bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of the auxiliary α2δ1 voltage sensitive calcium channel subunit in osteocytes and late-stage osteoblasts impairs femur strength and load-induced bone formation in male mice
Authors: Wright Christian S , Lewis Karl J , Semon Katelyn , Yi Xin , Reyes Fernandez Perla C , Rust Katie , Prideaux Matthew , Schneider Artur , Pederson Molly , Deosthale Padmini , Plotkin Lilian I , Hum Julia M , Sankar Uma , Farach-Carson Mary C , Robling Alexander G , Thompson William R 
Published: January 2024

Abstract
Osteocytes sense and respond to mechanical force by controlling the activity of other bone cells. However, the mechanisms by which osteocytes sense mechanical input and transmit biological signals remain unclear. Voltage-sensitive calcium channels (VSCCs) regulate calcium (Ca2+) influx in response to external stimuli. Inhibition or deletion of VSCCs impairs osteogenesis and skeletal responses to mechanical loading. VSCC activity is influenced by its auxiliary subunits, which bind the channel’s α1 pore-forming subunit to alter intracellular Ca2+ concentrations. The α2δ1 auxiliary subunit associates with the pore-forming subunit via a glycosylphosphatidylinositol anchor and regulates the channel’s calcium-gating kinetics. Knockdown of α2δ1 in osteocytes impairs responses to membrane stretch, and global deletion of α2δ1 in mice results in osteopenia and impaired skeletal responses to loading in vivo. Therefore, we hypothesized that the α2δ1 subunit functions as a mechanotransducer, and its deletion in osteocytes would impair skeletal development and load-induced bone formation. Mice (C57BL/6) with LoxP sequences flanking Cacna2d1, the gene encoding α2δ1, were crossed with mice expressing Cre under the control of the Dmp1 promoter (10 kb). Deletion of α2δ1 in osteocytes and late-stage osteoblasts decreased femoral bone quantity (P &lt; .05) by DXA, reduced relative osteoid surface (P &lt; .05), and altered osteoblast and osteocyte regulatory gene expression (P &lt; .01). Cacna2d1f/f, Cre + male mice displayed decreased femoral strength and lower 10-wk cancellous bone in vivo micro-computed tomography measurements at the proximal tibia (P &lt; .01) compared to controls, whereas Cacna2d1f/f, Cre + female mice showed impaired 20-wk cancellous and cortical bone ex vivo micro-computed tomography measurements (P &lt; .05) vs controls. Deletion of α2δ1 in osteocytes and late-stage osteoblasts suppressed load-induced calcium signaling in vivo and decreased anabolic responses to mechanical loading in male mice, demonstrating decreased mechanosensitivity. Collectively, the α2δ1 auxiliary subunit is essential for the regulation of osteoid-formation, femur strength, and load-induced bone formation in male mice.
Nonsteaming method improves the nutritional value and utilization efficiency of silkworm artificial diets
Authors: Wang Guang , Xu Xiang-Xing , Ma Lu , Yang Jia-Meng , Yang Bao-Cheng , Peng Ru-Ji , Pan Zhong-Hua , Sima Yang-Hu , Xu Shi-Qing 
Published: January 2024

Abstract
Artificial diets for silkworms overcome the seasonal limitations of traditional rearing methods with fresh mulberry leaves. However, the current wet artificial diets, steamed at high temperatures, are not favored by silkworms, and they are cumbersome and challenging to preserve. These conditions adversely affected the development of artificial diet-based sericulture production. In this study, we disinfected dry powder diets with radiation and added distilled water without steaming before use. Then, the nutritional value of finished diets and their impact on silkworm development was assessed. Compared with steamed diets, nonsteamed diets were more attractive to silkworms. Chemical assays showed significantly more essential nutrients for silkworms, including l-ascorbic acid, vitamin B1, vitamin B2, and urease in nonsteamed diets than in steamed diets. Feeding fifth-instar silkworm larvae with nonsteamed diets significantly improved the ammonia utilization efficiency of the diet and increased the cocoon shell rate and diet/silk protein conversion efficiency by 5.9% and 13.3%, respectively. When fed with nonsteamed diets, the abundance of aerobic microorganisms in silkworm intestines increased and the abundance of pathogenic bacteria decreased. Furthermore, the vitality of the silkworm, measured by the dead worm cocoon rate, significantly improved by 16.90%. In summary, preparing sterile wet diets without high-temperature steaming effectively improved the nutritional value of the diet and enhanced silkworm growth.
Development of platensimycin, platencin, and platensilin overproducers by biosynthetic pathway engineering and fermentation medium optimization
Authors: Fluegel Lucas L , Deng Ming-Rong , Su Ping , Kalkreuter Edward , Yang Dong , Rudolf Jeffrey D , Dong Liao-Bin , Shen Ben 
Published: January 2024

Abstract

The platensimycin (PTM), platencin (PTN), and platensilin (PTL) family of natural products continues to inspire the discovery of new chemistry, enzymology, and medicine. Engineered production of this emerging family of natural products, however, remains laborious due to the lack of practical systems to manipulate their biosynthesis in the native-producing Streptomyces platensis species. Here we report solving this technology gap by implementing a CRISPR-Cas9 system in S. platensis CB00739 to develop an expedient method to manipulate the PTM, PTN, and PTL biosynthetic machinery in vivo. We showcase the utility of this technology by constructing designer recombinant strains S. platensis SB12051, SB12052, and SB12053, which, upon fermentation in the optimized PTM-MS medium, produced PTM, PTN, and PTL with the highest titers at 836 mg L−1, 791 mg L−1, and 40 mg L−1, respectively. Comparative analysis of these resultant recombinant strains also revealed distinct chemistries, catalyzed by PtmT1 and PtmT3, two diterpene synthases that nature has evolved for PTM, PTN, and PTL biosynthesis. The ΔptmR1/ΔptmT1/ΔptmT3 triple mutant strain S. platensis SB12054 could be envisaged as a platform strain to engineer diterpenoid biosynthesis by introducing varying ent-copalyl diphosphate-acting diterpene synthases, taking advantage of its clean metabolite background, ability to support diterpene biosynthesis in high titers, and the promiscuous tailoring biosynthetic machinery.

One-Sentence Summary
Implementation of a CRISPR-Cas9 system in Streptomyces platensis CB00739 enabled the construction of a suite of designer recombinant strains for the overproduction of platensimycin, platencin, and platensilin, discovery of new diterpene synthase chemistries, and development of platform strains for future diterpenoid biosynthesis engineering.
A phase II Japanese trial of 90-minute rituximab infusion for untreated B-cell lymphoma
Authors: Saito Toko , Nagai Hirokazu , Izutsu Koji , Ando Kiyoshi , Igarashi Tadahiko , Izumi Tohru , Ohashi Yasuo , Kamiyama Shuhei , Ishizawa Kenichi , Tobinai Kensei 
Published: January 2024

Abstract

Objective
This phase II clinical trial evaluated feasibility and tolerability of 90-minute rituximab infusion and a concentration of 4 mg/mL rituximab infusion in Japanese patients with previously untreated follicular lymphoma or diffuse large B-cell lymphoma.

Methods
Treatment was rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone. In cycle 1, rituximab at a dose of 375 mg/m2 (4 mg/mL) was administered at the standard infusion rate stipulated in the package insert. On confirmed tolerance of rituximab, patients received 90-minute infusion in second and subsequent cycles. The primary endpoint was incidence of grade 3 or higher infusion-related reactions during 90-minute rituximab infusion in cycle 2 of rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone.

Results
All 32 patients (median age 61.5 years, 16 males, 24 with diffuse large B-cell lymphoma) completed the prescribed six or eight cycles of treatment. One patient withdrew consent after cycle 1, and another developed grade 2 erythema and continued receiving 4 mg/mL at the standard infusion rate for cycle 2. The remaining 30 patients received 90-minute rituximab infusion; 28 (93.3%) completed cycle 2 at the scheduled infusion rate and dosage. No grade 3 or higher infusion-related reactions were associated with a concentration of 4 mg/mL rituximab dose or 90-min rituximab infusion in cycle 2. The most common infusion-related reaction symptoms were pruritus, hypertension and oropharyngeal discomfort. During the study, toxicities and adverse events were as expected, with no new safety signals.

Conclusion
High-concentration dosing (4 mg/mL) and 90-minute infusion of rituximab are feasible and tolerable in Japanese patients with previously untreated follicular lymphoma or diffuse large B-cell lymphoma.

Clinical trial number
JapicCTI-173 663.
Asymmetric crime dynamics in and out of lockdowns
Authors: Poblete-Cazenave Rubén 
Published: January 2024

Abstract
This article studies the dynamic impact of a temporary policy restricting social encounters due to coronavirus disease 2019 (COVID-19) on criminal activity in Bihar, India. Using a regression discontinuity design in time and criminal case—level and arrest data, I document an immediate drop in crime of over 35% due to the lockdown. Analysis over a longer timespan shows asymmetric dynamics by crime type. The lockdown was more effective in preventing personal crimes such as murders but was less effective in preventing property crimes, which increased beyond pre-lockdown levels once the lockdown was lifted. The increase in property crimes seems to be driven by temporal crime displacement from “former offenders” and not by “new offenders.” These asymmetric dynamics across crime types provide new insights into criminals’ intertemporal decisions (JEL K14, K42).
E3 ubiquitin ligase CBLB regulates innate immune responses and bacterial dissemination during nontuberculous mycobacteria infection
Authors: Sharma Jaishree , Mudalagiriyappa Srinivasu , Abdelaal Hazem F M , Kelly Thomas C , Choi Woosuk , Ponnuraj Nagendraprabhu , Vieson Miranda D , Talaat Adel M , Nanjappa Som Gowda 
Published: January 2024

Abstract
Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens causing pulmonary infection to fatal disseminated disease. NTM infections are steadily increasing in children and adults, and immune-compromised individuals are at a greater risk of fatal infections. The NTM disease's adverse pathology and resistance to antibiotics have further worsened the therapeutic measures. Innate immune regulators are potential targets for therapeutics to NTM, especially in a T cell–suppressed population, and many ubiquitin ligases modulate pathogenesis and innate immunity during infections, including mycobacterial infections. Here, we investigated the role of an E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (CBLB), in immunocompromised mouse models of NTM infection. We found that CBLB is essential to prevent bacterial growth and dissemination. Cblb deficiency debilitated natural killer cells, inflammatory monocytes, and macrophages in vivo. However, Cblb deficiency in macrophages did not wane its ability to inhibit bacterial growth or production of reactive oxygen species or interferon γ production by natural killer cells in vitro. CBLB restricted NTM growth and dissemination by promoting early granuloma formation in vivo. Our study shows that CBLB bolsters innate immune responses and helps prevent the dissemination of NTM during compromised T cell immunity.
Theory of communicative (dis)enfranchisement: introduction, explication, and application
Authors: Hintz Elizabeth A , Scharp Kristina M 
Published: January 2024

Abstract
In this essay, we set forth the theory of communicative (dis)enfranchisement (TCD). The TCD is useful for exploring the ramifications of the hegemonic ideologies which constrain and afford our everyday lives, and which are constructed and reflected in disenfranchising talk (DT). The TCD also asks what communication mechanisms work to reify and resist these hegemonic ideologies. We first introduce the warrant for this theorizing, then overview the assumptions of critical postmodernism and propositions of the TCD. We offer guidance for using the TCD via example research questions, suitable contexts, methodological tools, and conclusions researchers can potentially render. We offer criteria for evaluating the TCD regarding its consistency with critical postmodernism, utility as a heuristic framework, and capacity for claims-making. We respond to potential critiques of the TCD by distinguishing the TCD from six related bodies of communication theorizing, and by addressing the purported opaqueness of critical theorizing. Finally, we offer an example analysis to illustrate the TCD in research practice.
Merging Laggards
Authors: Padilla Jorge , Piccolo Salvatore , Reynolds Paul 
Published: January 2024

Abstract
We argue that mergers among market laggards (new entrants or innovation challengers) should be treated differently than those involving leaders (established players or first-mover innovators). We show that these mergers can be rivalry-enhancing, either by accelerating entry or promoting innovations, leading to lower quality-adjusted prices and higher consumer surplus. This is more likely to happen when entry (or innovation) costs are relatively high, so that entry (or innovation) is profitable only when it is limited to a few players. In these circumstances, if laggards enter, they will do so probabilistically and inefficiently since each of them would have to condition its entry to scenarios in which other laggards stay out, which may not be possible since entry decisions are secret. By removing or mitigating this coordination failure, a merger among laggards may lead to more entry (or innovation). Such a merger will also be more likely to benefit consumers when the products of laggards and leaders are sufficiently differentiated—that is, when competition is not too intense absent the merger. Importantly, we find that in the presence of fixed entry costs and endogenous entry, fixed cost synergies are relevant for assessing the welfare effects of mergers. These efficiencies enhance the social value of mergers among laggards insofar as they make entry into the market for the merged entity less costly, thereby expanding the spectrum of products available to consumer and increasing their welfare.
Fructose aggravates copper-deficiency-induced cardiac remodeling by inhibiting SERCA2a
Authors: Xu Yi , Xu Qiuxia , Zheng Zhirui , Jiang Xin , Shi Yuansen , Huang Yipu , Liu Yun 
Published: January 2024

Abstract

Objectives
Accumulating evidence demonstrates that copper deficiency (CuD) is a risk factor for cardiovascular diseases, besides, fructose has been strongly linked to the development of cardiovascular diseases. However, how CuD or fructose causes cardiovascular diseases is not clearly delineated. The present study aims to investigate the mechanism of CuD or fructose on cardiac remodeling.

Methods
We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague–Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks. In vitro study was performed by treating cardiomyocytes with tetrathiomolydbate (TM) and fructose. Echocardiography, histology analysis, immunofluorescence, western blotting, and qPCR were performed.

Key findings
Our findings revealed that CuD caused noticeable cardiac hypertrophy either in the presence or absence of fructose supplement. Fructose exacerbated CuD-induced cardiac remodeling and intramyocardial lipid accumulation. Furthermore, we presented that the inhibition of autophagic flux caused by Ca2+ disturbance is the key mechanism by which CuD- or fructose-induced cardiac remodeling. The reduced expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in cardiomyocytes accounts for the elevated cytoplasmic Ca2+ concentration.

Conclusions
Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.
Application of a derivative of human defensin 5 to treat ionizing radiation-induced enterogenic infection
Authors: Zhao Gaomei , He Yingjuan , Chen Yin , Jiang Yiyi , Li Chenwenya , Xiong Tainong , Han Songling , He Yongwu , Gao Jining , Su Yongping , Wang Junping , Wang Cheng 
Published: January 2024

Abstract
Enterogenic infection is a common complication for patients with radiation injury and requires efficient therapeutics in the clinic. Herein, we evaluated the promising drug candidate T7E21RHD5, which is a peptide derived from intestinal Paneth cell-secreted human defensin 5. Oral administration of this peptide alleviated the diarrhea symptoms of mice that received total abdominal irradiation (TAI, γ-ray, 12 Gy) and improved survival. Pathologic analysis revealed that T7E21RHD5 elicited an obvious mitigation of ionizing radiation (IR)-induced epithelial damage and ameliorated the reduction in the levels of claudin, zonula occluden 1 and occludin, three tight junction proteins in the ileum. Additionally, T7E21RHD5 regulated the gut microbiota in TAI mice by remodeling β diversity, manifested as a reversal of the inverted proportion of Bacteroidota to Firmicutes caused by IR. T7E21RHD5 treatment also decreased the abundance of pathogenic Escherichia–Shigella but significantly increased the levels of Alloprevotella and Prevotellaceae_NK3B31, two short-chain fatty acid-producing bacterial genera in the gut. Accordingly, the translocation of enterobacteria and lipopolysaccharide to the blood, as well as the infectious inflammatory responses in the intestine after TAI, was all suppressed by T7E21RHD5 administration. Hence, this versatile antimicrobial peptide possesses promising application prospects in the treatment of IR-induced enterogenic infection.
And how do LGB adults rate their orgasms in a relational context?
Authors: Sierra Juan Carlos , Muñoz-García Laura Elvira , Mangas Pablo 
Published: January 2024

Abstract

Background
Subjective orgasm experience (SOE) refers to the perception, assessment, and/or sensation of orgasm on a psychological level, with the particularity that the study of SOE in nonheterosexual populations is currently very scarce.

Aim
The study sought to analyze differences in SOE dimensions, comparing the intensity of each adjective of the Orgasm Rating Scale (ORS) and creating a ranking of the adjectives that better represent it in LGB men and women.

Methods
In a sample of 1475 adults organized into 4 groups according to the type of sexual relationships reported, comparisons were made using multivariate analysis of variance and chi-square tests.

Outcomes
Differences were obtained in the intensity of all the SOE dimensions, and in 23 of the 25 ORS adjectives.

Results
Lesbians and bisexual women reported higher intensity in SOE compared with bisexual and gay men.

Clinical Implications
Because the ORS has been established as a good tool for detecting orgasmic difficulties in nonheterosexual populations, this study could provide LGBT affirmative psychotherapy with evidence on how these individuals evaluate their orgasms in a relational context.

Strengths and Limitations
This study extends prior limited knowledge about how LGB people evaluate their orgasmic experiences in the context of sexual relationships. Despite this, the study poses limitations such as nonprobability sampling or the inclusion of exclusively cisgender and young individuals, making it difficult to generalize the results.

Conclusion
Although significant differences were found between LGB men and women, all groups agree on the adjectives they use to describe the subjective experience of orgasm in the context of sexual relationships; therefore, evidence is provided about how LGB people evaluate their orgasmic experiences in this context.
A HITRAN-formatted UV line list of S2-containing transitions involving X3 Σg-, B3 Σu-, and B″ 3 Πu electronic states
Authors: Gomez Frances M , Hargreaves Robert J , Gordon Iouli E 
Published: January 2024

ABSTRACT
The sulfur dimer (S2) is an important molecular constituent in cometary atmospheres and volcanic plumes on Jupiter’s moon Io. It is also expected to play an important role in the photochemistry of exoplanets. The ultraviolet (UV) spectrum of S2 contains transitions between vibronic levels above and below the dissociation limit, giving rise to a distinctive spectral signature. Using spectroscopic information from the literature, and the spectral simulation program PGOPHER, a UV line list of S2 is provided. This line list includes the primary $B\, ^{3}\Sigma ^{-}_{u}-X\, ^{3}\Sigma ^{-}_{g}$ (v′ = 0–27, v″ = 0–10) electronic transition, where vibrational bands with v′≥10 are pre-dissociated. Intensities have been calculated from existing experimental and theoretical oscillator strengths, and semi-empirical strengths for the pre-dissociated bands of S2 have been derived from comparisons with experimental cross-sections. The S2 line list also includes the $B^{\prime \prime }\, ^{3}\Pi _{u}-X\, ^{3}\Sigma ^{-}_{g}$ (v′ = 0–19, v″ = 0–10) vibronic bands due to the strong interaction with the B state. In summary, we present the new HITRAN-formatted S2 line list and its validation against existing laboratory spectra. The extensive line list covers the spectral range 21 700–41 300 cm−1 (∼242–461 nm) and can be used for modelling both absorption and emission.
Heating galaxy clusters with interacting dark matter
Authors: Shoji Yutaro , Kuflik Eric , Birnboim Yuval , Stone Nicholas C 
Published: January 2024

ABSTRACT
The overcooling of cool core clusters is a persistent puzzle in the astrophysics of galaxy clusters. We propose that it may naturally be resolved via interactions between the baryons of the intracluster medium (ICM) and its dark matter (DM). DM–baryon interactions can inject heat into the ICM to offset bremsstrahlung cooling, but these interactions are also strongly constrained by existing experiments and astrophysical observations. We survey existing constraints and combine these with the energetic needs of an observed sample of cool core clusters. We find that a robust parameter space exists for baryon–DM scattering solutions to the cooling flow problem, provided that only a sub-component of DM interacts strongly with the baryons. Interestingly, baryon–DM scattering is a thermally stable heating source so long as the baryon temperature is greater than 1/3 to 1/2 the DM temperature, a condition that seems to be satisfied observationally.
The formation of compact massive relic galaxies in MOND
Authors: Eappen Robin , Kroupa Pavel 
Published: January 2024

ABSTRACT
Compact massive relic galaxies are a class of galaxies that exhibit characteristics suggesting they have remained largely unchanged since their initial formation, making them ‘relics’ of the early Universe. These galaxies represent a distinct class characterized by strongly peaked high-velocity dispersion profiles with large rotational velocities. This study investigates the formation of such galaxies within the framework of Milgromian dynamics (MOND), offering a unique perspective on their origin without invoking the presence of cold or warm dark matter. Our analysis focuses on the collapse dynamics of isolated non-rotating post-big bang gas clouds, revealing kinematic and density profiles comparable to observed compact massive relic galaxies like NGC 1277, Mrk 1216, and PGC 032873. The findings underscore the natural emergence of compact massive relic galaxies within a MOND-based Universe, providing valuable insights into the interplay between gravitational dynamics and galaxy formation.