Periwinkles and parasites: the occurrence and phenotypic effects of parasites in Littorina saxatilis and L. arcana in northeastern England

Littorina saxatilis is a common intertidal gastropod on shores of the North Atlantic, and an 24 important study species for evolutionary investigations. Its congener L. arcana is much less 25 widely distributed, but both species are common at Old Peak, Yorkshire, UK. The parasite 26 profiles of L. saxatilis and L. arcana from this shore were determined histologically, revealing 27 a ciliated protist, Protophrya ovicola, an unidentified apicomplexan (present in <1% L. 28 saxatilis) and three trematode parasites tentatively assigned to Renicola sp., Microphallus 29 similis and M. pygmaeus. The profile data include prevalence information and associated 30 histology. Protophrya ovicola associated predominantly with the wave ecotype of L. saxatilis 31 (65%) rather than the crab ecotype (16%). Microphallus similis occurred at a higher 32 prevalence in the L. arcana population (38%) in comparison with the L. saxatilis population 33 (11%). Overall, there appeared to be a lower prevalence of trematodes in the high-shore L. 34 saxatilis. By modelling occurrence of individual parasites and shell morphometrics, an 35 assessment of parasite-associated morphological change was conducted. We conclude that 36 parasitism appeared not to cause shell-shape change, but rather that snails of a certain shell 37 shape were more likely to display infection. Records of parasites in L. saxatilis and L. arcana 38 are briefly reviewed, showing that the diversity of parasites reported here is relatively low

Adaptation to a steep environmental gradient and an associated barrier to gene exchange in Littorina saxatilis

Steep environmental gradients offer important opportunities to study the interaction between natural selection and gene flow. Allele frequency clines are expected to form at loci under selection but unlinked neutral alleles may pass easily across these clines unless a generalized barrier evolves. Here we consider the distribution of forms of the intertidal gastropod Littorina saxatilis, analyzing shell shape and AFLP loci on two rocky shores in Britain. On the basis of previous work, the AFLP loci were divided into differentiated and undifferentiated groups. On both shores, we have shown a sharp cline in allele frequencies between the two morphs for differentiated AFLP loci. This is coincident with a habitat transition on the shore where the two habitats (cliff and boulder field) are immediately contiguous. The allele frequency clines coincide with a cline in shell morphology. In the middle of the cline, linkage disequilibrium for the differentiated loci rises in accordance with expectation. The clines are extremely narrow relative to dispersal, probably as a result of both strong selection and habitat choice. An increase in FST for undifferentiated AFLPs between morphs, relative to within-morph comparisons, is consistent with there being a general barrier to gene flow across the contact zone. These features are consistent either with an episode of allopatric divergence followed by secondary contact or with primary, non-allopatric, divergence. Further data will be needed to distinguish between these alternatives

Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK

葡萄糖是生物中最基本、最主要的营养物质，它不仅是机体能量的主要来源，也是生物质合成的主要原料。因此，葡萄糖的水平对于生物体是极其重要的。然而，在生活中，体内葡萄糖水平的波动是十分常见的，这是因为我们不可能每时每刻都在摄入葡萄糖：睡一大觉、剧烈运动几个小时或者太忙了没时间吃饭，都会引起葡萄糖水平的显著下降。这时，机体能够触发一套有效的过程应对这类“不利情况”，其中最为关键的就是激活“代谢的核心调节”——AMPK。在葡萄糖水平下降时，被激活的AMPK能够迅速启动脂肪、蛋白质的分解代谢，关闭它们的合成代谢，从而起到维持机体的能量和物质代谢的平衡，弥补机体因葡萄糖不足引起的胁迫压力。那么，机体如何感受葡萄糖水平下降，并“传递”给AMPK使其激活呢？林圣彩教授课题组的这项研究正是发现了生理状态下机体感受葡萄糖水平的机制。通过研究他们发现，无论在不含葡萄糖的细胞培养条件下，还是在饥饿的低血糖的动物体内，都不能观测到AMP水平的上升，这充分说明了机体有一套尚不为人知的、独立于AMP的感应葡萄糖水平的机制。在进一步的研究中他们揭示了这一完整过程：葡萄糖水平下降将引起的葡萄糖代谢中间物——果糖1,6-二磷酸（fructose-1,6-bisphosphate）水平的下降，该过程进一步地被糖酵解通路上的代谢酶——醛缩酶（aldolase）感应，因为醛缩酶正是将含有6个碳原子的果糖1,6-二磷酸裂解成三碳糖的酶，一旦醛缩酶“吃不到”由葡萄糖衍生的果糖1,6-二磷酸，它便“翻脸”，传递给也正是林圣彩教授课题组先前发现的溶酶体途径进而激活AMPK。该过程完全不涉及AMP水平，即能量水平的变化，是一条全新的、完全建立在实际的生理情况上的通路。林圣彩教授进一步地把葡萄糖水平总结为一种“状态信号”，以区别于传统的“能量信号”。据悉，该葡萄糖感知通路的发现对开发用于治疗肥胖症，乃至延长寿命的药物具有深远的意义。【Abstract】The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK)1, but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK2, 3, 4, 5. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation6, 7. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.D.G.H. was supported by an Investigator Award from the Wellcome Trust (097726) and a Programme Grant from Cancer Research UK (C37030/A15101). S.-C.L. was supported by grants from the National Key Research and Development Project of China (2016YFA0502001) and the National Natural Science Foundation of China (#31430094, #31690101, #31571214, #31601152 and #J1310027)

Role of Surface Area, Primary Particle Size, and Crystal Phase on Titanium Dioxide Nanoparticle Dispersion Properties

Characterizing nanoparticle dispersions and understanding the effect of parameters that alter dispersion properties are important for both environmental applications and toxicity investigations. The role of particle surface area, primary particle size, and crystal phase on TiO2 nanoparticle dispersion properties is reported. Hydrodynamic size, zeta potential, and isoelectric point (IEP) of ten laboratory synthesized TiO2 samples, and one commercial Degussa TiO2 sample (P25) dispersed in different solutions were characterized. Solution ionic strength and pH affect titania dispersion properties. The effect of monovalent (NaCl) and divalent (MgCl2) inert electrolytes on dispersion properties was quantified through their contribution to ionic strength. Increasing titania particle surface area resulted in a decrease in solution pH. At fixed pH, increasing the particle surface area enhanced the collision frequency between particles and led to a higher degree of agglomeration. In addition to the synthesis method, TiO2 isoelectric point was found to be dependent on particle size. As anatase TiO2 primary particle size increased from 6 nm to 104 nm, its IEP decreased from 6.0 to 3.8 that also results in changes in dispersion zeta potential and hydrodynamic size. In contrast to particle size, TiO2 nanoparticle IEP was found to be insensitive to particle crystal structure

Computational Models of Classical Conditioning guest editors’ introduction

In the present special issue, the performance of current computational models of classical conditioning was evaluated under three requirements: (1) Models were to be tested against a list of previously agreed-upon phenomena; (2) the parameters were fixed across simulations; and (3) the simulations used to test the models had to be made available. These requirements resulted in three major products: (a) a list of fundamental classical-conditioning results for which there is a consensus about their reliability; (b) the necessary information to evaluate each of the models on the basis of its ordinal successes in accounting for the experimental data; and (c) a repository of computational models ready to generate simulations. We believe that the contents of this issue represent the 2012 state of the art in computational modeling of classical conditioning and provide a way to find promising avenues for future model development

Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses

Intrinsic antioxidant defenses are important for neuronal longevity. We found that in rat neurons, synaptic activity, acting via NMDA receptor (NMDAR) signaling, boosted antioxidant defenses by making changes to the thioredoxin-peroxiredoxin (Prx) system. Synaptic activity enhanced thioredoxin activity, facilitated the reduction of overoxidized Prxs and promoted resistance to oxidative stress. Resistance was mediated by coordinated transcriptional changes; synaptic NMDAR activity inactivated a previously unknown Forkhead box O target gene, the thioredoxin inhibitor Txnip. Conversely, NMDAR blockade upregulated Txnip in vivo and in vitro, where it bound thioredoxin and promoted vulnerability to oxidative damage. Synaptic activity also upregulated the Prx reactivating genes Sesn2 (sestrin 2) and Srxn1 (sulfiredoxin), via C/EBPβ and AP-1, respectively. Mimicking these expression changes was sufficient to strengthen antioxidant defenses. Trans-synaptic stimulation of synaptic NMDARs was crucial for boosting antioxidant defenses; chronic bath activation of all (synaptic and extrasynaptic) NMDARs induced no antioxidative effects. Thus, synaptic NMDAR activity may influence the progression of pathological processes associated with oxidative damage