bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gallus gallus RJF reference genome reveals an MHCY haplotype organized in gene blocks that contain 107 loci including 45 specialized, polymorphic MHC class I loci, 41 C-type lectin-like loci, and other loci amid hundreds of transposable elements
Authors: Goto Ronald M , Warden Charles D , Shiina Takashi , Hosomichi Kazuyoshi , Zhang Jibin , Kang Tae Hyuk , Wu Xiwei , Glass Marla C , Delany Mary E , Miller Marcia M
Published: August 2022

MHCY is a second major histocompatibility complex-like gene region in chickens originally identified by the presence of major histocompatibility complex class I-like and class II-like gene sequences. Up to now, the MHCY gene region has been poorly represented in genomic sequence data. A high density of repetitive sequence and multiple members of several gene families prevented the accurate assembly of short-read sequence data for MHCY. Identified here by single-molecule real-time sequencing sequencing of BAC clones for the Gallus gallus Red Jungle Fowl reference genome are 107 MHCY region genes (45 major histocompatibility complex class I-like, 41 c-type-lectin-like, 8 major histocompatibility complex class IIβ, 8 LENG9-like, 4 zinc finger protein loci, and a single only zinc finger-like locus) located amid hundreds of retroelements within 4 contigs representing the region. Sequences obtained for nearby ribosomal RNA genes have allowed MHCY to be precisely mapped with respect to the nucleolar organizer region. Gene sequences provide insights into the unusual structure of the MHCY class I molecules. The MHCY class I loci are polymorphic and group into 22 types based on predicted amino acid sequences. Some MHCY class I loci are full-length major histocompatibility complex class I genes. Others with altered gene structure are considered gene candidates. The amino acid side chains at many of the polymorphic positions in MHCY class I are directed away rather than into the antigen-binding groove as is typical of peptide-binding major histocompatibility complex class I molecules. Identical and nearly identical blocks of genomic sequence contribute to the observed multiplicity of identical MHCY genes and the large size (>639 kb) of the Red Jungle Fowl MHCY haplotype. Multiple points of hybridization observed in fluorescence in situ hybridization suggest that the Red Jungle Fowl MHCY haplotype is made up of linked, but physically separated genomic segments. The unusual gene content, the evidence of highly similar duplicated segments, and additional evidence of variation in haplotype size distinguish polymorphic MHCY from classical polymorphic major histocompatibility complex regions.
Heterogeneity in viral populations increases the rate of deleterious mutation accumulation
Authors: Allman Brent , Koelle Katia , Weissman Daniel
Published: August 2022

RNA viruses have high mutation rates, with the majority of mutations being deleterious. We examine patterns of deleterious mutation accumulation over multiple rounds of viral replication, with a focus on how cellular coinfection and heterogeneity in viral output affect these patterns. Specifically, using agent-based intercellular simulations we find, in agreement with previous studies, that coinfection of cells by viruses relaxes the strength of purifying selection and thereby increases the rate of deleterious mutation accumulation. We further find that cellular heterogeneity in viral output exacerbates the rate of deleterious mutation accumulation, regardless of whether this heterogeneity in viral output is stochastic or is due to variation in the cellular multiplicity of infection. These results highlight the need to consider the unique life histories of viruses and their population structure to better understand observed patterns of viral evolution.
Stress granule assemblyin vivois deficient in the CNS of mutant TDP-43 ALS mice
Authors: Dubinski Alicia , Gagné Myriam , Peyrard Sarah , Gordon David , Talbot Kevin , Vande Velde Christine
Published: August 2022

Responding effectively to external stress is crucial for neurons. Defective stress granule dynamics has been hypothesized as one of the pathways that renders motor neurons in amyotrophic lateral sclerosis (ALS) more prone to early death. Specifically, it is thought that stress granules seed the cytoplasmic TDP-43 inclusions that are observed in the neurons of most ALS patients, as well as ~50% of all frontotemporal dementia (FTD) patients. In this study, we tested this hypothesis in an intact mammalian nervous system. We established an in vivo heat stress paradigm in mice that effectively triggers the eIF2α pathway and the formation of stress granules in the CNS. In non-transgenic mice, we report an age-dependent decline in the formation of heat-induced stress granules, with 18-month-old animals showing a significant impairment. Furthermore, although neuronal stress granules were robustly observed in non-transgenic mice and SOD1G93A mice, they were largely absent in age-matched TDP-43M337V animals. The observed defect in stress granule formation in TDP-43M337V mice correlated with deficits in expression of key protein components typically required for phase separation. Lastly, while TDP-43 was not localized to stress granules, we observed complete nuclear depletion of TDP-43 in a subset of neurons, with the highest proportion being in the TDP-43M337V mice. Overall, our results indicate that mutant TDP-43 expression is associated with defective stress granule assembly and increased TDP-43 nuclear depletion in the mammalian nervous system, which could be relevant to ALS/FTD pathogenesis.
Tracing the Development of the Proportionality Analysis in Relation to Forced Evictions under the ICESCR
Authors: Grohmann Nils-Hendrik
Published: August 2022

Since 2013, the Committee on Economic, Social and Cultural Rights can examine individual communications under the Optional Protocol to the International Covenant on Economic, Social and Cultural Rights (ICESCR). This opens up the possibility to interpret Covenant provisions in a thorough manner. With regard to forced evictions and the right to housing under Article 11 ICESCR, one can discern a fast-developing approach concerning the proportionality analysis of evictions, entailing the establishment of specific criteria that may guide such analysis. This paper seeks to delineate these developments and will also shed light on possible general trends on the topic of limitations within the Committee’s emerging jurisprudence. In doing so, the paper will address if, and how, the developing proportionality analysis under the individual complaints procedure takes into consideration multi-discriminatory dimensions of State measures and how it specifically relates to or incorporates other ICESCR-concepts, such as minimum core obligations or the reasonableness review under Article 8(4) OP ICESCR.
Postvaccination Symptoms After a Third Dose of mRNA SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease: Results From CORALE-IBD
Authors: Li Dalin , Debbas Philip , Mujukian Angela , Cheng Susan , Braun Jonathan , McGovern Dermot P B , Melmed Gil Y ,   CORALE-IBD Study Group, Banty Andrea , Feldman Edward , Ha Christina , Lee Susie , Rabizadeh Shervin , Stein Theodore , Solomon Theodore , Syal Gaurav , Targan Stephan , Vasiliauskas Eric , Ziring David , Bonthala Niru , Botwin Gregory S , Hampton Melissa , Mengesha Emebet , Khanishian Elizabeth , Pozdnyakova Valeriya , Gu Phillip , White Shane , Zamudio Cindy , Gonzalez Daniel , Parry Alyssa , Hanna Mary , Chan Justin , Ebinger Joe , Joung Sandy , Wu Min , Hoang Amy , Wynter Timothy , Sun Nancy , Figueiredo Jane C , Merchant Akil , Merin Noah , Reckamp Karen L , Appel Keren , Kumar Rashmi , Boland Brigid , Charabaty Aline , Chiorean Michael , Cohen Erica , Flynn Ann , Valentine John , Ehrlich Adam C , Fudman David , Horizon Arash , Karayev Dmitry , Kretzmann Benjamin , Hou Jason , Hwang Caroline , Lazarev Mark , Lum Donald , Fausel Rebecca , Reddy Swapna , McConnell Ryan , Mattar Mark C , Metwally Mark , Ostrov Arthur , Parekh Nimisha , Raffals Laura , Rubin David T , Sheibani Sarah , Siegel Corey A , Wolf Douglas , Younes Ziad , Damas Oriana
Published: August 2022

Background

The safety of a third dose of SARS-CoV-2 mRNA vaccination in patients with inflammatory bowel disease is unknown.

Methods

We compared symptoms following a third SARS-CoV-2 mRNA vaccine dose with symptoms after the second dose in IBD.

Results

The study group included 594 patients (70% female, 58% BNT162b2). Overall, 41% reported symptoms after a third dose. Symptom frequency and severity were lower after the third dose relative to the second dose for every organ system, except for gastrointestinal symptoms which were marginally worse.

Conclusion

The frequency and severity of symptoms after a third mRNA vaccine dose are generally similar or milder than after a second dose for most organ systems.
Porcelain aorta does not mean inoperability but needs special strategies
Authors: Carrel Thierry , Vogt Paul Robert
Published: August 2022

Porcelain aorta is not an absolute contraindication for aortic valve and/or coronary bypass grafting but it requires a special strategy and individualized approach to minimize the risk of embolic complications and technical problems during opening and/or closing the aortotomy.
Radiological unilateral pleuroparenchymal fibroelastosis as a notable late complication after lung cancer surgery: incidence and perioperative associated factors
Authors: Inafuku Kenji , Sekine Akimasa , Arai Hiromasa , Hagiwara Eri , Komatsu Shigeru , Iwasawa Tae , Misumi Toshihiro , Kikunishi Noritake , Tajiri Michihiko , Okudela Koji , Rino Yasushi , Ogura Takashi
Published: August 2022

OBJECTIVES

Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by pleural-parenchymal involvement, predominantly in the upper lobes. Unilateral upper lung field pulmonary fibrosis (upper-PF) that is radiologically consistent with PPFE reportedly develops after lung cancer surgery in the operated side and presents many clinical characteristics in common with PPFE. However, the incidence and perioperative associated factors remain unclear.

METHODS

All consecutive patients with lung cancer resected completely from 2008 to 2016 were investigated retrospectively. Pre-/postoperative characteristics were compared between patients with and without unilateral upper-PF. Cumulative incidence curves were estimated using competing risk analysis.

RESULTS

Among the 587 included patients, 25 patients (4.3%) were diagnosed as unilateral upper-PF. The 3-, 5- and 10-year cumulative incidence of unilateral upper-PF was 2.3%, 3.3% and 5.3%, respectively. In multivariable analysis, male sex, presence of a pulmonary apical cap, lobar resection and low % vital capacity (%VC < 80%) were independent perioperative associated factors. The 10-year cumulative incidence was 6.3% in patients treated with lobar resection, 8.0% in male patients, 10.3% in patients with pulmonary apical cap and 14.5% in patients with low %VC. Postoperative pleural effusion at 6 months after surgery was much more common in the patients who later developed unilateral upper-PF (96.0% vs 24.2%). This pleural effusion persisted and was accompanied thereafter by pleural thickening and subpleural pulmonary fibrosis. During the clinical courses of 25 patients with unilateral upper-PF, 18 patients presented symptoms related to upper-PF and 6 patients died.

CONCLUSIONS

Unilateral upper-PF is an occasional but under-recognized late complication after lung cancer surgery.
A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine
Authors: Bloomfield-Clagett Bartholt , Ballard Elizabeth D , Greenstein Deanna K , Wilkinson Samuel T , Grunebaum Michael F , Murrough James W , Mathew Sanjay J , Phillips Jennifer L , Fava Maurizio , Sanacora Gerard , Zarate Carlos A
Published: August 2022

Background

Clinical trials of intravenous (IV) racemic (R,S)-ketamine (hereafter referred to as IV ketamine) have consistently reported rapid and substantial reductions in overall depressive symptoms compared with saline (inactive placebo) or midazolam (active placebo). The evidence for IV ketamine’s specific effects on suicidal ideation is less clear, however. This study sought to examine whether differential placebo (saline or midazolam) response to overall depressive symptoms vs suicidal ideation may help explain these divergent findings.

Methods

Data for this participant-level integrative data analysis were drawn from 151 participants across 10 studies, and linear regression was used to examine the relationship between placebo response for suicidal ideation vs other depressive symptoms indexed from standard rating scales—specifically, depressed mood, anhedonia, anxiety, and guilt—over time.

Results

For participants receiving saline placebo (n = 46), greater placebo response was observed for suicidal ideation compared with other symptoms indexed from standard depression rating scales, except for anxiety. For those receiving midazolam placebo (n = 105), greater placebo response was observed for suicidal ideation compared with depressed mood or anhedonia, and no significant differences were observed when comparing suicidal ideation with anxiety or guilt.

Conclusions

Taken together, the results provide preliminary evidence of a differential placebo response for suicidal ideation vs other depressive symptoms, while anxiety and suicidal ideation appear to produce similar placebo response profiles. These findings may help explain the more modest findings in clinical IV ketamine trials for suicidal ideation than overall depression.
CCR4 plays a pivotal role in Th17 cell recruitment and expansion in a mouse model of rheumatoid arthritis
Authors: Honzawa Tatsuma , Matsuo Kazuhiko , Hosokawa Shunya , Kamimura Mayu , Kaibori Yuichiro , Hara Yuta , Nagakubo Daisuke , Oiso Naoki , Kawada Akira , Otsuka Atsushi , Yoshie Osamu , Nakayama Takashi
Published: August 2022

T helper 17 (Th17) cells express CC chemokine receptor 4 (CCR4) and secrete cytokines such as interleukin-17A (IL-17A) and granulocyte macrophage colony-stimulating factor (GM-CSF), while dendritic cells (DCs) produce CC chemokine ligand 22 (CCL22), a CCR4 ligand, upon stimulation with GM-CSF. Th17 cells are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA). CCL22 has also been shown to be up-regulated in the synovial tissues of RA patients. Here, we investigated the role of CCR4 in collagen-induced arthritis (CIA), a mouse model of RA. DBA/1J mice efficiently developed CIA as shown by erythema, paw swelling, joint rigidity, and joint destruction. Th17 cells were increased in the arthritic joints and regional lymph nodes (LNs) of CIA mice. A fraction of Th17 cells were also shown to produce GM-CSF. On the other hand, we observed no significant increases of Th2 cells or Treg cells, the T cell subsets also known to express CCR4, in these tissues. We further observed clusters of CCR4-expressing memory Th17 cells and CCL22-producing DCs in the regional LNs of CIA mice, supporting the role of the CCR4-CCL22 axis in the expansion of Th17 cells in the regional LNs. Compound 22, a CCR4 inhibitor, ameliorated the disease severity with reduction of Th17 cells in the arthritic joints and regional LNs and Th17-DC clusters in the regional LNs. We further confirmed that CCR4-deficient mice in the C57BL/6J background were highly resistant to CIA induction compared with wild-type mice. Collectively, CCR4 contributes to the pathogenesis of CIA and may thus represent a new therapeutic target for RA.
Clinical and microbiological evaluation of temocillin for bloodstream infections with Enterobacterales: a Belgian single-centre retrospective study
Authors: Oosterbos Julie , Schalkwijk Maaike , Thiessen Steven , Oris Els , Coppens Guy , Lagrou Katrien , Steensels Deborah
Published: August 2022

Background

Expanding the use of temocillin could be an important weapon in the fight against antimicrobial resistance. However, EUCAST defined clinical breakpoints for a limited number of species and only for urinary tract infections (UTI), including urosepsis but excluding severe sepsis and septic shock. Moreover, a dosage of 2 g q8h is advised in most cases.

Objectives

Evaluation of temocillin use for the treatment of bacteraemia, correlating clinical and microbiological outcomes with infection site, infection severity, temocillin dosage, Enterobacterales species and MIC.

Patients and methods

All adult patients with blood cultures positive for temocillin-susceptible Enterobacterales and treated with temocillin for ≥72 h from June 2018 until June 2021 were considered for inclusion. The primary outcome was clinical success, defined as resolution of infection signs, no relapse of the same infection and no antibiotic switch due to insufficient clinical improvement. The secondary outcome was microbiological success.

Results

In total, 182 episodes were included [140 UTI versus 42 non-UTI, 171 Escherichia coli, Klebsiella species (except Klebsiella aerogenes) and Proteus mirabilis (EKPs) versus 11 non-EKPs]. Clinical and microbiological failure were low (8% and 3%, respectively). No difference in outcome was observed for dosages of 2 g q12h versus 2 g q8h, either for EKP versus non-EKP isolates or MIC values ≤8 versus 16 mg/L. Considering only bacteraemia episodes of UTI origin, using the 16 mg/L breakpoint, there was no difference in success rate between regimens of 2 g q12h and 2 g q8h.

Conclusions

Temocillin 2 g q12h can be successfully used for the treatment of systemic UTI. Prospective studies are needed to assess outcomes and evaluate non-inferiority compared with other broad-spectrum antibiotics in non-UTI infections, including bacteraemia.
Statistical Capacity Matters: The Long-Term Effects of Africa’s Slave Trade on Development Reflected by Nighttime Light Intensity
Authors: Gören Erkan , Winkler Adalbert
Published: August 2022

Empirical research depends on reliable data. Yet, in many countries, statistical agencies do not have the capacity to collect high-quality data on economic development. This is especially the case in Africa, where the capacity to collect such data is affected by the same historical factors that explain economic development—in particular, the slave trade. We hypothesise that the impact of the slave trade on economic development in Africa is biased because cross-country heterogeneity in statistical capacity related to the slave trade creates a non-classical measurement error in gross domestic product (GDP) per capita. Our empirical evidence supports this view. When replacing GDP per capita by nighttime light intensity per capita—an indicator of economic development unrelated to statistical capacity—the impact of the slave trade on economic development drops by a factor of 2–4 depending on model specification and estimation methodology (OLS, IV and high-dimensional sparse models). Various robustness tests further corroborate our main hypothesis.
The effects of supplementation of noni (Morinda citrifolia L.) fruit polysaccharides-rich extract on antioxidant status and immune function in cashmere goats
Authors: Zhang Qingyue , Li Yinhao , Yin Guolin , Li Yuan , Zhao Yanli , Guo Xiaoyu , Guo Yongmei , Yan Sumei
Published: August 2022

This experiment was designed to examine the effects of a dietary supplementation of polysaccharides-rich noni (Morinda citrifolia L.) fruit extract (NFP) on the anti-oxidant enzyme activities, cytokines level, and expression of corresponding genes in blood of cashmere goats. Twelve castrated, 2-yr-old male cashmere goats (45.44 ± 3.30 kg of BW ± SD) were used in a 2 × 2 crossover design: the basal diet with or without (CON) supplementation of NFP at 4 g per kg DM (0.4%). Each period lasted for 29 d, including 1 wk for diet transition, 20 d for adaptation, and the last 2 d for sampling. The results showed that NFP supplementation increased (P < 0.05) the levels of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and the activities of catalase (CAT), glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and total superoxide dismutase (T-SOD) in serum. The expressions of CAT, GPx4, TrxR, SOD1, IL-6, and TNF-α genes were upregulated (P < 0.05), whereas the levels of malondialdehyde (P = 0.015) and reactive oxygen species (P = 0.051) in serum were reduced. The body weight gain of goats was increased (P = 0.006) with a nonsignificant increase of feed intake with NFP supplementation. In conclusion, dietary NFP supplementation enhanced the antioxidant status and immune function in blood of cashmere goats.
The Ambrosia BeetleMegaplatypus mutatus: A Threat to Global Broad-Leaved Forest Resources
Authors: Ceriani-Nakamurakare Esteban , Robles Carolina , González-Audino Paola , Dolinko Andrés , Mc Cargo Patricia , Corley Juan , Allison Jeremy , Carmarán Cecilia
Published: August 2022

We provide scientists and decision-makers with up-to-date information on Megaplatypus mutatus (Coleoptera: Curculionidae: Platypodinae), a forest insect native to South America that has invaded other regions. Emphasis is given to information that may prove relevant for the development of early detection, containment and management programs and improved risk analyses. The increase in global movement of people and goods, coupled with expected climatic scenarios, suggests that M. mutatus may arrive and establish populations in new areas. The major impact of this forest pest has always been reported in exotic tree species, even within its native range. The absence of a coevolutionary history with ‘naïve’ host trees is a relevant factor when analyzing and understanding the magnitude of the problem posed by this beetle and fungi associated with it. Notably, among preferred hosts are the widely planted Eucalyptus and Populus spp., facilitating the invasion of this insect into new regions and posing a threat to commercial forestry.
Muslim saints contested: Ibn Taymiyya’s critique of al-Qushayrī’s Risāla
Authors: Gasimov Kamal
Published: August 2022

This article analyses Ibn Taymiyya’s neglected commentary on ʿAbū al-Qāsim al-Qushayrī ’s Epistle on Sufism (al-Risāla al-Qushayriyya fī ʿilm al-taṣawwuf), in which he wages several intellectual battles simultaneously: with Ashʿarī theologians of earlier centuries, such as al-Qushayrī himself; with his Ashʿarī contemporaries like Ibn Jahbal al-Kilābī; and with advocates in Damascus and Cairo of Ibn al-ʿArabī’s monistic teachings. Ibn Taymiyya deploys a set of historical and discursive arguments rooted in the early Sufi historiography to argue that both Ashaʿrīs and monistic-minded Sufis do not have a rightful claim to the heritage of the early Sufi authorities. In the struggle to define ‘Islamic orthodoxy’, Ashaʿrīs and Ḥanbalīs evince two radically different approaches to Sufi sayings. Al-Qushayrī and Ibn Jahbal affirm the harmony between Sufi utterances and the rational proofs of speculative theology (kalām), while, in stark contrast, Ibn Taymiyya accentuates their ascetic-mystical connotations. This Ḥanbalī–Ashʿarī debate comprised two conflicting attitudes to the notion of ‘Muslim sainthood’ (wilāya): the Ashʿarīs insisted that early Sufi saintly figures (awliyāʾ) mastered the principles of kalām in order to explain the nature of God to different classes of the Muslim community, while Ibn Taymiyya believed that this type of theological reasoning undermined the very foundations of the spiritual teachings of the early Sufis and retarded the spiritual growth of those who undertook the Sufi path. These polemical exchanges demonstrate that Sufi figures, concepts, images, and texts became central to the articulation of theological arguments during the early Mamluk sultanate.
Anti-tumor effects of Thymus Caramanicus Jalas extract in mice through oxidative stress, inflammation and apoptosis
Authors: Hassanshahi Jalal , Hajializadeh Zahra , Niknia Seddigheh , Mahmoodi Mehdi , Kaeidi Ayat
Published: August 2022

Objective

Breast cancer causes death in women. Thymus Caramanicus Jalas (TCJ) as a polyphenolic plant has an antiproliferative effect. Accordingly, this investigation studied the TCJ extract anti-tumor effects in a breast cancer model.

Methods

Twenty-four female BALB/c mice were used in 4 groups including (1) breast cancer (control); (2), (3) and (4) breast cancer + 100, 300 and 500 mg/kg of TCJ extract (once daily for 20-days after breast tumor induction). The breast tumour was induced by 4T1 cell carcinoma injection. Then tumor size and weight were measured. Tumor necrosis factor-α (TNF-α), nuclear factor κ-B (NF-κB), interleukin-6 (IL-6) as inflammatory markers and also Bcl-2, Bax, cytosolic cytochrome-c, apoptosis-inducing factor, and cleaved caspase-3 as biochemical apoptosis markers were evaluated in tumor tissue with western blotting analysis. Also, malondialdehyde (MDA) concentration, hydrogen peroxidase (H2O2), catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were exanimated.

Key findings

Treatment with TCJ extract (500 mg/kg) decreased the tumor volume, tumor weight, GPx, SOD, and catalase enzyme activity versus the control group (P < 0.05). Also, TCJ (500 mg/kg) extract increased MDA, H2O2, inflammatory and apoptosis markers versus control (P < 0.05).

Conclusions

Current study showed that TCJ can induce anti-tumour effects via promoting inflammation, apoptosis, and oxidative stress in breast tumour tissue.
Characterization of the PHOSPHATE RESPONSE 2-dependent and -independent Pi-starvation response secretome in rice
Authors: Du Zezhen , Deng Suren , Wu Zixuan , Cai Hongmei , Xu Fangsen , Shi Lei , Wang Sheliang , Ding Guangda , Wang Chuang
Published: August 2022

Many proteins secreted from plant cells into the surrounding extracellular space help maintain cell structure and regulate stress responses in the external environment. In this study, under Pi-replete and depleted conditions, 652 high-confidence secreted proteins were quantified from wild-type (WT) and PHOSPHATE RESPONSE 2 (OsPHR2)-overexpressing suspension-cultured cells (SCCs). These proteins were functionally grouped as phosphatases, signal transduction proteins, pathogen-related (PR) proteins, cell wall-remodeling proteins, and reactive oxygen species (ROS) metabolism proteins. Although PHOSPHATE RESPONSE (PHR) transcription factors regulate two-thirds of Pi-responsive genes at the transcriptional level, only 30.6% of the Pi-starvation-regulated secreted proteins showed significant changes in OsPHR2-overexpressing SCCs. The OsPHR2-dependent systemic Pi signaling pathway mainly regulates phosphatases and PR proteins, which are involved in the utilization of organophosphate, pathogen resistance, and colonization by rhizosphere microorganisms. The OsPHR2-independent local Pi signaling pathway, on the other hand, largely regulated ROS metabolism proteins, cell wall-remodeling proteins, and signal transduction proteins, which are involved in modifying cell wall structure and root architecture. The functions of differentially expressed secreted proteins between WT and OsPHR2-overexpressing plants under Pi-sufficient and Pi-deficient conditions were further confirmed by analysis of the acid phosphatase activity, ROS content, and cell wall composition.
ASAS-SN follow-up of IceCube high-energy neutrino alerts
Authors: Necker Jannis , de Jaeger Thomas , Stein Robert , Franckowiak Anna , Shappee Benjamin J , Kowalski Marek , Kochanek Christopher S , Stanek Krzysztof Z , Beacom John F , Desai Dhvanil D , Neumann Kyle , Jayasinghe Tharindu , Holoien T W-S , Thompson Todd A , Holmbo Simon
Published: August 2022

We report on the search for optical counterparts to IceCube neutrino alerts released between 2016 April and 2021 August with the All-Sky Automated Survey for SuperNovae (ASAS-SN). Despite the discovery of a diffuse astrophysical high-energy neutrino flux in 2013, the source of those neutrinos remains largely unknown. Since 2016, IceCube has published likely astrophysical neutrinos as public real-time alerts. Through a combination of normal survey and triggered target-of-opportunity observations, ASAS-SN obtained images within 1 h of the neutrino detection for 20 per cent (11) of all observable IceCube alerts and within one day for another 57 per cent (32). For all observable alerts, we obtained images within at least two weeks from the neutrino alert. ASAS-SN provides the only optical follow-up for about 17 per cent of IceCube’s neutrino alerts. We recover the two previously claimed counterparts to neutrino alerts, the flaring-blazar TXS 0506 + 056 and the tidal disruption event AT2019dsg. We investigate the light curves of previously detected transients in the alert footprints, but do not identify any further candidate neutrino sources. We also analysed the optical light curves of Fermi 4FGL sources coincident with high-energy neutrino alerts, but do not identify any contemporaneous flaring activity. Finally, we derive constraints on the luminosity functions of neutrino sources for a range of assumed evolution models.
Impact of intrinsic alignments on clustering constraints of the growth rate
Authors: Zwetsloot Karel , Chisari Nora Elisa
Published: August 2022

Intrinsic alignments between galaxies and the large-scale structure contaminate galaxy clustering analyses and impact constraints on galaxy bias and the growth rate of structure in the Universe. This is the result of alignments inducing a selection effect on spectroscopic samples which is correlated with the large-scale structure. In this work, we quantify the biases on galaxy bias and the growth rate when alignments are neglected. We also examine different options for the mitigation of alignments by considering external priors on the effect and different probe combinations. We find that conservative analyses that restrict to kmax = 0.1 Mpc−1 are not significantly affected. However, analyses that aim to go to higher wave numbers could evidence a significant contamination from alignments. In those cases, including a prior on alignment amplitude, or combining clustering with the position-intrinsic shape correlation of galaxies, can recover the same expected constraining power, or even inform bias and growth rate measurements.
The sensitivity of the redshift distribution to galaxy demographics
Authors: Sudek Philipp , de la Bella Lucia F , Amara Adam , Hartley William G
Published: August 2022

Photometric redshifts are commonly used to measure the distribution of galaxies in large surveys. However, the demands of ongoing and future large-scale cosmology surveys place very stringent limits on the redshift performance that are difficult to meet. A new approach to meet this precision need is forward modelling, which is underpinned by realistic simulations. In the work presented here, we use simulations to study the sensitivity of redshift distributions to the underlying galaxy population demographics. We do this by varying the redshift evolving parameters of the Schechter function for two galaxy populations: star-forming and quenched galaxies. Each population is characterized by eight parameters. We find that the redshift distribution of shallow surveys, such as the Sloan Digital Sky Survey (SDSS), is mainly sensitive to the parameters for quenched galaxies. However, for deeper surveys such as the Dark Energy Survey (DES) and the Hyper Suprime-Cam (HSC), the star-forming parameters have a stronger impact on the redshift distribution. Specifically, the slope of the characteristic magnitude, aM, for star-forming galaxies has overall the strongest impact on the redshift distribution. Decreasing aM by 148 per cent (its given uncertainty) shifts the mean redshift by ∼45 per cent. We explore which combination of colour and magnitude measurements is most sensitive to aM and we find that each colour–magnitude pair studied is similarly affected by a modification of aM.
Optical spectroscopy of the extremely metal-deficient star-forming galaxy HSC J1631+4426: a test of the strong-line method
Authors: Thuan T X , Guseva N G , Izotov Y I
Published: August 2022

Recently, Kojima and co-authors have reported a record low oxygen abundance, 12 + logO/H = 6.90 ± 0.03, or 1.6 per cent of solar metallicity, in the low-mass star-forming galaxy HSC J1631 + 4426. This exceptionally low oxygen abundance was obtained by the direct method, using the [O iii]λ4363Å emission line. However, using the strong-line method by Izotov et al. (2019b), these authors have derived a significantly higher metallicity 12 + logO/H = 7.175 ± 0.005. To clarify the situation, we have obtained new observations of HSC J1631 + 4426 with the Large Binocular Telescope (LBT)/Multi-Object Dual Spectrograph (MODS). We have derived a higher oxygen abundance, 12 + logO/H = 7.14 ± 0.03, using the direct method, a value similar to the oxygen abundance obtained by the strong-line method. Thus, HSC J1631 + 4426 has a metallicity close to that of the well known blue compact dwarf galaxy I Zw 18.
Origin and Evolution of Nitrogen Fixation in Prokaryotes
Authors: Pi Hong-Wei , Lin Jinn-Jy , Chen Chi-An , Wang Po-Hsiang , Chiang Yin-Ru , Huang Chieh-Chen , Young Chiu-Chung , Li Wen-Hsiung
Published: August 2022

The origin of nitrogen fixation is an important issue in evolutionary biology. While nitrogen is required by all living organisms, only a small fraction of bacteria and archaea can fix nitrogen. The prevailing view is that nitrogen fixation first evolved in archaea and was later transferred to bacteria. However, nitrogen-fixing (Nif) bacteria are far larger in number and far more diverse in ecological niches than Nif archaea. We, therefore, propose the bacteria-first hypothesis, which postulates that nitrogen fixation first evolved in bacteria and was later transferred to archaea. As >30,000 prokaryotic genomes have been sequenced, we conduct an in-depth comparison of the two hypotheses. We first identify the six genes involved in nitrogen fixation in all sequenced prokaryotic genomes and then reconstruct phylogenetic trees using the six Nif proteins individually or in combination. In each of these trees, the earliest lineages are bacterial Nif protein sequences and in the oldest clade (group) the archaeal sequences are all nested inside bacterial sequences, suggesting that the Nif proteins first evolved in bacteria. The bacteria-first hypothesis is further supported by the observation that the majority of Nif archaea carry the major bacterial Mo (molybdenum) transporter (ModABC) rather than the archaeal Mo transporter (WtpABC). Moreover, in our phylogeny of all available ModA and WtpA protein sequences, the earliest lineages are bacterial sequences while archaeal sequences are nested inside bacterial sequences. Furthermore, the bacteria-first hypothesis is supported by available isotopic data. In conclusion, our study strongly supports the bacteria-first hypothesis.
Distinct, opposing functions for CFIm59 and CFIm68 in mRNA alternative polyadenylation of Pten and in the PI3K/Akt signalling cascade
Authors: Tseng Hsin-Wei , Mota-Sydor Anthony , Leventis Rania , Jovanovic Predrag , Topisirovic Ivan , Duchaine Thomas F
Published: August 2022

Precise maintenance of PTEN dosage is crucial for tumor suppression across a wide variety of cancers. Post-transcriptional regulation of Pten heavily relies on regulatory elements encoded by its 3′UTR. We previously reported the important diversity of 3′UTR isoforms of Pten mRNAs produced through alternative polyadenylation (APA). Here, we reveal the direct regulation of Pten APA by the mammalian cleavage factor I (CFIm) complex, which in turn contributes to PTEN protein dosage. CFIm consists of the UGUA-binding CFIm25 and APA regulatory subunits CFIm59 or CFIm68. Deep sequencing analyses of perturbed (KO and KD) cell lines uncovered the differential regulation of Pten APA by CFIm59 and CFIm68 and further revealed that their divergent functions have widespread impact for APA in transcriptomes. Differentially regulated genes include numerous factors within the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signalling pathway that PTEN counter-regulates. We further reveal a stratification of APA dysregulation among a subset of PTEN-driven cancers, with recurrent alterations among PI3K/Akt pathway genes regulated by CFIm. Our results refine the transcriptome selectivity of the CFIm complex in APA regulation, and the breadth of its impact in PTEN-driven cancers.
Armed conflicts and kidney patients: a consensus statement from the Renal Disaster Relief Task Force of the ERA
Authors: Sever Mehmet S , Vanholder Raymond , Luyckx Valerie , Eckardt Kai-Uwe , Kolesnyk Mykola , Wiecek Andrzej , Pawlowicz-Szlarska Ewa , Gallego Daniel , Shroff Rukshana , Škoberne Andrej , Nistor Ionut , Sekkarie Mohamed , Ivanov Dmytro , Noruišiene Edita , Tuglular Serhan
Published: August 2022

During conflicts, people with kidney disease, either those remaining in the affected zones or those who are displaced, may be exposed to additional threats because of medical and logistical challenges. Acute kidney injury developing on the battlefield, in field hospitals or in higher-level hospital settings is characterized by poor outcomes. People with chronic kidney disease may experience treatment interruptions, contributing to worsening kidney function. Patients living on dialysis or with a functioning graft may experience limitations of dialysis possibilities or availability of immunosuppressive medications, increasing the risk of severe complications including death. When patients must flee, these threats are compounded by unhealthy and insecure conditions both during displacement and/or at their destination. Measures to attenuate these risks may only be partially effective. Local preparedness for overall and medical/kidney-related disaster response is essential. Due to limitations in supply, adjustments in dialysis frequency or dose, switching between hemodialysis and peritoneal dialysis and changes in immunosuppressive regimens may be required. Telemedicine (if possible) may be useful to support inexperienced local physicians in managing medical and logistical challenges. Limited treatment possibilities during warfare may necessitate referral of patients to distant higher-level hospitals, once urgent care has been initiated. Preparation for disasters should occur ahead of time. Inclusion of disaster nephrology in medical and nursing curricula and training of patients, families and others on self-care and medical practice in austere settings may enhance awareness and preparedness, support best practices adapted to the demanding circumstances and prepare non-professionals to lend support.
National-level overall survival patterns for molecularly-defined diffuse glioma types in the United States
Authors: Ostrom Quinn T , Shoaf Madison L , Cioffi Gino , Waite Kristin , Kruchko Carol , Wen Patrick Y , Brat Daniel J , Barnholtz-Sloan Jill S , Iorgulescu J Bryan
Published: August 2022

Background

Molecularly-defined diffuse glioma types—including IDH-wildtype glioblastoma, IDH-mutant astrocytoma, IDH-mutant 1p/19q-codeleted oligodendroglioma, and H3 K27M-mutant diffuse midline glioma—were incorporated into U.S. cancer registry reporting for individuals with brain tumors beginning in 2018. We leveraged these new data to estimate the national-level overall survival (OS) patterns associated with glioma integrated diagnoses.

Methods

Individuals diagnosed with diffuse gliomas in 2018 and had brain molecular marker data were identified within the U.S. National Cancer Database. OS was estimated using Kaplan–Meier methods and stratified by WHO CNS grade, age, sex, tumor size, treatment, extent of resection, and MGMT promoter methylation. Additionally, the effects of WHO CNS grade were examined among individuals with IDH-wildtype astrocytic gliomas.

Results

8651 individuals were identified. One-year OS was 53.7% for WHO grade 4 IDH-wildtype glioblastomas; 98.0%, 92.4%, and 76.3% for WHO grade 2, 3, and 4 IDH-mutant astrocytomas, respectively; 97.9% and 94.4% for WHO grade 2 and 3 IDH-mutant 1p/19q-codeleted oligodendrogliomas, respectively; and 55.9% for H3 K27M-mutant diffuse midline gliomas. Among IDH-wildtype glioblastomas, median OS was 17.1 months and 12.4 months for methylated and unmethylated MGMT promoters. Additionally, IDH-wildtype diffuse astrocytic gliomas reported as WHO grade 2 or 3 demonstrated longer OS compared to grade 4 tumors (both P < .001).

Conclusions

Our findings provide the initial national OS estimates for molecularly-defined diffuse gliomas in the United States and illustrate the importance of incorporating such data into cancer registry reporting.
Sexually Transmitted Infection Testing in the National Veterans Health Administration Patient Cohort During the Coronavirus Disease 2019 Pandemic
Authors: Beste Lauren A , Keddem Shimrit , Borgerding Joleen , Lowy Elliott , Gardella Carolyn , McFarland Lorenzo , Comstock Emily , Fonseca Giuseppe Allan , Van Epps Puja , Ohl Michael , Hauser Ronald G , Ross David , Maier Marissa M
Published: August 2022

Background

We performed a retrospective study of chlamydia, gonorrhea, syphilis, and human immunodeficiency virus (HIV) testing in the Veterans Health Administration (VHA) during 2019–2021.

Methods

We determined the annual number of chlamydia, gonorrhea, syphilis, and HIV tests from 2019 through 2021 using electronic health record data. We calculated rates by age, birth sex, race, census region, rurality, HIV status, and use of preexposure prophylaxis.

Results

The VHA system experienced a 24% drop in chlamydia/gonorrhea testing, a 25% drop in syphilis testing, and a 29% drop in HIV testing in 2020 versus 2019. By the conclusion of 2021, testing rates had recovered to 90% of baseline for chlamydia/gonorrhea, 91% for syphilis, and 88% for HIV. Declines and subsequent improvements in sexually transmitted infection (STI) testing occurred unequally across age, sex, race, and geographic groups. Testing for all 4 STIs in 2021 remained below baseline in rural Veterans. Excluding those aged <25 years, women experienced a steeper decline and slower recovery in chlamydia/gonorrhea testing relative to men, but quicker recovery in HIV testing. Asian Americans and Hawaiian/Pacific Islanders had a steeper decline and a slower recovery in testing for chlamydia/gonorrhea. Black and White Veterans had slower recovery in HIV testing compared with other race groups. People living with HIV experienced a smaller drop in testing for syphilis compared with people without HIV, followed by a near-total recovery of testing by 2021.

Conclusions

After dramatic reductions from 2019 to 2020, STI testing rates returned to near-baseline in 2021. Testing recovery lagged in rural, female, Asian American, Hawaiian/Pacific Islander, and Black Veterans.
Stomatal Development and Gene Expression in Rice Florets
Authors: Bertolino Lígia T , Caine Robert S , Zoulias Nicholas , Yin Xiaojia , Chater Caspar C C , Biswal Akshaya , Quick William P , Gray Julie E
Published: August 2022

Stomata play a fundamental role in modulating the exchange of gases between plants and the atmosphere. These microscopic structures form in high numbers on the leaf epidermis and are also present on flowers. Although leaf stomata are well studied, little attention has been paid to the development or function of floral stomata. Here, we characterize in detail the spatial distribution and development of the floral stomata of the indica rice variety IR64. We show that stomatal complexes are present at low density on specific areas of the lemma, palea and anthers and are morphologically different compared to stomata found on leaves. We reveal that in the bract-like organs, stomatal development follows the same cell lineage transitions as in rice leaves and demonstrate that the overexpression of the stomatal development regulators OsEPFL9-1 and OsEPF1 leads to dramatic changes in stomatal density in rice floral organs, producing lemma with approximately twice as many stomata (OsEPFL9-1_oe) or lemma where stomata are practically absent (OsEPF1_oe). Transcriptomic analysis of developing florets also indicates that the cellular transitions during the development of floral stomata are regulated by the same genetic network used in rice leaves. Finally, although we were unable to detect an impact on plant reproduction linked to changes in the density of floral stomata, we report alterations in global gene expression in lines overexpressing OsEPF1 and discuss how our results reflect on the possible role(s) of floral stomata.
BORON-ENHANCED BIOLOGICAL EFFECTIVENESS OF PROTON IRRADIATION: STRATEGY TO ASSESS THE UNDERPINNING MECHANISM
Authors: Kundrát Pavel , Pachnerová Brabcová Kateřina , Jelínek Michaelidesová Anna , Zahradníček Oldřich , Danilová Irina , Štěpán Václav , Jamborová Zuzana , Davídková Marie
Published: August 2022

Proton radiotherapy for the treatment of cancer offers an excellent dose distribution. Cellular experiments have shown that in terms of biological effects, the sharp dose distribution is further amplified, by as much as 75%, in the presence of boron. It is a matter of debate whether the underlying physical processes involve the nuclear reaction of 11B with protons or 10B with secondary neutrons, both producing densely ionizing short-ranged particles. Likewise, potential roles of intercellular communication or boron acting as a radiosensitizer are not clear. We present an ongoing research project based on a multiscale approach to elucidate the mechanism by which boron enhances the effectiveness of proton irradiation in the Bragg peak. It combines experimental with simulation tools to study the physics of proton–boron interactions, and to analyze intra- and inter-cellular boron biology upon proton irradiation.
THE IMPORTANCE OF FEEDBACK IN MONITORING PATIENTS’ RADIATION DOSES IN MAMMOGRAPHY
Authors: Horváthová Martina , Bárdyová Zuzana , Gomola Igor
Published: August 2022

The majority of medical facilities in the Slovak Republic archive diagnostic images of their patients in a picture archiving and communicating system (PACS). Data from the PACS system can be used to analyse patient radiation dose and perform internal and external quality control through dose monitoring software systems. However, appropriate use of such systems requires the provision of feedback and the ability of staff to identify causes of diagnostic reference level exceedances. The present pilot study evaluated the use of a Dose quality control system (DQC) for monitoring the radiation dose of the patients in the ongoing mammography screening, with subsequent identification of alerts triggered by the system.
OPTIMISATION OF ABDOMINAL CT EXAM PROTOCOLS IN OBESE PATIENTS
Authors: Balogová Zdenka , Súkupová Lucie
Published: August 2022

Obesity is marked as a global epidemic, and the number of obese people is steadily increasing. This disease affects various aspects of health care, which also includes radiodiagnostic imaging modalities. CT exams of bariatric patients are becoming common in radiological practice and bring problems of both technical and physical nature. Obesity affects the quality of CT images, therefore, optimisation of the used CT protocols is important, which is difficult to be carried out on patients, because of the principles of radiation protection and ethical point of view. This study evaluates and compares three available CT protocols for examination of the abdomen in terms of image quality, radiation dose and scan time on two CT scanners of the manufacturer Siemens. For optimisation, an anthropomorphic phantom of the abdomen was used, which, by its size and attenuation of the used materials, suitably simulated an obese patient.