bluuebunny/crossref_metadata_2025 huggingface dataset:
TRPM channels are required for rhythmicity in the ultradian defecation rhythm of C. elegans
Authors: Kwan Claire SM , Vázquez-Manrique Rafael P , Ly Sung , Goyal Kshamata , Baylis Howard A
Published: May 2008

Background

Ultradian rhythms, rhythms with a period of less than 24 hours, are a widespread and fundamental aspect of life. The mechanisms underlying the control of such rhythms remain only partially understood. Defecation in C. elegans is a very tightly controlled rhythmic process. Underlying the defecation motor programme is an oscillator which functions in the intestinal cells of the animal. This mechanism includes periodic calcium release and subsequent intercellular calcium waves which in turn regulate the muscle contractions that make up the defecation motor programme. Here we investigate the role of TRPM cation channels in this process.

Results

We use RNA interference (RNAi) to perturb TRPM channel gene expression. We show that combined knock down of two of the TRPM encoding genes, gon-2 and gtl-1, results in an increase in the variability of the cycle but no change in the mean, in normal culture conditions. By altering the mean using environmental (temperature) and genetic approaches we show that this increase in variability is separable from changes in the mean. We show that gon-2 and gtl-1 interact with components of the calcium signalling machinery (itr-1 the C. elegans inositol 1,4,5-trisphosphate receptor) and with plasma membrane ion channels (flr-1 and kqt-3) which are known to regulate the defecation oscillator. Interactions with these genes result in changes to the mean period and variability. We also show that knocking down a putative transcription factor can suppress the increased variability caused by reduction of gon-2 and gtl-1 function. We also identify a previously unrecognised tendency of the defecation cycle to compensate for cycles with aberrant length by adjusting the length of the following cycle.

Conclusion

Thus TRPM channels regulate the variability of the defecation oscillator in C. elegans. We conclude that the mean and the variability of the defecation oscillator are separable. Our results support the notion that there is a strong underlying pacemaker which is able to function independently of the observable defecation rhythm and is not perturbed by increases in the variability of the cycle.

The interaction of gon-2 and gtl-1 with other components of the oscillator shows that TRPM channels play an important role in the oscillator machinery. Such a role may be through either regulation of cation levels or membrane properties or both. Specifically our results support previous proposals that gon-2 and gtl-1 regulate IP3 signalling and that kqt-3 may act by altering calcium influx.

Our results provide novel insights into the properties of the defecation oscillator and thus to our understanding of ultradian rhythms.
Harm reduction and equity of access to care for French prisoners: a review
Authors: Michel Laurent , Carrieri MPatrizia , Wodak Alex
Published: May 2008

Background

Despite France being regarded as a model of efficient harm reduction policy and equity of access to care in the general community, the health of French inmates is a critical issue, as harm reduction measures are either inaccessible or only partially implemented in French prisons.

Method

Using specific inclusion and exclusion criteria, information was collected and analyzed about HIV, HBV and HCV prevalence, risk practices, mortality, access to harm reduction measures and care for French prison inmates.

Results

Data about the occurrence of bloodborne diseases, drug use and access to care in prisons remain limited and need urgent updating. Needle exchange programs are not yet available in French prisons and harm reduction interventions and access to OST remain limited or are heterogeneous across prisons. The continuity of care at prison entry and after release remains problematic and should be among the primary public health priorities for French prisoners.

Conclusion

Preventive and harm reduction measures should be urgently introduced at least as pilot programs. The implementation of such measures, not yet available in French prisons, is not only a human right for prison inmates but can also provide important public health benefits for the general population.
Nitrofurantoin-induced pulmonary fibrosis: a case report
Authors: Goemaere Natascha N T , Grijm Karin , van Hal Peter Th W , den Bakker Michael A
Published: May 2008

Introduction

Nitrofurantoin is a commonly used drug in the treatment and prevention of urinary tract infections. Many adverse effects of nitrofurantoin have been documented, including aplastic anemia, polyneuritis, and liver and pulmonary toxicity.

Case presentation

We describe the clinical history and the autopsy findings in a 51-year-old woman with lung fibrosis of unknown etiology. She had a history of recurrent urinary tract infections, treated with nitrofurantoin for many years. She was referred to our hospital for screening for lung transplantation because of severe pulmonary restriction and dyspnea. Unfortunately, she died as a result of progressive respiratory insufficiency. At autopsy bilateral patchy, sharply circumscribed fibrotic areas in the upper and lower lobes of the lungs were seen with honeycombing. Microscopically, end-stage interstitial fibrosis with diffuse alveolar damage was observed. Due to the atypical distribution of the fibrosis involving both the lower and upper lobes of the lung, the microscopic pattern of the fibrosis and the history of long-term nitrofurantoin use, we concluded that this drug induced the lung fibrosis. The recurrent urinary tract infections were probably caused by a diverticulum of the urinary bladder, which was discovered at autopsy.

Conclusion

This case shows that the use of nitrofurantoin may cause severe pulmonary disease. Patients with long-term use of nitrofurantoin should be monitored regularly for adverse pulmonary effects.
Transcriptome analysis reveals new insight into appressorium formation and function in the rice blast fungus Magnaporthe oryzae
Authors: Oh Yeonyee , Donofrio Nicole , Pan Huaqin , Coughlan Sean , Brown Douglas E , Meng Shaowu , Mitchell Thomas , Dean Ralph A
Published: May 2008

Background

Rice blast disease is caused by the filamentous Ascomycetous fungus Magnaporthe oryzae and results in significant annual rice yield losses worldwide. Infection by this and many other fungal plant pathogens requires the development of a specialized infection cell called an appressorium. The molecular processes regulating appressorium formation are incompletely understood.

Results

We analyzed genome-wide gene expression changes during spore germination and appressorium formation on a hydrophobic surface compared to induction by cAMP. During spore germination, 2,154 (approximately 21%) genes showed differential expression, with the majority being up-regulated. During appressorium formation, 357 genes were differentially expressed in response to both stimuli. These genes, which we refer to as appressorium consensus genes, were functionally grouped into Gene Ontology categories. Overall, we found a significant decrease in expression of genes involved in protein synthesis. Conversely, expression of genes associated with protein and amino acid degradation, lipid metabolism, secondary metabolism and cellular transportation exhibited a dramatic increase. We functionally characterized several differentially regulated genes, including a subtilisin protease (SPM1) and a NAD specific glutamate dehydrogenase (Mgd1), by targeted gene disruption. These studies revealed hitherto unknown findings that protein degradation and amino acid metabolism are essential for appressorium formation and subsequent infection.

Conclusion

We present the first comprehensive genome-wide transcript profile study and functional analysis of infection structure formation by a fungal plant pathogen. Our data provide novel insight into the underlying molecular mechanisms that will directly benefit efforts to identify fungal pathogenicity factors and aid the development of new disease management strategies.
Calorie Restriction Modulates Inactivity-Induced Changes in the Inflammatory Markers C-Reactive Protein and Pentraxin-3
Authors: Bosutti Alessandra , Malaponte Grazia , Zanetti Michela , Castellino Pietro , Heer Martina , Guarnieri Gianfranco , Biolo Gianni
Published: May 2008

Context: Energy balance and physical activity potentially influence systemic inflammation.

Objective: Our objective was to test the hypothesis that moderate energy restriction may prevent activation of inactivity-induced inflammatory response.

Design: Participants were studied four times at the end of 14-d periods of experimental bed rest or controlled ambulation, after receiving eucaloric or hypocaloric diets.

Setting: The study was conducted at the clinical research center of the German Space Agency.

Subjects: Nine healthy young volunteers participated.

Interventions: Energy intake was calibrated to physical activity and decreased by about 20% in hypocaloric conditions.

Main Outcome Measures: Changes in body fat by dual-energy x-ray absorptiometry as well as plasma inflammatory markers and cytokine mRNA levels in blood cells were measured.

Results: Fat mass did not change significantly in eucaloric conditions and decreased in hypocaloric periods (−1.0 ± 0.3 and −1.0 ± 0.3 kg in ambulatory and bed rest, respectively). Bed rest in eucaloric conditions increased plasma C-reactive protein (CRP) (+143 ± 53%) and both the ratios between plasma IL-6 and IL-10 (4±1 times) and white blood cell IL-6 and IL-10 mRNAs (5 ± 1 times). Energy restriction prevented bed-rest-mediated increases in CRP and the IL-6 to IL-10 ratio. Bed rest increased (P = 0.03) long pentraxin-3 (PTX3) plasma concentration, without significant activity-by-diet interaction. In all conditions (n = 36), CRP and PTX3 were inversely correlated (r = −0.61; P < 0.001). Changes in fat mass, leptin, and IL-6 directly correlated with CRP and inversely correlated with PTX3. IL-10 inversely correlated with CRP and directly correlated with PTX3 (r = 0.52; P < 0.01).

Conclusions: Calorie restriction prevents the inflammatory response induced by 14 d of bed rest. We suggest an inverse regulation of CRP and PTX3 in response to changes in energy balance.
High Plasma Retinol Binding Protein-4 and Low Plasma Adiponectin Concentrations Are Associated with Severity of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus
Authors: Choi Sung Hee , Kwak Soo Heon , Youn Byung-Soo , Lim Soo , Park Young Joo , Lee Hyewon , Lee Namseok , Cho Young Min , Lee Hong Kyu , Kim Young-Bum , Park Kyong Soo , Jang Hak C.
Published: May 2008

Context: Women with previous gestational diabetes mellitus (pGDM) are at high risk of developing type 2 diabetes mellitus in the future. The role of adipokines in women with pGDM has not been established.

Objective: We investigated whether circulating adipokine concentration is associated with abnormal glucose homeostasis in women with pGDM.

Design, Setting, Patients, and Main Outcome Measures: We measured the plasma concentrations of retinol-binding protein-4 (RBP4), transthyretin (TTR), and adiponectin and metabolic parameters in four groups of women who exhibited normal glucose tolerance (NGT) during a previous pregnancy (NP, n = 17), NGT after GDM (GDM-NGT, n = 72), impaired glucose tolerance after GDM (GDM-IGT, n = 60), and type 2 diabetes after GDM (GDM-DM, n = 8).

Results: Plasma RBP4 concentration was significantly higher in women with GDM-DM, GDM-IGT, and GDM-NGT than in those with NP. RBP4 concentration correlated positively with TTR concentration; fasting plasma glucose, insulin, and triglyceride concentrations; blood pressure; abdominal fat area; and homeostasis model assessment of insulin resistance. Plasma TTR concentration was elevated in women with GDM-DM compared with other groups. In contrast, adiponectin concentration was lowest in the GDM-DM group and correlated inversely with parameters of insulin resistance. Resistin concentration was higher only in the GDM-NGT and GDM-IGT groups, whereas leptin did not differ between groups. Plasma RBP4 and adiponectin concentrations were inversely correlated.

Conclusions: The severity of glucose intolerance in women with pGDM is associated with high RBP4 and low adiponectin concentrations.
Determination of Free Growth Hormone
Authors: Frystyk Jan , Andreasen Caroline Marie , Fisker Sanne
Published: May 2008

Context: Approximately 50% of circulating GH is bound to the high-affinity GH-binding protein (GHBP), which is known to affect the pharmacokinetics, bioactivity, and quantitative determination of GH. Nevertheless, the presence of GHBP is rarely taken into account in the clinical use of GH measurements.

Objective: Our objective was to develop an assay for free GH in serum.

Methods: We used ultrafiltration by centrifugation. Due to the small molecular difference between GH and GHBP, the size of GHBP and GHBP-GH complexes was increased by preincubation of serum with a monoclonal GHBP antibody (MAb 263).

Results: The ultrafiltration membrane almost completely retained all GHBP (>98.5%) and allowed free passage of unbound GH (>98.4%). Addition of increasing concentrations of GHBP reduced free GH dose dependently, and measured and calculated levels of free GH changed in parallel. During an insulin-tolerance test, free and total GH changed in parallel in all individuals (n = 11) and their peak values as well as area under the curve values were positively correlated (r = 0.89; P < 0.001 and r = 0.92; P < 0.001, respectively). Of note, the relative levels of free GH (calculated as the area under the curve of free to total GH) was inversely correlated with GHBP (r = −0.94; P < 0.001).

Conclusion: It is possible to measure free GH in human serum. Free GH correlated positively with total GH and inversely with GHBP. Measurement of free GH may be a helpful future tool in the management of GH disorders and in studies of GH-GHBP interrelationships.
A Common Variation in Deiodinase 1 Gene DIO1 Is Associated with the Relative Levels of Free Thyroxine and Triiodothyronine
Authors: Panicker Vijay , Cluett Christie , Shields Beverley , Murray Anna , Parnell Kirstie S. , Perry John R. B. , Weedon Michael N. , Singleton Andrew , Hernandez Dena , Evans Jonathan , Durant Claire , Ferrucci Luigi , Melzer David , Saravanan Ponnusamy , Visser Theo J. , Ceresini Graziano , Hattersley Andrew T. , Vaidya Bijay , Dayan Colin M. , Frayling Timothy M.
Published: May 2008

Introduction: Genetic factors influence circulating thyroid hormone levels, but the common gene variants involved have not been conclusively identified. The genes encoding the iodothyronine deiodinases are good candidates because they alter the balance of thyroid hormones. We aimed to thoroughly examine the role of common variation across the three deiodinase genes in relation to thyroid hormones.

Methods: We used HapMap data to select single-nucleotide polymorphisms (SNPs) that captured a large proportion of the common genetic variation across the three deiodinase genes. We analyzed these initially in a cohort of 552 people on T4 replacement. Suggestive findings were taken forward into three additional studies in people not on T4 (total n = 2513) and metaanalyzed for confirmation.

Results: A SNP in the DIO1 gene, rs2235544, was associated with the free T3 to free T4 ratio with genome-wide levels of significance (P = 3.6 × 10−13). The C-allele of this SNP was associated with increased deiodinase 1 (D1) function with resulting increase in free T3/T4 ratio and free T3 and decrease in free T4 and rT3. There was no effect on serum TSH levels. None of the SNPs in the genes coding for D2 or D3 had any influence on hormone levels.

Conclusions: This study provides convincing evidence that common genetic variation in DIO1 alters deiodinase function, resulting in an alteration in the balance of circulating free T3 to free T4. This should prove a valuable tool to assess the relative effects of circulating free T3vs. free T4 on a wide range of biological parameters.
Inducible expression of microRNA-194 is regulated by HNF-1α during intestinal epithelial cell differentiation
Authors: Hino Kimihiro , Tsuchiya Kiichiro , Fukao Taro , Kiga Kotaro , Okamoto Ryuichi , Kanai Takanori , Watanabe Mamoru
Published: May 2008

Maintenance of the intestinal epithelium is based on well-balanced molecular mechanisms that confer the stable and continuous supply of specialized epithelial cell lineages from multipotent progenitors. Lineage commitment decisions in the intestinal epithelium system involve multiple regulatory systems that interplay with each other to establish the cellular identities. Here, we demonstrate that the microRNA system could be involved in intestinal epithelial cell differentiation, and that microRNA-194 (miR-194) is highly induced during this process. To investigate this inducible expression mechanism, we identified the genomic structure of the miR-194-2, -192 gene, one of the inducible class of miR-194 parental genes. Furthermore, we identified its transcriptional regulatory region that contains a consensus-binding motif for hepatocyte nuclear factor-1α (HNF-1α), which is well known as a transcription factor to regulate gene expression in intestinal epithelial cells. By chromatin immunoprecipitation assay and luciferase reporter analysis, we revealed that pri-miR-194-2 expression is controlled by HNF-1α, and its consensus binding region is required for the transcription of pri-miR-194-2 in vivo in an intestinal epithelial cell line, Caco-2. Our observations indicate that microRNA genes could be targets of lineage-specific transcription factors and that microRNAs are regulated by a tissue-specific manner in the intestinal epithelium. Therefore, our work suggests that induced expression of these microRNAs have important roles in intestinal epithelium maturation.
Treatment Options in Insulin Resistance Obesity–Related Acanthosis Nigricans
Authors: Romo Anthony , Benavides Sandra
Published: May 2008

Objective:

To evaluate the literature to determine which oral and topical medications are most effective In the treatment of insulin resistance obesity–related acanthosis nigricans (IRORAN).

Data Sources:

A MEDLINE literature search was conducted (1950–January 2008) using the search terms acanthosis nigricans (AN), metformin, rosiglita-zone, octreotide, retinoic acid, acitretin, etretinate, and isotretinoin. The search was limited to articles on treatment of IRORAN in humans written in the English language. Articles were retrieved and all references were reviewed.

Study Selection and Data Extraction:

Articles selected for inclusion were limited to AN related to obesity with no other underlying etiology. Clinical trials and case repons using monotherapy were included.

Data Synthesis:

Metformin, rosiglitazone, octreotide, vitamin D analogs, and retinoic acid have been used in the treatment of IRORAN. In one randomized trial, metformin 500 mg 3 times daily was compared with rosiglitazone 4 mg once daily. Neither treatment demonstrated significant Improvements in AN; however, rosiglitazone did significantly decrease serum insulin levels. In a second clinical trial and in several case reports, AN and hyperinsulinemia did show improvement with metformin treatment. After a 6-month period, octreotide improved IRORAN, body weight, and glucose/insulin response to a meal. The improvements persisted for 6 additional months after discontinuation of octreotide. Vitamin D analogs and retinoids produced inconsistent results in 5 separate case reports.

Conclusions:

IRORAN is a growing problem, particularly in children and adolescents, secondary to the Increase in the prevalence of obesity. Treatment of IRONAN should focus on reversal of the underlying hyperinsulinemia. Patients with IRORAN may benefit from a trial of metformin for Improvement of lesions and underlying hyperinsulinemia.
Severe Myalgia Associated with Adalimumab Treatment in a Patient with Crohn's Disease
Authors: Hinojosa Joaquín , Borrás-Blasco Joaquín , Maroto Nuria , Rosique-Robles J Dolores , Alos Rafael , Casterá MD Elvira
Published: May 2008

Objective:

To report a case of severe myalgia associated with adalimumab in a patient with Crohn's disease.

Case Summary:

A 44-year-old woman was diagnosed as having ileocecal Crohn's disease with perianal fistula lesions. She was treated with 3 infusions of infliximab 5 mg/kg, which stabilized her condition. However, when reactivation of Crohn's disease occurred, Infliximab was discontinued. Eight weeks after infliximab was suspended, treatment with adalimumab was started, with an initial dose of 160 mg followed by 80 mg in week 2; 46 hours after the first dose, the woman complained of generalized severe pain in her upper and lower extremities. Results of all laboratory tests were within normal limits. A diagnosis of severe drug-related myalgia was made. We suspected that adalimumab was the causative agent since it was the only drug that had been added before the musculoskeletal symptoms appeared. Adalimumab was stopped and treatment with Ibuprofen and tramadol was started. Fifteen days after stopping adalimumab, the patient reported complete resolution of her muscle pain.

Discussion:

Myalgia following administration of adalimumab Is uncommon. This adverse reaction rarely is severe enough to result in cessation of the drug. In our patient, the most likely cause of the severe myalgias was considered to be adalimumab. The onset and resolution of the signs and symptoms followed a reasonable temporal sequence following drug initiation and discontinuation. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered probable.

Conclusions:

This case documents the importance of recognizing the possibility of musculoskeletal adverse reactions even with medications like adalimumab, which have a good safety profile. These findings should further alert clinicians to the potential for myalgias associated with adalimumab administration.
Surface area and layer charge of smectite from CEC and EGME/H2O-retention measurements
Authors: Środoń Jan , McCarty Douglas K.
Published: May 2008

The total specific surface area (TSSA) and smectitic layer charge (Qs) calculated from the structural formulae and unit-cell dimensions of 12 pure smectite samples were used as a reference in the design and evaluation of TSSA and Qs measurement techniques based on cation exchange capacity (CEC), H2O retention at 47% RH, and ethylene glycol monoethyl ether (EGME) retention. A thermogravimetric analysis-mass spectrometry (TGA-MS) technique was used to study the release of H2O from smectite on heating, and to introduce a correction for H2O remaining in the smectite after heating to 110°C, because the sample weight at this temperature has been used routinely as a reference in CEC and EGME sorption measurements. A temperature of 200°C was found to be the optimum reference for such measurements.

A good agreement between Qs from the structural formula and from CEC was obtained when this correction was applied. The TSSA of smectite was measured with similar accuracy (mean error of ±5–7%) by three techniques: (1) using mean H2O coverage; (2) using mean EGME coverage; and (3) using a combination of H2O coverage and CEC. A reduction of the mean error from 5–7% to 4% can be obtained by averaging these measurements, and a further reduction to 3% by introducing corrections for the dependence of H2O and EGME coverage on layer charge. The study demonstrates that Ca2+-smectite samples at 47% RH have H2O contents corresponding to 88–107% of the theoretical mass of a monolayer and offers an explanation of this variation.
The Yellow Register Archives of Imperial Ming China
Authors: Zhang Wenxian
Published: May 2008

China has a long record of archival development, reaching back through the history of all its dynasties. From the late fourteenth century to the early seventeenth century, the Ming Empire (1368–1644 CE) constructed and operated its Yellow Register Archives in Nanjing to house population surveys used to determine imperial taxation. Although the actual archival records were destroyed, primary documents compiled by Ming archival officials survived, revealing the development of the imperial archives in premodern China. Those documents not only reveal the administrative structures and fiscal strengths of the Ming Dynasty but also present a comprehensive picture of archival practices in Ming China. As one of the world’s largest archival operations in history until its destruction in 1645, the Ming Yellow Register repository represents an important and fascinating chapter in the development of human record keeping and management.
Constructing topological parallelisms of PG(3, ℝ) via rotation of generalized line pencils
Authors: Betten Dieter , Riesinger Rolf
Published: May 2008

Let Q be an elliptic quadric of the real projective 3-space PG(3, ℝ) and denote by Q
¬i
the set of non-interior points with respect to Q. A simple covering of Q
¬i
by 2-secants of Q is called generalized line star with respect to Q. In [D. Betten, R. Riesinger, Topological parallelisms of the real projective 3-space. Results Math. 47 (2005), 226–241. MR2153495 (2006b:51009) Zbl 1088.51005] the authors give a construction P such that is a parallelism of PG(3, ℝ); cf. Theorem 1 below. In the present article, we are mainly interested in the plane analogues of gl-stars: the gl-pencils with respect to a conic; cf. Definition 3. If a gl-star is generated by rotating a gl-pencil about an axis , then we call a latitudinal gl-star and a latitudinal parallelism. We present a general construction process for gl-pencils by giving generating functions. Along this way we prove the existence of non-Clifford latitudinal parallelisms in PG(3, ℝ); moreover, we show that each latitudinal parallelism is topological.
Staircase kernels
Authors: Magazanik Evelyn , Perles Micha A.
Published: May 2008

Let S ⊂ ℝ2 be a compact staircase connected set with stdiam(S) = n. In [E. Magazanik, M. A. Perles, Staircase connected sets. Discrete Comput. Geom.
37 (2007), 587–599. MR2321743 Zbl] we showed that Ker
r
(S) is nonempty if , and for , Ker
r
(S) is staircase connected. In this paper we determine the possible values of the staircase diameter of Ker
r
(S) for , and present interesting facts about Ker
r
(S) when and .
Polar spaces, BLT-sets and generalized quadrangles
Authors: Knarr Norbert
Published: May 2008

We generalize an earlier construction of generalized quadrangles from polar spaces of rank 3 to polar spaces of arbitrary rank.
Quadratic modules of polynomials in two variables
Authors: Cabral Maria Eugênia Canto , Prestel Alexander
Published: May 2008

Leth1,…,hs∈ ℝ[X, Y] and assume that the setW(h) := {(a, b) ∈ ℝ2|hi(a, b) ≥ 0 for all 1 ≤i≤s} is compact and non-empty. We give an effective method to decide from the knowledge ofh1,…,hswhether every polynomialf∈ ℝ[X, Y], strictly positive onW(h), has a representationf=σ0+h1σ1+···+hsσswith eachσibeing a sum of squares in ℝ[X, Y].
On rational maps from a general surface in to surfaces of general type
Authors: Guerra Lucio , Pirola Gian Pietro
Published: May 2008

We study dominant rational maps from a general surface in to surfaces of general type. We prove restrictions on the target surfaces, and special properties of these rational maps. We show that for small degree the general surface has no such map. Moreover a slight improvement of a result of Catanese, on the number of moduli of a surface of general type, is also obtained.
Distinctive morphological features, life-cycle phases and seasonal variations in subtropical populations ofDictyota dichotoma(Dictyotales, Phaeophyceae)
Authors: Tronholm Ana , Sansón Marta , Afonso-Carrillo Julio , De Clerck Olivier
Published: May 2008

Although it has been suggested that the distribution ofDictyota dichotomais probably restricted to the European Atlantic Ocean and the Mediterranean Sea, its occurrence in the Canary Islands (new southernmost distribution limit) is confirmed by nuclear ribosomal sequence data (LSU rDNA). Even thoughD. dichotomahas been described and illustrated prominently in early studies of brown algae, the species remains difficult to characterize due to considerable morphological plasticity. An exhaustive analysis of several quantitative characters confirms significant morphological variation both seasonally and between life-cycle phases. The species may be characterized in the Canary Islands only by the following qualitative features: erect thallus attached by a single holdfast, subdichotomous branches always of similar width, straight terminal segments and smooth margins and an entirely unilayered medulla. In the Canary Islands,D. dichotomais an aseasonal annual with at least three overlapping generations in which sporophytes and gametophytes grow simultaneously. Thallus life span seems to be less than 3 months. The species occurs throughout the year, but as cryptic microthalli in autumn. Two abundance peaks were detected with the maximum value in February (6.2 thalli m-2). The optimum reproductive stage (88.3% fertile specimens) occurred in winter and the maximum vegetative stage (maximum thallus length: 18.6 cm) in summer. Sporophytes outnumbered gametophytes throughout the year, with ratios decreasing from 13.2±1.1 in winter to 1.9±0.2 in summer. Gametophytes made up to 25% of the population and fertile thalli were always dominant. The populations from the Canaries exhibited a temporal displacement compared to northern populations with the favorable period in the coldest season (winter) and the resting period in the warmest season (autumn).
Laurencia caduciramulosa(Ceramiales, Rhodophyta) from the Canary Islands, Spain: a new record for the eastern Atlantic Ocean
Authors: Cassano Valéria , Candelaria Gil-Rodríguez Maria , Sentíes Abel , Toyota Fujii Mutue
Published: May 2008

Laurencia caduciramulosais recorded for the first time for the eastern Atlantic Ocean off Tenerife, Canary Islands, Spain. The specimens were collected in 2006, growing epilithically in the lower intertidal zone on moderately exposed rocky shores. This species is characterized by reduced size, a well-developed stolon-like basal system and erect axes with abundant deciduous branchlets that function as propagules, except on the uppermost portions of the branches, where they form crowns of branchlets. As in all other reports of this species, gametangia and sporangia were not observed. This study expands the geographical distribution ofL. caduciramulosato the eastern Atlantic Ocean.
Dynamic Spectrotemporal Feature Selectivity in the Auditory Midbrain
Authors: Lesica Nicholas A. , Grothe Benedikt
Published: May 2008

The transformation of auditory information from the cochlea to the cortex is a highly nonlinear process. Studies using tone stimuli have revealed that changes in even the most basic parameters of the auditory stimulus can alter neural response properties; for example, a change in stimulus intensity can cause a shift in a neuron's preferred frequency. However, it is not yet clear how such nonlinearities contribute to the processing of spectrotemporal features in complex sounds. Here, we use spectrotemporal receptive fields (STRFs) to characterize the effects of stimulus intensity on feature selectivity in the mammalian inferior colliculus (IC). At low intensities, we find that STRFs are relatively simple, typically consisting of a single excitatory region, indicating that the neural response is simply a reflection of the stimulus amplitude at the preferred frequency. In contrast, we find that STRFs at high intensities typically consist of a combination of an excitatory region and one or more inhibitory regions, often in a spectrotemporally inseparable arrangement, indicating selectivity for complex auditory features. We show that a linear–nonlinear model with the appropriate STRF can predict neural responses to stimuli with a fixed intensity, and we demonstrate that a simple extension of the model with an intensity-dependent STRF can predict responses to stimuli with varying intensity. These results illustrate the complexity of auditory feature selectivity in the IC, but also provide encouraging evidence that the prediction of nonlinear responses to complex stimuli is a tractable problem.
Lapsing during Sleep Deprivation Is Associated with Distributed Changes in Brain Activation
Authors: Chee Michael W. L. , Tan Jiat Chow , Zheng Hui , Parimal Sarayu , Weissman Daniel H. , Zagorodnov Vitali , Dinges David F.
Published: May 2008

Lapses of attention manifest as delayed behavioral responses to salient stimuli. Although they can occur even after a normal night's sleep, they are longer in duration and more frequent after sleep deprivation (SD). To identify changes in task-associated brain activation associated with lapses during SD, we performed functional magnetic resonance imaging during a visual, selective attention task and analyzed the correct responses in a trial-by-trial manner modeling the effects of response time. Separately, we compared the fastest 10% and slowest 10% of correct responses in each state. Both analyses concurred in finding that SD-related lapses differ from lapses of equivalent duration after a normal night's sleep by (1) reduced ability of frontal and parietal control regions to raise activation in response to lapses, (2) dramatically reduced visual sensory cortex activation, and (3) reduced thalamic activation during lapses that contrasted with elevated thalamic activation during nonlapse periods. Despite these differences, the fastest responses after normal sleep and after SD elicited comparable frontoparietal activation, suggesting that performing a task while sleep deprived involves periods of apparently normal neural activation interleaved with periods of depressed cognitive control, visual perceptual functions, and arousal. These findings reveal for the first time some of the neural consequences of the interaction between efforts to maintain wakefulness and processes that initiate involuntary sleep in sleep-deprived persons.
Ablation of Kv3.1 and Kv3.3 Potassium Channels Disrupts Thalamocortical OscillationsIn VitroandIn Vivo
Authors: Espinosa Felipe , Torres-Vega Miguel A. , Marks Gerald A. , Joho Rolf H.
Published: May 2008

The genesKcnc1andKcnc3encode the subunits for the fast-activating/fast-deactivating, voltage-gated potassium channels Kv3.1 and Kv3.3, which are expressed in several brain regions known to be involved in the regulation of the sleep–wake cycle. When these genes are genetically eliminated, Kv3.1/Kv3.3-deficient mice display severe sleep loss as a result of unstable slow-wave sleep. Within the thalamocortical circuitry, Kv3.1 and Kv3.3 subunits are highly expressed in the thalamic reticular nucleus (TRN), which is thought to act as a pacemaker at sleep onset and to be involved in slow oscillatory activity (spindle waves) during slow-wave sleep. We showed that in cortical electroencephalographic recordings of freely moving Kv3.1/Kv3.3-deficient mice, spectral power is reduced up to 70% at frequencies <15 Hz. In addition, the number of sleep spindlesin vivoas well as rhythmic rebound firing of TRN neuronsin vitrois diminished in mutant mice. Kv3.1/Kv3.3-deficient TRN neurons studiedin vitroshow ∼60% increase in action potential duration and a reduction in high-frequency firing after depolarizing current injections and during rebound burst firing. The results support the hypothesis that altered electrophysiological properties of TRN neurons contribute to the reduced EEG power at slow frequencies in the thalamocortical network of Kv3-deficient mice.
Response of a Neuronal Model of Tuberous Sclerosis to Mammalian Target of Rapamycin (mTOR) Inhibitors: Effects on mTORC1 and Akt Signaling Lead to Improved Survival and Function
Authors: Meikle Lynsey , Pollizzi Kristen , Egnor Anna , Kramvis Ioannis , Lane Heidi , Sahin Mustafa , Kwiatkowski David J.
Published: May 2008

Tuberous sclerosis (TSC) is a hamartoma syndrome attributable to mutations in either TSC1 or TSC2 in which brain involvement causes epilepsy, mental retardation, and autism. We have reported recently (Meikle et al., 2007) a mouse neuronal model of TSC in which Tsc1 is ablated in most neurons during cortical development. We have tested rapamycin and RAD001 [40-O-(2-hydroxyethyl)-rapamycin], both mammalian target of rapamycin mTORC1 inhibitors, as potential therapeutic agents in this model. Median survival is improved from 33 d to more than 100 d; behavior, phenotype, and weight gain are all also markedly improved. There is brain penetration of both drugs, with accumulation over time with repetitive treatment, and effective reduction of levels of phospho-S6, a downstream target of mTORC1. In addition, there is restoration of phospho-Akt and phospho-glycogen synthase kinase 3 levels in the treated mice, consistent with restoration of Akt function. Neurofilament abnormalities, myelination, and cell enlargement are all improved by the treatment. However, dysplastic neuronal features persist, and there are only modest changes in dendritic spine density and length. Strikingly, mice treated with rapamycin or RAD001 for 23 d only (postnatal days 7–30) displayed a persistent improvement in phenotype, with median survival of 78 d. In summary, rapamycin/RAD001 are highly effective therapies for this neuronal model of TSC, with benefit apparently attributable to effects on mTORC1 and Akt signaling and, consequently, cell size and myelination. Although caution is appropriate, the results suggest the possibility that rapamycin/RAD001 may have benefit in the treatment of TSC brain disease, including infantile spasms.
CITED2 Signals through Peroxisome Proliferator-Activated Receptor-γ to Regulate Death of Cortical Neurons after DNA Damage
Authors: Gonzalez Yasmilde Rodriguez , Zhang Yi , Behzadpoor Doreh , Cregan Sean , Bamforth Simon , Slack Ruth S. , Park David S.
Published: May 2008

DNA damage is an important initiator of neuronal apoptosis and activates signaling events not yet fully defined. Using the camptothecin-induced DNA damage model in neurons, we previously showed that cyclin D1-associated cell cycle cyclin-dependent kinases (Cdks) (Cdk4/6) and p53 activation are two major events leading to activation of the mitochondrial apoptotic pathway. With gene array analyses, we detected upregulation of Cited2, a CBP (cAMP response element-binding protein-binding protein)/p300 interacting transactivator, in response to DNA damage. This upregulation was confirmed by reverse transcription-PCR and Western blot. CITED2 was functionally important because CITED2 overexpression promotes death, whereas CITED2 deficiency protects. Cited2 upregulation is upstream of the mitochondrial death pathway (BAX, Apaf1, or cytochromecrelease) and appears to be independent of p53. However, inhibition of the Cdk4 blocked Cited2 induction. The Cited2 prodeath mechanism does not involve Bmi-1 or p53. Instead, Cited2 activates peroxisome proliferator-activated receptor-γ (PPARγ), an activity that we demonstrate is critical for DNA damage-induced death. These results define a novel neuronal prodeath pathway in which Cdk4-mediated regulation of Cited2 activates PPARγ and consequently caspase.
GABA Regulates Excitatory Synapse Formation in the Neocortex via NMDA Receptor Activation
Authors: Wang Doris D. , Kriegstein Arnold R.
Published: May 2008

The development of a balance between excitatory and inhibitory synapses is a critical process in the generation and maturation of functional circuits. Accumulating evidence suggests that neuronal activity plays an important role in achieving such a balance in the developing cortex, but the mechanism that regulates this process is unknown. During development, GABA, the primary inhibitory neurotransmitter in adults, excites neurons as a result of high expression of the Na+-K+-2Cl−cotransporter (NKCC1). Using NKCC1 RNA interference knockdownin vivo, we show that GABA-induced depolarization is necessary for proper excitatory synapse formation and dendritic development of newborn cortical neurons. Blocking NKCC1 with the diuretic bumetanide during development leads to similar persistent changes in cortical circuitry in the adult. Interestingly, expression of a voltage-independent NMDA receptor rescues the failure of NKCC1 knockdown neurons to develop excitatory AMPA transmission, indicating that GABA depolarization cooperates with NMDA receptor activation to regulate excitatory synapse formation. Our study identifies an essential role for GABA in the synaptic integration of newborn cortical neurons and suggests an activity-dependent mechanism for achieving the balance between excitation and inhibition in the developing cortex.
General Võ Nguyên Giáp and the Mysterious Evolution of the Plan for the 1968 Tết Offensive
Authors: Pribbenow Merle L.
Published: May 2008

The 1968 Tết Offensive was the brainchild of Communist Party Secretary Lê Duẩn and General Văn Tiến Dũng. The Hà Nội government wanted to exploit the 1968 US presidential elections by opening negotiations with the United States. When General Võ Nguyên Giáp failed to devise a workable plan to win a military victory to give the communists leverage in the planned negotiations, Lê Duẩn and Văn Tiến Dũng pushed the risky plan for a nationwide "general offensive" through a reluctant Politburo in spite of opposition from General Võ Nguyên Giáp and Hồ Chí Minh.
Analysis of theDrosophila melanogasterTestes Transcriptome Reveals Coordinate Regulation of Paralogous Genes
Authors: Mikhaylova Lyudmila M , Nguyen Kimberly , Nurminsky Dmitry I
Published: May 2008

Gene duplications have been broadly implicated in the generation of testis-specific genes. To perform a comprehensive analysis of paralogous testis-biased genes, we characterized the testes transcriptome of Drosophila melanogaster by comparing gene expression in testes vs. ovaries, heads, and gonadectomized males. A number of the identified 399 testis-biased genes code for the known components of mature sperm. Among the detected 69 genes downregulated in testes, a large fraction is required for viability. By analyzing paralogs of testis-biased genes, we identified “co-regulated” paralogous pairs in which both genes are testis biased, “anti-regulated” pairs in which one paralog is testis biased and the other downregulated in testes, and “neutral” pairs in which one paralog is testis biased and the other constitutively expressed. The numbers of identified co-regulated and anti-regulated pairs were higher than expected by chance. Testis-biased genes included in these pairs show decreased frequency of lethal mutations, suggesting their specific role in male reproduction. These genes also show exceptionally high interspecific variability of expression in comparison between D. melanogaster and the closely related D. simulans. Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.
Linkage Disequilibrium Under Genetic Hitchhiking in Finite Populations
Authors: Pfaffelhuber P , Lehnert A , Stephan W
Published: May 2008

The model of genetic hitchhiking predicts a reduction in sequence diversity at a neutral locus closely linked to a beneficial allele. In addition, it has been shown that the same process results in a specific pattern of correlations (linkage disequilibrium) between neutral polymorphisms along the chromosome at the time of fixation of the beneficial allele. During the hitchhiking event, linkage disequilibrium on either side of the beneficial allele is built up whereas it is destroyed across the selected site. We derive explicit formulas for the expectation of the covariance measure D and standardized linkage disequilibrium $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\sigma}}_{D}^{2}\) \end{document}$ between a pair of polymorphic sites. For our analysis we use the approximation of a star-like genealogy at the selected site. The resulting expressions are approximately correct in the limit of large selection coefficients. Using simulations we show that the resulting pattern of linkage disequilibrium is quickly—i.e., in <0.1N generations—destroyed after the fixation of the beneficial allele for moderately distant neutral loci, where N is the diploid population size.
A Statistical Model for Testing the Pleiotropic Control of Phenotypic Plasticity for a Count Trait
Authors: Ma Chang-Xing , Yu Qibin , Berg Arthur , Drost Derek , Novaes Evandro , Fu Guifang , Yap John Stephen , Tan Aixin , Kirst Matias , Cui Yuehua , Wu Rongling
Published: May 2008

The differences of a phenotypic trait produced by a genotype in response to changes in the environment are referred to as phenotypic plasticity. Despite its importance in the maintenance of genetic diversity via genotype-by-environment interactions, little is known about the detailed genetic architecture of this phenomenon, thus limiting our ability to predict the pattern and process of microevolutionary responses to changing environments. In this article, we develop a statistical model for mapping quantitative trait loci (QTL) that control the phenotypic plasticity of a complex trait through differentiated expressions of pleiotropic QTL in different environments. In particular, our model focuses on count traits that represent an important aspect of biological systems, controlled by a network of multiple genes and environmental factors. The model was derived within a multivariate mixture model framework in which QTL genotype-specific mixture components are modeled by a multivariate Poisson distribution for a count trait expressed in multiple clonal replicates. A two-stage hierarchic EM algorithm is implemented to obtain the maximum-likelihood estimates of the Poisson parameters that specify environment-specific genetic effects of a QTL and residual errors. By approximating the number of sylleptic branches on the main stems of poplar hybrids by a Poisson distribution, the new model was applied to map QTL that contribute to the phenotypic plasticity of a count trait. The statistical behavior of the model and its utilization were investigated through simulation studies that mimic the poplar example used. This model will provide insights into how genomes and environments interact to determine the phenotypes of complex count traits.
Gene Expression Profiling of Flagellar Disassembly in Chlamydomonas reinhardtii
Authors: Chamberlain Kara L , Miller Steven H , Keller Laura R
Published: May 2008

Flagella are sensory organelles that interact with the environment through signal transduction and gene expression networks. We used microarray profiling to examine gene regulation associated with flagellar length change in the green alga Chlamydomonas reinhardtii. Microarrays were probed with fluorescently labeled cDNAs synthesized from RNA extracted from cells before and during flagellar assembly or disassembly. Evaluation of the gene expression profiles identified >100 clones showing at least a twofold change in expression during flagellar length changes. Products of these genes are associated not only with flagellar structure and motility but also with other cellular responses, including signal transduction and metabolism. Expression of specific genes from each category was further characterized at higher resolution by using quantitative real-time PCR (qRT–PCR). Analysis and comparison of the gene expression profiles coupled to flagellar assembly and disassembly revealed that each process involves a new and uncharacterized whole-cell response to flagellar length changes. This analysis lays the groundwork for a more comprehensive understanding of the cellular and molecular networks regulating flagellar length changes.