High-fat diet (HFD)-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, ...learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group) or a HFD (60% of calorie from fat; HFD group) for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a) a significant decrease of insulin receptor substrate (IRS-1) phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b) these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c) primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment); this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a) an inactivation of the IRS-1 and, consequentially, (b) a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c) a suppression of the ERK/CREB pathway, and (d) a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity). It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts profoundly on brain activity, i.e., synaptic plasticity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Exercise interventions in individuals with Parkinson's disease incorporate goal-based motor skill training to engage cognitive circuitry important in motor learning. With this exercise ...approach, physical therapy helps with learning through instruction and feedback (reinforcement) and encouragement to perform beyond self-perceived capability. Individuals with Parkinson's disease become more cognitively engaged with the practice and learning of movements and skills that were previously automatic and unconscious. Aerobic exercise, regarded as important for improvement of blood flow and facilitation of neuroplasticity in elderly people, might also have a role in improvement of behavioural function in individuals with Parkinson's disease. Exercises that incorporate goal-based training and aerobic activity have the potential to improve both cognitive and automatic components of motor control in individuals with mild to moderate disease through experience-dependent neuroplasticity. Basic research in animal models of Parkinson's disease is beginning to show exercise-induced neuroplastic effects at the level of synaptic connections and circuits.
Context:
In cross-sectional studies, serum TSH concentrations increase with age. This has not been examined longitudinally, and it is uncertain whether the TSH increase reflects healthy aging or ...occult thyroid failure.
Methods:
We measured serum TSH, free T4, thyroid peroxidase, and thyroglobulin antibodies in 1100 participants in the 1981 and 1994 Busselton Health Surveys and derived a reference group of 908 individuals without thyroid disease or thyroid antibodies. We examined changes in thyroid function longitudinally and, in 781 participants, explored associations with the CAPZB polymorphism rs10917469.
Results:
At 13 yr follow-up, mean serum TSH increased from 1.49 to 1.81 mU/liter, a change in mean TSH (ΔTSH) of 0.32 mU/liter 95% confidence interval (CI) 0.27, 0.38, P < 0.001, whereas mean free T4 concentration was unchanged (16.6 vs. 16.6 pmol/liter, P = 0.7). The TSH increase was most marked in the elderly, such that gender-adjusted ΔTSH increased by 0.08 mU/liter (95% CI 0.04, 0.11) for each decade of baseline age. People with higher baseline TSH values had proportionally smaller increases in TSH, with each additional 1.0 mU/liter of baseline TSH associated with a 0.13 mU/liter decrease (age and gender adjusted) in ΔTSH (95% CI 0.09, 0.16). The ΔTSH did not differ significantly by CAPZB genotype.
Conclusions:
Aging is associated with increased serum TSH concentrations, with no change in free T4 concentrations. The largest TSH increase is in people with the lowest TSH at baseline. This suggests that the TSH increase arises from age-related alteration in the TSH set point or reduced TSH bioactivity rather than occult thyroid disease.
•Use bibliometric and survey data to analyze the dynamics of size, knowledge variety, and creativity in scientific teams.•Team size has inverted-U relation with novelty and continually increasing ...relation with impact.•Size–novelty relationship is driven by effect of knowledge variety.•Knowledge variety does not have a direct effect on impact, net of novelty and size.•Suggests the need for a governance approach to scientific work and S&T policies unpacking novelty and impact.
The increasing dominance of team science highlights the importance of understanding the effects of team composition on the creativity of research results. In this paper, we analyze the effect of team size, and field and task variety on creativity. Furthermore, we unpack two facets of creativity in science: novelty and impact. We find that increasing team size has an inverted-U shaped relation with novelty. We also find that the size–novelty relationship is largely due to the relation between size and team field or task variety, consistent with the information processing perspective. On the other hand, team size has a continually increasing relation with the likelihood of a high-impact paper. Furthermore, variety does not have a direct effect on impact, net of novelty. This study develops our understanding of team science and highlights the need for a governance approach to scientific work. We also advance the creativity literature by providing an ex ante objective bibliometric measure that distinguishes novelty from impact, and illustrate the distinct team-level drivers of each. We conclude with a discussion of the policy implications of our findings.
Changing demographics of scientific careers Milojević, Staša; Radicchi, Filippo; Walsh, John P.
Proceedings of the National Academy of Sciences - PNAS,
12/2018, Letnik:
115, Številka:
50
Journal Article
Recenzirano
Odprti dostop
Contemporary science has been characterized by an exponential growth in publications and a rise of team science. At the same time, there has been an increase in the number of awarded PhD degrees, ...which has not been accompanied by a similar expansion in the number of academic positions. In such a competitive environment, an important measure of academic success is the ability to maintain a long active career in science. In this paper, we study workforce trends in three scientific disciplines over half a century. We find dramatic shortening of careers of scientists across all three disciplines. The time over which half of the cohort has left the field has shortened from 35 y in the 1960s to only 5 y in the 2010s. In addition, we find a rapid rise (from 25 to 60% since the 1960s) of a group of scientists who spend their entire career only as supporting authors without having led a publication. Altogether, the fraction of entering researchers who achieve full careers has diminished, while the class of temporary scientists has escalated. We provide an interpretation of our empirical results in terms of a survival model from which we infer potential factors of success in scientific career survivability. Cohort attrition can be successfully modeled by a relatively simple hazard probability function. Although we find statistically significant trends between survivability and an author’s early productivity, neither productivity nor the citation impact of early work or the level of initial collaboration can serve as a reliable predictor of ultimate survivability.
Summary
Serum thyroid‐stimulating hormone (TSH) testing is the best screening tool for thyroid dysfunction. When TSH levels are in the reference range, additional tests such as free thyroxine, free ...triiodothyronine or thyroid antibodies rarely add value, except in patients with pituitary disease, when TSH is unreliable.
Overt hypothyroidism and subclinical hypothyroidism with TSH levels > 10 mU/L can be treated without further investigation. The health impact of subclinical hypothyroidism with mildly elevated levels of TSH (4–10 mU/L) remains uncertain, particularly in older people; treatment or observation are reasonable options.
Thyroxine remains standard treatment for hypothyroidism, with optimal dosage determined by clinical response and serum TSH.
Hyperthyroidism is commonly caused by Graves' disease, thyroiditis or toxic nodular goitre. The cause should be established before offering treatment. Radionuclide scanning is the imaging modality of choice. Positive TSH‐receptor antibodies indicate Graves' disease.
Thyroid ultrasound is indicated for assessment of palpable goitre and thyroid nodules. It is not part of routine assessment of hyperthyroidism or hypothyroidism. Overzealous use of ultrasound identifies clinically unimportant thyroid nodules and can lead to overdiagnosis of thyroid cancer.
For thyroid nodules, the key investigation is ultrasound‐guided fine needle aspiration biopsy, depending on size and sonographic appearance. Biopsy should not be performed routinely on small nodules < 1 cm.
It remains controversial whether pregnant women should be screened for thyroid disease. Reference intervals for thyroid function tests during pregnancy are not well established, and it is uncertain whether thyroxine treatment for pregnant women with serum TSH levels between 2.5 and 4.0 mU/L is beneficial. Iodine supplementation is recommended during pregnancy.
Circulating concentrations of thyrotropin (TSH) and thyroxine (T4) are tightly regulated. Each individual has setpoints for TSH and free T4 which are genetically determined, and subject to ...environmental and epigenetic influence. Pituitary-thyroid axis setpoints are probably established in utero, with maturation of thyroid function continuing until late gestation. From neonatal life (characterized by a surge of TSH and T4 secretion) through childhood and adolescence (when free triiodothyronine levels are higher than in adults), thyroid function tests display complex, dynamic patterns which are sexually dimorphic. In later life, TSH increases with age in healthy older adults without an accompanying fall in free T4, indicating alteration in TSH setpoint. In view of this, and evidence that mild subclinical hypothyroidism in older people has no health impact, a strong case can be made for implementation of age-related TSH reference ranges in adults, as is routine in children.
Abstract
We analyse the environmental properties of 370 local early-type galaxies (ETGs) in the MASSIVE and ATLAS3D surveys, two complementary volume-limited integral-field spectroscopic (IFS) galaxy ...surveys spanning absolute K-band magnitude − 21.5 ≳ MK
≳ −26.6, or stellar mass
$8\times 10^{9} \lesssim M_* \lesssim 2\times 10^{12}\,\text{M}_{\odot }$
. We find these galaxies to reside in a diverse range of environments measured by four methods: group membership (whether a galaxy is a brightest group/cluster galaxy, satellite or isolated), halo mass, large-scale mass density (measured over a few Mpc) and local mass density (measured within the Nth neighbour). The spatially resolved IFS stellar kinematics provide robust measurements of the spin parameter λe and enable us to examine the relationship among λe, M
* and galaxy environment. We find a strong correlation between λe and M
*, where the average λe decreases from ∼0.4 to below 0.1 with increasing mass, and the fraction of slow rotators f
slow increase from ∼10 to 90 per cent. We show for the first time that at fixed M
*, there are almost no trends between galaxy spin and environment; the apparent kinematic morphology–density relation for ETGs is therefore primarily driven by M
* and is accounted for by the joint correlations between M
* and spin, and between M
* and environment. A possible exception is that the increased f
slow at high local density is slightly more than expected based only on these joint correlations. Our results suggest that the physical processes responsible for building up the present-day stellar masses of massive galaxies are also very efficient at reducing their spin, in any environment.
•Invention-level US survey data on rates and impacts of invention collaboration.•About 10% of inventions involve an external co-inventor; about 25% involve external (non-co-inventor) ...collaboration.•Heterogeneous collaboration, university-industry and vertical collaboration associated with higher invention quality.•Commercialization rates are related to vertical collaboration, and non-invention collaboration heterogeneity.
Much current work in management of innovation argues that it is becoming increasingly necessary for inventors and their firms to exploit information and capabilities outside the firm in order to combine one’s own resources with resources from the external environment. Building on this prior work, we examine the relationship between collaboration and innovation. Using detailed information on a sample of triadic patents, with over 1900 responses in the US, we report on the rates of collaboration of various forms, and test the effects of collaboration. Our results suggest that just over 10% of inventions involve an external co-inventor and about 23% involve external (non-co-inventor) collaborators (with 27% involving any external collaborators). We find evidence that heterogeneous collaboration and university-industry collaboration in inventing drive higher invention quality. However, vertical collaboration at the inventing stage is relatively more critical to commercialization at the implementation stage than is university-industry collaboration. These results suggest that the impact of different forms of collaborative innovation may vary depending on the stage of the innovation process.
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