bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candida
-induced granulocytic myeloid-derived suppressor cells are protective against polymicrobial sepsis
Authors: Esher Righi Shannon , Harriett Amanda J. , Lilly Elizabeth A. , Fidel Paul L. , Noverr Mairi C. 
Published: September 2023

ABSTRACT

Polymicrobial intra-abdominal infections (IAI) can lead to life-threatening sepsis with significant morbidity and mortality, especially when pathogenic fungi are involved. We have employed an established clinically relevant mouse model of fungal/bacterial IAI and shown that immunization with low-virulence
Candida
species, that is,
Candida dubliniensis
, can induce responses that protect against sepsis via the suppression of lethal inflammation. This protection is dependent on long-lived Gr-1
+
polymorphonuclear leukocytes that display characteristics consistent with myeloid-derived suppressor cells (MDSCs) and trained innate immunity. Here we aimed to functionally and phenotypically characterize these protective Gr-1
+
leukocytes. Compared to nonimmunized control mice, we observed increased levels of CD11b
+
Gr-1
+
cells systemically and locally in the peritoneal cavity of immunized mice. Isolated peritoneal Gr-1
+
cells displayed hallmark MDSC phenotypes including increased T-cell suppressor activity and increased MDSC effector activity. Furthermore, we observed increased levels of the anti-inflammatory MDSC cytokine interleukin (IL)-10 in the peritoneal cavity of immunized mice and, in contrast, increased inflammatory responses when Gr-1
+
leukocytes were depleted from immunized mice prior to challenge. Flow cytometric analysis revealed that Ly6G
+
granulocytic MDSCs (G-MDSCs) were preferentially increased over Ly6C
+
monocytic MDSCs (M-MDSCs) in immunized mice. Importantly, G-MDSCs, but not M-MDSCs, as well as IL-10 production, are required for full protection against lethal sepsis. From these data, we conclude that the Gr-1
+
leukocytes that protect against polymicrobial sepsis are bona fide MDSCs and hypothesize that the mechanism of MDSC-mediated protection includes abrogation of lethal inflammation by IL-10.

IMPORTANCE

Polymicrobial intra-abdominal infections are serious clinical infections that can lead to life-threatening sepsis, which is difficult to treat in part due to the complex and dynamic inflammatory responses involved. Our prior studies demonstrated that immunization with low-virulence
Candida
species can provide strong protection against lethal polymicrobial sepsis challenge in mice. This long-lived protection was found to be mediated by trained Gr-1
+
polymorphonuclear leukocytes with features resembling myeloid-derived suppressor cells (MDSCs). Here we definitively characterize these cells as MDSCs and demonstrate that their mechanism of protection involves the abrogation of lethal inflammation, in part through the action of the anti-inflammatory cytokine interleukin (IL)-10. These studies highlight the role of MDSCs and IL-10 in controlling acute lethal inflammation and give support for the utility of trained tolerogenic immune responses in the clinical treatment of sepsis.
Antibiotic that inhibits
trans
-translation blocks binding of EF-Tu to tmRNA but not to tRNA
Authors: Marathe Neeraja , Nguyen Ha An , Alumasa John N. , Kuzmishin Nagy Alexandra B. , Vazquez Michael , Dunham Christine M. , Keiler Kenneth C. 
Published: September 2023

ABSTRACT

trans-
Translation is conserved throughout bacteria and is essential in many species. High-throughput screening identified a tetrazole-based
trans
-translation inhibitor, KKL-55, that has broad-spectrum antibiotic activity. A biotinylated version of KKL-55 pulled down elongation factor thermo-unstable (EF-Tu) from bacterial lysates. Purified EF-Tu bound KKL-55
in vitro
with a
K
d
= 2 µM, confirming a high-affinity interaction. An X-ray crystal structure showed that KKL-55 binds in domain 3 of EF-Tu, and mutation of residues in the binding pocket abolished KKL-55 binding. RNA-binding assays
in vitro
showed that KKL-55 inhibits binding between EF-Tu and transfer-messenger RNA (tmRNA) but not between EF-Tu and tRNA. These data demonstrate a new mechanism for the inhibition of EF-Tu function and suggest that this specific inhibition of EF-Tu•tmRNA binding is a viable target for antibiotic development.

IMPORTANCE

Elongation factor thermo-unstable (EF-Tu) is a universally conserved translation factor that mediates productive interactions between tRNAs and the ribosome. In bacteria, EF-Tu also delivers transfer-messenger RNA (tmRNA)-SmpB to the ribosome during
trans
-translation. We report the first small molecule, KKL-55, that specifically inhibits EF-Tu activity in
trans
-translation without affecting its activity in normal translation. KKL-55 has broad-spectrum antibiotic activity, suggesting that compounds targeted to the tmRNA-binding interface of EF-Tu could be developed into new antibiotics to treat drug-resistant infections.
Complete genome sequence of
Cellulomonas
sp., strain ES6, a chromate-reducing bacterium isolated from chromium-contaminated subsurface sediment
Authors: Perea Katheryn R. , DeVeaux Linda C. , Lee Brady D. , Losey Nathaniel A. 
Published: September 2023

ABSTRACT

Cellulomonas
sp. strain ES6 is a chromate-reducing bacterium isolated from chromium contaminated subsurface sediment. Illumina MiSeq and Oxford Nanopore sequencing were used to assemble the genome sequence which consisted of a single circular chromosome of 4.13 Mb, contained 3,960 protein encoding genes and with an overall G + C content 75.38%.
Supplemental Material: Westward underthrusting of thick North American crust: The dominant thickening process that built the Cordilleran orogenic plateau
Authors: Long Sean P. 
Published: September 2023

<p>Includes a figure with detailed versions of all seven cross sections, a summary of rock units on each cross section, and supporting data for cross section reconstructions, shortening and extension calculations, stratigraphic thicknesses, and measured thickening and thinning components. </p>
Management of epilepsy during pregnancy and lactation
Authors: Hope Omotola A , Harris Katherine MJ 
Published: September 2023

ABSTRACT
Epilepsy is a group of neurological diseases characterized by susceptibility to recurrent seizures. Antiseizure medications (ASMs) are the mainstay of treatment, but many antiseizure medications with variable safety profiles have been approved for use. For women with epilepsy in their childbearing years, the safety profile is important for them and their unborn children, because treatment is often required to protect them from seizures during pregnancy and lactation. Since no large randomized controlled trials have investigated safety in this subgroup of people with epilepsy, pregnancy registries, cohort and case-control studies from population registries, and a few large prospective cohort studies have played an important role. Valproate, in monotherapy and polytherapy, has been associated with elevated risk of major congenital malformations and neurodevelopmental disorders in children born to mothers who took it. Topiramate and phenobarbital are also associated with elevated risks of congenital malformations and neurodevelopmental disorders, though the risks are lower than those of valproate. Lamotrigine and levetiracetam are relatively safe. Insufficient data exist to reach strong conclusions about the newest antiseizure medications such as eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. Besides antiseizure medications, other treatments such as vagal nerve stimulation, responsive neurostimulation, and deep brain stimulation are likely safe. In general, breastfeeding does not appear to add any additional long term risks to the child. Creative ways of optimizing registry enrollment and data collection are needed to enhance patient safety.
Centrifuge modeling of slope failure induced by elevated gas pressure in wet municipal solid waste landfill
Authors: Hu Jie , Chen Yun Min , Li Jing Hang , Ke Han , Li Jun Chao 
Published: September 2023

Understanding triggering mechanisms of slope failure is of great importance to the stability analysis and safety warning of waste landfill. This paper presents a centrifuge model test on slope failure induced by elevated gas pressure in wet landfill. The formation process of liquid level and gas pressure in the landfill is simulated by means of liquid and gas injections under a centrifugal acceleration of 66.7 g. The injected liquid contains surfactants, which allow it to generate foam in the waste pores when mixed with the injected gas. The pore gas and liquid pressures under two-phase flow condition are monitored separately to clarify the instability process. It is found that the continuous gas injection makes the pore gas pressure increase to peak values of 83.0 kPa–100.8 kPa, which are higher than the peak liquid pressures of 61.3 kPa–75.6 kPa. The formation of high gas pressure zone is attributed to the low gas permeability, which is affected by high liquid saturation as well as foam generation. The slope failure occurs when the pore gas pressure increases to the peak value and the corresponding shear strength decreases to the critical value. Although the gas injection raises the liquid level, the factor of safety of landfill slope will be overestimated if only considering the effect of liquid pressure. According to the response curves of displacement to gas pressure rise, the critical ratios of gas pressure to earth pressure are determined to be 0.74–0.84, which fall within the range of the prototype landfill. The difference between foam and air on pore pressure distribution is also calculated and discussed.
Tillage and nitrogen rate effects on winter wheat yield in a wheat–sorghum rotation
Authors: Majrashi Mosaed A. , Obour Augustine K. , Moorberg Colby J. , Lollato Romulo P. , Holman Johnathon D. , Du Juan , Mikha Maysoon M. , Assefa Yared 
Published: September 2023

The objectives of this study were to quantify long-term tillage practice and nitrogen (N) fertilizer rate effects on yield and N use in a winter wheat ( Triticum aestivum L.)–grain sorghum ( Sorghum bicolor L. Moench)–fallow (W–S–F) rotation. The experimental design was a randomized complete block with a split–split-plot arrangement. The main plot treatments were crop rotation phases W–S–F, S–F–W, and F–W–S. The sub-plots were tillage practices, i.e., conventional tillage (CT), reduced tillage (RT), and no-tillage (NT). And the sub-sub-plot treatments were N rates of 0, 45, 90, and 134 kg ha−1. Wheat yield increased at rates of 15.6, 9.3, 22.8, and 25.7 kg ha−1 for a kg N ha−1 increase in very low-, low-, high-, and very high-yielding environments (average yields of ∼2000, 2500, 2800, and 4400 kg ha−1), respectively. On average, winter wheat yields were 7%–9% greater for CT compared with both NT and RT. Winter wheat removed about 52 kg N ha−1 from the unfertilized control treatment, but N uptake varied by N rate and growing conditions. Nitrogen use efficiency, N agronomic efficiency, and applied N recovery decreased as the N rate increased. Across environments, wheat yield increased by 16, 20, and 17 kg ha−1 for each additional kg ha−1 N applied under CT, NT, and RT, respectively, and additional 2–2.5 kg ha−1 yield increases for a mm increase in fallow precipitation. We concluded that wheat yield response to N is highly dependent on growing conditions, and NT required greater N fertilization than CT and RT for similar yields.
Array analysis of seismic noise at the Sos Enattos mine, the Italian candidate site for the Einstein Telescope
Authors: Saccorotti Gilberto , Giunchi Carlo , D’Ambrosio Michele , Gaviano Sonja , Naticchioni Luca , D’Urso Domenico , Rozza Davide , Cardini Alessandro , Contu Andrea , Dordei Francesca , Cadeddu Matteo , Tuveri Matteo , Migoni Carlo , Punturo Michele , Allocca Annalisa , Calloni Enrico , Cardello Giovanni Luca , D’Onofrio Luca , Davari Nazanin , Dell’Aquila Daniele , De Rosa Rosario , Carpinelli Massimo , Di Fiore Luciano , di Giovanni Matteo , Errico Luciano , Fiori Irene , Tringali Maria Concetta , Harms Jan , Koley Soumen , Longo Vittorio , Majorana Ettore , Mangano Valentina , Olivieri Marco , Paoletti Federico , Pesenti Luca , Puppo Paola , Rapagnani Piero , Razzano Massimiliano , Ricci Fulvio , Sipala Valeria , Tosta e Melo Iara , Trozzo Lucia 
Published: September 2023

AbstractThe area surrounding the dismissed mine of Sos Enattos (Sardinia, Italy) is the Italian candidate site for hosting Einstein Telescope (ET), the third-generation gravitational wave (GW) observatory. One of the goals of ET is to extend the sensitivity down to frequencies well below those currently achieved by GW detectors, i.e. down to 2 Hz. In the bandwidth [1,10] Hz, the seismic noise of anthropogenic origin is expected to represent the major perturbation to the operation of the infrastructure, and the site that will host the future detector must fulfill stringent requirements on seismic disturbances. In this paper we describe the operation of a temporary, 15-element, seismic array deployed in close proximity to the mine. Signals of anthropogenic origin have a transient nature, and their spectra are characterized by a wide spectral lobe spanning the [3,20] Hz frequency interval. Superimposed to this wide lobe are narrow spectral peaks within the [3,8] Hz frequency range. Results from slowness analyses suggest that the origin of these peaks is related to vehicle traffic along the main road running east of the mine. Exploiting the correlation properties of seismic noise, we derive a dispersion curve for Rayleigh waves, which is then inverted for a shallow velocity structure down to depths of $$\approx$$
≈
150 m. This data, which is consistent with that derived from analysis of a quarry blast, provide a first assessment of the elastic properties of the rock materials at the site candidate to hosting ET.
SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment
Authors: Sodir Nicole M. , Pathria Gaurav , Adamkewicz Joanne I. , Kelley Elizabeth H. , Sudhamsu Jawahar , Merchant Mark , Chiarle Roberto , Maddalo Danilo 
Published: September 2023

Abstract

The protein phosphatase SHP2/PTPN11 has been reported to be a key modulator of proliferative pathways in a wide range of malignancies. Intriguingly, SHP2 has also been described as a critical regulator of the tumor microenvironment. Based on this evidence SHP2 is considered a multifaceted target in cancer, spurring the notion that the development of direct inhibitors of SHP2 would provide the twofold benefit of tumor intrinsic and extrinsic inhibition. In this review, we will discuss the role of SHP2 in cancer and the tumor microenvironment, and the clinical strategies in which SHP2 inhibitors are leveraged as combination agents to improve therapeutic response.

Significance:
The SHP2 phosphatase functions as a pleiotropic factor, and its inhibition not only hinders tumor growth but also reshapes the tumor microenvironment. Although their single-agent activity may be limited, SHP2 inhibitors hold the potential of being key combination agents to enhance the depth and the durability of tumor response to therapy.
Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction
Authors: Adams William P. , Raisch Tristan B. , Zhao Yajun , Davalos Rafael , Barrett Sarah , King D. Ryan , Bain Chandra B. , Colucci-Chang Katrina , Blair Grace A. , Hanlon Alexandra , Lozano Alicia , Veeraraghavan Rengasayee , Wan Xiaoping , Deschenes Isabelle , Smyth James W. , Hoeker Gregory S. , Gourdie Robert G. , Poelzing Steven 
Published: September 2023

BACKGROUND:
Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces.

METHODS:
Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs.

RESULTS:
CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width.

CONCLUSIONS:
Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.
Clonal Hematopoiesis in Clinical and Experimental Heart Failure With Preserved Ejection Fraction
Authors: Cochran Jesse D. , Yura Yoshimitsu , Thel Mark C. , Doviak Heather , Polizio Ariel H. , Arai Yuka , Arai Yohei , Horitani Keita , Park Eunbee , Chavkin Nicholas W. , Kour Anupreet , Sano Soichi , Mahajan Nitin , Evans Megan , Huba Mahalia , Naya Nadia Martinez , Sun Hanna , Ban Young Ho , Hirschi Karen K. , Toldo Stefano , Abbate Antonio , Druley Todd E. , Ruberg Frederick L. , Maurer Mathew S. , Ezekowitz Justin A. , Dyck Jason R.B. , Walsh Kenneth 
Published: September 2023

BACKGROUND:
Clonal hematopoiesis (CH), which results from an array of nonmalignant driver gene mutations, can lead to altered immune cell function and chronic disease, and has been associated with worse outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the role of CH in the prognosis of HF with preserved ejection fraction (HFpEF) has been understudied. This study aimed to characterize CH in patients with HFpEF and elucidate its causal role in a murine model.

METHODS:
Using a panel of 20 candidate CH driver genes and a variant allele fraction cutoff of 0.5%, ultradeep error-corrected sequencing identified CH in a cohort of 81 patients with HFpEF (mean age, 71±6 years; ejection fraction, 63±5%) and 36 controls without a diagnosis of HFpEF (mean age, 74±7 years; ejection fraction, 61.5±8%). CH was also evaluated in a replication cohort of 59 individuals with HFpEF.

RESULTS:

Compared with controls, there was an enrichment of
TET2
-mediated CH in the HFpEF patient cohort (12% versus 0%, respectively;
P
=0.02). In the HFpEF cohort, patients with CH exhibited exacerbated diastolic dysfunction in terms of E/e′ (14.9 versus 11.7, respectively;
P
=0.0096) and E/A (1.69 versus 0.89, respectively;
P
=0.0206) compared with those without CH. The association of CH with exacerbated diastolic dysfunction was corroborated in a validation cohort of individuals with HFpEF. In accordance, patients with HFpEF, an age ≥70 years, and CH exhibited worse prognosis in terms of 5-year cardiovascular-related hospitalization rate (hazard ratio, 5.06;
P
=0.042) compared with patients with HFpEF and an age ≥70 years without CH. To investigate the causal role of CH in HFpEF, nonconditioned mice underwent adoptive transfer with
Tet2
–wild-type or
Tet2
-deficient bone marrow and were subsequently subjected to a high-fat diet/L-NAME (N
ω
-nitro-l-arginine methyl ester) combination treatment to induce features of HFpEF. This model of
Tet2
-CH exacerbated cardiac hypertrophy by heart weight/tibia length and cardiomyocyte size, diastolic dysfunction by E/e′ and left ventricular end-diastolic pressure, and cardiac fibrosis compared with the
Tet2
–wild-type condition.

CONCLUSIONS:

CH is associated with worse heart function and prognosis in patients with HFpEF, and a murine experimental model of
Tet2
-mediated CH displays greater features of HFpEF.
On the Efficacy of Monin–Obukhov and Bulk Richardson Surface-Layer Parameterizations over Drylands
Authors: Lee Temple R. , Pal Sandip , Krishnan Praveena , Hirth Brian , Heuer Mark , Meyers Tilden P. , Saylor Rick D. , Schroeder John 
Published: September 2023

Abstract
Surface-layer parameterizations for heat, mass, momentum, and turbulence exchange are a critical component of the land surface models (LSMs) used in weather prediction and climate models. Although formulations derived from Monin–Obukhov similarity theory (MOST) have long been used, bulk Richardson (Rib) parameterizations have recently been suggested as a MOST alternative but have been evaluated over a limited number of land-cover and climate types. Examining the parameterizations’ applicability over other regions, particularly drylands that cover approximately 41% of terrestrial land surfaces, is a critical step toward implementing the parameterizations into LSMs. One year (1 January–31 December 2018) of eddy covariance measurements from a 10-m tower in southeastern Arizona and a 200-m tower in western Texas were used to determine how well the Rib parameterizations for friction velocity (), sensible heat flux (H), and turbulent kinetic energy (TKE) compare against MOST-derived parameterizations of these quantities. Independent of stability, wind speed regime, and season, the Rib and TKE parameterizations performed better than the MOST parameterizations, whereas MOST better represented H. Observations from the 200-m tower indicated that the parameterizations’ performance degraded as a function of height above ground. Overall, the Rib parameterizations revealed promising results, confirming better performance than traditional MOST relationships for kinematic (i.e., ) and turbulence (i.e., TKE) quantities, although caution is needed when applying the Rib H parameterizations to drylands. These findings represent an important milestone for the applicability of Rib parameterizations, given the large fraction of Earth’s surface covered by drylands.

Significance Statement
Weather forecasting models rely upon complex mathematical relationships to predict temperature, wind, and moisture. Monin–Obukhov similarity theory (MOST) has long been used to forecast these quantities near the land surface, even though MOST’s limitations are well known in the scientific community. Researchers have suggested an alternative to MOST called the bulk Richardson (Rib) approach. To allow for the Rib approach to be used in weather forecasting models, the approach needs to be tested over different land-cover and climate types. In this study, we applied the Rib approach to dry areas of the United States and found that the approach better represented turbulence variables than MOST relationships. These findings are an important step toward using Rib relationships in weather forecasting models.