bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Obesity Paradox in A Murine Model of Sepsis: Improved Survival Despite Increased Organ Injury in Obese Mice
Authors: Lewis Erick D. , Williams Holden C. , Bruno Maria E.C. , Stromberg Arnold J. , Saito Hiroshi , Johnson Lance A. , Starr Marlene E. 
Published: September 2021

ABSTRACT
Despite the known deleterious effects of obesity, clinical data indicate that overweight or obese patients experience higher rates of sepsis survival compared to normal and underweight patients; a phenomenon called the obesity paradox. Results from preclinical sepsis studies have not been able to replicate these findings. The objective of this study was to test the existence of the obesity paradox in a murine model of cecal slurry (CS)-induced sepsis with insulin-resistant diet-induced obese mice. Male C57BL/6 mice were provided high-fat (HFD) or low-fat (LFD) diets for 20 weeks. HFD-fed mice experienced higher rates of survival compared to LFD-fed mice after septic challenge induced by CS injection (66% vs. 25%, P = 0.01, survival assessed for 14 days). Despite the survival advantage, HFD-fed mice had higher rates of positive bacterial cultures and increased markers of kidney injury. Circulating levels of IL-6, IL-1β, TNFα, and IL-23 were equivalent 24 h after CS-injection; however, IL-17A was uniquely increased in HFD-fed mice. While LFD-fed mice maintained euglycemia, HFD-fed mice were hyperglycemic 6 and 12 h after CS-injection. Stable isotope resolved metabolomics analysis of liver tissue showed diverging pathways of glucose utilization during sepsis, with LFD-fed mice significantly upregulating glycolytic activity and HFD-fed mice decreasing glucose entry into the TCA cycle. This murine study corroborates clinical data that obesity confers a survival benefit in sepsis, albeit at the expense of more significant organ injury. The mechanisms promoting survival in the obese remain unknown; however, this model appears to be well-poised to begin answering this question. Differences in glucose utilization are a novel target to investigate this paradox.
Diagnosis of Acute Promyelocytic Leukemia After Presentation to Neuro-Ophthalmology
Authors: Paxton Andrew B. , Micieli Jonathan A. 
Published: September 2021

Background:
Acute promyelocytic leukemia (APML) is a medical emergency that can initially present with neuro-ophthalmologic signs. Early recognition is crucial, and immediate treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) can be life-saving. The goal of this study was to describe patients who first presented to neuro-ophthalmology and were subsequently diagnosed with APML.

Methods:
We retrospectively reviewed consecutive patients seen at a tertiary neuro-ophthalmology centre. Patients with an unknown diagnosis of APML at presentation who subsequently went on to receive this diagnosis were included. Clinical characteristics, neuro-ophthalmologic findings, and outcome were retrieved.

Results:
A total of 3 patients (2 women and 1 men) with a mean age of 30.7 (range 24–33) years were included in the study. Neuro-ophthalmologic diagnoses at presentation were severe hemorrhagic papilledema related to dural venous sinus thrombosis, hemorrhagic bilateral optic disc edema, and left homonymous hemianopia related to an occipital lobe hemorrhage. At diagnosis, the average hemoglobin was 83.7g/L (range 78–104), and the platelet count was 39.3 × 109/L (range 15–77). All patients were treated with ATRA and ATO. One patient developed papilledema and sixth nerve palsies related to this treatment, which resolved with acetazolamide. Clinical follow-up ranged from 6 to 12 months, and all patients were in clinical remission about systemic APML.

Conclusion:
Neuro-ophthalmologic symptoms may be the first manifestations of APML, and a complete blood count is an essential test in patients presenting with optic disc edema, especially if hemorrhagic.
Establishing the Minimum Intensity of Transcranial Magnetic Stimulation Superconditioning Pulses to Effect Inhibition and Facilitation of Motor Evoked Potentials
Authors: Calancie Blair M. , Chin Stella , Wang Dongliang 
Published: September 2021

Purpose:
Previously, we showed that a three-pulse train of weak transcranial magnetic stimulation (TMS) pulses—a superconditioning (SC) train—when followed by a stronger TMS pulse could enhance the inhibition or facilitation of the resultant motor evoked potential (MEP) compared with that seen with traditional dual-pulse inputs. The purpose of the present study was to establish the relative minimum intensity of SC pulses needed to influence MEP output and whether this differed for upper- versus lower-limb muscles.

Methods:
We examined 33 older adult subjects, targeting abductor pollicis brevis and tibialis anterior muscles. Older subjects were included in the anticipation of using findings from this study to guide further studies in persons with amyotrophic lateral sclerosis. Three-pulse trains of SC inputs of different intensities were delivered either 1 millisecond before (for inhibition) or 10 millisecond before (for facilitation) a stronger TMS test pulse. Motor evoked potential magnitudes for SC +test sets were normalized to test input responses and were compared within and between subjects.

Results and conclusions:
For inhibition, the minimum intensity of SC pulses needed to influence the follow-on MEP was found to be 60% of the target muscle's resting three-pulse MEP threshold for most abductor pollicis brevis and tibialis anterior muscles (2-millisecond interpulse intervals). For facilitation, somewhat higher intensities (70%) were typically needed to cause facilitation. Both values of SC pulses for inhibition/facilitation are considerably lower than the intensity of the conditioning pulse—often reported as 80% of the single-pulse threshold—typically used in dual-pulse TMS paradigms. This approach may allow testing of upper motor neuron function using weaker stimulus pulse intensities than are typically employed, improving testing compliance in persons whose thresholds are elevated because of injury or disease.
Modeling the Impact of Electrode/Tissue Geometry on Electrical Stimulation in Stereo-EEG
Authors: Shindhelm Alexis C. , Thio Brandon J. , Sinha Saurabh R. 
Published: September 2021

Purpose:
Electrical stimulation through depth electrodes is used to map function and seizure onset during stereoelectroencephalography in patients undergoing evaluation for epilepsy surgery. Factors such as electrode design, location, and orientation are expected to impact effects of electrical stimulation.

Methods:
We developed a steady-state finite element model of brain tissue including five layers (skull through white matter) and an implanted electrode to explore the impact of electrode design and placement on the activation of brain tissue by electrical stimulation. We calculated electric potentials, current densities, and volume of tissue activated (Vol

act
) in response to constant current bipolar stimulation. We modeled two depth electrode designs (3.5- and 4.43-mm intercontact spacing) and varied electrode location and orientation.

Results:
The electrode with greater intercontact spacing produced 8% to 23% larger Vol

act
(1% to 16% considering only gray matter). Vertical displacement of the electrodes by half intercontact space increased Vol

act
for upward displacement (6% to 83% for all brain tissue or −5% to 96% gray matter only) and decreased Vol

act
(1% to 16% or 24% to 49% gray matter only) for downward displacement. Rotating the electrode in the tissue by 30° to 60° with respect to the vertical axis increased Vol

act
by 30% to 90% (20%–48% gray matter only).

Conclusions:
Location and orientation of depth electrodes with respect to surrounding brain tissue have a large impact on the amount of tissue activated during electrical stimulation mapping in stereoelectroencephalography. Electrode design has an impact, although modest for commonly used designs. Individualization of stimulation intensity at each location remains critical, especially for avoiding false-negative results.
Temporal irreversibility of neural dynamics as a signature of consciousness
Authors: de la Fuente Laura , Zamberlan Federico , Bocaccio Hernán , Kringelbach Morten , Deco Gustavo , Sanz Perl Yonatan , Tagliazucchi Enzo 
Published: September 2021

AbstractEven though the fundamental laws of physics are the same when the direction of time is inverted, dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of the physical world, and thus its covariance with the level of conscious awareness. Inspired by recent developments in stochastic thermodynamics, we implemented a data-driven and model-free deep learning framework to decode the temporal inversion of electrocorticography signals acquired from non-human primates. Brain activity time series recorded during conscious wakefulness could be distinguished from their inverted counterparts with high accuracy, both using frequency and phase information. However, classification accuracy was reduced for data acquired during deep sleep and under ketamine-induced anesthesia; moreover, the predictions obtained from multiple independent neural networks were less consistent for sleep and anesthesia than for conscious wakefulness. Finally, the analysis of feature importance scores highlighted transitions between slow (≈20 Hz) and fast frequencies (> 40 Hz) as the main contributors to the temporal asymmetry observed during conscious wakefulness. Our results show that a preferred temporal direction is simultaneously manifest in the neural activity evoked by conscious mentation and in the phenomenology of the passage of time, establishing common ground to tackle the relationship between brain and subjective experience.
HyperEx: A Tool to Extract Hypervariable Regions from 16S rRNA Sequencing Data
Authors: Ebou Anicet , Koua Dominique , Zeze Adolphe 
Published: September 2021

ABSTRACTThe 16S ribosomal RNA gene is one of the most studied genes in biology. This 16S ribosomal RNA importance is due to its wide application in phylogenetics and taxonomic elucidation of bacteria and archaea. Indeed, 16S ribosomal RNA is present in almost all bacteria and archaea and has, among many other useful characteristics, a low mutation rate. The 16S ribosomal RNA is composed of nine hypervariable regions which are commonly targeted by high throughput sequencing technologies in identification or community studies like metabarcoding studies. Unfortunately, the hypervariable regions do not have the same taxonomic resolution among all bacteria taxa. This requires a preliminaryin silicoanalysis to determine the best hypervariable regions to target in a particular study. Nevertheless, to the best of our knowledge, no automated primer-based open-source tool exists to extract hypervariable regions from complete or near-complete 16S rRNA sequencing data. Here we present HyperEx which efficiently extracts the hypervariable region of interest based on embedded primers or user-given primers. HyperEx implements the Myers algorithm for the exact pairwise sequence alignment. HyperEx is freely available under the MIT license as an operating system independent Rust command-line tool athttps://github.com/Ebedthan/hyperexandhttps://crates.io.
Silencing of hippocampal synaptic transmission impairs spatial reward search on a head-fixed tactile treadmill task
Authors: Jordan Jake T. , Gonçalves J. Tiago 
Published: September 2021

AbstractHead-fixed linear treadmill tasks have been used to study hippocampal physiology in mice. Although some hippocampal neurons establish place fields along linear treadmills, it is not clear if the hippocampus is required for spatial memory on this task. Using a Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) approach, we found that silencing hippocampal output on rewarded treadmill tasks impaired search for rewards signaled by spatial cues but did not impair search for rewards signaled by local cues, recapitulating findings from other behavior tasks. These findings serve to contextualize data on hippocampal physiology from mice performing this task.
Enhancer-priming in ageing human bone marrow mesenchymal stromal cells contributes to immune traits
Authors: Lai Mang Ching , Ruiz-Velasco Mariana , Arnold Christian , Sigalova Olga , Bunina Daria , Berest Ivan , Ding Ximing , Hennrich Marco L. , Poisa-Beiro Laura , Claringbould Annique , Mathioudaki Anna , Pabst Caroline , Ho Anthony D. , Gavin Anne-Claude , Zaugg Judith B. 
Published: September 2021

AbstractBone marrow mesenchymal stromal cells (BMSCs) can differentiate into adipocytes and osteoblasts, and are important regulators of the haematopoietic system. Ageing associates with an increased ratio of bone marrow adipocytes to osteoblasts and immune dysregulation. Here, we carried out an integrative multiomics analysis of ATAC-Seq, RNA-Seq and proteomics data from primary human BMSCs in a healthy cohort age between 20 - 60. We identified age-sensitive elements uniquely affecting each molecular level where transcription is mostly spared, and characterised the underlying biological pathways, revealing the interplay of age-related gene expression mechanism changes spanning multiple gene regulatory layers. Through data integration with enhancer-mediated gene regulatory network analysis, we discovered that enhancers and transcription factors influence cell differentiation potential in the ageing BMSCs. By combining our results with genome-wide association study data, we found that age-specific changes could contribute to common traits related to BMSC-derived tissues such as bone and adipose tissue, and to immune-related traits on a systemic level such as asthma. We demonstrate here that a multiomics approach is crucial for unravelling complex information, providing new insights on how ageing contributes to bone marrow- and immune-related disorders.
Quantifying the Effect of Anti-cancer Compound (Piperlongumine) on Cancer Cells Using Single-Cell Force Spectroscopy
Authors: de Alcântara-Contessoto Nayara Sousa , Cornélio Marinônio Lopes , Kiang Ching-Hwa 
Published: September 2021

AbstractNatural compounds have shown a great potential in anti-cancer research by tumor growth inhibition and anti-metastatic properties. Piperlongumine (PL) is a natural compound derived from pepper species that has been demonstrated to have anti-cancer effect on HeLa cells. Here we focus on understanding the mechanical properties of HeLa cells under PL treatment, using Atomic Force Microscopy (AFM) based single-cell manipulation technique. We used AFM to pull single HeLa cells and acquired the force-distance curves that presented stepwise patterns. We analyzed the step force (SF) and observed that cells treated with PL exhibit higher force compared to control cells. This SF increase was also observed in experiments performed on substrates of different stiffness. Therefore, analyzing SF, it is possible to investigate the effect of PL on the mechanical properties of the HeLa cells. The understanding of the PL action on HeLa cells’ mechanical properties may help in the development of effective therapeutic drugs against cancers.
The Immunomodulatory Effects of Social Isolation in Mice are Linked to Temperature Control
Authors: Hamilton Alice , Rizzo Raffaella , Brod Samuel , Ono Masahiro , Perretti Mauro , Cooper Dianne , D’Acquisto Fulvio 
Published: September 2021

AbstractLiving in isolation is considered an emerging societal problem that negatively affects the physical wellbeing of its sufferers in ways that we are just starting to appreciate. This study investigates the immunomodulatory effects of social isolation in mice, utilising a two-week program of sole cage occupancy followed by the testing of immune-inflammatory resilience to bacterial sepsis. Our results revealed that mice housed in social isolation showed an increased ability to clear bacterial infection compared to control socially housed animals. These effects were associated with specific changes in whole blood gene expression profile and an increased production of classical pro-inflammatory cytokines. Interestingly, equipping socially isolated mice with artificial nests as a substitute for their natural huddling behaviour reversed the increased resistance to bacterial sepsis. These results further highlight the ability of the immune system to act as a sensor of our living conditions and to respond in a compensatory fashion to external challenges that might threaten the survival of the host.
Experimental evolution of insect resistance to two pesticide classes reveals mechanistic diversity and context-dependent fitness costs
Authors: Birnbaum Stephanie S.L. , Schulz Nora K.E. , Garrett Destane S. , Tate Ann T. 
Published: September 2021

AbstractDoes rapid adaptation to stressors evolve through similar underlying mechanisms among diverse populations, or are there many roads to a similar phenotype? The experimental evolution of pesticide resistance in insects provides a powerful model to study the diverse evolutionary signatures of adaptation and their associated costs. Here, we selected for resistance to two pesticides (organophosphates and pyrethroids) in six field-derived populations of the red flour beetle (Tribolium castaneum). After several generations of selection, we performed transcriptomic analyses and measured survival, development, and fecundity in the presence and absence of pesticides to detect fitness costs of resistance evolution. All pesticide-selected populations exhibited significantly improved survival after pesticide exposure without substantial fitness costs, compared to control populations. Populations that evolved to resist organophosphates had distinct gene expression in the presence and absence of organophosphates, supporting different detoxification mechanisms and cuticular modifications among populations. In contrast, pyrethroid resistant populations demonstrated common differential expression of cytochrome P450 transcripts. Furthermore, some populations evolved similar mechanisms against both pesticides while others showed little overlap in their evolved responses, suggesting variation in potential cross-resistance phenotypes. Overall, between populations, we observed both parallel and divergent patterns in gene expression associated with acquired pesticide resistance, without ubiquitous fitness costs.
Sexual signals persist over deep time: ancient co-option of bioluminescence for courtship displays in cypridinid ostracods
Authors: Ellis Emily A. , Goodheart Jessica A. , Hensley Nicholai M. , González Vanessa L. , Reda Nicholas J. , Rivers Trevor J. , Morin James G. , Torres Elizabeth , Gerrish Gretchen A. , Oakley Todd H. 
Published: September 2021

AbstractAlthough the the diversity, beauty, and intricacy of sexually selected courtship displays command the attention of evolutionists, the longevity of these traits in deep time is poorly understood. Population-based theory suggests sexual selection could either lower or raise extinction risk, resulting in high or low persistence of lineages with sexually selected traits. Furthermore, empirical studies that directly estimate longevity of sexually selected traits are uncommon. Sexually selected signals - including bioluminescent courtship - originated multiple times during evolution, allowing empirical study of their longevity after careful phylogenetic and divergence time analyses. Here, we estimate the first transcriptome-based molecular phylogeny and divergence times of Cypridinidae. We report extreme longevity of bioluminescent courtship, a trait important in mate choice and probably under sexual selection. Our relaxed-clock estimates of divergence times coupled with stochastic character mapping show luminous courtship evolved only once in Cypridinidae in a Sub-Tribe we name Luxorina at least 151 Million Years Ago (Ma) from cypridinid ancestors that used bioluminescence only in anti-predator displays, defining a Tribe we name Luminini. This time-calibrated molecular phylogeny of cypridinids will serve as a foundation for integrative and comparative studies on the biochemistry, molecular evolution, courtship, diversification, and ecology of cypridinid bioluminescence. The persistence of luminous courtship for hundreds of millions of years indicates that rates of speciation within the group exceeded extinction risk, allowing for the persistence of a diverse clade of signalling species and that sexual selection did not cause rapid loss of associated traits.
Movement-Dependent Electrical Stimulation for Volitional Strengthening of Cortical Connections in Behaving Monkeys
Authors: Moorjani Samira , Walvekar Sarita , Fetz Eberhard E. , Perlmutter Steve I. 
Published: September 2021

AbstractCorrelated activity of neurons can lead to long-term strengthening or weakening of the connections between them. In addition, the behavioral context, imparted by execution of physical movements or the presence of a reward, can modulate the plasticity induced by Hebbian mechanisms. In the present study, we have combined behavior and induced neuronal correlations to strengthen connections in the motor cortex of adult behaving monkeys. Correlated activity was induced using an electrical-conditioning protocol in which stimuli gated by voluntary movements were used to produce co-activation of neurons at motor-cortical sites involved in those movements. Delivery of movement-dependent stimulation resulted in small increases in the strength of associated cortical connections immediately after conditioning. Remarkably, when paired with further repetition of the movements that gated the conditioning stimuli, there were substantially larger gains in the strength of cortical connections, that occurred in a use-dependent manner, without delivery of additional conditioning stimulation. In the absence of such movements, little change was observed in the strength of motor-cortical connections. Performance of the motor behavior in the absence of conditioning also did not produce any changes in connectivity. Our results show that combining movement-gated stimulation with further natural use of the “conditioned” pathways after stimulation ends can produce use-dependent strengthening of connections in adult primates, highlighting an important role for behavior in cortical plasticity. Our data also provide strong support for combining movement-gated stimulation with use-dependent physical rehabilitation for strengthening connections weakened by a stroke or spinal-cord injury.Significance StatementWe describe an electrical-conditioning protocol in adult behaving monkeys in which stimuli gated by voluntary movements were used to strengthen connections between motor-cortical neurons involved in those movements. Movement-gated stimulation created a plastic landscape in which repetition of the movements that gated conditioning stimuli produced strengthening of cortical connections, in a use-dependent manner, long after stimulation had ended, a finding that is both novel and unique. In the absence of such behavior, little change was observed in the strength of connections. Similarly, movements alone did not produce any changes in connectivity. Our data highlight a critical role for behavior in plasticity and provide strong support for combining movement-gated stimulation with use-dependent rehabilitation for strengthening connections weakened by injury or disease.