bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing the impact of autotrophic and heterotrophic metabolism on the nutrient regulation of TOR
Authors: Mallén‐Ponce Manuel J. , Pérez‐Pérez María Esther , Crespo José L. 
Published: September 2022

SummaryThe target of rapamycin (TOR) protein kinase is a master regulator of cell growth in all eukaryotes, from unicellular yeast and algae to multicellular animals and plants. Target of rapamycin balances the synthesis and degradation of proteins, lipids, carbohydrates and nucleic acids in response to nutrients, growth factors and cellular energy to promote cell growth. Among nutrients, amino acids (AAs) and glucose are central regulators of TOR activity in evolutionary distant eukaryotes such as mammals, plants and algae. However, these organisms obtain the nutrients through totally different metabolic processes. Although photosynthetic eukaryotes can use atmospheric CO2 as the sole carbon (C) source for all reactions in the cell, heterotrophic organisms get nutrients from other sources of organic C including glucose. Here, we discuss the impact of autotrophic and heterotrophic metabolism on the nutrient regulation of TOR, focusing on the role of AAs and C sources upstream of this signaling pathway.
What will happen when we become immortal?
Authors: Totschnig Wolfhart 
Published: September 2022

AbstractMany researchers are working toward the goal of finding a treatment that halts or even reverses the aging process of the human body, a treatment that would make the recipient potentially immortal. The hope that they will succeed in the relatively near future is gaining ground among academics and laypeople alike. What will happen if this hope becomes reality? Specifically, how will our political and social institutions and practices be affected by that discovery? These are the questions raised in the present paper. Concretely, I will discuss three political and social problems that the invention of an immortality treatment is likely to provoke, namely the struggle for access to that treatment, the threat of overpopulation, and the friction between potentially immortal individuals.
Peripheral blood CD4+ T cell count predicts recurrence of condyloma acuminatum after photodynamic therapy in HIV‐positive patients
Authors: Gu Li , Zhou Shu , Shi Zhinan , Zhai Xiaoyu , Gu Liqun , Zhou Bingrong , Hua Hui 
Published: September 2022

AbstractBackgroundFew studies have reported postoperative relapse of condyloma acuminatum (CA) after 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) in human immunodeficiency virus (HIV) positive patients.MethodsThe clinical data of HIV‐positive CA patients treated with ALA‐PDT from October 2018 to December 2019 were analyzed retrospectively. Univariate and multivariate Cox regression was used to analyze the variables related to postoperative recurrence. Pearson correlation test was employed to analyze the correlation between CD4+ T cell count and postoperative recurrence rate. Kaplan–Meier method was used to compare the CA recurrence after ALA‐PDT in low CD4 group and high CD4 group.ResultsA total of 38 HIV‐positive patients with CA were included in the study. Among them, 26 patients experienced CA recurrence within 6 months, and the recurrence rate was 68.4%. CD4+ T cell count was 187.0 (79.0–596.0) cells/μl in relapsed patients and 406.0 (89.0–612.0) cells/μl in non‐relapsed patients, showing a statistically significant difference (p = .005). Pearson correlation coefficient analysis revealed a negative correlation between CD4+ T cell count and postoperative recurrence rate (p = .005, r = −.443). Univariate regression analysis showed that CD4+ T cell count was correlated with postoperative recurrence, hazard ratio (HR) was 0.99 [95% Confidence interval (CI) = 0.99–1.0, p = .012]. Multivariate Cox regression analysis showed that with the low CD4+ T cell count as the reference, the high CD4+ T cell count was negatively correlated with postoperative recurrence (HR = 0.09, 95% CI 0.01–0.87, p = .038).ConclusionsPeripheral blood CD4+ T cell count can predict the CA recurrence rate after ALA‐PDT in HIV‐positive patients.
Evolutionary relationship analysis of STARD gene family and VvSTARD5 improves tolerance of salt stress in transgenic tomatoes
Authors: Lu Shixiong , He Honghong , Wang Ping , Gou Huiming , Cao Xuejing , Ma Zonghuan , Chen Baihong , Mao Juan 
Published: September 2022

AbstractThe steroidogenic acute regulatory protein‐related lipid transfer domain (STARD) forms a protein that can bind membrane‐derived phospholipid second messengers and plasma membranes. Although it has been reported in many plants, the evolutionary relationship of the STARD gene family has not been systematically analyzed, and functions of the HD‐START and HD‐START‐MEKHLA domain subgroup genes under hormone and abiotic stress are also unclear in grapes. This study identified and analyzed 23 VvSTARD genes, which were distinctly divided into five subgroups according to five conserved domain types. The analyses of codon preference, selective pressure, and synteny relationship revealed that grape had higher homology with Arabidopsis compared with rice. Interestingly, the expression levels of VvSTARD genes in subgroups 1, 2, and 3 exhibited significant upregulation under NaCl treatment at 24 h, but VvSTARD genes in subgroups 4 and 5 were upregulated under methyl jasmonate (MeJA) treatment at 24 h. The subcellular localization showed that VvSTARD5 was localized in the nucleus. Additionally, under NaCl treatment at 24 h, there were an obvious decrease in the relative electrical leakages and the content of malondialdehyde (MDA), while the relative expression level of VvSTARD5 and content of proline were obviously enhanced in three transgenic lines. Therefore, the overexpression of VvSTARD5 greatly increased the salt tolerance of transgenic tomatoes. Collectively, this study preliminarily explores the comprehensive function of the STARD gene family in grapes and verifies the function of VvSTARD5 in response to salt.
A seed‐like proteome in oil‐rich tubers
Authors: Niemeyer Philipp William , Irisarri Iker , Scholz Patricia , Schmitt Kerstin , Valerius Oliver , Braus Gerhard H. , Herrfurth Cornelia , Feussner Ivo , Sharma Shrikant , Carlsson Anders S. , de Vries Jan , Hofvander Per , Ischebeck Till 
Published: September 2022

SUMMARYThere are numerous examples of plant organs or developmental stages that are desiccation‐tolerant and can withstand extended periods of severe water loss. One prime example are seeds and pollen of many spermatophytes. However, in some plants, also vegetative organs can be desiccation‐tolerant. One example are the tubers of yellow nutsedge (Cyperus esculentus), which also store large amounts of lipids similar to seeds. Interestingly, the closest known relative, purple nutsedge (Cyperus rotundus), generates tubers that do not accumulate oil and are not desiccation‐tolerant. We generated nanoLC‐MS/MS‐based proteomes of yellow nutsedge in five replicates of four stages of tuber development and compared them to the proteomes of roots and leaves, yielding 2257 distinct protein groups. Our data reveal a striking upregulation of hallmark proteins of seeds in the tubers. A deeper comparison to the tuber proteome of the close relative purple nutsedge (C. rotundus) and a previously published proteome of Arabidopsis seeds and seedlings indicates that indeed a seed‐like proteome was found in yellow but not purple nutsedge. This was further supported by an analysis of the proteome of a lipid droplet‐enriched fraction of yellow nutsedge, which also displayed seed‐like characteristics. One reason for the differences between the two nutsedge species might be the expression of certain transcription factors homologous to ABSCISIC ACID INSENSITIVE3, WRINKLED1, and LEAFY COTYLEDON1 that drive gene expression in Arabidopsis seed embryos.
Integration of physiologically relevant photosynthetic energy flows into whole genome models of light‐driven metabolism
Authors: Broddrick Jared T. , Ware Maxwell A. , Jallet Denis , Palsson Bernhard O. , Peers Graham 
Published: September 2022

SUMMARYCharacterizing photosynthetic productivity is necessary to understand the ecological contributions and biotechnology potential of plants, algae, and cyanobacteria. Light capture efficiency and photophysiology have long been characterized by measurements of chlorophyll fluorescence dynamics. However, these investigations typically do not consider the metabolic network downstream of light harvesting. By contrast, genome‐scale metabolic models capture species‐specific metabolic capabilities but have yet to incorporate the rapid regulation of the light harvesting apparatus. Here, we combine chlorophyll fluorescence parameters defining photosynthetic and non‐photosynthetic yield of absorbed light energy with a metabolic model of the pennate diatom Phaeodactylum tricornutum. This integration increases the model predictive accuracy regarding growth rate, intracellular oxygen production and consumption, and metabolic pathway usage. Through the quantification of excess electron transport, we uncover the sequential activation of non‐radiative energy dissipation processes, cross‐compartment electron shuttling, and non‐photochemical quenching as the rapid photoacclimation strategy in P. tricornutum. Interestingly, the photon absorption thresholds that trigger the transition between these mechanisms were consistent at low and high incident photon fluxes. We use this understanding to explore engineering strategies for rerouting cellular resources and excess light energy towards bioproducts in silico. Overall, we present a methodology for incorporating a common, informative data type into computational models of light‐driven metabolism and show its utilization within the design–build–test–learn cycle for engineering of photosynthetic organisms.
A conscious minimally invasive approach to remove follicular cysts and infundibular keratinizing acanthomas in five dogs
Authors: Loek Rachael , Gardiner David , Laporte Carine 
Published: September 2022

AbstractFollicular cysts and infundibular keratinizing acanthomas are common benign cutaneous lesions in dogs. Current treatment options include surgical excision under general anaesthesia, cryotherapy, carbon dioxide laser and retinoids, each with potential disadvantages. We describe a conscious, minimally invasive, surgical excision procedure with high success rate and no complications in five dogs.
Modal Analysis for Localization of Harmonic Oscillations in Nonlinear Oscillator Arrays
Authors: Harata Yuji , Ikeda Takashi 
Published: September 2022

Abstract
When a nonlinear oscillator array is harmonically excited, specific oscillators in the array may oscillate with large amplitudes. This is known as the localization phenomenon; however, the reason for localization has not been clarified thus far. Thus, the aim of this study is to elucidate the reason for localization in nonlinear oscillator arrays. We theoretically investigated the behavior of a nonlinear oscillator array, which consists of N Duffing oscillators connected by linear springs under external and harmonic forces. The equations of motion in physical coordinates are transformed into modal equations of motion, which reveal that the array forms an autoparametric system in the modal coordinates when it consists of identical oscillators. The first mode of vibration is directly excited by the external force, whereas the remaining modes are indirectly excited by the nonlinear terms coupled with the first mode. The approximate solutions of the harmonic oscillations were obtained using van der Pol's method. The frequency response curves (FRCs) for both the physical and modal coordinates for N = 2 and 3 are presented. Localization can occur when multiple modes are excited simultaneously. Furthermore, the effects of imperfections in the restoring forces on the responses of the two-Duffing-oscillator array are examined.
Potential for a precision measurement of solar pp neutrinos in the Serappis experiment
Authors: Bieger Lukas , Birkenfeld Thilo , Blum David , Depnering Wilfried , Enqvist Timo , Enzmann Heike , Gao Feng , Genster Christoph , Göttel Alexandre , Grewing Christian , Gromov Maxim , Hackspacher Paul , Hagner Caren , Heinz Tobias , Kampmann Philipp , Karagounis Michael , Kruth Andre , Kuusiniemi Pasi , Lachenmaier Tobias , Liebau Daniel , Liu Runxuan , Loo Kai , Ludhova Livia , Meyhöfer David , Müller Axel , Muralidharan Pavithra , Oberauer Lothar , Othegraven Rainer , Parkalian Nina , Pei Yatian , Pilarczyk Oliver , Rebber Henning , Robens Markus , Roth Christian , Sawatzki Julia , Schweizer Konstantin , Settanta Giulio , Slupecki Maciej , Smirnov Oleg , Stahl Achim , Steiger Hans , Steinmann Jochen , Sterr Tobias , Stock Matthias Raphael , Tang Jian , Theisen Eric , Tietzsch Alexander , Trzaska Wladyslaw , van den Boom Johannes , van Waasen Stefan , Vollbrecht Cornelius , Wiebusch Christopher , Wonsak Bjoern , Wurm Michael , Wysotzki Christian , Xu Yu , Yegin Ugur , Zambanini Andre , Züfle Jan 
Published: September 2022

AbstractThe Serappis (SEarch for RAre PP-neutrinos In Scintillator) project aims at a precision measurement of the flux of solar pp neutrinos on the few-percent level. Such a measurement will be a relevant contribution to the study of solar neutrino oscillation parameters and a sensitive test of the equilibrium between solar energy output in neutrinos and electromagnetic radiation (solar luminosity constraint). The concept of Serappis relies on a small organic liquid scintillator detector ($$\sim $$
∼
20 m$$^3$$

3

) with excellent energy resolution ($$\sim $$
∼
2.5% at 1 MeV), low internal background and sufficient shielding from surrounding radioactivity. This can be achieved by a minor upgrade of the OSIRIS facility at the site of the JUNO neutrino experiment in southern China. To go substantially beyond current accuracy levels for the pp flux, an organic scintillator with ultra-low $$ {^{14}\hbox {C}}$$

14

C

levels (below $$10^{-18}$$

10

-
18

) is required. The existing OSIRIS detector and JUNO infrastructure will be instrumental in identifying suitable scintillator materials, offering a unique chance for a low-budget high-precision measurement of a fundamental property of our Sun that will be otherwise hard to access.
Fe–In2O3 Induced Catalytic Degrading Congo Red under Ultrasonic Irradiation
Authors: Zhang Gehong , Yan Zhiyang , Zhang Jie , Sun Jian , Ma Donghua , Zhao Pingge 
Published: September 2022

In this work, the azo dye Congo red (CR) was degraded by a Fe–In2O3 catalyst under the irradiation of ultrasonic. The Fe–In2O3 catalyst was prepared by a fast and moderate solvothermal method followed by the characterization of X-ray diffraction and scanning electron microscope. The effects of operating parameters, such as catalyst composition, catalyst dosage, initial dye concentration, ultrasonic power and ultrasonic frequency on degradation process were discussed. In the experiment, the optimum CR removal of 97.75% in 60[Formula: see text]min was achieved under the conditions, i.e., catalyst dosage of 0.06[Formula: see text][Formula: see text], CR concentration of 10[Formula: see text][Formula: see text], ultrasonic frequency of 45[Formula: see text]kHz and ultrasonic power of 100[Formula: see text]W. Besides, the CR degradation behavior by the catalyst with ultrasonic is well in accordance with the first-order kinetic model.
Therapeutic Effects of the Proximal Femoral Nail for the Treatment of Unstable Intertrochanteric Fractures
Authors: Cai Yuwei , Zhu Wenjun , Wang Nan , Yu Zhongxiang , Chen Yu , Xu Shengming , Feng Juntao 
Published: September 2022

Objective. The aim of this study was to analyze the clinical effect of the proximal femoral nail on elderly patients with unstable intertrochanteric fracture and the effect of the proximal femoral nail on serum levels of matrix metalloproteinases (MMPs) and osteoprotegerin (OPG). Methods. The elderly patients with unstable intertrochanteric fracture of the femur admitted to our hospital from January 2017 to January 2021 were studied. 100 patients were randomly divided into two groups: the control group (n = 50) and the observation group (n = 50). The patients in the control group were treated with a proximal femoral locking compression plate. The patients in the observation group were treated with the proximal femoral antirotation intramedullary nail. The clinical therapeutic effects of the two groups and the changes in serum MMPs and OPG levels before and after treatment were analyzed. Results. Compared with the control group, the operation time, postoperative landing time, and fracture healing time of the observation group were significantly shortened, and intraoperative blood loss was significantly reduced (

P

< 0.05). Compared with the control group, the total effective rate of patients in the observation group was significantly higher (

P

< 0.05). After treatment, the levels of CRP, IL1β, IL2, MMP-2, MMP-6, TIMP-1, and RANKL decreased significantly in both groups (

P

< 0.05), while the levels of OPG increased significantly (

P

< 0.05). Compared with the control group, the changes in the above indexes were more obvious in the observation group (

P

< 0.05). Conclusion. The proximal femoral antirotation intramedullary nail has a better therapeutic effect on elderly patients with unstable intertrochanteric fracture, and the level of MMPs and OPG may be related to the treatment process.
Lipid Metabolic Reprogramming Extends beyond Histologic Tumor Demarcations in Operable Human Pancreatic Cancer
Authors: Pirhonen Juho , Szkalisity Ábel , Hagström Jaana , Kim Yonghyo , Migh Ede , Kovács Mária , Hölttä Maarit , Peränen Johan , Seppänen Hanna , Haglund Caj , Gil Jeovanis , Rezeli Melinda , Malm Johan , Horvath Peter , Markó-Varga György , Puolakkainen Pauli , Ikonen Elina 
Published: September 2022

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignancies and potentially curable only with radical surgical resection at early stages. The tumor microenvironment has been shown to be central to the development and progression of PDAC. A better understanding of how early human PDAC metabolically communicates with its environment and differs from healthy pancreas could help improve PDAC diagnosis and treatment. Here we performed deep proteomic analyses from diagnostic specimens of operable, treatment-naïve PDAC patients (n = 14), isolating four tissue compartments by laser-capture microdissection: PDAC lesions, tumor-adjacent but morphologically benign exocrine glands, and connective tissues neighboring each of these compartments. Protein and pathway levels were compared between compartments and with control pancreatic proteomes. Selected targets were studied immunohistochemically in the 14 patients and in additional tumor microarrays, and lipid deposition was assessed by nonlinear label-free imaging (n = 16). Widespread downregulation of pancreatic secretory functions was observed, which was paralleled by high cholesterol biosynthetic activity without prominent lipid storage in the neoplastic cells. Stromal compartments harbored ample blood apolipoproteins, indicating abundant microvasculature at the time of tumor removal. The features best differentiating the tumor-adjacent exocrine tissue from healthy control pancreas were defined by upregulation of proteins related to lipid transport. Importantly, histologically benign exocrine regions harbored the most significant prognostic pathways, with proteins involved in lipid transport and metabolism, such as neutral cholesteryl ester hydrolase 1, associating with shorter survival. In conclusion, this study reveals prognostic molecular changes in the exocrine tissue neighboring pancreatic cancer and identifies enhanced lipid transport and metabolism as its defining features.

Significance:
In clinically operable pancreatic cancer, regions distant from malignant cells already display proteomic changes related to lipid transport and metabolism that affect prognosis and may be pharmacologically targeted.
Potent and Selective PTDSS1 Inhibitors Induce Collateral Lethality in Cancers with PTDSS2 Deletion
Authors: Yoshihama Yohei , Namiki Hidenori , Kato Taiga , Shimazaki Naomi , Takaishi Sachiko , Kadoshima-Yamaoka Kumiko , Yukinaga Hideo , Maeda Naoyuki , Shibutani Tomoko , Fujimoto Kazunori , Hirasawa Makoto , Goto Hiroki , Wada Naoya , Tsutsumi Shinji , Hirota Yasuhide , Ishikawa Tomoki , Yamamoto Shoji 
Published: September 2022

Abstract
Targeting collateral deletion of housekeeping genes caused by the loss of tumor suppressor genes is a potential strategy to identify context-specific, molecular-targeted therapies in cancer. In mammals, phosphatidylserine (PS) synthesis depends on two redundant PS synthetases, PTDSS1 and PTDSS2, and PTDSS2 is located at a tumor-suppressive locus, 11p15.5. Here, we sought to determine whether PTDSS2 loss would confer vulnerability to disruption of PTDSS1 function. PTDSS2 was lost in a wide range of cancer types, and PTDSS1 depletion specifically suppressed growth in PTDSS2-deficient cancer cell lines. Potent and selective PTDSS1 inhibitors were developed whose activity phenocopied the effect of PTDSS1 depletion, and in vivo treatment of PTDSS2-deleted tumors with these inhibitors led to tumor regression. Whole-transcriptome analysis revealed that inhibition of PTDSS1 in PTDSS2-depleted cells activated the endoplasmic reticulum (ER) stress response downstream of PS depletion. ER stress-mediated cell death induced by PTDSS1 inhibitors activated tumor immunity through the secretion of HMGB1 protein followed by activation of bone marrow-derived dendritic cells. PTDSS2 loss showed intratumoral heterogeneity in clinical samples, raising concerns about resistance to PTDSS1 inhibition. However, the PTDSS1 inhibitor effectively suppressed the growth of tumor containing both PTDSS2 wild-type and knockout cells in immunocompetent mice, showing potency for overcoming tumor heterogeneity by modulating the tumor immune microenvironment. Thus, these newly developed PTDSS1 inhibitors provide a therapeutic option for treating cancer with PTDSS2 loss, harnessing the synthetic lethality of PTDSS1/2.

Significance:
This study identifies a specific dependency on PTDSS1 for phosphatidylserine synthesis following PTDSS2 deletion and introduces novel PTDSS1 inhibitors as a therapeutic option to induce collateral lethality in cancer with PTDSS2 loss.
RARγ: The Bone of Contention for Endothelial Cells in Prostate Cancer Metastasis
Authors: Bhowmick Snigdha , Bhowmick Neil A. 
Published: September 2022

Excessive bone deposition associated with prostate cancer bone metastases is believed to aid in metastatic progression. One mechanism of osteoblast expansion is the transdifferentiation of bone marrow endothelial cells. Prostate cancer cells contribute several secreted factors, including bone morphogenetic protein 4 (BMP4), to the microenvironment that support osteoblastic transdifferentiation. In this issue of Cancer Research, Yu and colleagues share their findings of how BMP-mediated endothelial conversion can be inhibited by treatment with retinoic acid receptor (RAR) agonists. Using agonists like the all-trans retinoic acid or palovarotene, the authors demonstrated the role of the interaction of BMP-activated SMAD1 with RARγ for osteoblastic differentiation. RARγ agonists potentiated the proteasomal degradation of the Smad1–RARγ complex, blocking BMP signaling. Because palovarotene is clinically effective in the treatment of aberrant bone formation found in fibrodysplasia ossificans progressiva, its repurposing for the treatment of osteoblastic cancer metastasis is promising. However, patient selection and dose-finding studies will be critical for the translation of these findings to complement standard of care for patients with bone metastatic prostate cancer.See related article by Yu et al., p. 3158