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Strigolactones (SLs), a class of carotenoid-derived hormones, play a crucial role in flowering plants by regulating underground communication with symbiotic arbuscular mycorrhizal fungi (AM) and controlling shoot and root architecture. While the functions of core SL genes have been characterized in many plants, their roles in non-tracheophyte plants like liverworts require further investigation. In this study, we employed the model liverwort species Marchantia polymorpha, which lacks detectable SL production and orthologs of key SL biosynthetic genes, including CAROTENOID CLEAVAGE DIOXYGENASE 8 (CCD8) and MORE AXILLARY GROWTH 1 (MAX1). However, it retains some SL pathway components, including DWARF27 (D27) and CCD7. To help elucidate the function of these remaining components in M. polymorpha, knockout mutants were generated for MpD27--1, MpD27--2 and MpCCD7. Phenotypic comparisons of these mutants with the wild-type control revealed a novel role for these genes in regulating the release of gemmae from the gemma cup and the germination and growth of gemmae in the dark. Mpd27--1, Mpd27--2, and Mpccd7 mutants showed lower transcript abundance of genes involved in photosynthesis, such as EARLY LIGHT INDUCED (ELI), and stress responses such as LATE EMBRYOGENESIS ABUNDANT (LEA) but exhibited higher transcript levels of ETHYLENE RESPONSE FACTORS (ERFs) and SL and carotenoid related genes, such as TERPENE SYNTHASE (TS), CCD7 and LECITHIN-RETINAL ACYL TRANSFERASE (LRAT). Furthermore, the mutants of M. polymorpha in the SL pathway exhibited increased contents of carotenoid. This unveils a previously unrecognized role for MpD27--1, MpD27--2 and MpCCD7 in controlling release, germination, and growth of gemmae in response to varying light conditions. These discoveries enhance our comprehension of the regulatory functions of SL biosynthesis genes in non-flowering plants. [ABSTRACT FROM AUTHOR]

The basidiomycete fungus Mycena citricolor hosts on about 80 plant families. The asexual morph causes the disease known as American leaf spot of coffee (Coffea arabica). We isolated and characterized 15 isolates of M. citricolor collected from coffee plants, shade trees and weeds. Cultures on potato‐dextrose‐agar + yeast extract (PDAY) medium were kept for a week in complete darkness. The cultures were then exposed to light for 7 weeks and co‐cultivated with coffee foliar discs, to stimulate the production of gemmifers. We evaluated the speed of growth, appearance, colour of the mycelium and gemmifers production capacity. All isolates conformed to the typical cultural characteristics of M. citricolor, with beige/white thin and slightly aerial mycelium. The whitest isolate was from Persea americana, which had the slowest growth rate in vitro (6.4 mm/day), while the isolate from weed Kalanchoe pinnata was the fastest, with a speed of 9 mm/day. The most gemmifer‐producing isolates were those isolated from the coffee cultivar Catimor‐Costa Rica 95, Citharexylum donnell‐smithii and Cissus verticillata, with over 200 gemmifers per Petri dish. Isolates from Erythrina and Ipomoea nil produced <50 gemmifers on average. The Composite Aggressiveness Index (CAI) was determined on 2‐year‐old detached coffee branches of the Caturra variety foliage. The least aggressive isolate was from Erythrina poeppigiana (CAI = 0) and the most aggressive was from Kalanchoe pinnata (CAI = 18.87). The isolate from the coffee cultivar Catimor‐Costa Rica 95 was more aggressive than that from the cultivar Caturra (CAI = 9.94 vs. CAI = 3.66). Moreover, successful infection occurred only when the apex of gemmae made direct contact with the coffee leaf when using the inoculum derived from C. verticillata and Anredera cordifolia. These results show the variability in the population of the pathogen. This is the first study that characterizes the growth, morphology, reproduction and aggressiveness of M. citricolor obtained from hosts other than coffee. In addition, it is the first to report the use of coffee foliar discs to induce gemmifer production in vitro and to assess and quantify the effect of gemma position when inoculating coffee leaves. [ABSTRACT FROM AUTHOR]

Introduction Large Language Models (LLMs) like ChatGPT have become increasingly prevalent. In medicine, many potential areas arise where LLMs may offer added value. Our research focuses on the use of open-source LLM alternatives like Llama 3, Gemma, Mistral, and Mixtral to extract medical parameters from German clinical texts. We concentrate on German due to an observed gap in research for non-English tasks. Objective To evaluate the effectiveness of open-source LLMs in extracting medical parameters from German clinical texts, specially focusing on cardiovascular function indicators from cardiac MRI reports. Methods We extracted 14 cardiovascular function indicators, including left and right ventricular ejection fraction (LV-EF and RV-EF), from 497 variously formulated cardiac magnetic resonance imaging (MRI) reports. Our systematic analysis involved assessing the performance of Llama 3, Gemma, Mistral, and Mixtral models in terms of right annotation and named entity recognition (NER) accuracy. Results The analysis confirms strong performance with up to 95.4% right annotation and 99.8% NER accuracy across different architectures, despite the fact that these models were not explicitly fine-tuned for data extraction and the German language. Conclusion The results strongly recommend using open-source LLMs for extracting medical parameters from clinical texts, including those in German, due to their high accuracy and effectiveness even without specific fine-tuning. [ABSTRACT FROM AUTHOR]

Large language models (LLMs) are transformer-based neural networks that can provide human-like responses to questions and instructions. LLMs can generate educational material, summarize text, extract structured data from free text, create reports, write programs, and potentially assist in case sign-out. LLMs combined with vision models can assist in interpreting histopathology images. LLMs have immense potential in transforming pathology practice and education, but these models are not infallible, so any artificial intelligence generated content must be verified with reputable sources. Caution must be exercised on how these models are integrated into clinical practice, as these models can produce hallucinations and incorrect results, and an over-reliance on artificial intelligence may lead to de-skilling and automation bias. This review paper provides a brief history of LLMs and highlights several use cases for LLMs in the field of pathology. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs), a class of carotenoid-derived hormones, play a crucial role in flowering plants by regulating underground communication with symbiotic arbuscular mycorrhizal fungi (AM) and controlling shoot and root architecture. While the functions of core SL genes have been characterized in many plants, their roles in non-tracheophyte plants like liverworts require further investigation. In this study, we employed the model liverwort species Marchantia polymorpha, which lacks detectable SL production and orthologs of key SL biosynthetic genes, including CAROTENOID CLEAVAGE DIOXYGENASE 8 (CCD8) and MORE AXILLARY GROWTH 1 (MAX1). However, it retains some SL pathway components, including DWARF27 (D27) and CCD7. To help elucidate the function of these remaining components in M. polymorpha, knockout mutants were generated for MpD27–1, MpD27–2 and MpCCD7. Phenotypic comparisons of these mutants with the wild-type control revealed a novel role for these genes in regulating the release of gemmae from the gemma cup and the germination and growth of gemmae in the dark. Mpd27–1, Mpd27–2, and Mpccd7 mutants showed lower transcript abundance of genes involved in photosynthesis, such as EARLY LIGHT INDUCED (ELI), and stress responses such as LATE EMBRYOGENESIS ABUNDANT (LEA) but exhibited higher transcript levels of ETHYLENE RESPONSE FACTORS (ERFs) and SL and carotenoid related genes, such as TERPENE SYNTHASE (TS), CCD7 and LECITHIN-RETINAL ACYL TRANSFERASE (LRAT). Furthermore, the mutants of M. polymorpha in the SL pathway exhibited increased contents of carotenoid. This unveils a previously unrecognized role for MpD27–1, MpD27–2 and MpCCD7 in controlling release, germination, and growth of gemmae in response to varying light conditions. These discoveries enhance our comprehension of the regulatory functions of SL biosynthesis genes in non-flowering plants.

SUMMARY: A combination of streamlined genetics, experimental tractability and relative morphological simplicity compared to vascular plants makes the liverwort Marchantia polymorpha an ideal model system for studying many aspects of plant biology. Here we describe a transformation vector combining a constitutive fluorescent membrane marker with a nuclear marker that is regulated by nearby enhancer elements and use this to produce a library of enhancer trap lines for Marchantia. Screening gemmae from these lines allowed the identification and characterization of novel marker lines, including markers for rhizoids and oil cells. The library allowed the identification of a margin tissue running around the thallus edge, highlighted during thallus development. The expression of this marker is correlated with auxin levels. We generated multiple markers for the meristematic apical notch region, which have different spatial expression patterns, reappear at different times during meristem regeneration following apical notch excision and have varying responses to auxin supplementation or inhibition. This reveals that there are proximodistal substructures within the apical notch that could not be observed otherwise. We employed our markers to study Marchantia sporeling development, observing meristem emergence as defining the protonema‐to‐prothallus stage transition, and subsequent production of margin tissue during the prothallus stage. Exogenous auxin treatment stalls meristem emergence at the protonema stage but does not inhibit cell division, resulting in callus‐like sporelings with many rhizoids, whereas pharmacologically inhibiting auxin synthesis and transport does not prevent meristem emergence. This enhancer trap system presents a useful resource for the community and will contribute to future Marchantia research. [ABSTRACT FROM AUTHOR]

In this paper, we explore potential genetic factors in control of flax phenotypes associated with fiber by mining a collection of 306 flax accessions from the Federal Research Centre of the Bast Fiber Crops, Torzhok, Russia. In total, 11 traits were assessed in the course of 3 successive years. A genome-wide association study was performed for each phenotype independently using six different single-locus models implemented in the GAPIT3 R package. Moreover, we applied a multivariate linear mixed model implemented in the GEMMA package to account for trait correlations and potential pleiotropic effects of polymorphisms. The analyses revealed a number of genomic variants associated with different fiber traits, implying the complex and polygenic control. All stable variants demonstrate a statistically significant allelic effect across all 3 years of the experiment. We tested the validity of the predicted variants using gene expression data available for the flax fiber studies. The results shed new light on the processes and pathways associated with the complex fiber traits, while the pinpointed candidate genes may be further used for marker-assisted selection. [ABSTRACT FROM AUTHOR]

Sexual reproduction is almost universal in vertebrates; therefore, each animal species which uses it must have a mechanism for designating sex as male or female. Fish, especially, have a wide range of sex determining systems. In the present study, we aimed to identify a genetic basis for sex determination in the common creek chub (Semotilus atromaculatus) using genotyping‐by‐sequencing data. No sex‐associated markers were found by RADSex or a GWAS using GEMMA; however, Weir and Cockerham locus‐specific FST analysis and discriminant analysis of principal components revealed genetic differentiation between the sexes at several loci. While no explicit sex determination mechanism has been yet discovered in creek chub, these loci are potential candidates for future studies. Incompatible systems are thought to increase reproductive isolation but interspecific hybridization is common among groups such as cyprinid minnows; thus, studies such as ours can provide insight into hybridization and evolutionary diversification of this clade. We also highlight technical challenges involved in studying sex determination in evolutionary groups with extremely variable mechanisms and without heteromorphic sex chromosomes. [ABSTRACT FROM AUTHOR]

Since its discovery in 1909, the Moho was routinely studied by seismological methods. However, from the 1950s, a possible alternative was introduced by gravimetric inversion. Thanks to satellite gravity missions launched from the beginning of the 21st century, a global inversion became feasible, e.g., leading to the computation of the GEMMA model in 2012. This model was computed inverting the GOCE second radial derivatives of the anomalous potential by a Wiener filter, which was applied in the spherical harmonic domain, considering a two-layer model with lateral and vertical density variations. Moreover, seismic information was introduced in the inversion to deal with the joint estimation/correction of both density and geometry of the crustal model. This study aims at revising the GEMMA algorithm from the theoretical point of view, introducing a cleaner formalization and studying the used approximations more thoroughly. The updates are on: (1) the management of the approximations due to the forward operator linearization required for the inversion; (2) the regularization of spherical harmonic coefficients in the inversion by proper modelling the Moho signal and the gravity error covariances; (3) the inclusion of additional parameters and their regularization in the Least Squares adjustment to correct the density model by exploiting seismic information. Thanks to these updates, a significant improvement from the computational point of view is achieved too, thus the convergence of the iterative solution and the differences with respect to the previous algorithm can be assessed by closed-loop tests, showing the algorithm performance in retrieving the simulated "true" Moho. [ABSTRACT FROM AUTHOR]

Virus-like particles (VLPs) are proteinaceous shells derived from viruses lacking any viral genomic material. Adeno-associated virus (AAV) is a non-enveloped icosahedral virus used as VLP delivery system in gene therapy (GT). Its success as vehicle for GT is due to its selective tropism, high level of transduction, and low immunogenicity. In this study, two preparations of AAV serotype 8 (AAV8) VLPs either carrying or lacking completely genomic cargo (i.e., non-viral ssDNA) have been investigated by means of a native nano-electrospray gas-phase electrophoretic mobility molecular analyzer (GEMMA) (native nES GEMMA) and native nano-electrospray ionization quadrupole reflectron time-of-flight mass spectrometry (MS) (native nESI QRTOF MS). nES GEMMA is based on electrophoretic mobility principles: single-charge nanoparticles (NPs), that is, AAV8 particle, are separated in a laminar sheath flow of dry, particle-free air and a tunable orthogonal electric field. Thus, the electrophoretic mobility diameter (EMD) of a bio-NP (i.e., diameter of globular nano-objects) is obtained at atmospheric pressure, which can be converted into its MW based on a correlation. First is the native nESI QRTOF. MS's goal is to keep the native biological conformation of an analyte during the passage into the vacuum. Subsequently, highly accurate MW values are obtained from multiple-charged species after deconvolution. However, once applied to the analysis of megadalton species, native MS is challenging and requires customized instrumental modifications not readily available on standard devices. Hence, the analysis of AAV8 VLPs via native MS in our hands did not produce a defined charge state assignment, that is, charge deconvolution for exact MW determination was not possible. Nonetheless, the method we present is capable to estimate the MW of VLPs by combining the results from native nES GEMMA and native ESI QRTOF MS. In detail, our findings show a MW of 3.7 and 5.0 MDa for AAV8 VLPs either lacking or carrying an engineered genome, respectively. [ABSTRACT FROM AUTHOR]

In this paper, we explore potential genetic factors in control of flax phenotypes associated with fiber by mining a collection of 306 flax accessions from the Federal Research Centre of the Bast Fiber Crops, Torzhok, Russia. In total, 11 traits were assessed in the course of 3 successive years. A genome-wide association study was performed for each phenotype independently using six different single-locus models implemented in the GAPIT3 R package. Moreover, we applied a multivariate linear mixed model implemented in the GEMMA package to account for trait correlations and potential pleiotropic effects of polymorphisms. The analyses revealed a number of genomic variants associated with different fiber traits, implying the complex and polygenic control. All stable variants demonstrate a statistically significant allelic effect across all 3 years of the experiment. We tested the validity of the predicted variants using gene expression data available for the flax fiber studies. The results shed new light on the processes and pathways associated with the complex fiber traits, while the pinpointed candidate genes may be further used for marker-assisted selection.

Since its discovery in 1909, the Moho was routinely studied by seismological methods. However, from the 1950s, a possible alternative was introduced by gravimetric inversion. Thanks to satellite gravity missions launched from the beginning of the 21st century, a global inversion became feasible, e.g., leading to the computation of the GEMMA model in 2012. This model was computed inverting the GOCE second radial derivatives of the anomalous potential by a Wiener filter, which was applied in the spherical harmonic domain, considering a two-layer model with lateral and vertical density variations. Moreover, seismic information was introduced in the inversion to deal with the joint estimation/correction of both density and geometry of the crustal model. This study aims at revising the GEMMA algorithm from the theoretical point of view, introducing a cleaner formalization and studying the used approximations more thoroughly. The updates are on: (1) the management of the approximations due to the forward operator linearization required for the inversion; (2) the regularization of spherical harmonic coefficients in the inversion by proper modelling the Moho signal and the gravity error covariances; (3) the inclusion of additional parameters and their regularization in the Least Squares adjustment to correct the density model by exploiting seismic information. Thanks to these updates, a significant improvement from the computational point of view is achieved too, thus the convergence of the iterative solution and the differences with respect to the previous algorithm can be assessed by closed-loop tests, showing the algorithm performance in retrieving the simulated “true” Moho.

As stony coral tissue loss disease (SCTLD) swept through the Florida Reef Tract, one of the most severely impacted species was the iconic pillar coral, Dendrogyra cylindrus. As the species’ population experienced a precipitous decline, a collaborative rescue project collected colony fragments for safekeeping at onshore and offshore nursery facilities. Between 2015 and 2019, a total of 574 fragments representing 128 genotypes were collected. These are currently dispersed among five facilities where they continue to provide opportunities to (1) refine best husbandry practices for D. cylindrus, (2) develop treatment options for SCTLD that have been adapted for use on other species, (3) maximize growth and fragmentation to provide the live tissue needed for eventual restoration, and (4) provide a source of parent colonies for assisted sexual reproduction and new genetic diversity. With the wild pillar coral population in Florida at the end of 2020 at less than 6% of its known 2014 population and continuing to decline, the rescued ex situ colonies represent the entirety of the restoration potential for this species in Florida.

Digital Twin (DT) represents the next wave in modelling, simulation and optimization technology. A key enabling technology of the DT is the real-time coupling of the digital models with the controllers of the physical plant. To implement the DT through real-time coupling, common approaches and vocabularies are desirable for the automation software to facilitate the exchange of information between the PLCs and the digital models. However, the scarce adoption of guidelines and standards within the industrial practice of PLC programming complicates this context. To face this challenge, this paper proposes a methodology for PLC code to standardize the vocabulary and the management of the operational modes of industrial automation systems. The methodology consists of a GEMMA-GRAFCET representation and a Hierarchical Design Pattern. By implementing the approach to a case study, it is demonstrated that the methodology generates a standard interface for the communication between PLCs and digital models within a DT architecture. [ABSTRACT FROM AUTHOR]

Genetic modifications such as mutation and transformation are powerful tools to study the function of genes and proteins in the model liverwort Marchantia polymorpha, but maintaining the resulting germplasm requires a practical, reliable method. Cryopreservation methods allow researchers to maintain mutant and transgenic lines of M. polymorpha. To date, two methods have been developed for cryopreservation of M. polymorpha gemmae: in the first method, unencapsulated gemmae are stored in liquid nitrogen at −­196 °C, and in the second method, encapsulated gemmae are stored in liquid nitrogen at −­196 °C or a deep freezer at −80 °C. In the present study, we developed a simple method named CRUNC (cr yopreservation of un en c apsulated gemmae), which can be used to store unencapsulated, dried gemmae of wild-type and transgenic M. polymorpha lines in liquid nitrogen and in freezers at −80 °C and −20 °C. Using the CRUNC method, we observed a high recovery rate (as high as 100%) and successful long-term (5 months) storage of the gemmae. Therefore, the CRUNC method is practical for maintaining valuable M. polymorpha germplasm.

Within the Industry 4.0 revolution, manufacturing enterprises are transforming to intelligent enterprises constituted by Smart Manufacturing Systems (SMSs). A key capability of SMSs is the ability to connect and communicate with each other through Industrial Internet of Things technologies, and protocols with standard syntax and semantics. In this context, the GEMMA-GRAFCET Methodology (GG-Methodology) provides a standard approach and vocabulary for the management of the Operational Modes (OMs) of SMSs through the automation software, bringing a common understanding of the exchanged data. Considering the lack of tools to implement the methodology, this work introduces an online tool based on Model-Driven Engineering–GEMMA-GRAFCET Generator (GG-Generator)–to specify and generate PLCopen XML code compliant with the GG-Methodology. The proposed GG-Generator is applied to a case study and validated using Virtual Commissioning and Dynamic Software Testing. Due to the consistency obtained between the GG-Methodology and the generated PLC code, the GG-Generator is expected to support the adoption of the methodology, thus contributing to the interoperability of SMSs through the standardization of the automation software for the management of their OMs.

Introduction. Blackcurrant (Ribes nigrum L.) is a frequently grown cultivated in different parts of the world with a temperate climate. Fruits have a sour taste and they are rich rich source of vitamin C and rutine, organic acids, pectins, essential oils, as well as micro- and macronutrients. Material and method. Several studies have recently been carried out on several vegetable materials in order to find antioxidant and anti-inflammatory substances for the use of vegetable products in various food products or medicinal preparations as substitutes for synthetic substances. Results and discussions. Ribes nigrum contains a large number of phenolic compounds. The blackcurrant shows a number of health benefits attributed to the anti-inflammatory and antioxidant potential.

Bryophytes represent a sister to the rest of land plants. Despite their evolutionary importance and relatively simple body plan, a comprehensive understanding of the cell types and transcriptional states that underpin the temporal development of bryophytes has not been achieved. Using time-resolved single-cell RNA sequencing, we define the cellular taxonomy of Marchantia polymorpha across asexual reproduction phases. We identify two maturation and aging trajectories of the main plant body of M. polymorpha at single-cell resolution: the gradual maturation of tissues and organs along the tip-to-base axis of the midvein and the progressive decline of meristem activities in the tip along the chronological axis. Specifically, we observe that the latter aging axis is temporally correlated with the formation of clonal propagules, suggesting an ancient strategy to optimize allocation of resources to producing offspring. Our work thus provides insights into the cellular heterogeneity that underpins the temporal development and aging of bryophytes. [Display omitted] • We generate a reference cell census for bryophytes • The collection of cell-type-specific genes accelerates gene discovery • We define the maturation and aging trajectory of M. polymorpha at single-cell resolution • The vigor of parent plants is determined by the number of offspring Wang et al. profile transcriptomes of dormant gemmae and developing thalli of different stages at single-cell resolution, defining two maturation and aging axes of the main plant body of M. polymorpha. The inference of continuous developmental trajectories for each cell type provides insight into the maturation program of M. polymorpha. [ABSTRACT FROM AUTHOR]

In vegetative reproduction of Marchantia polymorpha (M. polymorpha), propagules, called gemmae, are formed in gemma cups. Despite its significance for survival, control of gemma and gemma cup formation by environmental cues is not well understood. We show here that the number of gemmae formed in a gemma cup is a genetic trait. Gemma formation starts from the central region of the floor of the gemma cup, proceeds to the periphery, and terminates when the appropriate number of gemmae is initiated. The MpKARRIKIN INSENSITIVE2 (MpKAI2)-dependent signaling pathway promotes gemma cup formation and gemma initiation. The number of gemmae in a cup is controlled by modulating the ON/OFF switch of the KAI2-dependent signaling. Termination of the signaling results in the accumulation of MpSMXL, a suppressor protein. In the Mp smxl mutants, gemma initiation continues, leading to the formation of a highly increased number of gemmae in a cup. Consistent with its function, the MpKAI2-dependent signaling pathway is active in gemma cups where gemmae initiate, as well as in the notch region of the mature gemma and midrib of the ventral side of the thallus. In this work, we also show that GEMMA CUP-ASSOCIATED MYB1 works downstream of this signaling pathway to promote gemma cup formation and gemma initiation. We also found that the availability of potassium affects gemma cup formation independently from the KAI2-dependent signaling pathway in M. polymorpha. We propose that the KAI2-dependent signaling pathway functions to optimize vegetative reproduction by adapting to the environment in M. polymorpha. • KAI2-dependent signaling promotes gemma cup formation and gemma initiation • The number of gemmae is controlled by modulating the ON/OFF of the KAI2-signaling • The potassium availability affects gemma cup formation • GCAM1 works downstream of the KAI2-dependent signaling to promote vegetative reproduction Plants have a remarkable ability to produce clonal plantlets from vegetative organs. Komatsu et al. show that KAI2-dependent signaling of KL, an as-yet-identified plant hormone, promotes clonal plantlet formation in the liverwort Marchantia polymorpha. The number of clonal plantlets is modulated by controlling the ON/OFF timing of the KL signaling. [ABSTRACT FROM AUTHOR]

During the development of hypertrophic cardiomyopathy, the heart returns to fetal energy metabolism where cells utilize more glucose instead of fatty acids as a source of energy. Metabolism of glucose can increase synthesis of the extracellular glycosaminoglycan hyaluronan, which has been shown to be involved in the development of cardiac hypertrophy and fibrosis. The aim of this study was to investigate hyaluronan metabolism in cardiac tissue from patients with hypertrophic cardiomyopathy in relation to cardiac growth. NMR and qRT-PCR analysis of human cardiac tissue from hypertrophic cardiomyopathy patients and healthy control hearts showed dysregulated glucose and hyaluronan metabolism in the patients. Gas phase electrophoresis revealed a higher amount of low molecular mass hyaluronan and larger cardiomyocytes in cardiac tissue from patients with hypertrophic cardiomyopathy. Histochemistry showed high concentrations of hyaluronan around individual cardiomyocytes in hearts from hypertrophic cardiomyopathy patients. Experimentally, we could also observe accumulation of low molecular mass hyaluronan in cardiac hypertrophy in a rat model. In conclusion, the development of hypertrophic cardiomyopathy with increased glucose metabolism affected both hyaluronan molecular mass and amount. The process of regulating cardiomyocyte size seems to involve fragmentation of hyaluronan.

Introduction. Blackcurrant (Ribes nigrum L.) is a frequently grown cultivated in different parts of the world with a temperate climate. Fruits have a sour taste and they are rich rich source of vitamin C and rutine, organic acids, pectins, essential oils, as well as micro- and macronutrients. Material and method. Several studies have recently been carried out on several vegetable materials in order to find antioxidant and anti-inflammatory substances for the use of vegetable products in various food products or medicinal preparations as substitutes for synthetic substances. Results and discussions. Ribes nigrum contains a large number of phenolic compounds. The blackcurrant shows a number of health benefits attributed to the anti-inflammatory and antioxidant potential. [ABSTRACT FROM AUTHOR]

Ribonucleotide Reductase (RNR) is the sole enzyme that catalyzes the reduction of ribonucleotides into deoxyribonucleotides. Even though RNR is a recognized target for antiproliferative molecules, and the main target of the approved drug hydroxyurea, few new leads targeted to this enzyme have been developed. We have evaluated a recently identified set of RNR inhibitors with respect to inhibition of the human enzyme and cellular toxicity. One compound, NSC73735, is particularly interesting; it is specific for leukemia cells and is the first identified compound that hinders oligomerization of the mammalian large RNR subunit. Similar to hydroxyurea, it caused a disruption of the cell cycle distribution of cultured HL-60 cells. In contrast to hydroxyurea, the disruption was reversible, indicating higher specificity. NSC73735 thus defines a potential lead candidate for RNR-targeted anticancer drugs, as well as a chemical probe with better selectivity for RNR inhibition than hydroxyurea. [ABSTRACT FROM AUTHOR]