The Effects of Optogenetic Activation of Astrocytes on Spike-and-Wave Discharges in Genetic Absence Epileptic Rats

Background: Absence seizures (petit mal seizures) are characterized by a brief loss of consciousness without loss of postural tone. The disease is diagnosed by an electroencephalogram (EEG) showing spike–wave discharges (SWD) caused by hypersynchronous thalamocortical (TC) oscillations. There has been an explosion of research highlighting the role of astrocytes in supporting and modulating neuronal activity. Despite established in vitro evidence, astrocytes’ influence on the TC network remains to be elucidated in vivo in the absence epilepsy (AE). Purpose: In this study, we investigated the role of astrocytes in the generation and modulation of SWDs. We hypothesize that disturbances in astrocytes’ function may affect the pathomechanism of AE. Methods: To direct the expression of channelrhodopsin-2 (ChR2) rAAV8-GFAP-ChR2(H134R)-EYFP or to control the effect of surgical intervention, AAV-CaMKIIa-EYFP was injected into the ventrobasal nucleus (VB) of the thalamus of 18 animals. After four weeks following the injection, rats were stimulated using blue light (~473 nm) and, simultaneously, the electrophysiological activity of the frontal cortical neurons was recorded for three consecutive days. The animals were then perfused, and the brain tissue was analyzed by confocal microscopy. Results: A significant increase in the duration of SWD without affecting the number of SWD in genetic absence epileptic rats from Strasbourg (GAERS) compared to control injections was observed. The duration of the SWD was increased from 12.50 ± 4.41 s to 17.44 ± 6.07 following optogenetic stimulation in GAERS. The excitation of the astrocytes in Wistar Albino Glaxo Rijswijk (WAG-Rij) did not change the duration of SWD; however, stimulation resulted in a significant increase in the number of SWD from 18.52 ± 11.46 bursts/30 min to 30.17 ± 18.43 bursts/30 min. Whereas in control injection, the duration and the number of SWDs were similar at pre- and poststimulus. Both the background and poststimulus average firing rates of the SWD in WAG-Rij were significantly higher than the firing recorded in GAERS. Conclusion: These findings suggest that VB astrocytes play a role in modulating the SWD generation in both rat models with distinct mechanisms and can present an essential target for the possible therapeutic approach for AE

In vitro longitudinal lumbar spinal cord preparations to study sensory and recurrent motor microcircuits of juvenile mice

In vitro spinal cord preparations have been extensively used to study microcircuits involved in the control of movement. By allowing precise control of experimental conditions coupled with state-of-the-art genetics, imaging, and electrophysiological techniques, isolated spinal cords from mice have been an essential tool in detailing the identity, connectivity, and function of spinal networks. The majority of the research has arisen from in vitro spinal cords of neonatal mice, which are still undergoing important postnatal maturation. Studies from adults have been attempted in transverse slices, however, these have been quite challenging due to the poor motoneuron accessibility and viability, as well as the extensive damage to the motoneuron dendritic trees. In this work, we describe two types of coronal spinal cord preparations with either the ventral or the dorsal horn ablated, obtained from mice of different postnatal ages, spanning from preweaned to 1 mo old. These semi-intact preparations allow recordings of sensory-afferent and motor-efferent responses from lumbar motoneurons using whole cell patch-clamp electrophysiology. We provide details of the slicing procedure and discuss the feasibility of whole cell recordings. The in vitro dorsal and ventral horn-ablated spinal cord preparations described here are a useful tool to study spinal motor circuits in young mice that have reached the adult stages of locomotor development

Chiropractic manipulation increases maximal bite force in healthy individuals

Recent research has shown that chiropractic spinal manipulation can alter central sensorimotor integration and motor cortical drive to human voluntary muscles of the upper and lower limb. The aim of this paper was to explore whether spinal manipulation could also influence maximal bite force. Twenty-eight people were divided into two groups of 14, one that received chiropractic care and one that received sham chiropractic care. All subjects were naive to chiropractic. Maximum bite force was assessed pre- and post-intervention and at 1-week follow up. Bite force in the chiropractic group increased compared to the control group (p = 0.02) post-intervention and this between-group difference was also present at the 1-week follow-up (p < 0.01). Bite force in the chiropractic group increased significantly by 11.0% (±18.6%) post-intervention (p = 0.04) and remained increased by 13.0% (±12.9%, p = 0.04) at the 1 week follow up. Bite force did not change significantly in the control group immediately after the intervention (−2.3 ± 9.0%, p = 0.20), and decreased by 6.3% (±3.4%, p = 0.01) at the 1-week follow-up. These results indicate that chiropractic spinal manipulation can increase maximal bite force

İnşaat Şirketleri için Bilgisayar Destekli Bir Portföy Değerlendirme ve Yönetim Aracının Geliştirilmesi

TÜBİTAK MAG Proje15.09.2016Günümüzde inşaat projeleri giderek karmaşık bir hal almakta, inşaat şirketleri birden çok projeyi eş zamanlı yürütmek durumunda kalmaktadır. Bu kapsamda, şirketlerin geleneksel proje yönetim teknikleri yerine, bütüncül bir yönetim anlayışı sunan portföy yönetimini benimsemeleri gereği doğmaktadır. Portföy yönetimi, projelerin başta şirketin stratejik hedefleri olmak üzere birçok faktörün bir arada değerlendirilmesi sonucunda portföydeki yerlerinin belirlenmesini ve mevcut kaynakların bu doğrultuda projeler arasında paylaştırılmasını kapsamaktadır. Böylelikle şirket stratejisi ve durumuna uygun, kaynakların daha verimli kullanıldığı ve şirket başarısı odaklı bir proje portföyü elde edilmektedir. İnşaat projelerinin karmaşık, değişken, çok ortaklı ve koşullara duyarlı yapısı düşünüldüğünde; bu alanda geliştirilebilecek proje portföy yönetimine yardımcı bir aracın önemi artmaktadır. Bunun yanı sıra, portföy yönetimi odaklı çalışmalarda projeler arası ilişkilerin yeterince kapsamlı ve güvenilir bir yöntemle ele alınamadığı da görülmektedir. Dolayısıyla bu araştırma-geliştirme projesinde, inşaat projeleri arasındaki ilişkilerin belirlenmesini ve proje portföy yönetim sürecine dahil edilmesini sağlayacak, portföyün nasıl yönetilmesi gerektiğine dair yönlendirme yapabilecek akıllı ve dinamik bir aracın geliştirilmesi amaçlanmıştır. Proje kapsamında, öncelikle proje portföy yönetimi alanında literatür taraması yapılmış ve portföy yönetimi anlayışının inşaat şirketlerine adapte edilmesini sağlayacak bir ihtiyaç analizi çalışması yapılmıştır. Aracın geliştirilmesi için bir yazılım firmasından hizmet alımı yapılmış, aracın geliştirim süreci ve nihai hali çeşitli anketler ve şirket profesyonelleriyle yapılan çalışmalarla desteklenerek aracın kullanılabilirliği doğrulanmıştır. Çalışma sonunda; şirketlerin kurumsal belleklerini oluşturarak şirket için en uygun olan portföy seçiminin şirket stratejisine, portföy düzeyinde risk ve beklenen karlılığa göre yapılmasını sağlayabilecek, proje ilişkileri ve portföyün özelliklerine göre yönetim önerileri sunabilecek bir portföy yönetim aracı geliştirilmiştir. Aracın büyük ölçekli inşaat şirketlerinin portföy yönetimlerine yardımcı olacağı, böylelikle şirketlerin yönetim anlayışının tekil projelerin başarısından şirket başarısına yönelebileceği düşünülmektedir. Bu doğrultuda araç uluslararası alanda faaliyet gösteren şirketler için uygun portföylerin oluşturulması ve etkin bir şekilde yönetilmesini sağlayabilecek ve şirketlerin sürdürülebilir rekabet avantajı kazanması mümkün olabilecekti

The Effects of Optogenetic Activation of Astrocytes on Spike-and-Wave Discharges in Genetic Absence Epileptic Rats

Background: Absence seizures (petit mal seizures) are characterized by a brief loss of consciousness without loss of postural tone. The disease is diagnosed by an electroencephalogram (EEG) showing spike–wave discharges (SWD) caused by hypersynchronous thalamocortical (TC) oscillations. There has been an explosion of research highlighting the role of astrocytes in supporting and modulating neuronal activity. Despite established in vitro evidence, astrocytes’ influence on the TC network remains to be elucidated in vivo in the absence epilepsy (AE). Purpose: In this study, we investigated the role of astrocytes in the generation and modulation of SWDs. We hypothesize that disturbances in astrocytes’ function may affect the pathomechanism of AE. Methods: To direct the expression of channelrhodopsin-2 (ChR2) rAAV8-GFAP-ChR2(H134R)-EYFP or to control the effect of surgical intervention, AAV-CaMKIIa-EYFP was injected into the ventrobasal nucleus (VB) of the thalamus of 18 animals. After four weeks following the injection, rats were stimulated using blue light (~473 nm) and, simultaneously, the electrophysiological activity of the frontal cortical neurons was recorded for three consecutive days. The animals were then perfused, and the brain tissue was analyzed by confocal microscopy. Results: A significant increase in the duration of SWD without affecting the number of SWD in genetic absence epileptic rats from Strasbourg (GAERS) compared to control injections was observed. The duration of the SWD was increased from 12.50 ± 4.41 s to 17.44 ± 6.07 following optogenetic stimulation in GAERS. The excitation of the astrocytes in Wistar Albino Glaxo Rijswijk (WAG-Rij) did not change the duration of SWD; however, stimulation resulted in a significant increase in the number of SWD from 18.52 ± 11.46 bursts/30 min to 30.17 ± 18.43 bursts/30 min. Whereas in control injection, the duration and the number of SWDs were similar at pre- and poststimulus. Both the background and poststimulus average firing rates of the SWD in WAG-Rij were significantly higher than the firing recorded in GAERS. Conclusion: These findings suggest that VB astrocytes play a role in modulating the SWD generation in both rat models with distinct mechanisms and can present an essential target for the possible therapeutic approach for AE

Coculture model of blood-brain barrier on electrospun nanofibers

The blood–brain barrier (BBB) is a control mechanism that limits the diffusion of many substances to the central nervous system (CNS). In this study, we designed an in-vitro 3-dimensional BBB system to obtain a fast and reliable model to mimic drug delivery characteristics of the CNS. A support membrane of polycaprolactone nanofiber surfaces was prepared using electrospinning. After confirming the fiber morphology and size, endothelial cells (HUVEC) and glial cells were cultured on either side of this membrane. The model’s similarity to in vivo physiology was tested with a home-designed transmembrane resistance (TR) device, with positive and negative control molecules. Finally, 2 doses of methotrexate (MTX), a chemotherapy agent, were applied to the model, and its permeability through the model was determined indirectly by a vitality test on the MCF-7 cell line. Nicotine, the positive control, completed its penetration through the model almost instantly, while albumin, the negative control, was blocked significantly even after 2 days. MTX reached a deadly threshold 24 h after application. The TR value of the model was promising, being around 260 ohm.cm2. The provided model proposes a disposable and reliable tool for investigating drug permeability through the BBB and has the potential to reduce the number of animal experiments

İnşaat Şirketleri İçin bir Proje Portföy Yönetim Aracı COPPMAN

Günden güne gelişmekte olan inşaat sektöründe projeler giderek karmaşık bir hal almakta, bu gelişimin doğal bir sonucu olarak da inşaat şirketleri birden çok projeyi eş zamanlı yürütmek durumunda kalmaktadır. Bu kapsamda, şirketlerin geleneksel yönetim teknikleri yerine, bütüncül bir yönetim anlayışı sunan portföy yönetimini benimsemeleri gereği doğmaktadır. Bu çalışmada, bu amaca hizmet etmek üzere geliştirilmiş olan bir portföy yönetim aracı (COPPMAN) sunulmaktadır. Aracın geliştirilmesi amacıyla proje portföy yönetimi alanında literatür taraması yapılmış ve portföy yönetimi anlayışının inşaat şirketlerine adapte edilmesi sağlanmıştır. Bu kapsamda geliştirilen araç, şirketlerin kurumsal belleklerini de kullanarak; şirket için uygun olan portföy seçiminin, şirket stratejisine, portföy düzeyinde risk ve karlılığa göre yapılmasını sağlayabilecek bir portföy yönetim sistemi sunmaktadır. Buna ek olarak, araç proje ilişkilerine ve portföyün özelliklerine göre yönetim önerileri sunabilmektedir. Aracın büyük ölçekli inşaat şirketlerinin portföy yönetimlerine yardımcı olacağı, böylelikle şirketlerin yönetim anlayışının tekil projelerin başarısından şirket başarısına yönelebileceği düşünülmektedir. Bu doğrultuda araç şirketler için uygun portföylerin oluşturulması ve etkin bir şekilde yönetilmesini sağlayabilecek ve şirketlerin rekabet avantajı kazanması mümkün olabilecektir

Construction Project Portfolio Management Tool (COPPMAN)

Most of the today’s construction organizations are executing several projects concurrently; however, their management routines do not respond to the need of concurrent execution of projects. Portfolio management enables effective management of the right projects for the organization considering its resources, capabilities, strategic objectives, environmental factors, etc. Tools to support decision-making at the portfolio level are needed for successful project management, portfolio management and strategic management of companies; however, there have been very scarce studies responding to this need in the industry. This study reports fundamentals of a tool (alpha version) that has been designed as a decision support tool for portfolio management specific for construction companies. The tool (COPPMAN) will be improved by further testing its validity, reliability and usability within construction companies with real project portfolios. The final version of the tool is believed to be useful for adoption of portfolio management principles in construction companies by capturing project knowledge, enabling analysis of portfolios considering interdependencies between projects, enabling selection of the best portfolio considering strategic priorities of the company and facilitating decision-making by providing visual representations of alternative scenarios