bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE LIVED EXPERIENCE OF THE PERSON DEPENDENT ON HAEMODIALYSIS
Authors: Calvey Dympna , Mee Lorraine 
Published: October 2011

SUMMARYThe phenomenon of experiencing life dependent on haemodialysis is infinitely multi‐faceted. It effects all aspects of people's lives, and not only their lives, but those of the people around them. Busy dialysis units often do not have time to explore these effects on the lives of their patients outside the clinical setting.Aims: The aim of this qualitative study was to step into the lives of seven patients once they were outside the dialysis unit.Method: Seven chronic haemodialysis patients were selected and interviewed using an in‐depth semi‐structured approach, following the philosophy of Heidegger. Data was analysed using Colaizzi's seven‐stage process.Results: The strongest common theme emerged through descriptions of the patient's ‘Sense of Self’, within which emerged sub‐themes; The Future Self, The Living Self, The Mortal/Fragile Self and The Growing/Learning Self. These were further explored and related back to importance of awareness of such findings within the renal haemodialysis practice setting.
Randomized comparison of etanercept with usual therapy in an Asian population with active rheumatoid arthritis: the APPEAL trial
Authors: KIM Ho‐Youn , HSU Ping‐Ning , BARBA Merle , SULAIMAN Wahinnuddin , ROBERTSON Debbie , VLAHOS Bonnie , KHANDKER Rezaul , NAB Henk , FREUNDLICH Bruce , KOENIG Andrew 
Published: October 2011

AbstractAim:  Rheumatoid arthritis (RA) is an important rheumatologic disease in Asia‐Pacific countries, as in other parts of the world. However, limited information is available regarding RA therapy in this region. The Asia‐Pacific Study in Patients to be Treated With Etanercept or an Alternative Listed DMARD (APPEAL) compared efficacy and safety of etanercept (ETN) + methotrexate (MTX) versus usual disease‐modifying anti‐rheumatic drugs (DMARDs) + MTX (reflecting regional practice) in subjects with moderate to severe RA from multiple Asia‐Pacific countries.Method:  In this open‐label, active‐comparator, parallel‐design, multicenter study, subjects (n = 300) in the Asia‐Pacific region were randomized to ETN + MTX (n = 197) or DMARD + MTX (n = 103). The primary efficacy endpoint was the American College of Rheumatology (ACR) response (ACR‐N) area under the curve (AUC) over 16 weeks.Results:  Baseline characteristics were similar between groups. At Week 16, ACR‐N AUC indicated a significantly greater response with ETN + MTX compared with DMARD + MTX (mean difference –145.3; P < 0.001). Significantly greater proportions of subjects achieved ACR 20, 50 and 70 responses with ETN + MTX versus DMARD + MTX at Week 16 (P < 0.05). Low Disease Activity Score based on a 28‐joint count (DAS28 < 3.2) was also achieved by significantly more subjects in the ETN + MTX group versus the DMARD + MTX group (P < 0.001). Greater improvements were shown for DAS28, pain visual analogue scale, health assessment questionnaire, and physician and patient global assessments (P < 0.05) for ETN + MTX versus DMARD + MTX. No new safety signals were found.Conclusion:  In this Asia‐Pacific population of subjects with moderate to severe RA, ETN + MTX showed superior efficacy versus usual DMARD + MTX regimens, with similar safety profiles.
A Novel Metabolite of Antituberculosis Therapy Demonstrates Host Activation of Isoniazid and Formation of the Isoniazid-NAD
+
Adduct
Authors: Mahapatra Sebabrata , Woolhiser Lisa K. , Lenaerts Anne J. , Johnson John L. , Eisenach Kathleen D. , Joloba Moses L. , Boom W. Henry , Belisle John T. 
Published: October 2011

ABSTRACT

One of the most effective and widely used antituberculosis (anti-TB) drugs is isoniazid (INH), a prodrug activated via oxidation that forms an adduct with NAD
+
to inhibit NADH-dependent targets of
Mycobacterium tuberculosis
, such as enoyl-acyl carrier protein reductase (InhA). The metabolic by-products and potentially toxic intermediates resulting from INH therapy have been identified through a large body of work. However, an INH-NAD adduct or structures related to this adduct have not been identified in specimens from human TB patients or animal models of TB. Analyses by mass spectrometry of urine collected from TB patients in a study conducted by the NIAID-funded Tuberculosis Research Unit identified 4-isonicotinoylnicotinamide (C
12
H
9
N
3
O
2
) as a novel metabolite of INH therapy. This compound was formed by
M. tuberculosis
strains in a KatG-dependent manner but could also be produced by mice treated with INH independent of an
M. tuberculosis
infection. Thus, the 4-isonicotinoylnicotinamide observed in human urine samples is likely derived from the degradation of oxidized INH-NAD adducts and provides direct evidence of host INH activation.
F18, a Novel Small-Molecule Nonnucleoside Reverse Transcriptase Inhibitor, Inhibits HIV-1 Replication Using Distinct Binding Motifs as Demonstrated by Resistance Selection and Docking Analysis
Authors: Lu Xiaofan , Liu Li , Zhang Xu , Lau Terrence Chi Kong , Tsui Stephen Kwok Wing , Kang Yuanxi , Zheng Purong , Zheng Bojian , Liu Gang , Chen Zhiwei 
Published: October 2011

ABSTRACTNonnucleoside reverse transcriptase inhibitors (NNRTIs) are one of the key components of antiretroviral therapy drug regimen against human immunodeficiency virus type 1 (HIV-1) replication. We previously described a newly synthesized small molecule, 10-chloromethyl-11-demethyl-12-oxo-calanolide A (F18), a (+)-calanolide A analog, as a novel anti-HIV-1 NNRTI (H. Xue et al., J. Med. Chem. 53:1397–1401, 2010). Here, we further investigated its antiviral range, drug resistance profile, and underlying mechanism of action. F18 consistently displayed potent activity against primary HIV-1 isolates, including various subtypes of group M, circulating recombinant form (CRF) 01_AE, and laboratory-adapted drug-resistant viruses. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (50% effective concentration, 1.0 nM), which was in stark contrast to the extensively used NNRTIs nevirapine and efavirenz. Moreover, we induced F18-resistant viruses byin vitroserial passages and found that the mutation L100I appeared to be the dominant contributor to F18 resistance, further suggesting a binding motif different from that of nevirapine and efavirenz. F18 was nonantagonistic when used in combination with other antiretrovirals against both wild-type and drug-resistant viruses in infected peripheral blood mononuclear cells. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). Furthermore,in silicodocking analysis suggested that F18 may bind to the HIV-1 reverse transcriptase differently from other NNRTIs. This study presents F18 as a new potential drug for clinical use and also presents a new mechanism-based design for future NNRTI.
Macrophyte Species Drive the Variation of Bacterioplankton Community Composition in a Shallow Freshwater Lake
Authors: Zeng Jin , Bian Yuanqi , Xing Peng , Wu Qinglong L. 
Published: October 2011

ABSTRACT
Macrophytes play an important role in structuring aquatic ecosystems. In this study, we explored whether macrophyte species are involved in determining the bacterioplankton community composition (BCC) in shallow freshwater lakes. The BCC in field areas dominated by different macrophyte species in Taihu Lake, a large, shallow freshwater lake, was investigated over a 1-year period. Subsequently, microcosm experiments were conducted to determine if single species of different types of macrophytes in an isolated environment would alter the BCC. Denaturing gradient gel electrophoresis (DGGE), followed by cloning and sequence analysis of selected samples, was employed to analyze the BCC. The DGGE results of the field investigations indicated that the BCC changed significantly from season to season and that the presence of different macrophyte species resulted in lower BCC similarities in the summer and fall. LIBSHUFF analysis of selected clone libraries from the summer demonstrated different BCCs in the water column surrounding different macrophytes. Relative to the field observations, the microcosm studies indicated that the BCC differed more pronouncedly when associated with different species of macrophytes, which was also supported by LIBSHUFF analysis of the selected clone libraries. Overall, this study suggested that macrophyte species might be an important factor in determining the composition of bacterial communities in this shallow freshwater lake and that the species-specific influence of macrophytes on BCC is variable with the season and distance.
Effect of Honey on Streptococcus mutans Growth and Biofilm Formation
Authors: Nassar Hani M. , Li Mingyun , Gregory Richard L. 
Published: October 2011

ABSTRACT

Because of the tradition of using honey as an antimicrobial medicament, we investigated the effect of natural honey (NH) on
Streptococcus mutans
growth, viability, and biofilm formation compared to that of an artificial honey (AH). AH contained the sugars at the concentrations reported for NH. NH and AH concentrations were obtained by serial dilution with tryptic soy broth (TSB). Several concentrations of NH and AH were tested for inhibition of bacterial growth, viability, and biofilm formation after inoculation with
S. mutans
UA159 in 96-well microtiter plates to obtain absorbance and CFU values. Overall, NH supported significantly less (
P
< 0.05) bacterial growth than AH at 25 and 12.5% concentrations. At 50 and 25% concentrations, both honey groups provided significantly less bacterial growth and biofilm formation than the TSB control. For bacterial viability, the results for all honey concentrations except 50% NH were not significantly different from those for the TSB control. NH was able to decrease the maximum velocity of
S. mutans
growth compared to AH. In summary, NH demonstrated more inhibition of bacterial growth, viability, and biofilm formation than AH. This study highlights the potential antibacterial properties of NH and could suggest that the antimicrobial mechanism of NH is not solely due to its high sugar content.
Heme-Biosynthetic Porphobilinogen Deaminase Protects Aspergillus nidulans from Nitrosative Stress
Authors: Zhou Shengmin , Narukami Toshiaki , Nameki Misuzu , Ozawa Tomoko , Kamimura Yosuke , Hoshino Takayuki , Takaya Naoki 
Published: October 2011

ABSTRACT

Microorganisms have developed mechanisms to combat reactive nitrogen species (RNS); however, only a few of the fungal genes involved have been characterized. Here we screened RNS-resistant
Aspergillus nidulans
strains from fungal transformants obtained by introducing a genomic DNA library constructed in a multicopy vector. We found that the
AN0121.3
gene (
hemC
) encodes a protein similar to the heme biosynthesis enzyme porphobilinogen deaminase (PBG-D) and facilitates RNS-tolerant fungal growth. The overproduction of PBG-D in
A. nidulans
promoted RNS tolerance, whereas PBG-D repression caused growth that was hypersensitive to RNS. PBG-D levels were comparable to those of cellular protoheme synthesis as well as flavohemoglobin (FHb; encoded by
fhbA
and
fhbB
) and nitrite reductase (NiR; encoded by
niiA
) activities. Both FHb and NiR are hemoproteins that consume nitric oxide and nitrite, respectively, and we found that they are required for maximal growth in the presence of RNS. The transcription of
hemC
was upregulated by RNS. These results demonstrated that PBG-D is a novel NO-tolerant protein that modulates the reduction of environmental NO and nitrite levels by FHb and NiR.
Roles of Diet and the Acid Tolerance Response in Survival of Common Salmonella Serotypes in Feces of Finishing Pigs
Authors: Rajtak Ursula , Boland Fiona , Leonard Nola , Bolton Declan , Fanning Séamus 
Published: October 2011

ABSTRACTThe persistence ofSalmonellain the environment is an important factor influencing the transmission of infection in pig production. This study evaluated the effects of acid tolerance response (ATR), organic acid supplementation, and physical properties of feed on the survival of a five-strainSalmonellamixture in porcine feces held at 4 and 22°C for 88 days. Acid-adapted or non-acid-adapted nalidixic acid-resistantSalmonellastrains were used to inoculate feces of pigs fed four different diets, which consisted of a nonpelleted, finely ground meal feed or a finely ground, pelleted feed that was left unsupplemented or was supplemented with K-diformate. Organic acid supplementation and physical properties of feed markedly influencedSalmonellasurvival, but the effects were highly dependent on storage temperature; survival was unaffected by ATR. The most pronounced effects were observed at 22°C, a temperature similar to that of finishing pig houses. The supplementation of meal diets with K-diformate significantly reduced the duration of survival (P< 0.1) and increased rates of decline (P< 0.0001) of salmonellae in feces compared to survival in feces of pigs fed unsupplemented meal. The pelleting of feed, compared to feeding meal, significantly reduced (P< 0.1) the duration of survival in feces held at 22°C. Only minor effects of feed form and acid supplementation on survivor numbers were observed at 4°C. Differences in the fecal survival ofSalmonellacould not be related to diet-induced changes in fecal physiochemical parameters. The predominant survival ofS. entericaserovar Typhimurium DT193 and serotype 4,[5],12:i:- in porcine feces demonstrates the superior ability of these serotypes to survive in this environment. Fecal survival and transmission ofSalmonellain pig herds may be reduced by dietary approaches, but effects are highly dependent on environmental temperature.
When Second Best Is Good Enough: Another Probabilistic Look at Saturation Mutagenesis
Authors: Nov Yuval 
Published: October 2011

ABSTRACT
We developed new criteria for determining the library size in a saturation mutagenesis experiment. When the number of all possible distinct variants is large, any of the top-performing variants (e.g., any of the top three) is likely to meet the design requirements, so the probability that the library contains at least one of them is a sensible criterion for determining the library size. By using a criterion of this type, one may significantly reduce the library size and thus save costs and labor while minimally compromising the quality of the best variant discovered. We present the probabilistic tools underlying these criteria and use them to compare the efficiencies of four randomization schemes: NNN, which uses all 64 codons; NNB, which uses 48 codons; NNK, which uses 32 codons; and MAX, which assigns equal probabilities to each of the 20 amino acids. MAX was found to be the most efficient randomization scheme and NNN the least efficient. TopLib, a computer program for carrying out the related calculations, is available through a user-friendly Web server.
Growth Rate-Dependent Control in Enterococcus faecalis: Effects on the Transcriptome and Proteome, and Strong Regulation of Lactate Dehydrogenase
Authors: Mehmeti Ibrahim , Faergestad Ellen M. , Bekker Martijn , Snipen Lars , Nes Ingolf F. , Holo Helge 
Published: October 2011

ABSTRACT

Enterococcus faecalis
V583 was grown in a glucose-limited chemostat at three different growth rates (0.05, 0.15, and 0.4 h
−1
). The fermentation pattern changed with growth rate, from a mostly homolactic profile at a high growth rate to a fermentation dominated by formate, acetate, and ethanol production at a low growth rate. A number of amino acids were consumed at the lower growth rates but not by fast-growing cells. The change in metabolic profile was caused mainly by decreased flux through lactate dehydrogenase. The transcription of
ldh
-
1
, encoding the principal lactate dehydrogenase, showed very strong growth rate dependence and differed by three orders of magnitude between the highest and the lowest growth rates. Despite the increase in
ldh
-1 transcript, the content of the Ldh-1 protein was the same under all conditions. Using microarrays and quantitative PCR, the levels of 227 gene transcripts were found to be affected by the growth rate, and 56 differentially expressed proteins were found by proteomic analyses. Few genes or proteins showed a growth rate-dependent increase or decrease in expression across the whole range of conditions, and many showed a maximum or minimum at the middle growth rate (i.e., 0.15 h
−1
). For many gene products, a discrepancy between transcriptomic and proteomic data were seen, indicating posttranscriptional regulation of expression.
Bacterial Cell Surface Damage Due to Centrifugal Compaction
Authors: Peterson Brandon W. , Sharma Prashant K. , van der Mei Henny C. , Busscher Henk J. 
Published: October 2011

ABSTRACT

Centrifugal damage has been known to alter bacterial cell surface properties and interior structures, including DNA. Very few studies exist on bacterial damage caused by centrifugation because of the difficulty in relating centrifugation speed and container geometry to the damage caused. Here, we provide a simple, versatile method of analysis for describing the compaction of bacteria during centrifugation based on a proposed centrifugation coefficient,
C
. Values of
C
can be related to different bacterial cell surface properties. Changing the geometry of the centrifugation container or centrifugation speeds changed the value of
C
significantly. Initial deposition rates of
Staphylococcus aureus
ATCC 12600 to a glass surface decayed exponentially from 4,217 to 1,478 cm
−2
s
−1
with increasing
C
, while the proportion of staphylococci with a zeta potential of around −15 mV decreased from 97 to 58%. These surface-sensitive parameters were used independently to derive a critical centrifugation coefficient (0.040), above which centrifugation was considered to impact the outcome of surface-sensitive experiments due to cell surface damage. The critical centrifugation coefficient could successfully predict staphylococcal cell surface damage, i.e., a significant change in initial deposition rate or zeta potential distribution, in 84% of all cases included here, whereas the centrifugation speed could predict damage in only 58% of all cases. Moreover, controlling the centrifugation coefficient within narrow limits over a series of experiments yielded 43% smaller standard deviations in initial staphylococcal deposition rates than with centrifugation at fixed speeds for replicate experiments.
Increased Frequency of Regulatory T Cells and T Lymphocyte Activation in Persons with Previously Treated Extrapulmonary Tuberculosis
Authors: de Almeida Alexandre S. , Fiske Christina T. , Sterling Timothy R. , Kalams Spyros A. 
Published: October 2011

ABSTRACTExtrapulmonary tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4+T lymphocytes in general, are important in the host immune response toMycobacterium tuberculosis. We evaluated T lymphocytes from patients after recovery from extrapulmonary tuberculosis, which may reflect conditions beforeM. tuberculosisinfection. A case-control study was conducted among HIV-uninfected adults with previously treated extrapulmonary tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary tuberculosis, (ii) close tuberculosis contacts withM. tuberculosisinfection, and (iii) close tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4+CD25hiCD127lowFoxP3+cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 extrapulmonary tuberculosis cases, 18 pulmonary tuberculosis controls, 17 controls withM. tuberculosisinfection, and 18 controls withoutM. tuberculosisinfection. The median Treg cell proportion was highest among persons with previous extrapulmonary tuberculosis (1.23%) compared to subjects with pulmonary tuberculosis (0.56%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.20%) (P= 0.001). The median proportion of CD4+T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4+T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.32%) (P= 0.005). Compared with controls, persons with previously treated extrapulmonary tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4+T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for extrapulmonary tuberculosis.
Efg1 Controls Caspofungin-Induced Cell Aggregation of Candida albicans through the Adhesin Als1
Authors: Gregori Christa , Glaser Walter , Frohner Ingrid E. , Reinoso-Martín Cristina , Rupp Steffen , Schüller Christoph , Kuchler Karl 
Published: October 2011

ABSTRACT

Echinocandin drugs such as caspofungin (CASP), micafungin, and anidulafungin inhibit fungal cell wall biogenesis by blocking Fks1-mediated β-glucan deposition into the cell surface. Candins have become suitable drugs to treat life-threatening diseases caused by several fungal species, including
Candida albicans
, that are pathogenic for humans
.
Here, we present the discovery of a novel CASP-induced flocculation phenotype of
C. albicans
, which formed large cell aggregates in the presence of CASP. High concentrations of sugars such as mannose or glucose inhibit CASP-induced flocculation and improve survival of
C. albicans
cells exposed to CASP. Notably, exposure of
C. albicans
cells to CASP triggers Efg1-dependent expression of the adhesin
ALS1
and induces invasive growth on agar plates. Indeed, cells lacking either Efg1 or Als1 show strongly diminished CASP-induced flocculation, and the absence of Efg1 leads to marked CASP hypersensitivity. On the other hand, CASP-induced invasive growth is enhanced in cells lacking Efg1. Hence, CASP stress drives an Efg1-dependent response, indicating that this multifunctional transcriptional regulator, which is otherwise involved in filamentation, white-to-opaque switching, and virulence, also modulates cell wall remodeling upon CASP challenge. Taken together, our data suggest that CASP-induced cell wall damage activates Efg1 in parallel with the known cell integrity stress signaling pathway to coordinate cell wall remodeling.