Influence of activity in a heterogeneous environment on the dynamics of fish growth: an individual-based model of roacl

A spatio-temporal individual-based model (IBM), including bioenergetic principles, is used to investigate how energy costs coupled to activity represent a variable fraction in a heterogeneous environment and how this is related to another energetic criterion, the potential individual growth, under the conditions of a structured environment. With this approach, it is possible to connect simulated spatio-temporal activity patterns with the energetic needs required for these activities. By using simple foraging rules and a modified random walk model it is possible to reproduce spatial distributions and length frequency distributions. The simulated spatial distribution of roach Rutilus rutilus in Lake Belau, Germany, results in a mean weekly activity multiplier [(standard metabolic rate + activity costs) (standard metabolic rate)⁻¹] of 1–9 with deviations >100% during a simulated year. These deviations are of key importance to differences in the growth rate of individual simulated roach.     

酵母鉴定程序在酵母分类鉴定中的应用

本文介绍了Barnett等1985年编制并由剑桥大学发行的计算机软件《酵母鉴定程序》,以及如何使用该程序在IBM PC DOS操作系统上进行酵母菌的分类鉴定。我们使用该程序对从云南鸡足山和紫金山两地森林土壤中分离到的82株酵母菌进行了分类鉴定,其中:鉴定到种的有47株,占总株数的57.3％;鉴定到属但未能直接定到种的有21株,占总株数的25.6％;暂未定名的有14株,占总株数的17.1％。     

Computational analysis of a flapping uvula on aerodynamics and pharyngeal wall collapsibility in sleep apnea

Studying the airflows and the resultant aerodynamic pressure/force in the pharyngeal airway is critical for understanding the pathophysiology of snoring and sleep apnea. In this work, an experiment-driven computational study was conducted to examine the aerodynamics in human pharyngeal airway. An anatomically accurate pharynx model associated with different uvula kinematics was reconstructed from human magnetic resonance image (MRI) and high-speed photography. An immersed-boundary-method (IBM)-based direct numerical simulation (DNS) flow solver was adopted to simulate the corresponding unsteady flows in all their complexity. Analyses were performed on vortex dynamics and pressure fluctuations in the pharyngeal airway and force oscillations on the pharyngeal wall under the influence of varying airway obstructions, uvula flapping mode, and uvula flapping frequencies. It was found the vortex formation, aerodynamic pressure, and pharyngeal wall force were significantly affected by the width of the pharyngeal airway. By contrast, the influences from the uvula flapping mode were insignificant when other parameters were similar. Fast Fourier transformation (FFT) and continuous wavelet transform (CWT) analysis of the pressure time history revealed the existence of higher order harmonics of base frequency with significant pressure amplitudes and energy intensities. It was also found the airway pressure and pharyngeal wall force oscillate more dramatically at higher uvula flapping frequencies, which tends to promote the collapse of pharyngeal wall and initiates sleep apnea.     

Quality Control of Membraneless Organelles

The formation of membraneless organelles (MLOs) by phase separation has emerged as a new way of organizing the cytoplasm and nucleoplasm of cells. Examples of MLOs forming via phase separation are nucleoli in the nucleus and stress granules in the cytoplasm. The main components of these MLOs are macromolecules such as RNAs and proteins. In order to assemble by phase separation, these proteins and RNAs have to undergo many cooperative interactions. These cooperative interactions are supported by specific molecular features within phase-separating proteins, such as multivalency and the presence of disordered domains that promote weak and transient interactions. However, these features also predispose phase-separating proteins to aberrant behavior. Indeed, evidence is emerging for a strong link between phase-separating proteins, MLOs, and age-related diseases. In this review, we discuss recent progress in understanding the formation, properties, and functions of MLOs. We pay special attention to the emerging link between MLOs and age-related diseases, and we explain how changes in the composition and physical properties of MLOs promote their conversion into an aberrant state. Furthermore, we discuss the key role of the protein quality control machinery in regulating the properties and functions of MLOs and thus in preventing age-related diseases.     

Phase separation in chlorophyll a containing dipalmitoyllecithin vesicles. A fluorescence and photoacoustic study

Chlorophyll a was incorporated into dipalmitoyllecithin vesicles in different concentrations. Depending on the physical state of the lipid, the chlorophyll can aggregate into domains. This phase separation was demonstrated by fluorescence as well as by photoacoustic measurements.     

Structural Basis for Bivalent Smac-Mimetics Recognition in the IAP Protein Family

XIAP is an apoptotic regulator protein that binds to the effector caspases -3 and -7 through its BIR2 domain, and to initiator caspase-9 through its BIR3 domain. Molecular docking studies suggested that Smac-DIABLO may antagonize XIAP by concurrently targeting both BIR2 and BIR3 domains; on this basis bivalent Smac-mimetic compounds have been proposed and characterized. Here, we report the X-ray crystal structure of XIAP-BIR3 domain in complex with a two-headed compound (compound 3) with improved efficacy relative to its monomeric form. A small-angle X-ray scattering study of XIAP-BIR2BIR3, together with fluorescence polarization binding assays and compound 3 cytotoxicity tests on HL60 leukemia cell line are also reported. The crystal structure analysis reveals a network of interactions supporting XIAP-BIR3/compound 3 recognition; moreover, analytical gel-filtration chromatography shows that compound 3 forms a 1:1 stoichiometric complex with a XIAP protein construct containing both BIR2 and BIR3 domains. On the basis of the crystal structure and small-angle X-ray scattering, a model of the same BIR2-BIR3 construct bound to compound 3 is proposed, shedding light on the ability of compound 3 to relieve XIAP inhibitory effects on caspase-9 as well as caspases -3 and -7. A molecular modeling/docking analysis of compound 3 bound to cIAP1-BIR3 domain is presented, considering that Smac-mimetics have been shown to kill tumor cells by inducing cIAP1 and cIAP2 ubiquitination and degradation. Taken together, the results reported here provide a rationale for further development of compound 3 as a lead in the design of dimeric Smac mimetics for cancer treatment.     

Distinct roles of the two isoforms of the dynamin-like GTPase Mgm1 in mitochondrial fusion

The mitochondrial dynamin-like GTPase Mgm1 exists as a long (l-Mgm1) and a short isoform (s-Mgm1). They both are essential for mitochondrial fusion. Here we show that the isoforms interact in a homotypic and heterotypic manner. Their submitochondrial distribution between inner boundary membrane and cristae was markedly different. Overexpression of l-Mgm1 exerts a dominant negative effect on mitochondrial fusion. A functional GTPase domain is required only in s-Mgm1 but not in l-Mgm1. We propose that l-Mgm1 acts primarily as an anchor in the inner membrane that in concert with the GTPase activity of s-Mgm1 mediates the fusion of inner membranes.     

Simulation of trait- and density-mediated indirect effects induced by piscivorous predators

The study demonstrates how to use a spatially explicit individual-based model (IBM) to tackle the problem of resolving density-mediated (DMII) and trait-mediated indirect interactions (TMII) when manipulative experimentation is difficult on the scale of community-level interactions in the real word. As an example we simulated predator-induced behavioural changes in a roach (Rutilus rutilus (L.)) population before and after stocking a lake with an additional pelagic predator (Sander lucioperca (L.)). By this it was possible to calculate bioenergetic gains and costs of trait changes as well as the relative proportions of DMIIs and TMIIs in roach consumption on littoral and pelagic resources in the lake food web. Despite higher net activity costs of 64%, roach migrating horizontally over the diel cycle had a net benefit (higher energy intake of 75%) compared to roach that were restricted to the littoral as a behavioural response to the new predator. By separating the components of the indirect predator effects, we demonstrate that a predator-induced modification in prey traits (behaviour, feeding activity) could contribute substantially to the net indirect effect of a predator even when there are strong density effects. When considering the predation pressure by roach on pelagic resources, the net TMIIs due to the behavioural adaptation of the consumer in response to the predator were 13–14 times stronger than the DMIIs alone. When comparing the different effects on littoral resources it can be shown that the TMIIs approximately compensate the DMIIs thus resulting in a nearly zero net effect.

Zusammenfassung

In der vorliegenden Arbeit wurde ein räumlich explizites individuenbasiertes Modell (IBM) verwendet, um dichteabhängige (DMII) und eigenschaftsabhängige (TMII) indirekte Interaktionen zu vergleichen. Da sich dies auf der Ebene der Lebensgemeinschaft unter realen experimentellen Bedingungen als besonders schwierig erwiesen hat, wurden räuberinduzierte Verhaltensänderungen einer Plötzenpopulation (Rutilus rutilus (L.)) vor und nach dem Besatz mit einem zusätzlichen pelagischen Räuber, dem Zander (Sander lucioperca (L.)), simuliert. Dadurch war es möglich, sowohl die energetischen Kosten und Nutzen der räuberinduzierten Verhaltensänderung als auch die relativen Anteile von DMIIs and TMIIs an der Plötzenkonsumtion auf litorale und pelagische Ressourcen innerhalb des Nahrungsnetzes zu kalkulieren. Verglichen mit den Plötzen, welche sich aufgrund des neuen Räubers vor allem im Litoral aufhielten, hatten die täglich (horizontal) wandernden Plötzen trotz höherer Nettoaktivitätskosten von 64% eine größere Energieaufnahme von 75%. Durch die Auflösung der verschiedenen indirekten Räubereffekte konnten wir demonstrieren, dass räuberinduzierte Modifikationen von Beuteeigenschaften (Verhalten, Fraßaktivität) erheblich zu den indirekten Nettoeffekten eines Räubers beitragen können, auch wenn starke dichteabhängige Effekte vorhanden sind. Wenn man die Plötzenkonsumtion auf pelagische Ressourcen betrachtet, so ergeben sich 13-14 fach stärkere TMIIs als DMIIs. Wenn man die verschiedenen Effekte auf litorale Ressourcen vergleicht, zeigt es sich, dass TMIIs die DMIIs kompensieren, wodurch der indirekte Nettoeffekt fast null beträgt.     

A mechanistic insight into SMAC peptide interference with XIAP-Bir2 inhibition of executioner caspases

X-linked inhibitor of apoptosis protein (XIAP) inhibits apoptosis mainly through inhibition of caspase-9 and executioner caspases of -3 and -7. The inhibition of the former protease is implemented through the bacculoviral inhibitory repeat-3 (Bir3) domain, while the inhibition of the latter is accomplished by the interaction of the linker region located between the Bir1 and the Bir2 domains with their active sites. Both modes of inhibition are antagonized by SMAC, which is released from mitochondria during the initiation of the intrinsic apoptosis pathway. Although the mechanism of SMAC interference in Bir3 inhibition of caspase-9 is clearly established, the mechanism by which SMAC interferes with the inhibition of the executioner caspases by XIAP remains largely unknown. To address this issue, we performed a limited proteolysis of glutathione S-transferase (GST)-tagged XIAP-Bir2 by trypsin in the presence and in the absence of SMAC peptide. Under these conditions, the proteolysis of the linker region was diminished considerably. Furthermore, the rate of association of caspase-3 and -7 with XIAP in the presence of the SMAC peptide was reduced drastically, suggesting that SMAC peptide restricts the exposure of the linker region. A limited proteolysis of caspase-7 in the presence of GST-Bir2 and GST-NBir3 (the Bir3 domain of human NAIP) as negative controls was also performed. Matrix-assisted laser desorption/ionization time-of-flight analysis of the fragments revealed the identity of protected sites, suggesting that the Bir2 domain makes numerous contacts with the large subunit of caspase-7. These, combined with the results from Far-Western experiments, strongly suggest that the groove for the inhibitor(s)-of-apoptosis-protein-binding motif on the Bir2 favors binding to the N-terminus of the large subunit rather than to the small subunit of caspase-7. Our results further show that the active-site pocket of caspase-7 is first occupied by the linker region, followed by the interaction of the N-terminus of the enzyme with the SMAC-binding site of the Bir2 domain.