bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is autism due to brain desynchronization?
Authors: Welsh John P. , Ahn Edward S. , Placantonakis Dimitris G. 
Published: November 2004

AbstractThe hypothesis is presented that a disruption in brain synchronization contributes to autism by destroying the coherence of brain rhythms and slowing overall cognitive processing speed. Particular focus is on the inferior olive, a precerebellar structure that is reliably disrupted in autism and which normally generates a coherent 5–13 Hz rhythmic output. New electrophysiological data reveal that the continuity of the rhythmical oscillation in membrane potential generated by inferior olive neurons requires the formation of neuronal assemblies by the connexin36 protein that mediates electrical synapses and promotes neuronal synchrony. An experiment with classical eyeblink conditioning is presented to demonstrate that the inferior olive is necessary to learn about sequences of stimuli presented at intervals in the range of 250–500 ms, but not at 700 ms, revealing that a disruption of the inferior olive slows stimulus processing speed on the time scale that is lost in autistic children. A model is presented in which the voltage oscillation generated by populations of electrically synchronized inferior olivary neurons permits the utilization of sequences of stimuli given at, or faster than, 2 per second. It is expected that the disturbance in inferior olive structure in autism disrupts the ability of inferior olive neurons to become electrically synchronized and to generate coherent rhythmic output, thereby impairing the ability to use rapid sequences of cues for the development of normal language skill. Future directions to test the hypothesis are presented.
SPACES OF LIPSCHITZ TYPE ON METRIC SPACES AND THEIR APPLICATIONS
Authors: Yang Dachun , Lin Yong 
Published: November 2004

AbstractNew spaces of Lipschitz type on metric-measure spaces are introduced and they are shown to be just the well-known Besov spaces or Triebel–Lizorkin spaces when the smooth index is less than 1. These theorems also hold in the setting of spaces of homogeneous type, which include Euclidean spaces, Riemannian manifolds and some self-similar fractals. Moreover, the relationships amongst these Lipschitz-type spaces, Hajłasz–Sobolev spaces, Korevaar–Schoen–Sobolev spaces, Newtonian Sobolev space and Cheeger–Sobolev spaces on metric-measure spaces are clarified, showing that they are the same space with equivalence of norms. Furthermore, a Sobolev embedding theorem, namely that the Lipschitz-type spaces with large orders of smoothness can be embedded in Lipschitz spaces, is proved. For metric-measure spaces with heat kernels, a Hardy–Littlewood–Sobolev theorem is establish, and hence it is proved that Lipschitz-type spaces with small orders of smoothness can be embedded in Lebesgue spaces.AMS 2000 Mathematics subject classification: Primary 42B35. Secondary 46E35; 58J35; 43A99
Inhibition of calcium‐calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
Authors: Rosignoli Florencia , Roca Valeria , Meiss Roberto , Pregi Nicolás , Leirós Claudia Pérez 
Published: November 2004

Nitric oxide is an intracellular and diffusible messenger of neurotransmitters involved in salivary secretion, as well as an inflammatory mediator in salivary gland diseases. It is synthesized by three different isoforms of nitric oxide synthase (NOS), each subject to a fine transcriptional, post‐transcriptional and/or post‐translational regulation. Our purpose was to study the possible mechanisms leading to NOS downregulation in submandibular glands of normal mice and in the nonobese diabetic (NOD) mouse model of salivary dysfunction with lower NOS activity.
NOS activity and cGMP accumulation were determined by radioassays in submandibular glands of both mice in the presence of the protein kinase inhibitors KN‐93 and bisindolylmaleimide. NOS I mRNA and protein expression and localization were assessed by RT–PCR, Western blot and immunohistochemistry.
A downregulatory effect of calcium–calmodulin kinase II (CaMK II) on NOS activity in submandibular glands of both NOD and BALB/c mice was observed. Our results are consistent with a physiological regulation of NOS activity by this kinase but not by PKC in normal BALB/c mice. They are also supportive of a role for CaMK II in the lack of detectable NOS activity in submandibular glands of NOD mice. KN‐93 also restored cGMP accumulation in NOD submandibular glands.
The downregulation of NOS in NOD mice seems to be mainly mediated by this kinase rather than the result of a lower expression or different cellular localization of the enzyme. It was not related to different substrate or cofactors availability either.

British Journal of Pharmacology (2004) 143, 1058–1065. doi:10.1038/sj.bjp.0705952
Platelet–leukocyte aggregation induced by PAR agonists: regulation by nitric oxide and matrix metalloproteinases
Authors: Chung Ada W Y , Radomski Anna , Alonso‐Escolano David , Jurasz Paul , Stewart Michael W , Malinski Tadeusz , Radomski Marek W 
Published: November 2004

Platelet–leukocyte aggregation (PLA) links haemostasis to inflammation. The role of nitric oxide (NO) and matrix metalloproteinases (MMP‐1, ‐2, ‐3, ‐9) in PLA regulation was studied.
Homologous human platelet–leukocyte suspensions were stimulated with thrombin (0.1–3 nM) and other proteinase activated receptor‐activating peptides (PAR‐AP), including PAR1AP (0.5–10 μM), PAR4AP (10–70 μM), and thrombin receptor‐activating peptide (1–35 μM).
PLA was studied using light aggregometry with simultaneous measurement of oxygen‐derived free radicals, dual colour flow cytometry, and phase‐contrast microscopy.
The release of NO was measured using a porphyrinic nanosensor, while MMPs were investigated by Western blot, substrate degradation assays, immunofluorescence microscopy, and flow cytometry. The levels of P‐selectin and microparticles (MP) in PLA were measured by flow cytometry.
PLA was also characterized using pharmacological agents: S‐nitroso‐glutathione (GSNO, 0.01–10 μM), 1H‐Oxadiazole quinoxalin‐1‐one (ODQ, 1 μM), NG‐L‐nitro‐L‐arginine methyl ester (L‐NAME, 100 μM) and compounds that modulate the actions of MMPs such as phenanthroline (100 μM), monoclonal anti‐MMP antibodies, and purified MMPs.
PAR agonists concentration‐dependently induced PLA, an effect associated with the release of microparticles (MP) and the translocation of P‐selectin to the platelet surface.
NO and radicals were also released during PLA. Inhibition of NO bioactivity by the concomitant release of free radicals or by the treatment with L‐NAME or ODQ stimulated PLA, while pharmacological administration of GSNO decreased PLA.
PAR agonist‐induced PLA resulted in the liberation of MMP‐1, ‐2, ‐3, and ‐9.
During PLA, MMPs were present on the cell surface, as shown by flow cytometry and immunofluorescence.
PLA led to the activation of latent MMPs to active MMPs, as shown by Western blot and substrate degradation assays.
Inhibition of MMPs actions by phenanthroline and by the antibodies attenuated PLA. In contrast, purified active, but not latent, MMPs amplified thrombin‐induced PLA.
It is concluded that NO and MMP‐1, ‐2, ‐3, and ‐9 play an important role in regulation of PAR agonist‐induced PLA.

British Journal of Pharmacology (2004) 143, 845–855. doi:10.1038/sj.bjp.0705997
Erythromycin exerts in vivo anti‐inflammatory activity downregulating cell adhesion molecule expression
Authors: Sanz María‐Jesús , Nabah Yafa Naim Abu , Cerdá‐Nicolás Miguel , O'Connor José‐Enrique , Issekutz Andrew C , Cortijo Julio , Morcillo Esteban J 
Published: November 2004

Macrolides have long been used as anti‐bacterial agents; however, there is some evidence that may exert anti‐inflammatory activity. Therefore, erythromycin was used to characterize the mechanisms involved in their in vivo anti‐inflammatory activity.
Erythromycin pretreatment (30 mg kg−1 day−1 for 1 week) reduced the lipopolysaccharide (LPS; intratracheal, 0.4 mg kg−1)‐induced increase in neutrophil count and elastase activity in the bronchoalveolar lavage fluid (BALF) and lung tissue myeloperoxidase activity, but failed to decrease tumor necrosis factor‐α and macrophage‐inflammatory protein‐2 augmented levels in BALF. Erythromycin pretreatment also prevented lung P‐selectin, E‐selectin, intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) mRNA upregulation in response to airway challenge with LPS.
Mesentery superfusion with LPS (1 μg ml−1) induced a significant increase in leukocyte–endothelial cell interactions at 60 min. Erythromycin pretreatment abolished the increases in these parameters.
LPS exposure of the mesentery for 4 h caused a significant increase in leukocyte rolling flux, adhesion and emigration, which were inhibited by erythromycin by 100, 93 and 95%, respectively.
Immunohistochemical analysis showed that LPS exposure of the mesentery for 4 h caused a significant enhancement in P‐selectin, E‐selectin, ICAM‐1 and VCAM‐1 expression that was downregulated by erythromycin pretreatment.
Flow cytometry analysis indicated that erythromycin pretreatment inhibited LPS‐induced CD11b augmented expression in rat neutrophils.
In conclusion, erythromycin inhibits leukocyte recruitment in the lung and this effect appears mediated through downregulation of CAM expression. Therefore, macrolides may be useful in the control of neutrophilic pulmonary diseases.

British Journal of Pharmacology (2005) 144, 190–201. doi:10.1038/sj.bjp.0706021
A newly identified zona pellucida glycoprotein, ZPD, and dimeric ZP1 of chicken egg envelope are involved in sperm activation on sperm–egg interaction
Authors: OKUMURA Hiroki , KOHNO Yoshinori , IWATA Yuki , MORI Hitoshi , AOKI Naohito , SATO Chihiro , KITAJIMA Ken , NADANO Daita , MATSUDA Tsukasa 
Published: November 2004

Fertilization begins with interaction between the sperm and the egg. The surface of the vertebrate oocyte is covered with the egg envelope, which is composed of ZP (zona pellucida) glycoproteins. We have identified two glycoproteins, ZP1/gp97 and ZPC/gp42, as the major components of the chicken egg envelope. In the present study, another 42 kDa protein, designated ZPD, has been found as a new major component of the chicken egg envelope. ZPD was specifically released from the egg envelope by ultrasonication treatment without urea. ZPD cDNA was cloned using a chicken granulosa cell cDNA pool. The deduced amino acid sequence showed that preproprotein of ZPD is composed of 418 amino acid residues with four potential N-glycosylation sites and includes a ZP domain, common in vertebrate ZP glycoproteins, and a transmembrane domain. ZPD belongs phylogenetically to a distinct group from known ZP glycoprotein subfamilies, ZPA, ZPB, and ZPC. In two-dimensional gel electrophoresis ZPD proteins were identified to be several isoforms with different pI values between 5 and 7. ZP1, ZPC and the newly identified ZPD were confirmed to be the major components of chicken egg envelope by MS of proteolytic digests of whole egg envelope. The in vitro incubation of chicken sperm with calcium ionophore A23187 induced sperm activation, resulting in the fragmentation and release of a 41 kDa PNA (peanut agglutinin)-positive glycoprotein and the decrease or loss of sperm PNA-stainability. The incubation with ZPD and dimeric ZP1, but not ZPC and monomeric ZP1, also induced the decrease or loss of sperm PNA-stainability, suggesting the in vitro sperm activation by these ZP components. Collectively, ZPD might bind loosely to egg envelope matrix and play a key role in the sperm activation on avian sperm–egg interaction.
Proteomic characterization of two snake venoms: Naja naja atra and Agkistrodon halys
Authors: LI Shuting , WANG Jingqiang , ZHANG Xumin , REN Yan , WANG Ning , ZHAO Kang , CHEN Xishu , ZHAO Caifeng , LI Xiaolei , SHAO Jianmin , YIN Jianning , WEST Matthew B. , XU Ningzhi , LIU Siqi 
Published: November 2004

Snake venom is a complex mixture of proteins and peptides, and a number of studies have described the biological properties of several venomous proteins. Nevertheless, a complete proteomic profile of venom from any of the many species of snake is not available. Proteomics now makes it possible to globally identify proteins from a complex mixture. To assess the venom proteomic profiles from Naja naja atra and Agkistrodon halys, snakes common to southern China, we used a combination strategy, which included the following four different approaches: (i) shotgun digestion plus HPLC with ion-trap tandem MS, (ii) one-dimensional SDS/PAGE plus HPLC with tandem MS, (iii) gel filtration plus HPLC with tandem MS and (iv) gel filtration and 2DE (two-dimensional gel electrophoresis) plus MALDI–TOF (matrix-assisted laser desorption ionization–time-of-flight) MS. In the present paper, we report the novel identification of 124 and 74 proteins and peptides in cobra and viper venom respectively. Functional analysis based upon toxin categories reveals that, as expected, cobra venom has a high abundance of cardio- and neurotoxins, whereas viper venom contains a significant amount of haemotoxins and metalloproteinases. Although approx. 80% of gel spots from 2DE displayed high-quality MALDI-TOF-MS spectra, only 50% of these spots were confirmed to be venom proteins, which is more than likely to be a result of incomplete protein databases. Interestingly, these data suggest that post-translational modification may be a significant characteristic of venomous proteins.
Differential activation of NFκB/RelA‐p50 and NFκB/p50‐p50 in control and alcohol‐drinking rats subjected to carrageenin‐induced pleurisy
Authors: Singh Ashok K. , Jiang Yin 
Published: November 2004

BACKGROUND: Carrageenin (CAR) injection into the pleural cavity causes local inflammation called carrageenin‐induced pleurisy (CAR‐IP). Inflammation onset is characterized by an activation of pro‐inflammatory NFκB, RelA‐p50, while inflammation resolution is characterized by an activation of an anti‐inflammatory NFκB, p50‐p50, that re‐establishes homeostasis, an essential process for an organism′s survival. Although chronic alcohol intake disrupts inflammation, the mechanism behind the development of inflammatory disorder in alcoholics is not yet known. Therefore, the aim of this investigation was to study the effects of ethanol intake on CAR‐IP and NFκB activation in pleural fluid neutrophils in P rats.Methods: Alcohol‐preferring, P rats were given free choice of alcohol (15% ethanol) and water or water alone (for control) for 15 days. Then, each rat was injected with 0.2 ml of 2% CAR into the pleural cavity under light ether anesthesia. At different time intervals after the CAR injection, rats were anesthetized and their blood and pleural fluid samples were collected. Pleural fluid inflammatory cells were identified with Turk′s or Wright‐Giemsa staining. Different cell types were sorted using a fluorescence‐activated cell sorter. Pleural fluid neutrophils were examined for apoptosis and activation of the two NFκB subspecies.Results: In control rats, fluid began to accumulate in the pleural cavity 0.5 h after, which peaked 24 h after, CAR injection. Then, the values declined gradually. The increase in pleural fluid correlated with RelA‐p50 activation, while the decline in pleural fluid correlated with p50‐p50 activation and apoptosis in neutrophils. In alcohol‐drinking rats, pleural fluid remained elevated for up to 6 days after CAR injection. Neutrophils from alcohol‐drinking rats exhibited suppressed apoptosis, augmented RelA‐p50 activation, and suppressed p50‐p50 activation.Conclusions: Alcohol intake prolonged inflammation in P rats. An alcohol‐induced upregulation of RelA‐p50 activation and downregulation of p50‐p50 activation may be causally related to the alcohol‐induced inflammation dysregulation.
Effects of ′casoparan′, a peptide isolated from casein hydrolysates with mastoparan‐like properties
Authors: Lebrun Ivo , Cavallaro Valéria , Juliano Luiz , Juliano Maria A. , e Silva Maria C. C. de Sousa 
Published: November 2004

CASEIN, a protein found in milk of several species, is divided into different chains from 19 to 25 kDa. Casein is also considered as a source of amino acids and generating peptides with biological activities such as opiate, immunostimulating, antibacterial, peptidase inhibitors, among others.In this work, Sephadex G‐10 chromatography followed by high‐performance liquid chromatography isolation purified NZCase TT, an industrial culture media for tetanus toxin production. In the first step, four pools were isolated and tested in different assays: isolated smooth muscle assay (guinea pig ileum, rat uterus), phagocytosis in vitro of opsonized sheep red blood cells, and hydrogen peroxide (H2O2) release from mouse peritoneal macrophages.Pool III was the main active pool being able to potentiate bradykinin action in guinea pig ileum, stimulating phagocitic activity by resident macrophages and increasing H2O2 release from macrophages previously activated with bacille Calmette Guérin.Using mass spectra the primary structure of the main peptide from pool III was obtained – INKKI, which corresponds to β‐casein fragment 26‐30.The immunostimulating action is probably related to a direct action in macrophage cells.
Serum procalcitonin and cerebrospinal fluid cytokines level in children with meningitis
Authors: Taskın Erdal , Turgut Mehmet , Kılıc Mehmet , Akbulut Handan , Aygun A. Denizmen 
Published: November 2004

Aims: To determine the level of serum procalcitonin and cerebrospinal fluid cytokines in children with bacterial or viral meningitis and to document the use of these parameters in differential diagnosis.Results: Before the start of antibiotic treatment, serum procalcitonin and tumor necrosis factor alpha levels were found to be higher in acute bacterial meningitis compared with viral meningitis and with the control group. Similarly, cerebrospinal fluid interleukin‐6 levels were found to be significantly higher in children with acute bacterial meningitis compared with viral meningitis. However, no significant difference was determined between groups in respect to the cerebrospinal fluid interleukin‐8 level.Conclusion: Serum procalcitonin and cerebrospinal fluid tumor necrosis factor alpha levels can be used in the early diagnosis of bacterial meningitis. Similarly, they may be useful adjuncts in differential diagnosis of bacterial and viral meningitis.
Inhaled corticosteroid effects both eosinophilic and non‐eosinophilic inflammation in asthmatic patients
Authors: Basyigit Ilknur , Yildiz Fusun , Ozkara Sevgiye Kacar , Boyaci Hasim , Ilgazli Ahmet 
Published: November 2004

AIM: To determine induced sputum cell counts and interleukin‐8 (IL‐8), tumor necrosis factor alpha (TNF‐α) and leukotriene B4 (LTB4) levels as markers of neutrophilic inflammation in moderate persistent asthma, and to evaluate the response to inhaled steroid therapy.Methods: Forty‐five moderate asthmatic patients and 10 non‐smoker controls were included in this study. All patients received inhaled corticosteroid (800 μg of budesonide) for 12 weeks. Before and after treatment pulmonary function tests were performed, and symptom scores were determined. Blood was drawn for analysis of serum inflammatory markers, and sputum was induced.Results: Induced sputum cell counts and inflammatory markers were significantly higher in patients with asthma than in the control group. The induced sputum eosinophil counts of 12 patients (26%) were found to be less than 5%, the non‐eosinophilic group, and sputum neutrophil counts, IL‐8 and TNF‐α levels were significantly higher than the eosinophilic group (neutrophil, 50±14% versus 19±10%, p < 0.01). In both groups, there was a significant decrease in sputum total cell counts and serum and sputum IL‐8, TNF‐α and LTB4 levels after the treatment. There was no change in sputum neutrophil counts. Although the sputum eosinophil count decreased only in the eosinophilic subjects, there was no significant difference in inflammatory markers between the groups. The symptom scores were significantly improved after treatment, while the improvement did not reach statistical significance on pulmonary function test parameters.Conclusion: Notably, in chronic asthma there is a subgroup of patients whose predominant inflammatory cells are not eosinophils. Sputum neutrophil counts and neutrophilic inflammatory markers are significantly higher in these patients. In the non‐eosinophilic group, inhaled steroid caused an important decrease in inflammatory markers; however, there was no change in the sputum eosinophil and neutrophil counts.
Mitochondrial Dysfunction by Synthetic Ligands of Peroxisome Proliferator Activated Receptors (PPARs)
Authors: Scatena Roberto , Martorana Giuseppe , Bottoni Patrizia , Giardina Bruno 
Published: November 2004

AbstractPPARs are a class of nuclear receptors involved in lipid and glucidic metabolism, immune regulation and cell differentiation. This spectrum of biological activities stimulated pharmacological research to synthetize different molecules with PPARs binding activity with beneficial therapeutic effects. As a matter of fact, some synthetic PPAR‐ligands have been already employed in pharmacotherapy: PPAR‐α ligands, such as fibrates, are used in hyperlipidemias and thiazolidinediones, mainly PPAR‐γ ligands, are employed as insulin sensitizers. However, both classes of drugs showed pharmacotoxicological profiles which cannot be fully ascribed to activation of their specific receptors and which are causing a growing incidence of dramatic side effects (rhabdomyolysis, acute liver failure, heart failure, etc.). A re‐evaluation of the biological activities of PPAR synthetic ligands, in particular of the mitochondrial dysfunction based on a rotenone‐like Complex I partial inhibition and of its consequent metabolic adaptations, seems to explain some of the pathophysiologic aspects of PPARs allowing a better definition of the therapeutic properties of the so‐called PPAR‐ligands. IUBMB Life, 56: 477‐482, 2004
Cloning and Heterologous Expression of a Methanococcus vannielii Gene Encoding a Selenium‐Binding Protein
Authors: Self William , Pierce Renee , Stadtman TC 
Published: November 2004

AbstractThe activation and incorporation of selenium into selenocysteine containing selenoproteins has been well established in an Escherichia coli model system but there is little specific information concerning the transport and intracellular trafficking of selenium in biological systems in general. A selenium transport role is a possible function of a novel 42 kDa selenium‐binding protein that recently was purified from Methanococcus vannielii. The gene encoding a monomer of this protein (Sbp) has been cloned, sequenced and heterologously expressed in E. coli. The 8.8 kDa gene product contains 81 amino acids. The recombinant Sbp (rSbp) protein was shown to bind selenium from added selenite. The bound selenium appeared predominantly in dimeric and tetrameric forms of the protein. The gene encoding Sbp occurs in an operon that contains a carbonic anhydrase gene and selenocysteine‐containing formate dehydrogenase genes, suggesting possible roles in selenium‐dependent formate metabolism. IUBMB Life, 56: 501‐507, 2004
Ribosomal RNA Processing and Ribosome Biogenesis in Eukaryotes
Authors: Nazar Ross 
Published: November 2004

AbstractIn eukaryotes nearly 500 rRNAs, ribosomal proteins, snoRNAs and trans‐acting factors contribute to ribosome biogenesis. After more than 30 years of intense research, the incredible complexities of nucleolar function are revealed but details often remain unclear. Here we review this progress and the many intriguing questions which remain. IUBMB Life, 56: 457‐465, 2004