Nephridiophagids are unicellular eukaryotes that parasitize the Malpighian tubules of numerous insects. Their life cycle comprises multinucleate vegetative plasmodia that divide into oligonucleate and uninucleate cells, and sporogonial plasmodia that form uninucleate spores. Nephridiophagids are poor in morphological characteristics, and although they have been tentatively identified as early-branching fungi based on the SSU rRNA gene sequences of three species, their exact position within the fungal...
During the Miocene, Hyaenidae was a highly diverse family of Carnivora that has since been severely reduced to four extant genera, each of which contains only a single species. These species include the bone-cracking spotted, striped, and brown hyenas, and the specialised insectivorous aardwolf. Previous genome studies have analysed the evolutionary histories of the spotted and brown hyenas, but little is known about the remaining two species. Moreover, the genomic underpinnings of scavenging and...
Studying the development of fitness related traits in hybrids from populations diverging in sympatry is a fundamental approach to understand the processes of speciation. However, such traits are often affected by covariance structures that complicate the comprehension of these processes, especially because the interactive relationships between traits of different nature (e.g. morphology, behaviour, life-history) remain largely unknown in this context. In a common garden setup, we conducted an extensive...
The complete tree of life is now available, but methods to visualise it are still needed to meet needs in research, teaching and science communication. Dynamic visualisation of million-tip trees requires many challenges in data synthesis, data handling and computer graphics to be overcome. Our approach is to automate data processing, synthesise data from a wide range of available sources, then to feed these data to a client-side visualisation engine in parts. We develop a way to store the whole tree...
Studies of convergence in wild populations have been instrumental in understanding adaptation by providing strong evidence for natural selection. At the genetic level, we are beginning to appreciate that the re-use of the same genes in adaptation occurs through different mechanisms and can be constrained by underlying trait architectures and demographic characteristics of natural populations. Here, we explore these processes in naturally adapted high- (HP) and low-predation (LP) populations of the...
The wealth of high-quality genomes for numerous species has motivated many investigations into the genetic underpinnings of phenotypes. Comparative genomics methods approach this task by identifying convergent shifts at the genetic level that are associated with traits evolving convergently across independent lineages. However, these methods have complex statistical behaviors that are influenced by non-trivial and oftentimes unknown confounding factors. Consequently, using standard statistical analyses...
Understanding whether and how temperature increases alter the effects of mutations on protein stability is crucial for understanding the limits to thermal adaptation by organisms. Currently, it is generally assumed that the stability effects of mutations are independent of temperature. Yet, mutations should become increasingly destabilizing as temperature rises due to the increase in the energy of atoms. Here, by performing an extensive computational analysis on the essential enzyme adenylate kinase...
Reef-building corals are foundational species in coral reef ecosystems and are threatened by many stressors including rising ocean temperatures. In 2015/16 and 2016/17, corals around the world experienced consecutive bleaching events and most coral populations are projected to experience temperatures above their current bleaching thresholds annually by 2050. Adaptation to higher temperatures is therefore necessary if corals are to persist in a warming future. While many aspects of heat stress have...
It is assumed that host genetic variability for susceptibility to infection will necessarily condition the evolution of viruses, either by driving them to diversification into strains that track the different host defense alleles (e.g., antigenic diversity), or by canalization to infect only the most susceptible genotypes. Associated to these processes, virulence may or may not increase. To tackle these questions, we performed evolution experiments with turnip mosaic virus (TuMV) in Arabidopsis thaliana...
With rising antibiotic resistance, alternative treatments for communicable diseases are increasingly relevant. One possible alternative for some types of infections is honey, used in wound care since before 2000 BCE and more recently in licensed, medical-grade products. However, it is unclear whether medical application of honey results in the evolution of bacterial honey resistance, and whether this has collateral effects on other bacterial traits such as antibiotic resistance. Here, we used single-step...
Cobalamin is a cofactor present in essential metabolic pathways in animals and one of the water-soluble vitamins. It is a complex compound synthesized solely by prokaryotes. Cobalamin dependence is scattered across the tree of life. In particular, fungi and plants were deemed devoid of cobalamin. We demonstrate that cobalamin is utilized by all fungal lineages, except for Dikarya. This observation is supported by the genomic presence of both B12 dependent enzymes and cobalamin modifying enzymes....
How an organisms sensory system functions is central to how it navigates its environment and meets the behavioural challenges associated with survival and reproduction. Comparing sensory systems across species can reveal how facets of behaviour and ecology promote adaptive shifts in the relative importance of certain environmental cues. The insect olfactory system is prominent model for investigating how ecological factors impact sensory reception and processing. Notably work in Lepidoptera led to...
Reef-building corals are foundational species in coral reef ecosystems and are threatened by many stressors including rising ocean temperatures. In 2015/16 and 2016/17, corals around the world experienced consecutive bleaching events and most coral populations are projected to experience temperatures above their current bleaching thresholds annually by 2050. Adaptation to higher temperatures is therefore necessary if corals are to persist in a warming future. While many aspects of heat stress have...
Lateral gene transfer (LGT) has been documented in a broad range of prokaryotes and eukaryotes, and it can promote adaptation. LGT of functional nuclear genes has been reported among some plants, but systematic studies are needed to assess the frequency and facilitators of LGT in the group. We scan the genomes of a diverse set of 17 grass species that span more than 50 million years of divergence and include major crops to identify grass-to-grass protein-coding LGT. We identify LGT in 13 species,...
Targeted sequencing using Angiosperms353 has emerged as a low-cost tool for phylogenetics, with early results spanning scales from all flowering plants to within genera. The use of universal markers at narrower scales--within populations-- would eliminate the need for specific marker development while retaining the benefits of full-gene sequences. However, it is unclear whether the Angiosperms353 markers provide sufficient variation within species to calculate demographic parameters. Using herbarium...
A large and rapidly expanding literature has grown out of the observation that humans carry a genetic legacy reflecting ancient inter-breeding with archaic hominins such as Neanderthals and Denisovans. However, a recent study suggests that a commonly used statistic used to assess legacy size, D, is driven mainly by heterozygous sites in Africa acting to increase divergence from our common ancestor rather than introgressed fragments outside Africa reducing divergence. To test this new model, I analysed...
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Persistent swallowing disorders (SD) are non-pulmonary complications of mechanical ventilation (MV). However, there are few clinical studies on persistent SD in critically ill patients undergoing tracheal intu...
Data on outcome of critically ill children with cirrhosis are scarce. We aimed to evaluate the prognostic accuracy of sequential organs scoring systems in children with cirrhosis admitted to Paediatric Intensi...
Early treatment is advocated in the management of patients with suspected sepsis in the emergency department (ED). We sought to understand the association between the ED treatments and outcome in patients admi...
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Thyroid, Ahead of Print.
Thyroid, Ahead of Print.
Thyroid, Ahead of Print.
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Abstract Epigenetic dysregulation is a hallmark of cancer, and aberrant methylation of cytosine residues plays a crucial role in abnormal gene expression in cancer cells. Recent studies demonstrate that 5-hydroxymethylcytosine (5-hmC) generated through 5-methylcytosine (5-mC) oxidation is significantly depleted in various cancers. However, whether 5-hmC levels change during the stepwise progression of thyroid carcinoma and the mechanisms underlying this effect remain unknown....
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Tissue Engineering Part A, Ahead of Print.
Tissue Engineering Part A, Ahead of Print.
Tissue Engineering Part A, Ahead of Print.
Tissue Engineering Part A, Ahead of Print.
Tissue Engineering Part A, Ahead of Print.
Tissue Engineering Part A, Ahead of Print.
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Cetacean vertebral trabecular bone volume fraction was greatest in rigid‐torso shallow divers, smallest in flexible‐torso deep divers, and intermediate in rigid‐torso deep divers. Degree of anisotropy was greater in rigid‐torso swimmers compared to their flexible‐torso counterparts. Despite having osteoporotic skeletons overall, cetacean vertebrae show greater bone volume fraction, trabecular thickness, and degree of anisotropy than previously documented in terrestrial mammalian bone. Abstract...
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Abstract Mountain ecosystems cover a large proportion of Earth and represent important environments for a range of different taxa, including nocturnal primates. This group of primates is generally understudied because of their small size and their cryptic and nocturnal nature. Thus, much of their ecology and distribution still remains unknown, especially in mountain ecosystems. We investigated the effects of altitude and seasonality (wet vs. dry season) on observed species richness...
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Abstract Purpose of Review Social support is an important yet often overlooked aspect of chronic pain management. Understanding the impact of social support on patients with chronic pain and determining if a relationship exists between a patient’s perceived social support and their perceived quality of life is a crucial component to completely treating a pain patient. We sought to develop an intervention for patients with chronic...
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Journal of Neurotrauma, Ahead of Print.
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Abstract The recent approval of Palforzia for treatment of peanut allergy by the US Food and Drug Administration (USFDA) predicts that additional products for oral immunotherapy (OIT) are on the horizon. In this article, the authors review the legal framework by which the USFDA regulates products for OIT of food allergy and the clinical data that demonstrated that the safety and effectiveness profile of Palforzia supported approval and conclude with a discussion of oral food...
Abstract Background Olfactory dysfunction (OD) has been gaining recognition as a symptom of COVID-19, but its clinical utility has not been well defined. Objectives To quantify the clinical utility of identifying OD in the diagnosis of COVID-19 and determine an estimate of the frequency of OD amongst these patients. ...
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Abstract Purpose In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [18F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [18F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer’s tonsillar ring. To improve the accuracy for detecting primary tumors...
Abstract Objectives The aim of this study was to [1] characterize distribution of Erdheim-Chester Disease (ECD) by 18F-FDG PET/CT and [2] determine the utility of metabolic (18F-FDG PET/CT) imaging versus anatomic imaging (CT or MRI) in evaluating ECD patients for clinical trial eligibility. Methods 18F-FDG PET/CT and corresponding CT or MRI studies...
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Endothelin signaling promotes melanoma in the mouse brain
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Long noncoding RNA (lncRNA) Linc00337 has been implicated in lung, gastric, colorectal and esophageal squamous cell carcinoma progression via various mechanisms; however, its clinicopathological significance a...
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Currently, there is minimal data available highlighting the prevalence of venous thromboembolism in patients infected with coronavirus disease 2019 (COVID-19). This case report with a literature review emphasi...
The understanding of coronavirus disease 2019 (COVID-19) is rapidly evolving. Although it is primarily a respiratory illness, other manifestations, such as Guillain-Barré syndrome, immune thrombocytopenia, and...
The symptoms of drug-induced hepatic injury are manifold; however, the presence of ascites indicates a severe disease condition. The rapid accumulation of ascites is distressing and requires palliative treatme...
The incidence of angioimmunoblastic T-cell lymphoma is rare worldwide, and it has a poor prognosis. There is no proven or standard first-line therapy that works for the majority of patients with angioimmunobla...
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A recently deorphanized receptor, GPR18 showed to act with several endogenous cannaboinoid ligands. Among several potent functionalities the receptor activation also leads to the induction of anti‐infammatory and antinociceptive action. By using highly selective agonist of GPR18, PSB‐KK‐1415 we achieved an inflammation alleviation in two mouse models of colitis and a reduction in pain‐induced behaviors in mouse model of inflammatory pain. Abstract Background GPR18 is a recently deorphanized...
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Circular RNA hsa_circ_0003204 promotes cervical cancer cell proliferation, migration, and invasion by regulating MAPK pathway. Cancer Biol Ther. 2020 Oct 13;:1-11 Authors: Huang XB, Song KJ, Chen GB, Liu R, Jiang ZF, He YL Abstract Cervical cancer (CC) is the second most common malignancy in women worldwide. The mechanism underlying CC development remains unclear. Recently, Circular RNAs (circRNAs)have attracted attention because of its role...
Prolyl endopeptidase inhibitor Y-29794 blocks the IRS1-AKT-mTORC1 pathway and inhibits survival and in vivo tumor growth of triple-negative breast cancer. Cancer Biol Ther. 2020 Oct 12;:1-8 Authors: Perez RE, Calhoun S, Shim D, Levenson VV, Duan L, Maki CG Abstract Prolyl endopeptidase (PREP), also known as prolyl oligopeptidase (POP), is an enzyme that cleaves short peptides (<30 amino acids in length) on the C-terminal side of proline....
Expression of STAT1 is positively correlated with PD-L1 in human ovarian cancer. Cancer Biol Ther. 2020 Oct 12;:1-9 Authors: Liu F, Liu J, Zhang J, Shi J, Gui L, Xu G Abstract Signal transducer and activator of transcription 1 (STAT1) is related to the immune microenvironment of tumorigenesis. The programmed cell death 1 (PD-1) and its ligand (PD-L1) have been reported to be important in immunotherapy by mediating tumor immune evasion. Blocking...
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High-throughput RNA sequencing unveiled the complexity of transcriptome and significantly increased the records of long noncoding RNAs (lncRNAs) which were reported to participate in a variety of biological processes. Identification of lncRNAs is a key step of lncRNA analysis, and a bunch of bioinformatics tools have been developed for this purpose in recent years. While these tools allow us to identify lncRNA more efficiently and accurately, they may produce inconsistent results, making selection...
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On April 17, 2020, the FDA approved tucatinib in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. This was the first new molecular entity evaluated under Project Orbis, an FDA Oncology Center of Excellence initiative which supports concurrent review of oncology drugs by multiple...
Purpose:Preclinical and early clinical data suggested that combining histone deacetylase (HDAC) and mTOR inhibitors can synergistically inhibit Hodgkin lymphoma.Patients and Methods:During the dose-escalation study (ClinicalTrials.gov number: NCT01087554) with the HDAC inhibitor vorinostat and the mTOR inhibitor sirolimus (V+S), a patient with Hodgkin lymphoma refractory to nine prior therapies demonstrated a partial response (PR) lasting for 18.5 months, which promoted additional enrollment of patients...
Purpose.Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors). Experimental Design. Here, we developed a novel digital droplet PCR (ddPCR) assay, that incorporates features to...
Background RNA-sequencing-based subtyping of pancreatic ductal adenocarcinoma (PDAC) has been reported by multiple research groups, each using different methodologies and patient cohorts. 'Classical' and 'basal-like' PDAC subtypes are associated with survival differences, with basal-like tumors associated with worse prognosis. We amalgamated various PDAC subtyping tools to evaluate the potential of such tools to be reliable in clinical practice. Methods Sequencing data for 574 PDAC tumors was...
The recent impressive clinical responses to antibody-based immunotherapy have prompted the identification of clinically relevant tumor antigens that can serve as targets in solid tumors. Among them, B7-H3, a member of the B7 ligand family, represents an attractive target for antibody-based immunotherapy: it is overexpressed on differentiated malignant cells and cancer initiating cells, with limited heterogeneity, and high frequency (60% of 25,000 tumor samples) in many different cancer types, but...
Purpose: Approximately 30% of patients with chronic lymphocytic leukemia (CLL) can be grouped into subsets with stereotyped B cell receptor immunoglobulin (BcR IG) displaying remarkable similarity in the heavy complementarity-determining region 3 (VH CDR3). Here, we investigated whether the consensus VH CDR3 sequences from CLL stereotyped subsets can be exploited for immunotherapy approaches. Experimental Design: Immunogenic epitopes from the consensus VH CDR3 sequence of the clinically aggressive...
Coronavirus disease 2019 (COVID-19) is a novel infectious disease that has spread world-wide. In the United States, COVID-19 disproportionately affects racial and ethnic minorities, particularly African Americans, with an observed two-fold higher rate for hospitalization and greater than two-fold higher rate for death as compared to White Americans. The disparity seen with COVID-19 is consistent with patterns of disparities observed for cancer; it is well-documented that 5-year survival rates for...
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The way leaves reflect light, known as plant reflectance spectra, can illuminate the evolutionary history of seed plants, according to researchers. The researchers found that by measuring the light spectrum reflected by leaves, they can identify the plant and its chemistry, evolution and place in the tree of life.
Researchers have established an automated pipeline to create mutations in genomic enhancers that let them watch evolution unfold before their eyes. Their findings on fruit flies may also be relevant to the understanding of human diseases, requiring researchers to reassess assumptions about how enhancers contribute to human health.
Combining genetic and experimental data into models about the influenza virus can help predict more accurately which strains will be most common during the next winter, says a study published recently in eLife.
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Globozoospermia is a rare form of male infertility where men produce round-headed sperm that are incapable of fertilizing an oocyte naturally. In a previous study where we undertook a whole exome screen to define novel genetic causes of globozoospermia, we identified homozygous mutations in the gene PDCD2L. Two brothers carried a p.(Leu225Val) variant predicted to introduce a novel splice donor site, thus presenting PDCD2L as a potential regulator of male fertility. In this study, we generated a...
In sorghum [Sorghum bicolor (L.) Moench], hybrid cultivars for the biofuel industry are desired. Along with selection based on testcross performance, evaluation of the breeding population per se is also important for the success of hybrid breeding. In addition to additive genetic effects, non-additive (i.e., dominance and epistatic) effects are expected to contribute to the performance of early generations. Unfortunately, studies on early generations in sorghum breeding programs are limited. In this...
Gene copy number variation across individuals has been shown to track population structure and be a source of adaptive genetic variation with significant fitness impacts. In this study, we report opposite results for both predictions based on the analysis of gene copy number variants (CNVs) of Suillus brevipes, a mycorrhizal fungus adapted to coastal and montane habitats in California. In order to assess whether gene copy number variation mirrored population structure and selection in this species,...
A suitable pairwise relatedness estimation is key to genetic studies. Several methods are proposed to compute relatedness in autopolyploids based on molecular data. However, unlike diploids, autopolyploids still need further studies considering scenarios with many linked molecular markers with known dosage. In this study, we provide guidelines for plant geneticists and breeders to access trustworthy pairwise relatedness estimates. To this end, we simulated populations considering different ploidy...
Epigenetic silencing by Polycomb group (PcG) complexes can promote epithelial-mesenchymal transition (EMT) and stemness and is associated with malignancy of solid cancers. Here we report a role for Drosophila PcG repression in a partial EMT event that occurs during wing disc eversion, an early event during metamorphosis. In a screen for genes required for eversion we identified the PcG genes Sex combs extra (Sce) and Sex combs midleg (Scm). Depletion of Sce or Scm resulted in internalised wings and...
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Conditions: Nasopharyngeal Carcinoma; Recurrent Nasopharyngeal Carcinoma; Metastatic Nasopharyngeal Carcinoma; Chemotherapy Effect; Immunotherapy; Molecular Targeted TherapyIntervention: Drug: Apatinib plus CamrelizumabSponsor: Sun Yat-sen UniversityRecruiting
Condition: Pituitary AdenomaInterventions: Procedure: Endonasal endoscopic pituitary surgery in semi-sitting position; Procedure: Endonasal endoscopic pituitary surgery in supine positionSponsor: University Hospital, Basel, SwitzerlandNot yet recruiting
Conditions: Dysphagia; Dysphonia; Subglottic Stenosis; Voice Disorders; Swallowing Disorder; Covid19; SARS (Severe Acute Respiratory Syndrome); SARS Pneumonia; Quality of Life; SARS-CoV-2 InfectionInterventions: Diagnostic Test: Fibreoptic Endoscopic Evaluation of Swallowing (FEES); Diagnostic Test: Videofluoroscopy; Other: Dysphagia Handicap Index (DHI); Other: Voice Symptom Scale (VoiSS)Sponsor: Cambridge University Hospitals NHS Foundation TrustRecruiting
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The Cutoff Point and Diagnostic Accuracy of the Voice Handicap Index in Cantonese-Speaking Population. J Voice. 2020 Oct 09;: Authors: Ng E, Law T, Tang EC, Ho FN, Tong MC, Lee KY Abstract BACKGROUND: Voice Handicap Index (VHI) has been used extensively in research and clinical settings. It has been suggested to be used as a diagnostic tool in the literature. However, little is known if it could be applied as a diagnostic tool to the Cantonese-speaking...
FDA Supplemental Approval Summary: Lenvatinib for the Treatment of Unresectable Hepatocellular Carcinoma. Oncologist. 2020 Oct 12;: Authors: Nair A, Reece K, Donoghue MB, Yuan WV, Rodriguez L, Keegan P, Pazdur R Abstract On August 16, 2018, the Food and Drug Administration (FDA) approved lenvatinib (Lenvima®, Eisai Inc.) for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Approval was based on an international,...
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Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c07378
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