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"Barton, Brenda"
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Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after fecal microbiota transplant in inflammatory bowel disease
Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn’s disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14–29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3–92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.
Journal Article
Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease
A child with a neuronal ceroid lipofuscinosis was found to carry loss-of-function mutations in the gene
MFSD8
(
CLN7
). A year after genetic diagnosis, the child began treatment with an oligonucleotide drug that was designed to correct the aberrant pre–messenger RNA splicing caused by one of these mutations.
Journal Article
Direct care nurses’ perceptions of their roles in clinical research: An integrated review of the literature
Purpose To review the extant literature relevant to perceptions by direct care nurses toward clinical research endeavors. Design An integrative review guided by the socioecological model was conducted. Methods Five databases were searched to identify relevant peer‐reviewed articles; there was no limitation on publication date. Findings The final sample (N = 9) was systematically appraised. Numerous barriers to direct care nurses’ ability to perform study activities on clinical research trials were encountered at all levels: (1) personal—comprehension, education, and training; (2) interpersonal—communication issues within or from the study team, failure to advocate for the patient; (3) organizational—lack of leadership support, knowledge, and time; and (4) community—insufficient guidance and oversight by research‐governing bodies. Conclusions Direct care nurses report numerous barriers to completing protocol‐administered activities for their patients participating in clinical research. A dearth of robust research exists in describing the reasons for, or persistence of, barriers faced by direct care nurses to assisting with research, and there have been little to no interventions to address them. Clinical relevance As translational research evolves and becomes more complex, there is the need to ensure both the care of clinical research participants and the integrity of the research. Direct care nurses are critical to this endeavor, and potential barriers they face may have significant ramifications for the research enterprise. Recognition of these barriers and eventual interventions designed to address them are needed.
Journal Article
MicroRNA control of PHABULOSA in leaf development: importance of pairing to the microRNA 5' region
MicroRNAs (miRNAs) are ∼22‐nucleotide noncoding RNAs that can regulate gene expression by directing mRNA degradation or inhibiting productive translation. Dominant mutations in
PHABULOSA
(
PHB
) and
PHAVOLUTA
(
PHV
) map to a miR165/166 complementary site and impair miRNA‐guided cleavage of these mRNAs
in vitro
. Here, we confirm that disrupted miRNA pairing, not changes in PHB protein sequence, causes the developmental defects in
phb‐d
mutants.
In planta
, disrupting miRNA pairing near the center of the miRNA complementary site had far milder developmental consequences than more distal mismatches. These differences correlated with differences in miRNA‐directed cleavage efficiency
in vitro
, where mismatch scanning revealed more tolerance for mismatches at the center and 3′ end of the miRNA compared to mismatches to the miRNA 5′ region. In this respect, miR165/166 resembles animal miRNAs in its pairing requirements. Pairing to the 5′ portion of the small silencing RNA appears crucial regardless of the mode of post‐transcriptional repression or whether it occurs in plants or animals, supporting a model in which this region of the silencing RNA nucleates pairing to its target.
Journal Article
Establishing a Framework for the Ad/Abaxial Regulatory Network of Arabidopsis: Ascertaining Targets of Class III HOMEODOMAIN LEUCINE ZIPPER and KANADI Regulation
The broadly conserved Class III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) and KANADI transcription factors have opposing and transformational effects on polarity and growth in all tissues and stages of the plant's life. To obtain a comprehensive understanding of how these factors work, we have identified transcripts that change in response to induced HD-ZIPIII or KANADI function. Additional criteria used to identify high-confidence targets among this set were presence of an adjacent HD-ZIPIII binding site, expression enriched within a subdomain of the shoot apical meristem, mutant phenotype showing defect in polar leaf and/or meristem development, physical interaction between target gene product and HD-ZIPIII protein, opposite regulation by HD-ZIPIII and KANADI, and evolutionary conservation of the regulator-target relationship. We find that HD-ZIPIII and KANADI regulate tissue-specific transcription factors involved in subsidiary developmental decisions, nearly all major hormone pathways, and new actors (such as INDETERMINATE DOMAIN4) in the ad/abaxial regulatory network. Multiple feedback loops regulating HD-ZIPIII and KANADI are identified, as are mechanisms through which HD-ZIPIII and KANADI oppose each other. This work lays the foundation needed to understand the components, structure, and workings of the ad/abaxial regulatory network directing basic plant growth and development.
Journal Article
Arabidopsis KANADI1 Acts as a Transcriptional Repressor by Interacting with a Specific cis-Element and Regulates Auxin Biosynthesis, Transport, and Signaling in Opposition to HD-ZIPIII Factors
The formation of leaves and other lateral organs in plants depends on the proper specification of adaxial-abaxial (upper-lower) polarity. KANADI1 (KAN1), a member of the GARP family of transcription factors, is a key regulator of abaxial identity, leaf growth, and meristem formation in Arabidopsis thaliana. Here, we demonstrate that the Myb-like domain in KAN1 binds the 6-bp motif GNATA(A/T) and that this motif alone is sufficient to squelch transcription of a linked reporter in vivo. In addition, we report that KAN1 acts as a transcriptional repressor. Among its targets are genes involved in auxin biosynthesis, auxin transport, and auxin response. Furthermore, we find that the adaxializing HD-ZIPIII transcription factor REVOLUTA has opposing effects on multiple components of the auxin pathway. We hypothesize that HD-ZIPIII and KANADI transcription factors pattern auxin accumulation and responsiveness in the embryo. Specifically, we propose the opposing actions of KANADI and HD-ZIPIII factors on cotyledon formation (KANADI represses and HD-ZIPIII promotes cotyledon formation) occur through their opposing actions on genes acting at multiple steps in the auxin pathway.
Journal Article
Engineered immunogens to elicit antibodies against conserved coronavirus epitopes
Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.
A pan-betacoronavirus vaccine will likely require the elicitation of antibodies against spike regions conserved across diverse coronaviruses. Here, authors computationally engineer and experimentally validate immunogens to elicit antibodies against two such spike regions.
Journal Article
Mervyn LeRoy Comes to Town
Mervyn LeRoy Comes to Town is the first book devoted to the career of one of the director/producers who in the early years of sound cinema was instrumental in establishing the Hollywood model of production that would endure for more than half a century. As a director and producer, LeRoy was responsible for turning out more than sixty feature films in a career that spanned five decades; as a studio executive, he contributed substantially to the success of the industry during the challenging period of the Depression and also in the period of realignment and readjustment that followed the end of World War II. This book offers chapters devoted to individual films such as Little Caesar, Waterloo Bridge, 30 Seconds over Tokyo, Gypsy, and Quo Vadis.
eBook
Implications of trophic discrimination factor selection for stable isotope food web models of low trophic levels in the Arctic nearshore
Stable isotope analysis (SIA) has become a useful tool to investigate food web structures in Arctic marine ecosystems. This method requires assumptions about how isotopes are assimilated from food into tissues. Few controlled lab experiments have determined the appropriate trophic discrimination factors (TDFs) for Arctic marine species, thus many studies have resorted to using global averages or values determined from species in different habitats or taxa. We examined the trophic niche space for prey resources predicted from the isotopic ratios of fish collected in the coastal Beaufort and Chukchi Seas using several published Arctic marine TDFs. The different predictions were compared to highlight the implications of selecting appropriate TDFs in Arctic marine food web models. Predicted trophic niche space of prey resources differed greatly depending on the TDFs used, and the most appropriate TDFs from those that are currently available were identified for modeling Arctic nearshore lower trophic levels.
Journal Article