bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strong, Recent Selective Sweeps Reshape Genetic Diversity in Freshwater BivalveMegalonaias nervosa
Authors: Rogers Rebekah L , Grizzard Stephanie L , Garner Jeffrey T 
Published: February 2023

AbstractFreshwater Unionid bivalves have recently faced ecological upheaval through pollution, barriers to dispersal, harvesting, and changes in fish–host prevalence. Currently, over 70% of species in North America are threatened, endangered or extinct. To characterize the genetic response to recent selective pressures, we collected population genetic data for one successful bivalve species, Megalonaias nervosa. We identify megabase-sized regions that are nearly monomorphic across the population, signals of strong, recent selection reshaping diversity across 73 Mb total. These signatures of selection are greater than is commonly seen in population genetic models. We observe 102 duplicate genes with high dN/dS on terminal branches among regions with sweeps, suggesting that gene duplication is a causative mechanism of recent adaptation in M. nervosa. Genes in sweeps reflect functional classes important for Unionid survival, including anticoagulation genes important for fish host parasitization, detox genes, mitochondria management, and shell formation. We identify sweeps in regions with no known functional impacts, suggesting mechanisms of adaptation that deserve greater attention in future work on species survival. In contrast, polymorphic transposable elements (TEs) appear to be detrimental and underrepresented among regions with sweeps. TE site frequency spectra are skewed toward singleton variants, and TEs among regions with sweeps are present at low frequency. Our work suggests that duplicate genes are an essential source of genetic novelty that has helped this species succeed in environments where others have struggled. These results suggest that gene duplications deserve greater attention in non-model population genomics, especially in species that have recently faced sudden environmental challenges.
How SMT Could Become More Welcoming
Authors: Manabe Noriko 
Published: February 2023

AbstractContinuing Stephen Lett’s (2023) argument that pedagogy was undervalued by SMT at its inception, this essay considers the signs and implications of continued marginalization of teaching. While position statements can influence the atmosphere of a society, they are peripheral to its operations, which determine who is included or excluded. SMT could help expand the pipeline for women and minoritized groups and identities by formulating and reinforcing ethical guidelines, not just at SMT events but in the music theory profession as a whole. A set of questions is provided for assessing the potential for harmful behaviors in institutional gatekeeping, from teaching to graduate admissions and programs, faculty searches, and tenure and promotion. Deeper engagement by SMT and its membership—through the formation of guidelines for searches and tenure processes, the formation of an ethics committee tasked with review and adjudication, and mentorship for job candidates and junior faculty—should help to broaden the demographics.
O Give Me a Home
Authors: McCreless Patrick 
Published: February 2023

Abstract
This essay examines Stephen Lett’s (2023) critique of North American music theory in general, and of the Society for Music Theory in particular, from the point of view of the binary inclusion/exclusion. Drawing on my own experience, I acknowledge that in many respects his critique of the Society for Music Theory (SMT), from its very inception, as creating an exclusionary, “stratified” space, is on target. Yet I contest his reading of the history and current functioning of the Society and of the broader discipline as a wholesale enterprise of coloniality. Although he insists that this metaphor, as applied to the SMT, is not to be read as involving the type of violence inflicted by colonial powers on native peoples, his consistent, governing language of displacement, pushing out, building fences, and defending territory, belies this denial, and produces a narrative that often suggests a level of hostility incompatible with both history and current experience.
Characterization of an atypical but widespread type IV secretion system for transfer of the integrative and conjugative element (ICEclc) inPseudomonas putida
Authors: Daveri Andrea , Benigno Valentina , van der Meer Jan Roelof 
Published: February 2023

AbstractConjugation of DNA relies on multicomponent protein complexes bridging two bacterial cytoplasmic compartments. Whereas plasmid conjugation systems have been well documented, those of integrative and conjugative elements (ICEs) have remained poorly studied. We characterize here the conjugation system of the ICEclc element in Pseudomonas putida UWC1 that is a model for a widely distributed family of ICEs. By in frame deletion and complementation, we show the importance on ICE transfer of 22 genes in a 20-kb conserved ICE region. Protein comparisons recognized seven homologs to plasmid type IV secretion system components, another six homologs to frequent accessory proteins, and the rest without detectable counterparts. Stationary phase imaging of P. putida ICEclc with in-frame fluorescent protein fusions to predicted type IV components showed transfer-competent cell subpopulations with multiple fluorescent foci, largely overlapping in dual-labeled subcomponents, which is suggestive for multiple conjugation complexes per cell. Cross-dependencies between subcomponents in ICE-type IV secretion system assembly were revealed by quantitative foci image analysis in a variety of ICEclc mutant backgrounds. In conclusion, the ICEclc family presents an evolutionary distinct type IV conjugative system with transfer competent cells specialized in efficient transfer.
Ultradeep characterisation of translational sequence determinants refutes rare-codon hypothesis and unveils quadruplet base pairing of initiator tRNA and transcript
Authors: Höllerer Simon , Jeschek Markus 
Published: February 2023

AbstractTranslation is a key determinant of gene expression and an important biotechnological engineering target. In bacteria, 5′-untranslated region (5′-UTR) and coding sequence (CDS) are well-known mRNA parts controlling translation and thus cellular protein levels. However, the complex interaction of 5′-UTR and CDS has so far only been studied for few sequences leading to non-generalisable and partly contradictory conclusions. Herein, we systematically assess the dynamic translation from over 1.2 million 5′-UTR-CDS pairs in Escherichia coli to investigate their collective effect using a new method for ultradeep sequence-function mapping. This allows us to disentangle and precisely quantify effects of various sequence determinants of translation. We find that 5′-UTR and CDS individually account for 53% and 20% of variance in translation, respectively, and show conclusively that, contrary to a common hypothesis, tRNA abundance does not explain expression changes between CDSs with different synonymous codons. Moreover, the obtained large-scale data provide clear experimental evidence for a base-pairing interaction between initiator tRNA and mRNA beyond the anticodon-codon interaction, an effect that is often masked for individual sequences and therefore inaccessible to low-throughput approaches. Our study highlights the indispensability of ultradeep sequence-function mapping to accurately determine the contribution of parts and phenomena involved in gene regulation.
Recovering false negatives in CRISPR fitness screens with JLOE
Authors: Dede Merve , Hart Traver 
Published: February 2023

AbstractIt is widely accepted that pooled library CRISPR knockout screens offer greater sensitivity and specificity than prior technologies in detecting genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the assumption that CRISPR screens are saturating has been largely untested. Through integrated analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we show that a typical CRISPR screen has a ∼20% false negative rate, in addition to library-specific false negatives. Replicability falls sharply as gene expression decreases, while cancer subtype-specific genes within a tissue show distinct profiles compared to false negatives. Cumulative analyses across tissues improves our understanding of core essential genes and suggest only a small number of lineage-specific essential genes, enriched for transcription factors that define pathways of tissue differentiation. To recover false negatives, we introduce a method, Joint Log Odds of Essentiality (JLOE), which builds on our prior work with BAGEL to selectively rescue the false negatives without an increased false discovery rate.
Ribosomes lacking bS21 gain function to regulate protein synthesis inFlavobacterium johnsoniae
Authors: McNutt Zakkary A , Roy Bappaditya , Gemler Bryan T , Shatoff Elan A , Moon Kyung-Mee , Foster Leonard J , Bundschuh Ralf , Fredrick Kurt 
Published: February 2023

AbstractRibosomes of Bacteroidia (formerly Bacteroidetes) fail to recognize Shine-Dalgarno (SD) sequences even though they harbor the anti-SD (ASD) of 16S rRNA. Inhibition of SD-ASD pairing is due to sequestration of the 3’ tail of 16S rRNA in a pocket formed by bS21, bS18, and bS6 on the 30S platform. Interestingly, in many Flavobacteriales, the gene encoding bS21, rpsU, contains an extended SD sequence. In this work, we present genetic and biochemical evidence that bS21 synthesis in Flavobacterium johnsoniae is autoregulated via a subpopulation of ribosomes that specifically lack bS21. Mutation or depletion of bS21 in the cell increases translation of reporters with strong SD sequences, such as rpsU’-gfp, but has no effect on other reporters. Purified ribosomes lacking bS21 (or its C-terminal region) exhibit higher rates of initiation on rpsU mRNA and lower rates of initiation on other (SD-less) mRNAs than control ribosomes. The mechanism of autoregulation depends on extensive pairing between mRNA and 16S rRNA, and exceptionally strong SD sequences, with predicted pairing free energies of &lt; –13 kcal/mol, are characteristic of rpsU across the Bacteroidota. This work uncovers a clear example of specialized ribosomes in bacteria.
The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials
Authors: Fischer Jordie A J , Cherian Arlin M , Bone Jeffrey N , Karakochuk Crystal D 
Published: February 2023

Abstract

Context
Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.

Objective
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.

Data sources
A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks’ supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.

Data extraction
Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.

Data analysis
Compared with other iron supplements, supplementation with ferrous bisglycinate for 4–20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15–0.94; P &lt; 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17–0.76; P &lt; 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.

Conclusion
Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.

PROSPERO registration no
CRD42020196984.
Outcome of Patients With Malignant Peripheral Nerve Sheath Tumors Enrolled on Sarcoma Alliance for Research Through Collaboration (SARC) Phase II Trials
Authors: Akshintala Srivandana , Mallory Nicole C , Lu Yao , Ballman Karla V , Schuetze Scott M , Chugh Rashmi , Maki Robert G , Reinke Denise K , Widemann Brigitte C , Kim AeRang 
Published: February 2023

Abstract

Background
Evaluation of prior phase II trials for malignant peripheral nerve sheath tumors (MPNST) may help develop more suitable trial endpoints in future studies.

Methods
We analyzed outcomes of patients with recurrent or unresectable/metastatic MPNST enrolled on prior Sarcoma Alliance for Research through Collaboration (SARC) phase II trials and estimated the progression-free survival (PFS). PFS from SARC006 (NCT 00304083), the phase II trial of upfront chemotherapy in chemotherapy naïve patients, was analyzed separately. Impact of baseline enrollment characteristics on PFS was evaluated.

Results
Sixty-four patients (29 male, 35 female, median age 39 years (range 15-81)) with MPNST were enrolled on 1 of 5 trials of single agent or combination therapy that were determined to be inactive. Patients had received a median of 1 (range 0-5) prior systemic therapy, and most had undergone prior surgery (77%) and radiation (61%). Seventy-three percent had metastatic disease at enrollment. Median PFS was 1.77 months (95% CI, 1.61-3.45), and the PFS rate at 4 months was 15%. Greater number of prior systemic therapies and worse performance status were associated with inferior PFS. There was no significant difference in PFS based on age at enrollment, treatment trial, response criteria, presence of metastatic disease, disease site at enrollment, and prior surgery or radiation. In comparison, on the SARC006 trial the PFS rate at 4 months was 94% in 40 patients.

Conclusion
These data provide a historical baseline PFS that may be used as a comparator in future clinical trials for patients with MPNST.
Effects of Electrical Brain Stimulation on Motor Learning
Authors: Karabanov Anke Ninija , Tzvi-Minker Elinor 
Published: February 2023

Abstract
Motor learning is important for many aspects of daily life and includes the acquisition of new skills as well as the adaptation of a known motor pattern to novel environmental conditions. Transcranial electric stimulation (TES) can be applied in connection with motor learning to boost performance in health and disease. In this chapter, we review the ability of TES, in its different forms, to interact with learning, retention, and adaptation of motor skills. We will discuss the influence of stimulation settings, stimulation timing, and the specific cortical target on different forms of motor learning, and relate behavioral effects of stimulation to local brain activity and interregional connectivity. We conclude the chapter highlighting the applied aspect of TES research in motor skill learning on rehabilitation of patients suffering stroke and movement disorders, as well as in experts seeking to boost performance.
Green means go: Green light promotes hypocotyl elongation via brassinosteroid signaling
Authors: Hao Yuhan , Zeng Zexian , Zhang Xiaolin , Xie Dixiang , Li Xu , Ma Libang , Liu Muqing , Liu Hongtao 
Published: February 2023

Abstract
Although many studies have elucidated the mechanisms by which different wavelengths of light (blue, red, far-red, or ultraviolet-B [UV-B]) regulate plant development, whether and how green light regulates plant development remains largely unknown. Previous studies reported that green light participates in regulating growth and development in land plants, but these studies have reported conflicting results, likely due to technical problems. For example, commercial green light-emitting diode light sources emit a little blue or red light. Here, using a pure green light source, we determined that unlike blue, red, far-red, or UV-B light, which inhibits hypocotyl elongation, green light promotes hypocotyl elongation in Arabidopsis thaliana and several other plants during the first 2–3 d after planting. Phytochromes, cryptochromes, and other known photoreceptors do not mediate green-light-promoted hypocotyl elongation, but the brassinosteroid (BR) signaling pathway is involved in this process. Green light promotes the DNA binding activity of BRI1-EMS-SUPPRESSOR 1 (BES1), a master transcription factor of the BR pathway, thus regulating gene transcription to promote hypocotyl elongation. Our results indicate that pure green light promotes elongation via BR signaling and acts as a shade signal to enable plants to adapt their development to a green-light-dominant environment under a canopy.
ETHYLENE RESPONSE FACTORS 4.1/4.2 with an EAR motif repress anthocyanin biosynthesis in red-skinned pears
Authors: Sun Hongye , Hu Kangdi , Wei Shuwei , Yao Gaifang , Zhang Hua 
Published: February 2023

Abstract
Red-skinned pears (Pyrus L.) are preferred to consumers for their attractive color and abundant anthocyanins. Pyrus ETHYLENE RESPONSE FACTOR 3 (PyERF3) positively regulates anthocyanin biosynthesis through interacting with Pyrus myeloblastosis family 114 (PyMYB114) and Pyrus basic helix-loop-helix 3 (PybHLH3) in red-skinned pears. However, the role of APETALA2/ethylene response factors (AP2/ERFs), which negatively regulate anthocyanin biosynthesis, remains unclear in red-skinned pears. Here, we validated that 2 AP2/ERFs, PyERF4.1 and PyERF4.2, screened from the transcriptome data of ‘Starkrimson’ pear (Pyrus communis L.) and its green mutant, inhibit anthocyanin biosynthesis in transgenic pear calli, as well as in overexpression and gene-edited tomato (Solanum lycopersicum) fruits. Meanwhile, the co-transformation of PyERF4.1/PyERF4.2 with PyERF3–PyMYB114–PybHLH3 inhibited anthocyanin biosynthesis in pear fruits and strawberry (Fragaria vesca) receptacles. Further assays showed that PyMYB114 activated the transcription of PyERF4.1/PyERF4.2; PyERF4.1/PyERF4.2 then interacted with PyERF3 to affect the stability of the PyERF3–PyMYB114–PybHLH3 complex, thereby inhibiting the transcription of the anthocyanin biosynthesis gene Pyrus anthocyanidin synthase (PyANS). Furthermore, deletion of the ERF-associated-amphiphilic repression (EAR) motif eliminated the inhibitory effect of PyERF4.1/PyERF4.2 on anthocyanin biosynthesis, and a mutation of the PyERF4.2-EAR motif (LxLxM to LxLxL) strengthened the inhibitory effect, demonstrating that the EAR motif is indispensable for the inhibitory effect of PyERF4.1/PyERF4.2 on anthocyanin biosynthesis in pears. Our study has shed light on a feedback regulatory loop mechanism that balances the excessive accumulation of anthocyanins in red-skinned pears, providing insights into the regulatory mechanism of anthocyanin biosynthesis and the regulatory network of coloration in red-skinned pears.
Dual biologic therapy for the treatment of rheumatic diseases and asthma: a case series
Authors: Malik Mariam , Jones Bryony , Williams Emma , Kurukulaaratchy Ramesh , Holroyd Chris , Mason Alice 
Published: February 2023

Abstract

Objective
Combination biological therapies are being considered increasingly for patients with multiple co-morbidities requiring biologics. There are limited data available on this approach, and concerns remain about the possible risk of adverse events, particularly infection.

Methods
We present three patients on dual biologics for rheumatic disease and asthma. The biologic combinations used were etanercept and mepolizumab, infliximab and omalizumab, and etanercept and omalizumab. The time on combination biologic therapies ranged from 24 to 36 months. Patients were monitored for any serious adverse events.

Results
All three patients were able to tolerate combined biologic therapies, with no serious adverse events. All three patients gained improvement in their rheumatic and asthma disease control, with reduction in disease activity scores and reduction in steroid usage.

Conclusion
The decision to start dual biologic therapy should be considered carefully, on a case-by-case basis. The number of patients who are on combination biological therapy is small, and data are sparse. Real-world data are needed to examine the long-term benefits and risks of different forms of combination biologic therapies.
In-depth characterization of pulmonary arterial hypertension in mixed connective tissue disease: a French national multicentre study
Authors: Chaigne Benjamin , Chevalier Kevin , Boucly Athenaïs , Agard Christian , Baudet Antoine , Bourdin Arnaud , Chabanne Céline , Cottin Vincent , Fesler Pierre , Goupil François , Jego Patrick , Launay David , Lévesque Hervé , Maurac Arnaud , Mohamed Shirine , Tromeur Cécile , Rottat Laurence , Sitbon Olivier , Humbert Marc , Mouthon Luc 
Published: February 2023

Abstract

Objective
Pulmonary arterial hypertension (PAH) is a leading cause of death in MCTD. We aimed to describe PAH in well-characterized MCTD patients.

Methods
MCTD patients enrolled in the French Pulmonary Hypertension Registry with a PAH diagnosis confirmed by right heart catheterization were included in the study and compared with matched controls: MCTD patients without PAH, SLE patients with PAH and SSc patients with PAH. Survival rates were estimated by the Kaplan–Meier method and risk factors for PAH in MCTD patients and risk factors for mortality in MCTD-PAH were sought using multivariate analyses.

Results
Thirty-six patients with MCTD-PAH were included in the study. Comparison with MCTD patients without PAH and multivariate analysis revealed that pericarditis, polyarthritis, thrombocytopenia, interstitial lung disease (ILD) and anti-Sm antibodies were independent predictive factors of PAH/PH in MCTD. Estimated survival rates at 1, 5 and 10 years following PAH diagnosis were 83%, 67% and 56%, respectively. MCTD-PAH presentation and survival did not differ from SLE-PAH and SSc-PAH. Multivariate analysis revealed that tobacco exposure was an independent factor predictive of mortality in MCTD-PAH.

Conclusion
PAH is a rare and severe complication of MCTD associated with a 56% 10-year survival. We identified ILD, pericarditis, thrombocytopenia and anti-Sm antibodies as risk factors for PAH in MCTD and tobacco exposure as a predictor of mortality in MCTD-PAH.