Miracle-dz/UniFAR-FTUs huggingface dataset:
m6A RNA methylation impacts fate choices during skin morphogenesis

N6-methyladenosine is the most prominent RNA modification in mammals. Here, we study mouse skin embryogenesis to tackle m6A’s functions and physiological importance. We first landscape the m6A modifications on skin epithelial progenitor mRNAs. Contrasting with in vivo ribosomal profiling, we unearth a correlation between m6A modification in coding sequences and enhanced translation, particularly of key morphogenetic signaling pathways. Tapping physiological relevance, we show that m6A loss profoundly alters these cues and perturbs cellular fate choices and tissue architecture in all skin lineages. By single-cell transcriptomics and bioinformatics, both signaling and canonical translation pathways show significant downregulation after m6A loss. Interestingly, however, many highly m6A-modified mRNAs are markedly upregulated upon m6A loss, and they encode RNA-methylation, RNA-processing and RNA-metabolism factors. Together, our findings suggest that m6A functions to enhance translation of key morphogenetic regulators, while also destabilizing sentinel mRNAs that are primed to activate rescue pathways when m6A levels drop.
Heterologous Expression of the Unusual Terreazepine Biosynthetic Gene Cluster Reveals a Promising Approach for Identifying New Chemical Scaffolds

Here, we provide evidence that Aspergillus terreus encodes a biosynthetic gene cluster containing a repurposed indoleamine 2,3-dioxygenase (IDO) dedicated to secondary metabolite synthesis. The discovery of this neofunctionalized IDO not only enabled discovery of a new compound with an unusual chemical scaffold but also provided insight into the numerous strategies fungi employ for diversifying and protecting themselves against secondary metabolites. The observations in this study set the stage for further in-depth studies into the function of duplicated IDOs present in fungal biosynthetic gene clusters and presents a strategy for accessing the biosynthetic potential of gene clusters containing duplicated primary metabolic genes. ABSTRACT Advances in genome sequencing have revitalized natural product discovery efforts, revealing the untapped biosynthetic potential of fungi. While the volume of genomic data continues to expand, discovery efforts are slowed due to the time-consuming nature of experiments required to characterize new molecules. To direct efforts toward uncharacterized biosynthetic gene clusters most likely to encode novel chemical scaffolds, we took advantage of comparative metabolomics and heterologous gene expression using fungal artificial chromosomes (FACs). By linking mass spectral profiles with structural clues provided by FAC-encoded gene clusters, we targeted a compound originating from an unusual gene cluster containing an indoleamine 2,3-dioxygenase (IDO). With this approach, we isolate and characterize R and S forms of the new molecule terreazepine, which contains a novel chemical scaffold resulting from cyclization of the IDO-supplied kynurenine. The discovery of terreazepine illustrates that FAC-based approaches targeting unusual biosynthetic machinery provide a promising avenue forward for targeted discovery of novel scaffolds and their biosynthetic enzymes, and it also represents another example of a biosynthetic gene cluster “repurposing” a primary metabolic enzyme to diversify its secondary metabolite arsenal. IMPORTANCE Here, we provide evidence that Aspergillus terreus encodes a biosynthetic gene cluster containing a repurposed indoleamine 2,3-dioxygenase (IDO) dedicated to secondary metabolite synthesis. The discovery of this neofunctionalized IDO not only enabled discovery of a new compound with an unusual chemical scaffold but also provided insight into the numerous strategies fungi employ for diversifying and protecting themselves against secondary metabolites. The observations in this study set the stage for further in-depth studies into the function of duplicated IDOs present in fungal biosynthetic gene clusters and presents a strategy for accessing the biosynthetic potential of gene clusters containing duplicated primary metabolic genes.
Communal Coping and Self-Care in Black and White Individuals Living with Type 2 Diabetes

ABSTRACT Type 2 diabetes mellitus is both prevalent and profoundly impactful, and how people cope with the illness is related to a variety of individual and relational outcomes. The goal of this investigation was to test the logic of the recently extended Theoretical Model of Communal Coping (TMCC), a communication theory that argues that race (in this study, Black and White) moderates the relationship between communal coping and disease-related outcomes (i.e., glucose, diet, and exercise self-care). In general, survey data from 348 participants (n = 224 Black participants, n = 124 White participants) revealed that although communal coping was directly and positively related to self-care, the relationship between communal coping and self-care was stronger for Black participants than White participants. The results of the study have implications for the TMCC and for researchers, families managing type 2 diabetes, and healthcare practitioners.
In vitro sensitivity of two species of Sclerotinia spp. and Sclerotium cepivorum to agents of biological control and fungicides.

The in vitro response of two Sclerotinia minor-, five S. sclerotiorumand two Sclerotium cepivorum-isolates to 16 biological control agents and eight fungicides was evaluated. A split plot experimental design was used, with a factorial arrangement correction for each pathogen. Factor A corresponded to fungi isolates and Factor B to control agents. The comparison of means was carried out using a Tukey test (P<0.05), having 11 evaluations every 24 h of the Mycelial radial growth rates (Mrgr). In any case no effect was found, alone or in interactions with control agents. Dicloran, Benomyl, Tebuconazole and CyprodinilFludioxonil inhibited the mycelial growth of all fungi with a final average of 1.0 Mrgr, and in greater proportion than biological agents (BA). The BA that propitiated the lesser mycelial growth towards S. minor were: Microorganisms (BPGPlus), Trichoderma sp. (Trichoderma), T. viride (Esporalis) and Bacillus subtillis (Serenade max); with isolates of S. sclerotiorum, Trichoderma sp. (Trichoderma), Trichoderma harzianum (Natucontrol), Microorganisms (BPG-Plus) and T.
Prospects of using Azotobacter, Azospirillum and cyanobacteria as supplements of urea nitrogen for rice production in Bangladesh

The responses to inoculation with (i) Azotobacter and Azospirillum of boro rice under five levels of nitrogen (N) fertiliser (0, 60, 80, 100 and 120 kg N/ha from urea) and (ii) blue-green algae (BGA) of transplanted aman rice under four levels of N fertiliser (0, 20, 30 and 40 kg N/ha from urea) were examined in two field experiments in Bangladesh. Maximum grain yield (8.43 t/ha) was recorded with Azospirillum at 100 kg N/ha, 1.34 t/ha higher than the yield obtained with 120 kg N/ha applied alone, suggesting the benefit of reducing N application by 20 kg/ha with extra yield. Similarly, Azotobacter showed the potential to save 20 kg N/ha with additional yield of 1.24 t/ha. Mixed cultures (Azospirillum + Azotobacter) were statistically similar to individual cultures at all the N rates, showing that single species inoculation suffices to increase grain yield and suggesting a common mechanism of the effect. In the case of aman rice, grain yield increased significantly from N fertilisation at 20 kg N/ha without inoculation, but increasing N rates above this rate only gave a nonsignificant trend in increasing grain yield. With inoculation treatments, grain yield responses to added N were significant up to 40 kg N/ha, indicating that BGA increases the rice plants’ capacity to use more fertiliser-N for grain production. The grain yield obtained by the local isolates at 30 kg N/ha were higher than the yield obtained at 40 kg N/ha without inoculation, indicating the prospect of reducing urea by 25%, although the yields were lower than those obtained at 40 kg N/ha with these inoculants.
Assessment of Sesame Street online autism resources: Impacts on parental implicit and explicit attitudes toward children with autism

The current study sought to characterize implicit bias toward children with autism and examine whether viewing educational materials about autism would change attitudes toward children with autism. A website developed by Sesame Street containing information about autism and resources for families was distributed to parents of children with autism (n = 473) and parents of children without autism (n = 707). Pre- and post-test measures of implicit bias toward children with autism; explicit attitudes and knowledge about autism; and parenting confidence, strain, and stigma were completed before and after the website was presented. Results indicated that parents of children with autism showed less implicit bias compared with those of non-autistic children during the pre-test, but the groups did not differ at the post-test. Parents without autistic children and those with more negative explicit attitudes showed a greater reduction in implicit bias from the pre- to the post-test. In addition, for parents of children with autism, a more positive change in explicit attitudes and increased knowledge from the pre- to the post-test was associated with more empowerment at the post-test. Together, our findings suggest that the online educational resources can reduce implicit bias against children with autism and help mitigate some of the psychological issues associated with parenting children with autism.
Grassroots Mental Health Groups’ Use of Advocacy Strategies in Social Media Messaging

Mental health concerns are a public health crisis. Stigma is the primary reason why individuals do not disclose or seek treatment. Stigma is constructed communicatively, and destigmatization efforts—such as advocacy messaging—are also communicative. I employ a case study approach to describe how two mental health groups use advocacy strategies in their social media messaging to help audience members mitigate mental health concerns and challenge stigma. I found content creators use a variety of advocacy strategies in their messaging, including awareness-raising, support of policy initiatives, and the promotion of diversity and inclusivity. Although not the primary goal of these groups’ messaging, advocacy strategies were important to content creators and audience members, and 80% of audience members interviewed engaged in advocacy work for the organizations. I provide a nuanced view of mental health communication advocacy strategies, make recommendations for health communication professionals, and demonstrate the need for future studies.
Developments of 3D Printing Microfluidics and Applications in Chemistry and Biology: a Review

Three-dimensional (3D) printing, also called additive manufacturing (AM) or rapid prototyping (RP), is a layer by layer manufacturing method and now has been widely used in many areas such as organ printing, aerospace and industrial design. Now 3D printed microfluidics attract more and more interests for its rapid printing in the lab. In this review, we focused on the advances of 3D printed microfluidic chips especially the use in the chemistry and biology (vascularization and organs on chips). Based on the brief review of different 3D printing methods, we discussed how to choose the suitable 3D printing methods to print the desired microfluidics. We predict that microfluidics will be evolved from 2D chips to 3D cubes, printed hydrogel-based microfluidics will be reported and widely used, sensors & actuators could be integrated in the microfluidics during printing, and rapid assembling chips with printed microfluidic modules will be popular in the near future.
Is exposure to indoor secondhand smoke associated with poor mental health? Results from non-conflict and post-conflict setting

ABSTRACT The purpose of this study was to examine the association between exposure to indoor SHS and self-reported HRQoL among healthy non-smoking students at the University of Belgrade, Serbia and Kosovska Mitrovica located in the post-conflict Kosovo province. Students who presented at Student Public Health Center in Belgrade in 2009 and Kosovska Mitrovica in 2015 for mandatory health checks were invited to participate. Data were collected using socio-demographic and behavioral questionnaire, health-related quality of life questionnaire Short Form-36 (SF-36) and Beck Depression Inventory (BDI). A total of 82.3% students in Belgrade sample and 76.0% in Kosovska Mitrovica sample reported daily exposure to indoor SHS. After adjustment for socio-demographic characteristics and behavior, daily exposure to indoor SHS for more than 6 hours was associated with poorer Vitality (β = −5.55, 95% confidence interval [CI] −9.49, −1.61) and Mental Health (β = 5.00, 95% CI-8.94, −1.07) only among students at the University of Belgrade. This study showed that the association between longer daily indoor SHS exposure and poor mental health HRQoL was not consistent in non-conflict and post-conflict setting. This association was not found in a post-conflict setting. Strict no smoking policies are needed in student housing, university campuses and all public spaces.
Polymer Selection for Hot-Melt Extrusion Coupled to Fused Deposition Modelling in Pharmaceutics

Three-dimensional (3D) printing offers the greatest potential to revolutionize the future of pharmaceutical manufacturing by overcoming challenges of conventional pharmaceutical operations and focusing design and production of dosage forms on the patient’s needs. Of the many technologies available, fusion deposition modelling (FDM) is considered of the lowest cost and higher reproducibility and accessibility, offering clear advantages in drug delivery. FDM requires in-house production of filaments of drug-containing thermoplastic polymers by hot-melt extrusion (HME), and the prospect of connecting the two technologies has been under investigation. The ability to integrate HME and FDM and predict and tailor the filaments’ properties will extend the range of printable polymers/formulations. Hence, this work revises the properties of the most common pharmaceutical-grade polymers used and their effect on extrudability, printability, and printing outcome, providing suitable processing windows for different raw materials. As a result, formulation selection will be more straightforward (considering the characteristics of drug and desired dosage form or release profile) and the processes setup will be more expedite (avoiding or mitigating typical processing issues), thus guaranteeing the success of both HME and FDM. Relevant techniques used to characterize filaments and 3D-printed dosage forms as an essential component for the evaluation of the quality output are also presented.
Cholesterol‐conjugated bovine serum albumin nanoparticles as a tamoxifen tumor‐targeted delivery system

In the present study, we introduced cholesterol (CLO)‐conjugated bovine serum albumin nanoparticles (BSA NPs) as a new system for indirect targeting drug delivery. Tamoxifen, as an anticancer drug, was loaded on BSA NPs (BSA‐TAX NPs); CLO was then conjugated to the BSA‐TAX NPs surface for the targeted delivery of NPs system, by 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide/N‐hydroxy succinimide carbodiimide chemistry (CLO‐BSA‐TAX NPs). The physicochemical properties, toxicity, in vitro, and in vivo biocompatibility of the BSA NPs system were characterized on cancer cell lines (4T1). The results revealed that the BSA NPs system has a regular spherical shape and negative zeta‐potential values. The drug release of BSA NPs system has shown controlled and pH‐dependent drug release behavior. BSA NPs system was biocompatible but it was potentially toxic on the cancer cell line. The CLO‐BSA‐TAX NPs exhibited higher toxicity against cancer cell lines than other NPs formulation (BSA NPs and BSA‐TAX NPs). It can be concluded that the CLO, as an indirect targeting agent, enhances the toxicity and specificity of NPs system on cancer cell lines. It could potentially be suitable approaches to targeting the tumors in clinical cancer therapy.
Infection With a Novel Rickettsiella Species in Emperor Scorpions (Pandinus imperator)

Rickettsiella infection was diagnosed in 4 adult emperor scorpions (Pandinus imperator) from 2 different collections over a 3-year period. One case had a 2-day history of weakness, failure to lift the tail, or respond to stimulation, with rapid progression to death. The other 3 cases were found dead. There were no gross lesions, but histologically the hemolymphatic vasculature and sinuses, presumed hematopoietic organ, heart, midgut and midgut diverticula, nerves, and skeletal muscle were infiltrated with phagocytic and granular hemocytes with necrosis. Phagocytic hemocytes contained abundant intracellular microorganisms that were Fite’s acid-fast-positive, Macchiavello-positive, variably gram-positive or gram-negative, and Grocott’s methenamine silver-negative. By transmission electron microscopy, hemocytes contained numerous phagocytic vacuoles with small dense bacterial forms (mean 0.603 × 0.163 μm) interspersed with large bacterial forms (mean 1.265 × 0.505 μm) and few intermediary forms with electron-dense nucleoids and membrane-bound crystalline arrays (average 4.72 μm). Transmission electron microscopy findings were consistent with bacteria of the family Coxiellaceae. Based on sequencing the 16S ribosomal RNA gene, the identity was confirmed as Rickettsiella, and phylogenetic analysis of protein-coding genes gidA, rspA, and sucB genes suggested the emperor scorpion pathogen as a new species. This study identifies a novel Rickettsiella causing infection in emperor scorpions and characterizes the unique pathological findings of this disease. We suggest this organism be provisionally named Rickettsiella scorpionisepticum.
Isolation and diversity of crude oil-degrading bacteria from Dalian Bay

[Objective] In order to investigate the diversity of crude oil-degrading bacteria in the seawater,mud and sponge samples from Dalian Bay,and obtain new oil-degrading bacteria. [Methods] Crude oil was used as sole carbon source to enrich and isolate the potential oil-degrading bacteria from samples of seawater,mud or sponge.Phylogenetic analysis was conducted by 16S rRNA gene sequences of the bacteria. [Results] After screening via morphological and 16S rRNA gene sequences analysis 50 strains belonging to 22 genera were obtained.Among them,6 strains shared 16S rRNA gene sequence identities of 95% 97% with the most similar strains,were speculated new species.Further experiments revealed oil-degrading capability of 45 strains. [Conclusion] This study demonstrated a high diversity of the cultivable oil-degrading bacteria in Dalian Bay,and obtained new resources in bioremediation of marine oil pollution.
Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease

A major focus of Alzheimer's disease (AD) research has been finding sensitive outcome measures to disease progression in preclinical AD, as intervention studies begin to target this population. We hypothesize that tailored measures of longitudinal change of the medial temporal lobe (MTL) subregions (the sites of earliest cortical tangle pathology) are more sensitive to disease progression in preclinical AD compared to standard cognitive and plasma NfL measures. Longitudinal T1‐weighted MRI of 337 participants were included, divided into amyloid‐β negative (Aβ−) controls, cerebral spinal fluid p‐tau positive (T+) and negative (T−) preclinical AD (Aβ+ controls), and early prodromal AD. Anterior/posterior hippocampus, entorhinal cortex, Brodmann areas (BA) 35 and 36, and parahippocampal cortex were segmented in baseline MRI using a novel pipeline. Unbiased change rates of subregions were estimated using MRI scans within a 2‐year‐follow‐up period. Experimental results showed that longitudinal atrophy rates of all MTL subregions were significantly higher for T+ preclinical AD and early prodromal AD than controls, but not for T− preclinical AD. Posterior hippocampus and BA35 demonstrated the largest group differences among hippocampus and MTL cortex respectively. None of the cross‐sectional MTL measures, longitudinal cognitive measures (PACC, ADAS‐Cog) and cross‐sectional or longitudinal plasma NfL reached significance in preclinical AD. In conclusion, longitudinal atrophy measurements reflect active neurodegeneration and thus are more directly linked to active disease progression than cross‐sectional measurements. Moreover, accelerated atrophy in preclinical AD seems to occur only in the presence of concomitant tau pathology. The proposed longitudinal measurements may serve as efficient outcome measures in clinical trials.
The transcriptional elongation rate regulates alternative polyadenylation in yeast

Yeast cells undergoing the diauxic response show a striking upstream shift in poly(A) site utilization, with increased use of ORF-proximal poly(A) sites resulting in shorter 3’ mRNA isoforms for most genes. This altered poly(A) pattern is extremely similar to that observed in cells containing Pol II derivatives with slow elongation rates. Conversely, cells containing derivatives with fast elongation rates show a subtle downstream shift in poly(A) sites. Polyadenylation patterns of many genes are sensitive to both fast and slow elongation rates, and a global shift of poly(A) utilization is strongly linked to increased purine content of sequences flanking poly(A) sites. Pol II processivity is impaired in diauxic cells, but strains with reduced processivity and normal Pol II elongation rates have normal polyadenylation profiles. Thus, Pol II elongation speed is important for poly(A) site selection and for regulating poly(A) patterns in response to environmental conditions.
Lost Touch? Implications of Physical Touch for Physical Health

Abstract Objectives Growing research on the impact of physical touch on health has revealed links to lower blood pressure, higher oxytocin levels, and better sleep, but links to inflammation have not been fully explored. Physical touch may also buffer stress, underscoring its importance during the stressful time of living in the COVID-19 global pandemic – a time that has substantially limited social interactions and during which physical touch has been specifically advised against. Methods We analyze nationally representative longitudinal data on older adults (N=1124) from the National Social Life, Health, and Aging Project using cross-lagged path models. Results More frequent physical touch is significantly related to a lower likelihood of subsequent elevated inflammation. Discussion These findings highlight the importance of finding safe ways to incorporate physical touch, even in the aftermath of the COVID-19 pandemic.
Polyelectrolyte Multilayer Capsule (PEMC)-Based Scaffolds for Tissue Engineering

Tissue engineering (TE) is a highly multidisciplinary field that focuses on novel regenerative treatments and seeks to tackle problems relating to tissue growth both in vitro and in vivo. These issues currently involve the replacement and regeneration of defective tissues, as well as drug testing and other related bioapplications. The key approach in TE is to employ artificial structures (scaffolds) to support tissue development; these constructs should be capable of hosting, protecting and releasing bioactives that guide cellular behaviour. A straightforward approach to integrating bioactives into the scaffolds is discussed utilising polyelectrolyte multilayer capsules (PEMCs). Herein, this review illustrates the recent progress in the use of CaCO3 vaterite-templated PEMCs for the fabrication of functional scaffolds for TE applications, including bone TE as one of the main targets of PEMCs. Approaches for PEMC integration into scaffolds is addressed, taking into account the formulation, advantages, and disadvantages of such PEMCs, together with future perspectives of such architectures.