Impaired translation initiation activation and reduced protein synthesis in weaned piglets fed a low-protein diet

Weanling mammals (including infants) often experience intestinal dysfunction when fed a high-protein diet. Recent work with the piglet (an animal model for studying human infant nutrition) shows that reducing protein intake can improve gut function during weaning but compromises the provision of essential amino acids (EAA) for muscle growth. The present study was conducted with weaned pigs to test the hypothesis that supplementing deficient EAA (Lys, Met, Thr, Trp, Leu, Ile and Val) to a low-protein diet may maintain the activation of translation initiation factors and adequate protein synthesis in tissues. Pigs were weaned at 21 days of age and fed diets containing 20.7, 16.7 or 12.7% crude protein (CP), with the low-CP diets supplemented with EAA to achieve the levels in the high-CP diet. On Day 14 of the trial, tissue protein synthesis was determined using the phenylalanine flooding dose method. Reducing dietary CP levels decreased protein synthesis in pancreas, liver, kidney and longissimus muscle. A low-CP diet reduced the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) in skeletal muscle and liver while increasing the formation of an inactive eIF4E.4E-BP1 complex in muscle. Dietary protein deficiency also decreased the phosphorylation of mammalian target of rapamycin (mTOR) and the formation of an active eIF4E.eIF4G complex in liver. These results demonstrate for the first time that chronic feeding of a low-CP diet suppresses protein synthesis in animals partly by inhibiting mTOR signaling. Additionally, our findings indicate that supplementing deficient EAA to low-protein diets is not highly effective in restoring protein synthesis or whole-body growth in piglets. We suggest that conditionally essential amino acids (e.g., glutamine and arginine) may be required to maintain the activation of translation initiation factors and optimal protein synthesis in neonates.     

Systematic analysis of biochemical performance and the microbial community of an activated sludge process using ozone-treated sludge for sludge reduction

Two lab-scale bioreactors (reactors 1 and 2) were employed to examine the changes in biological performance and the microbial community of an activated sludge process fed with ozonated sludge for sludge reduction. During the 122 d operation, the microbial activities and community in the two reactors were evaluated. The results indicated that, when compared with the conventional reactor (reactor 1), the reactor that was fed with the ozonated sludge (reactor 2) showed good removal of COD, TN and cell debris, without formation of any excess sludge. In addition, the protease activity and intracellular ATP concentration of reactor 2 were increased when compared to reactor 1, indicating that reactor 2 had a better ability to digest proteins and cell debris. DGGE analysis revealed that the bacterial communities in the two reactors were different, and that the dissimilarity of the bacterial population was nearly 40%. Reactor 2 also contained more protozoa and metazoa, which could graze on the ozone-treated sludge debris directly.     

The effects of the bacterial interaction with visible-light responsive titania photocatalyst on the bactericidal performance

Bactericidal activity of traditional titanium dioxide (TiO₂) photocatalyst is effective only upon irradiation by ultraviolet light, which restricts the potential applications of TiO₂ for use in our living environments. Recently carbon-containing TiO₂ was found to be photoactive at visible-light illumination that affords the potential to overcome this problem; although, the bactericidal activity of these photocatalysts is relatively lower than conventional disinfectants. Evidenced from scanning electron microscopy and confocal Raman spectral mapping analysis, we found the interaction with bacteria was significantly enhanced in these anatase/rutile mixed-phase carbon-containing TiO₂. Bacteria-killing experiments indicate that a significantly higher proportion of all tested pathogens including Staphylococcus aureus, Shigella flexneri and Acinetobacter baumannii, were eliminated by the new nanoparticle with higher bacterial interaction property. These findings suggest the created materials with high bacterial interaction ability might be a useful strategy to improve the antimicrobial activity of visible-light-activated TiO₂.     

A habitat-based model for the spread of hantavirus between reservoir and spillover species

New habitat-based models for spread of hantavirus are developed which account for interspecies interaction. Existing habitat-based models do not consider interspecies pathogen transmission, a primary route for emergence of new infectious diseases and reservoirs in wildlife and man. The modeling of interspecies transmission has the potential to provide more accurate predictions of disease persistence and emergence dynamics. The new models are motivated by our recent work on hantavirus in rodent communities in Paraguay. Our Paraguayan data illustrate the spatial and temporal overlaps among rodent species, one of which is the reservoir species for Jabora virus and others which are spillover species. Disease transmission occurs when their habitats overlap. Two mathematical models, a system of ordinary differential equations (ODE) and a continuous-time Markov chain (CTMC) model, are developed for spread of hantavirus between a reservoir and a spillover species. Analysis of a special case of the ODE model provides an explicit expression for the basic reproduction number, , such that if , then the pathogen does not persist in either population but if , pathogen outbreaks or persistence may occur. Numerical simulations of the CTMC model display sporadic disease incidence, a new behavior of our habitat-based model, not present in other models, but which is a prominent feature of the seroprevalence data from Paraguay. Environmental changes that result in greater habitat overlap result in more encounters among various species that may lead to pathogen outbreaks and pathogen establishment in a new host.     

Starving Neurons Show Sex Difference in Autophagy

Sex-dependent differences in adaptation to famine have long been appreciated, thought to hinge on female versus male preferences for fat versus protein sources, respectively. However, whether these differences can be reduced to neurons, independent of typical nutrient depots, such as adipose tissue, skeletal muscle, and liver, was heretofore unknown. A vital adaptation to starvation is autophagy, a mechanism for recycling amino acids from organelles and proteins. Here we show that segregated neurons from males in culture are more vulnerable to starvation than neurons from females. Nutrient deprivation decreased mitochondrial respiration, increased autophagosome formation, and produced cell death more profoundly in neurons from males versus females. Starvation-induced neuronal death was attenuated by 3-methyladenine, an inhibitor of autophagy; Atg7 knockdown using small interfering RNA; or l-carnitine, essential for transport of fatty acids into mitochondria, all more effective in neurons from males versus females. Relative tolerance to nutrient deprivation in neurons from females was associated with a marked increase in triglyceride and free fatty acid content and a cytosolic phospholipase A2-dependent increase in formation of lipid droplets. Similar sex differences in sensitivity to nutrient deprivation were seen in fibroblasts. However, although inhibition of autophagy using Atg7 small interfering RNA inhibited cell death during starvation in neurons, it increased cell death in fibroblasts, implying that the role of autophagy during starvation is both sex- and tissue-dependent. Thus, during starvation, neurons from males more readily undergo autophagy and die, whereas neurons from females mobilize fatty acids, accumulate triglycerides, form lipid droplets, and survive longer.Sex-dependent differences in adaptation to famine have long been appreciated (1, 2), thought to hinge on a female preference for fat sources, in contrast to a male preference for protein sources (3). Fatty acid metabolism is different between sexes normally (4) and under conditions of starvation (1, 2). During exercise, in addition to increases in carbohydrate requirement, men increase their need for amino acids, whereas women increase mobilization of fat (5). Furthermore, sex-dependent responses to nutritional stress associated with either self-induced weight loss or illness-related cachexia also exist (6, 7).An important adaptation to starvation is autophagy (autophagy-associated proteins, abbreviated ATG). Classic, starvation-induced autophagy is initiated by nutrient and amino acid deprivation, glucagon, and cAMP (8, 9). ATG7, a ubiquitin E1-like enzyme, is essential for autophagy, with phosphorylation of preautophagosomal membranes, formation of ATG12-ATG5 complexes, and processing of ATG8/LC3 (microtubule-associated protein light chain-3) as other crucial steps in this process (10). Starvation-induced autophagy is regulated by class III phosphatidylinositol 3-kinase and the Bcl-2-interacting partner, Beclin-1 (11). The autophagosomes then engulf cytoplasmic material and/or organelles, such as mitochondria, the latter sometimes referred to as “mitophagy,” disassembling large proteins and organelles to recycle amino acids and other nutrients, an important response to starvation (12).It is unknown whether starvation can induce autophagy in the brain; however, there is evidence that critical starvation can result in brain atrophy in humans. It has been reported that ∼30% of people during a prolonged hunger strike (mean of 199 days) will show brain tissue loss (13), and brain shrinkage in patients with anorexia nervosa is well documented (14, 15). Although 48 h of food deprivation does not produce detectable autophagy in brains from mice (16), the aforementioned reports are consistent with long durations of starvation as a bona fide stimulus for autophagy in brain. There are recent studies suggesting that other stimuli can induce autophagy in the brain, such as trauma (17) and ischemia (18), and that autophagy may contribute to neuronal death. There is also evidence for autophagy in the human brain after trauma and critical illness (19), which probably includes both elements of malnutrition and systemic stress. A potential role for brain atrophy as a contributor to neurological morbidity in the critically ill and injured is an emerging topic (20).     

UV-B滤减处理下烟草光合作用参数对光照度的响应

以烟草栽培品种K326为材料,通过覆盖不同的透明薄膜滤减UV-B辐射,研究了100%（CK）、75%（T₁）、50% (T₂)、35%（T₃）UV-B辐射透过率处理下,烟草成熟初期光合参数与50和150 cm高度光照度的关系。结果表明：对于T₁、T₃,烟叶净光合速率的变化主要是气孔因素,而T₂主要是非气孔因素;通过对4类处理的平均水分利用效率的比较,发现可能存在一个UV-B辐射对水分利用效率影响的阈值范围;150 cm高度光照度除了对蒸腾速率和T₂处理的气孔导度起促进作用外,对其他光合参数都有一定的抑制作用;而不同处理的烟叶光合参数对50和150 cm高度上的光照度的响应都较为一致,在敏感程度上则存在差异。     

Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents

Curcumin has a surprisingly wide range of chemo-preventive and chemo-therapeutic activities and is under investigation for the treatment of various human cancers. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Although a number of synthetic modifications of curcumin have been studied intensively in order to develop a molecule with enhanced bioactivities, few synthetic studies were done for the improvement of pharmacokinetic profiles. In the present study, a series of mono-carbonyl analogues of curcumin were designed and synthesized by deleting the reactive β-diketone moiety, which was considered to be responsible for the pharmacokinetic limitation of curcumin. The results of the in vitro stability studies and in vivo pharmacokinetic studies indicated that the stability of these mono-carbonyl analogues was greatly enhanced in vitro and their pharmacokinetic profiles were also significantly improved in vivo. Furthermore, the cytotoxic activities of mono-carbonyl analogues were evaluated in seven different tumor cell lines by MTT assay and the structure–activity relation (SAR) was discussed and concluded. The results suggest that the five-carbon linker-containing analogues of curcumin may be favorable for the curcumin-based drug development both pharmacokinetically and pharmacologically.     

蚂蚁分子系统学研究进展

蚂蚁是分布广泛、种类和数量丰富的社会性昆虫.蚂蚁的传统分类学研究存在一定局限性,而分子生物学为蚂蚁的系统学研究提供了新途径.概述了蚂蚁分子系统学在研究内容和技术方法上的研究进展,并对今后的研究做了展望.     

Clarithromycin–Amoxycillin‐Containing Triple Therapy: A Valid Empirical First‐Line Treatment for Helicobacter pylori Eradication in Hong Kong?

Background: Recent studies have suggested the eradication rate for Helicobacter pylori infection with standard amoxycillin–clarithromycin‐containing triple therapy as first‐line treatment have fallen below 80%. Levofloxacin‐containing triple therapy was proposed as an alternative. The aim of this study is to compare the efficacy and tolerability of the standard 7‐day clarithromycin‐containing triple therapy against the 7‐day levofloxacin‐containing triple therapy, and to assess whether the classical triple therapy is still valid as empirical first‐line treatment for H. pylori infection in Hong Kong. Methods: Three hundred consecutive H. pylori‐positive patients were randomized to receive either 1 week of EAL (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and levofloxacin 500 mg daily) or EAC (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and clarithromycin 500 mg b.d.). H. pylori status was rechecked by ¹³C‐urea breath test 6 weeks after treatment. Patients who failed either of the first‐line eradication therapy were invited to undergo H. pylori susceptibility testing. Results: H. pylori eradication was achieved in 128 of 150 (85.3%) patients in EAL and 139 of 150 (92.7%) patients in EAC groups, respectively (p = .043), for both intention‐to‐treat and per‐protocol analysis. More patients in the clarithromycin‐ than the levofloxacin‐containing therapy group developed side effects from the medication (21.3% vs 13.3%, p = .060). Nine patients (six from the EAL group and three from the EAC group) who failed their corresponding eradication therapy returned for susceptibility testing. All nine isolates were highly resistant to levofloxacin (minimum inhibitory concentration or MIC > 32 μg/mL), whereas only two of the six isolates from the EAL group were resistant to clarithromycin (MIC > 0.5 μg/mL). Conclusions: The standard 7‐day clarithromycin‐containing triple therapy is still valid as the most effective empirical first‐line eradication therapy for H. pylori infection in Hong Kong, as prevalence of primary resistance of H. pylori to amoxycillin and clarithromycin remains low. Patients who failed their empirical first‐line eradication therapy should undergo H. pylori susceptibility testing to guide further treatment.