Genetic evidence indicates that brain-derived neurotrophic factor (BDNF) signaling through the TrkB receptor plays a critical role in the control of energy balance. Mutations in the BDNF or the ...TrkB-encoding NTRK2 gene have been found to cause severe obesity in humans and mice. However, it remains unknown which brain neurons express TrkB to control body weight. Here, we report that TrkB-expressing neurons in the dorsomedial hypothalamus (DMH) regulate food intake. We found that the DMH contains both glutamatergic and GABAergic TrkB-expressing neurons, some of which also express the leptin receptor (LepR). As revealed by Fos immunohistochemistry, a significant number of TrkB-expressing DMH (DMHTrkB) neurons were activated upon either overnight fasting or after refeeding. Chemogenetic activation of DMHTrkB neurons strongly suppressed feeding in the dark cycle when mice are physiologically hungry, whereas chemogenetic inhibition of DMHTrkB neurons greatly promoted feeding in the light cycle when mice are physiologically satiated, without affecting feeding in the dark cycle. Neuronal tracing revealed that DMHTrkB neurons do not innervate neurons expressing agouti-related protein in the arcuate nucleus, indicating that DMHTrkB neurons are distinct from previously identified LepR-expressing GABAergic DMH neurons that suppress feeding. Furthermore, selective Ntrk2 deletion in the DMH of adult mice led to hyperphagia, reduced energy expenditure, and obesity. Thus, our data show that DMHTrkB neurons are a population of neurons that are necessary and sufficient to suppress appetite and maintain physiological satiation. Pharmacological activation of these neurons could be a therapeutic intervention for the treatment of obesity.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Brain-derived neurotrophic factor (BDNF) is a key regulator of energy balance; however, its underlying mechanism remains unknown. By analyzing BDNF-expressing neurons in paraventricular hypothalamus ...(PVH), we have uncovered neural circuits that control energy balance. The Bdnf gene in the PVH was mostly expressed in previously undefined neurons, and its deletion caused hyperphagia, reduced locomotor activity, impaired thermogenesis, and severe obesity. Hyperphagia and reduced locomotor activity were associated with Bdnf deletion in anterior PVH, whereas BDNF neurons in medial and posterior PVH drive thermogenesis by projecting to spinal cord and forming polysynaptic connections to brown adipose tissues. Furthermore, BDNF expression in the PVH was increased in response to cold exposure, and its ablation caused atrophy of sympathetic preganglionic neurons. Thus, BDNF neurons in anterior PVH control energy intake and locomotor activity, whereas those in medial and posterior PVH promote thermogenesis by releasing BDNF into spinal cord to boost sympathetic outflow.
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•The PVH is a key structure that produces BDNF to control energy balance•The majority of BDNF neurons in the PVH are distinct from previously defined ones•BDNF neurons in the anterior PVH inhibit feeding and stimulate locomotor activity•BDNF neurons in the medial and posterior PVH drive adaptive thermogenesis
Distinct subsets of BDNF-expressing neurons in the paraventricular hypothalamus (PVH) control different aspects of energy balance, with those in the anterior PVH suppressing food intake and promoting locomotor activity and those in the medial and posterior PVH driving adaptive thermogenesis through polysynaptic connections to brown adipose tissues.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Improvements in the quantification and visual analysis of data, plotted across non-standardized graphs, are possible with the equations introduced in this paper. Equation 1 (an expression of graphic ...scale variability) forms part of the foundation for Equation 2 (an expansion on the traditional calculation of the tangent inverse of a line’s algebraic slope). These equations provide clarification regarding aspects of “slope” and graphic scaling that have previously confused mathematicians. The apparent lack of correspondence between geometric slope (the angle of inclination) and algebraic slope (the m in y = mx + b) on “non-homogeneous” graphs (graphs where the scale values/distances on the y-axis are not the same as on the x-axis) is identified and directly resolved. This is important because nearly all behavior analytic graphs are “non-homogeneous” and problems with consistent visual inspection of such graphs have yet to be fully resolved. This paper shows how the precise geometric slope for any trend line on any non-homogeneous graph can quickly be determined—potentially improving the quantification and visual analysis of treatment effects in terms of the amount/magnitude of change in slope/variability. The equations herein may also be used to mathematically control for variability inherent in a graph’s idiosyncratic construction, and thus facilitate valid comparison of data plotted on various non-standard graphs constructed with very different axes scales—both within and across single case design research studies. The implications for future research and the potential for improving effect size measures and meta-analyses in single-subject research are discussed.
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The TrkB receptor is critical for the control of energy balance, as mutations in its gene (NTRK2) lead to hyperphagia and severe obesity. The main neural substrate mediating the appetite-suppressing ...activity of TrkB, however, remains unknown. Here, we demonstrate that selective Ntrk2 deletion within paraventricular hypothalamus (PVH) leads to severe hyperphagic obesity. Furthermore, chemogenetic activation or inhibition of TrkB-expressing PVH (PVH
) neurons suppresses or increases food intake, respectively. PVH
neurons project to multiple brain regions, including ventromedial hypothalamus (VMH) and lateral parabrachial nucleus (LPBN). We find that PVH
neurons projecting to LPBN are distinct from those to VMH, yet Ntrk2 deletion in PVH neurons projecting to either VMH or LPBN results in hyperphagia and obesity. Additionally, TrkB activation with BDNF increases firing of these PVH neurons. Therefore, TrkB signaling is a key regulator of a previously uncharacterized neuronal population within the PVH that impinges upon multiple circuits to govern appetite.
The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and ...their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin
. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force
. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton
. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results
, and point to future measurements that can distinguish between these mechanisms.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Making treatment decisions based upon graphed data is important in helping professions. A small amount of research has compared usability between equal-interval and semi-log graphs, but no prior ...studies have compared different types of semi-log graphs. Using a randomized, cross-over, experimental design with 72 participants, this study examined the relative usability and acceptability of three types of graphs: Regular (equal-interval), Standard Celeration Chart (SCC; semi-log), and Standard Behavior Graph (SBG; semi-log). All participants used each graph across three usability tasks (Plotting Data, Writing Values, and Interpreting Trends). For the Plotting and Writing tasks, the equal-interval graph produced the greatest rate of correct responses. However, for the Interpreting task the SBG produced the greatest rate of corrects, while the equal-interval graph produced the smallest rate. User acceptability mainly favored the equal-interval and SBG graphs. Study findings and implications are discussed with respect to graph usability and acceptability during day-to-day practice.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abstract
All experiments observing dilepton pairs (e.g.
e
+
e
-
,
μ
+
μ
-
) must confront the existence of a
combinatoric
background caused by the combining of tracks not arising from the
same ...physics vertex. Some method must be devised to calculate and
remove this background. In this document we describe a particular
event-mixing method relying on many of the unique aspects of the
SeaQuest spectrometer and data. The method described here
calculates the combinatoric background with correct normalization;
i.e., there is no need to assign a floating normalization factor
that is then determined in a subsequent fitting procedure. Numerous
tests are applied to demonstrate the reliability of the method.
(1) Background: Integrated standardized patient examinations (ISPEs) allow students to demonstrate competence with curricular learning and communication. Digital recordings of these experiences ...provide an objective permanent record, allowing students to review and improve their performance. Although recordings have been utilized as a tool in physical therapy education, no studies have described the impact of reviewing recordings of ISPE. This qualitative pilot study aimed to investigate student perceptions and learning after reviewing their recordings of ISPE. (2) Methods: Second-year Doctor of Physical Therapy students (n= 23) participated in the study by completing an anonymous online survey after reviewing their recordings from three ISPEs. Thematic analysis was used to identify codes and central themes from the survey data. (3) Results: The results showed that 95.6% of students found the video review process beneficial. Five themes emerged: (i) digital recordings provide an objective performance assessment, (ii) approaches to self-review vary, (iii) it provides an opportunity for growth, (iv) a holistic review is possible, and (v) students need structure and guidance in the process. (4) Conclusions: Study findings indicate that a review of the recordings of ISPEs facilitates the development of clinical skills for physical therapy students. Implementing an explicit framework for reviewing the recordings may enhance the process and facilitate further promotion of reflection-on-action.
Animal welfare and conservation breeding have overlapping and compatible goals that are occasionally divergent. Efforts to improve enclosures, provide enriching experiences, and address behavioral ...and physical needs further the causes of animal welfare in all zoo settings. However, by mitigating stress, increasing behavioral competence, and enhancing reproduction, health, and survival, conservation breeding programs must also focus on preparing animals for release into the wild. Therefore, conservation breeding facilities must strike a balance of promoting high welfare, while minimizing the effects of captivity to increase population sustainability. As part of the Hawaii Endangered Bird Conservation Program, San Diego Zoo Global operates two captive breeding facilities that house a number of endangered Hawaiian bird species. At our facilities we aim to increase captive animal welfare through husbandry, nutrition, behavior-based enrichment, and integrated veterinary practices. These efforts help foster a captive environment that promotes the development of species-typical behaviors. By using the "Opportunities to Thrive" guiding principles, we outline an outcome-based welfare strategy, and detail some of the related management inputs, such as transitioning to parental rearing, and conducting veterinary exams remotely. Throughout we highlight our evidence-based approach for evaluating our practices, by monitoring welfare and the effectiveness of our inputs. Additionally we focus on some of the unique challenges associated with improving welfare in conservation breeding facilitates and outline concrete future steps for improving and evaluating welfare outcomes that also meet conservation goals.
Brain-derived neurotrophic factor (BDNF) is a key neuropeptide in the central regulation of energy balance. The Bdnf gene contains nine promoters, each producing specific mRNA transcripts that encode ...a common protein. We sought to assess the phenotypic outcomes of disrupting BDNF production from individual Bdnf promoters. Mice with an intact coding region but selective disruption of BDNF production from Bdnf promoters I, II, IV, or VI (Bdnf-e1
, -e2
, -e4
, and -e6
) were created by inserting an enhanced green fluorescent protein-STOP cassette upstream of the targeted promoter splice donor site. Body composition was measured by MRI weekly from age 4 to 22 wk. Energy expenditure was measured by indirect calorimetry at 18 wk. Food intake was measured in Bdnf-e1
and Bdnf-e2
mice, and pair feeding was conducted. Weight gain, lean mass, fat mass, and percent fat of Bdnf-e1
and Bdnf-e2
mice (both sexes) were significantly increased compared with wild-type littermates. For Bdnf-e4
and Bdnf-e6
mice, obesity was not observed with either chow or high-fat diet. Food intake was increased in Bdnf-e1
and Bdnf-e2
mice, and pair feeding prevented obesity. Mutant and wild-type littermates for each strain (both sexes) had similar total energy expenditure after adjustment for body composition. These findings suggest that the obesity phenotype observed in Bdnf-e1
and Bdnf-e2
mice is attributable to hyperphagia and not altered energy expenditure. Our findings show that disruption of BDNF from specific promoters leads to distinct body composition effects, with disruption from promoters I or II, but not IV or VI, inducing obesity.
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