.2-mediated Glc absorption from the rhizosphere changed the carbon assimilate allocation between apple shoot and root, which regulated plant growth. Additionally, a grafting experiment in tomato confirmed that increasing the Glc uptake capacity in the root overexpressing MdHT1.2 could facilitate carbohydrate partitioning to the fruit. Collectively, our study demonstrated that MdHT1.2 functions on the root epidermis to absorb rhizospheric Glc, which regulates the carbohydrate allocation for plant growth and fruit sugar accumulation.
Functional specialization of expanded orange carotenoid protein paralogs in subaerial Nostoc species
Authors: Yang Yi-Wen , Liu Ke , Huang Da , Yu Chen , Chen Si-Zhuo , Chen Min , Qiu Bao-Sheng
Published: April 2023

Orange carotenoid protein (OCP) is a photoactive protein that participates in the photoprotection of cyanobacteria. There are 2 full-length OCP proteins, 4 N-terminal paralogs (helical carotenoid protein [HCP]), and 1 C-terminal domain-like carotenoid protein (CCP) found in Nostoc flagelliforme, a desert cyanobacterium. All HCPs (HCP1 to 3 and HCP6) from N. flagelliforme demonstrated their excellent singlet oxygen quenching activities, in which HCP2 was the strongest singlet oxygen quencher compared with others. Two OCPs, OCPx1 and OCPx2, were not involved in singlet oxygen scavenging; instead, they functioned as phycobilisome fluorescence quenchers. The fast-acting OCPx1 showed more effective photoactivation and stronger phycobilisome fluorescence quenching compared with OCPx2, which behaved differently from all reported OCP paralogs. The resolved crystal structure and mutant analysis revealed that Trp111 and Met125 play essential roles in OCPx2, which is dominant and long acting. The resolved crystal structure of OCPx2 is maintained in a monomer state and showed more flexible regulation in energy quenching activities compared with the packed oligomer of OCPx1. The recombinant apo-CCP obtained the carotenoid pigment from holo-HCPs and holo-OCPx1 of N. flagelliforme. No such carotenoid transferring processes were observed between apo-CCP and holo-OCPx2. The close phylogenetic relationship of OCP paralogs from subaerial Nostoc species indicates an adaptive evolution toward development of photoprotection: protecting cellular metabolism against singlet oxygen damage using HCPs and against excess energy captured by active phycobilisomes using 2 different working modes of OCPx.
Risk factors for common mental disorders in young refugees from Iran, Somalia and Syria to Sweden
Authors: Yang Lijun , Mittendorfer-Rutz Ellenor , Amin Ridwanul , Helgesson Magnus
Published: April 2023

Background

Our primary aim was to determine sociodemographic and health-related risk factors for diagnosed common mental disorders (CMDs) among young refugees in Sweden.

Methods

All young adult refugees from Iran, Somalia and Syria (n = 7192), who were residents in Sweden in 2009, were followed from 2010 to 2013 regarding diagnosed CMDs. Cox regression models were used to compute hazard ratios (HRs) of CMDs with 95% confidence intervals (CIs).

Results

Those arriving as unaccompanied refugee minors had a lower risk of being diagnosed with CMDs (HR: 0.7; 95%CI: 0.6–0.9) than those arriving as accompanied refugee minors. A higher risk of being diagnosed with CMDs was also found in female refugees (HR: 1.3; 95%CI: 1.1–1.5) compared with male refugees. In addition, individuals with a low (HR: 1.7; 95%CI: 1.3–2.3) or a medium (HR: 1.4; 95%CI: 1.1–1.8) educational level were found to have a higher risk of being diagnosed with CMDs compared with individuals with a high educational level. Refugees from Iran (HR: 2.3; 95%CI: 1.8–2.9) had a higher risk of a diagnosis of a CMD than refugees from Somalia. Moreover, refugees with a diagnosis of a mental disorder other than a CMD (HR: 4.2; 95%CI: 2.8–6.1), digestive (HR: 1.5; 95%CI: 1.0–2.2) or musculoskeletal diseases (HR: 1.5; 95%CI: 1.0–2.2) had a higher risk of being diagnosed with subsequent CMDs, compared with those with no such disorders.

Conclusions

Pre-existing diagnoses of mental disorders other than CMDs, and digestive and musculoskeletal disorders should be carefully considered in clinical assessments to initiate early interventions to prevent CMDs.
Limited recourse? Is there an alternative statutory approach to priority of liens and payment of trustees’ creditors?
Authors: Holden Richard
Published: April 2023

Equity Trust (Jersey) Limited v Halabi held that successive trustees’ liens rank pari passu, rather than by priority in time. It held this to be the English law, Jersey law being presumed the same unless established otherwise. However, does Jersey law already contain its own provision for pari passu ranking of trustees’ liens and indemnities? This article considers Article 32 of the Trusts (Jersey) Law 1984, as well as similar provisions in Guernsey and the BVI, which appear to have provided for pari passu satisfaction not only of trustees’ creditors, but also trustees’ liens to secure such satisfaction, all along.
Weight of evidence for cross-species conservation of androgen receptor-based biological activity
Authors: Vliet Sara M F , Markey Kristan J , Lynn Scott G , Adetona Anna , Fallacara Dawn , Ceger Patricia , Choksi Neepa , Karmaus Agnes L , Watson AtLee , Ewans Andrew , Daniel Amber B , Hamm Jonathan , Vitense Kelsey , Wolf Kaitlyn A , Thomas Amy , LaLone Carlie A
Published: April 2023

The U.S. Environmental Protection Agency’s Endocrine Disruptor Screening Program (EDSP) is tasked with assessing chemicals for their potential to perturb endocrine pathways, including those controlled by androgen receptor (AR). To address challenges associated with traditional testing strategies, EDSP is considering in vitro high-throughput screening assays to screen and prioritize chemicals more efficiently. The ability of these assays to accurately reflect chemical interactions in nonmammalian species remains uncertain. Therefore, a goal of the EDSP is to evaluate how broadly results can be extrapolated across taxa. To assess the cross-species conservation of AR-modulated pathways, computational analyses and systematic literature review approaches were used to conduct a comprehensive analysis of existing in silico, in vitro, and in vivo data. First, molecular target conservation was assessed across 585 diverse species based on the structural similarity of ARs. These results indicate that ARs are conserved across vertebrates and are predicted to share similarly susceptibility to chemicals that interact with the human AR. Systematic analysis of over 5000 published manuscripts was used to compile in vitro and in vivo cross-species toxicity data. Assessment of in vitro data indicates conservation of responses occurs across vertebrate ARs, with potential differences in sensitivity. Similarly, in vivo data indicate strong conservation of the AR signaling pathways across vertebrate species, although sensitivity may vary. Overall, this study demonstrates a framework for utilizing bioinformatics and existing data to build weight of evidence for cross-species extrapolation and provides a technical basis for extrapolating hAR-based data to prioritize hazard in nonmammalian vertebrate species.
Focus on the Plant Endomembrane System in Molecular Plant-Microbe Interactions
Authors: Burch-Smith Tessa M. , Wang Aiming , Park Eunsook , Jin Hailing , Wang Dong
Published: April 2023

Interactions between plants and microbes are ubiquitous. The outcomes of these interactions involve interkingdom communication, with myriad, diverse signals moving between microbes and their potential plant hosts. Years of biochemical, genetic, and molecular biology research have provided an overview of the landscape of the repertoires of effectors and elicitors encoded by microbes that allow them to stimulate and manipulate responses from their potential plant hosts. Similarly, considerable insight into the plant machinery and capacity for responding to microbes has been gained. The advent of new bioinformatics and modeling approaches has greatly contributed to our understanding of how these interactions occur, and it is expected that these tools, coupled with burgeoning genome sequencing data, will eventually allow the prediction of the outcome of these interactions and whether they will result in a relationship that benefits one or both partners. As a complement to these studies, cell biological studies are elucidating how cells in the plant hosts behave in response to microbial signals. Such studies have brought new attention to the indispensable role of the plant endomembrane system in determining the outcome of plant-microbe interactions. This Focus Issue addresses not only how the plant endomembrane acts locally to mediate responses to microbes but, also, the importance of the plant endomembrane beyond the plant cell borders for cross-kingdom effects.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.
Strategies for Advancing Equity in Frontline Clinical Assessment
Authors: Onumah Chavon M. , Pincavage Amber T. , Lai Cindy J. , Levine Diane L. , Ismail Nadia J. , Alexandraki Irene , Osman Nora Y.
Published: April 2023

Educational equity in medicine cannot be achieved without addressing assessment bias. Assessment bias in health professions education is prevalent and has extensive implications for learners and, ultimately, the health care system. Medical schools and educators desire to minimize assessment bias, but there is no current consensus on effective approaches. Frontline teaching faculty have the opportunity to mitigate bias in clinical assessment in real time. Based on their experiences as educators, the authors created a case study about a student to illustrate ways bias affects learner assessment. In this paper, the authors use their case study to provide faculty with evidence-based approaches to mitigate bias and promote equity in clinical assessment. They focus on 3 components of equity in assessment: contextual equity, intrinsic equity, and instrumental equity. To address contextual equity, or the environment in which learners are assessed, the authors recommend building a learning environment that promotes equity and psychological safety, understanding the learners’ contexts, and undertaking implicit bias training. Intrinsic equity, centered on the tools and practices used during assessment, can be promoted by using competency-based, structured assessment methods and employing frequent, direct observation to assess multiple domains. Instrumental equity, focused on communication and how assessments are used, includes specific, actionable feedback to support growth and use of competency-based narrative descriptors in assessments. Using these strategies, frontline clinical faculty members can actively promote equity in assessment and support the growth of a diverse health care workforce.