bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis
Authors: Ren Bo , Yang Jinshou , Wang Chengcheng , Yang Gang , Wang Huanyu , Chen Yuan , Xu Ruiyuan , Fan Xuning , You Lei , Zhang Taiping , Zhao Yupei 
Published: August 2021

Abstract
Background
Pancreatic cancer’s poor prognosis is caused by distal metastasis, which is associated with epigenetic changes. However, the role of the 3D epigenome in pancreatic cancer biology, especially its metastasis, remains unclear.

Methods
Here, we developed high-resolution 3D epigenomic maps of cells derived from normal pancreatic epithelium, primary and metastatic pancreatic cancer by in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq to identify key genes involved in pancreatic cancer metastasis

Results
We found that A/B compartments, contact domains, and chromatin loops changed significantly in metastatic pancreatic cancer cells, which are associated with epigenetic state alterations. Moreover, we found that upregulated genes, which were located in switched compartments, changed contact domains, and metastasis-specific enhancer-promoter loops, were related to cancer metastasis and poor prognosis of patients with pancreatic cancer. We also found that transcription factors in specific enhancer-promoter loop formation were also associated with metastasis. Finally we demonstrated that LIPC, looped to metastasis-specific enhancers, could promote pancreatic cancer metastasis.

Conclusions
These results highlight the multiscale 3D epigenome reprogramming during pancreatic cancer metastasis and expand our knowledge of mechanisms of gene regulation during pancreatic cancer metastasis.
Higher temperatures reduce the number of Trypanosoma cruzi parasites in the vector Triatoma pallidipennis
Authors: González-Rete Berenice , Gutiérrez-Cabrera Ana E. , de Fuentes-Vicente José Antonio , Salazar-Schettino Paz María , Cabrera-Bravo Margarita , Córdoba-Aguilar Alex 
Published: August 2021

AbstractBackgroundRelatively little is known about how pathogens transmitted by vector insects are affected by changing temperatures analogous to those occurring in the present global warming scenario. One expectation is that, like their ectothermic vectors, an increase in temperature could reduce their fitness. Here, we have investigated the effect of high temperatures on the abundance ofTrypanosoma cruziparasites during infection in the vectorTriatoma pallidipennis.MethodsWe exposedT. pallidipennisnymphs to two strains (Morelos and Chilpancingo) ofT. cruzi. Once infected, the fifth-instar bugs were distributed among three different temperature groups, i.e. 20, 30, and 34 °C, and the resulting parasites were counted when the bugs reached adulthood.ResultsThe number of parasites increased linearly with time at 20 °C and, to a lesser extent, at 30 °C, especially in the Chilpancingo compared to the Morelos strain. Conversely, at 34 °C, the number of parasites of both strains decreased significantly compared to the other two temperatures.ConclusionsThese results suggest negative effects on the abundance ofT. cruziinT. pallidipennisat high temperatures. This is the first evidence of the effect of high temperatures on a pathogenic agent transmitted by an insect vector in the context of global warming. Further tests should be done to determine whether this pattern occurs with other triatomine species andT. cruzistrains.Graphical abstract
ADAMTS-1: a novel target gene of an estrogen-induced transcription factor, EGR1, critical for embryo implantation in the mouse uterus
Authors: Park Mira , Park So Hee , Park Hyunsun , Kim Hye-Ryun , Lim Hyunjung J. , Song Haengseok 
Published: August 2021

Abstract
Background
Recently, we demonstrated that estrogen (E2) induces early growth response 1 (Egr1) to mediate its actions on the uterine epithelium by controlling progesterone receptor signaling for successful embryo implantation. EGR1 is a transcription factor that regulates the spectrum of target genes in many different tissues, including the uterus. E2-induced EGR1 regulates a set of genes involved in epithelial cell remodeling during embryo implantation in the uterus. However, only few target genes of EGR1 in the uterus have been identified.

Result
The expression of ADAM metallopeptidase with thrombospondin type 1 motif 1 (Adamts-1) was significantly downregulated in the uteri of E2-treated ovariectomized (OVX) Egr1(−/−) mice. Immunostaining of ADAMTS-1 revealed its exclusive expression in the uterine epithelium of OVX wild-type but not Egr1(−/−) mice treated with E2. The expression profiles of Adamts-1 and Egr1 were similar in the uteri of E2-treated OVX mice at various time points tested. Pre-treatment with ICI 182, 780, a nuclear estrogen receptor (ER) antagonist, effectively inhibited the E2-dependent induction of Egr1 and Adamts-1. Pharmacologic inhibition of E2-induced ERK1/2 or p38 phosphorylation interfered with the induction of EGR1 and ADAMTS-1. Furthermore, ADAMTS-1, as well as EGR1, was induced in stroma cells surrounding the implanting blastocyst during embryo implantation. Transient transfection with EGR1 expression vectors significantly induced the expression of ADAMTS-1. Luciferase activity of the Adamts-1 promoter containing EGR1 binding sites (EBSs) was increased by EGR1 in a dose-dependent manner, suggesting functional regulation of Adamts-1 transcription by EGR1. Site-directed mutagenesis of EBS on the Adamts-1 promoter demonstrated that EGR1 directly binds to the EBS at -1151/-1134 among four putative EBSs.

Conclusions
Collectively, we have demonstrated that Adamts-1 is a novel target gene of E2-ER-MAPK-EGR1, which is critical for embryo implantation in the mouse uterus during early pregnancy.
Feature compensation based on the normalization of vocal tract length for the improvement of emotion-affected speech recognition
Authors: Geravanchizadeh Masoud , Forouhandeh Elnaz , Bashirpour Meysam 
Published: August 2021

AbstractThe performance of speech recognition systems trained with neutral utterances degrades significantly when these systems are tested with emotional speech. Since everybody can speak emotionally in the real-world environment, it is necessary to take account of the emotional states of speech in the performance of the automatic speech recognition system. Limited works have been performed in the field of emotion-affected speech recognition and so far, most of the researches have focused on the classification of speech emotions. In this paper, the vocal tract length normalization method is employed to enhance the robustness of the emotion-affected speech recognition system. For this purpose, two structures of the speech recognition system based on hybrids of hidden Markov model with Gaussian mixture model and deep neural network are used. To achieve this goal, frequency warping is applied to the filterbank and/or discrete-cosine transform domain(s) in the feature extraction process of the automatic speech recognition system. The warping process is conducted in a way to normalize the emotional feature components and make them close to their corresponding neutral feature components. The performance of the proposed system is evaluated in neutrally trained/emotionally tested conditions for different speech features and emotional states (i.e., Anger, Disgust, Fear, Happy, and Sad). In this system, frequency warping is employed for different acoustical features. The constructed emotion-affected speech recognition system is based on the Kaldi automatic speech recognition with the Persian emotional speech database and the crowd-sourced emotional multi-modal actors dataset as the input corpora. The experimental simulations reveal that, in general, the warped emotional features result in better performance of the emotion-affected speech recognition system as compared with their unwarped counterparts. Also, it can be seen that the performance of the speech recognition using the deep neural network-hidden Markov model outperforms the system employing the hybrid with the Gaussian mixture model.
Predicted antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir can potentially bind to neutralize SARS-CoV-2 conserved proteins
Authors: Halder Umesh C. 
Published: August 2021

Abstract
Background
Novel Coronavirus disease 2019 or COVID-19 has become a threat to human society due to fast spreading and increasing mortality. It uses vertebrate hosts and presently deploys humans. Life cycle and pathogenicity of SARS-CoV-2 have already been deciphered and possible drug target trials are on the way.

Results
The present study was aimed to analyze Non-Structural Proteins that include conserved enzymes of SARS-CoV-2 like papain-like protease, main protease, Replicase, RNA-dependent RNA polymerase, methyltransferase, helicase, exoribonuclease and endoribonucleaseas targets to all known drugs. A bioinformatic based web server Drug ReposeER predicted several drug binding motifs in these analyzed proteins. Results revealed that anti-viral drugs Darunavir,Amprenavir, Rimantadine and Saquinavir were the most potent to have 3D-drug binding motifs that were closely associated with the active sites of the SARS-CoV-2 enzymes .

Conclusions
Repurposing of the antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir to treat COVID-19 patients could be useful that can potentially prevent human mortality.

Graphic abstract
Magnitude of undernutrition and associated factors among children with cardiac disease at University of Gondar hospital, Ethiopia
Authors: Asrade Mulat , Shehibo Abdulkadir , Tigabu Zemene 
Published: August 2021

Abstract
Background
Undernutrition and cardiac disease are interconnected in a vicious cycle. Little is known about the effect of undernutrition on cardiac disease among children in low- and middle-income countries (LMICs). This study aimed to assess magnitude of undernutrition and associated factors among children with cardiac disease at University of Gondar hospital, northwest Ethiopia.

Method
This hospital-based cross-sectional study included children with cardiac disease presenting to the pediatric outpatient clinic at University of Gondar Hospital, Ethiopia. A self-administered questionnaire was administered to participating families, and medical records were reviewed. All participants who fulfill the inclusion criteria were included. Anthropometric measurements were made and the presence of malnutrition was diagnosed according to the WHO criteria. Associated factors of undernutrition analyzed by using binary logistic regression model. Variables with p-value ≤0.2 in bivariate analysis were fitted to the final multivariable analysis and those variables with p-value ≤0.05 were considered as having statistically significant association to the outcome variable. AOR and 95% confidence interval was calculated to assess the strength of association between the variables.

Result
A total of 269 patients participated in the study. 177 (65.7%) were undernourished, of whom 96 (54.5%) were underweight, 70 (39.7%) were stunted, and 95 (53.9%) were wasted. Pulmonary hypertension (adjusted odds ratio [AOR] = 3.82, 95%CI 1.80–8.10), NYHA/modified Ross class III and IV heart failure (AOR = 4.64, 1.69–12.72) and cardiac chamber enlargement (AOR = 2.91, 1.45–5.66) were associated with undernutrition.

Conclusion
Undernutrition is common among children with cardiac disease in northern Ethiopia. Children with pulmonary hypertension, high-grade heart failure, and cardiac chamber enlargement may warrant close follow-up for malnutrition.
Three dimensions of the relationship between gender role attitudes and fertility intentions
Authors: Lappegård Trude , Neyer Gerda , Vignoli Daniele 
Published: August 2021

AbstractThe relationship between gender role attitudes and fertility intentions is highly debated among social scientists. We emphasize the need for a multidimensional theoretical and empirical approach to extend the two-step behavioral gender revolution approach to a three-step attitudinal gender revolution approach distinguishing between gender roles in the public sphere, mothers’ role in the family, and fathers’ role in the family. Using the Generations and Gender Survey of eight European countries, we demonstrate the usefulness of such an approach. Gender equal attitudes related to the public sphere are more widespread than those concerning mothers’ or fathers’ roles in the family. Our results show that the association between gender role attitudes and fertility intentions varies—in terms of significance and magnitude—according to the dimension considered (gender roles in the public sphere, mothers’ and fathers’ role in the family), gender, parity, and country. We conclude that without a clear concept of and empirical distinction between the various elements of the gender role attitudes/fertility nexus, scientific investigations will continue to send conflicting messages.
PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism
Authors: Khan Aliya A , Rejnmark Lars , Rubin Mishaela , Schwarz Peter , Vokes Tamara , Clarke Bart , Ahmed Intekhab , Hofbauer Lorenz , Marcocci Claudio , Pagotto Uberto , Palermo Andrea , Eriksen Erik , Brod Meryl , Markova Denka , Smith Alden , Pihl Susanne , Mourya Sanchita , Karpf David B , Shu Aimee D 
Published: August 2021

Abstract

Context
Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH). TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of hypoparathyroidism.

Objective
This work aimed to investigate the safety, tolerability, and efficacy of daily TransCon PTH in adults with hypoparathyroidism.

Methods
This phase 2, randomized, double-blind, placebo-controlled 4-week trial with open-label extension enrolled 59 individuals with hypoparathyroidism. Interventions included TransCon PTH 15, 18, or 21 µg PTH(1-34)/day or placebo for 4 weeks, followed by a 22-week extension during which TransCon PTH dose was titrated (6-60 µg PTH[1-34]/day).

Results
By Week 26, 91% of participants treated with TransCon PTH achieved independence from standard of care (SoC, defined as active vitamin D = 0 μg/day and calcium [Ca] ≤ 500 mg/day). Mean 24-hour urine Ca (uCa) decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n = 44) while normal serum Ca (sCa) was maintained and serum phosphate and serum calcium-phosphate product fell within the normal range. By Week 26, mean scores on the generic 36-Item Short Form Health Survey domains increased from below normal at baseline to within the normal range. The Hypoparathyroidism Patient Experience Scale symptom and impact scores improved through 26 weeks. TransCon PTH was well tolerated with no treatment-related serious or severe adverse events.

Conclusion
TransCon PTH enabled independence from oral active vitamin D and reduced Ca supplements (≤ 500 mg/day) for most participants, achieving normal sCa, serum phosphate, uCa, serum calcium-phosphate product, and demonstrating improved health-related quality of life. These results support TransCon PTH as a potential hormone replacement therapy for adults with hypoparathyroidism.
Low Skeletal Muscle Mass Is Associated With Perioperative Neurocognitive Disorder Due To Decreased Neurogenesis in Rats
Authors: Nemoto Akira , Goyagi Toru , Nemoto Wataru , Nakagawasai Osamu , Tan-No Koichi , Niiyama Yukitoshi 
Published: August 2021

BACKGROUND:
Perioperative neurocognitive disorder (PND) is a postsurgical complication associated with neuroinflammation and impaired hippocampal neurogenesis, in which brain-derived neurotrophic factor (BDNF) plays a key role. Sarcopenia refers to age-related muscle loss that causes cognitive decline, muscle atrophy, and postoperative delirium. Rats with tail suspension (TS) were used to represent a low-activity model, which involves decreased hind limb function by TS. This hind limb unloading by TS can induce sarcopenia in 2 weeks. However, the relationship between PND and muscle atrophy is unclear. In this experiment, we investigated whether preoperative muscle atrophy induced by TS would affect neurogenesis and accelerate PND in rats.

METHODS:
Sixty 21-week-old rats were assigned to 4 groups: the TS group, the TS with surgery (TS + S) group, the control group, and the control with surgery (control + S) group. After the abdominal manipulation under 3% sevoflurane anesthesia, cognitive function was assessed using the Morris water maze test and a fear-conditioning test. Neurogenesis was evaluated by checking BDNF secretion and immunohistochemical staining in the hippocampus.

RESULTS:
The TS + S group showed impaired swimming latency (difference of means = 12.4 versus control + S; 95% confidence interval [CI], 2.0–22.7; P = .016) (difference of means = 15.2 versus TS; 95% CI, 0.4–30.1; P = .043) and path length (difference of means = 147.8 versus control + S; 95% CI, 20.7–274.9; P = .020) in the maze test and cued fear memory (difference of means = −26.0 versus TS; 95% CI, −46.4 to −5.6; P = .006) (difference of means = −22.3 versus control + S; 95% CI, −42.7 to −1.9; P = .026) in the fear-conditioning test. The postoperative levels of BDNF in the TS + S and TS groups were reduced compared with the other groups (P = .002). The number of neural precursors in the dentate gyrus was significantly lower in the TS + S group (P < .001).

CONCLUSIONS:
We observed that preoperative hind limb muscle atrophy, indicated by TS, was associated with an increased occurrence of PND through the reduction in BDNF and neurogenesis after abdominal surgery in young adult rats. Therefore, we concluded that preoperative low skeletal muscle mass can induce PND due to impaired postoperative neurogenesis. Our findings might indicate that low-cost perioperative interventions, such as preoperative exercise, is beneficial to preventing PND.
Metabolism navigates neural cell fate in development, aging and neurodegeneration
Authors: Traxler Larissa , Lagerwall Jessica , Eichhorner Sophie , Stefanoni Davide , D'Alessandro Angelo , Mertens Jerome 
Published: August 2021

ABSTRACT
An uninterrupted energy supply is critical for the optimal functioning of all our organs, and in this regard the human brain is particularly energy dependent. The study of energy metabolic pathways is a major focus within neuroscience research, which is supported by genetic defects in the oxidative phosphorylation mechanism often contributing towards neurodevelopmental disorders and changes in glucose metabolism presenting as a hallmark feature in age-dependent neurodegenerative disorders. However, as recent studies have illuminated roles of cellular metabolism that span far beyond mere energetics, it would be valuable to first comprehend the physiological involvement of metabolic pathways in neural cell fate and function, and to subsequently reconstruct their impact on diseases of the brain. In this Review, we first discuss recent evidence that implies metabolism as a master regulator of cell identity during neural development. Additionally, we examine the cell type-dependent metabolic states present in the adult brain. As metabolic states have been studied extensively as crucial regulators of malignant transformation in cancer, we reveal how knowledge gained from the field of cancer has aided our understanding in how metabolism likewise controls neural fate determination and stability by directly wiring into the cellular epigenetic landscape. We further summarize research pertaining to the interplay between metabolic alterations and neurodevelopmental and psychiatric disorders, and expose how an improved understanding of metabolic cell fate control might assist in the development of new concepts to combat age-dependent neurodegenerative diseases, particularly Alzheimer's disease.
Loss of kinesin-8 improves the robustness of the self-assembled spindle in Schizosaccharomyces pombe
Authors: Pineda-Santaella Alberto , Fernández-Castillo Nazaret , Jiménez-Martín Alberto , Macías-Cabeza María del Carmen , Sánchez-Gómez Ángela , Fernández-Álvarez Alfonso 
Published: August 2021

ABSTRACT
Chromosome segregation in female meiosis in many metazoans is mediated by acentrosomal spindles, the existence of which implies that microtubule spindles self-assemble without the participation of the centrosomes. Although it is thought that acentrosomal meiosis is not conserved in fungi, we recently reported the formation of self-assembled microtubule arrays, which were able to segregate chromosomes, in fission yeast mutants, in which the contribution of the spindle pole body (SPB; the centrosome equivalent in yeast) was specifically blocked during meiosis. Here, we demonstrate that this unexpected microtubule formation represents a bona fide type of acentrosomal spindle. Moreover, a comparative analysis of these self-assembled spindles and the canonical SPB-dependent spindle reveals similarities and differences; for example, both spindles have a similar polarity, but the location of the γ-tubulin complex differs. We also show that the robustness of self-assembled spindles can be reinforced by eliminating kinesin-8 family members, whereas kinesin-8 mutants have an adverse impact on SPB-dependent spindles. Hence, we consider that reinforced self-assembled spindles in yeast will help to clarify the molecular mechanisms behind acentrosomal meiosis, a crucial step towards better understanding gametogenesis.
Sleep and conditioning of the siphon withdrawal reflex in Aplysia
Authors: Thiede Kathrin I. , Born Jan , Vorster Albrecht P. A. 
Published: August 2021

ABSTRACT
Sleep is essential for memory consolidation after learning as shown in mammals and invertebrates such as bees and flies. Aplysia californica displays sleep, and sleep in this mollusk was also found to support memory for an operant conditioning task. Here, we investigated whether sleep in Aplysia is also required for memory consolidation in a simpler type of learning, i.e. the conditioning of the siphon withdrawal reflex. Two groups of animals (Wake, Sleep, each n=11) were conditioned on the siphon withdrawal reflex, with the training following a classical conditioning procedure where an electrical tail shock served as the unconditioned stimulus (US) and a tactile stimulus to the siphon as the conditioned stimulus (CS). Responses to the CS were tested before (pre-test), and 24 and 48 h after training. While Wake animals remained awake for 6 h after training, Sleep animals had undisturbed sleep. The 24 h test in both groups was combined with extinction training, i.e. the extended presentation of the CS alone over two blocks. At the 24 h test, siphon withdrawal duration in response to the CS was distinctly enhanced in both Sleep and Wake groups with no significant difference between groups, consistent with the view that consolidation of a simple conditioned reflex response does not require post-training sleep. Surprisingly, extinction training did not reverse the enhancement of responses to the CS. On the contrary, at the 48 h test, withdrawal duration in response to the CS was even further enhanced across both groups. This suggests that processes of sensitization, an even simpler non-associative type of learning, contributed to the withdrawal responses. Our study provides evidence for the hypothesis that sleep preferentially benefits consolidation of more complex learning paradigms than conditioning of simple reflexes.