bluuebunny/crossref_metadata_2025 huggingface dataset:
HMGN3 represses transcription of epithelial regulators to promote migration of cholangiocarcinoma in a SNAI2‐dependent manner
Authors: Sorin Supannika , Kubota Sho , Hamidi Sofiane , Yokomizo‐Nakano Takako , Vaeteewoottacharn Kulthida , Wongkham Sopit , Waraasawapati Sakda , Pairojkul Chawalit , Bai Jie , Morii Mariko , Sheng Guojun , Sawanyawisuth Kanlayanee , Sashida Goro
Published: May 2022

High mobility group nucleosome‐binding protein 3 (HMGN3), a member of the HMGN family, modulates the structure of chromatin and regulates transcription through transcription factors. HMGN3 has been implicated in the development of various cancers; however, the underlying mechanisms remain unclear. We herein demonstrated that the high expression of HMGN3 correlated with the metastasis of liver fluke infection‐induced cholangiocarcinoma (CCA) in patients in northeastern Thailand. The knockdown of HMGN3 in CCA cells significantly impaired the oncogenic properties of colony formation, migration, and invasion. HMGN3 inhibited the expression of and blocked the intracellular polarities of epithelial regulator genes, such as the CDH1/E‐cadherin and TJAP1 genes in CCA cells. A chromatin immunoprecipitation sequencing analysis revealed that HMGN3 required the transcription factor SNAI2 to bind to and repress the expression of epithelial regulator genes, at least in part, due to histone deacetylases (HDACs), the pharmacological inhibition of which reactivated these epithelial regulators in CCA, leading to impairing the cell migration capacity. Therefore, the overexpression of HMGN3 represses the transcription of and blocks the polarities of epithelial regulators in CCA cells in a manner that is dependent on the SNAI2 gene and HDACs.
Immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies, in a patient with melanoma treated with BRAF/MEK inhibitors
Authors: Rodríguez Castells Marta , Galisteo Lencastre Veiga Carlos , Fernández-Morales Luis Antonio , Ejarque Martínez Clara , Soriano Sánchez Sandra , López Zurita Natalia , Climent Vicente Carla , Andreu Cobo Pablo , Sierra Boadas Marina , García García Yolanda , Seguí Palmer Miquel Àngel
Published: May 2022

The effect of serine/threonine-protein kinase B-Raf/mitogen-activated protein kinase (BRAF/MEK) inhibitors on the immune system is not clearly described, but rare cases of autoimmune phenomena have been reported. The clinical case we present below is the first report of a necrotizing myopathy related to dabrafenib/trametinib treatment. A 48-year-old man started dabrafenib/trametinib for stage IV BRAF-V600E mutated cutaneous melanoma. After the first month, he presented with grade 3 pyrexia (Common Terminology Criteria for Adverse Events [CTCAE] v.5.0.) and increased creatinine-kinase levels. A diagnosis of immune-mediated necrotizing myopathy, antisignal recognition particle (anit-SRP) positive, was made. At disease progression, dabrafenib/trametinib was restarted, triggering a new episode of grade 2 pyrexia and myositis. Treatment was changed to encorafenib/binimetinib without repeating pyrexia or limiting creatinine-kinase elevation, presenting even a loss of anti-SRP antibodies. Given the temporal relationship, the fact that re-exposition induced a new worsening of the myopathy and the loss of the anti-SRP antibodies after changing treatment, we infer that there possibly is a clear relationship between dabrafenib/trametinib treatment and the myopathy.
BMI and miscarriage after IVF
Authors: Bellver José
Published: May 2022

Purpose of review

To summarize recent findings related to the risk of miscarriage in women with elevated BMI undergoing IVF, and the mechanisms involved in said risk.

Recent findings

Miscarriage rates are increased in overweight and obese women in both natural and assisted reproduction. Oocyte and embryo quality assessed according to classic morphological static parameters does not seem to be affected by excessive female body weight. Despite the initial lack of consensus between studies regarding embryo morphokinetics in obese women, blastocyst formation and quality have recently been shown to be similar across BMI groups, even in the case of euploid embryos. However, some metabolomic differences have been described in oocytes and embryos from obese women, thus pointing to a functional alteration. In women with elevated BMI, the percentage of aneuploid embryos is similar to that of normal weight women, and rates of miscarriage are higher, despite the transfer of euploid embryos. Therefore, the origin of the increased pregnancy loss rate after IVF in these women may be related to metabolomic, epigenetic or mitochondrial oocyte and embryo disturbances, or to the abnormal endocrine, metabolic and inflammatory uterine environment induced by obesity, which seems to be also responsible for other numerous complications during pregnancy and the in-utero fetal programming of postnatal diseases. A displacement of the window of implantation in obese women undergoing artificial endometrial preparation has recently been described and may be related to the poorer embryo implantation rates and increased risk of miscarriage observed following fresh and frozen embryo transfers with autologous oocytes, and with donated ova in recipients with extremely high BMI.

Female obesity is related to poorer outcome in natural and assisted conception, including an increased risk of miscarriage. Embryo morphology, assessed by conventional methods or by morphokinetics, does not seem to be affected by excess weight, with similar blastocyst formation and quality than normal weight women reported in IVF cycles. Embryo aneuploidy is not increased, and higher miscarriages rates are seen after euploid embryo transfer in obese women. Disturbances of the uterus or its environment induced by female obesity seem to be the most likely cause of the increased risk of miscarriage, although metabolomic, epigenetic or mitochondrial oocyte and embryo dysfunction cannot be ruled out as cannot congenital anomalies. In the context of all the above, weight reduction before pregnancy should be advised in obese women trying to become pregnant.
Racial disparities in access to reproductive health and fertility care in the United States
Authors: Beroukhim Gabriela , Mahabamunuge Jasmin , Pal Lubna
Published: May 2022

Purpose of review

To examine the status of racial and ethnic inequalities in fertility care in the United States (U.S.) at inception of 2022. This review highlights addressable underpinnings for the prevalent differentials in access to and utilization of infertility treatments and underscores gaps in preventive care as key contributors to racial and ethnic disparities in risk burden for subfertility and infertility.

Recent findings

Significant gaps in access to and utilization of fertility care are consistently reported among racial and ethnic minorities, particularly Black and Hispanic women. Access to and utilization of contraceptives, human papilloma virus vaccination rates, preexposure prophylaxis use, and differentials in treatment of common gynecologic disorders are relevant to the prevalent racial and ethnic disparities in reproductive health. The spectrum of differential in reproductive wellness and the magnitude of reproductive health burden afflicting racial minorities in the U.S. raise concerns regarding systemic and structural racism as plausible contributors to the prevalent state of affairs.

Despite efforts to reform unequal reproductive health practices and policies, racial and ethnic disparities in fertility care are pervasive and persistent. In addition to measures aimed at reducing barriers to care, societal efforts must prioritize health disparity research to systematically examine underpinnings, and addressing structural racism and interpersonal biases, to correct the prevalent racial inequities and mitigate disparities.
The true incidence of recurrent implantation failure
Authors: Macklon Nick S.
Published: May 2022

Purpose of review

To review the merits and limitations of current definitions of recurrent implantation failure (RIF), how they translate into estimates of incidence and to summarize how emerging concepts of individualizing the recognition of this condition can assist in changing the way RIF is identified, studied and managed.

Recent findings

The notion of a one size fits all definition of RIF is seen to be of limited clinical value, as the individual risk of repeated IVF failure has many determinants and causes. Novel approaches provide a means of identifying ‘actionable’ RIF in individual patients.

Uncertainties as to what constitutes, causes and defines RIF have served to limit progress in its management. A new approach promises to permit progress from the current impasse.
Evaluation of endometrial receptivity and implantation failure
Authors: Bui Anthony H. , Timmons Douglas B. , Young Steven L.
Published: May 2022

Purpose of review

To succinctly review the basic mechanisms of implantation and luteal phase endometrial differentiation, the etiologies of impaired endometrial function and receptivity, and the current methods that exist to evaluate and treat impaired endometrial receptivity.

Recent findings

Human embryo implantation requires bidirectional communication between blastocyst and a receptive endometrium. Etiologies of impaired endometrial receptivity are varied. Some of these include delayed endometrial maturation, structural abnormalities, inflammation, and progesterone resistance. Current methods to evaluate endometrial receptivity include ultrasonography, hysteroscopy, and endometrial biopsy. Treatments are limited, but include operative hysteroscopy, treatment of endometriosis, and personalized timing of embryo transfer.

Although some mechanisms of impaired endometrial receptivity are well understood, treatment options remain limited. Future efforts should be directed towards developing interventions targeted towards the known mediators of impaired endometrial receptivity.
Neurological disorders and small bowel dysmotility
Authors: Kamperidis Nikolaos , Nightingale Jeremy
Published: May 2022

Purpose of review

Small bowel dysmotility is common in the context of neurological disorders. Overlooking it can have an adverse impact on patient's quality of life and neurological outcomes. This review focuses on describing the mechanisms and effects of enteric dysmotility in neurological patients and providing treatment options.

Recent findings

Small bowel dysmotility is prevalent among neurological patients. The definition and diagnosis of small bowel dysmotility is a challenge; however, up to two-thirds of neurological patients may experience associated symptoms. Small bowel dysmotility can affect the absorption of nutrients and medication, impacts on social and professional function and can result in malnutrition and its associated morbidity and mortality.

Small bowel dysmotility due to a neuropathy can result from acute or chronic disorders in the central and peripheral nervous system and includes the cerebral cortex, brain stem, spinal cord, parasympathetic (vagus) and sympathetic nerves and the myenteric and submucosal plexuses of the intestine. Generalized muscle disorders can also cause an enteral myopathy. Generally, the disorders may be degenerative or inflammatory. Both enteric neuropathy and myopathy may cause symptoms of abdominal pain, nausea/vomiting, bloating, constipation or diarrhoea and can cause malnutrition. The symptoms need to be addressed in order of importance to the patient and malnutrition prevented or treated.
A training and implementation model for head and neck oncology service delivery in Mozambique
Authors: Chulam Thiago C. , Bambo Arquimedes Wamarremula Pedro , Machava Pedro Rafael , Kowalski Luiz P.
Published: May 2022

Purpose of review

There is an extreme shortage of head and neck surgeons in Africa. In Mozambique prior to 2000, there were no surgeons with specific training in head and neck surgical oncology. Here, we introduce a training model and report our experience with implementation following the training of the first two head and neck surgeons from Mozambique.

Recent findings

This training program, undertaken in Brazil, facilitated the formation of the first two head and neck surgeons from Mozambique. These surgeons received comprehensive training in head and neck surgical oncology and multidisciplinary care, allowing them to then treat their patients under continuous online mentorship collaboration. This model is expected to help in the local formation of new specialists and in the establishment of this specialty in Mozambique.

The program started with remote training and support provided by the MD Anderson Cancer Center, in Texas, USA, as part of the Extension for Community Healthcare Outcomes program. Further training was then undertaken at an established fellowship program in Brazil as a focal point for 2 years, and the knowledge gained was replicated and disseminated locally.
Pediatric platelet transfusions in critical illness: a narrative review of recent studies
Authors: Atchison Christie , Mahmood Hera , Nellis Marianne E.
Published: May 2022

Purpose of review

We sought to describe the current use of platelet transfusions, harms associated with platelet transfusion, new methods of platelet processing that attempt to address these harms, and recent platelet transfusion guidance specific to critically ill children.

Recent findings

Platelet transfusions have been associated with significant morbidity and mortality. New processing techniques, such as pathogen reduction, have been developed to combat infectious risks but in a recent trial of platelet transfusion thresholds in neonates, transfusing platelets more liberally was associated with increased bleeding and mortality.

Recent efforts to develop evidence-based guidelines for platelet transfusion in critically ill children were limited by the lack of evidence. However, given the significant risks, restrictive transfusion thresholds should be considered.
Bivalirudin in pediatric extracorporeal membrane oxygenation
Authors: Ryerson Lindsay M. , McMichael Ali B.V.
Published: May 2022

Purpose of review

This review summarizes the current literature surrounding the use of bivalirudin as an alternative anticoagulant for pediatric extracorporeal membrane oxygenation (ECMO) patients.

Recent findings

Recent single center studies describe that bivalirudin may be associated with decreased blood product transfusion, decreased cost and similar clinical outcomes for pediatric ECMO patients who have failed unfractionated heparin (UFH) anticoagulation. aPTT is the most common test to monitor bivalirudin but has several limitations. Other tests including dilute thrombin time (dTT) and viscoelastic assays are promising but more study is needed. Current evidence suggests that bivalirudin is a well tolerated and effective alternative anticoagulant for pediatric ECMO patients who have failed UFH anticoagulation but prospective studies are needed to confirm these results.

Bivalirudin is a promising alternative anticoagulant for pediatric ECMO patients who have failed UFH. Large prospective, multicenter studies are needed to confirm safety and efficacy.
Cross-cultural adaptation and validation of the Athlete Fear Avoidance Questionnaire in Italian university athletes with musculoskeletal injuries
Authors: Monticone Marco , Dover Geoffrey , Massidda Myosotis , Giordano Andrea , Franchignoni Franco
Published: May 2022

The aim of this study was to translate, culturally adapt and validate an Italian version of the Athlete Fear Avoidance Questionnaire (AFAQ-I). We conducted a cross-sectional evaluation of the psychometric properties of the AFAQ-I in university athletes with musculoskeletal injuries, culturally adapting it in accordance with international standards. Psychometric evaluation included the assessment of structural validity (exploratory factor analysis), internal consistency (Cronbach’s alpha and inter-item correlation), test-retest reliability [intraclass correlation coefficient, (ICC) (2,1)], measurement error and minimum detectable change (MDC). To examine construct validity, we compared (Spearman ρ) the AFAQ-I with a numerical pain rating scale (NPRS), the Pain Catastrophizing Scale (PCS) and the Fear Avoidance Beliefs Questionnaire (FABQ) subscales [FABQ-Physical Activity (FABQ-PA) and FABQ-Work (FABQ-W)]. The AFAQ-I was administered to 133 university athletes with musculoskeletal injuries (95 males and 38 females; mean age 25 years, SD 5; mean average pain duration 5.6 months, SD 8.7). Factor analysis revealed an acceptable 1-factor 10-item solution (explained common variance at minimum rank factor analysis: 0.74) although a couple of items (#6 and 9) presented low factor loadings, suggesting the presence of a small secondary dimension. Cronbach’s alpha was 0.78 and the average inter-item correlation was 0.27. ICC (2,1) was 0.95 and the MDC was 4.4 points. As hypothesized a priori, the AFAQ-I moderately correlated with NPRS (ρ = 0.42), PCS (ρ = 0.59), FABQ-PA (ρ = 0.40) and FABQ-W (ρ = 0.34). In conclusion, the AFAQ-I is a valid Italian translation of AFAQ that demonstrates acceptable psychometric properties. However, we recommend further analysis of the construct definition of the AFAQ and additional examination of its structural validity.
Genetic basis of speciation and adaptation: from loci to causative mutations
Authors: Kitano Jun , Ishikawa Asano , Ravinet Mark , Courtier-Orgogozo Virginie
Published: May 2022

Does evolution proceed in small steps or large leaps? How repeatable is evolution? How constrained is the evolutionary process? Answering these long-standing questions in evolutionary biology is indispensable for both understanding how extant biodiversity has evolved and predicting how organisms and ecosystems will respond to changing environments in the future. Understanding the genetic basis of phenotypic diversification and speciation in natural populations is key to properly answering these questions. The leap forward in genome sequencing technologies has made it increasingly easier to not only investigate the genetic architecture but also identify the variant sites underlying adaptation and speciation in natural populations. Furthermore, recent advances in genome editing technologies are making it possible to investigate the functions of each candidate gene in organisms from natural populations. In this article, we discuss how these recent technological advances enable the analysis of causative genes and mutations and how such analysis can help answer long-standing evolutionary biology questions.

This article is part of the theme issue ‘Genetic basis of adaptation and speciation: from loci to causative mutations’.
The genetic basis of structural colour variation in mimetic
Heliconius
butterflies
Authors: Brien Melanie N. , Enciso-Romero Juan , Lloyd Victoria J. , Curran Emma V. , Parnell Andrew J. , Morochz Carlos , Salazar Patricio A. , Rastas Pasi , Zinn Thomas , Nadeau Nicola J.
Published: May 2022

Structural colours, produced by the reflection of light from ultrastructures, have evolved multiple times in butterflies. Unlike pigmentary colours and patterns, little is known about the genetic basis of these colours. Reflective structures on wing-scale ridges are responsible for iridescent structural colour in many butterflies, including the Müllerian mimics
Heliconius erato
and
Heliconius melpomene.
Here, we quantify aspects of scale ultrastructure variation and colour in crosses between iridescent and non-iridescent subspecies of both of these species and perform quantitative trait locus (QTL) mapping. We show that iridescent structural colour has a complex genetic basis in both species, with offspring from crosses having a wide variation in blue colour (both hue and brightness) and scale structure measurements. We detect two different genomic regions in each species that explain modest amounts of this variation, with a sex-linked QTL in
H. erato
but not
H. melpomene.
We also find differences between species in the relationships between structure and colour, overall suggesting that these species have followed different evolutionary trajectories in their evolution of structural colour. We then identify genes within the QTL intervals that are differentially expressed between subspecies and/or wing regions, revealing likely candidates for genes controlling structural colour formation.

This article is part of the theme issue ‘Genetic basis of adaptation and speciation: from loci to causative mutations’.
The selfing syndrome and beyond: diverse evolutionary consequences of mating system transitions in plants
Authors: Tsuchimatsu Takashi , Fujii Sota
Published: May 2022

The shift from outcrossing to self-fertilization (selfing) is considered one of the most prevalent evolutionary transitions in flowering plants. Selfing species tend to share similar reproductive traits in morphology and function, and such a set of traits is called the ‘selfing syndrome’. Although the genetic basis of the selfing syndrome has been of great interest to evolutionary biologists, knowledge of the causative genes or mutations was limited until recently. Thanks to advances in population genomic methodologies combined with high-throughput sequencing technologies, several studies have successfully unravelled the molecular and genetic basis for evolution of the selfing syndrome inCapsella,Arabidopsis,Solanumand other genera. Here we first introduce recent research examples that have explored the loci, genes and mutations responsible for the selfing syndrome traits, such as reductions in petal size or in pollen production, that are mainly relevant to pre-pollination processes. Second, we review the relationship between the evolution of selfing and interspecific pollen transfer, highlighting the findings of post-pollination reproductive barriers at the molecular level. We then discuss the emerging view of patterns in evolution of the selfing syndrome, such as the pervasive involvement of loss-of-function mutations and the relative importance of selection versus neutral degradation.

This article is part of the theme issue ‘Genetic basis of adaptation and speciation: from loci to causative mutations’.
Extensive simulations assess the performance of genome-wide association mapping in variousSaccharomyces cerevisiaesubpopulations
Authors: Peter Jackson , Friedrich Anne , Liti Gianni , Schacherer Joseph
Published: May 2022

With the advent of high throughput sequencing technologies, genome-wide association studies (GWAS) have become a powerful paradigm for dissecting the genetic origins of the observed phenotypic variation. We recently completely sequenced the genome of 1011Saccharomyces cerevisiaeisolates, laying a strong foundation for GWAS. To assess the feasibility and the limits of this approach, we performed extensive simulations using five selected subpopulations as well as the total set of 1011 genomes. We measured the ability to detect the causal genetic variants involved in Mendelian and more complex traits using a linear mixed model approach. The results showed that population structure is well accounted for and is not the main problem when the sample size is high enough. While the genetic determinant of a Mendelian trait is easily mapped in all studied subpopulations, discrepancies are seen between datasets when performing GWAS on a complex trait in terms of detection, false positive and false negative rate. Finally, we performed GWAS on the different defined subpopulations using a real quantitative trait (resistance to copper sulfate) and showed the feasibility of this approach. The performance of each dataset depends simultaneously on several factors such as sample size, relatedness and population evolutionary history.

This article is part of the theme issue ‘Genetic basis of adaptation and speciation: from loci to causative mutations’.
Speciation and adaptation research meets genome editing
Authors: Ansai Satoshi , Kitano Jun
Published: May 2022

Understanding the genetic basis of reproductive isolation and adaptive traits in natural populations is one of the fundamental goals in evolutionary biology. Genome editing technologies based on CRISPR-Cas systems and site-specific recombinases have enabled us to modify a targeted genomic region as desired and thus to conduct functional analyses of target loci, genes and mutations even in non-conventional model organisms. Here, we review the technical properties of genome editing techniques by classifying them into the following applications: targeted gene knock-out for investigating causative gene functions, targeted gene knock-in of marker genes for visualizing expression patterns and protein functions, precise gene replacement for identifying causative alleles and mutations, and targeted chromosomal rearrangement for investigating the functional roles of chromosomal structural variations. We describe examples of their application to demonstrate functional analysis of naturally occurring genetic variations and discuss how these technologies can be applied to speciation and adaptation research.

This article is part of the theme issue ‘Genetic basis of adaptation and speciation: from loci to causative mutations’.
JMM Profile: Avian influenza: a veterinary pathogen with zoonotic potential
Authors: Patapiou Patapios A. , Slomka Marek J. , Seekings Amanda H. , James Joe , Thomas Saumya S. , Reid Scott M. , Hansen Rowena D. E. , Lewis Nicola S. , Banyard Ashley C.
Published: May 2022

Avian influenza viruses (AIVs) are classified as either low pathogenicity (LP; generally causing sub-clinical to mild infections) or high pathogenicity (HP; capable of causing significant mortality events in birds). To date, HPAIVs appear o be restricted to the haemagglutinin (HA) glycoprotein H5 and H7 AIV subtypes. Both LPAIV and HPAIV H5 and H7 AIV subtypes are classified as the causative agents of notifiable disease in poultry. A broad range of non-H5/non-H7 LPAIVs also exist that have been associated with more severe disease outcomes in avian species. As a result, the constant threat from AIVs causes significant economic damage in poultry production systems worldwide. The close proximity between mammalian and susceptible avian species in some environments provides the opportunity for both inter-host transmission and mammalian adaptation, potentially resulting in novel AIV strains capable of infecting humans.
Clinical and microbiological investigation into mixed growth urine cultures
Authors: Folaranmi Tolulope , Harley Clare , Jolly Jim , Kirby Andrew
Published: May 2022

Introduction. Urine samples submitted for investigation of urinary tract infection (UTI) may identify more than one bacterial isolate. These samples may be reported as ‘mixed growth urine culture’ (MGUC). The clinical significance of MGUC remains controversial.

Hypothesis/Gap Statement. The impact of MGUC on patient management is not known and should be assessed.

To describe MGUC and assess its impact on patient management.

Methodology. Microbiology laboratory reports (Leeds, UK) were retrospectively analysed and urine cultures reported as MGUC from a 1 week period underwent detailed laboratory analysis. Semi-structured interviews of NHS clinicians’ response to MGUC reports were explored for emergent themes.

Results. In 2018, 12.4 % (14,323/115,664) of urine specimens processed to detect bacterial pathogens were reported as MGUC. Among a total of 200 MGUC samples identified within 1 week in 2019, detailed laboratory analysis identified 459 bacterial isolates. Enterococcus species (30.1 %) and

Escherichia coli

(27.5 %) were the most frequently isolated and the most frequent organism combination (24 %). In total, 65.5 % cultures contained two organisms and 82.5 % of all MGUC contained at least one

Enterobacterales

. Interviews found clinicians believed MGUC reports represented detection of many commensal bacteria. Clinicians indicated they were more likely to diagnose and treat a UTI when provided with urine culture reports derived from detailed microbial analysis of MGUC, including identity and antibiotic sensitivity of organisms.

Conclusions. This study highlights the potential underuse of information derived from microbiological analysis of urine samples. Interpretive commentary on reports together with education for interpretation of enhanced reports should be explored further to improve outcomes in patients with UTI.
Differences in non-linearities determine retinal cell types
Authors: Trapani Francesco , Spampinato Giulia , Yger Pierre , Marre Olivier
Published: May 2022

Classifying neurons in different types is still an open challenge. In the retina, recent works have taken advantage of the ability to record a large number of cells to classify ganglion cells into different types based on functional information. While the first attempts in this direction used the receptive field properties of each cell to classify them, more recent approaches have proposed to cluster ganglion cells directly based on their response to standard stimuli. These two approaches have not been compared directly. Here we recorded the responses of a large number of ganglion cells and compared two methods for classifying them into types, one based on the receptive field properties, and the other one using their responses to standard stimuli. We show that the stimulus-based approach allows separating more types than the receptive field-based method, leading to a better classification. This better granularity is due to the fact that the stimulus-based method takes into account not only the linear part of ganglion cell function, but also non-linearities. A careful characterization of non-linear processing is thus key to allow functional classification of sensory neurons.
Improving Interdisciplinary Teaching through a Complexity Lens
Authors: Neitzel Sarah , Zhao Yuhao , Eaton Carrie Diaz
Published: May 2022

In this article, we discuss the use of bipartite network analysis to understand and improve interdisciplinary teaching practice. We theorize mathematics and biology as part of a coevolving mutualistic ecosystem. As part of an interdisciplinary teaching initiative, we inventoried mathematics topics appearing in the marine biology classroom and their associated marine context. We then apply techniques of mutualistic bipartite networks analysis to this system to understand the use of mathematical concepts in a marine biology classroom. By analyzing the frequency and distribution of mathematics topics, we see that a variety of mathematical concepts are used across the course with most appearing only a few times. While this is an inherent trait of mutualistic coevolutionary networks, it can create a logistical challenge to supporting mathematics in the marine biology classroom. We find that marine biology topics containing the most mathematics are either close to the instructor’s research area or were introduced through externally developed educational resources. Finally, we analyze groups of topics that appear connected to each other more frequently to inform both interdisciplinary education development as well as disciplinary support. We also suggest ways to use network metrics to track interdisciplinary connections over time, helping us understand the impact of interventions on interdisciplinary teaching practice.
Ultraviolet Rate Constants of Pathogenic Bacteria: A Database of Genomic Modeling Predictions
Authors: Kowalski Wladyslaw , Bahnfleth William P. , Brais Normand , Walsh Thomas J.
Published: May 2022

A database of bacterial ultraviolet (UV) susceptibilities is developed from an empirical model that correlates genomic parameters with UV rate constants. Software is used to count and evaluate potential ultraviolet photodimers and identifying hot spots in bacterial genomes. The method counts dimers that potentially form between adjacent bases that occur at specific genomic motifs such as TT, TC, CT, & CC. Hot spots are identified where clusters of three or more consecutive pyrimidines can enhance absorption of UV photons. The model incorporates nine genomic parameters into a single variable for each species that represents its relative dimerization potential. The bacteria model is based on a curve fit of the dimerization potential to the ultraviolet rate constant data for 92 bacteria species represented by 216 data sets from published studies. There were 4 outliers excluded from the model resulting in a 98% Confidence Interval. The curve fit resulted in a Pearson correlation coefficient of 80%. All identifiable bacteria important to human health, including zoonotic bacteria, were included in the database and predictions of ultraviolet rate constants were made based on their specific genomes. This database is provided to assist healthcare personnel and researchers in the event of outbreaks of bacteria for which the ultraviolet susceptibility is untested and where it may be hazardous to assess due to virulence. Rapid sequencing of the complete genome of any emerging pathogen will now allow its ultraviolet susceptibility to be estimated with equal rapidity. Researchers are invited to challenge these predictions.

Importance

This research demonstrates the feasibility of using the complete genomes of bacteria to determine their susceptibility to ultraviolet light. Ultraviolet rate constants can now be estimated in advance of any laboratory test. The genomic methods developed herein allow for the assembly of a complete database of ultraviolet susceptibilities of pathogenic bacteria without resorting to laboratory tests. This UV rate constant information can be used to size effective ultraviolet disinfection systems for any specific bacterial pathogen when it becomes a problem.
Identification and Assessment of Systematic Measurement Error on Electrophysiological Recordings of Neural Cell Cultures
Authors: Stone Tyler , Kiehl Thomas R. , Bergeron Charles
Published: May 2022

Microelectrode arrays (MEA) hold great promise for a broad range of applications that require reliable characterization of the growth and function of neurons in culture. Widespread adoption of this platform depends on analytical methods to extract meaning from highly variable and noisy observations. In analyzing a comprehensive database of MEA recordings, we discovered that 22% of the electrodes presented systematic patterns of under- or non-detection of spike activity. Going undetected, principal components analysis (PCA) of these data reveal trends that would have lead to incorrect biological interpretations. We fully document thesedefectiveor biased electrodes, and distinguish two forms of defectiveness, via representations that aid in detecting them. We also showcase our approach for analyzing these data that permit for post-analytic review and correction. Repeating our PCA oncleaneddata, we discover a more complex interplay of biological variability. Finally, we make a case for transparency in data reporting and propose best practices for experimental and analysis phases.
Role for DNA double strand end-resection activity of RecBCD in control of aberrant chromosomal replication initiation in Escherichia coli
Authors: Goswami Sayantan , Gowrishankar Jayaraman
Published: May 2022

Replication of the circular bacterial chromosome is initiated from a locus oriC with the aid of an essential protein DnaA. One approach to identify factors acting to prevent aberrant oriC-independent replication initiation in Escherichia coli has been that to obtain mutants which survive loss of DnaA. Here we show that a ΔrecD mutation, associated with attenuation of RecBCD’s DNA double strand end-resection activity, provokes abnormal replication and rescues ΔdnaA lethality in two situations: (i) in absence of 5’-3’ single-strand DNA exonuclease RecJ, or (ii) when multiple two-ended DNA double strand breaks (DSBs) are generated either by I-SceI endonucleolytic cleavages or by radiomimetic agents phleomycin or bleomycin. One-ended DSBs in the ΔrecD mutant did not rescue ΔdnaA lethality. With two-ended DSBs in the ΔrecD strain, ΔdnaA viability was retained even after linearization of the chromosome. Data from genome-wide DNA copy number determinations in ΔdnaA-rescued cells lead us to propose a model that nuclease-mediated DNA resection activity of RecBCD is critical for prevention of a σ-mode of rolling-circle over-replication when convergent replication forks merge and fuse, as may be expected to occur during normal replication at the chromosomal terminus region or during repair of two-ended DSBs following “ends-in” replication.
SARS-CoV-2 neutralising antibody activity in a highly vaccinated population: Longitudinal serology studies in Singapore
Authors: Clapham Hannah E , Chia Wanni , Zhang Jinyan , Wang Lin-Fa , Tam Clarence C
Published: May 2022

Background

There is continuing uncertainty regarding the longevity of immunological responses to both SARS-CoV-2 natural infection and COVID-19 vaccines.

Methods

We analysed data from two serological cohorts in Singapore among residents of a COVID-19 affected migrant worker dormitory between May-July 2020, and among mRNA COVID-19 vaccine recipients between May 2021 and January 2022. We compared SARS-CoV-2 neutralising antibody levels by age group, sex, presence of pre-existing medical conditions, type of mRNA vaccine received and number of doses received. We investigated the effect of time since infection or vaccination on antibody levels in naturally infected individuals and two- and three-dose vaccinees.

Results

After two vaccine doses, neutralising antibody responses were higher in Spikevax (Moderna) recipients, females, younger individuals and those with no underlying medical conditions. However, antibody levels waned to similar levels in all groups over time. A third dose boosted these to similarly high levels in all groups. Waning was apparent among two-dose but not three-dose recipients over a period of six months. Both two and three-dose vaccine recipients showed consistently higher neutralising antibody levels compared with naturally infected individuals over the 12-week period following infection or vaccination.

Conclusions

Our findings support the broad use of booster doses to improve population protection from COVID-19. However, recent increases in transmission of new SARS-CoV-2 variants, even in the presence of high levels of neutralising antibody in a highly vaccinated population, point to vaccine breakthrough as an important mechanism for maintaining SARS-CoV-2 circulation and indicate the need for variant-specific or universal COVID-19 vaccines.

Younger individuals, females and those with no pre-existing conditions have higher neutralising antibody levels after two doses of COVID-19 mRNA vaccine. Subsequently these wane to levels seen in other groups. A booster dose promotes similarly high levels in all groups.
Single cell RNA-seq by mostly-natural sequencing by synthesis
Authors: Simmons Sean K. , Lithwick-Yanai Gila , Adiconis Xian , Oberstrass Florian , Iremadze Nika , Geiger-Schuller Kathryn , Thakore Pratiksha I. , Frangieh Chris J. , Barad Omer , Almogy Gilad , Rozenblatt-Rosen Orit , Regev Aviv , Lipson Doron , Levin Joshua Z.
Published: May 2022

Massively parallel single cell RNA-seq (scRNA-seq) for diverse applications, from cell atlases to functional screens, is increasingly limited by sequencing costs, and large-scale low-cost sequencing can open many additional applications, including patient diagnostics and drug screens. Here, we adapted and systematically benchmarked a newly developed, mostly-natural sequencing by synthesis method for scRNA-seq. We demonstrate successful application in four scRNA-seq case studies of different technical and biological types, including 5’ and 3’ scRNA-seq, human peripheral blood mononuclear cells from a single individual and in multiplex, as well as Perturb-Seq. Our data show comparable results to existing technology, including compatibility with state-of-the-art scRNA-seq libraries independent of the sequencing technology used – thus providing an enhanced cost-effective path for large scale scRNA-seq.
Lack of ITS sequence homogenization in congeneric plant species with different ploidy levels
Authors: Osuna-Mascaró Carolina , de Casas Rafael Rubio , Berbel Modesto , Gómez José M. , Perfectti Francisco
Published: May 2022

The internal transcribed spacers (ITS) exhibit concerted evolution by the fast homogenization of these sequences at the intragenomic level. However, the rate and extension of this process are unclear and might be conditioned by the number and divergence of the different ITS copies. In some cases, such as hybrid species and polyploids, ITS sequence homogenization appears incomplete, resulting in multiple haplotypes within the same organism. Here, we studied the dynamics of concerted evolution in 85 individuals of seven plant species of the genus Erysimum (Brassicaceae) with multiple ploidy levels. We estimated the rate of concerted evolution and the degree of sequence homogenization separately for ITS1 and ITS2 and whether these varied with ploidy. Our results showed incomplete sequence homogenization, especially for polyploid samples, indicating a lack of concerted evolution in these taxa. Homogenization was usually higher in ITS2 than in ITS1, suggesting that concerted evolution operates more efficiently on the former. Furthermore, the hybrid origin of several species appears to contribute to the maintenance of high haplotype diversity, regardless of the level of ploidy. These findings indicate that sequence homogenization of ITS is a dynamic and complex process that might result in varying intra- and inter-genomic diversity levels.
Genomics for reproduction in Anas platyrynchos-a novel report
Authors: Debnath Manti , Pal Aruna , Chakraborty Argha , Pal Subhomoy , Pal Abantika
Published: May 2022

Anas platyrynchos (ducks) are reared mostly for egg, which are very nutritious, that fetch better prices, however duck meat possess rich nutrient content. They possess the unique characteristics of disease resistance to the common avian diseases, even asymptomatic to avian influenza, with a scopeto evolve as one of the best poultry species The major limitation encountered is the lowered average egg production as well as higher age at first egg (an indicator for sexual maturity) for the indigenous ducks compared to that of exotic ones. In this current study, we attempt to explore the genes responsible for duck reproduction in terms of sexual maturity,egg production and fertility of the ducks. We had compared the genomic constitution for the Bengal duck with highest egg production with that of non-layer (infertile or sexually immature) ducks. We characterized the genes in indigenous ducks from ovarian tissues, identified important domains for characterized genes for the first time, and studied differential mRNA expression profiling for these genes with respect to layer and non-layer groups. Upregulation was observed for ESR2, DIAPH2, KMT2E, ASCF2 genes for Bengal duck in highest egg producing duck in comparison to non-layer duck, whereas downregulation was observed for KSR1, A2M, BMPR1B, ACVR1. In the next step, we explored the association with the genes which were actually responsible for egg production. Thus, duck may be utilized as a model for studying the molecular aspect of reproduction. Genes upregulated may be utilized forknock inof gene, whereas down regulated genes may beknocked outorknocked downthrough gene editing technologies for the improvement of reproductive performance of the duck in future. Molecular biomarkers may be developed with these genes for early selection of better reproducing ducks at day of hatch or even earlier.
Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge
Authors: Sun Si , Li Entao , Zhao Gan , Tang Jie , Zuo Qianfei , Cai Larry , Xu Chuanfei , Sui Cheng , Ou Yangxue , Liu Chang , Li Haibo , Ding Yuan , Li Chao , Lu Dongshui , Zhang Weijun , Luo Ping , Cheng Ping , Gao Yuwei , Tu Changchun , Pitard Bruno , Rosenecker Joseph , Wang Bin , Liu Yan , Zou Quanming , Guan Shan
Published: May 2022

The ongoing SARS-CoV-2 pandemic represents a brutal reminder of the continual threat of mucosal infectious diseases. Mucosal immunity may provide robust protection at the predominant sites of SARS-CoV-2 infection. However, it remains unclear whether respiratory mucosal administration of DNA vaccines could confer protective immune responses against SARS-CoV-2 challenge due to the insurmountable barriers posed by the airway. Here, we applied self-assembled peptide-poloxamine nanoparticles with mucus-penetrating properties for pulmonary inoculation of a COVID-19 DNA vaccine (pSpike/PP-sNp). Not only displays the pSpike/PP-sNp superior gene-transfection and favorable biocompatibility in the mouse airway, but pSpike/PP-sNp promotes a tripartite immunity consisting of systemic, cellular and mucosal immune responses that are characterized by mucosal IgA secretion, high levels of neutralizing antibodies, and resident memory phenotype T-cell responses in the lungs of mice. Most importantly, pSpike/PP-sNp completely eliminates SARS-CoV-2 infection in both upper and lower respiratory tracts and enables 100% survival rate of mice following lethal SARS-CoV-2 challenge. Our findings indicate PP-sNp might be a promising platform in mediating DNA vaccines to elicit all-around mucosal immunity against SARS-CoV-2.
Arabidopsis thaliana induces multigenerational stress tolerance against biotic and abiotic stressors and memorization of host colonization in Bacillus subtilis
Authors: Gilhar Omri , Olender Tsviya , Aharoni Asaph , Friedman Jonathan , Kolodkin-Gal Ilana
Published: May 2022

Bacillus subtilis is a beneficial bacterium that supports plant growth and protects it from bacterial, fungal, and viral infections. Here using a simplified system of B. subtilis, and Arabidopsis thaliana interactions, we found that history-dependent behavior is a potentially important manifestation of host colonization, worth classifying and quantifying. To study history-dependent adaptation to plant hosts, we develop a simple framework for measuring the physiological memory of B. subtilis following its interaction with Arabidopsis thaliana. We found that A. thaliana secretions reduce the lag time in pre-exposed bacteria compared with naïve B. subtilis cells, even after their complete removal. Pre-exposed B. subtilis cells colonized plant roots more efficiently than naïve bacteria, and were more resistant to biotic and abiotic stressors such as salicylic acid, and high salinity. Descendants of bacteria treated with plant secretions had an advantage in the competition against unexposed bacteria for root colonization. The effect of plant secretions was independent of their roles as nitrogen and carbon sources. Transcriptome analysis of both ancestors and descendants revealed that a specific set of plant-induced processes, among them c-di-AMP homeostasis, and the general stress response, maintain the signature of association with the plant in descendants of pre-exposed bacteria. Consistently, plant secretions compensated for the loss of c-di-AMP cyclases but required the general stress response and the master regulator Spo0A to exert their short and long-term effects.

Overall, our work demonstrates that bacterial memory manifested by multigenerational reversible adaptation to plant hosts confirms an advantage to symbiotic bacteria during competition.