scholarly journals Genetic and physiological mechanisms of freezing tolerance in locally adapted populations of a winter annual

2019 ◽  
Author(s):  
Brian J. Sanderson ◽  
Sunchung Park ◽  
M. Inam Jameel ◽  
Joshua C. Kraft ◽  
Michael F. Thomashow ◽  
...  
Keyword(s):  
Local Adaptation ◽  
Freezing Tolerance ◽  
Adaptive Response ◽  
Sequence Polymorphism ◽  
Loss Of Function ◽  
Physiological Mechanisms ◽  
Naturally Occurring ◽  
Before And After ◽  
Winter Annual ◽  
Insight Into

ABSTRACTPremise of the studyDespite myriad examples of local adaptation, the phenotypes and genetic variants underlying such adaptive differentiation are seldom known. Recent work on freezing tolerance and local adaptation in ecotypes of Arabidopsis thaliana from Sweden and Italy provides the essential foundation for uncovering the genotype-phenotype-fitness map for an adaptive response to a key environmental stress.MethodsHere we examine the consequences of a naturally occurring loss of function (LOF) mutation in an Italian allele of the gene that encodes the transcription factor CBF2, which underlies a major freezing tolerance locus. We used four lines with a Swedish genetic background, each containing a LOF CBF2 allele. Two lines had introgression segments containing of the Italian CBF2 allele, and two were created using CRISPR-Cas9. We used a growth chamber experiment to quantify freezing tolerance and gene expression both before and after cold acclimation.Key resultsFreezing tolerance was greater in the Swedish (72%) compared to the Italian (11%) ecotype, and all four experimental CBF2 LOF lines had reduced freezing tolerance compared to the Swedish ecotype. Differential expression analyses identified ten genes for which all CBF2 LOF lines and the IT ecotype showed similar patterns of reduced cold responsive expression compared to the SW ecotype.ConclusionsWe identified ten genes that are at least partially regulated by CBF2 that may contribute to the differences in cold acclimated freezing tolerance between the Italian and Swedish ecotypes. These results provide novel insight into the molecular and physiological mechanisms connecting a naturally occurring sequence polymorphism to an adaptive response to freezing conditions.

scholarly journals Genetic and physiological mechanisms of freezing tolerance in locally adapted populations of a winter annual

2019 ◽  
Vol 107 (2) ◽  
pp. 250-261 ◽  
Author(s):  
Brian J. Sanderson ◽  
Sunchung Park ◽  
M. Inam Jameel ◽  
Joshua C. Kraft ◽  
Michael F. Thomashow ◽  
...  
Keyword(s):  
Freezing Tolerance ◽  
Physiological Mechanisms ◽  
Winter Annual

scholarly journals A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Michelle C Ward ◽  
Yoav Gilad
Keyword(s):  
Transcriptional Response ◽  
Induced Pluripotent Stem Cell ◽  
Loss Of Function ◽  
Before And After ◽  
Species Comparisons ◽  
Induced Pluripotent ◽  
Species Specific ◽  
Direct Inter ◽  
Insight Into ◽  
Gene Expression Levels

Despite anatomical similarities, there are differences in susceptibility to cardiovascular disease (CVD) between primates; humans are prone to myocardial ischemia, while chimpanzees are prone to myocardial fibrosis. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) allow for direct inter-species comparisons of the gene regulatory response to CVD-relevant perturbations such as oxygen deprivation, a consequence of ischemia. To gain insight into the evolution of disease susceptibility, we characterized gene expression levels in iPSC-CMs in humans and chimpanzees, before and after hypoxia and re-oxygenation. The transcriptional response to hypoxia is generally conserved across species, yet we were able to identify hundreds of species-specific regulatory responses including in genes previously associated with CVD. The 1,920 genes that respond to hypoxia in both species are enriched for loss-of-function intolerant genes; but are depleted for expression quantitative trait loci and cardiovascular-related genes. Our results indicate that response to hypoxic stress is highly conserved in humans and chimpanzees.

scholarly journals Naturally-Occurring Rare Mutations Cause Mild to Catastrophic Effects in the Multifunctional and Cancer-Associated NQO1 Protein

2020 ◽  
Vol 10 (4) ◽  
pp. 207
Author(s):  
Juan Luis Pacheco-García ◽  
Mario Cano-Muñoz ◽  
Isabel Sánchez-Ramos ◽  
Eduardo Salido ◽  
Angel L. Pey
Keyword(s):  
Local Stability ◽  
Genetic Diseases ◽  
Loss Of Function ◽  
Rare Mutations ◽  
Naturally Occurring ◽  
Molecular Determinants ◽  
Functional Features ◽  
And Function ◽  
Insight Into ◽  
High Throughput Manner

The functional and pathological implications of the enormous genetic diversity of the human genome are mostly unknown, primarily due to our unability to predict pathogenicity in a high-throughput manner. In this work, we characterized the phenotypic consequences of eight naturally-occurring missense variants on the multifunctional and disease-associated NQO1 protein using biophysical and structural analyses on several protein traits. Mutations found in both exome-sequencing initiatives and in cancer cell lines cause mild to catastrophic effects on NQO1 stability and function. Importantly, some mutations perturb functional features located structurally far from the mutated site. These effects are well rationalized by considering the nature of the mutation, its location in protein structure and the local stability of its environment. Using a set of 22 experimentally characterized mutations in NQO1, we generated experimental scores for pathogenicity that correlate reasonably well with bioinformatic scores derived from a set of commonly used algorithms, although the latter fail to semiquantitatively predict the phenotypic alterations caused by a significant fraction of mutations individually. These results provide insight into the propagation of mutational effects on multifunctional proteins, the implementation of in silico approaches for establishing genotype-phenotype correlations and the molecular determinants underlying loss-of-function in genetic diseases.

scholarly journals Systemic Lupus Erythematosus before and after COVID-19 Lockdown: How the Perception of Disease Changes through the Lenses of Narrative Medicine

Healthcare ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 726
Author(s):  
Fulvia Ceccarelli ◽  
Venusia Covelli ◽  
Giulio Olivieri ◽  
Francesco Natalucci ◽  
Fabrizio Conti
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Narrative Medicine ◽  
Good Control ◽  
Final Analysis ◽  
Point Of View ◽  
Systemic Lupus ◽  
Before And After ◽  
Text Content ◽  
Insight Into

Background: The COVID-19 pandemic contributes to the burden of living with different diseases, including Systemic Lupus Erythematosus (SLE). We described, from a narrative point of view, the experiences and perspectives of Italian SLE adults during the COVID-19 emergency, by distinguishing the illness experience before and after the lockdown. Methods: Fifteen patients were invited to participate. Illness narratives were collected between 22 and 29 March 2020 using a written modality to capture patients’ perspectives before and after the COVID-19 lockdown. We performed a two-fold analysis of collected data by distinguishing three narrative types and a qualitative analysis of content to identify the relevant themes and sub-themes reported. Results: Eight narratives included in the final analysis (mean length 436.9 words) have been written by eight females (mean age 43.3 ± 9.9 years, mean disease duration 13.1 ± 7.4 years). Six patients provided a quest narrative, one a chaos and the remaining one a restitution narrative. By text content analysis, we identified specific themes, temporally distinct before and after the lockdown. Before COVID-19, all the patients referred to a good control of disease, however the unexpected arrival of the COVID-19 emergency broke a balance, and patients perceived the loss of health status control, with anxiety and stress. Conclusions: We provided unique insight into the experiences of people with SLE at the time of COVID-19, underlining the perspective of patients in relation to the pandemic.

scholarly journals Responsiveness to exogenous cAMP of a Saccharomyces cerevisiae strain conferred by naturally occurring alleles of PDE1 and PDE2.

Genetics ◽  
1993 ◽  
Vol 135 (2) ◽  
pp. 321-326 ◽  
Author(s):  
H Mitsuzawa
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Slow Growth ◽  
Loss Of Function ◽  
Wild Type ◽  
Triple Mutant ◽  
Apparent Absence ◽  
Camp Pathway ◽  
Naturally Occurring ◽  
Elevated Activity ◽  
Growth Phenotype

Abstract The Saccharomyces cerevisiae strain P-28-24C, from which cAMP requiring mutants derived, responded to exogenously added cAMP. Upon the addition of cAMP, this strain showed phenotypes shared by mutants with elevated activity of the cAMP pathway. Genetic analysis involving serial crosses of this strain to a strain with another genetic background revealed that the responsiveness to cAMP results from naturally occurring loss-of-function alleles of PDE1 and PDE2, which encode low and high affinity cAMP phosphodiesterases, respectively. In addition, P-28-24C was found to carry a mutation conferring slow growth that lies in CYR1, which encodes adenylate cyclase, and the slow growth phenotype caused by the cyr1 mutation was suppressed by the pde2 mutation. Therefore P-28-24C is fortuitously a pde1 pde2 cyr1 triple mutant. Responsiveness to cAMP conferred by pde mutations suggests that S. cerevisiae cells are permeable to cAMP to some extent and that the apparent absence of effect of exogenously added cAMP on wild-type cells is due to immediate degradation by cAMP phosphodiesterases.

scholarly journals Discoloration of Historical Plastic Objects: New Insight into the Degradation of β-Naphthol Pigment Lakes

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2278
Author(s):  
Anna Micheluz ◽  
Eva Mariasole Angelin ◽  
João Almeida Lopes ◽  
Maria João Melo ◽  
Marisa Pamplona
Keyword(s):  
Light Exposure ◽  
Molecular Structures ◽  
Conservation Science ◽  
Organic Pigment ◽  
Organic Pigments ◽  
Before And After ◽  
The Individual ◽  
Determining Factor ◽  
Insight Into ◽  
Historical Samples

Light is a determining factor in the discoloration of plastics, and photodegradation processes can affect the molecular structures of both the polymer and colorants. Limited studies focused on the discoloration of heritage plastics in conservation science. This work investigated the discoloration of red historical polyethylene (PE) objects colored with PR 48:2 and PR 53:1. High-density and low-density PE reference polymers, neat pigment powders, and historical samples were assessed before and after accelerated photoaging. The applied methodology provided insight into the individual light-susceptibility of polyethylenes, organic pigment lakes, and their combined effect in the photoaging of historical plastic formulations. After light exposure, both PE references and historical samples yellowed, PR53:1 faded, and PR 48:2 darkened; however, both organic pigments faded severely in the historical samples. This highlights the role played by the plastic binder likely facilitating the pigment photofading. Fourier transform infrared spectroscopy and mass spectrometry techniques—EGA-MS, PY-GC/MS, and TD-GC/MS—were successfully employed for characterizing the plastic formulations and degradation. The identification of phthalic compounds in both aged β-naphthol powders opens new venues for studies on their degradation. This work’s approach and analytical methods in studying the discoloration of historical plastics are novel, proving their efficacy, reliability, and potentiality.

scholarly journals Evolution of halophytes: multiple origins of salt tolerance in land plants

2010 ◽  
Vol 37 (7) ◽  
pp. 604 ◽  
Author(s):  
Timothy J. Flowers ◽  
Hanaa K. Galal ◽  
Lindell Bromham
Keyword(s):  
Salt Tolerance ◽  
Novel Species ◽  
Complex Trait ◽  
Land Plants ◽  
Salt Tolerant ◽  
Physiological Mechanisms ◽  
Multiple Origins ◽  
Naturally Occurring ◽  
Tolerant Plants

The evolution of salt tolerance is interesting for several reasons. First, since salt-tolerant plants (halophytes) employ several different mechanisms to deal with salt, the evolution of salt tolerance represents a fascinating case study in the evolution of a complex trait. Second, the diversity of mechanisms employed by halophytes, based on processes common to all plants, sheds light on the way that a plant’s physiology can become adapted to deal with extreme conditions. Third, as the amount of salt-affected land increases around the globe, understanding the origins of the diversity of halophytes should provide a basis for the use of novel species in bioremediation and conservation. In this review we pose the question, how many times has salt tolerance evolved since the emergence of the land plants some 450–470 million years ago? We summarise the physiological mechanisms underlying salt-tolerance and provide an overview of the number and diversity of salt-tolerant terrestrial angiosperms (defined as plants that survive to complete their life cycle in at least 200 mM salt). We consider the evolution of halophytes using information from fossils and phylogenies. Finally, we discuss the potential for halophytes to contribute to agriculture and land management and ask why, when there are naturally occurring halophytes, it is proving to be difficult to breed salt-tolerant crops.

A reactive center loop–based prediction platform to enhance the design of therapeutic SERPINs

2021 ◽  
Vol 118 (45) ◽  
pp. e2108458118
Author(s):  
Wariya Sanrattana ◽  
Thibaud Sefiane ◽  
Simone Smits ◽  
Nadine D. van Kleef ◽  
Marcel H. Fens ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Serine Proteases ◽  
Protein C ◽  
Activated Protein C ◽  
Reactive Center Loop ◽  
Physiological Processes ◽  
Naturally Occurring ◽  
Reactive Center ◽  
Insight Into

Serine proteases are essential for many physiological processes and require tight regulation by serine protease inhibitors (SERPINs). A disturbed SERPIN–protease balance may result in disease. The reactive center loop (RCL) contains an enzymatic cleavage site between the P1 through P1’ residues that controls SERPIN specificity. This RCL can be modified to improve SERPIN function; however, a lack of insight into sequence–function relationships limits SERPIN development. This is complicated by more than 25 billion mutants needed to screen the entire P4 to P4’ region. Here, we developed a platform to predict the effects of RCL mutagenesis by using α1-antitrypsin as a model SERPIN. We generated variants for each of the residues in P4 to P4’ region, mutating them into each of the 20 naturally occurring amino acids. Subsequently, we profiled the reactivity of the resulting 160 variants against seven proteases involved in coagulation. These profiles formed the basis of an in silico prediction platform for SERPIN inhibitory behavior with combined P4 to P4’ RCL mutations, which were validated experimentally. This prediction platform accurately predicted SERPIN behavior against five out of the seven screened proteases, one of which was activated protein C (APC). Using these findings, a next-generation APC-inhibiting α1-antitrypsin variant was designed (KMPR/RIRA; / indicates the cleavage site). This variant attenuates blood loss in an in vivo hemophilia A model at a lower dosage than the previously developed variant AIKR/KIPP because of improved potency and specificity. We propose that this SERPIN-based RCL mutagenesis approach improves our understanding of SERPIN behavior and will facilitate the design of therapeutic SERPINs.

Sign in / Sign up

Export Citation Format

Share Document