bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ribosome Assembly Factor Reh1 is Released from the Polypeptide Exit Tunnel in the Pioneer Round of Translation
Authors: Musalgaonkar Sharmishtha , Yelland James , Chitale Ruta , Rao Shilpa , Ozadam Hakan , Cenik Can , Taylor David , Johnson Arlen 
Published: October 2023

AbstractAssembly of functional ribosomal subunits and successfully delivering them to the translating pool is a prerequisite for protein synthesis and cell growth. InS. cerevisiae,the ribosome assembly factor Reh1 binds to pre-60S subunits at a late stage during their cytoplasmic maturation. Previous work shows that the C-terminus of Reh1 inserts into the polypeptide exit tunnel (PET) of the pre-60S subunit. Unlike canonical assembly factors, which associate exclusively with pre-60S subunits, we observed that Reh1 sediments with polysomes in addition to free 60S subunits. We therefore investigated the intriguing possibility that Reh1 remains associated with 60S subunits after the release of the anti-association factor Tif6 and after subunit joining. Here, we show that Reh1-bound nascent 60S subunits associate with 40S subunits to form actively translating ribosomes. Using selective ribosome profiling, we found that Reh1-bound ribosomes populate open reading frames near start codons. Reh1-bound ribosomes are also strongly enriched for initiator tRNA, indicating they are associated with early elongation events. Using single particle cryo-electron microscopy to image cycloheximide-arrested Reh1-bound 80S ribosomes, we found that Reh1-bound 80S contain A site peptidyl tRNA, P site tRNA and eIF5A indicating that Reh1 does not dissociate from 60S until early stages of translation elongation. We propose that Reh1 is displaced by the elongating peptide chain. These results identify Reh1 as the last assembly factor released from the nascent 60S subunit during its pioneer round of translation.
Physiological concentrations of calcium interact with alginate and extracellular DNA in the matrices ofPseudomonas aeruginosabiofilms to impede phagocytosis by neutrophils
Authors: Wells Marilyn J. , Currie Hailey , Gordon Vernita D. 
Published: October 2023

AbstractBiofilms are communities of interacting microbes embedded in a matrix of polymer, protein, and other materials. Biofilms develop distinct mechanical characteristics that depend on their predominant matrix components. These matrix components may be produced by microbes themselves or, for infectionsin vivo, incorporated from the host environment.Pseudomonas aeruginosais a human pathogen that forms robust biofilms that extensively tolerate antibiotics and effectively evade clearance by the immune system. Two of the important bacterial-produced polymers in the matrices ofP. aeruginosabiofilms are alginate and extracellular DNA (eDNA), both of which are anionic and therefore have the potential to interact electrostatically with cations. Many physiological sites of infection contain significant concentrations of the calcium ion (Ca2+). In this study we investigate the structural and mechanical impacts of Ca2+supplementation in alginate-dominated biofilms grownin vitroand we evaluate the impact of targeted enzyme treatments on clearance by immune cells. We use multiple particle tracking microrheology to evaluate the changes in biofilm viscoelasticity caused by treatment with alginate lyase and/or DNAse I. For biofilms grown without Ca2+, we correlate a decrease in relative elasticity with increased phagocytic success. However, we find that growth with Ca2+supplementation disrupts this correlation except in the case where both enzymes are applied. This suggests that the calcium cation may be impacting the microstructure of the biofilm in non-trivial ways. Indeed, confocal laser scanning fluorescence microscopy and scanning electron microscopy reveal unique Ca2+-dependent eDNA and alginate microstructures. Our results suggest that the presence of Ca2+drives the formation of structurally and compositionally discrete microdomains within the biofilm through electrostatic interactions with the anionic matrix components eDNA and alginate. Further, we observe that these structures serve a protective function as the dissolution of both components is required to render biofilm bacteria vulnerable to phagocytosis by neutrophils.Abstract Figure
Heterotypic responses against nsp12/nsp13 from prior SARS-CoV-2 infection associates with lower subsequent endemic coronavirus incidence
Authors: Bean David J. , Monroe Janet , Liang Yan Mei , Borberg Ella , Senussi Yasmeen , Swank Zoe , Chalise Sujata , Walt David , Weinberg Janice , Sagar Manish 
Published: October 2023

SummaryImmune responses from prior SARS-CoV-2 infection and COVID-19 vaccination do not prevent re-infections and may not protect against future novel coronaviruses (CoVs). We examined the incidence of and immune differences against human endemic CoVs (eCoV) as a proxy for response against future emerging CoVs. Assessment was among those with known SARS-CoV-2 infection, COVID-19 vaccination but no documented SARS-CoV-2 infection, or neither exposure. Retrospective cohort analyses suggest that prior SARS-CoV-2 infection, but not COVID-19 vaccination alone, protects against subsequent symptomatic eCoV infection. CD8+T cell responses to the non-structural eCoV proteins, nsp12 and nsp13, were significantly higher in individuals with previous SARS-CoV-2 infection as compared to the other groups. The three groups had similar cellular responses against the eCoV spike and nucleocapsid, and those with prior spike exposure had lower eCoV-directed neutralizing antibodies. Incorporation of non-structural viral antigens in a future pan-CoV vaccine may improve protection against future heterologous CoV infections.
Risk and return in the biotech industry
Authors: Bruneo Hassan , Giacomini Emanuela , Iannotta Giuliano , Murthy Anant , Patris Julien 
Published: October 2023

PurposeBiotech companies stand as key actors in pharmaceutical innovation. The high risk and long timelines inherent with their R&D investments might hinder their access to funding, potentially stifling innovation. This study aims to explore into the appeal of biotech companies to capital market investors, whose financial backing could bolster the growth of the biotechnology sector.Design/methodology/approachThis paper uses a dataset of 774 US publicly listed biotech firms to investigate their risk and return characteristics by comparing them to pharmaceutical firms and a sample of matched non-biotech R&D-intensive firms over the sample period 1980–2021. Tests show that the conclusions remain consistent across diverse methodological approaches.FindingsThe paper shows that biotech companies are riskier than the average firm in the market index but outperform on a risk-adjusted basis both the market and a matched group of R&D-intensive firms. This is particularly true for large capitalization biotech, which is also shown to provide a diversification benefit by reducing the downside risk in past crisis periods.Originality/valueThis paper provides insight relevant to the current debate about the overall performance of the biotech industry in terms of policy changes and their impact on small, early-stage biotech firms. While small and early-stage biotech firms are playing an increasing role in scientific innovation, this study confirms their greater vulnerability to financial risks and the importance of access to capital markets in enabling those companies to survive and evolve into larger biotech.
Precipitation predictability drives evolution of drought strategies in the common poppy, Papaver rhoeas
Authors: Springer Katja , Coquery Thibault , Holland Vera , Fitze Patrick S. , Scheepens J. F. , March‐Salas Martí 
Published: October 2023

Abstract

Current climate change leads to an increase in the frequency and intensity of droughts and to a decreased precipitation predictability. The few studies investigating plant evolutionary responses to contrasting predictability regimes showed that intrinsic precipitation predictability shapes plant phenotypic variation, drives evolution of phenotypic plasticity and can vary in strength and direction of selection. This suggests that the selection pressure induced by decreased precipitation predictability may lead to plants coping better with severe drought events.

To investigate whether past precipitation predictability influences plant responses to different drought conditions, we performed a common‐garden experiment applying control, short‐term and long‐term drought treatments on seedlings of Papaver rhoeas (Papaveraceae) whose progenitors experienced less versus more precipitation predictability treatments for three consecutive generations. In addition, to assess whether competition modulates plant responses, half of the plants were grown together with the widespread herbaceous plant Galium album (Rubiaceae).

In the presence of long drought episodes, plants whose progenitors experienced less predictable precipitation survived longer than those whose progenitors experienced more predictable precipitation. Furthermore, plants whose progenitors experienced less predictable precipitation had lower biomass, which is likely to reduce water loss via transpiration, and, across all drought treatments, they showed lower root investment. However, no trait differences were detected under competition, indicating that interspecific competition may limit the expression of evolutionary responses to changes induced by precipitation predictability.

Altogether our results indicate that lower precipitation predictability mainly promotes the evolution of drought‐escape and drought‐avoidance strategies. Overall, our experiment highlights that precipitation predictability is an important evolutionary driver of plant functional responses, potentially shifting evolutionary trajectories of plants under increasing intensity of drought events.

Read the free Plain Language Summary for this article on the Journal blog.
THE(CULTURAL)WAR OF THE WORLDS: Framing Urban Redevelopment as ‘Terraforming’
Authors: Garfield‐Abrams Jennifer L. , Corcoran Thomas , Wynn Jonathan R. 
Published: October 2023

AbstractExternal forces always shape the social construction of ‘the local’. In this article we offer a framework for understanding how external players and strategies reconfigure the social and symbolic character of local culture for new investments and new populations. We aim not only to propose a theory of urban cultural processing by nonlocals—what we call ‘urban cultural terraforming’—but to identify pressure points for local groups to make claims on or even commandeer reshaping local culture. Using two cases, casino development in a deindustrialized city and state‐designated cultural districts, we illustrate how ‘cultural terraformers’ use identifiable strategies (e.g. colonization of local sentiment, re‐creating partnerships and respatializing) to change local culture, and how groups struggle to avoid marginalization.
Microscopic anatomy of the subcommissural organ in the brain of the adult greater cane rat (Rodentia: Thryonomyidae)
Authors: Gilbert T. T. , Olopade F. E. , Ladagu A. D. , Lanipekun D. O. , Fatola O. I. , Folarin O. R. , Olopade J. O. 
Published: October 2023

AbstractThe subcommissural organ (SCO) is a well‐developed gland present in the brain of vertebrates. The SCO secretes glycoproteins into the circulating cerebrospinal fluid and these assemble to form Reissner's fibre. It also plays an important function in neurogenesis and axonal guidance during embryogenesis. This study delves into the microscopic anatomy of the SCO in the adult greater cane rat (GCR), shedding light on its histoarchitectural characteristics. By utilizing histological techniques and microscopic analysis, we investigated the SCO's location and cellular composition within the brain of adult GCR. Our findings showed that the SCO in this species is located ventrally to the posterior commissure (PC) and dorsally to the third ventricle. The SCO consists of specialized ependymal or nuclear cell layer and apical processes lining the third ventricle. Moreover, the SCO's proximity to the PC and the third ventricle highlights its strategic position within the brain's ventricular system. With immunohistochemical analyses, the SCO cells expressed glial fibrillary protein when immunolabelled with Glial fibrillary acid protein (GFAP) antibody, a marker for astrocytes/astrocytic‐like cells. Few microglia‐like cells were immuno‐positive for Ionized calcium‐binding adapter molecule 1 (Iba1) antibody, that are existing within the SCO. However, the SCO in the GCR showed a negative immunostaining to NeuN antibody. This study contributes to our understanding of the microscopic anatomy of the SCO in a lesser‐studied mammalian species. Further research into the SCO's functional significance especially during development in the GCR, may hold promise for more insights into neurological health and pathology.
Surgical accuracy of CAD/CAM splints using virtual surgical planning in orthognathic surgery: policy implications for healthcare in Australia
Authors: Delpachitra Seth Navinda , Bordbar Patrishia 
Published: October 2023

AbstractBackgroundThis study examines post‐surgical outcomes of maxillary position using virtual surgical planning (VSP) with computer designed and manufactured surgical splints, without the use of costly patient specific implants (PSI), in the treatment of routine nonsyndromic orthognathic patients. The cost of these personalized medical devices and their impact in the setting of cranio‐maxillofacial surgery is currently under review by The Department of Health and Aged Care in Australia.MethodsThis is a single‐centre retrospective analysis of 49 patients who underwent bimaxillary orthognathic surgery by a single surgeon at Epworth Richmond Hospital (Victoria, Australia) over a period spanning 2016 to 2020. Patients were included in the study provided their surgery was facilitated using VSP with manufacture of computer designed occlusal splints.ResultsUse of computer designed and manufactured splints were highly reliable in reproducing the virtual surgical plan, when using palatal plane, upper incisor angulation, and anterior upper facial height.ConclusionUse of computer designed and manufactured splints provide a method of leveraging the accuracy of VSP methods, without the additional costs associated with PSI. These findings may assist in appropriate resource allocation and case stratification in patients undergoing orthognathic surgery.
Language outcomes at 18–24 months of preterm infants from US Spanish‐ and English‐speaking homes
Authors: Feragne Megan , Tucker Richard , Mayne Julia , Vohr Betty 
Published: October 2023

AbstractAimTo evaluate the association of Spanish compared to English primary household language on preterm (PT) infants' language outcomes in the United States and to examine associations with socio‐economic factors.MethodsThis was a retrospective cohort of PT infants born <32 weeks gestation from Spanish‐speaking (n = 95) and English‐speaking homes (n = 1030) born 2005–2019. Language (primary outcome) and cognitive and motor skills (secondary outcomes) were measured using the BSID‐III at 18–24 months corrected age. Group differences were evaluated using bivariate comparisons and logistic regression analyses.ResultsMothers reporting Spanish‐speaking homes had higher rates of public insurance and lower educational achievement. Group newborn characteristics were similar. Preterm infants from Spanish‐speaking homes had significantly lower BSID‐III language composite, cognitive composite, receptive and expressive scores compared to infants from English‐speaking homes. Logistic regression modelling identified independent negative effects of Spanish‐speaking household OR 3.26 (CI 1.89–5.62) and public insurance OR 2.31 (CI 1.71–3.12) with a protective benefit derived from breast milk OR 0.68 (CI 0.50–0.92) when adjusting for medical morbidities, socio‐economic factors and gestational age.ConclusionPublic health policies and interventions in the United States should target language and cognitive outcomes of PT infants from Spanish‐speaking homes.
First dye identification analyses conducted on textiles from Old Dongola (Sudan, 17th–18th centuries CE)
Authors: Wozniak Magdalena M. , Witkowski Bartłomiej , Gierczak Tomasz , Biesaga Magdalena 
Published: October 2023

AbstractThe Middle Nile Valley offers exceptional environmental conditions that allow the preservation of organic materials, including textiles. This paper presents the results of the analysis of 17 samples collected from wool, cotton, and silk textiles excavated in the ancient capital of Old Dongola from layers dated to the 17th and 18th centuries CE. Chemical analysis using high performance liquid chromatography coupled with mass spectrometry (HPLC‐MS/MS) have identified both plant and animal dyes. Locally produced textiles, mostly from wool and decorated with blue, green, orange, and yellow hues, were dyed with woad (Isatis tinctoria), flavonoid plants, and madder‐type roots, which were already known and used by medieval dyers in that area. For the first time, kermes (Kermes vermilio) and lac‐dye (Kerria species) have been also identified as a dye source in samples from this group. Imported fabrics, of cotton and silk, were dyed blue with woad (I. tinctoria) but also with indigo (Indigofera tinctoria); dyer's broom (Genista tinctoria) and kermes (K. vermilio) were other dyes identified in this second group. The results of this study provide the first dye identification for textiles produced in the 17th–18th c. Sudan and contribute new data to the research on textile production and trade in post‐medieval Sudan.
Posaconazole‐ibrutinib interaction cannot be avoided by staggered dosing: How to optimize ibrutinib dose during posaconazole treatment
Authors: Olkkola Aleksi M. , Tapaninen Tuija , Tornio Aleksi , Hauta‐aho Milka , Lapatto‐Reiniluoto Outi , Neuvonen Mikko , Kiiski Johanna I. , Neuvonen Pertti J. , Niemi Mikko , Backman Janne T. 
Published: October 2023

AimsIbrutinib is used in the treatment of certain B‐cell malignancies. Due to its CYP3A4‐mediated metabolism and highly variable pharmacokinetics, it is prone to potentially harmful drug‐drug interactions.MethodsIn a randomized, placebo‐controlled, three‐phase crossover study, we examined the effect of the CYP3A4‐inhibiting antifungal posaconazole on ibrutinib pharmacokinetics. Eleven healthy participants ingested repeated doses of 300 mg of posaconazole either in the morning or in the evening, or placebo. A single dose of ibrutinib (30, 70 or 140 mg, respectively) was administered at 9 AM, 1 or 12 h after the preceding posaconazole/placebo dose.ResultsOn average, morning posaconazole increased the dose‐adjusted geometric mean area under the plasma concentration‐time curve from zero to infinity (AUC0‐∞) and peak plasma concentration (Cmax) of ibrutinib 9.5‐fold (90% confidence interval [CI] 6.3‐14.3, P < 0.001) and 8.5‐fold (90% CI 5.7‐12.8, P < 0.001), respectively, while evening posaconazole increased those 10.3‐fold (90% CI 6.7‐16.0, P < 0.001) and 8.2‐fold (90% CI 5.2‐13.2, P < 0.001), respectively. Posaconazole had no significant effect on the half‐life of ibrutinib, but substantially reduced the metabolite PCI‐45227 to ibrutinib AUC0‐∞ ratio. There were no significant differences in ibrutinib pharmacokinetics between morning and evening posaconazole phases.ConclusionsPosaconazole increases ibrutinib exposure substantially, by about 10‐fold. This interaction cannot be avoided by dosing the drugs 12 h apart. In general, a 70‐mg daily dose of ibrutinib should not be exceeded during posaconazole treatment to avoid potentially toxic systemic ibrutinib concentrations.
“Time to be free”: Playful agency in LOVE's in‐school programme for at‐risk youth
Authors: Hausfather Nadia , Montreuil Marjorie , Ménard Jean‐Frédéric , Carnevale Franco A. 
Published: October 2023

AbstractResearch increasingly suggests that positive youth development programmes play an important part in preventing youth violence and promoting positive developmental trajectories. We conducted a focussed ethnography of LOVE, a social development programme aimed at supporting youth who have been exposed to violence. Building on a previous study's exploration of this programme's afterschool setting, we examined the programme's social functioning in school settings. Findings underline the role of playfulness—alongside an egalitarian/friendly approach, gentle authority/structure, strengths‐based support and a safe space to express vulnerability—to foster in youth the ability to feel free, confident/empowered, connected/empathic and positive feelings about school and life.
Repeated detection of non‐alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults
Authors: Kim Jin Hwa , Lyu Young Sang , Kim Mee Kyoung , Kim Sang Yong , Baek Ki‐Hyun , Song Ki‐Ho , Han Kyungdo , Kwon Hyuk‐Sang 
Published: October 2023

AbstractAimThis study aimed to investigate the effects of repeated detection of non‐alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults.Materials and MethodsIn this nationwide population‐based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20‐39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0‐4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points.ResultsThe multivariable‐adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57‐2.921), 3.45 (3.221‐3.694), 4.588 (4.303‐4.892) and 6.126 (5.77‐6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores.ConclusionsRepeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.