The Need to Feed Homeostatic and Hedonic Control of Eating

AbstractFeeding provides substrate for energy metabolism, which is vital to the survival of every living animal and therefore is subject to intense regulation by brain homeostatic and hedonic systems. Over the last decade, our understanding of the circuits and molecules involved in this process has changed dramatically, in large part due to the availability of animal models with genetic lesions. In this review, we examine the role played in homeostatic regulation of feeding by systemic mediators such as leptin and ghrelin, which act on brain systems utilizing neuropeptide Y, agouti-related peptide, melanocortins, orexins, and melanin concentrating hormone, among other mediators. We also examine the mechanisms for taste and reward systems that provide food with its intrinsically reinforcing properties and explore the links between the homeostatic and hedonic systems that ensure intake of adequate nutrition

Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial

There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited

Isokinetic eccentric exercise substantially improves mobility, muscle strength and size, but not postural sway metrics in older adults, with limited regression observed following a detraining period

© 2020, The Author(s). Introduction: Eccentric exercise can reverse age-related decreases in muscle strength and mass; however, no data exist describing its effects on postural sway. As the ankle may be more important for postural sway than hip and knee joints, and with older adults prone to periods of inactivity, the effects of two 6-week seated isokinetic eccentric exercise programmes, and an 8-week detraining period, were examined in 27 older adults (67.1 ± 6.0 years). Methods: Neuromuscular parameters were measured before and after training and detraining periods with subjects assigned to ECC (twice-weekly eccentric-only hip and knee extensor contractions) or ECCPF (identical training with additional eccentric-only plantarflexor contractions) training programmes. Results: Significant (P \u3c 0.05) increases in mobility (decreased timed-up-and-go time [− 7.7 to − 12.0%]), eccentric strength (39.4–58.8%) and vastus lateralis thickness (9.8–9.9%) occurred after both training programmes, with low-to-moderate weekly rate of perceived exertion (3.3–4.5/10) reported. No significant change in any postural sway metric occurred after either training programme. After 8 weeks of detraining, mobility (− 8.2 to − 11.3%), eccentric strength (30.5–50.4%) and vastus lateralis thickness (6.1–7.1%) remained significantly greater than baseline in both groups. Conclusion: Despite improvements in functional mobility, muscle strength and size, lower-limb eccentric training targeting hip, knee and ankle extensor muscle groups was not sufficient to influence static balance. Nonetheless, as the beneficial functional and structural adaptations were largely maintained through an 8-week detraining period, these findings have important implications for clinical exercise prescription as the exercise modality, low perceived training intensity, and adaptive profile are well suited to the needs of older adults

A Novel Tool for the Assessment of Pain: Validation in Low Back Pain

Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain

Internationalisation and migrant academics: the hidden narratives of mobility

Internationalisation is a dominant policy discourse in higher education today. It is invariably presented as an ideologically neutral, coherent, disembodied, knowledgedriven policy intervention - an unconditional good. Yet it is a complex assemblage of values linked not only to economic growth and prosperity, but also to global citizenship, transnational identity capital, social cohesion, intercultural competencies and soft power (Clifford and Montgomery 2014; De Wit et al. 2015; Kim 2017; Lomer 2016; Stier 2004). Mobility is the sine qua non of the global academy (Sheller 2014). International movements, flows and networks are perceived as valuable transnational and transferable identity capital and as counterpoints to intellectual parochialism. Fluidity metaphors abound as an antidote to stasis e.g. flows, flux and circulations (Urry 2007). For some, internationalisation is conceptually linked to the political economy of neoliberalism and the spatial extension of the market, risking commodification and commercialisation (Matus and Talburt 2009). Others raise questions about what/whose knowledge is circulating and whether internationalisation is a form of re-colonisation and convergence that seeks to homogenise higher education systems (Stromquist 2007). Internationalisation policies and practices, it seems, are complex entanglements of economic, political, social and affective domains. They are mechanisms for driving the global knowledge 2 economy and the fulfilment of personal aspirations (Hoffman 2009). Academic geographical mobility is often conflated with social mobility and career advancement (Leung 2017). However, Robertson (2010: 646) suggested that ‘the romance of movement and mobility ought to be the first clue that this is something we ought to be particularly curious about.

Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease

status: publishe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer, have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance

Synthesis, Structures, and Optical Properties of Ruthenium(II) Complexes of the Tris(1-pyrazolyl)methane Ligand

Four new complex salts [Ru^(II)Cl(Tpm)(L^A)_2][PF_6]_n [Tpm = tris(1-pyrazolyl)methane; n = 1, L^A = pyridine (py) 1 or ethyl isonicotinate (EIN) 2; n = 3, L^A = N-methyl-4,4′-bipyridinium (MeQ^+) 3 or N-phenyl-4,4′-bipyridinium (PhQ^+) 4] have been prepared and characterized. Electronic absorption spectra show intense d → π^* metal-to-ligand charge-transfer (MLCT) absorption bands, while cyclic voltammetry reveals a reversible Ru^(III/II) wave, accompanied by quasireversible or irreversible L^A-based reductions for all except 1. Single crystal X-ray structures have been obtained for 1•Me_2CO, 2, and 3•Me_2CO. For 2–4, molecular first hyperpolarizabilities β have been measured in acetonitrile solutions via the hyper-Rayleigh scattering (HRS) technique at 800 nm. Stark (electroabsorption) spectroscopic studies on the MLCT bands in frozen butyronitrile allow the indirect estimation of static first hyperpolarizabilities β_0. The various physical data obtained for 3 and 4 are compared with those reported previously for related cis-{Ru^(II)(NH_3)_4}^(2+) species [Coe, B. J. et al. J. Am. Chem. Soc. 2005, 127, 4845]. TD-DFT calculations on the complexes in 1–4 confirm that their lowest energy absorption bands are primarily Ru^(II) → L^A MLCT in character, while Ru^(II) → Tpm MLCT transitions are predicted at higher energies. DFT agrees with the Stark, but not the HRS measurements, in showing that β_0 increases with the electron-accepting strength of L^A. The 2D nature of the chromophores is evidenced by dominant β_(xxy) tensor components