bluuebunny/crossref_metadata_2025_split huggingface dataset:
Right posterior theta reflects human parahippocampal phase resetting by salient cues during goal-directed navigation
Authors: Güth Malte R. , Reid Andrew , Zhang Yu , Huntgeburth Sonja C. , Mill Ravi D. , Dagher Alain , Kerns Kim , Holroyd Clay B. , Petrides Michael , Cole Michael W. , Baker Travis E. 
Published: November 2024

AbstractAnimal and computational work indicate that phase resetting of theta oscillations (4-12 Hz) in the parahippocampal gyrus (PHG) by salient events (e.g., reward, landmarks) facilitates the encoding of goal-oriented information during navigation. Although well-studied in animals, this mechanism has not been empirically substantiated in humans. In the present article, we present data from two studies (Study 1: asynchronous EEG-MEG | Study 2: simultaneous EEG-fMRI) to investigate theta phase resetting and its relationship to PHG BOLD activation in healthy adults (aged 18-34 years old) navigating a virtual T-maze to find rewards. In the first experiment, both EEG and MEG data revealed a burst of theta power over right-posterior scalp locations following feedback onset (termed right-posterior theta, RPT), and RPT power and measures of phase resetting were sensitive to the subject’s spatial trajectory. In Experiment 2, we used probabilistic tractography data from the human connectome project to segment the anterior and posterior PHG based on differential connectivity profiles to other brain regions. This analysis resulted in a PHG subdivision consisting of four distinct anterior and two posterior PHG clusters. Next, a series of linear mixed effects models based on simultaneous EEG-fMRI data revealed that single-trial RPT peak power significantly predicted single-trial hemodynamic responses in two clusters within the posterior PHG and one in the anterior PHG. This coupling between RPT power and PHG BOLD was exclusive to trials performed during maze navigation, and not during a similar task devoid of the spatial context of the maze. These findings highlight a role of PHG theta phase resetting for the purpose of encoding salient information during goal-directed spatial navigation. Taken together, RPT during virtual navigation integrates experimental, computational, and theoretical research of PHG function in animals with human cognitive electrophysiology studies and clinical research on memory-related disorders such as Alzheimer’s disease.
Evaluation of Brain Age as a Specific Marker of Brain Health
Authors: Tan Trevor Wei Kiat , Nguyen Kim-Ngan , Zhang Chen , Kong Ru , Cheng Susan F , Ji Fang , Chong Joanna Su Xian , Chong Eddie Jun Yi , Venketasubramanian Narayanaswamy , Orban Csaba , Chee Michael W. L. , Chen Christopher , Zhou Juan Helen , Yeo B. T. Thomas ,   Alzheimer’s Disease Neuroimaging Initiative,   Australian Imaging Biomarkers and Lifestyle Study of Aging
Published: November 2024

ABSTRACTBrain age is a powerful marker ofgeneralbrain health. Furthermore, brain age models are trained on large datasets, thus giving them a potential advantage in predictingspecificoutcomes – much like the success of finetuning large language models for specific applications. However, it is also well-accepted in machine learning that models trained to directly predict specific outcomes (i.e., direct models) often perform better than those trained on surrogate outcomes. Therefore, despite their much larger training data, it is unclear whether brain age models outperform direct models in predicting specific brain health outcomes. Here, we compare large-scale brain age models and direct models for predicting specific health outcomes in the context of Alzheimer’s Disease (AD) dementia. Using anatomical T1 scans from three continents (N = 1,848), we find that direct models outperform brain age models without finetuning. Finetuned brain age models yielded similar performance as direct models, but importantly, did not outperform direct models although the brain age models were pretrained on 1000 times more data than the direct models: N = 53,542 vs N = 50. Overall, our results do not discount brain age as a useful marker of general brain health. However, in this era of large-scale brain age models, our results suggest that small-scale, targeted approaches for extracting specific brain health markers still hold significant value.
Identification of Potential Hub Genes and Therapeutic Targets in Colorectal Cancer Using Integrated Bioinformatics Approaches
Authors: D Kamalakannan , R Manivannan , Kumar Suresh Gopal , Kumar Dilip 
Published: November 2024

AbstractIn this study, we took a comprehensive approach using bioinformatics to uncover potential therapeutic targets for colorectal cancer (CRC). We started by analyzing gene expression data from GEO2R to identify genes that were differentially expressed in CRC. Then, using FunRich software, we created Venn diagrams to visualize these genes. From the 191 upregulated genes we found, we focused on potential “hub genes” by looking at their network connections and strength, using the STRING database.To understand the roles of these hub genes, we performed functional analyses like Gene Ontology (GO) and pathway enrichment through the DAVID platform. This helped us pinpoint key biological processes and pathways linked to the genes we identified. We also looked at patient survival data from GEPIA, along with information on gene expression related to disease stages and metastatic progression. This helped us identify which hub genes were most relevant for CRC.In addition, we examined genetic changes and gene expression patterns in CRC patients through databases like cBioPortal and the Human Protein Atlas. This gave us more evidence supporting the involvement of these genes in the disease. Ultimately, our analysis highlighted CXCL8, FOXC1, ICOS, and MCF2 as potential hub genes with important roles in CRC. These genes may serve as useful biomarkers for both diagnosing CRC and predicting patient outcomes, and they could also help guide the development of targeted treatments to improve survival rates.
Ephaptic coupling enables action potential conduction
Authors: Waaben J. , Hofgaard J.P. , Pick G.L. , Loisel C. , Engstrøm T. , Holstein-Rathlou N.H. , Poelzing S. , Nielsen M.S. 
Published: November 2024

AbstractBackgroundCardiac action potentials are believed to propagate solely by electrotonic transmission via gap junctions. In the alternative theory of ephaptic transmission, changes in extracellular electrical fields and ion concentrations may enable a cardiomyocyte to activate its neighbors. The involvement of ephaptic mechanisms remain highly disputed and has been discounted due to the reported inability of an isolated cardiomyocyte to activate another.MethodsIsolated rat cardiomyocytes were subjected to whole cell patch clamp. Transmission of action potentials was tested in current clamp in isolated cardiomyocytes pushed together and in native cardiomyocyte pairs. Sodium channel activation and inactivation was tested in voltage clamp.ResultsIsolated cardiomyocytes were pushed together end-to-end and one stimulated to fire an action potential. In 10 attempts, 2 pairs showed successful transmission of action potentials, showing that ephaptic transmission is possible. In native pairs, subthreshold depolarization was transferred between cardiomyocytes of native electrically coupled pairs, however, only after a delay, which is not be explained from electrotonic theory. Once action potentials were elicited in one cardiomyocyte of a native pair, the neighbor was activated with delays under 2 msec. The activation delay did not correlate with gap junctional coupling, again suggesting the presence of an alternative mechanism. In voltage clamp of native cardiomyocyte pairs, one cardiomyocyte was held at -90 mV while depolarizing pulses were applied to its neighbor. Consistently, activation of sodium channels in the depolarized cell led to activation of sodium channels in the hyperpolarized cell, which fits well with ephaptic but not electrotonic theory. Ephaptic transmission requires a shielded local domain. To separate this, we measured steady state inactivation in native pairs. As expected, all channels inactivated at -40 mV. However, when maintaining a potential of – 40 mV for an extended period, sodium current elicited at 0 mV re-emerged by de-inactivation. The de-inactivation at -40 mV support that a shielded domain exists where potassium currents can hyperpolarize the local potential.ConclusionsWe show for the first time that ephaptic transmission is possible, that it is most likely in operation, also in the presence of gap junctional coupling, and finally our study suggests that data obtained in single cells may fail to reproduce key features of the electrophysiology of cardiomyocytes that interact with neighboring cardiomyocytes.
Contribution of ammonia oxidizers to inorganic carbon fixation in the dark ocean
Authors: Bayer Barbara , Kitzinger Katharina , Paul Nicola L. , Albers Justine B. , Saito Mak A. , Wagner Michael , Carlson Craig A. , Santoro Alyson E. 
Published: November 2024

AbstractAmmonia-oxidizing archaea are the most abundant chemolithoautotrophs in the ocean, comprising up to 40% of microbial cells in deep waters, and are assumed to dominate dissolved inorganic carbon (DIC) fixation below the sunlit surface layer. Yet, the supply of reduced nitrogen from particulate organic matter flux from the surface is insufficient to support the amount of nitrification required to sustain measured DIC fixation rates in the dark ocean. The aim of this study was to quantify the contribution of ammonia oxidizers to DIC fixation in the dark ocean. We used phenylacetylene - a specific inhibitor of the ammonia monooxygenase enzyme - to selectively inhibit ammonia oxidizers during two oceanographic expeditions in the eastern tropical and subtropical Pacific Ocean spanning 35º N to 10º S. We show that ammonia oxidizers contribute only a small fraction to dark DIC fixation, accounting for 2 to 22% of the depth-integrated rates in the eastern tropical Pacific. The highest contributions were observed at the depth of the nitrification maximum, where ammonia oxidation could account for up to 50% of dark DIC fixation. Our results help to reconcile the observed discrepancies between nitrogen supply and DIC fixation at depth, and provide a new perspective on global ocean chemolithoautotrophy, revealing that the majority of DIC fixation within the lower euphotic zone and below 200 m depth is not fueled by ammonia oxidation.SignificanceMicrobes in the ocean play important roles in the global carbon cycle and the ocean’s capacity to sequester carbon. Despite this importance, deciphering the contributions of different microbial metabolic processes to the oceanic carbon budget remains challenging. Particularly in the dark ocean, large discrepancies between organic matter fluxes and measured microbial metabolic rates are observed. We show that abundant chemoautotrophs – ammonia-oxidizing microbes – contribute only a small fraction to dark carbon fixation in the Pacific Ocean, challenging the current view that carbon fixation in the dark ocean is primarily sustained by nitrification. This work advances our understanding of microbial carbon processing, and offers new insights into the long-standing question of the main energy sources fueling carbon fixation in the dark ocean.
When sexual selection meets genetic drift: the coevolution of male traits and female preferences in finite populations
Authors: Xu Kuangyi 
Published: November 2024

AbstractFisher’s mechanism is central to sexual selection theories, where mate choice generates a genetic correlation between male trait and female preference alleles, driving the coevolution of the trait and preference with positive feedback. However, how Fisher’s mechanism operates in finite populations remains unclear, as sexual selection can interact with genetic drift, influencing both trait-preference correlation and allele frequencies. By using population genetic models, this study addresses the gap in our understanding of interactions between fundamental evolutionary forces. We show that more frequent recombination increases trait-preference correlations in infinitely large populations, unless a positive correlation initially exists. In finite populations, interactions between sexual selection and drift elevate trait-preference correlation when the male trait is rare but reduce the correlation when the trait is common, potentially making it negative when recombination is rare or population size is small. Also, these interactions tend to slow the spread of the male trait while promoting the evolution of preferences. These results differ from the Hill-Robertson effect under natural selection due to two key factors: mate choice generates positive linkage disequilibrium, and the strength of indirect selection on preferences increases with linkage disequilibrium. The fixation of trait and preference alleles is positively correlated. This correlation peaks at intermediate recombination rates and is often stronger in small populations than in large ones, so large population sizes tend to reduce the likelihood that both trait and preference alleles fix. We discuss how the results provide insights into the progression of sexual selection in nature.
Associations between DNA methylation and cognitive function in early-stage hormone receptor-positive breast cancer patients
Authors: Liu Shuwei , Liu Dongjing , Bender Catherine M. , Erickson Kirk I. , Sereika Susan M. , Shaffer John R. , Weeks Daniel E. , Conley Yvette P. 
Published: November 2024

AbstractBackgroundApproximately one-third of breast cancer (BC) patients show poorer cognitive function (CF) before receiving adjuvant therapy compared with age-matched healthy controls. However, the biological mechanisms driving CF variation in the context of BC remain unclear. In this study, we aimed to identify genes and biological pathways associated with CF in postmenopausal women with early-stage hormone receptor-positive (HR+) BC using DNA methylation (DNAm) data, a dynamic regulator of gene activity.MethodsEpigenome-wide association studies (EWAS) and differentially methylated region analyses were performed for each CF phenotype (seven objective domains and one subjective phenotype) using DNAm data from whole blood samples (n=109) taken at time of enrollment. Post-EWAS functional analyses were performed to enhance the understanding of the CF-related cytosine-phosphate-guanine (CpG) sites.ResultsWhen adjusting for age, verbal IQ scores, and global DNAm signature, cg10331779 nearCTNND2(p-value= 9.65 × 10−9) and cg25906741 inMLIP(p-value= 2.01 × 10−8) were associated with processing speed and subjective CF, respectively, while regions in/nearSLC6A11,PRKG1/CSTF2T, andFAM3Bfor processing speed, and regions in/nearPI4KBandSGCE/PEG10for mental flexibility were differentially methylated. In addition, beta-estradiol was identified as a common upstream regulator for all the CF phenotypes, suggesting an essential role of estrogen in explaining variation in CF of HR+ BC patients.ConclusionsIn our EWAS of 8 CF phenotypes, we found two epigenome-wide significant signals, one at cg10331779 nearCTNND2with processing speed and the other at cg25906741 inMLIPwith subjective CF. We also found three differentially methylated regions associated with processing speed and two associated with mental flexibility. These findings need replication in larger cohorts.
Phenotypic variation and weak behavioral isolation in a putative hybrid zone between AndeanAtlapetesbrushfinches (Passerellidae)
Authors: Muñoz-Quintana Gabriela , Cuervo Andrés M. 
Published: November 2024

ABSTRACTIndividuals in the contact zone between hybridizing species often exhibit intermediate phenotypes that vary smoothly in a clinal fashion from one species to the other. However, many tropical hybrid zones remain poorly documented due to limited specimens, small species ranges, and logistical challenges of accessing key localities within contact zones. We investigated phenotypic variation and species recognition between two endemic Andean brushfinches that replace each other geographically along the Central Cordillera of the Colombian Andes:Atlapetes fuscoolivaceus(Dusky-headed Brushfinch) andA. flaviceps(Yellow-headed Brushfinch). We scored phenotypic traits from 111 georeferenced photographs of live individuals and 40 museum specimens. Using cline-fit analyses for two hybrid indexes (face color pattern and overall body color), we tested whether phenotypic transitions were abrupt (suggesting a barrier, or a sharp replacement) or gradual (indicating hybridization) across their contact zone. We also conducted playback experiments to assess song discrimination as an indication of potential prezygotic reproductive barrier. Plumage traits varied clinally, with a center near Inzá, Cauca (2.55°N), and with notably different cline widths between facial (12 km) and body-color traits (73 km). This difference likely reflects greater sampling density for facial traits and possibly stronger selection on face coloration. TerritorialA. flavicepsindividuals responded to songs of both species (no difference in latency); however, response duration was longer when exposed to local songs, indicating weak behavioral isolation. Our results suggest that these two ecologically equivalent brushfinches maintain a hybrid zone where their ranges meet, with a smooth transition from a pure phenotypic form to the other, which is likely facilitated by weak prezygotic behavioral barriers to reproduction. This study represents the initial step in investigating phenotypic variation, speciation genomics, behavior and interaction at the hybrid zone betweenAtlapetesbrushfinches in the Colombian Andes.
Combined SNP parental haplotyping and intensity analysis identifies meiotic and mitotic aneuploidies and frequent segmental aneuploidies in preimplantation human embryos
Authors: Handyside Alan H , Newnham Louise , Newnham Matthew , Henning Dominika , Velebny Jan , Pozdena Jan , Krmelova Jindriska , Horak Jakub 
Published: November 2024

AbstractGenome-wide single nucleotide polymorphism (SNP) genotyping using microarrays and karyomapping (parental haplotyping) is a universal linkage-based method for preimplantation genetic testing of monogenic disease (PGT-M) and identification of chromosome aneuploidies, including meiotic trisomies, monosomies and deletions. Following IVF, embryos are biopsied at the blastocyst stage and several trophectoderm cells removed. Both parents, a close relative of known disease status and the biopsy samples are genotyped and parental haplotypes analysed. Here we extended the method by combining parental haplotyping with SNP intensity analysis. This enables identification of meiotic and mitotic, whole and segmental aneuploidies at high resolution. In 342 cycles of PGT-M in couples with a mean maternal age of 32.9±4.2 (SD), 37% (471/1270) of the biopsy samples were identified as aneuploid with an almost equal number of meiotic and mitotic aneuploidies. Meiotic aneuploidies were predominantly whole chromosome aneuploidies of maternal origin and increased with maternal age. Mitotic aneuploidies (with normal parental haplotype patterns) were mainly segmental imbalances. For PGT of aneuploidies (PGT-A) in infertile couples, identifying meiotic aneuploidies, which are almost all non-viable, provides a valuable option to avoid the discard of embryos with only mitotic aneuploidies of unknown clinical outcome.
Small form factor implantable neural probe with efficient flip chip μLED for in vivo optogenetics
Authors: Abrantes Mafalda , Pereira Tiago , Silva Patrícia , Falcão Margarida , Borme Jérôme , Alpuim Pedro , Jacinto Luis 
Published: November 2024

AbstractOptogenetics is a widely used tool to dissect neural circuits with optical stimulation, but it requires that light is delivered to photosensitive neurons inside the brain. Implantable neural probes with microscale LEDs (μLEDs) are an emerging approach to delivering light to the brain with superior light output control. However, approaches to integrate μLEDs in neural probes depend on complex fabrication processes. Here, we developed an implantable small form factor neural probe that integrates highly efficient commercial flip chip μLEDs using only standard lithography processes in silicon and a custom automated LED mounting approach with custom 3D-printed tools on a pick-and-place machine. The probe has a cross-sectional area under 0.013 mm2but can output up to 2.3 mW of optical power with an irradiance of 175 mW/mm2. Due to the high plug efficiency of the LED and wide large interconnect lines, the neural probe has improved heat dissipation properties and can perform stimulation protocols up to 50 Hz and 90% duty cycles without surpassing hotspot temperature elevations above 1 ºC. The neural probes were validated in vivo, with brain activity in the motor cortex of transgenic optogenetic mice being reliably modulated by pulsed light emitted from the probe.
Inhibition of Notch Signaling Attenuates Epileptic Discharges in the Adolescent Rat Brain after Status Epilepticus Induction
Authors: Liu Jie , Chen Jin , Yuan Ping 
Published: November 2024

AbstractBackgroundNotch signaling plays a critical role in neuroregeneration after injuries such as those caused by status epilepticus (SE).ObjectiveTo explore the effects of Notch signaling on epileptogenesis and the underlying mechanisms in adolescent rat brains in the acute phase after SE induction.MethodsN-[N-(3,5-difluorophenacetyl)- L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), which indirectly inhibits Notch, was injected into rats during the acute phase after SE induction to inhibit Notch signaling. Electroencephalogram (EEG) was used to observe spontaneous recurrent seizures. Differences in the synaptic structures of the hippocampus were observed by transmission electron microscopy. Nissl staining and Timm staining were used to observe the loss of hippocampal neurons and sprouting of mossy fibers, respectively, in the hippocampus at 28 days after SE.ResultsEEG illustrated that DAPT treatment reduced the severity of epileptic discharges after SE induction. Transmission electron microscopy revealed reductions in the presynaptic membrane active band length and postsynaptic membrane dense matter thickness in the CA1 region of the hippocampus. Meanwhile, Nissl staining demonstrated that DAPT treatment reduced the loss of hippocampal neuronal cell degeneration, and the hippocampal structure was repaired to a certain extent. Meanwhile, Timm staining illustrated that DAPT treatment did not affect mossy fiber sprouting (MFS) after SE induction.ConclusionInhibiting Notch signaling reduced EEG epileptic activity, attenuated synaptic damage, and partially restored the hippocampal neuronal structure. However, it did not alter MFS after SE induction.