bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pubertal timing and self-harm: a prospective cohort analysis of males and females
Authors: Roberts Elystan , Joinson Carol , Gunnell David , Fraser Abigail , Mars Becky 
Published: October 2020

Abstract

Aims
Early puberty is associated with an increased risk of self-harm in adolescent females but results for males are inconsistent. This may be due to the use of subjective measures of pubertal timing, which may be biased. There is also limited evidence for the persistence of pubertal timing effects beyond adolescence, particularly in males. The primary aim of the current study was therefore to examine the association between pubertal timing and self-harm in both sexes during adolescence and young adulthood, using an objective measure of pubertal timing (age at peak height velocity; aPHV). A secondary aim was to examine whether this association differs for self-harm with v. without suicidal intent.

Methods
The sample (n = 5369, 47% male) was drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort study. Mixed-effects growth curve models were used to calculate aPHV. Lifetime history of self-harm was self-reported at age 16 and 21 years, and associated suicidal intent was examined at age 16 years. Associations were estimated using multivariable logistic regression adjusted for a range of confounders. Missing data were imputed using Multiple Imputation by Chained Equations.

Results
Later aPHV was associated with a reduced risk of self-harm at 16 years in both sexes (females: adjusted per-year increase in aPHV OR 0.85; 95% CI 0.75–0.96; males: OR 0.72; 95% CI 0.59–0.88). Associations were similar for self-harm with and without suicidal intent. There was some evidence of an association by age 21 years in females (adjusted per-year increase in aPHV OR 0.91; 95% CI 0.80–1.04), although the findings did not reach conventional levels of significance. There was no evidence of an association by age 21 years in males (adjusted per-year increase in aPHV OR 0.99; 95% CI 0.74–1.31).

Conclusions
Earlier developing adolescents represent a group at increased risk of self-harm. This increased risk attenuates as adolescents transition into adulthood, particularly in males. Future research is needed to identify the modifiable mechanisms underlying the association between pubertal timing and self-harm risk in order to develop interventions to reduce self-harm in adolescence.
Faulting Processes Unveiled by Magnetic Properties of Fault Rocks
Authors: Yang Tao , Chou Yu‐Min , Ferré Eric C. , Dekkers Mark J. , Chen Jianye , Yeh En‐Chao , Tanikawa Wataru 
Published: October 2020

AbstractAs iron‐bearing minerals—ferrimagnetic minerals in particular—are sensitive to stress, temperature, and presence of fluids in fault zones, their magnetic properties provide valuable insights into physical and chemical processes affecting fault rocks. Here, we review the advances made in magnetic studies of fault rocks in the past three decades. We provide a synthesis of the mechanisms that account for the magnetic changes in fault rocks and insights gained from magnetic research. We also integrate nonmagnetic approaches in the evaluation of the magnetic properties of fault rocks. Magnetic analysis unveils microscopic processes operating in the fault zones such as frictional heating, energy dissipation, and fluid percolation that are otherwise difficult to constrain. This makes magnetic properties suited as a “strain indicator,” a “geothermometer,” and a “fluid tracer” in fault zones. However, a full understanding of faulting‐induced magnetic changes has not been accomplished yet. Future research should focus on detailed magnetic property analysis of fault zones including magnetic microscanning and magnetic fabric analysis. To calibrate the observations on natural fault zones, laboratory experiments should be carried out that enable to extract the exact physicochemical conditions that led to a certain magnetic signature. Potential avenues could include (1) magnetic investigations on natural and synthetic fault rocks after friction experiments, (2) laboratory simulation of fault fluid percolation, (3) paleomagnetic analysis of postkinematic remanence components associated with faulting processes, and (4) synergy of interdisciplinary approaches in mineral‐magnetic studies. This would help to place our understanding of the microphysics of faulting on a much stronger footing.
An Ephemeral Red Arc Appeared at 68° MLat at a Pseudo Breakup During Geomagnetically Quiet Conditions
Authors: Oyama S. , Shinbori A. , Ogawa Y. , Kellinsalmi M. , Raita T. , Aikio A. , Vanhamäki H. , Shiokawa K. , Virtanen I. , Cai L. , Workayehu A. B. , Pedersen M. , Kauristie K. , Tsuda T. T. , Kozelov B. , Demekhov A. , Yahnin A. , Tsuchiya F. , Kumamoto A. , Kasahara Y. , Matsuoka A. , Shoji M. , Teramoto M. , Lester M. 
Published: October 2020

AbstractVarious subauroral optical features have been studied by analyzing data collected during periods of geomagnetic disturbances. Most events have been typically found at geomagnetic latitudes of 45–60°. In this study, however, we present a red arc event found at geomagnetic 68° north (L ≈ 7.1) in the Scandinavian sector during a period of geomagnetically quiet conditions within a short intermission between two high‐speed solar wind events. The red arc appeared to coincide with a pseudo breakup at geomagnetic 71–72°N and a rapid equatorward expansion of the polar cap. However, the red arc disappeared in approximately 7 min. Simultaneous measurements with the Swarm A/C satellites indicated the appearance of the red arc at the ionospheric trough minimum and a conspicuous enhancement of the electron temperature, suggesting the generation of the arc by heat flux. Since there are meaningful differences in the red arc features from already‐known subauroral optical features such as the stable auroral red (SAR) arc, we considered that the red arc is a new phenomenon. We suggest that the ephemeral red arc may represent the moment of SAR arc birth associated with substorm particle injection, which is generally masked by bright dynamic aurorae.
On the Relationships Between Radar Reflectivity and Rainfall Rate and Kinetic Energy Resulting From a Weibull Drop Size Distribution
Authors: Assouline Shmuel 
Published: October 2020

AbstractThe rainfall rate is a crucial variable in modeling runoff and water erosion. Rainfall rates present a very large spatial and temporal variability. Radars are used to estimate the spatial and temporal changes in rainfall rates during storms. The radar reflectivity is strongly affected by the drop size distribution (DSD) that results from the relative intensity of the microphysical processes involved in rainfall formation. One of the mathematical models applied to quantify the DSD is the Weibull function. Rainfall rate and kinetic energy, and radar reflectivity, are all related to different moments of the DSD. An analytical expression for these moments is proposed in the case of the Weibull distribution. The resulting relationships between radar reflectivity, rainfall rate, and kinetic energy are presented. The use of a scaled DSD that is independent of rainfall rate and characterizes a specific location allows an a priori estimate of relationships between radar reflectivity, rainfall rate, and kinetic energy that will be also characteristics of that location. Radar reflectivity can be used to estimate the kinetic energy of rainfall events. This extends the application of radar to agriculture and environmental purposes such as potential rainfall damages estimates in terms of soil loss, erosion, and sediment transport.
Alteration of the steroidogenesis in boys with autism spectrum disorders
Authors: Janšáková Katarína , Hill Martin , Čelárová Diana , Celušáková Hana , Repiská Gabriela , Bičíková Marie , Máčová Ludmila , Ostatníková Daniela 
Published: October 2020

AbstractThe etiology of autism spectrum disorders (ASD) remains unknown, but associations between prenatal hormonal changes and ASD risk were found. The consequences of these changes on the steroidogenesis during a postnatal development are not yet well known. The aim of this study was to analyze the steroid metabolic pathway in prepubertal ASD and neurotypical boys. Plasma samples were collected from 62 prepubertal ASD boys and 24 age and sex-matched controls (CTRL). Eighty-two biomarkers of steroidogenesis were detected using gas-chromatography tandem-mass spectrometry. We observed changes across the whole alternative backdoor pathway of androgens synthesis toward lower level in ASD group. Our data indicate suppressed production of pregnenolone sulfate at augmented activities of CYP17A1 and SULT2A1 and reduced HSD3B2 activity in ASD group which is partly consistent with the results reported in older children, in whom the adrenal zona reticularis significantly influences the steroid levels. Furthermore, we detected the suppressed activity of CYP7B1 enzyme readily metabolizing the precursors of sex hormones on one hand but increased anti-glucocorticoid effect of 7α-hydroxy-DHEA via competition with cortisone for HSD11B1 on the other. The multivariate model found significant correlations between behavioral indices and circulating steroids. From dependent variables, the best correlation was found for the social interaction (28.5%). Observed changes give a space for their utilization as biomarkers while reveal the etiopathogenesis of ASD. The aforementioned data indicate a direction of the future research with a focus on the expression and functioning of genes associated with important steroidogenic enzymes in ASD patients from early childhood to adrenarche.
Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
Authors: Viviani Roberto , Messina Irene , Bosch Julia E. , Dommes Lisa , Paul Anna , Schneider Katharina L. , Scholl Catharina , Stingl Julia C. 
Published: October 2020

AbstractThe polymorphic drug-metabolizing enzyme CYP2D6, which is responsible for the metabolism of most psychoactive compounds, is expressed not only in the liver, but also in the brain. The effects of its marked genetic polymorphism on the individual capacity to metabolize drugs are well known, but its role in metabolism of neural substrates affecting behavior personality or cognition, suggested by its CNS expression, is a long-standing unresolved issue. To verify earlier findings suggesting a potential effect on attentional processes, we collected functional imaging data, while N = 415 participants performed a simple task in which the reward for correct responses varied. CYP2D6 allelic variants predicting higher levels of enzymatic activity level were positively associated with cortical activity in occipito-parietal areas as well as in a right lateralized network known to be activated by spatial attentional tasks. Reward-related modulation of activity in cortical areas was more pronounced in poor metabolizers. In conjunction with effects on reaction times, our findings provide evidence for reduced cognitive efficiency in rapid metabolizers compared to poor metabolizers in on-task attentional processes manifested through differential recruitment of a specific neural substrate.
Requirement for Serine-384 in Caspase-2 processing and activity
Authors: Zamaraev Alexey V. , Volik Pavel I. , Nilov Dmitry K. , Turkina Maria V. , Egorshina Aleksandra Yu. , Gorbunova Anna S. , Iarovenko Svetlana Iu. , Zhivotovsky Boris , Kopeina Gelina S. 
Published: October 2020

AbstractCaspase-2 is a unique and conservative cysteine protease which plays an important role in several cellular processes including apoptotic cell death. Although the molecular mechanisms of its activation remain largely unclear, a major role belongs to the architecture of the caspase-2 active center. We demonstrate that the substitution of the putative phosphorylation site of caspase-2, Serine-384 to Alanine, blocks caspase-2 processing and decreases its enzymatic activity. Strikingly, in silico analysis using molecular dynamics simulations has shown that Serine-384 is crucially involved in interactions within the caspase-2 active center. It stabilizes Arginine-378, which forms a crucial hydrogen bond with the aspartate residue of a substrate. Hence, Serine-384 is essential for supporting a proper architecture of the active center of caspase-2. Moreover, molecular modeling strongly proved steric inaccessibility of Ser-384 to be phosphorylated. Importantly, a multiple alignment has demonstrated that both Serine-384 and Arg-378 residues are highly conservative across all members of caspase family, which allows us to suggest that this diade is indispensable for caspase processing and activity. Spontaneous mutations in this diade might influence oncosuppressive function of caspases, in particular of caspase-2. Likewise, the mutation of Ser-384 is associated with the development of lung squamous cell carcinoma and adenocarcinoma. Taken together, we have uncovered a central feature of the caspase-2 activation mechanism which is crucial for the regulation of its signaling network.
Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C+ CD8+ T cells
Authors: Zhu Jiaqi , Feng Bing , Xu Yanping , Chen Wenyi , Sheng Xinyu , Feng Xudong , Shi Xiaowei , Liu Jingqi , Pan Qiaoling , Yu Jiong , Li Lanjuan , Cao Hongcui 
Published: October 2020

AbstractSystemic inflammatory processes, including alveolar injury, cytokine induction, and neutrophil accumulation, play key roles in the pathophysiology of acute lung injury (ALI). The immunomodulatory effects of mesenchymal stem cells (MSCs) can contribute to the treatment of inflammatory disorders. In previous studies, the focus was on innate immune cells and the effects of MSCs on ALI through CD8+T cells remain unclear. In the present study, lipopolysaccharide (LPS) was used to induce ALI in mice. ALI mice were treated with MSCs via intratracheal instillation. Survival rate, histopathological changes, protein levels, total cell count, cytokine levels, and chemokine levels in alveolar lavage fluid were used to determine the efficacy of MSCs. Mass cytometry and single-cell RNA sequencing (scRNA-seq) were used to characterize the CD8+T cells in the lungs. Ly6C−CD8+T cells are prevalent in normal mice, whereas a specialized effector phenotype expressing a high level of Ly6C is predominant in advanced disease. MSCs significantly mitigated ALI and improved survival. MSCs decreased the infiltration of CD8+T cells, especially Ly6C+CD8+T cells into the lungs. Mass cytometry revealed that CD8+T cells expressing high Ly6C and CXCR3 levels caused tissue damage in the lungs of ALI mice, which was alleviated by MSCs. The scRNA-seq showed that Ly6C+CD8+T cells exhibited a more activated phenotype and decreased expression of proinflammatory factors that were enriched the most in immune chemotaxis after treatment with MSCs. We showed that CD8+T cells play an important role in MSC-mediated ALI remission, and both infiltration quantity and proinflammatory function were inhibited by MSCs, indicating a potential mechanism for therapeutic intervention.
Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence
Authors: Walens Andrea , Lin Jiaxing , Damrauer Jeffrey S. , McKinney Brock , Lupo Ryan , Newcomb Rachel , Fox Douglas B. , Mabe Nathaniel W. , Gresham Jeremy , Sheng Zhecheng , Sibley Alexander B. , De Buysscher Tristan , Kelkar Hemant , Mieczkowski Piotr A. , Owzar Kouros , Alvarez James V. 
Published: October 2020

AbstractThe survival and recurrence of residual tumor cells following therapy constitutes one of the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how the clonal composition of tumors changes during relapse. We use cellular barcoding to monitor clonal dynamics during tumor recurrence in vivo. We find that clonal diversity decreases during tumor regression, residual disease, and recurrence. The recurrence of dormant residual cells follows several distinct routes. Approximately half of the recurrent tumors exhibit clonal dominance with a small number of subclones comprising the vast majority of the tumor; these clonal recurrences are frequently dependent upon Met gene amplification. A second group of recurrent tumors comprises thousands of subclones, has a clonal architecture similar to primary tumors, and is dependent upon the Jak/Stat pathway. Thus the regrowth of dormant tumors proceeds via multiple routes, producing recurrent tumors with distinct clonal composition, genetic alterations, and drug sensitivities.
Human running performance from real-world big data
Authors: Emig Thorsten , Peltonen Jussi 
Published: October 2020

AbstractWearable exercise trackers provide data that encode information on individual running performance. These data hold great potential for enhancing our understanding of the complex interplay between training and performance. Here we demonstrate feasibility of this idea by applying a previously validated mathematical model to real-world running activities of ≈ 14,000 individuals with ≈ 1.6 million exercise sessions containing duration and distance, with a total distance of ≈ 20 million km. Our model depends on two performance parameters: an aerobic power index and an endurance index. Inclusion of endurance, which describes the decline in sustainable power over duration, offers novel insights into performance: a highly accurate race time prediction and the identification of key parameters such as the lactate threshold, commonly used in exercise physiology. Correlations between performance indices and training volume and intensity are quantified, pointing to an optimal training. Our findings hint at new ways to quantify and predict athletic performance under real-world conditions.
Tailoring poplar lignin without yield penalty by combining a null and haploinsufficient CINNAMOYL-CoA REDUCTASE2 allele
Authors: De Meester Barbara , Madariaga Calderón Barbara , de Vries Lisanne , Pollier Jacob , Goeminne Geert , Van Doorsselaere Jan , Chen Mingjie , Ralph John , Vanholme Ruben , Boerjan Wout 
Published: October 2020

AbstractLignin causes lignocellulosic biomass recalcitrance to enzymatic hydrolysis. Engineered low-lignin plants have reduced recalcitrance but often exhibit yield penalties, offsetting their gains in fermentable sugar yield. Here, CRISPR/Cas9-generated CCR2(−/*) line 12 poplars have one knockout CCR2 allele while the other contains a 3-bp deletion, resulting in a 114I115A-to-114T conversion in the corresponding protein. Despite having 10% less lignin, CCR2(−/*) line 12 grows normally. On a plant basis, the saccharification efficiency of CCR2(−/*) line 12 is increased by 25–41%, depending on the pretreatment. Analysis of monoallelic CCR2 knockout lines shows that the reduced lignin amount in CCR2(−/*) line 12 is due to the combination of a null and the specific haploinsufficient CCR2 allele. Analysis of another CCR2(−/*) line shows that depending on the specific CCR2 amino-acid change, lignin amount and growth can be affected to different extents. Our findings open up new possibilities for stably fine-tuning residual gene function in planta.
Structural basis for the transition from translation initiation to elongation by an 80S-eIF5B complex
Authors: Wang Jinfan , Wang Jing , Shin Byung-Sik , Kim Joo-Ran , Dever Thomas E. , Puglisi Joseph D. , Fernández Israel S. 
Published: October 2020

AbstractRecognition of a start codon by the initiator aminoacyl-tRNA determines the reading frame of messenger RNA (mRNA) translation by the ribosome. In eukaryotes, the GTPase eIF5B collaborates in the correct positioning of the initiator Met-tRNAiMet on the ribosome in the later stages of translation initiation, gating entrance into elongation. Leveraging the long residence time of eIF5B on the ribosome recently identified by single-molecule fluorescence measurements, we determine the cryoEM structure of the naturally long-lived ribosome complex with eIF5B and Met-tRNAiMet immediately before transition into elongation. The structure uncovers an unexpected, eukaryotic specific and dynamic fidelity checkpoint implemented by eIF5B in concert with components of the large ribosomal subunit.
Characterization of two types of intranuclear hepatocellular inclusions in NAFLD
Authors: Schwertheim Suzan , Kälsch Julia , Jastrow Holger , Schaefer Christoph Matthias , Theurer Sarah , Ting Saskia , Canbay Ali , Wedemeyer Heiner , Schmid Kurt Werner , Baba Hideo Andreas 
Published: October 2020

AbstractNuclear inclusions (NI) are a common finding in hepatocytes from patients with liver disease especially in diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) but studies examining the shape and content of these inclusions in detail are lacking. In this study we define two distinct types of NI in NAFLD: inclusions bounded by the nuclear membrane, containing degenerative cell organelles and heterolysosomes (type1) and inclusions with deposits of glycogen but without any kind of organelles and delimiting membrane (type2). NI in 77 paraffin-embedded patients of NAFLD including NAFL and non-alcoholic steatohepatitis (NASH) were analyzed. In 4–12% of type1 NI immunopositivity for the autophagy-associated proteins LC3B, ubiquitin, p62/sequestosome1, cathepsin D and cathepsin B were detected with co-localizations of ubiquitin and p62; type2 NI showed no immunoreactivity. Three-dimensional reconstructions of isolated nuclei revealed that NI type1 are completely enclosed within the nucleus, suggesting that NI, although probably derived from cytoplasmic invaginations, are not just simple invaginations. Our study demonstrates two morphologically different types of inclusions in NAFLD, whereby both gained significantly in number in advanced stages. We suggest that the presence of autophagy-associated proteins and degenerated organelles within type1 NI plays a role in disease progression.
A periodic pumping technique of soil gas for 222Rn stabilization in large calibration chambers: part 2—theoretical formulation and experimental validation
Authors: Shetty Trilochana , Mayya Y. S. , Kumara K. Sudeep , Sahoo B. K. , Sapra B. K. , Karunakara N. 
Published: October 2020

AbstractIn an adjoining publication, we demonstrated the novel technique to harvest soil gas of natural origin as a highly efficient source of 222Rn for calibration applications in a large volume 222Rn calibration chamber. Its advantages over the use of conventional high strength 226Ra sources, such as the capability to serve as a non-depleting reservoir of 222Rn and achieve the desired concentration inside the calibration chamber within a very short time, devoid of radiation safety issues in source handling and licensing requirements from the regulatory authority, were discussed in detail. It was also demonstrated that stability in the 222Rn concentration in large calibration chambers could be achieved within ± 20% deviation from the desired value through a semi-dynamic mode of injection in which 222Rn laden air was periodically pumped to compensate for its loss due to leak and decay. The necessity of developing a theory for determining the appropriate periodicity of pumping was realized to get good temporal stability with a universally acceptable deviation of ≤ ± 10% in the 222Rn concentration. In this paper, we present a mathematical formulation to determine the injection periods (injection pump ON and OFF durations) for the semi-dynamic operation to achieve long term temporal stability in the 222Rn concentration in the chamber. These computed pumping parameters were then used to efficiently direct the injection of soil gas into the chamber. We present the mathematical formulation, and its experimental validations in a large volume calibration chamber (22 m3). With this, the temporal stability of 222Rn concentration in the chamber was achieved with a deviation of ~ 3% from the desired value.