bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Genedia MTB Detection Kit and the Cobas TaqMan MTB Assay for Detection of Mycobacterium tuberculosis in Respiratory Specimens
Authors: Huh Hee Jae , Kwon Hyeon Jeong , Ki Chang-Seok , Lee Nam Yong
Published: January 2015

The performance of the Genedia MTB detection kit was compared with that of the Cobas TaqMan MTB test using respiratory specimens. The Genedia and Cobas assays showed comparable sensitivities (81.8% and 78.8%, respectively) and specificities (99.8% and 99.5%, respectively), while the Genedia assay produced fewer invalid results and required less turnaround time and labor.
Volatile-Sulfur-Compound Profile Distinguishes Burkholderia pseudomallei from Burkholderia thailandensis
Authors: Inglis Timothy J. J. , Hahne Dorothee R. , Merritt Adam J. , Clarke Michael W.
Published: January 2015

Solid-phase microextraction gas chromatography-mass spectrometry (SPME-GCMS) was used to show that dimethyl sulfide produced by
Burkholderia pseudomallei
is responsible for its unusual truffle-like smell and distinguishes the species from
Burkholderia thailandensis
. SPME-GCMS can be safely used to detect dimethyl sulfide produced by agar-grown
B. pseudomallei
.
Impact of the Adenoviral E4 Orf3 Protein on the Activity and Posttranslational Modification of p53
Authors: DeHart Caroline J. , Perlman David H. , Flint S. J.
Published: January 2015

Our previous studies have established that the p53 populations that accumulate in normal human cells exposed to etoposide or infected by an E1B 55-kDa protein-null mutant of human adenovirus type 5 carry a large number of posttranslational modifications at numerous residues (C. J. DeHart, J. S. Chahal, S. J. Flint, and D. H. Perlman, Mol Cell Proteomics
13:
1–17, 2014,
http://dx.doi.org/10.1074/mcp.M113.030254
). In the absence of this E1B protein, the p53 transcriptional program is not induced, and it has been reported that the viral E4 Orf3 protein inactivates p53 (C. Soria, F. E. Estermann, K. C. Espantman, and C. C. O'Shea, Nature
466:
1076–1081, 2010,
http://dx.doi.org/10.1038/nature09307
). As the latter protein disrupts nuclear Pml bodies, sites at which p53 is modified, we used mass spectrometry to catalogue the posttranscriptional modifications of the p53 population that accumulates when neither the E1B 55-kDa nor the E4 Orf3 protein is made in infected cells. Eighty-five residues carrying 163 modifications were identified. The overall patterns of posttranslational modification of this population and p53 present in cells infected by an E1B 55-kDa-null mutant were similar. The efficiencies with which the two forms of p53 bound to a consensus DNA recognition sequence could not be distinguished and were lower than that of transcriptionally active p53. The absence of the E4 Orf3 protein increased expression of several p53-responsive genes when the E1B protein was also absent from infected cells. However, expression of these genes did not attain the levels observed when p53 was activated in response to etoposide treatment and remained lower than those measured in mock-infected cells.

IMPORTANCE
The tumor suppressor p53, a master regulator of cellular responses to stress, is inactivated and destroyed in cells infected by species C human adenoviruses, such as type 5. It is targeted for proteasomal degradation by the action of a virus-specific E3 ubiquitin ligase that contains the viral E1B 55-kDa and E4 Orf6 proteins, while the E4 Orf3 protein has been reported to block its ability to stimulate expression of p53-dependent genes. The comparisons reported here of the posttranslational modifications and activities of p53 populations that accumulate in infected normal human cells in the absence of both mechanisms of inactivation or of only the E3 ligase revealed little impact of the E4 Orf3 protein. These observations indicate that E4 Orf3-dependent disruption of Pml bodies does not have a major effect on the pattern of p53 posttranslational modifications in adenovirus-infected cells. Furthermore, they suggest that one or more additional viral proteins contribute to blocking p53 activation and the consequences that are deleterious for viral reproduction, such as apoptosis or cell cycle arrest.
Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands as Influenza Virus Vaccine Adjuvants Induce Rapid, Sustained, and Broadly Protective Responses
Authors: Goff Peter H. , Hayashi Tomoko , Martínez-Gil Luis , Corr Maripat , Crain Brian , Yao Shiyin , Cottam Howard B. , Chan Michael , Ramos Irene , Eggink Dirk , Heshmati Mitra , Krammer Florian , Messer Karen , Pu Minya , Fernandez-Sesma Ana , Palese Peter , Carson Dennis A.
Published: January 2015

Current vaccines against influenza virus infection rely on the induction of neutralizing antibodies targeting the globular head of the viral hemagglutinin (HA). Protection against seasonal antigenic drift or sporadic pandemic outbreaks requires further vaccine development to induce cross-protective humoral responses, potentially to the more conserved HA stalk region. Here, we present a novel viral vaccine adjuvant comprised of two synthetic ligands for Toll-like receptor 4 (TLR4) and TLR7. 1Z105 is a substituted pyrimido[5,4-b]indole specific for the TLR4-MD2 complex, and 1V270 is a phospholipid-conjugated TLR7 agonist. Separately, 1Z105 induces rapid Th2-associated IgG1 responses, and 1V270 potently generates Th1 cellular immunity. 1Z105 and 1V270 in combination with recombinant HA from the A/Puerto Rico/8/1934 strain (rPR/8 HA) effectively induces rapid and sustained humoral immunity that is protective against lethal challenge with a homologous virus. More importantly, immunization with the combined adjuvant and rPR/8 HA, a commercially available split vaccine, or chimeric rHA antigens significantly improves protection against both heterologous and heterosubtypic challenge viruses. Heterosubtypic protection is associated with broadly reactive antibodies to HA stalk epitopes. Histological examination and cytokine profiling reveal that intramuscular (i.m.) administration of 1Z105 and 1V270 is less reactogenic than a squalene-based adjuvant, AddaVax. In summary, the combination of 1Z105 and 1V270 with a recombinant HA induces rapid, long-lasting, and balanced Th1- and Th2-type immunity; demonstrates efficacy in a variety of murine influenza virus vaccine models assaying homologous, heterologous, and heterosubtypic challenge viruses; and has an excellent safety profile.

IMPORTANCE
Novel adjuvants are needed to enhance immunogenicity and increase the protective breadth of influenza virus vaccines to reduce the seasonal disease burden and ensure pandemic preparedness. We show here that the combination of synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity that is protective against influenza viruses in homologous, heterologous, and heterosubtypic challenge models. Combining TLR4 and TLR7 ligands balances Th1- and Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. The combined adjuvant has an attractive safety profile and the potential to augment seasonal-vaccine breadth, contribute to a broadly neutralizing universal vaccine formulation, and improve response time in an emerging pandemic.
Vpu Is the Main Determinant for Tetraspanin Downregulation in HIV-1-Infected Cells
Authors: Lambelé Marie , Koppensteiner Herwig , Symeonides Menelaos , Roy Nathan H. , Chan Jany , Schindler Michael , Thali Markus
Published: January 2015

Tetraspanins constitute a family of cellular proteins that organize various membrane-based processes. Several members of this family, including CD81, are actively recruited by HIV-1 Gag to viral assembly and release sites. Despite their enrichment at viral exit sites, the overall levels of tetraspanins are decreased in HIV-1-infected cells. Here, we identify Vpu as the main viral determinant for tetraspanin downregulation. We also show that reduction of CD81 levels by Vpu is not a by-product of CD4 or BST-2/tetherin elimination from the surfaces of infected cells and likely occurs through an interaction between Vpu and CD81. Finally, we document that Vpu-mediated downregulation of CD81 from the surfaces of infected T cells can contribute to preserving the infectiousness of viral particles, thus revealing a novel Vpu function that promotes virus propagation by modulating the host cell environment.

IMPORTANCE
The HIV-1 accessory protein Vpu has previously been shown to downregulate various host cell factors, thus helping the virus to overcome restriction barriers, evade immune attack, and maintain the infectivity of viral particles. Our study identifies tetraspanins as an additional group of host factors whose expression at the surfaces of infected cells is lowered by Vpu. While the downregulation of these integral membrane proteins, including CD81 and CD82, likely affects more than one function of HIV-1-infected cells, we document that Vpu-mediated lowering of CD81 levels in viral particles can be critical to maintaining their infectiousness.
Three testicles in one hemiscrotum: an unusual presentation of polyorchidism
Authors: Ellett Justin D , Rosoff James S , Prasad Michaella M
Published: January 2015

Polyorchidism, or more than one testicle in a hemiscrotum, is a relatively rare phenomenon. It is often associated with several other conditions, including inguinal hernia, testicular maldescent, testicular torsion, hydrocele or hypospadias. In this report, we describe a patient who presented with three testicles in one hemiscrotum, which is a highly unusual presentation for an already uncommon condition. We also review the relevant literature as it relates to the need for surveillance due to the increased risk for malignancy.
Hydrocephalus due to extreme dilation of Virchow-Robin spaces
Authors: Revel Frederic , Cotton Francois , Haine Max , Gilbert Thomas
Published: January 2015

Virchow-Robin spaces (VRS) are extensions of the subarachnoid space surrounding perforating blood vessels entering the brain parenchyma. VRS are fluid filled, but almost virtual and only visible on MRI of the brain when dilated. Such dilations are commonly asymptomatic. In rare cases, extreme dilations can be observed; the clinical repercussions of which remain unclear. We report the case of a patient presenting symptoms of normal pressure hydrocephalus due to extreme VRS mesencephalon dilations.
An unusual presentation of ulcerative colitis
Authors: Kesav Praveen , Khurana Dheeraj
Published: January 2015

Ulcerative colitis (UC) may have diverse extraintestinal manifestations. Nutritional deficiencies, medications or immune-mediated epiphenomena are considered to be pathogenic mechanisms involved. We describe a case of a 56-year-old woman who presented with rapidly progressive tingling paraesthesias in both lower limbs followed by sensory ataxia, ascending spastic quadriparesis, urgency and urge incontinence of 3 months duration. She had an episode of bloody diarrhoea 1 month later for which a colonoscopy was carried out with colonic biopsy features revealing a diagnosis of UC. In view of lack of alternative aetiology, the posterolateral column disease in our patient was attributed to an extraintestinal manifestation of UC. She improved dramatically with a course of intravenous steroids followed by tapering dose of oral steroids and oral mesalamine for her UC. Although rare, UC should be considered in the differential diagnosis of posterolateral column disease of the spinal cord in the appropriate clinical scenario.
Ischaemic necrosis of the tongue
Authors: McGoldrick David M , Khan Irfan , Cotter Chris J
Published: January 2015

Necrosis of the tongue is a rare clinical finding. The rich vascularity of the tongue means necrosis is uncommon but it has been reported secondary to giant cell arthritis, radiotherapy and ischaemia. We report the case of a 61-year-old man admitted with an acute abdomen, who later developed gross swelling of the tongue, secondary to ischaemic necrosis, which necessitated tracheostomy placement. The ischaemia was managed conservatively with heparinisation and by allowing the ischaemic area to demarcate and slough off naturally.
Nasoalveolar cyst: an enigma for the dentist
Authors: Misra Satya Ranjan , Gopal Maragathavalli , Mohanty Neeta , Rastogi Varun
Published: January 2015

A nasoalveolar cyst is a rare, non-odontogenic soft tissue cyst encountered in the anterior maxillary labial sulcus as an asymptomatic soft tissue swelling. Often, patients with these cysts report them to the dental clinic where they are mistaken for odontogenic lesions by the dental surgeon, especially if concomitant dental problems are present. They cannot be detected by routine conventional dental radiography as they are peripheral, lying within the mucosa thereby posing a diagnostic challenge. We document a case of a 47-year-old woman with a nasoalveolar cyst.
The relationship between the frequency of football practice during skeletal growth and the presence of a cam deformity in adult elite football players
Authors: Tak Igor , Weir Adam , Langhout Rob , Waarsing Jan Hendrik , Stubbe Janine , Kerkhoffs Gino , Agricola Rintje
Published: January 2015

Background/aim

Cam deformity (CD) is likely a bony adaptation in response to high-impact sports practice during skeletal growth. We ascertained whether a dose–response relationship exists between the frequency of football practice during skeletal growth and the presence of a CD in adulthood, and if the age at which a football player starts playing football is associated with the presence of a CD in adulthood.

Methods

Prevalence of a CD (α angle>60°) and a pathological CD (α angle>78°) was studied using standardised anteroposterior (AP) and frog-leg lateral (FLL) radiographs that were obtained during seasonal screening. The age of starting to play football with a low frequency (LF; ≤3 times/week) and high frequency (HF; ≥4 times/week) was retrospectively assessed. The differences in prevalence of a CD per hip, in either view, between groups were calculated by logistic regression with generalised estimating equations.

Results

63 players (mean(±SD) age 23.1(±4.2) years) participated, yielding 126 hips for analysis. The prevalence of a CD in the FLL was 40% (n=82) in players who started playing HF football from the age of 12 years or above, and 64% (n=44) in those playing HF football before the age of 12 years (p=0.042). This was also true for a pathological CD (12% vs 30%, p=0.038). The AP views revealed no difference.

Conclusions

Our results indicate a probable dose–response relationship between the frequency of football practice during skeletal growth and the development of a CD, which should be confirmed in future prospective studies.
Does teaching children to swim increase exposure to water or risk-taking when in the water? Emerging evidence from Bangladesh
Authors: Mecrow Tom Stefan , Linnan Michael , Rahman Aminur , Scarr Justin , Mashreky Saidur Rahman , Talab Abu , Rahman A K M Fazlur
Published: January 2015

Background

SwimSafe, a basic swimming and safe rescue curriculum, has been taught to large numbers of children in Bangladesh. Teaching swimming potentially increases risk if it increases water exposure or high-risk practices in water. This study compares water exposure and risk practices for SwimSafe graduates (SS) with children who learned swimming naturally.

Methods

Interviewers obtained detailed water exposure histories for the preceding 48 h from 3936 SS aged 6–14 and 3952 age-matched and sex-matched children who had learned swimming naturally. Frequencies of water exposure and water entries for swimming or playing were compared.

Results

There were 9741 entries into water among the 7046 participants in the 48 h prior to interview. About one-third (31.2%) had no water entries, one-tenth (10.5%) entered once, half (49.2%) entered twice and a tenth (9.1%) entered three or more times. Proportions of children in each group were similar. About 99.5% of both groups only entered the water for bathing. For those entering to swim or play, the mean number of entries was similar (SS 1.63, natural swimmer (NS) 1.36, p=0.40). Swimming or playing alone in the water was rare (1 SS, 0 NS).

Conclusions

Most water exposure for children is for bathing. Less than 1% swam or played in the water during the 48 h recall period (0.6% SS, 0.4% NS). Learning swimming in SwimSafe did not increase water exposure nor did it increase water entry for playing or swimming compared with children who learned to swim naturally.
Excessive fatal injury among migrant children in China: inequities in safety
Authors: Lin Guozhen , Zhang Xiao , Dong Hong , Shen Jichuan , Li Ke , Zhou Qin
Published: January 2015

The wide variability in economic development levels among different regions in China results in the migration of millions of households to more developed areas. Death records from 2008 to 2012 of children aged 0–17 years old from the vital surveillance system of Guangzhou were used to determine if death rates were different for resident and migrant children. A total of 1358 injury-related deaths were identified with rates rising slightly from 2008 to 2012 both in resident and migrant populations. The total crude incidence rate of injury death was significantly higher among migrant households (29.50/100 000) compared with resident households (8.42/100 000). The adjusted rate in migrant households was 3.50 (95% CI 3.14 to 3.89) times higher than in resident households. Drowning and traffic crashes represented the most common causes of death and residences were the most frequent site of injury-related death for both groups of children. Migrant children were at a significantly higher risk of injury-related mortality compared with local resident children.
Historical perspectives in clinical pathology: a history of glucose measurement
Authors: Moodley Nareshni , Ngxamngxa Unathi , Turzyniecka Magdalena J , Pillay Tahir S
Published: January 2015

This is the second in the series of historical articles dealing with developments in clinical pathology. As one of the most commonly measured analytes in pathology, the assessment of glucose dates back to the time of the ancient Egyptians. It was only in the 19th century that advances in chemistry led to the identification of the sugar in urine being glucose. The following century witnessed the development of more chemical and enzymatic methods which became incorporated into the modern analysers and point-of-care instruments which are as ubiquitous as the modern day cellphones. Tracking the milestones in these developments shows the striking paradigms and the many parallels in the development of other clinical chemistry methods.
Critical assessment of the morbidity associated with ruptured cerebral arteriovenous malformations
Authors: Majumdar Monica , Tan Lee A , Chen Michael
Published: January 2015

Background

An accurate understanding of the morbidity and mortality associated with brain arteriovenous malformation (AVM) hemorrhage is important in determining the management of unruptured AVMs. Recent studies suggest this morbidity to be lower than assumed. We sought to perform a detailed critical assessment of the morbidity associated with ruptured brain AVMs.

Methods

A retrospective chart review from a single-center tertiary care medical center was performed. Inclusion criteria were patients admitted with intracranial hemorrhage caused by a previously untreated AVM. Forty variables were analyzed including patient demographics, imaging findings, clinical course, and clinical examinations.

Results

From 2008 to 2013, of the 51 patients who fit our inclusion criteria, we found admission National Institutes of Health Stroke Scale (NIHSS) scores of 0, 1–9, and ≥10 in 22%, 24%, and 55%, respectively. Hematoma location was parenchymal in 33%, intraventricular in 10%, subarachnoid in 4%, and combined in 53%. Deep venous drainage was present in 35% of cases and associated aneurysms were present in 37%. 43% underwent emergency hematoma evacuation while four patients died during their admission. Of those who survived, 74% had neurologic deficits upon discharge (NIHSS ≥1), with 25.5% of patients having a severe deficit (NIHSS ≥10). On follow-up, 55% were independent in their daily activities of living.

Conclusions

Our assessment of morbidity associated with brain AVM rupture is higher than previously assumed and reported. These results should be further validated in a larger, more representative sample. An accurate understanding of the morbidity associated with AVM rupture is important as more patients with unruptured brain AVMs seek consultation.
Developing best practice guidelines on equine colic
Authors: Freeman S. L. , Curtis L.
Published: January 2015

Sarah Freeman and Laila Curtis describe an ongoing project that is aiming to develop evidence‐based, best practice guidelines to help owners and veterinary surgeons recognise the signs of colic in horses. They also report on the first of two multidisciplinary workshops during which the evidence was discussed by a range of different stakeholders
Conserving wildlife
Authors: Kock Richard
Published: January 2015

An interest in wildlife and natural systems has absorbed Richard Kock's working life
Effects of exercise accumulation on plasma lipids and lipoproteins
Authors: Wagganer Jason D. , Robison Charles E. , Ackerman Terry A. , Davis Paul G.
Published: January 2015

Debate exists as to whether improvements in some cardiometabolic risk factors following exercise training result more from the last session of, or from an accumulation of, exercise sessions. This study was designed to compare the effect of a single exercise session with 3 consecutive days of exercise on triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C). Twelve young adult (aged 22.5 ± 2.5 years), overweight (body mass index = 29.7 ± 4 kg·m–2), sedentary, black (n = 5) and white (n = 7) men (n = 6) and women (n = 6) completed, in random order, a single treadmill exercise session at 60% maximal oxygen uptake for 90 min (1EX), accumulated exercise sessions (same as for 1EX) for 3 consecutive days (3EX), and a control protocol (no exercise for 6 days). Plasma samples were collected from baseline through 24, 48, and 72 h postexercise. Significant treatment-by-time interactions (p < 0.05) existed in HDL-C and LDL-C. Postexercise responses of HDL-C differed at 48 h (1EX: –3.6, 3EX: + 3.7 mg·dL−1) and 72 h (1EX: –1.7, 3EX: + 3.2 mg·dL−1). LDL-C responses differed at 48 h (1EX: –16, 3EX: + 6 mg·dL−1). Although not statistically significant, TG concentrations decreased by 29% at 24 h after 3EX, compared with –7% after 1EX. An inverse relationship between baseline and postexercise reduction in TG was present with 3EX (r = –0.655; p < 0.05). In conclusion, 3EX increased HDL-C and decreased TG more than 1EX, while the decrease in LDL-C after 1EX was suppressed. Blood lipid panel changes may be due to more accumulated effects over time rather than just a result of the most recent exercise session.
Two-Temperature Generalized Thermo-Elastic Medium Thermally Excited by Time Exponentially Decaying Laser Pulse
Authors: Youssef Hamdy M. , El-Bary A. A.
Published: January 2015

This paper deals with a two-temperature thermoelastic material subjected to a laser heating pulse as the heat source. Closed form solutions for the temperature and stress fields due to time exponentially decaying laser pulse are presented using the state-space approach. The Laplace transformation method is employed in deriving the governing equations. The inversion of Laplace transform is obtained numerically by using the Riemann-sum approximation method. The results have been presented in figures to show the effect of the time exponentially decaying laser pulse, the two-temperature parameter and the absorption coefficient on all the fields studied. The results show that the two-temperature parameter and the absorption coefficient parameter have significant effects on all the field parameters studied.
On the Structure of Graded Leibniz Algebras
Authors: Martín Antonio J. Calderón , Delgado José M. Sánchez
Published: January 2015

We study the structure of graded Leibniz algebras with arbitrary dimension and over an arbitrary base field 𝕂. We show that any of such algebras 𝔏 with a symmetric G-support is of the form [Formula: see text] with U a subspace of 𝔏1, the homogeneous component associated to the unit element 1 in G, and any Ija well described graded ideal of 𝔏, satisfying [Ij, Ik]=0 if j ≠ k. In the case of 𝔏 being of maximal length, we characterize the gr-simplicity of the algebra in terms of connections in the support of the grading.
Tameness and Artinianness of Graded Generalized Local Cohomology Modules
Authors: Jahangiri M. , Shirmohammadi N. , Tahamtan Sh.
Published: January 2015

Let R=⊕n ≥ 0 Rn be a standard graded ring, 𝔞 ⊇ ⊕n > 0 Rn an ideal of R, and M, N two finitely generated graded R-modules. This paper studies the homogeneous components of graded generalized local cohomology modules. We show that for any i ≥ 0, the n-th graded component [Formula: see text] of the i-th generalized local cohomology module of M and N with respect to 𝔞 vanishes for all n ≫ 0. Some sufficient conditions are proposed to satisfy the equality [Formula: see text]. Also, some sufficient conditions are proposed for the tameness of [Formula: see text] such that [Formula: see text] or i= cd 𝔞(M,N), where [Formula: see text] and cd 𝔞(M,N) denote the R+-finiteness dimension and the cohomological dimension of M and N with respect to 𝔞, respectively. Finally, we consider the Artinian property of some submodules and quotient modules of [Formula: see text], where j is the first or last non-minimax level of [Formula: see text].
Generalized Derivations with Periodic Values
Authors: Liu Kun-Shan
Published: January 2015

Let R be a prime ring and n > 1 be a fixed positive integer. If g is a nonzero generalized derivation of R such that g(x)n=g(x) for all x ∈ R, then R is commutative except when R is a subring of the 2 × 2 matrix ring over a field. Moreover, we generalize the result to the case g(f(xi))n = g(f(xi)) for all x1, x2, …, xt∈ R, where f(Xi) is a multilinear polynomial.
Systematic studies on side-chain structures of phthalocyaninato-polysiloxanes: Polymerization and self-assembling behaviors
Authors: Yoneda Satoru , Sakurai Tsuneaki , Nakayama Toru , Kato Kenichi , Takata Masaki , Seki Shu
Published: January 2015

A series of dihydroxysilicon phthalocyanines having soluble side chains were synthesized and their bulk-state polymerization capability was investigated. Detailed spectroscopic study of the obtained phthalocyaninato-polysiloxanes revealed that strong electron donating ability and small steric hindrance of the peripheral substituents are the dominant factors to afford high-molecular weight polymers. The polymers show the behaviors of columnar liquid crystal (LC), which is clarified by the presence of clear X-ray diffraction patterns with a hexagonal lattice and birefringent textures in polarized optical microscopy. Because of the siloxane covalent bonds through central silicon atoms, phthalocyaninato-polysiloxanes accommodate one-dimensional phthalocyanine arrays with strong π-electronic couplings, thus exhibiting colmnar LC property even for the derivatives carrying short peripheral chains and leading to the relatively higher density of π-electron systems in the materials. This tendency is different from typical discotic small molecules that require optimum side chain structures for LC formation.
A new biological function of heme as a signaling molecule
Authors: Muraki Norifumi , Kitatsuji Chihiro , Aono Shigetoshi
Published: January 2015

This mini-review presents a recent development of a new function of heme as a signaling molecule especially in the regulation of gene expression. Heme is biosynthesized as a prosthetic group for heme proteins, which play crucial roles for respiration, photosynthesis, and many other metabolic reactions. In some bacteria, exogenous heme molecules are used as a heme or an iron sources to be uptaken into cytoplasm. As free heme molecules are cytotoxic, the intracellular concentrations of biosynthesized or uptaken heme should be strictly controlled. In this mini-review, we summarize the biochemical and biophysical properties of the transcriptional regulators and heme-sensor proteins responsible for these regulatory systems to maintain heme homeostasis.
Impact of ER stress-regulated ATF4/p16 signaling on the premature senescence of renal tubular epithelial cells in diabetic nephropathy
Authors: Liu Jun , Yang Ju-Rong , Chen Xiang-Mei , Cai Guang-Yan , Lin Li-Rong , He Ya-Ni
Published: January 2015

Premature senescence is an important event during diabetic nephropathy (DN) progression. Here, we investigated the role of endoplasmic reticulum (ER) stress-regulated activation of transcription factor 4 (ATF4)/p16 signaling in the premature senescence of renal tubular epithelial cells (RTECs) during DN development. In the renal tissues of Type 2 DN patients, we detected an increased number of senescent cells; elevated deposition of advanced glycation end products (AGEs); upregulated expression of ER stress marker, glucose-regulated protein 78; as well as overexpression of ATF4 and p16. Similarly, these phenomena were also observed in cultured mouse RTECs following AGE treatment. Interestingly, AGE-induced p16 expression and premature senescence were successfully attenuated by ER stress inhibitor and ATF4 gene silencing. Moreover, AGE-induced premature senescence was mimicked by ER stress inducers and ATF4 overexpression, while suppressed by p16 gene silencing. In addition, ER stress inducers can augment ATF4 expression. Therefore, our results demonstrate that the ER stress-regulated ATF4/p16 pathway is involved in the premature senescence of RTECs during DN progression.
In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation
Authors: Zimmerman Arthur D. , Harris Ruth B. S.
Published: January 2015

We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offering 30% sucrose solution in addition to chow and water or by infusing glucosamine. Mice were leptin resistant after 33 days of access to sucrose. Resistance was associated with increased activity of the HBP and with phosphorylation of transcription factor signal transducer and activator of transcription-3 Tyr705 [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver and hypothalamus. Intravenous infusion of glucosamine for 3 h stimulated pSTAT3(Y705) but prevented leptin-induced phosphorylation of STAT3(S727). In an in vitro system, glucose, glucosamine, and leptin each dose dependently increased O-linked β- N-acetylglucosamine ( O-GlcNAc) protein and pSTAT3(Y705) in HepG2 cells. To test the effect of glucose on leptin responsiveness cells were incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0 or 50 ng/ml leptin for 15 min. HG alone and LG + leptin produced similar increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase (GFAT), and pSTAT3(Y705) compared with LG media. Leptin did not stimulate these proteins in HG cells, suggesting leptin resistance. Leptin-induced pSTAT3(S727) was prevented by HG media. Inhibition of GFAT with azaserine prevented LG + leptin and HG stimulation of pSTAT3. These data demonstrate development of leptin resistance in sucrose-drinking mice and provide new evidence of leptin-induced stimulation of the HBP.
Early-life physical activity reverses metabolic and Foxo1 epigenetic misregulation induced by gestational sleep disturbance
Authors: Mutskov Vesco , Khalyfa Abdelnaby , Wang Yang , Carreras Alba , Nobrega Marcelo A. , Gozal David
Published: January 2015

Sleep disorders are highly prevalent during late pregnancy and can impose adverse effects, such as preeclampsia and diabetes. However, the consequences of sleep fragmentation (SF) on offspring metabolism and epigenomic signatures are unclear. We report that physical activity during early life, but not later, reversed the increased body weight, altered glucose and lipid homeostasis, and increased visceral adipose tissue in offspring of mice subjected to gestational SF (SFo). The reversibility of this phenotype may reflect epigenetic mechanisms induced by SF during gestation. Accordingly, we found that the metabolic master switch Foxo1 was epigenetically misregulated in SFo livers in a temporally regulated fashion. Temporal Foxo1 analysis and its gluconeogenetic targets revealed that the epigenetic abnormalities of Foxo1 precede the metabolic syndrome phenotype. Importantly, regular physical activity early, but not later in life, reversed Foxo1 epigenetic misregulation and altered the metabolic phenotype in gestationally SF-exposed offspring. Thus, we have identified a restricted postnatal period during which lifestyle interventions may reverse the Foxo1 epigenetically mediated risk for metabolic dysfunction later in the life, as induced by gestational sleep disorders.
Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation
Authors: Martinez Emily M. , Yoshida Miya C. , Candelario Tara Lynne T. , Hughes-Fulford Millie
Published: January 2015

Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity ( μg) conditions. Scientists on the ground use two models of simulated μg ( sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.
Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model
Authors: McConell Glenn K. , Kaur Gunveen , Falcão-Tebas Filippe , Hong Yet H. , Gatford Kathryn L.
Published: January 2015

In healthy humans and rodents, chronic and acute exercise improves subsequent insulin sensitivity of skeletal muscle. A large animal species with similar metabolic responses to exercise would permit longitudinal studies, including repeated biopsies of muscle and other tissues not possible in rodents, and enable study of interactions with insulin-resistant physiological states not feasible in humans. Therefore, we examined whether acute exercise increases insulin sensitivity in adult sheep. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp (HEC) in mature female sheep ( n = 7). Sheep were familiarized to treadmill walking and then performed an acute exercise bout (30 min, 8% slope, up to 4.4 km/h). A second HEC was conducted ∼18 h after the acute exercise. Musculus semimembranosus biopsies were obtained before and after each HEC. Glucose infusion rate during the HEC increased 40% ( P = 0.003) and insulin sensitivity (glucose infusion rate/plasma insulin concentration) increased 32% ( P = 0.028) after acute exercise. Activation of proximal insulin signaling in skeletal muscle after the HEC, measured as Ser473phosphorylation of Akt, increased approximately five-fold in response to insulin ( P < 0.001) and was unaltered by acute exercise performed 18 h earlier. PGC1αand GLUT4 protein, glycogen content and citrate synthase activity in skeletal muscle did not change in response to insulin or exercise. In conclusion, improved insulin sensitivity and unchanged proximal insulin signaling on the day after acute exercise in sheep are consistent with responses in humans and rodents, suggesting that the sheep is an appropriate large-animal model in which to study responses to exercise.
An angiotensin-(1–7) peptidase in the kidney cortex, proximal tubules, and human HK-2 epithelial cells that is distinct from insulin-degrading enzyme
Authors: Wilson Bryan A. , Cruz-Diaz Nildris , Marshall Allyson C. , Pirro Nancy T. , Su Yixin , Gwathmey TanYa M. , Rose James C. , Chappell Mark C.
Published: January 2015

Angiotensin 1–7 [ANG-(1–7)] is expressed within the kidney and exhibits renoprotective actions that antagonize the inflammatory, fibrotic, and pro-oxidant effects of ANG II. We previously identified an peptidase that preferentially metabolized ANG-(1–7) to ANG-(1–4) in the brain medulla and cerebrospinal fluid (CSF) of sheep (Marshall AC, Pirro NT, Rose JC, Diz DI, Chappell MC. J Neurochem 130: 313–323, 2014); thus the present study established the expression of the peptidase in the kidney. Utilizing a sensitive HPLC-based approach, we demonstrate a peptidase activity that hydrolyzed ANG-(1–7) to ANG-(1–4) in the sheep cortex, isolated tubules, and human HK-2 renal epithelial cells. The peptidase was markedly sensitive to the metallopeptidase inhibitor JMV-390; human HK-2 cells expressed subnanomolar sensitivity (IC50= 0.5 nM) and the highest specific activity (123 ± 5 fmol·min−1·mg−1) compared with the tubules (96 ± 12 fmol·min−1·mg−1) and cortex (107 ± 9 fmol·min−1·mg−1). The peptidase was purified 41-fold from HK-2 cells; the activity was sensitive to JMV-390, the chelator o-phenanthroline, and the mercury-containing compound p-chloromercuribenzoic acid (PCMB), but not to selective inhibitors against neprilysin, neurolysin and thimet oligopeptidase. Both ANG-(1–7) and its endogenous analog [Ala1]-ANG-(1–7) (alamandine) were preferentially hydrolyzed by the peptidase compared with ANG II, [Asp1]-ANG II, ANG I, and ANG-(1–12). Although the ANG-(1–7) peptidase and insulin-degrading enzyme (IDE) share similar inhibitor characteristics of a metallothiolendopeptidase, we demonstrate marked differences in substrate specificity, which suggest these peptidases are distinct. We conclude that an ANG-(1–7) peptidase is expressed within the renal proximal tubule and may play a potential role in the renal renin-angiotensin system to regulate ANG-(1–7) tone.
Role of Na+/Ca2+exchanger in Ca2+homeostasis in rat suprachiasmatic nucleus neurons
Authors: Wang Yi-Chi , Chen Ya-Shuan , Cheng Ruo-Ciao , Huang Rong-Chi
Published: January 2015

Intracellular Ca2+is critical to the central clock of the suprachiasmatic nucleus (SCN). However, the role of Na+/Ca2+exchanger (NCX) in intracellular Ca2+concentration ([Ca2+]i) homeostasis in the SCN is unknown. Here we show that NCX is an important mechanism for somatic Ca2+clearance in SCN neurons. In control conditions Na+-free solution lowered [Ca2+]iby inhibiting TTX-sensitive as well as nimodipine-sensitive Ca2+influx. With use of the Na+ionophore monensin to raise intracellular Na+concentration ([Na+]i), Na+-free solution provoked rapid Ca2+uptake via reverse NCX. The peak amplitude of 0 Na+-induced [Ca2+]iincrease was larger during the day than at night, with no difference between dorsal and ventral SCN neurons. Ca2+extrusion via forward NCX was studied by determining the effect of Na+removal on Ca2+clearance after high-K+-induced Ca2+loads. The clearance of Ca2+proceeded with two exponential decay phases, with the fast decay having total signal amplitude of ∼85% and a time constant of ∼7 s. Na+-free solution slowed the fast decay rate threefold, whereas mitochondrial protonophore prolonged mostly the slow decay. In contrast, blockade of plasmalemmal and sarco(endo)plasmic reticulum Ca2+pumps had little effect on the kinetics of Ca2+clearance. RT-PCR indicated the expression of NCX1 and NCX2 mRNAs. Immunohistochemical staining showed the presence of NCX1 immunoreactivity in the whole SCN but restricted distribution of NCX2 immunoreactivity in the ventrolateral SCN. Together our results demonstrate an important role of NCX, most likely NCX1, as well as mitochondrial Ca2+uptake in clearing somatic Ca2+after depolarization-induced Ca2+influx in SCN neurons.
Different types of retinal inhibition have distinct neurotransmitter release properties
Authors: Moore-Dotson Johnnie M. , Klein Justin S. , Mazade Reece E. , Eggers Erika D.
Published: January 2015

Neurotransmitter release varies between neurons due to differences in presynaptic mechanisms such as Ca2+ sensitivity and timing. Retinal rod bipolar cells respond to brief dim illumination with prolonged glutamate release that is tuned by the differential release of GABA and glycine from amacrine cells in the inner retina. To test if differences among types of GABA and glycine release are due to inherent amacrine cell release properties, we directly activated amacrine cell neurotransmitter release by electrical stimulation. We found that the timing of electrically evoked inhibitory currents was inherently slow and that the timecourse of inhibition from slowest to fastest was GABAC receptors > glycine receptors > GABAA receptors. Deconvolution analysis showed that the distinct timing was due to differences in prolonged GABA and glycine release from amacrine cells. The timecourses of slow glycine release and GABA release onto GABAC receptors were reduced by Ca2+ buffering with EGTA-AM and BAPTA-AM, but faster GABA release on GABAA receptors was not, suggesting that release onto GABAA receptors is tightly coupled to Ca2+. The differential timing of GABA release was detected from spiking amacrine cells and not nonspiking A17 amacrine cells that form a reciprocal synapse with rod bipolar cells. Our results indicate that release from amacrine cells is inherently asynchronous and that the source of nonreciprocal rod bipolar cell inhibition differs between GABA receptors. The slow, differential timecourse of inhibition may be a mechanism to match the prolonged rod bipolar cell glutamate release and provide a way to temporally tune information across retinal pathways.
The Association of 5-HTTLPR XLL Genotype with Higher Cortisol Levels in African Americans
Authors: Contreras-Sesvold Carmen L. , Abraham Preetha , Devaney Joseph M. , Harmon Brennan T. , Deuster Patricia A.
Published: January 2015

Genetic variants of the human serotonin transporter (SERT) may contribute to HPA axis dysregulation. SERT has two promoter region polymorphisms (5-HTTLPR: VNTR and SNP: rs25531), which may alter levels of SERT protein and its function. Combining these polymorphisms creates a functional polymorphism (FN) which may modulate mRNA expression. This study examines the relationship between these genetic variants and morning and evening salivary samples of both cortisol and dehydroepiandrosterone sulfate (DHEAS) concentrations in 269 African American (AA) adults. Resultant allele frequencies for the VNTR, SNP, and FN genotypes were 70% L (2% XLL), 84% A, and 54% LA (2% XLLA), respectively. The XLL genotype was associated with significantly higher concentrations of cortisol (~3X) and DHEAS (~2X) for both VNTR and FN polymorphisms. No significant differences were found for SNP genotypes. Conclusions were that persons with VNTR and FN XLL polymorphisms had significantly higher cortisol and DHEAS concentrations than other genotypes. AAs also appear to have a higher frequency of the rare XL allele than Caucasians. Whether the XLL genotype predisposes AAs to greater health challenges will require further research to determine the implications of these findings.
Indocyanine Green Assisted Removal of Orbital Lacrimal Duct Cysts in Children
Authors: Keren Shay , Dotan Gad , Leibovitch Leah , Selva Dinesh , Leibovitch Igal
Published: January 2015

Aim. To report on the use of indocyanine green (ICG) during surgical removal of pediatric orbital lacrimal duct cysts.Method. We conducted a retrospective review of our cases of surgical excision of orbital lacrimal duct cysts using intraoperative injection of indocyanine green (ICG), which was used following inadvertent cyst rupture and volume loss. The dye allowed complete cyst visualization and complete excision despite volume loss or cyst rupture.Results. The study included 6 children (3 boys, mean age of 4.2 ± 0.84 years, range 3–5 years). Mean follow-up period was 9.3 months. All cysts were located in the inferonasal quadrant of the orbit (4 in the right side). In all cases, ICG was injected into the cyst at the time of surgery following unintentional cyst rupture. After the dye injection, it was easy to identify the borders of the cyst, permitting complete cyst removal, without any intra- or postoperative complications. Pathological examination revealed that all cysts were of lacrimal duct origin.Conclusion. Intraoperative injection of ICG into orbital cysts in children can aid surgeons in identifying cyst borders following inadvertent rupture, allowing complete removal.
Biodiesel Production Process Optimization from Sugar Apple Seed Oil (Annona squamosa) and Its Characterization
Authors: Hotti Siddalingappa R. , Hebbal Omprakash D.
Published: January 2015

This paper presents the production of biodiesel from nonedible, renewable sugar apple seed oil and its characterization. The studies were carried out on transesterification of oil with methanol and sodium hydroxide as catalyst for the production of biodiesel. The process parameters such as catalyst concentration, reaction time, and reaction temperature were optimized for the production of sugar apple biodiesel (SABD). The biodiesel yield of 95.15% was noticed at optimal process parameters. The fuel properties of biodiesel produced were found to be close to that of diesel fuel and also they meet the specifications of ASTM standards.
Optimized Sedation Improves Colonoscopy Quality Long-Term
Authors: Triantafyllou Konstantinos , Sioulas Athanasios D. , Kalli Theodora , Misailidis Nikolaos , Polymeros Dimitrios , Papanikolaou Ioannis S. , Karamanolis George , Ladas Spiros D.
Published: January 2015

Background. Quality monitoring and improvement is prerequisite for efficient colonoscopy.Aim. To assess the effects of increased sedation administration on colonoscopy performance.Materials and Methods. During Era 1 we prospectively measured four colonoscopy quality indicators: sedation administration, colonoscopy completion rate, adenoma detection rate, and early complications rate in three cohorts: cohort A: intention for total colonoscopy cases; cohort B: cohort A excluding bowel obstruction cases; cohort C: CRC screening-surveillance cases within cohort B. We identified deficiencies and implemented our plan to optimize sedation. We prospectively evaluated its effects in both short- (Era 2) and long-term period (Era 3).Results. We identified that sedation administration and colonoscopy completion rates were below recommended standards. After sedation optimization its use rate increased significantly (38.1% to 55.8% to 69.5%) and colonoscopy completion rate increased from 88.3% to 90.6% to 96.4% in cohort B and from 93.2% to 95.3% to 98.3% in cohort C, in Eras 1, 2, and 3, respectively. Adenoma detection rate increased in cohort C (25.9% to 30.6% to 35%) and early complications rate decreased from 3.4% to 1.9% to 0.3%. Most endoscopists increased significantly their completion rate and this was preserved long-term.Conclusion. Increased sedation administration results in long-lasting improvement of colonoscopy quality indicators.