bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic control of the error-prone repair of a chromosomal double-strand break with 5′ overhangs in yeast
Authors: Shaltz Samantha , Jinks-Robertson Sue 
Published: July 2023

Abstract
A targeted double-strand break introduced into the genome of Saccharomyces cerevisiae is repaired by the relatively error-prone nonhomologous end joining (NHEJ) pathway when homologous recombination is not an option. A zinc finger nuclease cleavage site was inserted out-of-frame into the LYS2 locus of a haploid yeast strain to study the genetic control of NHEJ when the ends contain 5′ overhangs. Repair events that destroyed the cleavage site were identified either as Lys+ colonies on selective medium or as surviving colonies on rich medium. Junction sequences in Lys+ events solely reflected NHEJ and were influenced by the nuclease activity of Mre11 as well as by the presence/absence of the NHEJ-specific polymerase Pol4 and the translesion-synthesis DNA polymerases Pol ζ and Pol η. Although most NHEJ events were dependent on Pol4, a 29-bp deletion with endpoints in 3-bp repeats was an exception. The Pol4-independent deletion required translesion synthesis polymerases as well as the exonuclease activity of the replicative Pol δ DNA polymerase. Survivors were equally split between NHEJ events and 1.2 or 11.7 kb deletions that reflected microhomology-mediated end joining (MMEJ). MMEJ events required the processive resection activity of Exo1/Sgs1, but there unexpectedly was no dependence on the Rad1–Rad10 endonuclease for the removal of presumptive 3′ tails. Finally, NHEJ was more efficient in nongrowing than in growing cells and was most efficient in G0 cells. These studies provide novel insights into the flexibility and complexity of error-prone DSB repair in yeast.
Telehealth Use Among Older Adults With Sensory, Cognitive, and Physical Impairments: A Substitute or Supplement to Traditional Care?
Authors: Choi Shinae L , Carr Deborah , Namkung Eun Ha 
Published: July 2023

Abstract

Objectives
Telehealth use flourished during the COVID-19 pandemic, as older patients faced obstacles to seeking in-person care. Heavy reliance on telehealth may continue postpandemic, due to increased Medicare investments in its use. However, it is unclear if older adults with disabilities face obstacles to effective telehealth use. We evaluate (a) how sensory, physical, and cognitive impairments affect older adults’ use of telehealth only, traditional in-person care only, neither, or both (i.e., combined care); and (b) whether these patterns differ on the basis of socioeconomic and social resources that may facilitate telehealth use.

Method
Data are from the Self-Administered Questionnaire in the 2020 wave of the Health and Retirement Study (n = 4,453). We estimated multinomial logistic regression models to evaluate associations between impairments and health care service use and tested 2-way interaction terms to evaluate moderation effects.

Results
Persons without impairments were most likely to use combined care, considered the optimal form of care. Persons with vision or cognitive impairment were more likely to use telehealth or traditional care only, whereas persons with 3 or more physical limitations were least likely to use telehealth alone, relative to combined care. Patterns did not differ significantly on the basis of any of the potential moderators.

Discussion
We discuss implications for health care policy and practice, in light of reimbursement changes proposed by the Centers for Medicare and Medicaid Services for telehealth services. These proposals include the elimination of voice-only services which may be particularly beneficial to vision-impaired older adults.
PnMYB4 negatively modulates saponin biosynthesis in Panax notoginseng through interplay with PnMYB1
Authors: Man Jinhui , Shi Yue , Huang Yuying , Zhang Xiaoqin , Wang Xin , Liu Shanhu , He Gaojie , An Kelu , Han Dongran , Wang Xiaohui , Wei Shengli 
Published: July 2023

Abstract
Saponins are the main triterpenoid ingredients from Panax notoginseng, a well-known Chinese medicine, and are important sources for producing drugs to prevent and treat cerebrovascular and cardiovascular diseases. However, the transcriptional regulatory network of saponin biosynthesis in P. notoginseng is largely unknown. In the present study we demonstrated that one R2R3-MYB transcription factor, designated PnMYB4, acts as a repressor of saponin accumulation. Suppression of PnMYB4 in P. notoginseng calli significantly increased the saponin content and the expression level of saponin biosynthetic genes. PnMYB4 directly bound to the promoters of key saponin biosynthetic genes, including PnSS, PnSE, and PnDS, to repress saponin accumulation. PnMYB4 and the activator PnMYB1 could interacted with PnbHLH, which is a positive regulator of saponin biosynthesis, to modulate the biosynthesis of saponin. PnMYB4 competed with PnMYB1 for binding to PnbHLH, repressing activation of the promoters of saponin structural genes induced by the PnMYB1-PnbHLH complex. Our study reveals that a complex regulatory module of saponin biosynthesis is associated with positive and negative MYB transcriptional regulators and provides a theoretical basis for improving the content of saponins and efficacy of P. notoginseng.
Dynamic ranking and translation synchronization
Authors: Araya Ernesto , Karlé Eglantine , Tyagi Hemant 
Published: July 2023

Abstract
In many applications, such as sport tournaments or recommendation systems, we have at our disposal data consisting of pairwise comparisons between a set of $n$ items (or players). The objective is to use these data to infer the latent strength of each item and/or their ranking. Existing results for this problem predominantly focus on the setting consisting of a single comparison graph $G$. However, there exist scenarios (e.g. sports tournaments) where the pairwise comparison data evolve with time. Theoretical results for this dynamic setting are relatively limited, and are the focus of this paper. We study an extension of the translation synchronization problem, to the dynamic setting. In this set-up, we are given a sequence of comparison graphs $(G_t)_{t\in{{\mathscr{T}}}}$, where $ {{\mathscr{T}}} \subset [0,1]$ is a grid representing the time domain, and for each item $i$ and time $t\in{{\mathscr{T}}}$ there is an associated unknown strength parameter $z^*_{t,i}\in{{\mathbb{R}}}$. We aim to recover, for $t\in{{\mathscr{T}}}$, the strength vector $z^*_t=(z^*_{t,1},\dots ,z^*_{t,n})$ from noisy measurements of $z^*_{t,i}-z^*_{t,j}$, where $\left \{{i,j}\right \}$ is an edge in $G_t$. Assuming that $z^*_t$ evolves smoothly in $t$, we propose two estimators—one based on a smoothness-penalized least squares approach and the other based on projection onto the low-frequency eigenspace of a suitable smoothness operator. For both estimators, we provide finite sample bounds for the $\ell _2$ estimation error under the assumption that $G_t$ is connected for all $t\in{{\mathscr{T}}}$, thus proving the consistency of the proposed methods in terms of the grid size $|\mathscr{T}|$. We complement our theoretical findings with experiments on synthetic and real data.
Microencapsulation protected Lactobacillus viability and its activity in modulating the intestinal microbiota in newly weaned piglets
Authors: Li Linyan , Yin Fugui , Wang Xiaoyin , Yang Chongwu , Yu Hai , Lepp Dion , Wang Qi , Lessard Martin , Lo Verso Luca , Mondor Martin , Yang Chengbo , Nie Shaoping , Gong Joshua 
Published: July 2023

Abstract
Lactobacilli are sensitive to heat, which limits their application as probiotics in livestock production. Lactobacillus rhamnosus LB1 was previously shown to reduce enterotoxigenic Escherichia coli (ETEC) and Salmonella infections in pigs. To investigate its potential in the application, the bacterium was microencapsulated and examined for its survival from feed pelleting and long-term storage as well as its function in modulating pig intestinal microbiota. The in vitro studies showed that freshly microencapsulated Lactobacillus rhamnosus LB1 had viable counts of 9.03 ± 0.049 log10 colony-forming units/g, of which only 0.06 and 0.87 Log of viable counts were reduced after storage at 4 and 22 °C for 427 d. The viable counts of encapsulated Lactobacillus rhamnosus LB1 were 1.06 and 1.54 Log higher in the pelleted and mash feed, respectively, than the non-encapsulated form stored at 22 °C for 30 d. In the in vivo studies, 80 piglets (weaned at 21 d of age) were allocated to five dietary treatments for a 10-d growth trial. The dietary treatments were the basal diet (CTL) and basal diet combined with either non-encapsulated LB1 (NEP), encapsulated LB1 (EP), bovine colostrum (BC), or a combination of encapsulated LB1 and bovine colostrum (EP-BC). The results demonstrated that weaning depressed feed intake and reduced growth rates in pigs of all the treatments during 21 to 25 d of age; however, the body weight gain was improved during 25 to 31 d of age in all groups with the numerically highest increase in the EP-BC-fed pigs during 21 to 31 d of age. Dietary treatments with EP, particularly in combination with BC, modulated pig intestinal microbiota, including an increase in Lactobacillus relative abundance. These results suggest that microencapsulation can protect Lactobacillus rhamnosus LB1 against cell damage from a high temperature during processing and storage and there are possible complementary effects between EP and BC.
Bees and thrips carry virus-positive pollen in peach orchards in South Carolina, United States
Authors: Tayal Mandeep , Wilson Christopher , Cieniewicz Elizabeth 
Published: July 2023

Abstract
Prunus necrotic ringspot virus (PNRSV) and prune dwarf virus (PDV) are pollen-borne viruses of important stone fruit crops, including peaches, which can cause substantial yield loss. Although both horizontal and vertical (i.e., seed) transmission of both viruses occurs through pollen, the role of flower-visiting insects in their transmission is not well understood. Bees and thrips reportedly spread PNRSV and PDV in orchards and greenhouse studies; however, the field spread of PNRSV and PDV in peach orchards in the southeastern United States is not explored. We hypothesized that bees and thrips may facilitate virus spread by carrying virus-positive pollen. Our 2-yr survey results show that 75% of captured bees are carrying virus-positive pollen and moving across the orchard while a subsample of thrips were also found virus positive. Based on morphology, Bombus, Apis, Andrena, Eucera, and Habropoda are the predominant bee genera that were captured in peach orchards. Understanding the role of bees and thrips in the spread of PNRSV and PDV will enhance our understanding of pollen-borne virus ecology.
Protein availability on Qinghai–Tibetan Plateau meadows determines density and life-history characteristics of plateau pikas (Ochotona curzoniae)
Authors: Wu Xueqin , Shang Guozhen , Chen Huiqing , Wu Yan , Hou Chu , Yang Yuangang , Zhang Lu , Cao Yifan , Bian Jianghui 
Published: July 2023

Abstract
Plateau pikas (Ochotona curzoniae) play a keystone role in the alpine meadow ecosystem on the Qinghai–Tibetan Plateau (QTP). For decades, alpine meadows on the QTP have suffered from severe degradation, predominantly due to livestock grazing and frequent dramatic increases in plateau pikas. The cause has long been thought to be that livestock grazing provides open habitats for pikas. However, open habitats with low food nutrient quality are insufficient to maintain high-density populations. Feeding facilitation is a process or action undertaken by one species whose activity benefits another species. However, the facilitative effects on population consequences remain unclear. Here, we examined the impact of feeding facilitation on the population dynamics of plateau pikas. We hypothesize that the high protein amount provided by meadows that have been overgrazed would be an important factor leading to dramatic increases in plateau pikas. We found that plateau pikas preferred high-protein foods, and relatively abundant high-protein food resources were found in meadows following high levels of livestock grazing. Body mass and amount of protein in stomach digesta of pikas were higher in moderately and heavily grazed meadows than in lightly grazed meadow. Thus, pika population density was associated with high-protein food resources. A supplemental protein experiment confirmed that high-protein foods led to higher pika population density by increasing reproductive performance. Livestock grazing increased the abundance of plateau pikas by shifting plant nutrient contents toward higher protein conditions favorable to them. Feeding facilitation is an important factor that causes a dramatic increase in plateau pikas.
Institutions That Influence Cross-Boundary Forest Management: Four Cases of Shared Stewardship in Practice
Authors: Aldworth Tyler , Schultz Courtney 
Published: July 2023

Abstract
The USDA Forest Service’s 2018 Shared Stewardship Strategy emphasizes the need to coordinate work with actors across boundaries to increase the pace and scale of land management, particularly as it relates to forest restoration and wildfire mitigation. We researched how the Strategy was being implemented at the project level by conducting forty-four interviews with individuals closely involved with four large-scale cross-boundary hazardous fuels reduction projects. Our objectives were to identify institutions that facilitated and challenged cross-boundary work under the Strategy and document how actors innovated to overcome challenges they encountered. We found that Shared Stewardship had the greatest opportunity to shift the larger forest management paradigm within states that created new institutions specifically to support the Strategy and its objectives. However, numerous institutional challenges such as yearly funding levels and complex bureaucratic requirements, frustrated efforts to increase the pace and scale of management actions under the Strategy.
Study Implications: We conducted research on cross-boundary projects that met the intent of the USDA Forest Service’s Shared Stewardship Strategy. We found that the cross-boundary tenets of the Strategy were best supported when states worked together with the federal government to create new institutions that facilitate multijurisdictional work. Our interviewees said that various bureaucratic hurdles remain difficult to navigate, and that they believe annual funding appropriations are not currently enough to support significant increases in the pace and scale of management. Our interviewees said Shared Stewardship supported cross-boundary actions, but more remains to be done to best support multijurisdictional work.
Fisetin alleviates chronic urticaria by inhibiting mast cell activation via MRGPRX2
Authors: Zhang Yonghui , Huang Yihan , Dang Baowen , Hu Shiting , Zhao Chenrui , Wang Yuejin , Yuan Yujuan , Liu Rui 
Published: July 2023

Abstract

Objectives
The activation of mast cell (MC) plays an important part in the pathogenesis of chronic urticaria (CU), and the expression of MRGPRX2 (Mas-related G-protein coupled receptor X2) and the circulating levels of SP (substance P) in skin MC of CU patients increased. Fisetin is a natural flavonoid with anti-inflammatory and antiallergic pharmacological effects. This study aimed to investigate the inhibitory effect of fisetin on CU via MRGPRX2 and its possible molecular mechanisms.

Methods
OVA/SP co-stimulated and SP-stimulated CU like murine models were used to evaluate the effect of fisetin on CU. MRGPRX2/HEK293 cells and LAD2 cells were used to perform the antagonism effect of fisetin on MC via MRGPRX2.

Key findings
The results indicated that fisetin prevented urticaria-like symptoms in murine CU models, and inhibited MCs activation by suppressing calcium mobilization and degranulation of cytokines and chemokines via binding to MRGPRX2. The bioinformatics analysis showed that fisetin might have an interaction relationship with Akt in CU. The western blotting experiments showed that fisetin downregulated the phosphorylation levels of Akt, P38, NF-κB, and PLCγ in C48/80 activated LAD2 cells.

Conclusions
Fisetin alleviates CU progression by inhibiting mast cell activation via MRGPRX2, which may be a novel therapeutic candidate for CU.
Incidental aortocaval fistula in the setting of an unruptured abdominal aortic aneurysm
Authors: Sohail Amir H , Cohen Koral , Ho Kimberly , Cimaroli Sawyer , Brathwaite Collin E M , Shin Patrick 
Published: July 2023

Abstract
An aortocaval fistula, a rare abnormal vascular communication between the aorta and inferior vena cava, is most commonly associated with abdominal aortic aneurysms (AAAs). Other factors leading to aortocaval fistula formation include atherosclerosis, collagen vascular diseases, vasculitis, hematogenous infections, prior spinal surgery, malignancy and radiation exposure. In rare instances, aortocaval fistulas may be discovered incidentally on abdominal imaging. We report an unusual case of an incidental aortocaval fistula in a 93-year-old male patient with an unruptured AAA, presenting with shortness of breath, malaise and lethargy. The patient had no other obvious risk factors for aortocaval fistula formation. Multidetector computed tomography angiography helped identify the fistula, and the patient was eventually transferred to hospice for comfort measures. This case highlights the importance of detailed imaging and preoperative planning in managing aortocaval fistulas and associated AAAs.
Vietnam’s energy transition to 2050: is importing liquefied natural gas a good solution?
Authors: Minh Thong Le , Van Hiep Tran 
Published: July 2023

Abstract
Energy and the environment are among the biggest challenges facing humanity in the 21st century. The issue of the energy transition has become increasingly important as countries around the world seek to shift towards cleaner, more sustainable forms of energy. For a rapidly developing economy like Vietnam, the energy challenge becomes even more urgent. A reasonable energy transition strategy will be an important prerequisite for sustainable economic development, national security, environmental improvement and climate change mitigation. One potential solution that has been proposed is to increase imports of liquefied natural gas (LNG) to help meet Vietnam’s energy needs while reducing its reliance on coal. In this article, the author analyses the potential for Vietnam to import LNG in the future.
Partial stellar tidal disruption events and their rates
Authors: Bortolas Elisa , Ryu Taeho , Broggi Luca , Sesana Alberto 
Published: July 2023

ABSTRACT
Tidal disruption events (TDEs) of stars operated by massive black holes (MBHs) will be detected in thousands by upcoming facilities such as the Vera Rubin Observatory. In this work, we assess the rates of standard total TDEs, destroying the entire star, and partial TDEs, in which a stellar remnant survives the interaction, by solving 1D Fokker–Planck equations. Our rate estimates are based on a novel definition of the loss cone whose size is commensurate with the largest radius at which partial disruptions can occur, as motivated by relativistic hydrodynamical simulations. Our novel approach unveils two important results. First, partial TDEs can be more abundant than total disruptions by a factor of a few to a few tens. Second, the rates of complete stellar disruptions can be overestimated by a factor of a few to a few tens if one neglects partial TDEs, as we find that many of the events classified as total disruptions in the standard framework are in fact partial TDEs. Accounting for partial TDEs is particularly relevant for galaxies harbouring a nuclear stellar cluster featuring many events coming from the empty loss cone. Based on these findings, we stress that partial disruptions should be considered when constraining the luminosity function of TDE flares; accounting for this may reconcile the theoretically estimated TDE rates with the observed ones.
Structural basis for specific DNA sequence motif recognition by the TFAP2 transcription factors
Authors: Liu Ke , Xiao Yuqing , Gan Linyao , Li Weifang , Zhang Jin , Min Jinrong 
Published: July 2023

AbstractThe TFAP2 family regulates gene expression during differentiation, development, and organogenesis, and includes five homologs in humans. They all possess a highly conserved DNA binding domain (DBD) followed by a helix-span-helix (HSH) domain. The DBD-HSH tandem domain specifically binds to a GCC(N3)GGC consensus sequence, but the precise recognition mechanisms remain unclear. Here, we found that TFAP2 preferred binding to the GCC(N3)GGC sequence, and the pseudo-palindromic GCC and GGC motifs and the length of the central spacer between the two motifs determined their binding specificity. Structural studies revealed that the two flat amphipathic α-helical HSH domains of TFAP2A stacked with each other to form a dimer via hydrophobic interactions, while the stabilized loops from both DBD domains inserted into two neighboring major grooves of the DNA duplex to form base-specific interactions. This specific DNA binding mechanism controlled the length of the central spacer and determined the DNA sequence specificity of TFAP2. Mutations of the TFAP2 proteins are implicated in various diseases. We illustrated that reduction or disruption of the DNA binding ability of the TFAP2 proteins is the primary cause of TFAP2 mutation-associated diseases. Thus, our findings also offer valuable insights into the pathogenesis of disease-associated mutations in TFAP2 proteins.
Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells
Authors: Karschnia Philipp , Arrillaga-Romany Isabel C , Eichler April , Forst Deborah A , Gerstner Elizabeth , Jordan Justin T , Ly Ina , Plotkin Scott R , Wang Nancy , Martinez-Lage Maria , Winter Sebastian F , Tonn Joerg-Christian , Rejeski Kai , von Baumgarten Louisa , Cahill Daniel P , Nahed Brian V , Shankar Ganesh M , Abramson Jeremy S , Barnes Jeffrey A , El-Jawahri Areej , Hochberg Ephraim P , Johnson P Connor , Soumerai Jacob D , Takvorian Ronald W , Chen Yi-Bin , Frigault Matthew J , Dietrich Jorg 
Published: July 2023

Abstract

Background
Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for B-cell lymphomas; however, data for patients with central nervous system (CNS) involvement are limited.

Methods
We retrospectively report on CNS-specific toxicities, management, and CNS response of 45 consecutive CAR T-cell transfusions for patients with active CNS lymphoma at the Massachusetts General Hospital over a 5-year period.

Results
Our cohort includes 17 patients with primary CNS lymphoma (PCNSL; 1 patient with 2 CAR T-cell transfusions) and 27 patients with secondary CNS lymphoma (SCNSL). Mild ICANS (grade 1–2) was observed after 19/45 transfusions (42.2%) and severe immune effector cell-associated neurotoxicity syndrome (ICANS) (grade 3–4) after 7/45 transfusions (15.6%). A larger increase in C-reactive protein (CRP) levels and higher rates of ICANS were detected in SCNSL. Early fever and baseline C-reactive protein levels were associated with ICANS occurrence. CNS response was seen in 31 cases (68.9%), including a complete response of CNS disease in 18 cases (40.0%) which lasted for a median of 11.4 ± 4.5 months. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (hazard ratios [HR] per mg/d: 1.16, P = .031). If bridging therapy was warranted, the use of ibrutinib translated into favorable CNS-progression-free survival (5 vs. 1 month, HR 0.28, CI 0.1–0.7; P = .010).

Conclusions
CAR T-cells exhibit promising antitumor effects and a favorable safety profile in CNS lymphoma. Further evaluation of the role of bridging regimens and corticosteroids is warranted.