bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravaginal slingplasty sling is associated with increased risk of vaginal erosion
Authors: NYYSSÖNEN VIRVA , TALVENSAARI‐MATTILA ANNE , SANTALA MARKKU
Published: October 2009

Objective. Two structurally different polypropylene tapes are used in tension‐free vaginal tape (TVT) and intravaginal slingplasty sling (IVS) procedures for the treatment of female stress urinary incontinence. This study aimed to compare TVT and IVS operations for late postoperative complications, especially vaginal erosion. Design. A retrospective study. Setting. Oulu University Hospital, Finland. Sample. The study sample was constituted by 373 patients operatively treated for female urinary incontinence between January 2000 and June 2004. A total of 293 patients underwent the TVT operation and 80 patients the IVS operation. Methods. We analyzed the data using Fisher's Exact test, Pearson's chi‐squared test, and log linear test. For categorical variables we used risk ratios with 95% confidence intervals. Main outcome measures. The incidence of late complications, especially vaginal erosion. Results. Symptomatic erosion (p < 0.001; risk ratio 13.7; 95% confidence interval 4.03–46.8) was seen in 3 patients (1%) in the TVT group and in 13 patients (16%) in the IVS group. The median time to the onset of symptoms was 9 and 12 months in these groups, respectively. Conclusions. We suggest that the high vaginal erosion rate in the IVS group is associated with the tape material.
Assessment of the sentinel lymph node in patients with invasive squamous carcinoma of the vulva
Authors: ACHIMAS‐CADARIU PATRICIU , HARTER PHILIPP , FISSELER‐ECKHOFF ANNETTE , BEUTEL BIANCA , TRAUT ALEXANDER , DU BOIS ANDREAS
Published: October 2009

Objective. This study aims to evaluate the feasibility and diagnostic validity of the sentinel lymph node technique in detecting inguinal lymph node metastases in patients with invasive squamous cancer of the vulva. Design. Retrospective analysis of the in‐house tumor registry. Setting. Dr. Horst Schmidt Klinik, a tertiary gynecologic oncology unit in Wiesbaden, Germany, June 2000–May 2008. Population. All consecutive operated patients with primary envisaged diagnosis were included. Methods. The sentinel node identification technique was performed and patients were informed accordingly. Patients who consented and were found eligible underwent preoperative lymphscintigraphy on the day before surgery. Main outcome measures. Sentinel node detection in specimen from sentinel lymph node biopsy and from full lymphadenectomy (LNE); sentinel lymph node biopsy as a sole surgical groin procedure in patients with histological negative sentinel node; benefit with respect to side effects for sentinel lymph node biopsy compared to full LNE; complication rates; and recurrences of vulvar cancer. Results. In all, 46 of 59 patients with vulvar malignancy underwent inguinofemoral LNE, sentinel lymph node biopsy (SLB) of the groin followed by LNE, or SLB alone. Most patients had been diagnosed in the early stages of the disease. Since no false positive or false negative results were recorded, the sensitivity, specificity, positive predictive value and negative predictive value of the sentinel lymph node were 100%. However, in 6%, a sentinel lymph node could not be detected intraoperatively indicating a feasibility of 94%. Conclusion. The implementation of sentinel lymph node technique for groin staging in squamous cell vulvar cancer seems to provide a feasible and safe technique in tertiary gynecologic oncology.
Darwin and his publisher
Authors: McClay David
Published: October 2009

Charles Darwin's publisher John Murray played an important, if often underrated, role in bringing his theories to the public. As their letters and publishing archives show they had a friendly, business like and successful relationship. This was despite fundamental scientific and religious differences between the men. In addition to publishing Darwin, Murray also published many of the critical and supportive works and reviews which Darwin's own works excited.
Factors influencing the basal temperatures of a High Arctic polythermal glacier
Authors: Wohlleben Trudy , Sharp Martin , Bush Andrew
Published: October 2009

A number of glaciers in the Canadian High Arctic are composed primarily of cold ice, but the ice at or near their beds reaches the pressure-melting point (PMP) in the ablation zone. Past modelling studies have suggested that the basal temperatures of some of these glaciers reach the PMP where they should not, indicating that they are not in thermal equilibrium with present-day surface air temperatures. To investigate the possible reasons for thermal disequilibria in such glaciers, a two-dimensional ice temperature model was used to simulate the inferred thermal characteristics of John Evans Glacier, Ellesmere Island. Results indicate that while surface refreezing and historical ice-thickness changes have had a warming effect upon basal ice temperatures, supraglacial meltwater reaching the glacier bed provides the single most critical heat source for explaining the apparent thermal disequilibrium between present-day inferred ice–bed temperatures and those modelled under present-day boundary conditions.
Signature of ice streaming in Bjørnøyrenna, Polar North Atlantic, through the Pleistocene and implications for ice-stream dynamics
Authors: Andreassen Karin , Winsborrow Monica
Published: October 2009

The geomorphology of palaeo-ice-stream beds and the internal structure of underlying tills can provide important information about the subglacial conditions during periods of fast flow and quiescence. This paper presents observations from three-dimensional seismic data, revealing the geomorphology of buried beds of the Bjørnøyrenna (Bear Island Trough) ice stream, the main drainage outlet of the former Barents Sea ice sheet. Repeated changes in ice dynamics are inferred from the observed successions of geomorphic features. Megablocks, aligned in long chains parallel to inferred ice-stream flowlines, and forming dipping plates that are thrust one on top of another, are taken as evidence for conditions of compressive ice flow. Mega-scale glacial lineations (MSGL) and pull-apart of underlying sediment blocks suggest extensional flow. The observed pattern of megablocks and rafts overprinted by MSGL indicates a change in ice dynamics from a compressional to an extensional flow regime. Till stiffening, due to subglacial freezing, is the favoured mechanism for creating switches in sub-ice-stream conditions. The observed pattern of geomorphic features indicates that periods of slowdown or quiescence were commonly followed by reactivation and fast flow during several glaciations, suggesting that this may be a common behaviour of marine ice streams.
Rapid glacier sliding, reverse ice motion and subglacial water pressure during an autumn rainstorm
Authors: Fudge T.J. , Harper J.T. , Humphrey N.F. , Pfeffer W.T.
Published: October 2009

Measurements of basal water pressure from 15 boreholes located at both local (tens of meters) and regional (kilometers) length scales were used to elucidate the pressure/sliding relationship during an autumn rapid motion event on Bench Glacier, Alaska, USA. The 8 day event had two distinct phases, each with a ten-fold speed-up with respect to winter velocity. The water pressure in all 15 boreholes varied synchronously during the speed-up. The first phase of rapid sliding began after a peak in basal water pressure and continued while the pressure was elevated and stable, or decreasing. The second phase of rapid sliding occurred when the basal water pressure was low but increasing, and terminated before the pressure peaked. Pressure and velocity do not appear unrelated, but the pressure/sliding relationship was not consistently linked to increasing, decreasing or a critical water pressure. The pressure variations and sliding accelerations are a response to a warm rainstorm, although equally large input events occurred in weeks prior with no apparent response. Drainage system evolution therefore appears to play a key role in both the acceleration and the pressure/velocity relationship. Basal cavity dynamics are likely responsible for three episodes of reverse (up-valley) motion observed after enhanced sliding.
Transient effective stress variations forced by changes in conduit pressure beneath glaciers and ice sheets
Authors: Rempel Alan W.
Published: October 2009

The resistance to sliding beneath soft-bedded glaciers depends on the effective stress, N, which is controlled by the subglacial hydrological system. While large-scale water transport is primarily through conduits, the effective stress profile beneath most of the glacier base is expected to be controlled by seepage flows through the permeable sediments. Models of the response to forced changes of the near-conduit effective stress demonstrate that perturbations in N decay over a characteristic lateral distance that is typically only a few times the sediment thickness. This implies that only relatively small changes to the spatially averaged effective stress, can be produced if conduit spacing is comparatively large and the glacier and sediments remain in contact. To produce larger changes to , it is likely that flotation must be achieved beneath a significant portion of the glacier base. At higher values, spatial variations in N can produce gradients in the thickness, h, of a fringe of ice-infiltrated sediments immediately adjacent to the glacier base; this has implications for the development of glacial landforms when sliding causes sediment transport.
Ice flow across a warm-based/cold-based transition at a glacier margin
Authors: Moore Peter L. , Iverson Neal R. , Cohen Denis
Published: October 2009

Where polythermal glaciers have frozen margins that buttress otherwise temperate-based sliding ice, longitudinal compression can strongly influence ice-flow trajectory, and consequently sediment transport paths. Past efforts to model flow in the vicinity of a basal thermal transition (BTT) have generally relied on simplified boundary conditions or rheological idealizations, making these model results difficult to apply to real glacier termini. Herein, we present results of numerical simulations using a power-law rheology and with boundary conditions that better represent the frozen margin. Model results indicate that a transition to a non-sliding frozen margin causes a decline in surface velocity made possible by upward ice flow, implying either enhanced ablation for steady-state simulations or the formation of a surface bulge. Permitting ice loss by ablation combined with numerical smoothing of the basal slip transition subdues basal stress concentrations and thereby inhibits development of structural discontinuities such as thrust faults. Upward ice flow is accommodated by vertical extension up-glacier of the BTT. This strain regime can potentially account for key structural features in polythermal glacier termini without appealing to thrusting.
Seasonal evolution of supraglacial lake volume from ASTER imagery
Authors: Georgiou S. , Shepherd A. , McMillan M. , Nienow P.
Published: October 2009

Water stored in and released from supraglacial lakes is an important factor when considering the seasonal and long-term evolution of the Greenland ice sheet. Here we use a radiative transfer model to estimate changes in the depth and volume of a supraglacial lake on the surface of Jakobshavn Isbræ, West Greenland, between 2002 and 2005. When compared to estimates of the lake depth determined from airborne lidar observations, we estimate that the root-mean-square departure of the modelled lake depths was 0.3 m during cloud-free conditions. The maximum lake area, depth and volume were 3.4 km2, 9.6 ±1.0 m and (18.6±3.7)×106 m3, respectively. When sequenced according to the number of positive degree-days (PDDs) accumulated prior to each image, we observe that the lake volume evolves in three distinct phases. At the start of the melting season, the rate of filling is slow; after approximately 80 PDDs the rate of filling increases by a factor ∽3, and after approximately 125 PDDs the lake drains rapidly. We estimate that the lake drains at a minimum rate of (2.66±0.53)×106 m3 d–1 over a 6 day period.
Numerical modelling of historical front variations and the 21st-century evolution of glacier AX010, Nepal Himalaya
Authors: Adhikari Surendra , Huybrechts Philippe
Published: October 2009

Due to the lack of measurements of ice velocity, mass balance, glacier geometry and other baseline data, model-based studies of glacial systems in the Nepal Himalaya are very limited. Here a numerical ice-flow model has been developed for glacier AX010 in order to study its relation to local climate and investigate the possible causes of its general retreat since the end of the Little Ice Age. First, an attempt is made to simulate the historical front variations, considering each climatic parameter separately. Good agreement between the observations and model projections can be obtained under the assumption that variations in glacier front position are a response to changes in temperature alone. The same assumption is made about future changes to explore the 21st-century evolution of the glacier. Under a no-change scenario, the glacier will retreat by another ∽600m by AD 2100, whereas it is projected to vanish completely during this century for all trends with a temperature rise larger than +2.5˚C by AD 2100 with respect to the 1980–99 mean. With constant precipitation at the 1980–99 mean, the model predicts that the glacier will cease to exist at AD 2083, 2056 or 2049 if the temperature rises linearly by 3˚C, 4.5˚C or 6˚C respectively by the end of this century. With an additional range of precipitation changes between –30% and +30%, the life expectancy of glacier AX010 varies by 18, 6 and 2 years for the respective temperature rises. Thus the role of precipitation becomes minimal for the higher trends of temperature rise.
Role of the Ubiquitin Proteasome System in Regulating Skin Pigmentation
Authors: Ando Hideya , Ichihashi Masamitsu , Hearing Vincent J.
Published: October 2009

Pigmentation of the skin, hair and eyes is regulated by tyrosinase, the critical rate-limiting enzyme in melanin synthesis by melanocytes. Tyrosinase is degraded endogenously, at least in part, by the ubiquitin proteasome system (UPS). Several types of inherited hypopigmentary diseases, such as oculocutaneous albinism and Hermansky-Pudlak syndrome, involve the aberrant processing and/or trafficking of tyrosinase and its subsequent degradation which can occur due to the quality-control machinery. Studies on carbohydrate modifications have revealed that tyrosinase in the endoplasmic reticulum (ER) is proteolyzed via ER-associated protein degradation and that tyrosinase degradation can also occur following its complete maturation in the Golgi. Among intrinsic factors that regulate the UPS, fatty acids have been shown to modulate tyrosinase degradation in contrasting manners through increased or decreased amounts of ubiquitinated tyrosinase that leads to its accelerated or decelerated degradation by proteasomes.
Do extreme environments provide a refuge from pathogens? A phylogenetic test using serpentine flax
Authors: Springer Yuri P.
Published: October 2009

Abiotically extreme environments are often associated with physiologically stressful conditions, small, low‐density populations, and depauperate flora and fauna relative to more benign settings. A possible consequence of this may be that organisms that occupy these stressful habitats receive fitness benefits associated with reductions in the frequency and/or intensity of antagonistic species interactions. I investigated a particular form of this effect, formalized as the “pathogen refuge hypothesis,” through a study of 13 species of wild flax that grow on stressful serpentine soils and are often infected by a pathogenic fungal rust. The host species vary in the degree of their serpentine association: some specialize on extreme serpentine soils, while others are generalists that occur on soils with a wide range of serpentine influence. Phylogenetically explicit analyses of soil chemistry and field‐measured disease levels indicated that rust disease was significantly less frequent and severe in flax populations growing in more stressful, low‐calcium serpentine soils. These findings may help to explain the persistence of extremophile species in habitats where stressful physical conditions often impose strong autecological fitness costs on associated organisms. Ancestral state reconstruction of serpentine soil tolerance (approximated using soil calcium concentrations) suggested that the ability to tolerate extreme serpentine soils may have evolved multiple times within the focal genus.
Sex‐specific variation in the interaction between Distichlis spicata (Poaceae) and mycorrhizal fungi
Authors: Eppley Sarah M. , Mercer Charlene A. , Haaning Christian , Graves Camille B.
Published: October 2009

Associations between mycorrhizal fungi and plants can influence intraspecific competition and shape plant population structure. While variation in plant genotypes is known to affect mycorrhizal colonization in crop systems, little is known about how genotypes affect colonization in natural plant populations or how plant sex might influence colonization with mycorrhizal fungi in plant species with dimorphic sexual systems. In this study, we analyzed mycorrhizal colonization in males and females of the wetland dioecious grass Distichlis spicata, which has spatially segregated sexes. Our results suggest that D. spicata males and females interact with mycorrhizal fungi differently. We discuss the implications for the role of this sex‐specific symbiotic interaction in the maintenance of the within‐population sex ratio bias of D. spicata.
Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups
Authors: Rolland Julien , Cambeiro Xacobe C , Rodríguez-Escrich Carles , Pericàs Miquel A
Published: October 2009

A continuous flow system for the synthesis of enantioenriched diarylmethanols from aldehydes is described. The system uses an amino alcohol-functionalized polystyrene resin as the catalyst, and the arylating agent is conveniently prepared by transmetallation of triarylboroxins with diethylzinc.
Inhibition of Herpes Simplex Virus by Polyamines
Authors: Yudovin-Farber Ira , Gurt Irina , Hope Ronen , Domb Abraham J , Katz Ehud
Published: October 2009

Background:

Herpes simplex virus (HSV) establishes latent infection in humans with periodic reactivation. Acyclovir, valacyclovir and foscarnet are in medical use today against HSV type-1 (HSV-1) and type-2 (HSV-2), inhibiting the DNA synthesis of the viruses. Additional drugs that will affect the growth of these viruses by other mechanisms and also decrease the frequency of appearance of drug-resistant mutants are required.

Methods:

Cationic polysaccharides were synthesized by conjugation of various oligoamines to oxidized polysaccharides by reductive amination. Polycations of dextran, pullulan and arabinogalactan were grafted with oligoamines of 2–4 amino groups forming Schiff-base imine-based conjugates followed by reduction with borohydride to obtain the stable amine-based conjugate. Evaluation of toxicity to BS-C-1 cells and antiviral activity against HSV-1 and HSV-2 of the different compounds was performed in vitro by a semiquantitative assay. A quantitative study with a selected compound followed.

Results:

Structure–activity relationship studies showed that the nature of the grafted oligoamine of the polycation plays an essential role in the antiviral activity against HSV-1 and HSV-2. Dextran-propan-1,3-diamine (DPD) was found to be the most potent of all the compounds examined. DPD did not decrease the infectivity of HSV upon direct exposure to the virions. The growth of HSV was significantly inhibited when DPD was added to the host cells 1 h prior to infection, thus preventing the adsorption and penetration of the virus into the cells.

Conclusions:

Our in vitro data warrant clinical investigation. DPD could have an advantage as a topical application in combination therapy of HSV lesions.
Early Life Factors and Adult-onset Rheumatoid Arthritis
Authors: SIMARD JULIA F. , COSTENBADER KAREN H. , HERNÁN MIGUEL A. , LIANG MATTHEW H. , MITTLEMAN MURRAY A. , KARLSON ELIZABETH W.
Published: October 2009

Objective.

Early life factors have been associated with risk of developing autoimmune disease in adulthood. We investigated the association of preterm birth and being breastfed with the incidence of rheumatoid arthritis (RA) in 2 large prospective cohorts.

Methods.

We studied participants from the Nurses’ Health Study (NHS) and the Nurses’ Health Study II (NHSII) who provided information on perinatal factors. The NHS (n = 121,701) and NHSII (n = 116,608) are large prospective cohorts of women followed since 1976 and 1989, respectively. Incident RA was confirmed using the American College of Rheumatology criteria and a medical record review. Cox models were used to estimate the hazard ratio of RA associated with being born preterm and being breastfed and its duration, adjusting for potential confounders. Random effects metaanalytic methods were used to compute combined estimates from the 2 cohorts.

Results.

We found no statistically significant association between preterm birth and incident RA [relative risk (RR) = 1.1, 95% CI 0.8, 1.5]. Being breastfed was not associated with increased incidence of RA (RR = 1.0, 95% CI 0.7, 1.4), regardless of the duration of breastfeeding.

Conclusion.

In these cohorts of women, neither being preterm birth nor being breastfed was associated with the onset of RA.
Using a Mentorship Model to Prepare Newly Graduated Nurses for Competency
Authors: Komaratat Sirima , Oumtanee Areewan
Published: October 2009

This research was conducted to study the level of nursing competency of newly graduated nurses after using a mentorship model. Nineteen newly graduated nurses worked with a trained mentor. Before the experiment, newly graduated nurses were evaluated regarding their nursing competency by head nurses two times, with a 1-month interval between evaluations. Select experienced nurses were prepared in mentoring roles. The mentors and the newly graduated nurses worked together for 1 month. After that, newly graduated nurses were evaluated for nursing competency by head nurses again. All data were analyzed by median, quartile deviation, and Wilcoxon signed ranks test. The level of nursing competency of newly graduated nurses was higher using the mentor model. This finding showed that the mentor program increased the nursing competency of newly graduated nurses.

J Contin Educ Nurs
2009;40(10):475–480.
Preparing the Novice Critical Care Nurse: A Community-Wide Collaboration Using the Benefits of Simulation
Authors: Stefanski Robbie R. , Rossler Kelly L.
Published: October 2009

This article describes how exploring the need for a continuing education course for the critical care nursing community turned into the development of the Preparing the Critical Care Nurse program. The course offered an opportunity for collaboration between area hospitals and a college of nursing by facilitating the transition of undergraduate nurses to the critical care setting using high-fidelity simulation. Course development, implementation, evaluation, and suggestions for similar courses in the future are presented. Goals of the simulation component of the course were evaluated and addressed the participants' self-confidence and satisfaction with learning through simulation. A 6-month postevaluation provided insight into the participants' impressions of simulation as a learning tool as they currently practice critical care nursing.

J Contin Educ Nurs
2009;40(10):443–451.
Bulletin Board Basics
Authors: Stein Donna L.
Published: October 2009

Bulletin boards are ideal teaching tools. They are adaptable to many situations. Their advantages are explored in this column.

J Contin Educ Nurs
2009;40(10):440–441.
Reflection on Photographs: Exploring First-Year Nursing Students' Perceptions of Older Adults
Authors: Brand Gabrielle , McMurray Anne
Published: October 2009

Nursing students' exposure to clinical placements with older adults is instrumental in helping them adopt positive attitudes toward care of that population. This qualitative pilot study analyzed perceptions and expectations of a group of first-year students prior to a clinical placement with older adults. A photo-elicitation technique, involving viewing of realistic photographs of older adults being cared for, was used to help students clarify expectations. This was followed by thematic analysis of their perceptions and expectations. Analysis revealed five main themes: Dissecting What It Means to Be a Nurse, Revisioning Therapeutic Relationships in Terms of Dignity, Youthful Reflection on the Differences Between Young and Old, Feeling Challenged and Confronted, and Experiencing Sensitivity and Awkwardness Toward Older Adults' Nakedness. Engagement with images of older adults encouraged students to anticipate their clinical placement in an aged care setting in a more meaningful, reflective way than they may have done without prior exposure, suggesting a need for realistic pre-practice education.
Supporting Self-Determination of Older Adults in Community Health Settings: A Curriculum Development Project
Authors: Sikma Suzanne K.
Published: October 2009

This article describes a curriculum development project to strengthen the geriatric component of an RN-to-BSN program through creation of a multidisciplinary curricular framework that supports the self-determination of older adults and promotes best practices in geriatric community health nursing. The project involved integrating multidisciplinary theories with nursing competencies generated from interviews with geriatric community health nurses that subsequently were cross-validated with baccalaureate competencies for geriatric nursing care. The outcome was a theory and practice-based curricular model for teaching geriatric community health nursing used to strengthen the development of geriatric nursing competence of RN-to-BSN students.
The Specificity of Trimming of MHC Class I-Presented Peptides in the Endoplasmic Reticulum
Authors: Hearn Arron , York Ian A. , Rock Kenneth L.
Published: October 2009

Aminopeptidases in the endoplasmic reticulum (ER) can cleave antigenic peptides and in so doing either create or destroy MHC class I-presented epitopes. However, the specificity of this trimming process overall and of the major ER aminopeptidase ERAP1 in particular is not well understood. This issue is important because peptide trimming influences the magnitude and specificity of CD8 T cell responses. By systematically varying the N-terminal flanking sequences of peptides in a cell-free biochemical system and in intact cells, we elucidated the specificity of ERAP1 and of ER trimming overall. ERAP1 can cleave after many amino acids on the N terminus of epitope precursors but does so at markedly different rates. The specificity seen with purified ERAP1 is similar to that observed for trimming and presentation of epitopes in the ER of intact cells. We define N-terminal sequences that are favorable or unfavorable for Ag presentation in ways that are independent from the epitopes core sequence. When databases of known presented peptides were analyzed, the residues that were preferred for the trimming of model peptide precursors were found to be overrepresented in N-terminal flanking sequences of epitopes generally. These data define key determinants in the specificity of Ag processing.
Targeting of DC-SIGN on Human Dendritic Cells by Minor Fimbriated Porphyromonas gingivalis Strains Elicits a Distinct Effector T Cell Response
Authors: Zeituni Amir E. , Jotwani Ravi , Carrion Julio , Cutler Christopher W.
Published: October 2009

The oral mucosal pathogen Porphyromonas gingivalis expresses at least two adhesins: the 67-kDa mfa-1 (minor) fimbriae and the 41-kDa fimA (major) fimbriae. In periodontal disease, P. gingivalis associates in situ with dermal dendritic cells (DCs), many of which express DC-SIGN (DC-specific ICAM-3 grabbing nonintegrin; CD209). The cellular receptors present on DCs that are involved in the uptake of minor/major fimbriated P. gingivalis, along with the effector immune response induced, are presently unclear. In this study, stably transfected human DC-SIGN+/− Raji cell lines and monocyte-derived DCs (MoDCs) were pulsed with whole, live, wild-type Pg381 or isogenic major (DPG-3)-, minor (MFI)-, or double fimbriae (MFB)-deficient mutant P. gingivalis strains. The influence of blocking Abs, carbohydrates, full-length glycosylated HIV-1 gp120 envelope protein, and cytochalasin D on the uptake of strains and on the immune responses was determined in vitro. We show that the binding of minor fimbriated P. gingivalis strains to Raji cells and MoDCs is dependent on DC-SIGN, whereas the double fimbriae mutant strain does not bind. Binding to DC-SIGN on MoDCs is followed by the internalization of P. gingivalis into DC-SIGN-rich intracellular compartments, and MoDCs secrete low levels of inflammatory cytokines and remain relatively immature. Blocking DC-SIGN with HIV-1 gp120 prevents the uptake of minor fimbriated strains and deregulates the expression of inflammatory cytokines. Moreover, MoDCs promote a Th2 or Th1 effector response, depending on whether they are pulsed with minor or major fimbriated P. gingivalis strains, respectively, suggesting distinct immunomodulatory roles for the two adhesins of P. gingivalis.
PU.1 Regulates Positive Regulatory Domain I-Binding Factor 1/Blimp-1 Transcription in Lymphoma Cells
Authors: Desai Shruti , Bolick Sophia C. E. , Maurin Michelle , Wright Kenneth L.
Published: October 2009

The human positive regulatory domain I-binding factor 1 (PRDI-BF1) and its murine homolog Blimp-1 promote differentiation of mature B cells into Ab-secreting plasma cells. In contrast, ectopic expression of PRDI-BF1 in lymphoma cells can lead to inhibition of proliferation or apoptosis. However, little is currently known about the regulation of PRDM1, the gene encoding PRDI-BF1. This report establishes that in lymphoma cells stimulation through the BCR rapidly induces endogenous PRDM1 at the level of transcription with minor changes in mRNA stability. The induced PRDM1-encoded protein localizes to its target genes in vivo and suppresses their expression. In vivo genomic footprinting of the PRDM1 promoter in unstimulated lymphoma and myeloma cells reveals multiple common in vivo occupied elements throughout the promoter. Further functional and structural analysis of the promoter reveals that the promoter is preloaded and poised for activation in the B cell lines. The transcription factor PU.1 is shown to be required for the BCR-induced expression of PRDM1 in lymphoma cells and in PU.1-positive myeloma cells. Activation of PRDM1 is associated with loss of the corepressor transducin-like enhancer of split 4 from the PU.1 complex. These findings indicate that PRDM1 is poised for activation in lymphoma cells and therefore may be a potential therapeutic target to inhibit lymphoma cell proliferation and survival.
Ikaros Is a Regulator of Il10 Expression in CD4+ T Cells
Authors: Umetsu Sarah E. , Winandy Susan
Published: October 2009

IL-10 is a regulatory cytokine critical for controlling inflammatory responses. Here we show that Ikaros, a zinc finger DNA-binding protein, plays an important role in the regulation of Il10 in murine CD4+ T cells. Upon initial stimulation of the TCR, T cells deficient in Ikaros express significantly lower levels of IL-10 compared with wild-type T cells. In addition, under Th2 skewing conditions, which induce IL-10 production by wild-type T cells, Ikaros null T cells are unable to properly differentiate, producing only low levels of IL-10. Expression of a dominant-negative isoform of Ikaros in wild-type Th2 cells represses IL-10 production but does not significantly alter expression levels of the genes encoding the transcription factors GATA-3 and T-bet. Furthermore, expression of Ikaros in Ikaros null T cells restores expression of the Th2 cytokines IL-10 and IL-4 while reducing production of the Th1 cytokine, IFN-γ. Coexpression of Ikaros and GATA-3 further increases IL-10 production, showing that these two factors have an additive effect on activating Il10 expression. Finally, we show that Ikaros binds to conserved regulatory regions of the Il10 gene locus in Th2 cells, supporting a direct role for Ikaros in Il10 expression. Thus, we provide evidence for Ikaros as a regulator of Il10 and Ifng gene expression and suggest a role for Ikaros in directing lineage-specific cytokine gene activation and repression.
Ly49H Engagement Compensates for the Absence of Type I Interferon Signaling in Stimulating NK Cell Proliferation During Murine Cytomegalovirus Infection
Authors: Geurs Theresa L. , Zhao Yun M. , Hill Elaise B. , French Anthony R.
Published: October 2009

NK cells vigorously proliferate during viral infections, resulting in an expanded pool of innate lymphocytes that are able to participate in early host defense. The relative contributions of cytokines and activation receptors in stimulating NK cell proliferation during viral infections are not well characterized. In this study, we demonstrated that signaling through the NK cell activation receptor Ly49H was able to compensate for the absence of cytokine stimulation in the preferential phase of viral-induced proliferation during murine cytomegalovirus infection. In the absence of type I IFN stimulation, NK cell proliferation was strongly biased toward cells expressing the Ly49H receptor, even at early time points when minimal preferential Ly49H-mediated proliferation was observed in wild-type mice. In the absence of effective Ly49H signaling or following infection with virus that did not express the ligand for Ly49H, no difference was observed in the proliferation of subsets of NK cells that either express or lack expression of Ly49H, although the overall proliferation of NK cells in IFNαβR−/− mice was substantially reduced. These results highlight the contribution of NK cell activation receptors in stimulating proliferation and subsequent expansion of NK cells that are able to recognize virally infected cells.
HOXB4-Transduced Embryonic Stem Cell-Derived Lin−c-kit+ and Lin−Sca-1+ Hematopoietic Progenitors Express H60 and Are Targeted by NK Cells
Authors: Tabayoyong William B. , Salas Juan G. , Bonde Sabrina , Zavazava Nicholas
Published: October 2009

Embryonic stem (ES) cells are a novel source of cells, especially hematopoietic progenitor cells that can be used to treat degenerative diseases in humans. However, there is a need to determine how ES cell-derived progenitors are regulated by both the adaptive and innate immune systems post transplantation. In this study, we demonstrate that hematopoietic progenitor cells (HPCs) derived from mouse ES cells ectopically expressing HOXB4 fail to engraft long-term in the presence of NK cells. In particular, the H60-expressing Lin−c-kit+ and Lin−Sca-1+ subpopulations were preferentially deleted in Rag2−/−, but not in Rag2−/−γc−/− mice. Up-regulation of class I expression on HPCs prevented their lysis by NK cells, and Ab-mediated depletion of NK cells restored long-term HPC engraftment. In contrast to the notion that ES-derived cells are immune-privileged, we show in this study that NK cells form a formidable barrier to the long-term engraftment of ES cell-derived hematopoietic progenitors.
The Adaptor Protein Shc Plays a Key Role during Early B Cell Development
Authors: Giles Amber J. , Bender Timothy P. , Ravichandran Kodi S.
Published: October 2009

The adaptor protein Shc is phosphorylated downstream of many cell surface receptors, including Ag and cytokine receptors. However, the role of Shc in B cell development has not been addressed. Here, through conditional expression of a dominant negative Shc mutant and conditional loss of Shc protein expression, we tested a role for Shc during early B lymphopoiesis. We identified a requirement for Shc beginning at the transition from the pre-pro-B to pro-B stage, with a strong reduction in the number of pre-B cells. This developmental defect is due to increased cell death rather than impaired proliferation or commitment to the B lineage. Additional studies suggest a role for Shc in IL-7-dependent signaling in pro-B cells. Shc is phosphorylated in response to IL-7 stimulation in pro-B cells, and pro-B cells from mice with impaired Shc signaling display increased apoptosis. Together, these data demonstrate a critical role for Shc in early B lymphopoiesis with a requirement in early B cell survival. In addition, we also identify Shc as a required player in signaling downstream of the IL-7R in early B cells.
Adventitious Organogenesis
Authors: De Klerk Geert‐Jan
Published: October 2009

In plants, differentiated somatic cells may dedifferentiate and subsequently redifferentiate into (adventitious) shoots, roots, or embryos. The formation of adventitious shoots (caulogenesis) and roots (rhizogenesis) is specified with the term adventitious organogenesis, whereas somatic embryogenesis refers to the formation of adventitious (somatic) embryos. Adventitious organogenesis occurs frequently during natural life but may be achieved at very high frequencies in tissue culture. It is one of the basic tools in vegetative plant propagation and plant breeding. In propagation, adventitious formation of shoots is important in micropropagation of many crops and adventitious formation of roots from (micro)cuttings is required to obtain complete plants from excised shoots. In breeding, adventitious organogenesis is essential among others in transformation and haploid production. This article reviews adventitious organogenesis from the point of view of developmental biology and deals with physiological, biochemical, molecular, and genetic aspects. It covers both practical and fundamental aspects.
Antibody Engineering
Authors: Yoo Esther M. , Morrison Sherie L.
Published: October 2009

There is great potential for the use of antibodies for various applications in biotechnology, immunity and human health. In this article, we will describe the structure and function of immunoglobulins and the advances, as well as challenges in engineering antibodies. Many factors need to be considered to produce the most effective and relevant antibody for a given purpose. The five different immunoglobulin isotypes that differ in their role in the immune system are described. The various receptors and ligands that bind antibodies and engage in effector functions are also discussed. Using genetic modifications and manipulation, it is now possible to engineer antibodies, antibody fragments, and fusion proteins. In addition, the advantages and limitations in the use of various expression systems such as cell lines and transgenic animals are outlined. Antibodies have been studied extensively for decades and much is known about them. The many years of exploring the antibody molecule should be brought to fruition as we move our scientific knowledge from the laboratory to develop innovative tools for biology as well as treatments and prophylactics against pathogens and human diseases.
Apoptosis
Authors: Al‐Rubeai Mohamed , Khoo Soo Hean Gary , Singh Rabinder P.
Published: October 2009

Apoptosis is now acknowledged as a fundamentally important process that plays an essential role in embryogenesis and in the maintenance and functionality of the highly ordered cell populations that constitute higher organisms. In this article, we describe the biochemical basis of apoptosis, the morphological changes that accompany it, and some of the techniques that have been used to identify apoptotic cells. This is followed by a general discussion of the regulation and induction of apoptosis. We then describe studies that have investigated this phenomenon from a biotechnological perspective. Particular reference is made to the conditions that elicit an apoptotic response, the cell lines that are susceptible, and the cellular engineering approaches to enhance cell survival and productivity in the bioreactor environment.
Bioreactor Scale‐Up
Authors: Palomares Laura A. , Ramírez Octavio T.
Published: October 2009

Scaling‐up is a determinant step during process development. Successful scale‐up requires careful calculation of the geometric relations of the large‐scale bioreactor to avoid heterogeneities. In this article, the work done by various engineers in bioreactor design and prediction of possible environmental gradients in bioreactors is presented and discussed, with emphasis on reactors for cell culture. Several bioreactor configurations are discussed. Other issues such as heat transfer are also presented. The theoretical framework for predicting the behavior of large‐scale cultures is presented.
Microbial Primary Metabolites: Biosynthesis and Perspectives
Authors: Sanchez Sergio , Demain Arnold L.
Published: October 2009

The microbial production of primary metabolites contributes significantly to the quality of life. Fermentative production of these compounds is still an important goal of modern biotechnology. Through fermentation, microorganisms growing on inexpensive carbon and nitrogen sources produce valuable products such as amino acids, nucleotides, organic acids, and vitamins, which can be added to food to enhance its flavor, or increase its nutritive values. The contribution of microorganisms goes well beyond the food and health industries with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum‐derived products as well as the ethanol necessary for liquid fuel. Additional applications of primary metabolites lie in their impact as precursors of many pharmaceutical compounds. The roles of primary metabolites and the microbes which produce them will certainly increase in importance as time goes on.

Overproduction of microbial metabolites is related to developmental phases of microorganisms. Inducers, effectors, inhibitors, and various signal molecules play a role in different types of overproduction. Biosynthesis of enzymes catalyzing metabolic reactions in microbial cells is controlled by well‐known positive and negative mechanisms, for example, induction, nutritional regulation (carbon or nitrogen source regulation), and feedback regulation.

In the early years of fermentation processes, development of producing strains initially depended on classical strain breeding involving repeated random mutations, each followed by screening or selection. More recently, methods of molecular genetics have been used for the overproduction of primary metabolic products. The development of modern tools of molecular biology enabled more rational approaches for strain improvement. Techniques of transcriptome, proteome, and metabolome analysis, as well as metabolic flux analysis, have recently been introduced in order to identify new and important target genes and to quantify metabolic activities necessary for further strain improvement.
Carotenoids, Microbial Processes
Authors: Schmidt‐Dannert Claudia , Lee Pyung Cheon
Published: October 2009

Carotenoids are used commercially as food colorants, feed supplements, nutraceuticals, and for cosmetic and pharmaceutical purposes. However, only a handful of the more than several hundred different carotenoids identified in nature can be obtained in useful quantities by chemical synthesis, extraction from their natural sources or microbial fermentation. The current global market for all commercially used carotenoids is expected to rise at an average annual growth rate of 2.9% reaching over $1 billion in 2009. The over‐the‐counter and pharmaceutical sector has become a new market for carotenoids and, together with an increasing demand for carotenoids in traditional feed and food applications, pushes efforts for the production of diverse carotenoid structures in useful quantities. As an alternative to chemical synthesis and extraction from natural sources, microbial processes are being currently developed for the production of carotenoids. In this article we will discuss the recent progress made in the development of microbial processes for carotenoid production.
Cell Wall Disruption and Lysis
Authors: Garcia F. A. P.
Published: October 2009

The microbial world has been increasingly exploited for the production of useful materials. The disruption of the cell wall is a necessary step in the separation and purification of intracellular products. A general review of the chemical composition and structure of the cell wall is given for different kinds of microorganisms. The effects of cell growth conditions on the resistance of the cell wall to disruption are analysed and quantitative data of the cell wall strength is presented. Different methods of quantifying the efficiency of the disintegration process are commented. A review is made of the main technologies used for the disintegration of the cell wall, which have gained large acceptance for either analytical or preparative and large scale applications. The implications of the disruption process for further separation operations are also reviewed. New trends for process intensification by coupling the disruption/permeabilization step with primary capture techniques to yield pure target proteins in fewer process steps are also reviewed.
Chromatography, Industrial Scale, Validation: Checklists for Systems Compliance
Authors: Weinberg Sandy , Rockburne Carl A.
Published: October 2009

The US Food and Drug Administration provides a series of regulatory guidelines and directives definiing the required validation for chromotography systems. This validation process is critical to the demonstration of managerial control of the system, and provides the necessary credibility for the output of a chromatographic analysis. This article provides a checklist for that validation process, referencing the key points in that list to appropriate sections of the Good Manufacturing Practices, Code of Federal Requirements, and other significant guidelines. Taken in totality the checklist can provide a framework for the validation study; an internal quality assurance check on the validation and the controls of the chromatographic system; and the FDA‐required documentary evidence of managerial oversight.
Enzymes, Directed Evolution
Authors: Reetz Manfred T.
Published: October 2009

Directed evolution has emerged as a powerful method for engineering the catalytic profile of enzymes. It is based on repetitive cycles of random gene mutagenesis and expression coupled with efficient high‐throughput screening or selection for a given catalytic property such as thermostability, substrate acceptance, and/or enantioselectivity. In the 1990s, directed evolution was established on a broad front by applying standard mutagenesis methods such aserror‐prone polymerase chain reaction(epPCR), saturation mutagenesis, and DNA shuffling. The current challenge is to devise optimal strategies for probing protein sequence space, thereby allowing for fast directed evolution. This article covers the progress of the last few years.
Neurite Outgrowth on Nanocomposite Scaffolds Synthesized from PLGA and Carboxylated Carbon Nanotubes
Authors: Lee Hyun Jung , Yoon Ok Ja , Kim Do Hee , Jang Yeong Mi , Kim Hyun Woo , Lee Won Bok , Lee Nae‐Eung , Kim Sung Su
Published: October 2009

Carbon nanotubes (CNTs) have been suggested as suitable materials for biomedical applications, especially in the neural area. It is essential not only to investigate the biocompatibility of CNTs with the neural system but also to determine proper methods for applying CNTs to neuronal growth. This work represents the first application of CNTs by electrospun poly(D,L‐lactic‐co‐glycolic acid) (PLGA) scaffolds for a neural system. We synthesized electrospun nanocomposites of PLGA and single‐walled carbon nanotubes functionalized by carboxylic acid groups (c‐SWNTs), and investigated neurite outgrowth from SH‐SY5Y cells on these nanocomposites as compared to that on fibrous PLGA alone. Cells on our PLGA/c‐SWNT nanocomposite showed significantly enhanced mitochondrial function and neurite outgrowth compared to cells on PLGA alone. We concluded that c‐SWNTs incorporated into fibrous PLGA scaffolds exerted a positive role on the health of neural cells.