Miracle-dz/UniFAR-FTUs huggingface dataset:
Complete Genome Sequence of Rhodoferax sp. Strain BAB1, Isolated after Filter Sterilization of Tap Water

Here, we announce the complete genome sequence of Rhodoferax sp. strain BAB1, which was isolated from filter-sterilized tap water. The genome consists of a 3.82-Mb chromosome. Moreover, we provide base methylation data and evidence of incomplete retention by 0.22-μm filters for this putative novel Rhodoferax species. ABSTRACT Here, we announce the complete genome sequence of Rhodoferax sp. strain BAB1, which was isolated from filter-sterilized tap water. The genome consists of a 3.82-Mb chromosome. Moreover, we provide base methylation data and evidence of incomplete retention by 0.22-μm filters for this putative novel Rhodoferax species.
Early Morphofunctional Changes in AngII-Infused Mice Contribute to Regional Onset of Aortic Aneurysm and Dissection

Aortic aneurysms and dissections are silent and lethal conditions, whose pathogenesis remains incompletely understood. Although angiotensin II (AngII)-infused ApoE−/− mice have been widely used to study aortic aneurysm and dissection, early morphofunctional alterations preceding the onset of these conditions remain unknown. The goal of this study was to unveil early morphofunctional changes underlying the onset of aneurysm and dissection. At 3 days post-AngII infusion, suprarenal abdominal aorta presented significant volumetric dilatation and microstructural damage. Ex vivo assessment of vascular reactivity of the suprarenal dissection-prone aorta and its side branches, showed an endothelial and contractile dysfunctions that were severe in the suprarenal aorta, moderate distally, and absent in the side branches, mirroring the susceptibility to dissection of these different vascular segments. Early and specific morphofunctional changes of the suprarenal aorta may contribute to the regional onset of aortic aneurysm and dissection by exacerbating the biomechanical burden arising from its side branches.
Antibody–Drug Conjugates: The Last Decade

An armed antibody (antibody–drug conjugate or ADC) is a vectorized chemotherapy, which results from the grafting of a cytotoxic agent onto a monoclonal antibody via a judiciously constructed spacer arm. ADCs have made considerable progress in 10 years. While in 2009 only gemtuzumab ozogamicin (Mylotarg®) was used clinically, in 2020, 9 Food and Drug Administration (FDA)-approved ADCs are available, and more than 80 others are in active clinical studies. This review will focus on FDA-approved and late-stage ADCs, their limitations including their toxicity and associated resistance mechanisms, as well as new emerging strategies to address these issues and attempt to widen their therapeutic window. Finally, we will discuss their combination with conventional chemotherapy or checkpoint inhibitors, and their design for applications beyond oncology, to make ADCs the magic bullet that Paul Ehrlich dreamed of.
Epigenetic regulation of B-lymphocyte development by Mi-2/NuRD chromatin remodeling complexes

Chromatin Remodeling Complexes (CRCs) are multi-subunit assemblies of proteins that modulate nucleosome positioning. CRCs include Mi2/Nucleosomal Remodeling and Deacetylase (NuRD) complexes, which are important regulators of chromatin structure and gene expression. Mi-2/NuRD complexes combine key epigenetic regulators necessary for 1) binding and mobilization of nucleosomes, 2) histone deacetylation and demethylation, 3) binding to methylated DNA, and 4) recruitment of additional regulatory proteins to chromatin. The CD79a (Igα; mb-1) promoter is demethylated progressively during its activation in early B cell development. Demethylation of promoter CpGs is initiated by Early B cell Factor 1 (EBF1) and propagated by Paired box protein 5 (Pax5). This process is inhibited by Mi-2/NuRD in μM. 2 plasmacytoma cells. Knockdown of the ATPase/helicase subunit of Mi-2/NuRD, Mi-2β (also known as Chromodomain Helicase DNA-binding 4, or CHD4), enhanced activation by EBF1 and Pax5. I demonstrated that depletion of the Methyl Binding Domain protein 2 (MBD2) subunit of NuRD complexes increased CD79a transcriptional activation similarly in μM. 2 cells, but in synergy with EBF1 and Pax5.
Asymmetric Synthesis and Absolute Configuration of (-)-Trypargine

An asymmetric synthesis of (1S)-(-)-trypargine (1a) was accomplished. The Pictet-Spengler condensation of (+)-Nb-benzyl-D-tryptophan methyl ester ((+)-3) with α-ketoglutaric acid, followed by methylation of the resulting monocarboxylic acid ((-)-4a), provided (1S, 3R)-(-)-methyl 2-benzyl-3-methoxycarbonyl-1, 2, 3, 4-tetrahydro-9H-pyrido [3, 4-b] indole-1-propionate ((-)-6a), which was converted into (-)-trypargine (1a). The absolute configuration of natural trypargine (1a) at the C-1 position was determined to be S.
Tumor Infiltrating Regulatory T Cells in Sporadic and Colitis-Associated Colorectal Cancer: The Red Little Riding Hood and the Wolf

Regulatory T cells represent a class of specialized T lymphocytes that suppress unwanted immune responses and size the activation of the immune system whereby limiting collateral damages in tissues involved by inflammation. In cancer, the accumulation of Tregs is generally associated with poor prognosis. Many lines of evidence indicate that Tregs accumulation in the tumor microenvironment (TME) suppresses the immune response against tumor-associated antigens (TAA), thus promoting tumor progression in non-small cell lung carcinoma (NSLC), breast carcinoma and melanoma. In colorectal cancer (CRC) the effect of Tregs accumulation is debated. Some reports describe the association of high number of Tregs in CRC stroma with a better prognosis while others failed to find any association. These discordant results stem from the heterogeneity of the immune environment generated in CRC in which anticancer immune response may coexists with tumor promoting inflammation. Moreover, different subsets of Tregs have been identified that may exert different effects on cancer progression depending on tumor stage and their location within the tumor mass. Finally, Tregs phenotypic plasticity may be induced by cytokines released in the TME by dysplastic and other tumor-infiltrating cells thus affecting their functional role in the tumor. Here, we reviewed the recent literature about the role of Tregs in CRC and in colitis-associated colorectal cancer (CAC), where inflammation is the main driver of tumor initiation and progression. We tried to explain when and how Tregs can be considered to be the “good” or the “bad” in the colon carcinogenesis process on the basis of the available data concluding that the final effect of Tregs on sporadic CRC and CAC depends on their localization within the tumor, the subtype of Tregs involved and their phenotypic plasticity.
Lower limb joint biomechanics-based identification of gait transitions in between level walking and stair ambulation

Lower limb exoskeletons and lower limb prostheses have the potential to reduce gait limitations during stair ambulation. To develop robotic assistance devices, the biomechanics of stair ambulation and the required transitions to level walking have to be understood. This study aimed to identify the timing of these transitions, to determine if transition phases exist and how long they last, and to investigate if there exists a joint-related order and timing for the start and end of the transitions. Therefore, this study analyzed the kinematics and kinetics of both transitions between level walking and stair ascent, and between level walking and stair descent (12 subjects, 25.4 yrs, 74.6 kg). We found that transitions primarily start within the stance phase and end within the swing phase. Transition phases exist for each limb, all joints (hip, knee, ankle), and types of transitions. They have a mean duration of half of one stride and they do not last longer than one stride. The duration of the transition phase for all joints of a single limb in aggregate is less than 35% of one stride in all but one case. The distal joints initialize stair ascent, while the proximal joints primarily initialize the stair descent transitions. In general, the distal joints complete the transitions first. We believe that energy- and balance-related processes are responsible for the joint-specific transition timing. Regarding the existence of a transition phase for all joints and transitions, we believe that lower limb exoskeleton or prosthetic control concepts should account for these transitions in order to improve the smoothness of the transition and to thus increase the user comfort, safety, and user experience. Our gait data and the identified transition timings can provide a reference for the design and the performance of stair ambulation- related control concepts.
Databases and Bioinformatic Tools for Glycobiology and Glycoproteomics

Glycosylation plays critical roles in various biological processes and is closely related to diseases. Deciphering the glycocode in diverse cells and tissues offers opportunities to develop new disease biomarkers and more effective recombinant therapeutics. In the past few decades, with the development of glycobiology, glycomics, and glycoproteomics technologies, a large amount of glycoscience data has been generated. Subsequently, a number of glycobiology databases covering glycan structure, the glycosylation sites, the protein scaffolds, and related glycogenes have been developed to store, analyze, and integrate these data. However, these databases and tools are not well known or widely used by the public, including clinicians and other researchers who are not in the field of glycobiology, but are interested in glycoproteins. In this study, the representative databases of glycan structure, glycoprotein, glycan–protein interactions, glycogenes, and the newly developed bioinformatic tools and integrated portal for glycoproteomics are reviewed. We hope this overview could assist readers in searching for information on glycoproteins of interest, and promote further clinical application of glycobiology.
The responses of 17-years old Chinese fir shoots to elevated CO_2

The net photosynthesis (Pn) ,transpiration( TR) ,stomatal conductance( COND ),water use efficiency( WUE )and dark respiration( DR )of 17 year old Chinese fir shoots under ambient and elevated CO 2 conditions were measured with LiCor 6200 Photosynthesis system,and their responses to elevated CO 2 were discussed.It was suggested that compared to the ambient air CO 2 concentration. Pn under 45μmol/L CO 2 was doubled and COND and TR decreased to some extent,leading to the increase of WUE by 100%～200%;at the same time. DR reduced by 20%～72% and quantum efficiency increased by 40%～295%;light compensation point deereased while light saturation point and light inhibition point elevated.It was also found that with the increase of CO 2 concentration. Pn and WUE increased linearly until around 45μmol/L CO 2,the increasing rates reduced,but the CO 2 saturation point for Pn was higher than 117μmol/L.It was concluded that the increasing CO 2 concentration in the atmosphere would be beneficial to Chinese fir in a short term,but its long term responses are not determined and need to be further studied.
HIF‐1α‐induced up‐regulation of microRNA‐126 contributes to the effectiveness of exercise training on myocardial angiogenesis in myocardial infarction rats

Exercise training (ET) is a non‐drug natural rehabilitation approach for myocardial infarction (MI). Among the numerous beneficial effects of ET, myocardial angiogenesis is indispensable. In the present study, we investigated the role and mechanism of HIF‐1α and miR‐126 in ET‐induced MI myocardial angiogenesis which may provide new insights for MI treatment. Rat model of post‐MI and human umbilical vein endothelial cells (HUVECs) were employed for our research. Histomorphology, immunohistochemistry, quantitative real‐time PCR, Western blotting and small‐interfering RNA (siRNA) transfection were applied to evaluate the morphological, functional and molecular mechanisms. In vivo results showed that 4‐week ET could significantly increase the expression of HIF‐1α and miR‐126 and reduce the expression of PIK3R2 and SPRED1, while 2ME2 (HIF‐1α inhibitor) partially attenuated the effect of ET treatment. In vitro results showed that HIF‐1α could trigger expression of miR‐126 in HUVECs in both normoxia and hypoxia, and miR‐126 may be involved in the tube formation of HUVECs under hypoxia through the PI3K/AKT/eNOS and MAPK signalling pathway. In conclusion, we revealed that HIF‐1α, whose expression experiences up‐regulation during ET, could function as an upstream regulator to miR‐126, resulting in angiogenesis promotion through the PI3K/AKT/eNOS and MAPK signalling pathway and subsequent improvement of the MI heart function.
Nesting and fate of transplanted stem cells in hypoxic/ischemic injured tissues: The role of HIF1α/sirtuins and downstream molecular interactions

The nesting mechanisms and programming for the fate of implanted stem cells in the damaged tissue have been critical issues in designing and achieving cell therapies. The fracture site can induce senescence or apoptosis based on the surrounding harsh conditions, hypoxia, and oxidative stress (OS). Respiration deficiency, disruption in energy metabolism, and consequently OS induction change the biophysical, biochemical, and cellular components of the native tissue. Additionally, the homeostatic molecular players and cell signaling might be changed. Despite all aforementioned issues, in the native stem cell niche, physiological hypoxia is not toxic; rather, it is vitally required for homing, self‐renewal, and differentiation. Hence, the key macromolecular players involved in the support of stem cell survival and re‐adaptation to a new dysfunctional niche must be understood for managing the cell therapy outcome. Hypoxia‐inducible factor 1‐alpha is the master transcriptional regulator, involved in the cell response to hypoxia and the adaptation of stem cells to a new niche. This protein is regulated by interaction with sirtuins. Sirtuins are highly conserved NAD+‐dependent enzymes that monitor the cellular energy status and modulate gene transcription, genome stability, and energy metabolism in response to environmental signals to modulate the homing and fate of stem cells. Herein, new insights into the nesting of stem cells in hypoxic–ischemic injured tissues were provided and their programming in a new dysfunctional niche along with the involved complex macromolecular players were critically discussed.
Post‐hatching growth of the limbs in an altricial bird species

Abstract The fore‐ and hindlimbs of birds are specialized to perform different functions. The growth patterns of limb bones and their relationship with the ontogeny of locomotion are critical to our understanding of variation in morphological, physiological and life‐history traits within and among species. Unfortunately, the ontogenetic development of limb bones has not been well explored, especially in altricial birds. In this study, we sampled the entire measurements of the pigeon (Columba livia) of individual skeletons, to investigate the ontogenetic allometry of limb bones by reduced major axis regression. The ulna and humerus were found to be positively allometric in relation to body mass, with the ulna growing more rapidly than the humerus. Together with previous data, this suggests that strong positive allometric growth in forelimb bones could be a common trend among diverse Carinatae groups. Hindlimb was dominated by positive allometry, but was variable in the growth of the tarsometatarsus which included three allometric patterns. A greater dorsoventral diameter in the midsection of the humerus and ulna confers superior bending resistance and is ideal for flapping/gliding flight. Shape variation in the midsection of different hindlimb components reflects different mechanical loading, and the markedly inverse trend between the tibiotarsus and tarsometatarsus before 28 days of age also suggests loading change before fledging. Before fledging, the growth of the leg bones was prior to that of the wing bones. This kind of asynchronous development of the fore‐ and hindlimbs was associated with the establishment and improvement of different functions, and with shifts in the importance of different functions over time.
Profile and distribution characteristics of culturable airborne fungi in residential homes with children in Beijing, China

A survey was conducted to evaluate the characteristics of airborne fungi in 31 residential homes in Beijing that housed children. Indoor fungal concentrations in the homes ranged from 62 to 3498 colony forming units (CFU)/m3 (mean 837 CFU/m3). A total of 225 fungal isolates belonging to 24 genera and 65 species were identified in the air. The most common fungi were Penicillium, Cladosporium, Aspergillus, and Alternaria based on concentration proportion and frequency. Approximately 40% of the total number of isolated fungal species belonged to Penicillium, which represented the maximum proportion of the total fungal concentration at ∼32%, followed by Cladosporium, Aspergillus, non-sporing fungi, Monilia, and Alternaria. The most frequently ocurring fungal species were Cladosporium cladosporioides (8.44%), Penicillium chrysogenum (5.33%) and Penicillium funiculosum (4.89%). Fungal concentrations in residential homes with a male child were significantly higher than those with a female child (**P < 0.01). The highest fungal concentration was detected in summer, followed by spring and autumn, and the lowest was in winter (**P < 0.01). These results provide a database of airborne fungi exposure in Beijing homes, and suggest that the gender of children in residences has a significant influence on both the concentration and composition of airborne fungi.
Combined analysis of transcriptome and metabolome reveals the potential mechanism of coloration and fruit quality in yellow and purple Passiflora edulis Sims.

Passion fruit (Passiflora edulis Sims) can be divided into yellow and purple varieties. However, information about coloration and fruit quality between the two varieties is limited. To reveal the underlying mechanism of color formation in this fruit, combined analysis of the metabolome and transcriptome was conducted in this study. The results showed that most of the evaluated flavonols, anthocyanins and flavanols were significantly upregulated in purple fruit compared to their levels in yellow fruit. Flavonoid and flavonoid carbonoside accumulation was markedly higher in yellow fruit than in purple fruit. The accumulation of organic acids, phenolic acids, lipids, sugars and lignans was significantly different in the yellow and purple varieties. These results were consistent with the results from the RNA-Seq profile. This study will enable us to identify genes for targeted genetic engineering to improve the nutritional and market value of passion fruit. In addition, the peel and pulp of passion fruit contained certain health-promoting compounds, highlighting the potential application of passion fruit as a functional food and providing direction for future breeding programs and production.
Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer

Simple Summary Cancers are characterized by accumulation of genetic mutations in key cell cycle regulators that alter or disable the function of these genes. Such mutations can be inherited or arise spontaneously during the life of the individual. The MEN1 gene prevents uncontrolled cell division and it is considered a tumor suppressor. Inherited MEN1 mutations are associated with certain parathyroid and pancreatic syndromes while spontaneous mutations have been detected in cancer cells. We investigated whether inherited mutations appear in cancer cells which would suggest that patients with parathyroid and pancreatic syndromes have a predisposition to develop cancer. We find a weak correlation between the spectrum of inherited mutations and those appearing spontaneously. Thus, inherited MEN1 mutations may not be a good predictor of tumorigenesis. Abstract MENIN is a scaffold protein encoded by the MEN1 gene that functions in multiple biological processes, including cell proliferation, migration, gene expression, and DNA damage repair. MEN1 is a tumor suppressor gene, and mutations that disrupts MEN1 function are common to many tumor types. Mutations within MEN1 may also be inherited (germline). Many of these inherited mutations are associated with a number of pathogenic syndromes of the parathyroid and pancreas, and some also predispose patients to hyperplasia. In this study, we cataloged the reported germline mutations from the ClinVar database and compared them with the somatic mutations detected in cancers from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We then used statistical software to determine the probability of mutations being pathogenic or driver. Our data show that many confirmed germline mutations do not appear in tumor samples. Thus, most mutations that disable MEN1 function in tumors are somatic in nature. Furthermore, of the germline mutations that do appear in tumors, only a fraction has the potential to be pathogenic or driver mutations.
Hypoxia-Mediated Regulation of Histone Demethylases Affects Angiogenesis-Associated Functions in Endothelial Cells

Supplemental Digital Content is available in the text. Objective: Previous studies have demonstrated that the expression of several lysine (K)-specific demethylases (KDMs) is induced by hypoxia. Here, we sought to investigate the exact mechanisms underlying this regulation and its functional implications for endothelial cell function, such as angiogenesis. Approach and Results: We analyzed the expression changes of KDMs under hypoxia and modulation of HIF (hypoxia-inducible factor) expression using GRO-Seq and RNA-Seq in endothelial cells. We provide evidence that the majority of the KDMs are induced at the level of nascent transcription mediated by the action of HIF-1α and HIF-2α. Importantly, we show that transcriptional changes at the level of initiation represent the major mechanism of gene activation. To delineate the epigenetic effects of hypoxia and HIF activation in normoxia, we analyzed the genome-wide changes of H3K27me3 using chromosome immunoprecipitation-Seq. We discovered a redistribution of H3K27me3 at ≈2000 to 3000 transcriptionally active loci nearby genes implicated in angiogenesis. Among these, we demonstrate that vascular endothelial growth factor A (VEGFA) expression is partly induced by KDM4B- and KDM6B-mediated demethylation of nearby regions. Knockdown of KDM4B and KDM6B decreased cell proliferation, tube formation, and endothelial sprouting while affecting hundreds of genes associated with angiogenesis. These findings provide novel insights into the regulation of KDMs by hypoxia and the epigenetic regulation of VEGFA-mediated angiogenesis. Conclusions: Our study describes an additional level of epigenetic regulation where hypoxia induces redistribution of H3K27me3 around genes implicated in proliferation and angiogenesis. More specifically, we demonstrate that KDM4B and KDM6B play a key role in modulating the expression of the major angiogenic driver VEGFA. Graphic Abstract: A graphic abstract is available for this article.