bluuebunny/crossref_metadata_2025 huggingface dataset:
Mangrovimonas yunxiaonensis gen. nov., sp. nov., isolated from mangrove sediment
Authors: Li Yi , Bai Shijie , Yang Caiyun , Lai Qiliang , Zhang Huajun , Chen Zhangran , Wei Jun , Zheng Wei , Tian Yun , Zheng Tianling
Published: October 2012

A Gram-negative, short-rod-shaped, orange-pigmented bacterium, strain LYYY01T, was isolated from a mangrove sediment sample collected from Yunxiao mangrove National Nature Reserve, Fujian Province, China. 16S rRNA gene sequence comparisons showed that strain LYYY01T is a member of the family

Flavobacteriaceae

, forming a distinct lineage with species of the genera

Meridianimaribacter

,

Sediminibacter

,

Gelidibacter

and

Subsaximicrobium

. The 16S rRNA gene sequence similarity between strain LYYY01T and the type strains of related species ranged from 93.9 to 90.9 %. Growth was observed at temperatures from 10 to 38 °C, at salinities from 1 to 7 % and at pH from 6 to 10. The DNA G+C content of the strain was 38.6 mol% and the major respiratory quinone was menaquinone-6 (MK-6). The major fatty acids were iso-C15 : 1 (27.6 %), iso-C15 : 0 (24.0 %), iso-C17 : 0 3-OH (12.0 %) and iso-C16 : 0 3-OH (6.2 %). According to its morphology, physiology, fatty acid composition and 16S rRNA gene sequence data, strain LYYY01T is considered to represent a novel species of a new genus in the family

Flavobacteriaceae

, for which the name Mangrovimonas yunxiaonensis gen. nov., sp. nov. is proposed. The type strain of Mangrovimonas yunxiaonensis is LYYY01T ( = CGMCC 1.12280T = LMG 27142T).
DAC Is Involved in the Accumulation of the Cytochrome b
6/f Complex in Arabidopsis
Authors: Xiao Jianwei , Li Jing , Ouyang Min , Yun Tao , He Baoye , Ji Daili , Ma Jinfang , Chi Wei , Lu Congming , Zhang Lixin
Published: October 2012

The biogenesis and assembly of photosynthetic multisubunit protein complexes is assisted by a series of nucleus-encoded auxiliary protein factors. In this study, we characterize the dac mutant of Arabidopsis (Arabidopsis thaliana), which shows a severe defect in the accumulation of the cytochrome b  6/f complex, and provide evidence suggesting that the efficiency of cytochrome b  6/f complex assembly is affected in the mutant. DAC is a thylakoid membrane protein with two predicted transmembrane domains that is conserved from cyanobacteria to vascular plants. Yeast (Saccharomyces cerevisiae) two-hybrid and coimmunoprecipitation analyses revealed a specific interaction between DAC and PetD, a subunit of the cytochrome b  6/f complex. However, DAC was found not to be an intrinsic component of the cytochrome b  6/f complex. In vivo chloroplast protein labeling experiments showed that the labeling rates of the PetD and cytochrome f proteins were greatly reduced, whereas that of the cytochrome b  6 protein remained normal in the dac mutant. DAC appears to be a novel factor involved in the assembly/stabilization of the cytochrome b  6/f complex, possibly through interaction with the PetD protein.
Differential Control of Ethylene Responses byGREEN-RIPEandGREEN-RIPE LIKE1Provides Evidence for Distinct Ethylene Signaling Modules in Tomato
Authors: Ma Qian , Du Wenyan , Brandizzi Federica , Giovannoni James J. , Barry Cornelius S.
Published: October 2012

The factors that mediate specific responses to the plant hormone ethylene are not fully defined. In particular, it is not known how signaling at the receptor complex can control distinct subsets of ethylene responses. Mutations at the Green-ripe (Gr) and reversion to ethylene sensitivity1 (rte1) loci, which encode homologous proteins of unknown function, influence ethylene responses in tomato (Solanum lycopersicum) and Arabidopsis (Arabidopsis thaliana), respectively. In Arabidopsis, AtRTE1 is required for function of the ETR1 ethylene receptor and acts predominantly through this receptor via direct protein-protein interaction. While most eudicot families including the Brassicaceae possess a single gene that is closely related to AtRTE1, we report that members of the Solanaceae family contain two phylogenetically distinct genes defined by GR and GREEN-RIPE LIKE1 (GRL1), creating the possibility of subfunctionalization. We also show that SlGR and SlGRL1 are differentially expressed in tomato tissues and encode proteins predominantly localized to the Golgi. A combination of overexpression in tomato and complementation of the rte1-3 mutant allele indicates that SlGR and SlGRL1 influence distinct but overlapping ethylene responses. Overexpression of SlGRL1 in the Gr mutant background provides evidence for the existence of different ethylene signaling modules in tomato that are influenced by GR, GRL1, or both. In addition, overexpression of AtRTE1 in tomato leads to reduced ethylene responsiveness in a subset of tissues but does not mimic the Gr mutant phenotype. Together, these data reveal species-specific heterogeneity in the control of ethylene responses mediated by members of the GR/RTE1 family.
Molecular diagnosis of the myeloproliferative neoplasms: UK guidelines for the detection of JAK2 V617F and other relevant mutations
Authors: Bench Anthony J. , White Helen E. , Foroni Letizia , Godfrey Anna L. , Gerrard Gareth , Akiki Susanna , Awan Abida , Carter Ian , Goday‐Fernandez Andrea , Langabeer Stephen E. , Clench Tim , Clark Jordan , Evans Paul A. , Grimwade David , Schuh Anna , McMullin Mary F. , Green Anthony R. , Harrison Claire N. , Cross Nicholas C. P.
Published: October 2012

Molecular genetic assays for the detection of the JAK2 V617F (c.1849G>T) and other pathogenetic mutations within JAK2 exon 12 and MPL exon 10 are part of the routine diagnostic workup for patients presenting with erythrocytosis, thrombocytosis or otherwise suspected to have a myeloproliferative neoplasm. A wide choice of techniques are available for the detection of these mutations, leading to potential difficulties for clinical laboratories in deciding upon the most appropriate assay, which can lead to problems with inter‐laboratory standardization. Here, we discuss the most important issues for a clinical diagnostic laboratory in choosing a technique, particularly for detection of the JAK2 V617F mutation at diagnosis. The JAK2 V617F detection assay should be both specific and sensitive enough to detect a mutant allele burden as low as 1–3%. Indeed, the use of sensitive assays increases the detection rate of the JAK2 V617F mutation within myeloproliferative neoplasms. Given their diagnostic relevance, it is also beneficial and relatively straightforward to screen JAK2 V617F negative patients for JAK2 exon 12 mutations (in the case of erythrocytosis) or MPL exon 10 mutations (thrombocytosis or myelofibrosis) using appropriate assays. Molecular results should be considered in the context of clinical findings and other haematological or laboratory results.
Multiple brain infarcts in young adults: clues for etiologic diagnosis and prognostic impact
Authors: Mustanoja S. , Putaala J. , Haapaniemi E. , Strbian D. , Kaste M. , Tatlisumak T.
Published: October 2012

Background and purpose

There are little data on the etiology of multiple brain infarcts (MBI) and their impact on clinical outcome in young patients.

Methods

We studied 548 MRI‐imaged patients (15–49 years) with a first‐ever ischaemic stroke. Ischaemic lesions were categorized into three groups: single lesions, MBI in one or >1 circulation territories. Outcomes were unfavorable 3‐month modified Rankin Scale (mRS) score of ≥2 and, during long‐term follow‐up (mean 8.20 ± 4.01 years), recurrent ischaemic stroke or death from any cause.

Results

Multiple brain infarcts occurred in 185 patients (33.8%; mean age 39.2 ± 8.2), of which 144 patients (26.3%) had lesions located in a single territory and 41 patients (7.5%) in multiple territories. Patients with MBI in a single territory were more likely than patients with single lesions to have a high‐risk source of cardioembolism (CE) (9.0% vs. 3.0%; P = 0.001), large‐artery atherosclerosis (8.3% vs. 4.9%; P = 0.012), vertebral (22% vs. 10%; P < 0.001) or carotid artery dissections (8.3% vs. 6.3%; P = 0.036), and MBI in multiple territories a high‐risk source of CE (34% vs. 3.0%, P < 0.001). Adjusted for age, gender, baseline stroke severity, size of the largest lesion, and stroke subtype, MBI remained independently associated with an unfavorable 3‐month outcome (odds ratio 2.84, 95% confidence interval 1.22–6.61). In multivariate Cox proportional hazards analysis, MBI had independent influence on the risk for death (hazard ratio 3.75, 1.58–8.86), but not on recurrent ischaemic stroke.

Conclusions

Compared with the elderly, young stroke patients have a distinct stroke etiology underlying MBI, being an independent indicator of poor short‐term outcome and long‐term risk of death.
Combined treatment with recombinant tissue plasminogen activator and dexamethasone phosphate‐containing liposomes improves neurological outcome and restricts lesion progression after embolic stroke in rats
Authors: Tiebosch Ivo A. C. W. , Crielaard Bart J. , Bouts Mark J. R. J. , Zwartbol René , Salas‐Perdomo Angelica , Lammers Twan , Planas Anna M. , Storm Gert , Dijkhuizen Rick M.
Published: October 2012

Variable efficacies have been reported for glucocorticoid drugs as anti‐inflammatory treatment after stroke. We applied an alternative drug delivery strategy, by injection of dexamethasone phosphate‐containing liposomes in combination with recombinant tissue plasminogen activator (rtPA), in an experimental stroke model, and tested the hypothesis that this approach improves behavioral recovery and reduces lesion growth. Rats were subjected to right middle cerebral artery occlusion with a blood clot. After 2 h, animals were intravenously injected with rtPA plus empty long‐circulating liposomes (LCL), free dexamethasone phosphate (DXP), or DXP‐containing LCL (LCL‐DXP). Neurological status was evaluated with different behavioral tests up to 7 days after stroke. Lesion development was assessed by magnetic resonance imaging of tissue and perfusion parameters from 0–2 h until 7 days after stroke. Expression of brain inflammatory markers was measured with RT‐PCR at post‐stroke day 7. Treatment with rtPA plus LCL‐DXP resulted in significantly improved behavioral outcome as compared to treatment with rtPA plus empty LCL or free DXP. Acute and final brain lesion sizes were comparable between treatment groups; however a predictive algorithm revealed a significantly larger salvaged tissue area after treatment with LCL‐DXP. We conclude that delivery of dexamethasone phosphate via LCL in combination with rtPA‐induced thrombolysis can significantly improve outcome after stroke. Furthermore, magnetic resonance imaging‐based predictive algorithms provide a sensitive means to measure treatment effects on lesion development.
The inhibitory effect of S‐nitrosoglutathione on blood–brain barrier disruption and peroxynitrite formation in a rat model of experimental stroke
Authors: Khan Mushfiquddin , Dhammu Tajinder S. , Sakakima Harutoshi , Shunmugavel Anadakumar , Gilg Anne G. , Singh Avtar K. , Singh Inderjit
Published: October 2012

The hallmark of stroke injury is endothelial dysfunction leading to blood–brain barrier (BBB) leakage and edema. Among the causative factors of BBB disruption are accelerating peroxynitrite formation and the resultant decreased bioavailability of nitric oxide (NO). S‐nitrosoglutathione (GSNO), an S‐nitrosylating agent, was found not only to reduce the levels of peroxynitrite but also to protect the integrity of BBB in a rat model of cerebral ischemia and reperfusion (IR). A treatment with GSNO (3 μmol/kg) after IR reduced 3‐nitrotyrosine levels in and around vessels and maintained NO levels in brain. This mechanism protected endothelial function by reducing BBB leakage, increasing the expression of Zonula occludens‐1 (ZO‐1), decreasing edema, and reducing the expression of matrix metalloproteinase‐9 and E‐selectin in the neurovascular unit. An administration of the peroxynitrite‐forming agent 3‐morpholino sydnonimine (3 μmol/kg) at reperfusion increased BBB leakage and decreased the expression of ZO‐1, supporting the involvement of peroxynitrite in BBB disruption and edema. Mechanistically, the endothelium‐protecting action of GSNO was invoked by reducing the activity of nuclear factor kappa B and increasing the expression of S‐nitrosylated proteins. Taken together, the results support the ability of GSNO to improve endothelial function by reducing nitroxidative stress in stroke.
Comments on M. Kuhle and S. Kuhle (2012): ‘Hannibal Gone Astray? A Critical Comment on W. C. Mahaney et al., “The Traversette (Italia) Rockfall: Geomorphological Indicator of the Hannibalic Invasion Route” (Archaeometry, 52, 1 [2010] 156–72)’
Authors: Mahaney W. C.
Published: October 2012

The title of Kuhle and Kuhle's (2012) (hereafter K&K 2012) paper in Archaeometry appears to be mostly a tirade against the Traversette Route of Hannibal's Army, as originally favoured by Sir Gavin de Beer—a man possessed of singular scientific experience and near‐singular interest in Carthaginian history—in the mid‐part of the last century. The mere fact that Mahaney et al. (2010a,c) added to de Beer's corpus of evidence that Hannibal followed the southern route appears to have brought K&K (2012) to lodge not only a protest, but one of accusatory tone, stating that Mahaney et al. (2010c) had erroneously misinterpreted historical texts to prove the Col de la Traversette as the Punic Army col of passage into Italia. Aside from the fact that the tone of these allegations rises to a curious level, it is the intention of this discussion to put facts where they belong, rooted in what is known of the Hannibalic Invasion and what is inferred by the prevailing scientific evidence. It is important to note that there is not one preferred route as stated by K&K (2012), but three in fact (see Fig. 1 (a) in Mahaney et al. 2010c), and all have been discussed by a legion of historians (see, e.g., Freshfield 1886, 1899; de Beer 1969; Proctor 1971; Prevas 1998; Mahaney 2008).
L1 Cell Adhesion Molecule Signaling Is Inhibited by Ethanol In Vivo
Authors: Littner Yoav , Tang Ningfeng , He Min , Bearer Cynthia F.
Published: October 2012

Background

Fetal alcohol spectrum disorder is an immense public health problem. In vitro studies support the hypothesis that L1 cell adhesion molecule (L1) is a target for ethanol (EtOH) developmental neurotoxicity. L1 is critical for the development of the central nervous system. It functions through signal transduction leading to phosphorylation and dephosphorylation of tyrosines on its cytoplasmic domain. The function of L1 is also dependent on trafficking through lipid rafts (LRs). Our hypothesis is that L1 is a target for EtOH neurotoxicity in vivo. Our objective is to demonstrate changes in L1 phosphorylation/dephosphorylation and LR association in vivo.

Methods

Rat pups on postnatal day 6 are administered 4.5, 5.25, and 6 g/kg of EtOH divided into 2 doses 2 hours apart, then killed. Cerebella are rapidly frozen for assay. Blood is analyzed for blood EtOH concentration. L1 tyrosine phosphorylation is determined by immunoprecipitation and dephosphorylation of tyrosine 1176 determined by immunoblot. LRs are isolated by sucrose density gradient, and the distribution of L1 in LRs is determined.

Results

EtOH at all doses reduced the relative amount of Y1176 dephosphorylation as well as the relative amount of L1 phosphorylated on other tyrosines. The proportion of L1 present in LRs is significantly increased in pups who received 6 g/kg EtOH compared to intubated controls.

Conclusions

L1 is a target for EtOH developmental neurotoxicity in vivo.
The environmental business case and unenlightened shareholder value
Authors: Bradshaw Carrie
Published: October 2012

The business case for corporate environmental responsibility is the claim that behaving responsibly makes financial sense. It is impossible to exaggerate the contemporary significance of this claim, not least in legitimising environmental concerns in the corporate sphere. However, the business case is not without significant empirical and normative limitations, as is illustrated by the corporate environmental problem of supermarket waste. This paper evaluates enlightened shareholder value under s 172 of the Companies Act 2006 in light of such business case limitations. It suggests that s 172, by procedurally mandating the business case for corporate environmental responsibility, is a retrograde step which envisions not enlightened, but rather environmentally unenlightened, shareholders.
Testing a Model of Depression Among Thai Adolescents
Authors: Vatanasin Duangjai , Thapinta Darawan , Thompson Elaine Adams , Thungjaroenkul Petsunee
Published: October 2012

Problem

This predictive correlational study was designed to test a comprehensive model of depression for Thai adolescents.

Methods

This sample included 800 high school students in Chiang Mai, Thailand. Data were collected using self‐reported measures of depression, negative automatic thoughts, effective social problem solving, ineffective social problem solving, rumination, parental care, parental overprotection, and negative life events.

Findings

Structural equation modeling revealed that negative automatic thoughts, effective and ineffective social problem solving mediated the effects of rumination, negative life events, and parental care and overprotection on adolescent depression.

Conclusion

These findings provide new knowledge about identified factors and the mechanisms of their influence on depression among Thai adolescents, which are appropriate for targeting preventive interventions.
Current status of vaccination therapies in Alzheimer's disease
Authors: Karran Eric
Published: October 2012

The failure of two monoclonal antibodies, bapineuzumab and solanezumab, to meet their primary end point measures in phase 3 clinical testing for mild‐to‐moderate Alzheimer's disease (AD) is a serious blow to the field. These drugs were targeting the Abeta peptide, as were three previous drugs that also failed to meet their primary end points. These findings will call into question the role that Abeta plays in AD and will also provoke much circumspection in ‘big pharma’ as to whether they can continue to invest in clinical research in such an intractable disease. However, there is much data yet to be published on these trials and a careful analysis, and cross‐comparison of all of the data may well provide insights that will take the field closer to the phase 3 clinical success that is desperately needed by patients and healthcare providers worldwide. Although these failures are disappointing, now is not the time to falter in our pursuit of medicines for this devastating disease.
Oxidative stress markers are not associated with outcomes after pediatric heart surgery
Authors: Manso Paulo H. , Carmona Fabio , Dal‐Pizzol Felipe , Petronilho Fabrícia , Cardoso Fabíola , Castro Margaret , Carlotti Ana P. C. P.
Published: October 2012

Objectives

To investigate whether perioperative serum levels of oxidative stress markers, thiobarbituric acid reactive substances (TBARS), and carbonyl moieties are associated with outcomes in children after heart surgery.

Background

Oxidative stress markers are increased following heart surgery with cardiopulmonary bypass (CPB) and can play a role in ischemia–reperfusion injury, but its associations with myocardial dysfunction, low cardiac output syndrome (LCOS), and outcomes are not proven.

Methods

In a retrospective secondary analysis of a cohort study comprising 55 children (median age, 109 [2–611] days), we compared pre‐, intra‐ and postoperative serum levels of TBARS and carbonyl moieties among patients with and without postoperative LCOS, cyanotic and acyanotic congenital heart disease (CHD), and survivors and nonsurvivors. We also assessed the independent effect of TBARS and carbonyl moieties peak levels on the mortality‐adjusted hospital length of stay (aLOS).

Results

Patients who developed postoperative LCOS (n = 36) were significantly younger, more frequently cyanotic, more severely ill, and underwent more complex procedures with longer CPB. However, TBARS and carbonyl moieties serum levels did not change significantly over time. Moreover, they were not significantly different in patients with or without LCOS, cyanotic and acyanotic CHD, or survivors and nonsurvivors. There was a significant correlation between TBARS and tumor necrosis factor alpha (TNF‐α) peak serum levels. Neither TBARS nor carbonyl moieties peak serum levels were independently associated with aLOS.

Conclusions

In conclusion, oxidative stress markers TBARS and carbonyl moieties were not associated with the development of LCOS, the aLOS, or mortality in children after heart surgery with CPB.
Improving On‐time starts for patients scheduled with general anesthesia in a MRI suite
Authors: Mahmoud Mohamed A. , Koch Bernadette L. , Jones Blaise V. , Varughese Anna M.
Published: October 2012

Objective

We applied quality improvement methodology to identify unnecessary, redundant parts of processes that can lead to delayed on‐time starts for patients scheduled with general anesthesia (GA) in the radiology department.

Aim

To address the issue of delayed on‐time starts by improving work flow for the first patient scheduled with GA.

Background

Unplanned imaging in a high‐volume MRI suite can result in a significant ripple effect throughout the day. Delayed on‐time starts can lead to patient, family, and staff dissatisfaction due to significant wait times.

Materials and methods

The team conducted a 5 month improvement project. Baseline data were obtained from pilot time studies allowed the team to identify reasons why the first case was not starting on time and to identify several key drivers to improve the process. Using the framework of small tests of change or the Plan‐Do‐Study‐Act model, our key interventions primarily focused on standardizing the processes for completing the preimaging evaluation and for anesthesia induction. The primary objective measure of successful on‐time start was defined as obtaining the first MRI image within 10 min of the scheduled start time, for the first patients of the day scheduled with GA. The secondary outcome measure was the extent of the delay quantified in minutes.

Results

Prior to the initiation of the project, only 36% of the first patients scheduled with GA each day met the primary objective measure. At the conclusion of the project 84% started on time. The secondary measure also showed significant improvement.

Conclusions

Process improvement projects in anesthesia can yield positive results, using small incremental standardized changes. We used a quality improvement methods to successfully improve on‐time start for patients scheduled with GA in high‐volume MRI suite.
Equation-Solving DRESOR Method for Radiative Transfer in an Absorbing–Emitting and Isotropically Scattering Slab With Diffuse Boundaries
Authors: Guihua Wang , Huaichun Zhou , Qiang Cheng , Zhichao Wang
Published: October 2012

The distribution of ratios of energy scattered by the medium or reflected by the boundary surface (DRESOR) method can provide radiative intensity with high directional resolution, but also suffers the common drawbacks of the Monte Carlo method (MCM), i.e., it is time-consuming and produces unavoidable statistical errors. In order to overcome the drawbacks of the MCM, the so-called equation-solving DRESOR (ES-DRESOR) method, an equation-solving method to calculate the DRESOR values differently from the MCM used before, was proposed previously. In this method, a unit blackbody emission is supposed within a small zone around a specified point, while there is no emission elsewhere in a plane-parallel, emitting, absorbing, and isotropically scattering medium with transparent boundaries. The set of equations for the DRESOR values based on two expressions for the incident radiation was set up and solved successfully. In this paper, the ES-DRESOR method is extended to a one-dimensional system with diffusely reflecting boundaries. The principle and formulas are given. Several examples with different parameters are taken to examine the performance of the proposed method. The results showed that all the DRESOR values obtained using the ES-DRESOR method agree well with those got using MCM. The average relative error for the intensity obtained by the ES-DRESOR method is 9.446 × 10−6, lower by over 1 order of magnitude than the 2.638 × 10−4 obtained by the MCM under the same conditions. More importantly, the CPU time for computing the DRESOR values, which ranges from several hundred seconds to several thousand seconds using the MCM, is reduced to 0.167 s using the ES-DRESOR method. The computation time is shortened by about 3 orders of magnitude. The overall performance of the ES-DRESOR method is excellent.
Formulas in Physics Have a “Standard” Form
Authors: Moelter Matthew J. , Jackson Martin
Published: October 2012

We discuss the importance of the ordering of symbols in physics formulas and identify implicit conventions that govern the “standard” form for how formulas are written and interpreted. An important part of writing and reading this form is understanding distinctions among constants, parameters, and variables. We delineate these conventions and encourage instructors to make them explicit for students.
Elfn1 Regulates Target-Specific Release Probability at CA1-Interneuron Synapses
Authors: Sylwestrak Emily L. , Ghosh Anirvan
Published: October 2012

On the Receiving End

One type of neuron, the hippocampal pyramidal neuron, forms two different types of synapses with two different downstream partners. When the partner is an oriens-lacunosum moleculare (O-LM) interneuron, the pyramidal neuron only releases its synaptic vesicles with a low probability. When the cell on the receiving end is a parvalbumin (PV)-positive interneuron, the likelihood of synaptic vesicle release is high. How can the postsynaptic cell change the release characteristics of the presynaptic cell?
Sylwestrak and Ghosh
(p.
536
, published online 4 October; see the Perspective by

McBain

) describe how the extracellular leucine-rich repeat fibronectin containing 1 (Elfn1) protein in the postsynaptic OLM interneurons affects vesicle release probability in the presynaptic pyramidal neuron. Misexpression of Elfn1 in PV interneurons converted vesicle release to the OLM pattern. Thus, a regulator located in the postsynaptic cell can modulate the function of the synapse.
Intramitochondrial Transport of Phosphatidic Acid in Yeast by a Lipid Transfer Protein
Authors: Connerth Melanie , Tatsuta Takashi , Haag Mathias , Klecker Till , Westermann Benedikt , Langer Thomas
Published: October 2012

Mitochondrial Lipid Trafficking

Disturbances in cellular membrane lipid composition have severe functional consequences and are often associated with disease. How mitochondria—dynamic organelles that constantly fuse and divide—maintain their phospholipid composition and adjust it to physiological needs is unknown. Some phospholipids, like cardiolipin and phosphatidylethanolamine, are synthesized in the mitochondrial inner membrane from precursor molecules that are imported from the endoplasmic reticulum.

Connerth
et al.

(p.
815
) examined mechanisms determining the accumulation of cardiolipin in yeast mitochondria. A combination of quantitative lipidomics, yeast genetics, ultrastructural studies, and biochemical in vitro assays suggested that the protein Ups1 shuttles the precursor lipid phosphatidic acid between outer and inner mitochondrial membranes. Ups1 mediates lipid transport in complex with another mitochondrial protein, Mdm35, which stabilizes Ups1 in a transport-competent conformation and protects it against proteolysis. High cardiolipin concentrations inhibited the transport of phosphatidic acid by Ups1, which appears to provide a feedback control system that limits the accumulation of cardiolipin in mitochondrial membranes.
IRE1α Cleaves Select microRNAs During ER Stress to Derepress Translation of Proapoptotic Caspase-2
Authors: Upton John-Paul , Wang Likun , Han Dan , Wang Eric S. , Huskey Noelle E. , Lim Lionel , Truitt Morgan , McManus Michael T. , Ruggero Davide , Goga Andrei , Papa Feroz R. , Oakes Scott A.
Published: October 2012

To Die For

The unfolded protein response (UPR) adjusts the protein folding capacity of the endoplasmic reticulum (ER) to match demand. UPR signaling requires IRE1α, an ER transmembrane kinase-endoribonuclease (RNase) that becomes activated by unfolded protein accumulation within the ER and excises a segment in XBP1 messenger RNA (mRNA) to initiate production of the homeostatic transcription factor XBP1s. However, if ER stress is irremediable, sustained IRE1α RNase activity triggers cell death. Severe ER stress activates the protease Caspase-2 as an early apoptotic switch upstream of mitochondria. However, the molecular events leading from the detection of ER stress to Caspase-2 activation are unclear.

Upton
et al.

(p.
818
, published online 4 October) now report that IRE1α is the ER stress sensor that activates Caspase-2, and does so through a mechanism involving non-coding RNAs. Under irremediable ER stress, IRE1α's RNase triggers the rapid decay of select microRNAs that normally repress translation of Caspase-2 mRNA, rapidly increasing Caspase-2 levels as the first step in its activation.
Efficient Hybrid Solar Cells Based on Meso-Superstructured Organometal Halide Perovskites
Authors: Lee Michael M. , Teuscher Joël , Miyasaka Tsutomu , Murakami Takurou N. , Snaith Henry J.
Published: October 2012

Perovskite Photovoltaics

For many types of low-cost solar cells, including those using dye-sensitized titania, performance is limited by low open-circuit voltages.

Lee
et al.

(p.
643
, published online 4 October; see the Perspective by

Norris and Aydil

) have developed a solid-state cell in which structured films of titania or alumina nanoparticles are solution coated with a lead-halide perovskite layer that acts as the absorber and n-type photoactive layer. These particles are coated with a spirobifluorene organic-hole conductor in a solar cell with transparent oxide and metal contacts. For the alumina particles, power conversion efficiencies of up to 10.9% were obtained.
Enabling Scientific Innovation
Authors: Langer James S.
Published: October 2012

These should be wonderful times for physicists. Advances in experimental and computational capabilities have opened windows to research areas that previously had seemed out of our reach. We now can see in exquisite detail what atoms are doing inside complex materials, and we have the tools to test predictive theories of what's happening. We have been able do this in ways that are interesting not just to physicists but also to engineers, biologists, and many others. Examples abound in this issue of
Science
, which features a special section that focuses on physics in developmental biology (beginning on p. 209). Unfortunately, our ability to take advantage of these opportunities has been eroded in an environment where innovation and interdisciplinary research are systematically discouraged. Present funding levels in the United States cannot support a scientific community large enough to sustain a full range of world-leading research programs and to educate the new generations of scientists and engineers that the country needs. That problem cannot be solved quickly in today's political climate, but government funding agencies ought not to operate in ways that make it worse.
Aftershocks in the Courtroom
Authors: Cartlidge Edwin
Published: October 2012

An Italian judge will soon decide whether 30 people died because seven experts downplayed the risk of a major earthquake in L'Aquila in 2009.
Turning Back the Clock: Slowing the Pace of Prehistory
Authors: Gibbons Ann
Published: October 2012

New work suggests that mutations arise more slowly in humans than previously thought, raising questions about the timetable of evolutionary events.
Genetic Diversity of Clinical and Environmental Vibrio parahaemolyticus Strains from the Pacific Northwest
Authors: Paranjpye Rohinee , Hamel Owen S. , Stojanovski Asta , Liermann Martin
Published: October 2012

Since 1997, cases of
Vibrio parahaemolyticus
-related gastroenteritis from the consumption of raw oysters harvested in Washington State have been higher than historical levels. These cases have shown little or no correlation with concentrations of potentially pathogenic
V. parahaemolyticus
(positive for the thermostable direct hemolysin gene,
tdh
) in oysters, although significant concentrations of
tdh
+
V. parahaemolyticus
strains were isolated from shellfish-growing areas in the Pacific Northwest (PNW). We compared clinical and environmental strains isolated from the PNW to those from other geographic regions within the United States and Asia for the presence of virulence-associated genes, including the thermostable direct hemolysin (
tdh
), the thermostable-related hemolysin (
trh
), urease (
ureR
), the pandemic group specific markers
orf8
and
toxRS
, and genes encoding both type 3 secretion systems (T3SS1 and T3SS2). The majority of clinical strains from the PNW were positive for
tdh
,
trh
, and
ureR
genes, while a significant proportion of environmental isolates were
tdh
+
but
trh
negative. Hierarchical clustering grouped the majority of these clinical isolates into a cluster distinct from that including the pandemic strain RIMD2210633, clinical isolates from other geographical regions, and
tdh
+
,
trh
-negative environmental isolates from the PNW. We detected T3SS2-related genes (T3SS2β) in environmental strains that were
tdh
and
trh
negative. The presence of significant concentrations of
tdh
+
,
trh
-negative environmental strains in the PNW that have not been responsible for illness and T3SS2β in
tdh
- and
trh
-negative strains emphasizes the diversity in this species and the need to identify additional virulence markers for this bacterium to improve risk assessment tools for the detection of this pathogen.
Evaluation of a Genome-Scale
In Silico
Metabolic Model for Geobacter metallireducens by Using Proteomic Data from a Field Biostimulation Experiment
Authors: Fang Yilin , Wilkins Michael J. , Yabusaki Steven B. , Lipton Mary S. , Long Philip E.
Published: October 2012

Accurately predicting the interactions between microbial metabolism and the physical subsurface environment is necessary to enhance subsurface energy development, soil and groundwater cleanup, and carbon management. This study was an initial attempt to confirm the metabolic functional roles within an
in silico
model using environmental proteomic data collected during field experiments. Shotgun global proteomics data collected during a subsurface biostimulation experiment were used to validate a genome-scale metabolic model of
Geobacter metallireducens
—specifically, the ability of the metabolic model to predict metal reduction, biomass yield, and growth rate under dynamic field conditions. The constraint-based
in silico
model
of G. metallireducens
relates an annotated genome sequence to the physiological functions with 697 reactions controlled by 747 enzyme-coding genes. Proteomic analysis showed that 180 of the 637
G. metallireducens
proteins detected during the 2008 experiment were associated with specific metabolic reactions in the
in silico
model. When the field-calibrated Fe(III) terminal electron acceptor process reaction in a reactive transport model for the field experiments was replaced with the genome-scale model, the model predicted that the largest metabolic fluxes through the
in silico
model reactions generally correspond to the highest abundances of proteins that catalyze those reactions. Central metabolism predicted by the model agrees well with protein abundance profiles inferred from proteomic analysis. Model discrepancies with the proteomic data, such as the relatively low abundances of proteins associated with amino acid transport and metabolism, revealed pathways or flux constraints in the
in silico
model that could be updated to more accurately predict metabolic processes that occur in the subsurface environment.
Effect of the Bacillus atrophaeus subsp. globigii Spo0F H101R Mutation on Strain Fitness
Authors: Zhelev Doncho V. , Hunt Mia , Le Anna , Dupuis Christopher , Ren Suelynn , Gibbons Henry S.
Published: October 2012

Sporulation is a critical developmental process in
Bacillus
spp. that, once initiated, removes the possibility of further growth until germination. Therefore, the threshold conditions triggering sporulation are likely to be subject to evolutionary constraint. Our previous studies revealed two spontaneous hypersporulating mutants of
Bacillus atrophaeus
subsp.
globigii
, both containing point mutations in the
spo0F
gene. One of these strains (Detrick-2; contains the
spo0F101
allele with a C:T [His101Arg] substitution) had been deliberately selected in the early 1940s as an anthrax surrogate. To determine whether the experimental conditions used during the selection of the “military” strains could have supported the emergence of hypersporulating variants, the relative fitness of strain Detrick-2 was measured in several experimental settings modeled on experimental conditions employed during its development in the 1940s as a simulant. The congenic strain Detrick-1 contained a wild-type
spo0F
gene and sporulated like the wild-type strain. The relative fitness of Detrick-1 and Detrick-2 was evaluated in competition experiments using quantitative single nucleotide polymorphism (SNP)-specific real-time PCR assays directed at the C:T substitution. The ancestral strain Detrick-1 had a fitness advantage under all conditions tested except when competing cultures were subjected to frequent heat shocks. The hypersporulating strain gained the maximum fitness advantage when cultures were grown at low oxygen tension and when heat shock was applied soon after the formation of the first heat-resistant spores. This is interpreted as gain of fitness by the hypersporulating strain in fast-changing fluctuating environments as a result of the increased rate of switching to the sporulating phenotype.
Rare Branched Fatty Acids Characterize the Lipid Composition of the Intra-Aerobic Methane Oxidizer “Candidatus Methylomirabilis oxyfera”
Authors: Kool Dorien M. , Zhu Baoli , Rijpstra W. Irene C. , Jetten Mike S. M. , Ettwig Katharina F. , Sinninghe Damsté Jaap S.
Published: October 2012

The recently described bacterium “
Candidatus
Methylomirabilis oxyfera” couples the oxidation of the important greenhouse gas methane to the reduction of nitrite. The ecological significance of “
Ca
. Methylomirabilis oxyfera” is still underexplored, as our ability to identify the presence of this bacterium is thus far limited to DNA-based techniques. Here, we investigated the lipid composition of “
Ca
. Methylomirabilis oxyfera” to identify new, gene-independent biomarkers for the environmental detection of this bacterium. Multiple “
Ca
. Methylomirabilis oxyfera” enrichment cultures were investigated. In all cultures, the lipid profile was dominated up to 46% by the fatty acid (FA) 10-methylhexadecanoic acid (10MeC
16:0
). Furthermore, a unique FA was identified that has not been reported elsewhere: the monounsaturated 10-methylhexadecenoic acid with a double bond at the Δ7 position (10MeC
16:1Δ7
), which comprised up to 10% of the total FA profile. We propose that the typical branched fatty acids 10MeC
16:0
and 10MeC
16:1Δ7
are key and characteristic components of the lipid profile of “
Ca
. Methylomirabilis oxyfera.” The successful detection of these fatty acids in a peatland from which one of the enrichment cultures originated supports the potential of these unique lipids as biomarkers for the process of nitrite-dependent methane oxidation in the environment.
Anaerobic Oxidization of Methane in a Minerotrophic Peatland: Enrichment of Nitrite-Dependent Methane-Oxidizing Bacteria
Authors: Zhu Baoli , van Dijk Gijs , Fritz Christian , Smolders Alfons J. P. , Pol Arjan , Jetten Mike S. M. , Ettwig Katharina F.
Published: October 2012

The importance of anaerobic oxidation of methane (AOM) as a methane sink in freshwater systems is largely unexplored, particularly in peat ecosystems. Nitrite-dependent anaerobic methane oxidation (n-damo) was recently discovered and reported to be catalyzed by the bacterium “
Candidatus
Methylomirabilis oxyfera,” which is affiliated with the NC10 phylum. So far, several “
Ca
. Methylomirabilis oxyfera” enrichment cultures have been obtained using a limited number of freshwater sediments or wastewater treatment sludge as the inoculum. In this study, using stable isotope measurements and porewater profiles, we investigated the potential of n-damo in a minerotrophic peatland in the south of the Netherlands that is infiltrated by nitrate-rich ground water. Methane and nitrate profiles suggested that all methane produced was oxidized before reaching the oxic layer, and NC10 bacteria could be active in the transition zone where countergradients of methane and nitrate occur. Quantitative PCR showed high NC10 bacterial cell numbers at this methane-nitrate transition zone. This soil section was used to enrich the prevalent NC10 bacteria in a continuous culture supplied with methane and nitrite at an
in situ
pH of 6.2. An enrichment of nitrite-reducing methanotrophic NC10 bacteria was successfully obtained. Phylogenetic analysis of retrieved 16S rRNA and
pmoA
genes showed that the enriched bacteria were very similar to the ones found
in situ
and constituted a new branch of NC10 bacteria with an identity of less than 96 and 90% to the 16S rRNA and
pmoA
genes of “
Ca
. Methylomirabilis oxyfera,” respectively. The results of this study expand our knowledge of the diversity and distribution of NC10 bacteria in the environment and highlight their potential contribution to nitrogen and methane cycles.
Fatty Acid Cosubstrates Provide β-Oxidation Precursors for Rhamnolipid Biosynthesis in Pseudomonas aeruginosa, as Evidenced by Isotope Tracing and Gene Expression Assays
Authors: Zhang Lin , Veres-Schalnat Tracey A. , Somogyi Arpad , Pemberton Jeanne E. , Maier Raina M.
Published: October 2012

Rhamnolipids have multiple potential applications as “green” surfactants for industry, remediation, and medicine. As a result, they have been intensively investigated to add to our understanding of their biosynthesis and improve yields. Several studies have noted that the addition of a fatty acid cosubstrate increases rhamnolipid yields, but a metabolic explanation has not been offered, partly because biosynthesis studies to date have used sugar or sugar derivatives as the carbon source. The objective of this study was to investigate the role of fatty acid cosubstrates in improving rhamnolipid biosynthesis. A combination of stable isotope tracing and gene expression assays was used to identify lipid precursors and potential lipid metabolic pathways used in rhamnolipid synthesis when fatty acid cosubstrates are present. To this end, we compared the rhamnolipids produced and their yields using either glucose alone or glucose and octadecanoic acid-

d
35

as cosubstrates. Using a combination of sugar and fatty acids, the rhamnolipid yield was significantly higher (i.e., doubled) than when glucose was used alone. Two patterns of deuterium incorporation (either 1 or 15 deuterium atoms) in a single Rha-C
10
lipid chain were observed for octadecanoic acid-

d
35

treatment, indicating that in the presence of a fatty acid cosubstrate, both
de novo
fatty acid synthesis and β-oxidation are used to provide lipid precursors for rhamnolipids. Gene expression assays showed a 200- to 600-fold increase in the expression of
rhlA
and
rhlB
rhamnolipid biosynthesis genes and a more modest increase of 3- to 4-fold of the
fadA
β-oxidation pathway gene when octadecanoic acid was present. Taken together, these results suggest that the simultaneous use of
de novo
fatty acid synthesis and β-oxidation pathways allows for higher production of lipid precursors, resulting in increased rhamnolipid yields.
Engineering Filamentous Fungi for Conversion of
d
-Galacturonic Acid to
l
-Galactonic Acid
Authors: Kuivanen Joosu , Mojzita Dominik , Wang Yanming , Hilditch Satu , Penttilä Merja , Richard Peter , Wiebe Marilyn G.
Published: October 2012

d
-Galacturonic acid, the main monomer of pectin, is an attractive substrate for bioconversions, since pectin-rich biomass is abundantly available and pectin is easily hydrolyzed.
l
-Galactonic acid is an intermediate in the eukaryotic pathway for
d
-galacturonic acid catabolism, but extracellular accumulation of
l
-galactonic acid has not been reported. By deleting the gene encoding
l
-galactonic acid dehydratase (
lgd1
or
gaaB
) in two filamentous fungi, strains were obtained that converted
d
-galacturonic acid to
l
-galactonic acid. Both
Trichoderma reesei
Δ
lgd1
and
Aspergillus niger
Δ
gaaB
strains produced
l
-galactonate at yields of 0.6 to 0.9 g per g of substrate consumed. Although
T. reesei
Δ
lgd1
could produce
l
-galactonate at pH 5.5, a lower pH was necessary for
A. niger
Δ
gaaB
. Provision of a cosubstrate improved the production rate and titer in both strains. Intracellular accumulation of
l
-galactonate (40 to 70 mg g biomass
−1
) suggested that export may be limiting. Deletion of the
l
-galactonate dehydratase from
A. niger
was found to delay induction of
d
-galacturonate reductase and overexpression of the reductase improved initial production rates. Deletion of the
l
-galactonate dehydratase from
A. niger
also delayed or prevented induction of the putative
d
-galacturonate transporter An14g04280. In addition,
A. niger
Δ
gaaB
produced
l
-galactonate from polygalacturonate as efficiently as from the monomer.
Functional Analysis of the Lactobacillus casei BL23 Sortases
Authors: Muñoz-Provencio Diego , Rodríguez-Díaz Jesús , Collado María Carmen , Langella Philippe , Bermúdez-Humarán Luis G. , Monedero Vicente
Published: October 2012

Sortases are a class of enzymes that anchor surface proteins to the cell wall of Gram-positive bacteria.
Lactobacillus casei
BL23 harbors four sortase genes, two belonging to class A (
srtA1
and
srtA2
) and two belonging to class C (
srtC1
and
srtC2
). Class C sortases were clustered with genes encoding their putative substrates that were homologous to the SpaEFG and SpaCBA proteins that encode mucus adhesive pili in
Lactobacillus rhamnosus
GG. Twenty-three genes encoding putative sortase substrates were identified in the
L. casei
BL23 genome with unknown (35%), enzymatic (30%), or adhesion-related (35%) functions. Strains disrupted in
srtA1
,
srtA2
,
srtC1
, and
srtC2
and an
srtA1 srtA2
double mutant were constructed. The transcription of all four sortase encoding genes was detected, but only the mutation of
srtA1
resulted in a decrease in bacterial surface hydrophobicity. The β-
N
-acetyl-glucosaminidase and cell wall proteinase activities of whole cells diminished in the
srtA1
mutant and, to a greater extent, in the
srtA1 srtA2
double mutant. Cell wall anchoring of the staphylococcal NucA reporter protein fused to a cell wall sorting sequence was also affected in the
srtA
mutants, and the percentages of adhesion to Caco-2 and HT-29 intestinal epithelial cells were reduced for the
srtA1 srtA2
strain. Mutations in
srtC1
or
srtC2
result in an undetectable phenotype. Together, these results suggest that SrtA1 is the housekeeping sortase in
L. casei
BL23 and SrtA2 would carry out redundant or complementary functions that become evident when SrtA1 activity is absent.