bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deregulated Cdk5 promotes oxidative stress and mitochondrial dysfunction
Authors: Sun Kai‐Hui , De Pablo Yolanda , Vincent Fabien , Shah Kavita 
Published: August 2008

AbstractOxidative stress is one of the earliest events in Alzheimer’s disease (AD). A chemical genetic screen revealed that deregulated cyclin‐dependent kinase 5 (Cdk5) may cause oxidative stress by compromising the cellular anti‐oxidant defense system. Using novel Cdk5 modulators, we show the mechanism by which Cdk5 can induce oxidative stress in the disease’s early stage and cell death in the late stage. Cdk5 dysregulation upon neurotoxic insults results in reactive oxygen species (ROS) accumulation in neuronal cells because of the inactivation of peroxiredoxin I and II. Sole temporal activation of Cdk5 also increases ROS, suggesting its major role in this process. Cdk5 inhibition rescues mitochondrial damage upon neurotoxic insults, thereby revealing Cdk5 as an upstream regulator of mitochondrial dysfunction. As mitochondrial damage results in elevated ROS and Ca2+ levels, both of which activate Cdk5, we propose that a feedback loop occurs in late stage of AD and leads to cell death (active Cdk5 → ROS → excess ROS → mitochondrial damage → ROS → hyperactive Cdk5 → severe oxidative stress and cell injury → cell death). Cdk5 inhibition upon neurotoxic insult prevents cell death significantly, supporting this hypothesis. As oxidative stress and mitochondrial dysfunction play pivotal roles in promoting neurodegeneration, Cdk5 could be a viable therapeutic target for AD.
A coordinated approach to cutaneous wound healing: vibrational microscopy and molecular biology
Authors: Chan K. L. Andrew , Zhang Guojin , Tomic‐Canic Marjana , Stojadinovic Olivera , Lee Brian , Flach Carol R. , Mendelsohn Richard 
Published: August 2008

AbstractThe repair of cutaneous wounds in the adult body involves a complex series of spatially and temporally organized processes to prevent infection and restore homeostasis. Three characteristic phases of wound repair (inflammation, proliferation including re‐epithelialization and remodelling) overlap in time and space. We have utilized a human skin wound‐healing model to correlate changes in genotype and pheno‐type with infrared (IR) and confocal Raman spectroscopic images during the re‐epithelialization of excisional wounds. The experimental protocols validated as IR images clearly delineate the keratin‐rich migrating epithelial tongue from the collagen‐rich wound bed. Multivariate statistical analysis of IR datasets acquired 6 days post‐wounding reveal subtle spectral differences that map to distinct spatial distributions, which are correlated with immunofluorescent staining patterns of different keratin types. Images computed within collagen‐rich regions expose complementary spatial patterns and identify elastin in the wound bed. The temporal sequence of events is explored through a comparison of gene array analysis with confocal Raman microscopy. Our approach demonstrates the feasibility of acquiring detailed molecular structure information from the various proteins and their subclasses involved in the wound‐healing process.
Histochemical and ultrastructural characteristics of an interstitial cell type different from ICC and resident in the muscle coat of human gut
Authors: Pieri Laura , Vannucchi Maria Giuliana , Faussone‐Pellegrini Maria Simonetta 
Published: August 2008

AbstractCD117 (or c‐kit) is expressed by the interstitial cells of Cajal (ICC), which are located within the gastrointestinal (GI) muscle coat and directly involved in its motility. CD34 is expressed by several cell types some of which have features and location resembling the ICC; however, a sure identification of these cells is still lacking. In order to establish whether the CD34‐positive cells of the human GI tract are to be considered as ICC subpopulation or a novel independent cell type, and to hypothesize their nature and role, we verified CD34 and CD117 receptor expression under light and fluorescence microscope and performed a routine and a CD34‐immuno‐electron microscopy. CD34‐positive cells were seen in the entire human GI tract. In the muscularis propria, shared morphologies similar to the c‐kit‐positive cells, in the submucosa, resembled fibroblasts. Their ultrastructure resembled that of the fibrocytes/fibroblasts and of the interstitial Cajal‐like cells (ICLC). Double labelling and immunoelectro‐microscopy demonstrated that they are unequivocally different to the ICC and, due to the similarities with the ICLC, we identified them as ICLC. The novelty of these results is that two types of interstitial cells are present in the GI muscle coat of humans: the ICC and the ICLC. We hypothesize a mechanical role for the septal ICLC, those at the myenteric plexus level and those bordering the muscle layers; a helping role in neurotransmission is proposed for the ICLC intercalated with the intramuscular ICC, possibly in spreading the slow waves generated by the ICC. Furthermore, the possibility that the ICLC represent the adult mesenchymal stromal cells able to guarantee the ICC renewal deserves to be considered.
One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders
Authors: Paşca Sergiu P. , Dronca Eleonora , Kaucsár Tamás , Crǎciun Elena C. , Endreffy Emõke , Ferencz Beatrix K. , Iftene Felicia , Benga Ileana , Cornean Rodica , Banerjee Ruma , Dronca Maria 
Published: August 2008

AbstractAutism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), Asperger’s syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD‐NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B12 and the C677T polymorphism of the MTHFR gene in three groups of children diagnosed with AD (n= 15), AS (n= 5) and PDD‐NOS (n= 19) and their age‐ and sex‐matched controls (n= 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD‐NOS groups, lower plasma levels of methionine (P= 0.01 and P= 0.03, respectively) and α‐aminobutyrate were observed (P= 0.01 and P= 0.001, respectively). Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N‐dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum levels of vitamin B12 and folate were in the normal range. The results of the MTHFR gene analysis showed a normal distribution of the C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs.
Proteomics analysis of protein expression and specific protein oxidation in human papillomavirus transformed keratinocytes upon UVB irradiation
Authors: Perluigi Marzia , Giorgi Alessandra , Blarzino Carla , De Marco Federico , Foppoli Cesira , Di Domenico Fabio , Butterfield D. Allan , Schininà M. Eugenia , Cini Chiara , Coccia Raffaella 
Published: August 2008

AbstractIncreasing evidence supports the role of oxidative stress in cancer development. Ultraviolet (UV) irradiation is one of the major sources of oxidative stress through the generation of reactive oxygen species (ROS). Besides the physiological function of ROS in cellular homeostasis, accumulating reports suggest that ROS are involved in all stages of multistep cancer development. In order to investigate the involvement of oxidative damage into the mechanisms of tumour progression, we used a parallel proteomic approach to analyse the protein expression profile and to identify oxidatively modified proteins in human papillomavirus (HPV)‐transformed keratinocytes (HK‐168 cells) upon ultraviolet B (UVB) exposure. The HK‐168 cells were obtained from normal human epidermal keratinocytes transfected with the whole genome of the high‐risk HPV type 16, unanimously recognized as an etiological agent of cervical carcinoma. Because of its year‐long latency, this tumour offers a convenient model to study the role of environmental concurring agents in the multistep malignant progression. By the protein expression profile, we identified 21 proteins that showed different expression levels in HK‐168 cells treated with UVB in comparison with untreated cells. Focusing on the oxidative modifications occurring at the protein level, we identified five proteins that showed elevated protein carbonyls levels: α‐enolase, heat shock protein 75, annexin 2, elongation factor Tu and elongation factor γ. Our results indicate that UVB‐induced oxidative stress perturbs the normal redox balance and shifts HPV‐transformed keratinocytes into a state in which the carbonylation of specific proteins is systematically induced. We suggest that UVB‐induced modulation of protein expression combined with oxidative modification lead to protein dysfunction that might contribute to the malignant progression of transformed cells.
PREB regulates transcription of pancreatic glucokinase in response to glucose and cAMP
Authors: Muraoka Tomie , Murao Koji , Imachi Hitomi , Yu Xiao , Li Junhua , Wong Norman CW , Ishida Toshihiko 
Published: August 2008

AbstractProlactin regulatory element binding (PREB) is a transcription factor that regulates prolactin promoter activity in rat anterior pituitary. The PREB protein is not only expressed in the anterior pituitary but also in the pancreas. We have recently reported that in pancreatic β‐cells, PREB regulates the transcription of the insulin gene in response to glucose stimulation. In the current study, we have examined the role of PREB in regulating glucokinase (GK) in pancreatic β‐cells. To analyse the effects of PREB on GK gene transcription, we employed a reporter gene assay. In the cells expressing or with knocked down PREB, GK expression was determined. GK expression was regulated by glucose and cAMP, and both glucose and cAMP stimulated the expression of PREB in a dose‐dependent manner. Conversely, overexpression of PREB using a PREB‐expressing adenovirus increased the expression of the GK protein. GK enzymatic activity was also significantly increased in the cells that stably expressed PREB. In addition, PREB induced GK promoter activity. Chromatin immunoprecipitation (ChIP) analyses showed that PREB mediated its transcriptional effect by binding to the PREB‐responsive cis‐element of the GK promoter. Finally, we used siRNA to inhibit PREB expression in cells and demonstrated that the knockdown of PREB attenuated the effects of glucose and cAMP on GK expression. Our data show that in pancreatic β‐cells, PREB regulates the transcription of the GK gene in response to glucose and cAMP.
Relative torque contribution of vastus medialis muscle at different knee angles
Authors: De Ruiter C. J. , Hoddenbach J. G. , Huurnink A. , De Haan A. 
Published: August 2008

AbstractAim:  We investigated the relative contribution of the vastus medialis (VM) muscle to total isometric knee extension torque at 10°, 30°, 60° and 90° knee flexion. In the past a more prominent role of the VM muscle at more extended knee angles has been put forward. However, different components of the quadriceps muscle converge via a common distal tendon. We therefore hypothesized that the relative contribution of the VM to total knee extension torque would be similar across angles.Methods:  At each knee angle the EMG isometric torque relations [20%, 25%, 30%, 35% maximal voluntary contraction (MVC)] of the rectus femoris (RF), vastus lateralis (VL) and VM muscle were established in 10 healthy male subjects; rectified surface EMG was normalized to M‐wave area. Subsequently, the VM was functionally eliminated by selective electrical surface stimulation with occluded blood flow.Results:  There was no evidence for preferential activation of VM at any of the knee angles. Following VM elimination, total knee extension torque during maximal femoral nerve stimulation (three pulses at 300Hz) at 10°, 30°, 60° and 90°, respectively, decreased (P < 0.05) to (mean ± SD): 75.7 ± 12.2, 75.1 ± 9.3, 78.2 ± 7.2 and 76.0 ± 5.8% (P > 0.05 among knee angles). In addition, during voluntary contractions at 20% MVC the increases in torque output of RF and VL compensating for the loss of VM function were calculated from the increases in EMG and found to be similar (P > 0.05) at 10°, 30°, 60° and 90° values (%MVC), respectively, were: 9.1 ± 6.8, 7.5 ± 2.9, 5.9 ± 3.7 and 6.9 ± 3.4.Conclusion:  The present findings support our hypothesis that the VM contributes similarly to total knee extension torque at different knee angles.
“
Candidatus
Midichloria” Endosymbionts Bloom after the Blood Meal of the Host, the Hard Tick
Ixodes ricinus
Authors: Sassera Davide , Lo Nathan , Bouman Edwin A. P. , Epis Sara , Mortarino Michele , Bandi Claudio 
Published: August 2008

ABSTRACT

“
Candidatus
Midichloria mitochondrii,” an intracellular symbiont of the tick
Ixodes ricinus
, is the only described organism able to invade the mitochondria of any multicellular organism. We used quantitative PCR to examine cycles of bacterial growth and death throughout the host's development and found that they correspond with the phases of engorgement and molt, respectively.
Detection of
Bifidobacterium animalis
subsp.
lactis
(Bb12) in the Intestine after Feeding of Sows and Their Piglets
Authors: Solano-Aguilar Gloria , Dawson Harry , Restrepo Marta , Andrews Kate , Vinyard Bryan , Urban Joseph F. 
Published: August 2008

ABSTRACT

A real-time PCR method has been developed to distinguish
Bifidobacterium animalis
subspecies in the gastrointestinal tracts of pigs. Identification of a highly conserved single-copy
tuf
gene encoding the elongation factor Tu involved in bacterial protein biosynthesis was used as a marker to differentiate homologous
Bifidobacterium animalis
subsp.
lactis
(strain Bb12) from
Bifidobacterium animalis
subsp.
animalis
, as well as
Bifidobacterium suis
,
Bifidobacterium breve
,
Bifidobacterium longum
, several species of
Lactobacillus
, and
Enterococcus faecium
. Real-time PCR detection of serially diluted DNA extracted from a pure culture of Bb12 was linear for bacterial numbers ranging from 10 to 10,000
tuf
gene copies per PCR (
r
2
= 0.99). Relative differences in Bb12 bacterial numbers in pigs fed daily with Bb12 were determined after detection of Bb12
tuf
gene copies in DNA extracted from the intestinal contents. Piglets treated with Bb12 immediately after birth maintained a high level of Bb12 in their large intestines with continuous daily administration of Bb12. Piglets born to Bb12-treated sows during the last third of their gestation and also treated with Bb12 at birth (T/T group) had a higher number of Bb12 organisms per gram of intestinal contents compared to placebo-treated piglets born to placebo-treated sows (C/C group), Bb12-treated sows (T/C group), or piglets born to placebo sows but treated with Bb12 immediately after birth (C/T group). In addition, there was a significant increase in gene expression for Toll-like receptor 9 (TLR9) in piglets from the T/T group, with no change in TLR2 and TLR4. These findings suggest that the
tuf
gene represents a specific and functional marker for detecting
Bifidobacterium animalis
subsp.
lactis
strain Bb12 within the microbiota of the intestine.
RNA Arbitrarily Primed PCR and Fourier Transform Infrared Spectroscopy Reveal Plasticity in the Acid Tolerance Response ofStreptococcus macedonicus
Authors: Papadimitriou Konstantinos , Boutou Effrossyni , Zoumpopoulou Georgia , Tarantilis Petros A. , Polissiou Moschos , Vorgias Constantinos E. , Tsakalidou Effie 
Published: August 2008

ABSTRACTWe have previously reported that an acid tolerance response (ATR) can be induced inStreptococcus macedonicuscells at mid-log phase after autoacidification, transient exposure to acidic pH, or acid habituation, as well as at stationary phase. Here, we compared the transcriptional profiles of these epigenetic phenotypes, by RNA arbitrarily primed PCR (RAP-PCR), and their whole-cell chemical compositions, by Fourier transform infrared spectroscopy (FT-IR). RAP-PCR fingerprints revealed significant differences among the phenotypes, indicating that gene expression during the ATR is influenced not only by the growth phase but also by the treatments employed to induce the response. The genes coding for the mannose-specific IID component, the 1,2-diacylglycerol 3-glucosyltransferase, the 3-oxoacyl-acyl carrier protein, the large subunit of carbamoyl-phosphate synthase, and a hypothetical protein were found to be induced at least under some of the acid-adapting conditions. Furthermore, principal component analysis of the second-derivative-transformed FT-IR spectra segregatedS. macedonicusphenotypes individually in all spectral regions that are characteristic for major cellular constituents like the polysaccharides of the cell wall, fatty acids of the cell membrane, proteins, and other compounds that absorb in these regions. These findings provide evidence for major changes in cellular composition due to acid adaptation that were clearly different to some extent among the phenotypes. Overall, our data demonstrate the plasticity in the ATR ofS. macedonicus, which reflects the inherent ability of the bacterium to adjust the response to the distinctiveness of the imposed stress condition, probably to maximize its adaptability.
Changes in Bacterial Denitrifier Community Abundance over Time in an Agricultural Field and Their Relationship with Denitrification Activity
Authors: Dandie Catherine E. , Burton David L. , Zebarth Bernie J. , Henderson Sherri L. , Trevors Jack T. , Goyer Claudia 
Published: August 2008

ABSTRACT

This study measured total bacterial and denitrifier community abundances over time in an agricultural soil cropped to potatoes (
Solanum tuberosum
L.) by using quantitative PCR. Samples were collected on 10 dates from spring to autumn and from three spatial locations: in the potato “hill” between plants (H), close to the plant (H
p
), and in the “furrow” (F). The denitrification rates, N
2
O emissions, and environmental parameters were also measured. Changes in denitrifier abundance over time and spatial location were small (1.7- to 2.7-fold for the
nirK
,
nosZ
, and
cnorB
B
guilds), whereas the
cnorB
P
community (
Pseudomonas mandelii
and closely related spp.) showed an ∼4.6-fold change. The seasonal patterns of denitrifier gene numbers varied with the specific community: lower
nosZ
gene numbers in April and May than in June and July, higher
cnorB
P
gene numbers in May and June than in March and April and September and November, higher
nirK
gene numbers in early spring than in late autumn, and no change in
cnorB
B
gene numbers. Gene numbers were higher for the H
p
than the H location for the
nosZ
and
nirK
communities and for the
cnorB
P
community on individual dates, presumably indicating an effect of the plant on denitrifier abundance. Higher
cnorB
P
gene numbers for the H location than the F location and for
nosZ
and
cnorB
B
on individual dates reflect the effect of spatial location on abundance. Denitrifier abundance changes were not related to any environmental parameter, although a weak relationship exists between
cnorB
P
gene numbers, extractable organic carbon values, and temperature. Denitrification and N
2
O emissions were mostly regulated by inorganic nitrogen availability and water-filled pore space but were uncoupled from denitrifier community abundances measured in this system.
Bacterial Community in the Crop of the Hoatzin, a Neotropical Folivorous Flying Bird
Authors: Godoy-Vitorino Filipa , Ley Ruth E. , Gao Zhan , Pei Zhiheng , Ortiz-Zuazaga Humberto , Pericchi Luis R. , Garcia-Amado Maria A. , Michelangeli Fabian , Blaser Martin J. , Gordon Jeffrey I. , Domínguez-Bello Maria G. 
Published: August 2008

ABSTRACTThe hoatzin is unique among known avian species because of the fermentative function of its enlarged crop. A small-bodied flying foregut fermenter is a paradox, and this bird provides an interesting model to examine how diet selection and the gut microbiota contribute to maximizing digestive efficiency. Therefore, we characterized the bacterial population in the crop of six adult hoatzins captured from the wild. A total of 1,235 16S rRNA gene sequences were grouped into 580 phylotypes (67% of the pooled species richness sampled, based on Good's coverage estimator, with CACEand Chao1 estimates of 1,709 and 1,795 species-level [99% identity] operational taxonomic units, respectively). Members of 9 of the ∼75 known phyla inBacteriawere identified in this gut habitat; theFirmicuteswere dominant (67% of sequences, belonging to the classesClostridia,Mollicutes, andBacilli), followed by theBacteroidetes(30%, mostly in the orderBacteroidales),Proteobacteria(1.8%), andLentisphaerae,Verrucomicrobia, TM7,Spirochaetes,Actinobacteria, andAminanaerobia(all <0.1%). The novelty in this ecosystem is great; 94% of the phylotypes were unclassified at the “species” level and thus likely include novel cellulolytic lineages.
The Obligate Mutualist
Wigglesworthia glossinidia
Influences Reproduction, Digestion, and Immunity Processes of Its Host, the Tsetse Fly
Authors: Pais Roshan , Lohs Claudia , Wu Yineng , Wang Jingwen , Aksoy Serap 
Published: August 2008

ABSTRACT

Tsetse flies (Diptera: Glossinidae) are vectors for trypanosome parasites, the agents of the deadly sleeping sickness disease in Africa. Tsetse also harbor two maternally transmitted enteric mutualist endosymbionts: the primary intracellular obligate
Wigglesworthia glossinidia
and the secondary commensal
Sodalis glossinidius
. Both endosymbionts are transmitted to the intrauterine progeny through the milk gland secretions of the viviparous female. We administered various antibiotics either continuously by per os supplementation of the host blood meal diet or discretely by hemocoelic injections into fertile females in an effort to selectively eliminate the symbionts to study their individual functions. A symbiont-specific PCR amplification assay and fluorescence in situ hybridization analysis were used to evaluate symbiont infection outcomes. Tetracycline and rifampin treatments eliminated all tsetse symbionts but reduced the fecundity of the treated females. Ampicillin treatments did not affect the intracellular
Wigglesworthia
localized in the bacteriome organ and retained female fecundity. The resulting progeny of ampicillin-treated females, however, lacked
Wigglesworthia
but still harbored the commensal
Sodalis
. Our results confirm the presence of two physiologically distinct
Wigglesworthia
populations: the bacteriome-localized
Wigglesworthia
involved with nutritional symbiosis and free-living
Wigglesworthia
in the milk gland organ responsible for maternal transmission to the progeny. We evaluated the reproductive fitness, longevity, digestion, and vectorial competence of flies that were devoid of
Wigglesworthia
. The absence of
Wigglesworthia
completely abolished the fertility of females but not that of males. Both the male and female
Wigglesworthia
-free adult progeny displayed longevity costs and were significantly compromised in their blood meal digestion ability. Finally, while the vectorial competence of the young newly hatched adults without
Wigglesworthia
was comparable to that of their wild-type counterparts, older flies displayed higher susceptibility to trypanosome infections, indicating a role for the mutualistic symbiosis in host immunobiology. The ability to rear adult tsetse that lack the obligate
Wigglesworthia
endosymbionts will now enable functional investigations into this ancient symbiosis.