bluuebunny/crossref_metadata_2025_split huggingface dataset:
Native store‐operated calcium channels are functionally expressed in mouse spinal cord dorsal horn neurons and regulate resting calcium homeostasis
Authors: Xia Jingsheng , Pan Rong , Gao Xinghua , Meucci Olimpia , Hu Huijuan 
Published: May 2014

Key pointsA previous study indicates that store‐operated calcium channels (SOCs) play a role in pain hypersensitivity. Here we report for the first time that SOCs are expressed and functional in spinal cord dorsal horn neurons.Using the small inhibitory RNA knockdown approach, we have demonstrated that Orai1 is necessary, and both STIM1 and STIM2 are important for SOC entry and SOC current in dorsal horn neurons.Our findings demonstrate that STIM1, STIM2 and Orai1 play an important role in resting Ca2+homeostasis.Our results also indicate that SOCs are involved in the function of neurokinin 1 receptors and activation of SOCs produces an excitatory action in dorsal horn neurons.The present study reveals that a novel calcium signal mediated by SOCs is present in dorsal horn neurons and provides a potential mechanism for SOC inhibition‐induced central analgesia.AbstractStore‐operated calcium channels (SOCs) are calcium‐selective cation channels that mediate calcium entry in many different cell types. Store‐operated calcium entry (SOCE) is involved in various cellular functions. Increasing evidence suggests that impairment of SOCE is responsible for numerous disorders. A previous study demonstrated that YM‐58483, a potent SOC inhibitor, strongly attenuates chronic pain by systemic or intrathecal injection and completely blocks the second phase of formalin‐induced spontaneous nocifensive behaviour, suggesting a potential role of SOCs in central sensitization. However, the expression of SOCs, their molecular identity and function in spinal cord dorsal horn neurons remain elusive. Here, we demonstrate that SOCs are expressed in dorsal horn neurons. Depletion of calcium stores from the endoplasmic reticulum (ER) induced large sustained calcium entry, which was blocked by SOC inhibitors, but not by voltage‐gated calcium channel blockers. Depletion of ER calcium stores activated inward calcium‐selective currents, which was reduced by replacing Ca2+with Ba2+and reversed by SOC inhibitors. Using the small inhibitory RNA knockdown approach, we identified both STIM1 and STIM2 as important mediators of SOCE and SOC current, and Orai1 as a key component of the Ca2+release‐activated Ca2+channels in dorsal horn neurons. Knockdown of STIM1, STIM2 or Orai1 decreased resting Ca2+levels. We also found that activation of neurokinin 1 receptors led to SOCE and activation of SOCs produced an excitatory action in dorsal horn neurons. Our findings reveal that a novel SOC signal is present in dorsal horn neurons and may play an important role in pain transmission.
Simultaneous Fermentation of Glucose and Xylose to Butanol by Clostridium sp. Strain BOH3
Authors: Xin Fengxue , Wu Yi-Rui , He Jianzhong 
Published: May 2014

ABSTRACT

Cellulose and hemicellulose constitute the major components in sustainable feedstocks which could be used as substrates for biofuel generation. However, following hydrolysis to monomer sugars, the solventogenic
Clostridium
will preferentially consume glucose due to transcriptional repression of xylose utilization genes. This is one of the major barriers in optimizing lignocellulosic hydrolysates that produce butanol. Unlike studies on existing bacteria, this study demonstrates that newly reported
Clostridium
sp. strain BOH3 is capable of fermenting 60 g/liter of xylose to 14.9 g/liter butanol, which is similar to the 14.5 g/liter butanol produced from 60 g/liter of glucose. More importantly, strain BOH3 consumes glucose and xylose simultaneously, which is shown by its capability for generating 11.7 g/liter butanol from a horticultural waste cellulosic hydrolysate containing 39.8 g/liter glucose and 20.5 g/liter xylose, as well as producing 11.9 g/liter butanol from another horticultural waste hemicellulosic hydrolysate containing 58.3 g/liter xylose and 5.9 g/liter glucose. The high-xylose-utilization capability of strain BOH3 is attributed to its high xylose-isomerase (0.97 U/mg protein) and xylulokinase (1.16 U/mg protein) activities compared to the low-xylose-utilizing solventogenic strains, such as
Clostridium
sp. strain G117. Interestingly, strain BOH3 was also found to produce riboflavin at 110.5 mg/liter from xylose and 76.8 mg/liter from glucose during the fermentation process. In summary,
Clostridium
sp. strain BOH3 is an attractive candidate for application in efficiently converting lignocellulosic hydrolysates to biofuels and other value-added products, such as riboflavin.
The Temperature Gradient-Forming Device, an Accessory Unit for Normal Light Microscopes To Study the Biology of Hyperthermophilic Microorganisms
Authors: Mora Maximilian , Bellack Annett , Ugele Matthias , Hopf Johann , Wirth Reinhard 
Published: May 2014

ABSTRACT

To date, the behavior of hyperthermophilic microorganisms in their biotope has been studied only to a limited degree; this is especially true for motility. One reason for this lack of knowledge is the requirement for high-temperature microscopy—combined, in most cases, with the need for observations under strictly anaerobic conditions—for such studies. We have developed a custom-made, low-budget device that, for the first time, allows analyses in temperature gradients up to 40°C over a distance of just 2 cm (a biotope-relevant distance) with heating rates up to ∼5°C/s. Our temperature gradient-forming device can convert any upright light microscope into one that works at temperatures as high as 110°C. Data obtained by use of this apparatus show how very well hyperthermophiles are adapted to their biotope: they can react within seconds to elevated temperatures by starting motility—even after 9 months of storage in the cold. Using the temperature gradient-forming device, we determined the temperature ranges for swimming, and the swimming speeds, of 15 selected species of the genus
Thermococcus
within a few months, related these findings to the presence of cell surface appendages, and obtained the first evidence for thermotaxis in
Archaea
.
Genetic Diversity and Virulence Potential of Shiga Toxin-Producing Escherichia coli O113:H21 Strains Isolated from Clinical, Environmental, and Food Sources
Authors: Feng Peter C. H. , Delannoy Sabine , Lacher David W. , dos Santos Luis Fernando , Beutin Lothar , Fach Patrick , Rivas Marta , Hartland Elizabeth L. , Paton Adrienne W. , Guth Beatriz E. C. 
Published: May 2014

ABSTRACT

Shiga toxin-producing
Escherichia coli
strains of serotype O113:H21 have caused severe human diseases, but they are unusual in that they do not produce adherence factors coded by the locus of enterocyte effacement. Here, a PCR microarray was used to characterize 65 O113:H21 strains isolated from the environment, food, and clinical infections from various countries. In comparison to the pathogenic strains that were implicated in hemolytic-uremic syndrome in Australia, there were no clear differences between the pathogens and the environmental strains with respect to the 41 genetic markers tested. Furthermore, all of the strains carried only Shiga toxin subtypes associated with human infections, suggesting that the environmental strains have the potential to cause disease. Most of the O113:H21 strains were closely related and belonged in the same clonal group (ST-223), but CRISPR analysis showed a great degree of genetic diversity among the O113:H21 strains.
Identification and Characterization of a Novel Secreted Glycosidase with Multiple Glycosidase Activities in Streptococcus intermedius
Authors: Imaki Hidenori , Tomoyasu Toshifumi , Yamamoto Naoki , Taue Chiharu , Masuda Sachiko , Takao Ayuko , Maeda Nobuko , Tabata Atsushi , Whiley Robert A. , Nagamune Hideaki 
Published: May 2014

ABSTRACT

Streptococcus intermedius
is a known human pathogen and belongs to the anginosus group (
S. anginosus
,
S. intermedius
, and
S. constellatus
) of streptococci (AGS). We found a large open reading frame (6,708 bp) in the
lac
operon, and bioinformatic analysis suggested that this gene encodes a novel glycosidase that can exhibit β-
d
-galactosidase and
N
-acetyl-β-
d
-hexosaminidase activities. We, therefore, named this protein “multisubstrate glycosidase A” (MsgA). To test whether MsgA has these glycosidase activities, the
msgA
gene was disrupted in
S. intermedius
. The
msgA
-deficient mutant no longer showed cell- and supernatant-associated β-
d
-galactosidase, β-
d
-fucosidase,
N
-acetyl-β-
d
-glucosaminidase, and
N
-acetyl-β-
d
-galactosaminidase activities, and all phenotypes were complemented in
trans
with a recombinant plasmid carrying
msgA
. Purified MsgA had all four of these glycosidase activities and exhibited the lowest

K
m

with 4-methylumbelliferyl-linked
N
-acetyl-β-
d
-glucosaminide and the highest
k
cat
with 4-methylumbelliferyl-linked β-
d
-galactopyranoside. In addition, the purified LacZ domain of MsgA had β-
d
-galactosidase and β-
d
-fucosidase activities, and the GH20 domain exhibited both
N
-acetyl-β-
d
-glucosaminidase and
N
-acetyl-β-
d
-galactosaminidase activities. The β-
d
-galactosidase and β-
d
-fucosidase activities of MsgA are thermolabile, and the optimal temperature of the reaction was 40°C, whereas almost all enzymatic activities disappeared at 49°C. The optimal temperatures for the
N
-acetyl-β-
d
-glucosaminidase and
N
-acetyl-β-
d
-galactosaminidase activities were 58 and 55°C, respectively. The requirement of sialidase treatment to remove sialic acid residues of the glycan branch end for glycan degradation by MsgA on human α
1
-antitrypsin indicates that MsgA has exoglycosidase activities. MsgA and sialidase might have an important function in the production and utilization of monosaccharides from oligosaccharides, such as glycans for survival in a normal habitat and for pathogenicity of
S. intermedius
.
KRAS,NRASandBRAFmutations in Greek and Romanian patients with colorectal cancer: a cohort study
Authors: Negru Serban , Papadopoulou Eirini , Apessos Angela , Stanculeanu Dana Lucia , Ciuleanu Eliade , Volovat Constantin , Croitoru Adina , Kakolyris Stylianos , Aravantinos Gerasimos , Ziras Nikolaos , Athanasiadis Elias , Touroutoglou Nikolaos , Pavlidis Nikolaos , Kalofonos Haralabos P , Nasioulas George 
Published: May 2014

ObjectivesTreatment decision-making in colorectal cancer is often guided by tumour tissue molecular analysis. The aim of this study was the development and validation of a high-resolution melting (HRM) method for the detection ofKRAS,NRASandBRAFmutations in Greek and Romanian patients with colorectal cancer and determination of the frequency of these mutations in the respective populations.SettingDiagnostic molecular laboratory located in Athens, Greece.Participants2425 patients with colorectal cancer participated in the study.Primary and secondary outcome measures2071 patients with colorectal cancer (1699 of Greek and 372 of Romanian origin) were analysed forKRASexon 2 mutations. In addition, 354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected to fullKRAS(exons 2, 3 and 4),NRAS(exons 2, 3 and 4) andBRAF(exon 15) analysis.KRAS,NRASandBRAFmutation detection was performed by a newly designed HRM analysis protocol, followed by Sanger sequencing.ResultsKRASexon 2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian patients. Among the 354 patients who were subjected to fullKRAS,NRASandBRAFanalysis, 40.96% hadKRASexon 2 mutations (codons 12/13). Among theKRASexon 2 wild-type patients 15.31% harboured additionalRASmutations and 12.44%BRAFmutations. The newly designed HRM method used showed a higher sensitivity compared with the sequencing method.ConclusionsThe HRM method developed was shown to be a reliable method forKRAS,NRASandBRAFmutation detection. Furthermore, no difference in the mutation frequency ofKRAS,NRASandBRAFwas observed between Greek and Romanian patients with colorectal cancer.
Which features of primary care affect unscheduled secondary care use? A systematic review
Authors: Huntley Alyson , Lasserson Daniel , Wye Lesley , Morris Richard , Checkland Kath , England Helen , Salisbury Chris , Purdy Sarah 
Published: May 2014

ObjectivesTo conduct a systematic review to identify studies that describe factors and interventions at primary care practice level that impact on levels of utilisation of unscheduled secondary care.SettingObservational studies at primary care practice level.ParticipantsStudies included people of any age of either sex living in Organisation for Economic Co-operation and Development (OECD) countries with any health condition.Primary and secondary outcome measuresThe primary outcome measure was unscheduled secondary care as measured by emergency department attendance and emergency hospital admissions.Results48 papers were identified describing potential influencing features on emergency department visits (n=24 studies) and emergency admissions (n=22 studies). Patient factors associated with both outcomes were increased age, reduced socioeconomic status, lower educational attainment, chronic disease and multimorbidity. Features of primary care affecting unscheduled secondary care were more complex. Being able to see the same healthcare professional reduced unscheduled secondary care. Generally, better access was associated with reduced unscheduled care in the USA. Proximity to healthcare provision influenced patterns of use. Evidence relating to quality of care was limited and mixed.ConclusionsThe majority of research was from different healthcare systems and limited in the extent to which it can inform policy. However, there is evidence that continuity of care is associated with reduced emergency department attendance and emergency hospital admissions.
Endometrial biopsy in women with abnormal uterine bleeding: inadequate and unassessable categorisation is not clinically relevant
Authors: Ewies Ayman A A , Shaaban Kadry A A , Merard Reena , Zanetto Ulises 
Published: May 2014

AimsInadequate endometrial biopsy comprises a dilemma for gynaecologists and histopathologists alike. This study was conducted to assess the clinical merit of classifying scant endometrial biopsy into inadequate and unassessable using McCluggage criteria.MethodsWe retrospectively classified 268 endometrial biopsies, initially reported as inadequate, into inadequate (n=74) and unassessable (n=174) using McCluggage criteria after excluding 20 cases; all taken from patients aged ≥50 years with abnormal uterine bleeding attending Sandwell and West Birmingham Hospitals, UK from 1 January 2007 until 30 September 2012. The electronic clinical records were reviewed to find out the consequent clinical decisions and final outcomes. The follow-up period was 15 months after including the last patient.ResultsThe median age was 57 years (range: 50–97), and the median number of visits to hospital till the diagnosis was achieved was 2 (range: 1–4). The final diagnosis of endometrial hyperplasia or cancer was reported in 9 cases; 5 (7.1%) with an initial finding of inadequate and 4 with unassessable (2.4%); the difference was statistically insignificant (p=0.13). More patients in the inadequate category (82.4%) underwent further investigations when compared with the unassessable category (68.4%); the difference was statistically significant (p=0.029). There was no statistically significant difference in the inadequate to unassessable ratio when the endometrial thickness was ≥5 mm or <5 mm within the Pipelle group (p=0.46) or the curettage group (p=0.34).ConclusionsOur findings suggest that categorising scant endometrial specimens into inadequate or unassessable has no clinical implications. The gynaecologist should interpret the histopathology report in the light of clinical scenario.
Mechanisms Promoting Escape from Mitotic Stress–Induced Tumor Cell Death
Authors: Sinnott Rebecca , Winters Leah , Larson Brittany , Mytsa Daniela , Taus Patrick , Cappell Kathryn M. , Whitehurst Angelique W. 
Published: May 2014

Abstract
Non–small cell lung cancer (NSCLC) is notorious for its paltry responses to first-line therapeutic regimens. In contrast to acquired chemoresistance, little is known about the molecular underpinnings of the intrinsic resistance of chemo-naïve NSCLC. Here we report that intrinsic resistance to paclitaxel in NSCLC occurs at a cell-autonomous level because of the uncoupling of mitotic defects from apoptosis. To identify components that permit escape from mitotic stress–induced death, we used a genome-wide RNAi-based strategy, which combines a high-throughput toxicity screen with a live-cell imaging platform to measure mitotic fate. This strategy revealed that prolonging mitotic arrest with a small molecule inhibitor of the APC/cyclosome could sensitize otherwise paclitaxel-resistant NSCLC. We also defined novel roles for CASC1 and TRIM69 in supporting resistance to spindle poisons. CASC1, which is frequently co-amplified with KRAS in lung tumors, is essential for microtubule polymerization and satisfaction of the spindle assembly checkpoint. TRIM69, which associates with spindle poles and promotes centrosomal clustering, is essential for formation of a bipolar spindle. Notably, RNAi-mediated attenuation of CASC1 or TRIM69 was sufficient to inhibit tumor growth in vivo. On the basis of our results, we hypothesize that tumor evolution selects for a permissive mitotic checkpoint, which may promote survival despite chromosome segregation errors. Attacking this adaptation may restore the apoptotic consequences of mitotic damage to permit the therapeutic eradication of drug-resistant cancer cells. Cancer Res; 74(14); 3857–69. ©2014 AACR.
Validating Self-Reported Mammography Use in Vulnerable Communities: Findings and Recommendations
Authors: Allgood Kristi L. , Rauscher Garth H. , Whitman Steven , Vasquez-Jones Giselle , Shah Ami M. 
Published: May 2014

Abstract
Background: Most health surveys ask women whether they have had a recent mammogram, all of which report mammography use (past 2 years) at about 70% to 80% regardless of race or residence. We examined the potential extent of overreporting of mammography use in low income African-American and Latina women, and whether self-report inaccuracies might bias estimated associations between patient characteristics and mammography use.
Methods: Using venue-based sampling in two poor communities on the west side of Chicago, we asked eligible women living in two west side communities of Chicago to complete a survey about breast health (n = 2,200) and to provide consent to view their medical record. Of the 1,909 women who screened eligible for medical record review, 1,566 consented (82%). We obtained medical records of all women who provided both permission and a valid local mammography facility (n = 1,221). We compared the self-reported responses from the survey with the imaging reports found in the medical record (documented). To account for missing data, we conducted multiple imputations for key demographic variables and report standard measures of accuracy.
Results: Although 73% of women self-reported a mammogram in the last 2 years, only 44% of self-reports were documented. Overreporting of mammography use was observed for all three ethnic groups.
Conclusions: These results suggest considerable overestimation of prevalence of use in these vulnerable populations.
Impact: Relying on known faulty self-reported mammography data as a measure of mammography use provides an overly optimistic picture of utilization, a problem that may be exacerbated in vulnerable minority communities. Cancer Epidemiol Biomarkers Prev; 23(8); 1649–58. ©2014 AACR.
Increased Lung and Bladder Cancer Incidence in Adults after In Utero and Early-Life Arsenic Exposure
Authors: Steinmaus Craig , Ferreccio Catterina , Acevedo Johanna , Yuan Yan , Liaw Jane , Durán Viviana , Cuevas Susana , García José , Meza Rodrigo , Valdés Rodrigo , Valdés Gustavo , Benítez Hugo , VanderLinde Vania , Villagra Vania , Cantor Kenneth P. , Moore Lee E. , Perez Saida G. , Steinmaus Scott , Smith Allan H. 
Published: May 2014

Abstract
Background: From 1958 to 1970, &gt;100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer.
Methods: We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls.
Results: ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and &gt;800 μg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96–3.71], and 5.24 (3.05–9.00; Ptrend &lt; 0.001) for lung cancer, and 1.00, 2.94 (1.29–6.70), and 8.11 (4.31–15.25; Ptrend &lt; 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (&gt;800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed.
Conclusion: Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure.
Impact: Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. Cancer Epidemiol Biomarkers Prev; 23(8); 1529–38. ©2014 AACR.
Dietary Insulin Index and Insulin Load in Relation to Endometrial Cancer Risk in the Nurses' Health Study
Authors: Prescott Jennifer , Bao Ying , Viswanathan Akila N. , Giovannucci Edward L. , Hankinson Susan E. , De Vivo Immaculata 
Published: May 2014

Abstract
Background: Although unopposed estrogen exposure is considered the main driver of endometrial carcinogenesis, factors associated with states of insulin resistance and hyperinsulinemia are independently associated with endometrial cancer risk. We used dietary insulin load and insulin index scores to represent the estimated insulin demand of overall diets and assessed their association with endometrial cancer risk in the prospective Nurses' Health Study.
Methods: We estimated incidence rate ratios (RR) and 95% confidence intervals (CI) for risk of invasive endometrial cancer using Cox proportional hazards models. Between the baseline dietary questionnaire (1980) and 2010, we identified a total of 798 incident-invasive epithelial endometrial adenocarcinomas over 1,417,167 person-years of follow-up.
Results: Dietary insulin scores were not associated with overall risk of endometrial cancer. Comparing women in the highest with the lowest quintile, the multivariable-adjusted RRs of endometrial cancer were 1.07 (95% CI, 0.84–1.35) for cumulative average dietary insulin load and 1.03 (95% CI, 0.82–1.31) for cumulative average dietary insulin index. Findings did not vary substantially by alcohol consumption, total dietary fiber intake, or body mass index and/or physical activity (Pheterogeneity ≥ 0.10).
Conclusions: Intake of a diet predicted to stimulate a high postprandial insulin response was not associated with endometrial cancer risk in this large prospective study. Considering the complex interplay of diet, lifestyle, and genetic factors contributing to the hyperinsulinemic state, dietary measures alone may not sufficiently capture absolute long-term insulin exposure.
Impact: This study is the first to investigate dietary insulin scores in relation to endometrial cancer risk. Cancer Epidemiol Biomarkers Prev; 23(8); 1512–20. ©2014 AACR.