bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of primary sclerosing cholangitis in Japan
Authors: Takikawa Hajime
Published: October 2007

At a workshop on primary sclerosing cholangitis (PSC) held during Digestive Disease Week – Japan 2003, 388 PSC cases in Japan were analyzed. Two peaks in the age distribution were also observed in this survey. Jaundice and itching, major symptoms in PSC patients included in the diagnostic criteria, were observed in only 28% and 16%, respectively. Alkaline phosphatase levels were less than twofold of the upper limit of the normal range in 35%. In this regard, the diagnostic criteria in 2003 from the Mayo Clinic, including cholestatic symptoms and two‐ to threefold increases in serum alkaline phosphatase, should be modified in Japan. Inflammatory bowel diseases were complicated in 37%, and autoimmune pancreatitis (AIP) in 7.2%. PSC cases with inflammatory bowel diseases were younger than the average, creating the firstpeak in age distribution, and have similar characteristics compared to patients with PSC in foreign countries. In addition, even after the exclusion of cases of sclerosing cholangitis complicated with AIP, the second peak in the age distribution was clearly evident. Recently, a concept of immunoglobulin G4‐related sclerosing cholangitis has been postulated, which has a similar pathogenesis to AIP but without apparent pancreatic lesions. PSC patients without apparent involvement of the pancreas may be present in older patients and seem to be specific to Japan.
Predictive role of anti‐gp210 and anticentromere antibodies in long‐term outcome of primary biliary cirrhosis
Authors: Nakamura Minoru , Komori Atsumasa , Ito Masahiro , Kondo Hisayoshi , Aiba Yoshihiro , Migita Kiyoshi , Nagaoka Shinya , Ohata Kazuyuki , Yano Koji , Abiru Seigo , Daikoku Manabu , Yatsuhashi Hiroshi , Shimoda Shinji , Ishibashi Hiromi
Published: October 2007

Because some of the autoreactive T‐cell clones specific for human PDC‐E2 cross‐react to mimicry peptides having an EIExDK motif derived from nuclear antigens such as human gp210 and sp100, we studied the clinical significance of antinuclear antibodies (ANA) in primary biliary cirrhosis (PBC) patients registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). We found that there are two different types of progression in PBC; one is a hepatic failure‐type progression which is represented by positive anti‐gp210 antibodies and the other is a portalhypertension‐type progression which is represented by positive anticentromere antibodies. We discuss the predictive role of these ANA in the long‐term outcome of PBC and the mechanisms by which two different PBC progression types occur based on molecular mimicry and aberrant expression of nuclear antigens.
Long‐term clinical outcome of living‐donor liver transplantation for primary biliary cirrhosis
Authors: Hashimoto Etsuko , Taniai Makiko , Yatsuji Satoru , Tokushige Katsutoshi , Shiratori Keiko , Yamamoto Masakazu , Fuchinoue Syouhei
Published: October 2007

Aim:  We described the recurrence of primary biliary cirrhosis (PBC) after living donor liver transplantation (LDLT) (Liver Transplantation, 7, 2001: 588). However, since the follow‐up period in that study was insufficiently long (median 35.5 months), we performed a long‐term study to further characterize recurrence of PBC after LDLT.

Patients:  From 1991 to 2006, 15 patients with end‐stage PBC underwent LDLT at Tokyo Women's Medical University. Of these patients, we studied 8 PBC patients (age 29 to 51 years, all females) who survived LDLT for more than 5 years. The follow‐up period for these patients ranged form 68 to 120 months. Immunosuppression was maintained with tacrolimus and prednisone. Laboratory examinations performed in every patient and donor before LDLT included routine biochemical studies, antimitochondrial antibody (AMA) by immunofluorescence (IF), anti‐M2 by enzyme‐linked immunosorbent assay as well as antinuclear antibody (ANA) by IF, and immunoglobulin. After LDLT, the same laboratory examinations were performed in patients every 6 months. Liver biopsy was performed when patients exhibited clinical or biochemical signs of graft dysfunction. In addition, protocol biopsy was performed every 1 to 2 years after LDLT.

Results:  At the time of LDLT, all patients had end‐stage cholestatic liver failure. Seven patients were positive for AMAand anti‐M2 while 1 patient was negative for these markers but strongly positive for ANA. Donors were blood relatives in 6 cases, and 2 donors who were not blood relatives still exhibited multiple HLA matches with the recipients. At the end of the study in May 2006, all patients were doing well. On laboratory examination, mild abnormal liver function test results were found in 4 patients: 3 were probably due to recurrence of PBC, 1 resulted from nonalcoholic steatohepatitis. Comparison of the AMA titer between before LDLT and the most recent follow‐up visit showed an increase in three patients, a decrease in two patients and no change in three patients. In contrast, the ANA titer increased in five patients. Histologically, strong evidence of recurrent PBC was found in 4 patients, and findings compatible with PBC were present in 2 additional patients.

Conclusions:  Although the number of our patients is small, our findings confirm that PBC can recur at high frequency after LDLT. However, this complication has not developed to advanced stages and has not caused appreciable symptoms in our patients, all of whom have a good quality of life.
Biliary innate immunity and cholangiopathy
Authors: Harada Kenichi , Nakanuma Yasuni
Published: October 2007

The intrahepatic biliary tree is a conduit of bile which contains pathogen‐associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) originated from intestinal flora. Human biliary epithelial cells (BEC) express toll‐like receptors (TLR) and intracellular adaptor molecules and secrete antibiotic peptides and (pro)inflammatory cytokines via the activation of nuclear transcription factors. However, although human bile contains several PAMPs in normal as well as diseased livers, PAMPs physiologically do not elicit an inflammatory response in the biliary tree, suggesting that tolerance against commensal PAMPs including LPS (endotoxin tolerance) is important in maintaining the homeostasis of biliary innate immunity. Negative regulators of intracellular TLR signalings, peroxisome proliferator activating receptor‐γ (PPAR‐γ) and IRAK‐M, are associated with the endotoxin tolerance in BEC. In vivo, PPAR‐γ and IRAK‐M are ubiquitously expressed in intrahepatic biliary epithelium, while the expression of PPAR‐γ is reduced in damaged bile ducts of primary biliary cirrhosis (PBC). In addition to antibiotic peptides, several cytokines andchemokines are also secreted from BEC as an innate immune response and these humoral components participate in attracting immunocytes and modulating peribiliary cytokine milieu. BEC have receptors for several cytokines and the expression of TLR in BEC is affected by cytokines, suggesting that biliary innate immunity is regulated by an acquired immunity. A T‐helper (Th)1‐type cytokine, interferon‐γ, downregulates PPAR‐γ and upregulates TLR, and consequently increases the susceptibility of biliary innate immunity. Because periductal cytokine milieu in PBC is Th1‐dominant, the increased susceptibility to PAMPs may be associated with the development of cholangiopathy in PBC. Biliary innate immunity is speculated to be associated with the pathogenesis of biliary diseases as well as the defense against biliary microbial infection.
Autoimmune hepatitis in childhood
Authors: Fujisawa Tomoo , Sogo Tsuyoshi , Komatsu Haruki , Inui Ayano
Published: October 2007

Autoimmune hepatitis (AIH) is a generally progressive inflammatory liver disease of unknown etiology that occurs in adults and children. Although the peak age of incidence is in prepubertal girls, AIH has been diagnosed as early 6 months of age. Two types of AIH are recognized according to the nature of the autoantibody detected in children at the time of diagnosis. The diagnosis of AIH is based on histological abnormalities, characteristic clinical and biochemical findings, and abnormal levels of serum globulin due almost exclusively to markedly increased immunoglobulin G including various autoantibodies. A genetic predisposition is suggested by the increase frequency of human leukocyte antigen (HLA) haplotypes HLA‐B8/DR3, and allotypes DR3 and DR4. However, the incidence of these HLA types is different in each country.Proposed triggers of AIH that may initiate the inflammatory process include some viral infections and some drugs. There is much information about adults with AIH, however, little information on AIH in children, especially in Japanese children. To clarify the clinicohistological features of AIH in Japanese children, we analyzed the clinical, pathological features and response to treatment in 12 Japanese children with AIH. Furthermore, we discuss several problems for diagnosis and treatment for AIH in children.
Roles of the novel interleukin‐12‐associated cytokine, interleukin‐23, in the regulation of T‐cell‐mediated immunity
Authors: Matsui Masanori
Published: October 2007

Interleukin (IL)‐12 is a heterodimeric proinflammatory cytokine formed by a 35‐kDa light chain (p35) and a 40‐kDa heavy chain (p40). This cytokine is a key regulator of cell‐mediated immunity, and therefore should have therapeutic potential in infectious diseases and tumors. Recently, a novel IL‐12‐associated cytokine, IL‐23 has been discovered. IL‐23 is also a heterodimer that consists of the p40 subunit of IL‐12 and a novel subunit, p19. Several studies have shown that IL‐23 possesses immunoadjuvant activity against tumor and infectious diseases as well as IL‐12. On the other hand, there is increasing evidence that IL‐12 and IL‐23 have discrete roles in the regulation of T‐cell‐mediated immunity despite their structural similarities. IL‐12 leads to the development ofinterferon‐γ‐producing T‐helper type 1 (Th1) cells, whereas IL‐23 amplifies and stabilizes a new CD4+ T‐cell subset, Th17 producing IL‐17. The IL‐23/Th17 axis rather than the IL‐12/Th1 axis contributes to several immune‐mediated inflammatory autoimmune diseases. Furthermore, IL‐23/IL‐17 promotes tumor incidence and growth. Therefore, IL‐23 and Th17 are attracting considerable attention at present. Taken together, these findings suggest that IL‐23 may be an immunoadjuvant against infectious diseases and tumors, and a viable target for the treatment of inflammatory diseases.
Engineering immune therapy against hepatitis B virus
Authors: Akbar Fazle , Yoshida Osamu , Abe Masanori , Hiasa Yoichi , Onji Morikazu
Published: October 2007

Approximately 350–400 million people worldwide are chronically infected with the hepatitis B virus (HBV). These individuals harbor the virus for their whole life and they transmit the virus to uninfected individuals. In addition, considerable numbers of chronic HBV carriers develop progressive liver diseases like chronic hepatitis B, liver cirrhosis and hepatocellular carcinoma. At present, antiviral agents like type‐1 interferons, lamivudine, adefovir and entacavir are used to treat a selected population of chronic HBV carriers. These antiviral treatments are not satisfactory in that they are unable to eradicate HBV, only partially efficient in less than 30% subjects, expensive, can have debilitating side‐effects and require constant monitoring. In addition, once treatment is stopped, the virus and clinical conditions return in many patients. Recent advancements in cellular and molecular biology indicate that the host's immune responses to HBV play cardinal roles during acquisition, pathogenesis, progression, and complications of chronic HBV infection. Immune responses are also important in the context of antiviraltherapy and clinical recovery. This explains why the efficacy of antiviral drugs is limited even in some selected patients with chronic HBV infection. Various published work now state that HBV‐specific immunity may be beneficial for patients with chronic HBV infection and non‐HBV‐specific immunity may be related to flare up of liver diseases. Accordingly, a new few field of immunological research and clinical application of prophylactic vaccines (vaccine therapy) has been started in chronic HBV carriers. Vaccine therapy has inspired optimism as a new therapeutic approach, but it is unlikely that the present regimen of vaccine therapy will stand the test of time. Based on present understandings about vaccine/host interactions, we provide herein an outline for engineering more potent regimen of HBV‐specific immune therapy against HBV.
Immune pathogenesis of sclerosing cholangitis in biliary atresia
Authors: Matsui Akira
Published: October 2007

Biliary atresia (BA) is the most frequent single life‐threatening hepatic disorder in early childhood in Japan, Europe and North America. It affects one in 9000 live‐born infants in our country. BA is characterized by complete inability to excrete bile associated with obstruction, destruction or absence of the extrahepatic bile ducts. Pathologic study of tissues removed from the porta hepatis and of the proximal extrahepatic bile ducts suggests that BA in the vast majority of infants results from a sclerosing, inflammatory lesion initiated in ductular tissues. Kasai procedure (KP) is in the first line of treatment for BA infants in the developed countries all over the world. In KP, bile duct remnants or fibrous tissues in front of the hepatic artery are dissected and a Roux‐en ‐Y anastomosis is fashioned between the area of the porta hepatic and the jejunum. KP has provided opportunities to survive years for some infants with BA with reasonable quality of life. However in BA, bile duct injury and sclerosing inflammation is ongoing even after apparently successful KP. A 10‐year survival rates with native liver is still 53% in 1999 according to multi‐centre analysis in Japan. BA is still the leading cause of paediatric liver transplantation. Poor prognosis of BA is, of course, due to unknown aetiology. Potential aetiologies for more common perinatal form of BA include viral infections, immune‐mediated injuries and autoimmune disease involving biliary systems. Details of each theory including our updated findings will be reviewed and discussed.
Diagnostic criteria for autoimmune hepatitis
Authors: Lohse Ansgar W. , Hennes Elke
Published: October 2007

Diagnosis of Autoimmune Hepatitis (AIH) often represents a clinical challenge. The clinical spectrum of disease is quite heterogeneous. AIH can affect patients of all age groups, both sexes, and any race and region. The course may range from subclinical and very mild to acute attacks of hepatitis up to fulminant hepatic failure. Other patients present very late with the picture of cryptogenic cirrhosis. Laboratory features may also differ. Autoantibodies vary, and some patients do not display any autoantibodies at the time of clinical presentation. SLA/LP‐autoantibodies are the only antibodies specific for the diagnosis of AIH, but they are only present in about 20% of cases. The most common feature in all patients with AIH is an elevation of IgG levels, usually a selective or highly preferential elevation of IgG in comparison to IgA and IgM. However, in some patients the relative increase in IgG levels may be within the normal limits, because the normal range is quite wide. The diagnosis of AIH should not be made without a liver biopsy showing inflammatory hepatitis. Histology mayshow typical features such as enrichment of plasma cells and piecemeal necroses, but distinction from other inflammatory liver disease including allergic drug reactions may be difficult.

The International Autoimmune Hepatitis Group has tried to define diagnostic criteria on the basis of consensus discussions. These were revised in 1999 in the light of some clinical studies. However, the criteria are complicated, and not useful in everyday practise. In addition, the criteria were only designed as a scientific tool in order to create comparable groups in publication from different centres. Therefore, the International Autoimmune Hepatitis Group has re‐approached the problem with the aim of defining simplified criteria for everyday use. With the help of various specialised centres in the world we evaluated a number of hypothetical criteria, and found out, that four criteria with two categories are sufficient to either make or exclude the diagnosis of AIH with positive and negative predictive values well over 90%:

1 point
2 points

1. IgG
>16 g/l
>18 g/l

2. ANA, SMA
>1 : 40
>1 : 80 or SLA/LP+

3. Histology
compatible with
typical for AIH

4. Viral markers

negative

A value of 6 or more points makes the diagnosis of AIH very likely, a value of 7 or 8 points demonstrates definite AIH. The simplified criteria should help in the diagnosis of AIH in patients with liver disease, and they seem to be valid world‐wide. Prospective data are needed to validate these criteria further.
Spinoza’s Arguments for the Existence of God*
Authors: LIN MARTIN
Published: October 2007

It is often thought that, although Spinoza develops a bold and distinctive conception of God (the unique substance, or Natura Naturans, in which all else inheres and which possesses infinitely many attributes, including extension), the arguments that he offers which purport to prove God’s existence contribute nothing new to natural theology. Rather, he is seen as just another participant in the seventeenth century revival of the ontological argument initiated by Descartes and taken up by Malebranche and Leibniz among others. That this is the case is both puzzling and unfortunate. It is puzzling because although Spinoza does offer an ontological proof for the existence of God, he also offers three other non‐ontological proofs. It is unfortunate because these other non‐ontological proofs are both more convincing and more interesting than his ontological proof. In this paper, I offer reconstructions and assessments of all of Spinoza’s arguments and argue that Spinoza’s metaphysical rationalism and his commitment to something like a Principle of Sufficient Reason are the driving force behind Spinoza’s non‐ontological arguments.
Consumers Need Information: Supplementing Teleosemantics with an Input Condition
Authors: SHEA NICHOLAS
Published: October 2007

The success of a piece of behaviour is often explained by its being caused by a true representation (similarly, failure falsity). In some simple organisms, success is just survival and reproduction. Scientists explain why a piece of behaviour helped the organism to survive and reproduce by adverting to the behaviour’s having been caused by a true representation. That usage should, if possible, be vindicated by an adequate naturalistic theory of content. Teleosemantics cannot do so, when it is applied to simple representing systems (Godfrey‐Smith 1996). Here it is argued that the teleosemantic approach to content should therefore be modified, not abandoned, at least for simple representing systems. The new ‘infotel‐semantics’ adds an input condition to the output condition offered by teleosemantics, recognising that it is constitutive of content in a simple representing system that the tokening of a representation should correlate probabilistically with the obtaining of its specific evolutionary success condition.
Epistemic Instrumentalism and Reasons for Belief: A Reply to Tom Kelly’s “Epistemic Rationality as Instrumental Rationality: A Critique”
Authors: LEITE ADAM
Published: October 2007

Tom Kelly argues that instrumentalist accounts of epistemic rationality fail because what a person has reason to believe does not depend upon the content of his or her goals. However, his argument fails to distinguish questions about what the evidence supports from questions about what a person ought to believe. Once these are distinguished, the instrumentalist can avoid Kelly’s objections. The paper concludes by sketching what I take to be the most defensible version of the instrumentalist view.
Do shark declines create fear‐released systems?
Authors: Frid Alejandro , G. Baker Gregory , M. Dill Lawrence
Published: October 2007

We illustrate the theoretical plausibility that fishery removal of sharks can indirectly alter predation pressure on different fish species via the behavioural responses of mesoconsumers released from predator intimidation. Our dynamic state variable model of foraging decisions by harbour seals, a mesopredator, predicted indirect effects of the removal of Pacific sleeper sharks on two species consumed by seals, Pacific herring and walleye pollock, as mediated by seal behaviour. Herring, a fatty fish, form near‐surface aggregations that often are ephemeral and widely dispersed. Pollock are found in the deeper strata preferred by sharks and have lower energy density than herring, but also are larger and their more continuous distribution potentially makes them the more predictable resource for seals. During simulations, predation risk from sharks produced an asymmetric trophic cascade mediated by the seal's underutilisation of deeper, riskier strata. Risk management by seals reduced mortality on pollock, which required riskier access in deep strata, while increasing mortality on herring, which could be accessed with less risk in shallow strata. This effect, however, attenuated if herring were scarcer and seal energy state was poor. During shark removal scenarios, seals shifted to deeper strata, increasing pollock consumption and substantially decreasing use of herring; the proportional change was greatest if seals were in good energy state. Prior studies have addressed how shark declines might affect community structure through density responses by species consumed by sharks; earlier models incorporating antipredator behaviour of the mesopredator (i.e. Ecosim/Ecospace) allow for activity reduction but not for the spatial shifts that altered the asymmetric trophic cascade in our simulations. Our results suggest that shark declines might have stronger ecological consequences than previously recognised if we account for spatial and diet shifts by mesoconsumers released from shark intimidation.
Egg coloration and selection for crypsis in open‐nesting blackbirds
Authors: Westmoreland David , A. Kiltie Richard
Published: October 2007

High variation in egg coloration among birds has traditionally been explained as adaptation for camouflage. We tested this hypothesis by conducting reciprocal clutch exchanges (n=301) among Brewer's blackbirds Euphagous cyanocephalus, red‐winged blackbirds Agelaius phoeniceus, and yellow‐headed blackbirds Xanthocephalus xanthocephalus. We predicted that clutches placed against their natural nest backgrounds would have higher survival rates than heterospecific clutches. Intraspecific clutch exchanges were used as a control. Clutch survival was monitored for a 9‐d period at all nests, during which time incubation rhythm and nest defense were quantified. Intraspecific clutch exchanges did not influence incubation or nest defense. For two of the species, intraspecific clutch exchanges did not influence clutch survival; in red‐winged blackbirds, however, intraspecifically exchanged clutches had somewhat depressed survival curves relative to control clutches (P=0.08). The effect of interspecific clutch exchanges differed by host species. In Brewer's nests, eggs of the yellow‐headed blackbird had lower survival than Brewer's eggs (P=0.02), but survival of red‐winged blackbird eggs did not differ from Brewer's eggs (P=0.50). In nests of red‐winged blackbirds, all three clutch types had approximately equal survival. In yellow‐headed blackbird nests, eggs of the red‐winged blackbird had lower survival than yellow‐headed blackbird eggs (P=0.06), and survival of Brewer's eggs did not differ from yellow‐headed blackbird eggs (P=0.31). These findings support a role for egg coloration as camouflage in two of the three species studied.
The bug: A temperature-controlled experiment on a protoboard
Authors: Dixon Paul K.
Published: October 2007

We describe a temperature-controlled experiment suitable for undergraduate laboratory instruction in computer-based data acquisition and control. The experimental system, which we call “the bug,” is a simple and inexpensive three-component system made up of a thermistor, a heater resistor, and a ceramic capacitor bonded together. The thermistor and heater resistor combine to form the temperature measurement and control system. The ceramic ferroelectric capacitor is the component under study; the overall objective of the experiment is to measure its capacitance as a function of temperature. This simple and inexpensive system allows us to explore a significant range of computer-based data acquisition and control topics. Over a three-week period, our students develop a fully-automated, temperature-controlled experiment much like they would in a condensed-matter research lab. The difference is that the experiment costs just a few dollars to build and fits easily on an electronics prototyping breadboard.
Temperature dependence of the capacitance of a ferroelectric material
Authors: Bechhoefer John , Deng Yi , Zylberberg Joel , Lei Chao , Ye Zuo-Guang
Published: October 2007

We present an alternate version of the undergraduate laboratory experiment developed by Dixon [Am. J. Phys. 75, 1038–1045 (2007)] that is suitable for second-year students. We study the temperature variation of the capacitance of a ferroelectric ceramic derived from barium titanate, the Ba(Ti0.9Sn0.1)O3 solid solution. The ratio of tin to titanium is chosen to provide a convenient Curie temperature near 50°C. Using careful temperature control and real-time capacitance measurements, we track the time evolution of the capacitance in response to temperature changes at 5Hz for runs that last up to a day. At temperatures well above the Curie temperature, TC, the capacitance relaxation is well-described by a single exponential decay. Near TC, the relaxation is linear in the logarithm of time over more than three decades. For T>TC, the permittivity deviates from the Curie–Weiss law and follows another phenomenological form commonly used to describe relaxor perovskite-ceramic capacitors.
Knowledge organization and activation in physics problem solving
Authors: Sabella Mel S. , Redish Edward F.
Published: October 2007

Conceptual knowledge is only one aspect of a good knowledge structure: how and when knowledge is activated and used are also important. We explore knowledge organization in the context of the resources model of student thinking via observations of student problem-solving behavior on a mechanics task that integrates the concepts of force, motion, and energy. We document that both introductory and advanced students may have knowledge structures with local coherences that may inhibit their access to additional useful knowledge. These results suggest that instructors and researchers need to pay increased attention to how and when students use what they know as well as to what they know.
Young’s double-slit interference experiment with electrons
Authors: Frabboni S. , Gazzadi G. C. , Pozzi G.
Published: October 2007

In this short Note we report a method for producing samples containing two nano-sized slits suitable for demonstrating to undergraduate and graduate students the double-slit electron interference experiment in a conventional transmission electron microscope.
On some applications of Galilean electrodynamics of moving bodies
Authors: de Montigny M. , Rousseaux G.
Published: October 2007

We discuss the seminal article by Le Bellac and Lévy-Leblond in which they identified two Galilean limits (called “electric” and “magnetic” limits) of electromagnetism and their implications. Recent work has shed new light on the choice of gauge conditions in classical electromagnetism. We show that the recourse to potentials is compelling in order to demonstrate the existence of both (electric and magnetic) limits. We revisit some nonrelativistic systems and related experiments, in the light of these limits, in quantum mechanics, superconductivity, and the electrodynamics of continuous media. Much of the current technology where waves are not taken into account can be described in a coherent fashion by the two limits of Galilean electromagnetism instead of an inconsistent mixture of these limits.
The
Chlamydomonas
Genome Reveals the Evolution of Key Animal and Plant Functions
Authors: Merchant Sabeeha S. , Prochnik Simon E. , Vallon Olivier , Harris Elizabeth H. , Karpowicz Steven J. , Witman George B. , Terry Astrid , Salamov Asaf , Fritz-Laylin Lillian K. , Maréchal-Drouard Laurence , Marshall Wallace F. , Qu Liang-Hu , Nelson David R. , Sanderfoot Anton A. , Spalding Martin H. , Kapitonov Vladimir V. , Ren Qinghu , Ferris Patrick , Lindquist Erika , Shapiro Harris , Lucas Susan M. , Grimwood Jane , Schmutz Jeremy , Cardol Pierre , Cerutti Heriberto , Chanfreau Guillaume , Chen Chun-Long , Cognat Valérie , Croft Martin T. , Dent Rachel , Dutcher Susan , Fernández Emilio , Fukuzawa Hideya , González-Ballester David , González-Halphen Diego , Hallmann Armin , Hanikenne Marc , Hippler Michael , Inwood William , Jabbari Kamel , Kalanon Ming , Kuras Richard , Lefebvre Paul A. , Lemaire Stéphane D. , Lobanov Alexey V. , Lohr Martin , Manuell Andrea , Meier Iris , Mets Laurens , Mittag Maria , Mittelmeier Telsa , Moroney James V. , Moseley Jeffrey , Napoli Carolyn , Nedelcu Aurora M. , Niyogi Krishna , Novoselov Sergey V. , Paulsen Ian T. , Pazour Greg , Purton Saul , Ral Jean-Philippe , Riaño-Pachón Diego Mauricio , Riekhof Wayne , Rymarquis Linda , Schroda Michael , Stern David , Umen James , Willows Robert , Wilson Nedra , Zimmer Sara Lana , Allmer Jens , Balk Janneke , Bisova Katerina , Chen Chong-Jian , Elias Marek , Gendler Karla , Hauser Charles , Lamb Mary Rose , Ledford Heidi , Long Joanne C. , Minagawa Jun , Page M. Dudley , Pan Junmin , Pootakham Wirulda , Roje Sanja , Rose Annkatrin , Stahlberg Eric , Terauchi Aimee M. , Yang Pinfen , Ball Steven , Bowler Chris , Dieckmann Carol L. , Gladyshev Vadim N. , Green Pamela , Jorgensen Richard , Mayfield Stephen , Mueller-Roeber Bernd , Rajamani Sathish , Sayre Richard T. , Brokstein Peter , Dubchak Inna , Goodstein David , Hornick Leila , Huang Y. Wayne , Jhaveri Jinal , Luo Yigong , Martínez Diego , Ngau Wing Chi Abby , Otillar Bobby , Poliakov Alexander , Porter Aaron , Szajkowski Lukasz , Werner Gregory , Zhou Kemin , Grigoriev Igor V. , Rokhsar Daniel S. , Grossman Arthur R.
Published: October 2007

Chlamydomonas reinhardtii
is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of
Chlamydomonas
and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the
Chlamydomonas
genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
Dislocation Avalanches, Strain Bursts, and the Problem of Plastic Forming at the Micrometer Scale
Authors: Csikor Ferenc F. , Motz Christian , Weygand Daniel , Zaiser Michael , Zapperi Stefano
Published: October 2007

Under stress, many crystalline materials exhibit irreversible plastic deformation caused by the motion of lattice dislocations. In plastically deformed microcrystals, internal dislocation avalanches lead to jumps in the stress-strain curves (strain bursts), whereas in macroscopic samples plasticity appears as a smooth process. By combining three-dimensional simulations of the dynamics of interacting dislocations with statistical analysis of the corresponding deformation behavior, we determined the distribution of strain changes during dislocation avalanches and established its dependence on microcrystal size. Our results suggest that for sample dimensions on the micrometer and submicrometer scale, large strain fluctuations may make it difficult to control the resulting shape in a plastic-forming process.
New Worlds on the Horizon: Earth-Sized Planets Close to Other Stars
Authors: Gaidos Eric , Haghighipour Nader , Agol Eric , Latham David , Raymond Sean , Rayner John
Published: October 2007

The search for habitable planets like Earth around other stars fulfills an ancient imperative to understand our origins and place in the cosmos. The past decade has seen the discovery of hundreds of planets, but nearly all are gas giants like Jupiter and Saturn. Recent advances in instrumentation and new missions are extending searches to planets the size of Earth but closer to their host stars. There are several possible ways such planets could form, and future observations will soon test those theories. Many of these planets we discover may be quite unlike Earth in their surface temperature and composition, but their study will nonetheless inform us about the process of planet formation and the frequency of Earth-like planets around other stars.
Functional Divergence of Former Alleles in an Ancient Asexual Invertebrate
Authors: Pouchkina-Stantcheva Natalia N. , McGee Brian M. , Boschetti Chiara , Tolleter Dimitri , Chakrabortee Sohini , Popova Antoaneta V. , Meersman Filip , Macherel David , Hincha Dirk K. , Tunnacliffe Alan
Published: October 2007

Theory suggests it should be difficult for asexual organisms to adapt to a changing environment because genetic diversity can only arise from mutations accumulating within direct antecedents and not through sexual exchange. In an asexual microinvertebrate, the bdelloid rotifer, we have observed a mechanism by which such organisms could acquire the diversity needed for adaptation. Gene copies most likely representing former alleles have diverged in function so that the proteins they encode play complementary roles in survival of dry conditions. One protein prevents desiccation-sensitive enzymes from aggregating during drying, whereas its counterpart does not have this activity, but is able to associate with phospholipid bilayers and is potentially involved in maintenance of membrane integrity. The functional divergence of former alleles observed here suggests that adoption of asexual reproduction could itself be an evolutionary mechanism for the generation of diversity.
Microfluidic Adhesion Induced by Subsurface Microstructures
Authors: Majumder Abhijit , Ghatak Animangsu , Sharma Ashutosh
Published: October 2007

Natural adhesives in the feet of different arthropods and vertebrates show strong adhesion as well as excellent reusability. Whereas the hierarchical structures on the surface are known to have a substantial effect on adhesion, the role of subsurface structures such as the network of microchannels has not been studied. Inspired by these bioadhesives, we generated elastomeric layers with embedded air- or oil-filled microchannels. These adhesives showed remarkable enhancement of adhesion (∼30 times), which results from the crack-arresting properties of the microchannels, together with the surface stresses caused by the capillary force. The importance of the thickness of the adhesive layer, channel diameter, interchannel spacing, and vertical position within the adhesive has been examined for developing an optimal design of this microfluidic adhesive.
Fluorescence-Force Spectroscopy Maps Two-Dimensional Reaction Landscape of the Holliday Junction
Authors: Hohng Sungchul , Zhou Ruobo , Nahas Michelle K. , Yu Jin , Schulten Klaus , Lilley David M. J. , Ha Taekjip
Published: October 2007

Despite the recent advances in single-molecule manipulation techniques, purely mechanical approaches cannot detect subtle conformational changes in the biologically important regime of weak forces. We developed a hybrid scheme combining force and fluorescence that allowed us to examine the effect of subpiconewton forces on the nanometer scale motion of the Holliday junction (HJ) at 100-hertz bandwidth. The HJ is an exquisitely sensitive force sensor whose force response is amplified with an increase in its arm lengths, demonstrating a lever-arm effect at the nanometer-length scale. Mechanical interrogation of the HJ in three different directions helped elucidate the structures of the transient species populated during its conformational changes. This method of mapping two-dimensional reaction landscapes at low forces is readily applicable to other nucleic acid systems and their interactions with proteins and enzymes.
PKA Type IIα Holoenzyme Reveals a Combinatorial Strategy for Isoform Diversity
Authors: Wu Jian , Brown Simon H. J. , von Daake Sventja , Taylor Susan S.
Published: October 2007

The catalytic (C) subunit of cyclic adenosine monophosphate (cAMP)–dependent protein kinase (PKA) is inhibited by two classes of regulatory subunits, RI and RII. The RII subunits are substrates as well as inhibitors and do not require adenosine triphosphate (ATP) to form holoenzyme, which distinguishes them from RI subunits. To understand the molecular basis for isoform diversity, we solved the crystal structure of an RIIα holoenzyme and compared it to the RIα holoenzyme. Unphosphorylated RIIα(90-400), a deletion mutant, undergoes major conformational changes as both of the cAMP-binding domains wrap around the C subunit's large lobe. The hallmark of this conformational reorganization is the helix switch in domain A. The C subunit is in an open conformation, and its carboxyl-terminal tail is disordered. This structure demonstrates the conserved and isoform-specific features of RI and RII and the importance of ATP, and also provides a new paradigm for designing isoform-specific activators or antagonists for PKA.
Jupiter Cloud Composition, Stratification, Convection, and Wave Motion: A View from New Horizons
Authors: Reuter D. C. , Simon-Miller A. A. , Lunsford A. , Baines K. H. , Cheng A. F. , Jennings D. E. , Olkin C. B. , Spencer J. R. , Stern S. A. , Weaver H. A. , Young L. A.
Published: October 2007

Several observations of Jupiter's atmosphere made by instruments on the New Horizons spacecraft have implications for the stability and dynamics of Jupiter's weather layer. Mesoscale waves, first seen by Voyager, have been observed at a spatial resolution of 11 to 45 kilometers. These waves have a 300-kilometer wavelength and phase velocities greater than the local zonal flow by 100 meters per second, much higher than predicted by models. Additionally, infrared spectral measurements over five successive Jupiter rotations at spatial resolutions of 200 to 140 kilometers have shown the development of transient ammonia ice clouds (lifetimes of 40 hours or less) in regions of strong atmospheric upwelling. Both of these phenomena serve as probes of atmospheric dynamics below the visible cloud tops.
Io Volcanism Seen by New Horizons: A Major Eruption of the Tvashtar Volcano
Authors: Spencer J. R. , Stern S. A. , Cheng A. F. , Weaver H. A. , Reuter D. C. , Retherford K. , Lunsford A. , Moore J. M. , Abramov O. , Lopes R. M. C. , Perry J. E. , Kamp L. , Showalter M. , Jessup K. L. , Marchis F. , Schenk P. M. , Dumas C.
Published: October 2007

Jupiter's moon Io is known to host active volcanoes. In February and March 2007, the New Horizons spacecraft obtained a global snapshot of Io's volcanism. A 350-kilometer-high volcanic plume was seen to emanate from the Tvashtar volcano (62Â°N, 122Â°W), and its motion was observed. The plume's morphology and dynamics support nonballistic models of large Io plumes and also suggest that most visible plume particles condensed within the plume rather than being ejected from the source. In images taken in Jupiter eclipse, nonthermal visible-wavelength emission was seen from individual volcanoes near Io's sub-Jupiter and anti-Jupiter points. Near-infrared emission from the brightest volcanoes indicates minimum magma temperatures in the 1150- to 1335-kelvin range, consistent with basaltic composition.
New Horizons Mapping of Europa and Ganymede
Authors: Grundy W. M. , Buratti B. J. , Cheng A. F. , Emery J. P. , Lunsford A. , McKinnon W. B. , Moore J. M. , Newman S. F. , Olkin C. B. , Reuter D. C. , Schenk P. M. , Spencer J. R. , Stern S. A. , Throop H. B. , Weaver H. A.
Published: October 2007

The New Horizons spacecraft observed Jupiter's icy satellites Europa and Ganymede during its flyby in February and March 2007 at visible and infrared wavelengths. Infrared spectral images map H
2
O ice absorption and hydrated contaminants, bolstering the case for an exogenous source of Europa's ânon-iceâ surface material and filling large gaps in compositional maps of Ganymede's Jupiter-facing hemisphere. Visual wavelength images of Europa extend knowledge of its global pattern of arcuate troughs and show that its surface scatters light more isotropically than other icy satellites.
Clump Detections and Limits on Moons in Jupiter's Ring System
Authors: Showalter Mark R. , Cheng Andrew F. , Weaver Harold A. , Stern S. Alan , Spencer John R. , Throop Henry B. , Birath Emma M. , Rose Debi , Moore Jeffrey M.
Published: October 2007

The dusty jovian ring system must be replenished continuously from embedded source bodies. The New Horizons spacecraft has performed a comprehensive search for kilometer-sized moons within the system, which might have revealed the larger members of this population. No new moons were found, however, indicating a sharp cutoff in the population of jovian bodies smaller than 8-kilometer-radius Adrastea. However, the search revealed two families of clumps in the main ring: one close pair and one cluster of three to five. All orbit within a brighter ringlet just interior to Adrastea. Their properties are very different from those of the few other clumpy rings known; the origin and nonrandom distribution of these features remain unexplained, but resonant confinement by Metis may play a role.
Polar Lightning and Decadal-Scale Cloud Variability on Jupiter
Authors: Baines Kevin H. , Simon-Miller Amy A. , Orton Glenn S. , Weaver Harold A. , Lunsford Allen , Momary Thomas W. , Spencer John , Cheng Andrew F. , Reuter Dennis C. , Jennings Donald E. , Gladstone G. R. , Moore Jeffrey , Stern S. Alan , Young Leslie A. , Throop Henry , Yanamandra-Fisher Padma , Fisher Brendan M. , Hora Joseph , Ressler Michael E.
Published: October 2007

Although lightning has been seen on other planets, including Jupiter, polar lightning has been known only on Earth. Optical observations from the New Horizons spacecraft have identified lightning at high latitudes above Jupiter up to 80°N and 74°S. Lightning rates and optical powers were similar at each pole, and the mean optical flux is comparable to that at nonpolar latitudes, which is consistent with the notion that internal heat is the main driver of convection. Both near-infrared and ground-based 5-micrometer thermal imagery reveal that cloud cover has thinned substantially since the 2000 Cassini flyby, particularly in the turbulent wake of the Great Red Spot and in the southern half of the equatorial region, demonstrating that vertical dynamical processes are time-varying on seasonal scales at mid- and low latitudes on Jupiter.
Use of Synthetic Derivatives To Determine the Minimal Active Structure of Cytokine-Inducing Lipoteichoic Acid
Authors: Deininger Susanne , Figueroa-Perez Ignacio , Sigel Stefanie , Stadelmaier Andreas , Schmidt Richard R. , Hartung Thomas , von Aulock Sonja
Published: October 2007

Lipoteichoic acid (LTA) from gram-positive bacteria is the counterpart to lipopolysaccharide from gram-negative bacteria. LTA, which activates Toll-like receptor 2 (TLR2), induces a unique cytokine and chemokine pattern. The chemical synthesis of LTA proved its immunostimulatory properties. To determine the minimal active structure of LTA, we reduced synthetic LTA in a number of steps down to the synthetic anchor and employed these molecules to stimulate interleukin-8 (IL-8) release in human whole blood. Ten times more of the synthetic structures with four to six
d
-alanine-substituted polyglycerophosphate units (50 nM) than of the native LTA preparation was required to induce IL-8 release. A further reduction to three backbone units with two or no
d
-alanine residues resulted in cytokine induction only from 500 nM. The synthetic anchor was not able to induce IL-8 release even at 5 μM. When the LTA derivatives were used at 500 nM, they induced increasing levels of IL-8 and tumor necrosis factor alpha with increasing elongation of the backbone. Peritoneal macrophages were less responsive than human blood to the synthetic structures. Therefore, TLR2 dependency could be shown only with cells from TLR2-deficient mice for the two largest synthetic structures. This was confirmed by using TLR2-transfected HEK 293 cells. Taken together, these data indicate that although the synthetic anchor (which, unlike the native anchor, contains only myristic acid) cannot induce cytokine release, the addition of three backbone units, even without
d
-alanine substituents, confers this ability. Lengthening of the chain with
d
-alanine-substituted backbone units results in increased cytokine-inducing potency and a more sensitive response.
Longitudinal Tracking of Cytokines after Acute Exposure to Tuberculosis: Association of Distinct Cytokine Patterns with Protection and Disease Development
Authors: Hussain Rabia , Talat Najeeha , Shahid Firdaus , Dawood Ghaffar
Published: October 2007

Household contacts (HCs) of patients with tuberculosis (TB) are at higher risk of infection as well as the development of active disease. Longitudinal tracking of antigen-specific cytokines after acute exposure may significantly advance our understanding of the dynamic changes in cytokine patterns associated with disease establishment. To achieve this objective, we carried out a prospective cohort study with healthy HCs after exposure to TB. The patterns of cytokines (gamma interferon [IFN-γ] and interleukin 10 [IL-10]) in response to mycobacterial antigens (culture filtrate [CF] proteins) and nonspecific mitogens (phytohemagglutinin [PHA] and lipopolysaccharide [LPS]) were assessed at 0, 6, 12, and 24 months after exposure. Seven of 109 (6.4%) HCs developed active disease. Six of the seven individuals were females, and active disease developed between 12 and 15 months after exposure in 5/20 families. The most significant findings were the exponential increases (∼1,000-fold) in both the CF protein- and the PHA- or LPS-induced IFN-γ/IL-10 ratio in healthy HCs (
n
= 26), which peaked at 12 months, compared to the levels in HCs who developed disease (
n
= 7), in whom relatively flat responses were observed during the 24-month period. Linear trends for 0 to 12 and 0 to 24 months for the CF protein-induced IFN-γ/IL-10 ratio showed significant differences between the two groups, as determined by the use of the Mantel extension test for χ
2
analysis (odds ratio = 0.45; 95% confidence interval = 0.295 to 0.685;
P
= 0.0002). Our results strongly suggest that the magnitude of the IFN-γ/IL-10 ratio at 12 months after exposure may be a critical determinant in the resolution of infection. These studies provide new insights into the cytokine responses associated with disease establishment or the resolution of infection after natural exposure to TB and have implications for TB control programs as well vaccine efficacy studies.