bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the Dissipation on the Nonlinear Interactions and Turbulence of Gravity-Capillary Waves
Authors: Berhanu Michael
Published: April 2022

Gravity-capillary waves at the water surface are an obvious example illustrating wave propagation in the laboratory, and also nonlinear wave phenomena such as wave interactions or wave turbulence. However, at high-enough frequencies or small scales (i.e., the frequencies typically above 4 Hz or wavelengths below 10 cm), the viscous dissipation cannot be neglected, which complicates experimental, theoretical, and numerical approaches. In this review, we first derive, from the fundamental principles, the features of the gravity-capillary waves. We then discuss the origin and the magnitude of the viscous wave. dissipation in the laboratory and under field conditions. We then show that the significant level of dissipation has important consequences on nonlinear effects involving waves. The nonlinearity level quantified by the wave steepness must be large enough to overcome the viscous dissipation. Specifically, using water as fluid in the field and in the laboratory, nonlinear wave interactions and wave turbulence occur most of the time in a non-weakly nonlinear regime, when the waves are in the capillary or gravity-capillary range.
Evaluation of Pulsed Electric Field and Conventional Thermal Processing for Microbial Inactivation in Thai Orange Juice
Authors: Kantala Chatchawan , Supasin Supakiat , Intra Panich , Rattanadecho Phadungsak
Published: April 2022

A pulsed electric field (PEF) is a technology used for microbial inactivation in food and beverages. This study aimed to examine the effect of PEF treatment on microbial inactivation and quality parameters in Thai orange juice (TOJ). The results showed that PEF and conventional thermal pasteurization (CTP) can be performed for inactivation of Staphylococcus aureus and Escherichia coli in TOJ. A 5-log reduction was obtained after 10 pulses of PEF treatment when using and electrical field strength of 30 kV cm−1, and the microbial inactivation by the PEF treatment resulted from the electroporation more than the temperature. Moreover, PEF treatment affects the quality parameters less than CTP. Moreover, PEF treatment did not affect the TOJ quality parameters such as pH, commission international de l’eclairage (CIE), viscosity, and total soluble solid (TSS), but saved vitamin C and all sugar and all mineral (sucrose, glucose, fructose, sodium, lithium, potassium, magnesium, and calcium) values more than CTP treatment.
Nutritional Composition and Bioactive Compounds of Basil, Thyme and Sage Plant Additives and Their Functionality on Broiler Thigh Meat Quality
Authors: Vlaicu Petru Alexandru , Untea Arabela Elena , Turcu Raluca Paula , Saracila Mihaela , Panaite Tatiana Dumitra , Cornescu Gabriela Maria
Published: April 2022

Meat industries across the world are constantly focusing to find natural low-cost additives for the development of novel meat products to meet consumer demand for improving the health benefits. In this study, we investigated the chemical composition and the bioactive compounds of some herbal plants, namely basil, thyme, sage, and their functionality on broiler chicken thigh meat quality. Chemical composition, as well as total antioxidant activity, polyphenols, vitamin E lutein and zeaxanthin and the fatty acids of the plants, were analyzed. According to findings, total polyphenols was 21.53 mg gallic acid/g in basil, 31.73 mg gallic acid/g in thyme and 38.87 mg gallic acid/g in sage. The antioxidant capacity was 19.91 mM Trolox in basil, 54.09 mM Trolox in thyme and 54.09 mM Trolox in sage. Lutein and zeaxanthin from basil was 267.91 mg/kg, 535.79 mg/kg in thyme and 99.89 mg/kg, and vitamin E ranged from 291.71 mg/kg in basil to 379.37 mg/kg in thyme and 148.07 mg/kg in sage, respectively. After, we developed a trial on 120 unsexed broiler chickens (n = 30) which were separated into four groups with six replications of five chickens each: control (C); 1% basil (B); 1% thyme (T) and 1% sage (S). The B, T and S groups deposited significantly higher (p < 0.05) concentration of zinc, polyphenols, antioxidant capacity and vitamin E in meat samples compared with the C group. In the experimental groups, the proportion of total polyunsaturated fatty acids, the ratio of n-6 to n-3 fatty acids, and the ratio of polyunsaturated fatty acids to saturated fatty acids in the thigh muscles were significantly improved (p < 0.05). The tested plants exhibited a significant (p = 0.0007) hypocholesterolemic effect in the meat of the B (45.90 mg/g), T (41.60 mg/g) and S (48.80 mg/kg) experimental groups compared with the C (60.50 mg/g) group. These results support the application of the studied plants as natural sources of additives which could be effective in improving meat quality, from the human consumption perspective.
No More Glass Bottles? Canned Wine and Italian Consumers
Authors: Ruggeri Giordano , Mazzocchi Chiara , Corsi Stefano , Ranzenigo Benedetta
Published: April 2022

Packaging is an important economic component of the wine industry. However, while glass bottles are the leading wine container globally, their production and handling entail severe problems in increased carbon footprint impact and waste and logistic management. As a result, the wine packaging industry has developed and commercialised several alternatives to glass bottles, including aluminium cans. However, despite producers’ efforts in proposing alternative wine packaging, there are several barriers to their diffusion, especially in countries with a long tradition of wine consumption such as Italy, and it is still uncertain if and to what degree consumers would appreciate a wine in an aluminium can. This research investigates Italian wine consumers’ preferences and willingness to pay for canned wine through a survey and the contingent valuation method. We collected data from 551 consumers regarding attitudes and preferences about their wine consumption, alternative packaging acceptance, and motivations for accepting and refusing to buy it. Only a minority of the respondents declared they would buy canned wine, while the majority would refuse for reasons related to low-quality perception and poor consideration of alternative wine packaging. The lack of knowledge is one of the main obstacles to the diffusion of canned wine. However, canned wines could address different groups of wine drinkers and consumption occasions, increasing the opportunities for winemakers, especially among non-regular consumers.
On the VHE Spectrum and Formation of the Teraelectronvolt Pulsed Emission of the Crab Pulsar
Authors: Chkheidze Nino
Published: April 2022

In the present paper, a model for the pulsed γ-ray emission of the Crab pulsar from 0.01 GeV to 1 TeV in the context of synchrotron emission generated in the vicinity of a light cylinder is developed. The generation of such high energies through the synchrotron process requires the existence of very energetic plasma particles in pulsar magnetospheres. It is assumed that the emitting particles are ultra-relativistic primary beam electrons re-accelerated to very high energies due to the Landau damping process of a special type of parametrically driven Langmuir waves. This type of Langmuir wave carries energy released through the rotational slow-down of a pulsar and is very effective in supplying the resonant particles with energy from a natural reservoir. The model provides simultaneous generation of energetic γ-ray and low-frequency radio (0.1–1 GHz) emission in the same location of the pulsar magnetosphere. These two radiations processes are triggered by a single plasma process, namely excitation of the cyclotron instability. This provides a natural explanation for the observed coincidence of radio and γ-ray signals observed from the Crab pulsar.
Ground Displacements Estimation through GNSS and Geometric Leveling: A Geological Interpretation of the 2016–2017 Seismic Sequence in Central Italy
Authors: Salvini Riccardo , Vanneschi Claudio , Lanciano Chiara , Maseroli Renzo
Published: April 2022

Between August 2016 and January 2017, a very energetic seismic sequence induced substantial horizontal and vertical ground displacements in the Central Italian Apennines. After this event, the Italian Military Geographical Institute (IGM), owner and manager of the Italian geodetic networks, executed several topographic surveys in the earthquake area in order to update the coordinates of vertices belonging to the IGM95 geodetic network. The measurements began in the areas where the most significant deformation occurred: the localities of Amatrice and Accumoli, in the Rieti Province, and the area covering Norcia and Castelluccio, in the Province of Perugia, all the way to Visso (Province of Macerata). The activities described in this paper focused on the updated measurement of the IGM95 network points through GNSS and the restatement of extensive parts of the high precision geometric lines that were levelled until reaching stable zones. This unprecedented amount of data was used for a new geological interpretation of the seismic sequence, which confirms some of the previous hypotheses of the scientific community. In the analyzed territory, the latest estimate of the geodetic position points has allowed for an accurate determination of the east and the north and of the altitude components of the displacement induced by the earthquake through a comparison with the previous coordinates. The results confirm that the seismicity was induced by normal faults system activity. Still, they also indicate the possible influence of a significant regional thrust that conditioned the propagation of the seismicity in the area. The obtained maps of the displacement are coherent with other geodetic works and with a rupture propagation driven by the documented geotectonic structure.
Effects of Rhythm Step Training on Physical and Cognitive Functions in Adolescents: A Prospective Randomized Controlled Trial
Authors: Park Sang-Kyun , Jee Yong-Seok
Published: April 2022

Background: Rhythm step training (RST) for sensorimotor dual tasks is in the spotlight as it provides physical activity that is fun and allows participants to express various and creative movements, although it lacks a scientific evidence base. Therefore, this study was to investigate how RST affects the physical and cognitive functions of adolescents. Materials and Methods: A total of sixty-six female middle-schoolers were divided into non-exercise group (control group, CON, n = 22), step training group (STG, n = 22), and rhythm step training group (RSTG, n = 22). To verify the combined effects of music-based rhythm and exercise, the program was conducted for 45 min/session a day, three times a week for 12 weeks. Results: RST scores increased significantly in the STG and RSTG compared to the CON after 12 weeks. Specifically, the Δ% of RST scores in the RSTG (11.44%) was higher than those of STG (9.01%) and CON (3.91%). By the end of the experiment, the power (p < 0.001), agility (p < 0.001), muscle endurance (p < 0.001), dynamic or static balance (p < 0.001), and gait velocity (p < 0.001) of RSTG were significantly improved compared to the others. The Δ% of all variables in RSTG was higher than those of the CON or STG. In addition, the verbal memory (p < 0.001) and attention (p < 0.001) of cognitive function were significantly improved in RSTG. Specifically, there was more of an increase in Δ% of RSTG for verbal memory (7.52%) and attention (10.33%) than in the CON (verbal memory, 3.34%; attention, 5.83%) or STG (verbal memory, 5.85%; attention, 5.43%). Conclusions: This study confirms that RST had a positive effect on the physical and cognitive functions of female middle-schoolers. We propose that rhythmic exercise combined with music is beneficial for adolescents’ physical and cognitive health.
Psychosocial and Behavioral Effects of the COVID-19 Pandemic on Children and Adolescents with Autism and Their Families: Overview of the Literature and Initial Data from a Multinational Online Survey
Authors: Kreysa Helene , Schneider Dana , Kowallik Andrea Erika , Dastgheib Samaneh Sadat , Doğdu Cem , Kühn Gabriele , Ruttloff Jenny Marianne , Schweinberger Stefan R.
Published: April 2022

Since COVID-19 has become a pandemic, everyday life has seen dramatic changes affecting individuals, families, and children with and without autism. Among other things, these changes entail more time at home, digital forms of communication, school closures, and reduced support and intervention. Here, we assess the effects of the pandemic on quality of life for school-age autistic and neurotypical children and adolescents. First, we provide a comprehensive review of the current relevant literature. Next, we report original data from a survey conducted in several countries, assessing activities, well-being, and social life in families with autism, and their changes over time. We focus on differences between children with and without autism from within the same families, and on different outcomes for children with high- or low-functioning autism. While individuals with autism scored lower in emotional and social functioning than their neurotypical siblings, both groups of children showed comparable decreases in well-being and increases in anxiety, compared to before the pandemic. By contrast, decreases in adaptability were significantly more pronounced in autistic children and adolescents compared to neurotypical children and adolescents. Overall, although individual families reported some positive effects of pandemic restrictions, our data provide no evidence that these generalize across children and adolescents with autism, or even just to individuals with high-functioning autism. We discuss the increased challenges that need to be addressed to protect children and adolescents’ well-being under pandemic conditions, but also point out potentials in the present situation that could be used towards social participation and success in older children and young adults with autism.
A Comparison of Nursing and Pharmacy Students’ Perceptions of an Acute Care Simulation
Authors: Pence Jill , Ashe Shannon , Adunlin Georges , Beall Jennifer
Published: April 2022

Patient outcomes are improved when healthcare professionals work collaboratively. In order for future professionals to have these entry-level skills, students from different disciplines must work together in scenarios simulating patient care. This paper provides an overview of a large-scale, acute care simulation involving students of different disciplines, including nursing and pharmacy. A survey using the validated Student Perceptions of Interprofessional Clinical Education Revised (SPICE-R2) tool was administered to students participating in the simulation prior to and within 1 week of the simulation. There were between-group statistically significant differences on two items on the pre-simulation survey and two items on the post-simulation survey. Student participants reported more positive perceptions after the simulation on every item except for “During their education, health professional students should be involved in teamwork with students from other health professions to understand their perspective roles”. The authors concluded that an interprofessional acute care simulation allowed students in both professions to recognize the value of a team approach to patient care.
Uncontrolled Thyroid during Pregnancy Alters the Circulative and Exerted Metabolome
Authors: Fotakis Charalambos , Moros Giorgos , Kontogeorgou Anna , Iacovidou Nicoletta , Boutsikou Theodora , Zoumpoulakis Panagiotis
Published: April 2022

Normal levels of thyroid hormones (THs) are essential for a normal pregnancy outcome, fetal growth and the normal function of the central nervous system. Hypothyroidism, a common endocrine disorder during pregnancy, is a significant metabolic factor leading to cognitive impairments. It is essential to investigate whether patients with thyroid dysfunction may present an altered circulative and excreted metabolic profile, even after receiving treatment with thyroxine supplements. NMR metabolomics was employed to analyze 90 serum and corresponding colostrum samples. Parallel analyses of the two biological specimens provided a snapshot of the maternal metabolism through the excretive and circulating characteristics of mothers. The metabolomics data were analyzed by performing multivariate statistical, biomarker and pathway analyses. Our results highlight the impact of hypothyroidism on metabolites’ composition during pregnancy and lactation. Thyroid disorder causing metabolite fluctuations may lead to impaired lipid and glucose metabolic pathways as well as aberrant prenatal neurodevelopment, thus posing a background for the occurrence of metabolic syndrome or neurogenerative diseases later in life. This risk applies to not only untreated but also hypothyroid women under replacement therapy since our findings in both biofluids framed a different metabolic phenotype for the latter group, thus emphasizing the need to monitor women adequately after treatment initiation.
ABC Transporters in Human Diseases: Future Directions and Therapeutic Perspectives
Authors: Falguières Thomas
Published: April 2022

The goal of this Special Issue on “ABC Transporters in Human Diseases”, for which I was invited as a Guest Editor, was to provide an overview of the state-of-the-art research, understandings, and advances made in recent years on human diseases implicating ATP-binding cassette (ABC) transporters [...]
Are We Studying Non-Coding RNAs Correctly? Lessons from nc886
Authors: Lee Yong Sun
Published: April 2022

Non-coding RNAs (ncRNAs), such as microRNAs or long ncRNAs, have brought about a new paradigm in the regulation of gene expression. Sequencing technologies have detected transcripts with tremendous sensitivity and throughput and revealed that the majority of them lack protein-coding potential. Myriad articles have investigated numerous ncRNAs and many of them claim that ncRNAs play gene-regulatory roles. However, it is questionable whether all these articles draw conclusions through cautious gain- and loss-of function experiments whose design was reasonably based on an ncRNA’s correct identity and features. In this review, these issues are discussed with a regulatory ncRNA, nc886, as an example case to represent cautions and guidelines when studying ncRNAs.
Molecular Liver Fingerprint Reflects the Seasonal Physiology of the Grey Mouse Lemur (Microcebus murinus) during Winter
Authors: Chazarin Blandine , Benhaim-Delarbre Margaux , Brun Charlotte , Anzeraey Aude , Bertile Fabrice , Terrien Jérémy
Published: April 2022

Grey mouse lemurs (Microcebus murinus) are primates that respond to environmental energetic constraints through strong physiological seasonality. They notably fatten during early winter (EW), and mobilize their lipid reserves while developing glucose intolerance during late winter (LW), when food availability is low. To decipher how the hepatic mechanisms may support such metabolic flexibility, we analyzed the liver proteome of adult captive male mouse lemurs, whose seasonal regulations are comparable to their wild counterparts. We highlight profound hepatic changes that reflect fat accretion in EW at the whole-body level, without triggering an ectopic storage of fat in the liver, however. Moreover, molecular regulations are consistent with the decrease in liver glucose utilization in LW, and therefore with reduced tolerance to glucose. However, no major regulation was seen in insulin signaling/resistance pathways. Fat mobilization in LW appeared possibly linked to the reactivation of the reproductive system while enhanced liver detoxification may reflect an anticipation to return to summer levels of food intake. Overall, these results show that the physiology of mouse lemurs during winter relies on solid molecular foundations in liver processes to adapt fuel partitioning while opposing the development of a pathological state despite large lipid fluxes.
The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms
Authors: Caban Miłosz , Owczarek Katarzyna , Lewandowska Urszula
Published: April 2022

Eye diseases are associated with visual impairment, reduced quality of life, and may even lead to vision loss. The efficacy of available treatment of eye diseases is not satisfactory. The unique environment of the eye related to anatomical and physiological barriers and constraints limits the bioavailability of existing agents. In turn, complex ethiopathogenesis of ocular disorders that used drugs generally are non-disease specific and do not act causally. Therefore, there is a need for the development of a new therapeutic and preventive approach. It seems that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have a significant role in the development and progression of eye diseases and could be used in the therapy of these disorders as pharmacological targets. MMPs and TIMPs play an important role in the angiogenesis, epithelial-mesenchymal transition, cell invasion, and migration, which occur in ocular diseases. In this review, we aim to describe the participation of MMPs and TIMPs in the eye diseases, such as age-related macular degeneration, cataract, diabetic retinopathy, dry eye syndrome, glaucoma, and ocular cancers, posterior capsule opacification focusing on potential mechanisms.
Neuroepigenetic Mechanisms of Action of Ultrashort Peptides in Alzheimer’s Disease
Authors: Ilina Anastasiia , Khavinson Vladimir , Linkova Natalia , Petukhov Mikhael
Published: April 2022

Epigenetic regulation of gene expression is necessary for maintaining higher-order cognitive functions (learning and memory). The current understanding of the role of epigenetics in the mechanism of Alzheimer’s disease (AD) is focused on DNA methylation, chromatin remodeling, histone modifications, and regulation of non-coding RNAs. The pathogenetic links of this disease are the misfolding and aggregation of tau protein and amyloid peptides, mitochondrial dysfunction, oxidative stress, impaired energy metabolism, destruction of the blood–brain barrier, and neuroinflammation, all of which lead to impaired synaptic plasticity and memory loss. Ultrashort peptides are promising neuroprotective compounds with a broad spectrum of activity and without reported side effects. The main aim of this review is to analyze the possible epigenetic mechanisms of the neuroprotective action of ultrashort peptides in AD. The review highlights the role of short peptides in the AD pathophysiology. We formulate the hypothesis that peptide regulation of gene expression can be mediated by the interaction of short peptides with histone proteins, cis- and transregulatory DNA elements and effector molecules (DNA/RNA-binding proteins and non-coding RNA). The development of therapeutic agents based on ultrashort peptides may offer a promising addition to the multifunctional treatment of AD.
Expression of NGF/proNGF and Their Receptors TrkA, p75NTR and Sortilin in Melanoma
Authors: Marsland Mark , Dowdell Amiee , Jiang Chen Chen , Wilmott James S. , Scolyer Richard A. , Zhang Xu Dong , Hondermarck Hubert , Faulkner Sam
Published: April 2022

There is increasing evidence that nerve growth factor (NGF) and its receptors, the neurotrophic receptor tyrosine kinase 1 (NTRK1/TrkA), the common neurotrophin receptor (NGFR/p75NTR) and the membrane receptor sortilin, participate in cancer growth. In melanoma, there have been some reports suggesting that NGF, TrkA and p75NTR are dysregulated, but the expression of the NGF precursor (proNGF) and its membrane receptor sortilin is unknown. In this study, we investigated the expression of NGF, proNGF, TrkA, p75NTR and sortilin by immunohistochemistry in a series of human tissue samples (n = 100), including non-cancerous nevi (n = 20), primary melanomas (n = 40), lymph node metastases (n = 20) and distant metastases (n = 20). Immunostaining was digitally quantified and revealed NGF and proNGF were expressed in all nevi and primary melanomas, and that the level of expression decreased from primary tumors to melanoma metastases (p = 0.0179 and p < 0.0001, respectively). Interestingly, TrkA protein expression was high in nevi and thin primary tumors but was strongly downregulated in thick primary tumors (p < 0.0001) and metastases (p < 0.0001). While p75NTR and sortilin were both expressed in most nevi and melanomas, there was no significant difference in expression between them. Together, these results pointed to a downregulation of NGF/ProNGF and TrkA in melanoma, and thus did not provide evidence to support the use of anti-proNGF/NGF or anti-TrkA therapies in advanced and metastatic forms of melanoma.
Modulation of Metabolic Hormone Signaling via a Circadian Hormone and Biogenic Amine in Drosophila melanogaster
Authors: Braco Jason T. , Nelson Jonathan M. , Saunders Cecil J. , Johnson Erik C.
Published: April 2022

In insects, adipokinetic hormone is the primary hormone responsible for the mobilization of stored energy. While a growing body of evidence has solidified the role of adipokinetic hormone (AKH) in modulating the physiological and behavioral responses to metabolic stress, little is known about the upstream endocrine circuit that directly regulates AKH release. We evaluated the AKH-producing cell (APC) transcriptome to identify potential regulatory elements controlling APC activity and found that a number of receptors showed consistent expression levels, including all known dopamine receptors and the pigment dispersing factor receptor (PDFR). We tested the consequences of targeted genetic knockdown and found that APC limited expression of RNAi elements corresponding to each dopamine receptor and caused a significant reduction in survival under starvation. In contrast, PDFR knockdown significantly extended lifespan under starvation, whereas expression of a tethered PDF in APCs resulted in significantly shorter lifespans. These manipulations caused various changes in locomotor activity under starvation. We used live-cell imaging to evaluate the acute effects of the ligands for these receptors on APC activation. Dopamine application led to a transient increase in intracellular calcium in a trehalose-dependent manner. Furthermore, coapplication of dopamine and ecdysone led to a complete loss of this response, suggesting that these two hormones act antagonistically. We also found that PDF application led to an increase in cAMP in APCs and that this response was dependent on expression of the PDFR in APCs. Together, these results suggest a complex circuit in which multiple hormones act on APCs to modulate metabolic state.
Significant Therapeutic Effects of Adult Human Neural Stem Cells for Spinal Cord Injury Are Mediated by Monocyte Chemoattractant Protein-1 (MCP-1)
Authors: Kim Chung Kwon , Won Jeong-Seob , An Jae Yeol , Lee Ho Jin , Nam Ah-Jin , Nam Hyun , Lee Ji Yeoun , Lee Kyung-Hoon , Lee Sun-Ho , Joo Kyeung Min
Published: April 2022

The limited capability of regeneration in the human central nervous system leads to severe and permanent disabilities following spinal cord injury (SCI) while patients suffer from no viable treatment option. Adult human neural stem cells (ahNSCs) are unique cells derived from the adult human brain, which have the essential characteristics of NSCs. The objective of this study was to characterize the therapeutic effects of ahNSCs isolated from the temporal lobes of focal cortical dysplasia type IIIa for SCI and to elucidate their treatment mechanisms. Results showed that the recovery of motor functions was significantly improved in groups transplanted with ahNSCs, where, in damaged regions of spinal cords, the numbers of both spread and regenerated nerve fibers were observed to be higher than the vehicle group. In addition, the distance between neuronal nuclei in damaged spinal cord tissue was significantly closer in treatment groups than the vehicle group. Based on an immunohistochemistry analysis, those neuroprotective effects of ahNSCs in SCI were found to be mediated by inhibiting apoptosis of spinal cord neurons. Moreover, the analysis of the conditioned medium (CM) of ahNSCs revealed that such neuroprotective effects were mediated by paracrine effects with various types of cytokines released from ahNSCs, where monocyte chemoattractant protein-1 (MCP-1, also known as CCL2) was identified as a key paracrine mediator. These results of ahNSCs could be utilized further in the preclinical and clinical development of effective and safe cell therapeutics for SCI, with no available therapeutic options at present.
2-Pyridine Carboxaldehyde for Semi-Automated Soft Spot Identification in Cyclic Peptides
Authors: Zhang Haiying , Chacko Silvi , Cannon Joe R.
Published: April 2022

Cyclic peptides are an attractive option as therapeutics due to their ability to disrupt crucial protein–protein interactions and their flexibility in display type screening strategies, but they come with their own bioanalytical challenges in metabolite identification. Initial amide hydrolysis of a cyclic peptide results in a ring opening event in which the sequence is linearized. Unfortunately, the mass of the singly hydrolyzed sequence is the same (M + 18.0106 Da) irrespective of the initial site of hydrolysis, or soft spot. Soft spot identification at this point typically requires time-consuming manual interpretation of the tandem mass spectra, resulting in a substantial bottleneck in the hit to lead process. To overcome this, derivatization using 2-pyridine carboxaldehyde, which shows high selectivity for the alpha amine on the N-terminus, was employed. This strategy results in moderate- to high-efficiency derivatization with a unique mass tag and diagnostic ions that serve to highlight the first amino acid in the newly linearized peptide. The derivatization method and analytical strategy are demonstrated on a whole cell lysate digest, and the soft spot identification strategy is shown with two commercially available cyclic peptides: JB1 and somatostatin. Effective utilization of the automated sample preparation and interpretation of the resulting spectra shown here will serve to reduce the hit-to-lead time for generating promising proteolytically stable peptide candidates.
Antisense Oligonucleotides Conjugated with Lipophilic Compounds: Synthesis and In Vitro Evaluation of Exon Skipping in Duchenne Muscular Dystrophy
Authors: Marchesi Elena , Cortesi Rita , Preti Lorenzo , Rimessi Paola , Sguizzato Maddalena , Bovolenta Matteo , Perrone Daniela
Published: April 2022

Our groups previously reported that conjugation at 3′-end with ursodeoxycholic acid (UDCA) significantly enhanced in vitro exon skipping properties of ASO 51 oligonucleotide targeting the human DMD exon 51. In this study, we designed a series of lipophilic conjugates of ASO 51, to explore the influence of the lipophilic moiety on exon skipping efficiency. To this end, three bile acids and two fatty acids have been derivatized and/or modified and conjugated to ASO 51 by automatized solid phase synthesis. We measured the melting temperature (Tm) of lipophilic conjugates to evaluate their ability to form a stable duplex with the target RNA. The exon skipping efficiency has been evaluated in myogenic cell lines first in presence of a transfection agent, then in gymnotic conditions on a selection of conjugated ASO 51. In the case of 5′-UDC-ASO 51, we also evaluated the influence of PS content on exon skipping efficiency; we found that it performed better exon skipping with full PS linkages. The more efficient compounds in terms of exon skipping were found to be 5′-UDC- and 5′,3′-bis-UDC-ASO 51.
Plant Cell Wall Proteomes: The Core of Conserved Protein Families and the Case of Non-Canonical Proteins
Authors: San Clemente Hélène , Kolkas Hasan , Canut Hervé , Jamet Elisabeth
Published: April 2022

Plant cell wall proteins (CWPs) play critical roles during plant development and in response to stresses. Proteomics has revealed their great diversity. With nearly 1000 identified CWPs, the Arabidopsis thaliana cell wall proteome is the best described to date and it covers the main plant organs and cell suspension cultures. Other monocot and dicot plants have been studied as well as bryophytes, such as Physcomitrella patens and Marchantia polymorpha. Although these proteomes were obtained using various flowcharts, they can be searched for the presence of members of a given protein family. Thereby, a core cell wall proteome which does not pretend to be exhaustive, yet could be defined. It comprises: (i) glycoside hydrolases and pectin methyl esterases, (ii) class III peroxidases, (iii) Asp, Ser and Cys proteases, (iv) non-specific lipid transfer proteins, (v) fasciclin arabinogalactan proteins, (vi) purple acid phosphatases and (vii) thaumatins. All the conserved CWP families could represent a set of house-keeping CWPs critical for either the maintenance of the basic cell wall functions, allowing immediate response to environmental stresses or both. Besides, the presence of non-canonical proteins devoid of a predicted signal peptide in cell wall proteomes is discussed in relation to the possible existence of alternative secretion pathways.
Differential Effects of Cytopathic Hypoxia on Human Retinal Endothelial Cellular Behavior: Implication for Ischemic Retinopathies
Authors: El-tanani Shaimaa , Yumnamcha Thangal , Singh Lalit Pukhrambam , Ibrahim Ahmed S.
Published: April 2022

Loss of barrier integrity of retinal endothelial cells (RECs) is an early feature of ischemic retinopathies (IRs), but the triggering mechanisms remain incompletely understood. Previous studies have reported mitochondrial dysfunction in several forms of IRs, which creates a cytopathic hypoxic environment where cells cannot use oxygen for energy production. Nonetheless, the contribution of cytopathic hypoxia to the REC barrier failure has not been fully explored. In this study, we dissect in-depth the role of cytopathic hypoxia in impairing the barrier function of REC. We employed the electric cell-substrate impedance sensing (ECIS) technology to monitor in real-time the impedance (Z) and hence the barrier functionality of human RECs (HRECs) under cytopathic hypoxia-inducing agent, Cobalt(II) chloride (CoCl2). Furthermore, data were deconvoluted to test the effect of cytopathic hypoxia on the three key components of barrier integrity; Rb (paracellular resistance between HRECs), α (basolateral adhesion between HRECs and the extracellular matrix), and Cm (HREC membrane capacitance). Our results showed that CoCl2 decreased the Z of HRECs dose-dependently. Specifically, the Rb parameter of the HREC barrier was the parameter that declined first and most significantly by the cytopathic hypoxia-inducing agent and in a dose-dependent manner. When Rb began to fall to its minimum, other parameters of the HREC barrier, including α and Cm, were unaffected. Interestingly, the compromised effect of cytopathic hypoxia on Rb was associated with mitochondrial dysfunction but not with cytotoxicity. In conclusion, our results demonstrate distinguishable dielectric properties of HRECs under cytopathic hypoxia in which the paracellular junction between adjacent HRECs is the most vulnerable target. Such selective behavior could be utilized to screen agents or genes that maintain and strengthen the assembly of HRECs tight junction complex.
Effectiveness of a New Self-Marking Technique in Aedes aegypti under Laboratory Conditions
Authors: Diouf Gorgui , Seck Momar Talla , Fall Assane Guèye , Bassène Mireille Djimangali , Biteye Biram , Bakhoum Mame Thierno , Ciss Mamadou
Published: April 2022

In the implementation of mosquito control strategy programs using Sterile Insect Technique and other rear and release strategies, knowledge on the dispersion, competitiveness and survival of mosquitos is considered essential. To assess these parameters, marking techniques are generally used to differentiate colony mosquitoes from wild ones. Most of the existing mosquito marking methods require numerous manipulations that can impact their quality. In this study, we have developed a self-marking technique that can reduce the damage associated with mosquito handling. The marking technique consisted of adding fluorescent powder (DayGlo: A-17-N Saturn yellow) directly to the surface water of the receptacle containing Aedes aegypti male pupae. Different quantities of powder were used, and marking efficacy, powder persistence and mosquito survival were assessed. The results show a mean marking rate of 98 ± 1.61%, and the probability of marking increased significantly (p < 0.001) with increasing concentrations of fluorescent powder. Fluorescent powder persisted up to 20 days and did not induce a negative effect on mosquito survival (χ2 = 5.3, df = 7, p = 0.63). In addition, powder transfer did not occur between marked and unmarked populations. This marking method significantly reduces human intervention and mosquito handling during the marking process, improving the quality of marked mosquitoes used to assess SIT programs.
Association between Subjective and Objective Assessment of Enucleation Outcome Depending on the Presence of an Orbital Implant in Patients with Uveal Melanoma
Authors: Pociej-Marciak Weronika , Romanowska-Dixon Bożena , Żuber-Łaskawiec Katarzyna , Globočnik Petrovič Mojca , Karska-Basta Izabella
Published: April 2022

We aimed to assess the cosmetic outcome of patients who underwent enucleation for uveal melanoma. The subjective assessment was based on a questionnaire, including four questions on postoperative cosmetic outcome. As part of the objective assessment, the following features were evaluated using a four-point scale: the symmetry of the upper eyelid sulcus, color matching between the prosthetic and healthy eye, prosthetic eye motility, and eyelid position. We enrolled 90 patients after enucleation (58 with and 32 without an orbital implant). The overall subjective assessment scores were 3.5/4 and 3.3/4 points in patients with and without an implant, respectively. The overall objective assessment scores were 3.3/4 and 2.3/4 in patients with and without an implant, respectively (p < 0.001). The cosmetic outcome was rated significantly higher by patients than by investigators (p < 0.05). There was no significant association between the overall subjective and objective assessment of the cosmetic outcome in any of the groups. Cosmetic outcome after enucleation for uveal melanoma was highly rated by patients. It was rated higher by patients than by investigators. The presence of an orbital implant was associated with higher objective assessment scores in terms of the symmetry of the upper lid sulcus, prosthetic eye motility, and eyelid position.
Vertical Motion Control of an Underwater Glider with a Command Filtered Adaptive Algorithm
Authors: Li Mingjie , Yao Baoheng , Yu Caoyang , Lian Lian
Published: April 2022

Underwater gliders are widely used in oceanic observation, which are driven by a hydraulic buoyancy regulating system and a movable mass. Better motion performance can help us to accomplish observation tasks better. Therefore, a command filtered adaptive algorithm with a detailed system dynamic model is proposed for underwater gliders in this paper. The dynamic model considers seawater density variation, temperature variation and hull deformation according to dive depth. The hydraulic pump model and the movable mass dynamic are also taken into account. An adaptive nonlinear control strategy based on backstepping technique is developed to compensate the uncertainties and disturbances in the control system. To deal with the command saturation and calculation of derivatives in the backstepping process, command filtered method is employed. The stability of the whole system is proved through the Lyapunov theory. Comparative simulations are conducted to verify the effectiveness of the proposed controller. The results demonstrate that the proposed algorithm can improve the motion control performance for underwater gliders under uncertainties and disturbances.
Explosion Characteristics of Hydrogen Gas in Varying Ship Ventilation Tunnel Geometries: An Experimental Study
Authors: Park Soung Woo , Kim Jeong Hwan , Seo Jung Kwan
Published: April 2022

Hydrogen is widely regarded as a key element of prospective energy solutions for alleviating environmental emission problems. However, hydrogen is classified as a high-risk gas because of its wide explosive range, high overpressure, low ignition energy, and fast flame propagation speed compared with those of hydrocarbon-based gases. In addition, deflagration can develop into detonation in ventilation or explosion guide tunnels if explosion overpressure occurs, leading to the explosion of all combustible gases. However, quantitative evidence of an increase in the explosion overpressure of ventilation tunnels is unavailable because the explosive characteristics of hydrogen gas are insufficiently understood. Therefore, this study investigated an explosion chamber with the shape of a ventilation pipe in a ship compartment. The effect of tunnel length on explosion overpressure was examined experimentally. For quantitative verification, the size of the hydrogen gas explosion overpressure was analyzed and compared with experimental values of hydrocarbon-based combustible gases (butane and LPG (propane 98%)). The experimental database can be used for explosion risk analyses of ships when designing ventilation holes and piping systems and developing new safety guidelines for hydrogen carriers and hydrogen-fueled ships.
Past, Present, and Future Perspectives on Whey as a Promising Feedstock for Bioethanol Production by Yeast
Authors: Zou Jing , Chang Xuedong
Published: April 2022

Concerns about fossil fuel depletion and the environmental effects of greenhouse gas emissions have led to widespread fermentation-based production of bioethanol from corn starch or sugarcane. However, competition for arable land with food production has led to the extensive investigation of lignocellulosic sources and waste products of the food industry as alternative sources of fermentable sugars. In particular, whey, a lactose-rich, inexpensive byproduct of dairy production, is available in stable, high quantities worldwide. This review summarizes strategies and specific factors essential for efficient lactose/whey fermentation to ethanol. In particular, we cover the most commonly used strains and approaches for developing high-performance strains that tolerate fermentation conditions. The relevant genes and regulatory systems controlling lactose utilization and sources of new genes are also discussed in detail. Moreover, this review covers the optimal conditions, various feedstocks that can be coupled with whey substrates, and enzyme supplements for increasing efficiency and yield. In addition to the historical advances in bioethanol production from whey, this review explores the future of yeast-based fermentation of lactose or whey products for beverage or fuel ethanol as a fertile research area for advanced, environmentally friendly uses of industrial waste products.
A Giraffe in the Botanic Garden of Pisa (Tuscany, Northern Italy)
Authors: Bedini Gianni , Farina Simone
Published: April 2022

The Botanic Garden of Pisa was established in 1543 as a teaching tool and research facility. As with the vast majority of its sister institutions, it focuses on plant collections. However, for a short time in the first half of the XIX century, the Botanic Garden exhibited a living giraffe, a cow, and a calf. Due to the transient nature of the exhibition, it could have easily gone unnoticed but for the fortuitous representation of the animals in a drawing of the same period and for sparse notes archived in the libraries of Pisa University. Furthermore, a XIX-century publication on the morphological and behavioural traits of three antelopes indirectly suggests that those animals had been kept in the Botanic Garden for research purposes. This paper presents the evidence of the living animal display in the Botanic Garden of Pisa and the context in which it was collected.
Nature-Based Solutions for the Sustainable Management of Urban Soils and Quality of Life Improvements
Authors: Petrova Slaveya , Velcheva Iliana , Nikolov Bogdan , Angelov Nikola , Hristozova Gergana , Zaprjanova Penka , Valcheva Ekaterina , Golubinova Irena , Marinov-Serafimov Plamen , Petrov Petar , Stefanova Veneta , Varbanova Evelina , Georgieva Deyana , Stefanova Violeta , Marhova Mariyana , Tsankova Marinela , Iliev Ivan
Published: April 2022

The rehabilitation and restoration of land-based ecosystems is a key strategy for recovering the services (goods and resources) ecosystems offer to humankind. The use of nature-based solutions (NBSs) to restore degraded soil functions and improve soil quality can be a sustainable and successful strategy to enhance their ecosystem services by working together with the forces of nature and using well-designed measures that require less maintenance, are more cost-effective, and if constructed in the right way may even be more effective over long periods because nature’s forces can increase the structural efficiency. In this study, we aimed to (i) evaluate the bioremediation capacity of some grasses and their suitability for lawn planting in settlements (in residential and non-residential areas, along roads, etc.) and (ii) propose technological solutions for their practical application in an urban environment. Emphasis was placed on the potential of some perennial grasses and their application for the bioremediation of polluted urban soils, including perennial ryegrass (Lolium perenne L.), crested wheatgrass (Agropyron cristatum L.), tall fescue (Festuca arundinacea Schreb), and bird’s foot trefoil (Lotus corniculatus L.). A case study from the city of Plovdiv (Bulgaria) is presented, together with an effective technological solution for the establishment of urban lawns and the roadside green buffer patches.
A pH-Gated Functionalized Hollow Mesoporous Silica Delivery System for Photodynamic Sterilization in Staphylococcus aureus Biofilm
Authors: Zhao Nanxin , Cai Rongfeng , Zhang Yuting , Wang Xiaoli , Zhou Nandi
Published: April 2022

Multidrug-resistant bacteria are increasing, particularly those embedded in microbial biofilm. These bacteria account for most microbial infections in humans. Traditional antibiotic treatment has low efficiency in sterilization of biofilm-associated pathogens, and thus the development of new approaches is highly desired. In this study, amino-modified hollow mesoporous silica nanoparticles (AHMSN) were synthesized and used as the carrier to load natural photosensitizer curcumin (Cur). Then glutaraldehyde (GA) and polyethyleneimine (PEI) were used to seal the porous structure of AHMSN by the Schiff base reaction, forming positively charged AHMSN@GA@PEI@Cur. The Cur delivery system can smoothly diffuse into the negatively charged biofilm of Staphylococcus aureus (S. aureus). Then Cur can be released to the biofilm after the pH-gated cleavage of the Schiff base bond in the slightly acidic environment of the biofilm. After the release of the photosensitizer, the biofilm was irradiated by the blue LED light at a wavelength of 450 nm and a power of 37.4 mV/cm2 for 5 min. Compared with the control group, the number of viable bacteria in the biofilm was reduced by 98.20%. Therefore, the constructed pH-gated photosensitizer delivery system can efficiently target biofilm-associated pathogens and be used for photodynamic sterilization, without the production of antibiotic resistance.