Procedures utilizing Chelex100 chelating resin have been developed for extracting DNA from forensic-type samples for use with the PCR. The procedures are simple, rapid, involve no organic solvents ...and do not require multiple tube transfers for most types of samples. The extracion of DNA from semen and very small blood stains using Chelex 100 is as efficient or more efficient than using proteinase K and phenol-chloroform extraction. DNA extracted from bloodstains seems less prone to contain PCR inhibitors when prepared by this method. The Chelex method has been used with amplification and typing at the HLA DQα locus to obtain the DQα genotypes of many different types of samples, including whole blood, bloodstains, seminal stains, buccal swabs, hair and post-coital samples. The results of a concordance study are presented in which the DQα genotypes of 84 samples prepared using Chelex or using conventional phenol-chloroform extraction are compared. The genotypes obtained using the two different extraction methods were identical for all samples tested.
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.
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.
We report that two oncogenes coamplified on chromosome 3q26, PRKCI and SOX2, cooperate to drive a stem-like phenotype in lung squamous cell carcinoma (LSCC). Protein kinase Cι (PKCι) phosphorylates ...SOX2, a master transcriptional regulator of stemness, and recruits it to the promoter of Hedgehog (Hh) acyltransferase (HHAT) that catalyzes the rate-limiting step in Hh ligand production. PKCι-mediated SOX2 phosphorylation is required for HHAT promoter occupancy, HHAT expression, and maintenance of a stem-like phenotype. Primary LSCC tumors coordinately overexpress PKCι, SOX2, and HHAT and require PKCι-SOX2-HHAT signaling to maintain a stem-like phenotype. Thus, PKCι and SOX2 are genetically, biochemically, and functionally linked in LSCC, and together they drive tumorigenesis by establishing a cell-autonomous Hh signaling axis.
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•PRKCI and SOX2 are coamplified and coordinately overexpressed in LSCC tumors•PKCι transcriptionally regulates expression of Hedgehog acyltransferase (HHAT)•PKCι directly phosphorylates and recruits SOX2 to the HHAT promoter•PKCι and SOX2 activate autocrine Hh signaling to maintain LSCC stem-like cells
Justilien et al. find a functional link between proteins encoded by PRKCI and SOX2 that are often coamplified in lung squamous cell carcinoma. PKCι phosphorylates SOX2, enabling it to increase HHAT expression that, in turn, activates cell-autonomous Hedgehog signaling to sustain a stem-like phenotype.
•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
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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.
Recovery of the immune system after exercise Peake, Jonathan M; Neubauer, Oliver; Walsh, Neil P ...
Journal of applied physiology (1985),
2017-May-01, Letnik:
122, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The notion that prolonged, intense exercise causes an "open window" of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without ...sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions e.g., natural killer (NK) cells, γδ T cells, and CD8
T cells. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes.
The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed during early embryogenesis to establish full developmental potential. ...Previous studies have suggested that the paternal genome is actively demethylated in the zygote while the maternal genome undergoes subsequent passive demethylation via DNA replication during cleavage. Active demethylation is known to depend on 5mC oxidation by Tet dioxygenases and excision of oxidized bases by thymine DNA glycosylase (TDG). Here we show that both maternal and paternal genomes undergo widespread active and passive demethylation in zygotes before the first mitotic division. Passive demethylation was blocked by the replication inhibitor aphidicolin, and active demethylation was abrogated by deletion of Tet3 in both pronuclei. At actively demethylated loci, 5mCs were processed to unmodified cytosines. Surprisingly, the demethylation process was unaffected by the deletion of TDG from the zygote, suggesting the existence of other demethylation mechanisms downstream of Tet3-mediated oxidation.
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•Maternal and paternal genomes both undergo active demethylation in mouse zygotes•Both zygotic genomes also undergo replication-dependent passive demethylation•At actively demethylated loci, 5mCs are processed to unmodified cytosines•Active demethylation depends on Tet3 dioxygenase, but not on TDG glycosylase
In one-cell mouse embryos, the maternal and paternal genomes both undergo global Tet3-dependent active demethylation and replication-mediated passive demethylation. Surprisingly, the active demethylation pathway does not require TDG.
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