bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular epidemiology of HIV: Tracking AIDS pandemic
Authors: Takebe Yutaka , Kusagawa Shigeru , Motomura Kazushi
Published: April 2004

Abstract
Background
: Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) epidemic is a global threat to maternal and child health, especially in developing countries. It is estimated that 800 000 children are infected and 580 000 children die of AIDS‐related illnesses every year. Molecular epidemiology has been a useful tool in analyzing the origin of HIV and tracking the course of global HIV spread. This article provides an overview of recent advances in the field of molecular epidemiology of HIV across the world, and discuss the biological implications.

Methods
: Based on the near full‐length or partial nucleotide sequence information, the phylogeny and recombinant structure of HIV strains are analyzed. Using genotype classification of HIV as a molecular marker, the origin and the genesis of HIV epidemic are investigated.

Results
: The HIV‐1 group M, a major HIV group responsible for current AIDS pandemic, began its expansion in human population approximately 70 years ago and diversified rapidly over time, now comprising a number of different subtypes and circulating recombinant forms (CRF). Of note, recent studies revealed that new recombinant strains are arising continually, becoming a powerful force in the spread of HIV‐1 across the globe.

Conclusion
: Global dissemination of HIV is a dramatic and deadly example of recent genome emergence and expansion. Molecular epidemiological investigation is expected to provide information critical for prevention and future vaccine strategies.
Periventricular low intensities on fluid attenuated inversion recovery imaging in the newborn infant: Relationships to the clinical data and long‐term outcome
Authors: Iwata Osuke , Iwata Sachiko , Tamura Masanori , Nakamura Tomohiko , Hirabayashi Shinnichi , Fueki Noboru , Kondou Yoshiaki , Hizume Eriko , Kihara Hideki
Published: April 2004

Abstract
Background
: The author's previous study showed that it is possible to predict the severity of white matter injury in early infancy by using fluid attenuated inversion recovery (FLAIR) imaging. A follow‐up study was performed in order to assess the correlation between the incidence of periventricular low intensities on FLAIR imaging (F‐PVLI) and the clinical data including the physiological variables at birth and the long‐term outcome of the infant.

Methods
: The authors reviewed MRI of 328 newborn infants, which were obtained before 2 months corrected age. Abnormal findings in the periventricular white matter and other part of the brain were recorded. Periventricular abnormal intensities were sorted into four groups according to the FLAIR grade, which comprised normal, F‐PVLI 1 (focal), F‐PVLI 2 (extensive), cystic periventricular leukomalacia (C‐PVL), and diffused leukomalacia.

Results
: Significantly more periventricular abnormal intensities were detected by FLAIR imaging than by conventional T1 and T2 weighted imaging. In the groups of F‐PVLI 2 and C‐PVL, the birth weight (BW), gestational age (GA), blood pH and base excess at birth were significantly lower than in the normal group. However, when the study population was defined into very low birth weight infants, F‐PVLI 2 had significantly larger BW and GA than normal. The FLAIR grade had a strong correlation with the developmental outcome at 12 and 36 months corrected age.

Conclusion
: F‐PVLI is a silent but very important white matter injury, which has many features in common with C‐PVL. FLAIR imaging could be a strong tool in screening newborn infants at high risk of neurological impairment.
Inositol (1,4,5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity
Authors: Wen Ben G. , Pletcher Mathew T. , Warashina Masaki , Choe Sun Hui , Ziaee Niusha , Wiltshire Tim , Sauer Karsten , Cooke Michael P.
Published: April 2004

The mechanisms governing positive selection of T cells in the thymus are still incompletely understood. Here, we describe aN-ethyl-N-nitrosourea induced recessive mouse mutant,Ms. T-less, which lacks T cells in the peripheral blood because of a complete block of thymocyte development at the CD4+CD8+stage. Single nucleotide polymorphism mapping and candidate gene sequencing revealed a nonsense mutation in the inositol (1,4,5) trisphosphate 3 kinase B (Itpkb) gene inMs. T-lessmice. Accordingly,Ms. T-lessthymocytes do not show detectable expression of Itpkb protein and have drastically reduced basal inositol (1,4,5) trisphosphate kinase activity. Itpkb converts inositol (1,4,5) trisphosphate to inositol (1,3,4,5) tetrakisphosphate, soluble second messengers that have been implicated in Ca2+signaling. Surprisingly, Ca2+responses show no significant differences between wild type (WT) and mutant thymocytes. However, extracellular signal-regulated kinase (Erk) activation in response to suboptimal antigen receptor stimulation is attenuated inMs. T-lessthymocytes, suggesting a role forItpkbin linking T cell receptor signaling to efficient and sustained Erk activation.
Catalytic asymmetric addition of diorganozinc reagents to
N
-phosphinoylalkylimines
Authors: Côté Alexandre , Boezio Alessandro A. , Charette André B.
Published: April 2004

The synthesis of α-chiral amines bearing two alkyl groups has been hampered by the accessibility and stability of the alkylimine precursor. Herein, we report an efficient strategy to generate the alkyl-substituted imine
in situ
that is compatible with the Me-DuPHOS monoxide·Cu(I) catalyzed addition of diorganozinc reagents. The sulfinic acid adduct of the imine is readily prepared by mixing diphenylphosphinic amide, the aldehyde, and sulfinic acid. The sulfinic acid adduct is generally isolated by filtration. The addition of diorganozinc reagents in the presence of Me-DuPHOS monoxide·Cu(I) and the
in situ
-generated imines affords the corresponding α-chiral amines in high yields and enantiomeric excesses.
Comparison of the genome of the oral pathogen
Treponema denticola
with other spirochete genomes
Authors: Seshadri Rekha , Myers Garry S. A. , Tettelin Hervé , Eisen Jonathan A. , Heidelberg John F. , Dodson Robert J. , Davidsen Tanja M. , DeBoy Robert T. , Fouts Derrick E. , Haft Dan H. , Selengut Jeremy , Ren Qinghu , Brinkac Lauren M. , Madupu Ramana , Kolonay Jamie , Durkin Scott A. , Daugherty Sean C. , Shetty Jyoti , Shvartsbeyn Alla , Gebregeorgis Elizabeth , Geer Keita , Tsegaye Getahun , Malek Joel , Ayodeji Bola , Shatsman Sofiya , McLeod Michael P. , Šmajs David , Howell Jerrilyn K. , Pal Sangita , Amin Anita , Vashisth Pankaj , McNeill Thomas Z. , Xiang Qin , Sodergren Erica , Baca Ernesto , Weinstock George M. , Norris Steven J. , Fraser Claire M. , Paulsen Ian T.
Published: April 2004

We present the complete 2,843,201-bp genome sequence of
Treponema denticola
(ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the
T. denticola
genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The
T. denticola
genome is considerably larger in size than the genome of the related syphilis-causing spirochete
Treponema pallidum
. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function.
Roles of substrate availability and infection of resting and activated CD4
+
T cells in transmission and acute simian immunodeficiency virus infection
Authors: Zhang Zhi-Qiang , Wietgrefe Stephen W. , Li Qingsheng , Shore Marta Dykhuizen , Duan Lijie , Reilly Cavan , Lifson Jeffrey D. , Haase Ashley T.
Published: April 2004

In studies of sexual mucosal transmission and early stages of simian immunodeficiency virus (SIV) and HIV infections, productive infection predominates in CD4
+
T cell populations, in both ostensibly resting and activated cells. The surprising ability of SIV and HIV to replicate in resting cells
in vivo
, in contrast to propagation of infection
in vitro
, suggested a model in which during the early stages of infection these viruses exploit the greater availability of resting cells to maintain unbroken chains of transmission from an infected resting cell to another resting cell nearby. Because immune activation in response to infection provides more activated CD4
+
T cells, these viruses take advantage of the greater efficiency of virus production and spread in activated cells for propagation and dissemination of infection. In this article, we report the results of experimental tests of this model, including visualization at the light microscopic level and direct analysis of virus production by cells in tissues. Analysis of tissues of rhesus macaques inoculated intravaginally or i.v. with SIV supports the proposed roles of target cell availability, susceptibility, and virus production by infected resting and activated CD4
+
T cells in mucosal transmission and early infection, and points to a potential role for topical anti-inflammatory agents in moderating the initial propagation of infection.
Maternal investment affects offspring phenotypic plasticity in a viviparous cockroach
Authors: Holbrook Glenn L. , Schal Coby
Published: April 2004

Maternal effects, crossgenerational influences of the mother's phenotype on phenotypic variation in offspring, can profoundly influence the fitness of offspring. In insects especially, social interactions during larval development also can alter life-history traits. To date, however, no experimental design, to our knowledge, has manipulated the prenatal and postnatal environments independently to investigate their interaction. We report here that the degree of maternal nutrient investment in developing embryos of the viviparous cockroachDiploptera punctatainfluences how quickly neonate males become adults and how large they are at adulthood. An offspring's probability of reaching adulthood in fewer than four molts increased with birth weight: the heavier neonates were, consequently, more likely to become smaller adults. Social interaction also affected nymphal development and adult size. Nymphs reared in pairs molted fewer times than solitary nymphs and, thus, became smaller adults. The social effect on developmental trajectory was, however, eliminated by experimentally increasing the level of maternal nutrient investment per offspring, which was accomplished by removing one of the female's paired ovaries (allometric engineering). We conclude that a particular prenatal environment can result in different offspring phenotypes under different postnatal social conditions. By investing more in each offspring, however,D. punctatamothers, because they are viviparous, are able to produce broods with environmentally (socially) independent phenotypes.
Beyond sensory images: Object-based representation in the human ventral pathway
Authors: Pietrini Pietro , Furey Maura L. , Ricciardi Emiliano , Gobbini M. Ida , Wu W.-H. Carolyn , Cohen Leonardo , Guazzelli Mario , Haxby James V.
Published: April 2004

We investigated whether the topographically organized, category-related patterns of neural response in the ventral visual pathway are a representation of sensory images or a more abstract representation of object form that is not dependent on sensory modality. We used functional MRI to measure patterns of response evoked during visual and tactile recognition of faces and manmade objects in sighted subjects and during tactile recognition in blind subjects. Results showed that visual and tactile recognition evoked category-related patterns of response in a ventral extrastriate visual area in the inferior temporal gyrus that were correlated across modality for manmade objects. Blind subjects also demonstrated category-related patterns of response in this “visual” area, and in more ventral cortical regions in the fusiform gyrus, indicating that these patterns are not due to visual imagery and, furthermore, that visual experience is not necessary for category-related representations to develop in these cortices. These results demonstrate that the representation of objects in the ventral visual pathway is not simply a representation of visual images but, rather, is a representation of more abstract features of object form.
Canonical pathway of nuclear factor κB activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis
Authors: Monaco Claudia , Andreakos Evangelos , Kiriakidis Serafim , Mauri Claudia , Bicknell Colin , Foxwell Brian , Cheshire Nicholas , Paleolog Ewa , Feldmann Marc
Published: April 2004

Nuclear factor κB (NF-κB) activation has been observed in human atherosclerotic plaques and is enhanced in unstable coronary plaques, but whether such activation has a protective or pathophysiological role remains to be determined. We addressed this question by developing a short-term culture system of cells isolated from human atherosclerotic tissue, allowing efficient gene transfer to directly investigate signaling pathways in human atherosclerosis. We found that NF-κB is activated in these cells and that this activity involves p65, p50, and c-Rel but not p52 or RelB. This NF-κB activation can be blocked by overexpression of IκBα or dominant-negative IκB kinase (IKK)-2 but not dominant-negative IKK-1 or NF-κB-inducing kinase, resulting in selective inhibition of inflammatory cytokines (tumor necrosis factor α, IL-6, and IL-8), tissue factor, and matrix metalloproteinases without affecting the antiinflammatory cytokine IL-10 or tissue inhibitor of matrix metalloproteinases. Our results demonstrate that the canonical pathway of NF-κB activation that involves p65, p50, c-Rel, and IKK-2 is activated in human atherosclerosis and results in selective up-regulation of major proinflammatory and prothrombotic mediators of the disease.
Ubiquitylation of synphilin-1 and α-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease
Authors: Liani Esti , Eyal Allon , Avraham Eyal , Shemer Revital , Szargel Raymonde , Berg Daniela , Bornemann Antje , Riess Olaf , Ross Christopher A. , Rott Ruth , Engelender Simone
Published: April 2004

Parkinson's disease (PD) is a neurodegenerative disease characterized by Lewy body formation and death of dopaminergic neurons. Mutations in α-synuclein and parkin cause familial forms of PD. Synphilin-1 was shown to interact with α-synuclein and to promote the formation of cytosolic inclusions. We now report that synphilin-1 interacts with the E3 ubiquitin-ligases SIAH-1 and SIAH-2. SIAH proteins ubiquitylate synphilin-1 both
in vitro
and
in vivo
, promoting its degradation by the ubiquitin–proteasome system. Inability of the proteasome to degrade synphilin-1/SIAH complex leads to a robust formation of ubiquitylated cytosolic inclusions. Ubiquitylation is required for inclusion formation, because a catalytically inactive mutant of SIAH-1, which still binds to synphilin-1, fails to promote inclusions. Like synphilin-1, α-synuclein associates with SIAH in intact cells, but the interaction with SIAH-2 was much stronger that with SIAH-1.
In vitro
experiments show that SIAH-2 monoubiquitylates α-synuclein. Further evidence that SIAH proteins may play a role in inclusion formation comes from the demonstration of SIAH immunoreactivity in Lewy bodies of PD patients.
Photocleavable fluorescent nucleotides for DNA sequencing on a chip constructed by site-specific coupling chemistry
Authors: Seo Tae Seok , Bai Xiaopeng , Ruparel Hameer , Li Zengmin , Turro Nicholas J. , Ju Jingyue
Published: April 2004

DNA sequencing by synthesis on a solid surface offers new paradigms to overcome limitations of electrophoresis-based sequencing methods. Here we report DNA sequencing by synthesis using photocleavable (PC) fluorescent nucleotides [dUTP-PC-4,4-difluoro-4-bora-3α,4α-diaza-
s
-indacene (Bodipy)-FL-510, dCTP-PC-Bodipy-650, and dUTP-PC-6-carboxy-X-rhodamine (ROX)] on a glass chip constructed by 1,3-dipolar azide-alkyne cycloaddition coupling chemistry. Each nucleotide analogue consists of a different fluorophore attached to the base through a PC 2-nitrobenzyl linker. We constructed a DNA microarray by using the 1,3-dipolar cycloaddition chemistry to site-specifically attach azido-modified DNA onto an alkyne-functionalized glass chip at room temperature under aqueous conditions. After verifying that the polymerase reaction could be carried out successfully on the above-described DNA array, we then performed a sequencing reaction on the chip by using a self-primed DNA template. In the first step, we extended the primer using DNA polymerase and dUTP-PC-Bodipy-FL-510, detected the fluorescent signal from the fluorophore Bodipy-FL-510, and then cleaved the fluorophore using 340 nm UV irradiation. This process was followed by extension of the primer with dCTP-PC-Bodipy-650 and the subsequent detection of the fluorescent signal from Bodipy-650 and its photocleavage. The same procedure was also performed by using dUTP-PC-ROX. The entire process was repeated five times by using the three fluorescent nucleotides to identify 7 bases in the DNA template. These results demonstrate that the PC nucleotide analogues can be incorporated accurately into a growing DNA strand during polymerase reaction on a chip, and the fluorophore can be detected and then efficiently cleaved using near-UV irradiation, thereby allowing the continuous identification of the template sequence.
The change of the brain activation patterns as children learn algebra equation solving
Authors: Qin Yulin , Carter Cameron S. , Silk Eli M. , Stenger V. Andrew , Fissell Kate , Goode Adam , Anderson John R.
Published: April 2004

In a brain imaging study of children learning algebra, it is shown that the same regions are active in children solving equations as are active in experienced adults solving equations. As with adults, practice in symbol manipulation produces a reduced activation in prefrontal cortex area. However, unlike adults, practice seems also to produce a decrease in a parietal area that is holding an image of the equation. This finding suggests that adolescents' brain responses are more plastic and change more with practice. These results are integrated in a cognitive model that predicts both the behavioral and brain imaging results.
Direct continuities between cisternae at different levels of the Golgi complex in glucose-stimulated mouse islet beta cells
Authors: Marsh Brad J. , Volkmann Niels , McIntosh J. Richard , Howell Kathryn E.
Published: April 2004

Direct continuity between the membranes of cisternae in the Golgi complex in mammalian cells rarely has been observed; when seen, its documentation has been equivocal. Here we have used dual-axis electron microscope tomography to examine the architecture of the Golgi in three dimensions at ≈6-nm resolution in rapidly frozen, freeze-substituted murine cells that make and secrete insulin in response to glucose challenge. Our data show three types of direct connections between Golgi cisternae that are normally distinct from one another. These connections all “bypass” interceding cisternae. We propose that when pancreatic beta cells are stimulated to synthesize and secrete insulin rapidly
in vivo
, such connections provide a continuous lumen that facilitates the rapid transit of large amounts of newly made protein for secretion. The heterotypic fusion of cisternae, even transiently, raises important questions about the molecular mechanisms that (
i
) facilitate the fusion/fission of cisternal membranes and control the directionality and specificity of such events, and (
ii
) retain Golgi processing enzymes at specific places within individual cisternae when two cisternae at different levels in the Golgi have fused, maintaining the sequential processing hierarchy that is a hallmark of Golgi organization.
Genome-wide comparative analysis of the transposable elements in the related species
Arabidopsis thaliana
and
Brassica oleracea
Authors: Zhang Xiaoyu , Wessler Susan R.
Published: April 2004

Transposable elements (TEs) are the major component of plant genomes where they contribute significantly to the >1,000-fold genome size variation. To understand the dynamics of TE-mediated genome expansion, we have undertaken a comparative analysis of the TEs in two related organisms: the weed
Arabidopsis thaliana
(125 megabases) and
Brassica oleracea
(≈600 megabases), a species with many crop plants. Comparison of the whole genome sequence of
A. thaliana
with a partial draft of
B. oleracea
has permitted an estimation of the patterns of TE amplification, diversification, and loss that has occurred in related species since their divergence from a common ancestor. Although we find that nearly all TE lineages are shared, the number of elements in each lineage is almost always greater in
B. oleracea
. Class 1 (retro) elements are the most abundant TE class in both species with LTR and non-LTR elements comprising the largest fraction of each genome. However, several families of class 2 (DNA) elements have amplified to very high copy number in
B. oleracea
where they have contributed significantly to genome expansion. Taken together, the results of this analysis indicate that amplification of both class 1 and class 2 TEs is responsible, in part, for
B. oleracea
genome expansion since divergence from a common ancestor with
A. thaliana
. In addition, the observation that
B. oleracea
and
A. thaliana
share virtually all TE lineages makes it unlikely that wholesale removal of TEs is responsible for the compact genome of
A. thaliana
.
Modulation of energy-dependent quenching of excitons in antennae of higher plants
Authors: Avenson Thomas J. , Cruz Jeffrey A. , Kramer David M.
Published: April 2004

Energy-dependent exciton quenching, or q
E
, protects the higher plant photosynthetic apparatus from photodamage. Initiation of q
E
involves protonation of violaxanthin deepoxidase and P
sbS
, a component of the photosystem II antenna complex, as a result of lumen acidification driven by photosynthetic electron transfer. It has become clear that the response of q
E
to linear electron flow, termed “q
E
sensitivity,” must be modulated in response to fluctuating environmental conditions. Previously, three mechanisms have been proposed to account for q
E
modulation: (
i
) the sensitivity of q
E
to the lumen pH is altered; (
ii
) elevated cyclic electron flow around photosystem I increases proton translocation into the lumen; and (
iii
) lowering the conductivity of the thylakoid ATP synthase to protons (
g
H+
) allows formation of a larger steady-state proton motive force (
pmf
). Kinetic analysis of the electrochromic shift of intrinsic thylakoid pigments, a linear indicator of transthylakoid electric field component, suggests that, when CO
2
alone was lowered from 350 ppm to 50 ppm CO
2
, modulation of q
E
sensitivity could be explained solely by changes in conductivity. Lowering both CO
2
(to 50 ppm) and O
2
(to 1%) resulted in an additional increase in q
E
sensitivity that could not be explained by changes in conductivity or cyclic electron flow associated with photosystem I. Evidence is presented for a fourth mechanism, in which changes in q
E
sensitivity result from variable partitioning of proton motive force into the electric field and pH gradient components. The implications of this mechanism for the storage of proton motive force and the regulation of the light reactions are discussed.
Myristoylated Naked2 escorts transforming growth factor α to the basolateral plasma membrane of polarized epithelial cells
Authors: Li Cunxi , Franklin Jeffrey L. , Graves-Deal Ramona , Jerome W. Gray , Cao Zheng , Coffey Robert J.
Published: April 2004

The epidermal growth factor receptor ligands transforming growth factor α (TGFα) and amphiregulin are delivered to the basolateral surface of polarized epithelial cells where they are cleaved by TACE/ADAM17. Basolateral sorting information resides in their cytoplasmic tail domains, but tail-interacting proteins required for basolateral trafficking have not been identified. Naked (NKD)1 and NKD2 are mammalian homologs of
Drosophila
Naked Cuticle, which negatively regulates canonical Wnt signaling by binding Dishevelled. We present evidence that NKD2, but not NKD1, binds to basolateral sorting motifs in the cytoplasmic tail of TGFα. Processing and cell-surface delivery of TGFα are accelerated in NKD2-overexpressing Madin–Darby canine kidney cells. NKD2 is myristoylated on glycine, the second residue. On expression of myristoylation-defective (G2A) NKD2, neither NKD2 nor TGFα appears at the basolateral plasma membrane of polarized Madin–Darby canine kidney cells; however, membrane staining for TGFα is restored on silencing expression of this mutant NKD2. Amphiregulin does not interact with NKD2 and retains its basolateral localization in G2A-NKD2-expressing cells, as do Na
+
, K
+
ATPase α1 and E-cadherin. These data identify an unexpected function for NKD2, i.e., myristoylation-dependent escort of TGFα to the basolateral plasma membrane of polarized epithelial cells.
A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism
Authors: Kim Joseph A. , Pollak Kelly A. , Hjelmstad Gregory O. , Fields Howard L.
Published: April 2004

Repeated exposure to drugs of abuse produces forms of experience-dependent plasticity including behavioral sensitization. Although a single exposure to many addicting substances elicits locomotor sensitization, there is little information regarding the motivational effects of such single exposures. This study demonstrates that a single cocaine exposure enhances both rewarding and aversive forms of opioid place conditioning. Rats were given a single injection of cocaine (15 mg/kg i.p.) in their home cage at different times before conditioning. This treatment enhanced conditioned place preference (CPP) to morphine (2 × 10 mg/kg s.c.) if training began 1 or 5 but not 10 days after the cocaine injection. A single cocaine exposure also enhanced conditioned place aversion (CPA) to the κ-opioid receptor agonist U69593 (2 × 0.16 mg/kg s.c.). Compared to morphine CPP, U69593 CPA was delayed and persistent. It was not observed at 1 day but appeared if the conditioning began 5 or 10 days after the cocaine injection. Although the cocaine-induced enhancements of both morphine CPP and U69593 CPA followed different time courses, suggesting different mechanisms, both effects were blocked by injection of the
N
-methyl-
d
-aspartate receptor antagonist MK-801 (0.5 nmol bilaterally) into the ventral tegmental area, immediately before the cocaine injection. Thus, through a circuit involving the ventral tegmental area, a single cocaine exposure enhanced both μ-opioid receptor reward and κ-opioid receptor aversion.
T Cell Receptor Engagement Leads to Phosphorylation of Clathrin Heavy Chain during Receptor Internalization
Authors: Crotzer Victoria L. , Mabardy Allan S. , Weiss Arthur , Brodsky Frances M.
Published: April 2004

T cell receptor (TCR) internalization by clathrin-coated vesicles after encounter with antigen has been implicated in the regulation of T cell responses. We demonstrate that TCR internalization after receptor engagement and TCR signaling involves inducible phosphorylation of clathrin heavy chain (CHC) in both CD4+ and CD8+ human T cells. Studies with mutant Jurkat T cells implicate the Src family kinase Lck as the responsible enzyme and its activity in this process is influenced by the functional integrity of the downstream signaling molecule ZAP-70. CHC phosphorylation positively correlates with ligand-induced TCR internalization in both CD4+ and CD8+ T cells, and CHC phosphorylation as a result of basal Lck activity is also implicated in constitutive TCR endocytosis by CD4+ T cells. Remarkably, irreversible CHC phosphorylation in the presence of pervanadate reduced both constitutive and ligand-induced TCR internalization in CD4+ T cells, and immunofluorescence studies revealed that this inhibition affected the early stages of TCR endocytosis from the plasma membrane. Thus, we propose that CHC phosphorylation and dephosphorylation are involved in TCR internalization and that this is a regulatory mechanism linking TCR signaling to endocytosis.
KSHV vFLIP Is Essential for the Survival of Infected Lymphoma Cells
Authors: Guasparri Ilaria , Keller Shannon A. , Cesarman Ethel
Published: April 2004

Primary effusion lymphomas (PELs) associated with infection by the Kaposi's sarcoma–associated herpesvirus (KSHV/HHV-8) have constitutive nuclear factor (NF)–κB activity that is essential for their survival, but the source of this activity is unknown. We report that viral FADD-like interleukin-1-β–converting enzyme [FLICE/caspase 8]-inhibitory protein (FLIP) activates NF-κB more potently than cellular FLIP in B cells and that it is largely responsible for NF-κB activation in latently infected PEL cells. Elimination of vFLIP production in PEL cells by RNA interference results in significantly decreased NF-κB activity, down-regulation of essential NF-κB–regulated cellular prosurvival factors, induction of apoptosis, and enhanced sensitivity to external apoptotic stimuli. vFLIP is the first virally encoded gene shown to be essential for the survival of naturally infected tumor cells.
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Authors: Viglietta Vissia , Baecher-Allan Clare , Weiner Howard L. , Hafler David A.
Published: April 2004

CD4+CD25+ regulatory T cells contribute to the maintenance of peripheral tolerance by active suppression because their deletion causes spontaneous autoimmune diseases in mice. Human CD4+ regulatory T cells expressing high levels of CD25 are suppressive in vitro and mimic the activity of murine CD4+CD25+ regulatory T cells. Multiple sclerosis (MS) is an inflammatory disease thought to be mediated by T cells recognizing myelin protein peptides. We hypothesized that altered functions of CD4+CD25hi regulatory T cells play a role in the breakdown of immunologic self-tolerance in patients with MS. Here, we report a significant decrease in the effector function of CD4+CD25hi regulatory T cells from peripheral blood of patients with MS as compared with healthy donors. Differences were also apparent in single cell cloning experiments in which the cloning frequency of CD4+CD25hi T cells was significantly reduced in patients as compared with normal controls. These data are the first to demonstrate alterations of CD4+CD25hi regulatory T cell function in patients with MS.
Differentiation of Cytoplasmic and Meiotic Spindle Assembly MCAK Functions by Aurora B-dependent Phosphorylation
Authors: Ohi Ryoma , Sapra Tanuj , Howard Jonathan , Mitchison Timothy J.
Published: April 2004

The KinI kinesin MCAK is a microtubule depolymerase important for governing spindle microtubule dynamics during chromosome segregation. The dynamic nature of spindle assembly and chromosome-microtubule interactions suggest that mechanisms must exist that modulate the activity of MCAK, both spatially and temporally. In Xenopus extracts, MCAK associates with and is stimulated by the inner centromere protein ICIS. The inner centromere kinase Aurora B also interacts with ICIS and MCAK raising the possibility that Aurora B may regulate MCAK activity as well. Herein, we demonstrate that recombinant Aurora B-INCENP inhibits Xenopus MCAK activity in vitro in a phosphorylation-dependent manner. Substituting endogenous MCAK in Xenopus extracts with the alanine mutant XMCAK-4A, which is resistant to inhibition by Aurora B-INCENP, led to assembly of mono-astral and monopolar structures instead of bipolar spindles. The size of these structures and extent of tubulin polymerization in XMCAK-4A extracts indicate that XM-CAK-4A is not defective for microtubule dynamics regulation throughout the cytoplasm. We further demonstrate that the ability of XMCAK-4A to localize to inner centromeres is abolished. Our results show that MCAK regulation of cytoplasmic and spindle-associated microtubules can be differentiated by Aurora B-dependent phosphorylation, and they further demonstrate that this regulation is required for bipolar meiotic spindle assembly.
The Royal Society and the South Seas
Authors: Fogg G.E.
Published: April 2004

Almost from its inception The Royal Society has had a particular interest in the seas of the Southern Hemisphere. The
Endeavour
voyage of circumnavigation in southern waters by James Cook and his naturalist Joseph Banks, which was initiated by the Society, had repercussions—far beyond its original astronomical purpose—in oceanography, biology, exploration and world politics. It left a tradition, which still continues in the Society, of promoting wide-ranging expeditions such as those of the
Erebus
and
Terror
, the
Challenger
and, more recently, those to the Great Barrier Reef, the Solomon Islands, the New Hebrides and the island of Aldabra. The sea areas covered are those lying between the South Polar Front and, approximately, the Equator. Small islands and inshore waters are included but not land-based expeditions, such as those to Southern Chile and the Matto Grosso. The contributions of both the Society and its Fellows acting individually have been numerous and varied but here attention is restricted to three interconnected topics: physical and geological oceanography, biogeography and the genesis of coral reefs.
Royal weather
Authors: Cook A.
Published: April 2004

Fellows of The Royal Society have been interested in weather from the earliest years of the Society. When John Locke was in Montpellier in 1676 he made many observations of the weather, which are in his unpublished
Journal
. Edmond Halley collected observations of winds worldwide from sea captains and published a chart of the trade winds in
Philosophical Transactions
. Robert Hooke devised a barometer for use at sea. Present Fellows are deeply involved with questions of change of climate. Our Archivist assembled a number of items from the Library for the New Frontiers in Science Soirées last year in an exhibition entitled ‘From Hooke to Houghton. Meteorology and The Royal Society’, which showed the continuing study by Fellows of weather and climate over three centuries. We reproduce some of the pictures here as a sample of those studies.
Plants illustrating exotic collections
Authors: Cook A.
Published: April 2004

The study of plants was nothing new when The Royal Society was founded, but some of our earliest Fellows changed it drastically. Perhaps they did not do this as suddenly or as completely as did Newton for dynamics, but in the long run they had at least as great an influence on views of the natural world and how to study it. Did God create all the great variety of plants no one (in Europe) had ever seen before, and if so why? Plants brought back by explorers, especially from North America, and plants looked at in the microscope, together with the taxonomic system constructed by Linnaeus, replaced the plants grown in monastic gardens and their successors in public botanic gardens, and the study of plants for purely medicinal uses.
Centenary of the NPL
Authors: Cook A.
Published: April 2004

The National Physical Laboratory (NPL) attained its centenary in 2000 and that was the occasion for a meeting in The Royal Society on 7 November 2000. The centenary is part of the record of The Royal Society because Fellows of the Society actively promoted the formation of the laboratory, and the programme of the Laboratory in its early years was guided by a committee of the Society. In addition, some of the researches of the Laboratory were supported by grants from the government grant administered by the Society. The relations between the early Laboratory and the Society are not unlike those between the Society and the early Royal Observatory more than 200 years earlier. The centenary of the NPL was indeed an event of the last year of the Second Millennium, and so we include this account of the meeting of 7 November, which includes Lord Sainsbury's and the President's Addresses and abstracts of the presentations from other speakers.
Book reviews
Authors: Cahn R.W
Published: April 2004

One book review in the January 2001 issue of
Notes and Records
:
Metals and the Royal Society
, by D. R. F. West and J. E. Harris,
reviewed by
R. W. Cahn.
JSTOR: an electronic archive from 1665
Authors: Taylor J.
Published: April 2004

Back in the last century (just over a year ago, actually), reading an original copy of a paper published in The Royal Society's
Philosophical Transactions
or
Proceedings
journals in, say, the 18th century required a visit to a library, probably by appointment and certainly with considerable inconvenience. Now, through JSTOR (an acronym for ‘journal storage’) scholars are able to call up the full text of papers to their desktops, 24 hours a day, seven days a week, from the comfort of their university libraries, offices and homes. The archive begins with the first issue of
Philosophical Transactions
published on 6 March 1665 and runs through to the December 1996 issues of the modern journals. This totals about 700 000 pages, all of which are completely browsable, searchable and retrievable. Each year a further 12 months of publishing will be added to the archive. Meanwhile, the Society's own electronic archive facilities record the papers published from January 1997 to date.
David Gregory on Newton's burning mirror
Authors: Simms D. L. , Hinkley P. L.
Published: April 2004

On the basis of the accessible surviving evidence, liberally interpreted, an earlier paper described Newton's burning mirror and assessed its effectiveness.
1
A hitherto unnoticed source in David Gregory's Memoranda has provided a little more information, which generally confirms the earlier account, but modifies one or two conjectures
2
(see Appendix).

In addition, the originality of Newton's idea for the mirror is examined and the fate of the mirror has been determined.
3
Translating Newton's
Principia
: The Marquise du Châtelet's revisions and additions for a French audience
Authors: Zinsser J. P.
Published: April 2004

In the 1740s, the Marquise du Châtelet translated Newton's
Principia
(1731, third edition) into French. Her's remains the standard translation. In addition, she wrote an extensive commentary in which she gave her own description of the
System of the World
, and analytical solutions to key disputed aspects of Newton's theory of universal gravitation. She also included summaries of two mathematical essays that clarified and confirmed Newton's application of his theory to observed phenomena: Aléxis–Claude Clairaut's on the shape of the Earth and Daniel Bernoulli's on the effects of the Sun and Moon on the tides.
Essay review: The genius of soane
Authors: Honer J.
Published: April 2004

At the mention of Sir John Soane, F.R.S., we might call to mind the Bank of England or a visit to the Dulwich Picture Gallery, or alternatively a conducted tour around the Soane Museum in Lincoln's Inn Fields by Sir John Summerson, its curator for nearly 40 years, until 1984. More recently our interest in Soane may have been stimulated by a visit to an exhibition of his work at the Royal Academy in the autumn of 1999.
Robert Balle, Merchant of Leghorn and Fellow of the Royal Society (
ca.
1640-
ca.
1734)
Authors: Fisher N. R. R.
Published: April 2004

The reasons why one English merchant, Robert Balle, should have wished to join The Royal Society in 1708 and become thereafter an active member of it are discussed in this paper. The author has used the Journal and Minute Books of The Royal Society, the correspondence of Sir Hans Sloane and other contemporary materials, published and unpublished. She concludes that the factors involved in Balle's decision included family connections, genuine interest in some of the subjects with which the Society was concerned and a belief in the need for the free exchange of ideas. They co–existed with Balle's wish to utilize membership of the Society to further his social and commercial ends and his use of scientific patronage for the enhancement of self–esteem and personal prestige. It is hoped that this study will contribute to the discussion on merchant membership of, and activity within, the early Royal Society.
The work-diaries of Robert Boyle: a newly discovered source and its internet publication
Authors: Hunter M. , Littleton C.
Published: April 2004

Boyle's ‘work-diaries’—his notes on his work experiments and on data given him by others —have been reassembled and transcribed, and are about to be published on the Web.
George Fordyce M.D., F.R.S (1736–1802): physician–chemist and eccentric
Authors: Coley N. G.
Published: April 2004

Educated at Aberdeen and Edinburgh at the height of the ‘golden age’ of Scottish medicine, George Fordyce came to London, where he began to lecture on chemistry and medical subjects. As a physician at St Thomas's Hospital he became an authority on fevers, but his scientific interests remained wide. He studied the animal fluids involved in digestion, the effects of heat on the body, the applications of chemistry to agriculture and industry, and the gain in weight of metals on calcination, among other problems. His work was highly regarded in his lifetime, but an eccentric lifestyle and a lack of concern for the social graces tended to reduce his standing among medical colleagues. He made no significant discoveries and although his contributions to medical education were important, he has been largely neglected.
Sea lions, greasepaint and the U-boat threat: Admiralty scientists turn to the music hall in 1916
Authors: Wilson D. A. H.
Published: April 2004

Attempts sponsored by the Admiralty's Board of Invention and Research (BIR) to train sea lions as submarine trackers from November 1916 to mid–1917, when there was considerable concern about the depredations of U–boats, involved a unique collaboration between Fellows of The Royal Society and music-hall celebrities. The official establishment, with its scientific advisers and somewhat reluctant naval representatives, met the world of music hall and circus entertainment, when sea lion ‘captains’ were called upon to assist their counterparts in the Royal Navy. Admiralty documents in the Public Record Office indicate that in 1916 Professor W.H. Bragg, F.R.S. of Section II of the BIR had been approached by ‘Captain’ Joseph Woodward, a music–hall sea lion trainer, who recommended his animals as a possible solution to the U–boat menace. Woodward's recommendation was taken seriously, and he was in due course taken on by the BIR as a consultant, provider of sea lions and experimenting participant. Experiments and trials took place in public swimming baths in Glasgow and Westminster, at Lake Bala and finally on the Solent, under the general supervision of Dr E.J. Allen, F.R.S., Director of the Marine Biological Association laboratories in Plymouth, and with the regular participation of Sir Richard Paget, Secretary of Section II, and Woodward's brother, Captain Fred. At first the aim was to train muzzled animals prior to meals to ignore fish alongside them in a tank in favour of an artificial underwater sound, after a conditioned approach to which they would be rewarded with food. Training would then be transferred to open water, using a submarine as the sound and food source, which the animals might learn to follow without the distraction of fish or of sounds other than those associated with submarines. Woodward's work consisted of a successful application of the same principle of conditioned response which Pavlov made quantifiable in his dogs, and the trials themselves represented a very unusual alliance between science and the performing arts.
Book reviews
Authors: reviewers Various
Published: April 2004

Six book reviews in the September 2001 issue of
Notes and Records
. John Archibald Wheeler and Kenneth Ford,
Geons, black holes and quantum foam—a life in physics
. Jon Parkin,
Science, religion and politics in Restoration England: Richard Cumberland's
De Legibus Naturae. Robert A. Hinde,
Why gods persist: a scientific approach to religion
. John Campbell,
Rutherford, scientist supreme
. Jean Medawar and David A. Pyke,
Hitler's gift. Scientists who fled Nazi Germany
. Helge Kragh,
The quantum generations: a history of physics in the twentieth century
.
A Norfolk network within The Royal Society
Authors: Richardson G.
Published: April 2004

The Royal Society in the eighteenth and nineteenth centuries provided a meeting place for the discussion of scientific matters, but many of the men who gathered there were connected outside the Society as friends, relatives, or colleagues. Dawson Turner (F.R.S. 1802) is the central figure in a network of Fellows of the first part of the nineteenth century, men linked by the coincidence of birth in the county of Norfolk. Turner communicated widely with people of his own locality, and with those who shared his botanical, antiquarian and artistic interests. Among these were Sir Astley Cooper (F.R.S. 1802), Sir James Edward Smith (F.R.S. 1785) and Sir William Jackson Hooker (F.R.S. 1812), each of whom achieved significantly greater notability in their chosen field than did Turner himself. Each in turn can also be placed within his own network of acquaintances within The Royal Society. Although apparently arbitrary, the connection of locality exemplifies the influence of existing relationships on the election of new Fellows, explaining links between Fellows with differing scientific interests and demonstrating how Fellows in the same field interacted outside the confines of The Royal Society. Finally, it presents a picture of how The Royal Society's meetings in London were mirrored throughout the provinces.
Schoolmaster-Fellows and the campaign for science education
Authors: Pippard B.
Published: April 2004

Until the middle of the nineteenth century, English schools and universities had little interest in science despite a growing awareness of industry's grave need for new ideas. Reform began in a few independent schools and was driven by a limited number of enthusiasts, who often went from their schools to be professors and to extend the process, especially in newly founded universities. The initial phase, lasting about 30 years, involved some two dozen schoolmasters, often self–educated, whose activities in teaching and research earned their election to the Fellowship. It is this group that forms the subject of the article.
Two Oxford science professors, F. Soddy and J. S. E. Townsend
Authors: Bleaney B.
Published: April 2004

A light–hearted account is given of incidents in the lives of Frederick Soddy, Nobel laureate in Chemistry 1921, and Dr Lee's Professor of Chemistry in Oxford, 1919–1936, together with Sir John Townsend, Wykeham Professor of Physics in Oxford, 1900–1941.
Book reviews
Authors: reviewers Various
Published: April 2004

Ten book reviews in the January 2002 issue of
Notes and Records
: Frances Ashcroft,
Life at the extremes: the science of survival
.
Rethinking the Scientific Revolution
, edited by Margaret J. Osler. Abraham Pais,
The genius of science. A portrait gallery of twentieth-century physicists
. Elly Dekker,
Globes at Greenwich
. John D. Barrow,
The book of nothing
. Adam Hart-Davis,
Chain reactions: pioneers of British science and technology and the stories that link them
.
Newton and religion: context, nature, and influence
, edited by James E. Force and Richard H. Popkin. Roy M. MacLeod,
The
‘creed of science’
in Victorian England
. R. A. Fortey, F.R.S.,
Trilobite! Eyewitness to evolution
. Owen Beattie and John Geiger,
Frozen in time: the fate of the Franklin expedition
.