Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-Human Primate iPSC Generation, Cultivation, and Cardiac Differentiation under Chemically Defined Conditions

Non-human primates (NHP) are important surrogate models for late preclinical development of advanced therapy medicinal products (ATMPs), including induced pluripotent stem cell (iPSC)-based therapies, which are also under development for heart failure repair. For effective heart repair by remuscularization, large numbers of cardiomyocytes are required, which can be obtained by efficient differentiation of iPSCs. However, NHP-iPSC generation and long-term culture in an undifferentiated state under feeder cell-free conditions turned out to be problematic. Here we describe the reproducible development of rhesus macaque (Macaca mulatta) iPSC lines. Postnatal rhesus skin fibroblasts were reprogrammed under chemically defined conditions using non-integrating vectors. The robustness of the protocol was confirmed using another NHP species, the olive baboon (Papio anubis). Feeder-free maintenance of NHP-iPSCs was essentially dependent on concurrent Wnt-activation by GSK-inhibition (Gi) and Wnt-inhibition (Wi). Generated NHP-iPSCs were successfully differentiated into cardiomyocytes using a combined growth factor/GiWi protocol. The capacity of the iPSC-derived cardiomyocytes to self-organize into contractile engineered heart muscle (EHM) was demonstrated. Collectively, this study establishes a reproducible protocol for the robust generation and culture of NHP-iPSCs, which are useful for preclinical testing of strategies for cell replacement therapies in NHP.
Population Characteristics of the Terrestrial Isopod Armadillidium Vulgare in California Grassland

A marking experiment with Uta stansburiana stelnegeri was conducted during the summer and fall of 1960 in a sandy mesquite area in western Texas; additional data on some aspects of the study were obtained in the summer of 1961. Many lizards were captured 5 or more times so that fairly reliable estimates of home range size were obtained. The home range averages . 06 acre in adult males, . 02 in adult females and . 01 in juveniles. This is smaller than averages reported for other North American lizards. In the study area immigration and emigration were negligible and estimates of population density showed 18.4 adults and 50 or more juveniles per acre. Most juvenile mortality occurs after hatching. Most of the adult lizards are monogamous. The home ranges of males in the breeding season show little or no overlap suggesting that the males display territoriality throughout the home range. The choice of home range and the ultimate size limit of the population seem to be determined by the position and number of pack rat nests in a given area. Distribution and abundance of vegetation and texture of the substratum are of secondary importance. The pack rat nests are importanlt to the lizards as shelters and retreats. Juveniles probably establish home ranges within or near those of the parent, a fact made possible by the death of the adults near the end of the reproductive season. The importance of specific plant species in the ecology of these lizards and possible predators, competitors, and other associates are discussed.
Carrier frequency of CFTR variants in the non‐Caucasian populations by genome aggregation database (gnomAD)‐based analysis

The complexity in the molecular diagnosis of Cystic Fibrosis (CF) also depends on the variable prevalence/incidence of the disease associated with the wide CFTR allelic heterogeneity among different populations. In fact, CF incidence in Asian and African countries is underestimated and the few patients reported so far have rare or unique CFTR pathogenic variants. To obtain insights into CF variants profile and frequency, we used the large population sequencing data in the Genome Aggregation Database (gnomAD). We selected 207 CF‐causing/varying clinical consequence variants from CFTR2 database and additional 15 variants submitted to the ClinVar database. Only 14 of these variants were found in the East‐Asian population, while for South‐Asian and African populations we identified 43 and 52 variants, respectively, confirming the peculiarity of the CFTR allelic spectrum with only few population‐specific variants. These data could be used to optimize CFTR carrier screening in non‐Caucasian subjects, choosing between the full gene sequencing and cost and time‐effective targeted panels.
Bioactive Potential of Extracts of Labrenzia aggregata Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial Source

Previous studies revealed the potential of Labrenzia aggregata USBA 371 to produce cytotoxic metabolites. This study explores its metabolic diversity and compounds involved in its cytotoxic activity. Extracts from the extracellular fraction of strain USBA 371 showed high levels of cytotoxic activity associated with the production of diketopiperazines (DKPs). We purified two compounds and a mixture of two other compounds from this fraction. Their structures were characterized by 1D and 2D nuclear magnetic resonance (NMR). The purified compounds were evaluated for additional cytotoxic activities. Compound 1 (cyclo (l-Pro-l-Tyr)) showed cytotoxicity to the following cancer cell lines: breast cancer 4T1 (IC50 57.09 ± 2.11 µM), 4T1H17 (IC50 40.38 ± 1.94), MCF-7 (IC50 87.74 ± 2.32 µM), murine melanoma B16 (IC50 80.87 ± 3.67), human uterus sarcoma MES-SA/Dx5 P-pg (−) (IC50 291.32 ± 5.64) and MES-SA/Dx5 P-pg (+) (IC50 225.28 ± 1.23), and murine colon MCA 38 (IC50 29.85 ± 1.55). In order to elucidate the biosynthetic route of the production of DKPs and other secondary metabolites, we sequenced the genome of L. aggregata USBA 371. We found no evidence for biosynthetic pathways associated with cyclodipeptide synthases (CDPSs) or non-ribosomal peptides (NRPS), but based on proteogenomic analysis we suggest that they are produced by proteolytic enzymes. This is the first report in which the cytotoxic effect of cyclo (l-Pro-l-Tyr) produced by an organism of the genus Labrenzia has been evaluated against several cancer cell lines.
Non-Mouse-Adapted H1N1pdm09 Virus as a Model for Influenza Research

The number of lung-adapted influenza viruses is limited. Most of them are not antigenically related to current circulating viruses. Viruses similar to recent strains are required for screening modern antiviral compounds and studying new vaccine candidates against novel influenza viruses. The process by which an influenza virus adapts to a new host is rather difficult. The aim of this study was to select a non-adapted current virus whose major biological properties correspond to those of classical lab-adapted viruses. Mice were inoculated intranasally with non-lung-adapted influenza viruses of subtype H1N1pdm09. They were monitored closely for body weight loss, mortality outcomes and gross pathology for 14 days following inoculation, as well as viral replication in lung tissue. Lung-adapted PR8 virus was used as a control. The tested viruses multiplied equally well in the lower respiratory tract of mice without prior adaptation but dramatically differed in lethality; the differences in their toxicity and pathogenicity in mice were established. A/South Africa/3626/2013 (H1N1)pdm09 virus was found to be an appropriate candidate to replace PR8 as a model virus for influenza research. No prior adaptation to the animal model is needed to reach the pathogenicity level of the classical mouse-adapted PR8 virus.
Fertilization of cumulus-free, zona-intact mouse ova in vitro at high and low sperm concentrations

The effect of varying the sperm concentration between 2 × 105 sperm/ml and 8 × 106 sperm/ml on fertilization of cumulus-free, zona-intact F1 (CBA × C57BL) mouse ova by QS and F1 (CBA × C57BL) mouse spermatozoa was studied. The spermatozoa from both strains of mice exhibited optimal fertilization rates at 2 × 106 sperm/ml. However, at sperm concentrations greater than 4 × 106 sperm/ml and less than 1 × 106 sperm/ml, fertilization rates were significantly reduced. F1 spermatozoa were more susceptible to dilution than QS spermatozoa. A significant interaction between strain and sperm concentration indicated that the two strains produced different fertilization rates at different sperm densities. Extracts of epididymal fluid, medium from capacitated spermatozoa, or ampulla fluid did not improve the fertilization rate at 2 × 105 sperm/ml, but retaining the cumulus oophorus did. The decrease in fertilization rate at 8 × 106 sperm/ml can in part be attributed to a nondialysable inhibitor from the neat sperm preparation that appeared to be of epididymal origin.
Drug-loading three-dimensional scaffolds based on hydroxyapatite-sodium alginate for bone regeneration.

Bone tissue engineering is a promising approach for tackling clinical challenges. Osteoprogenitor cells, osteogenic factors, and osteoinductive/osteoconductive scaffolds are employed in bone tissue engineering. However, scaffold materials remain limited due to their source, low biocompatibility and so on. In this study, a composite hydrogel scaffold composed of hydroxyapatite (HA) and sodium alginate (SA) was manufactured using three-dimensional printing. Naringin (NG) and calcitonin-gene-related peptide (CGRP) were used as osteogenic factors in the fabrication of drug-loaded scaffolds. Investigation using animal experiments, as well as scanning electron microscopy, cell counting kit-8 testing, alkaline phosphatase staining, and alizarin red-D staining of bone marrow mesenchymal stem cell culture showed that the three scaffolds displayed similar physicochemical properties and that the HA/SA/NG and HA/SA/CGRP scaffolds displayed better osteogenesis than that of the HA/SA scaffold. Thus, the HA/SA scaffold could be a biocompatible material with potential applications in bone regeneration. Meanwhile, NG and CGRP doping could result in better and more positive proliferation and differentiation. This article is protected by copyright. All rights reserved.
Reducing Nitrogen Dosage in Triticum durum Plants with Urea-Doped Nanofertilizers

Nanotechnology is emerging as a very promising tool towards more efficient and sustainable practices in agriculture. In this work, we propose the use of non-toxic calcium phosphate nanoparticles doped with urea (U-ACP) for the fertilization of Triticum durum plants. U-ACP nanoparticles present very similar morphology, structure, and composition than the amorphous precursor of bone mineral, but contain a considerable amount of nitrogen as adsorbed urea (up to ca. 6 wt % urea). Tests on Triticum durum plants indicated that yields and quality of the crops treated with the nanoparticles at reduced nitrogen dosages (by 40%) were unaltered in comparison to positive control plants, which were given the minimum N dosages to obtain the highest values of yield and quality in fields. In addition, optical microscopy inspections showed that Alizarin Red S stained nanoparticles were able to penetrate through the epidermis of the roots or the stomata of the leaves. We observed that the uptake through the roots occurs much faster than through the leaves (1 h vs. 2 days, respectively). Our results highlight the potential of engineering nanoparticles to provide a considerable efficiency of nitrogen uptake by durum wheat and open the door to design more sustainable practices for the fertilization of wheat in fields.
Teachers’ Constructivist and Ethical Beliefs

Teachers’ approaches and beliefs are key determinants of teachers’ practice. This study was designed to examine whether two aspects of Irish primary teacher beliefs are associated, their views on constructivist practices and their views on two ethical dimensions (idealism and relativism). The views of a sample of 35 teachers were assessed using the Constructivist Learning Environment Survey (CLES) and the Ethical Position Questionnaire (EPQ). Significant relationships were found between ethical position and scores on dimensions on the CLES. For example, idealistic teachers valued uncertainty and student negotiation more than teachers with high relativist scores. The results are discussed in the context of continuing professional development and future research.
Caracterização completa da madeira da espécie amazônica Paricá (Schizolobium amazonicum Herb) em peças de dimensões estruturais

A especie amazonica Parica (Schizolobium amazonicum Herb) apresenta rapidos incrementos em altura e diâmetro em poucos anos de cultivo e desenvolve uma madeira com pequena quantidade de nos e defeitos, caracteristica fundamental na sua utilizacao para fins estruturais. O objetivo deste trabalho foi determinar as propriedades de resistencia e rigidez de pecas da madeira Parica em dimensoes estruturais, de acordo com a norma ABNT NBR 7190: 2011, bem como realizar a classificacao visual das pecas para determinacao de defeitos como: nos, inclinacao de fibras, empenamentos, rachas e fendas. Conclui-se que a madeira de Parica e classificada como classe C 20 das dicotiledoneas e possui baixa densidade, boa resistencia a compressao paralela, grande potencial de utilizacao na construcao civil quando comparada com outras especies e, em relacao a classificacao visual, poucos nos, gra direita e poucos empenamentos e distorcoes.
Genetic resistance of spruce to gall-forming adelgids (Hemiptera: Adelgidae)

Adelgids (Hemiptera: Adelgidae) gall vegetative and reproductive shoots of interior spruce (Picea spp.), causing growth impairment, seed loss, and aesthetic decline. We tested the theory that susceptibility to galling is under genetic control in spruce. We assessed natural galling incidence in a spruce progeny test located in southern British Columbia. The experiment was composed of a replicated 13-parent incomplete, partial diallel with 42 full-sib families. Moderate evidence of genetic control of susceptibility–resistance was observed with individual narrow-sense heritability of 0.17. We observed considerable genetic variation among parents for resistance to gall formation as shown by high heritability (0.87) of family means. Breeding values for parental susceptibility to adelgid attack ranged between 0.25 and 0.76, indicating that selection for reduced susceptibility would be successful. The benefits of screening for resistance to adelgid attack are discussed in relation to adelgid pest management, ins.
Developmental Morphology of the Controversial Ramulus Organ of Tristicha trifaria (Subfamily Tristichoideae, Podostemaceae): Implications for Evolution of a Unique Body Plan in Podostemaceae

Premise of research. The Podostemaceae (riverweed family) show unique morphologies and are adapted to rheophytic habitats that experience torrential floods. The fact that the Podostemaceae are sister to the Hypericaceae family in molecular phylogenetic trees suggests that the unparalleled morphologies of the Podostemaceae could have been the result of saltational evolution from the normal body construction. However, their evolutionary course remains unresolved. To deduce the evolutionary course of the Podostemaceae, Tristichoideae is a key plant taxon because it belongs to the basalmost clade of the Podostemaceae and has a unique organ termed the “ramulus. ” The ramulus is not so deviated compared with the aggregated leaves of Podostemoideae and was once interpreted to be the determinate shoot for Terniopsis (another genus of Tristichoideae). Methodology. A specimen of Tristicha trifaria belonging to the basalmost clade of the species and having been previously collected in Cameroon was observed. Additional Afro-Madagascan specimens with apparently different branching patterns were also observed. Observation was conducted under both LM—using a resin sectioning method—and SEM. Pivotal results. The ramulus first develops endogenously in the root tissue. It has an apical meristem and forms scaly leaves similar to a shoot apical meristem and then undergoes repeated sympodial branching. New branches arise from extra-axillary buds of the basal scaly leaves from the previous branch and replaces the latter. In Tristicha, two new branches usually arise per existing branch, resulting in a more complicated gross morphology than Terniopsis, which has only one branch. Tristicha shoots are also characterized by a well-developed common base, which is a product of the basal intercalary growth of ramuli. Conclusions. The ramulus of Tristicha is interpreted to be the determinate shoot portion of a sympodially branched shoot system, as in Terniopsis, not as a leaf or a leaf-stem fuzzy organ. The Tristicha shoot that bears two new branches can be compared in construction with the double sheathed (bithecous) leaf of Podostemoideae.
Spawning Migration of Stream-Dwelling Dolly Varden in Spring-Fed Tributaries of the Shiisorapuchi River, Japan

ABSTRACT During the breeding seasons of 1998–2001, the spawning migration of stream-dwelling Dolly Varden (Salvelinus malma) was investigated in four small spring-fed tributaries of the Shiisorapuchi River, Hokkaido, Japan. From late September to late October, Dolly Varden continuously migrated into these tributaries from the mainstream without any clear peaks. Precipitation was positively correlated (P < 0.05) with the number of migrants in two tributaries, but not in the other two. No clear relationship was observed between the number of migrants and the water temperature for either the mainstream or the tributaries. Nocturnal migration behavior was recognized in one tributary, but it was diurnal in two tributaries, and there was no clear tendency in the other. Body size of migrating Dolly Varden was not correlated with the entry date for either sex. No significant difference in the entry date was observed between males and females for any tributary or for any year. However, the number of males entering a tributary was positively (P < 0.05) correlated with that of females, indicating a synchronous migration of males and females. Because the number of females was not correlated with any environmental factor, we suggest that male Dolly Varden migrate into tributaries following mature females, possibly via pheromonal stimuli.
Essential role of RelA Ser311 phosphorylation by ζPKC in NF‐κB transcriptional activation

The activation of the transcription factor NF‐κB is central to the control of the cellular response triggered by many stimuli. Once released from the inhibitory molecule IκB, NF‐κB is translocated to the nucleus, and it has to be phosphorylated to activate transcription. In ζ protein kinase C (PKC)‐deficient cells, NF‐κB is transcriptionally inactive and the phosphorylation of the RelA subunit in response to tumor necrosis factor (TNF‐α) is severely impaired. In vitro assays showed that ζPKC directly phosphorylates RelA. Here we demonstrate that Ser311 accounts for ζPKC phosphorylation of RelA and that this site is phosphorylated in vivo in response to TNF‐α. Also, an inactivating mutation of that residue severely impairs RelA transcriptional activity, blocks its anti‐apoptotic function and abrogates the interaction of RelA with the co‐activator CBP as well as its recruitment, and that of RNA polymerase II (Pol II) with the interleukin‐6 (IL‐6) promoter. The interaction of endogenous CBP with endogenous RelA is inhibited in ζPKC−/− cells, as well as the binding of Pol II to the IL‐6 promoter. These results demonstrate the mechanism whereby ζPKC regulates NF‐κB activation in vivo.
Genome-Wide Association Study Confirms Previous Findings of Major Loci Affecting Resistance to Piscine myocarditis virus in Atlantic Salmon (Salmo salar L.)

Cardiomyopathy syndrome is a viral disease of Atlantic salmon, mostly affecting fish during the late stages of production, resulting in significant losses to the industry. It has been shown that resistance to this disease has a strong genetic component, with quantitative trait loci (QTL) on chromosomes 27 (Ssa27) and Ssa12 to explain most of the additive genetic variance. Here, by analysing animals from a different year-class and a different population, we further aimed to confirm and narrow down the locations of these QTL. The data support the existence of the two QTL and suggest that the causative mutation on Ssa27 is most likely within the 10–10.5 Mbp segment of this chromosome. This region contains a cluster of major histocompatibility complex class I (MHC I) genes with the most strongly associated marker mapped to one of these loci. On Ssa12, the data confirmed the previous finding that the location of the causative mutation is within the 61.3 to 61.7 Mbp region. This segment contains several immune-related genes, but of particular interest are genes related to MHC II. Together, these findings highlight the likely key role of MHC genes in Atlantic salmon following infection with Piscine myocarditis virus (PMCV) and their potential impact on influencing the trajectory of this disease.
Influence of physiochemical properties on the subcutaneous absorption and bioavailability of monoclonal antibodies

ABSTRACT Many therapeutic monoclonal antibodies (mAbs) were initially developed for intravenous (IV) administration. As a means to improve mAb drug-ability and the patient experience, subcutaneous (SC) administration is an increasingly important delivery route for mAbs. Unlike IV administration, bioavailability limitations for antibodies have been reported following SC injection and can dictate whether a mAb is administered via this parenteral route. The SC bioavailability of antibodies has been difficult to predict, and it can be variable and partial, with values ranging from ~50% to 100%. The mechanisms leading to the incomplete bioavailability of some mAbs relative to others are not well understood. There are some limited data that suggest the physiochemical properties inherent to a mAb can contribute to its SC absorption, bioavailability, and in vivo fate. In this study, we evaluated the integrated influence of multiple mAb physiochemical factors on the SC absorption and bioavailability of six humanized mAbs in both rats and cynomolgus monkeys. We demonstrate the physiochemical properties of mAbs are critical to their rate and extent of SC absorption. The combination of high positive charge and hydrophobic interaction significantly reduced the rate of the evaluated mAb’s SC absorption and bioavailability. Reduction or balancing of both these attributes via re-engineering the mAbs restored desirable properties of the molecules assessed. This included reduced association with SC tissue, improvements in mAb absorption from the SC space and overall SC bioavailability. Our findings point to the importance of evaluating the relative balance between various physiochemical factors, including charge, hydrophobicity, and stability, to improve the SC drug-ability of mAbs for selecting or engineering mAbs with enhanced in vivo absorption and bioavailability following SC administration.