The effects of an obesogenic diet on behavior and cognition in zebrafish (Danio rerio): Trait average, variability, repeatability, and behavioral syndromes.

The obesity epidemic, largely driven by the accessibility of ultra-processed high-energy foods, is one of the most pressing public health challenges of the 21st century. Consequently, there is increasing concern about the impacts of diet-induced obesity on behavior and cognition. While research on this matter continues, to date, no study has explicitly investigated the effect of obesogenic diet on variance and covariance (correlation) in behavioral traits. Here, we examined how an obesogenic versus control diet impacts means and (co-)variances of traits associated with body condition, behavior, and cognition in a laboratory population of ~160 adult zebrafish (Danio rerio). Overall, an obesogenic diet increased variation in several zebrafish traits. Zebrafish on an obesogenic diet were significantly heavier and displayed higher body weight variability; fasting blood glucose levels were similar between control and treatment zebrafish. During behavioral assays, zebrafish on the obesogenic diet displayed more exploratory behavior and were less reactive to video stimuli with conspecifics during a personality test, but these significant differences were sex-specific. Zebrafish on an obesogenic diet also displayed repeatable responses in aversive learning tests whereas control zebrafish did not, suggesting an obesogenic diet resulted in more consistent, yet impaired, behavioral responses. Where behavioral syndromes existed (inter-class correlations between personality traits), they did not differ between obesogenic and control zebrafish groups. By integrating a multifaceted, holistic approach that incorporates components of (co-)variances, future studies will greatly benefit by quantifying neglected dimensions of obesogenic diets on behavioral changes.

Effects of rhBMP-2-loaded hydroxyapatite granules/beta-tricalcium phosphate hydrogel (HA/ß-TCP/hydrogel) composite on a rat model of caudal intervertebral fusion.

The effects and inflammation-related side effects of bone morphogenetic protein (BMP)-2 on posterior lumbar interbody fusion are controversial. One of the potential causes for the inconsistent results is the uncontrolled release of BMP-2 from the collagen carrier. Therefore, BMP delivery systems that support effective bone regeneration while attenuating the side effects are strongly sought for. We developed NOVOSIS putty (NP), a novel composite material of hydroxyapatite (HA), beta-tricalcium phosphate (ß-TCP)/hydrogel, and BMP-2, which can sustainably release BMP-2 over 2 weeks. This study was aimed at comparing the effects and side effects of NP and collagen sponge (CS) containing BMP-2 using a rat caudal intervertebral fusion model. The fusion rates of NP with low and high doses of BMP-2 were significantly higher than those of an iliac bone (IB) graft, but those of CS with low and high doses of BMP-2 were not different from those of the IB graft. Furthermore, the incidences of ectopic bone formation and soft tissue swelling were significantly lower in the NP group than in the CS group. The HA/ß-TCP/hydrogel carrier enabled superior bone induction with low-dose BMP-2 and decreased the incidence of side effects caused by high-dose BMP-2 vis-à-vis the collagen carrier.

The cell type-specific ER membrane protein UGS148 is not essential in mice.

Genomes of higher eukaryotes encode many uncharacterized proteins, and the functions of these proteins cannot be predicted from the primary sequences due to a lack of conserved functional domains. In this study, we focused on a poorly characterized protein UGS148 that is highly expressed in a specialized cell type called tanycytes that line the ventral wall of the third ventricle in the hypothalamus. Immunostaining of UGS148 revealed the fine morphology of tanycytes with highly branched apical ER membranes. Immunoprecipitation revealed that UGS148 associated with mitochondrial ATPase at least in vitro, and ER and mitochondrial signals occasionally overlapped in tanycytes. Mutant mice lacking UGS148 did not exhibit overt phenotypes, suggesting that UGS148 was not essential in mice reared under normal laboratory conditions. We also found that RNA probes that were predicted to uniquely detect UGS148 mRNA cross-reacted with uncharacterized RNAs, highlighting the importance of experimental validation of the specificity of probes during the hybridization-based study of RNA localization.

A novel nano-hydroxyapatite/synthetic polymer/bone morphogenetic protein-2 composite for efficient bone regeneration.

BACKGROUND: Efficient bone regeneration using recombinant human bone morphogenetic protein-2 (BMP-2) is needed to reduce side effects caused by high-dose BMP-2 use. The composite material of polylactic acid-polyethene glycol (PLA-PEG) for sustained release and an osteogenic nano-hydroxyapatite (nHAp) can contribute to efficient bone regeneration by BMP-2. STUDY DESIGN: An experimental in vitro and in vivo study. PURPOSE: The objective of this study is to investigate the effectiveness of a novel composite material of PLA-PEG and nHAp as a carrier for BMP-2. METHODS: The release kinetics of BMP-2 from the composites was investigated by ELISA. Thirty-six male Sprague-Dawley rats underwent posterolateral spinal fusion on L4-L5 with three different doses of BMP-2 (0 µg [control], 3 µg [low dose], and 10 µg [high dose]). Weekly µCT results and histology and a manual palpation test at 8 weeks postoperatively were used for assessment of the spinal fusion. RESULTS: ELISA demonstrated the sustained release of BMP-2 until day 21. µCT and manual palpation test demonstrated a solid fusion in 91.6% (11/12) of specimens in both the low- and high-dose groups. N mice in the control group attained bony fusion (0%, 0/9). nHAp was resorbed between 2 and 4 weeks postoperatively, and regenerated fusion mass at 8 weeks postoperatively consisted of only newly formed bone. CONCLUSIONS: The nHAp/PLA-PEG composite enabled efficient bone regeneration with low-dose BMP-2. The sustained release of BMP-2 by PLA-PEG and the osteogenic and biodegradable scaffold of nHAp might contribute to efficient bone regeneration. CLINICAL SIGNIFICANCE: This novel composite material has potential in clinical applications (spinal fusion, large bone defect and non-union) by enabling efficient bone formation by BMP-2.

Global associations between macronutrient supply and age-specific mortality.

Animal experiments have demonstrated that energy intake and the balance of macronutrients determine life span and patterns of age-specific mortality (ASM). Similar effects have also been detected in epidemiological studies in humans. Using global supply data and 1,879 life tables from 103 countries, we test for these effects at a macrolevel: between the nutrient supplies of nations and their patterns of ASM. We find that macronutrient supplies are strong predictors of ASM even after correction for time and economic factors. Globally, signatures of undernutrition are evident in the effects of low supply on life expectancy at birth and high mortality across ages, even as recently as 2016. However, in wealthy countries, the effects of overnutrition are prominent, where high supplies particularly from fats and carbohydrates are predicted to lead to high levels of mortality. Energy supplied at around 3,500 kcal/cap/d minimized mortality across ages. However, we show that the macronutrient composition of energy supply that minimizes mortality varies with age. In early life, 40 to 45% energy from each of fat and carbohydrate and 16% from protein minimizes mortality. In later life, replacing fat with carbohydrates to around 65% of total energy and reducing protein to 11% is associated with the lowest level of mortality. These results, particularly those regarding fats, accord both with experimental data from animals and within-country epidemiological studies on the association between macronutrient intake and risk of age-related chronic diseases.

Nonfamilial juvenile polyposis coli in a child: report of a case.

Juvenile polyposis coli (JPC) is an uncommon condition, manifesting as hamartomatous gastrointestinal polyposis with potential malignancy. This report describes a 15-month-old girl who was diagnosed to have nonfamilial JPC accompanied by macrocephaly, clubbed fingers, and mental retardation. Radiography of the colon by a barium enema and total colonoscopy demonstrated numerous colonic polyps. A barium meal study did not show any abnormality in the stomach, duodenum, or small intestine. She died at 6 years of age from hemorrhagic shock due to massive lower gastrointestinal bleeding associated with a rectal prolapse. The related literature is reviewed, and the treatments and complications of JPC in children are also discussed. We emphasize that family members of patients diagnosed with juvenile polyposis should be questioned and undergo appropriate examinations of the entire intestine from the stomach to the rectum.

Identification of a nonchordate-type classic cadherin in vertebrates: chicken Hz-cadherin is expressed in horizontal cells of the neural retina and contains a nonchordate-specific domain complex.

Classic cadherins mediate calcium-dependent cell-cell adhesion in a variety of animals, but there are marked differences in their domain structures between chordate and nonchordate animals. The extracellular domain of chordate-type classic cadherins (type I and type II classic cadherins) consists of five tandem repeats of conserved sequences called EC domains, whereas that of nonchordate-type classic cadherins (designated as type III classic cadherin) contains a variable number of EC domains, followed by a characteristic domain complex made of laminin-A globular domains and EGF-like repeats. In the present study, we identified a novel vertebrate type III cadherin showing high sequence similarity to Drosophila N-cadherin, and named this molecule chicken Hz-cadherin (cHz-cadherin), because of the distinct expression in horizontal cells of the neural retina. cHz-cadherin functioned as an adhesion molecule when introduced into cultured cells. Database search revealed one cHz-cadherin homologue in zebrafish and two in puffer fish, but none in other vertebrate species examined. These observations indicate that type III classic cadherins have been conserved in vertebrate species, being expressed by limited cells types, but lost in particular phylogenic groups of the vertebrates.