Rectification properties of conically shaped nanopores: consequences of miniaturization

Nanopores attracted a great deal of scientific interest as templates for biological sensors as well as model systems to understand transport phenomena at the nanoscale. The experimental and theoretical analysis of nanopores has been so far focused on understanding the effect of the pore opening diameter on ionic transport. In this article we present systematic studies on the dependence of ion transport properties on the pore length. Particular attention was given to the effect of ion current rectification exhibited for conically shaped nanopores with homogeneous surface charges. We found that reducing the length of conically shaped nanopores significantly lowered their ability to rectify ion current. However, rectification properties of short pores can be enhanced by tailoring the surface charge and the shape of the narrow opening. Furthermore we analyze the relationship of the rectification behavior and ion selectivity for different pore lengths. All simulations were performed using MsSimPore, a software package for solving the Poisson-Nernst-Planck (PNP) equations. It is based on a novel finite element solver and allows for simulations up to surface charge densities of -2 e/nm^2. MsSimPore is based on 1D reduction of the PNP model, but allows for a direct treatment of the pore with bulk electrolyte reservoirs, a feature which was previously used in higher dimensional models only. MsSimPore includes these reservoirs in the calculations; a property especially important for short pores, where the ionic concentrations and the electric potential vary strongly inside the pore as well as in the regions next to pore entrance

Myeloid STAT3 promotes formation of colitis-associated colorectal cancer in mice

Myeloid cells lacking STAT3 promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deleted STAT3 in murine myeloid cells (STAT3(Δm)) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3(Δm) mice. Gene expression profiling showed strong activation of T cells in the stroma of STAT3(Δm) CRCs. Moreover, STAT3(Δm) host mice were better able to control the growth of transplanted MC38 colorectal tumor cells which are known to be killed in a T cell-dependent manner. These data suggest that myeloid cells lacking STAT3 control formation of CRCs mainly via cross activation of T cells. Interestingly, the few CRCs that formed in STAT3(Δm) mice displayed enhanced stromalization but appeared normal in size indicating that they have acquired ways to escape enhanced tumor surveillance. We found that CRCs in STAT3(Δm) mice consistently activate STAT3 signaling which is implicated in immune evasion and might be a target to prevent tumor relapse

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Umsetzung von Biosicherheitsmassnahmen durch Klauenpfleger in der Schweiz

Biosicherheit umfasst im Zusammenhang mit Tierhaltung alle Massnahmen zur Verhinderung der Einschleppung von Krankheitserregern in einen Betrieb (externe Biosicherheit) und der Krankheitserregerverbreitung innerhalb eines Betriebs (interne Biosicherheit). Als wichtiger Risikofaktor für die Ausbreitung von Infektionskrankheiten gilt überbetrieblich arbeitendes Fachpersonal, zu dem auf Schweizer Rindviehbetrieben professionelle Klauenpfleger gehören. Um einen Überblick über die Umsetzung von Biosicherheitsmassnahmen durch Klauenpfleger zu geben, wurden in der vorliegenden Studie 49 Klauenpfleger, die am Schweizer Klauengesundheitsprogramm teilnahmen, zu diesem Thema von zwei Tierärzten befragt und während der Klauenpflege beobachtet. Die Datenbearbeitung erfolgte mit Hilfe eines Scoringsystems, wobei den verschiedenen Arbeitsweisen unter Berücksichtigung des angenommenen Übertragungspotenzials der Infektionskrankheiten Dermatitis digitalis (DD) und Salmonellose Punkte zugeteilt wurden. Die Arbeitsweise, die die ideale Biosicherheitsmassnahme darstellt, erhielt immer einen ganzen Punkt, weniger optimale Arbeitsweisen dagegen einen Zwischenwert oder keinen Punkt. Mithilfe des Scoringsystems konnten die Stärken und Defizite der Klauenpfleger bezüglich Biosicherheit genau benannt werden. Insgesamt ist der Implementierungsgrad von Biosicherheitsmassnahmen durch Klauenpfleger recht niedrig (53 %=Mittelwert des allgemeinen Gesamtbiosicherheitsscores der 49 Klauenpfleger). Klauenpfleger, die häufiger fachbezogene Fortbildungen besuchten, wiesen tendenziell einen höheren Umsetzungsgrad von Biosicherheitsmassnahmen auf. Die Antworten der Klauenpfleger und die Beobachtungen der Tierärzte wurden zudem miteinander verglichen, wobei festgestellt wurde, dass sich die Klauenpfleger meist selbst besser bezüglich Biosicherheit einschätzten als die Tierärzte sie beurteilten. Zusammenfassend ist unter Berücksichtigung der Ergebnisse dieser Studie die Verschleppung von Krankheitserregern wie DD-assoziierten Treponemen und Salmonellen im Rahmen der überbetrieblichen Klauenpflege möglich. In zukünftigen Aus- und Fortbildungen sollte daher ein Schwerpunkt auf Biosicherheit gelegt werden. Keywords: Biosicherheit; Fragebogen; Klauenpflege; Rindvieh; Scoringsystem; biosecurity; biosicurezza; biosécurité; bovin; bovini; cattle; cura degli zoccoli; hoof trimming; parage des onglons; questionario; questionnaire; scoring system; sistema di punteggio; système de notation