bluuebunny/crossref_metadata_2025 huggingface dataset:
Degassing of reduced carbon from planetary basalts
Authors: Wetzel Diane T. , Rutherford Malcolm J. , Jacobsen Steven D. , Hauri Erik H. , Saal Alberto E.
Published: April 2013

Degassing of planetary interiors through surface volcanism plays an important role in the evolution of planetary bodies and atmospheres. On Earth, carbon dioxide and water are the primary volatile species in magmas. However, little is known about the speciation and degassing of carbon in magmas formed on other planets (i.e., Moon, Mars, Mercury), where the mantle oxidation state [oxygen fugacity (fO2)] is different from that of the Earth. Using experiments on a lunar basalt composition, we confirm that carbon dissolves as carbonate at anfO2higher than -0.55 relative to the iron wustite oxygen buffer (IW-0.55), whereas at a lowerfO2, we discover that carbon is present mainly as iron pentacarbonyl and in smaller amounts as methane in the melt. The transition of carbon speciation in mantle-derived melts atfO2less than IW-0.55 is associated with a decrease in carbon solubility by a factor of 2. Thus, thefO2controls carbon speciation and solubility in mantle-derived melts even more than previous data indicate, and the degassing of reduced carbon from Fe-rich basalts on planetary bodies would produce methane-bearing, CO-rich early atmospheres with a strong greenhouse potential.
MicroRNA-92b regulates the development of intermediate cortical progenitors in embryonic mouse brain
Authors: Nowakowski Tomasz Jan , Fotaki Vassiliki , Pollock Andrew , Sun Tao , Pratt Thomas , Price David J.
Published: April 2013

Cerebral cortical neurons arise from radial glia (direct neurogenesis) or from intermediate progenitors (indirect neurogenesis); intriguingly, the sizes of intermediate progenitor populations and the cortices they generate correlate across species. The generation of intermediate progenitors is regulated by the transcription factor Tbr2, whose expression marks these cells. We investigated how this mechanism might be controlled. We found that acute blockade of mature microRNA biosynthesis in murine cortical progenitors caused a rapid cell autonomous increase in numbers of Tbr2-expressing cells. Acute microRNA-92b (miR-92b) gain of function caused rapid reductions in numbers of Tbr2-expressing cells and proliferating intermediate progenitors. Acute miR-92b loss of function had opposite effects. These findings indicate that miR-92b limits the production of intermediate cortical progenitors.
Deficiency of the RIIβ subunit of PKA affects locomotor activity and energy homeostasis in distinct neuronal populations
Authors: Zheng Ruimao , Yang Linghai , Sikorski Maria A. , Enns Linda C. , Czyzyk Traci A. , Ladiges Warren C. , McKnight G. Stanley
Published: April 2013

Significance

Genetic mutations in mice and humans have dramatic effects on the overall ability of the organism to regulate body weight and maintain a homeostatic balance between energy expenditure and calorie intake. We are studying mice with a null mutation in the RIIβ subunit of the cAMP-dependent protein kinase system that renders them lean and resistant to diet-induced obesity. These mice also exhibit greatly increased physical activity. Our studies show that the brain regulates all of these phenotypes, but, surprisingly, the specific neurons that determine the phenotypes are distinct and the increased physical activity is not required for the lean phenotype.
Overcoming drug-resistant herpes simplex virus (HSV) infection by a humanized antibody
Authors: Krawczyk Adalbert , Arndt Michaela A. E. , Grosse-Hovest Ludger , Weichert Wilko , Giebel Bernd , Dittmer Ulf , Hengel Hartmut , Jäger Dirk , Schneweis Karl E. , Eis-Hübinger Anna M. , Roggendorf Michael , Krauss Jürgen
Published: April 2013

Despite the availability of antiviral chemotherapy, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections remain a severe global health problem. Of particular concern is the growing incidence of drug resistance in immunocompromised patients, which stresses the urgency to develop new effective treatment alternatives. We have developed a humanized monoclonal antibody (mAb hu2c) that completely abrogates viral cell-to-cell spread, a key mechanism by which HSV-1/2 escapes humoral immune surveillance. Moreover, mAb hu2c neutralized HSV fully independent of complement and/or immune effector cell recruitment in a highly efficient manner. Prophylactic and therapeutic administration of mAb hu2c completely prevented infection-related mortality of severely immunodeficient mice being challenged with a lethal dose of HSV-1. The high neutralization capacity of mAb hu2c was fully maintained toward clinical HSV isolates being multiresistant to standard antiviral drugs, and infection was fully resolved in 7/8 nonobese diabetic/SCID mice being infected with a multidrug resistant HSV-1 patient isolate. Immunohistochemical studies revealed no significant cross-reactivity of the antibody toward human tissues. These features warrant further clinical development of mAb hu2c as an immunotherapeutic compound for the management of severe and particularly drug-resistant HSV infections.
Protein cold adaptation strategy via a unique seven-amino acid domain in the icefish (
Chionodraco hamatus
) PEPT1 transporter
Authors: Rizzello Antonia , Romano Alessandro , Kottra Gabor , Acierno Raffaele , Storelli Carlo , Verri Tiziano , Daniel Hannelore , Maffia Michele
Published: April 2013

Adaptation of organisms to extreme environments requires proteins to work at thermodynamically unfavorable conditions. To adapt to subzero temperatures, proteins increase the flexibility of parts of, or even the whole, 3D structure to compensate for the lower thermal kinetic energy available at low temperatures. This may be achieved through single-site amino acid substitutions in regions of the protein that undergo large movements during the catalytic cycle, such as in enzymes or transporter proteins. Other strategies of cold adaptation involving changes in the primary amino acid sequence have not been documented yet. In Antarctic icefish (
Chionodraco hamatus
) peptide transporter 1 (PEPT1), the first transporter cloned from a vertebrate living at subzero temperatures, we came upon a unique principle of cold adaptation. A de novo domain composed of one to six repeats of seven amino acids (VDMSRKS), placed as an extra stretch in the cytosolic COOH-terminal region, contributed per se to cold adaptation. VDMSRKS was in a protein region uninvolved in transport activity and, notably, when transferred to the COOH terminus of a warm-adapted (rabbit) PEPT1, it conferred cold adaptation to the receiving protein. Overall, we provide a paradigm for protein cold adaptation that relies on insertion of a unique domain that confers greater affinity and maximal transport rates at low temperatures. Due to its ability to transfer a thermal trait, the VDMSRKS domain represents a useful tool for future cell biology or biotechnological applications.
Evolutionary change during experimental ocean acidification
Authors: Pespeni Melissa H. , Sanford Eric , Gaylord Brian , Hill Tessa M. , Hosfelt Jessica D. , Jaris Hannah K. , LaVigne Michèle , Lenz Elizabeth A. , Russell Ann D. , Young Megan K. , Palumbi Stephen R.
Published: April 2013

Rising atmospheric carbon dioxide (CO2) conditions are driving unprecedented changes in seawater chemistry, resulting in reduced pH and carbonate ion concentrations in the Earth’s oceans. This ocean acidification has negative but variable impacts on individual performance in many marine species. However, little is known about the adaptive capacity of species to respond to an acidified ocean, and, as a result, predictions regarding future ecosystem responses remain incomplete. Here we demonstrate that ocean acidification generates striking patterns of genome-wide selection in purple sea urchins (Strongylocentrotus purpuratus) cultured under different CO2levels. We examined genetic change at 19,493 loci in larvae from seven adult populations cultured under realistic future CO2levels. Although larval development and morphology showed little response to elevated CO2, we found substantial allelic change in 40 functional classes of proteins involving hundreds of loci. Pronounced genetic changes, including excess amino acid replacements, were detected in all populations and occurred in genes for biomineralization, lipid metabolism, and ion homeostasis—gene classes that build skeletons and interact in pH regulation. Such genetic change represents a neglected and important impact of ocean acidification that may influence populations that show few outward signs of response to acidification. Our results demonstrate the capacity for rapid evolution in the face of ocean acidification and show that standing genetic variation could be a reservoir of resilience to climate change in this coastal upwelling ecosystem. However, effective response to strong natural selection demands large population sizes and may be limited in species impacted by other environmental stressors.
Transgene-based, female-specific lethality system for genetic sexing of the silkworm,
Bombyx mori
Authors: Tan Anjiang , Fu Guoliang , Jin Li , Guo Qiuhong , Li Zhiqian , Niu Baolong , Meng Zhiqi , Morrison Neil I. , Alphey Luke , Huang Yongping
Published: April 2013

Transgene-based genetic sexing methods are being developed for insects of agricultural and public health importance. Male-only rearing has long been sought in sericulture because males show superior economic characteristics, such as better fitness, lower food consumption, and higher silk yield. Here we report the establishment of a transgene-based genetic sexing system for the silkworm,
Bombyx mori
. We developed a construct in which a positive feedback loop regulated by sex-specific alternative splicing leads to high-level expression of the tetracycline-repressible transactivator in females only. Transgenic animals show female-specific lethality during embryonic and early larval stages, leading to male-only cocoons. This transgene-based female-specific lethal system not only has wide application in sericulture, but also has great potential in lepidopteran pest control.
Differential protein partitioning within the herpesvirus tegument and envelope underlies a complex and variable virion architecture
Authors: Bohannon Kevin Patrick , Jun Yonggun , Gross Steven P. , Smith Gregory Allan
Published: April 2013

Significance

Neuroinvasive herpesviruses cause diseases in humans ranging from cold sores to central nervous system infections. Unlike most icosahedral viruses, herpesvirus capsids are surrounded by protein layers that lack polyhedral architecture. The outer layers are critical for herpesvirus infectivity. Although the disorganized layers are visible by electron microscopy, the protein topography of these layers remains unclear. We fused fluorophores to virus proteins and pinpointed their positions within virions at nanometer resolution. The findings reveal a complex and variable asymmetric architecture, shed light on herpesvirus assembly, and provide a foundation for visualizing viral particle dynamics during herpesvirus infection.
Suppression of
Arabidopsis
protophloem differentiation and root meristem growth by CLE45 requires the receptor-like kinase BAM3
Authors: Depuydt Stephen , Rodriguez-Villalon Antia , Santuari Luca , Wyser-Rmili Céline , Ragni Laura , Hardtke Christian S.
Published: April 2013

Peptide signaling presumably occupies a central role in plant development, yet only few concrete examples of receptor-ligand pairs that act in the context of specific differentiation processes have been described. Here we report that second-site null mutations in the
Arabidopsis
leucine-rich repeat receptor-like kinase gene
barely any meristem 3
(
BAM3
) perfectly suppress the postembryonic root meristem growth defect and the associated perturbed protophloem development of the
brevis radix
(
brx
) mutant. The roots of
bam3
mutants specifically resist growth inhibition by the CLAVATA3/ENDOSPERM SURROUNDING REGION 45 (CLE45) peptide ligand. WT plants transformed with a construct for ectopic overexpression of CLE45 could not be recovered, with the exception of a single severely dwarfed and sterile plant that eventually died. By contrast, we obtained numerous transgenic
bam3
mutants transformed with the same construct. These transgenic plants displayed a WT phenotype, however, supporting the notion that CLE45 is the likely BAM3 ligand. The results correlate with the observation that external CLE45 application represses protophloem differentiation in WT, but not in
bam3
mutants.
BAM3, BRX
, and
CLE45
are expressed in a similar spatiotemporal trend along the developing protophloem, up to the end of the transition zone. Induction of
BAM3
expression upon CLE45 application, ectopic overexpression of
BAM3
in
brx
root meristems, and laser ablation experiments suggest that intertwined regulatory activity of
BRX
,
BAM3
, and
CLE45
could be involved in the proper transition of protophloem cells from proliferation to differentiation, thereby impinging on postembryonic growth capacity of the root meristem.
Repurposing the antimycotic drug flucytosine for suppression ofPseudomonas aeruginosapathogenicity
Authors: Imperi Francesco , Massai Francesco , Facchini Marcella , Frangipani Emanuela , Visaggio Daniela , Leoni Livia , Bragonzi Alessandra , Visca Paolo
Published: April 2013

Although antibiotic resistance represents a public health emergency, the pipeline of new antibiotics is running dry. Repurposing of old drugs for new clinical applications is an attractive strategy for drug development. We used the bacterial pathogenPseudomonas aeruginosaas a target for the screening of antivirulence activity among marketed drugs. We found that the antimycotic agent flucytosine inhibits the expression of the iron-starvation σ-factor PvdS, thereby repressing the production of majorP. aeruginosavirulence factors, namely pyoverdine, PrpL protease, and exotoxin A. Flucytosine administration at clinically meaningful dosing regimens suppressedP. aeruginosapathogenicity in a mouse model of lung infection. The in vitro and in vivo activity of flucytosine againstP. aeruginosa,combined with its desirable pharmacological properties, paves the way for clinical trials on the anti-P. aeruginosaefficacy of flucytosine in humans.
Genome-wide identification of
Bacillus subtilis
CodY-binding sites at single-nucleotide resolution
Authors: Belitsky Boris R. , Sonenshein Abraham L.
Published: April 2013

The CodY protein is a global transcriptional regulator that controls, directly or indirectly, expression of more than 100 genes and operons in
Bacillus subtilis
. We used in vitro DNA affinity purification combined with massively parallel sequencing, to identify
B. subtilis
chromosomal DNA fragments that bind CodY in vitro. A nonstandard strand-specific analysis of the data allowed us to pinpoint CodY-binding sites at single-nucleotide resolution. By comparing the extent of binding at decreasing CodY concentrations, we were able to classify binding regions according to their relative strengths and construct a subset of the 323 strongest CodY-binding regions that included sites associated with nearly all genes reported to be direct CodY targets. Many of the identified sites were located within coding regions. At such sites within the
ispA
,
rapA
, and
rapE
genes CodY-dependent repression was demonstrated using
lacZ
fusions and mutational analysis.
Crystal structure of glycoprotein E2 from bovine viral diarrhea virus
Authors: Li Yue , Wang Jimin , Kanai Ryuta , Modis Yorgo
Published: April 2013

Pestiviruses, including bovine viral diarrhea virus, are important animal pathogens and are closely related to hepatitis C virus, which remains a major global health threat. They have an outer lipid envelope bearing two glycoproteins, E1 and E2, required for cell entry. They deliver their genome into the host cell cytoplasm by fusion of their envelope with a cellular membrane. The crystal structure of bovine viral diarrhea virus E2 reveals a unique protein architecture consisting of two Ig-like domains followed by an elongated β-stranded domain with a new fold. E2 forms end-to-end homodimers with a conserved C-terminal motif rich in aromatic residues at the contact. A disulfide bond across the interface explains the acid resistance of pestiviruses and their requirement for a redox activation step to initiate fusion. From the structure of E2, we propose alternative possible membrane fusion mechanisms. We expect the pestivirus fusion apparatus to be conserved in hepatitis C virus.
Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus
Authors: Lipovsky Alex , Popa Andreea , Pimienta Genaro , Wyler Michael , Bhan Ashima , Kuruvilla Leena , Guie Marie-Aude , Poffenberger Adrian C. , Nelson Christian D. S. , Atwood Walter J. , DiMaio Daniel
Published: April 2013

Despite major advances in our understanding of many aspects of human papillomavirus (HPV) biology, HPV entry is poorly understood. To identify cellular genes required for HPV entry, we conducted a genome-wide screen for siRNAs that inhibited infection of HeLa cells by HPV16 pseudovirus. Many retrograde transport factors were required for efficient infection, including multiple subunits of the retromer, which initiates retrograde transport from the endosome to the trans-Golgi network (TGN). The retromer has not been previously implicated in virus entry. Furthermore, HPV16 capsid proteins arrive in the TGN/Golgi in a retromer-dependent fashion during entry, and incoming HPV proteins form a stable complex with retromer subunits. We propose that HPV16 directly engages the retromer at the early or late endosome and traffics to the TGN/Golgi via the retrograde pathway during cell entry. These results provide important insights into HPV entry, identify numerous potential antiviral targets, and suggest that the role of the retromer in infection by other viruses should be assessed.
Hypersensitive site 6 of the Th2 locus control region is essential for Th2 cytokine expression
Authors: Williams Adam , Lee Gap Ryol , Spilianakis Charalampos G. , Hwang Soo Seok , Eisenbarth Stephanie C. , Flavell Richard A.
Published: April 2013

The T helper type 2 (Th2) cytokine genes
Il4
,
Il5
, and
Il13
are contained within a 140-kb region of mouse chromosome 11 and their expression is controlled by a locus control region (LCR) embedded within this locus. The LCR is composed of a number of DNase I–hypersensitive sites (HSs), which are believed to encompass the regulatory core of the LCR. To determine the function of these sites, mutant mice were generated in which combinations of these HSs had been deleted from the endogenous LCR, and the effect on Th2 cytokine expression was assessed through the use of in vivo and in vitro models. These experiments revealed that, although all of the hypersensitive sites analyzed are important for appropriate LCR function, some sites are more important than others in regulating cytokine expression. Interestingly, each LCR mutation showed contrasting effects on cytokine expression, in some cases with mutants displaying opposing phenotypes between in vitro cultures and in vivo immunizations. These studies indicated that Rad50 hypersensitive site 6 was the singularly most important HS for Th2 cytokine expression, displaying consistent reductions in cytokine levels in all models tested. Furthermore analysis of chromatin modifications revealed that deletion of Rad50 hypersensitive site 6 impacted epigenetic modifications at the promoters of the
Il4
,
Il5
, and
Il13
genes as well as other regulatory sites within the Th2 locus.
Multifunctional three-dimensional macroporous nanoelectronic networks for smart materials
Authors: Liu Jia , Xie Chong , Dai Xiaochuan , Jin Lihua , Zhou Wei , Lieber Charles M.
Published: April 2013

Seamless and minimally invasive integration of 3D electronic circuitry within host materials could enable the development of materials systems that are self-monitoring and allow for communication with external environments. Here, we report a general strategy for preparing ordered 3D interconnected and addressable macroporous nanoelectronic networks from ordered 2D nanowire nanoelectronic precursors, which are fabricated by conventional lithography. The 3D networks have porosities larger than 99%, contain approximately hundreds of addressable nanowire devices, and have feature sizes from the 10-μm scale (for electrical and structural interconnections) to the 10-nm scale (for device elements). The macroporous nanoelectronic networks were merged with organic gels and polymers to form hybrid materials in which the basic physical and chemical properties of the host were not substantially altered, and electrical measurements further showed a >90% yield of active devices in the hybrid materials. The positions of the nanowire devices were located within 3D hybrid materials with ∼14-nm resolution through simultaneous nanowire device photocurrent/confocal microscopy imaging measurements. In addition, we explored functional properties of these hybrid materials, including (
i
) mapping time-dependent pH changes throughout a nanowire network/agarose gel sample during external solution pH changes, and (
ii
) characterizing the strain field in a hybrid nanoelectronic elastomer structures subject to uniaxial and bending forces. The seamless incorporation of active nanoelectronic networks within 3D materials reveals a powerful approach to smart materials in which the capabilities of multifunctional nanoelectronics allow for active monitoring and control of host systems.
Characterizing the Thermal Suitability of Instream Habitat for Salmonids: A Cautionary Example from the Rocky Mountains
Authors: Al‐Chokhachy Robert , Wenger Seth J. , Isaak Daniel J. , Kershner Jeffrey L.
Published: April 2013

Understanding a species’ thermal niche is becoming increasingly important for management and conservation within the context of global climate change, yet there have been surprisingly few efforts to compare assessments of a species’ thermal niche across methods. To address this uncertainty, we evaluated the differences in model performance and interpretations of a species’ thermal niche when using different measures of stream temperature and surrogates for stream temperature. Specifically, we used a logistic regression modeling framework with three different indicators of stream thermal conditions (elevation, air temperature, and stream temperature) referenced to a common set of Brook Trout Salvelinus fontinalis distribution data from the Boise River basin, Idaho. We hypothesized that stream temperature predictions that were contemporaneous with fish distribution data would have stronger predictive performance than composite measures of stream temperature or any surrogates for stream temperature. Across the different indicators of thermal conditions, the highest measure of accuracy was found for the model based on stream temperature predictions that were contemporaneous with fish distribution data (percent correctly classified = 71%). We found considerable differences in inferences across models, with up to 43% disagreement in the amount of stream habitat that was predicted to be suitable. The differences in performance between models support the growing efforts in many areas to develop accurate stream temperature models for investigations of species’ thermal niches.
Insensitivity and Oversensitivity to Answer Diagnosticity in Hypothesis Testing
Authors: Rusconi Patrice , McKenzie Craig R. M.
Published: April 2013

Two experiments examined how people perceive the diagnosticity of different answers (“yes” and “no”) to the same question. We manipulated whether the “yes” and the “no” answers conveyed the same amount of information or not, as well as the presentation format of the probabilities of the features inquired about. In Experiment 1, participants were presented with only the percentages of occurrence of the features, which most straightforwardly apply to the diagnosticity of “yes” answers. In Experiment 2, participants received in addition the percentages of the absence of features, which serve to assess the diagnosticity of “no” answers. Consistent with previous studies, we found that participants underestimated the difference in the diagnosticity conveyed by different answers to the same question. However, participants' insensitivity was greater when the normative (Bayesian) diagnosticity of the “no” answer was higher than that of the “yes” answer. We also found oversensitivity to answer diagnosticity, whereby participants valued as differentially diagnostic two answers that were normatively equal in terms of their diagnosticity. Presenting to participants the percentages of occurrence of the features inquired about together with their complements increased their sensitivity to the diagnosticity of answers. We discuss the implications of these findings for confirmation bias in hypothesis testing.
Smooth muscle fascicular reorientation is required for esophageal morphogenesis and dependent on Cdo
Authors: Romer Anthony I. , Singh Jagmohan , Rattan Satish , Krauss Robert S.
Published: April 2013

Postnatal maturation of esophageal musculature involves proximal-to-distal replacement of smooth muscle with skeletal muscle by elusive mechanisms. We report that this process is impaired in mice lacking the cell surface receptor Cdo and identify the underlying developmental mechanism. A myogenic transition zone containing proliferative skeletal muscle precursor cells migrated in a proximal–distal direction, leaving differentiated myofibers in its wake. Distal to the transition zone, smooth muscle fascicles underwent a morphogenetic process whereby they changed their orientation relative to each other and to the lumen. Consequently, a path was cleared for the transition zone, and smooth muscle ultimately occupied only the distal-most esophagus; there was no loss of smooth muscle. Cdo−/− mice were specifically defective in fascicular reorientation, resulting in an aberrantly proximal skeletal–smooth muscle boundary. Furthermore, Cdo−/− mice displayed megaesophagus and achalasia, and their lower esophageal sphincter was resistant to nitric oxide–induced relaxation, suggesting a developmental linkage between patterning and sphincter function. Collectively, these results illuminate mechanisms of esophageal morphogenesis and motility disorders.
Decontamination of Targeted Pathogens from Patient Rooms Using an Automated Ultraviolet-C-Emitting Device
Authors: Anderson Deverick J. , Gergen Maria F. , Smathers Emily , Sexton Daniel J. , Chen Luke F. , Weber David J. , Rutala William A.
Published: April 2013

Objective.

To determine the effectiveness of an automated ultraviolet-C (UV-C) emitter against vancomycin-resistant enterococci (VRE),Clostridium difficile, andAcinetobacterspp. in patient rooms.

Design.

Prospective cohort study.

Setting.

Two tertiary care hospitals.

Participants.

Convenience sample of 39 patient rooms from which a patient infected or colonized with 1 of the 3 targeted pathogens had been discharged.

Intervention.

Environmental sites were cultured before and after use of an automated UV-C-emitting device in targeted rooms but before standard terminal room disinfection by environmental services.

Results.

In total, 142 samples were obtained from 27 rooms of patients who were colonized or infected with VRE, 77 samples were obtained from 10 rooms of patients withC. difficileinfection, and 10 samples were obtained from 2 rooms of patients with infections due toAcinetobacter. Use of an automated UV-C-emitting device led to a significant decrease in the total number of colony-forming units (CFUs) of any type of organism (1.07 log10reduction;P< .0001), CFUs of target pathogens (1.35 log10reduction;P< .0001), VRE CFUs (1.68 log10reduction;P< .0001), and C.difficileCFUs (1.16 log10reduction;P< .0001). CFUs ofAcinetobacteralso decreased (1.71 log10reduction), but the trend was not statistically significantP= .25). CFUs were reduced at all 9 of the environmental sites tested. Reductions similarly occurred in direct and indirect line of sight.

Conclusions.

Our data confirm that automated UV-C-emitting devices can decrease the bioburden of important pathogens in real-world settings such as hospital rooms.
Probiotic Administration Reduces Mortality and Improves Intestinal Epithelial Homeostasis in Experimental Sepsis
Authors: Khailova Ludmila , Frank Daniel N. , Dominguez Jessica A. , Wischmeyer Paul E.
Published: April 2013

Background:

Recent clinical trials indicate that probiotic administration in critical illness has potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of probiotic-mediated protection against infection and sepsis remain elusive. The authors evaluated the effects of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) on mortality, bacterial translocation, intestinal epithelial homeostasis, and inflammatory response in experimental model of septic peritonitis.

Methods:

Cecal ligation and puncture (n = 14 per group) or sham laparotomy (n = 8 per group) were performed on 3-week-old FVB/N weanling mice treated concomitantly with LGG, BL, or vehicle (orally gavaged). At 24 h, blood and colonic tissue were collected. In survival studies, mice were given probiotics every 24 h for 7 days (LGG, n = 14; BL, n = 10; or vehicle, n = 13; shams, n = 3 per group).

Results:

Probiotics significantly improved mortality after sepsis (92 vs. 57% mortality for LGG and 92 vs. 50% mortality for BL; P = 0.003). Bacteremia was markedly reduced in septic mice treated with either probiotic compared with vehicle treatment (4.39 ± 0.56 vs. 1.07 ± 1.54; P = 0.0001 for LGG; vs. 2.70 ± 1.89; P = 0.016 for BL; data are expressed as mean ± SD). Sepsis in untreated mice increased colonic apoptosis and reduced colonic proliferation. Probiotics significantly reduced markers of colonic apoptosis and returned colonic proliferation to sham levels. Probiotics led to significant reductions in systemic and colonic inflammatory cytokine expression versus septic animals. Our data suggest that involvement of the protein kinase B pathway (via AKT) and down-regulation of Toll-like receptor 2/Toll-like receptor 4 via MyD88 in the colon may play mechanistic roles in the observed probiotic benefits.

Conclusions:

Our data demonstrate that probiotic administration at initiation of sepsis can improve survival in pediatric experimental sepsis. The mechanism of this protection involves prevention of systemic bacteremia, perhaps via improved intestinal epithelial homeostasis, and attenuation of the local and systemic inflammatory responses.
Extracardiac Off-Pump Fontan Completion for Single Ventricle with Dextrocardia
Authors: Goksel Onur S. , Gok Emre , Tireli Emin , Dayioglu Enver
Published: April 2013

Extracardiac off-pump is reported to result in better early hemodynamics and shorter mechanical ventilation periods. We present a case report of extracardiac off-pump Fontan in a 5-year-old girl with single ventricle and dextrocardia.
Healing Study of Porcine Heart Transapical Wounds Closed Using a Remote Automated Suturing Technology
Authors: Wilshire Candice L. , Kaufer James W. , Gorea Heather R. , Sauer Jude S. , Knight Peter A.
Published: April 2013

Objective

A safe and reliable direct percutaneous approach for transapical access to the left ventricle would be a significant advance toward decreasing the invasiveness of intracardiac interventions. This report presents results from a surviving porcine beating heart model in which transapical access sites were closed using an automated suturing technique ultimately intended for percutaneous use.

Methods

Through an approved protocol including general anesthesia, the cardiac apex in 10 beating pig hearts was surgically exposed, permitting transapical passage of a 0.035-in guidewire and a 5.5F, 0.9-mL Fogarty balloon catheter. An automated suturing device was passed over the guidewire and the Fogarty onto the transapical access site. Two pledgeted horizontal mattress sutures were simultaneously placed concentrically around the apical access site with a single squeeze of the device's lever. A 25F dilator was passed into the left ventricle over the guidewire and subsequently removed. The sutures were then secured using pledgeted titanium knots. Chest wall and skin incisions were closed. The animals were recovered from anesthesia and resumed a normal diet.

Results

Under general anesthesia, the transapical access site of each animal was re-exposed, five at 1-week and five at 2-week intervals. Hemostasis was complete, and all wounds healed well.

Conclusions

The evaluation of transapical wound closures in this surviving porcine heart model demonstrates complete hemostasis and excellent healing through the use of this automated remote suturing technology.
Sutureless Aortic Valve Implantation through an Upper V-Type Ministernotomy: An Innovative Approach in High-Risk Patients
Authors: Concistrè Giovanni , Miceli Antonio , Chiaramonti Francesca , Farneti Pierandrea , Bevilacqua Stefano , Varone Egidio , Solinas Marco , Glauber Mattia
Published: April 2013

Objective

Aortic valve replacement in minimally invasive approach has shown to improve clinical outcomes even with a prolonged cardiopulmonary bypass and aortic cross-clamp (ACC) time. Sutureless aortic valve implantation may ideally shorten operative time. We describe our initial experience with the sutureless 3f Enable (Medtronic, Inc, ATS Medical, Minneapolis, MN USA) aortic bioprosthesis implanted in minimally invasive approach in high-risk patients.

Methods

Between May 2010 and May 2011, thirteen patients with severe aortic stenosis underwent aortic valve replacement with the 3f Enable bioprosthesis through an upper V-type ministernotomy interrupted at the second intercostal space. The mean ± SD age was 77 ± 3.9 years (range, 72–83 years), 10 patients were women, and the mean ± SD logistic EuroSCORE was 15% ± 13.5%. Echocardiography was performed preoperatively, at postoperative day 1, at discharge, and at follow-up. Clinical data, adverse events, and patient outcomes were recorded retrospectively. The median follow-up time was 4 months (interquartile range, 2–10 months).

Results

Most of the implanted valves were 21 mm in diameter (19–25 mm). The CPB and ACC times were 100.2 ± 25.3 and 66.4 ± 18.6 minutes. At short-term follow-up, the mean ± SD pressure gradient was 14 ± 4.9 mm Hg; one patient showed trivial paravalvular leakage. No patients died during hospital stay or at follow-up.

Conclusions

The 3f Enable sutureless bioprosthesis implanted in minimally invasive approach through an upper V-type ministernotomy is a feasible, safe, and reproducible procedure. Hemodynamic and clinical data are promising. This innovative approach might be considered as an alternative in high-risk patients. Reduction of CPB and ACC time is possible with increasing of experience and sutureless evolution of actual technology.
Outcomes of Minimally Invasive Mitral Valve Surgery in Patients with an Ejection Fraction of 35% or Less
Authors: Santana Orlando , Reyna Javier , Pineda Andres M. , Mihos Christos G. , Elkayam Lior U. , Lamas Gervasio A. , Lamelas Joseph
Published: April 2013

Objective

We evaluated the outcomes of minimally invasive mitral valve surgery via a right anterior thoracotomy approach in patients with isolated severe mitral regurgitation and severely reduced left ventricular systolic function.

Methods

We retrospectively reviewed all minimally invasive mitral valve surgeries for mitral regurgitation in patients with an ejection fraction of 35% or less performed at our institution between December 2008 and June 2011. The operative times, lengths of stay, postoperative complications, and mortality were analyzed.

Results

We identified a total of 71 patients with severe mitral regurgitation and an ejection fraction of 35% or less who underwent minimally invasive mitral valve surgery. The mean ± SD age was 67 ± 10 years, and 44 of the patients were men (62%). The mean ± SD left ventricular ejection fraction was 27% ± 6%, and 28 patients (39%) had previous heart surgery. The median aortic cross-clamp and cardiopulmonary bypass times were 62 [interquartile range (IQR), 50–80) and 98 minutes (IQR, 92–124), respectively. There was no mitral regurgitation noted in any patient on postoperative transesophageal echocardiogram. The median intensive care unit length of stay was 51 hours (IQR, 42–86), and the median postoperative length of stay was 6 days (IQR, 5–9).

Conclusions

Minimally invasive mitral valve surgery for severe functional mitral regurgitation in patients with severe left ventricular dysfunction can be performed with a low morbidity and mortality.
The costs and benefits of flexibility as an expression of behavioural plasticity: a primate perspective
Authors: van Schaik Carel P.
Published: April 2013

Traditional neo-Darwinism ascribes geographical variation in morphology or in behaviour to varying selection on local genotypes. However, mobile and long-lived organisms cannot achieve local adaptation this way, leading to a renewed interest in plasticity. I examined geographical variation in orang-utan subsistence and social behaviour, and found this to be largely owing to behavioural plasticity, here called flexibility, both in the form of flexible individual decisions and of socially transmitted (cultural) innovations. Although comparison with other species is difficult, the extent of such flexibility is almost certainly limited by brain size. It is shown that brains can only increase relative to body size where the cognitive benefits they produce are reliably translated into improved survival rate. This means that organisms that are very small, face many predators, live in highly seasonal environments, or lack opportunities for social learning cannot evolve greater flexibility, and must achieve local adaptation through selection on specific genotypes. On the other hand, as body and brain size increase, local adaptation is increasingly achieved through selection on plasticity. The species involved are also generally those that most need it, being more mobile and longer-lived. Although high plasticity buffers against environmental change, the most flexible organisms face a clear limit because they respond slowly to selection. Thus, paradoxically, the largest-brained animals may actually be vulnerable to the more drastic forms of environmental change, such as those induced by human actions.
Phylogenetic signal in primate behaviour, ecology and life history
Authors: Kamilar Jason M. , Cooper Natalie
Published: April 2013

Examining biological diversity in an explicitly evolutionary context has been the subject of research for several decades, yet relatively recent advances in analytical techniques and the increasing availability of species-level phylogenies, have enabled scientists to ask new questions. One such approach is to quantify phylogenetic signal to determine how trait variation is correlated with the phylogenetic relatedness of species. When phylogenetic signal is high, closely related species exhibit similar traits, and this biological similarity decreases as the evolutionary distance between species increases. Here, we first review the concept of phylogenetic signal and suggest how to measure and interpret phylogenetic signal in species traits. Second, we quantified phylogenetic signal in primates for 31 variables, including body mass, brain size, life-history, sexual selection, social organization, diet, activity budget, ranging patterns and climatic variables. We found that phylogenetic signal varies extensively across and even within trait categories. The highest values are exhibited by brain size and body mass, moderate values are found in the degree of territoriality and canine size dimorphism, while low values are displayed by most of the remaining variables. Our results have important implications for the evolution of behaviour and ecology in primates and other vertebrates.
Plasticity and constraints on social evolution in African mole-rats: ultimate and proximate factors
Authors: Faulkes Chris G. , Bennett Nigel C.
Published: April 2013

Here, we review comparative studies of African mole-rats (family Bathyergidae) to explain how constraints acting at the ultimate (environmental) and proximate (organismal) levels have led to convergent gains and losses of sociality within this extensive adaptive radiation of subterranean rodents endemic to sub-Saharan Africa. At the ultimate level, living in environments that range from mesic through to arid has led to both variation and flexibility in social organization among species, culminating in the pinnacle of social evolution in the eusocial naked and Damaraland mole-rats (
Heterocephalus glaber
and
Fukomys damarensis
). The common mole-rat (
Cryptomys hottentotus
) provides a model example of how plasticity in social traits exists within a single species inhabiting areas with different ecological constraint. At the proximate level, reproductive strategies and cooperative breeding may be constrained by the correlated evolution of a suite of traits including physiological suppression of reproduction, the development of physiological and morphological castes, and the mode of ovulatory control and seasonality in breeding. Furthermore, recent neurobiological advances indicate that differential patterns of neurotransmitter expression within the forebrain may underpin (and limit) either a solitary or group living/cooperative lifestyle not only in mole-rats, but also more widely among disparate mammalian taxa.
Variation in grouping patterns, mating systems and social structure: what socio-ecological models attempt to explain
Authors: Koenig Andreas , Scarry Clara J. , Wheeler Brandon C. , Borries Carola
Published: April 2013

Socio-ecological models aim to predict the variation in social systems based on a limited number of ecological parameters. Since the 1960s, the original model has taken two paths: one relating to grouping patterns and mating systems and one relating to grouping patterns and female social structure. Here, we review the basic ideas specifically with regard to non-human primates, present new results and point to open questions. While most primates live in permanent groups and exhibit female defence polygyny, recent studies indicate more flexibility with cooperative male resource defence occurring repeatedly in all radiations. In contrast to other animals, the potential link between ecology and these mating systems remains, however, largely unexplored. The model of the ecology of female social structure has often been deemed successful, but has recently been criticized. We show that the predicted association of agonistic rates and despotism (directional consistency of relationships) was not supported in a comparative test. The overall variation in despotism is probably due to phylogenetic grade shifts. At the same time, it varies within clades more or less in the direction predicted by the model. This suggests that the model's utility may lie in predicting social variation within but not across clades.
Developmental constraints on behavioural flexibility
Authors: Holekamp Kay E. , Swanson Eli M. , Van Meter Page E.
Published: April 2013

We suggest that variation in mammalian behavioural flexibility not accounted for by current socioecological models may be explained in part by developmental constraints. From our own work, we provide examples of constraints affecting variation in behavioural flexibility, not only among individuals, but also among species and higher taxonomic units. We first implicate organizational maternal effects of androgens in shaping individual differences in aggressive behaviour emitted by female spotted hyaenas throughout the lifespan. We then compare carnivores and primates with respect to their locomotor and craniofacial adaptations. We inquire whether antagonistic selection pressures on the skull might impose differential functional constraints on evolvability of skulls and brains in these two orders, thus ultimately affecting behavioural flexibility in each group. We suggest that, even when carnivores and primates would theoretically benefit from the same adaptations with respect to behavioural flexibility, carnivores may nevertheless exhibit less behavioural flexibility than primates because of constraints imposed by past adaptations in the morphology of the limbs and skull. Phylogenetic analysis consistent with this idea suggests greater evolutionary lability in relative brain size within families of primates than carnivores. Thus, consideration of developmental constraints may help elucidate variation in mammalian behavioural flexibility.
An ActiveAc/DsTransposon System for Activation Tagging in Tomato Cultivar M82 Using Clonal Propagation
Authors: Carter Jared D. , Pereira Andy , Dickerman Allan W. , Veilleux Richard E.
Published: April 2013

Tomato (Solanum lycopersicum) is a model organism for Solanaceae in both molecular and agronomic research. This project utilized Agrobacterium tumefaciens transformation and the transposon-tagging construct Activator (Ac)/Dissociator (Ds)-ATag-Bar_gosGFP to produce activation-tagged and knockout mutants in the processing tomato cultivar M82. The construct carried hygromycin resistance (hyg), green fluorescent protein (GFP), and the transposase (TPase) of maize (Zea mays) Activator major transcript X054214.1 on the stable Ac element, along with a 35S enhancer tetramer and glufosinate herbicide resistance (BAR) on the mobile Ds-ATag element. An in vitro propagation strategy was used to produce a population of 25 T0 plants from a single transformed plant regenerated in tissue culture. A T1 population of 11,000 selfed and cv M82 backcrossed progeny was produced from the functional T0 line. This population was screened using glufosinate herbicide, hygromycin leaf painting, and multiplex polymerase chain reaction (PCR). Insertion sites of transposed Ds-ATag elements were identified through thermal asymmetric interlaced PCR, and resulting product sequences were aligned to the recently published tomato genome. A population of 509 independent, Ds-only transposant lines spanning all 12 tomato chromosomes has been developed. Insertion site analysis demonstrated that more than 80% of these lines harbored Ds insertions conducive to activation tagging. The capacity of the Ds-ATag element to alter transcription was verified by quantitative real-time reverse transcription-PCR in two mutant lines. The transposon-tagged lines have been immortalized in seed stocks and can be accessed through an online database, providing a unique resource for tomato breeding and analysis of gene function in the background of a commercial tomato cultivar.