bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain network analysis in Parkinson’s disease patients based on graph theory
Authors: Akbari Shirin , Deevband Mohammad Reza , Alvar Amin Asgharzadeh , Zadeh Emadodin Fatemi , Tabar Hashem Rafie , Kelley Patrick , Tavakoli Meysam 
Published: February 2023

AbstractDevelopment of Parkinson’s disease causes functional impairment in the brain network of Parkinson’s patients. The aim of this study is to analyze brain networks of people with Parkinson’s disease based on higher resolution parcellations and newer graphical features. The topological features of brain networks were investigated in Parkinson’s patients (19 individuals) compared to healthy individuals (17 individuals) using graph theory. In addition, four different methods were used in graph formation to detect linear and nonlinear relationships between functional magnetic resonance imaging (fMRI) signals. The functional connectivity between the left precuneus and the left amygdala, as well as between the vermis 1-2 and the left temporal lobe was evaluated for the healthy and the patient groups. The difference between the healthy and patient groups was evaluated by non-parametric t-test and U-test. Based on the results, Parkinson’s patients showed a significant decrease in centrality criterion compared to healthy subjects. Furtheremore, changes in regional features of brain network were observed. There was also a significant difference between the two groups of healthy subjects and Parkinson’s patients in different areas by applying centrality criterion and the correlation coefficients. The results obtained for topological features indicate changes in the functional brain network of Parkinson’s patients. Finally, similar areas obtained by all three methods of graph formation in the evaluation of connectivity between paired regions in the brain network of Parkinson’s patients increased the reliability of the results.
CETP inhibitor evacetrapib enters mouse brain tissue
Authors: Phénix Jasmine , Côté Jonathan , Dieme Denis , Recinto Sherilyn J , Oestereich Felix , Efrem Sasen , Haddad Sami , Bouchard Michèle , Munter Lisa Marie 
Published: February 2023

AbstractHigh levels of plasma cholesterol, especially high levels of low-density lipoprotein-cholesterol (LDL-C), have been associated with an increased risk of Alzheimer’s disease. The cholesteryl ester transfer protein (CETP) in plasma distributes cholesteryl esters between lipoproteins and increases LDL-C in plasma. Epidemiologically, decreased CETP activity has been associated with sustained cognitive performance during aging, longevity, and a lower risk of Alzheimer’s disease. Thus, pharmacological CETP inhibitors could potentially be repurposed for the treatment of Alzheimer’s disease as they are safe and effective at lowering CETP activity and LDL-C. While CETP is mostly expressed by the liver and secreted into the bloodstream, CETP is also expressed by astrocytes in the brain. It is therefore important to determine if CETP inhibitors can enter the brain. Here, we describe pharmacokinetic parameters of the CETP inhibitor evacetrapib in plasma, liver, and brain tissues in CETP transgenic mice. We show that evacetrapib crosses the blood-brain barrier and is detectable in brain tissue 0.5 h after a 40 mg/kg i.v. injection in a nonlinear function. We conclude that evacetrapib may prove to be a good candidate to treat CETP-mediated cholesterol dysregulation in Alzheimer’s disease.
Palmitoylation of gasdermin D directs its membrane translocation and pore formation in pyroptosis
Authors: Balasubramanian Arumugam , Ghimire Laxman , Hsu Alan Y. , Kambara Hiroto , Liu Xing , Hasegawa Tomoya , Xu Rong , Tahir Muhammad , Yu Hongbo , Lieberman Judy , Luo Hongbo R. 
Published: February 2023

ABSTRACTGasdermin D (GSDMD)-mediated macrophage pyroptosis plays a critical role in inflammation and host defense. Plasma membrane perforation elicited by caspase-cleaved GSDMD N-terminal domain (GSDMD-NT) triggers membrane rupture and subsequent pyroptotic cell death, resulting in release of pro-inflammatory IL-1β and IL-18. However, the biological processes leading to its membrane translocation and pore formation are not fully understood. Here, using a proteomics approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner and demonstrated that post-translational palmitoylation of GSDMD at Cys191/Cys192 (human/mouse) led to membrane translocation of GSDMD-NT but not full-length GSDMD. GSDMD lipidation, mediated by palmitoyl acyltransferases ZDHHC5/9 and facilitated by LPS-induced reactive oxygen species (ROS), was essential for GSDMD pore-forming activity and pyroptosis. Inhibition of GSDMD palmitoylation with palmitate analog 2-bromopalmitate or a cell permeable GSDMD-specific competing peptide suppressed pyroptosis and IL-1β release in macrophages, mitigated organ damage, and extended the survival of septic mice. Collectively, we establish GSDMD-NT palmitoylation as a key regulatory mechanism controlling GSDMD membrane localization and activation, providing a novel target for modulating immune activity in infectious and inflammatory diseases.One Sentence SummaryLPS-induced palmitoylation at Cys191/Cys192 is required for GSDMD membrane translocation and its pore-forming activity in macrophages.
Wnt/β-catenin signaling within multiple cell types dependent uponkramerregulatesDrosophilaintestinal stem cell proliferation
Authors: Sun Hongyan , Shah Adnan Shami , Bonfini Alessandro , Buchon Nicolas S. , Baskin Jeremy M. 
Published: February 2023

ABSTRACTThe gut epithelium is subject to constant renewal, a process reliant upon intestinal stem cell (ISC) proliferation that is driven by Wnt/β-catenin signaling. Despite the importance of Wnt signaling within ISCs, the relevance of Wnt signaling within other gut cell types and the underlying mechanisms that modulate Wnt signaling in these contexts remain incompletely understood. Using challenge of theDrosophilamidgut with a non-lethal enteric pathogen, we examine the cellular determinants of ISC proliferation, harnessingkramer, a recently identified regulator of Wnt signaling pathways, as a mechanistic tool. We find that Wnt signaling within Prospero-positive cells supports ISC proliferation and thatkramerregulates Wnt signaling in this context by antagonizingkelch, a Cullin-3 E3 ligase adaptor that mediates Dishevelled polyubiquitination. This work establisheskrameras a physiological regulator of Wnt/β-catenin signaling in vivo and suggests enteroendocrine cells as a new cell type that regulates ISC proliferation via Wnt/β-catenin signaling.
TET1 Catalytic Activity is Required for Reprogramming of Imprinting Control Regions and Patterning of Sperm-Specific Hypomethylated Regions
Authors: Prasasya Rexxi D. , Caldwell Blake A. , Liu Zhengfeng , Wu Songze , Leu Nicolae A. , Fowler Johanna M. , Cincotta Steven A. , Laird Diana J. , Kohli Rahul M. , Bartolomei Marisa S. 
Published: February 2023

SUMMARYDNA methylation erasure is required for mammalian primordial germ cell reprogramming. TET enzymes iteratively oxidize 5-methylcytosine to generate 5-hyroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxycytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during germline reprogramming remains unresolved due to the lack of genetic models that decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V).Tet1-/-,Tet1V/V, andTet1HxD/HxDsperm methylomes show that TET1Vand TET1HxDrescue mostTet1-/-hypermethylated regions, demonstrating the importance of TET1’s extra-catalytic functions. Imprinted regions, in contrast, require iterative oxidation. We further reveal a broader class of hypermethylated regions in sperm ofTet1mutant mice that are excluded fromde novomethylation during male germline development and depend on TET oxidation for reprogramming. Our study underscores the link between TET1-mediated demethylation during reprogramming and sperm methylome patterning.
3D Synaptic Organization of Layer III of the Human Anterior Cingulate and Temporopolar Cortex
Authors: Cano-Astorga Nicolás , Plaza-Alonso Sergio , DeFelipe Javier , Alonso-Nanclares Lidia 
Published: February 2023

AbstractThe human anterior cingulate and temporopolar cortices have been proposed as highly connected nodes involved in high-order cognitive functions, but their synaptic organization is still basically unknown due to the difficulties involved in studying the human brain. Using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to study the synaptic organization of the human brain obtained with a short post-mortem delay allows excellent results to be obtained. We have used this technology to analyze the neuropil (where the vast majority of synapses are found) of layer III of the anterior cingulate cortex (Brodmann’s area 24) and the temporopolar cortex, including the temporal pole (Brodmann’s area 38 ventral and dorsal) and anterior middle temporal gyrus (Brodmann’s area 21). Our results, based on 6695 synapses fully reconstructed in 3D, revealed that Brodmann’s areas 24, 21 and ventral area 38 showed similar synaptic density and synaptic size, whereas dorsal area 38 displayed the highest synaptic density and the smallest synaptic size. However, the proportion of the different types of synapses (excitatory and inhibitory), the postsynaptic targets and the shapes of excitatory and inhibitory synapses were similar, regardless of the region examined. These observations indicate that certain aspects of the synaptic organization are rather homogeneous, whereas others show specific variations across cortical regions. Since not all data obtained in a given cortical region can be extrapolated to other cortical regions, further studies on the other cortical regions and layers are necessary to better understand the functional organization of the human cerebral cortex.
CLE11 and CLE10 Suppress Mycorrhizal Colonisation in Tomato
Authors: Wulf Kate , Wang Chenglei , Ho-Plagaro Tania , Kwon Choon-Tak , Velandia Karen , Correa-Lozano Alejandro , Tamayo-Navarrete María Isabel , Sun Jiacan , Reid James B. , García Garrido Jose Manuel , Foo Eloise 
Published: February 2023

AbstractSymbioses with beneficial microbes are widespread in plants, but these relationships must balance the energy invested by the plants with the nutrients acquired. Symbiosis with arbuscular mycorrhizal (AM) fungi occurs throughout land plants but our understanding of the genes and signals that regulate colonisation levels is limited. Here, we demonstrate that in tomato two CLV3/EMBRYO-SURROUNDING REGION (CLE) peptides,SlCLE10 andSlCLE11, act to suppress AM colonisation of roots. Mutant studies and overexpression via hairy transformation indicateSlCLE11acts locally in the root to limit AM colonisation. Indeed,SlCLE11expression is strongly induced in AM colonised roots butSlCLE11is not required for phosphate suppression of AM colonisation.SlCLE11 may act through as yet uncharacterised signalling pathways, asSlCLE11does not suppress AM colonisation by acting through two previously characterised receptors with roles in regulating AM colonisation,SlFAB (CLAVATA1 orthologue) orSlCLV2.SlCLE10 appears to play a more minor or redundant role, ascle10mutants did not influence AM, although the fact that ectopic overexpression ofSlCLE10did suppress colonisation suggestsSlCLE10may play a role in regulating AM colonisation. Our findings show that CLE peptides regulate AM colonisation in the non-legume species tomato.
Early retinal deprivation crossmodally alters nascent subplate circuits and activity in the auditory cortex during the precritical period
Authors: Mukherjee Didhiti , Xue Binghan , Chen Chih-Ting , Chang Minzi , Kao Joseph P. Y. , Kanold Patrick O. 
Published: February 2023

AbstractSensory perturbation in one modality results in adaptive reorganization of neural pathways within the spared modalities, a phenomenon known as “crossmodal plasticity”, which has been examined during or after the classic ‘critical period’. Because peripheral perturbations can alter auditory cortex (ACX) activity and functional connectivity of the ACX subplate neurons (SPNs) even before the classic critical period, called the precritical period, we investigated if retinal deprivation at birth crossmodally alters ACX activity and SPN circuits during the precritical period.We deprived newborn mice of visual inputs after birth by performing bilateral enucleation. We performed in vivo imaging in the ACX of awake pups during the first two postnatal weeks to investigate cortical activity. We found that enucleation alters spontaneous and sound-evoked activity in the ACX in an age-dependent manner. Next, we performed whole-cell patch clamp recording combined with laser scanning photostimulation in ACX slices to investigate circuit changes in SPNs. We found that enucleation alters the intracortical inhibitory circuits impinging on SPNs shifting the excitation-inhibition balance towards excitation and this shift persists after ear opening. Together, our results indicate that crossmodal functional changes exist in the developing sensory cortices at early ages before the onset of the classic critical period.
Ketosis Prevents Abdominal Aortic Aneurysm Rupture Through CCR2 Downregulation and Enhanced MMP Balance
Authors: Sastriques-Dunlop Sergio , Elizondo-Benedetto Santiago , Arif Batool , Meade Rodrigo , Zaghloul Mohamed S. , English Sean J. , Liu Yongjian , Zayed Mohamed A. 
Published: February 2023

AbstractAbdominal aortic aneurysms (AAAs) are common in aging populations, and AAA rupture is associated with high morbidity and mortality. There is currently no effective medical preventative therapy for AAAs to avoid rupture. It is known that the monocyte chemoattractant protein (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA tissue inflammation, matrix-metalloproteinase (MMP) production, and in turn extracellular matrix (ECM) stability. However, therapeutic modulation of the CCR2 axis for AAA disease has so far not been accomplished. Since ketone bodies (KBs) are known to trigger repair mechanisms in response to vascular tissue inflammation, we evaluated whether systemicin vivoketosis can impact CCR2 signaling, and therefore impact AAA expansion and rupture. To evaluate this, male Sprague-Dawley rats underwent surgical AAA formation using porcine pancreatic elastase (PPE), and received daily β-aminopropionitrile (BAPN) to promote AAA rupture. Animals with formed AAAs received either a standard diet (SD), ketogenic diet (KD), or exogenous KB supplements (EKB). Animals that received KD and EKB reached a state of ketosis, and had significantly reduced AAA expansion and incidence of rupture. Ketosis also led to significantly reduced CCR2, inflammatory cytokine content, and infiltrating macrophages in AAA tissue. Additionally, animals in ketosis had improved balance in aortic wall matrix-metalloproteinase (MMP), reduced extracellular matrix (ECM) degradation, and higher aortic media Collagen content. This study demonstrates that ketosis plays an important therapeutic role in AAA pathobiology, and provides the impetus for future studies investigating the role of ketosis as a preventative strategy for individuals with AAAs.
Characterization of the growth behavior ofListeria monocytogenesinListeriasynthetic media
Authors: Schulz Lisa Maria , Konrath Alicia , Rismondo Jeanine 
Published: February 2023

AbstractThe foodborne pathogenListeria monocytogenescan grow in a wide range of environmental conditions. For the study of the physiology of this organism, several chemically defined media have been developed over the past decades. Here, we examined the ability ofL. monocytogeneswildtype strains EGD-e and 10403S to grow under salt and pH stress inListeriasynthetic medium (LSM). Furthermore, we determined that a wide range of carbon sources could support growth of both wildtype strains in LSM. However, for hexose phosphate sugars such as glucose-1-phosphate, bothL. monocytogenesstrains need to be pre-grown under conditions, where the major virulence regulator PrfA is active. In addition, growth of bothL. monocytogenesstrains was observed when LSM was supplemented with the amino acid sugarN-acetylmannosamine (ManNAc). We were able to show that some of the proteins encoded in the operonlmo2795-nanE, such as the ManNAc-6-phosphate epimerase NanE, are required for growth in presence of ManNAc. The first gene of the operon,lmo2795,encodes a transcriptional regulator of the RpiR family. Using electrophoretic mobility shift assays and quantitative real time PCR analysis, we were able to show that Lmo2795 binds to the promoter region of the operonlmo2795-nanEand activates its expression.Originality-Significance StatementCurrent knowledge of growth and survival of the human pathogenListeria monocytogenesunder diverse stress conditions is mostly generated in complex medium, a condition that is rarely found in the environment or host of the pathogen. Our work contributes to the characterization of the physiology ofL. monocytogenesgrown under nutrient limiting conditions and its growth requirements with regards to metabolizable carbon sources.
RIPK3-dependent necroptosis is the primary cause of RIPK1-deficient-induced immunodeficiency
Authors: Liu Xiaoyan , Zhu Xinxin , Shu Zhaoqian , Sun Liming , Wang Huayi 
Published: February 2023

AbstractRIPK1 (receptor-interacting serine/threonine kinase 1) plays a pivotal role in developing the immune system—patients with homozygous loss-of-function mutations of RIPK1 present with immunodeficiency and intestinal inflammation. Here, we reported that RIPK1-deficient rats represented defects of human patients and were certified as a suitable disease model. Knocking outRipk3rather thanCaspase-8nearly completely corrected immunodeficiency disorders, developmental defects, and necroptosis in the thymus of RIPK1-deficient rats. However, inflammatory enteritis was still detected in eitherRipk1/Ripk3-orRipk1/Casp-8-double deficient rats and only rescued inRipk1/Ripk3/Caspase-8-triple deficient rats, suggesting RIPK3 mediated necroptosis and Caspase-8 dependent apoptosis contribute in different part in RIPK1-deficient caused the syndrome. Moreover, RIPK1-deficient rat dermal fibroblasts (RDFs) showed sensitive necroptosis and impaired NF-κB activation, also reported inRIPK1-deficienthuman patients. And pharmacological inhibition of NF-κB activation could sensitize necroptosis of rat cells. Since mutations that damage NF-κB activation could cause immunodeficiency in human patients, it suggested that aberrantly activated necroptosis play a vital role in certain kinds of primary immunodeficiency syndromes and pharmacological inhibition of necroptosis could be a novel therapeutic strategy for those diseases.
A flexible Bayesian approach for estimating survival probabilities from age‐at‐harvest data
Authors: Skelly Brett P. , Clipp Hannah L. , Landry Stephanie M. , Rogers Rich , Phelps Quinton , Anderson James T. , Rota Christopher T. 
Published: February 2023

Abstract

Understanding survival probabilities is critical for the sustainable harvest of wildlife and fisheries populations. Age‐ and stage class‐specific survival probabilities are needed to inform a suite of population models used to estimate abundance and track population trends. However, current techniques for estimating survival probabilities using age‐at‐harvest methods require restrictive assumptions or incorporate potentially unknown parameters within the model.

Using a Bayesian approach, we developed a flexible age‐at‐harvest model that incorporates either age‐ or stage‐structured populations, while accounting for uncertainty in age structure, population growth rates and relative selectivity. Survival probabilities can vary by age or stage class, as well as by environmental covariates, and both population growth rates and selectivity for each age or stage class can be specified as fixed and known or these parameters can be specified as informative priors, allowing for the incorporation of expert opinion. We evaluated our model with simulations and empirical data from harvested bobcats Lynx rufus and American paddlefish Polyodon spathula.

Models fit to simulated age‐at‐harvest data yielded unbiased estimates of survival probability when population growth rates and selectivity were centered on the data‐generating parameter. We obtained unbiased estimates of survival probability even with biased prior estimates of selectivity and random departures from the assumed stage distribution, although the latter increased uncertainty in those estimates. We found biased estimates of survival probability when the prior distribution for population growth rate was not centered on the data‐generating value. When fit to empirical harvest data, our proposed age‐at‐harvest model produced estimates of survival probability congruent to those reported in the literature within similar geographic regions.

We demonstrate the utility of a novel age‐at‐harvest model that estimates survival probability and realistically account for uncertainty in model parameters, transcending the restrictive assumptions and auxiliary data requirements of other methods. Furthermore, we advise collecting information about population trends and age structure alongside age‐at‐harvest data to help reduce bias. Although our model cannot replace more rigorous methods, we believe our model will be transformative for wildlife and fisheries practitioners who collect age‐at‐harvest data to estimate age‐ or stage‐specific survival probabilities to help inform management decisions.
A retrospective study of colonoscopic surveillance in the elderly
Authors: McGuinness Matthew J. , Joseph Nejo , Richards Simon J. G. , Speight Julian M. 
Published: February 2023

AbstractBackgroundAotearoa New Zealand (AoNZ) guidelines suggest surveillance colonoscopy should be carefully considered after age 75. The authors noted a cluster of patients presenting in their 8th and 9th decade of life with a new colorectal cancer (CRC) having previously been declined surveillance colonoscopy.MethodsA 7‐year retrospective analysis was performed of patients who underwent a colonoscopy aged between 71 and 75 years in the period between 2006 and 2012. Kaplan–Meier graphs were created with survival measured from the time of index colonoscopy. Log rank tests were used to determine any difference in survival distribution. Relative risk (RR) was calculated, and 95% confidence intervals (CI) reported.ResultsA total of 623 patients met inclusion criteria; 461 (74%) had no indication for surveillance colonoscopy and 162 (26%) had an indication. Of the 162 patients with an indication, 91 (56.2%) underwent surveillance colonoscopies after the age of 75. Twenty‐three (3.7%) patients were diagnosed with a new CRC. Eighteen (78.2%) patients diagnosed with a new CRC underwent surgery. The median survival overall was 12.9 years (95% CI 12.2–13.5). This did not differ between patients with (13.1, 95% CI 12.1–14.1) or without (12.6, 95% CI 11.2–14.0) an indication for surveillance.ConclusionThis study found one quarter of patients who had a colonoscopy between the ages of 71–75 had an indication for surveillance colonoscopy. Most patients with a new CRC underwent surgery. This study suggests it may be appropriate to update the AoNZ guidelines and consider adopting a risk stratification tool to aid decision making.