bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of energy landscape roughness of folded and unfolded proteins
Authors: Milanesi Lilia , Waltho Jonathan P. , Hunter Christopher A. , Shaw Daniel J. , Beddard Godfrey S. , Reid Gavin D. , Dev Sagarika , Volk Martin
Published: November 2012

The dynamics of protein conformational changes, from protein folding to smaller changes, such as those involved in ligand binding, are governed by the properties of the conformational energy landscape. Different techniques have been used to follow the motion of a protein over this landscape and thus quantify its properties. However, these techniques often are limited to short timescales and low-energy conformations. Here, we describe a general approach that overcomes these limitations. Starting from a nonnative conformation held by an aromatic disulfide bond, we use time-resolved spectroscopy to observe nonequilibrium backbone dynamics over nine orders of magnitude in time, from picoseconds to milliseconds, after photolysis of the disulfide bond. We find that the reencounter probability of residues that initially are in close contact decreases with time following an unusual power law that persists over the full time range and is independent of the primary sequence. Model simulations show that this power law arises from subdiffusional motion, indicating a wide distribution of trapping times in local minima of the energy landscape, and enable us to quantify the roughness of the energy landscape (4–5
k
B
T
). Surprisingly, even under denaturing conditions, the energy landscape remains highly rugged with deep traps (>20
k
B
T
) that result from multiple nonnative interactions and are sufficient for trapping on the millisecond timescale. Finally, we suggest that the subdiffusional motion of the protein backbone found here may promote rapid folding of proteins with low contact order by enhancing contact formation between nearby residues.
Phototactic personality in fruit flies and its suppression by serotonin and
white
Authors: Kain Jamey S. , Stokes Chris , de Bivort Benjamin L.
Published: November 2012

Drosophila
typically move toward light (phototax positively) when startled. The various species of
Drosophila
exhibit some variation in their respective mean phototactic behaviors; however, it is not clear to what extent genetically identical individuals within each species behave idiosyncratically. Such behavioral individuality has indeed been observed in laboratory arthropods; however, the neurobiological factors underlying individual-to-individual behavioral differences are unknown. We developed “FlyVac,” a high-throughput device for automatically assessing phototaxis in single animals in parallel. We observed surprising variability within every species and strain tested, including identically reared, isogenic strains. In an extreme example, a domesticated strain of
Drosophila simulans
harbored both strongly photopositive and strongly photonegative individuals. The particular behavior of an individual fly is not heritable and, because it persists for its lifetime, constitutes a model system for elucidating the molecular mechanisms of personality. Although all strains assayed had greater than expected variation (assuming binomial sampling), some had more than others, implying a genetic basis. Using genetics and pharmacology, we identified the metabolite transporter White and
white
-dependent serotonin as suppressors of phototactic personality. Because we observed behavioral idiosyncrasy in all experimental groups, we suspect it is present in most behaviors of most animals.
Fluctuating shells under pressure
Authors: Paulose Jayson , Vliegenthart Gerard A. , Gompper Gerhard , Nelson David R.
Published: November 2012

Thermal fluctuations strongly modify the large length-scale elastic behavior of cross-linked membranes, giving rise to scale-dependent elastic moduli. Whereas thermal effects in flat membranes are well understood, many natural and artificial microstructures are modeled as thin elastic shells. Shells are distinguished from flat membranes by their nonzero curvature, which provides a size-dependent coupling between the in-plane stretching modes and the out-of-plane undulations. In addition, a shell can support a pressure difference between its interior and its exterior. Little is known about the effect of thermal fluctuations on the elastic properties of shells. Here, we study the statistical mechanics of shape fluctuations in a pressurized spherical shell, using perturbation theory and Monte Carlo computer simulations, explicitly including the effects of curvature and an inward pressure. We predict novel properties of fluctuating thin shells under point indentations and pressure-induced deformations. The contribution due to thermal fluctuations increases with increasing ratio of shell radius to thickness and dominates the response when the product of this ratio and the thermal energy becomes large compared with the bending rigidity of the shell. Thermal effects are enhanced when a large uniform inward pressure acts on the shell and diverge as this pressure approaches the classical buckling transition of the shell. Our results are relevant for the elasticity and osmotic collapse of microcapsules.
Sculpting of an erodible body by flowing water
Authors: Ristroph Leif , Moore Matthew N. J. , Childress Stephen , Shelley Michael J. , Zhang Jun
Published: November 2012

Erosion by flowing fluids carves striking landforms on Earth and also provides important clues to the past and present environments of other worlds. In these processes, solid boundaries both influence and are shaped by the surrounding fluid, but the emergence of morphology as a result of this interaction is not well understood. We study the coevolution of shape and flow in the context of erodible bodies molded from clay and immersed in a fast, unidirectional water flow. Although commonly viewed as a smoothing process, we find that erosion sculpts pointed and cornerlike features that persist as the solid shrinks. We explain these observations using flow visualization and a fluid mechanical model in which the surface shear stress dictates the rate of material removal. Experiments and simulations show that this interaction ultimately leads to self-similarly receding boundaries and a unique front surface characterized by nearly uniform shear stress. This tendency toward conformity of stress offers a principle for understanding erosion in more complex geometries and flows, such as those present in nature.
αvβ3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1
Authors: Gianni Tatiana , Leoni Valerio , Chesnokova Liudmila S. , Hutt-Fletcher Lindsey M. , Campadelli-Fiume Gabriella
Published: November 2012

Pathogens are sensed by Toll-like receptors (TLRs) and a growing number of non-TLR receptors. Integrins constitute a family of signaling receptors exploited by viruses and bacteria to access cells. By gain- and loss-of-function approaches we found that αvβ3-integrin is a sensor of and plays a crucial role in the innate defense against herpes simplex virus (HSV). αvβ3-integrin signaled through two pathways. One concurred with TLR2, affected activation/induction of interferons type 1 (IFNs-1), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and a polarized set of cytokines and receptors. The virion glycoproteins gH/gL sufficed to induce IFN1 and NF-κB via this pathway. The other pathway was TLR2-independent, involved sarcoma (SRC)-spleen tyrosine kinase (SYK)-Caspase recruitment domain-containing protein 9 (CARD9)-TRIF (TIR-domain-containing adapter-inducing interferon-β), and affected interferon regulatory factor 3 and 7 (IRF3-IRF7). The importance of αvβ3-integrin-mediated defense is reflected in the observation that HSV evolved the immediate-early infected cellular protein 0 (ICP0) protein to counteract it. We propose that αvβ3-integrin is considered a class of non-TLR pattern recognition receptors, a role likely exerted toward viruses and bacteria that interact with integrins and mount an innate response.
Function of glycoprotein E of herpes simplex virus requires coordinated assembly of three tegument proteins on its cytoplasmic tail
Authors: Han Jun , Chadha Pooja , Starkey Jason L. , Wills John W.
Published: November 2012

Glycoprotein E (gE) of HSV plays a key role in cell-to-cell spread and virus-induced cell fusion. Here, we report that this function of gE requires the cooperation of tegument proteins UL11, UL16, and UL21. We found that the four proteins come together with very high efficiency to form a complex in transfected cells and in a manner that is regulated and coordinated. In particular, the inefficient interaction of UL16 with each membrane protein (UL11 and gE) observed in pairwise transfections became efficient when other binding partners were present. The significance of these interactions was revealed in studies of viral mutants, which showed that each of these tegument proteins is critical for processing, transport, and biological activity of gE. These findings provide insights into the mechanisms of how gE executes its function and also have implications in understanding HSV assembly and budding.
Carbon dioxide reduction to methane and coupling with acetylene to form propylene catalyzed by remodeled nitrogenase
Authors: Yang Zhi-Yong , Moure Vivian R. , Dean Dennis R. , Seefeldt Lance C.
Published: November 2012

A doubly substituted form of the nitrogenase MoFe protein (α-70
Val
→Ala
, α-195
His→Gln
) has the capacity to catalyze the reduction of carbon dioxide (CO
2
) to yield methane (CH
4
). Under optimized conditions, 1 nmol of the substituted MoFe protein catalyzes the formation of 21 nmol of CH
4
within 20 min. The catalytic rate depends on the partial pressure of CO
2
(or concentration of HCO
3
−
) and the electron flux through nitrogenase. The doubly substituted MoFe protein also has the capacity to catalyze the unprecedented formation of propylene (H
2
C = CH-CH
3
) through the reductive coupling of CO
2
and acetylene (HC≡CH). In light of these observations, we suggest that an emerging understanding of the mechanistic features of nitrogenase could be relevant to the design of synthetic catalysts for CO
2
sequestration and formation of olefins.
Optimizing the temporal dynamics of light to human perception
Authors: Rieiro Hector , Martinez-Conde Susana , Danielson Andrew P. , Pardo-Vazquez Jose L. , Srivastava Nishit , Macknik Stephen L.
Published: November 2012

No previous research has tuned the temporal characteristics of light-emitting devices to enhance brightness perception in human vision, despite the potential for significant power savings. The role of stimulus duration on perceived contrast is unclear, due to contradiction between the models proposed by Bloch and by Broca and Sulzer over 100 years ago. We propose that the discrepancy is accounted for by the observer’s “inherent expertise bias,” a type of experimental bias in which the observer’s life-long experience with interpreting the sensory world overcomes perceptual ambiguities and biases experimental outcomes. By controlling for this and all other known biases, we show that perceived contrast peaks at durations of 50–100 ms, and we conclude that the Broca–Sulzer effect best describes human temporal vision. We also show that the plateau in perceived brightness with stimulus duration, described by Bloch’s law, is a previously uncharacterized type of temporal brightness constancy that, like classical constancy effects, serves to enhance object recognition across varied lighting conditions in natural vision—although this is a constancy effect that normalizes perception across temporal modulation conditions. A practical outcome of this study is that tuning light-emitting devices to match the temporal dynamics of the human visual system’s temporal response function will result in significant power savings.
Sprouty genes function in suppression of prostate tumorigenesis
Authors: Schutzman Jennifer L. , Martin Gail R.
Published: November 2012

Expression of Sprouty genes is frequently decreased or absent in human prostate cancer, implicating them as suppressors of tumorigenesis. Here we show they function in prostate tumor suppression in the mouse. Concomitant inactivation of
Spry1
and
Spry2
in prostate epithelium causes ductal hyperplasia and low-grade prostatic intraepithelial neoplasia (PIN). However, when
Spry1
and
Spry2
loss-of-function occurs in the context of heterozygosity for a null allele of the tumor suppressor gene
Pten
, there is a striking increase in PIN and evidence of neoplastic invasion. Conversely, expression of a
Spry2
gain-of-function transgene in
Pten
null prostatic epithelium suppresses the tumorigenic effects of loss of
Pten
function. We show that Sprouty gene loss-of-function results in hyperactive RAS/ERK1/2 signaling throughout the prostate epithelium and cooperates with heterozygosity for a
Pten
null allele to promote hyperactive PI3K/AKT signaling. Furthermore,
Spry2
gain-of-function can suppress hyperactivation of AKT caused by the absence of PTEN. Together, these results point to a key genetic interaction between Sprouty genes and
Pten
in prostate tumorigenesis and provide strong evidence that Sprouty genes can function to modulate signaling via the RAS/ERK1/2 and PI3K/AKT pathways. The finding that Sprouty genes suppress tumorigenesis caused by
Pten
loss-of-function suggests that therapeutic approaches aimed at restoring normal feedback mechanisms triggered by receptor tyrosine kinase signaling, including Sprouty gene expression, may provide an effective strategy to delay or prevent high-grade PIN and invasive prostate cancer.
Estrogen dependent activation function of ERβ is essential for the sexual behavior of mouse females
Authors: Antal Maria Cristina , Petit-Demoulière Benoît , Meziane Hamid , Chambon Pierre , Krust Andrée
Published: November 2012

We previously generated and characterized a genuine estrogen receptor (ER) β-null mouse line (named ERβ
ST
L−/L−
) and showed that ERβ
ST
L−/L−
mice were sterile, due to an ovulation impairment in females and to an unknown reason in males, as their reproductive organs and spermatozoid motility appeared normal. We report here an assessment of the sexual behavior of ERβ
ST
L−/L−
null mice. We found that ERβ
ST
L−/L−
males display mildly impaired sexual behavior and that ERβ
ST
L−/L−
females are significantly less receptive and less attractive than wild-type (WT) females. Decreased attractivity is also exhibited by ERβAF2
0
but not by ERβAF1
0
mutant females (females devoid of either AF2 or AF1 activation function of ERβ). Interestingly, by using an odor preference test, we have determined that the low attractiveness of ERβ
ST
L−/L−
and ERβAF2
0
females is related to a deficiency of a volatile chemosignal.
Bacterial quorum sensing, cooperativity, and anticipation of stationary-phase stress
Authors: Goo Eunhye , Majerczyk Charlotte D. , An Jae Hyung , Chandler Josephine R. , Seo Young-Su , Ham Hyeonheui , Lim Jae Yun , Kim Hongsup , Lee Bongsoo , Jang Moon Sun , Greenberg E. Peter , Hwang Ingyu
Published: November 2012

Acyl-homoserine lactone–mediated quorum sensing (QS) regulates diverse activities in many species of
Proteobacteria
. QS-controlled genes commonly code for production of secreted or excreted public goods. The acyl-homoserine lactones are synthesized by members of the LuxI signal synthase family and are detected by cognate members of the LuxR family of transcriptional regulators. QS affords a means of population density-dependent gene regulation. Control of public goods via QS provides a fitness benefit. Another potential role for QS is to anticipate overcrowding. As population density increases and stationary phase approaches, QS might induce functions important for existence in stationary phase. Here we provide evidence that in three related species of the genus
Burkholderia
QS allows individuals to anticipate and survive stationary-phase stress. Survival requires QS-dependent activation of cellular enzymes required for production of excreted oxalate, which serves to counteract ammonia-mediated alkaline toxicity during stationary phase. Our findings provide an example of QS serving as a means to anticipate stationary phase or life at the carrying capacity of a population by activating the expression of cytoplasmic enzymes, altering cellular metabolism, and producing a shared resource or public good, oxalate.
The relative age effect among elite youth competitive swimmers
Authors: Costa Aldo M. , Marques Mário C. , Louro Hugo , Ferreira Sandra S. , Marinho Daniel A.
Published: November 2012

The aim of this study was to analyse the relative age effect (RAE) in competitive swimming. The best 50 Portuguese swimmers (12‐ to 18‐year‐olds) for the main individual swimming pool events of both genders were considered. Analysis was conducted on 7813 swimming event participants, taking account of respective swimmer birth dates and the Fédération Internationale de Natation points gained. Differences in the distribution of birth dates by quarter year were determined using the Chi‐square. A one‐way analysis of variance ANOVA was used to test for differences measured in points between individuals by quarterly birth year intervals. A two‐way analysis of variance ANOVA was also conducted to test the interaction between gender and seasonal birth date with regard to performance. The results show an inequitable distribution (p<0.01) of birth dates by quarter for almost all age groups and both genders. However, the distribution of birth dates by quarter for each considered swim event shows that RAE seems to exist only for 12‐year‐old females and 12‐ to 15‐year‐old males. Analysing mean swimming performance, post‐hoc results (p<0.01) show no consistency in RAE. Higher performance occurs among older swimmers only in 100 m butterfly (female 1998, 1st≠2nd quarter, p=0.003). The results also show no interaction between gender and seasonal birth date (p<0.01). Findings of this study show that a higher number of swimmers, particular males, are born in the first two quarters of the year, although there is mostly no effect of seasonal birth date on performance differences within the top 50 swimmers.
Influence of a 2‐year strength training programme on power performance in elite youth soccer players
Authors: Sander André , Keiner Michael , Wirth Klaus , Schmidtbleicher Dietmar
Published: November 2012

In soccer, strength, power and speed are very important because of the large number of power actions performed during the game. Therefore, the aim of this study was to examine the influence of periodised strength training for power performance more than 2 years. In this study, 134 elite youth soccer players were recruited from two youth training centres. The cohorts were arranged as follows: A (under 19 years), B (under 17 years) and C (under 15 years). The participants in each cohort were divided into two groups. One group (Strength training group [STG]) was subjected to regular soccer training in addition to strength training twice a week for 2 years. The other group (Control group [CG]) completed only the regular soccer training. The strength training was periodised with hypertrophy and intramuscular coordination blocks. For strength training, both the front squat and the back squat were performed once a week. The subjects were tested on the one‐repetition maximum (1RM) of the front and back squat and a linear sprint over 30 m. There was significantly better performance from the STG on 1RM (p <0.001). In the sprint, the STG displayed significantly better improvements (p <0.05 to p <0.001) of up to 6%. The effects of strength training are reflected in the sprint performance. Therefore, it seems beneficial for youth to perform strength training to exploit the reserve capacity in sprint performances.
A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
Authors: Zhang Lin , Orban Martin , Lorenz Michael , Barocke Verena , Braun Daniel , Urtz Nicole , Schulz Christian , von Brühl Marie-Luise , Tirniceriu Anca , Gaertner Florian , Proia Richard L. , Graf Thomas , Bolz Steffen-Sebastian , Montanez Eloi , Prinz Marco , Müller Alexandra , von Baumgarten Louisa , Billich Andreas , Sixt Michael , Fässler Reinhard , von Andrian Ulrich H. , Junt Tobias , Massberg Steffen
Published: November 2012

Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P–S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia.
Permeant calcium ion feed-through regulation of single inositol 1,4,5-trisphosphate receptor channel gating
Authors: Vais Horia , Foskett J. Kevin , Ullah Ghanim , Pearson John E. , Daniel Mak Don-On
Published: November 2012

The ubiquitous inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) Ca2+ release channel plays a central role in the generation and modulation of intracellular Ca2+ signals, and is intricately regulated by multiple mechanisms including cytoplasmic ligand (InsP3, free Ca2+, free ATP4−) binding, posttranslational modifications, and interactions with cytoplasmic and endoplasmic reticulum (ER) luminal proteins. However, regulation of InsP3R channel activity by free Ca2+ in the ER lumen ([Ca2+]ER) remains poorly understood because of limitations of Ca2+ flux measurements and imaging techniques. Here, we used nuclear patch-clamp experiments in excised luminal-side-out configuration with perfusion solution exchange to study the effects of [Ca2+]ER on homotetrameric rat type 3 InsP3R channel activity. In optimal [Ca2+]i and subsaturating [InsP3], jumps of [Ca2+]ER from 70 nM to 300 µM reduced channel activity significantly. This inhibition was abrogated by saturating InsP3 but restored when [Ca2+]ER was raised to 1.1 mM. In suboptimal [Ca2+]i, jumps of [Ca2+]ER (70 nM to 300 µM) enhanced channel activity. Thus, [Ca2+]ER effects on channel activity exhibited a biphasic dependence on [Ca2+]i. In addition, the effect of high [Ca2+]ER was attenuated when a voltage was applied to oppose Ca2+ flux through the channel. These observations can be accounted for by Ca2+ flux driven through the open InsP3R channel by [Ca2+]ER, raising local [Ca2+]i around the channel to regulate its activity through its cytoplasmic regulatory Ca2+-binding sites. Importantly, [Ca2+]ER regulation of InsP3R channel activity depended on cytoplasmic Ca2+-buffering conditions: it was more pronounced when [Ca2+]i was weakly buffered but completely abolished in strong Ca2+-buffering conditions. With strong cytoplasmic buffering and Ca2+ flux sufficiently reduced by applied voltage, both activation and inhibition of InsP3R channel gating by physiological levels of [Ca2+]ER were completely abolished. Collectively, these results rule out Ca2+ regulation of channel activity by direct binding to the luminal aspect of the channel.
The impact of multivessel disease with and without a co‐existing chronic total occlusion on short‐ and long‐term mortality in ST‐elevation myocardial infarction patients with and without cardiogenic shock
Authors: Hoebers Loes P. , Vis Marije M. , Claessen Bimmer E. , van der Schaaf René J. , Kikkert Wouter J. , Baan Jan , de Winter Robbert J. , Piek Jan J. , Tijssen Jan G.P. , Dangas George D. , Henriques José P.S.
Published: November 2012

Aims

To evaluate the impact of multivessel disease (MVD) with and without a chronic total occlusion (CTO) on early and late mortality in ST‐elevation myocardial infarction (STEMI) patients with and without cardiogenic shock (CS).

Methods and results

A total of 5018 STEMI patients were treated with primary percutaneous coronary intervention and stratified according to the presence of CS and the extent of coronary artery disease into single vessel disease (SVD), MVD without a CTO, and MVD with a CTO. We performed a landmark mortality analysis up to 5‐year follow‐up with a landmark set at 30 days. In patients without CS (n = 4409), only MVD with a CTO was an independent predictor for 30‐day [hazard ratio (HR) 2.8, P < 0.01] and 5‐year mortality (HR 1.7, P < 0.01), whereas MVD without a CTO was not associated with increased mortality. In CS patients (n = 609), MVD with and without a CTO were independent predictors for 30‐day mortality (HR 2.2, P < 0.01 and HR 1.8, P < 0.01). In 30‐day CS survivors, only MVD with a CTO was associated with a trend towards increased mortality (HR 1.7, P = 0.06).

Conclusion

In non‐CS STEMI patients with MVD, the presence of a co‐existing CTO in a non‐infarct‐related artery drives early and late mortality. In patients with CS, MVD with and without a CTO were predictors for short‐term mortality.
RETINAL DETACHMENT IN A PATIENT WITH LEBER CONGENITAL AMAUROSIS
Authors: Cunningham Matthew A. , Boldt H. Culver , Stone Edwin M.
Published: November 2012

Purpose:

To report the unique presentation of a patient with Leber congenital amaurosis who developed a tractional retinal detachment involving the macula and underwent successful pars plana vitrectomy surgery.

Methods:

Retrospective interventional case report. Chart review.

Results:

A 54-year-old white woman, with molecularly confirmed CEP290-associated Leber congenital amaurosis, who initially presented with Snellen visual acuity of 20/200 in the right eye and 20/125 in the left eye and constricted visual fields. The maculae were flat, the vessels were attenuated, and the periphery was flat with diffuse atrophic changes and bone spicule–like pigmentation in both eyes. Follow-up examination, 3 years later, demonstrated a temporal tractional retinal detachment in the left eye, which involved the macula; however, the vision was stable. She presented 4 months later, and her vision declined to light perception in the left eye and the traction retinal detachment now involved the entire macula. A pars plana vitrectomy was performed, and 8 months later, the visual acuity improved to 20/300 in the left eye and the periphery was attached 360° with extensive bone spicule–like pigmentation and laser scars.

Conclusion:

Leber congenital amaurosis is a rare inherited retinal disease that can be complicated by tractional retinal detachment. Vitrectomy surgery can be used successfully to repair retinal detachments in this patient population. The patient had subsequent improvement in visual acuity and anatomical reattachment.
Methylophaga nitratireducenticrescens sp. nov. and Methylophaga frappieri sp. nov., isolated from the biofilm of the methanol-fed denitrification system treating the seawater at the Montreal Biodome
Authors: Villeneuve Céline , Martineau Christine , Mauffrey Florian , Villemur Richard
Published: November 2012

Two bacterial strains, designated JAM1Tand JAM7T, were isolated from a methanol-fed denitrification system treating seawater at the Montreal Biodome, Canada. They were affiliated within the genusMethylophagaof theGammaproteobacteriaby analysis of the 16S rRNA gene sequences. Strain JAM1Thad the capacity to grow under denitrifying conditions by reducing nitrate into nitrite which is unique among the species of the genusMethylophaga. Major fatty acids were C16 : 1ω7cor ω6c, C16 : 0and C18 : 1ω7cor ω6c. The major ubiquinone was Q8. Both strains required vitamin B12and Na+ions for growth. The genomes of strains JAM1Tand JAM7Thave been completely sequenced and showed a DNA G+C content of 44.7 mol% and 47.8 mol%, respectively. Growth occurred at pH 6–11 and at 0.5–8 % NaCl. Both genomes contained predicted ORFs encoding the key enzymes of the ribulose monophosphate pathway. Also, operons encoding two nitrate reductases (Nar), two nitric oxide reductases (Nor), one nitrous oxide reductase (Nos) and one truncated nitrite reductase (NirK) were clustered in a 67 kb chromosomal region in strain JAM1T. No such operons were found in strain JAM7T. These results supported the affiliation of the two strains as novel species within the genusMethylophaga. The namesMethylophaga nitratireducenticrescenssp. nov. for type strain JAM1T( = DSM 25689T = ATCC BAA-2433T) andMethylophaga frappierisp. nov. for type strain JAM7T( = DSM 25690T = ATCC BAA-2434T) are proposed.
Spirochaeta sphaeroplastigenens sp. nov., a halo-alkaliphilic, obligately anaerobic spirochaete isolated from soda lake Lonar
Authors: Vishnuvardhan Reddy S. , Aspana S. , Tushar D. L. , Sasikala Ch. , Ramana Ch. V.
Published: November 2012

Two helical-shaped bacteria (strains JC133Tand JC143), which stain Gram-negative, were isolated from an alkaline soda lake, Lonar, India. Both strains were obligate anaerobes, mesophilic and required halo-alkaline conditions for growth. Both strains were resistant to rifampicin and kanamycin, but sensitive to gentamicin, tetracycline, ampicillin and chloramphenicol. Both strains had phosphatidylglycerol (PG), diphosphotidylglycerol (DPG), glycolipid (GL) and four unidentified lipids (L1–4) as the major polar lipids. C18 : 1ω7cwas the predominant cellular fatty acid with significant proportions of C16 : 0, C18 : 1ω9c, C14 : 0, C18 : 0, C16 : 1ω5c, C18 : 1ω5cand C20 : 1ω9c. The DNA G+C contents of strain JC131Tand JC143 were 58.2 and 58.5 mol%, respectively, and the two strains showed DNA reassociation >85 % (based on DNA–DNA hybridization). Based on the 16S rRNA gene sequence analysis, both strains were identified as belonging to the genusSpirochaetawithSpirochaeta alkalicaZ-7491T(99.6 % sequence similarity),Spirochaeta americanaASpG1T(99 %) and other members of the genusSpirochaeta(<93 %) as their closest phylogenetic neighbours. However, strain JC133Tand JC143 displayed less than 53.5 % binding (based on DNA–DNA hybridization) withS. alkalicaZ-7491TandS. americanaASpG1T. On the basis of physiological, biochemical, chemotaxonomic and molecular properties, strains JC133Tand JC143 can be differentiated from other members of the genusSpirochaetaand represent a novel species of the genusSpirochaeta, for which the nameSpirochaeta sphaeroplastigenenssp. nov. is proposed. The type strain is JC133T( = KCTC 15220T = NBRC 109056T).
Flavobacterium squillarum sp. nov., isolated from a freshwater shrimp culture pond, and emended descriptions of

Flavobacterium haoranii

,

Flavobacterium cauense

,

Flavobacterium terrae

and

Flavobacterium aquatile
Authors: Sheu Shih-Yi , Lin Yang-Shun , Chen Wen-Ming
Published: November 2012

A bacterial strain, designated CMJ-5T, was isolated from a freshwater shrimp culture pond in Taiwan and characterized using a polyphasic taxonomic approach. Cells of strain CMJ-5T were Gram-stain-negative, strictly aerobic, non-motile, yellow-pigmented rods surrounded by a thick capsule. Growth occurred at 20–35 °C (optimum, 30 °C), at pH 6.5–8.0 (optimum, pH 7.0) and with 0–0.5 % NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain CMJ-5T belonged to the genus

Flavobacterium

and was related most closely to

Flavobacterium haoranii

LQY-7T with sequence similarity of 94.4 %. Strain CMJ-5T contained iso-C15 : 0 (37.5 %), iso-C17 : 0 3-OH (13.4 %), iso-C15 : 0 3-OH (13.1 %) and iso-C15 : 1 G (11.2 %) as the predominant fatty acids. The major isoprenoid quinone was MK-6. The polar lipid profile consisted of phosphatidylethanolamine and several uncharacterized aminophospholipids and phospholipids. The major polyamine was homospermidine. The G+C content of the genomic DNA was 42.4 mol%. On the basis of phylogenetic inference and phenotypic data, strain CMJ-5T should be classified as a representative of a novel species, for which the name Flavobacterium squillarum sp. nov. is proposed. The type strain is CMJ-5T ( = BCRC 80405T = LMG 26890T = KCTC 23915T). Emended descriptions of

Flavobacterium haoranii

,

Flavobacterium cauense

,

Flavobacterium terrae

and

Flavobacterium aquatile

are also proposed.
Biomechanics of Lateral Interbody Spacers: Going Wider for Going Stiffer
Authors: Pimenta Luiz , Turner Alexander W. L. , Dooley Zachary A. , Parikh Rachit D. , Peterson Mark D.
Published: November 2012

This study investigates the biomechanical stability of a large interbody spacer inserted by a lateral approach and compares the biomechanical differences with the more conventional transforaminal interbody fusion (TLIF), with and without supplemental pedicle screw (PS) fixation. Twenty-four L2-L3 functional spinal units (FSUs) were tested with three interbody cage options: (i) 18 mm XLIF cage, (ii) 26 mm XLIF cage, and (iii) 11 mm TLIF cage. Each spacer was tested without supplemental fixation, and with unilateral and bilateral PS fixation. Specimens were subjected to multidirectional nondestructive flexibility tests to 7.5 N·m. The range of motion (ROM) differences were first examined within the same group (per cage) using repeated-measures ANOVA, and then compared between cage groups. The 26 mm XLIF cage provided greater stability than the 18 mm XLIF cage with unilateral PS and 11 mm TLIF cage with bilateral PS. The 18 mm XLIF cage with unilateral PS provided greater stability than the 11 mm TLIF cage with bilateral PS. This study suggests that wider lateral spacers are biomechanically stable and offer the option to be used with less or even no supplemental fixation for interbody lumbar fusion.
The Rubisco Small Subunit Is Involved in Tobamovirus Movement and Tm-22-Mediated Extreme Resistance
Authors: Zhao Jinping , Liu Qi , Zhang Haili , Jia Qi , Hong Yiguo , Liu Yule
Published: November 2012

The multifunctional movement protein (MP) of Tomato mosaic tobamovirus (ToMV) is involved in viral cell-to-cell movement, symptom development, and resistance gene recognition. However, it remains to be elucidated how ToMV  MP plays such diverse roles in plants. Here, we show that ToMV  MP interacts with the Rubisco small subunit (RbCS) of Nicotiana benthamiana in vitro and in vivo. In susceptible N. benthamiana plants, silencing of NbRbCS enabled ToMV to induce necrosis in inoculated leaves, thus enhancing virus local infectivity. However, the development of systemic viral symptoms was delayed. In transgenic N. benthamiana plants harboring Tobacco mosaic virus resistance-22 (Tm-22), which mediates extreme resistance to ToMV, silencing of NbRbCS compromised Tm-22-dependent resistance. ToMV was able to establish efficient local infection but was not able to move systemically. These findings suggest that NbRbCS plays a vital role in tobamovirus movement and plant antiviral defenses.
Mosquito ecology and control of malaria
Authors: Godfray H. Charles J.
Published: November 2012

Mosquitoes transmit some of the most important infectious diseases of man including malaria that today kills around 0·6–1·2 million people a year, the majority children in low‐income countries.

There is increasing realisation that no single intervention is likely to halt malaria and a multipronged approach is needed including vector control.

Very effective vector control measures are currently available, most involving insecticides, although there is evidence of growing problems with the spread of resistance. A variety of novel genetic approaches to vector control are under active development.

Research on targeting the mosquito has been greatly facilitated by huge investment in molecular resources, including the provision of numerous full‐genome sequences.

Vector control is applied population biology, and I argue here that further progress will require as much attention to mosquito ecology as has been paid to mosquito molecular biology.
Habitat selection guiding agri‐environment schemes for a farmland specialist, the brown hare
Authors: Petrovan S. O. , Ward A. I. , Wheeler P. M.
Published: November 2012

Habitat improvements through agri‐environment schemes are the most important tool for reversing biodiversity declines in European farmland. However, little is known about their impact on mammals, including the brown hare, a priority species for conservation in the UK. We studied radio‐collared hares for 13 months in a mixed agricultural area using ‘homing in’ to provide high spatial‐resolution fixes. Hares selected agri‐environment field margins during both active and inactive periods and used the areas in the middle of large fields less frequently than those closer to the field boundaries. Blocks of woods and lines of trees were selected as resting sites while sheep‐grazed fields were generally avoided throughout the year. We suggest that agri‐environment schemes targeted at creating and increasing non‐farmed habitat features associated with field boundaries and reducing sward depletion through less intensive or mixed grazing regimes could prove beneficial for populations of this priority species in farmland.
On not airing our dirty laundry: Intergroup contexts suppress ingroup criticism among strongly identified group members
Authors: Packer Dominic J.
Published: November 2012

Not every situation affords the appropriate setting to articulate group problems, and I predicted that strongly identified members would be particularly sensitive to the intergroup context in which ingroup criticism is expressed. In Study 1, strongly but not weakly identified members reduced criticism of their ingroup when communicating with an outgroup (vs. ingroup) audience, and this effect was mediated by concerns for the reputation of the group. In Study 2, heightening the salience of intergroup competition suppressed criticism among group members high (but not low) in the solidarity component of identification, even though they were communicating with an ingroup audience. These findings show that even when criticizing their group, strongly identified members are attuned to the collective interest: they are more willing to articulate problems to an insider than when asked to do so by an outgroup member or when reminded of a competitive intergroup dynamic.
Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels
Authors: Qin Xin , Yue Zhichao , Sun Baonan , Yang Wenzhong , Xie Jia , Ni Eric , Feng Yi , Mahmood Rafat , Zhang Yanhui , Yue Lixia
Published: November 2012

Background and Purpose

Transient receptor potential melastatin 7 (TRPM7) is a unique channel kinase which is crucial for various physiological functions. However, the mechanism by which TRPM7 is gated and modulated is not fully understood. To better understand how modulation of TRPM7 may impact biological processes, we investigated if TRPM7 can be regulated by the phospholipids sphingosine (SPH) and sphingosine‐1‐phosphate (S1P), two potent bioactive sphingolipids that mediate a variety of physiological functions. Moreover, we also tested the effects of the structural analogues of SPH, N,N‐dimethyl‐D‐erythro‐sphingosine (DMS), ceramides and FTY720 on TRPM7.

Experimental Approach

HEK293 cells stably expressing TRPM7 were used for whole‐cell, single‐channel and macropatch current recordings. Cardiac fibroblasts were used for native TRPM7 current recording.

Key Results

SPH potently inhibited TRPM7 in a concentration‐dependent manner, whereas S1P and other ceramides did not produce noticeable effects. DMS also markedly inhibited TRPM7. Moreover, FTY720, an immunosuppressant and the first oral drug for treatment of multiple sclerosis, inhibited TRPM7 with a similar potency to that of SPH. In contrast, FTY720‐P has no effect on TRPM7. It appears that SPH and FTY720 inhibit TRPM7 by reducing channel open probability. Furthermore, endogenous TRPM7 in cardiac fibroblasts was markedly inhibited by SPH, DMS and FTY720.

Conclusions and Implications

This is the first study demonstrating that SPH and FTY720 are potent inhibitors of TRPM7. Our results not only provide a new modulation mechanism of TRPM7, but also suggest that TRPM7 may serve as a direct target of SPH and FTY720, thereby mediating S1P‐independent physiological/pathological functions of SPH and FTY720.

Linked Article

This article is commented on by Rohacs, pp. 1291–1293 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12070
Gene Expression in the Human Brain: The Current State of the Study of Specificity and Spatiotemporal Dynamics
Authors: Naumova Oksana Yu. , Lee Maria , Rychkov Sergei Yu. , Vlasova Natalia V. , Grigorenko Elena L.
Published: November 2012

Gene expression is one of the main molecular processes regulating the differentiation, development, and functioning of cells and tissues. In this review a handful of relevant terms and concepts are introduced and the most common techniques used in studies of gene expression/expression profiling (also referred to as studies of the transcriptome or transcriptomics) are described. The main foci of this review are the advancements in studies of the transcriptome in the human brain, the transcriptome's variability across different brain structures, and the systematic changes that occur through different developmental stages across the life span in general and childhood in particular. Finally, the question of how the accumulating data on the spatial and temporal dynamics of the transcriptome may shed light on the molecular mechanisms of the typical and atypical development of the central nervous system is addressed.
Prospective longitudinal study of corneal collagen cross‐linking in progressive keratoconus
Authors: Viswanathan Deepa , Males John
Published: November 2012

Background

Collagen cross‐linking has been reported to be effective in treating progressive keratoconus, and this study aims to evaluate the long‐term efficacy of this procedure.

Design

Prospective longitudinal interventional study of patients with progressive keratoconus who underwent cross‐linking in a tertiary referral hospital.

Participants

Thirty‐five patients (51 eyes) who underwent cross‐linking with a mean follow‐up of 14.38 ± 9.36 months (range 6–48) were compared with a control group of 25 fellow eyes that did not undergo the procedure.

Methods

Cross‐linking was performed using 0.1% riboflavin (in 20% dextran T500) and ultraviolet A irradiation (370 nm, 3 mW/cm2, 30 min).

Main Outcome Measures

Maximum keratometry in dioptres, logMAR best spectacle‐corrected visual acuity, cylindrical power, manifest refraction spherical equivalent and central corneal thickness.

Results

Analysis of the treated group demonstrated a significant flattening of maximum keratometry by 0.96 ± 2.33 dioptres (P = 0.005) and a significant improvement in visual acuity by 0.05 ± 0.13 logMAR (P = 0.04). In the control group, maximum keratometry increased significantly by 0.43 ± 0.85 dioptres (P = 0.05), and visual acuity decreased by mean 0.05 ± 0.14 (P = 0.2). No statistical differences were noted regarding cylindrical power, spherical equivalent or corneal thickness in both groups.

Conclusions

Results indicate that corneal collagen cross‐linking using riboflavin and ultraviolet A is effective as a therapeutic option in cases of progressive keratoconus by reducing the corneal curvature and by improving the visual acuity in these patients.
Experimental measure of retinal impact force resulting from intraocular foreign body dropped onto retina through media of differing viscosity
Authors: Ernst Benjamin J , Velez‐Montoya Raul , Kujundzic Damir , Kujundzic Elmira , Olson Jeffrey L
Published: November 2012

Background

To evaluate and compare the perfluorocarbon liquid, silicone oil, and viscoelastic against standard saline, in their ability to dampen the impact force of a foreign body, dropped within the eye. In an experimental surgical model in where cohesive and adhesive forces of the substances are not enough to float heavy‐than‐water foreign bodies.

Methods

A model of ophthalmic surgery was constructed. A BB pellet was dropped from 24 mm onto a force transducer through four different fluids: balanced salt solution, perfluoro‐n‐octane, viscoelastic, and silicone oil. The impact energy (force) for each case was measured and recorded by the force transducer. The mean force of impact for each fluid was compared using the Student t‐test.

Results

Silicone oil resulted in the lowest force of impact. Both silicone oil and viscoelastic dampened the impact an order of magnitude more than perfluoro‐n‐octane and balanced salt solution.

Conclusions

Silicone oil and viscoelastic cushioned the force from a dropped BB. They may be useful adjuncts to prevent iatrogenic retinal injury during vitrectomy for intraocular foreign body removal.
Cardiac injury in refractory status epilepticus
Authors: Hocker Sara , Prasad Abhiram , Rabinstein Alejandro A.
Published: November 2012

Purpose:  We sought to describe the spectrum of cardiac injury in refractory status epilepticus (RSE).

Methods:  We reviewed all patients with RSE between 1999 and 2011 at Mayo Clinic. RSE was defined as generalized convulsive or nonconvulsive status epilepticus (SE) that continued despite initial therapies. Exclusion criteria were age <18 years, anoxic SE, psychogenic SE, simple partial SE, absence SE, and repeat RSE. Patients were divided into those with (transient left ventricular [LV] dysfunction; electrocardiography [ECG] abnormality—new T‐wave inversion, ST elevation or ST depression, or QTc prolongation; and/or elevated blood troponin T levels) versus those without evidence of cardiac injury.

Key Findings:  We identified 59 consecutive patients with RSE. In 24 patients no cardiac‐specific diagnostic studies were obtained. Twenty‐two of the remaining 35 patients demonstrated markers of cardiac injury. General anesthesia was necessary for control of seizures in 31 of 35 patients for 10.5 ± 17.4 days. Twenty‐three patients had troponin levels drawn at onset of SE, of which nine were abnormal. ECG findings at onset of SE included ST elevation (11.4%), ST depression (5.7%), new T‐wave inversion (37.1%), and nonspecific ST changes (37.1%). Cardiac arrhythmias included ventricular tachycardia/fibrillation (11.4%), atrioventricular block (2.9%), atrial fibrillation/flutter (20.0%), sinus bradycardia (48.6%), and sinus tachycardia (65.7%). Intervention was required for cardiac arrhythmias in 42.9%. QTc was prolonged in 22.9% of patients. One patient met criteria for non–ST‐elevation myocardial infarction (NSTEMI). Three of 14 patients evaluated with ECG during SE demonstrated reversible systolic dysfunction. In‐hospital mortality was 34.3%. Outcome was worse in the group with markers of cardiac injury but the difference was not statistically significant (p = 0.14).

Significance:  Markers of cardiac injury are common in RSE and may be underrecognized in this population. These disturbances may require specific treatment and are often reversible. Routine performance of ECG and troponin followed by an echocardiography in those with repolarization abnormalities is probably justified. This was a biased sample of patients with severe RSE who had cardiac studies performed. The prevalence of findings in this study refers to this subgroup only.