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- Jersin, R. A., et al.
(författare)
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Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:3, s. 680-695
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Tidskriftsartikel (refereegranskat)abstract
- Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.
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- Dherbecourt, J. B., et al.
(författare)
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Design and pre-development of an airborne multi-species differential absorption Lidar system for water vapor and HDO isotope, carbon dioxide, and methane observation
- 2021
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE-Intl Soc Optical Eng.
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Konferensbidrag (refereegranskat)abstract
- We report on the current design and preliminary developments of the airborne Lidar Emitter and Multi-species greenhouse gases Observation iNstrument (LEMON), which is aiming at probing H2O and its isotope HDO at 1982 nm, CO2 at 2051 nm, and potentially CH4 at 2290 nm, with the Differential Absorption Lidar method (DIAL). The infrared emitter is based on the combination of two Nested Cavity OPOs (NesCOPOs) with a single optical parametric amplifier (OPA) line for high-energy pulse generation. This configuration is enabled by the use of high-aperture periodically poled KTP crystals (PPKTP), which provide efficient amplification in the spectral range of interest around 2 μm with slight temperature adjustments. The parametric stages are pumped with a Nd:YAG laser providing 200 mJ nanosecond double pulses at 75 Hz. According to parametric conversion simulations supported by current laboratory experiments, output energies in the 40 - 50 mJ range are expected in the extracted signal beam whilst maintaining a good beam quality (M2 < 2). The ruler for all the optical frequencies involved in the system is planned to be provided by a GPS referenced frequency comb with large mode spacing (1 GHz) against which the emitter output pulses can be heterodyned. The frequency precision measurement is expected to be better than 200 kHz for the optical frequencies of interest. The presentation will give an overview of the key elements of design and of preliminary experimental characterizations of sub-systems building blocks.
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- Dherbecourt, J. B., et al.
(författare)
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Lidar Emitter and Multi-species greenhouse gases Observation iNstrument (LEMON) : advances on a multi-species differential absorption Lidar system
- 2022
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Ingår i: 73rd International Astronautical Congress, IAC 2022. - : International Astronautical Federation, IAF.
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Konferensbidrag (refereegranskat)abstract
- In the frame of LEMON project (Lidar Emitter and Multi-species greenhouse gases Observation iNstrument - European Union's Horizon 2020 research and innovation program, GA n°821868), we are developing a multi-species differential absorption Lidar (DIAL). The goal is to benefit from innovative technological developments in terms of optical emitter, spectral reference, to be able to address H2O and its isotope HDO at 1982 nm, CO2 at 2051 nm, and potentially CH4 at 2290 nm, for future ground-based range-resolved DIAL sensing, and with the prospect of future airborne integrated-path DIAL (IPDA). The infrared emitter is based on the combination of two specific, patented, no-seeder Nested Cavity OPOs (NesCOPOs) coupled to a single optical parametric amplifier (OPA) line for high energy pulses generation. Specific developments are also pursued on the frequency reference for the emitter, which is planned to be provided by a GPS referenced frequency comb against which the emitter output pulses can be heterodyned. Besides the instrument design, specific tests experiments have been carried out, covering a wide panel of activities: radiation testing of some critical components to assess the potential of some key components for future space applications, emitter and frequency reference testing, preliminary DIAL tests with laboratory test-beds and comparison with specific in-situ calibration instruments as well as additional innovative techniques evaluation for the emitter. The final instrument design was carried out and the sub-units are now being built.
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- Hokken-Koelega, A. C. S., et al.
(författare)
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International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood
- 2023
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Ingår i: Endocrine Reviews. - : The Endocrine Society. - 0163-769X .- 1945-7189. ; 44:3, s. 539-565
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Tidskriftsartikel (refereegranskat)abstract
- This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < -2.5 SDS at age 2 years or < -2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle.
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- de Vries, Claire E. E., et al.
(författare)
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Outcomes of the first global multidisciplinary consensus meeting including persons living with obesity to standardize patient-reported outcome measurement in obesity treatment research
- 2022
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Ingår i: Obesity Reviews. - : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:8
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Tidskriftsartikel (refereegranskat)abstract
- Quality of life is a key outcome that is not rigorously measured in obesity treatment research due to the lack of standardization of patient-reported outcomes (PROs) and PRO measures (PROMs). The S.Q.O.T. initiative was founded to Standardize Quality of life measurement in Obesity Treatment. A first face-to-face, international, multidisciplinary consensus meeting was conducted to identify the key PROs and preferred PROMs for obesity treatment research. It comprised of 35 people living with obesity (PLWO) and healthcare providers (HCPs). Formal presentations, nominal group techniques, and modified Delphi exercises were used to develop consensus-based recommendations. The following eight PROs were considered important: self-esteem, physical health/functioning, mental/psychological health, social health, eating, stigma, body image, and excess skin. Self-esteem was considered the most important PRO, particularly for PLWO, while physical health was perceived to be the most important among HCPs. For each PRO, one or more PROMs were selected, except for stigma. This consensus meeting was a first step toward standardizing PROs (what to measure) and PROMs (how to measure) in obesity treatment research. It provides an overview of the key PROs and a first selection of the PROMs that can be used to evaluate these PROs.
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- Williams, S, et al.
(författare)
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Remote consultations in primary care across low-, middle- and high-income countries: Implications for policy and care delivery
- 2023
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Ingår i: Journal of health services research & policy. - : SAGE Publications. - 1758-1060 .- 1355-8196. ; 28:3, s. 181-189
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic mandated a substantial switch in primary health care delivery from an in-person to a mainly remote telephone or video service. As the COVID-19 pandemic approaches its third year, limited progress appears to have been made in terms of policy development around consultation methods for the post-acute phase of the pandemic. In September 2020, the International Primary Care Respiratory Group convened a global panel of primary care clinicians – including family physicians, paediatricians, pharmacists, academics and patients – to consider the policy and health management implications of the move to remote consultations in the primary care setting. The group gave special consideration to how and how far remote consultations should be integrated into routine primary health care delivery. Remote consultations can be a useful alternative to in-person consultations in primary care not only in situations where there is a need for viral infection control but also for the routine delivery of chronic disease management. However, they may not be more time efficient for the clinician, and they can add to the workload and work-related stress for primary care practitioners if they remain the dominant consultation mode. Remote consultations are also less appropriate than in-person consultations for new disease diagnosis, dealing with multiple issues and providing complex care. Ensuring health care professionals have the appropriate skill set to effectively deliver remote consultations, administrative and/or IT support and appropriate reimbursement will be key to achieving optimal integration of remote consultations into routine clinical practice. Addressing digital access and digital literacy issues at a societal level will also be essential to ensure individuals have fair and equitable access to the internet and sufficient security for exchange of personal and health-related data.
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- Martins Dos Santos, Vitor, et al.
(författare)
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Systems Biology in ELIXIR: modelling in the spotlight
- 2022
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Ingår i: F1000Research. - : F1000 Research Ltd. - 1759-796X .- 2046-1402. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.
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