bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibacterial Activity and Action Mechanism of Synthetic Interleukin‐8 Derived Peptides Against Flavobacterium psychrophilum
Authors: Santana Paula A. , Tamayo Laura , Stambuk Felipe , Aguilar Luis Felipe , Cortés Marcos , Guzmán Fanny , Forero Juan Carlos , Romero María Soledad , Álvarez Claudio A.
Published: December 2024

In Chile, Atlantic salmon and rainbow trout face significant production challenges due to the presence of Flavobacterium psychrophilum, which generates severe disease issues and economic losses. To address this, the salmon industry relies on vaccines and antibiotics, the latter raising concerns about bacterial resistance. For that reason, our study explores an alternative strategy for controlling F. psychrophilum infections based on host defence peptides. We previously identified and characterised IL‐8‐derived salmonid peptides (ssIL‐8α and omIL‐8α) with potential antimicrobial properties. In the current study, we further investigated the antibacterial activity and mechanism of action of these peptides against F. psychrophilum. First, we demonstrated the antibacterial activity of ssIL‐8α and omIL‐8α synthetic peptides. Then we evaluated the effects of these peptides on membrane fluidity and localisation on bacterial cells by fluorescence microscopy as well as its impact on bacterial morphology and ultrastructure by electron microscopy. The results indicate that the ssIL‐8α at 30 μM exhibits superior efficacy in inhibiting the growth of F. psychrophilum. Also, both ssIL‐8α and omIL‐8α can bind to pathogen membrane, but ssIL‐8α exhibits a higher binding capacity compared to omIL‐8α against F. psychrophilum. omIL‐8α exhibited the ability to induce early membrane alterations within 15 min, at concentrations of 15 or 30 μM. The SEM and TEM micrographs showed membrane disruption of the bacteria after incubation with ssIL‐8α or omIL‐8α. However, the damage was more pronounced in the ssIL‐8α treatment, as evidenced by a complete detachment of the outer membrane after a 20‐min exposure of F. psychrophilum. This study reveals that these peptides significantly alter bacterial membrane morphology, leading to bacterial death, highlighting their potential as alternative treatments in flavobacterial disease control. This work contributes to understanding host defence peptides' role in combating bacterial infections and reducing antibiotic resistance in aquaculture.
Venous thromboembolism in patients aged ≥90 years: Trends in clinical features, treatment, and outcomes—RIETE registry
Authors: Lafaie Ludovic , Poenou Géraldine , Hanon Olivier , Otálora Sonia , Jiménez Luciano López , Ballaz Aitor , Soler Silvia , Fernández Manuel Jesús Núñez , Bertoletti Laurent , Monreal Manuel ,   the RIETE investigators
Published: December 2024

Background

Data on patients aged 90 or older are rare. This study aims to describe clinical characteristics, treatment strategies, and clinical outcomes (rates of VTE recurrence, major bleeding, and mortality), during the first 3 months of anticoagulant treatment for VTE, depending on the treatment period.

Methods

We analyzed data from RIETE, an ongoing global observational registry of patients with objectively confirmed acute VTE, grouped in 5‐year intervals (2004–2008, 2009–2013, 2014–2018, and 2019–2023).

Results

Among 3477 patients aged 90 or older, clinical characteristics have changed over time (less heart failure, more dementia), with an increase in PE diagnoses from 57% in 2004–2008 to 69% in 2019–2023 (p‐trends <0.001), but of lower severity. For long‐term therapy, there was an increase in patients receiving DOACs (p‐trends <0.001), with a decrease in patients on VKAs (p‐trends <0.001). Mortality and fatal PE respectively showed a temporal trend: 19% and 4% in 2004–2008 to 15% (p‐trends 0.026) and 2% (p‐trends 0.002) in 2019–2023. In multivariable analyses, fatal PE declined from 2004 to 2023 (HR: 0.91; 95% CI: 0.87–0.96). Compared with VKAs, receiving LMWH during the first 3 months of anticoagulation was associated with a higher risk of major bleeding (HR: 1.91; 95% CI: 1.16–3.14) and death (HR: 2.20; 95% CI: 1.71–2.82). The effect seems to be the opposite for DOACs (HR: 0.50; 95% CI: 0.20–1.30 for major bleeding; HR: 0.86; 95% CI: 0.57–1.28 for all‐cause death).

Conclusions

Fatal PE declined from 2004 to 2023, despite an increase in the diagnosis of PE. Since the arrival of DOACs, there seems to be better management of the therapeutic and diagnostic aspects of VTE in this population, underlining the need for further research on patients aged 90 or older.
Lower density of calretinin‐immunopositive neurons in the putamen of subjects with schizophrenia
Authors: Kelmer Paz , Hoppa Paulina , Frank Erzsébet , Tyler Teadora , Adorjan Istvan
Published: December 2024

Schizophrenia (SCH) is a chronic and serious mental illness which puts an enormous burden on the individual, families, and society. It is well established that altered dopamine signaling and excitatory‐inhibitory imbalance contributes to the symptoms of schizophrenia. Recent neuroimaging and histological studies suggest that the striatum is a key area involved in SCH, however, our knowledge of how specific cell neuronal subtypes of certain subcortical structures may be impaired is incomplete. To this date, no detailed investigation of the putamen has ever been published regarding neuroanatomical changes in SCH. Here we tested whether the density of calretinin immunopositive (CR+) neurons and DARPP32+ neurons is altered in the putamen of patients with SCH. We used immunohistochemistry to reveal CR+ and DARPP32+ neurons in six samples from patients with SCH and six age‐ and gender‐matched control subjects. In line with previous studies, we detected small, medium, and large CR+ neurons. The density of small CR+ neurons was significantly lower in SCH (p = 0.0076). Medium and large CR+ and DARPP32+ neuronal density was not significantly different between groups. The present study substantiates previous results showing significantly lower density of small CR+ interneurons in the caudate nucleus in samples from patients with schizophrenia, highlighting the involvement of the striatum in the disorder. Our results warrant further studies focusing on the role of CR+ interneurons in the regulation of information processing in the fronto‐striatal networks, evidently key structures in schizophrenia.
Chronic silencing of subsets of cortical layer 5 pyramidal neurons has a long‐term influence on the laminar distribution of parvalbumin interneurons and the perineuronal nets
Authors: Szabó Florina P. , Sigutova Veronika , Schneider Anna M. , Hoerder‐Suabedissen Anna , Molnár Zoltán
Published: December 2024

Neural networks are established throughout cortical development, which require the right ratios of glutamatergic and GABAergic neurons. Developmental disturbances in pyramidal neuron number and function can impede the development of GABAergic neurons, which can have long‐lasting consequences on inhibitory networks. However, the role of deep‐layer pyramidal neurons in instructing the development and distribution of GABAergic neurons is still unclear. To unravel the role of deep‐layer pyramidal neuron activity in orchestrating the spatial and laminar distribution of parvalbumin neurons, we selectively manipulated subsets of layer 5 projection neurons. By deleting Snap25 selectively from Rbp4‐Cre + pyramidal neurons, we abolished regulated vesicle release from subsets of cortical layer 5 projection neurons. Our findings revealed that chronically silencing subsets of layer 5 projection neurons did not change the number and distribution of parvalbumin neurons in the developing brain. However, it did have a long‐term impact on the laminar distribution of parvalbumin neurons and their perineuronal nets in the adult primary motor and somatosensory cortices. The laminar positioning of parvalbumin neurons was altered in layer 4 of the primary somatosensory cortex in the adult Snap25 cKO mice. We discovered that the absence of layer 5 activity only had a transient effect on the soma morphology of striatal PV neurons during the third week of postnatal development. We also showed that the relationship between parvalbumin neurons and the perineuronal nets varied across different cortical layers and regions; therefore, their relationship is far more complex than previously described. The current study will help us better understand the bidirectional interaction between deep‐layer pyramidal cells and GABAergic neurons, as well as the long‐term impact of interrupting pyramidal neuron activity on inhibitory network formation.
Insights into Argentavis magnificens (Aves, Teratornithidae) lifestyle based on neuroanatomy
Authors: Etchegorry Milagros Torres , Degrange Federico J.
Published: December 2024

Teratornithidae is an extinct bird family, likely related to Cathartidae, known exclusively from the Americas. They were once thought to be scavengers, but recent theories suggest they were opportunistic or piscivorous birds capable of swallowing prey whole. The most notable species, Argentavis magnificens, had a wingspan of 6 to 8 m and weighed 70 to 80 kg. In order to infer paleobiological aspects of this bird, its endocast (as a proxy for brain morphology), reconstructed from computed tomography scans of the holotype skull, is here described and compared to that of other bird species of zoophagous feeding habits with different flight styles. The brain of Argentavis presents a general appearance similar to that of Cathartidae, being dorsoventrally flattened and anteroposteriorly elongated, with small optic lobes in relation to the total encephalic surface. The estimated volume of the bulbi olfactorii is very similar to that of the Andean Condor Vultur gryphus. The main difference observed with Cathartidae is the marked development of the eminentiae sagittales present in Argentavis (structures closely related to the perception of visual information), which are more similar to those of the Accipitriformes and Falconiformes analyzed. The results obtained here suggest that Argentavis was a scavenger or even maybe a kleptoparasitic bird, relying more on vision than on smell (similar to that observed in the Andean Condor). Furthermore, the inner ear and flocculi exhibit characteristics similar to birds without acrobatic flight, indicating that Argentavis had a soaring flight and inhabited open areas without much vegetation.
Corticosteroid‐responsive narcolepsy type II after COVID‐19: A relevant differential diagnosis of post‐COVID syndrome (a case report)
Authors: Künstler Erika C. S. , Menrad Solveig , Utech Isabelle , Finke Kathrin , Rupprecht Sven
Published: December 2024

Excessive daytime sleepiness is a possible symptom of post‐COVID syndrome and is also the cardinal symptom of narcolepsy, a rare life‐long sleep disorder with a possible autoimmune background. Recent reports indicate that COVID‐19 infection may trigger narcolepsy. However, it remains unclear how best to identify and treat such cases. A 25‐year‐old male developed daytime sleepiness after COVID‐19 infection. A diagnosis of narcolepsy type II was made based on pathologically shortened sleep latencies in polysomnography and multiple sleep latency tests (MSLT) together with several sleep‐onset REM‐sleep periods (SOREMs). Pupillography and neuropsychological testing revealed reduced alertness levels. Hypocretin levels in the cerebrospinal fluid were borderline. Based on the postulated autoimmune background of narcolepsy, we performed an intravenous high‐dose corticosteroid pulse therapy with methylprednisolone. Narcoleptic symptoms immediately and consistently remitted after the corticosteroid pulse. Follow‐up after 4 months revealed normalisation of sleep latencies, no further SOREMs in the MSLT, and increased alertness in pupillography and neurocognitive testing. No further wakefulness promoting drug therapy was required. Narcolepsy should be considered in the differential diagnosis of post‐COVID syndrome with leading symptoms of daytime sleepiness. Furthermore, immunosuppressive therapy may offer a treatment option in managing an otherwise lifelong disorder in select cases.
Assessing the psychometric properties of the Biphasic Sleep Scale (BiSS): A novel 16‐item self‐report measure
Authors: Jahrami Haitham , Trabelsi Khaled , Pakpour Amir H. , Ammar Achraf , Husain Waqar , Pandi‐Perumal Seithikurippu R. , Saif Zahra , Seeman Mary V. , Vitiello Michael V.
Published: December 2024

Biphasic sleep, characterized by nighttime sleep plus daytime napping, has demonstrated some cognitive, health and performance impacts when compared with consolidated monophasic sleep. This motivated the development and validation of the Biphasic Sleep Scale, reported in this paper. Scale development involved a literature review, expert input and individual interviews. The 16‐item Biphasic Sleep Scale was then administered to an international online sample (n = 6965) alongside well‐established validated sleep scales. To ensure a robust evaluation of the Biphasic Sleep Scale, the sample was divided into two parts: with 15% (n = 1000) of the participants allocated to the exploratory analytic phase; and the remaining 85% (n = 5965) reserved for confirmatory analyses. Psychometric evaluation included both exploratory and confirmatory factor analysis, reliability analysis, correlations, network analysis, and item response theory. Exploratory factor analysis indicated a three‐factor structure assessing daytime napping as to likelihood, consequences and effect on nighttime sleep. Confirmatory factor analysis largely confirmed this model with no sex invariance. The three‐factor structure showed adequate fit. The Biphasic Sleep Scale demonstrated good internal consistency (α = 0.88, Ω = 0.89). Network analysis revealed varying centrality and connectivity of items. Item response theory found items covering a range of biphasic sleep levels. Significant positive correlations with sleep criteria provided evidence for convergent validity. Further testing is warranted to confirm the factor structure, refine model parsimony, and establish clinical utility. With additional validation, it is hoped that the Biphasic Sleep Scale will become a widely utilized tool.
Interaction rewiring can buffer the reduction of long‐distance dispersal of seeds when large birds go extinct: an allometric perspective
Authors: Borah Binod , Beckman Noelle G.
Published: December 2024

The loss of large frugivorous birds can impact their plant partners through loss of ecological services, like long‐distance dispersal of seeds. Yet, interaction rewiring, or the redistribution of interactions among remaining bird species, might help counteract the loss of long‐distance dispersal from large bird extinctions. Here, we tested if rewiring could mitigate loss of long‐distance dispersal and whether its effectiveness differed among plants with small and large fruits at different scales. We analyzed interaction data from eight Andean bird–plant seed dispersal networks, simulated extinction of large birds, allowed for lost interactions to rewire based on previous observed interactions, trait‐matching between birds and plants, and similarity in body sizes among birds (trait‐resemblance), and related changes in long‐distance dispersal to fruit‐size ratios. At the local scale, reduction in long‐distance dispersal varied among individual networks depending on whether rewiring occurred or not and the type of rewiring. At the regional scale, after aggregating results across local networks, reduction in long‐distance dispersal was between 20 and 40% for relatively small‐fruited plants (size ratio ≤ 0.25) and between 40 and 80% for relatively large‐fruited plants (size ratio ≥ 0.75) without interaction rewiring. However, with rewiring, reduction in long‐distance dispersal of smaller‐fruited plants was limited to 4% and between 4 and 10% for larger‐fruited plants. Thus, interaction rewiring can buffer losses in ecological functions, such as long‐distance dispersal, in response to large bird extinction, although relatively large‐fruited plants remain more vulnerable than smaller‐fruited plants.
Do green finance and energy prices unlock environmental sustainability in Pakistan? Fresh evidence from RALS‐EG cointegration
Authors: Ali Mumtaz , Igunnu Peter Oluwasegun , Tursoy Turgut
Published: December 2024

Even in the face of daunting challenges like climate change in Pakistan, every small step towards conservation and sustainability is a beacon of hope for a brighter, environmental quality. Thus, this study assesses the effect of green financing, economic growth, human capital, oil price, gas price and technological innovation on Pakistan's carbon dioxide emissions. The Residual Augmented Least Square‐Engle and Granger (RLAS‐EG) cointegration is performed to evaluate the effective long‐term association among variables and the Autoregressive Distributed Lag (ARDL) model to assess the coefficients. The results indicate that green finance, human capital and oil prices decrease carbon emissions in both the short and long term. Economic growth and increases in gas prices contribute to long‐term effects, whereas economic expansion decreases carbon emissions in the near term. The outcomes suggest endorsing policies that facilitate sustainable economic growth, enhance the uptake of environmentally friendly investments, foster technical advancements and bolster resilience against catastrophic events as measures to address climate change and mitigate CO2 emissions in Pakistan.
The E3 ubiquitin ligase TaGW2 facilitates TaSnRK1γ and TaVPS24 degradation to enhance stripe rust susceptibility in wheat
Authors: Li Shumin , Li Tian , Zhang Peiyin , Wang Xuemin , Feng Wenxuan , Zhang Yifang , Chen Bin , Liu Yuling , Zhan Gangming , Hao Chenyang , Zhang Xueyong , Kang Zhensheng , Mao Hude
Published: December 2024

Wheat stripe rust, caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst), threatens global wheat production, and therefore discovering genes involved in stripe rust susceptibility is essential for balancing yield with disease resistance in sustainable breeding strategies. Although TaGW2 is well known to negatively regulate wheat kernel size and weight, its role in stress response remains unclear. Here, we found that TaGW2 transcription levels increased following inoculation with Pst or treatment with flg22 or chitin. TaGW2 knockdown lines showed enhanced resistance to multiple Pst races, while TaGW2 overexpression reduced host defence response, promoted Pst growth and development and increased wheat susceptibility to Pst. Additionally, TaGW2 could mediate the ubiquitination and degradation of both TaSnRK1γ and TaVPS24 via the 26S proteasome pathway. Silencing TaSnRK1γ or TaVPS24 in wheat increased sensitivity to Pst, whereas overexpressing either gene enhanced wheat defence response, indicating that TaSnRK1γ and TaVPS24 act as positive regulators of Pst resistance. This study reveals a previously unrecognized mechanism inhibiting plant immunity to Pst through TaGW2‐mediated ubiquitination and degradation of TaSnRK1γ and TaVPS24. This work also provides crucial genetic resources for breeding high‐yield, stripe rust‐resistant wheat varieties.
Early flowering enhances performance among conspecifics
Authors: Moreno‐Colom P. , Montesinos‐Navarro A.
Published: December 2024

Timing plays a crucial role in plant survival as it determines the environmental conditions during which each phenophase develops. In Mediterranean regions, with high temperatures and low precipitation during summer, the timing of flowering may impact plant performance. Different species avoid harsh abiotic conditions by flowering weeks or months earlier than others. On a shorter time scale, conspecifics that flower just a few days earlier may also gain biotic advantages, such as reduced competition for nutrients or pollinators.

We propose that earlier flowering, whether by days for conspecifics or by weeks to months for different species, allows plants to avoid biotic and abiotic stress, respectively, leading to increased reproductive success and growth. We hypothesize that: (i) earlier‐flowering species will have higher growth and reproductive success than other species co‐occurring in the community, and (ii) earlier‐flowering conspecifics will show higher growth and reproductive success than the average of their co‐occurring conspecifics. A field study was conducted in SE Spain using 98 co‐occurring individuals of four species. We monitored phenology, water loss, and growth over a growing season and estimated relative individual reproduction.

Early‐flowering species did not show higher relative reproduction than late, co‐occurring flowering species, although they differed in water loss. However, early‐flowering conspecifics had higher growth and relative reproduction than later‐flowering conspecifics, but did not differ in water loss.

Our results suggest that early flowering might reduce intraspecific competition among conspecifics, rather than enhance performance of those species that avoid harsh summer conditions (high temperatures and low precipitations).
Association of short‐term exposure to PM1 with hospital admission from total and cause‐specific respiratory diseases
Authors: Zhong Chenghui , Tian Qi , Wei Jing , Lu Wenfeng , Xu Ruijun , Lan Meiqi , Hu Nan , Qiu Lan , Zhang Han , Li SaiFeng , Shi Chunxiang , Liu Yuewei , Zhou Yun
Published: December 2024

Background and Objective

Evidence of short‐term exposure to particulate matter with an aerodynamic diameter ≤1 μm (PM1) on hospital admission for respiratory diseases (RDs) is limited. We aimed to estimate the associated risk of PM1 on hospital admissions for RDs.

Methods

In this time‐stratified case‐crossover study, we assigned cases who had been admitted to hospital for RDs in Guangdong, China between 2016 and 2019. Exposure to PM1 was assigned on the basis of the patient's residence for each case day and its control days. Conditional logistic regression models and distributed lag nonlinear models were used to quantify the association of PM1 exposure with hospital admission for RDs at lag 0–1 days.

Results

A total of 408, 658 hospital admissions for total RDs were recorded in the study period. Each 10 μg/m3 increase in PM1 was significantly associated with a 1.39% (95% confidence interval [CI]: 0.87%–1.91%), 1.97% (95% CI: 1.06%–2.87%) and 1.69% (95% CI: 0.67%–2.71%) increase in odds of hospital admissions for total RDs, chronic obstructive pulmonary disease (COPD) and pneumonia. The excess fraction of hospital admission for total RDs attributable to PM1 exposure was 6.03%, while 6.59% for COPD and 7.48% for pneumonia. Besides, higher excess fractions were more pronounced for hospital admission of total RDs in older patients (>75 years).

Conclusion

Our results support that PM1 is associated with increased risks of hospital admissions for RDs. It emphasizes the needs to pay attention to the effects of PM1 on respiratory health, especially among elderly patients.
White Migration—From the Context of Migration in East Asia
Authors: Debnár Miloš
Published: December 2024

This article discusses recent development in the emerging field of white migration studies and particularly focuses on the studies on Western or white migrants in Japan and China in the past decade. It is outlining the main contribution of these studies to critical whiteness studies and migration studies as well as it identifies some of the lacunas in the research and possible theoretical and conceptual directions in which the research in this field can develop further. The article argues that establishing the transnational movement of white bodies as white migrations—what have been rather associated with privilege and different categories of mobility—contributes to contesting of the racialized categories of migration and understanding of the position of whiteness and role of white privilege in the context of global migration. The article suggests that by using common frameworks and concepts with the mainstream migration research and further analysis of the local contexts, the white migration research can contribute to our understanding of whiteness in the context of global migration without reinstating it as a Eurocentric category of research even more.
Phototropin switches between cis‐ and trans‐autophosphorylation in light‐induced chloroplast relocation in Marchantia polymorpha
Authors: Noguchi Minoru , Noda Saki , Matsubayashi Yoshikatsu , Kodama Yutaka
Published: December 2024

In the accumulation response, chloroplasts move toward weak blue light (BL) to maximize photosynthetic efficiency; in the avoidance response, they move away from strong BL to reduce photodamage. The BL receptor kinase phototropin (phot) mediates these chloroplast relocation responses, and the chloroplast relocation response requires phot kinase activity. Upon receiving BL, phot undergoes autophosphorylation; however, the molecular mechanisms that regulate chloroplast relocation through phot autophosphorylation remain unclear. In this study, we conducted biochemical experiments using phot in the liverwort Marchantia polymorpha and revealed that phot employs cis‐autophosphorylation under weak BL and both cis‐ and trans‐autophosphorylation under strong BL. Inhibiting trans‐autophosphorylation reduced phot autophosphorylation and suppressed the avoidance response, but not the accumulation response. These findings suggest that phot employs two modes of autophosphorylation to alternate between the accumulation and avoidance responses in plants.
The number of positive solutions for n$n$‐coupled elliptic systems
Authors: Jing Yongtao , Liu Haidong , Liu Yanyan , Liu Zhaoli , Wei Juncheng
Published: December 2024

We study the number of positive solutions to the ‐coupled elliptic system
where , , , , , and for . We prove new multiplicity and uniqueness results for positive solutions of the system, whether the system has a variational structure or not. In some cases, we provide a rather complete characterization on the exact number of positive solutions. The results we obtain reveal that the positive solution set of this system has very different structures in the three cases , , and . Moreover, when , very different structures of the positive solution set can also be seen in the case where close to 2 and the case where close to . Similar results are given for elliptic systems with subcritical Sobolev exponents. These results substantially generalize and improve existing results in the literature. To show the effect of the uniqueness result, we apply it to prove existence of a positive solution to a 2‐coupled nonlinear Schrödinger system with critical exponent and  potentials.
Structural insights into the high basal activity and inverse agonism of the orphan receptor GPR6 implicated in Parkinson’s disease
Authors: Barekatain Mahta , Johansson Linda C. , Lam Jordy H. , Chang Hao , Sadybekov Anastasiia V. , Han Gye Won , Russo Joseph , Bliesath Joshua , Brice Nicola L. , Carlton Mark B. L. , Saikatendu Kumar S. , Sun Hukai , Murphy Sean T. , Monenschein Holger , Schiffer Hans H. , Popov Petr , Lutomski Corinne A. , Robinson Carol V. , Liu Zhi-Jie , Hua Tian , Katritch Vsevolod , Cherezov Vadim
Published: December 2024

GPR6 is an orphan G protein–coupled receptor with high constitutive activity found in D2-type dopamine receptor–expressing medium spiny neurons of the striatopallidal pathway, which is aberrantly hyperactivated in Parkinson’s disease. Here, we solved crystal structures of GPR6 without the addition of a ligand (a pseudo-apo state) and in complex with two inverse agonists, including CVN424, which improved motor symptoms in patients with Parkinson’s disease in clinical trials. In addition, we obtained a cryo–electron microscopy structure of the signaling complex between GPR6 and its cognate G
s
heterotrimer. The pseudo-apo structure revealed a strong density in the orthosteric pocket of GPR6 corresponding to a lipid-like endogenous ligand. A combination of site-directed mutagenesis, native mass spectrometry, and computer modeling suggested potential mechanisms for high constitutive activity and inverse agonism in GPR6 and identified a series of lipids and ions bound to the receptor. The structures and results obtained in this study could guide the rational design of drugs that modulate GPR6 signaling.
Rapid pyrolysis of paleo-oil pools recorded by fluid inclusions in an Ediacaran carbonate reservoir, southern China: Implications for the end-Guadalupian mass extinction
Authors: Yang Peng , Jin Zhijun , Liu Keyu , Lu Xuesong , Li Changwei , Gui Lili , Liu Jianliang , Fan Junjia , Wang Shunyu , Xu Yang
Published: December 2024

Thermogenic greenhouse gas emission associated with large igneous province emplacement has previously been hypothesized as a possible contributor to global warming that triggered mass extinctions in Earth’s history, yet this issue remains inadequately understood due to a lack of robust evidence. We present a well-preserved mineralogical, fluid inclusion, and geochemical record indicating a rapid pyrolysis of vast paleo-oil pools in an Ediacaran carbonate reservoir in the central Sichuan Basin (southern China) relating to the eruption of the Emeishan large igneous province that potentially contributed to the end-Guadalupian extinction (ca. 259 Ma). We conclude that the pyrolysis of the paleo-oil pools occurred at ca. 258.4 ± 7.3 Ma associated with the emplacement of the Emeishan large igneous province, causing a rapid increase of temperature and pressure with an estimated transient reservoir pressure of nearly twice that of the lithostatic pressure. A subsequent drop in the formation pressure occurred as the temperature continued to rise, indicating that massive over-pressured methane in the reservoir had been rapidly emitted into the atmosphere along faults or magmatic pipes, ultimately contributing to the end-Guadalupian extinction. Our study highlights the significance of massive emission of thermogenic methane related to large igneous provinces for climate change, carbon cycling, and biological evolution in Earth’s history.
Formation of rare-element pegmatites in the Chinese Altai: Contribution of two-stage melting
Authors: Liu Siyu , Wang Rui , Botcharnikov Roman E. , Sha Hao
Published: December 2024

With increasing discoveries of rare-element pegmatites in metamorphic-migmatitic belts, the role of partial melting of metamorphic protoliths in the formation of pegmatites has attracted significant attention. A previously proposed two-stage melting model for metamorphic sedimentary rocks and subsequent granitic rocks can explain the formation of Li-mineralized pegmatitic magmas, although systematic geologic examples are still missing. Here, we present systematic geochemical data from lithium-cesium-tantalum (LCT) pegmatites (with ages of 400−150 Ma), S-type granitoids (500−350 Ma), and metasedimentary rocks of the Habahe group (HGMRs, 600−450 Ma) in the Chinese Altai orogenic belt, providing evidence of a two-stage melting process occurring in nature. Zircon Hf-O isotope analyses and whole-rock geochemistry suggest pegmatite formation in the Permian−Jurassic (280−150 Ma) as a result of the anatexis of S-type granitoids, which originally crystallized from partial melts of HGMRs. The content of rare elements increases progressively from HGMRs to S-type granitoids to LCT pegmatites, aligning with the modeled melting process. The two-stage melting of the source HGMR protolith resulted in significant extraction of rare elements, with the maximum enrichment factors for Li, Be, Rb, Cs, Nb, and Ta reaching 20, 31, 31, 120, 45, and 44, respectively. This pronounced metal enrichment led to the formation of rare-element mineral assemblages of spodumene, pollucite, and columbite group minerals. This study confirms that multistage crustal melting can be efficient in the enrichment and mineralization of rare elements.
Supplemental Material: Fluid evolution and connections between porphyry-type and skarn-type ore in an intracontinental porphyry-skarn Cu-Au system: Evidence from apatite textures, composition, and oxygen isotopes at Dongguashan Cu-Au (Mo) deposit, eastern China
Authors: Xiao Xin , al. et
Published: December 2024

Tables S1–S4 and Supplemental Text S1.
Optimized Feeding of a Humic Substance or Protease Complex in Channel Catfish Ictalurus punctatus (Rafinesque): Implications for Performance, Immunity, and Intestinal Microbiota
Authors: Oladipupo Abdulmalik A. , Kelly Anita M. , Davis D. Allen , Bruce Timothy J.
Published: December 2024

Previously, dietary humic substances (HSs) or protease complexes (PCs) in fingerling channel catfish Ictalurus punctatus (Rafinesque) have demonstrated potential for health enhancement. Two trials were conducted to elucidate an optimal HS or PC administration plan for growth and health promotion. The first feeding trial was conducted within a recirculating aquaculture system. Catfish fingerlings were fed a commercial control (28% protein) or supplemented diet (control + PC or HS). Diets were administered through four feeding regimens of either HS, or PC‐supplemented diet. After 60 days, continuous feeding of diets with HS or PC contributed to improved feed efficiency and weight gain of the fish. Similarly, catfish growth was enhanced following the application of HS or PC for the final 4 weeks. Serum lysozyme activity was relatively improved in catfish when a PC or HS diets were offered for 60 days. Feeding either of the supplements for the final 4 weeks improved skin lysozyme activity compared to the control group. In the second trial, catfish were fed either the commercial control diet, PC‐supplemented diet, or HS‐supplemented diet in an outdoor production environment for 60 days. Both HS and PC catfish groups had higher survival rates than the control group. Furthermore, growth performance was superior in additive‐fed groups. After HS or PC application, gut microbiota analysis from catfish fecal at two time points revealed significant variation in alpha diversity, community abundance, and beta diversity. However, the association of dietary HS or PC on improved survival, immunity, and gut microbiota modulations presents their importance as functional immunostimulants in catfish aquaculture.
Biophysical Constraints to Robusta Coffee Productivity in Low, Moderate, and High Rainfall Areas
Authors: Nakyagaba Winfred Nabiteeko , Talwana Herbert , Kyamanywa Samuel , Kagezi Godfrey H. , Bamutaze Yazid , Mfitumukiza David , Twinomuhangi Revocatus , Bukomeko Hannington , Mukasa David , Fungo Bernard , Piet van Asten , Jassogne Laurence
Published: December 2024

Globally, coffee (Coffea spp.) is a major commodity in terms of production and trade. Although Uganda is seventh among the major producing countries, yields remain low at 500 kg/ha. Understanding the biophysical constraining factors is vital to inform efforts toward closing the yield gap. A diagnostic study was conducted in 150 coffee fields to determine the most yield‐limiting factors under varying rainfall thresholds, categorized as low ≤ 1100 mm/year, moderate ≥ 1100 to 1200 mm/year, and high ≥ 1200 mm/year. Robusta yield, soil parameters, pest and disease proportions, and tree and banana intercrop densities were measured under the thresholds. Parametric methods and the boundary line approach were used to analyze limiting factors and yield gaps. The results indicated that yields were significantly (p < 0.001) higher in moderate (960 ± 234 kg ha−1) than low (803 ± 188 kg ha−1) and high (713 ± 193 kg ha−1) rainfall thresholds. The proportion of pests and diseases doubled in high than low rainfall thresholds. Soil parameters and tree or banana intercrop were the main yield‐limiting factors. Magnesium limited yield in 47%, 26%, and 14% of coffee fields, causing 23%, 20%, and 21% yield gaps in high, moderate, and low thresholds, respectively. The maximum yield was 1492 kg ha−1; the explainable yield gap was 32%. A larger yield gap of 42%, 36%, and 32% was observed in high, moderate, and low rainfall thresholds. Therefore, long‐term integrated soil fertility and tree or banana intercrop management are suggested for high thresholds, focusing on pests and diseases in moderate and low rainfall thresholds. Additionally, frequent field monitoring is needed to determine the prevalence of pests and diseases at different times of the year and season. Hence, matching thresholds of rainfall variability to the Robusta coffee yield is critical for closing the yield gap and achieving Uganda’s anticipated 20 million 60‐kg bags year−1.
COVID‐19 and Pregnancy Outcomes: A Descriptive Study From a Tertiary Hospital in Ras Al Khaimah, UAE
Authors: M. Sami Manal , Al Zuheiri Shatha , Sabaneh Nour K. , Amir Abdul Latif Mustafa , Al-Blooshi Shooq Yousef , Osman Mira
Published: December 2024

Background: Over 768 million cases of COVID‐19 infection have been reported worldwide, with pregnant women being the most vulnerable members of society during such an infectious disease outbreak. In the United Arab Emirates, there are limited studies explaining the effects of COVID‐19 on pregnant women and their fetuses. In this study, the maternal and fetal outcomes in pregnant women with COVID‐19 in a tertiary maternal hospital, United Arab Emirates, were examined.

Materials and Methods: A descriptive study was conducted in a tertiary hospital for Obstetrics and Gynecology in Ras Al Khaimah, UAE. The study included all pregnant women who tested positive for COVID‐19 infection from April 2020 to September 2021.

Results: The study revealed that a higher number of COVID‐19‐infected pregnant patients presented in their third trimester (69.1%). The comorbidity of body mass index (BMI) had the most effect on the severity/hospitalization status of the patients (p = 0.018). In the nonhospitalized group, fever was the most common symptom (26%), whereas in the hospitalized group, cough was the most common symptom (94%). Emergency cesarean delivery was found to be significant (p = 0.0007) in hospitalized patients. COVID‐19 pneumonia was the prevailing adverse maternal outcome. NICU admission and prematurity were the most frequent neonatal outcomes.

Conclusions: In conclusion, our findings show that adverse maternal outcomes, obesity, and mode of delivery were related to COVID‐19 severity in pregnant patients. However, there was no effect generally on the adverse fetal outcomes except for jaundice and birth weight.
Supplementary Figure 1 from Discovery of RGT-018: A Potent, Selective, and Orally Bioavailable SOS1 Inhibitor for KRAS-Driven Cancers
Authors: Xiao Fei , Wang Kailiang , Wang Xinjuan , Li Huijuan , Hu Zhilong , Ren Xiaoming , Huang Wei , Feng Teng , Yao Lili , Lin Jing , Li Chunlai , Zhang Zhuanzhuan , Mei Liufeng , Zhu Xiaotian , Zhong Wenge , Xie Zhi
Published: December 2024

Supplementary Figure 1
Supplementary Table S3 from TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B.
Published: December 2024

Supplementary Table S3. Transcriptomic and proteomic data analysis.
Table S3 from Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2–p53 Antagonist Suitable for Intermittent Dose Schedules
Authors: Gollner Andreas , Rudolph Dorothea , Weyer-Czernilofsky Ulrike , Baumgartinger Rosa , Jung Peter , Weinstabl Harald , Ramharter Jürgen , Grempler Rolf , Quant Jens , Rinnenthal Jörg , Pérez Pitarch Alejandro , Golubovic Bojana , Gerlach Daniel , Bader Gerd , Wetzel Kristiane , Otto Sebastian , Mandl Christian , Boehmelt Guido , McConnell Darryl B. , Kraut Norbert , Sini Patrizia
Published: December 2024

TaqMan primer and probe sets used for RT-PCR.
Supplementary Figure S8 from TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B.
Published: December 2024

Supplementary Figure S8. TR-107 reduces total ATP production confirming an inactivation of OXPHOS and suppressed glycolytic compensatory response. Colorectal cancer cells (A) DLD-1, (B) LS1034, (C) HT29, and (D) HCT116 were treated with vehicle control (0.1% DMSO) or indicated concentrations of TR-107 for 12 hours. Quantification of OCR and PER was measured with the Seahorse XF Real-Time ATP Rate Assay. Mitochondrial, glycolytic, and total ATP production rates were calculated using OCR and PER values as described in Materials and Methods. Data are presented as mean ± SD values (N=6). *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
Supplementary Figure S5 from TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B.
Published: December 2024

Supplementary Figure S5. TR-107 treatment dysregulates the cell cycle and leads to cytostatic arrest of CRC cells. Colorectal cancer cells (A) LoVo, (B) NCI-H508, (C) LS 174T, and (D) RKO were treated with vehicle control (0.1% DMSO) or indicated concentrations of TR-107 for 24, 48, and 72 hours. Cells were collected at each time point and cell cycle analysis was measured using fluorescence-activated cell sorting (FACS) as described in Materials and Methods. Data are presented as mean ± SD values (N=3). *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
Table S10 from Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2–p53 Antagonist Suitable for Intermittent Dose Schedules
Authors: Gollner Andreas , Rudolph Dorothea , Weyer-Czernilofsky Ulrike , Baumgartinger Rosa , Jung Peter , Weinstabl Harald , Ramharter Jürgen , Grempler Rolf , Quant Jens , Rinnenthal Jörg , Pérez Pitarch Alejandro , Golubovic Bojana , Gerlach Daniel , Bader Gerd , Wetzel Kristiane , Otto Sebastian , Mandl Christian , Boehmelt Guido , McConnell Darryl B. , Kraut Norbert , Sini Patrizia
Published: December 2024

Summary of brigimadlin protein binding in plasma of different species.
Figure S5 from Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2–p53 Antagonist Suitable for Intermittent Dose Schedules
Authors: Gollner Andreas , Rudolph Dorothea , Weyer-Czernilofsky Ulrike , Baumgartinger Rosa , Jung Peter , Weinstabl Harald , Ramharter Jürgen , Grempler Rolf , Quant Jens , Rinnenthal Jörg , Pérez Pitarch Alejandro , Golubovic Bojana , Gerlach Daniel , Bader Gerd , Wetzel Kristiane , Otto Sebastian , Mandl Christian , Boehmelt Guido , McConnell Darryl B. , Kraut Norbert , Sini Patrizia
Published: December 2024

Modulation of p53 target genes in LU0861 tumor-bearing mice treated with brigimadlin.
Supplementary Figure S14 from TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B.
Published: December 2024

Supplementary Figure S14. TR-107 treatment impacts the transcriptomic profile of DLD-1 cells. (A) and (B) RT-PCR analysis of components of ISR and ferroptosis pathways in DLD-1 after 24 and 72 hours of TR-107 treatment, respectively. The green lane denotes a 2-fold cut-off, and the red lane – is a 0.5-fold cut-off. Data are presented as mean ± SD values (N=3). *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
Supplementary Figure S1 from TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B.
Published: December 2024

Supplementary Figure S1. Assessment of IC50 of TR-107 in NIH 3T3 cells. (A) NIH 3T3 cells were treated with vehicle control (0.1% DMSO) or various log-fold concentrations of TR-107 as described in Materials and Methods. CellTiter-Glo cell viability assay was performed 72 hours post-treatment. IC50 values (nmol/L) were calculated with GraphPad Prism and listed on each respective graph. Data are presented as mean ± SD (N=6).
Suppl Fig 3 from Fatty Acid Derivatization and Cyclization of the Immunomodulatory Peptide RP-182 Targeting CD206high Macrophages Improve Antitumor Activity
Authors: Singh Sitanshu S. , Calvo Raul , Kumari Anju , Sable Rushikesh V. , Fang Yuhong , Tao Dingyin , Hu Xin , Castle Sarah Gray , Nahar Saifun , Li Dandan , Major Emily , Sanchez Tino W. , Kato Rintaro , Xu Xin , Zhou Jian , Liu Liang , LeClair Christopher A. , Simeonov Anton , Baljinnyam Bolormaa , Henderson Mark J. , Marugan Juan , Rudloff Udo
Published: December 2024

Suppl Fig 3
Suppl Fig 2 from Fatty Acid Derivatization and Cyclization of the Immunomodulatory Peptide RP-182 Targeting CD206high Macrophages Improve Antitumor Activity
Authors: Singh Sitanshu S. , Calvo Raul , Kumari Anju , Sable Rushikesh V. , Fang Yuhong , Tao Dingyin , Hu Xin , Castle Sarah Gray , Nahar Saifun , Li Dandan , Major Emily , Sanchez Tino W. , Kato Rintaro , Xu Xin , Zhou Jian , Liu Liang , LeClair Christopher A. , Simeonov Anton , Baljinnyam Bolormaa , Henderson Mark J. , Marugan Juan , Rudloff Udo
Published: December 2024

Suppl Fig 2
Suppl Fig 1 from Fatty Acid Derivatization and Cyclization of the Immunomodulatory Peptide RP-182 Targeting CD206high Macrophages Improve Antitumor Activity
Authors: Singh Sitanshu S. , Calvo Raul , Kumari Anju , Sable Rushikesh V. , Fang Yuhong , Tao Dingyin , Hu Xin , Castle Sarah Gray , Nahar Saifun , Li Dandan , Major Emily , Sanchez Tino W. , Kato Rintaro , Xu Xin , Zhou Jian , Liu Liang , LeClair Christopher A. , Simeonov Anton , Baljinnyam Bolormaa , Henderson Mark J. , Marugan Juan , Rudloff Udo
Published: December 2024

Suppl Fig 1
Figure S1 from Targeting PDHK1 by DCA to Restore NK Cell Function in Hepatocellular Carcinoma
Authors: Yang Xinyi , Liu Yuanyuan , Wang Peng , Li Min , Xiang Tong , Xie Songzuo , Li Minxing , Wang Yan , Weng Desheng , Zhao Jingjing
Published: December 2024

Fig. S1 DCA enhances the function of NK cells exhausted by huh7 tumor cells (A) Flow cytometry detection of NK cell phenotypes used in in vitro and in vivo experiments. (B) The flow cytometric data on a full panel of NK cell markers. (C) Left: The positive levels of Granzyme B, TNF-α, IFN-γ, perforin and CD107a in huh7 tumor-infiltration NK cells treated with or without 8mM DCA at an E:T ratio of 2:1 was detected by flow cytometry. Right: Statistical analysis of Granzyme B, TNF-α, IFN-γ, perforin and CD107a produced by huh7 tumor-infiltration NK cells with or without 8mM DCA. (n = 3, two independent samples t-test, two-sided). Statistical analysis of Granzyme B, TNF-α, IFN-γ and perforin produced by huh7 tumor-infiltration NK cells with or without 8mM DCA at E:T ratio of 5:1(D) and 10:1(E) was detected by flow cytometry (n=3, two independent samples t-test, two-sided). (F) Left: The positive levels of CD69 and TIM-3 in NK cells were detected by flow cytometry. Right: Statistical analysis of CD69 and TIM-3 expressed by NK cells. (n=3, two independent samples t-test, two-sided). Results represent the mean ± SEM, from three to four independent experiments. **P < 0.01; ***P < 0.001; ****P < 0.0001. Abbreviations: NK, natural killer; DCA, dichloroacetate.
Supplementary Table 4 from Immunoproteasome Activation Expands the MHC Class I Immunopeptidome, Unmasks Neoantigens, and Enhances T-cell Anti-Myeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Guo Chunna , Mosley Amber L. , Malek Ehsan , Federov Yuriy , Adams Drew J. , Driscoll James J.
Published: December 2024

Supplementary Table 4