bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaffolding the Attention-Deficit/Hyperactivity Disorder Brain Using Random Noise Stimulation
Authors: Berger Itai , Dakwar-Kawar Ornella , Grossman Ephraim S. , Nahum Mor , Kadosh Roi Cohen 
Published: September 2019

AbstractVarious methods have been attempted to effectively ameliorate psychiatric and neurological conditions in children and adults. One of the attractive ideas is to develop interventions to create a lasting, rather than only an immediate, effect. Neurostimulation has been shown to yield long-term effect when combined with cognitive training in healthy young adults. We examined whether such approach could benefit children with attention deficit hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood. We used a randomized double-blind active-controlled crossover study of 19 unmedicated children (aged 7–12 years old) with attention deficit hyperactivity disorder, who received either transcranial direct current stimulation or random noise stimulation while completing five-day executive functions training, which includes working memory, cognitive flexibility, and inhibition tasks. Both stimulation protocols have previously shown potential for inducing lasting benefits in adults, while transcranial direct current stimulation was examined in multiple attention deficit hyperactivity disorder studies and has been highlighted as a promising method for treating neuropsychological deficits. For our primary outcome, transcranial random noise stimulation yielded a clinical improvement as indicated by the reduced attention deficit hyperactivity disorder rating scale score from baseline, and in comparison to the changes observed in transcranial direct current stimulation. Moreover, the effect of brain stimulation one week after completion of treatment yielded further improvement, suggesting a neuroplasticity-related effect. Finally, transcranial random noise stimulation improved working memory compared to transcranial direct current stimulation, and a larger transcranial random noise stimulation effect on attention deficit hyperactivity disorder rating scale was predicted for those patients who showed the greatest improvement in working memory. Our results provide a promising direction toward a novel intervention in attention deficit hyperactivity disorder, which is shown to have a lasting effect via the modulating of neuroplasticity, rather than a merely immediate effect as was shown for in previous medical interventions.
New mutant mouse models clarify the role of NAIPs, phosphorylation, NLRP3, and tumors in NLRC4 inflammasome activation
Authors: Tenthorey Jeannette L. , Chavez Roberto A. , Thompson Thornton W. , Deets Katherine A. , Vance Russell E. , Rauch Isabella 
Published: September 2019

ABSTRACTThe NAIP/NLRC4 inflammasome is a cytosolic sensor of bacteria that activates Caspase-1 and initiates potent downstream immune responses. Structural, biochemical, and genetic data all demonstrate that the NAIP proteins act as receptors for specific bacterial ligands, while NLRC4 is a downstream adaptor protein that multimerizes with NAIPs to form a macromolecular structure called an inflammasome. However, several aspects of NLRC4 biology remain unresolved. For example, in addition to its clear function in responding to bacteria, NLRC4 has also been proposed to initiate anti-tumor responses, though the underlying mechanism is unknown. NLRC4 has also been shown to be phosphorylated on serine 533, and this modification was suggested to be important for NLRC4 function. In the absence of S533 phosphorylation, it was further proposed that another inflammasome component, NLRP3, can induce NLRC4 activation. We generated a new Nlrc4-deficient mouse line as well as mice encoding phosphomimetic S533D and non-phosphorylatable S533A NLRC4 proteins. Using these genetic models in vivo and in vitro, we fail to observe a role for phosphorylation in NLRC4 inflammasome function. Furthermore, we find no role for NLRP3 in NLRC4 function, or for NLRC4 in a model of melanoma. These results simplify and clarify our understanding of the mechanism of NAIP/NLRC4 activation and its biological functions.
Reliability of Mismatch Negativity Event-Related Potentials in a Multisite, Traveling Subjects Study
Authors: Roach Brian J. , Carrión Ricardo E. , Hamilton Holly K. , Bachman Peter , Belger Aysenil , Duncan Erica , Johannesen Jason , Light Gregory A. , Niznikiewicz Margaret , Addington Jean , Bearden Carrie E. , Cadenhead Kristin S. , Cannon Tyrone D. , Cornblatt Barbara A. , McGlashan Thomas H. , Perkins Diana O. , Seidman Larry , Tsuang Ming , Walker Elaine F. , Woods Scott W. , Mathalon Daniel H. 
Published: September 2019

AbstractObjectiveMismatch negativity (MMN) is an auditory event-related potential (ERP) used to study schizophrenia and psychosis risk. MMN reliability from a multisite, traveling subjects study was compared using different ERP referencing, averaging, and scoring techniques.MethodsReliability of frequency, duration, and double (frequency+duration) MMN was determined from eight traveling subjects, tested on two occasions at eight EEG laboratory sites. Deviant-specific variance components were estimated for MMN peak amplitude and latency measures using different ERP processing methods. Generalizability (G) coefficients were calculated using two-facet (site, occasion), fully-crossed models and single-facet (occasion) models within each laboratory to assess MMN reliability.ResultsG-coefficients calculated from two-facet models indicated fair (0.4<G<=0.6) duration MMN reliability at electrode Fz, but poor (G<0.4) double and frequency MMN reliability. Single-facet G-coefficients averaged across laboratory resulted in improved reliability (G>0.5). Reliability of MMN amplitude was greater than latency, and reliability with mastoid referencing significantly outperformed nose-referencing.ConclusionsEEG preprocessing methods have a significant impact on the reliability of MMN amplitude. Within site MMN reliability can be excellent, consistent with prior single site studies.SignificanceWith standardized data collection and ERP processing, MMN can be reliably obtained in multisite studies, providing larger samples sizes within rare patient groups.
Microscale physiological events on the human cortical surface
Authors: Paulk Angelique C. , Yang Jimmy C. , Cleary Daniel R. , Soper Daniel J. , Halgren Milan , O’Donnell Alexandra R. , Lee Sang Heon , Ganji Mehran , Ro Yun Goo , Oh Hongseok , Hossain Lorraine , Lee Jihwan , Tchoe Youngbin , Rogers Nicholas , Kiliç Kivilcim , Ryu Sang Baek , Lee Seung Woo , Hermiz John , Gilja Vikash , Ulbert István , Fabó Daniel , Devinsky Orrin , Madsen Joseph R. , Schomer Donald L. , Eskandar Emad N. , Lee Jong Woo , Maus Douglas , Devor Anna , Fried Shelley I. , Jones Pamela S. , Nahed Brian V. , Ben-Haim Sharona , Bick Sarah K. , Richardson Robert Mark , Raslan Ahmed M. T. , Siler Dominic A. , Cahill Daniel P. , Williams Ziv M. , Cosgrove G. Rees , Dayeh Shadi A. , Cash Sydney S. 
Published: September 2019

AbstractDespite ongoing advancements in our understanding of the local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their ‘intermediate’ microscale local circuit dynamics. Here, we utilized ultrahigh density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper layers of the grey matter. They were also observed in rodents, non-human primates, and semi-chronic recordings in humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that with the proper combination of high resolution microelectrodes and analytic techniques it is possible to capture neuronal dynamics that lay between somatic action potentials and aggregate population activity and that understanding these intermediate microscale dynamics may reveal important details of the full circuit behavior in human cognition.
A unifying framework for synaptic organization on cortical dendrites
Authors: Kirchner Jan H. , Gjorgjieva Julijana 
Published: September 2019

AbstractDendritic synaptic inputs are organized into functional clusters with remarkable subcellular precision at the micron level. This organization emerges during early postnatal development through patterned spontaneous activity and manifests both locally where nearby synapses are significantly correlated, and globally with distance to the soma. We propose a biophysically motivated synaptic plasticity model to dissect the mechanistic origins of this organization during development, and elucidate synaptic clustering of different stimulus features in the adult. Our model captures local clustering of orientation in ferret vs. receptive field overlap in mouse visual cortex based on the cortical magnification of visual space. Including a back-propagating action potential explains branch clustering heterogeneity in the ferret, and produces a global retinotopy gradient from soma to dendrite in the mouse. Therefore, our framework suggests that sub-cellular precision in connectivity can already be established in development, and unifies different aspects of synaptic organization across species and scales.
The Sle1 Cell Wall Amidase Controls Daughter Cell Splitting, Cell Size, and β-Lactam Resistance in Community Acquired Methicillin ResistantStaphylococcus aureusUSA300
Authors: Thalsø-Madsen Ida , Torrubia Fernando Ruiz , Xu Lijuan , Petersen Andreas , Jensen Camilla , Frees Dorte 
Published: September 2019

SummaryMost clinically relevant methicillin resistantStaphylococcus aureus(MRSA) strains have become resistant to β-lactams antibiotics through horizontal acquisition of themecAgene encoding PBP2a, a peptidoglycan transpeptidase with low affinity for β-lactams. The level of resistance conferred bymecAis, however, strain dependent and the mechanisms underlying this phenomenon remain poorly understood. We here show that β-lactam resistance correlates to expression of the Sle1 cell wall amidase in the fast spreading and highly virulent community-acquired MRSA USA300 clone. Sle1 is a substrate of the ClpXP protease, and while the high Sle1 levels in cells lacking ClpXP activity confer β-lactam hyper-resistance, USA300 cells lacking Sle1 are as sensitive to β-lactams as cells lackingmecA. This finding prompted us to assess the cellular roles of Sle1 in more detail, and we demonstrate that high Sle1 levels accelerate the onset of daughter cells splitting and decrease cell size. Vice versa, oxacillin decreases the Sle1 level, and imposes a cell-separation defect that is antagonized by high Sle1 levels, suggesting that high Sle1 levels increase tolerance to oxacillin by promoting cell separation. In contrast, increased oxacillin sensitivity ofsle1cells appears linked to a synthetical lethal effect on septum synthesis. In conclusion, this study demonstrates that Sle1 is a key factor in resistance to β-lactam antibiotics in the JE2 USA300 model strain, and that PBP2a is required for expression of Sle1 in JE2 cells exposed to oxacillin.ImportanceThe bacteriumStaphylococcus aureusis a major cause of human disease, and the global spread ofS. aureusresistant to β-lactam antibiotics (MRSA) has made treatment increasingly difficult. β-lactams interfere with cross-linking of the bacterial cell wall, however, the killing mechanism of this important class of antibiotics is still not fully understood. Here we provide novel insight into this topic by showing that β-lactam resistance is controlled by the Sle1 cell wall amidase in the fast spreading and highly virulent MRSA USA300 clone. We show that Sle1 high levels accelerate the onset of daughter cells splitting and decrease cell size. Vice versa, oxacillin decreases the Sle1 level, and imposes a cell-separation defect that is antagonized Sle1. The key finding that resistance to β-lactams correlates positively to expression of Sle1 indicates that, inS. aureus,the detrimental effects of β-lactam antibiotics are linked to inhibition of daughter cells splitting.
PHENOTYPIC AND GENETIC CORRELATION BETWEEN SLEEP, BEHAVIOR, AND MACROSCALE CORTICAL GREY MATTER
Authors: Tahmasian Masoud , Samea Fateme , Khazaie Habibolah , Zarei Mojtaba , Kharabian Shahrzad , Hoffstaedter Felix , Camilleri Julia A. , Kochunov Peter , Yeo B.T. Thomas , Eickhoff Simon B. , Valk Sofie L. 
Published: September 2019

AbstractHumans need about 7 to 9 hours of sleep per night. Sleep habits are heritable, associated with brain function and structure, and intrinsically related to well-being, mental and physical health. This raises the question whether associations between sleep, mental and physical health can be attributed to a shared macroscale neurobiology.Combining neuroimaging and behavioral genetic approaches in two independent large-scale datasets (n=1887) we demonstrate phenotypic and genetic correspondence between sleep, intelligence, and BMI. Sleep was associated with local thickness variation in frontal, temporal, and occipital cortices. Using a comprehensive multivariate approach, we identified two robust latent components highlighting the interdigitation of sleep, intelligence, BMI, and depression and their shared relation to regions in unimodal and heteromodal association cortices. Latent relationships were heritable and driven by shared additive genetic factors. These observations provide a system-level perspective on the interrelation of sleep, mental, and physical conditions, anchored in grey-matter neuroanatomy.
An integrative model finds comparable contributions to drug resistance from poor drug adherence and adapting bacteria
Authors: Mathews Roshan P. , Prakash Meher K. 
Published: September 2019

AbstractAntibiotic resistance is a compound effect of several factors in the infection to healing cycle, from molecular factors such as mutation rate of bacteria to habitual behaviors such as adherence to a prescribed drug. Usually each of these factors is modeled separately from biochemistry, evolutionary biology or population health perspectives. To develop an understanding for the drug resistance at a population level, which is of high global significance, it is important to weigh all these factors in an integrated model. We develop RASAID, a model for resistance considering bacterial adaptation, infection spread, population adherence, immunity, and drug dosage. We apply the model to antibiotic resistance in the spread of resistant strains of Streptococcus Pneumoniae (Sp) in a finite community. We analyze the contributions from several factors to resistance, with a goal towards asking how important is the pursuit of newer drug developments relative to improving the awareness about the good practices in drug usage.
Lesions of canine prostate underwent laser ablation, radiofrequency ablation, and microwave ablation: Lesions’ shapes and clinical significances
Authors: Ruiqing Liu , Lianzhong Zhang , Shaobo Duan , Huicun Cao , Guangshao Cao , Zhiyang Chang , Ye Zhang , Yaqiong Li , Yuejin Wu , Luwen Liu 
Published: September 2019

AbstractObjectiveTo explore the shapes and clinical significances of the lesions of canine prostate underwent laser ablation (LA), radiofrequency ablation (RFA), and microwave ablation (MWA).MethodsHere, 6 male Beagle dogs were randomly assigned to LA, RFA, and MWA groups, respectively. The ablations were conducted with the doses commonly applied in clinical practice (LA: 3 W/1200 J; RFA and MWA: 30 W/120 s) for one region in the left and right lobes of the prostate, which totally resulted in 12 lesions. An energy transmitter was inserted via the perineum under the guidance of transrectal ultrasound (TRUS) and the ablation process was observed dynamically. After ablation, the efficacy was assessed by contrast-enhanced ultrasonography (CEUS), and transverse diameter (TRD), anteroposterior diameter (APD), and longitudinal diameter (TRD) were measured. Then, the volume (V) was calculated according to the following formulae, V = 1/6 × π × (MLD × APD × LD), and ratio (R) R =[(MLD + APD)/2 × LD], which was used to show the shape of the lesion (The closer R is to 1, the more spherical it is).ResultsThe shapes and sizes of the lesions underwent the three techniques varied under the clinically commonly used doses. The R values, reflecting the changes in shapes of lesions, were 0.89±0.02, 0.72±0.01, and 0.65±0.03 for RFA, MWA, and LA, respectively, which were significantly different (P =0.027). The volumes of the lesions underwent the three ablation techniques significantly varied as well (P=0.001), which were 2.17±0.10, 1.51±0.20, and 0.79±0.07 ml for MWA, LA, and RFA, respectively. Conclusion: The above-mentioned three techniques could be used for ablation of prostate cancer using the clinically commonly used doses. The shapes of the lesions underwent the three ablation techniques varied evidently, with the lesions received RFA and LA were more spherical and oval, respectively, while the shapes of lesions underwent MWA were between spherical and oval. The lesions received MWA and RFA had the largest and smallest sizes, respectively, while sizes of lesions underwent LA were in the middle. These findings may assist physicians to select an appropriate therapeutic method for treatment of prostate disease.
Adrenergic C1 neurons are part of the circuitry that recruits active expiration in response to hypoxia
Authors: Malheiros-Lima Milene R. , Silva Josiane N. , Souza Felipe C. , Takakura Ana C. , Moreira Thiago S. 
Published: September 2019

AbstractBreathing results from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFRG) driving active expiration. The pFRG is silent during resting and become rhythmically active during high metabolic demand such as hypoxia. Catecholaminergic C1 cells are activated by hypoxia, which is a strong stimulus for active expiration. We hypothesized that the C1 cells and pFRG may constitute functionally distinct but interacting populations in order to contributes to control expiratory activity during hypoxia. We found that: a) C1 neurons are activated by hypoxia and project to pFRG region; b) active expiration elicited by hypoxia was blunted after blockade of ionotropic glutamatergic antagonist at the level of pFRG and c) selective depletion of C1 neurons eliminated the active expiration elicited by hypoxia. The results suggest that C1 cells may regulate the respiratory cycle including the active expiration under hypoxic condition.
TPM3.1 association with actin stress fibers is required for lens epithelial to mesenchymal transition
Authors: Parreno Justin , Amadeo Michael B. , Kwon Elizabeth H. , Fowler Velia M. 
Published: September 2019

AbstractPurposeEpithelial to mesenchymal transition (EMT) is a cause of anterior and posterior subcapsular cataracts. Central to EMT is the formation of actin stress fibers. Targeting specific, stress fiber associated tropomyosin in epithelial cells may be a means to prevent stress fiber formation and repress lens EMT.MethodsWe identified Tpm isoforms in mouse immortalized lens epithelial cells and isolated whole lenses by semi-quantitative PCR followed Sanger sequencing. We focused on the role of one particular tropomyosin isoform, Tpm3.1, in EMT. To stimulate EMT, we cultured cells or native lenses in TGFβ2. To test the function of Tpm3.1, we exposed cells or whole lenses to a Tpm3.1-specific chemical inhibitor, TR100, as well as investigated lenses from Tpm3.1 knockout mice. We examined stress fiber formation by confocal microscopy and assessed EMT progression by αsma mRNA (qPCR) and protein (WES immunoassay) analysis.ResultsLens epithelial cells express eight tropomyosin isoforms. Cell culture studies showed that TGFβ2 treatment results in an upregulation of Tpm3.1, which associates with actin in stress fibers. TR100 prevents stress fiber formation and reduces αsma in TGFβ2 treated cells. We confirmed the role of Tpm3.1 in lens epithelial cells in the native lens ex vivo. Culture of whole lenses in the presence of TGFβ2 results in stress fiber formation at the basal regions of epithelial cells. Knockout of Tpm3.1 or treatment of lenses with TR100 prevents basal stress fiber formation and reduces epithelial αsma levels.ConclusionTargeting specific stress fiber associated tropomyosin isoform, Tpm3.1, is a means to represses lens EMT.
Dynamic actin crosslinking governs the cytoplasm’s transition to fluid-like behavior
Authors: Chaubet Loïc , Chaudhary Abdullah R. , Heris Hossein K. , Ehrlicher Allen J. , Hendricks Adam G. 
Published: September 2019

AbstractCells precisely control their mechanical properties to organize and differentiate into tissues. The architecture and connectivity of cytoskeletal filaments changes in response to mechanical and biochemical cues, allowing the cell to rapidly tune its mechanics from highly-crosslinked, elastic networks to weakly-crosslinked viscous networks. While the role of actin crosslinking in controlling actin network mechanics is well-characterized in purified actin networks, its mechanical role in the cytoplasm of living cells remains unknown. Here, we probe the frequency-dependent intracellular viscoelastic properties of living cells using multifrequency excitation and in situ optical trap calibration. At long timescales in the intracellular environment, we observe that the cytoskeleton becomes fluid-like. The mechanics are well-captured by a model in which actin filaments are dynamically connected by a single dominant crosslinker. A disease-causing point mutation (K255E) of the actin crosslinker α-actinin 4 (ACTN4) causes its binding kinetics to be insensitive to tension. Under normal conditions, the viscoelastic properties of wild type (WT) and K255E+/- cells are similar. However, when tension is reduced through myosin II inhibition, WT cells relax 3x faster to the fluid-like regime while K255E+/- cells are not affected. These results indicate that dynamic actin crosslinking enables the cytoplasm to flow at long timescales.
Neutrophils mediate the capture of peritoneal contaminants by fat-associated lymphoid clusters of the omentum
Authors: Jackson-Jones Lucy H. , Smith Peter , Magalhaes Marlène S. , Portman Jordan R. , Mylonas Katie J. , Nixon Mark , Henderson Beth E.P. , Dobie Ross , Henderson Neil C. , Mole Damian J. , Bénézech Cécile 
Published: September 2019

AbstractThe omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs), which collects peritoneal contaminants and provides a first layer of immunological defence within the abdomen. Using single-cell RNA sequencing and spatial analysis of omental stromal cells, we reveal that the surface of FALCs are covered with specialised mesothelial cells, which we name FALC cover cells. We demonstrate that CXCL1 is expressed by FALC cover cells and that CXCL1 is critical for the retention and accumulation of neutrophils within FALCs during peritonitis. We show that protein arginine deiminase 4 mediates the formation of dense neutrophil aggregates, which are required for the neutralisation of particles present in the peritoneal cavity. Finally, we provide confirmatory evidence in humans with acute appendicitis, that the omentum is also a site of neutrophil recruitment and bacterial capture, and is thus an important component of the immunological defence against the propagation of peritoneal contaminants.