bluuebunny/crossref_metadata_2025 huggingface dataset:
Xylose Metabolism in Bacteria—Opportunities and Challenges towards Efficient Lignocellulosic Biomass-Based Biorefineries
Authors: Domingues Rafael , Bondar Maryna , Palolo Inês , Queirós Odília , de Almeida Catarina Dias , Cesário M. Teresa
Published: September 2021

In a sustainable society based on circular economy, the use of waste lignocellulosic biomass (LB) as feedstock for biorefineries is a promising solution, since LB is the world’s most abundant renewable and non-edible raw material. LB is available as a by-product from agricultural and forestry processes, and its main components are cellulose, hemicellulose, and lignin. Following suitable physical, enzymatic, and chemical steps, the different fractions can be processed and/or converted to value-added products such as fuels and biochemicals used in several branches of industry through the implementation of the biorefinery concept. Upon hydrolysis, the carbohydrate-rich fraction may comprise several simple sugars (e.g., glucose, xylose, arabinose, and mannose) that can then be fed to fermentation units. Unlike pentoses, glucose and other hexoses are readily processed by microorganisms. Some wild-type and genetically modified bacteria can metabolize xylose through three different main pathways of metabolism: xylose isomerase pathway, oxidoreductase pathway, and non-phosphorylative pathway (including Weimberg and Dahms pathways). Two of the commercially interesting intermediates of these pathways are xylitol and xylonic acid, which can accumulate in the medium either through manipulation of the culture conditions or through genetic modification of the bacteria. This paper provides a state-of-the art perspective regarding the current knowledge on xylose transport and metabolism in bacteria as well as envisaged strategies to further increase xylose conversion into valuable products.
Experimental Study on Micro-Grinding of Ceramics for Micro-Structuring
Authors: Na Yung , Lee Ui Seok , Kim Bo Hyun
Published: September 2021

In this study, micro-grinding was performed to investigate the machining characteristics of alumina and zirconia. The machining of ceramics remains highly challenging owing to their properties, such as high brittleness and wear resistance, which leads to a shorter tool life and high machining costs. Polycrystalline diamond (PCD) was selected as the tool material, as it is suitable for machining hard and brittle materials, and micro-electrical discharge machining (EDM) was used to fabricate PCD micro-tools. When using a resistor-capacitor generator circuit in micro-EDM, the discharging energy is related to the working capacitance, and by controlling the working capacitance, the different edge radii and the surface roughness of the tool can be easily achieved. The feed rate, depth of cut, and rotation speed were set as experimental parameters to investigate the grinding characteristics of the ceramics. During the experiment, the grinding force and roughness of the bottom surface were monitored, and the roughness of the machined surfaces was measured using a three-dimensional surface profiler. A working capacitance of 1000 pF was used to fabricate a tool with an edge radius of 3.5 µm. The lower radius of the tool edge resulted in a decrease of the cutting force by 50% at most and a surface roughness of 19 nm Ra.
Framework for the Ensemble of Feature Selection Methods
Authors: Mera-Gaona Maritza , López Diego M. , Vargas-Canas Rubiel , Neumann Ursula
Published: September 2021

Feature selection (FS) has attracted the attention of many researchers in the last few years due to the increasing sizes of datasets, which contain hundreds or thousands of columns (features). Typically, not all columns represent relevant values. Consequently, the noise or irrelevant columns could confuse the algorithms, leading to a weak performance of machine learning models. Different FS algorithms have been proposed to analyze highly dimensional datasets and determine their subsets of relevant features to overcome this problem. However, very often, FS algorithms are biased by the data. Thus, methods for ensemble feature selection (EFS) algorithms have become an alternative to integrate the advantages of single FS algorithms and compensate for their disadvantages. The objective of this research is to propose a conceptual and implementation framework to understand the main concepts and relationships in the process of aggregating FS algorithms and to demonstrate how to address FS on datasets with high dimensionality. The proposed conceptual framework is validated by deriving an implementation framework, which incorporates a set of Phyton packages with functionalities to support the assembly of feature selection algorithms. The performance of the implementation framework was demonstrated in several experiments discovering relevant features in the Sonar, SPECTF, and WDBC datasets. The experiments contrasted the accuracy of two machine learning classifiers (decision tree and logistic regression), trained with subsets of features generated either by single FS algorithms or the set of features selected by the ensemble feature selection framework. We observed that for the three datasets used (Sonar, SPECTF, and WD), the highest precision percentages (86.95%, 74.73%, and 93.85%, respectively) were obtained when the classifiers were trained with the subset of features generated by our framework. Additionally, the stability of the feature sets generated using our ensemble method was evaluated. The results showed that the method achieved perfect stability for the three datasets used in the evaluation.
Dynamic Behavior Analysis of the Winding Rotor with Structural Coupling and Time-Frequency Varying Parameters: Simulation and Measurement
Authors: Ma Xunxun , Li Shujia , Tian Wangliang , Qu Xiqiang , Wang Shengze , Wang Yongxing
Published: September 2021

To satisfy the requirements of high speed, large capacity and constant winding, a textile winding rotor needs to work in a wide rotation speed range and frequently pass through critical speed points. Thus, the winding rotor adopts the flexible long shaft coupling structure and flexible support with rubber O-rings. This kind of rotor has a multi-coupling structure and frequency-dependent parameters characteristics, especially representative and universal in the dynamic analysis method of the high-speed rotor. In this paper, an approach was proposed to investigate the dynamic behavior of the winding rotor considering the flexible coupling and frequency-dependent supporting parameters. Firstly, a dynamic model of the winding rotor was established by using a Timoshenko beam element. Its dynamic behaviors were simulated by considering the time-varying rotation speed and the frequency-dependent parameters of flexible support. Secondly, a non-contact measuring device was developed for measuring the vibration displacement of the winding rotor in three different speed-up times. Finally, based on simulation and measurement data, how flexible support parameters and the speed-up time affect the winding rotor passing through the critical speed point of the rotor smoothly is revealed. The methods and findings reported here can be used for theoretical and experimental vibration analysis of other types of high-speed flexible rotors.
Facing the Pandemic: A Perspective on Patachitra Artists of West Bengal
Authors: Zanatta Maura , Roy Anjali Gera
Published: September 2021

The COVID-19 pandemic has intensely impacted art production and the art market all around the world. This is dramatically visible inside the Patua or Patachitra communities in Medinipur, West Bengal, where Patachitras’ scrolls characterise the economy of folk-art communities in the so-called villages of painters. Patachitras’ singing pictures belong to an ancestral tradition of storytelling and performing art. For centuries, new themes have been embodied inside the Patuas’ repertoire, creating a living heritage that has always reflected the political, religious, cultural, and social main events and, ultimately, COVID-19. Resilience has always been an important component of this heritage, as social changes and new kinds of entertainment have changed the audience addressed and the performances’ function. In the last few decades, the role of travelling artists has resisted and been readapted to the global art market by approaching art fairs and festivals both inside and outside the villages. Now, the impact of COVID-19 on the economy of these artists has been severe, as art fairs and exhibitions have been cancelled, and lockdown orders have stopped tourism and travels, significantly reducing their income. Thus, new approaches and virtual spaces of exhibiting are being experimented with to support the survival of these artists and keep the performances’ essence alive. This article aims to address how the pandemic has affected Patuas’ art market and production both from an economic and social perspective. The difficulties encountered due to the restrictive measures and the impossibility of performing will be analysed through an empirical approach. Based on telephonic interviews conducted with 30 hereditary Patuas from Naya between April 2020 to April 2021 as part of the project “Folk Artists in the Time of Coronavirus”, the article hopes to shed light on the impact of the pandemic on hereditary, performing castes in India, which might mirror the experiences of similar groups in the rest of South Asia. The article will also try to outline the future perspectives for the art market of these folk artists. The article consists of two parts: the first traces the transformative journey of Patachitra and Patachitrakars, and the second focuses on the impact of the pandemic through deploying the concepts of precarity, precariousness, and resilience.
The Last Mosque in Tel Aviv, and Other Stories of Disjuncture
Authors: Webster-Kogen Ilana
Published: September 2021

Ruins serve as a poignant reminder of loss and destruction. Yet, ruins are not always physical, and they are not always best understood through visual language—the sense memory of loss extends for displaced people far beyond crumbling monuments. Exploring the sonic element of loss and displacement is key to understanding the way people relate to the spaces they have to leave. This article explores the particular disjuncture of staging and commemorating Arabness in Tel Aviv, the “Hebrew City.” The disjuncture of being Arab in Tel Aviv is apparent to any visitor who walks down the beach promenade, and this article examines the main sites of Arab contestation on the border with Jaffa. Most apparent to a visitor is the Hassan Bek Mosque, the most visible Islamic symbol in Tel Aviv; I describe the process of gaining admission as a non-Muslim, and of discussing the painful and indelible memory of 1948 with worshipers. Delving deeper into the affective staging of ruin, I trace Umm Kulthum’s famous concert in Jaffa (officially Palestine at the time), and examine the way her imprint has moved across the troubled urban border of Tel Aviv-Jaffa. A ruins-based analysis of the urban sites of disjuncture in Tel Aviv, therefore, offers a glimpse into underground sonic subcultures that hide in plain sight.
Sources of PM2.5-Associated PAHs and n-alkanes in Changzhou China
Authors: Sun Ning , Li Xudong , Ji Ye , Huang Hongying , Ye Zhaolian , Zhao Zhuzi
Published: September 2021

Polycyclic aromatic hydrocarbons (PAHs) and n-alkanes are important specific organic constituents in fine particulate matter (PM2.5). Seventy-five PM2.5 samples were collected in Spring Changzhou, to investigate the concentrations and sources of n-alkanes (C9–C40) and PAHs. The average concentrations of total PAHs (∑PAHs) and n-alkanes (∑n-alkanes) were 4.37 ± 4.95 ng/m3 and 252.37 ± 184.02 ng/m3, ranging from 0.43 to 22.22 ng/m3 and 57.37 to 972.17 ng/m3, respectively. The average concentrations of ∑n-alkanes and ∑PAHs were higher in severely polluted days (PM2.5 ≥ 150 μg/m3) in comparison to other days. Up to 85% of PAHs were four- and five-ring compounds, and the middle-chain-length n-alkanes (C25–C35) were the most abundant species (80.9%). The molecular distribution of n-alkanes was characterized by odd-number carbon predominance (carbon preference index, CPI > 1), with a maximum centered at C27, C29, and C31 revealing a significant role of biogenic sources. Principal component analysis suggested that the biogenic sources that contributed the most to n-alkanes and PAHs were from coal combustion (46.3%), followed by biomass burning (16.0%), and vehicular exhaust (10.3%). The variation in the concentration of n-alkanes and PAHs from different air mass transports was not agreement with the change in PM2.5 mass, indicating that regional transport had important impacts on the characterization of PM2.5. The results of our study can provide useful information for evaluating the influence of anthropogenic and biogenic activities on organic matters (n-alkanes and PAHs).
The Yin and Yang of Type I IFNs in Cancer Promotion and Immune Activation
Authors: Musella Martina , Galassi Claudia , Manduca Nicoletta , Sistigu Antonella
Published: September 2021

Type I Interferons (IFNs) are key regulators of natural and therapy-induced host defense against viral infection and cancer. Several years of remarkable progress in the field of oncoimmunology have revealed the dual nature of these cytokines. Hence, Type I IFNs may trigger anti-tumoral responses, while leading immune dysfunction and disease progression. This dichotomy relies on the duration and intensity of the transduced signaling, the nature of the unleashed IFN stimulated genes, and the subset of responding cells. Here, we discuss the role of Type I IFNs in the evolving relationship between the host immune system and cancer, as we offer a view of the therapeutic strategies that exploit and require an intact Type I IFN signaling, and the role of these cytokines in inducing adaptive resistance. A deep understanding of the complex, yet highly regulated, network of Type I IFN triggered molecular pathways will help find a timely and immune“logical” way to exploit these cytokines for anticancer therapy.
Effect of Vitamin B2 and Vitamin E on Cancer-Related Sarcopenia in a Mouse Cachexia Model
Authors: Mori Takuya , Goto Kei , Kawahara Isao , Nukaga Shota , Wakatsuki Yuma , Mori Shiori , Fujiwara-Tani Rina , Kishi Shingo , Sasaki Takamitsu , Ohmori Hitoshi , Kido Akira , Honoki Kanya , Tanaka Yasuhito , Kuniyasu Hiroki
Published: September 2021

Cancer-related sarcopenia is associated with impaired energy metabolism and increased oxidative stress production in skeletal muscles. With an aim to treat cancer-related sarcopenia using dietary intervention, we investigated the effects of vitamin B2 (VB2) and vitamin E (VE), which are recognized to have antioxidant effects, on CT26 mouse colon cancer cells and skeletal muscles in vitro and in vivo. VB2 suppressed tumor growth by suppressing cell proliferation and inducing more pronounced apoptosis by increasing the production of adenosine triphosphate (ATP) and reactive oxygen species (ROS). VE suppressed tumor growth by suppressing cell proliferation and increasing apoptosis by decreasing the production of ATP and ROS. In C2C12 mouse skeletal myoblast cells, VB2 treatment increased the production of ATP and ROS and VE treatment decreased the production of ATP and ROS; both treatments suppressed skeletal myoblast maturation. In the mouse model, intraperitoneal inoculation (peritoneal model) resulted in marked macrophage infiltration and elevated blood tumor necrosis factor-α and high-mobility group box-1 inflammatory cytokine levels, leading to cachexia. In contrast, subcutaneous inoculation (subcutaneous model) showed poor macrophage infiltration and low inflammatory cytokine levels, without cachexia. VB2 and VE activated macrophages and exacerbated cancer-related sarcopenia in the peritoneal model, whereas VB2 and VE treatment did not exhibit significant changes in sarcopenia in the subcutaneous model. In order to improve cancer-related sarcopenia by dietary intervention, it is important to consider the effect on inflammatory cytokines.
Immunological Status of Bladder Cancer Patients Based on Urine Leukocyte Composition at Radical Cystectomy
Authors: Cantó Elisabet , Faba Óscar Rodríguez , Zamora Carlos , Mulet Maria , Garcia-Cuerva Maria Soledad , Palomino Ana , Anguera Georgia , Breda Alberto , Maroto Pablo , Vidal Sílvia
Published: September 2021

Background: Bladder cancer (BC) is the ninth most common malignancy worldwide, with high rates of recurrence. The use of urine leukocyte composition at the time of radical cystectomy (RC) as a marker for the study of patients’ immunological status and to predict the recurrence of muscle-invasive bladder cancer (MIBC) has received little attention. Methods: Urine and matched peripheral blood samples were collected from 24 MIBC patients at the time of RC. Leukocyte composition and expression of PD-L1 and PD-1 in each subpopulation were determined by flow cytometry. Results: All MIBC patients had leukocytes in urine. There were different proportions of leukocyte subpopulations. The expression of PD-L1 and PD-1 on each subpopulation differed between patients. Neoadjuvant chemotherapy (NAC), smoking status, and the affectation of lymph nodes influenced urine composition. We observed a link between leukocytes in urine and blood circulation. Recurrent patients without NAC and with no affectation of lymph nodes had a higher proportion of lymphocytes, macrophages, and PD-L1+ neutrophils in urine than non-recurrent patients. Conclusions: Urine leukocyte composition may be a useful tool for analyzing the immunological status of MIBC patients. Urine cellular composition allowed us to identify a new subgroup of LN− patients with a higher risk of recurrence.
Alzheimer’s Disease: A Molecular View of β-Amyloid Induced Morbific Events
Authors: Mohamed Asik Rajmohamed , Suganthy Natarajan , Aarifa Mohamed Asik , Kumar Arvind , Szigeti Krisztián , Mathe Domokos , Gulyás Balázs , Archunan Govindaraju , Padmanabhan Parasuraman
Published: September 2021

Amyloid-β (Aβ) is a dynamic peptide of Alzheimer’s disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by β- and γ-secretases and engenders the Aβ. In addition, externally produced Aβ gets inside the cells by receptors mediated internalization. An elevated amount of Aβ yields spontaneous aggregation which causes organelles impairment. Aβ stimulates the hyperphosphorylation of tau protein via acceleration by several kinases. Aβ travels to the mitochondria and interacts with its functional complexes, which impairs the mitochondrial function leading to the activation of apoptotic signaling cascade. Aβ disrupts the Ca2+ and protein homeostasis of the endoplasmic reticulum (ER) and Golgi complex (GC) that promotes the organelle stress and inhibits its stress recovery machinery such as unfolded protein response (UPR) and ER-associated degradation (ERAD). At lysosome, Aβ precedes autophagy dysfunction upon interacting with autophagy molecules. Interestingly, Aβ act as a transcription regulator as well as inhibits telomerase activity. Both Aβ and p-tau interaction with neuronal and glial receptors elevate the inflammatory molecules and persuade inflammation. Here, we have expounded the Aβ mediated events in the cells and its cosmopolitan role on neurodegeneration, and the current clinical status of anti-amyloid therapy.
The FcγRIII Engagement Augments PMA-Stimulated Neutrophil Extracellular Traps (NETs) Formation by Granulocytes Partially via Cross-Talk between Syk-ERK-NF-κB and PKC-ROS Signaling Pathways
Authors: Lu Cheng-Hsun , Li Ko-Jen , Wu Cheng-Han , Shen Chieh-Yu , Kuo Yu-Min , Hsieh Song-Chou , Yu Chia-Li
Published: September 2021

Polymorphonuclear neutrophils (PMNs) are the most abundant white blood cell in the circulation capable of neutrophil extracellular traps (NETs) formation after stimulation. Both NADPH oxidase-dependent and -independent pathways are involved in NET formation. The IgG is the most abundant immunoglobulin in human serum. However, the impact of the circulating IgG on NET formation is totally unexplored. In this study, the all-trans retinoic acid (ATRA)-induced mature granulocytes (dHL-60) were pre-treated with monomeric human IgG, papain-digested Fab fragment, crystallizable IgG Fc portion, rituximab (a human IgG1), or IgG2. The NET formation of the dHL-60 in the presence/absence of phorbol 12-myristate 13-acetate (PMA) stimulation was then measured by the fluorescent area after SYTOX green nucleic acid stain. The intracellular reactive oxygen species (ROS) generation was measured by flow cytometry. Total and phosphorylated Syk, SHP-1, and ERK were detected by immunoblot. We found that human monomeric IgG and its subclasses IgG1 and IgG2 per se induced negligible NET formation of dHL-60, but the FcγRIII engagement by these IgG subclasses and Fc portion augment PMA-stimulated dHL-60 NET formation in a dose-dependent manner. Furthermore, we found that increased Syk and ERK phosphorylation, intracellular ROS generation, and pro-inflammatory cytokines, IL-8 and TNF-α, production could be induced after FcγRIII engagement. Blocking FcγRIII engagement by a specific antibody diminished the augmented NET formation. In conclusion, we discovered that cross-talk between FcγRIII engagement-induced Syk-ERK and PMA-induced PKC signaling pathways augment NET formation of dHL-60 via increased ROS generation and pro-inflammatory cytokines, IL-8 and TNF-α, production.
Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections
Authors: Sigmund Irene K. , Puchner Stephan E. , Windhager Reinhard
Published: September 2021

Accurate preoperative diagnosis of periprosthetic joint infections (PJIs) can be very challenging, especially in patients with chronic PJI caused by low-virulence microorganisms. Serum parameters, such as serum C-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR), are—among other diagnostic test methods—widely used to distinguish septic from aseptic failure after total hip or knee arthroplasty and are recommended by the AAOS in the preoperative setting. However, they are systemic parameters, and therefore, unspecific. Nevertheless, they may be the first and occasionally the only preoperative indication, especially when clinical symptoms are lacking. They are easy to obtain, cheap, and are available worldwide. In the last decade, different novel serum biomarkers (percentage of neutrophils, neutrophils to lymphocytes ratio, platelet count to mean platelet volume ratio, fibrinogen, D-Dimer, Il-6, PCT) were investigated to find a more specific and accurate serum parameter in the diagnosis of PJI. This article reviews the diagnostic value of established (serum CRP, ESR, WBC) and ‘novel’ serum inflammatory biomarkers (fibrinogen, D-dimer, interleukin-6 (IL-6), procalcitonin, percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), platelet count to mean platelet volume ratio (PC/mPV)) for the preoperative diagnosis of periprosthetic joint infections.
Prolyl-Isomerase Pin1 Controls Key fMLP-Induced Neutrophil Functions
Authors: Bedouhene Samia , Liu Min , Senani Nassima , Boussetta Tarek , Pintard Coralie , Dang Pham My-Chan , El-Benna Jamel
Published: September 2021

Neutrophils are key cells of the innate immune and inflammatory responses. They are the first blood cells to migrate to the infection site where they release high amounts of reactive oxygen species (ROS) and several peptides and enzymes required for microbial killing. However, excessive neutrophil activation can induce tissue injury participating in inflammation, thus the characterization of the enzymes involved in neutrophil activation could help to identify new pharmacological targets to treat inflammation. The prolyl-isomerase Pin1 is a ubiquitous enzyme involved in several functions, however, its role in neutrophil functions is less known. In this study, we show that the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP or fMLF), a G-protein coupled receptor (GPCR) agonist-induced Pin1 activation in human neutrophils. PiB and juglone, two Pin1 inhibitors inhibited Pin1 activity in neutrophils and consequently inhibited fMLP-induced chemotaxis and -degranulation of azurophil and specific granules as measured by myeloperoxidase and neutrophil gelatinase-associated lipocalin (NGAL) release respectively. We also showed that PiB inhibited TNFα + fMLP-induced superoxide production, confirming the effect of juglone. These data show that inhibitors of Pin1 impaired key pro-inflammatory neutrophil functions elicited by GPCR activation and suggest that Pin1 could control neutrophil inflammatory functions.
Derivation and Characterization of EGFP-Labeled Rabbit Limbal Mesenchymal Stem Cells and Their Potential for Research in Regenerative Ophthalmology
Authors: Khorolskaya Julia I. , Perepletchikova Daria A. , Kachkin Daniel V. , Zhurenkov Kirill E. , Alexander-Sinkler Elga I. , Ivanova Julia S. , Mikhailova Natalia A. , Blinova Miralda I.
Published: September 2021

The development of cell-based approaches to the treatment of various cornea pathologies, including limbal stem cell deficiency (LSCD), is an area of current interest in regenerative biomedicine. In this context, the shortage of donor material is urgent, and limbal mesenchymal stem cells (L-MSCs) may become a promising cell source for the development of these novel approaches, being established mainly within the rabbit model. In this study, we obtained and characterized rabbit L-MSCs and modified them with lentiviral transduction to express the green fluorescent protein EGFP (L-MSCs-EGFP). L-MSCs and L-MSCs-EGFP express not only stem cell markers specific for mesenchymal stem cells but also ABCG2, ABCB5, ALDH3A1, PAX6, and p63a specific for limbal epithelial stem cells (LESCs), as well as various cytokeratins (3/12, 15, 19). L-MSCs-EGFP have been proven to differentiate into adipogenic, osteogenic, and chondrogenic directions, as well as to transdifferentiate into epithelial cells. The possibility of using L-MSCs-EGFP to study the biocompatibility of various scaffolds developed to treat corneal pathologies was demonstrated. L-MSCs-EGFP may become a useful tool for studying regenerative processes occurring during the treatment of various corneal pathologies, including LSCD, with the use of cell-based technologies.
Decreased MicroRNA-150 Exacerbates Neuronal Apoptosis in the Diabetic Retina
Authors: Yu Fei , Ko Michael L. , Ko Gladys Y.-P.
Published: September 2021

Diabetic retinopathy (DR) is a chronic complication associated with diabetes and the number one cause of blindness in working adults in the US. More than 90% of diabetic patients have obesity-associated type 2 diabetes (T2D), and 60% of T2D patients will develop DR. Photoreceptors undergo apoptosis shortly after the onset of diabetes, which contributes to the retinal dysfunction and microvascular complications leading to vision impairment. However, how diabetic insults cause photoreceptor apoptosis remains unclear. In this study, obesity-associated T2D mice and cultured photoreceptors were used to investigate how decreased microRNA-150 (miR-150) and its downstream target were involved in photoreceptor apoptosis. In the T2D retina, miR-150 was decreased with its target ETS-domain transcription factor (ELK1) and phosphorylated ELK1 at threonine 417 (pELK1T417) upregulated. In cultured photoreceptors, treatments with palmitic acid (PA), to mimic a high-fat environment, decreased miR-150 but upregulated ELK1, pELK1T417, and the translocation of pELK1T417 from the cytoplasm to the cell nucleus. Deletion of miR-150 (miR-150−/−) exacerbates T2D- or PA-induced photoreceptor apoptosis. Blocking the expression of ELK1 with small interfering RNA (siRNA) for Elk1 did not rescue PA-induced photoreceptor apoptosis. Translocation of pELK1T417 from cytoplasm-to-nucleus appears to be the key step of diabetic insult-elicited photoreceptor apoptosis.
In-Situ Monitoring of Real-Time Loop-Mediated Isothermal Amplification with QCM: Detecting Listeria monocytogenes
Authors: Wachiralurpan Sirirat , Phung-On Isaratat , Chanlek Narong , Areekit Supatra , Chansiri Kosum , Lieberzeit Peter A.
Published: September 2021

Functionalized DNA sequences are promising sensing elements to combine with transducers for bio-sensing specific target microbes. As an application example, this paper demonstrates in situ detection of loop-mediated isothermal amplification products by hybridizing them with thiolated-ssDNA covalently anchored on the electrodes of a quartz crystal microbalance (QCM). Such hybridization leads to a frequency signal, which is suitable for monitoring real-time LAMP amplification based on mass-sensing: it detects interactions between the complementary nucleobases of LAMP products in solution and the thiolated-ssDNA probe sequence on the gold surface. Target DNA LAMP products cause irreversible frequency shifts on the QCM surfaces during hybridization in the kHz range, which result from both changes in mass and charge on the electrode surface. In order to confirm the LAMP assay working in the QCM sensing system at elevated temperature, the sky blue of positive LAMP products solution was achieved by using the Hydroxy Naphthol Blue (HNB) and agarose gel electrophoresis. Since on-QCM sensing of DNA hybridization leads to irreversible sensor responses, this work shows characterization by X-ray photoelectron spectroscopy (XPS) core spectra of S2p, N1s, Mg1s, P2p and C1s. XPS results confirmed that indeed both DNA and by-products of LAMP attached to the surface. Listeria monocytogenes DNA served to study in-situ detection of amplified LAMP products on DNA-functionalized surfaces.
Are There Any Cognitive and Behavioral Changes Potentially Related to Quarantine Due to the COVID-19 Pandemic in People with Mild Cognitive Impairment and AD Dementia? A Longitudinal Study
Authors: Tsatali Marianna , Moraitou Despina , Poptsi Eleni , Sia Eleni , Agogiatou Christina , Gialaouzidis Moses , Tabakis Irene-Maria , Avdikou Konstantina , Bakoglidou Evaggelia , Batsila Georgia , Bekiaridis-Moschou Dimitrios , Chatziroumpi Ourania , Diamantidou Alexandra , Gavra Andromachi , Kouroundi Eleni , Liapi Despina , Markou Nefeli , Ouzouni Fani , Papasozomenou Chrysa , Soumpourou Aikaterini , Tsolaki Magdalini
Published: September 2021

The aim of the study was to examine potential cognitive, mood (depression and anxiety) and behavioral changes that may be related to the quarantine and the lockdown applied during the COVID-19 pandemic in Greek older adults with mild cognitive impairment (MCI), and AD dementia in mild and moderate stages. Method: 407 older adults, diagnosed either with MCI or AD dementia (ADD), were recruited from the Day Centers of the Greek Association of Alzheimer Disease and Related Disorders (GAADRD). Neuropsychological assessment was performed at baseline (at the time of diagnosis) between May and July of 2018, as well as for two consecutive follow-up assessments, identical in period, in 2019 and 2020. The majority of participants had participated in non-pharmacological interventions during 2018 as well as 2019, whereas all of them continued their participation online in 2020. Results: Mixed measures analysis of variance showed that participants’ ‘deterioration difference—D’ by means of their performance difference in neuropsychological assessments between 2018–2019 (D1) and 2019–2020 (D2) did not change, except for the FUCAS, RAVLT, and phonemic fluency tests, since both groups resulted in a larger deterioration difference (D2) in these tests. Additionally, three path models examining the direct relationships between performance in tests measuring mood, as well as everyday functioning and cognitive measures, showed that participants’ worsened performance in the 2019 and 2020 assessments was strongly affected by NPI performance, in sharp contrast to the 2018 assessment. Discussion: During the lockdown period, MCI and ADD patients’ neuropsychological performance did not change, except from the tests measuring verbal memory, learning, and phonemic fluency, as well as everyday functioning. However, the natural progression of the MCI as well as ADD condition is the main reason for participants’ deterioration. Mood performance became increasingly closely related to cognition and everyday functioning. Hence, the role of quarantine and AD progression are discussed as potential factors associated with impairments.
Therapeutic Potential of Targeting the SUMO Pathway in Cancer
Authors: Kukkula Antti , Ojala Veera K. , Mendez Lourdes M. , Sistonen Lea , Elenius Klaus , Sundvall Maria
Published: September 2021

SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Key oncoproteins and tumor suppressors are SUMO substrates. In addition to alterations in SUMO pathway activity due to conditions typically present in cancer, such as hypoxia, the SUMO machinery components are deregulated at the genomic level in cancer. The delicate balance between SUMOylation and deSUMOylation is regulated by SENP enzymes possessing SUMO-deconjugation activity. Dysregulation of SUMO machinery components can disrupt the balance of SUMOylation, contributing to the tumorigenesis and drug resistance of various cancers in a context-dependent manner. Many molecular mechanisms relevant to the pathogenesis of specific cancers involve SUMO, highlighting the potential relevance of SUMO machinery components as therapeutic targets. Recent advances in the development of inhibitors targeting SUMOylation and deSUMOylation permit evaluation of the therapeutic potential of targeting the SUMO pathway in cancer. Finally, the first drug inhibiting SUMO pathway, TAK-981, is currently also being evaluated in clinical trials in cancer patients. Intriguingly, the inhibition of SUMOylation may also have the potential to activate the anti-tumor immune response. Here, we comprehensively and systematically review the recent developments in understanding the role of SUMOylation in cancer and specifically focus on elaborating the scientific rationale of targeting the SUMO pathway in different cancers.
Niraparib Suppresses Cholangiocarcinoma Tumor Growth by Inducing Oxidative and Replication Stress
Authors: Bezrookove Vladimir , Patino John M. , Nosrati Mehdi , Desprez Pierre-Yves , McAllister Sean , Soroceanu Liliana , Baron Ari , Osorio Robert , Kashani-Sabet Mohammed , Dar Altaf A.
Published: September 2021

Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer, an aggressive malignancy with limited therapeutic options. PARP (poly (ADP-ribose) polymerase) 1 and 2 are important for deoxyribonucleotide acid (DNA) repair and maintenance of genomic stability. PARP inhibitors (PARPi) such as niraparib have been approved for different malignancies with genomic alteration in germline BRCA and DNA damage response (DDR) pathway genes. Genomic alterations were analyzed in DDR genes in CCA samples employing The Cancer Genome Atlas (TCGA) database. Mutations were observed in various DDR genes, and 35.8% cases had alterations in at least one of three genes (ARID1A, BAP1 and ATM), suggesting their susceptibility to PARPi. Niraparib treatment suppressed cancer cell viability and survival, and also caused G2/M cell cycle arrest in patient-derived xenograft cells lines (PDXC) and established CCA cells harboring DDR gene mutations. PARPi treatment also induced apoptosis and caspase3/7 activity in PDXC and CCA cell lines, and substantially reduced expression of BCL2, BCL-XL and MCL1 proteins. Niraparib caused a significant increase in oxidative stress, and induced activation of DNA damage markers, phosphorylation of CHK2 and replication fork stalling. Importantly, niraparib, in combination with gemcitabine, produced sustained and robust inhibition of tumor growth in vivo in a patient-derived xenograft (PDX) model more effectively than either treatment alone. Furthermore, tissue samples from mice treated with niraparib and gemcitabine display significantly lower expression levels of pHH3 and Ki-67, which are a mitotic and proliferative marker, respectively. Taken together, our results indicate niraparib as a novel therapeutic agent alone or in combination with gemcitabine for CCA.
Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer
Authors: Hrudka Jan , Jelínková Karolína , Fišerová Hana , Matěj Radoslav , Mandys Václav , Waldauf Petr
Published: September 2021

Heat shock proteins (HSPs) are evolutionarily conserved chaperones occurring in virtually all living organisms playing a key role in the maintenance of cellular homeostasis. They are constitutively expressed to prevent and repair protein damage following various physiological and environmental stressors. HSPs are overexpressed in various types of cancers to provide cytoprotective function, and they have been described to influence prognosis and response to therapy. Moreover, they have been used as a tumor marker in blood serum biochemistry and they represent a potentially promising therapeutic target. To clarify prognostic significance of two canonical HSPs (27 and 70) and less known HSP110 (previously known as HSP105) in colorectal carcinoma (CRC), we retrospectively performed HSP immunohistochemistry on tissue microarrays from formalin-fixed paraffin-embedded tumor tissue from 297 patients with known follow-up. Survival analysis (univariate Kaplan–Meier analysis with the log-rank test and multivariate Cox regression) revealed significantly shorter overall survival (OS, mean 5.54 vs. 7.07, p = 0.033) and borderline insignificantly shorter cancer specific survival (CSS, mean 6.3 vs. 7.87 years, p = 0.066) in patients with HSP70+ tumors. In the case of HSP27+ tumors, there was an insignificantly shorter OS (mean 6.36 vs. 7.13 years, p = 0.2) and CSS (mean 7.17 vs. 7.95 years, p = 0.2). HSP110 showed no significant impact on survival. Using Pearson’s chi-squared test, there was a significant association of HSP27 and HSP70 expression with advanced cancer stage. HSP27+ tumors were more frequently mismatch-repair proficient and vice versa (p = 0.014), and they occurred more often in female patients and vice versa (p = 0.015). There was an enrichment of left sided tumors with HSP110+ compared to the right sided (p = 0.022). In multivariate Cox regression adjusted on the UICC stage, grade and right/left side; both HSPs 27 and 70 were not independent survival predictors (p = 0.616 & p = 0.586). In multivariate analysis, only advanced UICC stage (p = 0) and right sided localization (p = 0.04) were independent predictors of worse CSS. In conclusion, from all three HSPs examined in our study, only HSP70 expression worsened CRC prognosis, although stage-dependent. The contribution of this article may be seen as a large survival analysis of HSPs 27 and 70 and the largest analysis of HSP110 described in CRC.
Dual Targeting of EGFR with PLK1 Exerts Therapeutic Synergism in Taxane-Resistant Lung Adenocarcinoma by Suppressing ABC Transporters
Authors: Shin Sol-Bi , Kim Dae-Hoon , Kim Da-Eun , Aldonza Mark Borris D. , Kim Yoosik , Yim Hyungshin
Published: September 2021

To overcome the limitations of chemoresistance, combination therapies using druggable targets have been investigated. Our previous studies led us to hypothesize that the downregulation of PLK1 expression or activity can be one strategy to overcome the hurdles of taxane resistance by the downregulation of ABC transporters. To explore this, various versions of PLK1 including a constitutively active version, kinase-dead form, and polo-box domain mutant were expressed in paclitaxel-resistant lung adenocarcinoma (LUADTXR). Targeting PLK1 using shRNA or non-functional mutants downregulated ABCB1, ABCC9, and ABCG2 in LUADTXR cells, which was similar to the downregulation effects from treatment with PLK1 inhibitors. The high expression of EGFR in LUAD led us to administer gefitinib, showing a markedly reduced EGFR level in LUADTXR cells. When gefitinib and PLK1 inhibitors were combined, LUADTXR cells tended to undergo apoptosis more effectively than parental cells, showing a synergistic effect on the downregulation of ABC transporters through c-Myc and AP-1. Clinical data provide evidence for the relevance between survival rates and expressions of PLK1 and EGFR in LUAD patients. Based on these results, we suggest that a combination of gefitinib and PLK1 inhibitors exerts strong synergism in LUADTXR, which helps to overcome the limitations associated with taxanes.
NCOR1 Sustains Colorectal Cancer Cell Growth and Protects against Cellular Senescence
Authors: St-Jean Stéphanie , De Castro Ariane Cristina , Lecours Mia , Jones Christine , Rivard Nathalie , Rodier Francis , Perreault Nathalie , Boudreau François
Published: September 2021

NCOR1 is a corepressor that mediates transcriptional repression through its association with nuclear receptors and specific transcription factors. Some evidence supports a role for NCOR1 in neonatal intestinal epithelium maturation and the maintenance of epithelial integrity during experimental colitis in mice. We hypothesized that NCOR1 could control colorectal cancer cell proliferation and tumorigenicity. Conditional intestinal epithelial deletion of Ncor1 in ApcMin/+ mice resulted in a significant reduction in polyposis. RNAi targeting of NCOR1 in Caco-2/15 and HT-29 cell lines led to a reduction in cell growth, characterized by cellular senescence associated with a secretory phenotype. Tumor growth of HT-29 cells was reduced in the absence of NCOR1 in the mouse xenografts. RNA-seq transcriptome profiling of colon cancer cells confirmed the senescence phenotype in the absence of NCOR1 and predicted the occurrence of a pro-migration cellular signature in this context. SOX2, a transcription factor essential for pluripotency of embryonic stem cells, was induced under these conditions. In conclusion, depletion of NCOR1 reduced intestinal polyposis in mice and caused growth arrest, leading to senescence in human colorectal cell lines. The acquisition of a pro-metastasis signature in the absence of NCOR1 could indicate long-term potential adverse consequences of colon-cancer-induced senescence.
Defining the Tumor Microenvironment by Integration of Immunohistochemistry and Extracellular Matrix Targeted Imaging Mass Spectrometry
Authors: Rujchanarong Denys , Lefler Julia , Saunders Janet E. , Pippin Sarah , Spruill Laura , Bethard Jennifer R. , Ball Lauren E. , Mehta Anand S. , Drake Richard R. , Ostrowski Michael C. , Angel Peggi M.
Published: September 2021

Breast stroma plays a significant role in breast cancer risk and progression yet remains poorly understood. In breast stroma, collagen is the most abundantly expressed protein and its increased deposition and alignment contributes to progression and poor prognosis. Collagen post-translation modifications such as hydroxylated-proline (HYP) control deposition and stromal organization. The clinical relevance of collagen HYP site modifications in cancer processes remains undefined due to technical issues accessing collagen from formalin-fixed, paraffin-embedded (FFPE) tissues. We previously developed a targeted approach for investigating collagen and other extracellular matrix proteins from FFPE tissue. Here, we hypothesized that immunohistochemistry staining for fibroblastic markers would not interfere with targeted detection of collagen stroma peptides and could reveal peptide regulation influenced by specific cell types. Our initial work demonstrated that stromal peptide peak intensities when using MALD-IMS following IHC staining (αSMA, FAP, P4HA3 and PTEN) were comparable to serial sections of nonstained tissue. Analysis of histology-directed IMS using PTEN on breast tissues and TMAs revealed heterogeneous PTEN staining patterns and suggestive roles in stromal protein regulation. This study sets the foundation for investigations of target cell types and their unique contribution to collagen regulation within extracellular matrix niches.
A ‘Defective’ Conjugated Porous Poly-Azo as Dual Photocatalyst
Authors: Nath Ipsita , Chakraborty Jeet , Abednatanzi Sara , Van Der Voort Pascal
Published: September 2021

A heterogeneous photocatalyst amenable to catalyze different chemical reactions is a highly enabling and sustainable material for organic synthesis. Herein we report the synthesis and characterization of an azobenzene-based organic π–conjugated porous polymer (AzoCPP) as heterogeneous dual photocatalyst manifesting net-oxidative bromination of arenes and dehydroxylation of boronic acids to corresponding phenols. Hierarchical porosity and high surface area of the nano-sized AzoCPP allowed superior catalyst-substrate contact during catalyses, whereas the inherent structural defect present in the CPP backbone resulted in low-energy sinks functioning as de facto catalytic sites. A combination of these two structure-property aspects of AzoCPP, in addition to the dielectric constant manipulation of the system, led to excellent catalytic performance. The protocols remained valid for a wide substrate scope and the catalyst was recycled multiple times without substantial loss in catalytic activity. With the aid of subsequent control experiments and analytical characterizations, mechanisms for each catalysis are proposed and duly corroborated.
Neuropathology and Inflammatory Cell Characterization in 10 Autoptic COVID-19 Brains
Authors: Colombo Daniele , Falasca Laura , Marchioni Luisa , Tammaro Antonella , Adebanjo Ganiyat Adenike Ralitsa , Ippolito Giuseppe , Zumla Alimuddin , Piacentini Mauro , Nardacci Roberta , Del Nonno Franca
Published: September 2021

COVID-19 presents with a wide range of clinical neurological manifestations. It has been recognized that SARS-CoV-2 infection affects both the central and peripheral nervous system, leading to smell and taste disturbances; acute ischemic and hemorrhagic cerebrovascular disease; encephalopathies and seizures; and causes most surviving patients to have long lasting neurological symptoms. Despite this, typical neuropathological features associated with the infection have still not been identified. Studies of post-mortem examinations of the cerebral cortex are obtained with difficulty due to laboratory safety concerns. In addition, they represent cases with different neurological symptoms, age or comorbidities, thus a larger number of brain autoptic data from multiple institutions would be crucial. Histopathological findings described here are aimed to increase the current knowledge on neuropathology of COVID-19 patients. We report post-mortem neuropathological findings of ten COVID-19 patients. A wide range of neuropathological lesions were seen. The cerebral cortex of all patients showed vascular changes, hyperemia of the meninges and perivascular inflammation in the cerebral parenchyma with hypoxic neuronal injury. Perivascular lymphocytic inflammation of predominantly CD8-positive T cells mixed with CD68-positive macrophages, targeting the disrupted vascular wall in the cerebral cortex, cerebellum and pons were seen. Our findings support recent reports highlighting a role of microvascular injury in COVID-19 neurological manifestations.