bluuebunny/crossref_metadata_2025 huggingface dataset:
Eccrine Porocarcinoma of the Head: An Important Differential Diagnosis in the Elderly Patient
Authors: Gerber Peter Arne , Schulte Klaus-Werner , Ruzicka Thomas , Bruch-Gerharz Daniela
Published: January 2008

Background: Eccrine porocarcinoma is a rare malignant tumor of the sweat gland, characterized by a broad spectrum of clinicopathologic presentations. Surprisingly, unlike its benign counterpart eccrine poroma, eccrine porocarcinoma is seldom found in areas with a high density of eccrine sweat glands, like the palms or soles. Instead, eccrine porocarcinoma frequently occurs on the lower extremities, trunk and abdomen, but also on the head, resembling various other skin tumors, as illustrated in the patients described herein. Observations: We report 5 cases of eccrine porocarcinoma of the head. All patients were initially diagnosed as having epidermal or melanocytic skin tumors. Only after histopathologic examination were they classified as eccrine porocarcinoma, showing features of epithelial tumors with abortive ductal differentiation. Characteristic clinical, histopathologic and immunohistochemical findings of eccrine porocarcinomas are illustrated. Conclusion: Eccrine porocarcinomas are potentially fatal adnexal malignancies, in which extensive metastatic dissemination may occur. Porocarcinomas are commonly overlooked, or misinterpreted as squamous or basal cell carcinomas as well as other common malignant and even benign skin tumors. Knowledge of the clinical pattern and histologic findings, therefore, is crucial for an early therapeutic intervention, which can reduce the risk of tumor recurrence and serious complications.
Sirolimus-Induced Inflammatory Papules with Acquired Reactive Perforating Collagenosis
Authors: Lübbe J. , Sorg O. , Malé P.-J. , Saurat J.-H. , Masouyé I.
Published: January 2008

Sirolimus is an immunosuppressive macrolide with antineoplasic properties that is increasingly used in posttransplantation immunosuppression. The treatment is frequently associated with cutaneous side effects such as sirolimus-associated acneiform facial dermatitis, which has been observed in up to 50% of treated patients. We report a 51-year-old female with liver transplantation who developed inflammatory papules and nodules on the face and the upper chest 3 weeks after the initiation of sirolimus therapy. Sequential biopsies revealed lymphocytic infiltration of the dermis with a peculiar pattern of sebotropism, while older lesions showed acquired reactive perforating collagenosis. The lesions were responsive to hydroxychloroquine treatment despite continued sirolimus treatment.
Soluble Form of Vascular Cell Adhesion Molecule 1 Induces Migration and Proliferation of Vascular Smooth Muscle Cells
Authors: Lee Hwan Myung , Kim Hyo Jin , Won Kyung-Jong , Choi Wahn Soo , Park Seung Hwa , Song Hyuk , Park Pyo-Jam , Park Tae-Kyu , Lee Chang-Kwon , Kim Bokyung
Published: January 2008

Background: Serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1) shed from its membrane-bound form are elevated in hypertension. This study clarified the effects of sVCAM-1 on vascular responses in rat aortic smooth muscle cells (RASMCs). Methods: Boyden chamber, 5-bromo-2′-deoxyuridine incorporation and ex vivo aortic ring assays for migration and proliferation, and Western blot for the kinase activity were used. Results: Spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were compared functionally. sVCAM-1 increased RASMC migration and proliferation, which were greater in SHR compared with WKY rats. RASMCs expressed the very late antigen 4α receptor integrin with no difference between SHR and WKY rats. Inhibitors of phosphoinositide kinase 3 (PI3K) and spleen tyrosine kinase (Syk) and small interference RNA-Syk abolished the sVCAM-1-induced migration, proliferation and phosphorylation of focal adhesion kinase. The phosphorylation of Syk was significantly greater in RASMCs from SHR than from WKY rats. sVCAM-1 increased aortic sprout outgrowth, which was inhibited by inhibitors of PI3K and Syk. Conclusions: This study suggests that sVCAM-1 promotes the RASMC migration and proliferation via the focal adhesion kinase pathway regulated by Syk and PI3K, and the altered sVCAM-1-induced responses during hypertension are closely associated with the increments in intracellular signal transmission.
Relationship between Nocturnal Urinary Cortisol Excretion and Symptom Severity in Subgroups of Patients with Depressive Episodes
Authors: Wedekind Dirk , Preiss Birgit , Cohrs Stefan , Ruether Eckart , Huether Gerald , Adler Lothar
Published: January 2008

Introduction: The aim of this naturalistic study was to gain more information about the elevation of basal hypothalamic-pituitary-adrenal (HPA) activity in relationship to symptom severity in specific subtypes of depressive episodes. Method: Hamilton Depression Rating Scale scores and aggregated nocturnal urinary cortisol excretion were measured in 4 groups of inpatients with depressive episodes (n = 48; monopolar nonpsychotic, monopolar psychotic, bipolar nonpsychotic and bipolar psychotic) at the beginning and at the end of inpatient treatment. Results: The initial elevation of nocturnal urinary cortisol excretion was most pronounced in psychotic patients. At the end of treatment, the Hamilton Depression Rating Scale scores had decreased significantly in all patients to comparable levels, whereas the nocturnal cortisol excretion values were still relatively elevated in mono- and bipolar psychotic patients compared to mono- and bipolar nonpsychotic ones. Conclusion: The observation that the basal HPA activity remains elevated even after remission of symptoms in patients with psychotic depression supports the concept that a dysfunctional regulation of the HPA system is possibly a trait- rather than a state-related feature.
N.F.S. Grundtvig, Niels Bukh and Other 'Japanese' Heroes. The Educators Obara Kuniyoshi and Matsumae Shigeyoshi and Their Lessons from the Past of a Foreign Country
Authors: Mehl Margaret
Published: January 2008

Obara Kuniyoshi (1887–1977), the founder of Tamagawa Gakuen, and Matsumae Shigeyoshi (1901–1991), the founder of Tôkai Educational System (TES), were both inspired by Denmark and Danish education, although in different ways. Obara, a representative of the New Education Movement in Japan, became interested in Denmark when he heard about Danish gymnastics, which seemed to be ideally suited to his vision of rigorous but non-competitive physical education. In 1931, two years after founding his own school, he succeeded in inviting the Danish gymnast Niels Bukh and a group of his students to Japan. The interest in gymnastics sparked off a wider interest in Denmark. Matsumae Shigeyoshi's attention was drawn to Denmark and to the Danish folk high schools as a result of his encounter with Uchimura Kanzô. Although not an educator by training, he decided to devote his life to education. This article explores the role of cultural borrowing in the thought and educational praxis of Obara and Matsumae. Although they uncritically accepted a Danish cultural memory (Denmark's recovery from military defeat in the nineteenth century through spiritual strength and education) and cultivated a stereotypical image, the adaptation of this image to suit their own needs represents a highly creative process which resulted in two successful private schools.
When the Medium Is the Message: The Ideological Role of Yoshino Sakuzô's Minponshugi in Mobilising the Japanese Public
Authors: McCormick Brett
Published: January 2008

Democratic ideology functioned in Japanese society as part of the national political ethos from 1889 onward. Within the broader ideological discourse, it played a role in conditioning the state-subject relationships that in early Shôwa proved conducive to mass social mobilisation for war. Foremost among the proponents of this democratic ideology was Yoshino Sakuzô, whose democratic theories functioned in practice to promote a sociopolitical hegemony that allowed the imperial state to govern both by coercion and suasion. Yoshino's minponshugi theories constructed a liberalism strictly within a nationalist state-centered theoretical paradigm. Despite negligible functionality, individual participation in social structures like political parties, public political campaigns, and voting, had enduring ideological effect. If ideology within a state interpellates subjects as citizens, like a policeman's hail, 'Hey, you there!' might minponshugi have functioned like the hail from the loudspeaker of a campaign truck in early Shôwa Tokyo as, 'Hey, you there, constituent and voter'?
Regional Integration and Business Interests: A Comparative Study of Europe and Southeast Asia
Authors: Yoshimatsu Hidetaka
Published: January 2008

This article aims to articulate business representation in the process towards creating a unified market by comparing the regional integration process in Europe in the 1980s and in Southeast Asia in the new millennium. Both the European Community (EC) and the Association of Southeast Asian Nations (ASEAN) adopted the creation of a single market as a feasible strategy to respond to an economic hardship. In this process, US business associations played a critical role in identifying problems and issues in promoting actual integration. As for local business, the existing business associations did not function effectively and a new association comprising individual business executives was formed. Importantly, an initiative to create a new association came not from the private sector in Europe but from the member states in Southeast Asia. This difference led to disparities in the relative influence of the two associations on the actual integration processes.
China Through Western Eyes. A Case Study of the BBC Television Documentary Roads to Xanadu
Authors: Cao Qing
Published: January 2008

Despite a growing body of literature on the study of the Western media's portrayal of China, little attention has been paid to the structures underlying the representation of China. This essay aims to address this issue through an in-depth analysis of a British television documentary series, Roads to Xanadu (1990). It focuses on dominant perspectives constructed in the series by analysing documentary narrative as a mode of realising discourse. The essay argues that underlying the representation is a technological view of society. Shifting between realpolitik industrialism and liberal democratic humanism, the series attempts to arrive at a unified and unifying version of 'progress' through a modernist discourse.
Deterioration in Cognitive Function in Children With Benign Epilepsy of Childhood With Central Temporal Spikes Treated With Sulthiame
Authors: Wirrell Elaine , Sherman Elisabeth M. S. , Vanmastrigt Robert , Hamiwka Lorie
Published: January 2008

The purpose of this study was to determine if reduction in spike frequency in children with benign epilepsy of childhood with centrotemporal spikes treated with sulthiame correlates with improved neuropsychologic function. Six untreated children (5 boys, 1 girl) with a mean (standard deviation) age of 9.1 years (1.5 years) underwent overnight ambulatory electroencephalograph recording and neuropsychologic evaluation at baseline and after 6 months of sulthiame monotherapy. The Reliable Change Index was used to determine whether a statistically reliable change in neuropsychologic function occurred. All children continued receiving sulthiame monotherapy (dose range, 8.0-9.3 mg/kg per day) for the study period without further seizures. Although spike frequency was reduced in all 6 children (3 showing a decrease to less than 10% of baseline), they all demonstrated significant deterioration in their reading ability, 5 had significant declines in general memory, and more than half had reduction in attention skills and mathematics ability. Although sulthiame was effective at seizure control and significantly reduced spike frequency in children, it was also associated with deterioration in cognitive function.
When Epilepsy Interferes With Word Comprehension: Findings in Landau-Kleffner Syndrome
Authors: Castillo Eduardo M. , Butler Ian J. , Baumgartner James E. , Passaro Antony , Papanicolaou Andrew C.
Published: January 2008

Landau-Kleffner syndrome is characterized by a regression in receptive language. The factors that affect the clinical expression of this syndrome remain unclear. This study presents neuroimaging findings in 2 patients showing different clinical evolutions. Linguistic regression persisted in 1 patient and evolved positively in the other. In patient A (with severe linguistic regression) there was an overlap between areas engaged during word recognition and those involved in generating the epileptiform activity; in patient B (with better linguistic evolution), receptive language was predominantly represented in the right hemisphere (unaffected). Patient A underwent multiple subpial transections. The 2-year follow-up indicated linguistic improvement, absence of epileptiform activity, and activation of the left temporal cortex during word comprehension. These results suggest that the resolution of the linguistic deficit in Landau-Kleffner syndrome may be modulated by the language-specific cortex freed from interfering epileptiform activity or by reorganization of the receptive language cortex triggered by the epileptic activity.
New Incidence, Prevalence, and Survival of Aicardi Syndrome From 408 Cases
Authors: Kroner Barbara L. , Preiss Liliana R. , Ardini Mary-Anne , Gaillard William D.
Published: January 2008

We sought to determine the incidence, prevalence, and life expectancy of Aicardi syndrome from 408 cases compiled from multiple international sources. Last known age ranged from less than 1 month to 42 years. The incidence rates per live births for the United States and The Netherlands were 1 per 105 000 and 1 per 93 000, respectively. The prevalence in the United States is greater than 853 cases, and the worldwide estimate is several thousand. Forty-five cases were deceased (age range, 1 month to 33 years), and the risk of death peaked at age 16. The probability of survival at 27 years of age was 0.62 (95% CI, 0.47-0.77). The risk of death by age follows other congenital neurological disorders with a wide range in severity of functional disability. The longer life expectancy found in our study hints at a higher functioning capacity in Aicardi syndrome and may inform counseling to families.
Promoting Local Democracy in Education
Authors: Mintrom Michael
Published: January 2008

Scholars have recently explored the relationship between local democracy and education from two distinct perspectives. The first views local democracy as inherently good and offers suggestions for deepening the practice of democracy. The second perspective questions the merits of local democratic control of schools. Contributors to this perspective have focused on tensions between democratic governance and the pursuit of improved student outcomes. This essay assesses recent reform strategies and their implications for democratic practice. Emphasis is placed on how policy design might simultaneously support both the deepening of democracy and improved student outcomes.
RhoA activation and actin reorganization involved in endothelial CAM-mediated endocytosis of anti-PECAM carriers: critical role for tyrosine 686 in the cytoplasmic tail of PECAM-1
Authors: Garnacho Carmen , Shuvaev Vladimir , Thomas Anu , McKenna Lindsay , Sun Jing , Koval Michael , Albelda Steven , Muzykantov Vladimir , Muro Silvia
Published: January 2008

Platelet-endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane glycoprotein involved in leukocyte transmigration, represents a good target for endothelial drug delivery (eg, using antibody-directed nanocarriers, anti-PECAM/NCs). Although endothelial cells do not internalize PECAM antibodies, PECAM-1 engagement by multivalent anti-PECAM conjugates and nanocarriers causes endocytosis via a nonclassic CAM-mediated pathway. We found that endothelial uptake of multivalent anti-PECAM complexes is associated with PECAM-1 phosphorylation. Using model REN cells expressing a series of PECAM-1 deletion and point mutants, we found that the PECAM-1 cytoplasmic domain and, more precisely, PECAM-1 tyrosine 686, is critical in mediating RhoA activation and recruitment of EGFP-RhoA to anti-PECAM/NC binding sites at the plasmalemma, actin polymerization into phalloidin-positive stress fibers, and finally CAM endocytosis of anti-PECAM/NCs. Endothelial targeting and endocytosis of anti-PECAM/NCs were markedly efficient and did not compromise endothelial barrier function in vitro (determined by immunostaining of VE-cadherin and 125I-albumin transport across endothelial monolayers) or in vivo (determined by electron microscopy imaging of pulmonary capillaries and 125I-albumin transport from the blood into the lung tissue after intravenous injection of anti-PECAM/NCs in mice). These results reveal PECAM-1 signaling and interactions with the cytoskeleton, which are required for CAM-endocytosis, and may provide safe intra-endothelial drug delivery by anti-PECAM/NCs.
Abolition of stress-induced protein synthesis sensitizes leukemia cells to anthracycline-induced death
Authors: Gausdal Gro , Gjertsen Bjørn Tore , McCormack Emmet , Van Damme Petra , Hovland Randi , Krakstad Camilla , Bruserud Øystein , Gevaert Kris , Vandekerckhove Joël , Døskeland Stein Ove
Published: January 2008

Anthracycline action has been thought to involve the neosynthesis of proapoptotic gene products and to therefore depend on protein synthesis for optimal effect. We found that inhibition of general, but not rapamycin-sensitive (cap-dependent), protein synthesis in the preapoptotic period enhanced anthracycline-induced acute myelogenous leukemia (AML) cell death, both in vitro and in several animal AML models. Pre-apoptotic anthracycline-exposed AML cells had altered translational specificity, with enhanced synthesis of a subset of proteins, including endoplasmatic reticulum chaperones. The altered translational specificity could be explained by perturbation (protein degradation, truncation, or dephosphorylation) of the cap-dependent translation initiation machinery and of proteins control-ing translation of specific mRNAs. We propose that judiciously timed inhibition of cap-independent translation is considered for combination therapy with anthracyclines in AML.
The Aiolos transcription factor is up-regulated in chronic lymphocytic leukemia
Authors: Duhamel Marianne , Arrouss Issam , Merle-Béral Hélène , Rebollo Angelita
Published: January 2008

The Aiolos transcription factor, member of the Ikaros family of zinc finger proteins, plays an important role in the control of mature B lymphocyte differentiation and proliferation, and its function appears to be modulated through alternative splicing. To assess Aiolos isoform role in humans' pathologies, we studied Aiolos variant distribution and expression in mature B lymphoproliferative disorders (chronic lymphocytic leukemia [CLL] and other B-cell lymphomas). We demonstrated that more than 80% of expressed Aiolos in normal as well as in malignant B cells is of the hAio1 type, and we showed for the first time a homogeneous overexpression of the total amounts of Aiolos transcripts in the B cells of CLL patients, independently of ZAP-70 and IgVH mutational status prognosis factors. This up-regulation of Aiolos, confirmed at protein level, seems independent of Aiolos promoter H3K9 acetylation and H3K4 trimethylation.
Differential production of superoxide by neuronal mitochondria
Authors: Hoegger Mark J , Lieven Christopher J , Levin Leonard A
Published: January 2008

Background

Mitochondrial DNA (mtDNA) mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON) results from one of three point mutations mtDNA coding for complex I components, but is only manifested in retinal ganglion cells (RGCs), a central neuron contained within the retina. Given that RGCs use superoxide for intracellular signaling after axotomy, and that LHON mutations increase superoxide levels in non-RGC transmitochondrial cybrids, we hypothesized that RGCs regulate superoxide levels differently than other neuronal cells. To study this, we compared superoxide production and mitochondrial electron transport chain (METC) components in isolated RGC mitochondria to mitochondria isolated from cerebral cortex and neuroblastoma SK-N-AS cells.

Results

In the presence of the complex I substrate glutamate/malate or the complex II substrate succinate, the rate of superoxide production in RGC-5 cells was significantly lower than cerebral or neuroblastoma cells. Cerebral but not RGC-5 or neuroblastoma cells increased superoxide production in response to the complex I inhibitor rotenone, while neuroblastoma but not cerebral or RGC-5 cells dramatically decreased superoxide production in response to the complex III inhibitor antimycin A. Immunoblotting and real-time quantitative PCR of METC components demonstrated different patterns of expression among the three different sources of neuronal mitochondria.

Conclusion

RGC-5 mitochondria produce superoxide at significantly lower rates than cerebral and neuroblastoma mitochondria, most likely as a result of differential expression of complex I components. Diversity in METC component expression and function could explain tissue specificity in diseases associated with inherited mtDNA abnormalities.
Usefulness of manufactured tomato extracts in the diagnosis of tomato sensitization: Comparison with the prick-prick method
Authors: Ferrer Ángel , Huertas Ángel J , Larramendi Carlos H , García-Abujeta Jose L , Bartra Joan , Lavín Jose R , Andreu Carmen , Pagán Juan A , López-Matas María A , Fernández-Caldas Enrique , Carnés Jerónimo
Published: January 2008

Background

Commercial available skin prick test with fruits can be negative in sensitized or allergic patients due to a reduction in biological activity during the manufacturing process. Prick-prick tests with fresh foods are often preferred, but they are a non-standardized procedure. The usefulness of freeze-dried extracts of Canary Islands tomatoes, comparing the wheal sizes induced by prick test with the prick-prick method in the diagnosis of tomato sensitization has been analyzed.

The objective of the study was to assess the potential diagnostic of freeze-dried extracts of Canary Islands tomatoes, comparing the wheal sizes induced by prick test with the prick-prick method.

Methods

Two groups of patients were analyzed: Group I: 26 individuals reporting clinical symptoms induced by tomato contact or ingestion. Group II: 71 control individuals with no symptoms induced by tomato: 12 of them were previously skin prick test positive to a tomato extract, 39 were atopic and 20 were non-atopic. All individuals underwent prick-prick with fresh ripe peel Canary tomatoes and skin prick tested with freeze-dried peel and pulp extracts obtained from peel and pulp of Canary tomatoes at 10 mg/ml. Wheal sizes and prick test positivity (≥ 7 mm2) were compared between groups.

Results

In group I, 21 (81%) out of 26 patients were prick-prick positive. Twenty patients (77%) had positive skin prick test to peel extracts and 12 (46%) to pulp extracts. Prick-prick induced a mean wheal size of 43.81 ± 40.19 mm2compared with 44.25 ± 36.68 mm2induced by the peel extract (Not significant), and 17.79 ± 9.39 mm2induced by the pulp extract (p < 0.01).

In group II, 13 (18%) out of 71 control patients were prick-prick positive. Twelve patients (all of them previously positive to peel extract) had positive skin prick test to peel and 3 to pulp. Prick-prick induced a mean wheal size of 28.88 ± 13.12 mm2compared with 33.17 ± 17.55 mm2induced by peel extract (Not significant), and 13.33 ± 4.80 mm2induced by pulp extract (p < 0.05 with peel extract and prick-prick).

Conclusion

Canary peel tomato extract seems to be as efficient as prick-prick tests with ripe tomatoes to diagnose patients sensitized to tomato. The wheal sizes induced by prick-prick and peel extracts were very similar and showed a high correlation coefficient.
Roles of adjuvant and route of vaccination in antibody response and protection engendered by a synthetic matrix protein 2-based influenza A virus vaccine in the mouse
Authors: Mozdzanowska Krystyna , Zharikova Darya , Cudic Mare , Otvos Laszlo , Gerhard Walter
Published: January 2008

Background

The M2 ectodomain (M2e) of influenza A virus (IAV) strains that have circulated in humans during the past 90 years shows remarkably little structural diversity. Since M2e-specific antibodies (Abs) are capable of restricting IAV replication in vivo but are present only at minimal concentration in human sera, efforts are being made to develop a M2e-specific vaccine. We are exploring a synthetic multiple antigenic peptide (MAP) vaccine and here report on the role of adjuvants (cholera toxin and immunostimulatory oligodeoxynucleotide) and route of immunization on Ab response and strength of protection.

Results

Independent of adjuvants and immunization route, on average 87% of the M2e-MAP-induced Abs were specific for M2e peptide and a variable fraction of these M2e(pep)-specific Abs (average 15%) cross-reacted with presumably native M2e expressed by M2-transfected cells. The titer of these cross-reactive M2e(pep-nat)-specific Abs in sera of parenterally immunized mice displayed a sigmoidal relation to level of protection, with EC50of ~20 μg Ab/ml serum, though experiments with passive M2e(pep-nat) Abs indicated that serum Abs did not fully account for protection in parenterally vaccinated mice, particularly in upper airways. Intranasal vaccination engendered stronger protection and a higher proportion of G2a Abs than parenteral vaccination, and the strength of protection failed to correlate with M2e(pep-nat)-specific serum Ab titers, suggesting a role of airway-associated immunity in protection of intranasally vaccinated mice. Intranasal administration of M2e-MAP without adjuvant engendered no response but coadministration with infectious IAV slightly enhanced the M2e(pep-nat) Ab response and protection compared to vaccination with IAV or adjuvanted M2e-MAP alone.

Conclusion

M2e-MAP is an effective immunogen as ~15% of the total M2e-MAP-induced Ab response is of desired specificity. While M2e(pep-nat)-specific serum Abs have an important role in restricting virus replication in trachea and lung, M2e-specific T cells and/or locally produced Abs contribute to protection in upper airways. Intranasal vaccination is preferable to parenteral vaccination, presumably because of induction of local protective immunity by the former route. Intranasal coadministration of M2e-MAP with infectious IAV merits further investigation in view of its potential applicability to human vaccination with live attenuated IAV.
Concurrent infections by all four dengue virus serotypes during an outbreak of dengue in 2006 in Delhi, India
Authors: Bharaj Preeti , Chahar Harendra S , Pandey Anubhav , Diddi Kavita , Dar Lalit , Guleria Randeep , Kabra Sushil K , Broor Shobha
Published: January 2008

Background

Co-circulation of multiple dengue virus serotypes has been reported from many parts of the world including India, however concurrent infection with more than one serotype of dengue viruses in the same individual is rarely documented. An outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) occurred in and around Delhi in 2006. This is the first report from India with high percentage of concurrent infections with different dengue virus serotypes circulating during one outbreak.

Results

Acute phase sera from patients were tested for the presence of dengue virus RNA by RT-PCR assay. Of the 69 samples tested for dengue virus RNA, 48 (69.5%) were found to be positive. All the four dengue virus serotypes were found to be co-circulating in this outbreak with DENV-3 being the predominant serotype. In addition in 9 of 48 (19%) dengue virus positive samples, concurrent infection with more than one dengue virus serotype were identified.

Conclusion

This is the first report in which concurrent infections with different dengue virus serotypes is being reported during an outbreak from India. Delhi is now truly hyperendemic for dengue.
Energy balance, leptin, NEFA and IGF-I plasma concentrations and resumption of post partum ovarian activity in swedish red and white breed cows
Authors: Konigsson Kristian , Savoini Giovanni , Govoni Nadia , Invernizzi Guido , Prandi Alberto , Kindahl Hans , Veronesi Maria Cristina
Published: January 2008

In the purpose to provide further information in respect of the relationship between metabolism and post partum (PP) ovarian activity resumption in dairy cows, the aim of the present study was to characterize the energy balance (EB) and leptin, NEFA and IGF-I plasma levels in Swedish Red and White (SRW) cows with and without ovarian activity re-initiation within 7 weeks PP. The study was conducted on 12 primiparous SRW cows fed the same diet as total mixed ration for ad libitum intake. The EB was calculated weekly from parturition until seven weeks PP. Blood samples were collected weekly from one week before until 7 weeks after calving for leptin, NEFA and IGF-I analysis. For progesterone (P4) analysis, blood samples were collected two times per week from parturition until the end of the study. P4 profile was used in addition to the clinical examination to detect cows with and without ovarian activity resumption. The clinical and ultrasonographic examination, coupled with P4 profile analysis showed the resumption of ovarian activity within 7 weeks after calving in 8 (group A) and no ovarian resumption in 4 cows (group B). No significant differences were detected in the whole period of observation in the amount of milk production between the two groups, while the mean milk protein content was significantly lower in group B at the third week PP. The calculated EB was negative in both groups in the first three weeks after calving, but more marked in group B. NEFA and Leptin plasma levels did not show significant differences between the two groups. In conclusion, the results of the present study showed that, when low milk producing primiparous cows are concerned, no significant differences in BW loss, milk yield, EB and leptin and NEFA plasma levels between the cows with and without resumption of ovarian activity within 7 weeks post partum were seen. However, significantly higher IGF-I levels in the first two weeks after calving were found in cows with post partum ovarian activity resumption, highlighting the important role of IGF-I as sensitive signal between metabolism and reproduction.
Culture and Genetic Modification of Mouse Germline Stem Cells
Authors: KANATSU‐SHINOHARA MITO , SHINOHARA TAKASHI
Published: January 2008

Abstract:Spermatogenesis depends on a population of cells called spermatogonial stem cells, which self‐renew to support male reproduction throughout life. In 2003, the long‐term culture of spermatogonial stem cells of mice proved to be successful. In the presence of glial cell‐line‐derived neurotrophic factor, germline stem (GS) cells were established from postnatal mouse testis. These cells proliferated over a 2‐year period (>1085‐fold) and restored fertility to congenitally infertile recipient mice following transplantation into the seminiferous tubules. Unlike other germline cells that often acquire genetic and epigenetic changesin vitro, the GS cells retained their euploid karyotype and androgenetic imprint during the 2‐year experimental period, and they produced normal fertile offspring. Mutagenization of the GS cells was successful using gene trapping and gene targeting vectors to produce homozygous knockout offspring, thereby providing a new approach to germline modification. In the course of the gene targeting experiments, establishment of embryonic‐stem (ES)‐like cells was also successful [i.e., multipotent germline stem (mGS) cells] from postnatal mouse testis. These mGS cells were phenotypically similar to the ES/embryonic germ cells, except for their genomic imprinting pattern. They differentiated into various types of somatic cellsin vitrounder the conditions used to induce the differentiation of the ES cells, and the mGS cells formed germline chimeras when injected into blastocysts. These new spermatogonial stem‐cell lines will be useful for studying the mechanism of spermatogenesis, and they have important implications for developing new transgenic or medical technologies.
Noncoding RNAs of the Mammalian Testis
Authors: IGUCHI NAOKO , XU MINGANG , HORI TAMAKI , HECHT NORMAN B.
Published: January 2008

Abstract: In eukaryotic cells, the vast majority of transcribed sequences are extragenic with no known functions. Translin is a DNA/RNA‐binding protein involved in mRNA transport and translation in postmeiotic male germ cells. In an effort to identify meiotic target RNAs of Translin, reversible RNA protein cross‐linking and immunoprecipitations with an affinity purified antibody to Translin were performed. Four new meiotically expressed mRNAs and one noncoding RNA with Translin binding sites were identified. Following sequencing, the noncoding RNA, Nct1, was 100% identical to a site on mouse chromosome 2. A second partially homologous sequence, Nct2, was detected nearby. Nct 1 and 2 contained sequences identical to piRNAs. Nct1 and 2 appear to be male germ cell‐specific transcripts and are predominantly detected in pachytene spermatocytes. Focusing on the abundant single‐copy PIWI‐interacting RNA (piRNA), germline small RNA (gsRNA10) (the gsRNA10 sequence is identical to 29 nt in Nct1), we find that gsRNA10 increases greatly as spermatogenesis proceeds with concomitant decreases in Nct1 and 2. The piRNA gsRNA10 binds to the germ cell‐specific Y‐box protein, MSY2, but not to Translin. Although the size of the primary transcript(s) encoding the piRNAs in the locus on chromosome 2 is not known, we propose that Nct1 and 2 are part of a piRNA precursor.
Role of Connexin 43 in Sertoli Cells of Testis
Authors: SRIDHARAN SANTHI , BREHM RALPH , BERGMANN MARTIN , COOKE PAUL S.
Published: January 2008

Abstract: Connexin 43 (CX43, also known as GJA1) is the predominant testicular gap‐junction protein. In the seminiferous epithelium, gap junctions occur between adjacent Sertoli cells and between Sertoli and germ cells. The specific role of CX43 in Sertoli cell has been difficult to study because of the neonatal lethality of the Cx43 global knockout. Recently two laboratories have independently developed a Sertoli cell conditional Cx43 knockout using Cre‐loxP methodology. These have allowed the role of CX43 in Sertoli cells to be determined while circumventing lethal abnormalities in organs such as the heart seen in Cx43 global knockouts. In this review the focus is on the insights into the role of CX43 in Sertoli cells derived from these new model systems. Results indicate that CX43 is essential for cessation of proliferation and normal maturation in Sertoli cells. In addition, CX43 in Sertoli cells is required for spermatogenesis, but not early germ cell proliferation. These model systems show that CX43 is important in Sertoli cell development, and will be useful in further studies of its role in Sertoli cell and testis biology.
Sox8 and Sertoli‐cell Function
Authors: KENNEDY CLAIRE L. , KOOPMAN PETER , MISHINA YUJI , O'BRYAN MOIRA K.
Published: January 2008

Abstract: SOX8 is a transcription factor that belongs to the SoxE group of high mobility group (HMG) superfamily of genes. As Sox8 is widely expressed during development, and has male‐specific expression at the critical period for sex determination, it was initially hypothesized that its inactivation would result in abnormal sex determination. Though knockout males showed normal sexual development, they did however display a progressive seminiferous tubule failure and infertility. Young males could occasionally sire litters, though fecundity decreased with age in parallel with an increase in the degeneration and disorganization of the seminiferous epithelium. SOX8 is a product of the adult Sertoli cells. Sox8 knockout males showed a progressive dysregulation of the spermatogenic cycle, including sloughing of spermatocytes and round spermatids into the epididymis and spermiation failure. Sperm that did reach the epididymis showed an age‐dependent decrease in both total and progressive motility in addition to overall number. We conclude that SOX8 transactivated genes have key roles in adult Sertoli‐cell function and its elimination results in progressive male infertility.
Potential Functions of Retinoic Acid Receptor A in Sertoli Cells and Germ Cells During Spermatogenesis
Authors: DOYLE TIMOTHY J. , BRAUN KIRT W. , MCLEAN DEREK J. , WRIGHT RAYMOND W. , GRISWOLD MICHAEL D. , KIM KWAN HEE
Published: January 2008

Abstract: Elucidation of the retinoid signaling circuitry in the testis is critical to understanding how male germ cells develop to spermatozoa. Retinoic acid receptor A protein (RARA) is an essential mediator of retinoid signaling in the testis, as shown by a sterility phenotype observed for retinoic acid receptor A gene (Rara) knockout male mice. The seminiferous tubules of Rara knockout mice showed varying degrees of germ‐cell degeneration. A dramatic increase in apoptosis of early meiotic prophase spermatocytes was observed in these tubules compared to the wild‐type tubules. Germ‐cell loss was dependent on the stages of the spermatogenic cycle: germ‐cell loss was negligible in stages I–V, but severe after stages VIII and IX of the spermatogenic cycle. Using spermatogonial transplantation, the individual function of RARA in Sertoli cells or germ cells was determined. The wild‐type donor germ cells, transplanted into Rara knockout testes, colonized and proliferated in the RARA‐deficient microenvironment. The donor‐derived cells were mostly early meiotic prophase spermatocytes, with few more advanced germ cells detected. Conversely, when Rara‐deficient germ cells were injected into the microenvironment that express RARA, establishment of donor‐derived germ‐cell colonies was rare, but remarkably, once colonized, Rara‐deficient germ cells progressed normally through spermatogenesis. These results together suggest that RARA may function in Sertoli cells to promote the survival and development of early meiotic prophase spermatocytes, whereas RARA in germ cells functions to increase the proliferation and differentiation of spermatogonia, prior to meiotic prophase.
Toward Understanding the Core Meiotic Transcriptome in Mammals and Its Implications for Somatic Cancer
Authors: CHALMEL FREDERIC , LARDENOIS AURELIE , PRIMIG MICHAEL
Published: January 2008

Abstract: Progression through meiotic development is in part controlled by an expression program that coordinates the timing of induction and time of function of numerous loci essential for the process. Whole‐genome profiling of male germline expression in mouse, rat, and human provides important clues about the transcriptional regulatory machinery that drives the expression of its target genes. Among several thousand genes differentially expressed between testicular Sertoli and germ cells, a subset of conserved loci display highly similar meiotic and postmeiotic profiles across rodents and Homo sapiens. Mouse genes transcribed in the germline, but not in somatic control tissues, are frequently found to be important for sexual reproduction, thus correlating potentially specific expression and essential function in the male germline. In silico promoter analysis yields insight into DNA sequence conservation and the distribution of known regulatory elements within potential promoter regions of meiotic and postmeiotic genes. Some genes strongly expressed in male gonads are implicated in cancer, thus supporting the idea that gametogenesis and tumorigenesis may share molecular functions. Transcriptome, proteome, and protein network data reveal the kinetics of mRNA synthesis and translation in the germline, and help identify novel potentially important genes previously unassociated with the mammalian male germline.
Testicular Morphogenesis
Authors: GASSEI KATHRIN , SCHLATT STEFAN
Published: January 2008

Abstract: The organogenesis of a functional testis is the basis for male fertility and perpetuation of each species. In mammals, testicular development is dependent on two crucial events during embryonic and pubertal development. First, primary sex determination is initiated by expression of the Sry gene on the Y chromosome and directs the primordial gonad toward testicular development rather than ovarian differentiation. The male pathway comprises highly regulated cell differentiation of somatic cells within the gonadal primordium, as well as migration of mesonephric cells and primordial germ cells, ultimately leading to the formation of testis cords. These cords present the earliest visible sign of male gonadal differentiation. Second, during puberty immature Sertoli cells cease to proliferate and differentiate into their postmitotic, adult phenotype. The maturation of the Sertoli cells is pivotal for initiation and maintenance of spermatogenesis. The regulation of the two separate functions of Sertoli cells—during testis development and in spermatogenesis—are poorly understood. In this review, different models that have been used to study embryonic gonadal development and testicular maturation are compared. In vivo models, organ, and cell culture systems are discussed as regards their applicability to study testicular organogenesis. Then, a new tissue engineering approach is presented that mimics male embryonic gonadogenesis and that offers novel ways to study early testicular differentiation, as well as Sertoli cell maturation and spermatogonial stem‐cell niche formation.
Identification and Functional Analysis of a New WNT4 Gene Mutation among 28 Adolescent Girls with Primary Amenorrhea and Müllerian Duct Abnormalities: A French Collaborative Study
Authors: Philibert Pascal , Biason-Lauber Anna , Rouzier Roman , Pienkowski Catherine , Paris Françoise , Konrad Daniel , Schoenle Eugene , Sultan Charles
Published: January 2008

Context: Müllerian duct development depends on gene and hormone interactions. Female Wnt4-knockout mice lack müllerian ducts and are virilized due to the inappropriate expression of the enzymes required for androgen production (normally repressed in female ovary). The WNT4 mutation was recently reported to be associated with failure of müllerian duct formation and virilization in two 46, XX women.

Objectives: This collaborative work was designed to determine whether the WNT4 mutation could be identified in a group of adolescent girls with Mayer-Rokitansky-Küster-Hauser syndrome.

Results: We analyzed 28 DNA samples from adolescent girls with primary amenorrhea and failure of müllerian duct formation by direct sequencing and identified a new L12P mutation within exon 1 of the WNT4 gene. The substitution of leucine by proline is crucial for the conformation of the expressed protein. This amino acid substitution is unlikely to be a polymorphism because it was not found in 100 DNAs from control subjects. Functional analysis revealed that the mutation induces significantly increased expression of the enzymes involved in androgen biosynthesis (3β-hydroxysteroid dehydrogenase and 17α-hydroxylase). It is interesting to note that the adolescent carrying the mutation was referred to our clinic for primary amenorrhea and hyperandrogenism (severe acne and plasma testosterone: 1.8 vs. 1.2 nmol/liter in controls). She also presented with uterine hypoplasia and follicle depletion.

Conclusions: We suggest that in adolescent girls with primary amenorrhea, müllerian duct abnormalities, and hyperandrogenism, a WNT4 mutation should be sought. Moreover, our data confirm that WNT4 is involved in the regulation of müllerian duct development and ovarian androgen biosynthesis. WNT4 may also contribute to human follicle development and/or maintenance.
Microfilm, Paper, and OCR: Issues in Newspaper Digitization. The Utah Digital Newspapers Program
Authors: Arlitsch Kenning , Herbert John
Published: January 2008

The Marriott Library at the University of Utah (U of U) has a long history of large-scale newspaper projects beginning with the National Endowment for the Humanities' United States Newspapers Program (USNP) in the 1980s, in which the Library led the effort to catalog and microfilm Utah newspapers. This involvement continues today with the Utah Digital Newspaper (UDN) program, which is digitizing historic Utah newspapers, making them searchable and available on the Internet.
The Consequences of Response Nonlinearities for Interpretation of Spectrotemporal Receptive Fields
Authors: Christianson G. Björn , Sahani Maneesh , Linden Jennifer F.
Published: January 2008

Neurons in the central auditory system are often described by the spectrotemporal receptive field (STRF), conventionally defined as the best linear fit between the spectrogram of a sound and the spike rate it evokes. An STRF is often assumed to provide an estimate of the receptive field of a neuron, i.e., the spectral and temporal range of stimuli that affect the response. However, when the true stimulus–response function is nonlinear, the STRF will be stimulus dependent, and changes in the stimulus properties can alter estimates of the sign and spectrotemporal extent of receptive field components. We demonstrate analytically and in simulations that, even when uncorrelated stimuli are used, interactions between simple neuronal nonlinearities and higher-order structure in the stimulus can produce STRFs that show contributions from time–frequency combinations to which the neuron is actually insensitive. Only when spectrotemporally independent stimuli are used does the STRF reliably indicate features of the underlying receptive field, and even then it provides only a conservative estimate. One consequence of these observations, illustrated using natural stimuli, is that a stimulus-induced change in an STRF could arise from a consistent but nonlinear neuronal response to stimulus ensembles with differing higher-order dependencies. Thus, although the responses of higher auditory neurons may well involve adaptation to the statistics of different stimulus ensembles, stimulus dependence of STRFs alone, or indeed of any overly constrained stimulus–response mapping, cannot demonstrate the nature or magnitude of such effects.
Cdk5 Regulates the Phosphorylation of Tyrosine 1472 NR2B and the Surface Expression of NMDA Receptors
Authors: Zhang Shuo , Edelmann Lambert , Liu June , Crandall James E. , Morabito Maria A.
Published: January 2008

NMDA receptors (NMDARs) are a major class of ionotropic glutamate receptors that can undergo activity-dependent changes in surface expression. Clathrin-mediated endocytosis is a mechanism by which the surface expression of NR2B-containing NMDA receptors is regulated. The C terminus of the NMDA receptor subunit NR2B contains the internalization motif YEKL, which is the binding site for the clathrin adaptor AP-2. The tyrosine (Y1472) within the YEKL motif is phosphorylated by the Src family of kinases and this phosphorylation inhibits the binding of AP-2 and promotes surface expression of NMDA receptors. Cdk5 is a serine/threonine kinase that has been implicated in synaptic plasticity, learning, and memory. Here we demonstrate that inhibition of Cdk5 results in increased phosphorylation of Y1472 NR2B at synapses and decreased binding of NR2B to β2-adaptin, a subunit of AP-2, thus blocking the activity-dependent endocytosis of NMDA receptors. Furthermore, we show that inhibition of Cdk5 increases the binding of Src to postsynaptic density-95 (PSD-95), and that expression of PSD-95 facilitates the phosphorylation of Y1472 NR2B by Src. Together, these results suggest a model in which inhibition of Cdk5 increases the binding of Src to PSD-95 and the phosphorylation of Y1472 NR2B by Src, which results in decreased binding of NR2B to AP-2, and NR2B/NMDAR endocytosis. This study provides a novel molecular mechanism for the regulation of the surface expression of NR2B-containing NMDA receptors and gives insight into the Cdk5-dependent regulation of synaptic plasticity.