Obesity is a metabolic state generated by the expansion of adipose tissue. Adipose tissue expansion depends on the interplay between hyperplasia and hypertrophy, and is mainly regulated by a complex ...interaction between genetics and excess energy intake. However, the genetic regulation of adipose tissue expansion is yet to be fully understood. Obesity can be divided into common multifactorial/polygenic obesity and monogenic obesity, non-syndromic and syndromic. Several genes related to obesity were found through studies of monogenic non-syndromic obesity models. However, syndromic obesity, characterized by additional features other than obesity, suggesting a more global role of the mutant genes related to the syndrome and, thus, an additional peripheral influence on the development of obesity, were hardly studied to date in this regard. This review summarizes present knowledge regarding the hyperplasia and hypertrophy of adipocytes in common obesity. Additionally, we highlight the scarce research on syndromic obesity as a model for studying adipocyte hyperplasia and hypertrophy, focusing on Bardet-Biedl syndrome (BBS). BBS obesity involves central and peripheral mechanisms, with molecular and mechanistic alternation in adipocyte hyperplasia and hypertrophy. Thus, we argue that using syndromic obesity models, such as BBS, can further advance our knowledge regarding peripheral adipocyte regulation in obesity.
Bardet-Biedl syndrome (BBS) is an inherited disorder primarily ciliopathy with pleiotropic multi-systemic phenotypic involvement, including adipose, nerve, retinal, kidney, Etc. Consequently, it is ...characterized by obesity, cognitive impairment and retinal, kidney and cutaneous abnormalities. Initial studies, including ours have shown that BBS genes play a role in the early developmental stages of adipocytes and β-cells. However, this role in other BBS-related tissues is unknown.
We investigated BBS genes involvement in the proliferation and early differentiation of different BBS cell types.
The involvement of BBS genes in cellular proliferation were studied in seven in-vitro and transgenic cell models; keratinocytes (hHaCaT) and Ras-transfected keratinocytes (Ras-hHaCaT), neuronal cell lines (hSH-SY5Y and rPC-12), silenced BBS4 neural cell lines (siBbs4 hSH-SY5Y and siBbs4 rPC-12), adipocytes (m3T3L1), and ex-vivo transformed B-cells obtain from BBS4 patients, using molecular and biochemical methodologies.
RashHaCaT cells showed an accelerated proliferation rate in parallel to significant reduction in the transcript levels of BBS1, 2, and 4. BBS1, 2, and 4 transcripts linked with hHaCaT cell cycle arrest (G1 phase) using both chemical (CDK4 inhibitor) and serum deprivation methodologies. Adipocyte (m3T3-L1) Bbs1, 2 and 4 transcript levels corresponded to the cell cycle phase (CDK4 inhibitor and serum deprivation). SiBBS4 hSH-SY5Y cells exhibited early cell proliferation and differentiation (wound healing assay) rates. SiBbs4 rPC-12 models exhibited significant proliferation and differentiation rate corresponding to Nestin expression levels. BBS4 patients-transformed B-cells exhibited an accelerated proliferation rate (LPS-induced methodology).
In conclusions, the BBS4 gene plays a significant, similar and global role in the cellular proliferation of various BBS related tissues. These results highlight the universal role of the BBS gene in the cell cycle, and further deepen the knowledge of the mechanisms underlying the development of BBS.
•Bardet Biedl syndrome (BBS) genes are regulated by cellular proliferation.•LPS challenged BBS4 patients transformed primary B-cells show high proliferation rate.•Neuronal BBS4 silencing result in accelerated proliferation and differentiation.•BBS genes have shared role in BBS-related cells proliferation and differentiation.
In the western United States, pinyon-juniper woodlands have expanded by as much as sixfold among sagebrush landscapes since the late 19th century, with demonstrated negative impacts to the behavior, ...demography, and population dynamics of species that rely on intact sagebrush rangelands. Notably, greater sage-grouse (Centrocercus urophasianus) are unable to tolerate even low conifer cover, which can result in population declines and local extirpation, whereas removing expanding conifer cover has been demonstrated to increase sage grouse population growth rates and sagebrush obligate songbird abundance. Yet conifer management among sagebrush landscapes has been met with concerns about unintended impacts to species that rely on conifer woodlands, notably the pinyon jay (Gymnorhinus cyanocephalus), whose population declines are distinctive among birds breeding in pinyon-juniper woodlands. Spatial models of bird abundance can help management prioritize future actions in light of multiple species requirements, while also providing a framework to retroactively test the impact of past treatments. We used Breeding Bird Survey data to model indices to abundance in relation to multiscale habitat features including landcover, fire, topography, and climate variables for nine songbird species reliant on sagebrush and pinyon-juniper woodlands for breeding. Predictive maps allowed us to also examine the overlap of conifer management conducted by the Sage Grouse Initiative (SGI), which targets management of early successional conifers among priority sage-grouse habitats, with predicted indices to abundance of songbirds. Our findings demonstrate that targeted sage grouse habitat restoration under SGI was not at odds with protection of pinyon jay populations. Rather, conifer management has largely occurred among northern sagebrush landscapes where models suggest that past cuts likely benefit Brewer's sparrow and sage thrasher while avoiding pinyon jay habitats.
Falls are a major cause of morbidity and long-term hospitalization among growing older population. An automated and accurate fall-risk assessment system is vital to identify high fall-risk population ...and to prevent falls by early intervention. Therefore, this paper provides an objective, cost-effective, and unsupervised method to obtain functional balance and mobility assessment-based fall-risk of community-dwelling older adults. More specifically, waist-mounted triaxial accelerometer signals acquired from directed routine (supervised control movements) are used to estimate the well-known clinical assessment scoreBerg balance scale (BBS). The trunk acceleration signals are used to extract features and to find the optimal subset of features for each training data during repeated tenfold cross validation of the BBS estimation model. The average of two BBS estimates based on test and retest yielded a strong correlation p = 0.86 with the standard BBS score. Also, high correlation (p = 0.90) and low root-mean-square error (1.66) was observed between the two estimates of each subject. The proposed method is well suited for the assessment of balance impairment and prescreening of quantitative fall-risk in an unsupervised setting. It has the potential to act as a surrogate of the standard clinical assessment-BBS.
Multispecific antibodies recognize two or more epitopes located on the same or distinct targets. This added capability through protein design allows these man-made molecules to address unmet medical ...needs that are no longer possible with single targeting such as with monoclonal antibodies or cytokines alone. However, the approach to the development of these multispecific molecules has been met with numerous road bumps, which suggests that a new workflow for multispecific molecules is required. The investigation of the molecular basis that mediates the successful assembly of the building blocks into non-native quaternary structures will lead to the writing of a playbook for multispecifics. This is a must do if we are to design workflows that we can control and in turn predict success. Here, we reflect on the current state-of-the-art of therapeutic biologics and look at the building blocks, in terms of proteins, and tools that can be used to build the foundations of such a next-generation workflow.
Immunochromatographic assays (ICAs) are considered as a suitable diagnostic tool for the detection of mycotoxins. Mycotoxins and especially, ochratoxin A are analytes with more demanding sensitivity ...requirements. To enhance the sensitivity of current immunochromatographic assays for ochratoxin A (OTA), a novel sensitive ICA was developed in this study. In the assay, microspheres enclosing fluorescent europium (III) Eu(III) nanoparticles (EuNPs) were used as a label for OTA monoclonal antibody (OTA-mAb) conjugation. Accordingly, assay was called time-resolved fluorescent immunochromatographic assay (TRFICA). The test strip was composed of three parts: a sample pad, nitrocellulose membrane and an absorbent pad. As for detection, a proper concentration of conjugated microspheres was pipetted into the microtube and sample extract was added to it. Then the strip was inserted into the tube and the fluid flow along the strip. The TRFICA results were obtained in 8 min and read by a portable TRFICA strip reader. The established method allows quantitative determination of OTA with limit of detection as low as 1.0 μg kg−1 in the samples. For validation, spiked samples including wheat, maize, soybean and rice were respectively assayed by TRFICA and a standard high performance liquid chromatography equipped with a fluorescence detector (HPLC-FLD), and good agreement of results was obtained between two methods.
•Developing a time-resolved fluorescent immunochromatographic assay for ochratoxin A.•Using antibody conjugated fluorescent europium nanoparticles as label for detection.•The assay was used for ochratoxin A detection in agro-products.•The assay sensitivity increased compared to gold nanoparticles.•The results were reliable and in accordance with those obtained using HPLC.
Unbalanced walking is increasingly common among older adults; therefore, routinely assessing the balance of older adults is crucial. The traditional method of assessing balance uses scales, requires ...the supervision of a physical therapist (PT), and is time-consuming. The present study, therefore, proposes a deep learning (DL) model architecture that combines a convolutional neural network (CNN) and a long short-term memory (LSTM) network model to predict the scores of three scales, namely the Berg balance scale (BBS), timed up and go (TUG), and single-leg stance (SLS). The gait data of 15 m of walking were collected from seven inertial measurement units (IMUs) and input into the CNN-LSTM model for evaluation. The BBS and TUG only require the participants to wear two IMUs on the left and right thighs, respectively, for accurate predictions. The mean absolute errors (MAEs) of predicting the scores of the BBS and TUG are 1.2562 and 1.4016 s, respectively; however, the MAE of score predictions of SLS is higher than that of the BBS and TUG, indicating that gait data cannot be used for assessing SLS; moreover, participants only wear one IMU on the right calf for BBS and TUG evaluations, which yield MAEs of 1.4334 and 1.5229 s, respectively. The proposed system can quickly and accurately predict the scores of the BBS and TUG. The proposed model can assist PTs with making clinical decisions.
Brown bowel syndrome (BBS) is a rare condition associated with vitamin E deficiency and defined by prominent lipofuscin deposition in the muscularis propria. Eight unique cases of BBS were ...identified: 5 men and 3 women (mean age=58.6 y). Pertinent comorbidities included bariatric surgery=2, malnourishment=2, Crohn=2, cystic fibrosis=1, alcohol and cocaine abuse=1, and prior small bowel resections=1. Presenting symptoms included abdominal pain=3, bleeding=1, nausea and vomiting=1, and nonresponsiveness=1. Imaging studies were often abnormal: thickened bowel wall=3 (1 with a mass), small bowel obstruction=2, and edematous and dilated bowel wall=2. Most specimens were surgical resections (n=7, autopsy=1): extended right colectomy=2, small bowel only=5 (terminal ileum=3, jejunum=2). Two specimens were grossly described as mahogany, and 1 case contained a perforation. Histologic sections of all cases showed finely granular, brown cytoplasmic pigment in smooth muscle cells on hematoxylin and eosin. This pigment was most conspicuous in the muscularis propria (small bowel>colon), and it was not identified in the mucosa. The pigment was reactive with Fontana-Masson, carbol lipofuscin, Periodic acid-Schiff, and Periodic acid-Schiff with diastase, and electron microscopy was compatible with lipofuscin. The mean clinical follow-up was 208 weeks: 1 patient died of complications of encephalitis, the others were alive and well. BBS is important to recognize because it is linked with malnutrition, specifically vitamin E deficiency, and it can (rarely) clinically simulate malignancy. The diagnosis is based on the identification of the lipofuscin pigment in the cytoplasm of smooth muscle cells, which is most easily seen in the muscularis propria of the small bowel.
Environmental heterogeneity enhances species richness by creating niches and providing refugia. Spatial variation in climate has a particularly strong positive correlation with richness, but is often ...indirectly inferred from proxy variables, such as elevation and related topographic heterogeneity indices, or derived from interpolated coarse‐grain weather station data. Our aim was to develop new remotely sensed metrics of relative temperature and thermal heterogeneity, compare them with proxy measures, and evaluate their performance in predicting species richness patterns. We analyzed Landsat 8's Thermal Infrared Sensor data, calculated two thermal metrics during summer and winter, and compared their seasonal spatial patterns with those of elevation and topographic heterogeneity. We fit generalized least squares models to evaluate each variable's effect in predicting seasonal bird richness using data from the North American Breeding Bird Survey. Generally speaking, neither elevation nor topographic heterogeneity were good proxies for temperature or thermal heterogeneity, respectively. Relative temperature had a non‐linear relationship with elevation that was negatively quadratic in summer, but slightly positively quadratic in winter. Topographic heterogeneity had a stronger positive relationship with thermal heterogeneity in winter than in summer. The magnitude and direction of elevation–temperature and topographic heterogeneity–thermal heterogeneity relationships in each season also varied substantially across ecoregions. Remotely sensed metrics of relative temperature and thermal heterogeneity improved the predictive performance of species richness models, and both thermal variables had significant effects on bird richness that were independent of elevation and topographic heterogeneity. Thermal heterogeneity was positively related to total breeding bird richness, migrant breeding bird richness and resident bird richness, whereas topographic heterogeneity was negatively related to total breeding richness and unrelated to migrant or resident bird richness. Because thermal and topographic heterogeneity had contrasting seasonal patterns and effects on richness, they must be carefully contextualized when guiding conservation priorities.
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