Neural patterns of hippocampus and amygdala supporting memory over long timespans

Episodic memory is an imperfect record of events arranged in time and space. When dealing with the storage of memories, the brain is faced with a predicament: it must retain an acceptably faithful facsimile of transpired events while simultaneously permitting inevitable modifications to accommodate learning new information. In this thesis, I first review contemporary theories of how memories can be stored in a neural substrate within the hippocampus, particularly in regards to how they can be arranged in time. Next, using in vivo calcium imaging, I detail how hippocampal “time cell” sequences could support encoding of behavioral events along multiple temporal dimensions. In this study, I trained mice to run in place on a treadmill, thereby measuring single-cell activity in CA1 as a function of time. Neurons in CA1 formed sequences, each cell firing one after another as if forming a scaffold upon which memories can be laid. These sequences were relatively well-preserved over a period of four days, satisfying the first requirement that information must be stored for a memory to persist. Additionally, these sequences also changed over time, which may be revealing a mechanism for how memories can change over time to assimilate new information. In the next experiment, I describe a collaborative project where we used immunohistochemistry, optogenetics, and calcium imaging to investigate the long-term dynamics of a fear memory. After mice initially associated a context with an aversive stimulus, they were placed in the same context over two days where they gradually relearned that the context was harmless. This produced molecular and neurophysiological signatures consistent with memory modification. However, after re-triggering fear, mice reverted to fearful expression with commensurate neural correlates. Using optogenetics, these behaviors could also be reliably suppressed. Finally, I conclude by synthesizing these findings with hippocampal literature on sequence formation and consolidation by proposing a holistic view of how these features can support episodic memory

PRO-KONTRA PIDANA TAMBAHAN KEBIRI KIMIA TERHADAP PELAKU KEJAHATAN SEKSUAL TERHADAP ANAK DALAM PERSPEKTIF KOMISI NASIONAL HAK ASASI MANUSIA DAN KOMISI PERLINDUNGAN ANAK INDONESIA

Skripsi dengan judul “PRO-KONTRA PIDANA TAMBAHAN KEBIRI KIMIA TERHADAP PELAKU KEJAHATAN SEKSUAL TERHADAP ANAK DALAM PERSPEKTIF KOMISI NASIONAL HAK ASASI MANUSIA DAN KOMISI PERLINDUNGAN ANAK INDONESIA” ini bertujuan: Untuk mengetahui penerapan kebiri kimia dalam perspektif Komisi Nasional Hak Asasi Manusia (Komnas HAM), untuk mengetahui penerapan kebiri kimia dalam perspektif Komisi Perlindungan Anak Indonesia (KPAI), untuk mengetahui faktor penyebab sulitnya melaksanakan eksekusi hukuman kebiri kimia dalam kasus kejahatan seksual terhadap anak menurut perspektif Komisi Nasional Hak Asasi Manusia (Komnas HAM) dan Komisi Perlindungan Anak Indonesia. Penelitian ini menggunakan metode penelitian kualitatif. Data dan analisis dilakukan secara kualitatif tanpa menggunakan suatu perhitungan secara matematis. Sumber data diperoleh dari hasil pencarian data di lapangan melalui teknik wawancara dengan narasumber dan studi pustaka. Hasil penelitian dan pembahasan menunjukna bahwa penerapan pidana tambahan kebiri kimia dalam perspektif Komisi Nasional Hak Asasi Manusia (Komnas HAM) dan Komisi Perlindungan Anak Indonesia (KPAI) yakni, penerapan pidana tambahan berupa kebiri kimia merupakan hukuman yang melanggar Hak Asasi Manusia khususnya melanggar Hak atas Kesehatan dan Hak untuk Berketurunan, dengan adanya hukuman tambahan kebiri kimia pemerintah dianggap lebih serius dalam menangani pelaku kekerasan seksual terhadap anak. Faktor penyebab sulitnya melaksanakan eksekusi hukuman kebiri kimia dalam kasus kejahatan seksual terhadap anak yakni, Jaksa Penuntut Umum selaku eksekusi hukuman kebiri kimia belum dapat melaksanakan hukuman kebiri kimia, karena terpidana kekerasan seksual terhadap anak belum menjalankan pidana pokok berupa pidana penjara. Saran Penulis adalah Jaksa Penuntut Umum selaku eksekutor hukuman kebiri kimia harus lebih tegas terhadap dokter pelaksana untuk melaksanakan hukuman kebiri kimia, Komnas HAM dan KPAI harus melakukan pengkajian ulang terhadap hukuman pidana tambahan kebiri kimia, Jaksa Penuntut Umum harus melakukan sosialisasi kepada dokter pelaksana untuk melaksanakan hukuman kebiri kimia agar kedepannya tidak ada hambatan dalam melakukan eksekusi hukuman kebiri kimi

Validation of graft and standard liver size predictions in right liver living donor liver transplantation

Purpose: To assess the accuracy of a formula derived from 159 living liver donors to estimate the liver size of a normal subject: standard liver weight (g) = 218 + body weight (kg) × 12.3 + 51 (if male). Standard liver volume (SLV) is attained by a conversion factor of 1.19 mL/g. Methods: The total liver volume (TLV) of each of the subsequent consecutive 126 living liver donors was determined using the right liver graft weight (RGW) on the back table, right/left liver volume ratio on computed tomography, and the conversion factor. The estimated right liver graft weight (ERGW) was determined by the right liver volume on computed tomography (CT) and the conversion factor. SLV and ERGW were compared with TLV and RGW, respectively, by paired sample t test. Results: Donor characteristics of both series were similar. SLV and TLV were 1,099.6 ± 139.6 and 1,108.5 ± 175.2 mL, respectively, (R 2 = 0.476) (p = 0.435). The difference between SLV and TLV was only -8.9 ± 128.2 mL (-1.0 ± 11.7%). ERGW and RGW were 601.5 ± 104.1 and 597.1 ± 102.2 g, respectively (R 2 = 0.781) (p = 0.332). The conversion factor from liver weight to volume for this series was 1.20 mL/g. The difference between ERGW and RGW was 4.3 ± 49.8 g (0.3 ± 8.8%). ERGW was smaller than RGW for over 10% (range 0.21-40.66 g) in 18 of the 126 donors. None had the underestimation of RGW by over 20%. Conclusion: SLV and graft weight estimations were accurate using the formula and conversion factor. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

The Vicious Circle of Post-Soviet Neopatrimonialism in Russia

Published online: 10 Aug 2015, journal issue (vol.32, N5) appeared in 2016Since the collapse of Communism, Russia and some other post-Soviet states have attempted to pursue socio-economic reforms while relying upon the political institutions of neopatrimonialism. This politico-economic order was established to serve the interests of ruling groups and establish the major features of states, political regimes, and market economies. It provided numerous negative incentives for governing the economy and the state due to the unconstrained rent seeking behavior of major actors. Policy reform programs discovered these institutions to be incompatible with the priorities of modernization, and efforts to resolve these contradictions through a number of partial and compromise solutions often worsened the situation vis-à-vis preservation of the status quo. The ruling groups lack incentives for institutional changes, which could undermine their political and economic dominance, and are caught in a vicious circle: reforms often result in minor returns or cause unintended and undesired consequences. What are the possible domestic and international incentives to reject the political institutions of neopatrimonialism in post-Soviet states and replace them with inclusive economic and political ones?Peer reviewe

De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits:report of 25 new individuals and review of the literature

TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients