bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary iodide controls its own absorption through post‐transcriptional regulation of the intestinal Na+/I− symporter
Authors: Nicola Juan Pablo , Reyna‐Neyra Andrea , Carrasco Nancy , Masini‐Repiso Ana Maria 
Published: September 2012

Key points
Expression of the Na+/I− symporter (NIS) at the apical surface of the epithelium of the small intestine is key to I− absorption, the first step in I− metabolism.
Intracellular I− at high concentrations in enterocytes decreases its own NIS‐mediated uptake by a newly discovered mechanism, downregulating NIS expression at the plasma membrane, increasing NIS protein degradation and decreasing NIS mRNA levels by reducing NIS mRNA stability, involving the NIS 3′‐untranslated region.
In conclusion, we have uncovered that I− regulates intestinal NIS expression, and thus its own intestinal absorption, by a complex array of post‐transcriptional mechanisms.
Abstract  Dietary I− absorption in the gastrointestinal tract is the first step in I− metabolism. Given that I− is an essential constituent of the thyroid hormones, its concentrating mechanism is of significant physiological importance. We recently described the expression of the Na+/I− symporter (NIS) on the apical surface of the intestinal epithelium as a central component of the I− absorption system and reported reduced intestinal NIS expression in response to an I−‐rich diet in vivo. Here, we evaluated the mechanism involved in the regulation of NIS expression by I− itself in enterocytes. Excess I− reduced NIS‐mediated I− uptake in IEC‐6 cells in a dose‐ and time‐dependent fashion, which was correlated with a reduction of NIS expression at the plasma membrane. Perchlorate, a competitive inhibitor of NIS, prevented these effects, indicating that an increase in intracellular I− regulates NIS. Iodide induced rapid intracellular recruitment of plasma membrane NIS molecules and NIS protein degradation. Lower NIS mRNA levels were detected in response to I− treatment, although no transcriptional effect was observed. Interestingly, I− decreased NIS mRNA stability, affecting NIS translation. Heterologous green fluorescent protein‐based reporter constructs revealed a significant repressive effect of the I−‐targeting NIS mRNA 3′ untranslated region. In conclusion, excess I− downregulates NIS expression in enterocytes by virtue of a complex mechanism. Our data suggest that I− regulates intestinal NIS mRNA expression at the post‐transcriptional level as part of an autoregulatory effect of I− on its own metabolism.
Population-Based Study of the Increased Incidence of Skin and Soft Tissue Infections and Associated Antimicrobial Use
Authors: Marra Fawziah , Patrick David M. , Chong Mei , McKay Rachel , Hoang Linda , Bowie William R. 
Published: September 2012

ABSTRACT

Community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) has spread rapidly throughout the world in the last decade. We sought to demonstrate the impact of the emergence of CA-MRSA in Western Canada on physician visits, incision-and-drainage procedures, and antibiotic prescribing for skin and soft tissue infections (SSTI). We used the provincial physician billing system to determine the rate of physician visits (per 1,000 population per year) of SSTI and incision-and-drainage procedures. A database capturing all outpatient prescriptions in the province was anonymously linked to associated physician billing codes to quantify prescriptions associated with SSTI. Antibiotic prescriptions (overall and class specific) were expressed as their defined daily dose (DDD) per 1,000 inhabitants per day. Between 1996 and 2008, the rate of visits for all SSTI increased by 15%, and the majority of visits did not include an incision-and-drainage procedure. The rate of antibiotic prescribing for SSTI increased by 49%. The majority of this increase was attributable to the higher rates of use of clindamycin (627%), trimethoprim-sulfamethoxazole (380%), cephalosporins (160%), and amoxicillin-clavulanate (627%). Health care utilization and antibiotic prescribing rates for SSTI, but not incision-and-drainage procedures, have increased in association with the CA-MRSA epidemic. While much of the increase in antibiotic use reflects an appropriate change to trimethoprim-sulfamethoxazole, there is room for education regarding the limitations of cephalosporins and clindamycin, given current susceptibility profiles.
Identification of VanN-Type Vancomycin Resistance in an Enterococcus faecium Isolate from Chicken Meat in Japan
Authors: Nomura Takahiro , Tanimoto Koichi , Shibayama Keigo , Arakawa Yoshichika , Fujimoto Shuhei , Ike Yasuyoshi , Tomita Haruyoshi 
Published: September 2012

ABSTRACT

Five VanN-type vancomycin-resistant
Enterococcus faecium
strains were isolated from a sample of domestic chicken meat in Japan. All isolates showed low-level resistance to vancomycin (MIC, 12 mg/liter) and had the same pulsed-field gel electrophoresis profile. The vancomycin resistance was encoded on a large plasmid (160 kbp) and was expressed constitutively. The VanN-type resistance operon was identical to the first resistance operon to be reported, with the exception of a 1-bp deletion in

vanT
N

and a 1-bp substitution in

vanS
N

.
Effect of PTX3 and Voriconazole Combination in a Rat Model of Invasive Pulmonary Aspergillosis
Authors: Lo Giudice Pietro , Campo Silvia , De Santis Rita , Salvatori Giovanni 
Published: September 2012

ABSTRACT
This study evaluated the pharmacological activity of PTX3, administered in combination with voriconazole, in a rat model of pulmonary aspergillosis. The data indicated additive therapeutic activities of these compounds, as demonstrated by the amelioration of respiratory function changes, reduction of lung fungal burden, and increased survival. Overall, we provide clear evidence that the combination of PTX3 with a suboptimal dose of voriconazole might represent a therapeutic option under those clinical conditions where the use of voriconazole alone is not warranted for efficacy and tolerability reasons.
Effect of Transcriptional Activators SoxS, RobA, and RamA on Expression of Multidrug Efflux Pump AcrAB-TolC in Enterobacter cloacae
Authors: Pérez Astrid , Poza Margarita , Aranda Jesús , Latasa Cristina , Medrano Francisco Javier , Tomás María , Romero Antonio , Lasa Iñigo , Bou Germán 
Published: September 2012

ABSTRACT

Control of membrane permeability is a key step in regulating the intracellular concentration of antibiotics. Efflux pumps confer innate resistance to a wide range of toxic compounds such as antibiotics, dyes, detergents, and disinfectants in members of the
Enterobacteriaceae
. The AcrAB-TolC efflux pump is involved in multidrug resistance in
Enterobacter cloacae
. However, the underlying mechanism that regulates the system in this microorganism remains unknown. In
Escherichia coli
, the transcription of
acrAB
is upregulated under global stress conditions by proteins such as MarA, SoxS, and Rob. In the present study, two clinical isolates of
E. cloacae
, EcDC64 (a multidrug-resistant strain overexpressing the AcrAB-TolC efflux pump) and Jc194 (a strain with a basal AcrAB-TolC expression level), were used to determine whether similar global stress responses operate in
E. cloacae
and also to establish the molecular mechanisms underlying this response. A decrease in susceptibility to erythromycin, tetracycline, telithromycin, ciprofloxacin, and chloramphenicol was observed in clinical isolate Jc194 and, to a lesser extent in EcDC64, in the presence of salicylate, decanoate, tetracycline, and paraquat. Increased expression of the
acrAB
promoter in the presence of the above-described conditions was observed by flow cytometry and reverse transcription-PCR, by using a reporter fusion protein (green fluorescent protein). The expression level of the AcrAB promoter decreased in
E. cloacae
EcDC64 derivates deficient in SoxS, RobA, and RamA. Accordingly, the expression level of the AcrAB promoter was higher in
E. cloacae
Jc194 strains overproducing SoxS, RobA, and RamA. Overall, the data showed that SoxS, RobA, and RamA regulators were associated with the upregulation of
acrAB
, thus conferring antimicrobial resistance as well as a stress response in
E. cloacae
. In summary, the regulatory proteins SoxS, RobA, and RamA were cloned and sequenced for the first time in this species. The involvement of these proteins in conferring antimicrobial resistance through upregulation of
acrAB
was demonstrated in
E. cloacae
.
Comparison of Genospecies and Antimicrobial Resistance Profiles of Isolates in the Acinetobacter calcoaceticus-Acinetobacter baumannii Complex from Various Clinical Specimens
Authors: Tien Ni , You Bang-Jau , Chang Hui-Lan , Lin Hsiu-Shen , Lee Chin-Yi , Chung Tung-Ching , Lu Jang-Jih , Chang Chao-Chin 
Published: September 2012

ABSTRACT

This study was conducted to compare the prevalences of antimicrobial resistance profiles of clinical isolates in the
Acinetobacter calcoaceticus-Acinetobacter baumannii
complex from sterile and nonsterile sites and to further study the relationship of antimicrobial resistance profiles and genospecies by amplified rRNA gene restriction analysis (ARDRA). A total of 1,381 isolates were tested with 12 different antibiotics to show their antimicrobial susceptibility profiles. A total of 205 clinical isolates were further analyzed by ARDRA of the intergenic spacer (ITS) region of the 16S-23S rRNA gene. It was found that the overall percentage of isolates from nonsterile sites (urine, sputum, pus, or catheter tip) that were resistant to the 12 antibiotics tested was significantly higher than that of isolates from sterile sites (cerebrospinal fluid [CSF], ascites fluid, and bloodstream) (46% versus 22%;
P
< 0.05). After ARDRA, it was found that 97% of the 62 isolates resistant to all antibiotics tested were the
A. baumannii
genospecies, which was identified in only 31% of the isolates susceptible to all antibiotics tested. More genospecies diversity was identified in the isolates susceptible to all antibiotics tested, including genospecies of 13TU (34%), genotype 3 (29%), and
A. calcoaceticus
(5%). Furthermore, as 91% (10/11) of the isolates from CSF were susceptible to all antibiotics tested, the
A. calcoaceticus-A. baumannii
complex isolates with multidrug resistance could be less invasive than the more susceptible isolates. This study also indicated current emergence of carbapenem-, fluoroquinolone-, aminoglycoside-, and cephalosporin-resistant
A. calcoaceticus-A. baumannii
complex isolates in Taiwan.
Screening of Antifungal Azole Drugs and Agrochemicals with an Adapted alamarBlue-Based Assay Demonstrates Antibacterial Activity of Croconazole against Mycobacterium ulcerans
Authors: Scherr Nicole , Röltgen Katharina , Witschel Matthias , Pluschke Gerd 
Published: September 2012

ABSTRACT

An alamarBlue-based growth inhibition assay has been adapted for the thermosensitive and slow-growing pathogen
Mycobacterium ulcerans
. The standardized test procedure enables medium-throughput screening of preselected compound libraries. Testing of a set of 48 azoles with known antifungal activity led to the identification of an imidazole antifungal displaying an inhibitory dose (ID) of 9 μM for
M. ulcerans
.
Differences in the Frequency of 23S rRNA Gene Mutations in Mycoplasma pneumoniae between Children and Adults with Community-Acquired Pneumonia: Clinical Impact of Mutations Conferring Macrolide Resistance
Authors: Yoo Soo Jin , Kim Hyo-Bin , Choi Sang-Ho , Lee Sang-Oh , Kim Sung-Han , Hong Sang-Bum , Sung Heungsup , Kim Mi-Na 
Published: September 2012

ABSTRACTWe investigated the frequency and clinical significance of macrolide resistance in adult and pediatric patients with community-acquired pneumonia from aMycoplasma pneumoniaeinfection. The frequency of the A2063G mutation in the 23S rRNA gene was significantly higher in children than in adults (61.3% [19/31] and 13.3% [8/60], respectively;P< 0.001). Patients with macrolide-resistantM. pneumoniaeinfections showed a longer duration of fever (P= 0.021) and required a longer duration of antibiotic treatment (P= 0.007).
A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis
Authors: Johnson Todd J. , Clark Meredith R. , Albright Theodore H. , Nebeker Joel S. , Tuitupou Anthony L. , Clark Justin T. , Fabian Judit , McCabe R. Tyler , Chandra Neelima , Doncel Gustavo F. , Friend David R. , Kiser Patrick F. 
Published: September 2012

ABSTRACT

A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs.
In vitro
, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day
in vivo
sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 10
4
ng/g, 10
6
ng/g, and 10
1
ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic.
Targeting Essential Genes in Salmonella enterica Serovar Typhimurium with Antisense Peptide Nucleic Acid
Authors: Soofi Muhammad A. , Seleem Mohamed N. 
Published: September 2012

ABSTRACT

We investigated the capability of antisense peptide nucleic acids (PNAs) conjugated to the (KFF)
3
K cell-penetrating peptide to target possible essential genes (
ligA
,
rpoA
,
rpoD
,
engA
,
tsf
, and
kdtA
) in
Salmonella enterica
serovar Typhimurium and inhibit bacterial growth
in vitr
o and in cell culture. All targeted PNA-based gene inhibition has shown great potency in gene expression inhibition in a sequence-specific and dose-dependent manner at micromolar concentrations. Among tested PNAs, the anti-
rpoA
and -
rpoD
PNAs showed the greatest potency.
Noninvasive Determination of 2-[
18
F]-Fluoroisonicotinic Acid Hydrazide Pharmacokinetics by Positron Emission Tomography in Mycobacterium tuberculosis-Infected Mice
Authors: Weinstein E. A. , Liu L. , Ordonez A. A. , Wang H. , Hooker J. M. , Tonge P. J. , Jain S. K. 
Published: September 2012

ABSTRACT

Tuberculosis (TB) is a global pandemic requiring sustained therapy to facilitate curing and to prevent the emergence of drug resistance. There are few adequate tools to evaluate drug dynamics within infected tissues
in vivo
. In this report, we evaluated a fluorinated analog of isoniazid (INH), 2-[
18
F]fluoroisonicotinic acid hydrazide (2-[
18
F]-INH), as a probe for imaging
Mycobacterium tuberculosis
-infected mice by dynamic positron emission tomography (PET). We developed a tail vein catheter system to safely deliver drugs to
M. tuberculosis
aerosol-infected mice inside sealed biocontainment devices. Imaging was rapid and noninvasive, and it could simultaneously visualize multiple tissues. Dynamic PET imaging demonstrated that 2-[
18
F]-INH was extensively distributed and rapidly accumulated at the sites of infection, including necrotic pulmonary TB lesions. Compared to uninfected animals,
M. tuberculosis
-infected mice had a significantly higher PET signal within the lungs (
P
< 0.05) despite similar PET activity in the liver (
P
> 0.85), suggesting that 2-[
18
F]-INH accumulated at the site of the pulmonary infection. Furthermore, our data indicated that similar to INH, 2-[
18
F]-INH required specific activation and accumulated within the bacterium. Pathogen-specific metabolism makes positron-emitting INH analogs attractive candidates for development into imaging probes with the potential to both detect bacteria and yield pharmacokinetic data
in situ
. Since PET imaging is currently used clinically, this approach could be translated from preclinical studies to use in humans.
Role for Telomerase in Listeria monocytogenes Infection
Authors: Samba-Louaka Ascel , Stavru Fabrizia , Cossart Pascale 
Published: September 2012

ABSTRACTHuman telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase complex. Growing evidence suggests that hTERT also contributes to the cell physiology independently of telomere elongation. However, its role in bacterial infection is unknown. Here we show that hTERT is critical forListeria monocytogenesinfection, as the depletion of hTERT impaired bacterial intracellular replication. In addition, we observed thatL. monocytogenescaused a decrease in hTERT levels at early time points of the infectious process. This effect was mediated by the pore-forming toxin listeriolysin O (LLO) and did not require bacterial entry into host cells. Calcium influx through the LLO pores contributed to a proteasome-independent decrease in hTERT protein levels. Together, our data provide evidence that these bacteria trigger hTERT degradation, an event that is detrimental to bacterial replication.
Progressive Cross-Reactivity in IgE Responses: an Explanation for the Slow Development of Human Immunity to Schistosomiasis?
Authors: Fitzsimmons Colin M. , Jones Frances M. , Pinot de Moira Angela , Protasio Anna V. , Khalife Jamal , Dickinson Harriet A. , Tukahebwa Edridah M. , Dunne David W. 
Published: September 2012

ABSTRACT

People in regions of
Schistosoma mansoni
endemicity slowly acquire immunity, but why this takes years to develop is still not clear. It has been associated with increases in parasite-specific IgE, induced, some investigators propose, to antigens exposed during the death of adult worms. These antigens include members of the tegumental-allergen-like protein family (TAL1 to TAL13). Previously, in a group of
S. mansoni
-infected Ugandan males, we showed that IgE responses to three TALs expressed in worms (TAL1, -3, and -5) became more prevalent with age. Now, in a subcohort we examined associations of these responses with resistance to reinfection and use the data to propose a mechanism for the slow development of immunity. IgE was measured 9 weeks posttreatment and at reinfection at 2 years (
n
= 144). An anti-TAL5 IgE (herein referred to as TAL5 IgE) response was associated with reduced reinfection even after adjusting for age using regression analysis (geometric mean odds ratio, 0.24;
P
= 0.016). TAL5 IgE responders were a subset of TAL3 IgE responders, themselves a subset of TAL1 responders. TAL3 IgE and TAL5 IgE were highly cross-reactive, with TAL3 the immunizing antigen and TAL5 the cross-reactive antigen. Transcriptional and translational studies show that TAL3 is most abundant in adult worms and that TAL5 is most abundant in infectious larvae. We propose that in chronic schistosomiasis, older individuals have repeatedly experienced IgE antigens exposed when adult worms die (e.g., TAL3) and that this leads to increasing cross-reactivity with antigens of invading larvae (e.g., TAL5). Progressive accumulation of worm/larvae cross-reactivity could explain the age-dependent immunity observed in areas of endemicity.
Crucial Role of Gamma Interferon-Producing CD4+Th1 Cells but Dispensable Function of CD8+T Cell, B Cell, Th2, and Th17 Responses in the Control of Brucella melitensis Infection in Mice
Authors: Vitry Marie-Alice , De Trez Carl , Goriely Stanislas , Dumoutier Laure , Akira Shizuo , Ryffel Bernhard , Carlier Yves , Letesson Jean-Jacques , Muraille Eric 
Published: September 2012

ABSTRACTBrucellaspp. are facultative intracellular bacterial pathogens responsible for brucellosis, a worldwide zoonosis that causes abortion in domestic animals and chronic febrile disease associated with serious complications in humans. There is currently no approved vaccine against human brucellosis, and antibiotic therapy is long and costly. Development of a safe protective vaccine requires a better understanding of the roles played by components of adaptive immunity in the control ofBrucellainfection. The importance of lymphocyte subsets in the control ofBrucellagrowth has been investigated separately by various research groups and remains unclear or controversial. Here, we used a large panel of genetically deficient mice to compare the importance of B cells, transporter associated with antigen processing (TAP-1), and major histocompatibility complex class II-dependent pathways of antigen presentation as well as T helper 1 (Th1), Th2, and Th17-mediated responses on the immune control ofBrucella melitensis16 M infection. We clearly confirmed the key function played by gamma interferon (IFN-γ)-producing Th1 CD4+T cells in the control ofB. melitensisinfection, whereas IFN-γ-producing CD8+T cells or B cell-mediated humoral immunity plays only a modest role in the clearance of bacteria during primary infection. In the presence of a Th1 response, Th2 or Th17 responses do not really develop or play a positive or negative role during the course ofB. melitensisinfection. On the whole, these results could improve our ability to develop protective vaccines or therapeutic treatments against brucellosis.
Transient Deficiency of Dendritic Cells Results in Lack of a Merozoite Surface Protein 1-Specific CD4 T Cell Response during Peak Plasmodium chabaudi Blood-Stage Infection
Authors: Sponaas Anne-Marit , Belyaev Nikolai , Falck-Hansen Mika , Potocnik Alexandre , Langhorne Jean 
Published: September 2012

ABSTRACTSplenic dendritic cells are crucial for controlling the immune response to malaria by initiating a CD4 gamma interferon (IFN-γ) response early in a blood-stage infection, which contributes to parasite clearance as well as to acute-stage immunopathology. CD8−CD11chighdendritic cells have been described previously to be important antigen-presenting cells for induction of these CD4 T cell responses in the spleens ofPlasmodium chabaudi-infected mice. However, when isolated during the period of maximum parasitemia and shortly thereafter, the dendritic cells transiently lose their ability to stimulate T cells, recovering only as the parasitemia is controlled. This loss of a CD4 T cell response is also observedin vivoduring this part of the infection. CD4 T cells from a T cell receptor-transgenic mouse recognizing a peptide of merozoite surface protein 1 (MSP1) injected into BALB/c mice during peak parasitemia proliferate poorly, and very few cells produce IFN-γ and interleukin-2 (IL-2), compared with transgenic T cells injected earlier in the blood-stage infection. CD8−dendritic cells at day 10 can process and present peptides on major histocompatibility complex (MHC) class II with an efficiency similar to that of dendritic cells from earlier in infection. The failure of the day 10 dendritic cells to activate MSP1-specific CD4 T cells fullyin vitrois associated with reduced expression of CD86 and lower production of IL-12 rather than with induction of inhibitory DC receptors or production of IL-10.