bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Analysis of mcr-1-Carrying Plasmids From Gram-Negative Bacteria in a Dutch Tertiary Care Hospital: Evidence for Intrapatient and Interspecies Transmission Events
Authors: Strepis Nikolaos , Voor in ’t holt Anne F. , Vos Margreet C. , Zandijk Willemien H. A. , Heikema Astrid P. , Hays John P. , Severin Juliëtte A. , Klaassen Corné H. W.
Published: September 2021

The role of plasmids in the complex pandemic of antimicrobial resistance is increasingly being recognized. In this respect, multiple mobile colistin resistance (mcr) gene-carrying plasmids have been described. However, the characteristics and epidemiology of these plasmids within local healthcare settings are largely unknown. We retrospectively characterized the genetic composition and epidemiology of plasmids from mcr-1-positive bacterial isolates identified from patients from a large academic hospital in the Netherlands. Clinical Gram-negative bacteria with an MIC > 2 μg/mL for colistin, obtained from patients hospitalized at the Erasmus MC University Medical Center Rotterdam during the years 2010–2018, were screened for presence of the mcr-1 gene. Extracted plasmids from mcr-1-positive isolates were sequenced using a combination of short- and long-read sequencing platforms, characterized by incompatibility type and genetic composition and compared to publicly available mcr-1-carrying plasmid sequences. In 21 isolates from 14 patients, mcr-1 was located on a plasmid. These plasmids were of diverse genetic background involving Inc types IncX4, IncI2(delta), IncHI2, as well as double Inc types IncHI2/IncN and IncHI2/IncQ. mcr-1-carrying plasmids were found in Escherichia coli, Klebsiella pneumoniae, and Kluyvera georgiana, and within the chromosome of an ST147 K. pneumoniae isolate. In depth analysis indicated intrapatient, interpatient, and interspecies transmission events of mcr-1-carrying plasmids. In addition, our results show that the mcr-1 gene resides in a rich environment full of other (mcr-1 negative) plasmids and of many different Inc types, enabling interplasmidal transfer events and facilitating widespread dissemination of the mcr-1 gene. Multiple mcr-1-carrying plasmid transmission events had likely occurred among isolates from hospitalized patients. Recognition and identification of plasmid transmission events within hospitals is necessary in order to design and implement effective infection control measures.
Transcriptome-Based Selection and Validation of Reference Genes for Gene Expression Analysis of Alicyclobacillus acidoterrestris Under Acid Stress
Authors: Zhao Ning , Xu Junnan , Jiao Lingxia , Qiu Mengzhen , Zhang Jie , Wei Xinyuan , Fan Mingtao
Published: September 2021

Alicyclobacillus acidoterrestris is a major concern in fruit juice industry due to its spoilage potential of acidic fruit juice. Quantifying the expression levels of functional genes by real-time quantitative polymerase chain reaction (RT-qPCR) is necessary to elucidate the response mechanisms of A. acidoterrestris to acid stress. However, appropriate reference genes (RGs) for data normalization are required to obtain reliable RT-qPCR results. In this study, eight novel candidate RGs were screened based on transcriptome datasets of A. acidoterrestris under acid stress. The expression stability of eight new RGs and commonly used RG 16s rRNA was assessed using geNorm, NormFinder, and BestKeeper algorithms. Moreover, the comprehensive analysis using the RefFinder program and the validation using target gene ctsR showed that dnaG and dnaN were the optimal multiple RGs for normalization at pH 4.0; ytvI, dnaG, and 16s rRNA at pH 3.5; icd and dnaG at pH 3.0; and ytvI, dnaG, and spoVE at pH 2.5. This study revealed for the first time that A. acidoterrestris had different suitable RGs under different acid conditions, with implications for further deciphering the acid response mechanisms of this spoilage-causing bacterium.
Elongation at Midcell in Preparation of Cell Division Requires FtsZ, but Not MreB nor PBP2 in Caulobacter crescentus
Authors: van Teeseling Muriel C. F.
Published: September 2021

Controlled growth of the cell wall is a key prerequisite for bacterial cell division. The existing view of the canonical rod-shaped bacterial cell dictates that newborn cells first elongate throughout their side walls using the elongasome protein complex, and subsequently use the divisome to coordinate constriction of the dividing daughter cells. Interestingly, another growth phase has been observed in between elongasome-mediated elongation and constriction, during which the cell elongates from the midcell outward. This growth phase, that has been observed in Escherichia coli and Caulobacter crescentus, remains severely understudied and its mechanisms remain elusive. One pressing open question is which role the elongasome key-component MreB plays in this respect. This study quantitatively investigates this growth phase in C. crescentus and focuses on the role of both divisome and elongasome components. This growth phase is found to initiate well after MreB localizes at midcell, although it does not require its presence at this subcellular location nor the action of key elongasome components. Instead, the divisome component FtsZ seems to be required for elongation at midcell. This study thus shines more light on this growth phase in an important model organism and paves the road to more in-depth studies.
Discovery of Novel Viruses Associated With the Invasive Cane Toad (Rhinella marina) in Its Native and Introduced Ranges
Authors: Russo Alice G. , Harding Emma F. , Yan Grace J. H. , Selechnik Daniel , Ducatez Simon , DeVore Jayna L. , Zhou Jia , Sarma Roshmi R. , Lee Yin Peng , Richardson Mark F. , Shine Richard , Rollins Lee A. , White Peter A.
Published: September 2021

Cane toads (Rhinella marina) are notoriously successful invaders: from 101 individuals brought to Australia in 1935, poisonous toads now cover an area >1.2 million km2 with adverse effects on native fauna. Despite extensive research on the role of macroparasites in cane toad invasion, viral research is lagging. We compared viral prevalence and diversity between toads in their native range (French Guiana, n=25) and two introduced ranges: Australia (n=151) and Hawai’i (n=10) with a metatranscriptomic and metagenomic approach combined with PCR screening. Australian toads almost exclusively harbor one of seven viruses detected globally. Rhimavirus-A (Picornaviridae) exhibited low genetic diversity and likely actively infected 9% of sampled Australian toads extending across ~2,000km of Northern Australia and up to the current invasion front. In native range cane toads, we identified multiple phylogenetically distinct viruses (Iridoviridae, Picornaviridae, Papillomaviridae, and Nackedna-like virus). None of the same viruses was detected in both ranges, suggesting that Australian cane toads have largely escaped the viral infection experienced by their native range counterparts. The novel native range viruses described here are potential biocontrol agents, as Australian toads likely lack prior immunological exposure to these viruses. Overall, our evidence suggests that there may be differences between viruses infecting cane toads in their native vs. introduced ranges, which lays the groundwork for further studies on how these viruses have influenced the toads’ invasion history.
Molecular and Clinical Characterization of LIGHT/TNFSF14 Expression at Transcriptional Level via 998 Samples With Brain Glioma
Authors: Yang Ying , Lv Wen , Xu Shihai , Shi Fei , Shan Aijun , Wang Jin
Published: September 2021

LIGHT, also termed TNFSF14, has been reported to play a vital role in different tumors. However, its role in glioma remains unknown. This study is aimed at unveiling the characterization of the transcriptional expression profiling of LIGHT in glioma. We selected 301 glioma patients with mRNA microarray data from the CGGA dataset and 697 glioma patients with RNAseq data from the TCGA dataset. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analyses and figure generation were performed with R language. LIGHT expression showed a positive correlation with WHO grade of glioma. LIGHT was significantly increased in mesenchymal molecular subtype. Gene Ontology analysis demonstrated that LIGHT was profoundly involved in immune response. Moreover, LIGHT was found to be synergistic with various immune checkpoint members, especially HVEM, PD1/PD-L1 pathway, TIM3, and B7-H3. To get further understanding of LIGHT-related immune response, we put LIGHT together with seven immune signatures into GSVA and found that LIGHT was particularly correlated with HCK, LCK, and MHC-II in both datasets, suggesting a robust correlation between LIGHT and activities of macrophages, T-cells, and antigen-presenting cells (APCs). Finally, higher LIGHT indicated significantly shorter survival for glioma patients. Cox regression models revealed that LIGHT expression was an independent variable for predicting survival. In conclusion, LIGHT was upregulated in more malignant gliomas including glioblastoma, IDH wildtype, and mesenchymal subtype. LIGHT was mainly involved in the immune function of macrophages, T cells, and APCs and served as an independent prognosticator in glioma.
LBX2-AS1 as a Novel Diagnostic Biomarker and Therapeutic Target Facilitates Multiple Myeloma Progression by Enhancing mRNA Stability of LBX2
Authors: Jia Haipeng , Liu Yan , Lv Sulong , Qiao Ruifang , Zhang Xiaofen , Niu Fei , Shang Wenqing , Liu Shumei , Dong Jing , Zhang Zhirong
Published: September 2021

Objective: Multiple myeloma (MM) represents a common age-associated malignancy globally. The function and underlying mechanism of antisense lncRNA LBX2-AS1 remain ambiguous in multiple myeloma (MM). Herein, we aimed to observe the biological implication of this lncRNA in MM.

Methods: RT-qPCR was employed to examine circulating LBX2-AS1 and LBX2 in 60 paired MM and healthy subjects. Correlation between the two was analyzed by Pearson test. Under transfection with shLBX2-AS1, proliferation and apoptosis were evaluated in MM cells through CCK-8, colony formation and flow cytometry. LBX2 expression was examined in MM cells with shLBX2-AS1 or pcDNA3.1-LBX2 transfection. Following treatment with cycloheximide or actinomycin D, LBX2 expression was examined in pcDNA3.1-LBX2-transfected MM cells at different time points. Rescue assays were then presented. Finally, xenograft tumor models were established.

Results: Circulating LBX2-AS1 was up-regulated in MM patients and positively correlated to LBX2 expression. Area under the curve (AUC) of LBX2-AS1 expression was 0.7525. Its up-regulation was also found in MM cells and primarily distributed in cytoplasm. LBX2-AS1 knockdown distinctly weakened proliferative ability and induced apoptosis in MM cells. Overexpressing LBX2-AS1 markedly strengthened LBX2 expression by increasing its mRNA stability. Rescue assays showed that silencing LBX2-AS1 distinctly weakened the pcDNA3.1-LBX2-induced increase in proliferation and decrease in apoptosis for MM cells. Silencing LBX2-AS1 markedly weakened tumor growth.

Conclusion: Our data demonstrated that circulating LBX2-AS1 could be an underlying diagnostic marker in MM. Targeting LBX2-AS1 suppressed tumor progression by affecting mRNA stability of LBX2 in MM. Hence, LBX2-AS1 could be a novel therapeutic marker against MM.
Musk (Moschus moschiferus) Attenuates Changes in Main Olfactory Bulb of Depressed Mice: Behavioral, Biochemical, and Histopathological Evidence
Authors: Almohaimeed Hailah M. , Batawi Ashwaq H. , Mohammedsaleh Zuhair M. , Al Jaouni Soad , Mutlq Alsawat Samiah A. , Abd El Wahab Manal G. , AbdElfattah Amany A. , Ayuob Nasra N.
Published: September 2021

Background

Musk (Moschus moschiferus) has been described to have a significant impact on the central nervous system, as well as anticonvulsion and antidepressant effects. This study was designed to evaluate the efficacy of musk in alleviating alterations induced in olfactory bulb of depressed mice exposed to chronic stress and identify the mechanism behind it.

Methods

Fifty male albino mice were divided into five groups (n= 10 each): control, musk, chronic unpredictable mild stress (CUMS), fluoxetine-treated, and musk-treated groups were included in this study. Behavioral changes and serum levels of corticosterone and proinflammatory cytokines included tumor necrosis factor α, interleukin 6, and oxidant/antioxidant profile were assessed at the end of the experiment. Main olfactory bulb (MOB) has been processed for histopathological examination. Gene expression of caspase-3, glial fibrillary acidic protein, and Ki67 were assessed in the MOB using quantitative real-time polymerase chain reaction.

Results

The study showed that musk inhalation significantly reduced (p< 0.001) corticosterone level, immobility time, inflammatory cytokines, and oxidative stress markers in CUMS-exposed mice compared to the untreated CUMS group. Musk lessened CUMS-associated neuronal alterations in the MOB and significantly reduced apoptosis and enhanced neural cell proliferation (p< 0.001) comparable to fluoxetine. Musk significantly enhanced the level of antioxidants in the serum and significantly reduced inflammatory cytokines. The anti-inflammatory and antioxidant activity of musk and its constituents seemed to be behind its neuroprotective effect observed in this study.

Conclusion

Musk effectively ameliorated the chronic stress–induced behavioral, biochemical, and neuronal structural changes in MOB mostly through its antioxidant and anti-inflammatory effect.
Anatomical Organization of the Rat Subfornical Organ
Authors: Hicks Amirah-Iman , Kobrinsky Simona , Zhou Suijian , Yang Jieyi , Prager-Khoutorsky Masha
Published: September 2021

The subfornical organ (SFO) is a sensory circumventricular organ located along the anterodorsal wall of the third ventricle. SFO lacks a complete blood-brain barrier (BBB), and thus peripherally-circulating factors can penetrate the SFO parenchyma. These signals are detected by local neurons providing the brain with information from the periphery to mediate central responses to humoral signals and physiological stressors. Circumventricular organs are characterized by the presence of unique populations of non-neuronal cells, such as tanycytes and fenestrated endothelium. However, how these populations are organized within the SFO is not well understood. In this study, we used histological techniques to analyze the anatomical organization of the rat SFO and examined the distribution of neurons, fenestrated and non-fenestrated vasculature, tanycytes, ependymocytes, glia cells, and pericytes within its confines. Our data show that the shell of SFO contains non-fenestrated vasculature, while fenestrated capillaries are restricted to the medial-posterior core region of the SFO and associated with a higher BBB permeability. In contrast to non-fenestrated vessels, fenestrated capillaries are encased in a scaffold created by pericytes and embedded in a network of tanycytic processes. Analysis of c-Fos expression following systemic injections of angiotensin II or hypertonic NaCl reveals distinct neuronal populations responding to these stimuli. Hypertonic NaCl activates ∼13% of SFO neurons located in the shell. Angiotensin II-sensitive neurons represent ∼35% of SFO neurons and their location varies between sexes. Our study provides a comprehensive description of the organization of diverse cellular elements within the SFO, facilitating future investigations in this important brain area.
5-HT1A Receptors Alter Temporal Responses to Broadband Vocalizations in the Mouse Inferior Colliculus Through Response Suppression
Authors: Gentile Polese Arianna , Nigam Sunny , Hurley Laura M.
Published: September 2021

Neuromodulatory systems may provide information on social context to auditory brain regions, but relatively few studies have assessed the effects of neuromodulation on auditory responses to acoustic social signals. To address this issue, we measured the influence of the serotonergic system on the responses of neurons in a mouse auditory midbrain nucleus, the inferior colliculus (IC), to vocal signals. Broadband vocalizations (BBVs) are human-audible signals produced by mice in distress as well as by female mice in opposite-sex interactions. The production of BBVs is context-dependent in that they are produced both at early stages of interactions as females physically reject males and at later stages as males mount females. Serotonin in the IC of males corresponds to these events, and is elevated more in males that experience less female rejection. We measured the responses of single IC neurons to five recorded examples of BBVs in anesthetized mice. We then locally activated the 5-HT1A receptor through iontophoretic application of 8-OH-DPAT. IC neurons showed little selectivity for different BBVs, but spike trains were characterized by local regions of high spike probability, which we called “response features.” Response features varied across neurons and also across calls for individual neurons, ranging from 1 to 7 response features for responses of single neurons to single calls. 8-OH-DPAT suppressed spikes and also reduced the numbers of response features. The weakest response features were the most likely to disappear, suggestive of an “iceberg”-like effect in which activation of the 5-HT1A receptor suppressed weakly suprathreshold response features below the spiking threshold. Because serotonin in the IC is more likely to be elevated for mounting-associated BBVs than for rejection-associated BBVs, these effects of the 5-HT1A receptor could contribute to the differential auditory processing of BBVs in different behavioral subcontexts.
Regional Differences in Early BP Management After Acute Ischemic Stroke in the ENCHANTED International Randomized Controlled Trials
Authors: Chen Chen , Song Lili , Yang Jie , Lindley Richard , Robinson Thompson , Arima Hisatomi , Chalmers John , Anderson Craig S. , Wang Xia
Published: September 2021

Background and Aims: Epidemiological studies show significant variations in hypertension management within and between countries. The level of regional variation in early blood pressure (BP) management after acute stroke is uncertain.

Methods: Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), a partial-factorial, international randomized controlled trial of thrombolysis-eligible acute ischemic stroke (AIS) patients with elevated systolic BP (SBP >150 mmHg) assigned to intensive (target SBP 130-140 mmHg) vs. guideline-recommended (SBP <180 mmHg) treatment; BP management was compared among four regions: Western countries (Italy/United Kingdom/Spain/Australia), China (mainland), other Asia (Hong Kong/Taiwan/Singapore/Thailand/Vietnam/India), and South America (Chile/Brazil/Colombia).

Results: These analyses included 2,196 AIS [38% women, mean age 67 (12) years] patients. Commonly used intravenous BP-lowering agents were labetalol, nitroglycerin, and topical nitrates in Western countries; urapidil and sodium nitroprusside in China; nicardipine in other Asian countries; and sodium nitroprusside and labetalol in South America. Chinese patients were less likely to receive BP-lowering treatment in the first 24 h and be treated with multiple agents although they had smaller magnitude of SBP reduction and lower SBP variability.

Conclusion: Regional variations in early BP management in acute stroke translated into differences in early BP control parameters.
Objective Assessment of Hyposmia in Alzheimer's Disease From Image and Behavior by Combining Pleasant Odor With Unpleasant Odor
Authors: Feng Quanzhi , Liu Hui , Zhang Hui , Liu Yi , Zhang Huihong , Zhou Yuying , Liu Gang , Han Tong
Published: September 2021

Background: Olfactory functional magnetic resonance imaging (fMRI) of responses to a pleasant odor (PO) (lavender) can objectively evaluate olfactory dysfunction in Alzheimer's disease (AD) patients. The brain responses to a PO and unpleasant odor (UPO) were shown to differ in normal young people. Whether AD patients with olfactory dysfunction have the same brain response is not yet known.

Objective: Our aim was to explore whether olfactory fMRI with both a PO and UPO can provide more information regarding olfactory impairment in AD than a PO alone.

Methods: Twenty-five normal controls (NC), 26 individuals with mild cognitive impairment (MCI), and 22 AD patients underwent olfactory fMRI with lavender and pyridine odorants at three concentrations (0.10, 0.33, and 1.00%) with a 3.0-T MRI scanner.

Results: There were no differences in the number of activated voxels in the primary olfactory cortex (POC) between PO and UPO conditions in the NC, MCI, and AD groups (SPM, paired t-test, uncorrected p < 0.001, extent threshold = 70). In the right inferior frontal gyrus, orbital part (F3O), the number of activated voxels was greater with the UPO than with the PO in the NC group (SPM, paired t-test, uncorrected p < 0.001, extent threshold = 70), but there were no differences in the MCI and AD groups. Regardless of PO or UPO conditions, there were significant differences in the number of activated voxels in the POC among the NC, MCI, and AD groups. With increasing odor concentration, the number of activated voxels in the POC decreased in the NC group but increased in the AD group. When 0.10% UPO was presented, the NC group (21/25) showed a lower breathing amplitude and shorter inhalation time, whereas the AD patients (0/22) did not show such changes in breathing.

Conclusions: After PO and UPO inhalation, brain activation and respiratory behavior in AD patients were significantly different than in NC patients. Therefore, olfactory fMRI using both PO and UPO stimulation, compared with PO stimulation only, can provide more objective information regarding hyposmia associated with AD based on imaging and behavior.
1H Magnetic Resonance Spectroscopy to Understand the Biological Basis of ALS, Diagnose Patients Earlier, and Monitor Disease Progression
Authors: Caldwell Sarah , Rothman Douglas L.
Published: September 2021

At present, limited biomarkers exist to reliably understand, diagnose, and monitor the progression of amyotrophic lateral sclerosis (ALS), a fatal neurological disease characterized by motor neuron death. Standard MRI technology can only be used to exclude a diagnosis of ALS, but 1H-MRS technology, which measures neurochemical composition, may provide the unique ability to reveal biomarkers that are specific to ALS and sensitive enough to diagnose patients at early stages in disease progression. In this review, we present a summary of current theories of how mitochondrial energetics and an altered glutamate/GABA neurotransmitter flux balance play a role in the pathogenesis of ALS. The theories are synthesized into a model that predicts how pathogenesis impacts glutamate and GABA concentrations. When compared with the results of all MRS studies published to date that measure the absolute concentrations of these neurochemicals in ALS patients, results were variable. However, when normalized for neuronal volume using the MRS biomarker N-acetyl aspartate (NAA), there is clear evidence for an elevation of neuronal glutamate in nine out of thirteen studies reviewed, an observation consistent with the predictions of the model of increased activity of glutamatergic neurons and excitotoxicity. We propose that this increase in neuronal glutamate concentration, in combination with decreased neuronal volume, is specific to the pathology of ALS. In addition, when normalized to glutamate levels, there is clear evidence for a decrease in neuronal GABA in three out of four possible studies reviewed, a finding consistent with a loss of inhibitory regulation contributing to excessive neuronal excitability. The combination of a decreased GABA/Glx ratio with an elevated Glx/NAA ratio may enhance the specificity for 1H-MRS detection of ALS and ability to monitor glutamatergic and GABAergic targeted therapeutics. Additional longitudinal studies calculating the exact value of these ratios are needed to test these hypotheses and understand how ratios may change over the course of disease progression. Proposed modifications to the experimental design of the reviewed 1H MRS studies may also increase the sensitivity of the technology to changes in these neurochemicals, particularly in early stages of disease progression.
Assessment of Disrupted Brain Structural Connectome in Depressive Patients With Suicidal Ideation Using Generalized Q-Sampling MRI
Authors: Chen Vincent Chin-Hung , Kao Chun-Ju , Tsai Yuan-Hsiung , Cheok Man Teng , McIntyre Roger S. , Weng Jun-Cheng
Published: September 2021

Suicide is one of the leading causes of mortality worldwide. Various factors could lead to suicidal ideation (SI), while depression is the predominant cause among all mental disorders. Studies have shown that alterations in brain structures and networks may be highly associated with suicidality. This study investigated both neurological structural variations and network alterations in depressed patients with suicidal ideation by using generalized q-sampling imaging (GQI) and Graph Theoretical Analysis (GTA). This study recruited 155 participants and divided them into three groups: 44 depressed patients with suicidal ideation (SI+; 20 males and 24 females with mean age = 42, SD = 12), 56 depressed patients without suicidal ideation (Depressed; 24 males and 32 females with mean age = 45, SD = 11) and 55 healthy controls (HC; nine males and 46 females with mean age = 39, SD = 11). Both the generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA) values were evaluated in a voxel-based statistical analysis by GQI. We analyzed different topological parameters in the graph theoretical analysis and the subnetwork interconnections in the Network-based Statistical (NBS) analysis. In the voxel-based statistical analysis, both the GFA and NQA values in the SI+ group were generally lower than those in the Depressed and HC groups in the corpus callosum and cingulate gyrus. Furthermore, we found that the SI+ group demonstrated higher global integration and lower local segregation among the three groups of participants. In the network-based statistical analysis, we discovered that the SI+ group had stronger connections of subnetworks in the frontal lobe than the HC group. We found significant structural differences in depressed patients with suicidal ideation compared to depressed patients without suicidal ideation and healthy controls and we also found several network alterations among these groups of participants, which indicated that white matter integrity and network alterations are associated with patients with depression as well as suicidal ideation.
The Role of Large-Scale Data Infrastructure in Developing Next-Generation Deep Brain Stimulation Therapies
Authors: Chen Witney , Kirkby Lowry , Kotzev Miro , Song Patrick , Gilron Ro’ee , Pepin Brian
Published: September 2021

Advances in neuromodulation technologies hold the promise of treating a patient’s unique brain network pathology using personalized stimulation patterns. In service of these goals, neuromodulation clinical trials using sensing-enabled devices are routinely generating large multi-modal datasets. However, with the expansion of data acquisition also comes an increasing difficulty to store, manage, and analyze the associated datasets, which integrate complex neural and wearable time-series data with dynamic assessments of patients’ symptomatic state. Here, we discuss a scalable cloud-based data platform that enables ingestion, aggregation, storage, query, and analysis of multi-modal neurotechnology datasets. This large-scale data infrastructure will accelerate translational neuromodulation research and enable the development and delivery of next-generation deep brain stimulation therapies.
Suppression, Maintenance, and Surprise: Neuronal Correlates of Predictive Processing Specialization for Musical Rhythm
Authors: Færøvik Ulvhild , Specht Karsten , Vikene Kjetil
Published: September 2021

Auditory repetition suppression and omission activation are opposite neural phenomena and manifestations of principles of predictive processing. Repetition suppression describes the temporal decrease in neural activity when a stimulus is constant or repeated in an expected temporal fashion; omission activity is the transient increase in neural activity when a stimulus is temporarily and unexpectedly absent. The temporal, repetitive nature of musical rhythms is ideal for investigating these phenomena. During an fMRI session, 10 healthy participants underwent scanning while listening to musical rhythms with two levels of metric complexity, and with beat omissions with different positional complexity. Participants first listened to 16-s-long presentations of continuous rhythms, before listening to a longer continuous presentation with beat omissions quasi-randomly introduced. We found deactivation in bilateral superior temporal gyri during the repeated presentation of the normal, unaltered rhythmic stimulus, with more suppression of activity in the left hemisphere. Omission activation of bilateral middle temporal gyri was right lateralized. Persistent activity was found in areas including the supplementary motor area, caudate nucleus, anterior insula, frontal areas, and middle and posterior cingulate cortex, not overlapping with either listening, suppression, or omission activation. This suggests that the areas are perhaps specialized for working memory maintenance. We found no effect of metric complexity for either the normal presentation or omissions, but we found evidence for a small effect of omission position—at an uncorrected threshold—where omissions in the more metrical salient position, i.e., the first position in the bar, showed higher activation in anterior cingulate/medial superior frontal gyrus, compared to omissions in the less salient position, in line with the role of the anterior cingulate cortex for saliency detection. The results are consistent with findings in our previous studies on Parkinson’s disease, but are put into a bigger theoretical frameset.
More Negative FRN From Stopping Searches Too Late Than Too Early: An ERP Study
Authors: Gao Mei , Yang Xiaolan , Zhang Linanzi , Ma Qingguo
Published: September 2021

It is widely known that the feedback from a decision outcome may evoke emotions like regret, which results from a comparison between the gain the decision-maker has made and the gain he/she might make. Less is known about how search behavior is linked to feedback in a sequential search task such as searching for jobs, employees, prices, investments, disinvestments, or other items. What are the neural responses once subjects decide to stop searching and receive the feedback that they stopped too early or too late compared with the optimal stopping time? In an experimental setting of a search task, we found that the feedback-related negativity (FRN) induced by the feedback from stopping too late was more negative than stopping too early, suggesting that subjects might experience stronger regret when stopping too late. Subjects preferred to stop searching earlier if the last feedback was that they stopped too late, and vice versa, although they did not always benefit more from such adjustment. This might reflect general patterns of human learning behavior, which also manifests in many other decisions. Gender differences and risk attitudes were also considered in the study.
Vasopressin but Not Oxytocin Responds to Birth Stress in Infants
Authors: Fill Malfertheiner Sara , Bataiosu-Zimmer Evelyn , Michel Holger , Fouzas Sotirios , Bernasconi Luca , Bührer Christoph , Wellmann Sven
Published: September 2021

Context

Birth triggers a large fetal neuroendocrine response, which is more pronounced in infants born vaginally than in those born by elective cesarean section (ECS). The two related peptides arginine vasopressin (AVP) and oxytocin (OT) play an essential role in peripheral and central stress adaptation and have a shared receptor mediating their function. Elevated cord blood levels of AVP and its surrogate marker copeptin, the C-terminal part of AVP prohormone, have been found after vaginal delivery (VD) as compared to ECS, while release of OT in response to birth is controversial. Moreover, AVP, copeptin and OT have not yet been measured simultaneously at birth.

Objective

To test the hypothesis that AVP but not OT levels are increased in infants arterial umbilical cord blood in response to birth stress and to characterize AVP secretion in direct comparison with plasma copeptin.

Methods

In a prospective single-center cross-sectional study, we recruited healthy women with a singleton pregnancy and more than 36 completed weeks of gestation delivering via VD or ECS (cesarean without prior uterine contractions or rupture of membranes). Arterial umbilical cord blood samples were collected directly after birth, centrifuged immediately and plasma samples were frozen. Concentrations of AVP and OT were determined by radioimmunoassay and that of copeptin by ultrasensitive immunofluorescence assay.

Results

A total of 53 arterial umbilical cord blood samples were collected, n = 29 from VD and n = 24 from ECS. Ten venous blood samples from pregnant women without stress were collected as controls. AVP and copeptin concentrations were significantly higher in the VD group than in the ECS group (both p < 0.001), median (range) AVP 4.78 (2.38–8.66) vs. 2.38 (1.79–3.88) (pmol/L), copeptin 1692 (72.1–4094) vs. 5.78 (3.14–17.97), respectively, (pmol/L). In contrast, there was no difference in OT concentrations (pmol/L) between VD and ECS, 6.00 (2.71–7.69) vs. 6.14 (4.26–9.93), respectively. AVP and copeptin concentrations were closely related (Rs = 0.700, p < 0.001) while OT did not show any correlation to either AVP or copeptin. In linear regression models, vaginal delivery and biochemical stress indicators, base deficit and pH, were independent predictors for both AVP and copeptin. OT was not linked to base deficit or pH.

Conclusion

Vaginal birth causes a profound secretion of AVP and copeptin in infants. Whereas AVP indicates acute stress events, copeptin provides information on cumulative stress events over a longer period. In contrast, fetal OT is unaffected by birth stress. Thus, AVP signaling but not OT mediates birth stress response in infants. This unique hormonal activation in early life may impact neurobehavioral development in whole life.
Ketone Bodies in the Brain Beyond Fuel Metabolism: From Excitability to Gene Expression and Cell Signaling
Authors: García-Rodríguez Darío , Giménez-Cassina Alfredo
Published: September 2021

Ketone bodies are metabolites that replace glucose as the main fuel of the brain in situations of glucose scarcity, including prolonged fasting, extenuating exercise, or pathological conditions such as diabetes. Beyond their role as an alternative fuel for the brain, the impact of ketone bodies on neuronal physiology has been highlighted by the use of the so-called “ketogenic diets,” which were proposed about a century ago to treat infantile seizures. These diets mimic fasting by reducing drastically the intake of carbohydrates and proteins and replacing them with fat, thus promoting ketogenesis. The fact that ketogenic diets have such a profound effect on epileptic seizures points to complex biological effects of ketone bodies in addition to their role as a source of ATP. In this review, we specifically focus on the ability of ketone bodies to regulate neuronal excitability and their effects on gene expression to respond to oxidative stress. Finally, we also discuss their capacity as signaling molecules in brain cells.
The Role of Fortified and Enriched Refined Grains in the US Dietary Pattern: A NHANES 2009–2016 Modeling Analysis to Examine Nutrient Adequacy
Authors: Papanikolaou Yanni , Fulgoni Victor L. III
Published: September 2021

Background: While dietary recommendations call for greater whole-grain intake and reduced refined grain consumption, there are limited peer-reviewed studies examining the influence of fortified/enriched refined grains on nutrient adequacy.

Methods: A modeling analysis using data from National Health and Nutrition Examination Survey (NHANES) 2009–2016 estimated usual daily intake of shortfall nutrients for Dietary Guidelines for Americans (DGA) in the current dietary pattern and when specific percentages of fortified/enriched refined grain foods (bread, ready-to-eat cereals, and all-grained foods) were removed from the diet (19–50-year-old adults, N = 11,169; 51–99-year-old adults, N = 9,641).

Results: While American adults are currently falling short of nutrient recommendations, eliminating 25, 50, and 100% of all grains consumed in the US dietary pattern resulted in a greater percentage of adults not meeting recommendations for several shortfall nutrients, including dietary fiber, folate DFE, iron, and magnesium. Removal of all grains led to a reduced energy intake by ~10% in both age groups examined. Currently, ~3.8% of 19–50-year-old adults meet the adequate intake (AI) for dietary fiber. Removal of 25, 50, and 100% of grains from the diet resulted in 2.6 ± 0.3, 1.8 ± 0.2, and 0.7 ± 0.1% of adults exceeded the AI for dietary fiber, respectively. Similarly, 11.0 and 13.8% of younger and older adults, respectively, fall short of folate, DFE recommendations with the current diet. Following the removal of 100% of grains from the diet, 43.4 ± 1.1 and 56.2 ± 1.0%, respectively, were below the estimated average requirement (EAR) for folate DFE. For iron, current dietary pattern consumption shows 8.4% and 0.8% of younger and older adults, respectively, are not meeting iron recommendations, however, removal of 100% of grains from the diet results in nearly 10 and 22% falling short of the EAR. Currently, about 51 and 54% of younger and older adults are below the EAR for magnesium; however, with the removal of 100% of grains, 68 and 73%, respectively, fall below the EAR.

Conclusion: Removal of specific refined grains led to an increased percentage of Americans not meeting recommendations for several shortfall nutrients, including dietary fiber, folate, iron, and magnesium.
Twenty-Year Trajectory-Patterns of Percentage Energy From Dietary Fat vs. Carbohydrate Throughout Adult Life and Associations With Cardio-Metabolic Disease and All-Cause Mortality
Authors: Guo Xiaoyu , Xu Xiaoqing , Gao Jian , Wang Weiqi , Hou Wanying , Wu Xiaoyan , Sun Changhao , Li Ying , Han Tianshu
Published: September 2021

Background: The health impacts of dietary fat-to-energy ratio (FER) compared to carbohydrate-to-energy ratio (CER) are widely discussed topics in public health. This study aimed to assess the health impacts of FER and CER by establishing trajectory-patterns of FER and CER over the course of adult life.

Methods: This study used the weighted longitudinal data of the China Health and Nutrition Survey, including eight surveys from 1991 to 2011. The trajectories of FER and CER were determined via latent class trajectory modeling. The trajectories were then cross-grouped into different trajectory-patterns. Multivariate Cox regression models were used to assess the relationship between these trajectory-patterns and cardio-metabolic diseases and all-cause mortality. Ten thousand nine hundred and twenty-six adults with a total of 50,693 observations across eight surveys were included.

Results: Compared to the trajectory-pattern of persistently low-FER (increased from 10 to 20%) and moderate-CER (stable and ranging from 55 to 65%) over the adult life-course, the two trajectory-patterns that showed changing to high-FER and low-CER were significantly associated with obesity [HR 1.83 [95% CI, 1.10–3.04]; HR 1.46 [95% CI, 1.02–2.17]], diabetes [HR 1.80 [95% CI, 1.03–3.16]; HR 1.49 [95% CI, 1.01–2.25]], and all-cause mortality [HR 2.29 [95% CI, 1.35–3.87]; HR 1.62 [95% CI, 1.18–2.22]]. In contrast, the trajectory-pattern of a persistently low-FER and high-CER diet was not associated with obesity [HR 1.19 [95% CI, 0.82–1.17]], diabetes [HR 1.41 [95% CI, 0.98–2.02]], cardiovascular-disease [HR 1.48 [95% CI, 0.91–2.39]], and all-cause mortality [HR 1.23 [95% CI, 0.94–1.61]].

Conclusions: This study indicates that changing to a high-FER and low-CER diet over the course of adult life was significantly associated with obesity, diabetes, and all-cause mortality in the Chinese adult population. In addition, low-FER and high-CER were not associated with cardio-metabolic disease and all-cause mortality. These observations may provide insights into nutritional policy and dietary guidelines.
Caloric Restriction Mimetics in Nutrition and Clinical Trials
Authors: Hofer Sebastian J. , Davinelli Sergio , Bergmann Martina , Scapagnini Giovanni , Madeo Frank
Published: September 2021

The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD+ precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.
Effects of Oats (Avena sativa L.) on Inflammation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Kim Sun Jo , Jung Cheol Woon , Anh Nguyen Hoang , Kim Suk Won , Park Seongoh , Kwon Sung Won , Lee Seul Ji
Published: September 2021

Background: Oat and its compounds have been found to have anti-inflammatory effects. Through this systematic review and meta-analysis, we aimed to determine an evidence-based link between oat consumption and inflammatory markers.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. By the end of April 2021, we included randomized controlled trials (RCTs) that investigated the anti-inflammatory effect of oat and oat-related products through screening PubMed, Embase, Web of Science, ClinicalTrial.gov, and CENTRAL. Meta-analysis was conducted with a random-effect model on the standardized mean difference (SMD) of the change scores of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Subgroup analyses were conducted to stratify confounding variables. The risk of bias was evaluated using the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to report the quality of evidence. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021245844).

Results: Systematic screening of five databases yielded 4,119 studies, of which 23 RCTs were finally selected. For the four systemic inflammatory markers analyzed, no significant alterations were found after oat consumption. However, oat intake was found to significantly decrease CRP levels in subjects with one or more health complications (SMD: −0.18; 95% CI: −0.36, 0.00; P = 0.05; I2 = 10%). Furthermore, IL-6 levels were significantly decreased in subjects with dyslipidemia (SMD = −0.34; 95% CI: −0.59, −0.10; P = 0.006; I2 = 0%). These beneficial effects might be attributed to the effects of avenanthramide and β-glucan.

Conclusions: Overall evidence supporting the alleviation of inflammatory response by oat intake was poor, calling for future studies including a larger sample size to confirm the findings.
Dietary Betaine Addition Alters Carcass Traits, Meat Quality, and Nitrogen Metabolism of Bama Mini-Pigs
Authors: Cheng Yating , Song Mingtong , Zhu Qian , Azad Md. Abul Kalam , Gao Qiankun , Kong Xiangfeng
Published: September 2021

Betaine is widely used as feed additives in animal husbandry as it can cause many benefits such as improving antioxidant ability, growth performance, and carcass traits. However, there are limited studies about the effects of betaine on the Bama mini-pigs. The present study was conducted to evaluate the effects of dietary betaine on carcass traits, meat quality, and nitrogen metabolism of pigs. Twenty-six pregnant Bama mini-pigs and then 104 weaned piglets were assigned for experimental treatments. The plasma and muscle samples were collected at 65-, 95-, and 125-d-old pigs, respectively. The results showed that betaine addition in the sow-offspring diets increased the lean meat rate in the 65-d-old pigs, whereas carcass weight, carcass yield, and loin-eye area were increased in the 95-d-old pigs, and carcass weight and backfat thickness in the 125-d-old pigs. Dietary betaine addition in the sow-offspring diets increased the contents of plasma Asp of 65-d-old, Met of 95- and 125-d-old, and Sar of 125-d-old pigs. Moreover, betaine addition increased the contents of Met, His, Ile, and Phe in Longissimus thoracis et lumborum, whereas those contents were decreased in biceps femoris and psoas major muscles at different stages. Betaine addition in the sow and piglets' diets regulated the muscle fiber-type and myogenic regulatory gene expressions. In summary, betaine addition in the sow and sow-offspring diets could improve the carcass traits and meat quality by altering the plasma biochemical parameters, amino acid composition, and gene expressions of skeletal muscle.