Richard K. Zimmer
Bio: Richard K. Zimmer is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: Sperm & Sperm chemotaxis. The author has an hindex of 25, co-authored 53 publications receiving 2597 citations. Previous affiliations of Richard K. Zimmer include University of Queensland & University of California.
Papers published on a yearly basis
TL;DR: Results indicate that hOR17-4 functions in human sperm chemotaxis and may be a critical component of the fertilization process, as well as a strong chemoattractant in subsequent behavioral bioassays.
Abstract: Although it has been known for some time that olfactory receptors (ORs) reside in spermatozoa, the function of these ORs is unknown. Here, we identified, cloned, and functionally expressed a previously undescribed human testicular OR, hOR17-4. With the use of ratiofluorometric imaging, Ca2+ signals were induced by a small subset of applied chemical stimuli, establishing the molecular receptive fields for the recombinantly expressed receptor in human embryonic kidney (HEK) 293 cells and the native receptor in human spermatozoa. Bourgeonal was a powerful agonist for both recombinant and native receptor types, as well as a strong chemoattractant in subsequent behavioral bioassays. In contrast, undecanal was a potent OR antagonist to bourgeonal and related compounds. Taken together, these results indicate that hOR17-4 functions in human sperm chemotaxis and may be a critical component of the fertilization process.
TL;DR: There are now vast new opportunities for determining how organisms respond to chemical signals and employ chemical defenses under environmentally realistic conditions, and integrating findings within a larger ecological and evolutionary framework should lead to improved understanding of natural physicochemical phenomena that constrain biological responses at the individual, population, and community levels of organization.
Abstract: Understanding the mechanisms by which environmental chemical signals, chemical defenses, and other chemical agents mediate various life-history processes can lead to important insights about the forces driving the ecology and evolution of marine systems. For chemical signals released into the environment, establishing the principles that mediate chemical production and transport is critical for interpreting biological responses to these stimuli within appropriate natural, historical contexts. Recent technological advancements provide outstanding opportunities for new discoveries, thus allowing quantification of interactions between hydrodynamic, chemical, and biological factors at numerous spatial and temporal scales. Past work on chemically mediated processes involving organisms and their environment have emphasized habitat colonization by larvae and trophic relationships. Future research priorities should include these topics as well as courtship and mating, fertilization, competition, symbiosis, and mi...
TL;DR: Evidence is provided that hOR17-4 activation is coupled to a cAMP-mediated signaling cascade and particulate AC is required for induction of hOR 17-4-mediated human sperm behavior and represents a promising target for future design of contraceptive drugs.
Abstract: Human sperm chemotaxis is a critical component of the fertilization process, but the molecular basis for this behavior remains unclear. Recent evidence shows that chemotactic responses depend on activation of the sperm olfactory receptor, hOR17-4. Certain floral scents, including bourgeonal, activate hOR17-4, trigger pronounced Ca(2+) fluxes, and evoke chemotaxis. Here, we provide evidence that hOR17-4 activation is coupled to a cAMP-mediated signaling cascade. Multidimensional protein identification technology was used to identify potential components of a G-protein-coupled cAMP transduction pathway in human sperm. These products included various membrane-associated adenylate cyclase (mAC) isoforms and the G(olf)-subunit. Using immunocytochemistry, specific mAC isoforms were localized to particular cell regions. Whereas mAC III occurred in the sperm head and midpiece, mAC VIII was distributed predominantly in the flagellum. In contrast, G(olf) was found mostly in the flagellum and midpiece. The observed spatial distribution patterns largely correspond to the spatiotemporal character of hOR17-4-induced Ca(2+) changes. Behavioral and Ca(2+) signaling responses of human sperm to bourgeonal were bioassayed in the presence, or absence, of the adenylate cyclase antagonist SQ22536. This specific agent inhibits particulate AC, but not soluble AC, activation. Upon incubation with SQ22536, cells ceased to exhibit Ca(2+) signaling, chemotaxis, and hyperactivation (faster swim speed and flagellar beat rate) in response to bourgeonal. Particulate AC is therefore required for induction of hOR17-4-mediated human sperm behavior and represents a promising target for future design of contraceptive drugs.
TL;DR: Relationships between hydrodynamic and chemical properties of the environ- ment and foraging success and efficiency suggest that variation in the physicochemical environment can influence the detectability of prey and strategies employed by foragers.
Abstract: The physicochemical environment can strongly constrain the outcome of ecological interactions such as predation, mating, and competition. This is especially true of processes mediated by the sense of olfaction, because wind and water currents control the dispersal of odor signals and act as ancillary cues during odor plume following. In the field, we examined how variations in the physical and chemical properties of odor plumes would alter the foraging behavior of the blue crab Callinectes sapidus, a common predator/ scavenger in tidal marsh creeks in the southeastern United States. We video-recorded re- sponses of naturally foraging crabs to odor plumes of varying composition and odor release rate (characteristic of clams of differing size). During each trial we presented crabs with an experimental plume that was a mixture of fluorescein-dyed seawater and clam mantle fluid, oyster mantle fluid, or a suite of amino acids, and a control plume which consisted of dyed seawater only. In addition to manipulating the chemical composition and odor release rate of the plume, we allowed flow speed to vary naturally with the tide. We tested for effects of odor composition, odor release rate, and flow speed on the success (i.e., finding the target) and efficiency (i.e., search path direction) of blue crab foraging. Mantle fluid solutions and wounded prey items elicited active search and upstream walking, while control and amino acid solutions had no effect on crab behavior. Odors released at a low rate (either low volume flow or low concentration) elicited fewer responses from crabs, and the resulting search was less efficient and less successful than responses to odors released at higher rates. Ambient current speed also affected both search success and efficiency. There was a decline in search success when current speed in the tidal channel was below 1 cm/s; search success remained constantly high, however, when current speed was above this threshold. Search efficiency was directly proportional to ambient current speeds. Such relationships between hydrodynamic and chemical properties of the environ- ment and foraging success and efficiency suggest that variation in the physicochemical environment can influence the detectability of prey and strategies employed by foragers. These results extend beyond the foraging of marine crustaceans into other olfactory- mediated interactions and habitats.
TL;DR: Analytical and numerical models were used to estimate the propulsive force generated by sperm swimming (Fswim) and the shear force produced by fluid motion within the vicinity of a rotating egg (Fshear), and male gametes were modeled as prolate spheroids to explain sperm–egg interactions.
Abstract: SUMMARY Fertilization is a complex interaction among biological traits of gametes and physical properties of the fluid environment. At the scale of fertilization (0.01–1 mm), sperm encounter eggs while being transported within a laminar (or viscous) shear flow. Varying laminar-shear in a Taylor-Couette flow tank, our experiments simulated important aspects of small-scale turbulence within the natural habitats of red abalone ( Haliotis rufescens ), a large marine mollusk and external fertilizer. Behavioral interactions between individual cells, sperm–egg encounter rates, and fertilization success were quantified, simultaneously, using a custom-built infrared laser and computer-assisted video imaging system. Relative to still water, sperm swam faster and moved towards an egg surface, but only in comparatively slow flows. Encounter rate, swim speed and orientation, and fertilization success each peaked at the lowest shear tested (0.1 s –1 ), and then decayed as shear increased beyond 1.0 s –1 . The decay did not result, however, from damage to either sperm or eggs. Analytical and numerical models were used to estimate the propulsive force generated by sperm swimming ( F swim ) and the shear force produced by fluid motion within the vicinity of a rotating egg ( F shear ). To first order, male gametes were modeled as prolate spheroids. The ratio F swim / F shear was useful in explaining sperm–egg interactions. At low shears where F swim / F shear >1, sperm swam towards eggs, encounter rates were pronounced, and fertilization success was very high; behavior overpowered fluid motion. In contrast, sperm swimming, encounter rate and fertilization success all decayed rapidly when F swim / F shear <1; fluid motion dominated behavior. The shears maximizing fertilization success in the lab typically characterized natural flow microenvironments of spawning red abalone. Gamete behavior thus emerges as a critical determinant of sexual reproduction in the turbulent sea.
TL;DR: This article aims to provide a comprehensive overview of the five main human GPCR families with a focus on gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.
Abstract: G protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and also the targets of many drugs. Understanding of the functional significance of the wide structural diversity of GPCRs has been aided considerably in recent years by the sequencing of the human genome and by structural studies, and has important implications for the future therapeutic potential of targeting this receptor family. This article aims to provide a comprehensive overview of the five main human GPCR families--Rhodopsin, Secretin, Adhesion, Glutamate and Frizzled/Taste2--with a focus on gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.
TL;DR: Knowledge of the biology of sperm transport can inspire improvements in artificial insemination, IVF, the diagnosis of infertility and the development of contraceptives.
Abstract: At coitus, human sperm are deposited into the anterior vagina, where, to avoid vaginal acid and immune responses, they quickly contact cervical mucus and enter the cervix. Cervical mucus filters out sperm with poor morphology and motility and as such only a minority of ejaculated sperm actually enter the cervix. In the uterus, muscular contractions may enhance passage of sperm through the uterine cavity. A few thousand sperm swim through the uterotubal junctions to reach the Fallopian tubes (uterine tubes, oviducts) where sperm are stored in a reservoir, or at least maintained in a fertile state, by interacting with endosalpingeal (oviductal) epithelium. As the time of ovulation approaches, sperm become capacitated and hyperactivated, which enables them to proceed towards the tubal ampulla. Sperm may be guided to the oocyte by a combination of thermotaxis and chemotaxis. Motility hyperactivation assists sperm in penetrating mucus in the tubes and the cumulus oophorus and zona pellucida of the oocyte, so that they may finally fuse with the oocyte plasma membrane. Knowledge of the biology of sperm transport can inspire improvements in artificial insemination, IVF, the diagnosis of infertility and the development of contraceptives.
University of Marburg1, University of Erlangen-Nuremberg2, Rovira i Virgili University3, Max Planck Society4, University of Göttingen5, University of California, Los Angeles6, International School for Advanced Studies7, University of Melbourne8, University of Trieste9, Ikerbasque10, University of Toronto11, Nanyang Technological University12, National Institutes of Health13, Stanford University14, Shanghai Jiao Tong University15, Tongji University16, University of Seville17, Karolinska Institutet18, Drexel University19, Sichuan University20, Rice University21, Northwestern University22, University of Basel23, Zhejiang University24, Heidelberg University25, University of Tokyo26, Harvard University27, University of Utah28, University of Michigan29, Swiss Federal Laboratories for Materials Science and Technology30, Seoul National University31, Saarland University32, Columbia University33, Chinese Academy of Sciences34, Kazan Federal University35, Emory University36, University of California, Irvine37, Autonomous University of Barcelona38, University of Massachusetts Amherst39, Pennsylvania State University40, Ghent University41, Imperial College London42, National Tsing Hua University43, South China University of Technology44, University of Ulm45, Hebrew University of Jerusalem46, Huazhong University of Science and Technology47, Peking University48
TL;DR: An overview of recent developments in nanomedicine is provided and the current challenges and upcoming opportunities for the field are highlighted and translation to the clinic is highlighted.
Abstract: The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
TL;DR: It is found that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs), and SCFAs produced by the gut microbiota modulate blood pressure via OlfR78 and Gpr41.
Abstract: Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.
TL;DR: The past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility, but translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples.
Abstract: Reproduction is required for the survival of all mammalian species, and thousands of essential 'sex' genes are conserved through evolution. Basic research helps to define these genes and the mechanisms responsible for the development, function and regulation of the male and female reproductive systems. However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. For other individuals with a known etiology, effective cures are lacking, although their infertility is often bypassed with assisted reproductive technologies (ART), some accompanied by safety or ethical concerns. Certainly, progress in the field of reproduction has been realized in the twenty-first century with advances in the understanding of the regulation of fertility, with the production of over 400 mutant mouse models with a reproductive phenotype and with the promise of regenerative gonadal stem cells. Indeed, the past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility. Translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples. Additionally, new approaches to contraception remain elusive. Nevertheless, the basic and clinical advances in the understanding of the molecular controls of reproduction are impressive and will ultimately improve patient care.