bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone strength and composition in spacefaring rodents: systematic review and meta-analysis
Authors: Goldsmith Matthew , Crooks Sequoia D. , Condon Sean F. , Willie Bettina M. , Komarova Svetlana V. 
Published: April 2022

AbstractStudying the effects of space travel on bone of experimental animals provides unique advantages, including the ability to perform post-mortem analysis and mechanical testing. To synthesize the available data to assess how much and how consistently bone strength and composition parameters are affected by spaceflight, we systematically identified studies reporting bone health in spacefaring animals from Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. Previously, we reported the effect of spaceflight on bone architecture and turnover in rodents and primates. For this study, we selected 28 articles reporting bone strength and composition in 60 rats and 60 mice from 17 space missions ranging from 7 to 33 days in duration. Whole bone mechanical indices were significantly decreased in spaceflight rodents, with the percent difference between spaceflight and ground control animals for maximum load of −15.24% [Confidence interval: −22.32, −8.17]. Bone mineral density and calcium content were significantly decreased in spaceflight rodents by −3.13% [−4.96, −1.29] and −1.75% [−2.97, −0.52] respectively. Thus, large deficits in bone architecture (6% loss in cortical area identified in a previous study) as well as changes in bone mass and tissue composition likely lead to bone strength reduction in spaceflight animals.
Nonlinear control of transcription through enhancer–promoter interactions
Authors: Zuin Jessica , Roth Gregory , Zhan Yinxiu , Cramard Julie , Redolfi Josef , Piskadlo Ewa , Mach Pia , Kryzhanovska Mariya , Tihanyi Gergely , Kohler Hubertus , Eder Mathias , Leemans Christ , van Steensel Bas , Meister Peter , Smallwood Sebastien , Giorgetti Luca 
Published: April 2022

AbstractChromosome structure in mammals is thought to regulate transcription by modulating three-dimensional interactions between enhancers and promoters, notably through CTCF-mediated loops and topologically associating domains (TADs)1–4. However, how chromosome interactions are actually translated into transcriptional outputs remains unclear. Here, to address this question, we use an assay to position an enhancer at large numbers of densely spaced chromosomal locations relative to a fixed promoter, and measure promoter output and interactions within a genomic region with minimal regulatory and structural complexity. A quantitative analysis of hundreds of cell lines reveals that the transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship. Mathematical modelling suggests that nonlinearity might arise from transient enhancer–promoter interactions being translated into slower promoter bursting dynamics in individual cells, therefore uncoupling the temporal dynamics of interactions from those of transcription. This uncovers a potential mechanism of how distal enhancers act from large genomic distances, and of how topologically associating domain boundaries block distal enhancers. Finally, we show that enhancer strength also determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation. Our measurements establish general principles for the context-dependent role of chromosome structure in long-range transcriptional regulation.
Prolonged viral suppression with anti-HIV-1 antibody therapy
Authors: Gaebler Christian , Nogueira Lilian , Stoffel Elina , Oliveira Thiago Y. , Breton Gaëlle , Millard Katrina G. , Turroja Martina , Butler Allison , Ramos Victor , Seaman Michael S. , Reeves Jacqueline D. , Petroupoulos Christos J. , Shimeliovich Irina , Gazumyan Anna , Jiang Caroline S. , Jilg Nikolaus , Scheid Johannes F. , Gandhi Rajesh , Walker Bruce D. , Sneller Michael C. , Fauci Anthony , Chun Tae-Wook , Caskey Marina , Nussenzweig Michel C. 
Published: April 2022

AbstractHIV-1 infection remains a public health problem with no cure. Anti-retroviral therapy (ART) is effective but requires lifelong drug administration owing to a stable reservoir of latent proviruses integrated into the genome of CD4+ T cells1. Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells2,3. Here we report on a clinical study in which people living with HIV received seven doses of a combination of two broadly neutralizing antibodies over 20 weeks in the presence or absence of ART. Without pre-screening for antibody sensitivity, 76% (13 out of 17) of the volunteers maintained virologic suppression for at least 20 weeks off ART. Post hoc sensitivity analyses were not predictive of the time to viral rebound. Individuals in whom virus remained suppressed for more than 20 weeks showed rebound viraemia after one of the antibodies reached serum concentrations below 10 µg ml−1. Two of the individuals who received all seven antibody doses maintained suppression after one year. Reservoir analysis performed after six months of antibody therapy revealed changes in the size and composition of the intact proviral reservoir. By contrast, there was no measurable decrease in the defective reservoir in the same individuals. These data suggest that antibody administration affects the HIV-1 reservoir, but additional larger and longer studies will be required to define the precise effect of antibody immunotherapy on the reservoir.
Somatic mutation rates scale with lifespan across mammals
Authors: Cagan Alex , Baez-Ortega Adrian , Brzozowska Natalia , Abascal Federico , Coorens Tim H. H. , Sanders Mathijs A. , Lawson Andrew R. J. , Harvey Luke M. R. , Bhosle Shriram , Jones David , Alcantara Raul E. , Butler Timothy M. , Hooks Yvette , Roberts Kirsty , Anderson Elizabeth , Lunn Sharna , Flach Edmund , Spiro Simon , Januszczak Inez , Wrigglesworth Ethan , Jenkins Hannah , Dallas Tilly , Masters Nic , Perkins Matthew W. , Deaville Robert , Druce Megan , Bogeska Ruzhica , Milsom Michael D. , Neumann Björn , Gorman Frank , Constantino-Casas Fernando , Peachey Laura , Bochynska Diana , Smith Ewan St. John , Gerstung Moritz , Campbell Peter J. , Murchison Elizabeth P. , Stratton Michael R. , Martincorena Iñigo 
Published: April 2022

AbstractThe rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans1–7. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans8, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.
Selective feeding of three bivalve species on the phytoplankton community in a marine pond revealed by high-throughput sequencing
Authors: Qiao Ling , Chang Zhiqiang , Li Jian , Li Tiejun 
Published: April 2022

AbstractThe study of the selective feeding of bivalves is necessary in order to improve our understanding of bivalve growth and development, which helps to better define the roles of bivalves in their ecosystems. Little information is currently available on the feeding preferences of bivalves in natural waters, since all diets are provided as single or mixed algae in experiments. In this study, high-throughput sequencing of the 23S rRNA gene was performed to explore differences in the feeding selectivity ofMercenaria mercenaria,Meretrix meretrixandRuditapes philippinarumduring different stages of their culturing to reveal their feeding preferences in natural waters. We found that the three bivalve species had different preferential selection of phytoplankton genera, indicating specific selection and avoidance of particular types of algae during their development in aquaculture.M. mercenariawas the most selective of the bivalves, followed byM. meretrixand thenR. philippinarum. With the growth ofM. mercenariaandM. meretrix, more kinds of phytoplankton could be ingested. In addition, high-throughput sequencing showed that some picophytoplankton includingSynechococcus,Microchloropsis,andChrysochromulinawere dominant in the hepatopancreas samples obtained from these three bivalves. Therefore, the importance of these pico-sized algae in bivalve diets should be reassessed.
Amplification of elliptically polarized sub-femtosecond pulses in neon-like X-ray laser modulated by an IR field
Authors: Khairulin I. R. , Antonov V. A. , Ryabikin M. Yu. , Berrill M. A. , Shlyaptsev V. N. , Rocca J. J. , Kocharovskaya Olga 
Published: April 2022

AbstractAmplification of attosecond pulses produced via high harmonic generation is a formidable problem since none of the amplifiers can support the corresponding PHz bandwidth. Producing the well defined polarization state common for a set of harmonics required for formation of the circularly/elliptically polarized attosecond pulses (which are on demand for dynamical imaging and coherent control of the spin flip processes) is another big challenge. In this work we show how both problems can be tackled simultaneously on the basis of the same platform, namely, the plasma-based X-ray amplifier whose resonant transition frequency is modulated by an infrared field.
Household air pollution from solid fuel use as a dose-dependent risk factor for cognitive impairment in northern China
Authors: Tseng Tzu-Wei Joy , Carter Ellison , Yan Li , Chan Queenie , Elliott Paul , Ezzati Majid , Kelly Frank , Schauer James J. , Wu Yangfeng , Yang Xudong , Zhao Liancheng , Baumgartner Jill 
Published: April 2022

AbstractThe relationship between exposure to household air pollution (HAP) from solid fuel use and cognition remains poorly understood. Among 401 older adults in peri-urban northern China enrolled in the INTERMAP-China Prospective Study, we estimated the associations between exposure to HAP and z-standardized domain-specific and overall cognitive scores from the Montreal Cognitive Assessment. Interquartile range increases in exposures to fine particulate matter (53.2-µg/m3) and black carbon (0.9-µg/m3) were linearly associated with lower overall cognition [− 0.13 (95% confidence interval: − 0.22, − 0.04) and − 0.10 (− 0.19, − 0.01), respectively]. Using solid fuel indoors and greater intensity of its use were also associated with lower overall cognition (range of point estimates: − 0.13 to − 0.03), though confidence intervals included zero. Among individual cognitive domains, attention had the largest associations with most exposure measures. Our findings indicate that exposure to HAP may be a dose-dependent risk factor for cognitive impairment. As exposure to HAP remains pervasive in China and worldwide, reducing exposure through the promotion of less-polluting stoves and fuels may be a population-wide intervention strategy to lessen the burden of cognitive impairment.
Oscillatory calcium release and sustained store-operated oscillatory calcium signaling prevents differentiation of human oligodendrocyte progenitor cells
Authors: Seidman Richard A. , Khattab Heba , Polanco Jessie J. , Broome Jacqueline E. , Sim Fraser J. 
Published: April 2022

AbstractEndogenous remyelination in demyelinating diseases such as multiple sclerosis is contingent upon the successful differentiation of oligodendrocyte progenitor cells (OPCs). Signaling via the Gαq-coupled muscarinic receptor (M1/3R) inhibits human OPC differentiation and impairs endogenous remyelination in experimental models. We hypothesized that calcium release following Gαq-coupled receptor (GqR) activation directly regulates human OPC (hOPC) cell fate. In this study, we show that specific GqR agonists activating muscarinic and metabotropic glutamate receptors induce characteristic oscillatory calcium release in hOPCs and that these agonists similarly block hOPC maturation in vitro. Both agonists induce calcium release from endoplasmic reticulum (ER) stores and store operated calcium entry (SOCE) likely via STIM/ORAI-based channels. siRNA mediated knockdown (KD) of obligate calcium sensors STIM1 and STIM2 decreased the magnitude of muscarinic agonist induced oscillatory calcium release and attenuated SOCE in hOPCs. In addition, STIM2 expression was necessary to maintain the frequency of calcium oscillations and STIM2 KD reduced spontaneous OPC differentiation. Furthermore, STIM2 siRNA prevented the effects of muscarinic agonist treatment on OPC differentiation suggesting that SOCE is necessary for the anti-differentiative action of muscarinic receptor-dependent signaling. Finally, using a gain-of-function approach with an optogenetic STIM lentivirus, we demonstrate that independent activation of SOCE was sufficient to significantly block hOPC differentiation and this occurred in a frequency dependent manner while increasing hOPC proliferation. These findings suggest that intracellular calcium oscillations directly regulate hOPC fate and that modulation of calcium oscillation frequency may overcome inhibitory Gαq-coupled signaling that impairs myelin repair.
Estradiol inhibits HIV-1BaL infection and induces CFL1 expression in peripheral blood mononuclear cells and endocervical mucosa
Authors: Verma N. , Mukhopadhyay S. , Barnable P. , Plagianos M. G. , Teleshova N. 
Published: April 2022

AbstractAn inhibitory effect of estradiol (E2) on HIV-1 infection was suggested by several reports. We previously identified increased gene expression of actin-binding protein cofilin 1 (CFL1) in endocervix in the E2-dominated proliferative phase of the menstrual cycle. Actin cytoskeleton has an integral role in establishing and spreading HIV-1 infection. Herein, we studied in vitro effects of E2 on HIV-1 infection and on CFL1 expression to gain insight into the mechanism of HIV-1 inhibition by E2. E2 dose-dependently inhibited HIV-1BaL infection in peripheral blood mononuclear cells (PBMCs) and endocervix. In PBMCs and endocervix, E2 increased protein expression of total CFL1 and phosphorylated CFL1 (pCFL1) and pCFL1/CFL1 ratios. LIMKi3, a LIM kinase 1 and 2 inhibitor, abrogated the phenotype and restored infection in both PBMCs and endocervix; inhibited E2-induced expression of total CFL1, pCFL1; and decreased pCFL1/CFL1 ratios. Knockdown of CFL1 in PBMCs also abrogated the phenotype and partially restored infection. Additional analysis of soluble mediators revealed decreased concentrations of pro-inflammatory chemokines CXCL10 and CCL5 in infected tissues incubated with E2. Our results suggest a link between E2-mediated anti-HIV-1 activity and expression of CFL1 in PBMCs and endocervical mucosa. The data support exploration of cytoskeletal signaling pathway targets for the development of prevention strategies against HIV-1.
Predicting outcomes for locally advanced rectal cancer treated with neoadjuvant chemoradiation with CT-based radiomics
Authors: Wang Fuqiang , Tan Boon Fei , Poh Sharon Shuxian , Siow Tian Rui , Lim Faye Lynette Wei Tching , Yip Connie Siew Poh , Wang Michael Lian Chek , Nei Wenlong , Tan Hong Qi 
Published: April 2022

AbstractA feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score (< 8) has been correlated with better outcomes and high NAR score (> 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR < 8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR > 16 and NAR < 8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model. The most important clinical features are age and CEA for NAR > 16 and NAR < 8 models respectively, while the most significant clinical features are age, surgical margin and NAR score across all the four survival models.
Instability motion characteristics of overburden rock and the distribution pattern of fissures in shallow thick seam mining
Authors: Li Jianwei , Liu Changyou , Guo Xinwei , Wu Xiangye 
Published: April 2022

AbstractThis paper analyzes the instability movement characteristics of overburden in shallow thick coal seam mining and its influence on the development and distribution of fault fractures. The similarity simulation experiment and theoretical analysis were combined based on the classification of the occurrence characteristics of the key bearing layer in the overburden rock of shallow thick seam mining. This study investigated the fracture characteristics and the instability motion mode of the key bearing layer in shallow thick seam mining and their effects on the distribution of fissures in the overburden rock. The results indicated that according to the horizon of the key bearing layer, the occurrence of overburden rock could be classified into 2 categories, i.e., the horizon of the key bearing layer within the caving zone and within the fissure zone. The horizon of the key bearing layer has a significant effect on the fracture characteristics and the instability motion mode of the key bearing layer. When the horizon of the key bearing layer is in the overburden caving zone, a "step rock beam" develops after fracture, and the instability motion mode is sliding instability. When the horizon of the key bearing layer is in the overburden fissure zone, a "masonry-like beam" develops after fracture, and the instability motion mode is rotary instability. The fracture instability of the key bearing layer could control the development and distribution of fissures in the overburden rock, and the whole favorable zone for the development of fissures extends along the advancing direction of the working face in a form of "diagonal stripes" with the instability motion of the key bearing layer.
RETRACTED ARTICLE: Functionalized graphene oxide nanosheets with folic acid and silk fibroin as a novel nanobiocomposite for biomedical applications
Authors: Eivazzadeh-Keihan Reza , Alimirzaloo Farkhondeh , Aghamirza Moghim Aliabadi Hooman , Bahojb Noruzi Ehsan , Akbarzadeh Ali Reza , Maleki Ali , Madanchi Hamid , Mahdavi Mohammad 
Published: April 2022

AbstractIn this paper, a novel graphene oxide-folic acid/silk fibroin (GO-FA/SF) nanobiocomposite scaffold was designed and fabricated using affordable and non-toxic materials. The GO was synthesized using the hummer method, covalently functionalized with FA, and then easily conjugated with extracted SF via the freeze-drying process. For characterization of the scaffold, several techniques were employed: Fourier-transform infrared (FT-IR), field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX), and thermogravimetric analysis (TGA). The cell viability method, hemolysis, and anti-biofilm assays were performed, exploring the biological capability of the nanobiocomposite. The cell viability percentages were 96.67, 96.35 and 97.23% for 24, 48, and 72 h, respectively, and its hemolytic effect was less than 10%. In addition, it was shown that this nanobiocomposite prevents the formation of Pseudomonas aeruginosa biofilm and has antibacterial activity.
Redeployment of odontode gene regulatory network underlies dermal denticle formation and evolution in suckermouth armored catfish
Authors: Mori Shunsuke , Nakamura Tetsuya 
Published: April 2022

AbstractOdontodes, i.e., teeth and tooth-like structures, consist of a pulp cavity and dentin covered by a mineralized cap. These structures first appeared on the outer surface of vertebrate ancestors and were repeatedly lost and gained across vertebrate clades; yet, the underlying genetic mechanisms and trajectories of this recurrent evolution remain long-standing mysteries. Here, we established suckermouth armored catfish (Ancistrus sp.; Loricariidae), which have reacquired dermal odontodes (dermal denticles) all over most of their body surface, as an experimental model animal amenable to genetic manipulation for studying odontode development. Our histological analysis showed that suckermouth armored catfish develop dermal denticles through the previously defined odontode developmental stages. De novo transcriptomic profiling identified the conserved odontode genetic regulatory network (oGRN) as well as expression ofpaired like homeodomain 2(pitx2), previously known as an early regulator of oGRN in teeth but not in other dermal odontodes, in developing dermal denticles. The early onset ofpitx2expression in cranial dermal denticle placodes implies its function as one of the inducing factors of the cranial dermal denticles. By comprehensively identifying the genetic program for dermal odontode development in suckermouth armored catfish, this work illuminates how dermal odontodes might have evolved and diverged in distinct teleost lineages via redeployment of oGRN.