bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brincidofovir inhibits polyomavirus infection
in vivo
Authors: Butic Arrienne B. , Katz Zoe E. , Jin Ge , Fukushima Koji , Hazama Masatoshi , Lukacher Aron E. , Lauver Matthew D. 
Published: July 2024

ABSTRACT

Polyomaviruses are species-specific DNA viruses that can cause disease in immunocompromised individuals. Despite their role as the causative agents for several diseases, there are no currently approved antivirals for treating polyomavirus infection. Brincidofovir (BCV) is an antiviral approved for the treatment of poxvirus infections and has shown activity against other double-stranded DNA viruses. In this study, we tested the efficacy of BCV against polyomavirus infection
in vitro
and
in vivo
using mouse polyomavirus (MuPyV). BCV inhibited virus production in primary mouse kidney cells and brain cortical cells. BCV treatment of cells transfected with MuPyV genomic DNA resulted in a reduction in virus levels, indicating that viral inhibition occurs post-entry. Although
in vitro
BCV treatment had a limited effect on viral DNA and RNA levels, drug treatment was associated with a reduction in viral protein, raising the possibility that BCV acts post-transcriptionally to inhibit MuPyV infection. In mice, BCV treatment was well tolerated, and prophylactic treatment resulted in a reduction in viral DNA levels and a potent suppression of infectious virus production in the kidney and brain. In mice with chronic polyomavirus infection, therapeutic administration of BCV decreased viremia and reduced infection in the kidney. These data demonstrate that BCV exerts antiviral activity against polyomavirus infection
in vivo
, supporting further investigation into the use of BCV to treat clinical polyomavirus infections.

IMPORTANCE

Widespread in the human population and able to persist asymptomatically for the life of an individual, polyomavirus infections cause a significant disease burden in the immunocompromised. Individuals undergoing immune suppression, such as kidney transplant patients or those treated for autoimmune diseases, are particularly at high risk for polyomavirus-associated diseases. Because no antiviral agent exists for treating polyomavirus infections, management of polyomavirus-associated diseases typically involves reducing or discontinuing immunomodulatory therapy. This can be perilous due to the risk of transplant rejection and the potential development of adverse immune reactions. Thus, there is a pressing need for the development of antivirals targeting polyomaviruses. Here, we investigate the effects of brincidofovir, an FDA-approved antiviral, on polyomavirus infection
in vivo
using mouse polyomavirus. We show that the drug is well-tolerated in mice, reduces infectious viral titers, and limits viral pathology, indicating the potential of brincidofovir as an anti-polyomavirus therapeutic.
Sac1 links phosphoinositide turnover to cryptococcal virulence
Authors: Gaylord Elizabeth A. , Choy Hau Lam , Chen Guohua , Briner Sydney L. , Doering Tamara L. 
Published: July 2024

ABSTRACT

Cryptococcus neoformans
is an environmentally acquired fungal pathogen that causes over 140,000 deaths per year. Cryptococcal infection occurs when infectious particles are deposited into the lung, where they encounter host phagocytic cells.
C. neoformans
may be engulfed by these phagocytes, an important step of infection that leads to outcomes ranging from termination of infection to cryptococcal dissemination. To study this critical process, we screened approximately 4,700 cryptococcal gene deletion mutants for altered uptake, using primary mouse and human phagocytic cells. Among the hits of these two screens, we identified 93 mutants with perturbed uptake in both systems, as well as others with differences in uptake by only one cell type. We further screened the hits for changes in thickness of the capsule, a protective polysaccharide layer around the cell which is an important cryptococcal virulence factor. The combination of our three screens yielded 45 mutants, including one lacking the phosphatidylinositol-4-phosphate phosphatase Sac1. In this work, we implicate Sac1 in both host cell uptake and capsule production. We found that
sac1
mutants exhibit lipid trafficking defects, reductions in secretory system function, and changes in capsule size and composition. Many of these changes occur specifically in tissue culture media, highlighting the role of Sac1 phosphatase activity in responding to the stress of host-like conditions. Overall, these findings show how genome-scale screening can identify cellular factors that contribute to our understanding of cryptococcal biology and demonstrate the role of Sac1 in determining fungal virulence.

IMPORTANCE

Cryptococcus neoformans
is a fungal pathogen with significant impact on global health. Cryptococcal cells inhaled from the environment are deposited into the lungs, where they first contact the human immune system. The interaction between
C. neoformans
and host cells is critical because this step of infection can determine whether the fungal cells die or proliferate within the human host. Despite the importance of this stage of infection, we have limited knowledge of cryptococcal factors that influence its outcome. In this study, we identify cryptococcal genes that affect uptake by both human and mouse cells. We also identify mutants with altered capsule, a protective coating that surrounds the cells to shield them from the host immune system. Finally, we characterize the role of one gene,
SAC1
, in these processes. Overall, this study contributes to our understanding of how
C. neoformans
interacts with and protects itself from host cells.
Multiple levels of transcriptional regulation control glycolate metabolism in
Paracoccus denitrificans
Authors: Schada von Borzyskowski Lennart , Hermann Lucas , Kremer Katharina , Barthel Sebastian , Pommerenke Bianca , Glatter Timo , Paczia Nicole , Bremer Erhard , Erb Tobias J. 
Published: July 2024

ABSTRACT

The hydroxyacid glycolate is a highly abundant carbon source in the environment. Glycolate is produced by unicellular photosynthetic organisms and excreted at petagram scales to the environment, where it serves as growth substrate for heterotrophic bacteria. In microbial metabolism, glycolate is first oxidized to glyoxylate by the enzyme glycolate oxidase. The recently described β-hydroxyaspartate cycle (BHAC) subsequently mediates the carbon-neutral assimilation of glyoxylate into central metabolism in ubiquitous Alpha- and Gammaproteobacteria. Although the reaction sequence of the BHAC was elucidated in
Paracoccus denitrificans
, little is known about the regulation of glycolate and glyoxylate assimilation in this relevant alphaproteobacterial model organism. Here, we show that regulation of glycolate metabolism in
P. denitrificans
is surprisingly complex, involving two regulators, the IclR-type transcription factor BhcR that acts as an activator for the BHAC gene cluster, and the GntR-type transcriptional regulator GlcR, a previously unidentified repressor that controls the production of glycolate oxidase. Furthermore, an additional layer of regulation is exerted at the global level, which involves the transcriptional regulator CceR that controls the switch between glycolysis and gluconeogenesis in
P. denitrificans
. Together, these regulators control glycolate metabolism in
P. denitrificans
, allowing the organism to assimilate glycolate together with other carbon substrates in a simultaneous fashion, rather than sequentially. Our results show that the metabolic network of Alphaproteobacteria shows a high degree of flexibility to react to the availability of multiple substrates in the environment.

IMPORTANCE

Algae perform ca. 50% of the photosynthetic carbon dioxide fixation on our planet. In the process, they release the two-carbon molecule glycolate. Due to the abundance of algae, massive amounts of glycolate are released. Therefore, this molecule is available as a source of carbon for bacteria in the environment. Here, we describe the regulation of glycolate metabolism in the model organism
Paracoccus denitrificans
. This bacterium uses the recently characterized β-hydroxyaspartate cycle to assimilate glycolate in a carbon- and energy-efficient manner. We found that glycolate assimilation is dynamically controlled by three different transcriptional regulators: GlcR, BhcR, and CceR. This allows
P. denitrificans
to assimilate glycolate together with other carbon substrates in a simultaneous fashion. Overall, this flexible and multi-layered regulation of glycolate metabolism in
P. denitrificans
represents a resource-efficient strategy to make optimal use of this globally abundant molecule under fluctuating environmental conditions.
Host cells reprogram lipid droplet synthesis through YY1 to resist PRRSV infection
Authors: Zheng Zifang , Ling Xue , Li Yang , Qiao Shuang , Zhang Shuangquan , Wu Jie , Ma Zhiqian , Li Mingyu , Guo Xuyang , Li Zhiwei , Feng Yingtong , Liu Xiao , Goodfellow Ian G. , Zheng Haixue , Xiao Shuqi 
Published: July 2024

ABSTRACT

Metabolism in host cells can be modulated after viral infection, favoring viral survival or clearance. Here, we report that lipid droplet (LD) synthesis in host cells can be modulated by yin yang 1 (YY1) after porcine reproductive and respiratory syndrome virus (PRRSV) infection, resulting in active antiviral activity. As a ubiquitously distributed transcription factor, there was increased expression of YY1 upon PRRSV infection both
in vitro
and
in vivo
. YY1 silencing promoted the replication of PRRSV, whereas YY1 overexpression inhibited PRRSV replication. PRRSV infection led to a marked increase in LDs, while YY1 knockout inhibited LD synthesis, and YY1 overexpression enhanced LD accumulation, indicating that YY1 reprograms PRRSV infection-induced intracellular LD synthesis. We also showed that the viral components do not colocalize with LDs during PRRSV infection, and the effect of exogenously induced LD synthesis on PRRSV replication is nearly lethal. Moreover, we demonstrated that YY1 affects the synthesis of LDs by regulating the expression of lipid metabolism genes. YY1 negatively regulates the expression of fatty acid synthase (FASN) to weaken the fatty acid synthesis pathway and positively regulates the expression of peroxisome proliferator-activated receptor gamma (PPARγ) to promote the synthesis of LDs, thus inhibiting PRRSV replication. These novel findings indicate that YY1 plays a crucial role in regulating PRRSV replication by reprogramming LD synthesis. Therefore, our study provides a novel mechanism of host resistance to PRRSV and suggests potential new antiviral strategies against PRRSV infection.

IMPORTANCE
Porcine reproductive and respiratory virus (PRRSV) has caused incalculable economic damage to the global pig industry since it was first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. It is well known that viruses are parasitic pathogens, and the completion of their replication life cycle is highly dependent on host cells. A better understanding of host resistance to PRRSV infection is essential for developing safe and effective strategies to control PRRSV. Here, we report a crucial host antiviral molecule, yin yang 1 (YY1), which is induced to be expressed upon PRRSV infection and subsequently inhibits virus replication by reprogramming lipid droplet (LD) synthesis through transcriptional regulation. Our work provides a novel antiviral mechanism against PRRSV infection and suggests that targeting YY1 could be a new strategy for controlling PRRSV.
Optimizing molecular assays for glyphosate and ALS-inhibitor resistance diagnostics in four weed species
Authors: Sulzback Juliano R.M. , Borgato Ednaldo A. , Cutti Luan , Hill Erin C. , Burns Erin E. , Patterson Eric L. 
Published: July 2024

Herbicide-resistant weeds pose a threat to food production in modern agriculture, causing US$32 billion in crop production losses worldwide. In Michigan, highly troublesome and widespread weeds include waterhemp, Palmer amaranth, common ragweed, and horseweed, with accessions that are resistant to glyphosate (Group 9) and ALS-inhibitors (Group 2), major herbicide sites of action utilized in soybean and corn cropping systems. Molecular assays for rapid resistance diagnostics to confirm the in-field status of herbicide resistance can assist with more effective, timely, and proactive management. In this research, we developed and tested PCR-based assays to identify target site resistance mechanisms to both herbicide groups through Sanger sequencing and EPSPS copy number variation. Nine different SNPs were identified in five ALS positions known to confer herbicide resistance among all species surveyed. Pro197Ser was the most frequent in horseweed and common ragweed accessions, whereas Trp574Leu was the predominant mutation in Palmer amaranth and waterhemp. Four horseweed accessions contained the Pro106Ser mutation in the EPSPS gene, which confers resistance to glyphosate. Additionally, waterhemp and Palmer amaranth had 2–7 and 20–160 copies of EPSPS, respectively. The assays were validated by comparing genotyping of several field-collected accessions of unknown resistance status with known resistant and susceptible accessions. The efficacy of genotyping assays was >98% and required only two days, confirming that molecular assays are a robust tool for rapid resistance diagnostics. These assays can help growers evaluate herbicide resistance status in weed populations within the same growing season, allowing them to adopt effective management practices.
Creative traces of <i>Los otros hombres en Eva</i>
Authors: Paoletta Anabel Edith , Rosso Martin Miguel 
Published: July 2024

This article shares the methodological guidelines carried out by the actors/researchers of the IPROCAE research group (Investigation of Creative Processes in performing Arts) belonging to the Facultad de Arte of the UNCPBA, and its main objetive is to study their own performing practice simultaneously with their realization in the work Los otros hombres en Eva.
The análisis of the creative process is developed base don the study of the genesis, on the figure of Eva Duarte de Peron and the different artistic approaches related to her mummification; examining the relationship between Theater and politics, in the form of militant theater of the 70s in Argentina; and reflexionating about the role of chance, or the existing random processes in the production of the contemporary Theater field, where it is used as a creative procedure and scenic construction tool.
One new species and a new record of saprobic fungi from Ananas comosus in northern Thailand
Authors: SHAH SUJIT , FARIAS ANTONIO ROBERTO GOMES DE 
Published: July 2024

Pineapple is one of the major crops in northern Thailand. Like all the other plants, it has associated with it, a wide range of fungi, which may be saprobic, pathogenic, or endophytic. This study investigated fungi associated with pineapple in Chiang Rai Province, northern Thailand. Based on morphology and multilocus phylogeny of the ITS and LSU sequence data, Anthracocystis ananatum is described as a new species with its detailed asexual morph. Compared to other Anthracocystis species, A. ananatum has a distinctive morphotype that includes septate hyphae, conidigenous cells, and conidiophores. In addition, Spegazzinia tessarthra is reported for the first time as a new host and geographic record. The complete descriptions, photo-micrographs, and phylogenies of the new species Anthracocystis ananatum and a new host and geographic record S. tessarthra are provided and discussed.
Ocean Complexity Shapes Sea Surface Temperature Variability in a CESM2 Coupled Model Hierarchy
Authors: Larson Sarah M. , McMonigal Kay , Okumura Yuko , Amaya Dillon , Capotondi Antonietta , Bellomo Katinka , Simpson Isla R. , Clement Amy C. 
Published: July 2024

Abstract
To improve understanding of ocean processes impacting monthly sea surface temperature (SST) variability, we analyze a Community Earth System Model, version 2, hierarchy in which models vary only in their degree of ocean complexity. The most realistic ocean is a dynamical ocean model, as part of a fully coupled model (FCM). The next most realistic ocean, from a mechanically decoupled model (MDM), is like the FCM but excludes anomalous wind stress–driven ocean variability. The simplest ocean is a slab ocean model (SOM). Inclusion of a buoyancy coupled dynamic ocean as in the MDM, which includes temperature advection and vertical mixing absent in the SOM, leads to dampening of SST variance everywhere and reduced persistence of SST anomalies in the high latitudes and equatorial Pacific compared to the SOM. Inclusion of anomalous wind stress–driven ocean dynamics as in the FCM leads to higher SST variance and longer persistence time scales in most regions compared to the MDM. The net role of the dynamic ocean, as an overall dampener or amplifier of anomalous SST variance and persistence, is regionally dependent. Notably, we find that efforts to reduce the complexity of the ocean models in the SOM and MDM configurations result in changes in the magnitude of the thermodynamic forcing of SST variability compared to the FCM. These changes, in part, stem from differences in the seasonally varying mixed layer depth and should be considered when attempting to quantify the relative contribution of certain ocean mechanisms to differences in SST variability between the models.
No Evidence of Winter Warming in Eurasia Following Large, Low-Latitude Volcanic Eruptions during the Last Millennium
Authors: Tejedor Ernesto , Polvani Lorenzo M. , Steiger Nathan J. , Vuille Mathias , Smerdon Jason E. 
Published: July 2024

Abstract
We critically reexamine the question of whether volcanic eruptions cause surface warming over Eurasia in winter, in the light of recent modeling studies that have suggested internal variability may overwhelm any forced volcanic response, even for the very largest eruptions during the Common Era. Focusing on the last millennium, we combine model output, instrumental observations, tree-ring records, and ice cores to build a new temperature reconstruction that specifically targets the boreal winter season. We focus on 20 eruptions over the last millennium with volcanic stratospheric sulfur injections (VSSIs) larger than the 1991 Pinatubo eruption. We find that only 7 of these 20 large events are followed by warm surface temperature anomalies over Eurasia in the first posteruption winter. Examining the 13 events that show cold posteruption anomalies, we find no correlation between the amplitude of winter cooling and VSSI mass. We also find no evidence that the North Atlantic Oscillation is correlated with VSSI in winter, a key element of the proposed mechanism through which large, low-latitude eruptions might cause winter warming over Eurasia. Furthermore, by inspecting individual eruptions rather than combining events into a superposed epoch analysis, we are able to reconcile our findings with those of previous studies. Analysis of two additional paleoclimatic datasets corroborates the lack of posteruption Eurasian winter warming. Our findings, covering the entire last millennium, confirm the findings of most recent modeling studies and offer important new evidence that large, low-latitude eruptions are not, in general, followed by significant surface wintertime warming over Eurasia.
Mapping Lightning Risk in Mexico: Integrating Natural Hazard and Social Vulnerability
Authors: Jaramillo Alejandro , Dominguez Christian 
Published: July 2024

Abstract
Lightning around the world poses a significant threat to life, infrastructure, and economic sectors. This study evaluates lightning risk at the municipal level in Mexico, recognizing the interplay of hazard and vulnerability in risk estimation. Despite declining lightning-related fatalities, possibly attributed to demographic shifts and improved urban infrastructure, persistent social vulnerability exists, particularly among rural populations engaged in labor-intensive agriculture with lower education levels. We estimate a risk map for lightning-related fatality risk in Mexico, where we identify high-risk regions along the Sierra Madre Occidental, the Pacific coast, and central and southeastern Mexico, marked by elevated lightning days and social vulnerability. The risk map integrates hazard and social vulnerability, capturing the distribution of fatality incidents, and it reveals that 82.1% of incidents occurred in municipalities categorized as “high” or “very high” risk. This result emphasizes the need to consider both physical hazard and social vulnerability for a comprehensive assessment of lightning risk. This study contributes to understanding lightning risk in Mexico, providing crucial insights at the municipality level for informing policymaking and targeting risk mitigation strategies. By highlighting the interrelation of hazard and social vulnerability, this research aligns with broader goals of enhancing local resilience and safety in the face of natural hazards, highlighting the ongoing need for disaster risk reduction efforts.

Significance Statement
This study provides a comprehensive evaluation of the risk of death by lightning at the municipality level in Mexico, considering the intricate interplay between hazard and social vulnerability. By analyzing both the physical hazard of lightning and the social vulnerability of exposed populations, the study provides a map estimating the risk level for each municipality. The risk map, capturing the interrelation of hazard and vulnerability, provides a powerful tool for policymakers and emergency responders. With 82.1% of lightning fatalities concentrated in municipalities with “high” and “very high” risk, this work underscores the need for comprehensive risk assessment strategies. This research contributes knowledge for informed decision-making, targeted interventions, and the ongoing pursuit of enhancing community resilience to lightning-related hazards.
Nanosheet integration of induced tunnel field-effect transistor with lower cost and lower power
Authors: Lin Jyi-Tsong , Kuo Chia-Yo 
Published: July 2024

AbstractNanosheet transistors are poised to become the preferred choice for the next generation of smaller-sized devices in the future. To address the future demand for high-performance and low-power computing applications, this study proposes a nanosheet structure with a vertically stacked design, featuring a high ION/IOFF ratio. This Nanosheet design is combined with an induced tunnel field-effect transistor. By utilizing SiGe with a carrier mobility three times that of Si and employing a line tunneling mechanism, the research successfully achieves superior Band to Band characteristics, resulting in improved switching behavior and a lower Subthreshold Swing (SS). Comparative studies were conducted on three TFET types: Nanosheet PIN TFET, Nanosheet Schottky iTFET, and Fin iTFET. Results show that the Nanosheet PIN TFET has a higher ION/IOFF ratio but poorer SSavg values at 47.63 mV/dec compared to the others. However, with a SiGe Body thickness of 3 nm, both Nanosheet iTFET and Fin iTFET exhibit higher ION/IOFF ratios and superior SSavg values at 17.64 mV/dec. These findings suggest the potential of Nanosheet iTFET and Fin iTFET for low-power, lower thermal budgets, and fast-switching applications.