Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-cell genomics unveiled a cryptic cyanobacterial lineage with a worldwide distribution hidden by a dinoflagellate host

Significance Cyanobacteria are an important component of marine microbial ecology, and thus their biodiversity has been extensively studied. Here, through whole-genome sequencing, we discovered that a marine cyanobacterium in a symbiotic association with a unicellular eukaryote (OmCyn) represents a previously under-described lineage within an ecologically important cyanobacterial group. Our metagenomic analyses showed that the cyanobacterium OmCyn thrives in global oceans, further suggesting the existence of other cryptic cyanobacterial lineages that have been overlooked because of their symbiotic lifestyle. Via comparison with genomes of free-living relatives, the OmCyn genome was shown to have a reductive nature, which apparently resulted from intimate association with the host. Together, our results expand current understanding of the biology of cyanobacteria and marine microbial ecology. Cyanobacteria are one of the most important contributors to oceanic primary production and survive in a wide range of marine habitats. Much effort has been made to understand their ecological features, diversity, and evolution, based mainly on data from free-living cyanobacterial species. In addition, symbiosis has emerged as an important lifestyle of oceanic microbes and increasing knowledge of cyanobacteria in symbiotic relationships with unicellular eukaryotes suggests their significance in understanding the global oceanic ecosystem. However, detailed characteristics of these cyanobacteria remain poorly described. To gain better insight into marine cyanobacteria in symbiosis, we sequenced the genome of cyanobacteria collected from a cell of a pelagic dinoflagellate that is known to host cyanobacterial symbionts within a specialized chamber. Phylogenetic analyses using the genome sequence revealed that the cyanobacterium represents an underdescribed lineage within an extensively studied, ecologically important group of marine cyanobacteria. Metagenomic analyses demonstrated that this cyanobacterial lineage is globally distributed and strictly coexists with its host dinoflagellates, suggesting that the intimate symbiotic association allowed the cyanobacteria to escape from previous metagenomic studies. Furthermore, a comparative analysis of the protein repertoire with related species indicated that the lineage has independently undergone reductive genome evolution to a similar extent as Prochlorococcus, which has the most reduced genomes among free-living cyanobacteria. Discovery of this cyanobacterial lineage, hidden by its symbiotic lifestyle, provides crucial insights into the diversity, ecology, and evolution of marine cyanobacteria and suggests the existence of other undiscovered cryptic cyanobacterial lineages.
Parental Socialization Styles: The Contribution of Paternal and Maternal Affect/Communication and Strictness to Family Socialization Style

The aim of this study is two-fold: (a) to determine the general degree of family affect/communication and strictness by examining the combination of the two classical dimensions of mother parenting style: affect/communication and strictness, and (b) to analyze the impact of both parents’ affect and strictness on the family style, thereby exploring the specific contribution made by each parent’s style and dimension. Participants were 1190 Spanish students, 47.1% boys and 52.3% girls (M = 14.68; SD = 1.76). The Affect Scale (EA-H) and the Rules and Demandingness Scale (ENE-H) (both by Fuentes, Motrico, and Bersabé, 1999) were used. Structural equation models (SEMs) were extracted using the EQS program. The results reveal that it is not the father’s and the mother’s parenting style combined, but rather the combination of maternal and paternal affect/communication, and maternal and paternal strictness which generates one perception of family affect and another of family strictness. The results also indicated that the weight of both dimensions varies in accordance with the parent’s gender, with maternal dimensions playing a more important role in family socialization style.
Adverse Childhood Experiences of Children Adopted from Care: The Importance of Adoptive Parental Warmth for Future Child Adjustment

We investigated the relationship between adverse childhood experiences (ACEs) and children’s internalising symptoms and externalising problems in the Wales Adoption Cohort Study, a prospective longitudinal study that used case file records (n = 374) for a sample of British children adopted from care (M = 2 years, 55% male). Parents (n = 96) completed questionnaires at 3–5 months, 15–17 months, and 31–33 months post-placement. We hypothesised that: (1) children adopted from care would have experienced more ACEs than children in the general population; (2) the number of ACEs would be associated with higher internalising symptom and externalising problem scores; and (3) adoptive parental warmth would moderate the relationship between ACEs and post-placement internalising symptoms and externalising problems. Nearly half (42%) of the children experienced four or more ACEs. Internalising symptoms and externalising problems were significantly higher than the UK general population. The number of ACEs was associated with internalising symptoms 3 years post-adoptive placement but this relationship was moderated by adoptive parental warmth. This study profiles the experiences and characteristics of a national sample of adopted children and highlights the potential importance of parent warmth as a factor that ameliorates the impact of ACEs on poor child outcomes.
Saliva and Serum Immune Responses in Apical Periodontitis

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01–8.33) and 4.91 (2.48–9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48–2.97)), serum IgG to bacterial antigens (4.66 (1.22–10.1)), and Gram-negative subgingival species (1.98 (1.16–3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05–21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis—a putative risk factor for systemic diseases.
White matter plasticity and maturation in human cognition

White matter plasticity likely plays a critical role in supporting cognitive development. However, few studies have used the imaging methods specific to white matter tissue structure or experimental designs sensitive to change in white matter necessary to elucidate these relations. Here we briefly review novel imaging approaches that provide more specific information regarding white matter microstructure. Furthermore, we highlight recent studies that provide greater clarity regarding the relations between changes in white matter and cognition maturation in both healthy children and adolescents and those with white matter insult. Finally, we examine the hypothesis that white matter is linked to cognitive function via its impact on neural synchronization. We test this hypothesis in a population of children and adolescents with recurrent demyelinating syndromes. Specifically, we evaluate group differences in white matter microstructure within the optic radiation; and neural phase synchrony in visual cortex during a visual task between 25 patients and 28 typically developing age‐matched controls. Children and adolescents with demyelinating syndromes show evidence of myelin and axonal compromise and this compromise predicts reduced phase synchrony during a visual task compared to typically developing controls. We investigate one plausible mechanism at play in this relationship using a computational model of gamma generation in early visual cortical areas. Overall, our findings show a fundamental connection between white matter microstructure and neural synchronization that may be critical for cognitive processing. In the future, longitudinal or interventional studies can build upon our knowledge of these exciting relations between white matter, neural communication, and cognition.
Molecular Informatics Studies of the Iron-Dependent Regulator (ideR) Reveal Potential Novel Anti-Mycobacterium ulcerans Natural Product-Derived Compounds

Buruli ulcer is a neglected tropical disease caused by the bacterium Mycobacterium ulcerans. Its virulence is attributed to the dermo-necrotic polyketide toxin mycolactone, whose synthesis is regressed when its iron acquisition system regulated by the iron-dependent regulator (ideR) is deactivated. Interfering with the activation mechanism of ideR to inhibit the toxin’s synthesis could serve as a possible cure for Buruli ulcer. The three-dimensional structure of the ideR for Mycobacterium ulcerans was generated using homology modeling. A library of 832 African natural products (AfroDB), as well as five known anti-mycobacterial compounds were docked against the metal binding site of the ideR. The area under the curve (AUC) values greater than 0.7 were obtained for the computed Receiver Operating Characteristics (ROC) curves, validating the docking protocol. The identified top hits were pharmacologically profiled using Absorption, Distribution, Metabolism, Elimination and Toxicity (ADMET) predictions and their binding mechanisms were characterized. Four compounds with ZINC IDs ZINC000018185774, ZINC000095485921, ZINC000014417338 and ZINC000005357841 emerged as leads with binding energies of −7.7 kcal/mol, −7.6 kcal/mol, −8.0 kcal/mol and −7.4 kcal/mol, respectively. Induced Fit Docking (IFD) was also performed to account for the protein’s flexibility upon ligand binding and to estimate the best plausible conformation of the complexes. Results obtained from the IFD were consistent with that of the molecular docking with the lead compounds forming interactions with known essential residues and some novel critical residues Thr14, Arg33 and Asp17. A hundred nanoseconds molecular dynamic simulations of the unbound ideR and its complexes with the respective lead compounds revealed changes in the ideR’s conformations induced by ZINC000018185774. Comparison of the lead compounds to reported potent inhibitors by docking them against the DNA-binding domain of the protein also showed the lead compounds to have very close binding affinities to those of the potent inhibitors. Interestingly, structurally similar compounds to ZINC000018185774 and ZINC000014417338, as well as analogues of ZINC000095485921, including quercetin are reported to possess anti-mycobacterial activity. Also, ZINC000005357841 was predicted to possess anti-inflammatory and anti-oxidative activities, which are relevant in Buruli ulcer and iron acquisition mechanisms, respectively. The leads are molecular templates which may serve as essential scaffolds for the design of future anti-mycobacterium ulcerans agents.
Anterior Cruciate Ligament Reconstruction in Young Female Athletes: Patellar Versus Hamstring Tendon Autografts

Background: Female athletes are 2 to 8 times more prone to anterior cruciate ligament (ACL) rupture than males. Furthermore, reinjury to the ipsilateral or contralateral knee can occur in >20% of athletes. Female sex and younger age are known risk factors for graft failure. The optimal graft choice for young females remains unknown and poorly studied. Purpose/Hypothesis: The authors aimed to compare clinical outcomes in young females who underwent ACL reconstruction (ACLR) with bone–patellar tendon–bone (BTB) and quadrupled hamstring (HS) autografts. It was hypothesized that no significant differences in outcomes exist between graft choices. Study Design: Cohort study; Level of evidence, 3. Methods: Female patients aged 15 to 25 years who underwent primary ACLR with BTB or HS autograft were included for review. Patients were subdivided into 2 age groups: 15 to 20 years and 21 to 25 years. The occurrence of chondral, meniscal, or ligamentous injury to either knee was recorded for comparison. Results: A total of 256 females were included (BTB, n = 175; HS, n = 81). The majority of patients were between the ages of 15 and 20 years (BTB, 80%; HS, 77.8%). Overall, graft rupture occurred in 23 patients (9%) and contralateral ACL tear occurred in 18 (7%). Subgroup analysis showed that 75% of BTB and 100% of HS graft retears occurred in females aged 15 to 20 years. Within this age group, there was a significantly lower rate of graft ruptures in the BTB group (6.4%) as compared with the HS group (17.5%, P = .02). Allograft augmentation was used in 4 of the 11 HS grafts that retore. When allograft-augmented grafts were excluded, there was no significant difference in graft failure rate between graft choices. Fifteen patients in the BTB group (12%) as opposed to 1 in the HS group (2%) reported extreme difficulty or the inability to kneel on the front of the knee (P = .04). Conclusion: In females aged 15 to 20 years undergoing ACLR, BTB autograft may lead to fewer graft ruptures than HS autograft. While this difference was not observed in females aged 21 to 25 years, a larger sample may be required to accept the null hypothesis in this age group. BTB autograft significantly increased the risk of kneeling pain as compared with HS regardless of age.
Prevalence of triangular fibrocartilage complex injuries in patients with distal radius fractures: a 3.0T magnetic resonance imaging study

Objective This study was performed to determine the prevalence of triangular fibrocartilage complex (TFCC) injuries as shown by 3.0T magnetic resonance imaging (MRI) in patients with distal radius fractures. Methods In total, 57 patients with distal radius fractures underwent 3.0T MRI examinations to observe the incidence of TFCC injuries after manual reduction and cast fixation. The fracture type was categorized by the AO classiﬁcation, and the TFCC injury pattern was evaluated using the Palmer classiﬁcation. The correlation between the location of the TFCC injury and the distal radius fracture pattern, distal radioulnar joint instability, or ulnar styloid fracture was analyzed. Results Fifty-five TFCC injuries were diagnosed. There was no significant relationship between the TFCC injury pattern and the type of distal radius fracture, distal radioulnar joint instability, or ulnar styloid fracture. Conclusions This study revealed a high prevalence of TFCC injuries in patients with distal radius fractures. The 3.0T MRI examination helps to assess TFCC injuries in patients with distal radius fractures. Clinical Trial Registration ChiCTR1800017101.
Larvicidal Compounds Extracted from Helicteres velutina K. Schum (Sterculiaceae) Evaluated against Aedes aegypti L.

Helicteres velutina K. Schum (Sterculiaceae), a member of Malvaceae sensu lato, is a Brazilian endemic plant that has been used by the indigenous tribe Pankarare as an insect repellent. A previous study has reported the isolation of terpenoids, flavonoids and pheophytins, in addition to the larvicidal activity of crude H. velutina extracts derived from the aerial components (leaves, branches/twigs, and flowers). The present study reports the biomonitoring of the effects of fractions and isolated compounds derived from H. velutina against A. aegypti fourth instar larvae. A crude ethanol extract was submitted to liquid–liquid extraction with hexane, dichloromethane, ethyl acetate and n-butanol to obtain their respective fractions. Larvicidal evaluations of the fractions were performed, and the hexane and dichloromethane fractions exhibited greater activities than the other fractions, with LC50 (50% lethal concentration) values of 3.88 and 5.80 mg/mL, respectively. The phytochemical study of these fractions resulted in the isolation and identification of 17 compounds. The molecules were subjected to a virtual screening protocol, and five molecules presented potential larvicidal activity after analyses of their applicability domains. When molecular docking was analysed, only three of these compounds showed an ability to bind with sterol carrier protein-2 (1PZ4), a protein found in the larval intestine. The compounds tiliroside and 7,4′-di-O-methyl-8-O-sulphate flavone showed in vitro larvicidal activity, with LC50 values of 0.275 mg/mL after 72 h and 0.182 mg/mL after 24 h of exposure, respectively. This is the first study to demonstrate the larvicidal activity of sulphated flavonoids against A. aegypti. Our results showed that the presence of the OSO3H group attached to C-8 of the flavonoid was crucial to the larvicidal activity. This research supports the traditional use of H. velutina as an alternative insecticide for the control of A. aegypti, which is a vector for severe arboviruses, such as dengue and chikungunya.
A cost analysis comparing telepsychiatry to in-person psychiatric outreach and patient travel reimbursement in Northern Ontario communities

Introduction Residents of Northern Ontario have limited access to local psychiatric care. To address this, three program models exist: (1) telepsychiatry; (2) psychiatrists traveling to underserved areas; and (3) reimbursing patients for travel to a psychiatrist. Evidence shows that telepsychiatry has comparable outcomes to in-person consultations. The objective of this study was to determine the cost difference between programs. Methods A cost-minimization analysis estimating cost per visit from a public healthcare payer economic costing perspective was conducted. Data on fixed and variable costs were obtained. Evidence-based assumptions were made where relevant. Base-case scenarios and a break-even analysis were completed, as well as deterministic and probabilistic sensitivity analyses, to explore the effects of parameter variability on program costs. Results Costs per visit were lowest in telepsychiatry (CAD$360) followed by traveling physicians (CAD$558) and patient reimbursement (CAD$620). Among the 100,000 Monte Carlo simulations, results showed telepsychiatry was the least costly program in 71.2% of the simulations, while the reimbursement and outreach programs were least costly in 15.1% and 13.7% of simulations, respectively. The break-even analysis found telepsychiatry was the least costly program after an annual patient visit threshold of approximately 76 visits (compared to traveling psychiatrists) and 126 visits (compared to reimbursed patients). Discussion Our analyses support telepsychiatry as the least costly program. These results have important implications for program planning, including the prioritization of telepsychiatry, increased integration of telepsychiatry with other modalities of outreach psychiatry, and limiting use of the patient remuneration program to where medically necessary, to reduce overall cost.
Caffeic Acid Phenethyl Ester Inhibits UV-Induced MMP-1 Expression by Targeting Histone Acetyltransferases in Human Skin

Caffeic acid phenethyl ester (CAPE), a naturally occurring bioactive compound, displays anti-inflammatory, anti-carcinogenic, and anti-microbial effects. However, the effect of CAPE on skin photoaging is unknown. Herein, we investigated the inhibitory effect of CAPE against ultraviolet (UV) irradiation-mediated matrix metalloproteinase (MMP)-1 expression and its underlying molecular mechanism. CAPE treatment suppressed UV-induced MMP-1 levels in both human dermal fibroblasts (HDF) and human skin tissues. While CAPE did not display any significant effects against the upstream regulatory pathways of MMP-1, CAPE was capable of reversing UV-mediated epigenetic modifications. CAPE suppressed UV-induced acetyl-histone H3 (Lys9) as well as total lysine acetylation in HDF cells. Similarly, CAPE also attenuated UV-induced lysine acetylations in human skin tissues, suggesting that the CAPE-mediated epigenetic alterations can be recapitulated in ex vivo conditions. CAPE was found to attenuate UV-induced histone acetyltransferase (HAT) activity in HDF. Notably, CAPE was able to directly inhibit the activity of several HATs including p300, CREP-binding protein (CBP), and p300/CBP-associated factor (PCAF), further confirming that CAPE can function as an epigenetic modulator. Thus, our study suggests that CAPE maybe a promising agent for the prevention of skin photoaging via targeting HATs.
Overcoming Iron Deficiency of an Escherichia coli tonB Mutant by Increasing Outer Membrane Permeability

The work presented here describes a positive genetic selection strategy for isolating mutations that destabilize the outer membrane permeability barrier of E. coli. Given the importance of the outer membrane in restricting the entry of antibiotics, characterization of the genes and their products that affect outer membrane integrity will enhance the understanding of bacterial membranes and the development of strategies to bypass the outer membrane barrier for improved drug efficacy. ABSTRACT The intake of certain nutrients, including ferric ion, is facilitated by the outer membrane-localized transporters. Due to ferric insolubility at physiological pH, Escherichia coli secretes a chelator, enterobactin, outside the cell and then transports back the enterobactin-ferric complex via an outer membrane receptor protein, FepA, whose activity is dependent on the proton motive force energy transduced by the TonB-ExbBD complex of the inner membrane. Consequently, ΔtonB mutant cells grow poorly on a medium low in iron. Prolonged incubation of ΔtonB cells on low-iron medium yields faster-growing colonies that acquired suppressor mutations in the yejM (pbgA) gene, which codes for a putative inner-to-outer membrane cardiolipin transporter. Further characterization of suppressors revealed that they display hypersusceptibility to vancomycin, a large hydrophilic antibiotic normally precluded from entering E. coli cells, and leak periplasmic proteins into the culture supernatant, indicating a compromised outer membrane permeability barrier. All phenotypes were reversed by supplying the wild-type copy of yejM on a plasmid, suggesting that yejM mutations are solely responsible for the observed phenotypes. The deletion of all known cardiolipin synthase genes (clsABC) did not produce the phenotypes similar to mutations in the yejM gene, suggesting that the absence of cardiolipin from the outer membrane per se is not responsible for increased outer membrane permeability. Elevated lysophosphatidylethanolamine levels and the synthetic growth phenotype without pldA indicated that defective lipid homeostasis in the yejM mutant compromises outer membrane lipid asymmetry and permeability barrier to allow enterobactin intake, and that YejM has additional roles other than transporting cardiolipin. IMPORTANCE The work presented here describes a positive genetic selection strategy for isolating mutations that destabilize the outer membrane permeability barrier of E. coli. Given the importance of the outer membrane in restricting the entry of antibiotics, characterization of the genes and their products that affect outer membrane integrity will enhance the understanding of bacterial membranes and the development of strategies to bypass the outer membrane barrier for improved drug efficacy.