bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling from theC. elegansHypodermis Non-autonomously Facilitates Short-term Associative Memory
Authors: Zhou Shiyi , Zhang Yanping , Kaletsky Rachel , Toraason Erik , Zhang Wenhong , Dong Meng-Qiu , Murphy Coleen T. 
Published: February 2023

AbstractMemory loss is one of the most debilitating symptoms of aging. While we normally think of memory regulation as autonomous to the brain, other factors outside of the brain can also affect neuron function. We have shown that the longevity insulin/IGF-1 signaling (IIS) pathway regulates neuron-specific activity, but whether the maintenance of memory through the IIS pathway is completely autonomous to the nervous system, or if there are systemic inputs, is unknown. We address this question using the auxin-inducible degradation (AID) system to degrade the IIS receptor, DAF-2, in specific tissues. Surprisingly, DAF-2 degradation specifically in the hypodermis improves memory in both young and agedC. elegansthrough the hypodermal expression of the diffusible Notch ligand, OSM-11. The Notch receptor LIN-12 is required for OSM-11’s effect on memory, as are the downstream transcription factor LAG-1 and co-activator SEL-8. Furthermore, mid-life overexpression of the Notch ligand OSM-11 improves memory and slows cognitive decline. Hypodermal DAF-2 degradation suppresses the expression ofins-19, whose downregulation extends memory. Together, our data suggest a model in which the hypodermis, a metabolic tissue, can non-autonomously regulate neuronal activity and function, indicating a systemic connection between metabolism and memory regulation.
Effects of isoflurane and urethane anesthetics on glutamate neurotransmission in rat brain usingin vivoamperometry
Authors: Beitchman Joshua A. , Krishna Gokul , Bromberg Caitlin E. , Thomas Theresa Currier 
Published: February 2023

ABSTRACTAspects of glutamate neurotransmission implicated in normal and pathological conditions are often evaluated usingin vivorecording paradigms in rats anesthetized with isoflurane or urethane. Urethane and isoflurane anesthesia influence glutamate neurotransmission through different mechanisms; however real-time outcome measures of potassium chloride (KCl)-evoked glutamate overflow and glutamate clearance kinetics have not been compared within and between regions of the brain. In the following experiments,in vivoamperometric recordings of KCl-evoked glutamate overflow and glutamate clearance kinetics (uptake rate and T80) in the cortex, hippocampus and thalamus were performed using glutamate-selective microelectrode arrays (MEAs) in young adult male, Sprague-Dawley rats anesthetized with isoflurane or urethane. Potassium chloride (KCl)-evoked glutamate overflow was similar under urethane and isoflurane anesthesia in all brain regions studied. Analysis of glutamate clearance determined that the uptake rate was significantly faster (53.2%, p<0.05) within the thalamus under urethane compared to isoflurane, but no differences were measured in the cortex or hippocampus. Under urethane, glutamate clearance parameters were region dependent, with significantly faster glutamate clearance in the thalamus compared to the cortex but not the hippocampus (p<0.05). No region dependent differences were measured for glutamate overflow using isoflurane. These data support that amperometric recordings of glutamate under isoflurane and urethane anesthesia result in mostly similar and comparable data. However, certain parameters of glutamate uptake vary based on choice of anesthesia and brain region. Special considerations must be given to these areas when considering comparison to previous literature and when planning future experiments.HighlightsKCl-evoked glutamate overflow was similar under urethane and isoflurane anesthesiaGlutamate clearance parameters were similar under both anesthesias in the cortex and hippocampus but not the thalamusGlutamate clearance kinetics differ between brain regions when anesthetized with urethane.Experimental design, brain region of interest, and outcome parameters of glutamate clearance should be considered when designing anesthetized amperometry recordings of glutamate.
An ancient thyrostimulin-like neuroendocrine pathway regulates growth inCaenorhabditis elegans
Authors: Kenis Signe , Istiban Majdulin Nabil , Van Damme Sara , Vandewyer Elke , Watteyne Jan , Schoofs Liliane , Beets Isabel 
Published: February 2023

AbstractIn vertebrates, thyrostimulin is a highly conserved glycoprotein hormone that, besides thyroid stimulating hormone (TSH), is a potent ligand of the TSH receptor. Thyrostimulin is considered the most ancestral glycoprotein hormone and orthologs of its subunits, GPA2 and GPB5, are widely conserved across vertebrate and invertebrate animals. Unlike TSH, however, the functions of the thyrostimulin neuroendocrine system remain largely unexplored. Here, we identify a functional thyrostimulin-like signaling system inCaenorhabditis elegans. We show that orthologs of GPA2 and GPB5, together with thyrotropin-releasing hormone (TRH) related neuropeptides, constitute a neuroendocrine pathway that promotes growth inC. elegans. GPA2/GPB5 signaling is required for normal body size and acts through activation of the glycoprotein hormone receptor ortholog FSHR-1.C. elegansGPA2 and GPB5 increase cAMP signaling by FSHR-1in vitro. Both subunits are expressed in enteric neurons and promote growth by signaling to their receptor in glial cells and the intestine. Impaired GPA2/GPB5 signaling causes bloating of the intestinal lumen. In addition, mutants lacking thyrostimulin-like signaling are defective in defecation behavior. Our study suggests that the thyrostimulin GPA2/GPB5 pathway is an ancient enteric neuroendocrine system that regulates intestinal function in ecdysozoans, and may ancestrally have been involved in the control of organismal growth.
Wnt-7a-positive dendritic cytonemes induce synaptogenesis in cortical neurons
Authors: Piers Thomas M. , Namboori Seema C. , Bhinge Akshay , Killick Richard , Scholpp Steffen 
Published: February 2023

SummaryNeuronal circuits evolve as a precisely patterned network. In this context, a growing neuron must locate the appropriate target area on a neurite of a neighbouring cell with which to connect. Controlled target selection involves dendritic filopodial contacts and requires the exact apposition of synaptic components. Calcium signalling has been postulated to trigger the transformation from dendritic filopodia into functional synapses. However, calcium is a rather unspecific signalling system, and it needs to be clarified how the exact development of synaptic connections is controlled. Similarly, Wnt/β-catenin signalling promotes synapse formation; however, how secreted Wnts induce and maintain synapses on neuronal dendrites is not well understood. Here, we show that Wnt-7a is tethered to the tips of dynamic dendritic filopodia during spine formation in human cortical neurons. These filopodia can activate Wnt signalling precisely at the contact sites on the dendrites of an adjacent neuron. Subsequently, local calcium transients can be observed at these Wnt-positive contact sites. Depleting either the filopodial-loaded Wnt or the extracellular calcium pool blocks the clustering of pre- and post-synaptic markers, hence the establishment of stable connections. Therefore, we postulate that local Wnt-7a signalling from the tip of the dendritic filopodia, verified by simultaneous calcium signalling, provides an elegant mechanism for orchestrating focal synapse maturation.
Computational prediction of human deep intronic variation
Authors: Barbosa Pedro , Savisaar Rosina , Carmo-Fonseca Maria , Fonseca Alcides 
Published: February 2023

AbstractThe adoption of whole genome sequencing in genetic screens has facilitated the detection of genetic variation in the intronic regions of genes, far from annotated splice sites. However, selecting an appropriate computational tool to differentiate functionally relevant genetic variants from those with no effect is challenging, particularly for deep intronic regions where independent benchmarks are scarce.In this study, we have provided an overview of the computational methods available and the extent to which they can be used to analyze deep intronic variation. We leveraged diverse datasets to extensively evaluate tool performance across different intronic regions, distinguishing between variants that are expected to disrupt splicing through different molecular mechanisms. Notably, we compared the performance of SpliceAI, a widely used sequence-based deep learning model, with that of more recent methods that extend its original implementation. We observed considerable differences in tool performance depending on the region considered, with variants generating cryptic splice sites being better predicted than those that affect splicing regulatory elements or the branchpoint region. Finally, we devised a novel quantitative assessment of tool interpretability and found that tools providing mechanistic explanations of their predictions are often correct with respect to the ground truth information, but the use of these tools results in decreased predictive power when compared to black box methods.Our findings translate into practical recommendations for tool usage and provide a reference framework for applying prediction tools in deep intronic regions, enabling more informed decision-making by practitioners.
The role of floral traits in community assembly processes at high elevations in the Himalayas
Authors: Ahmad Mustaqeem , Rosbakh Sergey , Bucher Solveig Franziska , Sharma Padma , Rathee Sonia , Uniyal Sanjay Kr. , Batish Daizy R. , Singh Harminder P. 
Published: February 2023

Abstract

There is a common agreement that, to maximise our understanding of trait‐based community assembly, traits related to different organs should be considered as they relate to different ecological niche axes. Floral traits, in particular, have been suggested to play an important role in the plant community assembly along with environmental gradients as they determine reproductive success, one of the key functions in plants. However, the role of floral traits in community assembly research remains largely unverified empirically.

Using a large and novel dataset on plant traits and plant communities, we analysed the variability of six floral traits of 139 herbaceous species in 21 sites located along an elevation gradient (2000–4000 m) in the western Himalayas. The variability of floral traits along the gradient was analysed using community‐weighted mean (CWM) trait values and functional diversities (FDs) calculated for each study community.

The CWMs showed that with increasing elevation, flowering began later, and flowers tended to be larger with decreasing specific flower area (SFA). Along with the convergence in the onset of flowering and SFA (i.e. lower FD at high‐elevation sites), these patterns suggest that abiotic filtering and plant–pollinator interactions could affect the floral trait composition of the communities. Most likely, increasing low‐temperature stress towards high‐elevation sites selected for late‐flowering species that produce flowers with larger display areas. The low abundance and activity of pollinators at high elevation could also explain why these traits were selected in the communities studied. Delayed flowering with increasing elevation might facilitate the phenological overlap of plants and their pollinators, as pollinator activity at higher elevation peaks in the second half of the vegetation period. The dominance of a species with low SFA and larger display area in high‐altitude communities could be attributable to increased flower longevity and attraction of pollinators, respectively, to maximise pollination success under pollinator scarcity.

Synthesis. Our study provides empirical support for the recent argument that floral traits contribute considerably to the assembly of plant communities along environmental gradients. Thus, such traits should be included in community assembly research as they represent key ecological functions for reproduction.
Infrared radiation blanching–inhibited browning and extended shelf life of pecan kernels
Authors: Luo Shui‐Zhong , Sun Ye , Yuan Xue , Pan Li‐Hua , Zheng Zhi , Zhao Yan‐Yan , Zhong Xi‐Yang 
Published: February 2023

AbstractTo evaluate infrared radiation (IR) blanching in comparison to conventional hot water (HW) blanching in inhibiting the browning and extending the shelf life of pecan kernels, the technology of IR blanching at 500–700 W for 90–45 s or HW blanching at 90°C for 60 s, and subsequently drying with hot air at 60, 70, and 80°C, respectively, was used, and then the activities of lipoxidase (LOX) and polyphenol oxidase (PPO), antioxidant capacities, color change, microscopic structure, and the shelf life of kernels were analyzed. Results showed that IR blanching not only significantly decreased the subsequent drying time but also effectively inactivated the activities of LOX and PPO, showing a lower residual activity of 15.74%–40.41% and 16.75%–56.25%, respectively. A higher retention of total phenolics was observed in kernels subjected to IR blanching, from 25.03 ± 0.04 to 29.50 ± 0.96 mg GAE/g compared with HW blanching (14.43 ± 0.07 mg GAE/g). Meanwhile, IR‐blanched samples showed lower peroxide values, p‐anisidine values, total color difference values, browning index, quinones contents, and lipofuscin‐like pigments levels but had higher 2,2‐diphenyl‐1‐picrylhydrazyl inhibition rate and better storage stabilities than HW‐blanched samples. The technology of IR blanching at 600 W for 60 s followed by drying with hot air at 70°C for 40 min is suitable for producing pecan kernels with better qualities and a longer shelf life, through inactivating the endogenous enzymatic reactions and inhibiting the formation of lipofuscin‐like pigments.Practical ApplicationBlanching is an essential pretreatment of food processing. Conventional blanching is achieved by hot water, which has some disadvantages of low‐intensity enzyme inactivation, loss of water‐soluble substances, etc. In this study, the potential of using infrared blanching, prior to drying, was studied to find solutions to improve the nutritional value, and the shelf life of pecan kernels. The results showed that infrared blanching at 600 W for 60 s followed by drying with hot air at 70°C for 40 min could inhibit the color degradation, improve the oxidation resistance, and prolong the shelf life of kernels.
MiR‐181a‐5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice
Authors: Sun Qiaoyi , Ma Li , Qiao Jing , Wang Xing , Li Jianguo , Wang Yuxi , Tan Ailing , Ye Zihui , Wu Yukang , Xi Jiajie , Kang Jiuhong 
Published: February 2023

AbstractHippocampal neural stem cell (NSC) proliferation is known to decline with age, which is closely linked to learning and memory impairments. In the current study, we found that the expression level of miR‐181a‐5p was decreased in the hippocampal NSCs of aged mice and that exogenous overexpression of miR‐181a‐5p promoted NSC proliferation without affecting NSC differentiation into neurons and astrocytes. The mechanistic study revealed that phosphatase and tensin homolog (PTEN), a negative regulator of the AKT signaling pathway, was the target of miR‐181a‐5p and knockdown of PTEN could rescue the impairment of NSC proliferation caused by low miR‐181a‐5p levels. Moreover, overexpression of miR‐181a‐5p in the dentate gyrus enhanced the proliferation of NSCs and ameliorated learning and memory impairments in aged mice. Taken together, our findings indicated that miR‐181a‐5p played a functional role in NSC proliferation and aging‐related, hippocampus‐dependent learning and memory impairments.
Interleukin‐22 alleviates alcohol‐associated hepatic fibrosis, inhibits autophagy, and suppresses the PI3K/AKT/mTOR pathway in mice
Authors: Meng Yu‐Xi , Zhao Rui , Huo Li‐Juan 
Published: February 2023

AbstractBackgroundAlcohol‐associated hepatic fibrosis is a widespread liver disease with no effective treatment. Recent studies have indicated that interleukin‐22 (IL‐22) can ameliorate alcohol‐associated liver disease. However, the mechanism underlying the role of IL‐22 in alcohol‐associated hepatic fibrosis remains unclear. Therefore, we investigated the effect of IL‐22 in a mouse model of alcohol‐associated hepatic fibrosis and its underlying mechanisms.MethodsAlcohol‐associated hepatic fibrosis was induced by feeding male C57BL/6J mice with a Lieber‐DeCarli liquid diet containing 4% ethyl alcohol for 8 weeks and injecting them with 5% tetrachloromethane (CCl4) intraperitoneally for the last 4 weeks. During the last 4 weeks, IL‐22 was also administered. We investigated the role of IL‐22 in autophagy and the PI3K/AKT/mTOR signaling pathway using a 3‐methyladenine intraperitoneal injection in the mice treated with IL‐22. The effects of IL‐22 on alcohol‐associated hepatic fibrosis, autophagy‐related gene expression, and PI3K/AKT/mTOR activity were assessed using histopathology, biochemical analysis, transmission electron microscopy, quantitative real‐time PCR, immunohistochemistry, and western blotting.ResultsMice treated with ethanol and CCl4 displayed distinct liver injuries, including hepatocyte necrosis, inflammatory cell infiltration, and hepatic fibrosis, which were substantially attenuated by IL‐22 treatment. In addition, we found that IL‐22 regulated the expression of autophagy‐related genes and inhibited the PI3K/AKT/mTOR pathway, as evidenced by the reduction in p‐PI3K, p‐AKT, and p‐mTOR expression after IL‐22 treatment.ConclusionsIL‐22 exerts a marked protective effect against alcohol‐associated hepatic fibrosis. Its effect may be partly related to the alteration of autophagy‐related gene expression and inhibition of the PI3K/AKT/mTOR pathway in the liver.
The significance of the Sikunga Fish Protected Area towards fisheries conservation in the Zambezi River, Namibia
Authors: Simasiku Evans , Hay Clinton 
Published: February 2023

AbstractLarge cichlids of the genera Oreochromis, Tilapia, Serranochromis and Sargochromis are the backbone of the gillnet fishery of the Zambezi River, but Oreochromis spp. is currently over‐exploited and at risk of local extinction. As a result, the Sikunga Fish Protected Area was established in 2012 to restore a decline in fish stocks of the Zambezi River, but its efficiency has never been assessed. The aim of this study was to compare fish assemblages, abundance and mean sizes between a fish protected area (Sikunga FPA) and nonprotected areas; the Sikunga Buffer Zone and the Lisikili Fished Area on the Zambezi River. Monthly gillnet surveys, using commercial gillnets, were conducted from July to December 2020. Overall catch rate (CPUE) by weight of all species differed significantly among the sampling sites (Kruskal–Wallis H‐test, range χ2(2) = −27.95, p = 0.0001). The highest CPUE was recorded at Sikunga Fish Protected Area (2.85 kg/set ± 0.42 (SE)), followed by the Sikunga Buffer Zone (0.93 kg/set ± 0.16 (SE)) and the Lisikili Fished Area (0.61 kg/set ± 0.14 (SE)). Further analyses showed that the mean sizes of O. andersonii, Coptodon rendalli, Serranochromis and macrocephalus were significantly larger at the Sikunga Fish Protected Area than at the Lisikili Fished Area. A particularly interesting observation pertains to a lack of variation in catch rates of Serranochromis macrocephalus and mean sizes of Clarias gariepinus between the protected and nonprotected areas, signifying that fish protected areas can be species‐specific, and not all species in a water body will respond positively to protection. The overall results of this study support the innovation of fish protected areas as a fundamental tool in attaining sustainable management of fishery resources in inland waters of Namibia and other developing countries.
Overall survival comparing laparoscopic to open surgery for right‐sided colon cancer: propensity score inverse probability weighting population study
Authors: Udayasiri Dilshan K. , Hiscock Richard , Jones Ian T. , Skandarajah Anita , Hayes Ian P. 
Published: February 2023

AbstractBackgroundThis retrospective cohort study reports on overall survival and short‐term complications, comparing laparoscopic to open resection for right‐sided colon cancers. It is one of the largest studies in the field with generalizable population‐level results.MethodThis study on right sided colon cancers used prospectively collected administrative data linked to a death registry over 5 years from 2014 to 2018. Exclusion criteria were private patients, patients aged less than 10 years, synchronous and metachronous cancers. Propensity score weighting was used to balance cohorts and Cox proportional hazards regression was used to assess the hazard of death. In addition, logistic regression analysis was used to assess secondary outcomes. For completeness, unweighted data was similarly analysed.ResultsThere were 3603 patients identified for the analysis: 1729 open patients and 1874 laparoscopic patients. Cox proportional hazards regression analysis of the weighted data showed no evidence of a statistically significant effect of laparoscopic surgery compared to open surgery on overall survival for right‐sided colon cancers (HR 0.86, 95% CI 0.71–1.04, P = 0.112). The weighted data showed lower odds of prolonged length of stay, return to theatre and discharge destination other than home in the laparoscopic cohort compared to the open cohort. There was no difference in inpatient mortality. Unweighted results were similar.ConclusionThis study validates the use of laparoscopic surgery for right‐sided colon cancer, showing similar long‐term overall survival and inpatient mortality compared to open surgery. It is superior to open surgery for the short‐term outcomes of LOS, return to theatre and discharge destination other than home.
Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline‐induced pulmonary hypertension
Authors: Teixeira‐Fonseca Jorge Lucas , de Lima Conceição Michael Ramon , Leal‐Silva Polyana , Roman‐Campos Danilo 
Published: February 2023

AbstractAtrial arrhythmias are a hallmark of heart diseases. The antiarrhythmic drug ranolazine with multichannel blocker properties is a promising agent to treat atrial arrhythmias. We therefore used the rat model of monocrotaline‐induced pulmonary‐hypertension to assess whether ranolazine can reduce the incidence of ex vivo atrial arrhythmias in isolated right atrium. Four‐week‐old Wistar rats were injected with 50 mg/kg of monocrotaline, and isolated right atrium function was studied 14 days later. The heart developed right atrium and right ventricular hypertrophy, and the ECG showed an increased P wave duration and QT interval, which are markers of the disease. Moreover, monocrotaline injection caused enhanced chronotropism and faster kinetics of contraction and relaxation in isolated right atrium. Additionally, in a concentration‐dependent manner, ranolazine showed chronotropic and ionotropic effects upon isolated right atrium, with higher potency in the control when compared with experimental model. Using a burst pacing protocol, the isolated right atrium from the monocrotaline‐treated animals was more susceptible to develop arrhythmias, and ranolazine was able to attenuate the phenotype. Thus, we concluded that the rat model of monocrotaline‐induced pulmonary‐hypertension develops right atrium remodelling, which increased the susceptibility to present ex vivo atrial arrhythmias, and the antiarrhythmic drug ranolazine ameliorated the phenotype.