Biofilms constitute an important issue in microbial ecology, due to their high ecological and economic relevance, but the impact of abiotic conditions and microbial key players on the development and functionality of a natural biofilm is still little understood. This study investigated the effects of light intensity (LI) and bed shear stress (BSS) and the role of dominant microbes during the formation of natural biofilms and particularly the process microbial biostabilization. A comprehensive analysis of microbial biomass, extracellular polymeric substances produced, and the identification of dominant bacterial and algal species was correlated with assessment of biofilm adhesiveness/stability. LI and BSS impacted the biofilms in very different ways: biofilm adhesiveness significantly increased with LI and decreased with BSS. Moreover, microbial biomass and the functional organization of the bacterial community increased with LI, while the dynamics in the bacterial community increased with BSS. Most stable biofilms were dominated by sessile diatoms like Achnanthidium minutissimum or Fragilaria pararumpens and bacteria with either filamentous morphology, such as Pseudanabaena biceps, or a potential high capacity for extracellular polymeric-substance production, such as Rubrivivax gelatinosus. In contrast, microbes with high motility, such as Nitzschia fonticola, Pseudomonas fluorescens, and Caulobacter vibrioides, dominated the least adhesive biofilms. Their movement and potential antibiotic production could have had a disruptive impact on the biofilm matrix, which decreased its stability. This is the first study to unveil the link between abiotic conditions and resulting shifts in key microbial players to impact the ecosystem-service microbial biostabilization.
The classical view holds that proteins fold into essentially unique three-dimensional structures before becoming biologically active. However, studies over the last several years have provided broad and convincing evidence that some proteins do not adopt a single structure and yet are fully functional. These intrinsically disordered proteins (IDPs) have been found to be highly prevalent in many genomes, including human, and play key roles in central cellular processes, such as regulation of transcription and translation, cell cycle, and cell signaling. Moreover, IDPs are overrepresented among proteins implicated in disease, including various cancers and neurodegenerative disorders. Intense efforts, by using both experimental and computational approaches, are consequently under way to uncover the molecular mechanisms that underpin the roles of IDPs in biology and disease. This review provides an introduction to the general biophysical properties of IDPs and discusses some of the recent emerging areas in IDP research, including the roles of IDPs in allosteric regulation, regulatory unfolding, and formation of intracellular membrane-less organelles. In addition, recent attempts at therapeutic targeting of IDPs by small molecules, noting in particular that IDPs represent a potentially important source of new drug targets in light of their central role in protein-protein interaction networks, are also reviewed.
The zygaenid moth Thyrassia penangae is a typical long-day species, entering winter diapause as a prepupa in a cocoon in response to short-day conditions during autumn. The previous photoperiodic responses under non-24-h light-dark cycle and Nanda-Hamner experiments (greatly extended dark periods coupled with a short photophase or a long photophase) revealed that the moth measured day length rather than night length in the determination of diapause. In this study, we further extend non-24-h light-dark cycle experiments and use the Bunsow experiment (the extended scotophase or photophase interrupted by 1-h light pulse or 1-h dark interruption) to test the photoperiodism for diapause induction of this moth. The extended non-24-h light-dark cycle experiment showed that when the length of photophase exceeded critical day length, diapause incidence was quite low regardless of scotophase duration. No circadian rhythmicity was found in Bunsow experiments. The incidence of diapause was consistently low when preinterruption photophase was longer than the critical day length. The two experiments provide further evidence that this moth measures day length instead of night length.
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The primary cilium (PC) is a plasma membrane-derived structure of great importance for cell and organismal physiology. Indeed, abnormalities in assembly or function of the PC trigger the onset of a group of genetic diseases collectively known as ciliopathies. In recent years, it has become evident that the integrity and function of the PC depends substantially on signaling elements such as phosphoinositides (PI) and their regulators. Because phospholipids such as PI(4,5)P-2 constitute recruitment platforms for cytoskeleton, signaling, and trafficking machinery, control over their levels is critical for PC function. Although information about phosphoinositol phosphate (PIP) kinases in the PC is scarce, a growing body of evidence supports a role for PIP phosphatases in cilia assembly/maintenance. Indeed, deficiencies in two 5' PIP phosphatases, Inpp5E and Ocrl1, are clearly linked to ciliopathies like Joubert/MORM syndromes, or ciliopathy-associated diseases like Lowe syndrome. Here, we review the unique roles of these proteins and their specific site of action for ensuring ciliary integrity. Further, we discuss the possibility that a phosphatase relay system able to pass PI control from a preciliary to an intraciliary compartment is in place to ensure PC integrity/function.
Images of sea urchin oocytes with hundreds of spermatozoa attached to their surface have fascinated scientists for over a century and led to the idea that oocytes have evolved mechanisms to allow the penetration of one spermatozoon while repelling supernumerary spermatozoa. Popular texts have extrapolated this concept, to the mammals and amphibians, and in many cases to include all the Phyla. Here, it is argued that laboratory experiments, using sea urchin oocytes deprived of their extracellular coats and inseminated at high densities, are artifactual and that the experiments leading to the idea of a fast block to polyspermy are flawed. Under natural conditions, the number of spermatozoa at the site of fertilization is extremely low, compared with the numbers generated. The sperm: oocyte ratio is regulated first by dilution in externally fertilizing species and the female reproductive tract in those with internal fertilization, followed by a bottleneck created by the oocytes extracellular coats. In order to progress to the oocyte plasma membrane, the fertilizing spermatozoon must encounter and respond to a correct sequence of signals from the oocytes extracellular coats. Those that do not, are halted in their progression by defective signaling and fall to the wayside. Final success and entry is finely tuned by the spermatozoon anchoring to an actin-rich predetermined site on the plasma membrane. In this review, the variation in the form, function, and number of gametes produced across the animal kingdom and the many ways in which sperm-oocyte interactions are regulated to reduce numbers are discussed. Since in nature, final sperm: oocyte ratios approach unity it would appear that selective pressures have favored the achievement of monospermy, rather than the evolution of polyspermy preventing mechanisms.
Purpose: Carbon dioxide (CO2) levels have been rising rapidly. Algae are single-cell organisms with highly efficient CO2 uptake mechanisms. Algae yield two to ten times more biomass versus terrestrial plants and can grow nearly anywhere. Large scale CO2 sequestration is not yet sustainable due to high amounts of nitrogen (N) and phosphate (P) needed to grow algae in media.Methods: Mutant strains of Chlamydomonas reinhardtii were created using ultraviolet light (2.2-3 K J/m(2)) and natural selection using media with 20%-80% lower N and P compared to standard Sueoka's high salt medium. Strains were selected based upon growth in media concentrations varying from 20% to 80% less N/P compared to control. Biomass was compared to wild-type control (CC-125) using direct counts, optical density dry weight, and mean doubling time.Results: Mean doubling time was 20 and 25 hours in the low N and N/P strains, respectively (vs 66 hours in control). Using direct counts, growth rates of mutant strains of low N and N/P cultures were not statistically different from control (P=0.37 and 0.70), respectively.Conclusion: Two new strains of algae, as well as wild-type control, were able to grow while using 20%-40% less N and P. Ultraviolet light-based modification of algae is an inexpensive and alternative option to genetic engineering techniques. This technique might make larger scale biosequestration possible.
5' AMP-activated protein kinase (AMPK) is considered the master metabolic regulator in all eukaryotes, as it maintains cellular energy homeostasis in a variety of tissues, including the brain. In humans, alterations in AMPK activity can lead to a wide spectrum of metabolic disorders. The relevance of this protein kinase in the pathogenesis of diabetes and metabolic syndrome is now well established. On the contrary, correlations between AMPK and brain physiopathology are still poorly characterized. The aim of this review is to summarize and discuss the current knowledge about the prospective involvement of AMPK in the onset and the progression of different neurological diseases.
Mechanistic target of rapamycin (mTOR) dysregulation is present in a variety of human pathologies including neurological disease, cancer, diabetes, and cardiac disease. Hyperactivation leads to increased protein synthesis and cell growth, which are essential for growth, development, and cancer. Inhibition of mTOR results in induction of autophagy, a cell survival mechanism thought to be deficient in neurodegeneration. Counteracting the balance of mTOR signaling with target specific inhibitors is of interest in pathological conditions where mTOR signaling is upregulated. The US Food and Drug Administration (FDA) has approved the use of rapamycin for treatment of renal cell, pancreatic neuroendocrine, and hormone positive breast cancer. Many clinical trials are underway to determine the efficacy of mTOR inhibitors in other pathologies as monotherapies or combinational therapies with chemotherapeutics, tyrosine kinase inhibitors, molecular targeted therapies, and vascular endothelial growth factor (VEGF) inhibitors. Collectively, this review is an overview of the current practices and outcomes of pharmaceutically targeting this highly studied mediator of normal and aberrant cell function.
Superresolution microscopy breaks the diffraction limit of light, making it possible to visualize a broad range of subcellular components with nearly molecular scale detail. The potential of this powerful tool is continuously growing since the implementation of optical config urations and data analyses compatible with the technically challenging, yet frequent in biology, thick and crowded samples. We review the principles underlying stimulated emission depletion, structured illumination, and single-molecule localization microscopy approaches, and their technical developments, with an emphasis on three-dimensional and live-cell imaging. Special attention is brought to the new requirements for probe efficiency, namely their size and their photophysical properties. Finally, recent applications exploring the interphase nucleus are described to illustrate the performance of superresolution techniques.
In eukaryotes, F-box proteins are one of the main components of the SCF complex that belongs to the family of ubiquitin E3 ligases, which catalyze protein ubiquitination and maintain the balance between protein synthesis and degradation. In the present study, we clarified the role and function of the gene encoding cyclin-like F-box protein from Medicago truncatula using transgenic plants of the model species M. truncatula, Lotus japonicas, and Arabidopsis thaliana generated by Agrobacterium-mediated transformation. Morphological and transcriptional analyses combined with flow cytometry and histochemistry demonstrated the participation of this protein in many aspects of plant growth and development, including processes of indirect somatic embryogenesis and symbiotic nodulation. The cyclin-like F-box gene showed expression in all plant organs and tissues comprised of actively dividing cells. The observed variations in root and hypocotyl growth, leaf and silique development, ploidy levels, and leaf parameters in the obtained transgenic lines demonstrated the effects of this gene on organ development. Furthermore, knockdown of cyclin-like F-box led to accumulation of higher levels of the G2/M transition-specific gene cyclin B1:1 (CYCB1:1), suggesting its possible role in cell cycle control. Together, the collected data suggest a similar role of the cyclin-like F-box protein in the three model species, providing evidence for the functional conservation of the studied gene.
The reprogramming of the mitochondria of cancer cells is essential for their growth. However, such reprogramming leads to the increased formation of reactive oxygen species, which can lead to damage to the organelle. This review summarizes the mechanisms that protect the mitochondrial network against oxidative stress. Further, since several transcription factors have now been linked to the mitochondrial unfolded protein response (UPRmt) and regulate the expression of one or more genes involved in these "mito-protective" mechanisms, the UPRmt is a prime candidate to coordinate the maintenance of the integrity of the mitochondria under oxidative stress conditions.
The maternal immune system plays a critical role in the establishment, maintenance, and completion of a healthy pregnancy. However, the specific mechanisms utilized to achieve these goals are not well understood. Various cells and molecules of the immune system are key players in the development and function of the placenta and the fetus. Effector cells of the immune system act to promote and yet limit placental development. The T helper 1 (Th1)/T helper 2 (Th2) immune shift during pregnancy is well established. A fine balance between proinflammatory and anti-inflammatory influences is required. We herein review the evidence regarding maternal tolerance of fetal tissues and the underlying cell-mediated immune and humoral (hormones and cytokines) mechanisms. We also note the many unanswered questions in our understanding of these mechanisms. In addition, we summarize the clinical manifestations of an altered maternal immune system during pregnancy related to susceptibility to common viral, bacterial, and parasitic infections, as well as to autoimmune diseases.
Background: The LIS-1 is an element that appears as a site-specific insertion event in some flax lines in response to certain growth conditions and can be transmitted to subsequent-generations. The origin of LIS-1 in the flax genome is uncertain. One possibility is that since LIS-1 does not exist intact in the progenitor line, it is assembled from small sequences found scattered throughout the genome, and that, under stressful growth conditions, induction occurs and these sequences are rearranged and assembled to form the intact LIS-1 element. It is unknown whether the intact LIS-1 element would remain stably integrated in other plant species or if it would be destabilized from their genome.Results: In this study, Agrobacterium-mediated plant transformation via floral dipping was used to transform different accessions of the Columbia ecotype of Arabidopsis thaliana, with either LIS-1 or the target site into which LIS-1 integrates. The stability and the inheritance patterns of both elements were followed in subsequent generations. Our results indicate that, in the different transformed accessions, the target site of LIS-1 remains stable in the T1 and T2 generations. However, LIS-1 is not found intact in any transformed A. thaliana plants. Instead, it goes through multiple fragmentation events, which seem to be genotype dependent. In the process, the region originally flanking LIS-1 in the T-DNA construct can be converted to the same sequence found at the target site in flax, followed by complete excision of all the flax DNA in the construct.Conclusion: These results demonstrate that the processes by which LIS-1 is produced in flax are also present in A. thaliana because both plants are capable of destabilizing the intact LIS-1 element.
Calcium (Ca2+) plays a central role in the contraction of the heart. It is the bi-directional link between electrical excitation of the heart and contraction. Electrical excitation initiates Ca2+influx across the sarcolemma and T-tubular membrane that triggered calcium release from the sarcoplasmic reticulum. Ca2+sparks are the elementary events of calcium release from the sarcoplasmic reticulum. Therefore, understanding the dynamics of Ca2+sparks is essential for understanding the function of the heart. To this end, numerous experimental and computational studies have focused on this topic, exploring the mechanisms of calcium spark initiation, termination, and regulation and what role these play in normal and patho-physiology. The proper understanding of Ca2+ spark regulation and dynamics serves as the foundation for our insights into a multitude of pathological conditions may develop that can be the result of structural and/or functional changes at the cellular or subcellular level. Computational modeling of Ca2+ spark dynamics has proven to be a useful tool to understand Ca2+ spark dynamics. This review addresses our current understanding of Ca2+ sparks and how synchronized SR Ca2+ release, in which Ca2+ sparks is a major pathway, is linked to the different cardiac diseases, especially arrhythmias.
Small GTPases play crucial roles in regulating polarized vesicle trafficking in a cell. These molecules are involved in diverse pathways and regulate cell shape, organelle integrity, and cell signaling. One of the most important cellular signaling centers is the primary or sensory cilium. Small GTPases orchestrate a diverse set of events to not only generate these structures but also mediate their function and maintenance during the life of the cell. In this review, we will discuss the various small GTPases involved in regulating cilia biogenesis and function and their involvement in human diseases.
Bardet-Biedl syndrome (BBS) is an autosomal recessive condition characterized by important clinical features, including obesity, blindness, renal cystic disease, and intellectual disability. BBS is caused by mutations in >20 genes, a subset of which form the so-called BBSome. The BBSome is a complex that coats intracellular vesicles and interacts with key proteins, such as small GTPases, that regulate the trafficking of these vesicles to the base of cilia. Cilia are microtubular protusions present on the surface of most cells that are defective in a key group of disorders known as ciliopathies, of which BBS is one. BBSome components particularly localize to the basal body of cilia, and also centrosomes, where they interact with pericentriolar material proteins that regulate their function. The BBSome also facilitates the transport of key cargo within cilia by acting as an adaptor protein for intraflagellar transport complexes, and as such BBS mutations lead to a variety of functional defects in cilia in a tissue-and cell-type-specific manner. This might include defects in photoreceptor trafficking linked to the connecting cilium, abnormal hedgehog signaling within bone, and aberrant calcium signaling in response to fluid flow along renal tubules, although the precise mechanisms are still not completely understood. Taken together, the BBSome is an important complex that may be targeted for treatment of a variety of common and important disorders, and understanding the precise function of the BBSome will be essential to capitalize on this translationally.
Background: The prevalence of childhood obesity has become a global concern and evolves from the complex interaction of multiple factors. In particular, the influence of socioeconomic status and ethnicity when combined with family dynamics are important, yet remain inconsistent in their association with childhood obesity. Parents, as influential family members, play a primary role in the development of their children's eating and activity behaviors that may contribute to increased weight. This integrative review 1) examines the parental role in the development of childhood obesity and 2) identifies implications for health programs and policies.Method: Systematic searches using five databases followed by a lateral search were conducted between April and June 2014. Inclusion criteria included empirical research published in the last 5 years addressing the role that parents with children 12 years and younger play in their child being or becoming obese. Nineteen publications were identified.Results: Six themes related to the association between parental role and childhood obesity emerged from our review. These themes included parenting style, parent influence on feeding, modeling, self-efficacy, concern, and bidirectional interaction of the parent-child dyad. Parenting style, modeling, and self-efficacy were not consistently associated with childhood obesity. Parental concern, however, was linked to specific feeding practices. Parental restriction and pressure to eat certain foods were both found to be inversely related to a child's weight status. Parent's role in promoting activity was infrequently addressed.Conclusion: When addressing eating and activity behaviors among children, the role that parents play in feeding their child and their concern for their child's health is critical. Including mothers and fathers as potential "agents of change" and considering their cultural norms are two elements necessary for effective health programming and policy development.
Antimicrobial resistance (AMR) is an increasing clinical problem precipitated by the inappropriate use of antibiotics in the later parts of the 20th Century. This problem, coupled with the lack of novel therapeutics in the development pipeline, means AMR is reaching crisis point, with an expected annual death rate of ten million people worldwide by 2050. To reduce, and to potentially remedy this problem, many researchers are looking into natural compounds with antimicrobial and/or antivirulence activity. Manuka honey is an ancient antimicrobial remedy with a good track record against a wide range of nosocomial pathogens that have increased AMR. Its inhibitory effects are the result of its constituent components, which add varying degrees of antimicrobial efficacy to the overall activity of manuka honey. The antimicrobial efficacy of manuka honey and some of its constituent components (such as methylglyoxal and leptosperin) are known to bestow some degree of antimicrobial efficacy to manuka honey. Despite growing in vitro evidence of its antimicrobial efficacy, the in vivo use of manuka honey (especially in a clinical environment) has been unexpectedly slow, partly due to the lack of mechanistic data. The mechanism by which manuka honey achieves its inhibitory efficacy has recently been identified against Staphylococcus aureus and Pseudomonas aeruginosa, with both of these contrasting organisms being inhibited through different mechanisms. Manuka honey inhibits S. aureus by interfering with the cell division process, whereas P. aeruginosa cells lyse in its presence due to the reduction of a key structural protein. In addition to these inhibitory effects, manuka honey is known to reduce virulence, motility, and biofilm formation. With this increasing in vitro dataset, we review the components and our mechanistic knowledge of manuka honey and how manuka honey could potentially be utilized in the future to impact positively on the treatment of microbial, resistant infections.
Lysosomes are acidic organelles that are involved in cellular digestion by endocy- tosis, phagocytosis, and autophagy. They contain more than 50 hydrolases that are capable of degrading all macromolecules. There is accumulating evidence that lysosomal enzymes can provoke apoptotic cell death. This has important implications for cancer, where proapoptotic genes are mutated and antiapoptotic genes are often overexpressed leading to chemoresistance. Lysosomes play a dual role in cancer development depending on their subcellular localization. When they are located extracellularly they can promote invasion, angiogenesis, and metastasis. However, when they are located intracellularly they can trigger apoptosis by leaking into the cytosol. In this review, we examine the pathways by which lysosomes can evoke both apoptosis and tumorigenesis. Although cancer cells have defects in their apoptotic machinery, they can still undergo lysosomal cell death. We offer several strategies to explain how targeting lysosomes can serve as a putative model for the development of novel anticancer agents. Furthermore, we propose that lysosomal cell death is an effective treatment against apoptosis-resistant can- cer cells and thus holds great potential as a therapeutic strategy for circumventing apoptosis deficiency in tumors.
