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The Journal of Pediatrics Mar 2021Ciliopathies are a collection of disorders related to cilia dysfunction. Cilia are specialized organelles that project from the surface of most cells. Motile and primary... (Review)
Review
Ciliopathies are a collection of disorders related to cilia dysfunction. Cilia are specialized organelles that project from the surface of most cells. Motile and primary (sensory) cilia are essential structures and have wide ranging functions. Our understanding of the genetics, pathophysiology, and clinical manifestations of motile ciliopathies, including primary ciliary dyskinesia (PCD), has rapidly advanced since the disease was linked to ciliary ultrastructural defects nearly five decades ago. We will provide an overview of different types of cilia, their role in child health and disease, focusing on motile ciliopathies, and describe recent advances that have led to improved diagnostics and may yield therapeutic targets to restore ciliary structure and function.
Topics: Cilia; Ciliary Motility Disorders; Humans
PubMed: 33242470
DOI: 10.1016/j.jpeds.2020.11.040 -
Seminars in Cell & Developmental Biology Feb 2021Polycystic kidney disease (PKD), comprising autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), is... (Review)
Review
Polycystic kidney disease (PKD), comprising autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), is characterized by incessant cyst formation in the kidney and liver. ADPKD and ARPKD represent the leading genetic causes of renal disease in adults and children, respectively. ADPKD is caused by mutations in PKD1 encoding polycystin1 (PC1) and PKD2 encoding polycystin 2 (PC2). PC1/2 are multi-pass transmembrane proteins that form a complex localized in the primary cilium. Predominant ARPKD cases are caused by mutations in polycystic kidney and hepatic disease 1 (PKHD1) gene that encodes the Fibrocystin/Polyductin (FPC) protein, whereas a small subset of cases are caused by mutations in DAZ interacting zinc finger protein 1 like (DZIP1L) gene. FPC is a type I transmembrane protein, localizing to the cilium and basal body, in addition to other compartments, and DZIP1L encodes a transition zone/basal body protein. Apparently, PC1/2 and FPC are signaling molecules, while the mechanism that cilia employ to govern renal tubule morphology and prevent cyst formation is unclear. Nonetheless, recent genetic and biochemical studies offer a glimpse of putative physiological malfunctions and the pathomechanisms underlying both disease entities. In this review, I summarize the results of genetic studies that deduced the function of PC1/2 on cilia and of cilia themselves in cyst formation in ADPKD, and I discuss studies regarding regulation of polycystin biogenesis and cilia trafficking. I also summarize the synergistic genetic interactions between Pkd1 and Pkhd1, and the unique tissue patterning event controlled by FPC, but not PC1. Interestingly, while DZIP1L mutations generate compromised PC1/2 cilia expression, FPC deficiency does not affect PC1/2 biogenesis and ciliary localization, indicating that divergent mechanisms could lead to cyst formation in ARPKD. I conclude by outlining promising areas for future PKD research and highlight rationales for potential therapeutic interventions for PKD treatment.
Topics: Adaptor Proteins, Signal Transducing; Adult; Basal Bodies; Child; Cilia; Drugs, Chinese Herbal; Flavonoids; Gene Expression; Humans; Kidney; Liver; Mutation; Polycystic Kidney, Autosomal Dominant; Polycystic Kidney, Autosomal Recessive; Receptors, Cell Surface; Signal Transduction; TRPP Cation Channels
PubMed: 32475690
DOI: 10.1016/j.semcdb.2020.05.003 -
Best Practice & Research. Clinical... Jul 2020Fertility awareness-based methods (FABMs) of family planning involve monitoring various signs and symptoms of fertility during the menstrual cycle to identify the... (Review)
Review
Fertility awareness-based methods (FABMs) of family planning involve monitoring various signs and symptoms of fertility during the menstrual cycle to identify the "fertile window," or the days of the cycle when unprotected intercourse is most likely to result in pregnancy. Signs and symptoms include menstrual cycle length, basal body temperature, urinary hormone measurements, and/or cervical fluid and may be used alone or in combination. Fertility signs reflect both physiological changes during the menstrual cycle and the life cycle of the ovum and sperm. Women learn to observe or measure and interpret these signs according to the instructions of their chosen FABM and avoid unprotected intercourse on fertile days. FABMs are appropriate for those who choose to use them, are able and willing to observe one or more fertility signs, and are in relationships that support the use of a coitus-related method such as a condom or abstaining from intercourse on fertile days.
Topics: Family Planning Services; Female; Fertility; Health Knowledge, Attitudes, Practice; Humans; Male; Menstrual Cycle; Natural Family Planning Methods; Pregnancy; Sex Education; Spermatozoa
PubMed: 32169418
DOI: 10.1016/j.bpobgyn.2019.12.003 -
Clinical Nutrition (Edinburgh, Scotland) Apr 2021The aim of this paper was to investigate and compare the effects of two iso-energetic hypo-caloric ketogenic hyper-ketonemic and non-ketogenic low carbohydrate high fat... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of calorie restricted low carbohydrate high fat ketogenic vs. non-ketogenic diet on strength, body-composition, hormonal and lipid profile in trained middle-aged men.
BACKGROUND & AIMS
The aim of this paper was to investigate and compare the effects of two iso-energetic hypo-caloric ketogenic hyper-ketonemic and non-ketogenic low carbohydrate high fat high cholesterol diets on body-composition, muscle strength and hormonal profile in experienced resistance-trained middle-aged men.
METHODS
Twenty non-competitive experienced resistance-trained middle-aged men were on the supervised calorie maintenance western diet and resistance-training regimen for 4 weeks and then divided into ketogenic and non-ketogenic groups for 8 weeks period. Keto bodies (β-hydroxybutyrate) levels were measured weekly, testosterone and insulin biweekly, strength and body-composition monthly, lipid profile and blood sugar level at the beginning and at the end of the study.
RESULTS
Both groups lost a similar amount of lean body mass and fat tissue (from F = 248.665, p < 0.001 to F = 21.943, p = 0.001), but preserved maximal upper and lower body strength (from F = 1.772, p = 0.238 to F = 0.595, p = 0.577). Basal testosterone and free testosterone increased (from F = 37.267, p = 0.001 to F = 16.261, p = 0.005) and insulin levels decreased significantly in both groups (F = 27.609, p = 0.001; F = 54.256, p < 0.001, respectively). No differences in lipid profile and blood sugar level were found (from F = 4.174, p = 0.058, to F = 0.065, p = 0.802).
CONCLUSIONS
Ketogenic diet with sustained hyper-ketonemia above 1 mol/l has the same impact as low carbohydrate non-ketogenic diet on muscle strength, body-composition, and hormonal and lipid profile in hypo-caloric dietary conditions in strength-trained middle-aged men.
Topics: Adult; Blood Glucose; Body Composition; Caloric Restriction; Diet, Ketogenic; Energy Intake; Healthy Volunteers; Humans; Insulin; Lipids; Male; Muscle Strength; Resistance Training; Sports Nutritional Physiological Phenomena; Testosterone; Weight Loss
PubMed: 33743284
DOI: 10.1016/j.clnu.2021.02.028 -
Current Opinion in Cell Biology Aug 2022Multiciliated cells (MCC) are evolutionary conserved, highly specialized cell types that contain dozens to hundreds of motile cilia that they use to propel fluid... (Review)
Review
Multiciliated cells (MCC) are evolutionary conserved, highly specialized cell types that contain dozens to hundreds of motile cilia that they use to propel fluid directionally. To template these cilia, each MCC produces between 30 and 500 basal bodies via a process termed centriole amplification. Much progress has been made in recent years in understanding the pathways involved in MCC fate determination, differentiation, and ciliogenesis. Recent studies using mammalian cell culture systems, mice, Xenopus, and other model organisms have started to uncover the mechanisms involved in centriole and cilia biogenesis. Yet, how MCC progenitor cells regulate the precise number of centrioles and cilia during their differentiation remains largely unknown. In this review, we will examine recent findings that address this fundamental question.
Topics: Animals; Cell Differentiation; Centrioles; Cilia; Mammals; Mice; Xenopus laevis
PubMed: 35716530
DOI: 10.1016/j.ceb.2022.102105 -
Trends in Cell Biology Aug 2020Centrioles organize the microtubule network and mitotic spindle and, as basal bodies, nucleate cilia and flagella. They undergo a beguiling process in which one appears...
Centrioles organize the microtubule network and mitotic spindle and, as basal bodies, nucleate cilia and flagella. They undergo a beguiling process in which one appears to give rise to another and at a baffling orthogonal geometry. Nucleic acid-based replication has been pondered during cycles of zeniths and nadirs of plausibility, the latter now the state. Centrioles can also arise de novo, and thus the longstanding focus on centriole 'replication' may have led us astray from ground truth. We are in an era in which the assembly pathways of most intracellular machines are becoming understood in considerable detail. But apart from knowing the structure and parts list, little in our extant knowledge conveys how centrioles arise. Here the matters at hand are summarized, and a siren call is sounded.
Topics: Animals; Ascaris; Centrioles; Ferns; Humans; Nucleic Acids
PubMed: 32456848
DOI: 10.1016/j.tcb.2020.05.001 -
Sub-cellular Biochemistry 2022Cilia are tail-like organelles responsible for motility, transportation, and sensory functions in eukaryotic cells. Cilia research has been providing multifaceted...
Cilia are tail-like organelles responsible for motility, transportation, and sensory functions in eukaryotic cells. Cilia research has been providing multifaceted questions, attracting biologists of various areas and inducing interdisciplinary studies. In this chapter, we mainly focus on efforts to elucidate the molecular mechanism of ciliary beating motion, a field of research that has a long history and is still ongoing. We also overview topics closely related to the motility mechanism, such as ciliogenesis, cilia-related diseases, and sensory cilia. Subnanometer-scale to submillimeter-scale 3D imaging of the axoneme and the basal body resulted in a wide variety of insights into these questions.
Topics: Axoneme; Cilia; Flagella
PubMed: 36151386
DOI: 10.1007/978-3-031-00793-4_15