The commands that control animal movement are transmitted from motor neurons to their target muscle cells at the neuromuscular junctions (NMJs). The NMJs contain many protein species whose role in ...transmission depends not only on their inherent properties, but also on how they are distributed within the complex structure of the motor nerve terminal and the postsynaptic muscle membrane. These molecules mediate evoked chemical transmitter release from the nerve and the action of that transmitter on the muscle. Human NMJs are among the smallest known and release the smallest number of transmitter "quanta". By contrast, they have the most deeply infolded postsynaptic membranes, which help to amplify transmitter action. The same structural features that distinguish human NMJs make them particularly susceptible to pathological processes. While much has been learned about the molecules which mediate transmitter release and action, little is known about the molecular processes that control the growth of the cellular and subcellular components of the NMJ so as to give rise to its mature form. A major challenge for molecular biologists is to understand the molecular basis for the development and maintenance of functionally important aspects of NMJ structure, and thereby to point to new directions for treatment of diseases in which neuromuscular transmission is impaired.
Neuromuscular junctions (NMJs) have long been studied as particularly accessible examples of chemical synapses. Nonetheless, some important features of neuromuscular transmission are still poorly ...understood. One of these is the low statistical variability of the number of transmitter quanta released from motor nerve terminals by successive nerve impulses. This variability is well-described by a binomial distribution, suggesting that the quanta released are drawn, at high probability, from a small subset of those in the terminals. However, the nature of that subset remains unclear. In an effort to clarify what is understood, and what is not, about quantal release at NMJs, this review addresses the relationship between NMJ structure and function. After setting the biological context in which NMJs operate, key aspects of the variability of release and the structure of the motor nerve terminals are described. These descriptions are then used to explore the functional logic of motor nerve terminal organization and the structural basis of the low variability of release. This analysis supports the suggestion that the probability of release differs significantly at the different 'active zones' from which quanta are released. Finally, after a brief consideration of how release is maintained in the long term, a comparison is made of the features of NMJs with those of some well-studied neuronal synapses. An important conclusion is that NMJs share some important features with neuronal synapses, so continuing efforts to understand how motor nerve terminals work are likely to have much more general implications.
The Enzyme Function Initiative, an NIH/NIGMS-supported Large-Scale Collaborative Project (EFI; U54GM093342; http://enzymefunction.org/), is focused on devising and disseminating bioinformatics and ...computational tools as well as experimental strategies for the prediction and assignment of functions (in vitro activities and in vivo physiological/metabolic roles) to uncharacterized enzymes discovered in genome projects. Protein sequence similarity networks (SSNs) are visually powerful tools for analyzing sequence relationships in protein families (H.J. Atkinson, J.H. Morris, T.E. Ferrin, and P.C. Babbitt, PLoS One 2009, 4, e4345). However, the members of the biological/biomedical community have not had access to the capability to generate SSNs for their “favorite” protein families. In this article we announce the EFI-EST (Enzyme Function Initiative-Enzyme Similarity Tool) web tool (http://efi.igb.illinois.edu/efi-est/) that is available without cost for the automated generation of SSNs by the community. The tool can create SSNs for the “closest neighbors” of a user-supplied protein sequence from the UniProt database (Option A) or of members of any user-supplied Pfam and/or InterPro family (Option B). We provide an introduction to SSNs, a description of EFI-EST, and a demonstration of the use of EFI-EST to explore sequence–function space in the OMP decarboxylase superfamily (PF00215). This article is designed as a tutorial that will allow members of the community to use the EFI-EST web tool for exploring sequence/function space in protein families.
•Sequence–function space can be visualized using protein sequence similarity networks.•The EFI-EST webtool is available for generating sequence similarity networks.•A tutorial is provided that describes the use of EFI-EST.•The community is encouraged to use EFI-EST without cost.
Telleman G, Raghoebar GM, Vissink A, den Hartog L, Huddleston Slater JJR, Meijer HJA. A systematic review of the prognosis of short (<10 mm) dental implants placed in the partially edentulous ...patient. J Clin Periodontol 2011; doi: 10.1111/j.1600‐051X.2011.01736.x.
Aim: This study evaluated, through a systematic review of the literature, the estimated implant survival rate of short (<10 mm) dental implants installed in partially edentulous patients.
Materials and methods: A systematic search was conducted in the electronic databases of MEDLINE (1980–October 2009) and EMBASE (1980–October 2009) to identify eligible studies. Two reviewers independently assessed the methodological quality of the articles using specific study design‐related quality assessment forms.
Results: Twenty‐nine methodologically acceptable studies were selected. A total of 2611 short implants (lengths 5–9.5 mm) were analysed. An increase in implant length was associated with an increase in implant survival (from 93.1% to 98.6%). Heterogeneity between studies was explored by subgroup analyses. The cumulative estimated failure rate of studies performed in the maxilla was 0.010 implants/year, compared with 0.003 found in the studies in the mandible. For studies that also included smokers, the failure rate was 0.008 compared with 0.004 found in studies that excluded smokers. Surface topography and augmentation procedure were not sources of heterogeneity.
Conclusion: There is fair evidence that short (<10 mm) implants can be placed successfully in the partially edentulous patient, although with a tendency towards an increasing survival rate per implant length, and the prognosis may be better in the mandible of non smoking patients.
Key issues relating to intrinsic defects, dopant incorporation, and lithium ion migration in the LiFePO4 electrode material have been investigated using well-established atomistic modeling ...techniques. Our simulation model shows good reproduction of the observed olivine-type structure of LiFePO4. The most favorable intrinsic defect is the Li−Fe “anti-site” pair in which a Li ion (on the M1 site) and an Fe ion (on the M2 site) are interchanged. This type of anti-site defect or “intersite exchange” has been observed in olivine silicates. The lowest Li migration energy is found for the pathway along the 010 channel, with a nonlinear, curved trajectory between adjacent Li sites. Trends in dopant substitution energetics of a range of cations with charges varying from +2 to +5 are also examined. Low favorable energies are found only for divalent dopants on the Fe site (such as Mn), which is in accord with experimental work. Our results suggest that, on energetic grounds, LiFePO4 is not tolerant to aliovalent doping (e.g., Al, Ga, Zr, Ti, Nb, Ta) on either Li (M1) or Fe (M2) sites.
Background
Neoadjuvant chemotherapy (NACT) is increasingly being offered to patients with breast cancer. No survival benefit has been demonstrated for NACT, but it may serve to reduce tumour size and ...improve prognosis through the attainment of a pathological complete response (pCR). The role and mode of MRI monitoring during NACT remain unclear.
Methods
Patients managed with NACT at a UK centre over 7 years were studied using a prospectively maintained database, which also included details of MRI. Clinicopathological and radiological predictors of NACT response were analysed in a univariable setting and survival analysis was undertaken using the Kaplan–Meier method.
Results
A total of 278 patients underwent surgery following NACT, of whom 200 (71·9 per cent) had residual invasive disease and 78 (28·1 per cent) achieved a pCR. Attaining a pCR improved survival significantly compared with that of patients with residual invasive disease (mean 77·1 versus 66·0 months; P = 0·004) and resulted in significantly fewer recurrences (6·0 versus 24·3 per cent; P = 0·001). The pCR rate varied significantly among molecular subgroups of breast cancer (P < 0·001): luminal A, 6 per cent; luminal B/human epidermal growth factor 2 receptor (Her2)‐negative, 21 per cent; luminal B/Her2‐positive, 35 per cent, Her2‐positive/non‐luminal, 72 per cent; and triple‐negative breast cancer (TNBC), 32 per cent. High‐grade disease (G3) correlated with an increased rate of pCR. A radiological response seen on the mid‐treatment MRI was predictive of pCR (sensitivity 77·6 per cent, but specificity only 53·3 per cent), as was complete radiological response at final MRI (specificity 97·6 per cent, but sensitivity only 32·2 per cent).
Conclusion
NACT allows identification of patient subgroups within TNBC and Her2‐positive cohorts with a good prognosis. MRI can be used to identify patients who are responding to treatment.
Mid‐neoadjuvant chemotherapy MRI useful
Confucianism and Catholicism , among the most
influential religious traditions, share an intricate relationship.
Beginning with the work of Matteo Ricci (1552-1610), the nature of
this relationship ...has generated great debate. These ten essays
synthesize in a single volume this historic conversation. Written
by specialists in both traditions, the essays are organized into
two groups. Those in the first group focus primarily on the
historical and cultural contexts in which Confucianism and
Catholicism encountered one another in the four major Confucian
cultures of East Asia: China, Vietnam, Korea, and Japan. The essays
in the second part offer comparative and constructive studies of
specific figures, texts, and issues in the Confucian and Catholic
traditions from both theological and philosophical perspectives. By
bringing these historical and constructive perspectives together,
Confucianism and Catholicism: Reinvigorating the Dialogue
seeks not only to understand better the past dialogue between these
traditions, but also to renew the conversation between them
today.
In light of the unprecedented expansion of Eastern Asian
influence in recent decades, and considering the myriad of
challenges and new opportunities faced by both the Confucian and
Catholic traditions in a world that is rapidly becoming globalized,
this volume could not be more timely. Confucianism and
Catholicism will be of interest to professional theologians,
historians, and scholars of religion, as well as those who work in
interreligious dialogue.
Contributors: Michael R. Slater, Erin M. Cline, Philip J.
Ivanhoe, Vincent Shen, Anh Q. Tran, S.J., Donald L. Baker, Kevin M.
Doak, Xueying Wang, Richard Kim, Victoria S. Harrison, and Lee H.
Yearley.
Within this article, it is shown that an electrochemical defluorination and additional fluorination of Ruddlesden–Popper-type La2NiO3F2 is possible within all-solid-state fluoride-ion batteries. ...Structural changes within the reduced and oxidized phases have been examined by X-ray diffraction studies at different states of charging and discharging. The synthesis of the oxidized phase La2NiO3F2+x proved to be successful by structural analysis using both X-ray powder diffraction and automated electron diffraction tomography techniques. The structural reversibility on re-fluorinating and re-defluorinating is also demonstrated. Moreover, the influence of different sequences of consecutive reduction and oxidation steps on the formed phases has been investigated. The observed structural changes have been compared to changes in phases obtained via other topochemical modification approaches such as hydride-based reduction and oxidative fluorination using F2 gas, highlighting the potential of such electrochemical reactions as alternative synthesis routes. Furthermore, the electrochemical routes represent safe and controllable synthesis approaches for novel phases, which cannot be synthesized via other topochemical methods. Additionally, side reactions, occurring alongside the desired electrochemical reactions, have been addressed and the cycling performance has been studied.
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