The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report ...an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric of the 5' end of the BDNF gene. The patient's genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyperactivity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior.
Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including ...neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat
mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat
mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat
mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat
mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat
mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat
mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.
We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
Background and purpose
Anosognosia and neglect may coexist in stroke patients. Neglect patients often report poor quality of life (QOL), whereas patients suffering from other cognition disorders with ...poor insight report better QOL. This study investigates the relationship between anosognosia, neglect and QOL amongst stroke survivors.
Methods
Stroke survivors who met the criteria were used as a sampling pool. Sixty stroke patients were observed in this study, amongst whom 20 patients with anosognosia and neglect (A+N+), 20 patients with neglect but not anosognosia (A−N+) and 20 patients with neither anosognosia nor neglect (A−N−) were selected from the sampling pool based on demographic characteristics matched with the A+N+ group. A questionnaire (SS‐QOL) was used to collect the QOL perceived by the stroke survivors.
Results
The perceived QOL of the A+N+ group was significantly better than those of the other groups, including the subscales of self‐care, mobility, work/productivity, upper extremity, mood, family role and social role. However, the A+N+ group had poor balance level and more fall incidents were reported.
Conclusion
The A+N+ group perceived better QOL but had more falls and poorer balance than the other groups. Health providers should work with caregivers aggressively in preventing accidents.
Abstract Objective Optimal hepatic venous tributary flow is correlated with liver function and regeneration. In left-lobe graft living donor liver transplantation, the stump of segment 5 and 8 ...hepatic veins (S5V and S8V) are ligated without performing hepatic tributary reconstruction. The aim of this article was to evaluate the different dominate hepatic vein patterns that affect left-lobe living donor safety. Materials and Methods A total of 44 donors who underwent left-lobe hepatectomy were divided into 2 groups, middle hepatic vein (MHV) dominance (group 1) and right hepatic vein (RHV) dominance (group 2), according to the dominant venous territory drainage from S5V and S8V or RHV. The clinical pathological data, postoperative laboratory data, complication, remnant liver volume and remnant liver regeneration rate at 6 months after surgery were compared. Results No difference was found in blood loss, postoperative liver function such as alanine transaminase value, complications, and hospital stays between groups. Group 1 had slightly higher total bilirubin level than group 2 (1.99 vs 1.79; P = .49). Group 2 had significantly better remnant liver regeneration rate than group 1 (89.2% vs 82.5%; P = .026). Conclusion It is important to recognize the dominant MHV group. Ligation large S5V and S8V in dominant MHV donors led to lower remnant liver regeneration in our series. This might be critical in extremely small RHV territory and potential large remnant liver congestion donors. Adjusting surgical planning, such as hepatic vein reconstruction, in this kind of donor might be appropriate for donor safety.
The fat mass and obesity-associated (FTO) gene was placed center stage when common intronic variants within the gene were robustly associated with human obesity. Murine models of perturbed Fto ...expression have shown effects on body weight and composition. However, a clear understanding of the link between FTO intronic variants and FTO activity has remained elusive. Two recent reports now indicate that obesity-associated SNPs appear functionally connected not with FTO but with two neighboring genes: IRX3 and RPGRIP1L. Here, we review these new findings and consider the implications for future analysis of GWAS hits.
Tung et al. review how common SNPs in the fat mass and obesity-associated (FTO) gene have been linked to human obesity by GWAS and discuss recent work suggesting that flanking genes, including IRX3 and RPGRIP1L, may also be important regulators of body weight.
Aspergillus fumigatus
is one of the most prominent opportunistic fungal pathogens in immunocompromised hosts. Early recognition of this infection along with prompt antifungal therapy may increase the ...survival rate. We expressed two potential bio-markers of
A. fumigatus
infection—galactomannoprotein Afmp1p and Afmp4p in
Pichia pastoris
. We generated 33 monoclonal antibodies (MAbs), 20 against recombinant Afmp1p (rAfmp1p) and the other 13 against recombinant Afmp4p (rAfmp4p). Subsequently, we developed two antigen-capture enzyme-linked immunosorbent assays (ELISAs) which employed MAbs as both the capture and the detection antibodies for rAfmp1p and rAfmp4p. The two antigen-capture ELISAs specifically detected Afmp1p/Afmp4p in cultures of
A. fumigatus
and had no cross-reaction with other tested pathogenic fungi, including
Penicillium marneffei
and other pathogenic
Aspergillus
species. The Afmp1p-captured ELISA would be positive even when the culture supernatant of
A. fumigatus
had been diluted to 128-fold of its original concentration. The two antigen ELISAs could capture circulating or excreted antigens during the acute phase of invasive aspergillosis (IA) in the animal model, and had no cross-reactivity to other
Aspergillus
-challenged animal models. We developed two antigen-capture ELISAs for the laboratory diagnosis of
A. fumigatus
infection. These two antigen-capture ELISAs may be useful in the clinical diagnosis of aspergillosis.
Vascularisation efficiency plays an essential role in the success of bulk transplantation, while biocompatibility and safety are major concerns in clinical applications. Fibrin-based hydrogels have ...been exploited as scaffolds for their advantages in biocompatibility, degradability and mass transportation in various forms. However, the mechanical strength and degree of vascularisation remain unsatisfactory for clinical usage. An interpenetrating hydrogel was developed by adding hyaluronic acid (HA) to a fibrin-based natural hydrogel. The vasculogenesis of endothelial cells (human umbilical vein endothelial cells, HUVECs) was characterised within the gel using both in vitro and in vivo animal studies. The in vitro vascular morphology analysis showed 17.9 % longer mean tube length and 14.3 % higher average thickness in 7 d cultivation within the HA-supplemented hydrogel. The in vivo results showed 51.6 % larger total tube area, 1.8 × longer average tube length and 81.6 % higher cell number in the HA-supplemented hydrogel compared to the hydrogel without HA. The experimental results demonstrated better vascularisation and cell recruitment in the HA- supplemented hydrogel. The material properties of the hydrogels were also analysed using atomic force microscopy (AFM). The results revealed 3.7 × higher elasticity of the HA-supplemented hydrogel, which provided better mechanical strength and support for easy handling during procedures. With the demonstrated advantages, the developed hydrogels showed promise for exploitation in various practical clinical applications.
More than one-half billion people are obese, and despite progress in genetic research, much of the heritability of obesity remains enigmatic. Here, we identify a Trim28-dependent network capable of ...triggering obesity in a non-Mendelian, “on/off” manner. Trim28+/D9 mutant mice exhibit a bi-modal body-weight distribution, with isogenic animals randomly emerging as either normal or obese and few intermediates. We find that the obese-“on” state is characterized by reduced expression of an imprinted gene network including Nnat, Peg3, Cdkn1c, and Plagl1 and that independent targeting of these alleles recapitulates the stochastic bi-stable disease phenotype. Adipose tissue transcriptome analyses in children indicate that humans too cluster into distinct sub-populations, stratifying according to Trim28 expression, transcriptome organization, and obesity-associated imprinted gene dysregulation. These data provide evidence of discrete polyphenism in mouse and man and thus carry important implications for complex trait genetics, evolution, and medicine.
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•Trim28 haploinsufficiency triggers stochastic bi-stable obesity or polyphenism•Non-classical imprinted gene dysregulation specifies “on” versus “off” obese states•Peg3 and Nnat perturbation trigger stochastic bi-stable obesity•Human BMI distributions and transcriptomes suggest Trim28-associated subpopulations
TRIM28 insufficiency in both mouse and human leads to polyphenism, wherein lean and obese phenotypes can arise from the identical genotypes through dysregulation of an imprinted gene network.
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