Novel Primate Model of Serotonin Transporter Genetic Polymorphisms Associated with Gene Expression, Anxiety and Sensitivity to Antidepressants

This is the final version of the article. It first appeared from Nature Publishing Group via https://dx.doi.org/10.1038/npp.2016.41Genetic polymorphisms in the repeat upstream region of the serotonin transporter gene (SLC6A4) are associated with individual differences in stress reactivity, vulnerability to affective disorders and response to pharmacotherapy. However, the molecular, neurodevelopmental and psychopharmacological mechanisms underlying the link between SLC6A4 polymorphisms and the emotionally vulnerable phenotype are not fully understood. Thus, using the marmoset monkey Callithrix jacchus we characterize here a new neurobiological model to help to address these questions. We first sequenced the marmoset SLC6A4 promoter and identified a double nucleotide polymorphism (−2053AC/CT) and two single nucleotide polymorphisms (−2022C/T and −1592G/C) within the repeat upstream region. We showed their association with gene expression using in vivo quantitative PCR and with affective behavior using a primate test of anxiety (human intruder test). The low-expressing haplotype (AC/C/G) was linked with high anxiety whilst the high-expressing one (CT/T/C) was associated with an active coping strategy in response to threat. Pharmacological challenge with an acute dose of the selective serotonin reuptake inhibitor (SSRI), citalopram, revealed a genotype-dependent behavioral response. Whilst individuals homozygous for the high anxiety-related haplotype AC/C/G exhibited a dose-dependent, anxiogenic response, individuals homozygous for the low anxiety-related haplotype CT/T/C showed an opposing, dose-dependent anxiolytic effect. These findings provide a novel genetic and behavioral primate model to study the molecular, neurodevelopmental and psychopharmacological mechanisms that underlie genetic variation-associated complex behaviors, with specific implications for the understanding of normal and abnormal serotonin actions and the development of personalized pharmacological treatments for psychiatric disorders.Work was supported by an MRC Programme (ACR; G0901884) and performed within the Behavioural and Clinical Neuroscience Institute, University of Cambridge, funded jointly by the Wellcome Trust and MRC. AMS was supported by a McDonnell Foundation grant (PI’s: E. Phelps, T.W. Robbins; Co-Investigators: ACR and J. LeDoux; 22002015501) and currently supported by MRC; YS supported by the Long Term Student Support Program provided by Osaka University and the Ministry of Education, Culture, Sports, Science and Technology of Japan; HC supported by MRC Career Development Award and ACFS/MI supported by grants from the MRC and Wellcome Trust. GC supported by the Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom. EHSS was self-funded

Synthetic biology and therapeutic strategies for the degenerating brain: Synthetic biology approaches can transform classical cell and gene therapies, to provide new cures for neurodegenerative diseases.

Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease-related genes. Ultimately, new intelligent delivery systems will provide targeted and sustained therapeutic benefits. New treatments will arise from combining ‘protect and repair’ strategies: the use of drug treatments, the promotion of neurotrophic factor synthesis, and gene targeting. Going beyond RNAi and artificial transcription factors, site-specific genome modification is likely to play an increasing role, especially with newly available gene editing tools such as CRISPR/Cas9 systems. Taken together, these advances will help develop safe and long-term therapies for many brain diseases in human patients

Heteroatom framework distribution and layer charge of sodium Taeniolite

The most advanced applications of clays depend crucially on their hydration state and swelling is probably the most important feature of expandable 2:1 layered silicate. Sodium Taeniolite, Na-TAE, a swelling trioctahedral fluormica, has been synthesized and studied using thermogravimetric analysis, X-ray diffraction, scanning electron microscopy and infrared and solid state NMR spectroscopies. The results indicated the formation of a swelling 2:1 phyllosilicate with actual layer charge lower than the nominal one. Herein, a new heteroatom distribution and more accurate composition could be deduced.Peer Reviewe

Converging Prefronto-Insula-Amygdala Pathways in Negative Emotion Regulation in Marmoset Monkeys

BACKGROUND: Impaired regulation of emotional responses to potential threat is a core feature of affective disorders. However, while the subcortical circuitry responsible for processing and expression of fear has been well characterized, the top-down control of this circuitry is less well understood. Our recent studies demonstrated that heightened emotionality, as measured both physiologically and behaviorally, during conditioned fear and innate/ social threat was induced, independently, by excitotoxic lesions of either the anterior orbitofrontal cortex (antOFC) or ventrolateral prefrontal cortex (vlPFC). An important outstanding question is whether the antOFC and vlPFC act on common or distinct downstream targets to regulate negative emotion. METHODS: The question was addressed by combining localized excitotoxic lesions in the PFC of a nonhuman primate and functional neuroimaging ([$^{18}$F]fluorodeoxyglucose positron emission tomography) with a fear-regulating extinction paradigm. Marmoset monkeys with unilateral lesions of either the antOFC or vlPFC were scanned immediately following exposure to a fearful or safe context, and differences in [$^{18}$F]fluorodeoxyglucose uptake were evaluated. RESULTS: [$^{18}$F]fluorodeoxyglucose uptake in the insula and amygdala of the intact hemisphere was significantly increased in response to the fearful context compared with the safe context. Such discrimination between the two contexts was not reflected in the activity of the insula-amygdala of the antOFC or vlPFC-lesioned hemisphere. Instead, uptake was at an intermediate level in both contexts. CONCLUSIONS: These findings demonstrate that the distinct control functions of the antOFC and vlPFC converge on the same downstream targets to promote emotion regulation, taking us closer to a mechanistic understanding of different forms of anxiety.This research was supported by a Medical Research Programme Grant (No. MR/M023990/1) from the Medical Research Council (to ACR) and was carried out within the Behavioural and Clinical Neuroscience Institute supported by a consortium award from the Wellcome Trust and the Medical Research Council

Registration of Rights of Scientific Institution's Inventions

Bakalaura darba mērķis ir noskaidrot zinātnisko institūciju tiesības uz izgudrojumu reģistrāciju, analizēt tiesisko regulējumu. Analīzē noskaidrojamas tiesību normas, uz kurām balstās institūciju tiesības uz patenta reģistrāciju, kas radīti darba tiesisko attiecību ietvaros. Bakalaura darba galvenie pamatuzdevumi ir: 1) izpētīt zinātnisko institūciju būtību; 2) izpētīt izgudrojuma jēdziena būtību un ar to radīšanu saistīto tiesību aizsardzību; 3) izpētīt reģistrācijas tiesību piekritību gadījumos, kad izgudrojums ir radīts darba tiesisko attiecību ietvaros; 4) sniegt priekšlikumus iespējamo problēmsituāciju risināšanā, kas saistītas ar izgudrotāja kā darbinieka un institūcijas kā darba devēja tiesībām uz intelektuālās darbības rezultātā iegūto izgudrojumu.Bachelor's work aim to find out scientific institutions rights to the registration of the invention, to analyze legislation. The analysis of the findings of law to which the institution is based right on the registration of patents, which would result in the employment relationship. Bachelor's work main missions are: 1) to explore scientific institutions character; 2) explore the inventions character and it’s legal protection; 3) to explore the legal jurisdiction of registration in cases where the invention has created in labor relations; 4) make suggestions of possible case studies, related to the inventor as an employee and as an employer's right to intellectual activity for the object