bluuebunny/crossref_metadata_2025 huggingface dataset:
Embryo and Endosperm Development Is Disrupted in the Female Gametophytic capulet Mutants of Arabidopsis
Authors: Grini Paul E , Jürgens Gerd , Hülskamp Martin
Published: April 2021

The female gametophyte of higher plants gives rise, by double fertilization, to the diploid embryo and triploid endosperm, which develop in concert to produce the mature seed. What roles gametophytic maternal factors play in this process is not clear. The female-gametophytic effects on embryo and endosperm development in the Arabidopsis mea, fis, and fie mutants appear to be due to gametic imprinting that can be suppressed by METHYL TRANSFERASE1 antisense (MET1 a/s) transgene expression or by mutation of the DECREASE IN DNA METHYLATION1 (DDM1) gene. Here we describe two novel gametophytic maternal-effect mutants, capulet1 (cap1) and capulet2 (cap2). In the cap1 mutant, both embryo and endosperm development are arrested at early stages. In the cap2 mutant, endosperm development is blocked at very early stages, whereas embryos can develop to the early heart stage. The cap mutant phenotypes were not rescued by wild-type pollen nor by pollen from tetraploid plants. Furthermore, removal of silencing barriers from the paternal genome by MET1 a/s transgene expression or by the ddm1 mutation also failed to restore seed development in the cap mutants. Neither cap1 nor cap2 displayed autonomous seed development, in contrast to mea, fis, and fie mutants. In addition, cap2 was epistatic to fis1 in both autonomous endosperm and sexual development. Finally, both cap1 and cap2 mutant endosperms, like wild-type endosperms, expressed the paternally inactive endosperm-specific FIS2 promoter GUS fusion transgene only when the transgene was introduced via the embryo sac, indicating that imprinting was not affected. Our results suggest that the CAP genes represent novel maternal functions supplied by the female gametophyte that are required for embryo and endosperm development.
Context Dependence of Meiotic Recombination Hotspots in Yeast: The Relationship Between Recombination Activity of a Reporter Construct and Base Composition
Authors: Petes Thomas D , Merker Jason D
Published: April 2021

Borde and colleagues reported that a reporter plasmid inserted at different genomic locations in Saccharomyces cerevisiae had different levels of meiotic recombination activity. We show that the level of recombination activity is very significantly correlated with the GC content of DNA sequences flanking the insertion.
Five RecA-like Proteins of Schizosaccharomyces pombe Are Involved in Meiotic Recombination
Authors: Grishchuk A L , Kohli J
Published: April 2021

The genome of Schizosaccharomyces pombe contains five genes that code for proteins with sequence similarity to the Escherichia coli recombination protein RecA: rad51+, rhp55+, rhp57+, rlp1+, and dmc1+. We analyzed the effect of deletion of each of these genes on meiotic recombination and viability of spores. Meiotic recombination levels were different from wild type in all recA-related mutants in several genetic intervals, suggesting that all five RecA homologs of S. pombe are required for normal levels of meiotic recombination. Spore viability was reduced in rad51, rhp55, and rhp57 mutants, but not in rlp1 and dmc1. It is argued that reduction of crossover is not the only cause for the observed reduction of spore viability. Analysis of double and triple mutants revealed that Rad51 and Dmc1 play major and partially overlapping roles in meiotic recombination, while Rhp55, Rhp57, and Rlp1 play accessory roles. Remarkably, deletion of Rlp1 decreases the frequency of intergenic recombination (crossovers), but increases intragenic recombination (gene conversion). On the basis of our results, we present a model for the involvement of five RecA-like proteins of S. pombe in meiotic recombination and discuss their respective roles.
Pka, Ras and RGS Protein Interactions Regulate Activity of AflR, a Zn(II)2Cys6 Transcription Factor in Aspergillus nidulans
Authors: Shimizu Kiminori , Hicks Julie K , Huang Tzu-Pi , Keller Nancy P
Published: April 2021

Sterigmatocystin (ST) is a carcinogenic polyketide produced by several filamentous fungi including Aspergillus nidulans. Expression of ST biosynthetic genes (stc genes) requires activity of a Zn(II)2Cys6 transcription factor, AflR. aflR is transcriptionally and post-transcriptionally regulated by a G-protein/cAMP/protein kinase A (PkaA) signaling pathway involving FlbA, an RGS (regulator of G-protein signaling) protein. Prior genetic data showed that FlbA transcriptional regulation of aflR was PkaA dependent. Here we show that mutation of three PkaA phosphorylation sites in AflR allows resumption of stc expression in an overexpression pkaA background but does not remediate stc expression in a ΔflbA background. This demonstrates negative regulation of AflR activity by phosphorylation and shows that FlbA post-transcriptional regulation of aflR is PkaA independent. AflR nucleocytoplasmic location further supports PkaA-independent regulation of AflR by FlbA. GFP-tagged AflR is localized to the cytoplasm when pkaA is overexpressed but nuclearly located in a ΔflbA background. aflR is also transcriptionally and post-transcriptionally regulated by RasA. RasA transcriptional control of aflR is PkaA independent but RasA post-transcriptional control of AflR is partially mediated by PkaA.
The PHOA and PHOB Cyclin-Dependent Kinases Perform an Essential Function in Aspergillus nidulans
Authors: Dou Xiaowei , Wu Dongliang , An Weiling , Davies Jonathan , Hashmi Shahr B , Ukil Leena , Osmani Stephen A
Published: April 2021

Unlike Pho85 of Saccharomyces cerevisiae, the highly related PHOA cyclin-dependent kinase (CDK) of Aspergillus nidulans plays no role in regulation of enzymes involved in phosphorous acquisition but instead modulates differentiation in response to environmental conditions, including limited phosphorous. Like PHO85, Aspergillus phoA is a nonessential gene. However, we find that expression of dominant-negative PHOA inhibits growth, suggesting it may have an essential but redundant function. Supporting this we have identified another cyclin-dependent kinase, PHOB, which is 77% identical to PHOA. Deletion of phoB causes no phenotype, even under phosphorous-limited growth conditions. To investigate the function of phoA/phoB, double mutants were selected from a cross of strains containing null alleles and by generating a temperature-sensitive allele of phoA in a ΔphoB background. Double-deleted ascospores were able to germinate but had a limited capacity for nuclear division, suggesting a cell cycle defect. Longer germination revealed morphological defects. The temperature-sensitive phoA allele caused both nuclear division and polarity defects at restrictive temperature, which could be complemented by expression of mammalian CDK5. Therefore, an essential function exists in A. nidulans for the Pho85-like kinase pair PHOA and PHOB, which may involve cell cycle control and morphogenesis.
A Microsatellite Variability Screen for Positive Selection Associated With the “Out of Africa” Habitat Expansion ofDrosophila melanogaster
Authors: Kauer M O , Dieringer D , Schlötterer C
Published: April 2021

We report a “hitchhiking mapping” study in D. melanogaster, which searches for genomic regions with reduced variability. The study's aim was to identify selective sweeps associated with the “out of Africa” habitat expansion. We scanned 103 microsatellites on chromosome 3 and 102 microsatellites on the X chromosome for reduced variability in non-African populations. When the chromosomes were analyzed separately, the number of loci with a significant reduction in variability only slightly exceeded the expectation under neutrality—six loci on the third chromosome and four loci on the X chromosome. However, non-African populations also have a more pronounced average loss in variability on the X chromosomes as compared to the third chromosome, which suggests the action of selection. Therefore, comparing the X chromosome to the autosome yields a higher number of significantly reduced loci. However, a more pronounced loss of variability on the X chromosome may be caused by demographic events rather than by natural selection. We therefore explored a range of demographic scenarios and found that some of these captured most, but not all aspects of our data. More theoretical work is needed to evaluate how demographic events might differentially affect X chromosomes and autosomes and to estimate the most likely scenario associated with the out of Africa expansion of D. melanogaster.
Heterochromatic Self-Association, a Determinant of Nuclear Organization, Does Not Require Sequence Homology in Drosophila
Authors: Sage Brian T , Csink Amy K
Published: April 2021

Chromosomes of higher eukaryotes contain blocks of heterochromatin that can associate with each other in the interphase nucleus. A well-studied example of heterochromatic interaction is the brownDominant (bwD) chromosome of D. melanogaster, which contains an ∼1.6-Mbp insertion of AAGAG repeats near the distal tip of chromosome 2. This insertion causes association of the tip with the centric heterochromatin of chromosome 2 (2h), which contains megabases of AAGAG repeats. Here we describe an example, other than bwD, in which distally translocated heterochromatin associates with centric heterochromatin. Additionally, we show that when a translocation places bwD on a different chromosome, bwD tends to associate with the centric heterochromatin of this chromosome, even when the chromosome contains a small fraction of the sequence homology present elsewhere. To further test the importance of sequence homology in these interactions, we used interspecific mating to introgress the bwD allele from D. melanogaster into D. simulans, which lacks the AAGAG on the autosomes. We find that D. simulans bwD associates with 2h, which lacks the AAGAG sequence, while it does not associate with the AAGAG containing X chromosome heterochromatin. Our results show that intranuclear association of separate heterochromatic blocks does not require that they contain the same sequence.
Genetic and Phenotypic Analysis of Alleles of the Drosophila Chromosomal JIL-1 Kinase Reveals a Functional Requirement at Multiple Developmental Stages
Authors: Zhang Weiguo , Jin Ye , Ji Yun , Girton Jack , Johansen Jørgen , Johansen Kristen M
Published: April 2021

In this study we provide a cytological and genetic characterization of the JIL-1 locus in Drosophila. JIL-1 is an essential chromosomal tandem kinase and in JIL-1 null animals chromatin structure is severely perturbed. Using a range of JIL-1 hypomorphic mutations, we show that they form an allelic series. JIL-1 has a strong maternal effect and JIL-1 activity is required at all stages of development, including embryonic, larval, and pupal stages. Furthermore, we identified a new allele of JIL-1, JIL-1h9, that encodes a truncated protein missing COOH-terminal sequences. Remarkably, the truncated JIL-1 protein can partially restore viability without rescuing the defects in polytene chromosome organization. This suggests that sequences within this region of JIL-1 play an important role in establishing and/or maintaining normal chromatin structure. By analyzing the effects of JIL-1 mutations we provide evidence that JIL-1 function is necessary for the normal progression of several developmental processes at different developmental stages such as oogenesis and segment specification. We propose that JIL-1 may exert such effects by a general regulation of chromatin structure affecting gene expression.
Rank-Based Statistical Methodologies for Quantitative Trait Locus Mapping
Authors: Zou Fei , Yandell Brian S , Fine Jason P
Published: April 2021

This article addresses the identification of genetic loci (QTL and elsewhere) that influence nonnormal quantitative traits with focus on experimental crosses. QTL mapping is typically based on the assumption that the traits follow normal distributions, which may not be true in practice. Model-free tests have been proposed. However, nonparametric estimation of genetic effects has not been studied. We propose an estimation procedure based on the linear rank test statistics. The properties of the new procedure are compared with those of traditional likelihood-based interval mapping and regression interval mapping via simulations and a real data example. The results indicate that the nonparametric method is a competitive alternative to the existing parametric methodologies.
Chromosome Condensation Defects in barren RNA-Interfered Drosophila Cells
Authors: Somma Maria Patrizia , Fasulo Barbara , Siriaco Giorgia , Cenci Giovanni
Published: April 2021

Barren, the Drosophila homolog of XCAP-H, is one of three non-SMC subunits of condensin, a conserved 13S multiprotein complex required for chromosome condensation. Mutations in barren (barr) were originally shown to affect sister-chromatid separation during mitosis 16 of the Drosophila embryo, whereas condensation defects were not detected. In contrast, mutations in yeast homologs of barren result in defective mitotic chromosome condensation as well as irregular chromatid separation. We have used double-stranded RNA-mediated interference (RNAi) to deplete Barren in Drosophila S2 cells. Our analyses indicate that inactivation of barr leads to extensive chromosome condensation and disrupts chromatid segregation.
Genomic Rearrangements at rrn Operons in Salmonella
Authors: Helm R Allen , Lee Alison G , Christman Harry D , Maloy Stanley
Published: April 2021

Most Salmonella serovars are general pathogens that infect a variety of hosts. These “generalist” serovars cause disease in many animals from reptiles to mammals. In contrast, a few serovars cause disease only in a specific host. Host-specific serovars can cause a systemic, often fatal disease in one species yet remain avirulent in other species. Host-specific Salmonella frequently have large genomic rearrangements due to recombination at the ribosomal RNA (rrn) operons while the generalists consistently have a conserved chromosomal arrangement. To determine whether this is the result of an intrinsic difference in recombination frequency or a consequence of lifestyle difference between generalist and host-specific Salmonella, we determined the frequency of rearrangements in vitro. Using lacZ genes as portable regions of homology for inversion analysis, we found that both generalist and host-specific serovars of Salmonella have similar tolerances to chromosomal rearrangements in vitro. Using PCR and genetic selection, we found that generalist and host-specific serovars also undergo rearrangements at rrn operons at similar frequencies in vitro. These observations indicate that the observed difference in genomic stability between generalist and host-specific serovars is a consequence of their distinct lifestyles, not intrinsic differences in recombination frequencies.
Epipelagic zooplankton diversity in the deep water region of the Gulf of Mexico: a metabarcoding survey
Authors: Martinez Miguel A , Hereu Clara María , Arteaga María Clara , Jiménez-Rosenberg Sylvia P A , Herzka Sharon Z , Saavedra-Flores Anaid , Robles-Flores Javier , Gomez-Reyes Ricardo , Batta-Lona Paola Gabriela , Gasca-Pineda Jaime , Galindo-Sánchez Clara E
Published: April 2021

Zooplankton is a key component in marine ecosystem health assessment. Here, we present a taxonomically comprehensive description of the zooplankton community (0–200 m) based on metabarcoding of the V9 hypervariable region of the 18S rRNA gene of 47 samples collected in the Gulf of Mexico (GoM) during summer 2015. Fourteen phyla were identified Arthropoda were dominant, with Calanidae, Metridinidae, and Euphausiidae as the most conspicuous families. Other abundant phyla were Cnidaria (Hydrozoa), Chordata (Tunicata), and Chaetognatha. The V9-18S sequence data were clustered into 1888 Operational Taxonomic Units (OTUs), of which 39 were cosmopolitan and belonging to various phyla, suggesting the presence of a core community with high local diversity throughout the GoM. Evaluation of metabarcoding sequences abundance showed overall positive correlations with morphologically quantified abundances except for specific groups. Cluster analysis of OTU distributions indicated two primary biographically distinctive groups of stations: one restricted to the Bay of Campeche, while the other occurred in the Central-West GoM, similar to previous descriptions of regional variation of the GoM based on environmental variables. Together these results provide a foundation for broad-scale zooplankton molecular biodiversity assessments in the southern GoM allowing evaluation of the effects of environmental changes on zooplankton communities.
Rebel Fragmentation and the Recruitment of Child Soldiers
Authors: Faulkner Christopher M , Doctor Austin C
Published: April 2021

The recruitment and use of children in armed conflict remains a prevalent feature of modern civil war. But which conflict actors are more likely to recruit children? We argue that the process by which rebel groups form shapes their recruitment strategies. Specifically, we contend that rebels that form as splinter factions from the ranks of pre-existing rebel organizations are more likely to recruit child soldiers than other rebel groups. Splinter groups face unique constraints as they materialize in the midst of an active conflict environment, necessitating that they mobilize a sufficient force to contend with existing competitors. As a result, rebel factions are more likely to pursue recruitment strategies that are low cost vis-à-vis alternatives, focusing on their immediate survival. Under such conditions, children become especially attractive recruits. Leveraging the Foundations of Rebel Group Emergence Dataset, our cross-national investigation of 237 rebel groups active between 1989 and 2011 provides robust support for our hypothesis that splinter factions are strongly associated with the recruitment of children.
Contrast-enhanced Mammography: A Guide to Setting Up a New Clinical Program
Authors: Kim Geunwon , Patel Bhavika , Mehta Tejas S , Du Linda , Mehta Rashmi J , Phillips Jordana
Published: April 2021

Contrast-enhanced mammography (CEM) is gaining rapid traction following the U.S. Food and Drug Administration approval for diagnostic indications. Contrast-enhanced mammography is an alternative form of mammography that uses a dual-energy technique for image acquisition after the intravenous administration of iodinated contrast material. The resulting exam includes a dual set of images, one that appears similar to a routine 2D mammogram and one that highlights areas of contrast uptake. Studies have shown improved sensitivity compared to mammography and similar performance to contrast-enhanced breast MRI. As radiology groups incorporate CEM into clinical practice they must first select the indications for which CEM will be used. Many practices initially use CEM as an MRI alternative or in cases recommended for biopsy. Practices should then define the CEM clinical workflow and patient selection to include ordering, scheduling, contrast safety screening, and managing imaging on the day of the exam. The main equipment requirements for performing CEM include CEM-capable mammography equipment, a power injector for contrast administration, and imaging-viewing capability. The main staffing requirements include personnel to place the intravenous line, perform the CEM exam, and interpret the CEM. To safely and appropriately perform CEM, staff must be trained in their respective roles and to manage potential contrast-related events. Lastly, informing referring colleagues and patients of CEM through marketing campaigns is helpful for successful implementation.
Prognostic role of interstitial pneumonia with or without emphysema in patients with clinical stage I lung cancer
Authors: Tsutani Yasuhiro , Kagimoto Atsushi , Handa Yoshinori , Mimae Takahiro , Miyata Yoshihiro , Okada Morihito
Published: April 2021

Objectives

The prognostic role of interstitial pneumonia with emphysema in lung cancer is not fully understood. This study aimed to examine the prognostic role of the presence of emphysema in patients with clinical stage I lung cancer and interstitial pneumonia.

Methods

The presence of interstitial pneumonia and emphysema was evaluated on preoperative high-resolution computed tomography. In total, 836 consecutive patients with clinical stage I lung cancer who underwent complete resection between April 2007 and March 2016 were retrospectively analyzed using the log-rank test and Cox proportional hazard model to examine survival differences.

Results

There was a significant difference in 5-year overall survival between patients with interstitial pneumonia and emphysema (n = 65) and those without (n = 771) (62.6% vs. 86.5%; P < 0.001). However, in patients with interstitial pneumonia on high-resolution computed tomography, there was no significant difference in 5-year overall survival between patients with emphysema (n = 65) and those without emphysema (n = 50) (62.6% vs. 59.4%, P = 0.84). Multivariable backward stepwise Cox proportional hazard analysis in patients with interstitial pneumonia showed that histology, %diffusing capacity of the lungs for carbon monoxide, radiologic interstitial pneumonia pattern and surgical procedure were independent prognostic factors for overall survival, but the presence of emphysema was not.

Conclusions

The presence of emphysema was not an independent prognostic factor for overall survival in patients with clinical stage I lung cancer with interstitial pneumonia. Poor survival of patients with IP and emphysema may be due to the presence of interstitial pneumonia.
The Semantics of Emotive Markers and Other Illocutionary Content
Authors: Rett Jessica
Published: April 2021

I identify a class of expressions called ‘emotive markers,’ exemplified by fortunately and alas, which encode not-at-issue information about the speaker’s emotive attitude towards the content of the utterances they occur in. I argue that there are important differences emotive markers and other encoders of not-at-issue content, in particular utterance modifiers like frankly or evidential adverbs like apparently. In contrast to these, emotive markers can result in Moore’s Paradox and always range over their local argument. I conclude that the contribution of emotive markers should be treated as ‘illocutionary content’, on par with the speaker’s other Discourse Commitments (Gunlogson, 2001), and I model this analysis in the dynamic sub-sentential update framework in Farkas & Bruce (2010).
Colour - Music: Experiments in the Educational Value of the Analogy Between Sound and Colour
Authors: Monteith E. R.
Published: April 2021

In order to avoid any misapprehension, it may be well to explain at the outset that the term “Colour-music” is used in this paper in a limited sense, as descriptive of the dual nature of the experiments, and not in the sense in which it is generally used, as the title of a separate art, in which the medium of sound is replaced by mobile colour. Such an art is far more nearly allied to painting than to music.
COVID-19 Contact Tracing in an Overseas U.S. Military Population
Authors: Sikorski Cynthia S , Scheel Misty D , Harris Stephanie M , Nefczyk Julia A
Published: April 2021

The purpose of this study was to describe the early epidemiology and contact tracing challenges for Covid-19 infection in an overseas military and DoD population.

From February 28, 2020 to April 27, 2020, patients who were diagnosed with Covid-19 infection completed a Centers for Disease Control Persons Under Investigation (PUI) form during their encounter with a medical provider. Positive results were forwarded to the Public Health Department. The results of the contact tracing and PUI form were entered into a database and analyzed.

Eight Covid-19 cases were diagnosed in this overseas population. Based on beneficiary population, the cumulative incidence was ∼80/100,000 persons. The age distribution ranged from 25 to 60 years, median 36 years. Most patients were male (75%). More infection occurred in those living off base in the community (87.5%). With the capability of on-site testing at the hospital, the median duration from symptom onset to diagnosis improved from 5 days to 1 day.

Disease contact tracing for DoD populations presents unique considerations in an overseas location. Public Health guidelines for the USA may have varying relevance in an overseas location. Rapid case identification with on-site testing is critical to disrupt disease transmission. Preventive measures for Covid-19 infection have decreased incidence of influenza-like illness.
Learning Fundamentals of Laparoscopic Surgery Manual Skills: An Institutional Experience With Remote Coaching and Assessment
Authors: Miles Shana , Donnellan Nicole
Published: April 2021

Introduction

COVID-19 has altered the landscape of traditional surgical education. This is a pilot study of remote coaching and assessment of Fundamentals of Laparoscopic Surgery (FLS) manual skills in obstetrics and gynecology residents.

Materials and Methods

PGY-3 obstetrics and gynecology residents participated in remote assessment of FLS manual skills using a live streaming platform. Learners who showed deficiencies in proficiency participated in live-streamed coaching sessions. The coaching sessions continued until the learner and coach mutually agreed that the learner was prepared for the skills portion of the FLS certification exam. The primary outcome was learner performance on skills assessment with external validation through the FLS manual skills exam pass rate.

Results

One learner demonstrated proficiency at baseline and the remaining nine underwent remote coaching sessions. Learners received a mean of two coaching sessions to reach mutually agreed readiness for the FLS exam as per learner and coach. All residents performed significantly better at the conclusion of the remote coaching series (11.3 ± 0.82) as compared to their baseline scores (8.8 ± 2.82) (P < .03; 95% CI, 0.31-4.69). Proficiency was externally validated through the FLS exam taken by each resident 1-2 weeks following their final assessment, with all learners passing the manual portion. The average satisfaction of learners with remote coaching was 77/100 (range 50-100). 100% of learners felt prepared for their FLS certification exam and 100% would recommend this remote training program to a colleague.

Conclusion

Remote coaching and assessment of FLS skills yields similar results to traditional face-to-face instruction.
Vulture Genomes Reveal Molecular Adaptations Underlying Obligate Scavenging and Low Levels of Genetic Diversity
Authors: Zou Dahu , Tian Shilin , Zhang Tongzuo , Zhuoma Nima , Wu Guosheng , Wang Muyang , Dong Lu , Rossiter Stephen J , Zhao Huabin
Published: April 2021

Obligate scavenging on the dead and decaying animal matter is a rare dietary specialization that in extant vertebrates is restricted to vultures. These birds perform essential ecological services, yet many vulture species have undergone recent steep population declines and are now endangered. To test for molecular adaptations underlying obligate scavenging in vultures, and to assess whether genomic features might have contributed to their population declines, we generated high-quality genomes of the Himalayan and bearded vultures, representing both independent origins of scavenging within the Accipitridae, alongside a sister taxon, the upland buzzard. By comparing our data to published sequences from other birds, we show that the evolution of obligate scavenging in vultures has been accompanied by widespread positive selection acting on genes underlying gastric acid production, and immunity. Moreover, we find evidence of parallel molecular evolution, with amino acid replacements shared among divergent lineages of these scavengers. Our genome-wide screens also reveal that both the Himalayan and bearded vultures exhibit low levels of genetic diversity, equating to around a half of the mean genetic diversity of other bird genomes examined. However, demographic reconstructions indicate that population declines began at around the Last Glacial Maximum, predating the well-documented dramatic declines of the past three decades. Taken together, our genomic analyses imply that vultures harbor unique adaptations for processing carrion, but that modern populations are genetically depauperate and thus especially vulnerable to further genetic erosion through anthropogenic activities.
The DNA binding domain of theVibrio vulnificusSmcR transcription factor is flexible and binds diverse DNA sequences
Authors: Newman Jane D , Russell Meghan M , Fan Lixin , Wang Yun-Xing , Gonzalez-Gutierrez Giovanni , van Kessel Julia C
Published: April 2021

Quorum sensing gene expression in vibrios is regulated by the LuxR/HapR family of transcriptional factors, which includes Vibrio vulnificus SmcR. The consensus binding site of Vibrio LuxR/HapR/SmcR proteins is palindromic but highly degenerate with sequence variations at each promoter. To examine the mechanism by which SmcR recognizes diverse DNA sites, we generated SmcR separation-of-function mutants that either repress or activate transcription but not both. SmcR N55I is restricted in recognition of single base-pair variations in DNA binding site sequences and thus is defective at transcription activation but retains interaction with RNA polymerase (RNAP) alpha. SmcR S76A, L139R and N142D substitutions disrupt the interaction with RNAP alpha but retain functional DNA binding activity. X-ray crystallography and small angle X-ray scattering data show that the SmcR DNA binding domain exists in two conformations (wide and narrow), and the protein complex forms a mixture of dimers and tetramers in solution. The three RNAP interaction-deficient variants also have two DNA binding domain conformations, whereas SmcR N55I exhibits only the wide conformation. These data support a model in which two mechanisms drive SmcR transcriptional activation: interaction with RNAP and a multi-conformational DNA binding domain that permits recognition of variable DNA sites.
Impact of Education and Data Feedback on Guideline-Concordant Prescribing for Urinary Tract Infections in the Outpatient Setting
Authors: Funaro Jason R , Moehring Rebekah W , Liu Beiyu , Lee Hui-Jie , Yang Siyun , Sarubbi Christina B , Anderson Deverick J , Wrenn Rebekah H
Published: April 2021

Background

Urinary tract infections (UTIs) are the most common outpatient indication for antibiotics and an important target for antimicrobial stewardship (AS) activities. With The Joint Commission standards now requiring outpatient AS, data supporting effective strategies are needed.

Methods

We conducted a 2-phase, prospective, quasi-experimental study to estimate the effect of an outpatient AS intervention on guideline-concordant antibiotic prescribing in a primary care (PC) clinic and an urgent care (UC) clinic between August 2017 and July 2019. Phase 1 of the intervention included the development of clinic-specific antibiograms and UTI diagnosis and treatment guidelines, presented during educational sessions with clinic providers. Phase 2, consisting of routine clinic- and provider-specific feedback, began ~12 months after the initial education. The primary outcome was percentage of encounters with first- or second-line antibiotics prescribed according to clinic-specific guidelines and was assessed using an interrupted time series approach.

Results

Data were collected on 4724 distinct patients seen during 6318 UTI encounters. The percentage of guideline-concordant prescribing increased by 22% (95% CI, 12% to 32%) after Phase 1 education, but decreased by 0.5% every 2 weeks afterwards (95% CI, –0.9% to 0%). Following routine data feedback in Phase 2, guideline concordance stabilized, and significant further decline was not seen (–0.6%; 95% CI, –1.6% to 0.4%). This shift in prescribing patterns resulted in a 52% decrease in fluoroquinolone use.

Conclusions

Clinicians increased guideline-concordant prescribing, reduced UTI diagnoses, and limited use of high-collateral damage agents following this outpatient AS intervention. Routine data feedback was effective to maintain the response to the initial education.
An unusual case of chronic abdominal pain: an association between Celiac disease and Crohn’s disease
Authors: Doya Leen Jamel , Naamah Maria , Karkamaz Noura , Hajo Narmin , Bijow Fareeda Wasfy , Ibrahim Ali , Issa Rana
Published: April 2021

Inflammatory bowel diseases (IBD) and Celiac disease (CeD) are immune-mediated gastrointestinal diseases with incompletely understood etiology. Both diseases show a multifactorial origin with a complex interplay between genetic, environmental factors, and some components of the commensal microbiota. The coexistence of celiac disease with Crohn’s disease is rarely reported in the literature. Here, we report a case of a 13-year-old Syrian male who presented with a history of abdominal pain, anorexia and pallor. CeD and Crohn’s disease was documented on gastrointestinal endoscopy and histological study. The patient was treated with a gluten-free, low fiber, high caloric diet, and a course of oral corticosteroids with an improvement in growth rate and abdominal pain.
Leydig cell hypoplasia type 1 diagnosed in early childhood with inactivating mutation in LHCGR gene
Authors: Çömlek Fatma Özgüç , Yıldız Raif , Seyrek Fatma , Tütüncüler Filiz
Published: April 2021

Leydig cell aplasia/hypoplasia is an autosomal recessive condition. In its complete form, these patients are 46XY but are cryptorchid and phenotypically female. Most cases reported in literature presented with in adolescence with pubertal delay. We reported a case with a predefined mutation in the LHCGR gene, presenting with swelling in the inguinal region and therefore diagnosed in early childhood. We wanted to emphasize the necessity of keeping Leydig cell hypoplasia in mind in the differential diagnosis of sexual development disorders in early childhood.
Effects of Antenatal Magnesium Sulfate on the Gut Function of Preterm (<32 weeks) Very Low Birth Weight Neonates: Experience from a Tertiary Institute in South India
Authors: Chandran Shanu , Tergestina Mintoo , Ross Benjamin , Joshi Avadhesh , Rebekah Grace , Kumar Manish
Published: April 2021

Objective

Antenatal magnesium sulfate (MgSO4) is found to have various adverse effects in newborn, but the effect on preterm gut is still unclear. This study aimed to evaluate the effects of antenatal MgSO4 on preterm gut function by assessing the clinical outcomes and mesenteric blood flow.

Methods

This was a prospective cohort study on all preterm very low birth weight (VLBW) neonates born at a tertiary care center in South India from November 2016 to August 2017. Neonates with antenatal magnesium (Mg) exposure were compared with those with no exposure for various neonatal outcome variables like time to reach full feeds, feed intolerance, necrotizing enterocolitis (NEC) and other preterm complications, serial serum Mg levels and superior mesenteric artery (SMA) Doppler velocity measurements at two time points (24–48 h and 4–5 days after birth).

Results

Out of 84 neonates, 56 neonates were exposed to antenatal Mg with a median cumulative maternal dose of 28 g and the rest 28 neonates had no exposure. The mean time to reach full feeds was the same in both groups (10.5 days). Feed intolerance episodes were similar in the first week of life between the exposed and unexposed groups (48.2% vs. 46.4%; p = 0.88). Univariate analysis revealed no difference between groups concerning rates of NEC (p = 0.17) or mortality (p = 0.39). There was no significant difference in SMA Doppler parameters and hypermagnesemia between the two groups.

Conclusion

Our study found no significant impact on postnatal feed tolerance and mesenteric blood flow among preterm VLBW neonates with antenatal MgSO4 exposure.
The Influence of Lower Temperature Induction of Valsa mali on the Infection of Apple Trees
Authors: Meng Xiang-long , Yang Rui , Liu An-tai , Hu Tong-le , Wang Ya-nan , Cao Ke-qiang , Wang Shu-tong
Published: April 2021

Apple valsa canker (AVC), caused by Valsa mali, is one of the most important diseases of apple trees in China. AVC occurred severely along with cold winter or cold spring. However, the effect of lower temperature on V. mali is poorly understood. This study evaluated the influence of lower temperature pretreatment of V. mali on the infection of apple twigs and leaves. The results showed that exposing V. mali to lower temperatures (between –10°C and 10°C) for more than 18 h significantly increased the disease severity of apple leaves and twigs, with a higher lesion area ratio (LAR), lesion length, and disease incidence (DI) than that at 25°C. In addition, cold treatment ranging from –5°C to 10°C promoted colony growth. Meanwhile, the relative expression of four cell wall degrading enzyme (CWDE)-related genes pretreated at –5°C and 5°C were significantly higher than that at 25°C. The results indicated that the virulence of V. mali mycelium is sensitive to lower temperatures. After sensing lower temperature changes, V. mali can adjust its infection of apple trees by regulating the expression of pathogenicity gene and growth rate. Spring has very frequent temperature changes, and V. mali is highly invasive in this season. Therefore, more attention should be paid in spring to protecting apple trees from infection of V. mali, by reducing pruning wound formation in spring and applying protective agents to pruning wounds in time.
Legacy Patient-reported Outcome Measures Can Be Reliably Translated to PROMIS Domains for Use in Adolescent Spinal Deformity
Authors: Yau Annie , Heath Madison R. , Nguyen Joseph T. , Fabricant Peter D.
Published: April 2021

Study Design.

Retrospective cohort study.

Objective.

The aim of this study was to determine whether Patient-reported Outcomes Measurement Information System (PROMIS) Pediatric Domain scores can be accurately and reliably predicted from legacy patient-reported outcome measures (PROMs) for use in adolescent idiopathic scoliosis.

Summary of Background Data.

Previous efforts have been made to develop translational models between PROMIS domains and legacy PROMs in adult spinal deformity, but translational models for pediatric and adolescent patients with spinal deformity have not yet been developed.

Methods.

Scores were retrospectively collected on pediatric patients 8–17 years old who were diagnosed with spinal asymmetry or scoliosis for the following PROMs: Scoliosis Research Society-22r (SRS-22r), Trunk Appearance Perception Scale (TAPS), Hospital for Special Surgery Functional Activity Brief Scale (HSS Pedi-FABS), and PROMIS Pediatric Domains: Pain Interference, Mobility, Physical Stress Experiences, Psychological Stress Experiences, and Physical Activity. Pearson correlations were calculated between legacy and PROMIS scores. In the derivation cohort, PROMIS domains were modeled from SRS-22r or HSS Pedi-FABS using linear regression. These equations were used to predict PROMIS scores in the test cohort to determine the reliability of the translation model.

Results.

A total of 1171 patients (68% female) with a mean age of 13.4 ± 2.3 years were included in the final analyses. PROMIS Pain Interference was dependent on SRS-22r domains Pain, Function, Mental Health, and Management Satisfaction, PROMIS Mobility was dependent on SRS-22r Pain, Function, Mental Health, and Self-Image, PROMIS Physical Stress Experiences and Psychological Stress Experiences were dependent on SRS-22r Pain, Mental Health, and Management Satisfaction, and PROMIS Physical Activity was dependent on HSS Pedi-FABS. (P < 0.05 for all). In the test cohort, all developed models for PROMIS domains demonstrated strong correlations between estimated and actual scores (r = 0.63–0.75).

Conclusion.

All of the evaluated PROMIS domains (Pain Interference, Mobility, Physical Stress Experiences, Psychological Stress Experiences, Physical Activity) were reliably translated directly from these legacy scores for pediatric and adolescent patients with spinal deformity.

Level of Evidence: 3
Minimally Invasive Surgery for Neuromuscular Scoliosis: Results and Complications at a Minimal Follow-up of 5 Years
Authors: Gaume Mathilde , Vergari Claudio , Khouri Nejib , Skalli Wafa , Glorion Christophe , Miladi Lotfi
Published: April 2021

Study Design.

A prospective study.

Objective.

The aim of this study was to report the results of an alternative technique to growing rods (GR) for neuromuscular scoliosis using a minimally invasive fusionless surgery with a minimum of 5 years’ follow-up.

Summary of Background Data.

Conservative treatment is not effective in progressive neuromuscular scoliosis. Early surgery using GR is increasingly advocated to control the deformity while preserving spinal and thoracic growth before arthrodesis. These techniques still provide a high rate of complications.

Methods.

The technique relies on a bilateral double rod sliding instrumentation anchored proximally by four hooks claws and distally to the pelvis by iliosacral screws through a minimally invasive approach. The clinical and radiological outcomes of 100 consecutive patients with neuromuscular scoliosis who underwent this fusionless surgery with a minimum follow-up of 5 years were reviewed.

Results.

6.5 ± 0.7 years after initial surgery, six patients were lost of follow-up and 11 died of unrelated raison. Of the 83 remaining patients at latest follow-up, mean Cobb angle was stable to 35.0° which correspond to 61% correction of the initial deformation. Mean pelvic obliquity was 29.6° (0.3°–80.0°) preoperatively and 7.2 (0.2°–23.5°) at latest follow-up. Correction of the hyper kyphosis remained stable. Skeletal maturity

was reached in 42 of 83 patients (50.6%). None of these patients has required spinal fusion. The global complication rate was 31.3%.

Conclusion.

The outcomes of this minimally invasive fusionless technique at 5 years follow-up showed a stable correction of spinal deformities and pelvic obliquity over time, with a reduced rate of complication. The arthrodesis was not required for all patients at skeletal maturity. This technique could be a good alternative to arthrodesis for neuromuscular scoliosis.

Level of Evidence: 3
Adolescents Treated for Attention-Deficit/Hyperactivity Disorder in Pediatric Primary Care: Characterizing Risk for Stimulant Diversion
Authors: Molina Brooke S. G. , Joseph Heather M. , Kipp Heidi L. , Lindstrom Rachel A. , Pedersen Sarah L. , Kolko David J. , Bauer Daniel J. , Subramaniam Geetha A.
Published: April 2021

Objective:

To describe the clinical and psychosocial characteristics, and their hypothesized interrelations, as it pertains to risk for stimulant diversion (sharing, selling, or trading) for adolescents in pediatric primary care treatment for attention-deficit/hyperactivity disorder.

Methods:

Baseline data for 341 adolescents in a cluster-randomized controlled trial of stimulant diversion prevention in pediatric primary care (NCT_03080259) were used to (1) characterize diversion and newly measured risk factors, (2) examine their associations with age and sex, and (3) test whether associations among risk factors were consistent with model-implied predictions. Data were collected through multi-informant electronic surveys from adolescents and parents.

Results:

Diversion was rare (1%) in this sample (Mage = 15, SD = 1.5, 74% male participants). Older age was associated with being approached to divert (r = 0.25, p < 0.001) and higher risk on variables pertinent to stimulant treatment, such as treatment disclosure (r = 0.12, p < 0.05), tolerance for stimulant misuse and diversion (r = 0.17, p < 0.05), and peer norms favorable to stimulant misuse and diversion (r values = 0.15–0.34, p < 0.001). Sex differences were minimal. Variables from our conceptual model and specific to stimulants (e.g., perceived likelihood of negative consequences from diversion and schoolmate stimulant misuse/diversion) were related in multivariable regressions to hypothesized immediate precursors of diversion (e.g., diversion intentions).

Conclusion:

Although diversion was rare for these primary care–treated adolescents, risk levels appear to be higher for older adolescents. Prevention may be most effective by capitalizing on current psychosocial strengths and discussing stimulant-specific attitudes, behaviors, and social norms before vulnerability to diversion increases in the final years of high school and into college.
Longitudinal Associations Between Parenting Practices and Youth Sleep Problems
Authors: Acosta Juliana , Parent Justin , DiMarzio Karissa , McMakin Dana L. , McKee Laura G. , Dale Chelsea F.
Published: April 2021

Objective:

Sleep problems among youth are highly prevalent and associated with adjustment difficulties. When considering influences on youth's sleep, bidirectional links between youth's sleep health and family functioning have been suggested. Parenting practices are among the many familial factors that could be transactionally related to poor sleep in youth; however, research is lacking on potential longitudinal associations between parenting practices and sleep problems in youth. In addition, sensitive periods for this link are mostly unknown. The current study examined longitudinal relations between constellations of parenting practices and youth sleep health to identify profiles of parenting practices that are predictive of sleep problems in youth across different developmental stages.

Method:

Participants were 292 parents (M = 36.51, SD = 7.3) of children between the ages of 3 and 14 years (M = 8.4, SD = 3.6). A person-centered approach was used to create profiles across traditionally labeled positive and negative parenting practices, as well as supportive and unsupportive parental emotion socialization strategies. Parenting profiles were then examined as longitudinal predictors of youth sleep problems.

Results:

Findings revealed 3 distinct parenting profiles, which were differentially associated with sleep problems in youth, with the first profile predicting the lowest levels of sleep problems and the third profile predicting the highest levels of sleep problems, particularly among peripubertal youth.

Conclusion:

This study extends previous findings by elucidating distinct constellations of parenting practices that are differentially predictive of youth sleep problems and highlighting parenting among the various family processes that can longitudinally contribute to youth's sleep health.
Severe Inflammation, Acute Kidney Injury, and Drug–Drug Interaction: Triple Penalty for Prolonged Elimination of Apixaban in Patients With Coronavirus Disease 2019: A Grand Round
Authors: Launay Manon , Demartin Anne-Laure , Ragey Sophie Perinel , Mismetti Patrick , Botelho-Nevers Elisabeth , Delavenne Xavier
Published: April 2021

In this article, we present a case of apixaban elimination prolonged by 450% in a patient with coronavirus disease 2019 because of multiple conditions, including drug–drug interaction, severe inflammation, and acute kidney injury. Therapeutic drug monitoring was used to explain unusual routine coagulation assays. This grand round highlights the importance of dialog between the clinician and a therapeutic drug monitoring consultant for optimal patient care.