Pre-emptive Quality Control of a Misfolded Membrane Protein by Ribosome-Driven Effects

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Frequency tuning curves of the dolphin's hearing: envelope-following response study

Simultaneous tone-tone masking in conjunction with the envelope-following response (EFR) recording was used to obtain tuning curves in dolphins (Turslops truncatus). The EFR was evoked by amplitude-modulated probes of various frequencies. A modulation rate of 600 Hz was found to fit the requirement to have a narrow spectrum and evoke EFR of large amplitude. Tuning curves were obtained within the frequency range from 11.2 to 110 kHz. The Q₁₀ values of the obtained tuning curves varied from 12–14 at the 11.2 kHz center frequency to 17–20 at the 64–90 kHz frequencies.Abbreviations ABR auditory brainstem response - EFR envelope following response - ERB equivalent rectangular bandwidth     

ABR frequency tuning curves in dolphins

Tone-tone masking was used to determine auditory brain-stem response tuning curves in dolphins (Tursiops truncatus) in a simultaneous-masking paradigm. The Q ₁₀ of the curves was as large as 16–19 in the frequency range 64–128 kHz. In the range 45–16 kHz, Q ₁₀ decreased proportionally to the frequency with the bandwidth of the curves being constant, about 3.5–4 kHz at the 10-dB level. Tuning curves below 45 kHz are supposed to reflect broad spectral bandwidth of the probe's effective part which is no longer than 0.5 ms, irrespective of actual probe duration. Tuning curves above 64 kHz are supposed to reflect the real frequency tuning of the dolphin's auditory system.Abbreviations ABR auditory brain stem response - AP action potential     

Particle deposition and sensory drive

The mutualism between chemical cues emitted into the air and variations in how primates respond to them using olfaction has demonstrated aspects of species‐specific adaptations. Building on this mutualism we can look at particle deposition as another means to understanding how various environments may have elicited biological changes that enable efficient communication. Research on particle movement and deposition within the nasal cavity is largely based on questions about health as it relates to drug delivery systems and overall olfactory function in modern humans. With increased access to 3D models and the use of computational fluid dynamic analysis, researchers have been able to simulate site‐specific deposition, to determine what particles are making it through the nasal cavity to the main olfactory epithelium, which ultimately leads to processing in the olfactory bulb. Here we discuss particle deposition research, sensory drive and their potential applications to evolutionary anthropology.     

Combinatorial metabolic pathway assembly approaches and toolkits for modular assembly

Synthetic Biology is a rapidly growing interdisciplinary field that is primarily built upon foundational advances in molecular biology combined with engineering design principles such as modularity and interoperability. The field considers living systems as programmable at the genetic level and has been defined by the development of new platform technologies and methodological advances. A key concept driving the field is the Design-Build-Test-Learn cycle which provides a systematic framework for building new biological systems. One major application area for synthetic biology is biosynthetic pathway engineering that requires the modular assembly of different genetic regulatory elements and biosynthetic enzymes. In this review we provide an overview of modular DNA assembly and describe and compare the plethora of in vitro and in vivo assembly methods for combinatorial pathway engineering. Considerations for part design and methods for enzyme balancing are also presented, and we briefly discuss alternatives to intracellular pathway assembly including microbial consortia and cell-free systems for biosynthesis. Finally, we describe computational tools and automation for pathway design and assembly and argue that a deeper understanding of the many different variables of genetic design, pathway regulation and cellular metabolism will allow more predictive pathway design and engineering.     

小鼠初级听皮质神经元的强度调谐特性与机制分析

强度是声音的基本参数之一,听神经元的强度调谐在听觉信息处理方面具有重要意义．以往研究发现γ-氨基丁酸(γ-aminobutyric acid, GABA)能抑制性输入在强度调谐的形成过程中起重要作用,但对抑制性输入与局部神经回路之间的关系并不清楚．本实验通过在体细胞外电生理记录和神经药理学方法,分析了小鼠初级听皮质神经元的强度调谐特性,结果显示：单调型神经元在声刺激强度自中等强度增高时潜伏期缩短(P < 0.05)且发放持续时间延长(P < 0.05),非单调型神经元在声刺激强度自最佳强度增高时潜伏期不变且发放持续时间缩短(P < 0.01)．注射GABA能阻断剂荷包牡丹碱(bicuculline, Bic)后,39.3%的神经元强度调谐类型不变,42.9%的神经元非单调性减弱,17.9%的神经元非单调性增强．表明GABA能抑制并非是形成非单调性的唯一因素,兴奋性输入本身的非单调性和高阈值非GABA能抑制的激活也可能在其中发挥作用．推测由兴奋性和抑制性输入所构成的局部神经功能回路及其整合决定了听皮质神经元的强度调谐特性．     

Crystallographic studies of V44 mutants of Clostridium pasteurianum rubredoxin: effects of side-chain size on reduction potential

Understanding the structural origins of differences in reduction potentials is crucial to understanding how various electron transfer proteins modulate their reduction potentials and how they evolve for diverse functional roles. Here, the high-resolution structures of several Clostridium pasteurianum rubredoxin (Cp Rd) variants with changes in the vicinity of the redox site are reported in order to increase this understanding. Our crystal structures of [V44L] (at 1.8 A resolution), [V44A] (1.6 A), [V44G] (2.0 A) and [V44A, G45P] (1.5 A) Rd (all in their oxidized states) show that there is a gradual decrease in the distance between Fe and the amide nitrogen of residue 44 upon reduction in the size of the side chain of residue 44; the decrease occurs from leucine to valine, alanine or glycine and is accompanied by a gradual increase in their reduction potentials. Mutation of Cp Rd at position 44 also changes the hydrogen-bond distance between the amide nitrogen of residue 44 and the sulfur of cysteine 42 in a size-dependent manner. Our results suggest that residue 44 is an important determinant of Rd reduction potential in a manner dictated by side-chain size. Along with the electric dipole moment of the 43-44 peptide bond and the 44-42 NH--S type hydrogen bond, a modulation mechanism for solvent accessibility through residue 41 might regulate the redox reaction of the Rds.     

Separation of Spatio-Temporal Receptive Fields into Sums of Gaussian Components

Visual cortical simple cells have been experimentally shown to reveal non-trivial spatio-temporal orientation tuning functions comprising different phases of specifically tuned enhanced and suppressed activity. A recently developed analytical method based on nonlinear neural field models suggests that such space-time responses should be approximately separable into a sum of temporally amplitude modulated Gaussian spatial components. In the present work, we investigate this possibility by means of numerical fits of sums of Gaussians to response functions observed in experiments and computer simulations. Because the theory relates each single component to a particular connectivity kernel between the underlying cell classes shaping the response, the relative contribution of feedforward and cortex-intrinsical excitatory and inhibitory feedback mechanisms to single cell tuning can be approached and quantified in experimental data.