bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation
Authors: Grace Peter M. , Strand Keith A. , Galer Erika L. , Urban Daniel J. , Wang Xiaohui , Baratta Michael V. , Fabisiak Timothy J. , Anderson Nathan D. , Cheng Kejun , Greene Lisa I. , Berkelhammer Debra , Zhang Yingning , Ellis Amanda L. , Yin Hang Hubert , Campeau Serge , Rice Kenner C. , Roth Bryan L. , Maier Steven F. , Watkins Linda R. 
Published: June 2016

Significance
Pain after disease/damage of the nervous system is predominantly treated with opioids, but without exploration of the long-term consequences. We demonstrate that a short course of morphine after nerve injury doubles the duration of neuropathic pain. Using genetic and pharmacological interventions, and innovative Designer Receptor Exclusively Activated by Designer Drugs disruption of microglia reactivity, we demonstrate that opioid-prolonged neuropathic pain arises from spinal microglia and NOD-like receptor protein 3 inflammasome formation/activation. Inhibiting these processes permanently resets amplified pain to basal levels, an effect not previously reported. These data support the “two-hit hypothesis” of amplification of microglial activation—nerve injury being the first “hit,” morphine the second. The implications of such potent microglial “priming” has fundamental clinical implications for pain and may extend to many chronic neurological disorders.
Mass spectrometry-based absolute quantification reveals rhythmic variation of mouse circadian clock proteins
Authors: Narumi Ryohei , Shimizu Yoshihiro , Ukai-Tadenuma Maki , Ode Koji L. , Kanda Genki N. , Shinohara Yuta , Sato Aya , Matsumoto Katsuhiko , Ueda Hiroki R. 
Published: June 2016

Significance
A method for absolute quantification of proteins for targeted proteomics is developed. It introduces a simple and high-throughput synthesis of internal standards for peptide quantification and thereby facilitates both multiplexed and sensitive absolute quantification of proteins. Application of this method to the systems-level dynamic analysis of core circadian clock proteins and detection of internal body time using quantified values of circadian clock proteins is shown. The results demonstrate the validity of the developed method in which quantified values from wild-type mice can predict the endogenous state of the circadian clock.
The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for TIF-1γ sumoylation and poly-SUMO chain elongation
Authors: Sohn Sook-Young , Hearing Patrick 
Published: June 2016

Significance
Viruses interplay with the host sumoylation system to manipulate diverse cellular responses. The adenovirus (Ad) early region 4 (E4)-ORF3 protein forms a dynamic nuclear network to interfere with and exploit host processes. Here we provide the first direct evidence to our knowledge that the Ad5 E4-ORF3 protein is a new type of viral small ubiquitin-like modifier (SUMO) E3 ligase that promotes substrate sumoylation and poly-SUMO3 chain formation. This explains the interrelationship between E4-ORF3–mediated substrate sumoylation and proteasomal degradation. Our study reveals that E4-ORF3 functions directly to regulate cellular enzymatic processes. Because E4-ORF3 does not share homology with any known ubiquitin or SUMO E3 ligases, these results confer an important clue to understand the mechanism by which E3 ligases transfer SUMOs from charged E2 to selected substrates and mediate chain elongation.
Argininosuccinate synthetase regulates hepatic AMPK linking protein catabolism and ureagenesis to hepatic lipid metabolism
Authors: Madiraju Anila K. , Alves Tiago , Zhao Xiaojian , Cline Gary W. , Zhang Dongyan , Bhanot Sanjay , Samuel Varman T. , Kibbey Richard G. , Shulman Gerald I. 
Published: June 2016

Significance
The CDC projects that by the year 2050 one in three adults will be affected by diabetes in the United States alone. A key feature of type 2 diabetes is insulin resistance, which is associated with ectopic lipid deposition in tissues such as the liver. We have discovered a novel regulatory mechanism in the liver linking protein catabolism and ureagenesis to increased lipid oxidation. By increasing urea production, flux through the enzyme argininosuccinate synthetase is enhanced, leading to activation of AMP-activated protein kinase and increased hepatic fat oxidation. These findings may lead to the development of new drugs designed to reduce fat accumulation in the liver and reverse insulin resistance.
A statistical property of fly odor responses is conserved across odors
Authors: Stevens Charles F. 
Published: June 2016

Significance
Although the brain has long been considered to use combinatorial codes (a defined population of neurons whose pattern of rates is specific to a particular object), in no case has the code been well-characterized. Here I characterize the fly odor code by showing it is maximum entropy; what this means is that the response to all odors is statistically the same. This characterization is a significant first step in cracking the odor code.
Whole-exome sequencing to analyze population structure, parental inbreeding, and familial linkage
Authors: Belkadi Aziz , Pedergnana Vincent , Cobat Aurélie , Itan Yuval , Vincent Quentin B. , Abhyankar Avinash , Shang Lei , El Baghdadi Jamila , Bousfiha Aziz ,   the Exome/Array Consortium, Alcais Alexandre , Boisson Bertrand , Casanova Jean-Laurent , Abel Laurent , Al-Herz Waleed , Arikan Cigdem , Arkwright Peter , Aydogmus Cigdem , Bernard Olivier , Blancas-Galicia Lizbeth , Boisson-Dupuis Stéphanie , Bonnet Damien , Stambouli Omar Boudghene , Boussofara Lobna , Boutros Jeannette , Bustamante Jacinta , Ciancanelli Michael , Cole Theresa , Condino-Neto Antonio , Desai Mukesh , Fieschi Claire , Franco José Luis , Ichai Philippe , Jouanguy Emmanuelle , Keser-Emiroglu Melike , Kilic Sara S , Mahdaviani Seyed Alireza , Mahlhoui Nizar , Mansouri Davood , Parvaneh Nima , Picard Capucine , Puel Anne , Raoult Didier , Rezaei Nima , Sanal Ozden , Ramon Silvia Sanchez , Vandenesch François , Vogt Guillaume , Zhang Shen-Ying 
Published: June 2016

Significance
We compared the information provided by whole-exome sequencing (WES) and genome-wide single-nucleotide variant arrays in terms of principal component analysis, homozygosity rate estimation, and linkage analysis using 110 subjects originating from different regions of the world. WES provided an accurate prediction of population substructure using high-quality variants with a minor allele frequency > 2% and reliable estimation of homozygosity rates using runs of homozygosity. Finally, homozygosity mapping in 15 consanguineous families showed that WES led to powerful linkage analyses, particularly in coding regions. Overall, our study shows that WES could be used for several analyses that are very helpful to optimize the search for disease-causing exome variants.
Envelope residue 375 substitutions in simian–human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques
Authors: Li Hui , Wang Shuyi , Kong Rui , Ding Wenge , Lee Fang-Hua , Parker Zahra , Kim Eunlim , Learn Gerald H. , Hahn Paul , Policicchio Ben , Brocca-Cofano Egidio , Deleage Claire , Hao Xingpei , Chuang Gwo-Yu , Gorman Jason , Gardner Matthew , Lewis Mark G. , Hatziioannou Theodora , Santra Sampa , Apetrei Cristian , Pandrea Ivona , Alam S. Munir , Liao Hua-Xin , Shen Xiaoying , Tomaras Georgia D. , Farzan Michael , Chertova Elena , Keele Brandon F. , Estes Jacob D. , Lifson Jeffrey D. , Doms Robert W. , Montefiori David C. , Haynes Barton F. , Sodroski Joseph G. , Kwong Peter D. , Hahn Beatrice H. , Shaw George M. 
Published: June 2016

Significance
Simian–human immunodeficiency viruses (SHIVs) are an invaluable tool for assessing HIV-1 vaccines, developing therapeutic “cure” strategies, and understanding viral immunopathogenesis. However, only limited success has been achieved in creating SHIVs that incorporate HIV-1 envelopes (Envs) that retain the antigenic features of clinically relevant viruses. Here we focus on a critical residue of the CD4-binding region, Env375, which is under strong positive selection across the broad range of primate lentiviruses. We find that genotypic variation of residue 375 allows for the creation of pathogenic SHIVs that retain the antigenicity, tier 2 neutralization sensitivity, and persistence properties characteristic of primary HIV-1 strains. Taken together, our findings suggest a new paradigm for SHIV design and modeling with important applications to HIV-1 vaccine, cure, and pathogenesis research.
The Influence of Agents
Authors: Wallace James D. 
Published: June 2016

… We learn from anatomy, that the immediate object of power in voluntary motion, is not the member itself which is moved, but certain muscles, and nerves, and animal spirits, and, perhaps, something still more minute and more unknown, through which the motion is successively propagated, ere it reach the member itself whose motion is the immediate object of volition. Can there be a more certain proof, that the power, by which the whole operation is performed … is, to the last degree, mysterious and unintelligible?Recent metaphysical theories, which stress the importance of an agent as a sort of cause, raise again the question of where and how in the chain of events involved in voluntary motion the human agent “immediately” exerts his influence. The matter is still every bit as mystifying as Hume suggests. We know that when a human being moves voluntarily, there are events in his central nervous system which are causes of the motion. Of course, nothing whatever need be known about these events in order to move voluntarily. Either human agents produce these events or they do not.
The Concept of Incorrigibility
Authors: Robinson Richard 
Published: June 2016

In the last thirty-five years philosophers have often referred to corrigible and incorrigible statements or judgements. This usage probably began with the Inaugural lecture of the Wykeham Professor of logic at Oxford University on 5 March, 1936, which was called ‘Truth and Corrigibility’ and discussed the theory that ‘all judgements are corrigible'. Price did not say there that he himself invented this usage. On the contrary, he said that “it is maintained by many philosophers that all judgements are corrigible”. But he gave no reference to support this statement; and it seems that in fact only Bradley preceded him in writing of a ‘corrigible statement', and Bradley did so only in a single (though thrice repeated) paragraph, once taken up by Russell. The effective disseminator of the notion was probably Price himself.The Oxford English Dictionary in 1893, when its C volume appeared, knew of no such thing as a corrigible judgement or statement. The possible owners of corrigibility then were things, men, disorders, votes, faults, weaknesses, passions, abuses, dispositions, inclinations, offenders, sinners, and necks. (“Bending down his corrigible neck”, Antony and Cleopatra, 4, 14, 74).
The Causality of God in Spinoza’s Philosophy
Authors: Watt A. J. 
Published: June 2016

Spinoza’s Ethics must contain some of philosophy’s most baffling statements. All things are animate; the order and connection of ideas is the same as the order and connection of things: what would I be committed to in agreeing (or disagreeing) with these doctrines? His austere mode of exposition, sparing of illustrations and discursive explanations, ensures that any answer must be highly speculative.His weakness for dark sayings seems to have communicated itself to some of his best-known commentators. Of course where a philosopher’s thought is itself opaque one would be unreasonable to expect lucidity in a commentator’s exposition of it. However he has been described as holding puzzling, to my mind unintelligible opinions on subjects concerning which, as far as I can see, his own statements more naturally suggest a much clearer and more comprehensible interpretation. There are problems enough in understanding his thought without adding needlessly to the list. I think there has been such an addition in discussion of his doctrines about the causal relationship between God and finite creatures, and this paper is devoted to suggesting another account of his thought on that topic which combines, I think, the advantages of being more intelligible and a more natural construction to place on his own statements, than the set of opinions generally laid at his door.
Carl Hempel: Explanations by Reasons
Authors: Patten Steven C. 
Published: June 2016

Carl Hempel has proposed the following model for explanations by reasons.(R) (i) A was in a situation of type C.(ii) A was a rational agent at the time.(iii) In a situation of type C, any rational agent will do X.(iv) Therefore, A did X.According to Hempel (R) overcomes the shortcomings of alternative accounts of explaining by reasons such as William Dray's model, in that the so-called evaluative principle is replaced by an empirical law. It is William Dray's contention that to understand the action of a rational agent is to see that his action was appropriate in his situation. Following Dray this then means that in explaining such an action one makes use of a normative ‘principle of action', not an empirical law, which has the form ‘when in a situation of type C1… Cn the thing to do is X'.
The Paradox of Omnipotence Revisited
Authors: Cowan J. L. 
Published: June 2016

A. (1) Either God can create a stone which He cannot lift, or He cannot create a stone which He cannot lift.(2) If God can create a stone which He cannot lift, then He is not omnipotent (since He cannot lift the stone in question).(3) If God cannot create a stone which He cannot lift, then He is not omnipotent (since He cannot create the stone in question).(4) Therefore, God is not omnipotent.In a paper published in Analysis I tried to show (a) that any attempt to find something wrong with all arguments of the general form of A above, any attempt to resolve the “paradox,” must fail, (b) that the reason these attempts must fail is that at least some arguments of this form are essentially sound, and (c) that the only thing which makes these arguments seem paradoxical, their conclusion to the effect that God is not omnipotent, is, like at least some versions of the arguments to this conclusion, quite correct.
Kripke on Naming and Necessity
Authors: De Sousa R. B. 
Published: June 2016

Some wag (was it Mark Twain?) reported the following story: Scholars have recently established that the Iliad and the Odyssey were not, after all, written by Homer. They were actually written by another author, of the same name.The majority of current theories of naming and reference, including ones as divergent in other respects as those of Russell and Searle, would rule this story impossible. They would do so on roughly these grounds: the sense and reference (one or the other, or one through the other, depending on the theory) of the name ‘Homer’ is determined, given the absence of other reliable testimony, by the sole description: ‘Author of the Iliad and the Odyssey’. ‘Homer is the author of the Iliad and the Odyssey’ is therefore known a priori, hence necessarily true. There could not be another author of that name and claim to fame.In lectures delivered at Princeton in the Winter of 1970, Saul Kripke offered a lucid alternative to such theories (which I shall lump together under the term ‘descriptivism’).
Physiological Changes and the Emotions
Authors: Lyons William 
Published: June 2016

I want to attempt to analyze a forgotten area in the philosophy of emotions, the relations between physiological changes and the emotions. I want to do this:(1) by first of all briefly setting out some distinctions necessary to the understanding of the position I will be arguing for,(2) then by trying to elucidate what exactly is to be understood by the term ‘physiological change’ in the context of an emotion,(3) by showing that particular physiological changes are not part of the concept of any particular emotion and are only linked causally to the cognitive-appetitive part of an occurrent emotional state (the description of which part, forms the concept of that particular emotion),(4) by showing, however, that the notion of a physiological change is part of the concept of an emotional state,(5) and, finally, by drawing out some consequences of this analysis.
Referring to What Does Not Exist
Authors: Vision Gerald 
Published: June 2016

Under the title of ‘the axiom of existence’, hereafter (AE), John R. Searle has reduced to compact dictum a view to which many philosophers subscribe:(AE) ‘Whatever is referred to must exist’.(A less equivocal, though inelegant formulation would be: ‘It is necessary that whatever is referred to exist at some time or other’.) In this paper I shall offer two major arguments against adopting (AE), at least on certain assumptions. There have been a number of defenses of (AE), among them those arguing that it is fundamental to any systematic philosophy of language or logic. With the exception of discussing some of Searle's remarks in part Ill of this paper I shall not comment on any of these defenses.
The-Meaning-of-a-Word
Authors: Munsat Stanley 
Published: June 2016

In his paper “The Meaning of a Word” J. L. Austin argues that a set of questions and (hence?) a set of answers to these questions is nonsensical. The philosophical claim that a question or answer is nonsense is an important part of the philosopher's stock and trade; for to ask and to propose answers to nonsensical questions is to reveal confusion and the tracking down and unraveling of confusion is one of the valuable contributions that philosophy has to make in the advancement of understanding.At the same time one must not accept too easily the charge that a question or a form of answer to a question is nonsensical, for to do this is to block off a whole avenue of inquiry and therein direct one's efforts away from a route that might yield positive results.
Aquinas on Inner Space
Authors: Centore F. F. 
Published: June 2016

Can one deny the intelligibility of “extramental nonbeing” in pure ontology while affirming its intelligibility in physics? When one sweeps the heavens clean of matter does one also necessarily affirm the existence of absolute nonbeing in those “clean” spaces? Does talking about space necessarily mean talking about nonbeing? How could there possibly be “space” which is not absolute nothingness? How, if at all, can statements about space be reconciled with such self-contradictory statements as “What is not, is“?The purpose of this brief paper is not to argue, within the context of the physical sciences, about whether or not there exist voids or absolutely empty spaces in the universe. Neither is it to discuss the existence or nonexistence of the aether. And although I shall be using texts taken from several famous historical figures, my purpose is not primarily historical.
On Causal Consequences
Authors: Frey R. G. 
Published: June 2016

In his Generalization in Ethics, Marcus Singer distinguishes between individual and collective consequences. According to Singer, the collective consequences of everyone's acting in a certain way is for certain kinds of acts not the sum of—or, more exactly, is greater than the sum of—the individual consequences of each individual act. The point is put more straightforwardly by Sir Roy Harrod:There are certain acts which when performed on n similar occasions have consequences more than n times as great as those resulting from one performance . ... For example, it may well happen that the loss of confidence due to a million lies uttered within certain limits of time and space is much more than a million times as great as the loss due to any one in particular.
Dreaming an Impossible Dream
Authors: Mannison D. S. 
Published: June 2016

Norman Malcolm wrote:That something is implausible or Impossible does not go to show that I did not dream it. In a dream I can do the impossible in every sense of the word.Malcolm nowhere suggests why this remark should be regarded as true. Indeed, many philosophers would regard it is palpably false. After all, it is not at all obvious that one can hope for, intend to do, or believe what is in every sense of the word, impossible. I think, however, that Malcolm's observation is correct; and this paper is devoted to showing why it is correct. In the concluding section I present an account of dreaming that shows why it is that impossible dreams are possible.“What can a person dream?” This is an odd query; and what it might mean to put this question (if, indeed, it is a sensible question) is not at all transparent. It is not like asking what a person might dream, when this is understood as a request for what someone is likely to dream, or what one may reasonably expect someone to dream, say, on the evening of a day in which one had visited a dentist.
The Unmakable-Because-Unliftable Stone
Authors: McLean Murdith 
Published: June 2016

It is customary to dismiss such queries as ‘Can God create a being he cannot control?’ and ‘Can God create a knot he cannot untie?’ with the comment that such questions in fact fail to specify a task for God to perform. The reason given is that omnipotence is included in the idea of God, with the alleged result that such expressions as ‘a being God cannot control’ and ‘a knot God cannot untie’ contain contradictions. J .L. Cowan has argued that this conventional response is mistaken, and subsequently expanded upon this contention in reply to some of its critics. I shall try to show that Cowan's defense of the coherence of expressions like these is mistaken, and with it his conclusion that since an omnipotent God clearly cannot perform such tasks the concept of omnipotence is self-contradictory.Cowan has no quarrel with one assumption of the customary reply. If the specification of a task is self-contradictory, he agrees that the inability of God to perform it is no blemish on his omnipotence.
David Lewis On Convention
Authors: Jamieson Dale 
Published: June 2016

A convention is a regularity in behavior, sustained by a system of preferences and expectations, that has a possible alternative: so claims David Lewis. That it is not, is what I hope to show.In Convention; A Philosophical Study, Lewis gives an analysis of what he hopes is “our common, established concept of convention.” In developing his analysis, Lewis extensively employs the technical vocabulary of game theory. According to Lewis conventions are established by “populations” in order to solve recurring “coordination problems.” Lewis gives eleven examples of “coordination problems” which he claims are solved by convention. One example is the following:Suppose several of us are driving on the same winding two-lane roads. It matters little to anyone whether he drives in the left or the right lane, provided the others do likewise. But if some drive in the left lane and some in the right, everyone is in danger of collision.