bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of noncanonical genomic imprinting in monoaminergic pathways on the regulation of social behaviors
Authors: O’Leary Erin M. , Rahman Samuel J. , Tamas Andrei L. , Huang Tony , Dweydari Moudar , Eggleston Rachel L. , Meling Daryl D. , Bonthuis Paul J. 
Published: March 2024

AbstractGenomic imprinting in the brain is theorized to provide parental control over offspring social behaviors. Noncanonical genomic imprinting is a form of epigenetic regulation in which one of a gene’s alleles, either that of maternal or paternal inheritance, exhibits a bias towards higher expression of one parental allele compared to the other. This bias can differ depending on tissue type, and the degree of the parental allele expression bias can even vary across anatomical domains within the same tissue. Dopa decarboxylase (Ddc) and tyrosine hydroxylase (Th) are both noncanonically imprinted genes that preferentially express their maternal alleles in the brain andDdcalso has a paternal allele expression bias in the periphery. These two genes encode catecholamine synthesis enzymes for the production of dopamine (DA), norepinephrine (NE), and epinephrine (E), andDdcis also in the serotonin (5-HT) synthesis pathway. These four neurotransmitters are critical regulators of social behavior and disruptions to them are implicated in human mental illnesses. Here we investigated the functional effects of noncanonical imprinting ofDdcandThon social behavior in mice. By using reciprocal heterozygous mutant mice, we tested the impacts ofDdcand/orThmaternally and paternally inherited alleles on aggression, social recognition, dominance, and social preference behaviors. We found thatDdcpaternal-null alleles affect aggression and social recognition behavior,Thmaternal-null alleles affect sociability preferences, and compound inheritance ofThandDdcmaternal-null alleles influence preferences for social novelty. These results are consistent withThandDdcmaternal allele biased expression in central monoaminergic systems regulating sociability, andDdcpaternal allele biased expression in peripheral monoaminergic systems regulating aggression and social recognition.
Two-photon imaging of excitatory and inhibitory neural response to infrared neural stimulation
Authors: Fu Peng , Liu Yin , Zhu Liang , Wang Mengqi , Yu Yuan , Yang Fen , Zhang Weijie , Zhang Hequn , Shoham Shy , Roe Anna Wang , Xi Wang 
Published: March 2024

AbstractSignificancePulsed infrared neural stimulation (INS, 1875 nm) is an emerging neurostimulation technology that delivers focal pulsed heat to activate functionally specific mesoscale networks and holds promise for clinical application. However, little is known about its effect on excitatory and inhibitory cell types in cerebral cortex.AimEstimates of summed population neuronal response timecourses provide a potential basis for neural and hemodynamic signals described in other studies.ApproachUsing two-photon calcium imaging in mouse somatosensory cortex, we have examined the effect of INS pulse train application on hSyn neurons and mDlx neurons tagged with GCaMP6s.ResultsWe find that, in anesthetized mice, each INS pulse train reliably induces robust response in hSyn neurons exhibiting positive going responses. Surprisingly, mDlx neurons exhibit negative going responses. Quantification using the index of correlation illustrates responses are reproducible, intensity-dependent, and distance-dependent. Also, a contralateral activation is observed when INS application.ConclusionsIn sum, the population of neurons stimulated by INS includes both hSyn and mDlx neurons; within a range of stimulation intensities, this leads to overall excitation in the stimulated population, leading to the previously observed activations at distant post-synaptic sites.
Enhanced intracranial aneurysm development in a rat model of polycystic kidney disease
Authors: Cayron Anne F. , Morel Sandrine , Azam Maral , Haemmerli Julien , Aoki Tomohiro , Bijlenga Philippe , Allémann Eric , Kwak Brenda R. 
Published: March 2024

AbstractBackgroundPolycystic kidney disease (PKD) patients have a high intracranial aneurysms (IAs) incidence and risk of rupture. The mechanisms that make PKD patients more vulnerable to IA disease are still not completely understood. The PCK rat is a well-known PKD model and has been extensively used to study cyst development and kidney damage. Here, we used this rat model to study IA induction and vulnerability.MethodsIAs were induced in wild-type (WT) and PCK rats and their incidence was followed. Variation in the anatomy of the circle of Willis was studied in PCK rats and PKD patients. The expression of tight junction proteins was examined by immunohistochemistry in rats and in human ruptured and unruptured IAs from patients enrolled in the @neurIST study.ResultsAn increased frequency of fatal aortic dissection was unexpectedly observed in PCK rats after IA induction, which was due to modifications in the elastic architecture of the aorta in combination with the induced hypertension. Interestingly, IAs developed faster in PCK rats compared to WT rats. Variations in the anatomy of the circle of Willis were identified in PCK rats and PKD patients, a risk factor that may (in part) explain the higher IA incidence found in these groups. At 2-weeks after induction, the endothelium of IAs from PCK rats showed a decrease in the tight junction proteins zonula occludens-1 and claudin-5. This decrease in tight junction proteins was also observed in the endothelium of human ruptured IAs compared to unruptured IAs, making it a potential marker of IA wall vulnerability.ConclusionsOur study showed that PCK rats are more sensitive to IA induction. Variations in the anatomy of the circle of Willis and impaired regulation of tight junction proteins might put PCK rats and PKD patients more at risk of developing vulnerable IAs.
Fetal Growth Associated with Maternal Rheumatoid Arthritis and Juvenile Idiopathic Arthritis
Authors: Chock Eugenia Y. , Liew Zeyan , Pedersen Lars Henning , Thunbo Mette Østergaard 
Published: March 2024

Structured AbstractBackgroundPrior studies indicated that women with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are at twice higher risk of developing adverse pregnancy outcomes, this include preterm births and infants with low birth weight. A wide knowledge gap exists in our current understanding of how RA and JIA affect fetal growth during pregnancy.ObjectiveWe aimed to evaluate fetal growth among patients with RA/JIA by comparing fetal growth indicators of offspring born to this population, compared to individuals without RA/JIA. We hypothesized that fetal growth among patients with RA/JIA is reduced, compared to individuals without RA/JIA.Study DesignWe conducted a population-based cohort study in Denmark from 2008-2018 which included 503,491 individuals with singleton pregnancies. Among them, 2,206 were patients with RA and JIA. We linked several nationwide databases and clinical registries in Denmark to achieve our aim. Through the Danish Fetal Medicine Database (DFMD), we obtained fetal biometric measurements gathered from second trimester fetal ultrasound scans. We used International Classification of Diseases (ICD)-10 codes to identify pregnant patients with RA/JIA from the Danish National Patient Registry and linked them to the DFMD, other variables of interest were obtained from different Danish clinical registries. Next, we computed fetal growth gradient between second trimester and birth, using the mean difference in Z-score distances for each fetal growth indicator. We also estimated the risk of small for gestational age (SGA), all outcomes were compared between pregnant individuals with and without RA/JIA and adjusted for confounders.ResultsMaternal RA and JIA was not associated with a reduction of estimated fetal weight (EFW) at mid-pregnancy [adjusted mean EFW Z-score difference of 0.05 (95% CI 0.01, 0.10;p=0.022)], but lower birth weights were observed among offspring [adjusted mean Z-score difference of -0.08 (95% CI -0.13, -0.04;p<0.001)]. We observed reduced mean Z-score differences in weight gradient from second trimester to birth among offspring of patients with RA/JIA who used corticosteroids [-0.26 (95% CI -0.11, -0.41;p<0.001)], and sulfasalazine [-0.61 (95% CI -0.45, -0.77;p<0.001)] during pregnancy. Maternal RA/JIA was also associated with SGA [aOR of 1.47 (95% CI 1.16, 1.83;p<0.001)]. Similarly, the risk estimates were higher among corticosteroid [aOR 3.44 (95% CI 2.14, 5.25;p<0.001)] and sulfasalazine [(aOR 2.28 (95% CI 1.22, 3.88;p=0.005)) users.ConclusionAmong pregnant patients with RA/JIA, fetal growth restriction may be most apparent after 18 to 22 weeks of gestational age. Closer antenatal monitoring around this period should be considered for this population.
Influence of environmental variables, small-scale fisheries and vessel traffic on the distribution and behavior of bottlenose dolphins in a tropical lagoon
Authors: Brevet M. , Jaquemet S. , Wagner J. , Kiszka JJ. 
Published: March 2024

AbstractThe distribution of marine predators is influenced by a variety of natural and, in some cases, anthropogenic environmental factors. In particular, the optimal foraging theory predicts that micro-habitat selection should be the result of a trade-off between prey availability, energy expenditure, and predation risk. In addition, the risk-disturbance hypothesis suggests that anthropogenic disturbance may be perceived by animals in the same way as predation risk. Habitat selection may also be locally influenced by individual behavior and physiological state (defining functional habitats): variation in their needs should affect their optimal trade-off. We tested these hypotheses in a population of bottlenose dolphins living in a tropical lagoon using a habitat modeling approach. Bottlenose dolphins were predominantly distributed within the lagoon, with a preference for the vicinity of fringing and inner reefs (with lower predation risk than the outer reef), and were located in areas of high fish productivity, consistent with optimal habitat selection. We also observed an interaction between habitat and dolphin behavior, suggesting the existence of functional habitats: foraging was more common in nearshore habitats with probable higher prey density while resting and socializing were more common further from shore. Similarly, females with calves were preferentially found in shallower waters compared to other social groups. We did not observe any effects of anthro-pogenic disturbance variables and therefore cannot conclude on the risk-disturbance hypothesis for this population.
CYB561 supports the neuroendocrine phenotype in castration-resistant prostate cancer
Authors: Azur Romie Angelo G. , Olarte Kevin Christian V. , Ybañez Weand S. , Ocampo Alessandria Maeve M. , Bagamasbad Pia D. 
Published: March 2024

AbstractCastration-resistant prostate cancer (CRPC) is associated with resistance to androgen deprivation therapy, and an increase in the population of neuroendocrine (NE) differentiated cells. It is hypothesized that NE differentiated cells secrete neuropeptides that support androgen-independent tumor growth and induce aggressiveness of adjacent proliferating tumor cells through a paracrine mechanism. The cytochrome b561 (CYB561) gene, which codes for a secretory vesicle transmembrane protein, is constitutively expressed in NE cells and highly expressed in CRPC. CYB561 is involved in the α-amidation-dependent activation of neuropeptides, and contributes to regulating iron metabolism which is often dysregulated in cancer. These findings led us to hypothesize that CYB561 may be a key player in the NE differentiation process that drives the progression and maintenance of the highly aggressive NE phenotype in CRPC. In our study, we found thatCYB561expression is upregulated in metastatic and NE prostate cancer (NEPC) tumors and cell lines compared to normal prostate epithelia, and that its expression is independent of androgen regulation. Knockdown ofCYB561in androgen-deprived LNCaP cells dampened NE differentiation potential and transdifferentiation-induced increase in iron levels. In NEPC PC-3 cells, depletion of CYB561 reduced the secretion of growth-promoting factors, lowered intracellular ferrous iron concentration, and mitigated the highly aggressive nature of these cells in complementary assays for cancer hallmarks. These findings demonstrate the role of CYB561 in facilitating transdifferentiation and maintenance of NE phenotype in CRPC through its involvement in neuropeptide biosynthesis and iron metabolism pathways.
Cold stress induces a rapid redistribution of the antagonistic marks H3K4me3 and H3K27me3 inArabidopsis thaliana
Authors: Faivre Léa , Kinscher Nathalie-Francesca , Kuhlmann Ana Belén , Xu Xiaocai , Kaufmann Kerstin , Schubert Daniel 
Published: March 2024

AbstractWhen exposed to low temperatures, plants undergo a drastic reprogramming of their transcriptome in order to adapt to their new environmental conditions, which primes them for potential freezing temperatures. While the involvement of transcription factors in this process, termed cold acclimation, has been deeply investigated, the potential contribution of chromatin regulation remains largely unclear. A large proportion of cold-inducible genes carries the repressive mark histone 3 lysine 27 trimethylation (H3K27me3), which has been hypothesized as maintaining them in a silenced state in the absence of stress, but which would need to be removed or counteracted upon stress perception. However, the fate of H3K27me3 during cold exposure has not been studied genome-wide. In this study, we offer an epigenome profiling of H3K27me3 and its antagonistic active mark H3K4me3 during short-term cold exposure. Both chromatin marks undergo rapid redistribution upon cold exposure, however, the gene sets undergoing H3K4me3 or H3K27me3 differential methylation are distinct, refuting the simplistic idea that gene activation relies on a switch from an H3K27me3 repressed chromatin to an active form enriched in H3K4me3. Coupling the ChIP-seq experiments with transcriptome profiling reveals that differential histone methylation correlates with changes in expression. Interestingly, only a subset of cold-regulated genes lose H3K27me3 during their induction, indicating that H3K27me3 is not an obstacle to transcriptional activation. In the H3K27me3 methyltransferasecurly leaf (clf)mutant, many cold regulated genes display reduced H3K27me3 levels but their transcriptional activity is not altered prior or during a cold exposure, suggesting that H3K27me3 may serve a more intricate role in the cold response than simply repressing the cold-inducible genes in naïve conditions.
A generalised protein identification method for novel and diverse sequencing technologies
Authors: Bhandari Bikash Kumar , Goldman Nick 
Published: March 2024

AbstractProtein sequencing is a rapidly evolving field with much progress towards the realisation of a new generation of protein sequencers. The early devices, however, may not be able to reliably discriminate all 20 amino acids, resulting in a partial, noisy and possibly error-prone signature of a protein. Rather than achievingde novosequencing, these devices may aim to identify target proteins by comparing such signatures to databases of known proteins. However, there are no broadly applicable methods for this identification problem. Here, we devise a hidden Markov model method to study the generalized problem of protein identification from noisy signature data. Using a hypothetical sequencing device that can simulate several novel devices, we show that on the human protein database (N=20,181) our method has a good performance under many different operating conditions such as various levels of signal resolvability, different numbers of discriminated amino acids, sequence fragments and insertion and deletion error rates. Our results demonstrate the possibility of protein identification with high accuracy on many early experimental devices. We anticipate our method to be applicable for a wide range of protein sequencing devices in the future.
Prostaglandin D2 synthase controls Schwann cells metabolism
Authors: Trimarco Amelia , Audano Matteo , Marca Rosa La , Cariello Mariaconcetta , Falco Marta , Pedretti Silvia , Imperato Gabriele , Cestaro Alessandro , Podini Paola , Dina Giorgia , Quattrini Angelo , Massimino Luca , Caruso Donatella , Mitro Nico , Taveggia Carla 
Published: March 2024

ABSTRACTWe previously reported that in the absence of Prostaglandin D2 synthase (L–PGDS) peripheral nerves are hypomyelinated in development and that with aging they present aberrant myelin sheaths. We now demonstrate that L–PGDS expressed in Schwann cells is part of a coordinated program aiming at preserving myelin integrity.In vivoandin vitrolipidomic, metabolomic and transcriptomic analyses confirmed that myelin lipids composition, Schwann cells energetic metabolism and key enzymes controlling these processes are altered in the absence of L–PGDS. Moreover, Schwann cells undergo a metabolic rewiring and turn to acetate as the main energetic source. Further, they produce ketone bodies to ensure glial cell and neuronal survival. Importantly, we demonstrate that all these changes correlate with morphological myelin alterations and describe the first physiological pathway implicated in preserving PNS myelin.Collectively, we posit that myelin lipids serve as a reservoir to provide ketone bodies, which together with acetate represent the adaptive substrates Schwann cells can rely on to sustain the axo-glial unit and preserve the integrity of the PNS.
Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals
Authors: Palou-Márquez Guillermo , Supek Fran 
Published: March 2024

AbstractNonsense-mediated mRNA decay (NMD) is a quality-control pathway that degrades mRNA bearing premature termination codons (PTCs) resulting from mutation or mis-splicing, and that additionally participates in gene regulation of unmutated transcripts. We analyzed ∼10,000 exomes and ∼27,000 transcriptomes from human tumors and healthy tissues to quantify individual-level NMD efficiency, and assess its variability between tissues and between individuals. This was done by monitoring allele-specific expression of germline PTCs, and independently supported by mRNA levels of endogenous NMD target transcripts. Nervous system and reproductive system tissues have lower NMD efficiency than other tissues such as the digestive tract. Next, there is considerable systematic inter-individual variability in NMD efficiency, and we identify two underlying mechanisms. First, in cancers there are somatic copy number alterations that robustly associate with NMD efficiency, prominently the commonly-occurring gain at chromosome 1q that encompasses two core NMD genes:SMG5andSMG7and additional functionally interacting genes such asPMF1andGON4L. Second, loss-of-function germline variants in various genes such as theKDM6Bchromatin modifier can associate with higher or lower NMD efficiency in individuals, affecting different tissues thereof. Variable NMD efficiency should have clinical implications as it modulates positive selection upon somatic nonsense mutations in tumor suppressor genes, and is associated with survival of cancer patients, with relevance to predicting immunotherapy responses across cancer types.
PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure
Authors: Strelkova Olga S. , Osgood Richard T. , Tian Chunjie J. , Zhang Xinyuan , Hale Evan , De-la-Torre Pedro , Hathaway Daniel M. , Indzhykulian Artur A. 
Published: March 2024

AbstractSensory hair cells of the cochlea are essential for hearing, relying on the mechanosensitive stereocilia bundle at their apical pole for their function. Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1) is a stereocilia protein required for normal hearing in mice, and for the formation of the transient stereocilia surface coat, expressed during early postnatal development. While the function of the stereocilia coat remains unclear, growing evidence supports PKHD1L1 as a human deafness gene. In this study we carry out in depth characterization of PKHD1L1 expression in mice during development and adulthood, analyze hair-cell bundle morphology and hearing function in aging PKHD1L1-defficient mouse lines, and assess their susceptibility to noise damage. Our findings reveal that PKHD1L1-deficient mice display no disruption to bundle cohesion or tectorial membrane attachment-crown formation during development. However, starting from 6 weeks of age, PKHD1L1-defficient mice display missing stereocilia and disruptions to bundle coherence. Both conditional and constitutive PKHD1L1 knock-out mice develop high-frequency hearing loss progressing to lower frequencies with age. Furthermore, PKHD1L1-deficient mice are susceptible to permanent hearing loss following moderate acoustic overexposure, which induces only temporary hearing threshold shifts in wild-type mice. These results suggest a role for PKHD1L1 in establishing robust sensory hair bundles during development, necessary for maintaining bundle cohesion and function in response to acoustic trauma and aging.
The Early Dodder Gets the Host: Decoding the Coiling Patterns ofCuscuta campestriswith Automated Image Processing
Authors: Bentelspacher Max , Amézquita Erik J. , Adhikari Supral , Barros Jaime , Park So-Yon 
Published: March 2024

AbstractCuscutaspp., commonly known as dodders, are rootless and leafless stem parasitic plants. Upon germination,Cuscutastarts rotating immediately in a counterclockwise direction (circumnutation) to locate a host plant, creating a seamless vascular connection to steal water and nutrients from its host. In this study, our aim was to elucidate the dynamics of the coiling patterns ofCuscuta, which is an essential step for successful parasitism. Using time-lapse photography, we recorded the circumnutation and coiling movements ofC. campestrisat different inoculation times on non- living hosts. Subsequent image analyses were facilitated through an in-house Python-based image processing pipeline to detect coiling locations, angles, initiation and completion times, and duration of coiling stages in between. The study revealed that the coiling efficacy ofC. campestrisvaried with the inoculation time of day, showing higher success and fastinitiation in morning than in evening. These observations suggest thatCuscuta, despite lacking leaves and a developed chloroplast, can discern photoperiod changes, significantly determining its parasitic efficiency. The automated image analysis results confirmed the reliability of our Python pipeline by aligning closely with manual annotations. This study provides significant insights into the parasitic strategies ofC. campestrisand demonstrates the potential of integrating computational image analysis in plant biology for exploring complex plant behaviors. Furthermore, this method provides an efficient tool for investigating plant movement dynamics, laying the foundation for future studies on mitigating the economic impacts of parasitic plants.