bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications of predator species richness in terms of zoonotic spillover transmission of filoviral hemorrhagic fevers in Africa
Authors: Chang Taehee , Cho Sung-il , Min Kyung-Duk
Published: February 2023

Previous studies found that higher species richness of predators could reduce spillover risks of rodent-borne diseases. However, the effects on bat-borne diseases remains to be investigated. To this regard, we evaluated associations between predator species richness and the spillover events ofEbolavirusandMarburgvirus, the highly pathogenic bat-borne diseases in Africa. Stacked species distribution model approach was used to estimate predator species richness and Logistic regression analyses that considered spatiotemporal autocorrelations were conducted. The results showed that the third quartile (OR = 0.02, 95% CI 0.00–0.84) and fourth quartile (0.07, 0.00–0.42) of species richness of Strigiformes and the third quartile (0.15, CI 0.01–0.73) and fourth quartile (0.53, 0.03–0.85) of Colubridae showed significantly lower risks of spillover transmission ofEbolavirus. However, no significant association was found between predator species richness andMarburgvirusspillover. The results support a possible effect of predator species diversity on spillover suppression.
CD4+ and CD8+ T cell and antibody correlates of protection against Delta vaccine breakthrough infection: A nested case-control study within the PITCH study
Authors: Neale Isabel , Ali Mohammad , Kronsteiner Barbara , Longet Stephanie , Abraham Priyanka , Deeks Alexandra S. , Brown Anthony , Moore Shona C. , Stafford Lizzie , Dobson Susan L. , Plowright Megan , Newman Thomas A.H. , Wu Mary Y ,   Crick COVID Immunity Pipeline, Carr Edward J , Beale Rupert , Otter Ashley D , Hopkins Susan , Hall Victoria , Tomic Adriana , Payne Rebecca P. , Barnes Eleanor , Richter Alex , Duncan Christopher J.A. , Turtle Lance , de Silva Thushan I. , Carroll Miles , Lambe Teresa , Klenerman Paul , Dunachie Susanna
Published: February 2023

T cell correlates of protection against SARS-CoV-2 infection after vaccination (‘vaccine breakthrough’) are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. We studied 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK study, including 32 cases (with SARS-CoV-2 positive testing after two vaccine doses during the Delta-dominant era) and 247 controls (no positive test nor anti-nucleocapsid seroconversion during this period). 28 days after second vaccination, before all breakthroughs occurred, cases had lower ancestral S- and RBD-specific immunoglobulin G titres and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls. In a subset of matched cases and controls, cases had lower CD4+ and CD8+ IFNγ and tumour necrosis factor responses to Delta S peptides with reduced CD8+ responses to Delta versus ancestral peptides compared with controls. Our findings support a protective role for T cells against Delta breakthrough infection.
Parental education and income are linked to offspring cortical brain structure and psychopathology at 9-11 years
Authors: Norbom Linn B. , Rokicki Jaroslav , Eilertsen Espen M. , Wiker Thea , Hanson Jamie , Dahl Andreas , Alnæs Dag , Fernández-Cabello Sara , Beck Dani , Agartz Ingrid , Andreassen Ole A. , Westlye Lars T. , Tamnes Christian K.
Published: February 2023

Background

A child’s socioeconomic environment can shape central aspects of their life, including vulnerability to mental disorders. Negative environmental influences in youth may interfere with the extensive and dynamic brain development occurring at this time. Indeed, there are numerous yet diverging reports of associations between parental socioeconomic status (SES) and child cortical brain morphometry. Most of these studies have used single metric- or unimodal analyses of standard cortical morphometry that downplay the probable scenario where numerous biological pathwaysin sumaccount for SES-related cortical differences in youth.

Methods

To comprehensively capture such variability, using data from 9758 children aged 8.9-11.1 years from the ABCD Study®, we employed linked independent component analysis (LICA) and fused vertex-wise cortical thickness, surface area, curvature and grey-/white-matter contrast (GWC). LICA revealed 70 uni- and multimodal components. We then assessed the linear relationships between parental education, parental income and each of the cortical components, controlling for age, sex, genetic ancestry, and family relatedness. We also assessed whether cortical structure moderated the negative relationships between parental SES and child general psychopathology.

Results

Parental education and income were both associated with larger surface area and higher GWC globally, in addition to local increases in surface area and to a lesser extent bidirectional GWC and cortical thickness patterns. The negative relation between parental income and child psychopathology were attenuated in children with a multimodal pattern of larger frontal- and smaller occipital surface area, and lower medial occipital thickness and GWC.

Conclusion

Structural brain MRI is sensitive to SES diversity in childhood, with GWC emerging as a particularly relevant marker together with surface area. In low-income families, having a more developed cortex across MRI metrics, appears beneficial for mental health.
Rational Prediction of PROTAC-compatible Protein-Protein Interfaces by Molecular Docking
Authors: Pereira Gilberto P. , Jiménez-García Brian , Pellarin Riccardo , Launay Guillaume , Wu Sangwook , Martin Juliette , Souza Paulo C. T.
Published: February 2023

Proteolysis targeting chimeras (PROTACS) are heterobifunctional ligands that mediate the interaction between a protein target and an E3 ligase, resulting in a ternary complex whose interaction with the ubiquitination machinery leads to target degradation. This technology is emerging as an exciting new avenue for therapeutic development, with several PROTACS currently undergoing clinical trials targeting cancer. Here, we describe a general and computationally efficient methodology combining restraint-based docking, energy-based rescoring, and a filter based on minimal solvent-accessible surface distance to produce PROTAC-compatible PPIs suitable for when there is noa prioriknown PROTAC ligand. In a benchmark employing a manually curated dataset of 13 ternary complex crystals, we achieved accuracy of 92% when starting from bound structures, and 77% when starting from unbound structures, respectively. Our method only requires that the ligand-bound structures of the monomeric forms of the E3 ligase and target proteins be given to run, making it general, accurate and highly efficient, with the ability to impact early stage PROTAC-based drug design campaigns where no structural information about the ternary complex structure is available.
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

Memory 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

Aspects 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.

Highlights

KCl-evoked glutamate overflow was similar under urethane and isoflurane anesthesia

Glutamate clearance parameters were similar under both anesthesias in the cortex and hippocampus but not the thalamus

Glutamate 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

In 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

Neuronal 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

The 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.
Formation of ibrutinib solvates: so similar, yet so different
Authors: Jirát Jan , Rohlíček Jan , Kaminský Jakub , Jirkal Tomáš , Ridvan Luděk , Skořepová Eliška , Zvoníček Vít , Dušek Michal , Šoóš Miroslav
Published: February 2023

The transformation processes of non-solvated ibrutinib into a series of halogenated benzene solvates are explored in detail here. The transformation was studied in real time by X-ray powder diffraction in a glass capillary. Crystal structures of chlorobenzene, bromobenzene and iodobenzene solvates are isostructural, whereas the structure of fluorobenzene solvate is different. Four different mechanisms for transformation were discovered despite the similarity in the chemical nature of the solvents and crystal structures of the solvates formed. These mechanisms include direct transformations and transformations with either a crystalline or an amorphous intermediate phase. The binding preference of each solvate in the crystal structure of the solvates was examined in competitive slurry experiments and further confirmed by interaction strength calculations. Overall, the presented system and online X-ray powder diffraction measurement provide unique insights into the formation of solvates.
Synthesis, crystal structure and thermal properties of di-μ-iodido-bis[bis(2-chloropyrazine-κN)copper(I)]
Authors: Näther Christian , Jess Inke
Published: February 2023

Reaction of copper(I) iodide in pure 2-chloropyrazine leads to the formation of a few crystals of the title compound, [Cu2I2(C4H3ClN2)4] or (CuI)2(2-chloropyrazine)4, which was characterized by single-crystal X-ray diffraction. In its crystal structure, the CuI cations are each tetrahedrally coordinated by two iodide anions and two 2-chloropyrazine ligands and are linked into binuclear complexes consisting of (CuI)2 rings located on centers of inversion. PXRD investigations of a few crystals obtained from the suspension indicate that the title compound is contaminated with a small amount of the 2-chloropyrazine-deficient compound CuI(2-chloropyrazine) already reported in the literature. PXRD investigations prove that the title compound immediately decomposes at room temperature into CuI(2-chloropyrazine) and this might be the reason why no pure samples can be obtained. TDA–TG–MS investigations shows two mass losses, the first of which corresponds to the formation of CuI(2-chloropyrazine), whereas in the second mass loss CuI is formed.
(E)-N-Phenyl-N-(phenylcarbamoyl)-3-[propyl(trimethylsilyl)amino]acrylamide chloroform hemisolvate
Authors: Herbig Marcus , Böhme Uwe
Published: February 2023

The title compound, C22H29N3O2Si·0.5CHCl3, crystallizes in the the triclinic space group P\overline{1} with two host molecules and one chloroform molecule in the asymmetric unit. The core of the molecule consists of a urea unit bound to a 3-amino-acryloyl group. These units are almost planar in both molecules [average deviation from plane of 0.05 (6) Å in molecule A and 0.04 (5) Å in molecule B]. The main difference between molecules A and B involves the dihedral angles of the phenyl groups. One phenyl ring makes dihedral angles of 71.14 (6)° (molecule A) and 82.81 (7)° (molecule B) with respect to the core (C4N3O2) of the molecule [14.56 (9)° (molecule A) and 5.7 (1)° (molecule B) for the other phenyl ring]. Another prominent feature is the intramolecular N—H...O hydrogen bond present in both crystallographically independent molecules.
15,15-Diphenyl-2,3,4,5,6,8,9,11,12-octahydroimidazo[2,1-h][1,4,12]trioxa[7]thia[9]azacyclotetradecin-14(15H)-one
Authors: Guerrab Walid , El Moutaouakil Ala Allah Abderrazzak , Alsubari Abdulsalam , Mague Joel T , Ramli Youssef
Published: February 2023

The title molecule, C23H26N2O4S, adopts a cup-shaped conformation. In the crystal, layers lying parallel to the ab plane are formed by C—H...O hydrogen bonds and C—H...π(ring) interactions. The layers stack along the c-axis direction through normal van der Waals interactions.
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

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.
Bleached broilers and divine fowls: The ritual economy of chickens in a South Indian city
Authors: Doron Assa
Published: February 2023

Commercial poultry operations are booming as demand for chicken soars in 21st‐century India. The industry relies on the models familiar from industrial countries: birds pumped with growth hormones and antibiotics designed to ensure rapid, standardized egg production and broiler meat. Nevertheless, during my fieldwork in India, locals insisted that broiler chickens were rarely used for ritual purposes. They explained that the gods were far more discerning and should only be offered the ‘country chicken’ (Natu kodi). The distinctive appearance of these ‘rural’ birds was seen to make them appropriate for ritual sacrifices, with transformative potential. Even urban dwellers seemed to prefer these much costlier indigenous birds – untouched by the homogenizing logic of industrial livestock production – especially for rituals. As I show in this essay, the ritual economy of chickens illustrates the process of ‘metabolic’ transformations, toxic entanglements and more‐than‐human encounters, as much as it reveals that of mutualism, with its vital and varied meanings tied to social relations and ecological sensibilities.
Intervention to address cardiovascular risk following hypertensive pregnancy
Authors: Magee L. A. , von Dadelszen P.
Published: February 2023

Linked article: This is a mini commentary on Hauspurg et al., pp. 715–726 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17381.
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

To 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 Application

Blanching 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

Hippocampal 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

Background

Alcohol‐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.

Methods

Alcohol‐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.

Results

Mice 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.

Conclusions

IL‐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

Large 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

Background

This 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.

Method

This 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.

Results

There 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.

Conclusion

This 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.
Nursery outbreak caused by enteroaggregative Escherichia coli serogroup O111:H21
Authors: Tré‐Hardy Marie , De Rauw Klara , Blairon Laurent , Simon Anne , Piérard Denis
Published: February 2023

This study describes, for the first time, the occurrence of an epidemic of enteroaggregative Escherichia coli (EAEC) O111:H21 in a Belgian nursery and describes a practical approach concerning its management. Few data exist in the literature on this type of outbreak. Clinical and microbiological investigations were needed to find a link between the cases and identify the causative agent. The microbiological procedure followed was first based on conventional analyses: isolation using selective cultures, identification by MALDI‐TOF MS, antibiogram, determination of the serogroup by agglutination, then whole genome sequencing. A total of 7/21 children were infected with this pathogen. Four cases could be confirmed by a molecular technique, wgMLST, as belonging to the same bacterial clone. The action plan put in place focused on symptomatic case eviction, strict general hygiene precaution as well as specific cleaning and disinfection measures. The epidemic did last only a few days. It appears important, in the context of an epidemic, that clinical laboratories standardize their practice by equipping themselves with molecular techniques such as a multiplex which does not focus only on the serotype O157:H7 and which make it possible to distinguish the different pathotypes of E. coli by targeting several virulence genes (stx, aggR…). However, cost/effectiveness studies are awaited to confirm the interest of a systematic search by molecular method for the pathogen involved in a suspected outbreak occurring in a nursery.
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

Atrial 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.
Indole‐3‐carbinol induces apoptosis in AGS cancer cells via mitochondrial pathway
Authors: Singh Alka Ashok , Jo Sung‐Han , Kiddane Anley Teferra , Niyonizigiye Irvine , Kim Gun‐Do
Published: February 2023

Indole‐3‐carbinol is produced from the cruciferous vegetables and broadly investigated for their various biological effects in in‐vitro and in‐vivo aspects. However, the anticancer activity of I3C and its molecular mechanisms have not been investigated in human adeno gastro carcinoma (AGS) cells. In our study of AGS cells, nuclear condensation was observed by 4′,6‐diamidino‐2‐phenylindole (DAPI) staining, cell death was confirmed by a cell viability assay, and fragmented DNA was observed at the IC50 dose by a DNA fragmentation assay. Apoptosis was evaluated by the qPCR technique. Treatment of the AGS cells with I3C at different concentrations has drastically decreased cell proliferation and differentiation. By releasing cytochrome‐c from mitochondria in the intrinsic pathway, I3C prevents the multiplication of AGS cells and initiates apoptosis. The WST‐1 assay result showed that I3C treatment against AGS cells had considerably reduced the viability of the cells. Furthermore, RT‐qPCR showed the fold change among the expressed proteins compared with reference gene β‐actin. Molecular docking revealed that I3C showed a strong binding affinity for the apoptotic protein 3DCY. The results show the caspase group of proteins contribute to the core of apoptotic machinery. I3C and its metabolites target a variety of components of cell‐cycle control via distinct signaling pathways in light of the rapid development of tumors and oncogenesis. The translational significance of I3C and its metabolites in cancer is highlighted by their wide range of antitumor activity and low toxicity. Furthermore, the novel prodrug I3C, which has overlapping underlying mechanisms, could encourage new strategies to decrease oncogenesis.
A review of clostridial diseases in rhinoceroses
Authors: Angwenyi Shaleen Kemunto Sarange , Hassell James , Miller Michele Ann , Mutinda Mathew , Vitali Francesca , Murray Suzan
Published: February 2023

Although rhinoceros conservation efforts are focused on anti‐poaching and combating wildlife trade, infectious diseases are an increasing threat to both free‐ranging and captive rhinoceros populations. Among these, clostridial infections with Clostridium perfringens, Paeniclostridium sordellii, and Clostridium novyi have caused acute disease in black and white rhinoceroses, characterized by a high mortality rate within very brief time spans. The acute nature, as well as limited knowledge of epidemiology, diagnosis, and management, make clostridial diseases an important threat to rhinoceros conservation. This article reviews historical cases of clostridial disease in rhinoceros with the aim of formulating a clearer understanding of the disease's epidemiology and using this information to make recommendations for its management in free‐ranging rhinoceroses. Acute colic and sudden death in rhinoceroses, together with necropsy findings of segmental hemorrhagic enteritis, should lead towards a tentative diagnosis of enteric clostridial disease, although detection and identification of specific toxins are required for a definitive diagnosis. Our findings indicate the need for further research into clostridial disease dynamics in wildlife species and provide the basis for this research in rhinoceroses.
Differences between kidney retransplant recipients as identified by machine learning consensus clustering
Authors: Thongprayoon Charat , Vaitla Pradeep , Jadlowiec Caroline C. , Mao Shennen A. , Mao Michael A. , Acharya Prakrati C. , Leeaphorn Napat , Kaewput Wisit , Pattharanitima Pattharawin , Tangpanithandee Supawit , Krisanapan Pajaree , Nissaisorakarn Pitchaphon , Cooper Matthew , Cheungpasitporn Wisit
Published: February 2023

Background

Our study aimed to characterize kidney retransplant recipients using an unsupervised machine‐learning approach.

Methods

We performed consensus cluster analysis based on the recipient‐, donor‐, and transplant‐related characteristics in 17 443 kidney retransplant recipients in the OPTN/UNOS database from 2010 to 2019. We identified each cluster's key characteristics using the standardized mean difference of >.3. We compared the posttransplant outcomes, including death‐censored graft failure and patient death among the assigned clusters

Results

Consensus cluster analysis identified three distinct clusters of kidney retransplant recipients. Cluster 1 recipients were predominantly white and were less sensitized. They were most likely to receive a living donor kidney transplant and more likely to be preemptive (30%) or need ≤1 year of dialysis (32%). In contrast, cluster 2 recipients were the most sensitized (median PRA 95%). They were more likely to have been on dialysis >1 year, and receive a nationally allocated, low HLA mismatch, standard KDPI deceased donor kidney. Recipients in cluster 3 were more likely to be minorities (37% Black; 15% Hispanic). They were moderately sensitized with a median PRA of 87% and were also most likely to have been on dialysis >1 year. They received locally allocated high HLA mismatch kidneys from standard KDPI deceased donors. Thymoglobulin was the most commonly used induction agent for all three clusters. Cluster 1 had the most favorable patient and graft survival, while cluster 3 had the worst patient and graft survival.

Conclusion

The use of an unsupervised machine learning approach characterized kidney retransplant recipients into three clinically distinct clusters with differing posttransplant outcomes. Recipients with moderate allosensitization, such as those represented in cluster 3, are perhaps more disadvantaged in the kidney retransplantation process. Potential opportunities for improvement specific to these re‐transplant recipients include working to improve opportunities to improve access to living donor kidney transplantation, living donor paired exchange and identifying strategies for better HLA matching.
The effect of insect food availability on songbird reproductive success and chick body condition: Evidence from a systematic review and meta‐analysis
Authors: Grames Eliza M. , Montgomery Graham A. , Youngflesh Casey , Tingley Morgan W. , Elphick Chris S.
Published: February 2023

Reports of declines in abundance and biomass of insects and other invertebrates from around the world have raised concerns about food limitation that could have profound impacts for insectivorous species. Food availability can clearly affect species; however, there is considerable variation among studies in whether this effect is evident, and thus a lack of clarity over the generality of the relationship. To understand how decreased food availability due to invertebrate declines will affect bird populations, we conducted a systematic review and used meta‐analytic structural equation modelling, which allowed us to treat our core variables of interest as latent variables estimated by the diverse ways in which researchers measure fecundity and chick body condition. We found a moderate positive effect of food availability on chick body condition and a strong positive effect on reproductive success. We also found a negative relationship between chick body condition and reproductive success. Our results demonstrate that food is generally a limiting factor for breeding songbirds. Our analysis also provides evidence for a consistent trade‐off between chick body condition and reproductive success, demonstrating the complexity of trophic dynamics important for these vital rates.
Distinct genetic basis of common epilepsies and structural magnetic resonance imaging measures
Authors: Stevelink Remi , Koeleman Bobby P. C. , Sisodiya Sanjay M. ,   International League Against Epilepsy Consortium on Complex Epilepsies
Published: February 2023

Focal and generalized epilepsies are associated with robust differences in magnetic resonance imaging (MRI) measures of subcortical structures, gray matter, and white matter. However, it is unknown whether such structural brain differences reflect the cause or consequence of epilepsy or its treatment. Analyses of common genetic variants underlying both common epilepsy risk and variability in structural brain measures can give further insights, as such inherited variants are not influenced by disease or treatment. Here, we performed genetic correlation analyses using data from the largest genome‐wide association study (GWAS) on common epilepsy (n = 27 559 cases and 42 436 controls) and GWASs on MRI measures of white (n = 33 292) or gray matter (n = 51 665). We did not detect any significant genetic correlation between any type of common epilepsy and any of 280 measures of gray matter, white matter, or subcortical structures. These results suggest that there are distinct genetic bases underlying risk of common epilepsy and for structural brain measures. This would imply that the genetic basis of normal structural brain variation is unrelated to that of common epilepsy. Structural changes in epilepsy could rather be the consequence of epilepsy, its comorbidities, or its treatment, offering a cumulative record of disease.