bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive strategies of a warm temperate vespertilionid, the large-footed myotis, Myotis moluccarum (Microchiroptera:Vespertilionidae)
Authors: Lloyd S. , Hall L. S. , Bradley A. J.
Published: January 2006

A population of M. moluccarum, which is known to be
polyoestrous and monotocous, giving birth to two consecutive offspring
annually, was investigated to determine the female reproductive cycle. The
population was visited, and observations recorded, at approximately 5-week
intervals from July 1994 to February 1995. At each visit, 2–4 females
were collected and their reproductive tracts were removed, fixed and processed
for light microscopy. During visits conducted after parturition periods, the
age of the offspring was estimated in order to determine the duration of
parturition.
The two gestation periods of the breeding season were of approximately equal
duration (11.5–12 weeks) despite the initial pregnancy occurring over
much cooler months. While some copulations take place prior to ovulation,
sperm storage is not a necessity, and copulation can occur until the time of
ovulation. First ovulations of the season take place in early August and
although several follicles may mature only one is ovulated. Analysis of
climatic variables indicates that females undergo the first ovulation and
pregnancy of the season during the cooler part of the year whereas lactation
occurs during the warmer, wetter months. A post-partum oestrus occurs soon
after parturition and adult males leave the population before the birth of the
second offspring. Individual variation in the time before the post-partum
oestrus may account for the reduced synchrony noted in the second parturition
period. Monthly changes in the corpus luteum and ovaries are documented.
The reproductive cycle of M. moluccarum resembles most
closely that of tropical and sub-tropical vespertilionids; however,
pre-ovulatory copulation, a short period of sperm storage and the development
of typical over-wintering follicles (aspects of reproduction seen in species
from cooler climates) remain inherent in the large-footed myotis.
Home-range fidelity in the Australian sleepy lizard, Tiliqua rugosa
Authors: Bull C. Michael , Freake Michael J.
Published: January 2006

A study was conducted at a semi-arid site near Mt Mary, South Australia.
Fifty-eight adult sleepy lizards, Tiliqua rugosa, were
radio-tagged and regularly located over the spring season, when they are most
active, for 2-5 years. Home-range area did not differ between males and
females. Changes in home-range position between years were assessed by the
distance between home-range centres measured at intervals of one, two, three
or four years. Mean distances for successive years were less than the span of
the home range in one year. The distance did not differ between sexes, it was
not related to lizard size, nor did it increase with increased time interval.
This implies that for the resident adult population, lizards retain their home
ranges for at least five years, and that the sexes do not differ in their
fidelity to home range.
Standard metabolic rates of three nectarivorous meliphagid passerine birds
Authors: Vitali S. D. , Withers P. C. , Richardson K. C.
Published: January 2006

Standard metabolic rate (VO2 STD) was determined for
three species of passerine bird from the family Meliphagidae to investigate
the possible effect of nectarivory on standard metabolic rate in this family.
The three species that we investigated did not show a significant departure
from allometric predictions of standard metabolic rate for passerine species.
Disparities between standard metabolic rate for meliphagids in the present
study and previous data appear to reflect methodological differences, and no
general allometric relationship is apparent for meliphagids at present. In
meliphagids, nectarivory per se is not an important
correlate with standard metabolic rate. Data from additional meliphagid
species, collected under standardised conditions, are required to confirm the
generality of the findings of the present study, that nectarivorous
meliphagids have a standard metabolic rate typical of passerine birds.
Demography and social organisation of the red-winged fairy-wren, Malurus elegans
Authors: Russell Eleanor , Rowley Ian
Published: January 2006

The red-winged fairy-wren, Malurus elegans, is endemic
to the high-rainfall region of south-western Australia. We studied it in
Eucalyptus diversicolor (karri) forest near Manjimup,
Western Australia from 1980 to 1995. After a detailed study of breeding
biology during 1980–86, we monitored dispersal and survival in known
groups during 1987–95. M. elegans bred
cooperatively, with 83% of groups (mean size 4.1) including one or more
non-breeding males or females that helped to rear young and defend the
territory. Survival of breeding adults (78%) and helper males
(76%) was high. Territories and groups persisted from year to year,
even though one or other of the breeding pair was replaced. Most known
dispersals were to a group only 1–2 territories distant. Dispersal was
female-biased, mostly in their third or fourth year. A behaviour not recorded
in other Malurus spp. was that some birds, chiefly
females, joined groups as helpers. The feeding rate of nestlings was not
related to group size, but in larger groups the share of work done by the
breeding female decreased. Helpers did not enhance the survival of breeding
females, and had little overall effect on the production of fledglings.
Females produced a mean of 2.4 fledglings, 1.8 independent young and 1.1
yearlings per year; survival of fledglings to the start of the following
breeding season was44.2% (31–61%). We argue that the high
levels of adult and juvenile survival influence many aspects of the social
system in M. elegans, such as large groups, the presence
of female helpers, occurrence of immigrant helpers and delayed dispersal. We
suggest that an important benefit of delayed dispersal and group living is in
promoting the survival of young birds, and increasing their chance of
acquiring a territory.
Spread dynamics of invasive species
Authors: Arim Matías , Abades Sebastián R. , Neill Paula E. , Lima Mauricio , Marquet Pablo A.
Published: December 2005

Species invasions are a principal component of global change, causing large losses in biodiversity as well as economic damage. Invasion theory attempts to understand and predict invasion success and patterns of spread. However, there is no consensus regarding which species or community attributes enhance invader success or explain spread dynamics. Experimental and theoretical studies suggest that regulation of spread dynamics is possible; however, the conditions for its existence have not yet been empirically demonstrated. If invasion spread is a regulated process, the structure that accounts for this regulation will be a main determinant of invasion dynamics. Here we explore the existence of regulation underlying changes in the rate of new site colonization. We employ concepts and analytical tools from the study of abundance dynamics and show that spread dynamics are, in fact, regulated processes and that the regulation structure is notably consistent among invasions occurring in widely different contexts. We base our conclusions on the analysis of the spread dynamics of 30 species invasions, including birds, amphibians, fish, invertebrates, plants, and a virus, all of which exhibited similar regulation structures. In contrast to current beliefs that species invasions are idiosyncratic phenomena, here we provide evidence that general patterns do indeed exist.
Enhancement of plasmid-mediated gene therapy for muscular dystrophy by directed plasmid integration
Authors: Bertoni Carmen , Jarrahian Sohail , Wheeler Thurman M. , Li Yining , Olivares Eric C. , Calos Michele P. , Rando Thomas A.
Published: December 2005

Plasmid-mediated gene therapy can restore dystrophin expression in skeletal muscle in the mdx mouse, a model of Duchenne muscular dystrophy. However, sufficient long-term expression and distribution of dystrophin remain a hurdle for translating this technology into a viable treatment for Duchenne muscular dystrophy. To improve plasmid-mediated gene therapy for muscle diseases, we studied the effects of targeted plasmid integration using a phage integrase (φC31) that can mediate the integration of suitably modified plasmids into the mammalian genome. Using a luciferase expression plasmid, we monitored plasmid gene expression noninvasively in living mice by bioluminescence imaging. Coinjection of an integrase plasmid resulted in 5- to 10-fold higher levels of sustained luciferase expression. Likewise, plasmid-mediated dystrophin expression in mdx muscle was enhanced by integration. Using a combination of dystrophin and luciferase plasmids, we analyzed the functional benefit of dystrophin expression in the dystrophic muscle. The expression of dystrophin slowed the loss of luciferase expression associated with muscle degeneration, and that protection was enhanced by targeted integration of the dystrophin plasmid. In the presence of integrase, dystrophin expression was distributed along a much greater length of individual fibers, and this was associated with increased protection against degenerative changes. These data demonstrate the importance of both the level and distribution of dystrophin expression to achieve therapeutic efficacy, and that the efficacy can be enhanced by targeted plasmid integration.
Evidence of a false thumb in a fossil carnivore clarifies the evolution of pandas
Authors: Salesa Manuel J. , Antón Mauricio , Peigné Stéphane , Morales Jorge
Published: December 2005

The “false thumb” of pandas is a carpal bone, the radial sesamoid, which has been enlarged and functions as an opposable thumb. If the giant panda (
Ailuropoda melanoleuca
) and the red panda (
Ailurus fulgens
) are not closely related, their sharing of this adaptation implies a remarkable convergence. The discovery of previously unknown postcranial remains of a Miocene red panda relative,
Simocyon batalleri
, from the Spanish site of Batallones-1 (Madrid), now shows that this animal had a false thumb. The radial sesamoid of
S. batalleri
shows similarities with that of the red panda, which supports a sister-group relationship and indicates independent evolution in both pandas. The fossils from Batallones-1 reveal
S. batalleri
as a puma-sized, semiarboreal carnivore with a moderately hypercarnivore diet. These data suggest that the false thumbs of
S. batalleri
and
Ailurus fulgens
were probably inherited from a primitive member of the red panda family (Ailuridae), which lacked the red panda's specializations for herbivory but shared its arboreal adaptations. Thus, it seems that, whereas the false thumb of the giant panda probably evolved for manipulating bamboo, the false thumbs of the red panda and of
S. batalleri
more likely evolved as an aid for arboreal locomotion, with the red panda secondarily developing its ability for item manipulation and thus producing one of the most dramatic cases of convergence among vertebrates.
Linoleic acid hydroperoxide reacts with hypochlorous acid, generating peroxyl radical intermediates and singlet molecular oxygen
Authors: Miyamoto Sayuri , Martinez Glaucia R. , Rettori Daniel , Augusto Ohara , Medeiros Marisa H. G. , Di Mascio Paolo
Published: December 2005

The reaction of hypochlorous acid (HOCl) with hydrogen peroxide is known to generate stoichiometric amounts of singlet molecular oxygen [O
2
(
1
Δ
g
)]. This study shows that HOCl can also react with linoleic acid hydroperoxide (LAOOH), generating O
2
(
1
Δ
g
) with a yield of 13 ± 2% at physiological pH. Characteristic light emission at 1,270 nm, corresponding to O
2
(
1
Δ
g
) monomolecular decay, was observed when HOCl was reacted with LAOOH or with liposomes containing phosphatidylcholine hydroperoxides, but not with cumene hydroperoxide or
tert
-butyl hydroperoxide. The generation of O
2
(
1
Δ
g
) was confirmed by the acquisition of the spectrum of the light emitted in the near-infrared region showing a band with maximum intensity at 1,270 nm and by the observation of the enhancing effect of deuterium oxide and the quenching effect of sodium azide. Mechanistic studies using
18
O-labeled linoleic acid hydroperoxide (LA
18
O
18
OH) showed that its reaction with HOCl yields
18
O-labeled O
2
(
1
Δ
g
) [
18
O
2
(
1
Δ
g
)], demonstrating that the oxygen atoms in O
2
(
1
Δ
g
) are derived from the hydroperoxide group. Direct analysis of radical intermediates in the reaction of LAOOH with HOCl by continuous-flow electron paramagnetic resonance spectroscopy showed a doublet signal with a
g
-value of 2.014 and a hyperfine coupling constant from the α-hydrogen of a
H
= 4.3 G, indicating the formation of peroxyl radicals. Taken together, our results clearly demonstrate that HOCl reacts with biologically relevant lipid hydroperoxides, generating O
2
(
1
Δ
g
). In addition, the detection of
18
O
2
(
1
Δ
g
) and peroxyl radicals strongly supports the involvement of a Russell mechanism in the generation of O
2
(
1
Δ
g
).
Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in
Mycobacterium tuberculosis
Authors: Manjunatha Ujjini H. , Boshoff Helena , Dowd Cynthia S. , Zhang Liang , Albert Thomas J. , Norton Jason E. , Daniels Lacy , Dick Thomas , Pang Siew Siew , Barry Clifton E.
Published: December 2005

PA-824 is a promising new compound for the treatment of tuberculosis that is currently undergoing human trials. Like its progenitors metronidazole and CGI-17341, PA-824 is a prodrug of the nitroimidazole class, requiring bioreductive activation of an aromatic nitro group to exert an antitubercular effect. We have confirmed that resistance to PA-824 (a nitroimidazo-oxazine) and CGI-17341 (a nitroimidazo-oxazole) is most commonly mediated by loss of a specific glucose-6-phosphate dehydrogenase (FGD1) or its deazaflavin cofactor F
420
, which together provide electrons for the reductive activation of this class of molecules. Although FGD1 and F
420
are necessary for sensitivity to these compounds, they are not sufficient and require additional accessory proteins that directly interact with the nitroimidazole. To understand more proximal events in the reductive activation of PA-824, we examined mutants that were wild-type for both FGD1 and F
420
and found that, although these mutants had acquired high-level resistance to PA-824 (and another nitroimidazo-oxazine), they retained sensitivity to CGI-17341 (and a related nitroimidazo-oxazole). Microarray-based comparative genome sequencing of these mutants identified lesions in Rv3547, a conserved hypothetical protein with no known function. Complementation with intact Rv3547 fully restored sensitivity to nitroimidazo-oxazines and restored the ability of Mtb to metabolize PA-824. These results suggest that the sensitivity of Mtb to PA-824 and related compounds is mediated by a protein that is highly specific for subtle structural variations in these bicyclic nitroimidazoles.
Preclinical and phase I clinical trial of blockade of IL-15 using Mikβ1 monoclonal antibody in T cell large granular lymphocyte leukemia
Authors: Morris John C. , Janik John E. , White Jeffrey D. , Fleisher Thomas A. , Brown Margaret , Tsudo Mitsuru , Goldman Carolyn K. , Bryant Bonita , Petrus Michael , Top Lois , Lee Cathryn C. , Gao Wendy , Waldmann Thomas A.
Published: December 2005

Twelve patients with T cell large granular lymphocyte leukemia and associated hematocytopenia were treated in a phase I dose-escalation trial with the murine monoclonal antibody Mikβ1. Mikβ1 identifies CD122, the β-subunit shared by the IL-2 and IL-15 receptors. At the doses administered in this study the antibody inhibited the actions of IL-15 on both natural killer and T cells and that of IL-2 when the intermediate-affinity IL-2 receptor was expressed. Mikβ1 treatment was not associated with significant toxicity or with the development of an immune response to the infused monoclonal antibody. At these doses of Mikβ1, >95% saturation of the IL-2/IL-15β receptor (CD122) on the surfaces of the leukemic cells was achieved. Furthermore, in seven patients this led to the down-modulation of the receptor from the surfaces of the leukemic cells. Nevertheless, no patients manifested a reduction in peripheral leukemic cell count or an amelioration of their hematocytopenia. This latter observation may reflect the fact that the monoclonal T cell large granular lymphocyte leukemia leukemic cells of the patients did not produce IL-2 or IL-15 or require their actions for cell survival. In light of the lack of toxicity and lack of immunogenicity of the antibody observed in the present study and the role for IL-15 in the pathogenesis of autoimmune diseases, clinical trials should be performed using the humanized version of Mikβ1 in groups of patients with human T cell lymphotropic virus I-associated myelopathy/tropical spastic paraparesis, rheumatoid arthritis, multiple sclerosis and refractory celiac disease.
Synchronous dynamic brain networks revealed by magnetoencephalography
Authors: Langheim Frederick J. P. , Leuthold Arthur C. , Georgopoulos Apostolos P.
Published: December 2005

We visualized synchronous dynamic brain networks by using prewhitened (stationary) magnetoencephalography signals. Data were acquired from 248 axial gradiometers while 10 subjects fixated on a spot of light for 45 s. After fitting an autoregressive integrative moving average model and taking the residuals, all pairwise, zero-lag, partial cross-correlations (

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) between the
i
and
j
sensors were calculated, providing estimates of the strength and sign (positive and negative) of direct synchronous coupling between neuronal populations at a 1-ms temporal resolution. Overall, 51.4% of

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were positive, and 48.6% were negative. Positive

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occurred more frequently at shorter intersensor distances and were 72% stronger than negative ones, on the average. On the basis of the estimated

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, dynamic neural networks were constructed (one per subject) that showed distinct features, including several local interactions. These features were robust across subjects and could serve as a blueprint for evaluating dynamic brain function.
Whorf hypothesis is supported in the right visual field but not the left
Authors: Gilbert Aubrey L. , Regier Terry , Kay Paul , Ivry Richard B.
Published: December 2005

The question of whether language affects perception has been debated largely on the basis of cross-language data, without considering the functional organization of the brain. The nature of this neural organization predicts that, if language affects perception, it should do so more in the right visual field than in the left visual field, an idea unexamined in the debate. Here, we find support for this proposal in lateralized color discrimination tasks. Reaction times to targets in the right visual field were faster when the target and distractor colors had different names; in contrast, reaction times to targets in the left visual field were not affected by the names of the target and distractor colors. Moreover, this pattern was disrupted when participants performed a secondary task that engaged verbal working memory but not a task making comparable demands on spatial working memory. It appears that people view the right (but not the left) half of their visual world through the lens of their native language, providing an unexpected resolution to the language-and-thought debate.
PKA-mediated phosphorylation regulates the function of activation-induced deaminase (AID) in B cells
Authors: Pasqualucci Laura , Kitaura Yasuyuki , Gu Hua , Dalla-Favera Riccardo
Published: December 2005

During humoral immune responses, two distinct genetic modification events diversify the Ig genes in germinal center (GC) B cells: somatic hypermutation and class switch recombination (CSR). Both processes require the activity of activation-induced cytidine deaminase (AID), an enzyme expressed specifically in GC B cells. However, the mechanisms that regulate AID activity are largely unknown. Here we report that protein kinase A (PKA) phosphorylates AID and regulates its activity in GC B cells. AID physically interacts with the PKA holoenzyme in the cytoplasm and is phosphorylated by the PKA catalytic subunit at specific residues. AID phosphorylation is required for CSR, because substitution of the two phosphorylation targets impairs its ability to rescue CSR in AID-deficient B cells. Pharmacologic inhibition of PKA prevents isotype class switching in a murine B-cell lymphoma cell line; conversely, B cells from mice where PKA activity is made constitutive by conditional deletion of the PKA regulatory subunit gene display enhanced CSR. These findings implicate PKA in the regulation of AID function and suggest that the control of T cell-dependent immune responses may be modulated, via AID, by signals that activate PKA.
Comparing Bloodstream Infection Rates: The Effect of Indicator Specifications in the Evaluation of Processes and Indicators in Infection Control (EPIC) Study
Authors: Braun Barbara I. , Kritchevsky Stephen B. , Kusek Linda , Wong Edward S. , Solomon Steven L. , Steele Lynn , Richards Cheryl L. , Gaynes Robert P. , Simmons Bryan ,   Evaluation of Processes and Indicators in Infection Control (EPIC) Study Group
Published: January 2006

Objective.

Bloodstream infection (BSI) rates are used as comparative clinical performance indicators; however, variations in definitions and data-collection approaches make it difficult to compare and interpret rates. To determine the extent to which variation in indicator specifications affected infection rates and hospital performance rankings, we compared absolute rates and relative rankings of hospitals across 5 BSI indicators.

Design.

Multicenter observational study. BSI rate specifications varied by data source (clinical data, administrative data, or both), scope (hospital wide or intensive care unit specific), and inclusion/exclusion criteria. As appropriate, hospital-specific infection rates and rankings were calculated by processing data from each site according to 2-5 different specifications.

Setting.

A total of 28 hospitals participating in the EPIC study.

Participants.

Hospitals submitted deidentified information about all patients with BSIs from January through September 1999.

Results.

Median BSI rates for 2 indicators based on intensive care unit surveillance data ranged from 2.23 to 2.91 BSIs per 1000 central-line days. In contrast, median rates for indicators based on administrative data varied from 0.046 to 7.03 BSIs per 100 patients. Hospital-specific rates and rankings varied substantially as different specifications were applied; the rates of 8 of 10 hospitals were both greater than and less than the mean. Correlations of hospital rankings among indicator pairs were generally low (rs = 0-0.45), except when both indicators were based on intensive care unit surveillance (rs = 0.83).

Conclusions.

Although BSI rates seem to be a logical indicator of clinical performance, the use of various indicator specifications can produce remarkably different judgments of absolute and relative performance for a given hospital. Recent national initiatives continue to mix methods for specifying BSI rates; this practice is likely to limit the usefulness of such information for comparing and improving performance.
Fungal Contamination in Hospital Environments
Authors: Perdelli F. , Cristina M. L. , Sartini M. , Spagnolo A. M. , Dallera M. , Ottria G. , Lombardi R. , Grimaldi M. , Orlando P.
Published: January 2006

Objectives.

To assess the degree of fungal contamination in hospital environments and to evaluate the ability of air conditioning systems to reduce such contamination.

Methods.

We monitored airborne microbial concentrations in various environments in 10 hospitals equipped with air conditioning. Sampling was performed with a portable Surface Air System impactor with replicate organism detection and counting plates containing a fungus-selective medium. The total fungal concentration was determined 72-120 hours after sampling. The genera most involved in infection were identified by macroscopic and microscopic observation.

Results.

The mean concentration of airborne fungi in the set of environments examined was 19 ± 19 colony-forming units (cfu) per cubic meter. Analysis of the fungal concentration in the different types of environments revealed different levels of contamination: the lowest mean values (12 ± 14 cfu/m3) were recorded in operating theaters, and the highest (45 ± 37 cfu/m3) were recorded in kitchens. Analyses revealed statistically significant differences between median values for the various environments. The fungal genus most commonly encountered was Penicillium, which, in kitchens, displayed the highest mean airborne concentration (8 ± 2.4 cfu/m3). The percentage (35%) of Aspergillus documented in the wards was higher than that in any of the other environments monitored.

Conclusions.

The fungal concentrations recorded in the present study are comparable to those recorded in other studies conducted in hospital environments and are considerably lower than those seen in other indoor environments that are not air conditioned. These findings demonstrate the effectiveness of air-handling systems in reducing fungal contamination.
Risk Factors and Outcomes Associated With Non–Enterococcus faecalis, Non–Enterococcus faeciumEnterococcal Bacteremia
Authors: Perio Marie A. de , Yarnold Paul R. , Warren John , Noskin Gary A.
Published: January 2006

Objectives.

To compare risk factors, clinical features, and outcomes in patients withEnterococcus avium,Enterococcus casseliflavus,Enterococcus durans,Enterococcus gallinarum, andEnterococcus mundtiibacteremia (cases) with those in patients withEnterococcus faecalisbacteremia (controls).

Design.

A retrospective case-control study.

Setting.

A 725-bed, university-affiliated, academic medical center.

Patients.

The clinical microbiology database at Northwestern Memorial Hospital from January 1994 to May 2003 was searched to identify cases; each case was matched to one control on the basis of date of admission.

Results.

Thirty-three cases were identified and matched with 33 controls. The mean duration of hospital stay was longer (29.7 vs 17.2 days;P= .03) and the mean time to acquisition of bacteremia was greater (16.5 vs 6.3 days;P= .003) for cases than controls. Cases were more likely to have underlying hematologic malignancies (P< .001), to have been treated with corticosteroids (P= .02), and to be neutropenic (P= .003). Controls were more likely to have an indwelling bladder catheter (P= .01), and cases were more likely to have the gastrointestinal tract as a source of infection (P= .007) and to have concurrent cholangitis (P= .002). There were no differences in severity of illness or in mortality rates.

Conclusions.

Compared with patients withE. faecalisbacteremia, patients with non-E. faecalis, non-Enterococcus faeciumenterococcal bacteremia were more likely to have a hematologic malignancy, prior treatment with corticosteroids, neutropenia, and cholangitis; longer duration of hospital stay was also identified as a clinical feature. However, non-E. faecalis, non-E. faeciumspecies are not associated with any differences in mortality.
Assessing sexual conflict in theDrosophila melanogasterlaboratory model system
Authors: Rice William R , Stewart Andrew D , Morrow Edward H , Linder Jodell E , Orteiza Nicole , Byrne Phillip G
Published: January 2006

We describe a graphical model of interlocus coevolution used to distinguish between the interlocus sexual conflict that leads to sexually antagonistic coevolution, and the intrinsic conflict over mating rate that is an integral part of traditional models of sexual selection. We next distinguish the ‘laboratory island’ approach from the study of both inbred lines and laboratory populations that are newly derived from nature, discuss why we consider it to be one of the most fitting forms of laboratory analysis to study interlocus sexual conflict, and then describe four experiments using this approach withDrosophila melanogaster. The first experiment evaluates the efficacy of the laboratory model system to study interlocus sexual conflict by comparing remating rates of females when they are, or are not, provided with a spatial refuge from persistent male courtship. The second experiment tests for a lag-load in males that is due to adaptations that have accumulated in females, which diminish male-induced harm while simultaneously interfering with a male's ability to compete in the context of sexual selection. The third and fourth experiments test for a lag-load in females owing to direct costs from their interactions with males, and for the capacity for indirect benefits to compensate for these direct costs.
APETALA2Regulates the Stem Cell Niche in theArabidopsisShoot Meristem
Authors: Würschum Tobias , Groß-Hardt Rita , Laux Thomas
Published: December 2005

Postembryonic organ formation in higher plants relies on the activity of stem cell niches in shoot and root meristems where differentiation of the resident cells is repressed by signals from surrounding cells. We searched for mutations affecting stem cell maintenance and isolated the semidominant l28 mutant, which displays premature termination of the shoot meristem and differentiation of the stem cells. Allele competition experiments suggest that l28 is a dominant-negative allele of the APETALA2 (AP2) gene, which previously has been implicated in floral patterning and seed development. Expression of both WUSCHEL (WUS) and CLAVATA3 (CLV3) genes, which regulate stem cell maintenance in the wild type, were disrupted in l28 shoot apices from early stages on. Unlike in floral patterning, AP2 mRNA is active in the center of the shoot meristem and acts via a mechanism independent of AGAMOUS, which is a repressor of WUS and stem cell maintenance in the floral meristem. Genetic analysis shows that termination of the primary shoot meristem in l28 mutants requires an active CLV signaling pathway, indicating that AP2 functions in stem cell maintenance by modifying the WUS-CLV3 feedback loop.
Regulation of Phosphate Homeostasis by MicroRNA in Arabidopsis
Authors: Chiou Tzyy-Jen , Aung Kyaw , Lin Shu-I , Wu Chia-Chune , Chiang Su-Fen , Su Chun-lin
Published: December 2005

In this study, we reveal a mechanism by which plants regulate inorganic phosphate (Pi) homeostasis to adapt to environmental changes in Pi availability. This mechanism involves the suppression of a ubiquitin-conjugating E2 enzyme by a specific microRNA, miR399. Upon Pi starvation, the miR399 is upregulated and its target gene, a ubiquitin-conjugating E2 enzyme, is downregulated in Arabidopsis thaliana. Accumulation of the E2 transcript is suppressed in transgenic Arabidopsis overexpressing miR399. Transgenic plants accumulated five to six times the normal Pi level in shoots and displayed Pi toxicity symptoms that were phenocopied by a loss-of-function E2 mutant. Pi toxicity was caused by increased Pi uptake and by translocation of Pi from roots to shoots and retention of Pi in the shoots. Moreover, unlike wild-type plants, in which Pi in old leaves was readily retranslocated to other developing young tissues, remobilization of Pi in miR399-overexpressing plants was impaired. These results provide evidence that miRNA controls Pi homeostasis by regulating the expression of a component of the proteolysis machinery in plants.
Association of HLA DQ4‐DR8 haplotype with papillary thyroid carcinomas
Authors: Porto Teresa , Coelho Ibraim , Boavida José , Pereira Clara , Nunes José M. , Mendonça Denisa , Martins Berta , Sobrinho Luís G. , Leite Valeriano
Published: January 2006

Objective  The association of the human leucocyte antigen (HLA) system with thyroid carcinomas is not clear. We sought to relate HLA alleles to susceptibility to papillary thyroid carcinoma (PTC) and also to clinical and pathological characteristics of PTC patients.

Design and patients  The distribution of HLA in 181 unrelated Caucasian patients with PTC was compared to the HLA distribution in 315 normal controls, 31 patients with follicular carcinoma (FTC), 29 patients with lymphocytic thyroiditis (LT) and 50 patients with multinodular goitre (MNG), using a microlymphocytotoxicity assay.

Results  Compared to normal controls, patients with PTC showed a significantly increased frequency of HLA‐DQ4 [12·8%vs. 3·5%, P = 0·0005, Pcorrected (Pc) = 0·0032, odds ratio (OR) = 4·058, 95% confidence interval (95% CI) = 1·820–9·045] and HLA‐DR8 (10·9%vs. 4·3%, P = 0·013, Pc > 0·05, OR = 2·752, 95% CI = 1·275–5·940). DQ4 and DR8 were also significantly increased in patients with MNG (DQ4, 16·3%; DR8, 16·3%) compared to controls (DQ4, P = 0·0019, Pc = 0·011, OR = 5·420, 95% CI = 1·978–14·852; DR8, P = 0·0044, Pc = 0·062). Linkage disequilibrium (LD) for these two alleles was present in controls (D = 0·0130, P = 9·7e‐57) and in MNG patients (D = 0·0730, P = 4·6e‐19) but not in PTC patients (D = 0·038, P > 0·05). In the subgroup of PTC subjects with concomitant nonthyroidal neoplasias (n = 27), there was a significant (P < 0·05) increase in the frequency of B57 (18·5%), DR11 (56·5%) and DQ3 (81·8%) compared to PTC patients without coexistent neoplasias (2·0%, 21% and 47%, respectively). No significant differences of HLA allele distribution was found in relation to PTC histology, age at diagnosis (> 45 or ≤ 45 years), gender or tumour–node–metastasis (TNM) staging. In patients with FTC, the frequency of DR17 (FTC = 51·6%; controls = 22·5%; P = 0·0009; Pc = 0·0138) was significantly increased compared to controls. Patients with LT showed a higher frequency of the DR11 allele (48·3%) than controls (DR11 = 21·3%; P = 0·0028, Pc = 0·039, OR = 3·445, 95% CI = 1·568–7·567).

Conclusions  We have typed the largest series of patients with thyroid carcinomas reported to date, and found that DR8 and DQ4 are independent susceptibility markers for PTC.
Yield strength of zirconia and glass fibre‐reinforced posts
Authors: PFEIFFER P. , SCHULZ A. , NERGIZ I. , SCHMAGE P.
Published: January 2006

summary  The aim of this in vitro study was to evaluate the yield strengths of glass fibre‐reinforced composite (FRC) posts and zirconia dioxide ceramic (ZDC) posts. Tapered glass FRC posts (DentinPost) and ZDC posts (Cerapost) of three sizes in diameter (ISO 50, 90, 110) were used for bending tests. Conventional prefabricated titanium posts of the same sizes served as control groups. The 0·2% yield strengths (R0·2) were tested on a universal testing machine. As zirconia posts fractured before they were yielded 0·2%, the fracture strength instead of the yield strength was recorded for these posts. One‐way and two‐way anova and Bonferroni–Dunn's multiple comparison tests were performed for the statistical analysis. The mean 0·2% yield strengths of the posts were 27 ± 1 N for glass fibre‐reinforced posts and 58 ± 4 N for zirconia posts of ISO 50 (control group: 54 ± 3 N). For ISO 90 yield strengths of 52 ± 4 N for glass fibre‐reinforced posts, 117 ± 20 N for zirconia posts and 117 ± 11 N for the control group were obtained. For ISO 110 mean yield strengths amounted to 73 ± 5 N for glass fibre‐reinforced posts, 166 ± 23 N for zirconia posts and 141 ± 12 N for the control group. Significantly higher yield strength was recorded for the zirconia and the titanium posts compared with the glass fibre‐reinforced posts for the tested ISO sizes.
Shade selection performed by novice dental professionals and colorimeter
Authors: KLEMETTI E. , MATELA A.‐M. , HAAG P. , KONONEN M.
Published: January 2006

summary  The objective of this study was to test inter‐observer variability in shade selection for porcelain restorations, using three different shade guides: Vita Lumin Vacuum, Vita 3D‐Master and Procera. Nineteen young dental professionals acted as observers. The results were also compared with those of a digital colorimeter (Shade Eye Ex; Shofu, Japan). Regarding repeatability, no significant differences were found between the three shade guides, although repeatability was relatively low (33–43%). Agreement with the colorimetric results was also low (8–34%). In conclusion, shade selection shows moderate to great inter‐observer variation. In teaching and standardizing the shade selection procedure, a digital colorimeter may be a useful educational tool.
Phylogeography, phylogeny and hybridization in trichechid sirenians: implications for manatee conservation
Authors: VIANNA JULIANA A. , BONDE ROBERT K. , CABALLERO SUSANA , GIRALDO JUAN PABLO , LIMA RÉGIS P. , CLARK ANNMARIE , MARMONTEL MÍRIAM , MORALES‐VELA BENJAMÍN , DE SOUZA MARIA JOSÉ , PARR LESLEE , RODRÍGUEZ‐LOPEZ MARTA A. , MIGNUCCI‐GIANNONI ANTONIO A. , POWELL JAMES A. , SANTOS FABRÍCIO R.
Published: January 2006

The three living species of manatees, West Indian (Trichechus manatus), Amazonian (Trichechus inunguis) and West African (Trichechus senegalensis), are distributed across the shallow tropical and subtropical waters of America and the western coast of Africa. We have sequenced the mitochondrial DNA control region in 330 Trichechus to compare their phylogeographic patterns. In T. manatus we observed a marked population structure with the identification of three haplotype clusters showing a distinct spatial distribution. A geographic barrier represented by the continuity of the Lesser Antilles to Trinidad Island, near the mouth of the Orinoco River in Venezuela, appears to have restricted the gene flow historically in T. manatus. However, for T. inunguis we observed a single expanding population cluster, with a high diversity of very closely related haplotypes. A marked geographic population structure is likely present in T. senegalensis with at least two distinct clusters. Phylogenetic analyses with the mtDNA cytochrome b gene suggest a clade of the marine Trichechus species, with T. inunguis as the most basal trichechid. This is in agreement with previous morphological analyses. Mitochondrial DNA, autosomal microsatellites and cytogenetic analyses revealed the presence of hybrids between the T. manatus and T. inunguis species at the mouth of the Amazon River in Brazil, extending to the Guyanas and probably as far as the mouth of the Orinoco River. Future conservation strategies should consider the distinct population structure of manatee species, as well as the historical barriers to gene flow and the likely occurrence of interspecific hybridization.
Inferring colonization history from analyses of spatial genetic structure within populations of Pinus strobus and Quercus rubra
Authors: JONES F. A. , HAMRICK J. L. , PETERSON C. J. , SQUIERS E. R.
Published: January 2006

Many factors interact to determine genetic structure within populations including adult density, the mating system, colonization history, natural selection, and the mechanism and spatial patterns of gene dispersal. We examined spatial genetic structure within colonizing populations of Quercus rubra seedlings and Pinus strobus juveniles and adults in an aspen–white pine forest in northern Michigan, USA. A 20‐year spatially explicit demographic study of the forest enables us to interpret the results in light of recent colonization of the site for both species. We assayed 217 Q. rubra seedlings and 171 P. strobus individuals at 11 polymorphic loci using nine allozyme systems. Plant genotypes and locations were used in an analysis of spatial genetic structure. Q. rubra and P. strobus showed similar observed levels of heterozygosity, but Q. rubra seedlings have less heterozygosity than expected. Q. rubra seedlings show spatial genetic clumping of individuals on a scale to 25 m and levels of genetic relatedness expected from the clumped dispersion of half‐siblings. In contrast, P. strobus has low levels of genetic relatedness at the smallest distance class and positive spatial genetic structure at scales < 10 m within the plot. The low density of adult Q. rubra outside the study plot and limited, spatially clumped rodent dispersal of acorns is likely responsible for the observed pattern of spatial genetic structure and the observed heterozygote deficit (i.e. a Wahlund effect). We attribute weaker patterns observed in P. strobus to the longer dispersal distance of seeds and the historical overlap of seed shadows from adults outside of the plot coupled with the overlap of seed shadows from younger, more recently established reproductive adults. The study demonstrates the utility of long‐term demographic data in interpreting mechanisms responsible for generating contemporary patterns of genetic structure within populations.
Iron‐sulphur clusters and the problem with oxygen
Authors: Imlay James A.
Published: January 2006

During the first billion years of life on the Earth, the environment was anaerobic. Iron and sulphur were plentiful, and they were recruited in the formation of iron‐sulphur (Fe‐S) clusters within ancient proteins. These clusters provided many enzymes with the ability to transfer electrons; to others they offered a cationic feature that tightly bound oxyanionic and nitrogenous metabolites. Still others acquired a crystallizing surface around which polypeptide could fold to establish a three‐dimensional structure. However, the subsequent oxygenation of the Earth's atmosphere by photosynthetic organisms created a threat to cluster‐dependent proteins that still has not been fully resolved. By oxidizing environmental iron, oxygen limits its bioavailability, requiring that organisms employ complex schemes with which to satisfy their iron requirement. More directly, oxygen species convert exposed Fe‐S clusters to unstable forms that quickly decompose. Some microbes responded to this dilemma by retreating to anaerobic habitats. Others abandoned the use of low‐potential electron‐transfer pathways, which rely upon the least stable cluster enzymes, and developed antioxidant strategies to protect the remainder. These adjustments were only partially successful: largely because of their reliance upon Fe‐S clusters, aerobes remain vulnerable to iron restriction and oxidative stress, features that higher organisms exploit in defending themselves against bacterial pathogens. Thus, the history of Fe‐S clusters is an unusual one that has profoundly shaped contemporary microbial ecology.
Predicting metals sensed by ArsR‐SmtB repressors: allosteric interference by a non‐effector metal
Authors: Harvie Duncan R. , Andreini Claudia , Cavallaro Gabriele , Meng Wenmao , Connolly Bernard A. , Yoshida Ken‐ichi , Fujita Yasutaro , Harwood Colin R. , Radford David S. , Tottey Stephen , Cavet Jennifer S. , Robinson Nigel J.
Published: January 2006

Many bacterial genomes encode multiple metal‐sensing ArsR‐SmtB transcriptional repressors. There is interest in understanding and predicting their metal specificities. Here we analyse twoarsR‐smtBgenes,ydeTandyozA(nowaseRandczrA) fromBacillus subtilis. Purified AseR and CzrA formed complexes in gel‐retardation and fluorescence‐anisotropy assays with fragments of promoters that were derepressed in ΔaseRand ΔczrAcells. Candidate (i) partly thiolate, α3‐helix (for AseR) and (ii) tetrahedral, non‐thiolate, α5‐helix (for CzrA) metal binding sites were predicted then testedin vitroand/orin vivo. The precedents are for such sites to sense arsenite/antimonite (α3) and zinc (α5). This correlated with the respective metal inducers of AseR and CzrA repressed promoters inB. subtilisand matched the metals that impaired formation of protein–DNA complexesin vitro. The putative sensory sites of 1024 ArsR‐SmtB homologues are reported. Although AseR did not sense zincin vivo, it bound zincin vitroexploiting α3 thiols, but AseR DNA binding was not impaired by zinc. If selectivity relies on discriminatory triggering of allostery not just selective metal binding, then tight non‐effector metal complexes could theoretically inhibit metal sensing. AseR remained arsenite‐sensitive in equimolar zinc, while CzrA remained zinc‐sensitive in equimolar arsenitein vitro. However, cupric ions did not impair CzrA–DNA complex formation but did inhibit zinc‐mediated allosteryin vitroand prevent zinc binding. Access to copper must be controlledin vivoto avoid formation of cupric CzrA.
Effects of Curcumin on Tumour Necrosis Factor‐α and Interleukin‐6 in the Late Phase of Experimental Acute Pancreatitis
Authors: Gulcubuk A. , Altunatmaz K. , Sonmez K. , Haktanir‐Yatkin D. , Uzun H. , Gurel A. , Aydin S.
Published: January 2006

Inflammatory cytokines have been demonstrated to play an important role in the induction and severity of acute pancreatitis (AP) in the recent studies. The aim of this study was to investigate the effects of curcumin on inflammatory cytokines, such as tumour necrosis factor (TNF)‐α and interleukin (IL)‐6 in the late phase of AP. The study was conducted on 40 male Wistar Albino rats. The animals were divided randomly into four equal groups. AP was induced by the infusion of 3% sodium taurocholate into the biliopancreatic duct (in groups I and II). Starting on day 20 prior to the induction of AP, rats in group I received daily dose of 100 mg/kg of curcumin, dissolved in 9% ethanol via an intragastric tube. The same procedure was repeated for 6 days following the onset of AP. Group III was infused only on saline solution. Group IV (curcumin control group) received 9% ethanol via an intragastric tube, during the experimental period (totally 26 days). All the animals were sacrificed on day 6 after the collection of blood samples and serum TNF‐α and IL‐6 levels were determined. Tissue samples were taken from pancreas, mesenteric lymph nodes, liver, lungs, spleen and the kidneys for histopathological evaluation. Serum TNF‐α and IL‐6 levels in the group, which received curcumin (group I), were determined to be significantly lower than those of the untreated group (group II) (P<0.05). No statistically significant difference was detected in terms of total histopathological scores in the treatment group versus untreated group. Curcumin has been shown to markedly reduce serum TNF‐α and IL‐6 levels in the late phase of AP, but failed in the prevention of tissue injury.
Conferring cadmium resistance to mature tobacco plants through metal‐adsorbing particles of tomato mosaic virus vector
Authors: Shingu Yoshinori , Yokomizo Satoko , Kimura Makoto , Ono Yoshiro , Yamaguchi Isamu , Hamamoto Hiroshi
Published: January 2006

Tomato mosaic virus vectors were designed that produced, by a translational readthrough, a fusion protein consisting of coat protein and metal‐binding peptide, as a result of which particles were expected to present the metal‐binding peptides on their surface. When inoculated in plants, they were expected to replicate and form a metal‐adsorbing artificial sink in the cytoplasm, so as to reduce metal toxicity. Vectors were constructed harbouring sequences encoding various lengths of polyhistidine as a metal‐binding peptide. One of the vectors, TLRT6His, which contains a 6 × histidine sequence, moved systemically in tobacco plants, and its particles were shown to retain cadmium ions by an in vitro assay. When a toxic amount of cadmium was applied, the toxic effect was much reduced in TLRT6His‐inoculated tobacco plants, probably as a result of cadmium adsorption by TLRT6His particles in the cytosol. This shows the possible use of an artificial sink for metal tolerance and the advantage of employing a plant viral vector for phytoremediation.