| 1. |
- Dore, Riccardo, et al.
(författare)
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Resistance to thyroid hormone induced tachycardia in RTHα syndrome
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.
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| 2. |
- Fischer, Alexander W., et al.
(författare)
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Leptin Raises Defended Body Temperature without Activating Thermogenesis
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 14:7, s. 1621-1631
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Tidskriftsartikel (refereegranskat)abstract
- Leptin has been believed to exert its weight-reducing action not only by inducing hypophagia but also by increasing energy expenditure/thermogenesis. Leptin-deficient ob/ob mice have correspondingly been thought to be thermogenically limited and to show hypothermia, mainly due to atrophied brown adipose tissue (BAT). In contrast to these established views, we found that BAT is fully functional and that leptin treatment did not increase thermogenesis in wildtype or in ob/ob mice. Rather, ob/ob mice showed a decreased but defended body temperature (i. e., were anapyrexic, not hypothermic) that was normalized to wild-type levels after leptin treatment. This was not accompanied by increased energy expenditure or BAT recruitment but, instead, was mediated by decreased tail heat loss. The weight-reducing hypophagic effects of leptin are, therefore, not augmented through a thermogenic effect of leptin; leptin is, however, pyrexic, i. e., it alters centrally regulated thresholds of thermoregulatory mechanisms, in parallel to effects of other cytokines.
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| 3. |
- Gachkar, Sogol, et al.
(författare)
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Aortic effects of thyroid hormone in male mice
- 2019
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Ingår i: Journal of Molecular Endocrinology. - 1479-6813. ; 62:3, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- It is well established that thyroid hormones are required for cardiovascular functions; however, the molecular mechanisms remain incompletely understood, especially the individual contributions of genomic and non-genomic signalling pathways. In this study, we dissected how thyroid hormones modulate aortic contractility. To test the immediate effects of thyroid hormones on vasocontractility, we used a wire myograph to record the contractile response of dissected mouse aortas to the adrenergic agonist phenylephrine in the presence of different doses of T3 (3,3',5-triiodothyronine). Interestingly, we observed reduced vasoconstriction under low and high T3 concentrations, indicating an inversed U-shaped curve with maximal constrictive capacity at euthyroid conditions. We then tested for possible genomic actions of thyroid hormones on vasocontractility by treating mice for 4 days with 1 mg/L thyroxine in drinking water. The study revealed that in contrast to the non-genomic actions the aortas of these animals were hyperresponsive to the contractile stimulus, an effect not observed in endogenously hyperthyroid TRβ knockout mice. To identify targets of genomic thyroid hormone action, we analysed aortic gene expression by microarray, revealing several altered genes including the well-known thyroid hormone target gene hairless. Taken together, the findings demonstrate that thyroid hormones regulate aortic tone through genomic and non-genomic actions, although genomic actions seem to prevail in vivo. Moreover, we identified several novel thyroid hormone target genes that could provide a better understanding of the molecular changes occurring in the hyperthyroid aorta.
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| 4. |
- Gaugel, Tristan, et al.
(författare)
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In-depth Analysis and Evaluation of Self-Organizing TDMA
- 2013
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Ingår i: IEEE Vehicular Networking Conference, VNC. - 2157-9865 .- 2157-9857. ; , s. 79-86
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Konferensbidrag (refereegranskat)abstract
- Recent studies suggest that Self-organizing Time- Division Multiple Access (STDMA) might be a better medium access strategy in inter-vehicle communication networks than Carrier Sense Multiple Access (CSMA), especially when con- sidering safety focused applications. Although it is necessary to completely understand a protocol and the effect of its ‘turning knobs’ on performance before adoption, STDMA has not yet been subjected to such rigorous treatment in the literature. In order to address this shortcoming we perform and present an in-depth analysis and evaluation of STDMA’s fundamental principles. In particular, we contribute a detailed and complete description of the STDMA protocol, followed by the analysis and evaluation of two key questions: How can packet collisions occur in STDMA and whether packet collisions are ‘contagious’. We further perform a fair comparison with CSMA on the basis of which we provide recommendations on the configuration of STDMA. Our results show that STDMA coordinates multiple access effectively – even in highly congested situations – as long as all transmitted packets are decoded successfully. When non-decodable (but still carrier-sensible) transmissions are present, STDMA effectiveness drops below that achieved by CSMA due to the lack of control information. To ensure reproducibility and encourage further inquiry we release the STDMA implementation used in this paper to the wireless networks research community.
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| 5. |
- Gaugel, Tristan, et al.
(författare)
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Understanding differences in MAC performance
- 2014
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Ingår i: IEEE WoWMoM Workshop on Smart Vehicles: Connectivity Technologies and ITS Applications. ; , s. Art. no. 6918995-
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Konferensbidrag (refereegranskat)abstract
- The suitability and performance of medium access protocols in vehicular environments is already being investigated over a long period of time. Carrier Sense Multiple Access (CSMA) has been shown to perform sufficiently well in most situations and being able to support safety and efficiency vehicular applications. Recently, Self-organizing Time-Division Multiple Access (STDMA) is being considered as an alternative and has been shown to coordinate the channel slightly better under certain situations. However, when comparing both protocols the precise details of radio and network conditions and parametrization of the protocols are decisive on which protocol takes a slight lead. Consequently, scenarios can be constructed quite easily in which one protocol is superior over the other one. The focus of this work is thus not to absolutely compare both protocols, but rather to understand the strengths and weaknesses of both protocols in certain situations. In particular, we consider i) to which degree hidden nodes influence the coordination ability, ii) how an extended carrier sensing range is beneficial and iii) how temporary fading influences the performance of both MAC protocols. Our results show that while an extended carrier sensing range is only beneficial for CSMA, the existence and severity of fading is far less detrimental for STDMA than for CSMA.
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| 6. |
- Martínez-Sánchez, Noelia, et al.
(författare)
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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
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Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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| 7. |
- Mittag, Jens, 1981, et al.
(författare)
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Enabling Accurate Cross-Layer PHY/MAC/NET Simulation Studies of Vehicular Communication Networks
- 2011
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Ingår i: Proceedings of the IEEE. - : Institute of Electrical and Electronics Engineers (IEEE). - 1558-2256 .- 0018-9219. ; 99:7, s. 1311-1326
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Tidskriftsartikel (refereegranskat)abstract
- Vehicle-to-vehicle and vehicle-to-roadside communications is required for numerous applications that aim at improving traffic safety and efficiency. In this setting, however, gauging system performance through field trials can be very expensive especially when the number of studied vehicles is high. Therefore, many existing studies have been conducted using either network or physical layer simulators; both approaches are problematic. Network simulators typically abstract physical layer details (coding, modulation, radio channels, receiver algorithms, etc.) while physical layer ones do not consider overall network characteristics (topology, network traffic types, and so on). In particular, network simulators view a transmitted frame as an indivisible unit, which leads to several limitations. First, the impact of the vehicular radio channel is typically not reflected in its appropriate context. Further, interference due to frame collisions is not modeled accurately ( if at all) and, finally, the benefits of advanced signal processing techniques, such as interference cancellation, are difficult to assess. To overcome these shortcomings we have integrated a detailed physical layer simulator into the popular NS-3 network simulator. This approach aims to bridge the gap between the physical and network layer perspectives, allow for more accurate channel and physical layer models, and enable studies on cross-layer optimization. In this paper, we exemplify our approach by integrating an IEEE 802.11a and p physical layer simulator with NS-3. Further, we validate the augmented NS-3 simulator against an actual IEEE 802.11 wireless testbed and illustrate the additional value of this integration.
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| 8. |
- Papanastasiou, Stylianos, 1978, et al.
(författare)
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Bridging the Gap Between Physical Layer Emulation and Network Simulation
- 2010
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Ingår i: IEEE Wireless Communications and Networking Conference, WCNC. - 1525-3511.
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Konferensbidrag (refereegranskat)abstract
- Many of the simulations reported in wireless networking literature contain several abstractions at the physical layer and the corresponding channel models. In particular, the basic simulation unit assumed in such simulations is the frame (or packet), which omits considerations of the signal processing details at the physical layer, such as frame construction and reception. Due to this abstraction, available channel models for network simulators are applied to frames as a whole and cannot reflect properly the effects of fast fading or frequency- selective channels. Moreover, it is not possible to study the mechanisms of the physical layer and their impact on higher layers such as the MAC. Therefore, we propose to address the lack of accurate physical layer representation in modern network simulators by incorporating a physical layer emulator for OFDM-based IEEE 802.11 communications into the popular NS-3 simulator. In this paper, we outline the architecture of the physical layer emulator and present initial results which highlight the promise of the new architecture in providing more detailed simulations to the networking community. The additional memory and computational requirements of the new model are also discussed.
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| 9. |
- Poll, Stefanie, et al.
(författare)
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Memory trace interference impairs recall in a mouse model of Alzheimer’s disease
- 2020
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Ingår i: Nature Neuroscience. - : Springer. - 1097-6256 .- 1546-1726. ; 23:8, s. 952-958
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Tidskriftsartikel (refereegranskat)abstract
- In Alzheimer’s disease (AD), hippocampus-dependent memories underlie an extensive decline. The neuronal ensemble encoding a memory, termed engram, is partially recapitulated during memory recall. Artificial activation of an engram can restore memory in a mouse model of early AD, but its fate and the factors that render the engram nonfunctional are yet to be revealed. Here, we used repeated two-photon in vivo imaging to analyze fosGFP transgenic mice (which express enhanced GFP under the Fos promoter) performing a hippocampus-dependent memory task. We found that partial reactivation of the CA1 engram during recall is preserved under AD-like conditions. However, we identified a novelty-like ensemble that interfered with the engram and thus compromised recall. Mimicking a novelty-like ensemble in healthy mice was sufficient to affect memory recall. In turn, reducing the novelty-like signal rescued the recall impairment under AD-like conditions. These findings suggest a novel mechanistic process that contributes to the deterioration of memories in AD.
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