bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of neutral lipids in peripheral blood mononuclear cells as a distinctive trait of Alzheimer patients and asymptomatic subjects at risk of disease
Authors: Pani Alessandra , Mandas Antonella , Diaz Giacomo , Abete Claudia , Cocco Pier Luigi , Angius Fabrizio , Brundu Annalisa , Muçaka Nico , Pais Maria Elena , Saba Antonio , Barberini Luigi , Zaru Cristina , Palmas Manuela , Putzu Paolo F , Mocali Alessandra , Paoletti Francesco , La Colla Paolo , Dessì Sandra 
Published: November 2009

Abstract

Background
Alzheimer's disease is the most common progressive neurodegenerative disease. In recent years, numerous progresses in the discovery of novel Alzheimer's disease molecular biomarkers in brain as well as in biological fluids have been made. Among them, those involving lipid metabolism are emerging as potential candidates. In particular, an accumulation of neutral lipids was recently found by us in skin fibroblasts from Alzheimer's disease patients. Therefore, with the aim to assess whether peripheral alterations in cholesterol homeostasis might be relevant in Alzheimer's disease development and progression, in the present study we analyzed lipid metabolism in plasma and peripheral blood mononuclear cells from Alzheimer's disease patients and from their first-degree relatives.

Methods
Blood samples were obtained from 93 patients with probable Alzheimer's disease and from 91 of their first-degree relatives. As controls we utilized 57, cognitively normal, over-65 year-old volunteers and 113 blood donors aged 21-66 years, respectively. Data are reported as mean ± standard error. Statistical calculations were performed using the statistical analysis software Origin 8.0 version. Data analysis was done using the Student t-test and the Pearson test.

Results
Data reported here show high neutral lipid levels and increased ACAT-1 protein in about 85% of peripheral blood mononuclear cells freshly isolated (ex vivo) from patients with probable sporadic Alzheimer's disease compared to about 7% of cognitively normal age-matched controls. A significant reduction in high density lipoprotein-cholesterol levels in plasma from Alzheimer's disease blood samples was also observed. Additionally, correlation analyses reveal a negative correlation between high density lipoprotein-cholesterol and cognitive capacity, as determined by Mini Mental State Examination, as well as between high density lipoprotein-cholesterol and neutral lipid accumulation. We observed great variability in the neutral lipid-peripheral blood mononuclear cells data and in plasma lipid analysis of the subjects enrolled as Alzheimer's disease-first-degree relatives. However, about 30% of them tend to display a peripheral metabolic cholesterol pattern similar to that exhibited by Alzheimer's disease patients.

Conclusion
We suggest that neutral lipid-peripheral blood mononuclear cells and plasma high density lipoprotein-cholesterol determinations might be of interest to outline a distinctive metabolic profile applying to both Alzheimer's disease patients and asymptomatic subjects at higher risk of disease.
Bovine viral diarrhea virus NS4B protein is an integral membrane protein associated with Golgi markers and rearranged host membranes
Authors: Weiskircher Erica , Aligo Jason , Ning Gang , Konan Kouacou V 
Published: November 2009

Abstract

Background
Very little is known about BVDV NS4B, a protein of approximately 38 kDa. However, a missense mutation in NS4B has been implicated in changing BVDV from a cytopathic to noncytopathic virus, suggesting that NS4B might play a role in BVDV pathogenesis. Though this is one possible function, it is also likely that NS4B plays a role in BVDV genome replication. For example, BVDV NS4B interacts with NS3 and NS5A, implying that NS4B is part of a complex, which contains BVDV replicase proteins. Other possible BVDV NS4B functions can be inferred by analogy to hepatitis C virus (HCV) NS4B protein. For instance, HCV NS4B remodels host membranes to form the so-called membranous web, the site for HCV genome replication. Finally, HCV NS4B is membrane-associated, implying that HCV NS4B may anchor the virus replication complex to the membranous web structure. Unlike its HCV counterpart, we know little about the subcellular distribution of BVDV NS4B protein. Further, it is not clear whether NS4B is localized to host membrane alterations associated with BVDV infection.

Results
We show first that release of infectious BVDV correlates with the kinetics of BVDV genome replication in infected cells. Secondly, we found that NS4B subcellular distribution changes over the course of BVDV infection. Further, BVDV NS4B is an integral membrane protein, which colocalizes mainly with the Golgi compartment when expressed alone or in the context of BVDV infection. Additionally, BVDV induces host membrane rearrangement and these membranes contain BVDV NS4B protein. Finally, NS4B colocalizes with replicase proteins NS5A and NS5B proteins, raising the possibility that NS4B is a component of the BVDV replication complex. Interestingly, NS4B was found to colocalize with mitochondria suggesting that this organelle might play a role in BVDV genome replication or cytopathogenicity.

Conclusion
These results show that BVDV NS4B is an integral membrane protein associated with the Golgi apparatus and virus-induced membranes, the putative site for BVDV genome replication. On the basis of NS4B Colocalization with NS5A and NS5B, we conclude that NS4B protein is an integral component of the BVDV replication complex.
Utility of a novel lipoarabinomannan assay for the diagnosis of tuberculous meningitis in a resource-poor high-HIV prevalence setting
Authors: Patel Vinod B , Bhigjee Ahmed I , Paruk Hoosain F , Singh Ravesh , Meldau Richard , Connolly Cathy , Ndung'u Thumbi , Dheda Keertan 
Published: November 2009

Abstract

Background
In Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients. Current diagnostic tools for TBM perform sub-optimally. In particular, the rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in resource-poor settings.

Methods
We evaluated the performance outcome of a novel standardized lipoarabinomannan (LAM) antigen-detection assay, using archived cerebrospinal fluid samples, in 50 African TBM suspects of whom 68% were HIV-positive.

Results
Of the 50 participants 14, 23 and 13 patients had definite, probable and non-TBM, respectively. In the non-TB group there were 5 HIV positive patients who were lost to follow-up and in whom concomitant infection with Mycobacterium tuberculosis could not be definitively excluded. The test sensitivities and specificities were as follows: LAM assay 64% and 69% (cut-point 0.22), smear microscopy 0% and 100% and PCR 93% and 77%, respectively.

Conclusion
In this preliminary proof-of-concept study, a rapid diagnosis of TBM could be achieved using LAM antigen detection. Although specificity was sub-optimal, the estimates provided here may be unreliable because of a classification bias inherent in the study design where it was not possible to exclude TBM in the presumed non-TBM cases owing to a lack of clinical follow-up. As PCR is largely unavailable, the LAM assay may well prove to be a useful adjunct for the rapid diagnosis of TBM in high HIV-incidence settings. These preliminary results justify further enquiry and prospective studies are now required to definitively establish the place of this technology for the diagnosis of TBM.
Differential Role of the Menthol-Binding Residue Y745 in the Antagonism of Thermally Gated TRPM8 Channels
Authors: Malkia Annika , Pertusa María , Fernández-Ballester Gregorio , Ferrer-Montiel Antonio , Viana Félix 
Published: November 2009

Background TRPM8 is a non-selective cation channel that belongs to the melastatin subfamily of the transient receptor potential (TRP) ion channels. TRPM8 is activated by voltage, cold and cooling compounds such as menthol. Despite its essential role for cold temperature sensing in mammals, the pharmacology of TRPM8 is still in its infancy. Recently, tyrosine 745 (Y745) was identified as a critical residue for menthol sensitivity of the channel. In this report, we study the effect of mutating this residue on the action of several known TRPM8 antagonists: BCTC, capsazepine, SKF96365, and clotrimazole as well as two new inhibitor candidates, econazole and imidazole. Results We show that Y745 at the menthol binding site is critical for inhibition mediated by SKF96365 of cold- and voltage-activated TRPM8 currents. In contrast, the inhibition by other antagonists was unaffected by the mutation (BCTC) or only partially reduced (capsazepine, clotrimazole, econazole), suggesting that additional binding sites exist on the TRPM8 channel from where the inhibitors exert their negative modulation. Indeed, a molecular docking model implies that menthol and SKF96365 interact readily with Y745, while BCTC is unable to bind to this residue. Conclusion In summary, we identify structural elements on the TRPM8 channel that are critical for the action of channel antagonists, providing valuable information for the future design of new, specific modulator compounds.
Temporal patterns of broad isoform expression during the development of neuronal lineages in Drosophila
Authors: Zhou Baohua , Williams Darren W , Altman Janet , Riddiford Lynn M , Truman James W 
Published: November 2009

Abstract
Background
During the development of the central nervous system (CNS) of Drosophila, neuronal stem cells, the neuroblasts (NBs), first generate a set of highly diverse neurons, the primary neurons that mature to control larval behavior, and then more homogeneous sets of neurons that show delayed maturation and are primarily used in the adult. These latter, 'secondary' neurons show a complex pattern of expression of broad, which encodes a transcription factor usually associated with metamorphosis, where it acts as a key regulator in the transitions from larva and pupa.

Results
The Broad-Z3 (Br-Z3) isoform appears transiently in most central neurons during embryogenesis, but persists in a subset of these cells through most of larval growth. Some of the latter are embryonic-born secondary neurons, whose development is arrested until the start of metamorphosis. However, the vast bulk of the secondary neurons are generated during larval growth and bromodeoxyuridine incorporation shows that they begin expressing Br-Z3 about 7 hours after their birth, approximately the time that they have finished outgrowth to their initial targets. By the start of metamorphosis, the oldest secondary neurons have turned off Br-Z3 expression, while the remainder, with the exception of the very youngest, maintain Br-Z3 while they are interacting with potential partners in preparation for neurite elaboration. That Br-Z3 may be involved in early sprouting is suggested by ectopically expressing this isoform in remodeling primary neurons, which do not normally express Br-Z3. These cells now sprout into ectopic locations. The expression of Br-Z3 is transient and seen in all interneurons, but two other isoforms, Br-Z4 and Br-Z1, show a more selective expression. Analysis of MARCM clones shows that the Br-Z4 isoform is expressed by neurons in virtually all lineages, but only in those cells born during a window during the transition from the second to the third larval instar. Br-Z4 expression is then maintained in this temporal cohort of cells into the adult.

Conclusion
These data show the potential for diverse functions of Broad within the developing CNS. The Br-Z3 isoform appears in all interneurons, but not motoneurons, when they first begin to interact with potential targets. Its function during this early sorting phase needs to be defined. Two other Broad isoforms, by contrast, are stably expressed in cohorts of neurons in all lineages and are the first examples of persisting molecular 'time-stamps' for Drosophila postembryonic neurons.
Promotion of embryonic cortico-cerebral neuronogenesis by miR-124
Authors: Maiorano Nicola Antonio , Mallamaci Antonello 
Published: November 2009

Abstract
Background
Glutamatergic neurons of the murine cerebral cortex are generated within periventricular proliferative layers of the embryonic pallium, directly from apical precursors or indirectly via their basal progenies. Cortical neuronogenesis is the result of different morphogenetic subroutines, including precursor proliferation and death, changes in histogenetic potencies, and post-mitotic neuronal differentiation. Control of these processes is extremely complex, involving numerous polypeptide-encoding genes. Moreover, many so-called 'non-coding genes' are also expressed in the developing cortex. Currently, their implication in corticogenesis is the subject of intensive functional studies. A subset of them encodes microRNAs (miRNAs), a class of small RNAs with complex biogenesis that regulate gene expression at multiple levels and modulate histogenetic progression and are implicated in refinement of positional information. Among the cortical miRNAs, miR-124 has been consistently shown to promote neuronogenesis progression in a variety of experimental contexts. Some aspects of its activity, however, are still controversial, and some have to be clarified. An in depth in vivo characterization of its function in the embryonic mammalian cortex is still missing.

Results
By integrating locked nucleic acid (LNA)-oligo in situ hybridization, electroporation of stage-specific reporters and immunofluorescence, we reconstructed the cortico-cerebral miR-124 expression pattern during direct neuronogenesis from apical precursors and indirect neuronogenesis via basal progenitors. The miR-124 expression profile in the developing embryonic cortex includes an abrupt upregulation in apical precursors undergoing direct neuronogenesis as well as a two-step upregulation in basal progenitors during indirect neuronogenesis. Differential post-transcriptional processing seems to contribute to this pattern. Moreover, we investigated the role of miR-124 in embryonic corticogenesis by gain-of-function approaches, both in vitro, by lentivirus-based gene transfer, and in vivo, by in utero electroporation. Following overexpression of miR-124, both direct neuronogenesis and progression of neural precursors from the apical to the basal compartment were stimulated.

Conclusion
We show that miR-124 expression is progressively up-regulated in the mouse embryonic neocortex during the apical to basal transition of neural precursor cells and upon their exit from cell cycle, and that miR-124 is involved in the fine regulation of these processes.
Role of the Wnt receptor Frizzled-1 in presynaptic differentiation and function
Authors: Varela-Nallar Lorena , Grabowski Catalina P , Alfaro Iván E , Alvarez Alejandra R , Inestrosa Nibaldo C 
Published: November 2009

Abstract
Background
The Wnt signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some Wnt signaling components are localized at central synapses, and it is thus possible that this pathway could be activated at the synapse.

Results
We examined the distribution of the Wnt receptor Frizzled-1 in cultured hippocampal neurons and determined that this receptor is located at synaptic contacts co-localizing with presynaptic proteins. Frizzled-1 was found in functional synapses detected with FM1-43 staining and in synaptic terminals from adult rat brain. Interestingly, overexpression of Frizzled-1 increased the number of clusters of Bassoon, a component of the active zone, while treatment with the extracellular cysteine-rich domain (CRD) of Frizzled-1 decreased Bassoon clustering, suggesting a role for this receptor in presynaptic differentiation. Consistent with this, treatment with the Frizzled-1 ligand Wnt-3a induced presynaptic protein clustering and increased functional presynaptic recycling sites, and these effects were prevented by co-treatment with the CRD of Frizzled-1. Moreover, in synaptically mature neurons Wnt-3a was able to modulate the kinetics of neurotransmitter release.

Conclusion
Our results indicate that the activation of the Wnt pathway through Frizzled-1 occurs at the presynaptic level, and suggest that the synaptic effects of the Wnt signaling pathway could be modulated by local activation through synaptic Frizzled receptors.
Validity issues in the assessment of alexithymia related to the developmental stages of emotional cognition and language
Authors: Nishimura Hiroki , Komaki Gen , Igarashi Tetsuya , Moriguchi Yoshiya , Kajiwara Sohei , Akasaka Toru 
Published: November 2009

Abstract

Objective
We examined developmental aspects of the emotional awareness of adolescents by evaluating their responses to a self-reported questionnaire based on the Toronto Alexithymia Scale-20 (TAS-20).

Methods
The items of the TAS-20 were modified to make them more understandable by adolescents, and nine new items related to a limited capacity for imagination were added. The Japanese Linguistic Ability Test and the multi-dimensional empathy scale for adolescents were administered to examine concurrent validity. Two hundred and two normative young adolescents and thirty-two adolescent patients with psychosomatic and/or behavioral problems participated in the study. Eighty junior high school students also participated in a separate examination of test-retest reliability.

Results
Thirteen items were extracted after exploratory and confirmatory factor analyses, and four core factors were identified in the resulting scale: Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), Externally-Oriented Thinking (EOT) and Constricted Imaginal Capacities (CIC). Interestingly, scores on the multi-dimensional empathy scale correlated positively with DIF and DDF, but negatively with EOT and CIC. Higher DDF scores were associated with higher Japanese linguistic abilities. DIF/DDF scores were higher for females than males, irrespective of linguistic ability. Test-retest reliability coefficients were significant. The patient group showed significantly higher DIF scores than the normative students.

Conclusion
The present findings indicated that subjective difficulties in identifying and describing feelings are associated with empathetic and linguistic abilities. The developmental aspect to emotional awareness herein described suggests that self-reported questionnaires for alexithymia must be carefully constructed and examined, even for adults.
Ulceration of the oral mucosa induced by antidepressant medication: a case report
Authors: Bertini Fernanda , Costa Nívea Cristina Sena , Brandão Adriana Aigotti Haberbeck , Cavalcante Ana Sueli Rodrigues , Almeida Janete Dias 
Published: November 2009

Abstract

Introduction
Ulcers are frequent lesions of the oral mucosa. Generally, they are circumscribed round or elliptical lesions surrounded by an erythematous halo and covered with an inflammatory exudate in their central portion, and are accompanied by painful symptoms. Oral ulcers affect 20% of the population, especially adolescents and young adults. The etiopathogenesis includes immunological alterations, infections, nutritional deficiency, trauma, food and contact allergies, autoimmune diseases, neoplasms, and psychosomatic, genetic and environmental factors.

Case presentation
A 78-year-old Caucasian woman was referred by her dentist to our outpatient clinic with a 4-week history of an oral ulceration after using an antidepressant (sertraline hydrochloride). On the basis of the clinical findings and anamnesis, the occurrence of the lesion was attributed to the use of the drug. Exfoliative cytology was performed, to reassure the patient that it was not oral cancer, which revealed the presence of a nonspecific inflammatory reaction. The drug was replaced and resolution of symptoms was observed.

Conclusion
Exfoliative cytology should be the complementary examination of choice in cases of oral ulcers with a suspicion of drug interaction. Although this is a rare event in dental practice, dentists should be aware of the diagnostic possibility of drug-induced ulcers and should cooperate with the clinician to adjust the prescribed medication to resolve the symptoms.
An atypical case of hepatic cavernous hemangioma
Authors: Brogna Alfio , Ferrara Rosario , Bucceri Anna Maria , Virgilio Carla , Scalisi Giuseppe 
Published: November 2009

Abstract

Introduction
The case of an atypical hepatic angiocavernoma is referred. The lesion, first described as a hypoechogenic area compared to the surrounding parenchyma, with anechogenic shoots inside, suggestive for vascular structures developed one year later into a totally asonic area with frayed margins. This change is very unusual and uncommon for this kind of lesions.

Case presentation
The case of a 74-year old caucasian male, complaining of slight dyspeptic symptoms (post-prandial fullness and bloating) is referred. The routine blood tests were all normal. Abdominal ultrasound showed a large, roughly round-shaped lesion (diameter 14 cm) in the VIII hepatic segment diagnosed as hepatic angiocavernoma, which turned unexpectedly in a cystic like lesion one year later.

Conclusion
The atypical angioma's degeneration could account for one of the causes of the patient's exitus. It could be related to blood seizure by the large hepatic angioma due to the intratumoural haemorrhage.
ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature
Authors: Alivernini Stefano , Laria Antonella , Gremese Elisa , Zoli Angelo , Ferraccioli Gianfranco 
Published: November 2009

AbstractIntroductionThe aim of our analysis was to compare the gaining of a major response (disease activity score [DAS] remission or American College of Rheumatology 70% improvement criteria [ACR70]) by switching between all the available biological therapies in rheumatoid arthritis.MethodsA systematic review was performed including studies, published before December 2008, in which a second biological agent was used and clinical outcomes were evaluated after a first biological failure.ResultsNine articles were included. Switching from etanercept and/or infliximab to adalimumab is effective with an ACR70 response ranging from 5% to 33%. Rituximab may be slightly more effective than switching to a second anti-tumor necrosis factor-alpha (anti-TNFα), reaching an ACR70 or DAS remission response in 12% and 9%, respectively. Clinical trials confirmed the efficacy in switching to abatacept (gain of effect 10.2%). Tocilizumab allows DAS28 (DAS using 28 joint counts) remission in 30.1% but ACR70 only in 12.4% of patients refractory to anti-TNFα.ConclusionsThe efficacy of a second biological agent, irrespective of the mode of action, in reaching an ACR70 or DAS remission after a first biologic is observed from 5% to 15% and from 9% to 15.4%, respectively (except in two studies).