bluuebunny/crossref_metadata_2025 huggingface dataset:
Buddha from space—An ancient object of art made of a Chinga iron meteorite fragment*
Authors: BUCHNER Elmar , SCHMIEDER Martin , KURAT Gero , BRANDSTÄTTER Franz , KRAMAR Utz , NTAFLOS Theo , KRÖCHERT Jörg
Published: September 2012

Abstract–  The fall of meteorites has been interpreted as divine messages by multitudinous cultures since prehistoric times, and meteorites are still adored as heavenly bodies. Stony meteorites were used to carve birds and other works of art; jewelry and knifes were produced of meteoritic iron for instance by the Inuit society. We here present an approximately 10.6 kg Buddhist sculpture (the “iron man”) made of an iron meteorite, which represents a particularity in religious art and meteorite science. The specific contents of the crucial main (Fe, Ni, Co) and trace (Cr, Ga, Ge) elements indicate an ataxitic iron meteorite with high Ni contents (approximately 16 wt%) and Co (approximately 0.6 wt%) that was used to produce the artifact. In addition, the platinum group elements (PGEs), as well as the internal PGE ratios, exhibit a meteoritic signature. The geochemical data of the meteorite generally match the element values known from fragments of the Chinga ataxite (ungrouped iron) meteorite strewn field discovered in 1913. The provenance of the meteorite as well as of the piece of art strongly points to the border region of eastern Siberia and Mongolia, accordingly. The sculpture possibly portrays the Buddhist god Vaiśravana and might originate in the Bon culture of the eleventh century. However, the ethnological and art historical details of the “iron man” sculpture, as well as the timing of the sculpturing, currently remain speculative.
Efficacy and safety of exenatide once‐weekly vs exenatide twice‐daily in Asian patients with type 2 diabetes mellitus
Authors: Ji Linong , Onishi Yukiko , Ahn Chul Woo , Agarwal Pankaj , Chou Chien‐Wen , Haber Harry , Guerrettaz Kelly , Boardman Marilyn K
Published: September 2012

Aims/Introduction

To compare safety and efficacy of the extended‐release formulation exenatide once weekly (EQW) vs exenatide twice daily (EBID) for 26 weeks in type 2 diabetes patients from China, India, Japan, South Korea and Taiwan.

Materials and Methods

A randomized, comparator‐controlled, open‐label study included 681 patients with type 2 diabetes inadequately controlled (hemoglobin A1c [HbA1c] ≥7 and ≤11%) with oral antihyperglycemic medications (OAMs). Patients added 2 mg EQW or 10 μg EBID to current OAMs. Safety was re‐evaluated 10 weeks after last treatment.

Results

EQW was superior to EBID on HbA1c measures at week 26 (Least‐squares mean treatment difference: −0.31% [95% confidence interval −0.49, −0.14%]). More EQW‐treated patients achieved target HbA1c ≤7.0% (P = 0.003), ≤6.5% (P < 0.001), or ≤6.0% (P = 0.003). Fasting serum glucose reductions were greater among EQW‐treated patients (P < 0.001). Blood glucose profiles improved in both treatment groups (P < 0.001). Weight loss occurred with both treatments, but was greater with EBID. Adverse events (≥10%, either group) were nausea, injection‐site induration, dyslipidemia and vomiting. Injection‐site induration was more frequent with EQW, whereas nausea, vomiting and hypoglycemia were less frequent. One episode each of major hypoglycemia (EBID) and pancreatitis (EQW) were reported.

Conclusion

In this population, EQW and EBID showed efficacious glucose and weight control; safety and tolerability were consistent with observations in non‐Asian patients. This trial was registered with ClinicalTrials.gov (no. NCT00917267).
Insulin degludec in Japanese patients with type 1 diabetes mellitus: A randomized controlled trial
Authors: Iwamoto Yasuhiko , Clauson Per , Nishida Tomoyuki , Kaku Kohei
Published: September 2012

Introduction

Insulin degludec is an ultra‐long‐acting insulin with a flat time‐action profile and duration of action >42 h. Data from several studies have shown insulin degludec to have a favorable therapeutic profile in type 1 and type 2 diabetes.

Materials and Methods

This was a 6‐week, parallel‐group, randomized controlled trial carried out in 65 Japanese patients with type 1 diabetes, previously treated with mealtime insulin aspart and either insulin glargine or neutral protamine Hagedorn insulin. Patients were randomized to receive either insulin degludec or insulin detemir, each once daily and at the same unit dose as pretrial basal insulin. During the trial, basal insulin was titrated according to a prespecified algorithm in order to achieve a fasting plasma glucose target of 80–109 mg/dL.

Results

No severe hypoglycemia occurred; there was no significant difference in confirmed hypoglycemia rates with insulin degludec and insulin detemir (rate ratio degludec/detemir 0.78; 95% confidence interval 0.45–1.34). The rate of nocturnal confirmed hypoglycemia was 69% lower with insulin degludec than with insulin detemir (rate ratio 0.31; 95% confidence interval 0.13–0.78). Final fasting plasma glucose levels were similar (insulin degludec 147 mg/dL, insulin detemir 136 mg/dL), despite differing baseline fasting plasma glucose levels.

Conclusions

In conclusion, no concerns relating to hypoglycemia or general safety were observed when initiating insulin degludec in Japanese patients with type 1 diabetes at the same unit dose as previous basal insulin. This trial was registered with ClinicalTrials.gov (no. NCT00841087).
Indonesian undergraduate dental students' perceptions toward implant treatment and education
Authors: Ariani Nina , Mursid Saraventi , Odang Roselani W. , Sukotjo Cortino , Kusdhany Lindawati S.
Published: September 2012

Objective

Indonesia foresees high demand in providing dental implant therapy and need to prepare competent graduating dentists. No information about undergraduate dental implant education in Indonesia has been reported in the literature. The objective of this study was to investigate dental students' perceptions towards implant treatment and education in one Indonesian dental school.

Methods

A survey was distributed to 166 fourth‐ and fifth‐year students of Faculty of Dentistry, University of Indonesia (FD‐UI). The survey consisted of 14 questions on students' perceptions on implant treatment, current undergraduate implant curriculum, and their future plans.

Results

One hundred and forty‐one students (85%) returned the survey. Dental implant was considered as a treatment of choice for restoring missing mandibular first molar and maxillary anterior tooth, but not edentulous mandible. The majority of students rated that the topic of implant dentistry was insufficiently covered during undergraduate education, were interested in learning more, and planned to include implant as part of their future practice.

Conclusion

Dental students of FD‐UI are aware of implant treatment as a restorative option in replacing a single missing tooth. There is a need for a nationwide discussion for introducing a comprehensive implant dentistry curriculum in undergraduate dental education in Indonesia.
Cell dynamics in cervical loop epithelium during transition from crown to root: implications for Hertwig's epithelial root sheath formation
Authors: Sakano M. , Otsu K. , Fujiwara N. , Fukumoto S. , Yamada A. , Harada H.
Published: September 2012

Background and Objective

Some clinical cases of hypoplastic tooth root are congenital. Because the formation of Hertwig's epithelial root sheath (HERS) is an important event for root development and growth, we have considered that understanding the HERS developmental mechanism contributes to elucidate the causal factors of the disease. To find integrant factors and phenomenon for HERS development and growth, we studied the proliferation and mobility of the cervical loop (CL).

Material and Methods

We observed the cell movement of CL by the DiI labeling and organ culture system. To examine cell proliferation, we carried out immunostaining of CL and HERS using anti‐Ki67 antibody. Cell motility in CL was observed by tooth germ slice organ culture using green fluorescent protein mouse. We also examined the expression of paxillin associated with cell movement.

Results

Imaging using DiI labeling showed that, at the apex of CL, the epithelium elongated in tandem with the growth of outer enamel epithelium (OEE). Cell proliferation assay using Ki67 immunostaining showed that OEE divided more actively than inner enamel epithelium (IEE) at the onset of HERS formation. Live imaging suggested that mobility of the OEE and cells in the apex of CL were more active than in IEE. The expression of paxillin was observed strongly in OEE and the apex of CL.

Conclusion

The more active growth and movement of OEE cells contributed to HERS formation after reduction of the growth of IEE. The expression pattern of paxillin was involved in the active movement of OEE and HERS. The results will contribute to understand the HERS formation mechanism and elucidate the cause of anomaly root.
Development and assessment of a novel real‐time PCR assay for quantitation of hepatitis D virus RNA to study viral kinetics in chronic hepatitis D
Authors: Katsoulidou A. , Manesis E. , Rokka C. , Issaris C. , Pagoni A. , Sypsa V. , Hatzakis A.
Published: September 2012

Hepatitis delta virus (HDV) infection is a usually severe type of viral hepatitis associated with increased mortality and rapid evolution to cirrhosis. Currently, treatment is limited to extended interferon administration and measurement of HDV RNA blood levels is essential to judge the response. The aim of this study was to develop a highly sensitive and reproducible real‐time reverse transcriptase‐polymerase chain reaction (real‐time RT‐PCR) for the quantitation of circulating HDV RNA of all clades (1–8), and assess its usefulness in the follow‐up of patients. The amplification was combined with molecular beacon technology using the LightCycler 2.0 system. The assay was specific and showed linearity over a wide range from 13 to 13 × 1010 copies/mL. The 95% detection limit was 43.2 copies/mL. Intra‐assay reproducibility, as expressed by the coefficient of variation, ranged from 1.84 to 18.61%, whereas the corresponding estimates for the inter‐assay variability ranged from 0.57 to 10.18%. Finally, the dynamic profiles of six patients regarding virological (HDV RNA, HBV DNA), biochemical and serological data were constructed. We were able to observe that most patients who were treated with an interferon‐based regime showed a significant reduction in delta viremia. In conclusion, our real‐time RT‐PCR for HDV RNA quantification combines high sensitivity and reproducibility in a high dynamic range, can provide important information for patient management and can be a useful tool for monitoring the response to antiviral therapies.
Early adjuvant use of nonopioids associated with reduced odds of serious postoperative opioid adverse events and need for rescue in children
Authors: Voepel‐Lewis Terri , Wagner Deborah , Burke Constance , Tait Alan R. , Hemberg Jennifer , Pechlivanidis Elsa , Malviya Shobha , Talsma AkkeNeel
Published: September 2012

Objectives

Examine factors associated with opioid adverse drug events (ADE) in children.

Specific Aims

Examine whether adjuvant nonopioid use is associated with a decreased probability of opioid‐ADEs and need for rescue.

Background

Opioid‐ADEs contribute to serious preventable harm for hospitalized children. Adjuvant nonopioid use may mitigate opioid risk postoperatively, yet few studies support this notion.

Method

This nested case–control study included children who required intervention or rescue from opioid‐ADEs and procedure‐matched controls. Data were recorded from medical records and primary outcomes included serious opioid‐ADEs (over‐sedation and respiratory depression) and need for rescue (e.g., naloxone, rapid response team). Hierarchical logistic regression (HLR) models examined relationships between factors and opioid‐ADEs. Early clinical signs and symptoms of deterioration were examined.

Results

Twenty five children with opioid‐ADEs and 98 children without events were included. ASA‐PS remained an independent risk factor (odds ratio, 2.56 [1.09, 6.03]; P = 0.031), while adjuvant nonopioids a risk reduction factor for opioid‐ADEs (OR, 0.16 [0.05, 0.47]; P = 0.001) and need for rescue (0.14 [0.04, 0.47]; P = 0.001). Supplemental oxygen use at PACU discharge was associated with an increased odds of opioid‐ADEs (OR, 3.72 [1.35, 10.23]; P = 0.007) and need for rescue (5.5 [1.7, 17.82]; P = 0.002).

Conclusions

Findings from this study suggest that strategies such as early use of adjuvant nonopioids may reduce risk of opioid‐ADEs postoperatively. Furthermore, children who require supplemental oxygen early postoperatively may be at heightened risk of later events.
CXCR7 mediates SDF1‐induced melanocyte migration
Authors: Lee Eunkyung , Han Jiyeon , Kim Kwangmi , Choi Hyunjung , Cho Eun‐Gyung , Lee Tae Ryong
Published: September 2012

Melanoblasts are derived from the neural crest and migrate to the dermal/epidermal border of skin and hair bulges. Although melanoblast migration during embryogenesis has been well investigated, there are only a few reports regarding the migration of mature melanocytes. Here, we demonstrate that a chemokine, stromal‐derived factor‐1 (SDF1, also known as CXCL12), and one of its receptor CXCR7 regulate normal human epidermal melanocyte (NHEM) migration. We found that SDF1 induces the directional migration of NHEMs. Interestingly, although both CXCR4 and CXCR7 are expressed in NHEMs, blockade of CXCR4 using a CXCR4‐specific neutralizing antibody did not exert any influence on the SDF1‐induced migration of NHEMs, whereas blockade of CXCR7 using a CXCR7‐specific neutralizing antibody did influence migration. Furthermore, SDF1‐induced NHEMs migration exhibited the early hallmark events of CXCR7 signaling associated with MAP kinase activation. It is known that the phosphorylation of ERK through CXCR7 signaling is mediated by β‐arrestins. The treatment of NHEMs with SDF1 resulted in the phosphorylation of ERK in a β‐arrestin 2‐dependent manner. These results suggest that melanocytes may have a unique mechanism of migration via SDF1/CXCR7 signaling that is different from that of other cell types.
Development of new in vivo imaging methodology and system for the rapid and quantitative evaluation of the visual appearance of facial skin firmness
Authors: Miyamoto Kukizo , Nagasawa Hitomi , Inoue Yasuko , Nakaoka Kenichi , Hirano Ayaka , Kawada Akira
Published: September 2012

Background/aims

Lack of firmness is a key sign of skin aging, but there are no methods for quantifying the firmness of facial skin as perceived visually. The objective of this study was to develop a convenient and accurate method for this purpose.

Methods

A compact imaging system (Magic Ring®) was developed to capture images of facial skin. By using an image‐analysis algorithm, the number of facial lines and their direction were analyzed to give an index termed the ‘Ageless Vector’. Correlations between the Ageless Vector and visually perceived facial skin firmness, mechanical skin firmness (R5), and actual age were examined for 108 Asian females. The technique was also used to assess the effects of a 14‐day skin‐moisturization regimen in 47 Asian female volunteers.

Results

The Ageless Vector showed highly significant correlation with visually perceived skin firmness (r = 0.816) and significant correlation with mechanical skin firmness (R5) (r = –0.775). Skin moisturization significantly improved both the Ageless Vector (P < 0.05) and the visual grading of apparent skin firmness.

Conclusions

We confirmed by two clinical studies that the imaging methodology using the Ageless Vector and the Magic Ring facial‐imaging system was sufficiently sensitive to permit the measurement of apparent visible skin firmness and that it is an excellent method suitable for practical in vivo applications.
Mass distribution and moments of inertia in the outer shells of the Earth
Authors: Caputo Michele , Caputo Riccardo
Published: September 2012

Terra Nova, 25, 38–47, 2013

Different mass distributions within the lithosphere and the sub‐lithospheric mantle have been considered here to calculate the moment of inertia of the outer shell of the Earth relative to many different axes. In particular, we seek for the maximum moment of inertia, MMI, which represents the theoretical rotation axis that the outer shell of the Earth should attain for maintaining equilibrium. For the present‐day distribution of mass at depth, we consider the most updated crustal, lithospheric and sub‐lithospheric models satisfying general geological and geophysical laws. When considering only the lithospheric shell, as if it were fully independent from the sub‐lithospheric mantle (i.e. totally decoupled), our numerical results show the complete lack of equilibrium in terms of moment of inertia with respect to the present‐day rotation axis. In further calculations, we also included the sub‐lithospheric mantle assuming different density values as well as different compensation depths. Among the numerous tests, the mass distribution models showing theoretical axes of rotation closest to the present‐day one are those obtained with a compensation depth of 400 km. The possible implications of these results in terms of westward plates drift and depth of possible decoupling layers within the mantle are discussed.
Arabidopsis wat1 (walls are thin1)‐mediated resistance to the bacterial vascular pathogen, Ralstonia solanacearum, is accompanied by cross‐regulation of salicylic acid and tryptophan metabolism
Authors: Denancé Nicolas , Ranocha Philippe , Oria Nicolas , Barlet Xavier , Rivière Marie‐Pierre , Yadeta Koste A. , Hoffmann Laurent , Perreau François , Clément Gilles , Maia‐Grondard Alessandra , van den Berg Grardy C.M. , Savelli Bruno , Fournier Sylvie , Aubert Yann , Pelletier Sandra , Thomma Bart P.H.J. , Molina Antonio , Jouanin Lise , Marco Yves , Goffner Deborah
Published: September 2012

Inactivation of Arabidopsis WAT1 (Walls Are Thin1), a gene required for secondary cell‐wall deposition, conferred broad‐spectrum resistance to vascular pathogens, including the bacteria Ralstonia solanacearum and Xanthomonas campestris pv. campestris, and the fungi Verticillium dahliae and Verticillium albo‐atrum. Introduction of NahG, the bacterial salicylic acid (SA)‐degrading salicylate hydroxylase gene, into the wat1 mutant restored full susceptibility to both R. solanacearum and X. campestris pv. campestris. Moreover, SA content was constitutively higher in wat1 roots, further supporting a role for SA in wat1‐mediated resistance to vascular pathogens. By combining transcriptomic and metabolomic data, we demonstrated a general repression of indole metabolism in wat1‐1 roots as shown by constitutive down‐regulation of several genes encoding proteins of the indole glucosinolate biosynthetic pathway and reduced amounts of tryptophan (Trp), indole‐3‐acetic acid and neoglucobrassicin, the major form of indole glucosinolate in roots. Furthermore, the susceptibility of the wat1 mutant to R. solanacearum was partially restored when crossed with either the trp5 mutant, an over‐accumulator of Trp, or Pro35S:AFB1‐myc, in which indole‐3‐acetic acid signaling is constitutively activated. Our original hypothesis placed cell‐wall modifications at the heart of the wat1 resistance phenotype. However, the results presented here suggest a mechanism involving root‐localized metabolic channeling away from indole metabolites to SA as a central feature of wat1 resistance to R. solanacearum.
Long‐range correlations in motor unit discharge times at low forces are modulated by visual gain and age
Authors: Jordan Kimberlee , Jesunathadas Mark , Sarchet Derek M. , Enoka Roger M.
Published: September 2012

New findings

What is the central question of this study?

Changes in visual gain do not influence the time‐dependent structure of motor unit discharge variability in young adults; however, the influence of visual gain on the regularity of motor unit discharge times in old adults is unknown.

What is the main finding and its importance?

We examined the association between visual information and the size and temporal structure of the variability in index finger force and motor unit discharge times when young and old adults performed isometric contractions with a hand muscle. We showed that the regularity with which motor units discharged action potentials decreased with increased gain of visual feedback, regardless of age.

The purpose of this investigation was to examine the association between visual information and the size and temporal structure of the variability in index finger force and motor unit discharge times when young and old adults performed isometric contractions with a hand muscle. Single motor units (n= 32) in the first dorsal interosseus muscle were recorded as subjects [16 young (18–35 years old) and 16 old (≥70 years old)] exerted a constant abduction force with the index finger during 60 s isometric contractions. The target force was displayed on a monitor in front of the subjects, and they were asked to match the index finger force to a target force. The amount of visual feedback, or gain of the signal, was varied between 24 (low gain) and 1175 pixels N−1 (high gain). In addition, some trials were performed in the absence of visual feedback. The dependent variables were the variability (standard deviation and coefficient of variation) and the regularity (detrended fluctuation analysis self‐similarity parameter, α) of motor unit discharge times and the abduction force. Motor unit discharge times became less regular with an increase in visual feedback gain for both young and old adults, whereas motor unit discharge variability was not influenced by changes in visual gain. The regularity of motor unit discharge times was less for old adults than for young adults, but the variability was greater for old adults. However, there was a significant association between the regularity of motor unit discharge times and the regularity of force for the old adults, but not the young adults. These observations suggest that adjustments in the synaptic inputs delivered to motor neurons with changes in the visual gain differed for young and old adults.
A Target Tracking Approach for Nonholonomic Agents Based on Artificial Potentials and Sliding Mode Control
Authors: Gazi Veysel , Fidan Barış , Ordóñez Raúl , İlter Köksal M.
Published: September 2012

In this paper, we consider the task of tracking a maneuvering target both with a single nonholonomic agent and a swarm of nonholonomic agents. In order to achieve the tracking task, a decentralized continuous-time control scheme, which combines artificial potentials and sliding mode control techniques, is developed via constructive analysis. The effectiveness of the proposed control scheme is established analytically and demonstrated via a set of simulation results.
Fuzzy Sliding Mode Control of Robotic Manipulators With Kinematic and Dynamic Uncertainties
Authors: Liu Haitao , Zhang Tie
Published: September 2012

Sliding mode control is a very attractive control scheme with strong robustness to structured and unstructured uncertainties as well as to external disturbances. In this paper, a robust fuzzy sliding mode controller, which is combined with an adaptive fuzzy logic system, is proposed to improve the control performance of the robotic manipulator with kinematic and dynamic uncertainties. In this controller, the sliding mode control is employed to improve the control accuracy and the robustness of the robotic manipulator, and the fuzzy logic control is adopted to approximate various uncertainties and to eliminate the chattering without the help of any prior knowledge of system uncertainties. The effectiveness of the proposed controller is then verified by the simulations on a 2-DOF (degrees of freedom) robotic manipulator and the experiments on an SCARA robot with four degrees of freedom. Simulated and experimental results indicate that the proposed controller is effective in the robust tracking of the robotic manipulator with kinematic and dynamic uncertainties.
Laser polishing of niobium for application to superconducting radio frequency cavities
Authors: Singaravelu Senthilraja , Klopf J. Michael , Xu Chen , Krafft Geoffrey , Kelley Michael J.
Published: September 2012

Superconducting radio frequency niobium cavities are at the heart of an increasing number of particle accelerators. Their performance is dominated by a several nanometer thick layer at the interior surface. Maximizing the smoothness of this surface is critical, and aggressive chemical treatments are now employed to this end. The authors describe laser-induced surface melting as an alternative “greener” approach. Selection of laser parameters guided by modeling achieved melting that reduced the surface roughness from the fabrication process. The resulting topography was examined by scanning electron microscope and atomic force microscope (AFM). Plots of power spectral density computed from the AFM data give further insight into the effect of laser melting on the topography of the mechanically polished (only) niobium.
Cilia at the Node of Mouse Embryos Sense Fluid Flow for Left-Right Determination via Pkd2
Authors: Yoshiba Satoko , Shiratori Hidetaka , Kuo Ivana Y. , Kawasumi Aiko , Shinohara Kyosuke , Nonaka Shigenori , Asai Yasuko , Sasaki Genta , Belo Jose Antonio , Sasaki Hiroshi , Nakai Junichi , Dworniczak Bernd , Ehrlich Barbara E. , Pennekamp Petra , Hamada Hiroshi
Published: September 2012

Distinguishing Right from Left

In most vertebrates during embryonic development, rotational movement of the cilia within a structure in the embryo, known as the node, generates unidirectional flow required for future left-right asymmetry of the internal organs. The flow may transport a determinant molecule or provide mechanical force. However, it is not clear how the flow is sensed.

Yoshiba
et al.

(p.
226
, published online 13 September; see the Perspective by

Norris and Grimes

) show that nodal flow in mouse embryos is sensed by the cilia of perinodal cells located at the edge of the node, in a manner dependent on Pkd2, a Ca
2+
-permeable cation channel that has been implicated in polycystic kidney disease in humans.
Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism
Authors: Baudouin Stéphane J. , Gaudias Julien , Gerharz Stefan , Hatstatt Laetitia , Zhou Kuikui , Punnakkal Pradeep , Tanaka Kenji F. , Spooren Will , Hen Rene , De Zeeuw Chris I. , Vogt Kaspar , Scheiffele Peter
Published: September 2012

Reversing Autism in Mice

Autism comprises a heterogeneous group of neurodevelopmental disorders characterized by defects in communication and social inter action. A group of nonsyndromic forms of autism is associated with mutations in the neuroligin genes, which encode postsynaptic adhesion molecules. Using a reversible knockout approach,

Baudouin
et al.

(p.
128
, published online 13 September) investigated the in vivo functions of neuroligin-3 in the mouse cerebellum. Mutant mice showed a major defect in metabotropic glutamate receptor–dependent, long-term potentiation; disrupted heterosynaptic competition; and ectopic synapse formation in vivo. These synaptic defects could be rescued by reactivation of the neuroligin gene in the adult.
A Genomic Regulatory Element That Directs Assembly and Function of Immune-Specific AP-1–IRF Complexes
Authors: Glasmacher Elke , Agrawal Smita , Chang Abraham B. , Murphy Theresa L. , Zeng Wenwen , Vander Lugt Bryan , Khan Aly A. , Ciofani Maria , Spooner Chauncey J. , Rutz Sascha , Hackney Jason , Nurieva Roza , Escalante Carlos R. , Ouyang Wenjun , Littman Dan R. , Murphy Kenneth M. , Singh Harinder
Published: September 2012

Helping T Helper Transcription

Members of the interferon response family of transcription factors (IRFs) are specifically expressed in immune cells and are known to regulate their differentiation. IRF4 and IRF8 regulate gene expression by binding to other transcription factors, which results in their recruitment to composite motifs in the genome. Although the specific mechanism of how this regulation works in some immune cells is understood, how it occurs in T cells is not clear because the transcription factors that normally partner with IRFs are absent. Using genomic analysis,

Glasmacher
et al.

(p.
975
, published online 13 September; see the Perspective by

Martinez and Rao

) now identify IRF4–AP-1 composite elements in T helper 17 (T
H
17) cells and show that IRF4 and the AP-1 factor Batf cooperatively assemble on a large array of genes required for T
H
17 cell differentiation and function. Assembly of such heterodimers was also observed in T
H
2 cells, B cells, and dendritic cells, which suggests the general importance of this motif in immune cell differentiation.
Synergistic Effects of High Hydrostatic Pressure, Mild Heating, and Amino Acids on Germination and Inactivation of Clostridium sporogenes Spores
Authors: Ishimori Takateru , Takahashi Katsutoshi , Goto Masato , Nakagawa Suguru , Kasai Yoshiaki , Konagaya Yukifumi , Batori Hiroshi , Kobayashi Atsushi , Urakami Hiroshi
Published: September 2012

The synergistic effects of high hydrostatic pressure (HHP), mild heating, and amino acids on the germination of
Clostridium sporogenes
spores were examined by determining the number of surviving spores that returned to vegetative growth after pasteurization following these treatments. Pressurization at 200 MPa at a temperature higher than 40°C and treatment with some of the 19
l
-amino acids at 10 mM or higher synergistically facilitated germination. When one of these factors was omitted, the level of germination was insignificant. Pressures of 100 and 400 MPa were less effective than 200 MPa. The spores were effectively inactivated by between 1.8 and 4.8 logs by pasteurization at 80°C after pressurization at 200 MPa at 45°C for 120 min with one of the amino acids with moderate hydrophobicity, such as Leu, Phe, Cys Met, Ala, Gly, or Ser. However, other amino acids showed poor inactivation effects of less than 0.9 logs. Spores in solutions containing 80 mM of either Leu, Phe, Cys, Met, Ala, Gly, or Ser were successfully inactivated by pasteurization by more than 5.4 logs after pressurization at 200 MPa at 70°C for 15 to 120 min. Ala and Met reduced the spore viability by 2.8 and 1.8 logs, respectively, by pasteurization at a concentration of 1 mM under 200 MPa at 70°C. These results indicate that germination of the spores is facilitated by a combination of high hydrostatic pressure, mild heating, and amino acids.
Germination and Amplification of Anthrax Spores by Soil-Dwelling Amoebas
Authors: Dey Rafik , Hoffman Paul S. , Glomski Ian J.
Published: September 2012

While anthrax is typically associated with bioterrorism, in many parts of the world the anthrax bacillus (
Bacillus anthracis
) is endemic in soils, where it causes sporadic disease in livestock. These soils are typically rich in organic matter and calcium that promote survival of resilient
B. anthracis
spores. Outbreaks of anthrax tend to occur in warm weather following rains that are believed to concentrate spores in low-lying areas where runoff collects. It has been concluded that elevated spore concentrations are not the result of vegetative growth as
B. anthracis
competes poorly against indigenous bacteria. Here, we test an alternative hypothesis in which amoebas, common in moist soils and pools of standing water, serve as amplifiers of
B. anthracis
spores by enabling germination and intracellular multiplication. Under simulated environmental conditions, we show that
B. anthracis
germinates and multiplies within
Acanthamoeba castellanii
. The growth kinetics of a fully virulent
B. anthracis
Ames strain (containing both the pX01 and pX02 virulence plasmids) and vaccine strain Sterne (containing only pX01) inoculated as spores in coculture with
A. castellanii
showed a nearly 50-fold increase in spore numbers after 72 h. In contrast, the plasmidless strain 9131 showed little growth, demonstrating that plasmid pX01 is essential for growth within
A. castellanii
. Electron and time-lapse fluorescence microscopy revealed that spores germinate within amoebal phagosomes, vegetative bacilli undergo multiplication, and, following demise of the amoebas, bacilli sporulate in the extracellular milieu. This analysis supports our hypothesis that amoebas contribute to the persistence and amplification of
B. anthracis
in natural environments.
Evidence that Cryptosporidium parvum Populations Are Panmictic and Unstructured in the Upper Midwest of the United States
Authors: Herges Grant R. , Widmer Giovanni , Clark Mark E. , Khan Eakalak , Giddings Catherine W. , Brewer Matt , McEvoy John M.
Published: September 2012

Cryptosporidium parvum
is a zoonotic protozoan parasite that causes cryptosporidiosis, an infectious diarrheal disease primarily affecting humans and neonatal ruminants. Understanding the transmission dynamics of
C. parvum
, particularly the specific contributions of zoonotic and anthroponotic transmission, is critical to the control of this pathogen. This study used a population genetics approach to better understand the transmission of
C. parvum
in the Upper Midwest United States. A total of 254
C. parvum
isolates from cases of human cryptosporidiosis in Minnesota and Wisconsin and diarrheic calves in Minnesota, Wisconsin, and North Dakota were genotyped at eight polymorphic loci. Isolates with a complete profile from all eight loci (
n
= 212) were used to derive a multilocus genotype (MLT), which was used in population genetic analyses. Among the 94 MLTs identified, 60 were represented by a single isolate. Approximately 20% of isolates belonged to MLT 2, a group that included both human and cattle isolates. Population analyses revealed a predominantly panmictic population with no apparent geographic or host substructuring.
Comparison of Methods for Evaluation of the Bactericidal Activity of Copper-Sputtered Surfaces against Methicillin-Resistant Staphylococcus aureus
Authors: Rio Laura , Kusiak-Nejman Ewelina , Kiwi John , Bétrisey Bertrand , Pulgarin César , Trampuz Andrej , Bizzini Alain
Published: September 2012

Bacteria can survive on hospital textiles and surfaces, from which they can be disseminated, representing a source of health care-associated infections (HCAIs). Surfaces containing copper (Cu), which is known for its bactericidal properties, could be an efficient way to lower the burden of potential pathogens. The antimicrobial activity of Cu-sputtered polyester surfaces, obtained by direct-current magnetron sputtering (DCMS), against methicillin-resistant
Staphylococcus aureus
(MRSA) was tested. The Cu-polyester microstructure was characterized by high-resolution transmission electron microscopy to determine the microstructure of the Cu nanoparticles and by profilometry to assess the thickness of the layers. Sputtering at 300 mA for 160 s led to a Cu film thickness of 20 nm (100 Cu layers) containing 0.209% (wt/wt) polyester. The viability of MRSA strain ATCC 43300 on Cu-sputtered polyester was evaluated by four methods: (i) mechanical detachment, (ii) microcalorimetry, (iii) direct transfer onto plates, and (iv) stereomicroscopy. The low efficacy of mechanical detachment impeded bacterial viability estimations. Microcalorimetry provided only semiquantitative results. Direct transfer onto plates and stereomicroscopy seemed to be the most suitable methods to evaluate the bacterial inactivation potential of Cu-sputtered polyester surfaces, since they presented the least experimental bias. Cu-polyester samples sputtered for 160 s by DCMS were further tested against 10 clinical MRSA isolates and showed a high level of bactericidal activity, with a 4-log
10
reduction in the initial MRSA load (10
6
CFU) within 1 h. Cu-sputtered polyester surfaces might be of use to prevent the transmission of HCAI pathogens.
Sequential Use of Nitrogen Compounds by Saccharomyces cerevisiae during Wine Fermentation: a Model Based on Kinetic and Regulation Characteristics of Nitrogen Permeases
Authors: Crépin Lucie , Nidelet Thibault , Sanchez Isabelle , Dequin Sylvie , Camarasa Carole
Published: September 2012

The efficiency of nitrogen use is a key determinant of the completion of alcoholic fermentation. We analyzed the kinetics of consumption of 18 nitrogen compounds by 14Saccharomyces cerevisiaestrains of various origins in a synthetic medium that mimicked a grape must. The kinetic profiles of total nitrogen consumption were diverse, but the order of nitrogen source consumption was similar for all strains. The nitrogen compounds could be classified into three groups, according to their order of use: prematurely consumed (Lys), early consumed (Asp, Thr, Glu, Leu, His, Met, Ile, Ser, Gln, and Phe), and late consumed (ammonium, Val, Arg, Ala, Trp, and Tyr). The initial concentrations of these compounds did not alter the order in which they were consumed, except for arginine and ammonium. Early consumed amino acids are transported by specific permeases under Ssy1p-Ptr3p-Ssy5 (SPS)-mediated control that are expressed at the beginning of consumption. Most nitrogen compounds consumed late are transported by permeases under nitrogen catabolite repression (NCR), and others (Val, Trp, and Tyr) are transported by SPS-regulated low-affinity permeases. Therefore, the kinetic characteristics of transporters, as well as SPS and NCR, are likely key factors controlling the temporal sequence of consumption of nitrogen compounds and constitute a system highly conserved inS. cerevisiaespecies. This work sheds new light on the mechanistic basis of the sequential use of different nitrogen compounds in complex environments.
The
pmr
Gene, Encoding a Ca
2+
-ATPase, Is Required for Calcium and Manganese Homeostasis and Normal Development of Hyphae and Conidia in Neurospora crassa
Authors: Bowman Barry J. , Abreu Stephen , Johl Jessica K. , Bowman Emma Jean
Published: September 2012

The
pmr
gene is predicted to encode a Ca
2+
-ATPase in the secretory pathway. We examined two strains of
Neurospora crassa
that lacked PMR: the Δ
pmr
strain, in which
pmr
was completely deleted, and

pmr
RIP

, in which the gene was extensively mutated. Both strains had identical, complex phenotypes. Compared to the wild type, these strains required high concentrations of calcium or manganese for optimal growth and had highly branched, slow-growing hyphae. They conidiated poorly, and the shape and size of the conidia were abnormal. Calcium accumulated in the Δ
pmr
strains to only 20% of the wild-type level. High concentrations of MnCl
2
(1 to 5 mM) in growth medium partially suppressed the morphological defects but did not alter the defect in calcium accumulation. The Δ
pmr
Δ
nca-2
double mutant (
nca-2
encodes a Ca
2+
-ATPase in the plasma membrane) accumulated 8-fold more calcium than the wild type, and the morphology of the hyphae was more similar to that of wild-type hyphae. Previous experiments failed to show a function for
nca-1
, which encodes a SERCA-type Ca
2+
-ATPase in the endoplasmic reticulum (B. J. Bowman, S. Abreu, E. Margolles-Clark, M. Draskovic, and E. J. Bowman, Eukaryot. Cell 10:654-661, 2011). The
pmr

RIP

Δ
nca-1
double mutant accumulated small amounts of calcium, like the Δ
pmr
strain, but exhibited even more extreme morphological defects. Thus, PMR can apparently replace NCA-1 in the endoplasmic reticulum, but NCA-1 cannot replace PMR. The morphological defects in the Δ
pmr
strain are likely caused, in part, by insufficient concentrations of calcium and manganese in the Golgi compartment; however, PMR is also needed to accumulate normal levels of calcium in the whole cell.
Analysis of the Regulated Transcriptome of Neisseria meningitidis in Human Blood Using a Tiling Array
Authors: Del Tordello Elena , Bottini Silvia , Muzzi Alessandro , Serruto Davide
Published: September 2012

Neisseria meningitidisis the major cause of septicemia and meningococcal meningitis. During the course of infection, the bacterium must adapt to different host environments as a crucial factor for survival and dissemination; in particular, one of the crucial factors inN. meningitidispathogenesis is the ability to grow and survive in human blood. We recently showed thatN. meningitidisalters the expression of 30% of the open reading frames (ORFs) of the genome during incubation in human whole blood and suggested the presence of fine regulation at the gene expression level in order to control this step of pathogenesis. In this work, we used a customized tiling oligonucleotide microarray to define the changes in the whole transcriptional profile ofN. meningitidisin a time course experiment ofex vivobacteremia by incubating bacteria in human whole blood and then recovering RNA at different time points. The application of a newly developed bioinformatic tool to the tiling array data set allowed the identification of new transcripts—small intergenic RNAs,cis-encoded antisense RNAs, mRNAs with extended 5′ and 3′ untranslated regions (UTRs), and operons—differentially expressed in human blood. Here, we report a panel of expressed small RNAs, some of which can potentially regulate genes involved in bacterial metabolism, and we show, for the first time inN. meningitidis, extensive antisense transcription activity. This analysis suggests the presence of a circuit of regulatory RNA elements used byN. meningitidisto adapt to proliferate in human blood that is worthy of further investigation.
Novel High-Molecular-Weight, R-Type Bacteriocins of Clostridium difficile
Authors: Gebhart Dana , Williams Steven R. , Bishop-Lilly Kimberly A. , Govoni Gregory R. , Willner Kristin M. , Butani Amy , Sozhamannan Shanmuga , Martin David , Fortier Louis-Charles , Scholl Dean
Published: September 2012

Clostridium difficile
causes one of the leading nosocomial infections in developed countries, and therapeutic choices are limited. Some strains of
C. difficile
produce phage tail-like particles upon induction of the SOS response. These particles have bactericidal activity against other
C. difficile
strains and can therefore be classified as bacteriocins, similar to the R-type pyocins of
Pseudomonas aeruginosa
. These R-type bacteriocin particles, which have been purified from different strains, each have a different
C. difficile
-killing spectrum, with no one bacteriocin killing all
C. difficile
isolates tested. We have identified the genetic locus of these “diffocins” (open reading frames 1359 to 1376) and have found them to be common among the species. The entire diffocin genetic locus of more than 20 kb was cloned and expressed in
Bacillus subtilis
, and this resulted in production of bactericidal particles. One of the interesting features of these particles is a very large structural protein of ∼200 kDa, the product of gene 1374. This large protein determines the killing spectrum of the particles and is likely the receptor-binding protein. Diffocins may provide an alternate bactericidal agent to prevent or treat infections and to decolonize individuals who are asymptomatic carriers.
Streptococcus pneumoniae Uses Glutathione To Defend against Oxidative Stress and Metal Ion Toxicity
Authors: Potter Adam J. , Trappetti Claudia , Paton James C.
Published: September 2012

The thiol-containing tripeptide glutathione is an important cellular constituent of many eukaryotic and prokaryotic cells. In addition to its disulfide reductase activity, glutathione is known to protect cells from many forms of physiological stress. This report represents the first investigation into the role of glutathione in the Gram-positive pathogen
Streptococcus pneumoniae
. We demonstrate that pneumococci import extracellular glutathione using the ABC transporter substrate binding protein GshT. Mutation of
gshT
and the gene encoding glutathione reductase (
gor
) increases pneumococcal sensitivity to the superoxide generating compound paraquat, illustrating the importance of glutathione utilization in pneumococcal oxidative stress resistance. In addition, the
gshT
and
gor
mutant strains are hypersensitive to challenge with the divalent metal ions copper, cadmium, and zinc. The importance of glutathione utilization in pneumococcal colonization and invasion of the host is demonstrated by the attenuated phenotype of the
gshT
mutant strain in a mouse model of infection.
Greater trochanteric pain syndrome: defining the clinical syndrome
Authors: Fearon Angela M , Scarvell Jennie M , Neeman Terry , Cook Jill L , Cormick Wes , Smith Paul N
Published: September 2012

Background

Effective treatment of hip pain improves population health and quality of life. Accurate differential diagnosis is fundamental to effective treatment. The diagnostic criteria for one common hip problem, greater trochanteric pain syndrome (GTPS) have not been well defined.

Purpose

To define the clinical presentation of GTPS.

Methods

Forty-one people with GTPS, 20 with hip osteoarthritis (OA), and 23 age-matched and sex-matched asymptomatic participants (ASC) were recruited. Inclusion and exclusion criteria ensured mutually exclusive groups. Assessment: the Harris hip score (HHS), a battery of clinical tests, and single leg stance (SLS). Participants identified the site of reproduced pain. Analysis: Fisher's exact test, analysis of variance (ANOVA) informed recursive partitioning to develop two classification trees.

Results

Maximum walking distance and the ability to manipulate shoes and socks were the only HHS domains to differentiate GTPS from OA (ANOVA: p=0.010 and <0.001); OR (95% CI) of 3.47 (1.09 to 10.93) and 0.06 (0.00 to 0.26), respectively. The lateral hip pain (LHP) classification tree: (dichotomous LHP associated with a flexion abduction external rotation (FABER) test) had a mean (SE) sensitivity and specificity of 0.81 (0.019) and 0.82 (0.044), respectively. A non-specific hip pain classification tree had a mean (SE) sensitivity and specificity of 0.78 (0.058) and 0.28 (0.080).

Conclusions

Patients with LHP in the absence of difficulty with manipulating shoes and socks, together with pain on palpation of the greater trochanter and LHP with a FABER test are likely to have GTPS.
Musculoskeletal disorders among municipal solid waste collectors in Mansoura, Egypt: a cross-sectional study
Authors: Abou-ElWafa Hala Samir , El-Bestar Sohair Fouad , El-Gilany Abdel-Hady , Awad Ehab El-Sayed
Published: September 2012

Objective

To assess the percentage of musculoskeletal complaints and their possible risk factors among municipal solid waste (MSW) collectors.

Design

A descriptive cross-sectional study with a comparison group.

Setting

Primary level of care, at the Western Municipality of Mansoura City, Egypt.

Participants

A total of 160 male MSW collectors fulfilled the eligibility criteria and 120 of them participated in the study (response rate of 75%). The inclusion criteria were permanent or temporary solid waste collectors employed for 1 year or more. A comparison group of 110 male service workers at the Faculty of Medicine, Mansoura University, comparable to MSW collectors in most of the variables.

Outcome

The percentage of musculoskeletal disorders (MSDs) among collectors, their risk factors (socio-demographic, psychosocial, physical), and the independent risk factors for having the disorders.

Results

The percentage of musculoskeletal complaints during the past 12 months was higher among MSW collectors (60.8%) than the comparison group (43.6%). Low back was the most frequently affected body region among MSW collectors. The differences in the distribution of musculoskeletal complaints between the two groups were statistically significant for the neck and hip/thigh regions. Logistic regression analysis revealed that the independent risk factors for musculoskeletal symptoms among MSW collectors were the longer duration of employment (OR=0.4, 95% CI=0.1 to 0.9); low decision latitude (OR=0.3, 95% CI=0.1 to 0.7); lifting, pulling; pushing/carrying loads >20 kg (OR=5.5, 95% CI=1.8 to 17.0) and walking for long periods of time (OR=2.6, 95% CI=1.1 to 6.6).

Conclusions

Musculoskeletal complaints are highly prevalent among MSW collectors which require engineering, medical and legislative measures. We suggest further research in the interventions that could reduce the high percentage among collectors.