bluuebunny/crossref_metadata_2025 huggingface dataset:
Private Enforcement of Corporate Law: An Empirical Comparison of the United Kingdom and the United States
Authors: Armour John , Black Bernard , Cheffins Brian , Nolan Richard
Published: December 2009

It is often assumed that strong securities markets require good legal protection of minority shareholders. This implies both “good” law—principally, corporate and securities law—and enforcement, yet there has been little empirical analysis of enforcement. We study private enforcement of corporate law in two common‐law jurisdictions with highly developed stock markets, the United Kingdom and the United States, examining how often directors of publicly traded companies are sued, and the nature and outcomes of those suits. We find, based a comprehensive search for filings over 2004–2006, that lawsuits against directors of public companies alleging breach of duty are nearly nonexistent in the United Kingdom. The United States is more litigious, but we still find, based on a nationwide search of court decisions between 2000–2007, that only a small percentage of public companies face a lawsuit against directors alleging a breach of duty that is sufficiently contentious to result in a reported judicial opinion, and a substantial fraction of these cases are dismissed. We examine possible substitutes in the United Kingdom for formal private enforcement of corporate law and find some evidence of substitutes, especially for takeover litigation. Nonetheless, our results suggest that formal private enforcement of corporate law is less central to strong securities markets than might be anticipated.
‘When will I see you again?’ Using local recurrence data to develop a regimen for routine surveillance in post‐treatment head and neck cancer patients
Authors: Lester S.E. , Wight R.G.
Published: December 2009

Objective:  To develop an evidence‐based regimen for routine surveillance of post‐treatment head and neck cancer patients.

Design:  Review of 10 years of prospectively collected patient data.

Main outcome measures:  Time of first presentation of ‘new cancer event’ (either first recurrence or second primary tumour). We did not evaluate whether or not the detected new cancer events were curable.

Results:  Data from patients with primary squamous cell carcinoma of the larynx, oropharynx and hypopharynx were analysed. A total of 676 previously undiagnosed squamous cell carcinomas were recorded in these regions. In these patients there were 105 recurrences and 20 second primary cancers were recorded; 95th percentile of “time to a new cancer event” was calculated in years. These were for larynx 4.7 years, oropharynx 2.7 years, hypopharynx 2.3 years. The time to new cancer event was similar for early and late laryngeal cancers. Only 36 (47%) of the hypopharyngeal cancers were treated with curative intent and of these 36% had a previously undiagnosed cancer event.

Conclusion:  Local data and published evidence support a follow‐up duration of 7 years for laryngeal primaries and 3 years for both oropharyngeal and hypopharyngeal primaries. Late stage oropharyngeal cancers may require longer follow up than early cancers. Patients who continue to smoke may need longer follow up. A change in local follow‐up protocol to this regimen would save 10 patient slots every week with no detriment to patient care.

Clin. Otolaryngol. 2009, 34, 546–551.
Patterns of hearing loss in tympanic membrane perforation resulting from physical blow to the ear: a prospective controlled cohort study
Authors: Orji F.T. , Agu C.C.
Published: December 2009

Objectives:  To evaluate the incidence and pattern of hearing loss in non‐explosive blast injury of the ear.

Study design:  Prospective clinical study.

Setting:  Tertiary referral centre.

Participants:  Consecutive patients who suffered physical blow to the ear resulting in tympanic membrane perforations without history of previous middle ear disease.

Main outcome measures:  Incidence of conductive and sensorineural hearing loss, extent of air–bone gap versus size and site of perforation, post‐healing hearing loss recovery.

Results:  Fifty‐one patients, 31 males (61%) and 20 females (39%) aged 10–56 years, were recruited over a 30 month study period. The prevalence of hearing loss was significantly more in the injured ears than contralateral normal ears (χ2 = 76.26; P = 0.000). Pure conductive hearing loss occurred in 39%, while 28% (14 patients) had mixed hearing loss. Three patterns of sensorineural loss were observed: dip involving several adjacent high frequencies, a dip in a single frequency, and two separate dips involving low and high frequencies. The extent of air–bone gap correlated with the size of perforation (r = 0.33; P = 0.01). Ears that sustained small tympanic membrane perforation showed significantly small average air–bone gap (t = 2.97; P = 0.005). The mean air–bone gap difference between the anterior and posterior perforations was not significant (t = 1.7; P = 0.09). Closure of air bone gap following healing was significant (t = 15.08; P < 0.01), while recovery of bone conduction abnormality was less favourable.

Conclusion:  Conductive hearing loss occurring in the speech frequencies was the most common form of hearing loss in this group of patients with non‐explosive blast injury to the ear. The accompanying sensorineural loss mostly affected several adjacent high frequencies. Healing of perforation favoured significant recovery of the conductive loss, but recovery of sensorineural loss was less favourable.

Clin. Otolaryngol. 2009, 34, 526–532.
Base of skull recurrences after treatment of salivary gland cancer with perineural invasion reduced by postoperative radiotherapy
Authors: Chen A.M. , Garcia J. , Granchi P. , Bucci M.K. , Lee N.Y.
Published: December 2009

Objectives:  To determine the effect of postoperative radiation therapy for salivary gland carcinomas in the presence of microscopic perineural invasion.

Design and setting:  Retrospective review at an academic tertiary center.

Participants:  One hundred and forty patients with pathological evidence of perineural invasion at the time of initial surgery for salivary gland carcinomas were analysed. Sixteen patients (11%) had major (named) nerve involvement. Ninety‐four patients (67%) received postoperative radiation therapy to the primary site, and the portal films of 65 of these patients were available for review.

Main outcome measures:  The incidence of skull base recurrences among patients treated by surgery with or without postoperative radiation therapy.

Results:  Ten patients experienced skull base recurrences. T4 disease and the omission of postoperative radiation therapy were identified as significant predictors of skull base recurrence. Postoperative radiation therapy reduced the actuarial probability of skull base recurrence from 15% to 5% (P = 0.03). The crude rates of skull base recurrence were 6% (2/35) and 10% (3/30), respectively, for patients whose skull base were and were not confirmed to be encompassed in the irradiation field. The 5‐year overall survival for patients who experienced a skull base recurrence was 19% compared to 91% for those who did not (P < 0.001).

Conclusion:  The use of postoperative radiation therapy significantly reduced the incidence of skull base recurrence among salivary gland carcinoma patients with perineural invasion.

Clin. Otolaryngol. 2009, 34, 539–545.
Correlation between subjective and objective evaluation of the nasal airway. A systematic review of the highest level of evidence
Authors: André R.F. , Vuyk H.D. , Ahmed A. , Graamans K. , Nolst Trenité G.J.
Published: December 2009

Background:  There is no consensus about the value of objective measurements of nasal patency.

Objective:  To assess the correlation between the subjective sense of nasal patency and the outcomes found with rhinomanometry and acoustic rhinometry.

Type of review:  Structured literature search.

Search strategy and evaluation method:  Review of English‐language articles in which correlations were sought between subjective nasal patency symptoms and objective scores as found with rhinomanometry [nasal airway resistance (NAR)] and acoustic rhinometry [minimal cross‐sectional area (MCA)]. Correlations were related to unilateral or combined assessment of nasal passages and to symptomatic nasal obstruction or unobstructed nasal breathing.

Results:  Sixteen studies with a level of evidence II‐a or II‐b fit the inclusion criteria and were further analysed. Almost every possible combination of correlations or lack thereof in relation to the variables included was found. However, when obstructive symptoms were present, a correlation between the patency symptoms with nasal airway resistance and minimal crosssectional area was found more often than in the absence of symptoms. In cases of bilateral assessment a correlation was found almost as often as it was not between patency symptoms and total nasal airway resistance or combined minimal crosssectional areas, while in the limited amount of studies in which unilateral assessment was done a correlation was found each time between patency symptoms and nasal airway resistance.

Conclusions:  The correlation between the outcomes found with rhinomanometry and acoustic rhinometry and an individual’s subjective sensation of nasal patency remains uncertain. Based on this review, it seems that the chance of a correlation is greater when each nasal passage is assessed individually and when obstructive symptoms are present. There still seems to be only a limited argument for the use of rhinomanometry or acoustic rhinometry in routine rhinologic practice or for quantifying surgical results.

Clin. Otolaryngol. 2009, 34, 518–525.
The Course of Dyadic Adjustment and Depressive Symptoms During and After Couples Therapy: A Prospective Follow‐up Study of Inpatient Treatment
Authors: Tilden Terje , Gude Tore , Hoffart Asle
Published: December 2009

A clinical sample of adult patients suffering from relational distress and concurrent psychiatric symptoms was followed from admission, through residential couple therapy, to 1‐year follow‐up. At follow‐up, 9.8% were separated. The remaining couples showed significant improvement in dyadic adjustment at posttreatment. However, at 1‐year follow‐up, a subgroup of 25% of the positive treatment responders had deteriorated to below their admission levels of dyadic adjustment. Contrary to expectation, the deteriorated group had showed significantly less distress both in depressive symptoms and in one early maladaptive schema domain—Impaired Autonomy—at admission, when compared with the rest of the sample, which suggests the need for further research and possible replication in this area.
Temporal patterns in the size of conservation land transactions
Authors: Davies Zoe G. , Kareiva Peter , Armsworth Paul R.
Published: December 2009

The full or partial acquisition of land remains a predominant focus of terrestrial conservation strategies. Non‐governmental organizations play an important role in habitat protection, yet few studies investigate their contribution to conservation investment. Here we examine temporal trends in the size of land transactions made by the world's largest land trust, The Nature Conservancy (TNC). We consider three dimensions of deal size (area, upfront cost, and relative cost per hectare) for two commonly used conservation approaches (fee simple acquisitions and conservation easements). Mean area of protected land parcels has been robust to the growing subdivision of properties for sale. Variation in the area and cost of transactions ranged between six and eight orders of magnitude, and increased through time as TNC undertook occasional large deals once established. Conservation planning approaches need to better account for the variation in deal sizes, and how this may change in response to dynamic budgets and priorities.
The relative contributions of changes in yield and land area to increasing crop output
Authors: LYWOOD WARWICK , PINKNEY JOHN , COCKERILL SAM
Published: December 2009

Global average yields of the world's main food crops have increased over the past 50 years, and these yield increases have varied over time. For most crops, yields have grown significantly faster during periods of higher demand growth, and the contribution of yield growth to output growth has varied between crops. These variations reflect the range of measures available to growers to enhance yields of each crop, which are typically not fully deployed during periods of low demand growth and low relative price. This paper applies two methods using consistent, long‐term historic relationships to demonstrate that crop yield, area and price changes are not independent, and that area changes and yield changes in response to market signals are different for different crops and regions. One of these methods is used to show the expected percentages of exogenous estimates of overall demand growth that will be met by yield growth and by land use change for a range of biofuel crops. The estimated percentage of incremental output growth delivered by yield growth is 78% for EU cereals, with the remainder being met by area growth.
Alternative Policy Responses to the Global Financial Crisis
Authors: Valentine Tom
Published: December 2009

Governments have reacted to the economic slowdown arising from the Global Financial Crisis by injecting a fiscal stimulus into their economies. This policy will be ineffective when the country has a floating exchange rate, because the resulting inflow of funds will cause the exchange rate to appreciate, offsetting the stimulus effect. The experience of the Great Depression has suggested a better package of policies to deal with a global slowdown.
The Global Financial Crisis of 2007–2009 – An Australian Perspective*
Authors: Eslake Saul
Published: December 2009

The global financial crisis was not wholly caused by ‘greed’ or ‘market fundamentalism’ but had many causes. Fortunately, governments and central banks have absorbed the lessons of mistakes made in the 1930s. Australian policy responses to the crisis have been particularly effective, although we cannot afford to be complacent.
The Runners-Up
Authors:   The News Staff
Published: December 2009

This year's runners-up for Breakthrough of the Year include new gamma-ray observations, the long-sought receptor for a key plant hormone, mock monopoles, a drug that increases life span, ice on the moon, gene-therapy successes, insights into the properties of graphene and how to use it to make novel devices, Hubble's rebirth, and the first x-ray laser.
Spineless Fish and Dark Flies Prove Gene Regulation Crucial
Authors: Pennisi Elizabeth
Published: December 2009

On page
1663
of this week's issue of
Science
and in

last week's
Science
Express

, two teams independently report that changes in regulatory DNA were responsible for an adaptation in natural populations of fish and insects. Each group has also pieced together details of the underlying genetic alterations in those animals.
Protection from Hemoglobin's Dark Side
Authors: Kelner Katrina L.
Published: December 2009

A naturally occurring protein that binds hemoglobin protects the brain from damage after a bleeding stroke, offering a potential therapeutic approach.
Cellular Immune Responses of Preterm Infants after Vaccination with Whole-Cell or Acellular Pertussis Vaccines
Authors: Vermeulen Françoise , Verscheure Virginie , Damis Eliane , Vermeylen Danièle , Leloux Gaëlle , Dirix Violette , Locht Camille , Mascart Françoise
Published: December 2009

Based on studies reporting specific antibody titers, it is recommended to vaccinate preterm infants againstBordetella pertussisaccording to their chronological age. However, as specific T-cell responses also are involved in the protection againstB. pertussis, we have determined whether highly preterm infants (<31 weeks) are able to mount these immune responses during vaccination. Forty-eight premature infants were vaccinated at 2, 3, and 4 months of their chronological age with an acellular (Pa;n= 24) or a whole-cell (Pw;n= 24) tetravalent diphtheria-tetanus-pertussis-polio vaccine, and blood samples were collected at 2, 3, and 6 months of age. Most of the Pa- and Pw-vaccinated infants developed at 3 or 6 months of age a gamma interferon (IFN-γ) response to theB. pertussisantigens, accompanied by an interleukin-5 (IL-5) and IL-13 secretion for the Pa-vaccinated infants. No association was found between a very low infant birth weight, the occurrence of severe infections, and corticosteroid treatment or the administration of gammaglobulins with a low level of antigen-induced IFN-γ secretion. We conclude that like full-term infants, most preterm infants are able to mount a specific cellular immune response to the administration of the first doses of an acellular or a whole-cell pertussis vaccine.
Rational Design and Evaluation of a Multiepitope Chimeric Fusion Protein with the Potential for Leprosy Diagnosis
Authors: Duthie Malcolm S. , Hay Marah N. , Morales Cecile Z. , Carter Lauren , Mohamath Raodoh , Ito Lucia , Oyafuso Luiza K. M. , Manini Marli I. P. , Balagon Marivic V. , Tan Esterlina V. , Saunderson Paul R. , Reed Steven G. , Carter Darrick
Published: December 2009

Despite the reduction in the number of leprosy cases registered worldwide as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains stable in many countries. This indicates that
Mycobacterium leprae
, the causative agent of leprosy, is still being transmitted and that, without an earlier diagnosis, transmission will continue and infection will remain a health problem. The current means of diagnosis of leprosy is based on the appearance of clinical symptoms, which in many cases occur after significant and irreversible nerve damage has occurred. Our recent work identified several recombinant antigens that are specifically recognized by leprosy patients. The goal of the present study was to produce and validate the reactivity of a chimeric fusion protein that possesses the antibody binding properties of several of these proteins. The availability of such a chimeric fusion protein will simplify future test development and reduce production costs. We first identified the antibody binding regions within our top five antigen candidates by performing enzyme-linked immunosorbent assays with overlapping peptides representing the amino acid sequences of each protein. Having identified these regions, we generated a fusion construct of these components (protein advances diagnostic of leprosy [PADL]) and demonstrated that the PADL protein retains the antibody reactivity of the component antigens. PADL was able to complement a protein that we previously produced (the leprosy IDRI [Infectious Disease Research Institute] diagnostic 1 [LID-1] protein) to permit the improved diagnosis of multibacillary leprosy and that had a good ability to discriminate patients with multibacillary leprosy from control individuals. A serological diagnostic test consisting of these antigens could be applied within leprosy control programs to reduce transmission and to limit the appearance of leprosy-associated disabilities and stigmatizing deformities by directing treatment.
Molecular Evidence of Persistent Epidemic and Evolution of Subgenotype B1 Coxsackievirus A16-Associated Hand, Foot, and Mouth Disease in China
Authors: Zhang Yong , Wang Dongyan , Yan Dongmei , Zhu Shuangli , Liu Jianfeng , Wang Haiyan , Zhao Shengcang , Yu Deshan , Nan Lijuan , An Junjing , Chen Li , An Hongqiu , Xu Aiqiang , Xu Wenbo
Published: December 2009

The molecular epidemiology of CVA16 in China between 1999 and 2008 reflects a pattern of endemic cocirculation of clusters B1a and B1b within subgenotype B1 viruses. The annual evolution rate of CVA16 was estimated as approximately 0.91 × 10−2substitutions per synonymous nucleotide/year and is slightly lower than that of HEV71.
ICP27 Phosphorylation Site Mutants Display Altered Functional Interactions with Cellular Export Factors Aly/REF and TAP/NXF1 but Are Able To Bind Herpes Simplex Virus 1 RNA
Authors: Corbin-Lickfett Kara A. , Rojas Santos , Li Ling , Cocco Melanie J. , Sandri-Goldin Rozanne M.
Published: December 2009

Herpes simplex virus 1 (HSV-1) protein ICP27 is a multifunctional regulatory protein that is phosphorylated. Phosphorylation can affect protein localization, protein interactions, and protein function. The major sites of ICP27 that are phosphorylated are serine residues 16 and 18, within a CK2 site adjacent to a leucine-rich region required for ICP27 export, and serine 114, within a PKA site in the nuclear localization signal. Viral mutants bearing serine-to-alanine or glutamic acid substitutions at these sites are defective in viral replication and gene expression. To determine which interactions of ICP27 are impaired, we analyzed the subcellular localization of ICP27 and its colocalization with cellular RNA export factors Aly/REF and TAP/NXF1. In cells infected with phosphorylation site mutants, ICP27 was confined to the nucleus even at very late times after infection. ICP27 did not colocalize with Aly/REF or TAP/NXF1, and overexpression of TAP/NXF1 did not promote the export of ICP27 to the cytoplasm. However,
in vitro
binding experiments showed that mutant ICP27 was able to bind to the same RNA substrates as the wild type. Nuclear magnetic resonance (NMR) analysis of the N terminus of ICP27 from amino acids 1 to 160, compared to mutants with triple substitutions to alanine or glutamic acid, showed that the mutations affected the overall conformation of the N terminus, such that mutant ICP27 was more flexible and unfolded. These results indicate that these changes in the structure of ICP27 altered
in vivo
protein interactions that occur in the N terminus but did not prevent RNA binding.
Novel Functions of the Alphavirus Nonstructural Protein nsP3 C-Terminal Region
Authors: Varjak Margus , Žusinaite Eva , Merits Andres
Published: December 2009

The functions of the alphavirus-encoded nonstructural protein nsP3 during infection are poorly understood. In contrast, nsP1, nsP2, and nsP4 have known enzymatic activities and functions. A functional analysis of the C-terminal region of nsP3 of Semliki Forest virus revealed the presence of a degradation signal that overlaps with a sequence element located between nsP3 and nsP4 that is required for proteolytic processing. This element was responsible for the short half-life (1 h) of individually expressed nsP3, and it also was functionally transferable to other proteins. Inducible cell lines were used to express native nsP3 or truncated mutants. The removal of 10 C-terminal amino acid (aa) residues from nsP3 increased the half-life of the protein approximately 8-fold. While the deletion of 30 C-terminal aa residues resulted in a similar stabilization, this deletion also changed the cellular localization of nsP3. This truncated mutant no longer exhibited a punctate localization in the cytoplasm, but instead filamentous stretches could be formed around the nuclei of induced cells, suggesting the existence of an additional functional element upstream of the degradation signal. C-terminally truncated uncleavable polyprotein P12
CA
3del30 was localized diffusely, which is in contrast to P12
CA
3, which is known to be associated with vesicle membranes. The induction of nsP3 or its truncated forms reduced the efficiency of virus multiplication in corresponding cells by affecting different steps of the infection cycle. The expression of nsP3 or a mutant lacking the 10 C-terminal aa residues repressed the establishment of infection, while the expression of nsP3 lacking 30 C-terminal aa residues led to the reduced synthesis of subgenomic RNA.
Testing the Balanced Electrostatic Interaction Hypothesis of Hepatitis B Virus DNA Synthesis by Using an
In Vivo
Charge Rebalance Approach
Authors: Chua Pong Kian , Tang Fan-Mei , Huang Jyuan-Yuan , Suen Ching-Shu , Shih Chiaho
Published: December 2009

Previously, a charge balance hypothesis was proposed to explain hepatitis B virus (HBV) capsid stability, assembly, RNA encapsidation, and DNA replication. This hypothesis emphasized the importance of a balanced electrostatic interaction between the positive charge from the arginine-rich domain (ARD) of the core protein (HBc) and the negative charge from the encapsidated nucleic acid. It remains unclear if any of the negative charge involved in this electrostatic interaction could come from the HBc protein
per se
, in addition to the encapsidated nucleic acid. HBc ARD IV mutant 173GG and ARD II mutant 173RR/R157A/R158A are arginine deficient and replication defective. Not surprisingly, the replication defect of ARD IV mutant 173GG can be rescued by restoring positively charged amino acids at the adjacent positions 174 and 175. However, most interestingly, it can be at least partially rescued by reducing negatively charged residues in the assembly domain, such as by glutamic acid-to-alanine (E-to-A) substitutions at position 46 or 117 and to a much lesser extent at position 113. Similar results were obtained for ARD II mutant 173RR/R157A/R158A. These amino acids are located on the inner surfaces of HBc icosahedral particles, and their acidic side chains point toward the capsid interior. For HBV DNA synthesis, the relative amount of positive versus negative charge in the electrostatic interactions is more important than the absolute amount of positive or negative charge. These results support the concept that balanced electrostatic interaction is important during the viral life cycle.
Inhibition of Sterol Biosynthesis Reduces Tombusvirus Replication in Yeast and Plants
Authors: Sharma Monika , Sasvari Zsuzsanna , Nagy Peter D.
Published: December 2009

The replication of plus-strand RNA viruses depends on subcellular membranes. Recent genome-wide screens have revealed that the sterol biosynthesis genes
ERG25
and
ERG4
affected the replication of
Tomato bushy stunt virus
(TBSV) in a yeast model host. To further our understanding of the role of sterols in TBSV replication, we demonstrate that the downregulation of
ERG25
or the inhibition of the activity of
Erg25p
with an inhibitor (6-amino-2-
n
-pentylthiobenzothiazole; APB) leads to a 3- to 5-fold reduction in TBSV replication in yeast. In addition, the sterol biosynthesis inhibitor lovastatin reduced TBSV replication by 4-fold, confirming the importance of sterols in viral replication. We also show reduced stability for the p92
pol
viral replication protein as well as a decrease in the
in vitro
activity of the tombusvirus replicase when isolated from APB-treated yeast. Moreover, APB treatment inhibits TBSV RNA accumulation in plant protoplasts and in
Nicotiana benthamiana
leaves. The inhibitory effect of APB on TBSV replication can be complemented by exogenous stigmasterol, the main plant sterol, suggesting that sterols are required for TBSV replication. The silencing of
SMO1
and
SMO2
genes, which are orthologs of
ERG25
, in
N. benthamiana
reduced TBSV RNA accumulation but had a lesser inhibitory effect on the unrelated
Tobacco mosaic virus
, suggesting that various viruses show different levels of dependence on sterol biosynthesis for their replication.
Role of Untranslated Regions in Regulation of Gene Expression, Replication, and Pathogenicity of Newcastle Disease Virus Expressing Green Fluorescent Protein
Authors: Kim Shin-Hee , Samal Siba K.
Published: December 2009

To gain insight into the role of untranslated regions (UTRs) in regulation of foreign gene expression, replication, and pathogenicity of Newcastle disease virus (NDV), a green fluorescent protein (GFP) gene flanked by 5′ and 3′ UTRs of each NDV gene was individually expressed by recombinant NDVs. UTRs of each gene modulated GFP expression positively or negatively. In particular, UTRs of the M and F genes enhanced levels of GFP expression at the junction of the P and M genes without altering replication of NDV, suggesting that UTRs could be used for enhanced expression of a foreign gene by NDV.
Stability of Murine Cytomegalovirus Genome after
In Vitro
and
In Vivo
Passage
Authors: Cheng Tammy P. , Valentine Mark C. , Gao Jian , Pingel Jeanette T. , Yokoyama Wayne M.
Published: December 2009

While large DNA viruses are thought to have low mutation rates, only a small fraction of their genomes have been analyzed at the single-nucleotide level. Here, we defined the genetic stability of murine cytomegalovirus (MCMV) by whole-genome sequencing. Independently assembled sequences of three sister plaques showed only two single-base-pair substitutions after
in vitro
passage.
In vivo
-passaged MCMV likewise demonstrated low mutation rates, comparable to those after
in vitro
passage, indicating high genome stability of MCMV at the single-nucleotide level in the absence of obvious selection pressure.
HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes
Authors: Nobile Cinzia , Rudnicka Dominika , Hasan Milena , Aulner Nathalie , Porrot Françoise , Machu Christophe , Renaud Olivier , Prévost Marie-Christine , Hivroz Claire , Schwartz Olivier , Sol-Foulon Nathalie
Published: December 2009

The HIV-1 Nef protein is a pathogenic factor modulating the behavior of infected cells. Nef induces actin cytoskeleton changes and impairs cell migration toward chemokines. We further characterized the morphology, cytoskeleton dynamics, and motility of HIV-1-infected lymphocytes. By using scanning electron microscopy, confocal immunofluorescence microscopy, and ImageStream technology, which combines flow cytometry and automated imaging, we report that HIV-1 induces a characteristic remodeling of the actin cytoskeleton. In infected lymphocytes, ruffle formation is inhibited, whereas long, thin filopodium-like protrusions are induced. Cells infected with HIV withnefdeleted display a normal phenotype, and Nef expression alone, in the absence of other viral proteins, induces morphological changes. We also used an innovative imaging system to immobilize and visualize living individual cells in suspension. When combined with confocal “axial tomography,” this technique greatly enhances three-dimensional optical resolution. With this technique, we confirmed the induction of long filopodium-like structures in unfixed Nef-expressing lymphocytes. The cytoskeleton reorganization induced by Nef is associated with an important impairment of cell movements. The adhesion and spreading of infected cells to fibronectin, their spontaneous motility, and their migration toward chemokines (CXCL12, CCL3, and CCL19) were all significantly decreased. Therefore, Nef induces complex effects on the lymphocyte actin cytoskeleton and cellular morphology, which likely impacts the capacity of infected cells to circulate and to encounter and communicate with bystander cells.
A CHEMICAL PROCEDURE FOR DETERMINATION OF THE C14-DISTRIBUTION IN LABELLEDD-FRUCTOSE AND OTHER KETOSES
Authors: Brice Carol , Perlin A. S.
Published: December 2009

A procedure is described for determining the activity of the individual carbon atoms in D-fructose labelled with C14, which is suitable for as little as 1 millimole of the sugar. The D-fructose is degraded by lead tetraacetate oxidation and the product is hydrolyzed to glycolic acid, formic acid, and D-glyceraldehyde. Glycolic acid is oxidized to formaldehyde (carbon-1) and carbon dioxide (carbon-2), and formic acid to carbon dioxide (carbon-3). D-Glyceraldehyde is degraded to carbon dioxide (carbons-4 and -5, combined) and formaldehyde (carbon-6); after reduction of a second portion of the D-glyceraldehyde to glycerol, the degradation products obtained are carbon dioxide (carbon-5) and formaldehyde (carbons-4 and -6, combined). The activity of carbon-1, -2, -3, -5, or -6 is thus determined directly, and of carbon-4 by difference in two ways. The procedure should also be applicable to C14-labelled L-sorbose. Lead tetraacetate oxidation of sedoheptulose followed by hydrolysis yields glycolic acid, formic acid, and D-erythrose. These three fragments are degraded in turn to afford a method for partial determination of the C14-distribution in samples of this important heptulose.
ADIPSIA PRODUCED BY HYPOTHALAMIC LESIONS IN THE RAT
Authors: Montemurro D. G. , Stevenson J. A. F.
Published: December 2009

With the use of the Horsley–Clarke stereotaxic instrument, bilateral electrolytic lesions were placed in the lateral hypothalamic areas of female Sprague–Dawley rats. Changes in food and water intake and body weight were correlated with the histological localization of the lesions. Rats with large lesions in the frontal plane of the middle of the tuber cinereum died within a week of the operation. Food and water administered by stomach tube did not prevent weight loss and death.Two rats developed adipsia which lasted 13 and 16 days respectively; 10 ml. of tap water per day by stomach tube resulted in increases in food intake and body weight during the period of adipsia. These rats had lesions in the lateral hypothalamic areas in the frontal plane of the middle of the tuber cinereum, but these were small and relatively asymmetrical.Another rat refused water from the time of operation until sacrifice (55 days). Administration of 20 ml. per day of tap water caused an increase in food intake and body weight, and a general improvement. Whenever intake of water was not imposed by stomach tube, however, the food intake dropped and body weight was lost. This animal failed to drink spontaneously. The lesions in this animal were more symmetrical, slightly more dorsal, and about 0.75 mm. more posterior than those which produced temporary adipsia. In the rat, an area essential to the regulation of voluntary consumption of water appears to be located in the lateral hypothalamic areas at about the plane of the posterior ventromedial nuclei and the anterior border of the premammillary nuclei.
ON THE ANTIGENICITY OF INSULIN
Authors: Moloney P. J. , Goldsmith L.
Published: December 2009

On the basis of body weight, mice showed a higher percentage survival to large doses of insulin than did rabbits and these in turn were more resistant to insulin than guinea pigs. Antibodies to insulin were induced in five species of animals. Anti-insulins produced by the guinea pig, rabbit, sheep, and horse can each neutralize insulin extracted from the pancreas of the rabbit, sheep, horse, pig, ox, and monkey (Macacus rhesus), but none of the four can neutralize insulin extracted from guinea-pig pancreas. Guinea-pig anti-insulin can neutralize endogenous mouse insulin; horse anti-insulin cannot. The problem of the relative effectiveness of insulin as an antigen is discussed.
STUDIES ON ALDOSTERONE: II. HYPERTENSION AS A CUMULATIVE EFFECT OF ALDOSTERONE ADMINISTRATION
Authors: Kumar D. , Hall A. E. D. , Nakashima R. , Gornall A. G.
Published: December 2009

Aldosterone has been injected subcutaneously into young rats in doses of 0.5 μg. per 48 hours and later 1.0 μg. per 24 hours. After 6–12 weeks a rise in blood pressure was noted which in about 5 or 6 months reached a maximum averaging 75 mm. above control values. This effect was noted in intact animals on a normal diet and was the same for either dose employed. The drinking of 1% saline instead of water had no significant effect on the result. In adrenalectomized rats a similar rise was noted and may have occurred sooner, but this observation requires confirmation. Aldosterone can account for at least part of the syndrome resulting from regeneration of cortical tissue in an enucleated adrenal. Desoxycorticosterone was tested in intact rats at dose levels of 25 μg. per 48 hours or 100 μg. daily and produced a smaller rise in blood pressure than that observed with aldosterone. None of the adrenalectomized rats showed protein in the urine, but one in five of the intact animals developed moderate to marked proteinuria after 1 to 5 months of hypertension. It is suggested that these observations may represent the experimental counterpart of human essential hypertension.
SEASONAL FLUCTUATIONS IN BLOOD VOLUME
Authors: Doupe J. , Ferguson M. H. , Hildes J. A.
Published: December 2009

The plasma volume was measured by T1824 dilution in groups of normal young male subjects at regular intervals over the course of 3 years. The plasma volume increased during the summer and decreased during the winter, but this change was variable from subject to subject and was not as marked during 1 year as during the other 2. Ascorbic acid in daily supplement of 400 mg., taken during the first year of the study, did not influence the plasma volume fluctuations. The red blood cell mass, circulating haemoglobin, and total circulating plasma protein varied in the same way and the mean corpuscular haemoglobin concentration also increased during the summer in 2 of the 3 years. The changes in plasma volume are attributed to the influence of environmental temperature and indicate some degree of seasonal acclimatization. Serial measurements of total body water and extracellular space on a few subjects suggest that the seasonal fluctuation affects mainly the vascular system.
A STUDY OF STEROID COLOR REACTIONS IN STRONG ACID
Authors: Linford J. H.
Published: December 2009

Steroids react with acid reagents to produce compounds possessing intense absorption bands in the visible and ultraviolet spectral regions. These bands have been correlated with the existence of specific chemical groups in the steroid molecule. An attempt has been made to deduce the type of resonant system responsible for the absorption of light, in order to present a unified explanation of this type of steroid color reaction. The results indicate that the steroid nucleus, through induction or resonance effects, permits intercoupling between specific groups at the C3, C11, and C17positions in a particular environment.
A METHOD FOR THE DETECTION OF ATYPICAL FORMS OF HUMAN SERUM CHOLINESTERASE. DETERMINATION OF DIBUCAINE NUMBERS
Authors: Kalow W. , Genest K.
Published: December 2009

Cases with atypical esterase activity were found by determining esterase inhibition in numerous sera. A suitable inhibitor was the local anaesthetic dibucaine (cinchocaine, TN Nupercaine, Perkain). A good discrimination between typical and atypical sera was obtained under the following conditions: The esterase activity of human serum diluted 1:100 was measured with a recording spectrophotometer at 240 mμ. The substrate was 5 × 10−5 M benzoylcholine dissolved in M/15 phosphate buffer, pH 7.4. The concentration of the inhibitor was 10−5 M. With the experimental temperature around 25 °C, the average inhibition of the typical enzyme was 78.8 ± 0.3%. The inhibition of the atypical esterases was less; in rare cases the inhibition was only 16%. For each person, the inhibition characteristics were constant over a period of several months, and independent of the esterase level. The degree of inhibition measured under these conditions and expressed in per cent has been termed "Dibucaine Number".
STUDIES ON WHEAT PLANTS USING C14 COMPOUNDS: III. THE UTILIZATION OF ACETATE FOR AMINO ACID BIOSYNTHESIS
Authors: Bilinski E. , McConnell W. B.
Published: December 2009

Sixteen amino acids were isolated from the gluten of wheat plants, the stems of which had been injected with acetate-1-C14 or -2-C14. With both tracers the C14 labelled amino acids varied markedly from each other in specific activity. Glutamic acid, proline, and arginine were most active, followed by the four-carbon amino acids aspartic acid and threonine, while the short-chain amino acids glycine, alanine, serine, and methionine possessed medium activity. Branched-chain and aromatic amino acids, and the two basic amino acids lysine and histidine were weakly labelled, but showed marked differences from each other not only in specific activity but in the relative amounts of carboxyl and methyl groups of acetate incorporated. Acetate-2-C14 generally gave amino acids of highest activity, but acetate-1-C14 was most effective for labelling glycine, histidine, and serine. Partial degradation by ninhydrin decarboxylation clearly showed that the carboxyl group of acetate tended, in general, to appear to a greater extent in the carboxyl group of amino acids than did the methyl group. Direct incorporation of the carboxyl carbon of acetate in C1 of leucine was observed.
CHEMICAL METHOD FOR THE DETERMINATION OF URINARY ALDOSTERONE
Authors: Nowaczynski Wojciech , Koiw Erich , Genest Jacques
Published: December 2009

A new method of purification of crude neutral extracts of urine for the isolation and determination of aldosterone is presented. The specificity and accuracy of the method depend upon the high degree of purity of the aldosterone isolated. The assertion that the substance isolated is aldosterone is based on the mobilities in the three chromatographic systems used, on the typical ultraviolet absorption curve, on the satisfactory agreement between the values obtained by ultraviolet absorption and by blue tetrazolium reaction, and by the typical chromogen spectra in concentrated sulphuric acid and in 100% phosphoric acid. Values obtained in nine normal subjects on ordinary diets vary from 2.2 to 10 μg. per day with a mean of 5.1. Illustrations of results obtained during pregnancy, anxiety state, and periods of high potassium and combined high sodium and potassium intake are presented.
THE MEASUREMENT OF THE RATE OF BLOOD FLOW IN THE CALF AND PAW OF DOGS BY THE VENOUS OCCLUSION PLETHYSMOGRAPH TECHNIQUE WITH A NOTE ON THE EFFECTS OF INTRAVENOUS ADRENALINE AND NORADRENALINE
Authors: Hatcher J. D. , Jennings D. B.
Published: December 2009

Anatomical and physiological evidence is presented which indicates that venous occlusion Plethysmographic measurements of blood flow in the calf and in the paw of dogs give an index of muscle and skin blood flow respectively.
THE EFFECT OF GROWTH HORMONE ON THE UTILIZATION OF 1-C14OCTANOIC ACID BY RAT LIVER SLICES
Authors: Perry W. F. , Friesen H. G.
Published: December 2009

Young ([Formula: see text] months), adult (4–5 months), and old (2(+) years) rats were injected with growth hormone intraperitoneally in doses of 4 mg./100 g. at various intervals of time before removal of the liver. Slices of liver were incubated with radioactive octanoic acid and the production of CO2and acetoacetic acid measured.In adult rats fed ad libitum, growth hormone injected 4 hours before the rats were killed had no consistent effect on acetoacetic acid or carbon dioxide production by the liver slices. In adult rats fasted 24 hours before they were killed, growth hormone was likewise found to have no effect on ketogenesis and CO2production irrespective of whether it was injected 4, 12, or 24 hours before the rats were killed. Young rats that were fasted 24 hours and to which growth hormone was administered at the 20th hour of fasting showed a slight ketogenesis but the values for the specific activity of the acetoacetic acid suggested the increased ketogenesis was not derived from the labelled fatty acid. No effect on CO2production was noted. In old rats that were fasted 24 hours and to which growth hormone was given at the 20th hour of fasting, a slight decrease in acetoacetic acid formation by the liver slices was observed which appeared to be due to an over-all reduction in fatty acid utilization. There was again no alteration in CO2production. Treatment of adult rats for 5 days with growth hormone, followed by incubation of the liver slices with octanoate, was found to influence neither ketogenesis nor CO2production.
ISOLATION OF LABELLED DEOXYRIBONUCLEIC ACID PHOSPHORUS BY A MODIFIED SCHMIDT AND THANNHAUSER PROCEDURE
Authors: Daoust R. , Hooper Catherine E. Stevens
Published: December 2009

The DNA phosphorus fraction of tissues was isolated by the method of Schmidt and Thannhauser modified so that the DNA phosphorus fraction attains a state of purity satisfactory for studies with radiophosphorus. This procedure was submitted to a series of test experiments. The results suggested that the DNA isolated by the procedure is practically free from contamination by other phosphorus-containing fractions, namely acid-soluble phosphorus, phospholipids, ribonucleic acid, and phosphoproteins. The modified method seems reliable for estimating the specific activity of DNA phosphorus following the administration of radiophosphorus to animals.
THROMBIN PROPERTIES
Authors: Ronwin Edward
Published: December 2009

The enzymatic properties of thrombin have been examined and compared with those of two related enzymes, plasmin and trypsin. The effects of factors such as pH, substrate specificity, ionic strength, cations, anions, and organic reagents on the enzymatic activity of thrombin have been studied. While the three enzymes discussed possess differences, such similarities as were observed are quite striking and permit their classification into one group as tryptic enzymes.
INHIBITION OF WALKER CARCINOMA 256 BY 6-AMINONICOTINAMIDE
Authors: McColl J. D. , Rice W. B. , Adamkiewicz V. W.
Published: December 2009

The nicotinamide antagonist, 6-aminonicotinamide, was administered for 2 days prior to, and for 10 days following, the transplant of a rapidly growing Walker carcinoma 256. At a dose which did not produce pronounced loss of body weight (0.5 mg./kg.), a significant inhibition of the tumor was observed. The degree of inhibition was similar to that obtained with the purine antagonist, 6-mercaptopurine, at a dose of 10 mg./kg.Splenomegalia was also significantly inhibited in those instances where there was an inhibition of tumor dimensions.
AEROBIC AND ANAEROBIC P32LABELLING OF PHOSPHOLIPIDS AND ADENOSINE PHOSPHATES IN HYPOTONIC HOMOGENATES OF RAT BRAIN
Authors: Berry J. F. , McMurray W. C.
Published: December 2009

Under aerobic conditions, a suitably 'reinforced' homogenate of rat brain prepared in distilled water was capable of labelling lipid P, ATP, ADP, and AMP from inorganic P32. The labelling was 'uncoupled' by the addition of DNP. The DNP decreased the specific activity of each of the above compounds and decreased the steady-state concentrations of ATP, with an increase in the concentrations of inorganic P, ADP, and AMP. Fluoride increased the specific activity of the lipid P and the steady-state concentration of ATP. Cyanide decreased the specific activity of lipid P and both the specific activity and the steady-state concentration of ATP.Under anaerobic conditions, the labelling of the lipid P and the adenosine phosphates was as good as that observed in the presence of oxygen. The anaerobic labelling of both lipid P and the adenosine phosphates was less sensitive to DNP or cyanide and more sensitive to iodoacetate than the aerobic labelling. In contrast to the aerobic labelling, the anaerobic labelling was inhibited by fluoride.In most instances, changes in the labelling of lipid P corresponded to those observed for the labelling of ATP. An exception was the labelling of lipid P that occurred under aerobic conditions in the presence of fluoride. Here the specific activity of the lipid P was related to the concentration rather than to the specific activity of ATP.
THE DISTRIBUTION OF RADIOACTIVE CARBON IN THE RAT AFTER THE ADMINISTRATION OF RANDOMLY LABELLED C14-β-CAROTENE
Authors: Willmer J. S. , Laughland D. H.
Published: December 2009

The distribution of C14 has been studied in rats following the oral administration of C14-β-carotene, which is known to be readily converted to vitamin A in the intestine. The rats were maintained in a respiration chamber and individuals removed at various time intervals up to 28 hours after dosing, and the concentration of C14 in tissues was determined. The counts per million per gram of tissue was higher in the adrenal glands and hypophysis than in the other organs examined. The pattern of C14 distribution in intestine, liver, kidneys, and blood appears consistent with current knowledge of the metabolism of vitamin A.