bluuebunny/crossref_metadata_2025 huggingface dataset:
Cdc42 localization and cell polarity depend on membrane traffic
Authors: Osmani Naël , Peglion Florent , Chavrier Philippe , Etienne-Manneville Sandrine
Published: December 2010

Cell polarity is essential for cell division, cell differentiation, and most differentiated cell functions including cell migration. The small G protein Cdc42 controls cell polarity in a wide variety of cellular contexts. Although restricted localization of active Cdc42 seems to be important for its distinct functions, mechanisms responsible for the concentration of active Cdc42 at precise cortical sites are not fully understood. In this study, we show that during directed cell migration, Cdc42 accumulation at the cell leading edge relies on membrane traffic. Cdc42 and its exchange factor βPIX localize to intracytosplasmic vesicles. Inhibition of Arf6-dependent membrane trafficking alters the dynamics of Cdc42-positive vesicles and abolishes the polarized recruitment of Cdc42 and βPIX to the leading edge. Furthermore, we show that Arf6-dependent membrane dynamics is also required for polarized recruitment of Rac and the Par6–aPKC polarity complex and for cell polarization. Our results demonstrate influence of membrane dynamics on the localization and activation of Cdc42 and consequently on directed cell migration.
Biphasic targeting and cleavage furrow ingression directed by the tail of a myosin II
Authors: Fang Xiaodong , Luo Jianying , Nishihama Ryuichi , Wloka Carsten , Dravis Christopher , Travaglia Mirko , Iwase Masayuki , Vallen Elizabeth A. , Bi Erfei
Published: December 2010

Cytokinesis in animal and fungal cells utilizes a contractile actomyosin ring (AMR). However, how myosin II is targeted to the division site and promotes AMR assembly, and how the AMR coordinates with membrane trafficking during cytokinesis, remains poorly understood. Here we show that Myo1 is a two-headed myosin II in Saccharomyces cerevisiae, and that Myo1 localizes to the division site via two distinct targeting signals in its tail that act sequentially during the cell cycle. Before cytokinesis, Myo1 localization depends on the septin-binding protein Bni5. During cytokinesis, Myo1 localization depends on the IQGAP Iqg1. We also show that the Myo1 tail is sufficient for promoting the assembly of a “headless” AMR, which guides membrane deposition and extracellular matrix remodeling at the division site. Our study establishes a biphasic targeting mechanism for myosin II and highlights an underappreciated role of the AMR in cytokinesis beyond force generation.
Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
Authors: Tanaka Atsushi , Cleland Megan M. , Xu Shan , Narendra Derek P. , Suen Der-Fen , Karbowski Mariusz , Youle Richard J.
Published: December 2010

Damage to mitochondria can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy. However, fusion of uncoupled mitochondria with polarized mitochondria can compensate for damage, reverse membrane depolarization, and obviate mitophagy. Parkin, an E3 ubiquitin ligase that is mutated in monogenic forms of Parkinson’s disease, was recently found to induce selective autophagy of damaged mitochondria. Here we show that ubiquitination of mitofusins Mfn1 and Mfn2, large GTPases that mediate mitochondrial fusion, is induced by Parkin upon membrane depolarization and leads to their degradation in a proteasome- and p97-dependent manner. p97, a AAA+ ATPase, accumulates on mitochondria upon uncoupling of Parkin-expressing cells, and both p97 and proteasome activity are required for Parkin-mediated mitophagy. After mitochondrial fission upon depolarization, Parkin prevents or delays refusion of mitochondria, likely by the elimination of mitofusins. Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy.
Acquisition and presentation of follicular dendritic cell–bound antigen by lymph node–resident dendritic cells
Authors: McCloskey Megan L. , Curotto de Lafaille Maria A. , Carroll Michael C. , Erlebacher Adrian
Published: December 2010

Follicular dendritic cells (DCs [FDCs]) are prominent stromal cell constituents of B cell follicles with the remarkable ability to retain complement-fixed antigens on their cell surface for extended periods of time. These retained immune complexes have long been known to provide the antigenic stimulus that drives antibody affinity maturation, but their role in cellular immunity has remained unclear. In this study, we show that FDC-retained antigens are continually sampled by lymph node–resident DCs for presentation to CD8 T cells. This novel pathway of antigen acquisition was detectable when FDCs were loaded with purified antigens bound into classical antigen–antibody immune complexes, as well as after pregnancy, when they are loaded physiologically with antigens associated with the complement-fixed microparticles released from the placenta into maternal blood. In both cases, ensuing antigen presentation was profoundly tolerogenic, as it induced T cell deletion even under inflammatory conditions. These results significantly broaden the scope of FDC function and suggest new ways that the complement system and persistent antigen presentation might influence T cell activation and the maintenance of peripheral immune tolerance.
Alan Kenneth Head AO FAA. 10 August 1925 — 9 January 2010
Authors: Humble Peter
Published: December 2010

Alan Head had many scientific interests. He was a mathematical physicist but was so widely read that he could turn his hand to almost anything that had a scientific basis. His achievements were in many fields: they ranged from a design for a giant radio telescope to writing a computer program to simulate the diffraction of electrons as they pass through a crystalline specimen containing defects on an atomic scale and to calculate the images produced by these defects; from the elastic properties of engineering materials to the aberrations in aplanatic, non-spherical lens systems; from the causes of fracture in solid state materials to the patented design for a refrigerator that obtains its cooling power by selectively radiating electromagnetic radiation through a ‘window’ in the Earth's atmosphere to outer space; from Galois theory to quantum computers. Perhaps his greatest success was the theory of fatigue in aluminium alloys used in the construction of jet aeroplanes. Not only was he able to establish the micromechanisms involved, but his analysis was also such that the time that the processes would take to produce a complete failure could be estimated. Without this analysis, commercial aviation as we know it today would have been totally unsafe. But knowing the effective lifetime of components and replacing them before the end of their lifetime meant that, provided that the relevant maintenance was performed diligently, travel by air could be safe. I think the project that gave Alan most pleasure was his understanding of Galois theory and being the first person to apply it to a practical case concerning the elastic anisotropy of crystalline materials (see the section below on the correspondence between Professor H. M. Edwards and Alan Head).

His work on fatigue and Galois theory epitomizes the value that Alan put on ‘theory’. Theory was only good if it led to a practical, useful result. Alan Head had a brilliant career, but his feet were always firmly on the ground. He was modest, quietly spoken and very approachable. He was a friend and mentor to many. There are more than 10 scientific topics (including those mentioned above) described in this short biography, and he made significant contributions to all of them. The memoir is in three parts: a narrative of Alan Head's life and career, recollections of him by his colleagues and family, and a list of his published works cited in the text.
Age-dependent gain of alternative splice forms and biased duplication explain the relation between splicing and duplication
Authors: Roux Julien , Robinson-Rechavi Marc
Published: December 2010

We analyze here the relation between alternative splicing and gene duplication in light of recent genomic data, with a focus on the human genome. We show that the previously reported negative correlation between level of alternative splicing and family size no longer holds true. We clarify this pattern and show that it is sufficiently explained by two factors. First, genes progressively gain new splice variants with time. The gain is consistent with a selectively relaxed regime, until purifying selection slows it down as aging genes accumulate a large number of variants. Second, we show that duplication does not lead to a loss of splice forms, but rather that genes with low levels of alternative splicing tend to duplicate more frequently. This leads us to reconsider the role of alternative splicing in duplicate retention.
A presynaptic role for FMRP during protein synthesis–dependent long-term plasticity in Aplysia
Authors: Till Sally M. , Li Hsiu-Ling , Miniaci Maria Concetta , Kandel Eric R. , Choi Yun-Beom
Published: December 2010

Loss of the Fragile X mental retardation protein (FMRP) is associated with presumed postsynaptic deficits in mouse models of Fragile X syndrome. However, the possible presynaptic roles of FMRP in learning-related plasticity have received little attention. As a result, the mechanisms whereby FMRP influences synaptic function remain poorly understood. To investigate the cellular locus of the effects of FMRP on synaptic plasticity, we cloned the Aplysia homolog of FMRP and find it to be highly expressed in neurons. By selectively down-regulating FMRP in individual Aplysia neurons at the sensory-to-motor neuron synapse reconstituted in co-cultures, we demonstrate that FMRP functions both pre- and postsynaptically to constrain the expression of long-term synaptic depression induced by repeated pulses of FMRF-amide. In contrast, FMRP has little to no effect on long-term synaptic facilitation induced by repeated pulses of serotonin. Since other components of signaling pathways involved in plasticity appear to be conserved between Aplysia and mammalian neurons, our findings suggest that FMRP can participate in both pre- and postsynaptic regulation of enduring synaptic plasticity that underlies the storage of certain types of long-term memory.
Castor Phospholipid:Diacylglycerol Acyltransferase Facilitates Efficient Metabolism of Hydroxy Fatty Acids in Transgenic Arabidopsis
Authors: van Erp Harrie , Bates Philip D. , Burgal Julie , Shockey Jay , Browse John
Published: December 2010

Producing unusual fatty acids (FAs) in crop plants has been a long-standing goal of green chemistry. However, expression of the enzymes that catalyze the primary synthesis of these unusual FAs in transgenic plants typically results in low levels of the desired FA. For example, seed-specific expression of castor (Ricinus communis) fatty acid hydroxylase (RcFAH) in Arabidopsis (Arabidopsis thaliana) resulted in only 17% hydroxy fatty acids (HFAs) in the seed oil. In order to increase HFA levels, we investigated castor phospholipid:diacylglycerol acyltransferase (PDAT). We cloned cDNAs encoding three putative PDAT enzymes from a castor seed cDNA library and coexpressed them with RcFAH12. One isoform, RcPDAT1A, increased HFA levels to 27%. Analysis of HFA-triacylglycerol molecular species and regiochemistry, along with analysis of the HFA content of phosphatidylcholine, indicates that RcPDAT1A functions as a PDAT in vivo. Expression of RcFAH12 alone leads to a significant decrease in FA content of seeds. Coexpression of RcPDAT1A and RcDGAT2 (for diacylglycerol acyltransferase 2) with RcFAH12 restored FA levels to nearly wild-type levels, and this was accompanied by a major increase in the mass of HFAs accumulating in the seeds. We show the usefulness of RcPDAT1A for engineering plants with high levels of HFAs and alleviating bottlenecks due to the production of unusual FAs in transgenic oilseeds.
Benign acral lesions showing parallel ridge pattern on dermoscopy
Authors: TANIOKA Miki
Published: December 2010

One of the recent advances in dermoscopy is the significance of parallel ridge pattern (PRP), which has 99% specificity in detecting both melanoma in situ and advanced melanoma on the acral volar skin. This review features exceptionally benign acral lesions showing PRP on dermoscopy. These benign lesions can be distinguished from malignant melanoma, because of the typical clinical history and associated symptoms. However, it is sometimes difficult for dermatologists to exclude malignant melanoma and a subsequent skin biopsy should be strongly recommended. These benign lesions include pigmentation due to a dye such as para‐phenylenediamine, acral pigmented macules associated with Peutz–Jeghers syndrome, anti‐cancer drug‐induced hyperpigmentation on the volar skin, acral subcorneal hemorrhage and pigmented warts.
Key points in the dermoscopic diagnosis of hypomelanotic melanoma and nodular melanoma
Authors: MOLONEY Fergal J. , MENZIES Scott W.
Published: December 2010

Nodular melanoma (NM) and amelanotic/hypomelanotic melanoma (AHM) often present a challenge to the diagnosing clinician. A significant proportion of AHM are nodular in nature. Such tumors may lack features of asymmetry and altered peripheral pigmentation routinely observed in other melanoma subtypes. This lack of distinguishing clinical features can potentially result in delayed diagnosis or inappropriate treatment. This review highlights the key points in evaluating the range of lesions where AHM or NM are considered in the differential diagnosis and summarizes current evidence in relation to pigmented and vascular dermoscopic diagnostic criteria for both.
Key points in dermoscopic differentiation between early acral melanoma and acral nevus
Authors: SAIDA Toshiaki , KOGA Hiroshi , UHARA Hisashi
Published: December 2010

Acral skin is the most prevalent site of malignant melanoma in non‐Caucasian populations. On acral skin, other various kinds of pigmented lesions are also detected. Particularly, melanocytic nevus is commonly seen on acral volar skin; approximately 10% of Japanese have a nevus on their soles. Prognosis of acral melanoma is still generally poor because of delayed detection in the advanced stages. To improve the prognosis, early detection is essential. Early acral melanoma is seen as a brownish macule, which is clinically quite similar to acral nevus. Therefore, clinicians often face a dilemma when they see a pigmented macule on acral volar skin. Introduction of dermoscopy was a great epoch in this field. Pigmentation pattern on dermoscopy is completely opposite between early acral melanoma and acral nevus; pigmentation on the ridges of the surface skin markings is detected in early acral melanoma, whereas pigmentation along the furrows of the skin markings is seen in acral nevus. We termed these dermoscopic patterns the parallel ridge pattern and the parallel furrow pattern, respectively. These features are highly helpful in the differentiation between the two biologically distinct entities. The sensitivity and specificity of the parallel ridge pattern in diagnosing early acral melanoma is 86% and 99%, respectively. However, we must be aware that dermoscopic features in acral nevus sometimes mimic the parallel ridge pattern and that other conditions also could show dermoscopic features similar to the parallel ridge pattern. In this review article, we summarize key points of the dermoscopic diagnosis of early acral melanoma and then describe the three‐step algorithm for the management of acral melanocytic lesions, which surely aids us in effectively detecting early acral melanoma and in reducing unnecessary resection of benign nevus.
Plasma dimethylarginines during the acute inflammatory response
Authors: Blackwell Scott , O’Reilly Denis St J. , Reid David , Talwar Dinesh
Published: December 2010

Eur J Clin Invest 2011; 41 (6): 635–641

Introduction  Asymmetric dimethylarginine (ADMA) concentrations are increased in critically ill patients and may play a role in multiple organ failure. However, plasma ADMA concentrations during the development of the inflammatory response have not been documented. We measured plasma ADMA, as well as urinary excretion of its major metabolite dimethylamine, and nitrate as a marker of nitric oxide synthase (NOS) activity, in a cohort of patients undergoing elective knee arthroplasty that is known to provoke a significant inflammatory response.

Methods  Thirty‐eight patients were recruited. Fasting venous blood samples were obtained pre‐operatively and at 12 h and daily until the fifth post‐operative day. ADMA and symmetric dimethylarginine (SDMA) were measured by high‐performance liquid chromatography (HPLC). Urinary dimethylamine and nitrate were measured pre‐operatively and on each of the post‐operative mornings using HPLC and expressed as a ratio to creatinine.

Results  Plasma ADMA fell by a median of 31% during the post‐operative period, reaching a nadir on day 2, and recovering to baseline by the end of the study. SDMA showed no significant changes. No increase in urinary dimethylamine excretion was noted until day 5 post‐op, whereupon it doubled. Urinary nitrate showed a small, but nonsignificant decrease on day 2, suggesting no major activation of NOS activity.

Conclusions  Plasma ADMA concentration decreases rapidly and transiently during the first 48 h of acute inflammation. This appears not be caused by increased catabolism and may reflect increased cellular partitioning. This may serve to regulate NOS activity and prevent harmful increases in inducible NOS in situations where it is not appropriate.
Elicitation of foliar resistance mechanisms transiently impairs root association with arbuscular mycorrhizal fungi
Authors: de Román Miriam , Fernández Iván , Wyatt Timon , Sahrawy Mariam , Heil Martin , Pozo María J.
Published: December 2010

1. Plants possess numerous mechanisms to control infections by deleterious organisms. Unspecific resistance mechanisms may, however, also exert ecological costs when they have a negative effect on beneficial plant–microbe interactions. Such negative effects may even cross the border between a plant’s aerial parts and its roots and then affect very central functions such as nutrient uptake and root resistance to micro‐organisms. Whereas an impaired nodulation indeed appears common after resistance expression in the leaves, contradictory results have been published for the case of arbuscular mycorrhizal (AM) fungi.

2. We analysed the effect of induction of resistance mechanisms in foliar tissues on AM colonization in soybean plants, using acibenzolar‐S‐methyl (ASM) as chemical elicitor. By determining different physiological and biochemical parameters, we assessed whether the effects are related to the activation of the plant defence mechanisms or rather to the re‐allocation of primary metabolites.

3. Colonization with AM fungi transiently decreased after pathogen resistance mechanisms were elicited in the aerial parts of the plant. The induction with ASM led to a significant, yet moderate, defence response in the roots, which was modulated in mycorrhizal plants. No allocation or fitness costs associated with the induction of resistance were detected in this study.

4. Synthesis. Our study confirms a transient negative impact of the elicitation of foliar defences on root–AM interactions. The results show that induced resistance to foliar pathogens can (i) move from the above‐ground to the below‐ground compartment and (ii) affect mutualistic micro‐organisms as well as plant pathogens. We also conclude that (iii) the negative effect is likely linked to changes in the defence status of the plant rather than to changes in resource allocation patterns and (iv) the AM association can modulate the activation of the plant defence mechanisms and overcome such effects.
Multitrophic interactions below and above ground: en route to the next level
Authors: van Dam Nicole M. , Heil Martin
Published: December 2010

1. Plants mediate multiple interactions between below‐ground (BG) and above‐ground (AG) heterotrophic communities that have no direct physical contact. These interactions can be positive or negative from the perspective of each player, can go from the BG to the AG community or vice versa, and comprise representatives of different phyla. Here we highlight emerging general patterns and discuss future research directions.

2. Ecologists initially postulated that root herbivores induce general stress responses, which increase the levels of primary (nutritional) compounds in the undamaged plant compartment and thereby facilitate future attack by AG herbivores. However, damage can also reduce the levels of primary compounds or increase contents of secondary (defensive) metabolites. Both effects may cause resistance phenotypes that play an important role in mediating BG–AG interactions. Systemically induced resistance does not only affect other herbivores but also pathogens in the AG and BG compartment and may inhibit beneficial organisms such as natural enemies of herbivores, microbial root symbionts and pollinators. Conversely, symbiotic mutualists such as mycorrhiza and rhizobia may affect AG and BG defence levels. Finally, BG–AG interactions may be costly if they impede optimal defence strategies in the undamaged compartment.

3. Synthesis. In order to better understand the adaptive value of BG–AG induced responses for the players involved and to identify the driving evolutionary forces, we need a better integration of studies at the community level with experiments on model systems that allow unravelling the genetic and physiological mechanisms of BG–AG interactions. Experiments preferably should be carried out at realistic densities and using the natural temporal sequence at which the various associations are established, because we can expect plants to be adapted only to events that are common over evolutionary time spans. Detailed mechanistic knowledge will help to reproduce relevant interactions in experiments that study multiple species in the field. This step will ultimately allow us to evaluate the importance of plant‐mediated interactions between BG and AG communities for the fitness of the species involved and for the structuring of natural communities.
Plant‐mediated interactions between above‐ and below‐ground communities at multiple trophic levels
Authors: Heil Martin
Published: December 2010

1. Above‐ground (AG) and below‐ground (BG) biota show little overlap and are usually investigated independently. However, both communities are connected by a group of organisms that intrinsically belong to both worlds: plants. The responses of plants to environmental stresses often move from the aerial compartments to the roots and vice versa and thereby enable interactions among species that never come into direct physical contact.

2. Plant‐mediated AG–BG interactions can have positive or negative effects on organisms from all phyla. For example, damage inflicted on roots or root symbioses with mycorrhizal fungi and rhizobia can affect the interactions between the aerial compartment and herbivores, pollinators, predators and parasitoids, whereas resistance expression in leaves can affect root herbivores as well as mutualistic or parasitic soil microorganisms. Given the tremendous diversity in the interacting organisms and also in the outcomes of the interactions, we are only just beginning to identify general patterns in the net effects of plant‐mediated interactions between AG and BG communities.

3.
Synthesis. The papers in this Special Feature reveal an important problem that remains to be solved: for most AG–BG interactions, the driving evolutionary forces remain to be identified. Because several plant responses in the context of AG–BG interactions ultimately result in negative effects on the plant itself, it appears obvious that in some cases the interacting partners manipulate the plant for their own benefit. In the future we will need to combine knowledge on the underlying physiological mechanisms with data on fitness effects. ‘Negative’ results, which demonstrate that the other compartment does NOT respond to a certain stress, or which demonstrate no or negative fitness effects on the involved species, are as important as reports on successful systemic resistance responses. Integrating knowledge on the physiological and genetic mechanisms with data on the fitness effects on all interacting partners will help to determine whether a certain AG–BG interaction is adaptive from the perspective of the plant, or the interacting organism, or both.
Effect of visual art on patient anxiety and agitation in a mental health facility and implications for the business case
Authors: NANDA U. , EISEN S. , ZADEH R. S. , OWEN D.
Published: December 2010

Accessible summary

The study investigated the impact of different visual art conditions on agitation and anxiety levels of patients by measuring the rate of pro re nata (PRN) incidents and collecting nurse feedback.

Visual art was displayed on a rotation basis on the walls of a small multi‐purpose lounge for psychiatric patients in an East Alabama Hospital. Patients occupied this room during a 3‐ to 4‐day stay while their psychiatric issues were addressed and diagnosed. The PRN data for the days on which different art conditions were displayed, was compared to the PRN data when no art was present. Interviews with the day and night shift nursing staff were conducted.

Results showed that PRN medication dispensed by nurses for anxiety and agitation was significantly lower on days when a realistic nature image of a landscape was displayed as compared to days when abstract art, abstract or no art was displayed. Cost of PRN medication was compared for the different conditions establishing a financial case an annual cost saving of $US4000–27 000, depending on type of art selected.

The study concluded that positive distractions, like visual art depicting restorative nature scenes, could help to reduce mental health patients' anxiety and agitation in healthcare settings. It also makes a case that the environment can have a powerful impact on healing and must be explored further for the mental health setting.

There is a growing body of evidence on the impact of the environment on health and well‐being. This study focuses on the impact of visual artworks on the well‐being of psychiatric patients in a multi‐purpose lounge of an acute care psychiatric unit. Well‐being was measured by the rate of pro re nata (PRN) medication issued by nurses in response to visible signs of patient anxiety and agitation. Nurses were interviewed to get qualitative feedback on the patient response. Findings revealed that the ratio of PRN/patient census was significantly lower on the days when a realistic nature photograph was displayed, compared to the control condition (no art) and abstract art. Nurses reported that some patients displayed agitated behaviour in response to the abstract image. This study makes a case for the impact of visual art on mental well‐being. The research findings were also translated into the time and money invested on PRN incidents, and annual cost savings of almost $US30 000 a year was projected. This research makes a case that simple environmental interventions like visual art can save the hospital costs of medication, and staff and pharmacy time, by providing a visual distraction that can alleviate anxiety and agitation in patients.
GhMYB25‐like: a key factor in early cotton fibre development
Authors: Walford Sally‐Ann , Wu Yingru , Llewellyn Danny J. , Dennis Elizabeth S.
Published: December 2010

MYB transcription factors have been implicated in regulation of the development of ovule epidermal cells into the elongated seed fibres of cotton. An R2R3 MYB, GhMYB25‐like, identified from its reduced expression in a fibreless mutant of cotton (Xu142 fl), is here shown to play a key role in the very early stages of fibre cell differentiation. A GhMYB25‐like promoter–GUS construct was expressed predominantly in the epidermal layers of cotton ovules before anthesis (−3 days post‐anthesis, dpa), increasing in expression in 0‐dpa ovules, primarily in those epidermal cells expanding into fibres, and then in elongating fibres at +3 dpa, declining thereafter. This was consistent with GhMYB25‐like transcript abundance during fibre development. RNA interference suppression of GhMYB25‐like resulted in cotton plants with fibreless seeds, but normal trichomes elsewhere, phenocopying the Xu142 fl mutant. Like Xu142 fl these plants had reduced expression of the fibre‐expressed MYBs, GhMYB25 and GhMYB109, indicating that GhMYB25‐like is upstream from those MYBs. This hierarchy was supported by the absence of any change in transcript level of GhMYB25‐like in GhMYB25‐ and GhMYB109‐silenced transgenic lines. Transgenic cotton with an additional copy of the native gene had elevated expression of GhMYB25‐like in ovules, but no obvious increase in fibre initials, suggesting that there may be other factors that interact with GhMYB25‐like to differentiate epidermal cells into fibre cells.
Members of an R2R3‐MYB transcription factor family in Petunia are developmentally and environmentally regulated to control complex floral and vegetative pigmentation patterning
Authors: Albert Nick W. , Lewis David H. , Zhang Huaibi , Schwinn Kathy E. , Jameson Paula E. , Davies Kevin M.
Published: December 2010

We present an investigation of anthocyanin regulation over the entire petunia plant, determining the mechanisms governing complex floral pigmentation patterning and environmentally induced vegetative anthocyanin synthesis. DEEP PURPLE (DPL) and PURPLE HAZE (PHZ) encode members of the R2R3‐MYB transcription factor family that regulate anthocyanin synthesis in petunia, and control anthocyanin production in vegetative tissues and contribute to floral pigmentation. In addition to these two MYB factors, the basic helix–loop–helix (bHLH) factor ANTHOCYANIN1 (AN1) and WD‐repeat protein AN11, are also essential for vegetative pigmentation. The induction of anthocyanins in vegetative tissues by high light was tightly correlated to the induction of transcripts for PHZ and AN1. Interestingly, transcripts for PhMYB27, a putative R2R3‐MYB active repressor, were highly expressed during non‐inductive shade conditions and repressed during high light. The competitive inhibitor PhMYBx (R3‐MYB) was expressed under high light, which may provide feedback repression. In floral tissues DPL regulates vein‐associated anthocyanin pigmentation in the flower tube, while PHZ determines light‐induced anthocyanin accumulation on exposed petal surfaces (bud‐blush). A model is presented suggesting how complex floral and vegetative pigmentation patterns are derived in petunia in terms of MYB, bHLH and WDR co‐regulators.
Haemolytic anaemia and renal failure associated with antibodies to trimethoprim and sulfamethoxazole
Authors: Arndt P. A. , Garratty G. , Wolf C. F. W. , Rivera M.
Published: December 2010

Aim: The aim of this study was to support a clinical diagnosis of drug‐induced immune haemolytic anaemia (DIIHA).

Background: DIIHA is rare and has only been described twice with the antibiotic combination of trimethoprim (TMP) and sulfamethoxazole (SMX).

Methods/Materials: Serologic tests for drug antibodies were performed using methods previously published by our laboratory.

Results: A 44‐year‐old woman experienced body aches, chills, chest pressure, nausea and a rash while receiving TMP–SMX; a week later her haemoglobin was low and she was in renal failure. At the hospital, the direct antiglobulin test (DAT) was positive (C3 only) and the serum reacted with all red blood cells (RBCs) by the gel method only (TMP–SMX is present in the RBC diluent used for the gel method). At the Red Cross immunohaematology laboratory, the patient's serum was reactive in the presence of TMP–SMX (haemolysis and positive antiglobulin test), pure TMP (positive antiglobulin test using anti‐IgG only) and pure SMX (haemolysis and positive antiglobulin test using both anti‐IgG and anti‐C3). The patient was treated with transfusions and haemodialysis and was discharged after a week in stable condition.

Conclusion: We describe a patient who appeared to have haemolytic anaemia and renal failure associated with antibodies to both TMP and SMX.
JC virus‐associated nephropathy: lack of convincing documentation of the diagnosis
Authors: Strøm E.H. , Reinholt F.P. , Midtvedt K.
Published: December 2010

E.H. Strøm, F.P. Reinholt, K. Midtvedt. JC virus‐associated nephropathy: lack of convincing documentation of the diagnosis. Transpl Infect Dis 2011: 13: 93–94. All rights reserved
Increased peripheral blood expression of electron transport chain genes in bipolar depression
Authors: Beech Robert D , Lowthert Lori , Leffert Janine J , Mason Portia N , Taylor Mary M , Umlauf Sheila , Lin Aiping , Lee Ji Young , Maloney Kathleen , Muralidharan Anjana , Lorberg Boris , Zhao Hongyu , Newton Samuel S , Mane Shrikant , Epperson C Neill , Sinha Rajita , Blumberg Hilary , Bhagwagar Zubin
Published: December 2010

Beech RD, Lowthert L, Leffert JJ, Mason PN, Taylor MM, Umlauf S, Lin A, Lee JY, Maloney K, Muralidharan A, Lorberg B, Zhao H, Newton SS, Mane S, Epperson CN, Sinha R, Blumberg H, Bhagwagar Z. Increased peripheral blood expression of electron transport chain genes in bipolar depression. Bipolar Disord 2010: 12: 813–824. © 2010 The Authors.Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  To identify specific genetic pathways showing altered expression in peripheral blood of depressed subjects with bipolar disorder (BPD).

Methods:  Illumina Sentrix BeadChip (Human‐6v2) microarrays containing >48,000 transcript probes were used to measure levels of gene expression in peripheral blood from 20 depressed subjects with BPD and in 15 healthy control subjects. Quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) was used to confirm a subset of these differences.

Results:  A total of 1,180 genes were differentially expressed between subjects with BPD and healthy controls (fold‐change >1.3, false discovery rate‐corrected p < 0.05, covaried for age and sex). Of these, 559 genes were up‐regulated in BPD subjects and 621 were down‐regulated. Surprisingly, there was no difference between medicated (n = 11) and unmedicated (n = 9) subjects with BPD for any of these genes. Pathway analysis using GeneGo MetaCore software showed that the most significantly affected pathway was the mitochondrial electron transport chain (ETC). Of the 85 objects (genes or proteins) in this pathway, 22 were up‐regulated and 2 down‐regulated in subjects with BPD. qRT‐PCR confirmed up‐regulation of nuclear encoded ETC genes in complexes I, III, IV, and V and, in addition, demonstrated up‐regulation of mitochondrially encoded genes in each of these complexes.

Conclusion:  These results suggest that increased expression of multiple components of the mitochondrial ETC may be a primary deficit in bipolar depression, rather than an effect of medication.
Short‐term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31‐phosphorus magnetic resonance spectroscopy study at 4T
Authors: Agarwal Nivedita , Sung Young‐Hoon , Jensen J Eric , daCunha Grace , Harper David , Olson David , Renshaw Perry F
Published: December 2010

Agarwal N, Sung YH, Jensen JE, daCunha G, Harper D, Olson D, Renshaw PF. Short‐term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31‐phosphorus magnetic resonance spectroscopy study at 4T. Bipolar Disord 2010: 12: 825–833. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Altered metabolism of membrane phospholipids has been implicated in bipolar disorder. In humans, uridine is an important precursor of cytidine diphosphate (CDP)‐choline, which plays a critical role in phospholipid synthesis and is currently being evaluated as a potential treatment for bipolar depression.

Methods:  A total of 17 healthy males (mean age ± SD: 32.73 ± 7.2 years; range: 21.8–46.4 years) were enrolled in this study. Subjects underwent a 31‐phosphorus magnetic resonance spectroscopy (31P‐MRS) acquisition at baseline and then again after seven days of either 2 g of uridine or placebo administration. A two‐dimensional chemical shift imaging 31P‐MRS acquisition collected spectral data from a 4 × 4 cluster of voxels acquired in the axial plane encompassing the subcortical structures as well as frontal‐temporal cortical gray and white matter. The slab thickness was 3 cm and the approximate total volume of brain sampled was 432 cm3. The spectra obtained were analyzed using a fully automated in‐house fitting algorithm. A population‐averaged generalized estimating equation was used to evaluate changes both in phosphomonoesters (PME) [phosphocholine (PCho) and phosphoethanolamine (PEtn)] and phosphodiesters (PDE) [glycerophosphocholine (GPCho) and glycerophosphethanolamine (GPEtn)]. Metabolite ratios were reported with respect to the total integrated 31P resonance area.

Results:  The uridine group had significantly increased total PME and PEtn levels over the one‐week period [6.32 and 7.17% for PME and PEtn, respectively (p < 0.001)]. Other metabolite levels such as PCho, PDE, GPEtn and GPCho showed no significant changes following either uridine or placebo (all p > 0.05).

Conclusions:  This is the first study to report a direct effect of uridine on membrane phospholipid precursors in healthy adults using 31P‐MRS. Sustained administration of uridine appears to increase PME in healthy subjects. Further investigation is required to clarify the effects of uridine in disorders with altered phospholipid metabolism such as bipolar disorder.
Transfusion practice and safety: current status and possibilities for improvement
Authors: Murphy M. F. , Stanworth S. J. , Yazer M.
Published: December 2010

Audits of practice and incident reporting, most notably to national haemovigilance schemes, indicate that poor hospital transfusion practice is frequent and occasionally results in catastrophic consequences for patients. Improvements in practice are needed and depend on a combined approach including a better understanding of the causes of errors; a reduction in the complexity of routine procedures taking advantage of new technology systems, which enforce agreed guidelines and policies; the setting and regular monitoring of performance standards for key aspects of the hospital transfusion process, improved organisation of transfusion in hospitals and staff training; and further research on the safe and effective use of blood and alternatives to donor blood. There needs to be a greater recognition that ‘transfusion safety’ applies to the hospital transfusion process as well as the contents of blood bags and that resources need to be provided for the improvement of transfusion safety and management in hospitals commensurate to their importance.
Hepatitis B, hepatitis C and HIV transfusion‐transmitted infections in the 21st century
Authors: Dwyre D. M. , Fernando L. P. , Holland P. V.
Published: December 2010

In the past, transfusion‐transmitted virus (TTV) infections were not uncommon. In recent years with advanced technologies and improved donor screening, the risk of viral transfusion transmission has been markedly reduced. Hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have all shown marked reduction in transmission rates. However, the newer technologies, including nucleic acid technology (NAT) testing, have affected the residual rates differently for these virally transmitted diseases. Zero risk, which has been the goal, has yet to be achieved. False negatives still persist, and transmissions of these viruses still occur, although rarely. It is known that HBV serological testing misses some infected units; likewise, HBV NAT–negative units have also been known to transmit the virus. Similarly, HIV minipool NAT–negative units have transmitted HIV, as recently as 2007; likely, these transmissions would have been prevented with single‐unit NAT testing. Newer technologies, such as pathogen inactivation (PI), will (ideally) eliminate these falsely test negative components, regardless of the original testing method used for detecting the viruses.
Human embryonic neural stem cell transplantation increases subventricular zone cell proliferation and promotes peri‐infarct angiogenesis after focal cerebral ischemia
Authors: Zhang Pengbo , Li Jie , Liu Yong , Chen Xinlin , Lu Haixia , Kang Qianyan , Li Weisong , Gao Ming
Published: December 2010

Neurogenesis and angiogenesis are two important processes that may contribute to the repair of brain injury after stroke. This study was designed to investigate whether transplantation of human embryonic neural stem cells (NSCs) into cortical peri‐infarction 24 h after ischemia effects cell proliferation in the subventricular zone (SVZ) and angiogenesis in the peri‐infarct zone. NSCs were prepared from embryonic human brains at 8 weeks gestation. Focal cerebral ischemia was induced by permanent occlusion of the middle cerebral artery of adult rats. Animals were randomly divided into two groups (n = 30, each) at 24 h after ischemia: NSC‐grafted and medium‐grafted groups. Toluidine blue staining and 5′‐bromo‐2′‐deoxyuridine (BrdU) or von Willebrand factor (vWF) immunohistochemistry were performed at 7, 14 and 28 days after transplantation. NSC transplantation increased the number of BrdU‐positive cells in the ischemic ipsilateral SVZ compared with the medium control at 7 days (P < 0.01). This difference in SVZ cell proliferation persisted at 14 days (P < 0.01), but was not significant at 28 days (P > 0.05). In addition, angiogenesis, as indicated by BrdU and vWF staining in cortical peri‐infarct regions, was augmented by 46% and 65% in NSC‐grafted rats versus medium‐grafted rats at 7 and 14 days, respectively (P < 0.05). However, this increase became non‐significant at 28 days (P > 0.05). Our results indicate that NSC transplantation enhances endogenous cell proliferation in the SVZ and promotes angiogenesis in the peri‐infarct zone, even if it is performed in the acute phase of ischemic injury.
Intravenous immunoglobulin therapy prevents development of autoimmune encephalomyelitis and suppresses activation of matrix metalloproteinases
Authors: Niimi Naoko , Kohyama Kuniko , Kamei Shintaro , Matsumoto Yoh
Published: December 2010

Although intravenous immunoglobulin (IVIG) has been reported to improve the status of expanded disability status scale (EDSS) of multiple sclerosis (MS) patients and reduce the annual relapse rate, some studies did not find its beneficial effects. In the present study, using an animal model for MS, we found that prophylactic, but not therapeutic, treatment successfully suppressed the disease development. During the search for factors involved in the disease suppression by IVIG, we obtained evidence suggesting that IVIG exerts its function, at least in part, by suppressing activation of matrix metalloproteinases (MMP)‐2 and ‐9. Gelatin zymography revealed that gelatinase activities were suppressed by IVIG treatment in the spinal cord, but not in plasma. This finding raises the possibility that IVIG blocks MMP activities at the interface between the blood stream and CNS. With in situ zymography, we also observed that gelatinase activities were expressed mainly in astrocytes in the inflamed spinal cord of control rats and that this expression was attenuated by the treatment. These findings provide useful information to set optimal conditions for IVIG treatment of MS and to obtain more beneficial effects.
Surgical procedures for benign prostatic hyperplasia: A nationwide survey in Japan
Authors: Masumori Naoya , Kamoto Toshiyuki , Seki Narihito , Homma Yukio
Published: December 2010

We investigated the trend in surgical procedures for benign prostatic hyperplasia (BPH) during the past 10 years in Japan. A questionnaire inquiring about the number of operations and surgical procedures for BPH in 1999, 2004 and 2009 was sent to 1824 institutes belonging to the Japanese Urological Association and/or the Japanese Clinical Urologists Association. Responses were obtained from 767 institutes (42.1%). The number of operations showed a gradual increase during the 10 years (n = 17 221 in 1999, 18 772 in 2004, 20 413 in 2009). Transurethral resection of the prostate, including transurethral resection in saline, was consistently the most common procedure (72.5% to 79.2%). Holmium laser enucleation of the prostate and transurethral enucleation with a bipolar system have dramatically increased, becoming the second most common in 2009 (n = 3416), although enucleation by open prostatectomy was still a viable option in 2009 (n = 555). Photoselective vaporization of the prostate was the third most common method in 2009 (n = 572). Coagulation and thermotherapy have become uncommon (n = 2039 in 1999, 217 in 2009), whereas incision and stenting were unchanged during the period. Thus, surgical procedures for BPH have been increasing in Japan during the past decade. Transurethral resection remains the standard, whereas enucleation and vaporization have been increasing.
Microbial keratitis in Waikato, New Zealand
Authors: Pandita Archana , Murphy Christopher
Published: December 2010

Abstract

Background:  Bacterial keratitis is a potentially sight‐threatening condition. This study is performed to identify the common causative organisms for bacterial keratitis in Waikato region and the antibiotic sensitivities to these organisms.

Design:  Retrospective, observational, case series.

Participants:  The microbiology records of all patients with bacterial keratitis who presented to the Ophthalmology department, Waikato Hospital, New Zealand between January 2003 and December 2007.

Methods:  The corneal scrape results were reviewed. Antibiotic sensitivity for the organism was tested following National Committee for Clinical Laboratory Standards (NCCLS) method.

Main Outcome Measures:  In vitro laboratory susceptibility testing of ocular isolates to various antibiotics.

Results:  A total of 265 scrapes were performed. Gram stain was positive in 35 (13.2%) eyes. Positive culture was seen in 174 (65.6%) scrapes; 78.2% were Gram‐positive and 20.2% were Gram‐negative organisms. Most common Gram‐positive organisms were coagulase‐negative Staphylococci (40.8%) and Staphylococcus aureus (11.5%). Most common Gram‐negative organisms were Moraxalla species (8.0%) and Pseudomonas aeroginosa (3.4%). Of the bacterial organisms 99% were sensitive to ciprofloxacin. All Gram‐negative organisms and 95.5% Gram‐positive organisms were sensitive to tobramycin; 96.6% Gram‐positive organisms and 98.3% Gram‐negative organisms were sensitive to cefuroxime.

Conclusions:  Our results are comparable to other regions in New Zealand but the incidence of coagulase‐negative Staphylococcus is much higher in this region compared with other New Zealand studies. It seems appropriate to start patients with corneal ulcers initially on fluoroquinolone monotherapy while awaiting culture results.