bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of synthetic peptide RP557 and its origin, LL-37, on carbapenem-resistant
Pseudomonas aeruginosa
Authors: Song Yun-Qi , Kyung Su Min , Kim Suji , Kim Gun , Lee So Yeong , Yoo Han Sang 
Published: August 2023

ABSTRACT

Pseudomonas aeruginosa
is a common bacterium in nosocomial infection. The biofilm-forming ability and antimicrobial resistance make
P. aeruginosa
biofilm infection refractory to patients requiring hospitalization, especially patients in the intensive care unit. Therefore, many alternative compounds have been developed. A newly synthesized peptide, RP557, derived from human cathelicidin LL-37, was evaluated for its antimicrobial and antibiofilm effect toward carbapenem-resistant
P. aeruginosa
(CRPA). The results showed that regardless of the resistance to carbapenems, the minimal inhibition concentrations of RP557 and LL-37 against
P. aeruginosa
were 32 µg/mL and 256 µg/mL, respectively. Both RP557 and LL-37 significantly reduced the
P. aeruginosa
biofilm mass at subMICs, while subMICs of carbapenems induced biofilm formation. RP557 could also remove approximately 50% of the mature biofilm at a concentration of 64 µg/mL, while 256 µg/mL LL-37 was needed to remove it. A quarter MIC of RP557 and LL-37 was used together with carbapenems (ertapenem, imipenem, and meropenem). The results show that both RP-557 and LL-37 might increase the susceptibility to CRPA by 4–16 times. Significant gene expression level changes were observed in RP557- or LL-37-treated CRPA. Confocal images showed that biofilm structures and biofilm cell viability were significantly reduced in the LL-37- or RP557-treated groups. Therefore, RP557 and its structural origin, LL-37, could be potential treatments for carbapenem-resistant
P. aeruginosa
infection, especially for chronic biofilm infection.

IMPORTANCE

Pseudomonas aeruginosa
is one of the major pathogens of nosocomial infection. Combined its biofilm-forming ability with carbapenem-resistance, it is hard to handle
P. aeruginosa
infection, especially for patients requiring hospitalization. Antimicrobial peptide is a type of potential compound for bacterial infection treatment. Among these, RP557 was found effective in inhibiting biofilm previously. By assessing its effect on both carbapenem-resistant
P. aeruginosa
planktonic cells and biofilm, our results offered a potential treatment for carbapenem-resistant
P. aeruginosa
infection. It could be helpful to treat severe nosocomial infection related to carbapenem-resistant bacteria and increase the patients’ survival rate.
Paleocene Glauconite of the Near-Volga Monocline of Submarine Volcanic Sedimentary Genesis
Authors: Nikulin Iv. Iv. , Boeva N. M. , Soboleva S. V. , Bortnikov N. S. 
Published: August 2023

Abstract
A new concept of the formation of glauconite from the Paleocene deposits of the sedimentary cover of the southwestern part of the Near-Volga monocline is presented. It was formed as a result of halmyrolysis of ash material in lake conditions. Glauconitization is confined to the Paleogene thermal maximum and the periphery of active volcanism along the entire mobile belt. In this connection, it is widely distributed in the Paleogene deposits. Structural and crystal-chemical features of glauconite, stages of crystallization of its aggregates, paragenetic associations with smectite, kaolinite, and zeolite, as well as the presence of ore minerals indicate its authigenic origin. The authigenic origin is confined to the formations of temporary, episodically submerging shallow marine basins. An applied scheme of discrimination of glauconites by their crystallochemical features has been developed. The discrimination diagram can be used to determine the specific conditions of the sedimentation basin, which are expressed in the progradation cycles of glauconite accumulation. The cycles were controlled by induced depressions within the Russian plate.
Allosteric Regulation of Switch-II Domain Controls KRAS Oncogenicity
Authors: Yang Moon Hee , Tran Timothy H. , Hunt Bethany , Agnor Rebecca , Johnson Christian W. , Shui Bing , Waybright Timothy J. , Nowak Jonathan A. , Stephen Andrew G. , Simanshu Dhirendra K. , Haigis Kevin M. 
Published: August 2023

Abstract

RAS proteins are GTPases that regulate a wide range of cellular processes. RAS activity is dependent on its nucleotide-binding status, which is modulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). KRAS can be acetylated at lysine 104 (K104), and an acetylation-mimetic mutation of K104 to glutamine (K104Q) attenuates the in vitro–transforming capacity of oncogenic KRAS by interrupting GEF-induced nucleotide exchange. To assess the effect of this mutation in vivo, we used CRISPR-Cas9 to generate mouse models carrying the K104Q point mutation in wild-type and conditional KrasLSL-G12D alleles. Homozygous animals for K104Q were viable, fertile, and arose at the expected Mendelian frequency, indicating that K104Q is not a complete loss-of-function mutation. Consistent with our previous findings from in vitro studies, however, the oncogenic activity of KRASG12D was significantly attenuated by mutation at K104. Biochemical and structural analysis indicated that the G12D and K104Q mutations cooperate to suppress GEF-mediated nucleotide exchange, explaining the preferential effect of K104Q on oncogenic KRAS. Furthermore, K104 functioned in an allosteric network with M72, R73, and G75 on the α2 helix of the switch-II region. Intriguingly, point mutation of glycine 75 to alanine (G75A) also showed a strong negative regulatory effect on KRASG12D. These data demonstrate that lysine at position 104 is critical for the full oncogenic activity of mutant KRAS and suggest that modulating the sites in its allosteric network may provide a unique therapeutic approach in cancers expressing mutant KRAS.

Significance:
An allosteric network formed by interaction between lysine 104 and residues in the switch-II domain is required for KRAS oncogenicity, which could be exploited for developing inhibitors of the activated oncoprotein.
Demethylation of EHMT1/GLP Protein Reprograms Its Transcriptional Activity and Promotes Prostate Cancer Progression
Authors: Besschetnova Anna , Han Wanting , Liu Mingyu , Gao Yanfei , Li Muqing , Wang Zifeng , Labaf Maryam , Patalano Susan , Venkataramani Kavita , Muriph Rachel E. , Macoska Jill A. , Siegfried Kellee R. , Evans Jason , Balk Steven P. , Gao Shuai , Han Dong , Cai Changmeng 
Published: August 2023

Epigenetic reprogramming, mediated by genomic alterations and dysregulation of histone reader and writer proteins, plays a critical role in driving prostate cancer progression and treatment resistance. However, the specific function and regulation of EHMT1 (also known as GLP) and EHMT2 (also known as G9A), well-known histone 3 lysine 9 methyltransferases, in prostate cancer progression remain poorly understood. Through comprehensive investigations, we discovered that both EHMT1 and EHMT2 proteins have the ability to activate oncogenic transcription programs in prostate cancer cells. Silencing EHMT1/2 or targeting their enzymatic activity with small-molecule inhibitors can markedly decrease prostate cancer cell proliferation and metastasis in vitro and in vivo. In-depth analysis of posttranslational modifications of EHMT1 protein revealed the presence of methylation at lysine 450 and 451 residues in multiple prostate cancer models. Notably, we found that lysine 450 can be demethylated by LSD1. Strikingly, concurrent demethylation of both lysine residues resulted in a rapid and profound expansion of EHMT1’s chromatin binding capacity, enabling EHMT1 to reprogram the transcription networks in prostate cancer cells and activate oncogenic signaling pathways. Overall, our studies provide valuable molecular insights into the activity and function of EHMT proteins during prostate cancer progression. Moreover, we propose that the dual-lysine demethylation of EHMT1 acts as a critical molecular switch, triggering the induction of oncogenic transcriptional reprogramming in prostate cancer cells. These findings highlight the potential of targeting EHMT1/2 and their demethylation processes as promising therapeutic strategies for combating prostate cancer progression and overcoming treatment resistance.

Significance:
In this study, we demonstrate that EHMT1 and EHMT2 proteins drive prostate cancer development by transcriptionally activating multiple oncogenic pathways. Mechanistically, the chromatin binding of EHMT1 is significantly expanded through demethylation of both lysine 450 and 451 residues, which can serve as a critical molecular switch to induce oncogenic transcriptional reprogramming in prostate cancer cells.
Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor
Authors: Lal Shruti , Bhola Neil E. , Sun Bee-Chun , Chen Yuping , Huang Tom , Morton Vivian , Chen Kevin X. , Xia Shanghua , Zhang Haoyu , Parikh Nehal S. , Ye Qiuping , Veiby O. Petter , Bellovin David I. , Ji Yuhua 
Published: August 2023

DNA-dependent protein kinase (DNA-PK), a driver of the non-homologous end-joining (NHEJ) DNA damage response pathway, plays an instrumental role in repairing double-strand breaks (DSB) induced by DNA-damaging poisons. We evaluate ZL-2201, an orally bioavailable, highly potent, and selective pharmacologic inhibitor of DNA-PK activity, for the treatment of human cancerous malignancies. ZL-2201 demonstrated greater selectivity for DNA-PK and effectively inhibited DNA-PK autophosphorylation in a concentration- and time-dependent manner. Initial data suggested a potential correlation between ataxia-telangiectasia mutated (ATM) deficiency and ZL-2201 sensitivity. More so, ZL-2201 showed strong synergy with topoisomerase II inhibitors independent of ATM status in vitro. In vivo oral administration of ZL-2201 demonstrated dose-dependent antitumor activity in the NCI-H1703 xenograft model and significantly enhanced the activity of approved DNA-damaging agents in A549 and FaDu models. From a phosphoproteomic mass spectrometry screen, we identified and validated that ZL-2201 and PRKDC siRNA decreased Ser108 phosphorylation of MCM2, a key DNA replication factor. Collectively, we have characterized a potent and selective DNA-PK inhibitor with promising monotherapy and combinatory therapeutic potential with approved DNA-damaging agents. More importantly, we identified phospho-MCM2 (Ser108) as a potential proximal biomarker of DNA-PK inhibition that warrants further preclinical and clinical evaluation.

Significance:
ZL-2201, a potent and selective DNA-PK inhibitor, can target tumor models in combination with DNA DSB-inducing agents such as radiation or doxorubicin, with potential to improve recurrent therapies in the clinic.
Seabirds in the North-East Atlantic
Authors: Häkkinen Henry , Petrovan Silviu O. , Taylor Nigel G. , Sutherland William J. , Pettorelli Nathalie 
Published: August 2023

This book was produced by the Zoological Society of London and the University of Cambridge with two aims: to assess seabirds’ vulnerability to climate change in the North-East Atlantic, and to identify potential conservation actions that could reduce this vulnerability.
'Seabirds in the North-East Atlantic' collates information from the scientific literature, non-governmental organisations’ reports, conservation practitioner input and online databases into a single volume, and provides a reference manual to assist conservation planning. It is intended to be used by anyone who wishes to identify climate change threats to seabirds; to compare threats between different areas of the North-East Atlantic; to start a quantitative climate change vulnerability assessment for a local population; or to review options for conservation action in response to climate change.
This book stems from research published in December 2022, but assessments may be updated based on feedback and newly available information. To check for updates to our assessments, please visit our website at: www.ZSL.org/seabird-guidelines.
5. Loons/Divers and Grebes (Gaviidae and Podicipedidae)
Authors: Häkkinen Henry , Petrovan Silviu O. , Taylor Nigel G. , Sutherland William J. , Pettorelli Nathalie 
Published: August 2023

With key information linked to thematic maps, this section evaluates the climate change vulnerability of five species of loons/divers and grebes (Gaviidae and Podicipedidae) – Arctic Loon, Common Loon, Red-Throated Loon, Horned Grebe, and Red-necked Grebe – in the North-East Atlantic. The assessments for every species cover three categories each: the exposure, or the magnitude in percentage and the characteristics of climate change; the sensitivity, or how much and by which climatic events the species are affected, depending on their biological features; the adaptive capacity, or the potential of species to respond to climate change.
Updates to this section will follow, as the impacts of climate change on loons/divers and grebes are currently unidentified.
8. Terns (Laridae)
Authors: Häkkinen Henry , Petrovan Silviu O. , Taylor Nigel G. , Sutherland William J. , Pettorelli Nathalie 
Published: August 2023

With key information linked to thematic maps, this section evaluates the climate change vulnerability of five terns (Laridae) species – Arctic Tern, Little Tern, Roseate Tern, Sandwich Tern, and Caspian Tern – in the North-East Atlantic. The assessments for every species cover three categories each: the exposure, or the magnitude in percentage and the characteristics of climate change; the sensitivity, or how much and by which climatic events the species are affected, depending on their biological features; the adaptive capacity, or the potential of species to respond to climate change.
Assessments of local conservation actions that can be implemented to reduce climate change impacts are listed here in readily consultable tables. This section focuses on the effectiveness of interventions to limit reduced prey availability and the destruction of terns’ nests caused by storms. Criteria of relevance, strength, and transparency measure the effectiveness of the actions.
Evaluation of WRF Model Boundary Layer Schemes in Simulating Temperature and Heat Extremes over the Middle East–North Africa (MENA) Region
Authors: Ntoumos Athanasios , Hadjinicolaou Panos , Zittis George , Constantinidou Katiana , Tzyrkalli Anna , Lelieveld Jos 
Published: August 2023

Abstract
We assess the sensitivity of the Weather Research and Forecasting (WRF) Model to the use of different planetary boundary layer (PBL) parameterizations focusing on air temperature and extreme heat conditions. This work aims to evaluate the performance of the WRF Model in simulating temperatures across the Middle East–North Africa (MENA) domain, explain the model biases resulting from the choice of different PBL schemes, and identify the best-performing configuration for the MENA region. Three different PBL schemes are used to downscale the ECMWF ERA-Interim climate over the MENA region at a horizontal resolution of 24 km, for the period 2000–10. These are the Mellor–Yamada–Janjić (MYJ), Yonsei University (YSU), and the asymmetric convective model, version 2 (ACM2). For the evaluation of the WRF runs, we used related meteorological variables from the ERA5 reanalysis, including summer maximum and minimum 2-m air temperature and heat extreme indices. Our results indicate that simulations tend to overestimate maximum temperatures and underestimate minimum temperatures, and we find that model errors are very dependent on the geographic location. The possible physical causes of model biases are investigated through the analysis of additional variables (such as boundary layer height, moisture, and heat fluxes). It is shown that differences among the PBL schemes are associated with differences in vertical mixing strength, which alters the magnitude of the entrainment of free-tropospheric air into the PBL. The YSU is found to be the best-performing scheme, and it is recommended in WRF climate simulations for the MENA region.
A Moist Potential Vorticity Model for Midlatitude Long-Lived Mesoscale Convective Systems over Land
Authors: Yang Qiu , Leung L. Ruby , Feng Zhe , Chen Xingchao 
Published: August 2023

Abstract
Mesoscale convective systems (MCSs) bring large amounts of rainfall and strong wind gusts to the midlatitude land regions, with significant impacts on local weather and hydrologic cycle. However, weather and climate models face a huge challenge in accurately modeling the MCS life cycle and the associated precipitation, highlighting an urgent need for a better understanding of the underlying mechanisms of MCS initiation and propagation. From a theoretical perspective, a suitable model to capture the realistic properties of MCSs and isolate the bare-bones mechanisms for their initiation, intensification, and eastward propagation is still lacking. To simulate midlatitude MCSs over land, we develop a simple moist potential vorticity (PV) model that readily describes the interactions among PV perturbations, air moisture, and soil moisture. Multiple experiments with or without various environmental factors and external forcing are used to investigate their impacts on MCS dynamics and mesoscale circulation vertical structures. The result shows that mechanical forcing can induce lower-level updraft and cooling, providing favorable conditions for MCS initiation. A positive feedback among surface winds, evaporation rate, and air moisture similar to the wind-induced surface heat exchange over tropical ocean is found to support MCS intensification. Both background surface westerlies and vertical westerly wind shear are shown to provide favorable conditions for the eastward propagation of MCSs. Last, our result highlights the crucial role of stratiform heating in shaping mesoscale circulation response. The model should serve as a useful tool for understanding the fundamental mechanisms of MCS dynamics.
Regimes of Soil Moisture–Wet-Bulb Temperature Coupling with Relevance to Moist Heat Stress
Authors: Kong Qinqin , Huber Matthew 
Published: August 2023

Abstract
Human heat stress depends jointly on atmospheric temperature and humidity. Wetter soils reduce temperature but also raise humidity, making the collective impact on heat stress unclear. To better understand these interactions, we use ERA5 to examine the coupling between daily average soil moisture and wet-bulb temperature (Tw) and its seasonal and diurnal cycle at global scale. We identify a global soil moisture–Tw coupling pattern with both widespread negative and positive correlations in contrast to the well-established cooling effect of wet soil on dry-bulb temperature. Regions showing positive correlations closely resemble previously identified land–atmosphere coupling hotspots where soil moisture effectively controls surface energy partition. Soil moisture–Tw coupling varies seasonally closely tied to monsoon development, and the positive coupling is slightly stronger and more widespread during nighttime. Local-scale analysis demonstrates a nonlinear structure of soil moisture–Tw coupling with stronger coupling under relatively dry soils. Hot days with high Tw values show wetter-than-normal soil, anomalous high latent and low sensible heat flux from a cooler surface, and a shallower boundary layer. This supports the hypothesis that wetter soil increases Tw by concentrating surface moist enthalpy flux within a shallower boundary layer and reducing free-troposphere-air entrainment. We identify areas of particular interest for future studies on the physical mechanisms of soil moisture–heat stress coupling. Our findings suggest that increasing soil moisture might amplify heat stress over large portions of the world including several densely populated areas. These results also raise questions about the effectiveness of evaporative cooling strategies in ameliorating urban heat stress.

Significance Statement
The purpose of this study is to provide a global picture of the relationship between soil moisture anomalies and a heat stress metric that includes the joint effects of temperature and humidity. This is important because a better understanding of this relationship will help improve the prediction of extreme heat stress events and inform strategies for ameliorating heat stress. We find a widespread positive correlation between soil moisture and heat stress, in contrast to studies relying on temperature alone. This raises the possibility that, over much of the world, and in the most populous regions, strategies like irrigation or “greening” that can reduce temperature might be ineffective or even harmful in reducing heat stress with humidity incorporated.
Motor neurone disease: A point-prevalence study of patient reported symptom prevalence, severity and palliative care needs
Authors: Runacres Fiona , Mathers Susan , Lee Sarah CM , Hearn Rowan , Gregory Sonia , Bear Natasha , Aoun Samar 
Published: August 2023

Background: Motor neurone disease is a rare but debilitating illness with incomplete evidence regarding patients’ symptom burden. Palliative care and generalist clinicians are often in-experienced in caring for these patients and assessing their needs. Aim: To identify the symptom prevalence and severity experienced by patients with motor neurone disease. Secondary objectives were to examine differences in symptom burden and clusters according to phenotype, functional status, palliative care provision and those in their last months of life. Design: A point prevalence study assessing patient-reported symptoms using a modified IPOS-Neuro assessment tool, incorporating 41 symptom items. Setting/participants: Patients with motor neurone disease attending the State-wide Progressive Neurological Disease Service or inpatient unit at Calvary Health Care Bethlehem, Melbourne Australia, from March to December 2021. Results: A total of 102 patients participated, the majority diagnosed with lumber-onset (30.4%), bulbar-onset (28.4%) and cervical-onset (25.5%) phenotypes. Patients experienced a median of 17 symptoms (range 2–32) with a median of 3 symptoms rated as severe/overwhelming (range 0–13). Motor and functional symptoms predominated, with differences in symptom clusters present according to phenotype. Patients had a higher number of severe/overwhelming symptoms if they were accessing palliative care services ( p = 0.005), in their last 6 months of life ( p = 0.003) and experiencing moderate or severe functional impairment ( p < 0.001). Conclusions: Patients with motor neurone disease report high symptom burden. A validated motor neurone disease-specific symptom assessment tool is needed to accurately assess patients, including important variations in symptom clusters according to phenotype. Further research must focus on evidence-based treatment guidelines for symptoms experienced commonly and severely.