Renal and extrarenal regulation of potassium

The ISN Forefronts in Nephrology Symposium took place 8–11 September 2005 in Kartause Ittingen, Switzerland. It was dedicated to the memory of Robert W. Berliner, who died at age 86 on 5 February 2002. Dr Berliner contributed in a major way to our understanding of potassium transport in the kidney. Starting in the late 1940s, without knowledge of how potassium was transported across specific nephron segments and depending only on renal clearance methods, he and his able associates provided a still-valid blueprint of the basic transport properties of potassium handling by the kidney. They firmly established that potassium was simultaneously reabsorbed and secreted along the nephron; that variations in secretion in the distal nephron segments play a major role in regulating potassium excretion; and that such secretion is modulated by sodium, acid–base factors, hormones, and diuretics. These conclusions were presented in a memorable Harvey Lecture some forty years ago, and they have remained valid ever since. The concepts have also provided the foundation and stimulation for later work on single nephrons, tubule cells, and transport proteins involved in potassium transport

Chiral sedimentation of extended objects in viscous media

We study theoretically the chirality of a generic rigid object's sedimentation in a fluid under gravity in the low Reynolds number regime. We represent the object as a collection of small Stokes spheres or stokeslets, and the gravitational force as a constant point force applied at an arbitrary point of the object. For a generic configuration of stokeslets and forcing point, the motion takes a simple form in the nearly free draining limit where the stokeslet radius is arbitrarily small. In this case, the internal hydrodynamic interactions between stokeslets are weak, and the object follows a helical path while rotating at a constant angular velocity $\omega$ about a fixed axis. This $\omega$ is independent of initial orientation, and thus constitutes a chiral response for the object. Even though there can be no such chiral response in the absence of hydrodynamic interactions between the stokeslets, the angular velocity obtains a fixed, nonzero limit as the stokeslet radius approaches zero. We characterize empirically how $\omega$ depends on the placement of the stokeslets, concentrating on three-stokeslet objects with the external force applied far from the stokeslets. Objects with the largest $\omega$ are aligned along the forcing direction. In this case, the limiting $\omega$ varies as the inverse square of the minimum distance between stokeslets. We illustrate the prevalence of this robust chiral motion with experiments on small macroscopic objects of arbitrary shape.Comment: 35 pages, 10 figures; Section VII.A redone and other edits made for clarity. Accepted by Phys. Rev.

Unusual electronic ground state of a prototype cuprate: band splitting of single CuO_2-plane Bi_2 Sr_(2-x) La_x CuO_(6+delta)

By in-situ change of polarization a small splitting of the Zhang-Rice singlet state band near the Fermi level has been resolved for optimum doped (x=0.4) Bi$_{2}$Sr$_{2-x}$La$_{x}$CuO$_{6+\delta}$ at the (pi,0)-point (R.Manzke et al. PRB 63, R100504 (2001). Here we treat the momentum dependence and lineshape of the split band by photoemission in the EDC-mode with very high angular and energy resolution. The splitting into two destinct emissions could also be observed over a large portion of the major symmetry line $\Gamma$M, giving the dispersion for the individual contributions. Since bi-layer effects can not be present in this single-layer material the results have to be discussed in the context of one-particle removal spectral functions derived from current theoretical models. The most prominent are microscopic phase separation including striped phase formation, coexisting antiferromagnetic and incommensurate charge-density-wave critical fluctuations coupled to electrons (hot spots) or even spin charge separation within the Luttinger liquid picture, all leading to non-Fermi liquid like behavior in the normal state and having severe consequences on the way the superconducting state forms. Especially the possibilty of observing spinon and holon excitations is discussed.Comment: 5 pages, 4 figure

Bloody Women: A critical-creative examination of how female protagonists have transformed contemporary Scottish and Nordic crime fiction

This study will explore the role of female authors and their female protagonists in contemporary Scottish and Nordic crime fiction. Authors including Val McDermid, Denise Mina, Lin Anderson and Liza Marklund are just a few of the women who have challenged the expectation of gender in the crime fiction genre. By setting their novels in contemporary society, they reflect a range of social and political issues through the lens of a female protagonist. By closely examining the female characters, all journalists, in Val McDermid’s Lindsay Gordon series; Denise Mina’s Paddy Meehan series; Anna Smith’s books about Rosie Gilmour; and Liza Marklund’s books about Annika Bengzton, I explore the issue of gender through these writers’ perspectives and also draw parallels between their societies. I document the influence of these writers on my own practice-based research, a novel, The Invisible Chains, set in post-Referendum Scotland. The thesis will examine and define the role of the female protagonist, offer a feminist reading of contemporary crime fiction, and investigate how the rise of human trafficking, the problem of domestic abuse in Scotland and society’s changing attitudes and values are reflected in contemporary crime novels, before discussing the narrative structures and techniques employed in the writing of The Invisible Chains. This novel allows us to consider the role of women in a contemporary and progressive society where women hold many senior positions in public life and examine whether they manage successfully to challenge traditional patriarchal hierarchies. The narrative is split between journalist Megan Ross, The Girl, a victim of human trafficking, and Trudy, who is being domestically abused, thus pulling together the themes of the critical genesis in the creative work. By focusing on the protagonist, the victims and raising awareness of human trafficking and domestic abuse, The Invisible Chains, an original creative work, reflects a contemporary society’s changing attitudes, problems and values

Leveraging large-deviation statistics to decipher the stochastic properties of measured trajectories

Extensive time-series encoding the position of particles such as viruses, vesicles, or individual proteins are routinely garnered in single-particle tracking experiments or supercomputing studies. They contain vital clues on how viruses spread or drugs may be delivered in biological cells. Similar time-series are being recorded of stock values in financial markets and of climate data. Such time-series are most typically evaluated in terms of time-averaged mean-squared displacements (TAMSDs), which remain random variables for finite measurement times. Their statistical properties are different for different physical stochastic processes, thus allowing us to extract valuable information on the stochastic process itself. To exploit the full potential of the statistical information encoded in measured time-series we here propose an easy-to-implement and computationally inexpensive new methodology, based on deviations of the TAMSD from its ensemble average counterpart. Specifically, we use the upper bound of these deviations for Brownian motion (BM) to check the applicability of this approach to simulated and real data sets. By comparing the probability of deviations for different data sets, we demonstrate how the theoretical bound for BM reveals additional information about observed stochastic processes. We apply the large-deviation method to data sets of tracer beads tracked in aqueous solution, tracer beads measured in mucin hydrogels, and of geographic surface temperature anomalies. Our analysis shows how the large-deviation properties can be efficiently used as a simple yet effective routine test to reject the BM hypothesis and unveil relevant information on statistical properties such as ergodicity breaking and short-time correlations. Video Abstract Video Abstract: Leveraging large-deviation statistics to decipher the stochastic properties of measured trajectorie

Super-resolution imaging of live sperm reveals dynamic changes of the actin cytoskeleton during acrosomal exocytosis

Filamentous actin (F-actin) is a key factor in exocytosis in many cell types. In mammalian sperm, acrosomal exocytosis (denoted the acrosome reaction or AR), a special type of controlled secretion, is regulated by multiple signaling pathways and the actin cytoskeleton. However, the dynamic changes of the actin cytoskeleton in live sperm are largely not understood. Here, we used the powerful properties of SiR-actin to examine actin dynamics in live mouse sperm at the onset of the AR. By using a combination of super-resolution microscopy techniques to image sperm loaded with SiR-actin or sperm from transgenic mice containing Lifeact-EGFP, six regions containing F-actin within the sperm head were revealed. The proportion of sperm possessing these structures changed upon capacitation. By performing live-cell imaging experiments, we report that dynamic changes of F-actin during the AR occur in specific regions of the sperm head. While certain F-actin regions undergo depolymerization prior to the initiation of the AR, others remain unaltered or are lost after exocytosis occurs. Our work emphasizes the utility of live-cell nanoscopy, which will undoubtedly impact the search for mechanisms that underlie basic sperm functions.Fil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Velasco Félix, Ángel G.. Universidad Nacional Autónoma de México; MéxicoFil: Rodriguez, Paulina Torres. Universidad Nacional Autónoma de México; MéxicoFil: Gervasi, Mar?á G.. University Of Massachusetts Amherst;Fil: Xu, Xinran. School Of Biomedical Engineering;Fil: Luque, Guillermina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Contreras-Jiménez, Gastón. Universidad Nacional Autónoma de México; MéxicoFil: Sánchez-Cárdenas, Claudia. Universidad Nacional Autónoma de México; MéxicoFil: Ramírez-Gómez, Héctor V.. Universidad Nacional Autónoma de México; MéxicoFil: Krapf, Diego. School Of Biomedical Engineering;Fil: Visconti, Pablo E.. University Of Massachusetts Amherst;Fil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Guerrero, Adán. Universidad Nacional Autónoma de México; MéxicoFil: Darszon, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Cdc42 localized in the CatSper signaling complex regulates cAMP‐dependent pathways in mouse sperm

Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca2+ transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 distribution in the principal piece is confined to four linear domains and this localization is disrupted in CatSper1-null sperm. Cdc42 inhibition impaired CatSper activity and other Ca2+-dependent downstream events resulting in a severe compromise of the sperm fertilizing potential. We also demonstrate that Cdc42 is essential for CatSper function by modulating cAMP production by soluble adenylate cyclase (sAC), providing a new regulatory mechanism for the stimulation of CatSper by the cAMP-dependent pathway. These results reveal a broad mechanistic insight into the regulation of Ca2+ in mammalian sperm, a matter of critical importance in male infertility as well as in contraception.Fil: Luque, Guillermina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Xu, Xinran. State University of Colorado - Fort Collins; Estados UnidosFil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. State University of Colorado - Fort Collins; Estados UnidosFil: Gervasi, María G.. University of Massachussets; Estados UnidosFil: Orta, Gerardo. Universidad Autonoma de México. Instituto de Biotecnología; MéxicoFil: De la Vega Beltrán, José L.. Universidad Autonoma de México. Instituto de Biotecnología; MéxicoFil: Stival, Cintia Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Gilio, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Visconti, Pablo E.. University of Massachussets; Estados UnidosFil: Krapf, Diego. State University of Colorado - Fort Collins; Estados UnidosFil: Darszon, Alberto. Universidad Autonoma de México. Instituto de Biotecnología; MéxicoFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Spectral content of a single non-Brownian trajectory

Time-dependent processes are often analysed using the power spectral density (PSD), calculated by taking an appropriate Fourier transform of individual trajectories and finding the associated ensemble-average. Frequently, the available experimental data sets are too small for such ensemble averages, and hence it is of a great conceptual and practical importance to understand to which extent relevant information can be gained from $S(f,T)$, the PSD of a single trajectory. Here we focus on the behavior of this random, realization-dependent variable, parametrized by frequency $f$ and observation-time $T$, for a broad family of anomalous diffusions---fractional Brownian motion (fBm) with Hurst-index $H$---and derive exactly its probability density function. We show that $S(f,T)$ is proportional---up to a random numerical factor whose universal distribution we determine---to the ensemble-averaged PSD. For subdiffusion ($H<1/2$) we find that $S(f,T)\sim A/f^{2H+1}$ with random-amplitude $A$. In sharp contrast, for superdiffusion $(H>1/2)$ $S(f,T)\sim BT^{2H-1}/f^2$ with random amplitude $B$. Remarkably, for $H>1/2$ the PSD exhibits the same frequency-dependence as Brownian motion, a deceptive property that may lead to false conclusions when interpreting experimental data. Notably, for $H>1/2$ the PSD is ageing and is dependent on $T$. Our predictions for both sub- and superdiffusion are confirmed by experiments in live cells and in agarose hydrogels, and by extensive simulations.Comment: 13 pages, 5 figures, Supplemental Material can be found at https://journals.aps.org/prx/supplemental/10.1103/PhysRevX.9.011019/prx_SM_final.pd