bluuebunny/crossref_metadata_2025_split huggingface dataset:
c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA
Authors: Li Bingyan , Zhang Guang , Wang Zhongyu , Yang Yang , Wang Chenfeng , Fang Debao , Liu Kaiyue , Wang Fang , Mei Yide 
Published: October 2021

AbstractThe c-Myc oncoprotein plays a prominent role in cancer initiation, progression, and maintenance. Long noncoding RNAs (lncRNAs) are recently emerging as critical regulators of the c-Myc signaling pathway. Here, we report the lncRNA USP2-AS1 as a direct transcriptional target of c-Myc. Functionally, USP2-AS1 inhibits cellular senescence and acts as an oncogenic molecule by inducing E2F1 expression. Mechanistically, USP2-AS1 associates with the RNA-binding protein G3BP1 and facilitates the interaction of G3BP1 to E2F1 3′-untranslated region, thereby leading to the stabilization of E2F1 messenger RNA. Furthermore, USP2-AS1 is shown as a mediator of the oncogenic function of c-Myc via the regulation of E2F1. Together, these findings suggest that USP2-AS1 is a negative regulator of cellular senescence and also implicates USP2-AS1 as an important player in mediating c-Myc function.
Effects of SARS CoV-2, COVID-19, and its vaccines on male sexual health and reproduction: where do we stand?
Authors: Lo Sharon P. , Hsieh Tung-Chin , Pastuszak Alexander W. , Hotaling James M. , Patel Darshan P. 
Published: October 2021

AbstractSince severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered, there have been questions surrounding the effects of coronavirus disease 2019 (COVID-19), and more recently the COVID-19 vaccine, on men’s health and fertility. Significant research has been conducted to study viral tropism, potential causes for gender susceptibility, the impact of COVID-19 on male sexual function in the acute and recovery phases, and the effects of the virus on male reproductive organs and hormones. This review provides a recent assessment of the literature regarding the impact of COVID-19 and its vaccine on male sexual health and reproduction.
Nuclear export of the pre-60S ribosomal subunit through single nuclear pores observed in real time
Authors: Ruland Jan Andreas , Krüger Annika Marie , Dörner Kerstin , Bhatia Rohan , Wirths Sabine , Poetes Daniel , Kutay Ulrike , Siebrasse Jan Peter , Kubitscheck Ulrich 
Published: October 2021

AbstractRibosomal biogenesis has been studied by biochemical, genetic and electron microscopic approaches, but live cell data on the in vivo kinetics are still missing. Here we analyse the export kinetics of the large ribosomal subunit (pre-60S particle) through single NPCs in human cells. We established a stable cell line co-expressing Halo-tagged eIF6 and GFP-fused NTF2 to simultaneously label pre-60S particles and NPCs, respectively. By combining single molecule tracking and super resolution confocal microscopy we visualize the dynamics of single pre-60S particles during export through single NPCs. For export events, maximum particle accumulation is found in the centre of the pore, while unsuccessful export terminates within the nuclear basket. The export has a single rate limiting step and a duration of ∼24 milliseconds. Only about 1/3 of attempted export events are successful. Our results show that the mass flux through a single NPC can reach up to ~125 MDa·s−1 in vivo.
A Newcastle disease virus expressing a stabilized spike protein of SARS-CoV-2 induces protective immune responses
Authors: Sun Weina , Liu Yonghong , Amanat Fatima , González-Domínguez Irene , McCroskery Stephen , Slamanig Stefan , Coughlan Lynda , Rosado Victoria , Lemus Nicholas , Jangra Sonia , Rathnasinghe Raveen , Schotsaert Michael , Martinez Jose L. , Sano Kaori , Mena Ignacio , Innis Bruce L. , Wirachwong Ponthip , Thai Duong Huu , Oliveira Ricardo Das Neves , Scharf Rami , Hjorth Richard , Raghunandan Rama , Krammer Florian , García-Sastre Adolfo , Palese Peter 
Published: October 2021

AbstractRapid development of COVID-19 vaccines has helped mitigating SARS-CoV-2 spread, but more equitable allocation of vaccines is necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine candidate based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here, we show that the NDV vector expressing an optimized spike antigen (NDV-HXP-S) is a versatile vaccine inducing protective antibody responses. NDV-HXP-S can be administered intramuscularly as inactivated vaccine or intranasally as live vaccine. We show that NDV-HXP-S GMP-produced in Vietnam, Thailand and Brazil is effective in the hamster model. Furthermore, we show that intramuscular vaccination with NDV-HXP-S reduces replication of tested variants of concerns in mice. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters.
Structure of PDE3A–SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells
Authors: Chen Jie , Liu Nan , Huang Yinpin , Wang Yuanxun , Sun Yuxing , Wu Qingcui , Li Dianrong , Gao Shuanhu , Wang Hong-Wei , Huang Niu , Qi Xiangbing , Wang Xiaodong 
Published: October 2021

AbstractMolecular glues are a class of small molecular drugs that mediate protein-protein interactions, that induce either the degradation or stabilization of target protein. A structurally diverse group of chemicals, including 17-β-estradiol (E2), anagrelide, nauclefine, and DNMDP, induces apoptosis by forming complexes with phosphodiesterase 3A (PDE3A) and Schlafen 12 protein (SLFN12). They do so by binding to the PDE3A enzymatic pocket that allows the compound-bound PDE3A to recruit and stabilize SLFN12, which in turn blocks protein translation, leading to apoptosis. In this work, we report the high-resolution cryo-electron microscopy structure of PDE3A-SLFN12 complexes isolated from cultured HeLa cells pre-treated with either anagrelide, or nauclefine, or DNMDP. The PDE3A-SLFN12 complexes exhibit a butterfly-like shape, forming a heterotetramer with these small molecules, which are packed in a shallow pocket in the catalytic domain of PDE3A. The resulting small molecule-modified interface binds to the short helix (E552-I558) of SLFN12 through hydrophobic interactions, thus “gluing” the two proteins together. Based on the complex structure, we designed and synthesized analogs of anagrelide, a known drug used for the treatment of thrombocytosis, to enhance their interactions with SLFN12, and achieved superior efficacy in inducing apoptosis in cultured cells as well as in tumor xenografts.
Fossil evidence unveils an early Cambrian origin for Bryozoa
Authors: Zhang Zhiliang , Zhang Zhifei , Ma Junye , Taylor Paul D. , Strotz Luke C. , Jacquet Sarah M. , Skovsted Christian B. , Chen Feiyang , Han Jian , Brock Glenn A. 
Published: October 2021

AbstractBryozoans (also known as ectoprocts or moss animals) are aquatic, dominantly sessile, filter-feeding lophophorates that construct an organic or calcareous modular colonial (clonal) exoskeleton1–3. The presence of six major orders of bryozoans with advanced polymorphisms in lower Ordovician rocks strongly suggests a Cambrian origin for the largest and most diverse lophophorate phylum2,4–8. However, a lack of convincing bryozoan fossils from the Cambrian period has hampered resolution of the true origins and character assembly of the earliest members of the group. Here we interpret the millimetric, erect, bilaminate, secondarily phosphatized fossil Protomelission gatehousei9 from the early Cambrian of Australia and South China as a potential stem-group bryozoan. The monomorphic zooid capsules, modular construction, organic composition and simple linear budding growth geometry represent a mixture of organic Gymnolaemata and biomineralized Stenolaemata character traits, with phylogenetic analyses identifying P. gatehousei as a stem-group bryozoan. This aligns the origin of phylum Bryozoa with all other skeletonized phyla in Cambrian Age 3, pushing back its first occurrence by approximately 35 million years. It also reconciles the fossil record with molecular clock estimations of an early Cambrian origination and subsequent Ordovician radiation of Bryozoa following the acquisition of a carbonate skeleton10–13.
Propulsion of magnetically actuated achiral planar microswimmers in Newtonian and non-Newtonian fluids
Authors: Chen Zhi , Wang Zihan , Quashie David , Benhal Prateek , Ali Jamel , Kim Min Jun , Cheang U Kei 
Published: October 2021

AbstractMagnetic achiral planar microswimmers can be massively fabricated at low cost and are envisioned to be useful for in vivo biomedical applications. To understand locomotion in representative in vivo environments, we investigated the swimming performance of achiral planar microswimmers in methylcellulose solutions. We observed that these microswimmers displayed very similar swimming characteristics in methylcellulose solutions as in water. Furthermore, this study indicated that the range of precession angles increased as the concentration of MC solution increased. Last, it was demonstrated that achiral planar microswimmers with similar precession angles exhibited nearly the same dimensionless speeds in different concentrations of the methylcellulose solutions. Upon understanding swimmer kinematics, more effective control over the achiral planar microswimmers can be achieved to perform multiple biomedical tasks in in vivo environments.
NRIP1 is activated by C-JUN/C-FOS and activates the expression of PGR, ESR1 and CCND1 in luminal A breast cancer
Authors: Binato Renata , Corrêa Stephany , Panis Carolina , Ferreira Gerson , Petrone Igor , da Costa Igor Rodrigues , Abdelhay Eliana 
Published: October 2021

AbstractUsing chip array assays, we identified differentially expressed genes via a comparison between luminal A breast cancer subtype and normal mammary ductal cells from healthy donors. In silico analysis confirmed by western blot and immunohistochemistry revealed that C-JUN and C-FOS transcription factors are activated in luminal A patients as potential upstream regulators of these differentially expressed genes. Using a chip-on-chip assay, we identified potential C-JUN and C-FOS targets. Among these genes, the NRIP1 gene was revealed to be targeted by C-JUN and C-FOS. This was confirmed after identification and validation with transfection assays specific binding of C-JUN and C-FOS at consensus binding sites. NRIP1 is not only upregulated in luminal A patients and cell lines but also regulates breast cancer-related genes, including PR, ESR1 and CCND1. These results were confirmed by NRIP1 siRNA knockdown and chip array assays, thus highlighting the putative role of NRIP1 in PGR, ESR1 and CCND1 transcriptional regulation and suggesting that NRIP1 could play an important role in breast cancer ductal cell initiation.
Estimating time-to-contact when vision is impaired
Authors: Hecht Heiko , Brendel Esther , Wessels Marlene , Bernhard Christoph 
Published: October 2021

AbstractOften, we have to rely on limited information when judging time-to-contact (TTC), as for example, when driving in foul weather, or in situations where we would need reading glasses but do not have them handy. However, most existing studies on the ability to judge TTC have worked with optimal visual stimuli. In a prediction motion task, we explored to what extent TTC estimation is affected by visual stimulus degradation. A simple computer-simulated object approached the observer at constant speed either with clear or impaired vision. It was occluded after 1 or 1.5 s. The observers extrapolated the object’s motion and pressed a button when they thought the object would have collided with them. We found that dioptric blur and simulated snowfall shortened TTC-estimates. Contrast reduction produced by a virtual semi-transparent mask lengthened TTC estimates, which could be the result of distance overestimation or speed underestimation induced by the lower contrast or the increased luminance of the mask. We additionally explored the potential influence of arousal and valence, although they played a minor role for basic TTC estimation. Our findings suggest that vision impairments have adverse effects on TTC estimation, depending on the specific type of degradation and the changes of the visual environmental cues which they cause.
Marine heatwaves in the Humboldt current system: from 5-day localized warming to year-long El Niños
Authors: Pietri Alice , Colas François , Mogollon Rodrigo , Tam Jorge , Gutierrez Dimitri 
Published: October 2021

AbstractDuring the last 4 decades punctual occurrences of extreme ocean temperatures, known as marine heatwaves (MHWs), have been regularly disrupting the coastal ecosystem of the Peru-Chile eastern boundary upwelling system. In fact, this coastal system and biodiversity hot-spot is regularly impacted by El Niño events, whose variability has been related to the longest and most intense MHWs in the world ocean. However the intensively studied El Niños tend to overshadow the MHWs of shorter duration that are significantly more common in the region. Using sea surface temperature data from 1982 to 2019 we investigate the characteristics and evolution of MHWs, distinguishing events by duration. Results show that long duration MHWs (> 100 days) preferentially affect the coastal domain north of 15° S and have decreased in both occurrence and intensity in the last four decades. On the other hand, shorter events, which represent more than 90% of all the observed MHWs, are more common south of 15° S and show an increase in their thermal impact as well as on the number of affected days, particularly those spanning 30–100 days. We also show that long duration MHWs variability in the coastal domain is well correlated with the remote equatorial variability while the onset of short events (< 10 days) generally goes along with a relaxation of the local coastal wind.
The c-Rel transcription factor limits early interferon and neuroinflammatory responses to prevent herpes simplex encephalitis onset in mice
Authors: Mancini Mathieu , Charbonneau Benoît , Langlais David , Vidal Silvia M. 
Published: October 2021

AbstractHerpes simplex virus type 1 (HSV-1) is the predominant cause of herpes simplex encephalitis (HSE), a condition characterized by acute inflammation and viral replication in the brain. Host genetics contribute to HSE onset, including monogenic defects in type I interferon signaling in cases of childhood HSE. Mouse models suggest a further contribution of immune cell-mediated inflammation to HSE pathogenesis. We have previously described a truncating mutation in the c-Rel transcription factor (RelC307X) that drives lethal HSE in 60% of HSV-1-infected RelC307X mice. In this study, we combined dual host-virus RNA sequencing with flow cytometry to explore cell populations and mechanisms involved in RelC307X-driven HSE. At day 5 postinfection, prior to HSE clinical symptom onset, elevated HSV-1 transcription was detected together with augmented host interferon-stimulated and inflammatory gene expression in the brainstems of high-responding RelC307X mice, predictive of HSE development. This early induction of host gene expression preceded pathological infiltration of myeloid and T cells in RelC307X mice at HSE onset by day 7. Thus, we establish c-Rel as an early regulator of viral and host responses during mouse HSE. These data further highlight the importance of achieving a balanced immune response and avoiding excess interferon-driven inflammation to promote HSE resistance.
Perceptions of AI engaging in human expression
Authors: Bower Alexander H. , Steyvers Mark 
Published: October 2021

AbstractThough humans should defer to the superior judgement of AI in an increasing number of domains, certain biases prevent us from doing so. Understanding when and why these biases occur is a central challenge for human-computer interaction. One proposed source of such bias is task subjectivity. We test this hypothesis by having both real and purported AI engage in one of the most subjective expressions possible: Humor. Across two experiments, we address the following: Will people rate jokes as less funny if they believe an AI created them? When asked to rate jokes and guess their likeliest source, participants evaluate jokes that they attribute to humans as the funniest and those to AI as the least funny. However, when these same jokes are explicitly framed as either human or AI-created, there is no such difference in ratings. Our findings demonstrate that user attitudes toward AI are more malleable than once thought—even when they (seemingly) attempt the most fundamental of human expressions.
In-depth proteomic profiling captures subtype-specific features of craniopharyngiomas
Authors: Kim Jung Hee , Kim Hyeyoon , Dan Kisoon , Kim Seong-Ik , Park Sung-Hye , Han Dohyun , Kim Yong Hwy 
Published: October 2021

AbstractCraniopharyngiomas are rare epithelial tumors derived from pituitary gland embryonic tissue. This epithelial tumor can be categorized as an adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) subtype with histopathological and genetic differences. Genomic and transcriptomic profiles of craniopharyngiomas have been investigated; however, the proteomic profile has yet to be elucidated and added to these profiles. Recent improvements in high-throughput quantitative proteomic approaches have introduced new opportunities for a better understanding of these diseases and the efficient discovery of biomarkers. We aimed to confirm subtype-associated proteomic changes between ACP and PCP specimens. We performed a system-level proteomic study using an integrated approach that combines mass spectrometry-based quantitative proteomic, statistical, and bioinformatics analyses. The bioinformatics analysis showed that differentially expressed proteins between ACP and PCP were significantly involved in mitochondrial organization, fatty acid metabolic processes, exocytosis, the inflammatory response, the cell cycle, RNA splicing, cell migration, and neuron development. Furthermore, using network analysis, we identified hub proteins that were positively correlated with ACP and PCP phenotypes. Our findings improve our understanding of the pathogenesis of craniopharyngiomas and provide novel insights that may ultimately translate to the development of craniopharyngioma subtype-specific therapeutics.
Nutritional restriction during the peri-conceptional period alters the myometrial transcriptome during the peri-implantation period
Authors: Drzewiecka Ewa Monika , Kozlowska Wiktoria , Zmijewska Agata , Franczak Anita 
Published: October 2021

AbstractThis study hypothesized that female peri-conceptional undernutrition evokes transcriptomic alterations in the pig myometrium during the peri-implantation period. Myometrium was collected on days 15–16 of pregnancy from pigs fed a normal- (n = 4) or restricted-diet (n = 4) from conception until day 9th of pregnancy, and the transcriptomic profiles of the tissue were compared using Porcine (V2) Expression Microarrays 4 × 44 K. In restricted diet-fed pigs, 1021 differentially expressed genes (DEGs) with fold change ≥ 1.5, P ≤ 0.05 were revealed, and 708 of them were up-regulated. Based on the count score, the top within GOs was GO cellular components “extracellular exosome”, and the top KEGG pathway was the metabolic pathway. Ten selected DEGs, i.e. hydroxysteroid (17β) dehydrogenase 8, cyclooxygenase 2, prostaglandin F receptor, progesterone receptor membrane component 1, progesterone receptor membrane component 2, annexin A2, homeobox A10, S-phase cyclin A-associated protein in the ER, SRC proto-oncogene, non-receptor tyrosine kinase, and proliferating cell nuclear antigen were conducted through qPCR to validate microarray data. In conclusion, dietary restriction during the peri-conceptional period causes alterations in the expression of genes encoding proteins involved i.a. in the endocrine activity of the myometrium, embryo-maternal interactions, and mechanisms regulating cell cycle and proliferation.
A pathophysiological model of gait captures the details of the impairment of pace/rhythm, variability and asymmetry in Parkinsonian patients at distinct stages of the disease
Authors: Godi Marco , Arcolin Ilaria , Giardini Marica , Corna Stefano , Schieppati Marco 
Published: October 2021

AbstractLocomotion in people with Parkinson’ disease (pwPD) worsens with the progression of disease, affecting independence and quality of life. At present, clinical practice guidelines recommend a basic evaluation of gait, even though the variables (gait speed, cadence, step length) may not be satisfactory for assessing the evolution of locomotion over the course of the disease. Collecting variables into factors of a conceptual model enhances the clinical assessment of disease severity. Our aim is to evaluate if factors highlight gait differences between pwPD and healthy subjects (HS) and do it at earlier stages of disease compared to single variables. Gait characteristics of 298 pwPD and 84 HS able to walk without assistance were assessed using a baropodometric walkway (GAITRite®). According to the structure of a model previously validated in pwPD, eight spatiotemporal variables were grouped in three factors: pace/rhythm, variability and asymmetry. The model, created from the combination of three factor scores, proved to outperform the single variables or the factors in discriminating pwPD from HS. When considering the pwPD split into the different Hoehn and Yahr (H&Y) stages, the spatiotemporal variables, factor scores and the model showed that multiple impairments of gait appear at H&Y stage 2.5, with the greatest difference from HS at stage 4. A contrasting behavior was found for the asymmetry variables and factor, which showed differences from the HS already in the early stages of PD. Our findings support the use of factor scores and of the model with respect to the single variables in gait staging in PD.
Multiple magnetic phase transitions with different universality classes in bilayer La$$_{1.4}$$Sr$$_{1.6}$$Mn$$_{2}$$O$$_7$$ manganite
Authors: Kumar Birendra , Tiwari Jeetendra Kumar , Chauhan Harish Chandr , Ghosh Subhasis 
Published: October 2021

AbstractHere, we report three magnetic transitions at 101 K (T$$_{C1}$$

C
1

), 246 K (T$$_{C2}$$

C
2

) and 295 K (T$$_{C3}$$

C
3

) in bilayer La$$_{1.4}$$

1.4

Sr$$_{1.6}$$

1.6

Mn$$_{2}$$

2

O$$_7$$

7

. The second order phase transitions have been identified at these transition points with the help of change in entropy analysis and modified Arrott plots (MAPs). The critical behavior around T$$_{C1}$$

C
1

, T$$_{C2}$$

C
2

and T$$_{C3}$$

C
3

have been studied by MAPs and Kouvel–Fisher method. Based on these analyses four magnetic phases are: (1) 2D Ising ferromagnetic (FM) below T$$_{C1}$$

C
1

,(2) 2D Heisenberg canted antiferromagnetic (CAFM-I) and FM clusters in temperature range T$$_{C1}$$

C
1

< T < T$$_{C2}$$

C
2

, (3) 2D Heisenberg CAFM-II and FM clusters with non magnetically interacting planes in temperature range T$$_{C2}$$

C
2

< T < T$$_{C3}$$

C
3

and (4) paramagnetic for T > T$$_{C3}$$

C
3

.