Miracle-dz/UniFAR-FTUs huggingface dataset:
A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis

Purpose: Cancer metastasis can occur at the early stage of tumor development when a primary tumor is at the microscopic size. In particular, the interaction of malignant cells with other cell types including cancer-associated fibroblasts (CAF) in promoting metastasis at the early stage of tumor development remains largely unknown. Here, we investigated the role of CAFs in facilitating the initial events of cancer metastasis when primary tumors were at microscopic sizes. Experimental Design: Multicolor-coded cancer cells and CAFs were coimplanted into the transparent zebrafish body and metastasis at a single-cell level was monitored in living animals. Healthy fibroblasts, tumor factor–educated fibroblasts, and CAFs isolated from various tumors were tested for their ability to facilitate metastasis. Results: We showed that CAFs promoted cancer cell metastasis at the very early stage during primary tumor development. When a primary tumor was at the microscopic size consisting of a few hundred cells, CAFs were able to hijack cancer cells for dissemination from the primary site. Surprisingly, a majority of metastatic cancer cells remained in tight association with CAFs in the circulation. Furthermore, stimulation of non–metastasis-promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to acquisition of their metastatic capacity. Conclusions: Cancer metastasis occurs at the very early stage of tumor formation consisting of only a few hundred cells. CAFs are the key cellular determinant for metastasis. Our findings provide novel mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs for cancer therapy should be aimed at the early stage during cancer development. Clin Cancer Res; 23(16); 4769–79. ©2017 AACR.
Reaction-Diffusion Pattern in Shoot Apical Meristem of Plants

A fundamental question in developmental biology is how spatial patterns are self-organized from homogeneous structures. In 1952, Turing proposed the reaction-diffusion model in order to explain this issue. Experimental evidence of reaction-diffusion patterns in living organisms was first provided by the pigmentation pattern on the skin of fishes in 1995. However, whether or not this mechanism plays an essential role in developmental events of living organisms remains elusive. Here we show that a reaction-diffusion model can successfully explain the shoot apical meristem (SAM) development of plants. SAM of plants resides in the top of each shoot and consists of a central zone (CZ) and a surrounding peripheral zone (PZ). SAM contains stem cells and continuously produces new organs throughout the lifespan. Molecular genetic studies using Arabidopsis thaliana revealed that the formation and maintenance of the SAM are essentially regulated by the feedback interaction between WUSHCEL (WUS) and CLAVATA (CLV). We developed a mathematical model of the SAM based on a reaction-diffusion dynamics of the WUS-CLV interaction, incorporating cell division and the spatial restriction of the dynamics. Our model explains the various SAM patterns observed in plants, for example, homeostatic control of SAM size in the wild type, enlarged or fasciated SAM in clv mutants, and initiation of ectopic secondary meristems from an initial flattened SAM in wus mutant. In addition, the model is supported by comparing its prediction with the expression pattern of WUS in the wus mutant. Furthermore, the model can account for many experimental results including reorganization processes caused by the CZ ablation and by incision through the meristem center. We thus conclude that the reaction-diffusion dynamics is probably indispensable for the SAM development of plants.
Spatial Differentiation in the Vegetative Mycelium of Aspergillus niger

ABSTRACT Fungal mycelia are exposed to heterogenic substrates. The substrate in the central part of the colony has been (partly) degraded, whereas it is still unexplored at the periphery of the mycelium. We here assessed whether substrate heterogeneity is a main determinant of spatial gene expression in colonies of Aspergillus niger. This question was addressed by analyzing whole-genome gene expression in five concentric zones of 7-day-old maltose- and xylose-grown colonies. Expression profiles at the periphery and the center were clearly different. More than 25% of the active genes showed twofold differences in expression between the inner and outermost zones of the colony. Moreover, 9% of the genes were expressed in only one of the five concentric zones, showing that a considerable part of the genome is active in a restricted part of the colony only. Statistical analysis of expression profiles of colonies that had either been or not been transferred to fresh xylose-containing medium showed that differential expression in a colony is due to the heterogeneity of the medium (e.g., genes involved in secretion, genes encoding proteases, and genes involved in xylose metabolism) as well as to medium-independent mechanisms (e.g., genes involved in nitrate metabolism and genes involved in cell wall synthesis and modification). Thus, we conclude that the mycelia of 7-day-old colonies of A. niger are highly differentiated. This conclusion is also indicated by the fact that distinct zones of the colony grow and secrete proteins, even after transfer to fresh medium.
Cognitive Function, Numeracy and Retirement Saving Trajectories

This paper examines the extent to which cognitive abilities relate to differences in trajectories for key economic outcomes as individuals move towards and through their retirement. We look at whether differences in baseline numeracy (measured in the English Longitudinal Study of Ageing in 2002) and broader cognitive ability predict the subsequent trajectories of outcomes such as wealth, retirement income and key dimensions of retirement expectations. Those with lower numeracy are shown to have different wealth trajectories both pre- and post-retirement than their more numerate counterparts, but the distributions of retirement expectations and net replacement rates are similar across numeracy groups.
Previously Published Works Uc Davis Title: Brief Report: Visual Processing of Faces in Individuals with Fragile X Syndrome: an Eye Tracking Study Brief Report: Visual Processing of Faces in Individuals with Fragile X Syndrome: an Eye Tracking Study

A University of California author or department has made this article openly available. Thanks to the Academic Senate's Open Access Policy, a great many UC-authored scholarly publications will now be freely available on this site. Let us know how this access is important for you. We want to hear your story! Abstract: Gaze avoidance is a hallmark behavioral feature of fragile X syndrome (FXS), but little is known about whether abnormalities in the visual processing of faces, including disrupted autonomic reactivity, may underlie this behavior. Eye tracking was used to record fixations and pupil diameter while adolescents and young adults with FXS and sex-and age-matched typically developing controls passively viewed photographs of faces containing either a calm, happy, or fearful expression, preceded by a scrambled face matched on luminance. Results provide quantitative evidence for significant differences in gaze patterns and increased pupillary reactivity when individuals with FXS passively view static faces. Such abnormalities have significant implications in terms of understanding causes of gaze avoidance observed in individuals with FXS. Abstract Gaze avoidance is a hallmark behavioral feature of fragile X syndrome (FXS), but little is known about whether abnormalities in the visual processing of faces, including disrupted autonomic reactivity, may underlie this behavior. Eye tracking was used to record fixations and pupil diameter while adolescents and young adults with FXS and sex-and age-matched typically developing controls passively viewed photographs of faces containing either a calm, happy, or fearful expression, preceded by a scrambled face matched on luminance. Results provide quantitative evidence for significant differences in gaze patterns and increased pupillary reactivity when individuals with FXS passively view static faces. Such abnormalities have significant implications in terms of understanding causes of gaze avoidance observed in individuals with FXS.
Brain Source Imaging in Preclinical Rat Models of Focal Epilepsy using High-Resolution EEG Recordings

Electroencephalogram (EEG) has been traditionally used to determine which brain regions are the most likely candidates for resection in patients with focal epilepsy. This methodology relies on the assumption that seizures originate from the same regions of the brain from which interictal epileptiform discharges (IEDs) emerge. Preclinical models are very useful to find correlates between IED locations and the actual regions underlying seizure initiation in focal epilepsy. Rats have been commonly used in preclinical studies of epilepsy1; hence, there exist a large variety of models for focal epilepsy in this particular species. However, it is challenging to record multichannel EEG and to perform brain source imaging in such a small animal. To overcome this issue, we combine a patented-technology to obtain 32-channel EEG recordings from rodents2 and an MRI probabilistic atlas for brain anatomical structures in Wistar rats to perform brain source imaging. In this video, we introduce the procedures to acquire multichannel EEG from Wistar rats with focal cortical dysplasia, and describe the steps both to define the volume conductor model from the MRI atlas and to uniquely determine the IEDs. Finally, we validate the whole methodology by obtaining brain source images of IEDs and compare them with those obtained at different time frames during the seizure onset.
Attitudes to cardiovascular health promotion among GPs and practice nurses.

BACKGROUND Cardiovascular health promotion is an important element of national health strategy, but doubts have been raised about current methods, and attitudes among general practice staff are ambivalent. OBJECTIVES We aimed to assess attitudes to cardiovascular health promotion, opinions about efficacy and perceptions of skills in lifestyle counselling in GPs and nurses from the same practices. METHOD A questionnaire survey of 107 GPs and 58 practice nurses from 19 group practices (100% response rate). RESULTS Practice nurses were seen to have the main responsibility for cardiovascular health promotion. Although attitudes to health promotion were generally positive, lack of training in lifestyle counselling was perceived to be a problem. Few responders believed that they were very influential in helping people change their lifestyles. Beliefs about the effectiveness of lifestyle counselling were mixed, with cigarette smoking, physical inactivity and obesity being seen as difficult to change. Beliefs in the effectiveness of lifestyle counselling were associated with positive attitudes towards health promotion and greater confidence in training. No association between personal health behaviour and attitudes towards health promotion were observed. CONCLUSIONS It is recognized that health promotion involves more than the provision of simple information and advice, but GPs and practice nurses lack confidence in lifestyle counselling skills. The attitudes of health professionals are crucial to the implementation of prevention strategies and require regular review.
Renal function in the AT1A receptor knockout mouse during normal and volume-expanded conditions.

BACKGROUND Genetically altered mice lacking the AT1A angiotensin II (Ang II) receptor were used to examine the role of AT1A receptors in regulating renal hemodynamics, sodium excretion, glomerulotubular balance, and Ang II levels in plasma and kidney during normal and volume-expanded conditions. METHODS AT1A receptor-deficient mice and their wild-type controls were anesthetized with inactin and ketamine, and were prepared to allow intravenous infusions of solutions and measurements of aortic pressure and urine collections. Inulin and para-aminohippurate (PAH) solutions were infused intravenously for clearance determinations under conditions of euvolemia (2.5 microliter/min infusion of isotonic saline) or volume-expansion conditions (12.5 microliter/min). After three 30-minute urine collections, blood samples were collected, and kidneys were harvested. Plasma and kidney Ang II measurements were made by radioimmunoassay. RESULTS In the euvolemic state, mean arterial pressures (MAPs) were significantly lower in the AT1A receptor-deficient mice (68 +/- 4 mm Hg) compared with wild-type controls (89 +/- 3 mm Hg). Despite the lower MAP, the glomerular filtration rate (GFR), renal plasma flow (RPF), absolute sodium excretion, and fractional sodium excretion were not significantly different between wild-type and AT1A-/- mice. Volume expansion did not alter MAP in wild-type mice, but significantly increased MAP in the AT1A-/- mice (68 +/- 4 to 83 +/- 5 mm Hg). Similar increases in GFR, RPF, absolute sodium excretion, and fractional sodium excretion in AT1A+/+ and AT1A-/- mice were observed. Glomerulotubular balance was not disrupted by the absence of AT1A receptors. During euvolemia, plasma Ang II concentrations were significantly higher in the AT1A-/- mice compared with wild-type mice (536 +/- 172 vs. 198 +/- 36 fmol/ml). Although volume expansion had no effect on plasma Ang II levels in the AT1A+/+ group, plasma Ang II concentrations were markedly suppressed in the AT1A-/- mice to levels that were not different from those in wild-type mice. In contrast, kidney tissue Ang II contents were reduced in the AT1A-/- mice and were not significantly altered during volume expansion in either the AT1A-/- or the AT1A+/+ mice. CONCLUSIONS The absence of AT1A receptors does not impair chronic regulation of renal blood flow, GFR, or glomerulotubular balance. The prompt restoration of MAP following volume expansion suggests that low blood pressure in the AT1A receptor-deficient mice is primarily due to reduced effective plasma and extracellular fluid volume. Normalization of plasma Ang II levels with volume expansion demonstrates a dominant effect of extracellular fluid volume and blood pressure over AT1A receptor-mediated short-loop feedback in the regulation of plasma Ang II levels.
On the State-Space Realization of LPV Input-Output Models: Practical Approaches

A common problem in the context of linear parameter-varying (LPV) systems is how input-output (IO) models can be efficiently realized in terms of state-space (SS) representations. The problem originates from the fact that in the LPV literature discrete-time identification and modeling of LPV systems is often accomplished via IO model structures. However, to utilize these LPV-IO models for control synthesis, commonly it is required to transform them into an equivalent SS form. In general, such a transformation is complicated due to the phenomenon of dynamic dependence (dependence of the resulting representation on time-shifted versions of the scheduling signal). This conversion problem is revisited and practically applicable approaches are suggested which result in discrete-time SS representations that have only static dependence (dependence on the instantaneous value of the scheduling signal). To circumvent complexity, a criterion is also established to decide when an linear-time invariant (LTI)-type of realization approach can be used without introducing significant approximation error. To reduce the order of the resulting SS realization, an LPV Ho-Kalman-type of model reduction approach is introduced, which, besides its simplicity, is capable of reducing even non-stable plants. The proposed approaches are illustrated by application oriented examples.
Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension

This review summarizes several scientific contributions at the recent Satellite Symposium of the European Society of Hypertension, held in Milan, Italy. Arterial stiffening and its hemodynamic consequences can be easily and reliably measured using a range of noninvasive techniques. However, like blood pressure (BP) measurements, arterial stiffness should be measured carefully under standardized patient conditions. Carotid-femoral pulse wave velocity has been proposed as the gold standard for arterial stiffness measurement and is a well recognized predictor of adverse cardiovascular outcome. Systolic BP and pulse pressure in the ascending aorta may be lower than pressures measured in the upper limb, especially in young individuals. A number of studies suggest closer correlation of end-organ damage with central BP than with peripheral BP, and central BP may provide additional prognostic information regarding cardiovascular risk. Moreover, BP-lowering drugs can have differential effects on central aortic pressures and hemodynamics compared with brachial BP. This may explain the greater beneficial effect provided by newer antihypertensive drugs beyond peripheral BP reduction. Although many methodological problems still hinder the wide clinical application of parameters of arterial stiffness, these will likely contribute to cardiovascular assessment and management in future clinical practice. Each of the abovementioned parameters reflects a different characteristic of the atherosclerotic process, involving functional and/or morphological changes in the vessel wall. Therefore, acquiring simultaneous measurements of different parameters of vascular function and structure could theoretically enhance the power to improve risk stratification. Continuous technological effort is necessary to refine our methods of investigation in order to detect early arterial abnormalities. Arterial stiffness and its consequences represent the great challenge of the twenty-first century for affluent countries, and “de-stiffening” will be the goal of the next decades.
Information Theoretic Measures for Clusterings Comparison: Variants, Properties, Normalization and Correction for Chance

Information theoretic measures form a fundamental class of measures for comparing clusterings, and have recently received increasing interest. Nevertheless, a number of questions concerning their properties and inter-relationships remain unresolved. In this paper, we perform an organized study of information theoretic measures for clustering comparison, including several existing popular measures in the literature, as well as some newly proposed ones. We discuss and prove their important properties, such as the metric property and the normalization property. We then highlight to the clustering community the importance of correcting information theoretic measures for chance, especially when the data size is small compared to the number of clusters present therein. Of the available information theoretic based measures, we advocate the normalized information distance (NID) as a general measure of choice, for it possesses concurrently several important properties, such as being both a metric and a normalized measure, admitting an exact analytical adjusted-for-chance form, and using the nominal [0,1] range better than other normalized variants.
A novel role for the rat retrosplenial cortex in cognitive control

By virtue of its frontal and hippocampal connections, the retrosplenial cortex is uniquely placed to support cognition. Here, we tested whether the retrosplenial cortex is required for frontal tasks analogous to the Stroop Test, i.e., for the ability to select between conflicting responses and inhibit responding to task-irrelevant cues. Rats first acquired two instrumental conditional discriminations, one auditory and one visual, set in two distinct contexts. As a result, rats were rewarded for pressing either the right or left lever when a particular auditory or visual signal was present. In extinction, rats received compound stimuli that either comprised the auditory and visual elements that signaled the same lever response (congruent) or signaled different lever responses (incongruent) during training. On conflict (incongruent) trials, lever selection by sham-operated animals followed the stimulus element that had previously been trained in that same test context, whereas animals with retrosplenial cortex lesions failed to disambiguate the conflicting response cues. Subsequent experiments demonstrated that this abnormality on conflict trials was not due to a failure in distinguishing the contexts. Rather, these data reveal the selective involvement of the rat retrosplenial cortex in response conflict, and so extend the frontal system underlying cognitive control.
FADE : A Layout Facility for Graph-based Diagrams

In this paper we present a novel approach to the layout problem of 2-dimensional graph-based diagrams. We introduce a framework for e(cid:14)ciently solving constrained layout problems encompassing geometrical and graph-based algorithms especially dedicated to the generation of diagrams. These concepts as well as the aesthetics for the read-ability of diagrams are presented by introducing FADE 1 . FADE is a user-parametrizable framework for the generation of EXPRESS-G diagrams. Our present implementation is discussed considering extensions to other classes of graphs and layout problems. Additionally,competitive approaches in this domain and their limitations are critically reviewed.
Caffeine increases sugar-sweetened beverage consumption in a free-living population: a randomised controlled trial

Excessive sugar-sweetened beverage (SSB) consumption has been associated with overweight and obesity. Caffeine is a common additive to SSB, and through dependence effects, it has the potential to promote the consumption of caffeine-containing foods. The objective of the present study was to assess the influence that caffeine has on the consumption of SSB. Participants (n 99) were blindly assigned to either a caffeinated SSB (C-SSB) or a non-caffeinated SSB (NC-SSB) group. Following randomisation, all participants completed a 9 d flavour-conditioning paradigm. They then completed a 28 d ad libitum intake intervention where they consumed as much or as little of C-SSB or NC-SSB as desired. The amount consumed (ml) was recorded daily, 4 d diet diaries were collected and liking of SSB was assessed at the start and end of the intervention. Participants (n 50) consuming the C-SSB had a daily SSB intake of 419 (sd 298) ml (785 (sd 559) kJ/d) over the 28 d intervention, significantly more than participants (n 49) consuming the NC-SSB (273 (sd 278) ml/d, 512 (sd 521) kJ/d) (P< 0·001). A trained flavour panel (n 30) found no difference in flavour between the C-SSB and NC-SSB (P>0·05). However, participants who consumed the C-SSB liked the SSB more than those who consumed the NC-SSB (6·3 v. 6·0 on a nine-point hedonic scale, P= 0·022). The addition of low concentrations of caffeine to the SSB significantly increases the consumption of the SSB. Regulating caffeine as a food additive may be an effective strategy to decrease the consumption of nutrient-poor high-energy foods and beverages.
Alcoholic Myopathy: Pathophysiologic Mechanisms and Clinical Implications

Skeletal muscle dysfunction (i.e., myopathy) is common in patients with alcohol use disorder. However, few clinical studies have elucidated the significance, mechanisms, and therapeutic options of alcohol-related myopathy. Preclinical studies indicate that alcohol adversely affects both anabolic and catabolic pathways of muscle-mass maintenance and that an increased proinflammatory and oxidative milieu in the skeletal muscle is the primary contributing factor leading to alcohol-related skeletal muscle dysfunction. Decreased regenerative capacity of muscle progenitor cells is emerging as an additional mechanism that contributes to alcohol-induced loss in muscle mass and impairment in muscle growth. This review details the epidemiology of alcoholic myopathy, potential contributing pathophysiologic mechanisms, and emerging literature on novel therapeutic options.