Bundles of Spider Silk,Braided into Sutures,Resist Basic Cyclic Tests: Potential Use for Flexor Tendon Repair

Repair success for injuries to the flexor tendon in the hand is often limited by the in vivo behaviour of the suture used for repair. Common problems associated with the choice of suture material include increased risk of infection, foreign body reactions, and inappropriate mechanical responses, particularly decreases in mechanical properties over time. Improved suture materials are therefore needed. As high-performance materials with excellent tensile strength, spider silk fibres are an extremely promising candidate for use in surgical sutures. However, the mechanical behaviour of sutures comprised of individual silk fibres braided together has not been thoroughly investigated. In the present study, we characterise the maximum tensile strength, stress, strain, elastic modulus, and fatigue response of silk sutures produced using different braiding methods to investigate the influence of braiding on the tensile properties of the sutures. The mechanical properties of conventional surgical sutures are also characterised to assess whether silk offers any advantages over conventional suture materials. The results demonstrate that braiding single spider silk fibres together produces strong sutures with excellent fatigue behaviour; the braided silk sutures exhibited tensile strengths comparable to those of conventional sutures and no loss of strength over 1000 fatigue cycles. In addition, the braiding technique had a significant influence on the tensile properties of the braided silk sutures. These results suggest that braided spider silk could be suitable for use as sutures in flexor tendon repair, providing similar tensile behaviour and improved fatigue properties compared with conventional suture materials.     

On the Influence of Freight Trains on Humans: A Laboratory Investigation of the Impact of Nocturnal Low Frequency Vibration and Noise on Sleep and Heart Rate

Background

A substantial increase in transportation of goods on railway may be hindered by public fear of increased vibration and noise leading to annoyance and sleep disturbance. As the majority of freight trains run during night time, the impact upon sleep is expected to be the most serious adverse effect. The impact of nocturnal vibration on sleep is an area currently lacking in knowledge. We experimentally investigated sleep disturbance with the aim to ascertain the impact of increasing vibration amplitude.

Methodology/Principal Findings

The impacts of various amplitudes of horizontal vibrations on sleep disturbance and heart rate were investigated in a laboratory study. Cardiac accelerations were assessed using a combination of polysomnography and ECG recordings. Sleep was assessed subjectively using questionnaires. Twelve young, healthy subjects slept for six nights in the sleep laboratory, with one habituation night, one control night and four nights with a variation of vibration exposures whilst maintaining the same noise exposure. With increasing vibration amplitude, we found a decrease in latency and increase in amplitude of heart rate as well as a reduction in sleep quality and increase in sleep disturbance.

Conclusions/Significance

We concluded that nocturnal vibration has a negative impact on sleep and that the impact increases with greater vibration amplitude. Sleep disturbance has short- and long-term health consequences. Therefore, it is necessary to define levels that protect residents against sleep disruptive vibrations that may arise from night time railway freight traffic.     

Side-by-side comparability of batch and continuous downstream for the production of monoclonal antibodies

Continuous processing is the future production method for monoclonal antibodies (mAbs). A fully continuous, fully automated downstream process based on disposable equipment was developed and implemented inside the MoBiDiK pilot plant. However, a study evaluating the comparability between batch and continuous processing based on product quality attributes was not conducted before. The work presented fills this gap comparing both process modes experimentally by purifying the same harvest material (side-by-side comparability). Samples were drawn at different time points and positions in the process for batch and continuous mode. Product quality attributes, product-related impurities, as well as process-related impurities were determined. The resulting polished material was processed to drug substance and further evaluated regarding storage stability and degradation behavior. The in-process control data from the continuous process showed the high degree of accuracy in providing relevant process parameters such as pH, conductivity, and protein concentration during the entire process duration. Minor differences between batch and continuous samples are expected as different processing conditions are unavoidable due to the different nature of batch and continuous processing. All tests revealed no significant differences in the intermediates and comparability in the drug substance between the samples of both process modes. The stability study of the final product also showed no differences in the stability profile during storage and forced degradation. Finally, online data analysis is presented as a powerful tool for online-monitoring of chromatography columns during continuous processing.     

Root–root interactions: extending our perspective to be more inclusive of the range of theories in ecology and agriculture using in-vivo analyses

Background

There is a large body of literature on competitive interactions among plants, but many studies have only focused on above-ground interactions and little is known about root–root dynamics between interacting plants. The perspective on possible mechanisms that explain the outcome of root–root interactions has recently been extended to include non-resource-driven mechanisms (as well as resource-driven mechanisms) of root competition and positive interactions such as facilitation. These approaches have often suffered from being static, partly due to the lack of appropriate methodologies for in-situ non-destructive root characterization.

Scope

Recent studies show that interactive effects of plant neighbourhood interactions follow non-linear and non-additive paths that are hard to explain. Common outcomes such as accumulation of roots mainly in the topsoil cannot be explained solely by competition theory but require a more inclusive theoretical, as well as an improved methodological framework. This will include the question of whether we can apply the same conceptual framework to crop versus natural species.

Conclusions

The development of non-invasive methods to dynamically study root–root interactions in vivo will provide the necessary tools to study a more inclusive conceptual framework for root–root interactions. By following the dynamics of root–root interactions through time in a whole range of scenarios and systems, using a wide variety of non-invasive methods, (such as fluorescent protein which now allows us to separately identify the roots of several individuals within soil), we will be much better equipped to answer some of the key questions in root physiology, ecology and agronomy.     

Diurnal and seasonal changes in semen quality of men in subfertile partnerships

ABSTRACT

Circadian and circannual rhythms influence not only the environment, but also human physiology. In times of increasing numbers of couples struggling with infertility, and thus increasing demand for successful assisted reproduction, the aim of our study was to evaluate circadian and circannual rhythms and their association with semen quality. A total of 12 245 semen samples from 7068 men, collected at the andrology laboratory of the Department of Reproductive Endocrinology, University Hospital Zurich, between 1994 and 2015, were uniformly analysed in terms of sperm concentration, total sperm count, progressive motility and normal morphology. On the basis of these four parameters, we retrospectively examined the circadian and circannual changes of semen quality. The Mann–Whitney U test and multiple linear regression analysis were used for the statistical evaluation. The semen samples collected in the early morning before 7:30 a.m. showed the highest levels in sperm concentration, total sperm count and normal morphology, all with statistical significance. Progressive motility did not show any significant alterations based on circadian rhythm. Furthermore, a significant increase in sperm concentration and total sperm count was found in spring, with significant decreases in the summer. The highest percentage of normal morphology was found in summer. For progressive motility, no significant seasonal variation could be demonstrated. Male semen quality varies with both circadian and circannual rhythms. Collection of semen in the early morning, where semen quality was highest, can be used to improve natural fertility as well as fertility resulting from assisted reproduction.     

Calmodulin-dependent activation and inactivation of anoctamin calcium-gated chloride channels

Calcium-dependent chloride channels serve critical functions in diverse biological systems. Driven by cellular calcium signals, the channels codetermine excitatory processes and promote solute transport. The anoctamin (ANO) family of membrane proteins encodes three calcium-activated chloride channels, named ANO 1 (also TMEM16A), ANO 2 (also TMEM16B), and ANO 6 (also TMEM16F). Here we examined how ANO 1 and ANO 2 interact with Ca²⁺/calmodulin using nonstationary current analysis during channel activation. We identified a putative calmodulin-binding domain in the N-terminal region of the channel proteins that is involved in channel activation. Binding studies with peptides indicated that this domain, a regulatory calmodulin-binding motif (RCBM), provides two distinct modes of interaction with Ca²⁺/calmodulin, one at submicromolar Ca²⁺ concentrations and one in the micromolar Ca²⁺ range. Functional, structural, and pharmacological data support the concept that calmodulin serves as a calcium sensor that is stably associated with the RCBM domain and regulates the activation of ANO 1 and ANO 2 channels. Moreover, the predominant splice variant of ANO 2 in the brain exhibits Ca²⁺/calmodulin-dependent inactivation, a loss of channel activity within 30 s. This property may curtail ANO 2 activity during persistent Ca²⁺ signals in neurons. Mutagenesis data indicated that the RCBM domain is also involved in ANO 2 inactivation, and that inactivation is suppressed in the retinal ANO 2 splice variant. These results advance the understanding of Ca²⁺ regulation in anoctamin Cl⁻ channels and its significance for the physiological function that anoctamin channels subserve in neurons and other cell types.     

Conformation constraint of anilides enabling the discovery of tricyclic lactams as potent MK2 non-ATP competitive inhibitors

Conformation restriction of linear N-alkylanilide MK2 inhibitors to their E-conformer was developed. This strategy enabled rapid advance in identifying a series of potent non-ATP competitive inhibitors that exhibited cell based activity in anti-TNFα assay.