Opposite allosteric mechanisms in TetR and CAP

Regulation of the DNA binding affinity of an oligomeric protein can be considered to consist of an intrinsic component, in which the affinity of an individual DNA‐binding domain is modulated in response to effector binding, and an extrinsic component, in which the relative position of the protein's two DNA‐binding domains are altered so that they can or cannot contact both half‐site operators simultaneously. We demonstrated directly that the TetR repressor utilizes an extrinsic mechanism and CAP, the catabolite activator protein, utilizes an intrinsic mechanism.     

Rights, indirect harms and the non-identity problem

The non‐identity problem is the problem of grounding moral wrongdoing in cases in which an action affects who will exist in the future. Consider a woman who intentionally conceives while on medication that is harmful for a fetus. If the resulting child is disabled as a result of the medication, what makes the woman's action morally wrong? I argue that an explanation in terms of harmful rights violations fails, and I focus on Peter Markie's recent rights‐based defense. Markie's analysis rests on the notion of an indirect harm, and I show that the calculation of an indirect harm relies on an improper baseline for the determination of whether or not an action adversely affects a patient's interests. I also defend an impersonal duty‐based analysis of the wrongdoing in non‐identity cases against an objection by Markie. I close by arguing that the rights‐based analysis is insensitive to context and that context is morally relevant in the determination of the moral valence of actions in cases of non‐identity. This failure provides a pro tanto reason to favor an impersonal duty‐based analysis of the wrongdoing in non‐identity cases.     

Effects of Triiodothyronine (T3) Supplementation Upon Ozone-Induced Lung Injury

Ozone exposure results in an acute decrease in the serum levels of thyroid hormones; the physiologic sequelae of this are unclear. Whereas thyroid hormone supplementation appears to benefit pulmonary function in septic, oxyradical models of injury, thyroid hormone increases ozone toxicity. We demonstrated an increase in metabolic rate and pulmonary injury in lungs from ozone exposed, T₃ treated animals. This was evidenced by an increase in pulmonary weight gain, vascular perfusion pressure, and decrease in compliance in the supplemented animals. However, an increase in alkane generation, as an index of lipid peroxidation, was not seen in the ozone exposed, hormonally treated animals. This suggests that although thyroid hormone supplementation increases metabolic rate and ozone toxicity, an increased rate of lipid peroxidation plays a minimal role.     

The leaf-clipping display: A newly-discovered expressive gesture in wild chimpanzees

Chimpanzees of the Mahale Mountains, Tanzania were discovered to show an expressive gesture using leaves, termed as “leaf-clipping display”. This behavioural signal is directed by an adult male to an estrous female as a possessive behaviour, or by an adolescent male as a courtship display, or by an estrous female to an adolescent male also as a solicitation of copulation. The signal also is used toward human observers as a signal of food-demanding. This behaviour pattern might originate in a displacement tool-making behaviour in conflict situations. The leaf-clipping display has not been observed in any other chimpanzee populations studied, and may probably be one example of the tradition drift in wild chimpanzees.     

An Ecosystem Health Index for a large and variable river basin: Methodology,challenges and continuous improvement in Queensland’s Fitzroy Basin

Report cards are an increasingly popular method for summarising and communicating relative environmental performance and ecosystem health, including in aquatic environments. They are usually underpinned by an Ecosystem Health Index (EHI) that combines various individual indicators to produce an overall ecosystem health “score”. As a result of public water quality concerns, an integrated means of monitoring and reporting on aquatic ecosystem health was needed for the Fitzroy Basin in central Queensland, Australia. The Fitzroy Partnership for River Health was formed to address this need, and developed an EHI and report card for the Basin using existing monitoring data collected from various third parties including regulated companies operations and government. At 142,000 square kilometres, the Fitzroy Basin is the largest catchment draining to the World Heritage Listed Great Barrier Reef. The Fitzroy Basin provides an example of how to deliver an effective aquatic ecosystem health reporting system in a large and complex river basin. We describe the methodology used to develop an adaptive EHI for the Fitzroy Basin that addresses variability, complexity and scale issues associated with reporting across large areas. As well, we report how to manage the design and reporting stages given limitations in data collection and scientific understanding.     

Biological properties of two models of calcitonin gene related peptide with idealized amphiphilic alpha-helices of different lengths

Previous studies on calcitonin gene related peptide (CGRP) have demonstrated that it has the characteristics of an amphiphilic peptide, and from an examination of the sequence, we have proposed that it contains an amphiphilic alpha-helix. We have synthesized two analogues of CGRP which have different lengths of idealized amphiphilic alpha-helical secondary structure. The first model, CGRM-1, has been substituted with residues generating an idealized amphiphilic alpha-helix in the region between residues 8 and 25, equivalent to approximately five turns of an alpha-helix. This peptide is not an agonist in any of our bioassays, but it does bind with low affinity to rCGRP receptors in crude liver membranes. Our second model, CGRM-2, has an idealized amphiphilic alpha-helix between residues 8 and 18, which is equivalent to approximately three turns of an alpha-helix. In an in vitro rat vas deferens assay, this peptide is an agonist with a potency one-fourth that of the native hormone. However, the potency of CGRM-2 in an adenylate cyclase assay is much lower, only 1/140th the potency of CGRP. Both model peptides display amphiphilic characteristics commensurate with their design. We conclude that there is an amphiphilic alpha-helix in rCGRP between residues 8 and 18 and that this helix terminates in the vicinity of residue 18.     

Meclizine Inhibits Mitochondrial Respiration through Direct Targeting of Cytosolic Phosphoethanolamine Metabolism

We recently identified meclizine, an over-the-counter drug, as an inhibitor of mitochondrial respiration. Curiously, meclizine blunted respiration in intact cells but not in isolated mitochondria, suggesting an unorthodox mechanism. Using a metabolic profiling approach, we now show that treatment with meclizine leads to a sharp elevation of cellular phosphoethanolamine, an intermediate in the ethanolamine branch of the Kennedy pathway of phosphatidylethanolamine biosynthesis. Metabolic labeling and in vitro enzyme assays confirmed direct inhibition of the cytosolic enzyme CTP:phosphoethanolamine cytidylyltransferase (PCYT2). Inhibition of PCYT2 by meclizine led to rapid accumulation of its substrate, phosphoethanolamine, which is itself an inhibitor of mitochondrial respiration. Our work identifies the first pharmacologic inhibitor of the Kennedy pathway, demonstrates that its biosynthetic intermediate is an endogenous inhibitor of respiration, and provides key mechanistic insights that may facilitate repurposing meclizine for disorders of energy metabolism.     

苜蓿丫纹夜蛾核型多角体病毒囊膜内核衣壳排列图式的电镜观察

核型多角体病毒有单核衣壳包埋型和多核衣壳包埋型之分,单核衣壳包埋型是在一个病毒囊膜内只包含一个核衣壳,而多核衣壳包埋型的特点是在一个病毒囊膜内包含有２个以上的核衣壳,由于多个核衣壳成束地被包装在同一个病毒囊膜内,又称病毒束［１,２］。Ｈｕｎｔｅｒ等表明在干果斑螟核型多角体病毒中,病毒囊膜内包含２～２３个核衣壳［３］。Ｆｒａｓｅｒ将苜蓿丫纹夜蛾核型多角体病毒接种于秋粘虫细胞系,超薄切片电镜观察,病毒囊膜内包含的核衣壳数变动于２～１７粒,但未研究其核衣壳在病毒囊膜内的排列结构［４］。本研究用苜蓿丫纹…     

Effects of Neurochemicals upon a Dinoflagellate Photoresponse*

SYNOPSIS Photoresponsiveness by Gymnodinium splendens Lebour was monitored quantitatively by a microscope-television system. Exposure to the catecholamines DOPA and Dopamine caused a decrease in light sensitivity, while 0.01 mM norepinephrine, epinephrine, or isoproterenol did not affect photoresponsiveness. Classical catecholamine blocking agents, dichloroisoproterenol, propranolol, and dibenzyline, and an inhibitor of DOPA synthesis, α-methyl-ρ-tyrosine, caused an increase in sensitivity. In addition, acetylcholine and an inhibitor of acetylcholinesterase activity, eserine, caused an increase in sensitivity, while an inhibitor of acetylcholine action atropine, had the opposite effect. These experiments suggest that G. splendens may have an antagonistic catecholamine-cholinergic system which participates in regulating photosensitivity.     

Adaptations to training at the individual anaerobic threshold

The individual anaerobic threshold (Th(an)) is the highest metabolic rate at which blood lactate concentrations can be maintained at a steady-state during prolonged exercise. The purpose of this study was to test the hypothesis that training at the Th(an) would cause a greater change in indicators of training adaptation than would training "around" the Th(an). Three groups of subjects were evaluated before, and again after 4 and 8 weeks of training: a control group, a group which trained continuously for 30 min at the Th(an) intensity (SS), and a group (NSS) which divided the 30 min of training into 7.5-min blocks at intensities which alternated between being below the Th(an) [Th(an) -30% of the difference between Th(an) and maximal oxygen consumption (VO2max)] and above the Th(an) (Th(an) +30% of the difference between Th(an) and VO2max). The VO2max increased significantly from 4.06 to 4.27 l.min-1 in SS and from 3.89 to 4.06 l.min-1 in NSS. The power output (W) at Th(an) increased from 70.5 to 79.8% VO2max in SS and from 71.1 to 80.7% VO2max in NSS. The magnitude of change in VO2max, W at Th(an), % VO2max at Th(an) and in exercise time to exhaustion at the pretraining Th(an) was similar in both trained groups. Vastus lateralis citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase activities increased to the same extent in both trained groups. While all of these training-induced adaptations were statistically significant (P < 0.05), there were no significant changes in any of these variables for the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protein phosphorylation in pancreatic islets: evidence for separate Ca2+ and cAMP-enhanced phosphorylation of two 57,000 Mr proteins

There is a phosphopeptide that has an Mr of 53,000 to 60,000 in insulin-secreting tissues and there is general agreement that this peptide can be phosphorylated in a calcium-dependent manner. The present report shows that there are at least two phosphoproteins with Mr's near 57,000 in rat pancreatic islet cytosol. One peptide has an Mr of 57,000, a pl of 7.5 - 8 and is phosphorylated in a Ca2+-enhanced manner, and the other has an Mr of 54,000, a pl of 5 - 5.5 and is phosphorylated in a cAMP-enhanced manner, as judged by two-dimensional polyacrylamide gel electrophoresis. Sepharose 4B chromatography indicated that the former polypeptide resides in a native protein complex that has an Mr of about 500,000 and the latter in a complex that has an Mr of about 180,000. Tritiated azido cyclic AMP binds to an islet polypeptide that has an Mr of 54,000. The results suggest that Ca2+ and cAMP could regulate stimulus-secretion coupling in pancreatic islets via protein phosphorylation.     

Sex Difference in Contusion of the Medial Femoral Condyle Rim-Association with MRI Occult Meniscal Tears in the ACL Deficient Knee

BackgroundMeniscal tears, specifically lateral meniscal tears, have a larger than expected un-derdiagnosis rate in the presence of an ACL tear. The purpose of our study was to search for an MRI bone contusion pattern associated with MRI occult meniscal tears in patients with an ACL tear, specifically a contusion of the rim of the medial femoral condyle (RMFC). Our hypothesis was that there would be a significant association between RMFC contusions and MRI occult meniscal tears in patients with an ACL tear. We also searched for a difference between sexes with respect to the presence of the RMFC contusion in the setting of an occult meniscal tear. We also categorized the type, size, and location of these occult meniscal tears in the setting of an ACL tear.Methods This was a retrospective study that examined characteristics of occult meniscal tears and their association with a RMFC bone contusion. IRB approval was obtained. The date range of the study was June 2009 through December 2015. 6392 consecutive knee MRI reports in patients with an ACL deficient knee were reviewed. The study group included 22 patients with MRI occult meniscal tears, the control group included 110 patients. Relevant statistical values were calculated.ResultsThe most common type of occult meniscal tears were small radial and small longitudinal tears of the lateral meniscus. Occult meniscal tears were associated with an RMFC contusion in the study group (p=0.0457), particularly in males (p = 0.0003). In males with a torn ACL, the sensitivity of an RMFC contusion for an occult meniscal tear was 80%.ConclusionIn males with an ACL tear, there was a significant association between a contusion of the RMFC and an occult meniscal tear (commonly small radial or small peripheral partial-thickness longitudinal tears). RMFC contusions were reliably identified by radiologists in this study.Level of Evidence: II     

Sec62 Protein Mediates Membrane Insertion and Orientation of Moderately Hydrophobic Signal Anchor Proteins in the Endoplasmic Reticulum (ER)

Nascent chains are known to be targeted to the endoplasmic reticulum membrane either by a signal recognition particle (SRP)-dependent co-translational or by an SRP-independent post-translational translocation route depending on signal sequences. Using a set of model and cellular proteins carrying an N-terminal signal anchor sequence of controlled hydrophobicity and yeast mutant strains defective in SRP or Sec62 function, the hydrophobicity-dependent targeting efficiency and targeting pathway preference were systematically evaluated. Our results suggest that an SRP-dependent co-translational and an SRP-independent post-translational translocation are not mutually exclusive for signal anchor proteins and that moderately hydrophobic ones require both SRP and Sec62 for proper targeting and translocation to the endoplasmic reticulum. Further, defect in Sec62 selectively reduced signal sequences inserted in an N_in-C_out (type II) membrane topology, implying an undiscovered role of Sec62 in regulating the orientation of the signal sequence in an early stage of translocation.     

肾上腺皮质激素在应激性高血压发病中的中枢机制

本工作观察到应激性高血压大鼠发病过程中伴随着出现血浆儿茶酚胺，皮质酮以及血糖，血脂的平行升高，肾上腺皮质激素微量注射至延髓头端腹外侧区可引起升压，加快心率及增强防御性升压反应，该作用可能是应激性高血压发病机制的重要环节之一，其机制可能通过对该区神经元的快速膜效应而实现，并与该区胆碱能系统活动的异常增强和钙通道的激活有关。     

Hepatic fatty acid-supported respiration in rats fed an energy-dense diet

The energy balance and hepatic fatty acid-supported respiration were studied in rats fed a control or an energy-dense diet. In addition, state 3 and 4 respiratory rates as well as ketone body production with palmitoylcarnitine as substrate were determined in isolated mitochondria. Metabolizable energy intake and energy expenditure increased in rats fed an energy-dense diet, but the gain in body weight and lipid content remained unchanged. No variation occurred in the mitochondrial palmitoylcarnitine utilization rate and ketone body production, but a significant increase in the mitochondrial content of ketone bodies and the serum levels was found in rats fed an energy-dense diet. Furthermore, we have shown a significant increase in fatty acid-stimulated respiration in hepatocytes from rats fed an energy-dense diet. The enhanced hepatic fatty acid utilization as an energy substrate found in rats fed an energy-dense diet may contribute to reduce the availability of lipids for storage, thus counteracting the development of obesity.     

Effects of ornithine or arginine administration on serum amino acid levels

In healthy humans after overnight fasting, an oral administration of ornithine induced a new steady state: an accumulation of serum alanine and proline, a decrease in serum valine concentration, transient reductions in serum urea and urinary urea contents, and then an increased urea excretion. On the other hand, an oral administration of arginine resulted in an anabolic state: decreases in serum leucine and isoleucine concentrations, reductions in serum glucose and free fatty acid contents and a rapid increase in serum insulin level. It was assumed that the effect of ornithine administration may be exerted through an activation of hepatic System A transport and that of arginine is an insulin-mediated action.     

Evolutionary stability: States and strategies

Different aspects and modifications of the definition of an evolutionarily stable (ES) strategy that have been considered in the literature can be incorporated in a unifying concept which regards the population context. This concept of evolutionary stability will generally characterize population states in both pure- and mixed-strategist models. In particular, it includes ES strategies, represented as a phenotype unique in an ES population. For an important class of mixed-strategist models, no strict ESS can exist. This will be the case whenever the success of an individual strategy is considered to follow as an average from the successes of its behavioural components. Instead, ESS results may be obtained from what will be called a “degenerate” form of the model, which is simply an ESS model on the level of elementary actions. Then, however, the correct interpretation of an ESS is not an individual phenotype but rather a population mixture of elementary actions. If an ES state exists in a mixed-strategist model it may be determined by an equilibrium condition; if there is an ES strategy, a different approach—mainly maximum considerations—is needed for finding it. An equilibrium condition does not hold for the components of an ES strategy straightforwardly; but it can be derived in terms of an auxiliary ESS model that considers first-order effects of the components. Several examples illustrate the significance of these results. Particularly, two models on “Games between Relatives” are reconsidered in order to display both their formal interrelation and the different meaning of their results in the context of mixed-strategist models.     

Behavioural fever boosts the inflammatory response in rainbow trout Oncorhynchus mykiss

Behavioural fever, manifested as an increased preferred temperature, was shown in rainbow trout Oncorhynchus mykiss following an injection of bacterial lipopolysaccharide. Simulated behavioural fever, through a 2·5° C water temperature rise following bacterial lipopolysaccharide injection, enhanced the expression of the cytokine interleukin-1β, in comparison with an untreated group held at the initial temperature. The present findings show that an important mediator in the immune response can be boosted through behavioural fever in fishes.     

农田防护林的可持续经营管理

林带更新的时空布局对持续发挥林网的防护效益具有重要意义。本文提出用拟法正林思想经营农田防扩林,以行政村为组织经营单位,通过逐步更新调整组织经营单位管理的林带,使整个林网体系形成自幼龄到成熟龄各龄级林带条数基本相等,空间上均匀配置的格局,从而确保时间上农田防护林生态服务的稳定和持续发挥。