Stemless shoulder arthroplasty: current status.
Since the original Neer humeral replacement in the 1950s, the standard primary anatomic total shoulder arthroplasty design has slowly evolved. Most recently, the humeral stem has become progressively shorter to help combat stem-related complications. Currently, there are several companies who have developed and marketed a stemless humeral arthroplasty component. Manufacturers' data for 5 stemless shoulder arthroplasty components currently on the market were analyzed and reviewed. A literature review of short-term results for stemless shoulder arthroplasty was completed. Of the stemless shoulder arthroplasty systems available on the market, 3 are currently undergoing clinical trials in the United States. The Tornier Simpliciti (Tornier, Edina, MN, USA) clinical trial began in 2011. The study with 2-year minimum follow-up results is scheduled for completion in November 2014. The Arthrex Eclipse (Arthrex, Naples, FL, USA) clinical trial was started in January 2013. The tentative study completion date is 2017. The Biomet Nano (Biomet, Warsaw, IN, USA) clinical trial began in October 2013 and also has a tentative completion date of 2017. No other clinical trial is currently under way in the United States. Early results for stemless shoulder arthroplasty indicate clinical results similar to standard stemmed shoulder arthroplasty. Radiographic analysis indicates implant stability without migration or subsidence at 2- to 3-year minimum follow-up.. Several stemless shoulder arthroplasty implants are available outside the United States. Early clinical and radiographic results are promising, but well-designed clinical studies and midterm results are lacking. Three clinical trials are currently under way in the United States with initial availability for use anticipated in 2015.


Mosquito larvicidal activity of Escherichia coli with combinations of genes from Bacillus thuringiensis subsp. israelensis.
The genes cryIVA and cryIVD, encoding 134- and 72-kDa proteins, respectively, and the gene for a regulatory 20-kDa polypeptide of Bacillus thuringiensis subsp. israelensis (serovar H14) were cloned in all seven possible combinations by the Escherichia coli expression vectors pT7 and pUHE. The four combinations containing cryIVA (cryIVA alone, with cryIVD, with the 20-kDa-protein gene, and with both) displayed high levels of mosquito larvicidal activity in pUHE. The toxicity of the combination of cryIVA and cryIVD, with or without the 20-kDa-protein gene, was higher than has ever been achieved with delta-endotoxin genes in recombinant E. coli. Fifty percent lethal concentrations against third-instar Aedes aegypti larvae for these clones decreased (i.e., toxicity increased) continuously to about 3 x 10(5) cells ml-1 after 4 h of induction. Larvicidal activities, obtained after 30 min of induction, were lower for clones in pT7 and decreased for an additional 3.5 h. Induction of either cryIVD or the 20-kDa-protein gene alone resulted in no larvicidal activity in either pT7 or pUHE20. Cloned together, these genes were slightly toxic in pT7 but not in pUHE20. Five minutes of induction of this combination (cryIVD with the 20-kDa-protein gene) in pT7 yielded a maximal mortality of about 40%, which decreased rapidly and disappeared completely after 50 min. CryIVD is thus apparently degraded in E. coli and partially stabilized by the 20-kDa regulatory protein. Larvicidal activity of the combination of cryIVA and cryIVD was sevenfold higher than that of cryIVA alone, probably because of the cross-stabilization of the polypeptides or the synergism between their activities.


From Shell Shock to Shellac: The Great War, Blindness, and Britain's Talking Book Library.
Britain's Talking Book Service began as a way of providing reading material to soldiers blinded during the First World War. This account traces the talking book's development from the initial experiments after the War to its debut and reception among blind soldiers and civilians in the 1930s. It has been put together using archives held by the Royal National Institute of Blind People (before its Royal Charter, the NIB) and Blind Veterans UK (formerly St. Dunstan's), the two organizations responsible for Britain's Talking Book Service. The essay's first section reconstructs the search for an alternative way of reading that would benefit people with vision impairments. The next part demonstrates the talking book's impact on the lives of people with disabilities, recovering the voices of blind readers left out of most histories of books, literacy, and reading practices in the twentieth century. The final section reconstructs a debate over the value of recorded books, showing that disputes over their legitimacy are as old as recorded books themselves. In sum, this essay confronts the central issue raised by the convergence of books, media, and disability in the War's aftermath: can a book talk?


Immunological characterization of the gag gene products of bovine immunodeficiency virus.
The bovine immunodeficiency virus (BIV) gag gene encodes a 53-kDa precursor (Pr53gag) that is involved in virus particle assembly and is further processed into the putative matrix (MA), capsid (CA), and nucleocapsid (NC) functional domains in the mature virus. Gag determinants are also found in the Gag-Pol polyprotein precursor. To immunologically identify the major precursors and processed products of the BIV gag gene, monospecific rabbit sera to recombinant BIV MA protein and Pr53gag and peptides predicted to correspond to the CA and NC proteins and the MA-CA cleavage site were developed and used in immunoprecipitations and immunoblots of BIV antigens. Monospecific antisera to native and recombinant human immunodeficiency virus type 1 proteins were also used to identify analogous BIV Gag proteins and to determine whether cross-reactive epitopes were present in the BIV Gag precursors or processed products. The BIV MA, CA, and NC Gag proteins were identified as p16, p26, and p13, respectively. In addition to BIV Pr53gag, the major Gag precursor, two other Gag-related precursors of 170 and 49 kDa were identified that have been designated pPr170gag-pol and Pr49gag, respectively; pPr170gag-pol is the Gag-Pol polyprotein precursor, and Pr49gag is the transframe Gag precursor present in pPr170gag-pol. Several alternative Gag cleavage products were also observed, including p23, which contains CA and NC determinants, and p10, which contains a peptide sequence conserved in the CA proteins of most lentiviruses. The monospecific antisera to human immunodeficiency virus type 1 CA (p24) and NC (p7) proteins showed cross-reactivity to and aided in the identification of analogous BIV proteins. Based on the present data, a scheme for the processing of BIV Gag precursors is proposed.


CD16 regulates TRIF-dependent TLR4 response in human monocytes and their subsets.
Blood monocytes recognize Gram-negative bacteria through the TLR4, which signal via MyD88- and TRIF-dependent pathway to trigger an immune-inflammatory response. However, a dysregulated inflammatory response by these cells often leads to severe pathologies such as sepsis. We investigated the role of CD16 in the regulation of human monocyte response to Gram-negative endotoxin and sepsis. Blood monocytes from sepsis patients demonstrated an upregulation of several TRIF-dependent genes as well as a selective expansion of CD16-expressing (CD16(+)) monocytes. Gene expression and biochemical studies revealed CD16 to regulate the TRIF-dependent TLR4 pathway in monocytes by activating Syk, IFN regulatory factor 3, and STAT1, which resulted in enhanced expression of IFNB, CCL5, and CXCL10. CD16 also upregulated the expression of IL-1R-associated kinase M and IL-1 receptor antagonist, which are negative regulators of the MyD88-dependent pathway. CD16 overexpression or small interfering RNA knockdown in monocytes confirmed the above findings. Interestingly, these results were mirrored in the CD16(+) monocyte subset isolated from sepsis patients, providing an in vivo confirmation to our findings. Collectively, the results from the current study demonstrate CD16 as a key regulator of the TRIF-dependent TLR4 pathway in human monocytes and their CD16-expressing subset, with implications in sepsis.


Neural mechanisms in asthma.
Advances in the understanding of neural mechanisms in asthma may provide novel therapeutic approaches in the treatment of asthma. Excessive activity of cholinergic nerves may be important in asthma. Dysfunction of M2 muscarinic receptors in asthma may lead to excessive bronchoconstriction and mucus secretion and can be induced in animal models by a range of stimuli including allergen, viral infection, ozone, eosinophil products and cytokines. Cholinergic mechanisms may be especially important in certain types of patients and anticholinergic agents provide protection against bronchospasm due to psychogenic factors or beta2-blockers. Non-adrenergic non-cholinergic (NANC) mechanisms, both inhibitory (i-NANC) and excitatory (e-NANC), may play a significant role in the pathophysiology of asthma. The putative neurotransmitters, vasoactive interstinal polypeptide (VIP) and nitric oxide (NO), mediate neural bronchodilation in human airways. There does not appear to be a defect in the i-NANC system in moderate or severe asthma. e-NANC is mediated by the sensory neuropeptides substance P (SP) and the more potent bronchoconstrictor neurokinin A (NKA). Various studies suggest that the SP content of human airways is increased in asthma. Tachykinins are not only present in sensory nerves, but also are produced by inflammatory cells such as alveolar macrophages, dendritic cells, eosinophils, lymphocytes and neutrophils. They can be released into the airways by stimuli such as allergen and ozone. Evidence suggests that in addition to smooth muscle contraction, which is mediated mainly by NK2 receptors, tachykinins also cause mucus secretion, plasma extravasation and stimulate inflammatory and immune cells. These effects are mediated by NK1 receptors. Recent studies have shown that NK2 receptor antagonists such as saredutant partially inhibit NKA-induced bronchoconstriction in asthmatics. Thus, tachykinin receptor antagonists have potential as therapies for asthma.


Blastomycosis in indiana: digging up more cases.
The endemic region of blastomycosis historically has included the state of Indiana. However, few published reports of blastomycosis exist to substantiate this distinction. A surge of patients with blastomycosis in central Indiana (Indianapolis and surrounding counties) beginning in 2005 prompted us to review our local experience. We propose that this surge was related to major highway construction around Indianapolis. We reviewed all microbiologically confirmed cases from four hospitals serving central Indiana. Chart review was completed for adult patients, and data were collected on clinical presentations, methods of diagnosis, comorbidities, radiologic findings, treatment, and outcomes. We plotted patient residence addresses with sites of highway construction. Fifty-nine patients were identified from laboratory results and physician referral. Interestingly, a surge of blastomycosis incidence occurred in 34 patients between 2005 and 2008 during which time major highway projects were under way around the Indianapolis metropolitan area. The majority of these patients presented acutely and with pulmonary involvement. Fungal culture and antigen testing were the most sensitive means to diagnosis. Antifungal therapy was highly effective. This urban outbreak of blastomycosis in Indianapolis should prompt clinicians to consider blastomycosis in this highly endemic area of histoplasmosis.


Search for Spectral Irregularities due to Photon-Axionlike-Particle Oscillations with the Fermi Large Area Telescope.
We report on the search for spectral irregularities induced by oscillations between photons and axionlike-particles (ALPs) in the γ-ray spectrum of NGC 1275, the central galaxy of the Perseus cluster. Using 6 years of Fermi Large Area Telescope data, we find no evidence for ALPs and exclude couplings above 5×10^{-12} GeV^{-1} for ALP masses 0.5≲m_{a}≲5 neV at 95% confidence. The limits are competitive with the sensitivity of planned laboratory experiments, and, together with other bounds, strongly constrain the possibility that ALPs can reduce the γ-ray opacity of the Universe.


Morphology of the thoracolumbar spine of the middle Miocene hominoid Nacholapithecus kerioi from northern Kenya.
A new caudal thoracic and a new lumbar vertebra of Nacholapithecus kerioi, a middle Miocene hominoid from northern Kenya, are reported. The caudal thoracic vertebral body of N. kerioi has a rounded median ventral keel and its lateral sides are moderately concave. The lumbar vertebral body has an obvious median ventral keel. Based on a comparison of vertebral body cranial articular surface size between the caudal thoracic vertebrae in the present study and one discussed in a previous study (KNM-BG 35250BO, a diaphragmatic vertebra), N. kerioi has at least two post-diaphragmatic vertebrae (rib-bearing lumbar-type thoracic vertebrae), unlike extant hominoids. It also has thick, rounded, and moderately long metapophyses on the lumbar vertebra that project dorsolaterally. The spinous process bases of its caudal thoracic and lumbar vertebrae originate caudally between the postzygapophyses, as described previously in the KNM-BG 35250 holotype specimen. In other words, the postzygapophyses of N. kerioi do not project below the caudal border of the spinous processes, similar to those of extant great apes, and unlike small apes and monkeys, which have more caudally projecting postzygapophyses. Nacholapithecus kerioi has a craniocaudally expanded spinous process in relation to vertebral body length, also similar to extant great apes. Both these spinous process features of N. kerioi differ from those of Proconsul nyanzae. The caudal thoracic vertebra of N. kerioi has a caudally-directed spinous process, whose tip is tear-drop shaped. These features resemble those of extant apes. The morphology of the spinous process tips presumably helps vertebral stability by closely stacking adjacent spinous process tips as seen in extant hominoids. The morphology of the spinous process and postzygapophyses limits the intervertebral space and contributes to the stability of the functional lumbar region as seen in extant great apes, suggesting that antipronograde activity was included in the positional behavior of N. kerioi.


Polycystic ovary syndrome: clinical and laboratory evaluation.
To evaluate clinically, and with laboratory, tests, women with polycystic ovary syndrome (PCO). One hundred and twelve women with PCO were studied. The following data was recorded: Current age; age at menarche; menstrual irregularity, occurrence of similar cases in the family; fertility, obstetric history; body mass index (BMI); and presence of hirsutism. Serum measurements of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, free testosterone, and dehydroepiandrosterone sulfate were taken. All patients presented either oligomenorrhea (31 percent), periods of secondary amenorrhea (9 percent), or both alterations (60 percent). The majority of the patients were infertile (75.6 percent). The LH/FSH ratio was higher than 2:1 in 55 percent of the patients and higher than 3:1 in 26.2 percent. The ultrasonographic aspect of the ovaries was considered to be normal in 31 percent. The main clinical feature of the PCO is the irregularity of menses since menarche, and that the laboratory tests would be important to exclude other disorders such as hyperprolactinemia or hyperandrogenemia caused by late-onset congenital adrenal hyperplasia.


Health status of non-Hispanic U.S.-born and foreign-born black and white persons: United States, 1992-95.
This report describes differences in selected sociodemographic and health characteristics of the non-Hispanic U.S. population by race (black and white) and nativity (U.S-born and foreign-born), using data from the 1992-95 National Health Interview Surveys (NHIS). Data were collected for a household, multistage probability sample representative of the U.S. civilian noninstitutionalized population. A total of 456,729 persons were included in these analyses for the 4 data years combined. Statistics were age adjusted to the 2000 U.S. standard population, and unadjusted estimates are also presented for comparison. Over 87 percent of the foreign-born black population assessed their health as being excellent or very good, significantly higher than U.S.-born black persons (52 percent), and similar to U.S.- and foreign-born white persons (69 percent for each group). Eleven percent of foreign-born black persons were limited in performing some type of activity, compared with 20 percent of their U.S.-born counterparts. Among white persons, 14 percent of foreign-born and 16 percent of U.S.-born individuals were limited in activity. The foreign-born black population, especially women, had the lowest current smoking prevalence of all of the study groups. The data show significant differences in health characteristics between groups classified by race and nativity. Information about the nativity status of black and white populations may be useful in public health efforts to eliminate health disparities.


Absence of both the 91kD and 22kD subunits of human neutrophil cytochrome b in two genetic forms of chronic granulomatous disease.
Chronic granulomatous disease (CGD) is a group of inherited disorders in which phagocytic cells fail to generate antimicrobial oxidants. The various forms of CGD can be classified in terms of the mode of inheritance (either X-linked or autosomal recessive), and whether the neutrophils display the absorbance spectrum of a unique b-type cytochrome important for the function of the respiratory burst oxidase. The finding that purified neutrophil cytochrome b is a heterodimer consisting of a 91kD glycosylated and a 22kD nonglycosylated polypeptide has raised the question of which subunits are absent (or defective) in the various types of CGD. To address this question we have studied the expression of the cytochrome b subunits in three genetically distinct forms of CGD: X-linked/cytochrome b-negative (X-), autosomal recessive/cytochrome b-negative (A-), and autosomal recessive/cytochrome b-positive (A+). Using polyclonal antibodies to each of the two subunits, we prepared Western blots of lysates of intact neutrophils from ten CGD patients. In the controls and three patients with A+ CGD, both cytochrome subunits were easily detected. Consistent with the previously reported finding in five X- patients, neither subunit could be identified in neutrophils from three additional X- patients. Both subunits were also undetectable in four patients with A- CGD (three females, one male). This latter group of patients most likely bears a normal 91kD gene, since the patients are genetically distinct from the 91kD-defective X- group. The mutation in A- CGD, therefore, probably involves the 22kD gene and the eventual expression of the 22kD subunit. Furthermore, the expression of the 91kD subunit in this group of patients appears to be prevented due to the 22kD mutation in a manner converse to that seen in the X- CGD patients. Based on these studies, we hypothesize that the stable of expression of either of the two cytochrome subunits is dependent upon the other.


VASIR: An Open-Source Research Platform for Advanced Iris Recognition Technologies.
The performance of iris recognition systems is frequently affected by input image quality, which in turn is vulnerable to less-than-optimal conditions due to illuminations, environments, and subject characteristics (e.g., distance, movement, face/body visibility, blinking, etc.). VASIR (Video-based Automatic System for Iris Recognition) is a state-of-the-art NIST-developed iris recognition software platform designed to systematically address these vulnerabilities. We developed VASIR as a research tool that will not only provide a reference (to assess the relative performance of alternative algorithms) for the biometrics community, but will also advance (via this new emerging iris recognition paradigm) NIST's measurement mission. VASIR is designed to accommodate both ideal (e.g., classical still images) and less-than-ideal images (e.g., face-visible videos). VASIR has three primary modules: 1) Image Acquisition 2) Video Processing, and 3) Iris Recognition. Each module consists of several sub-components that have been optimized by use of rigorous orthogonal experiment design and analysis techniques. We evaluated VASIR performance using the MBGC (Multiple Biometric Grand Challenge) NIR (Near-Infrared) face-visible video dataset and the ICE (Iris Challenge Evaluation) 2005 still-based dataset. The results showed that even though VASIR was primarily developed and optimized for the less-constrained video case, it still achieved high verification rates for the traditional still-image case. For this reason, VASIR may be used as an effective baseline for the biometrics community to evaluate their algorithm performance, and thus serves as a valuable research platform.


Tonic dopamine: opportunity costs and the control of response vigor.
Dopamine neurotransmission has long been known to exert a powerful influence over the vigor, strength, or rate of responding. However, there exists no clear understanding of the computational foundation for this effect; predominant accounts of dopamine's computational function focus on a role for phasic dopamine in controlling the discrete selection between different actions and have nothing to say about response vigor or indeed the free-operant tasks in which it is typically measured. We seek to accommodate free-operant behavioral tasks within the realm of models of optimal control and thereby capture how dopaminergic and motivational manipulations affect response vigor. We construct an average reward reinforcement learning model in which subjects choose both which action to perform and also the latency with which to perform it. Optimal control balances the costs of acting quickly against the benefits of getting reward earlier and thereby chooses a best response latency. In this framework, the long-run average rate of reward plays a key role as an opportunity cost and mediates motivational influences on rates and vigor of responding. We review evidence suggesting that the average reward rate is reported by tonic levels of dopamine putatively in the nucleus accumbens. Our extension of reinforcement learning models to free-operant tasks unites psychologically and computationally inspired ideas about the role of tonic dopamine in striatum, explaining from a normative point of view why higher levels of dopamine might be associated with more vigorous responding.


Room-temperature ferromagnetism in graphitic petal arrays.
We report room-temperature ferromagnetism of graphitic petal arrays grown on Si substrates by microwave plasma chemical vapor deposition without catalyst. The samples have been characterized by Raman and X-ray photoelectron spectroscopy to confirm the absence of possible ferromagnetic impurities. The petals exhibit ferromagnetic hysteresis with saturation magnetization of ∼4.67 emu cm(-3) and coercivity of ∼105 Oe at 300 K, comparable to the reported behavior of few-layer graphene. Upon O2 annealing the saturation magnetization and coercivity decreased to 2.1 emu cm(-3) and ∼75 Oe respectively. The origin of ferromagnetism is believed to arise from the edge defects and vacancies in the petals.


Characterization of the thymic IL-7 niche in vivo.
The thymus represents the "cradle" for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor for thymopoiesis, the "environmental niche" of thymic IL-7 activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice in which YFP is under control of IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co-express YFP and high levels of Il7 transcripts (IL-7(hi) cells). IL-7(hi) TECs arise during early fetal development, persist throughout life, and co-express homeostatic chemokines (Ccl19, Ccl25, Cxcl12) and cytokines (Il15) that are critical for normal thymopoiesis. In the adult thymus, IL-7(hi) cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7(hi) cells decreases with age, suggesting a mechanism for the age-related thymic involution that is associated with declining IL-7 levels. Our temporal-spatial analysis of IL-7-producing cells in the thymus in vivo suggests that thymic IL-7 levels are dynamically regulated under distinct physiological conditions. This IL-7 reporter mouse provides a valuable tool to further dissect the mechanisms that govern thymic IL-7 expression in vivo.


A new portable vibrator for plaster pouring: effect on the marginal fit at cylinder-abutment.
The aim of this study was to test a new portable vibrator for plaster pouring (developed for this purpose), comparing the effect of its use on the accuracy of working cast of implant-supported restorations to the conventional vibrator. From a master cast with 2 implants, 30 transfer moldings were made randomly and divided into three groups: group I (GI): pouring performed in an outsourced dental laboratory with conventional plaster vibrator (10 casts), group II (GII): pouring performed in the laboratory of the Federal University of Santa Catarina (UFSC) with conventional plaster vibrator (10 casts) and group III (GIII): pouring performed with the portable vibrator fabricated for this study (10 casts). The position of the analogue and marginal adaptation of the infrastructure were verified by testing the single screw on the master model and on the working model. The measurement of misfit was blindly performed with a precision microscope and analyzing unit, Quadra-Check 200. The data were statistically analyzed by analysis of variance (ANOVA) and the Holm-Sidak test (α=0.05). Means±standard deviations were as follows: GI: 19.19±4.73 µm; GII: 21.72±5.41 µm; GIII: 13.5±2.39 µm (P<0.05), with GIII significantly lower as compared to the other groups. Within the limitations of this study, it was concluded that a greater accuracy of working cast was achieved when a portable vibrator was used for casting molds.


Measurement of gastrointestinal pH profiles in normal ambulant human subjects.
Gastrointestinal (GI) pH has been measured in 66 normal subjects using a pH sensitive radiotelemetry capsule passing freely through the gastrointestinal tract. Signals were recorded with a portable solid state receiver and recording system, enabling unconstrained measurements with normal ambulatory activities for up to 48 h during normal GI transit. Capsule position in the gut was monitored by surface location using a directional detector. Gastric pH was highly acidic (range 1.0-2.5) in all subjects. The mean pH in the proximal small intestine was 6.6 (0.5) for the first hour of intestinal recording. By comparison the mean pH in the terminal ileum was 7.5 (0.4) (p less than 0.001). In all subjects there was a sharp fall in pH to a mean of 6.4 (0.4) (p less than 0.001) as the capsule passed into the caecum. Values are means (SD). pH then rose progressively from the right to the left colon with a final mean value of 7.0 (0.7) (p less than 0.001).


Clinical and radiological outcomes of hemivertebra resection for congenital scoliosis in children under age 10 years: More than 5-year follow-up.
The surgical treatment of congenital scoliosis under 10 years is difficult as it involves resecting vertebrae. Moreover, patient follow-up after surgery is extremely important because the patient is a child whose growth has not been completed. However, there are very few long-term follow-up studies after surgical treatment of congenital scoliosis. Therefore, this study is designed to evaluate surgical outcomes after posterior hemivertebra resection in children under 10 years and its long-term effects.Twenty-one patients with congenital scoliosis who were younger than 10 years at the time of the surgery and received posterior hemivertebra resection and fusion using pedicle screw fixation were included in this study.There were significant improvements in the main curve, coronal balance, sagittal vertical axis, thoracic kyphosis, and lumbar lordosis after surgery (P < .001, .021, .047, .043, .006, respectively). Coronal balance, sagittal vertical axis, thoracic kyphosis, and lumbar lordosis remained within the normal range during the follow-up period; however, main curve deteriorated significantly (P = .005). Trunk appearance of perception scale improved significantly after surgery (P = .031) and was maintained during the follow-up period (P = .078).In conclusion, posterior hemivertebra resection and fusion using pedicle screw fixation in patients under 10 years old with congenital scoliosis is a safe and effective procedure that can achieve rigid fixation and deformity correction. Complete resection of the hemivertebra is important for deformity correction and prevention of curve progression, and careful long-term follow-up is necessary.


Decreased binding of calmodulin to bull sperm proteins during heparin-induced capacitation.
The 125I-calmodulin gel overlay procedure was used to evaluate the effect of a heparin treatment on the calmodulin-binding proteins of bull spermatozoa. At concentrations that increase the in vitro fertilization rate of in vitro-matured oocytes, heparin induced a decrease in the binding to calmodulin (CaM) in 3 sperm proteins of 28, 30, and 49 kDa. The binding of these proteins to CaM was higher when Ca2+ was absent from the overlay procedure, and this binding was negatively correlated to the fertilization rate. These results suggest that sperm capacitation is associated with a decrease in the binding of CaM to the 28, 30, and 49 kDa sperm CaM-binding proteins. Implications of such a decrease are discussed.


The post hoc use of randomised controlled trials to explore drug associated cancer outcomes: methodological challenges.
Drug-induced cancer risk is of increasing interest. Both observational studies and data from clinical trials have linked several widely used treatments to cancer. When a signal for a potential drug-cancer association is generated, substantiation is required to assess the impact on public health before proper regulatory action can be taken. This paper aims to discuss challenges of exploring drug-associated cancer outcomes by post-hoc analyses of Randomised controlled trials (RCTs) designed for other purposes. METHODOLOGICAL CHALLENGES TO CONSIDER: We set out to perform a post-hoc nested case-control analysis in the ADVANCE trial in order to examine the association between insulin use and cancer. We encountered several methodological challenges that made the results difficult to interpret, including short duration of exposure of interest, lack of power, and correlation between exposure and potential confounders. Considering these challenges, we concluded that using the data would not enlighten the discussion about insulin use and cancer risk and only serve to further complicate any understanding. Therefore, we decided to use our experience to illustrate methodological challenges, which need to be addressed when re-analysing trial data for cancer related outcomes. Substantial amount of information on cancer outcomes is available from RCTs. Hence, making use of such data could save time and spare patients from inclusion in further trials. However, methodological challenges must be addressed to enhance the likelihood of reliable conclusions. Advantages of post-hoc analyses of RCTs include quality of data collected and sometimes randomisation to exposure of interest. Limitations include confounding and sample size, which is fixed to suit the purposes of the trial, insufficient duration of exposure and identification of underlying biological mechanisms relating treatment to cancer to formulate the most appropriate post-hoc study design.


Metagenomic analysis of bacterial community composition in Dhanaan: Ethiopian traditional fermented camel milk.
This study was conducted to evaluate the safety and bacterial profile of Dhanaan (Ethiopian traditional fermented camel milk). The composition of the microbial community in Dhanaan samples was analysed by a metagenomic approach of 16S rRNA gene amplicon sequencing. Metagenomic profiling identified 87 different bacterial microorganisms (OTUs) in six samples analysed. Although the Dhanaan samples contained various lactic acid bacteria (LAB), they also all contained undesirable microorganisms in large proportions. The following LAB genera were identified: Streptococcus, Lactococcus and Weissella. One Streptococcus species represented by OTU-1 (operational taxonomic unit) was found in all Dhanaan samples and the dominating species in four out of six samples. This common isolate was found to be closely related to S. lutetiensis and S. infantarius. Undesirable microorganisms from genera such as Escherichia, Klebsiella, Enterobacter, Acinetobacter and Clostridium were, however, also frequent, or even dominant in Dhanaan samples. Thus, this calls for a change in the Dahnaan manufacturing practice to an improved and safer production system. Starter cultures suitable for Dhanaan production might be developed from the Streptococcus, Weissella and Lactococcus microorganisms identified in this study. However, further safety evaluation and technological characterization need to be conducted on strains defined by OTU-1, OTU-2, OTU-3, OTU-8 and OTU-35 before they can be used as food grade starter cultures.


An In Vitro Comparison of the Incorporation, Growth, and Chondrogenic Potential of Human Bone Marrow versus Adipose Tissue Mesenchymal Stem Cells in Clinically Relevant Cell Scaffolds Used for Cartilage Repair.
To compare the incorporation, growth, and chondrogenic potential of bone marrow (BM) and adipose tissue (AT) mesenchymal stem cells (MSCs) in scaffolds used for cartilage repair. Human BM and AT MSCs were isolated, culture expanded, and characterised using standard protocols, then seeded into 2 different scaffolds, Chondro-Gide or Alpha Chondro Shield. Cell adhesion, incorporation, and viable cell growth were assessed microscopically and following calcein AM/ethidium homodimer (Live/Dead) staining. Cell-seeded scaffolds were treated with chondrogenic inducers for 28 days. Extracellular matrix deposition and soluble glycosaminoglycan (GAG) release into the culture medium was measured at day 28 by histology/immunohistochemistry and dimethylmethylene blue assay, respectively. A greater number of viable MSCs from either source adhered and incorporated into Chondro-Gide than into Alpha Chondro Shield. In both cell scaffolds, this incorporation represented less than 2% of the cells that were seeded. There was a marked proliferation of BM MSCs, but not AT MSCs, in Chondro-Gide. MSCs from both sources underwent chondrogenic differentiation following induction. However, cartilaginous extracellular matrix deposition was most marked in Chondro-Gide seeded with BM MSCs. Soluble GAG secretion increased in chondrogenic versus control conditions. There was no marked difference in GAG secretion by MSCs from either cell source. Chondro-Gide and Alpha Chondro Shield were permissive to the incorporation and chondrogenic differentiation of human BM and AT MSCs. Chondro-Gide seeded with BM MSCs demonstrated the greatest increase in MSC number and deposition of a cartilaginous tissue.


Anaerobic vs aerobic pathways of carbonyl and oxidant stress in human lens and skin during aging and in diabetes: A comparative analysis.
The effects of anaerobic (lens) vs aerobic (skin) environment on carbonyl and oxidant stress are compared using de novo and existing data on advanced glycation and oxidation products in human crystallins and collagen. Almost all modifications increase with age. Methylglyoxal hydroimidazolones, carboxymethyllysine, and carboxyethyllysine are severalfold higher in lens than in skin and markedly increase upon incubation of lens crystallins with 5mM ascorbic acid. In contrast, fructose-lysine, glucosepane crosslinks, glyoxal hydroimidazolones, metal-catalyzed oxidation (allysine), and H(2)O(2)-dependent modifications (2-aminoapidic acid and methionine sulfoxide) are markedly elevated in skin, but relatively suppressed in the aging lens. In both tissues ornithine is the dominant modification, implicating arginine residues as the principal target of the Maillard reaction in vivo. Diabetes (here mostly type 2 studied) increases significantly fructose-lysine and glucosepane in both tissues (P<0.001) but has surprisingly little effect on the absolute level of most other advanced glycation end products. However, diabetes strengthens the Spearman correlation coefficients for age-related accumulation of hydrogen peroxide-mediated modifications in the lens. Overall, the data suggest that oxoaldehyde stress involving methylglyoxal from either glucose or ascorbate is predominant in the aging noncataractous lens, whereas aging skin collagen undergoes combined attack by nonoxidative glucose-mediated modifications, as well as those from metal-catalyzed oxidation and H(2)O(2).


The BCI Competition 2003: progress and perspectives in detection and discrimination of EEG single trials.
Interest in developing a new method of man-to-machine communication--a brain-computer interface (BCI)--has grown steadily over the past few decades. BCIs create a new communication channel between the brain and an output device by bypassing conventional motor output pathways of nerves and muscles. These systems use signals recorded from the scalp, the surface of the cortex, or from inside the brain to enable users to control a variety of applications including simple word-processing software and orthotics. BCI technology could therefore provide a new communication and control option for individuals who cannot otherwise express their wishes to the outside world. Signal processing and classification methods are essential tools in the development of improved BCI technology. We organized the BCI Competition 2003 to evaluate the current state of the art of these tools. Four laboratories well versed in EEG-based BCI research provided six data sets in a documented format. We made these data sets (i.e., labeled training sets and unlabeled test sets) and their descriptions available on the Internet. The goal in the competition was to maximize the performance measure for the test labels. Researchers worldwide tested their algorithms and competed for the best classification results. This paper describes the six data sets and the results and function of the most successful algorithms.


Functional and comparative bioinformatic analysis of expressed genes from wheat spikes infected with Fusarium graminearum.
Fusarium head blight, caused by the fungus Fusarium graminearum, is a major disease on wheat (Triticum aestivum L.). Expressed sequence tags (ESTs) were used to identify genes expressed during the wheat-F. graminearum interaction. We generated 4,838 ESTs from a cDNA library prepared from spikes of the partially resistant cultivar Sumai 3 infected with F. graminearum. These ESTs were composed of 2,831 singlet (single-copy transcripts) and 715 contigs (multiple-copy transcripts) for a total of 3,546 non-redundant sequences. Four sets of nonredundant sequences were identified. One set contains numerous, common biotic and abiotic stress-related genes. Many of these stress-related genes were represented by multiple ESTs, indicating that they are abundantly expressed. A second set comprised 16 nonredundant sequences from F. graminearum that may be required for pathogenicity. A subset of these fungal genes encodes proteins associated with plant cell wall degradation. A third set of 326 nonredundant sequences had no DNA or amino acid sequence similarity to almost 1 million plant and over 7 million animal sequences in dbEST (as of 22 June 2001). Thus, these 326 nonredundant sequences have only been found in our F. graminearum-infected 'Sumai 3' cDNA library. A fourth set of 29 nonredundant sequences was found in our F. graminearum-infected wheat and another plant-pathogen interaction cDNA library. Some of these sequences encode proteins that may act in establishing various plant-fungal interactions.


The role of authority power in explaining procedural fairness effects.
Building on fairness heuristic theory, fairness theory, and trust development models, we argue that unfairly enacted procedures decrease followers' trust in the authority particularly when authorities have high power over their followers. Moreover, we expected trust to mediate procedural fairness effects on followers' attitudes (authorities' legitimacy and charisma attributed to authorities) and organizational citizenship behavior. Procedural fairness effects on these variables, as mediated by trust, should therefore also be stronger when authority power is high. The results of a single- and multisource field study and a laboratory experiment supported these predictions. These studies support the role of authority power as a theoretically and practically relevant moderator of procedural fairness effects and show that its effectiveness is explained through trust in authorities.


Susceptibility vessel sign on T2* magnetic resonance imaging and recanalization results of mechanical thrombectomy with stent retrievers: a multicentre cohort study.
The susceptibility vessel sign (SVS) on T2*-weighted magnetic resonance imaging has been reported in several studies as a negative predictor of early recanalization after intravenous thrombolysis. The meaning of SVS regarding the results of mechanical thrombectomy with stent retrievers was investigated. Susceptibility vessel sign presence and length were studied in 153 acute ischaemic stroke patients (82 men; mean ± SD age 59 ± 17 years, baseline National Institutes of Health Stroke Scale score 17.2 ± 6.5) from three stroke centres, treated with either mechanical thrombectomy alone (n = 84) or bridging therapy (n = 69). Variables were compared between recanalizers, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b, and non-recanalizers (TICI<2b). The SVS was present in 113 (73.8%) patients. There was no association between the presence of SVS and recanalization, obtained in 86 (56.2%) patients, in the whole population [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.53-2.92, P = 0.84) and in treatment subgroups (bridging: OR = 0.91, 95% CI 0.29-2.87, P = 1.0; thrombectomy alone: OR = 1.85, 95% CI 0.48-7.16, P = 0.54). However, in SVS+ patients, recanalization decreased with SVS length (OR 0.94 for each additional mm, 95% CI 0.89-0.99; P = 0.02). The success of recanalization in acute stroke patients treated with stent retrievers was related to thrombus length but not to the presence of SVS.


Corporations' use and misuse of evidence to influence health policy: a case study of sugar-sweetened beverage taxation.
Sugar sweetened beverages (SSB) are a major source of sugar in the diet. Although trends in consumption vary across regions, in many countries, particularly LMICs, their consumption continues to increase. In response, a growing number of governments have introduced a tax on SSBs. SSB manufacturers have opposed such taxes, disputing the role that SSBs play in diet-related diseases and the effectiveness of SSB taxation, and alleging major economic impacts. Given the importance of evidence to effective regulation of products harmful to human health, we scrutinised industry submissions to the South African government's consultation on a proposed SSB tax and examined their use of evidence. Corporate submissions were underpinned by several strategies involving the misrepresentation of evidence. First, references were used in a misleading way, providing false support for key claims. Second, raw data, which represented a pliable, alternative evidence base to peer reviewed studies, was misused to dispute both the premise of targeting sugar for special attention and the impact of SSB taxes on SSB consumption. Third, purposively selected evidence was used in conjunction with other techniques, such as selective quoting from studies and omitting important qualifying information, to promote an alternative evidential narrative to that supported by the weight of peer-reviewed research. Fourth, a range of mutually enforcing techniques that inflated the effects of SSB taxation on jobs, public revenue generation, and gross domestic product, was used to exaggerate the economic impact of the tax. This "hyperbolic accounting" included rounding up figures in original sources, double counting, and skipping steps in economic modelling. Our research raises fundamental questions concerning the bona fides of industry information in the context of government efforts to combat diet-related diseases. The beverage industry's claims against SSB taxation rest on a complex interplay of techniques, that appear to be grounded in evidence, but which do not observe widely accepted approaches to the use of either scientific or economic evidence. These techniques are similar, but not identical, to those used by tobacco companies and highlight the problems of introducing evidence-based policies aimed at managing the market environment for unhealthful commodities.


Evaluation of traditional instruction versus a self-learning computer module in teaching veterinary students how to pass a nasogastric tube in the horse.
To evaluate the effectiveness of a self-learning computer module (SLCM) versus traditional instruction in teaching how to pass a nasogastric tube (NG) in the horse. A double-blind, monocentric study. 52 third-year students in the DVM program were randomly assigned to two groups: traditional instruction (N = 25) or SLCM instruction (N = 27). Traditional instruction consisted of an instructor and live demonstration; SCLM students were given a CD-ROM each. Both sessions lasted one hour. The students were then united in one session to practice passing the NG tube. Their performance was videotaped and evaluated by two evaluators. Students were then given a multiple-choice knowledge quiz. One week later, a second demonstration of the same procedure by the two methods was administered, and students were allowed to choose either method of instruction. A Likert-scale questionnaire about their comfort, their confidence, and the appropriateness of the teaching method was given after the second demonstration. Data were analyzed by non-parametric tests. A focus-group study was conducted to determine students' perception of each teaching method. Nine participants in the experiment volunteered for these focus-group sessions. The sessions were audiotaped and transcribed. Students in the SLCM group performed significantly better on the test of knowledge than traditionally instructed students. The questionnaire found significant perceived benefits to computer-based instruction, including a preference for the computer-based module, better learning, and greater preparedness. In hands-on skill, time to pass the NG tube on the successful attempt was significantly shorter in the SLCM group than in the traditionally instructed group. The data from focus-group sessions suggest that while participants expressed satisfaction with both modes of instruction, the SLCM group reported somewhat higher levels of confidence in their skills prior to performing the procedure. Whereas the traditional group reported a strong preference for continued live demonstrations of the procedure, the SLCM group stated that the computer-assisted module alone provided them with effective instruction. Computer-assisted learning is an acceptable and effective method of training students to pass an NG tube with potential welfare, proficiency, and knowledge advantages.


Multiscale modeling of keratin, collagen, elastin and related human diseases: Perspectives from atomistic to coarse-grained molecular dynamics simulations.
Scleroproteins are an important category of proteins within the human body that adopt filamentous, elongated conformations in contrast with typical globular proteins. These include keratin, collagen, and elastin, which often serve a common mechanical function in structural support of cells and tissues. Genetic mutations alter these proteins, disrupting their functions and causing diseases. Computational characterization of these mutations has proven to be extremely valuable in identifying the intricate structure-function relationships of scleroproteins from the molecular scale up, especially if combined with multiscale experimental analysis and the synthesis of model proteins to test specific structure-function relationships. In this work, we review numerous critical diseases that are related to keratin, collagen, and elastin, and through several case studies, we propose ways of extensively utilizing multiscale modeling, from atomistic to coarse-grained molecular dynamics simulations, to uncover the molecular origins for some of these diseases and to aid in the development of novel cures and therapies. As case studies, we examine the effects of the genetic disease Epidermolytic Hyperkeratosis (EHK) on the structure and aggregation of keratins 1 and 10; we propose models to understand the diseases of Osteogenesis Imperfecta (OI) and Alport syndrome (AS) that affect the mechanical and aggregation properties of collagen; and we develop atomistic molecular dynamics and elastic network models of elastin to determine the role of mutations in diseases such as Cutis Laxa and Supravalvular Aortic Stenosis on elastin's structure and molecular conformational motions and implications for assembly.


Pay-for-performance as a cost-effective implementation strategy: results from a cluster randomized trial.
Pay-for-performance (P4P) has been recommended as a promising strategy to improve implementation of high-quality care. This study examined the incremental cost-effectiveness of a P4P strategy found to be highly effective in improving the implementation and effectiveness of the Adolescent Community Reinforcement Approach (A-CRA), an evidence-based treatment (EBT) for adolescent substance use disorders (SUDs). Building on a $30 million national initiative to implement A-CRA in SUD treatment settings, urn randomization was used to assign 29 organizations and their 105 therapists and 1173 patients to one of two conditions (implementation-as-usual (IAU) control condition or IAU+P4P experimental condition). It was not possible to blind organizations, therapists, or all research staff to condition assignment. All treatment organizations and their therapists received a multifaceted implementation strategy. In addition to those IAU strategies, therapists in the IAU+P4P condition received US $50 for each month that they demonstrated competence in treatment delivery (A-CRA competence) and US $200 for each patient who received a specified number of treatment procedures and sessions found to be associated with significantly improved patient outcomes (target A-CRA). Incremental cost-effectiveness ratios (ICERs), which represent the difference between the two conditions in average cost per treatment organization divided by the corresponding average difference in effectiveness per organization, and quality-adjusted life years (QALYs) were the primary outcomes. At trial completion, 15 organizations were randomized to the IAU condition and 14 organizations were randomized to the IAU+P4P condition. Data from all 29 organizations were analyzed. Cluster-level analyses suggested the P4P strategy led to significantly higher average total costs compared to the IAU control condition, yet this average increase of 5% resulted in a 116% increase in the average number of months therapists demonstrated competence in treatment delivery (ICER = $333), a 325% increase in the average number of patients who received the targeted dosage of treatment (ICER = $453), and a 325% increase in the number of days of abstinence per patient in treatment (ICER = $8.134). Further supporting P4P as a cost-effective implementation strategy, the cost per QALY was only $8681 (95% confidence interval $1191-$16,171). This study provides experimental evidence supporting P4P as a cost-effective implementation strategy. NCT01016704 .


Investigation of the Antioxidant and Hepatoprotective Potential of Hypericum mysorense.
Hypericum is a well-known plant genus in herbal medicine. Hypericum mysorense (Family: Hypericaceae), a plant belonging to the same genus, is well known in folklore medicine for its varied therapeutic potential. The aim of the present study was to investigate the different parts of the plant for antioxidant and hepatoprotective properties. The methanol extracts of Hypericum mysorense prepared from various parts of the plant were tested in vitro for their free radical scavenging activity against ABTS(•) (diammonium salt), DPPH(•) (1,1-diphenyl-2-picrylhydrazyl), NO(•), O₂(•-) and (•)OH radicals, using standard systems of assays. The total antioxidant capacity, total phenolic and total flavonoid content of the extracts were analyzed. Further, the leaf and flowering top extracts were tested for their in vivo antioxidant and hepatoprotective activities on Wistar rats using a carbon tetrachloride-induced hepatic injury model. The leaf and flowering top extract showed potent antioxidant activity and also possessed highest total phenolic and flavonoid content. The antioxidant activity and the total phenolic and flavonoid content present in these extracts showed a good correlation. The leaf and flowering top extracts at 200 mg/kg restored aspartate amino transferase (ASAT), alanine amino transferase (ALAT), alkaline phosphatase (ALP), total bilirubin and protein levels significantly in CCl₄-intoxicated rats. The tested extracts also showed a significant (p < 0.001) reduction in 2-thiobarbituric acid reactive substance (TBARS) levels with an increase in SOD and CAT levels. The histopathology of liver did not show any toxicity after the treatment with the extracts. The active extracts were standardized using two marker compounds, hyperoside and rutin, which were isolated from the plant by HPLC. HPLC studies revealed that the maximum concentration of hyperoside and rutin is present in the flowering top extract.


Synergies of Systems Biology and Synthetic Biology in Human Microbiome Studies.
A number of studies have shown that the microbial communities of the human body are integral for the maintenance of human health. Advances in next-generation sequencing have enabled rapid and large-scale quantification of the composition of microbial communities in health and disease. Microorganisms mediate diverse host responses including metabolic pathways and immune responses. Using a system biology approach to further understand the underlying alterations of the microbiota in physiological and pathological states can help reveal potential novel therapeutic and diagnostic interventions within the field of synthetic biology. Tools such as biosensors, memory arrays, and engineered bacteria can rewire the microbiome environment. In this article, we review the computational tools used to study microbiome communities and the current limitations of these methods. We evaluate how genome-scale metabolic models (GEMs) can advance our understanding of the microbe-microbe and microbe-host interactions. Moreover, we present how synergies between these system biology approaches and synthetic biology can be harnessed in human microbiome studies to improve future therapeutics and diagnostics and highlight important knowledge gaps for future research in these rapidly evolving fields.


Problem-solving skills and perceived stress among undergraduate students: The moderating role of hardiness.
This study was designed to examine the relationships between problem-solving skills, hardiness, and perceived stress and to test the moderating role of hardiness in the relationship between problem-solving skills and perceived stress among 500 undergraduates from Malaysian public universities. The analyses showed that undergraduates with poor problem-solving confidence, external personal control of emotion, and approach-avoidance style were more likely to report perceived stress. Hardiness moderated the relationships between problem-solving skills and perceived stress. These findings reinforce the importance of moderating role of hardiness as an influencing factor that explains how problem-solving skills affect perceived stress among undergraduates.


Stop the Noise: A Quality Improvement Project to Decrease Electrocardiographic Nuisance Alarms.
As many as 99% of alarm signals may not need any intervention and can result in patients' deaths. Alarm management is now a Joint Commission National Patient Safety Goal. To reduce the number of nuisance electrocardiographic alarm signals in adult patients on the medical cardiovascular care unit. A quality improvement process was used that included eliminating duplicative alarms, customizing alarms, changing electrocardiography electrodes daily, standardizing skin preparation, and using disposable electrocardiography leads. In the cardiovascular care unit, the mean number of electrocardiographic alarm signals per day decreased from 28.5 (baseline) to 3.29, an 88.5% reduction. Use of a bundled approach to managing alarm signals decreased the mean number of alarm signals in a cardiovascular care unit.


A Cutinase from Trichoderma reesei with a lid-covered active site and kinetic properties of true lipases.
Cutinases belong to the α/β-hydrolase fold family of enzymes and degrade cutin and various esters, including triglycerides, phospholipids and galactolipids. Cutinases are able to degrade aggregated and soluble substrates because, in contrast with true lipases, they do not have a lid covering their catalytic machinery. We report here the structure of a cutinase from the fungus Trichoderma reesei (Tr) in native and inhibitor-bound conformations, along with its enzymatic characterization. A rare characteristic of Tr cutinase is its optimal activity at acidic pH. Furthermore, Tr cutinase, in contrast with classical cutinases, possesses a lid covering its active site and requires the presence of detergents for activity. In addition to the presence of the lid, the core of the Tr enzyme is very similar to other cutinase cores, with a central five-stranded β-sheet covered by helices on either side. The catalytic residues form a catalytic triad involving Ser164, His229 and Asp216 that is covered by the two N-terminal helices, which form the lid. This lid opens in the presence of surfactants, such as β-octylglucoside, and uncovers the catalytic crevice, allowing a C11Y4 phosphonate inhibitor to bind to the catalytic serine. Taken together, these results reveal Tr cutinase to be a member of a new group of lipolytic enzymes resembling cutinases but with kinetic and structural features of true lipases and a heightened specificity for long-chain triglycerides.


Performance of the RAD-57 pulse CO-oximeter compared with standard laboratory carboxyhemoglobin measurement.
We assess agreement between carboxyhemoglobin levels measured by the Rad-57 signal extraction pulse CO-oximeter (RAD), a Food and Drug Administration-approved device for noninvasive bedside measurement, and standard laboratory arterial or venous measurement in a sample of emergency department (ED) patients with suspected carbon monoxide poisoning. The study was a cross-sectional cohort design using a convenience sample of adult and pediatric ED patients in a Level I trauma, burn, and hyperbaric oxygen referral center. Measurement of RAD carboxyhemoglobin was performed simultaneously with blood sampling for laboratory determination of carboxyhemoglobin level. The difference between the measures for each patient was calculated as laboratory carboxyhemoglobin minus carboxyhemoglobin from the carbon monoxide oximeter. The limits of agreement from a Bland-Altman analysis are calculated as the mean of the differences between methods ±1.96 SDs above and below the mean. Median laboratory percentage carboxyhemoglobin level was 2.3% (interquartile range 1 to 8.5; range 0% to 38%). The mean difference between laboratory carboxyhemoglobin values and RAD values was 1.4% carboxyhemoglobin (95% confidence interval [CI] 0.2% to 2.6%). The limits of agreement of differences of measurement made with the 2 devices were -11.6% and 14.4% carboxyhemoglobin. This range exceeded the value of ±5% carboxyhemoglobin defined a priori as clinically acceptable. RAD correctly identified 11 of 23 patients with laboratory values greater than 15% carboxyhemoglobin (sensitivity 48%; 95% CI 27% to 69%). There was one case of a laboratory carboxyhemoglobin level less than 15%, in which the RAD device gave a result greater than 15% (specificity of RAD 96/97=99%; 95% CI 94% to 100%). In the range of carboxyhemoglobin values measured in this sample, the level of agreement observed suggests RAD measurement may not be used interchangeably with standard laboratory measurement.


HLA variation and disease.
Fifty years since the first description of an association between HLA and human disease, HLA molecules have proven to be central to physiology, protective immunity and deleterious, disease-causing autoimmune reactivity. Technological advances have enabled pivotal progress in the determination of the molecular mechanisms that underpin the association between HLA genetics and functional outcome. Here, we review our current understanding of HLA molecules as the fundamental platform for immune surveillance and responsiveness in health and disease. We evaluate the scope for personalized antigen-specific disease prevention, whereby harnessing HLA-ligand interactions for clinical benefit is becoming a realistic prospect.


Asymmetric generalization in adaptation to target displacement errors in humans and in a neural network model.
Different error signals can induce sensorimotor adaptation during visually guided reaching, possibly evoking different neural adaptation mechanisms. Here we investigate reach adaptation induced by visual target errors without perturbing the actual or sensed hand position. We analyzed the spatial generalization of adaptation to target error to compare it with other known generalization patterns and simulated our results with a neural network model trained to minimize target error independent of prediction errors. Subjects reached to different peripheral visual targets and had to adapt to a sudden fixed-amplitude displacement ("jump") consistently occurring for only one of the reach targets. Subjects simultaneously had to perform contralateral unperturbed saccades, which rendered the reach target jump unnoticeable. As a result, subjects adapted by gradually decreasing reach errors and showed negative aftereffects for the perturbed reach target. Reach errors generalized to unperturbed targets according to a translational rather than rotational generalization pattern, but locally, not globally. More importantly, reach errors generalized asymmetrically with a skewed generalization function in the direction of the target jump. Our neural network model reproduced the skewed generalization after adaptation to target jump without having been explicitly trained to produce a specific generalization pattern. Our combined psychophysical and simulation results suggest that target jump adaptation in reaching can be explained by gradual updating of spatial motor goal representations in sensorimotor association networks, independent of learning induced by a prediction-error about the hand position. The simulations make testable predictions about the underlying changes in the tuning of sensorimotor neurons during target jump adaptation.


New mothers and media use: associations between blogging, social networking, and maternal well-being.
Drawing on Bronfenbrenner's ecological theory and prior empirical research, the current study examines the way that blogging and social networking may impact feelings of connection and social support, which in turn could impact maternal well-being (e.g., marital functioning, parenting stress, and depression). One hundred and fifty-seven new mothers reported on their media use and various well-being variables. On average, mothers were 27 years old (SD = 5.15) and infants were 7.90 months old (SD = 5.21). All mothers had access to the Internet in their home. New mothers spent approximately 3 hours on the computer each day, with most of this time spent on the Internet. Findings suggested that frequency of blogging predicted feelings of connection to extended family and friends which then predicted perceptions of social support. This in turn predicted maternal well-being, as measured by marital satisfaction, couple conflict, parenting stress, and depression. In sum, blogging may improve new mothers' well-being, as they feel more connected to the world outside their home through the Internet.


Genetics of color polymorphism in the pea aphid, Acyrthosiphon pisum.
The genetic basis of color polymorphism is explored in the pea aphid, Acyrthosiphon pisum (Harris) (Homoptera: Sternorrhyncha), in which two color morphs have been described (pink or green). Laboratory crosses and a Mendelian genetic analysis reveal that color polymorphism in pea aphids is determined by a single biallelic locus, which we name colorama, with alleles P and p, pink being dominant to green. The putative genotypes are Pp or PP for pink morphs, and pp for green morphs. This locus is shown to be autosomal. Last, there was no evidence of influence of the direction of the cross on color inheritance, thus showing that cytoplasmic effects and/or maternally-inherited symbionts play no role in the inheritance of color polymorphism in pea aphids. The existence of a simple genetic determinism for color polymorphism in a system in which genetic investigation is possible may facilitate investigations on the physiological and molecular mechanisms of genetically-based color morph variation, and the establishment of a link between this locus and fitness in a range of ecological conditions.


Wernicke's area homologue in chimpanzees (Pan troglodytes) and its relation to the appearance of modern human language.
Human language is distinctive compared with the communication systems of other species. Yet, several questions concerning its emergence and evolution remain unresolved. As a means of evaluating the neuroanatomical changes relevant to language that accompanied divergence from the last common ancestor of chimpanzees, bonobos and humans, we defined the cytoarchitectonic boundaries of area Tpt, a component of Wernicke's area, in 12 common chimpanzee brains and used design-based stereologic methods to estimate regional volumes, total neuron number and neuron density. In addition, we created a probabilistic map of the location of area Tpt in a template chimpanzee brain coordinate space. Our results show that chimpanzees display significant population-level leftward asymmetry of area Tpt in terms of neuron number, with volume asymmetry approaching significance. Furthermore, asymmetry in the number of neurons in area Tpt was positively correlated with asymmetry of neuron numbers in Brodmann's area 45, a component of Broca's frontal language region. Our findings support the conclusion that leftward asymmetry of Wernicke's area originated prior to the appearance of modern human language and before our divergence from the last common ancestor. Moreover, this study provides the first evidence of covariance between asymmetry of anterior and posterior cortical regions that in humans are important to language and other higher order cognitive functions.


A novel role for the Wnt inhibitor APCDD1 in adipocyte differentiation: Implications for diet-induced obesity.
Impaired adipogenic differentiation during diet-induced obesity (DIO) promotes adipocyte hypertrophy and inflammation, thereby contributing to metabolic disease. Adenomatosis polyposis coli down-regulated 1 (APCDD1) has recently been identified as an inhibitor of Wnt signaling, a key regulator of adipogenic differentiation. Here we report a novel role for APCDD1 in adipogenic differentiation via repression of Wnt signaling and an epigenetic linkage between miR-130 and APCDD1 in DIO. APCDD1 expression was significantly up-regulated in mature adipocytes compared with undifferentiated preadipocytes in both human and mouse subcutaneous adipose tissues. siRNA-based silencing of APCDD1 in 3T3-L1 preadipocytes markedly increased the expression of Wnt signaling proteins (Wnt3a, Wnt5a, Wnt10b, LRP5, and β-catenin) and inhibited the expression of adipocyte differentiation markers (CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ)) and lipid droplet accumulation, whereas adenovirus-mediated overexpression of APCDD1 enhanced adipogenic differentiation. Notably, DIO mice exhibited reduced APCDD1 expression and increased Wnt expression in both subcutaneous and visceral adipose tissues and impaired adipogenic differentiation in vitro Mechanistically, we found that miR-130, whose expression is up-regulated in adipose tissues of DIO mice, could directly target the 3'-untranslated region of the APCDD1 gene. Furthermore, transfection of an miR-130 inhibitor in preadipocytes enhanced, whereas an miR-130 mimic blunted, adipogenic differentiation, suggesting that miR-130 contributes to impaired adipogenic differentiation during DIO by repressing APCDD1 expression. Finally, human subcutaneous adipose tissues isolated from obese individuals exhibited reduced expression of APCDD1, C/EBPα, and PPARγ compared with those from non-obese subjects. Taken together, these novel findings suggest that APCDD1 positively regulates adipogenic differentiation and that its down-regulation by miR-130 during DIO may contribute to impaired adipogenic differentiation and obesity-related metabolic disease.


Role of folylpolyglutamates in biochemical modulation of fluoropyrimidines by leucovorin.
The growth-inhibitory effect of fluoropyrimidines combined with a short-term exposure to leucovorin and the pattern of polyglutamylation of folates were compared between parental CCRF-CEM cells and a cell line with impaired ability to form polyglutamates (CCRF-CEM/P). The combination of leucovorin with 5-fluorouracil or 5-fluorodeoxyuridine increased the growth inhibition of CCRF-CEM cells compared to the fluoropyrimidine alone in the parent cell line but not in CCRF-CEM/P cells. In addition, leucovorin produced a significant increase in the inhibition of intracellular thymidylate synthase activity caused by 5-fluorouracil or 5-fluorodeoxyuridine as compared to these drugs alone in CCRF-CEM cells, but no increase in inhibition over that produced by the single drugs alone was observed in CCRF-CEM/P cells. Although levels of 5,10-methylene tetrahydrofolate after leucovorin administration were similar in both cell lines, polyglutamylation of this coenzyme was decreased in the CCRF-CEM/P cell line. The inability of CCRF-CEM/P cells to form significant levels of polyglutamates of N5,N10-methylenete-trahydrofolate, may be responsible for the lack of enhanced cell kill observed when a short exposure to leucovorin is used with fluoropyrimidines.


Preliminary Results of Recent Deep Drilling on Cape Cod, Massachusetts.
In 1961 a 1000-foot drill hole near Harwich on Cape Cod, Massachusetts, penetrated 435 feet of Pleistocene deposits above 50 to 60 feet of crystalline limestone and phyllitic schist, and more than 500 feet of phyllitic schist with abundant quartz veins. Similar rock is known in the Pennsylvanian and Precambrian (?) sections of Massachusetts and Rhode Island. Material of Eocene age was found in earlier drilling near Provincetown, but none was identified from this hole.


Gastrin-releasing peptide mediates photic entrainable signals to dorsal subsets of suprachiasmatic nucleus via induction of Period gene in mice.
The suprachiasmatic nucleus (SCN), locus of the central circadian clock, consists of two neuronal populations (i.e., a light-recipient ventral SCN subpopulation directly entrained by light and a dorsal SCN subpopulation with an autonomous oscillatory function possessing an indirect or weak light response). However, the mechanism underlying the transmission of photic signals from the ventral to dorsal SCN remains unclear. Because gastrin-releasing peptide (GRP), expressed mainly in the ventral SCN, exerts phase-shifting actions, loss of the GRP receptor intuitively implies a reduction of photic information from the ventral to dorsal SCN. Therefore, using GRP receptor-deficient mice, we examined the involvement of GRP and the GRP receptor in light- and GRP-induced entrainment by the assessment of behavioral rhythm and induction of mousePeriod (mPer) gene in the SCN, which is believed to be a critical for photic entrainment. Administration of GRP during nighttime dose dependently produced a phase delay of behavior in wild-type but not GRP receptor-deficient mice. This phase-shift by GRP was closely associated with induction of mPer1 and mPer2 mRNA as well as c-Fos protein in the dorsal portion of the SCN, where the GRP receptor was also expressed abundantly. Both the light-induced phase shift in behavior and the induction of mPer mRNA and c-Fos protein in the dorsal SCN were attenuated in GRP receptor-deficient mice. Our present studies suggest that GRP neurons in the retinorecipient ventral area of the SCN convey the photic entrainable signals from the ventral SCN to the dorsal SCN via induction of the mPer gene.


The invasive phenotype of Shigella flexneri directs a distinct gene expression pattern in the human intestinal epithelial cell line Caco-2.
Invasion of the human colonic epithelium by Shigella flexneri causes inflammation that disrupts the intestinal barrier. Invaded intestinal epithelial cells are the major source of mediators recruiting the inflammatory infiltrate. To better characterize the global response of intestinal epithelial cells to Shigella invasion, Caco-2 cells were infected by an invasive isolate of S. flexneri 5a, and their transcriptome was analyzed by Affymetrix (Santa Clara, CA) microarrays (12,000 genes) and compared with these elicited by a non-invasive Shigella mutant and tumor necrosis factor (TNF)-alpha. The invasive and non-invasive strains enhanced transcription of a common pattern of 240 genes, among which genes encoding isoforms of cytochrome P-450 were induced. These genes were not induced by TNF-alpha. Conversely, both the invasive strain and TNF-alpha induced a common set of 18 genes, mainly encoding proinflammatory molecules. They also induced specific sets of genes. The transcriptome induced by the invasive strain was characterized by the induction of early genes (i.e. expressed within the first 45 min of invasion) and late genes (i.e. after 60 min of invasion) whose pattern was strongly biased toward stimulation of granulopoiesis, chemoattraction, activation, and adherence of polymorphonuclear leukocytes. When compared with a non-invasive Shigella and TNF-alpha, invasive Shigella induced a narrow transcriptome that seems to program infected epithelial cells to recruit a mucosal polymorphonuclear leukocyte to infiltrate. Dramatic increase in IL-8 gene transcription points to this chemokine as the major molecule orchestrating mucosal inflammation in shigellosis.


Effects of central and peripheral administration of leptin on pain threshold in rats and mice.
This study was planned to investigate the effects of exogenous leptin on the pain threshold. Adult male Wistar rats weighing 250-300 g and mice weighing 25-30 g were used in this study. Leptin was intracerebroventricularly (i. c. v.) injected in a dose of 3.5 micro g/rat. Mice were intraperitoneally (i. p.) injected with leptin in a dose of 25 micro g/mouse. Control animals were injected with the respective vehicle. The pain threshold test was performed using hot plate analgesia meter. The experiments were performed during the day and at night. The data were statistically analysed by Mann-Whitney U test. Level of significance was set at p<0.05. During the day, there were no significant changes in hot plate latencies half an hour after i.c.v. injection of vehicle or leptin in the control and leptin-treated rats, respectively. At night, like during the day, i.c.v. injection of neither vehicle nor leptin caused any significant change in pain sensitivity. In mice, i.p. injection of leptin decreased latencies significantly (p<0.05) during the day and at night. Thus, leptin caused an increase in pain sensitivity during the day and at night. These results clearly demonstrated that leptin has a decreasing-effect on pain threshold if it is peripherally administered in mice.


Interactive effects of iron and zinc on biochemical and functional outcomes in supplementation trials.
Iron and zinc are essential micronutrients for human health. Deficiencies in these 2 nutrients remain a global problem, especially among women and children in developing countries. Supplementation with iron and zinc as single micronutrients enhances distinct and unique biochemical and functional outcomes. These micronutrients have the potential to interact when given together; thus, it is important to assess the biochemical and functional evidence from clinical trials before supplementation policies are established. We reviewed randomized trials that assessed the effects of iron and zinc supplementation on iron and zinc status. On the basis of this review, zinc supplementation alone does not appear to have a clinically important negative effect on iron status. However, when zinc is given with iron, iron indicators do not improve as greatly as when iron is given alone. In most of the studies, iron supplementation did not affect the biochemical status of zinc, but the data are not clear regarding morbidity outcomes. Although some trials have shown that joint iron and zinc supplementation has less of an effect on biochemical or functional outcomes than does supplementation with either mineral alone, there is no strong evidence to discourage joint supplementation. Supplementation programs that provide iron and zinc together are an efficient way to provide both micronutrients, provided the benefits of individual supplementation are not lost. Further research is needed before health policies on joint supplementation programs can be established.


Long-term stability and temporal trends of organic contaminants in four collections of mussel tissue frozen standard reference materials.
The stability of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and chlorinated pesticides in frozen mussel tissue Standard Reference Materials (SRMs) stored at -80 °C was assessed by analyzing samples of SRM 1974, SRM 1974a, and SRM 1974b Organics in Mussel Tissue (Mytilus edulis) periodically over 25 y, 20 y, and 12 y, respectively. The most recent analyses were performed during the certification of the fourth release of this material, SRM 1974c. Results indicate the concentrations of these persistent organic pollutants have not changed during storage at -80 °C. In addition, brominated diphenyl ethers (BDEs) were quantified in each of the materials during this study. The stability information is important for on-going monitoring studies collecting large quantities of samples for future analyses (i.e., formally established specimen banking programs). Since all four mussel tissue SRMs were prepared from mussels collected at the same site in Dorchester Bay, MA, USA, the results provide a temporal trend study for these contaminants over a 17 year period (1987 to 2004).


Refining the evaluation of operating room performance.
An accurate and consistent evaluation of resident operative performance is necessary but difficult to achieve. This study continues the examination of the Southern Illinois University (SIU) operative performance rating system (OPRS) by studying additional factors that may influence reliability, accuracy, and interpretability of results. OPRS evaluations of surgical residents by faculty at SIU, from 2001 to 2008, were analyzed for the most frequently rated procedures to determine (1) the elapsed time from the procedure until completion of rating, (2) the patterns in responses of procedure-specific and global surgical skills items, and (3) whether particular evaluating surgeons differed in their stringency of ratings of resident operative performance. In all, 566 evaluations were analyzed, which consisted of open colectomy (n = 125), open inguinal hernia (n = 103), laparoscopic cholecystectomy (n = 199), and excisional biopsy (n = 139). The number of residents evaluated per training level (PGY) ranged from 88 to 161. The median time to completion of evaluations was 11 days, 9 hours. The quickest evaluation was 18 hours after assignment. Most were completed within 4.5 to 22 days. Procedure-specific and global scale scores resulted in similar rank-ordering of performances (single-measure intraclass correlation using the consistency model = 0.88; 95% confidence interval [CI] = 0.87-0.90) and similar absolute OPRS scores (single-measure intraclass correlation using the consistency model = 0.89; 95% CI, 0.87-0.90). Evaluating surgeons differed in stringency of ratings across procedures (average difference = 1.4 points of 5 possible points). Resident performance improved with increasing PGY level for all 4 procedures. Substantial time elapses between performance in the operating room and the completion of the evaluation. This raises the question of whether surgeons remember the nuances of the procedure well enough to rate performance accurately. The item type used for rating does not affect the absolute rating assigned or the rank ordering of the performance. Differences in stringency of evaluators indicate the need for multiple resident performance observations by multiple surgeons. These findings are the foundation for an upcoming multi-institutional trial.


Rapid, label-free CD4 testing using a smartphone compatible device.
The most recent guidelines have called for a significant shift towards viral load testing for HIV/AIDS management in developing countries; however point-of-care (POC) CD4 testing still remains an important component of disease staging in multiple developing countries. Advancements in micro/nanotechnologies and consumer electronics have paved the way for mobile healthcare technologies and the development of POC smartphone-based diagnostic assays for disease detection and treatment monitoring. Here, we report a simple, rapid (30 minutes) smartphone-based microfluidic chip for automated CD4 testing using a small volume (30 μL) of whole blood. The smartphone-based device includes an inexpensive (<$5) cell phone accessory and a functionalized disposable microfluidic device. We evaluated the performance of the device using spiked PBS samples and HIV-infected and uninfected whole blood, and compared the microfluidic chip results with the manual analysis and flow cytometry results. Through t-tests, Bland-Altman analyses, and regression tests, we have shown a good agreement between the smartphone-based test and the manual and FACS analysis for CD4 count. The presented technology could have a significant impact on HIV management in developing countries through providing a reliable and inexpensive POC CD4 testing.


Redox factor-1 (Ref-1) mediates the activation of AP-1 in HeLa and NIH 3T3 cells in response to heat shock.
The early response genes, c-Fos and c-Jun, are induced by environmental stress and are thought to modulate injury processes via the induction of AP-1-dependent target genes. AP-1 activation is thought to be regulated by changes in intracellular oxidation/reduction reactions involving the redox factor-1 (Ref-1) protein. In this study, NIH 3T3 and HeLa cells were used to determine whether heat shock induces the AP-1 transcription factor via signaling pathways involving Ref-1. Reverse transcriptase-polymerase chain reaction analysis and immunoblotting demonstrated that c-Fos and c-Jun were induced 2-10 h following heat shock, and this induction was accompanied by an increase in AP-1 DNA binding. Electrophoretic mobility shift assay extracts immunodepleted of Ref-1 protein demonstrated that the increase in AP-1 DNA-binding activity following heating was dependent upon the presence of Ref-1 and that Ref-1 regulates inducible, but not basal, AP-1 DNA-binding activity. This was confirmed by the restoration of heat-inducible DNA binding upon addition of Ref-1 to immunodepleted extracts. The ability of Ref-1 from heated cells to stimulate AP-1 DNA binding was abolished by chemical oxidation and restored by chemical reduction. These results indicate that heat shock activates c-Fos/c-Jun gene expression and AP-1 DNA binding and suggests that redox-sensitive signal transduction pathways involving Ref-1 may mediate heat-induced alterations in AP-1 activation.


Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.
Mitochondrial DNA (mtDNA), the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD) patients who had developed L-DOPA Induced Dyskinesia (LID), compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr) treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.


First Report of Pestalotiopsis theae on Loquat (Eriobotrya japonica) in Anhui Province of China.
Loquat, Eriobotrya japonica (Thunb.) Lindl., is an important fruit that is widely planted and used as an ornamental in Jingxian, Anhui Province, China. Loquat branches with severely spotted leaves and fruits were observed in this region in 2012. Symptoms on leaves consisted of small (0.5 to 1.2 cm in diameter), circular to oblong, greenish-brown lesions that coalesced to form isolated or confluent, dark brown spots. On fruit, the disease appeared as circular to elongated, sunken spots. Expanding lesions spread over the surface resulting in death of the fruit. Acervuli were observed within lesions. Isolations from symptomatic tissue onto potato dextrose agar (PDA) medium consistently yielded white fungal colonies of sparse aerial mycelium with acervuli containing black, slimy spore masses on the surface. The colony reached 8.0 cm diameter after 7-day culture on PDA at 24°C. Conidia produced in the culture were five-celled, narrow fusiform, straight or slightly curved, with a tapering base and 2 to 4 hyaline appentages (apical appentages measured 15 to 34 μm long and a single basal appentage was 5 to 9 μm long). Conidia were 24 to 32 × 5 to 8 μm with median cells 15 to 20 μm and two hyaline, cylindrical to conical apical cells typical of Pestalotiopsis spp. (3). A total of 12 isolates were obtained by isolation from the diseased fruit or leaves. Genomic DNA from the fungal isolates was purified using a DNA Gel Extraction Kit (AxyPrep, Hangzhou, China), and applied to a DNA Engine System PTC-200 (BIO-RAD, Watertown, MA) with ITS1 and ITS4 internal transcribed spacer (ITS) universal primers. The amplified sequences (533 bp) were analyzed together with other Pestalotiopsis sequences (1). ITS from all 12 of the fungal isolates were identical (99.5% similarity) to each other and to isolates of Pestalotiopsis theae, which infects tea trees in China (2). To demonstrate pathogenicity, suspensions (prepared in distilled water) of 106 conidia ml-1 of each isolate were sprayed on the loquat leaves in vivo and mature fruits in vitro. Distilled water was used as the control. More than 20 leaves and 10 mature fruits were sprayed for the treated and control plants, respectively, and the inoculation tests were repeated twice. The inoculated plants and fruit were kept in a humidity chamber for 7 days. Approximately 50% of the inoculated leaves and fruits developed blight symptoms similar to natural infections. P. theae was reisolated from diseased plants to complete Koch's postulates. Control plants sprayed with distilled water remained symptomless. There is a previous study reporting that P. guepini infected loquat in Argentina (4); however, to our knowledge, this is the first report of P. theae causing leaf and fruit spots on loquat in China. References: (1) R. Jeewon et al. Mol. Phylogenet. Evol. 25:378, 2002. (2) J. Y. Lu. Diagnosis of plant diseases. Page 194 in: Pestalotiopsis. J. Y. Lu, Z. G. Xu, Y. X. Chen, D. R. Shen, X. B. Zheng, and Y. Q. Cao, eds. China Agriculture Press, Beijing, 1995. (3) T. R. Nag Raj. Coelomycetous Anamorphs with Appendage-Bearing Conidia. Mycologue Publications, Waterloo, Canada, 1993. (4) A. E. Perelló and S. Larran. Plant Dis. 83:695, 1999.


Stabilization of high temperature hexagonal phase of SrAl2O4 at room temperature: role of ZnO.
Strontium aluminate (SrAl2O4) exhibits a monoclinic structure at room temperature (RT) and transforms to a hexagonal structure at above 650 °C, reported previously in the literature. In this article, we have shown a stable, high temperature hexagonal phase of SrAl2O4 (SAO) at RT by synthesizing a SAO-ZnO composite through a combustion technique. While SAO crystallizes in the monoclinic phase by adding 2.5 wt% of ZnO, a stable hexagonal phase of SAO at RT has been obtained for 20 wt% of ZnO. Further, the hexagonal phase of SAO transforms to a monoclinic phase after increasing the calcination temperature from 700 to 1200 °C. The role of ZnO in determining the structure and photoluminescence properties of these composites are discussed.


Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status.
Dietary intake of fructose corn syrup in sweetened beverages is associated with the development of metabolic syndrome and obesity. We hypothesized that inflammatory cytokines play a role in lipid storage and induction of liver injury. Therefore, this study intended to explore the expression of adipocytokines and its link to hepatic damage. Rats were assigned to drink water, cola soft drink (free access) and aspartame (240 mg/kg body weight/day orally) for 2 months. The lipid profiles, liver antioxidants and pathology, and mRNA expression of adipogenic cytokines were evaluated. Subchronic intake of soft drink or aspartame substantially induced hyperglycemia and hypertriacylglycerolemia, as represented by increased serum glucose, triacylglycerol, low-density lipoprotein and very low-density lipoprotein cholesterol, with obvious visceral fatty deposition. These metabolic syndromes were associated with the up-regulation of leptin and down-regulation of adiponectin and peroxisome proliferator activated receptor-γ (PPAR-γ) expression. Moreover, alterations in serum transaminases accompanied by hepatic oxidative stress involving induction of malondialdehyde and reduction of superoxide dismutase, catalase, and glutathione peroxidase and glutathione levels are indicative of oxidative hepatic damage. Several cytoarchitecture alterations were detected in the liver, including degeneration, infiltration, necrosis, and fibrosis, predominantly with aspartame. These data suggest that long-term intake of soft drink or aspartame-induced hepatic damage may be mediated by the induction of hyperglycemia, lipid accumulation, and oxidative stress with the involvement of adipocytokines.


Identification of mutations in the COL4A5 collagen gene in Alport syndrome.
X-linked Alport syndrome is a hereditary glomerulonephritis in which progressive loss of kidney function is often accompanied by progressive loss of hearing. Ultrastructural defects in glomerular basement membranes (GBM) of Alport syndrome patients implicate an altered structural protein as the cause of nephritis. The product of COL4A5, the alpha 5(IV) collagen chain, is a specific component of GBM within the kidney, and the gene maps to the same X chromosomal region as does Alport syndrome. Three structural aberrations were found in COL4A5, in intragenic deletion, a Pst I site variant, and an uncharacterized abnormality, which appear to cause nephritis and deafness, with allele-specific severity, in three Alport syndrome kindreds in Utah.


Development and use of fluorescent 16S rRNA-targeted probes for the specific detection of Methylophaga species by in situ hybridization in marine sediments.
Methylotrophic bacteria are widespread in nature. They may play an important role in the cycling of carbon and in the metabolism of dimethylsulfide in a marine environment. Bacteria belonging to the genus Methylophaga are a unique group of aerobic, halophilic, non-methane-utilizing methylotrophs. Two 16S rRNA-targeted oligonucleotide probes were developed for the specific detection of Methylophaga species, marine methylobacteria, by fluorescence in situ hybridization. Probe MPH-730 was highly specific for all members of the genus Methylophaga while probe MPHm-994 targeted exclusively M. marina. The application of these probes were demonstrated by the detection of Methylophaga species in enrichment cultures from various marine sediments. All isolates recovered were visualized by using the genus specific probe MPH-730. The results were confirmed by 16S rDNA sequencing which demonstrated that all selected isolates belong to Methylophaga. Five isolates could be detected by the M. marina-specific probe MPHm-994 and were confirmed by rRNA gene restriction pattern (ribotyping). With the development of these specific probes, fluorescence in situ hybridization shows that the genus Methylophaga is widespread in marine samples.


Ethanol inhibition of a T-type Ca²+ channel through activity of protein kinase C.
T-type calcium channels (T-channels) are widely distributed in the central and peripheral nervous system, where they mediate calcium entry and regulate the intrinsic excitability of neurons. T-channels are dysregulated in response to alcohol administration and withdrawal. We therefore investigated acute ethanol (EtOH) effects and the underlying mechanism of action in human embryonic kidney (HEK) 293 cell lines, as well as effects on native currents recorded from dorsal root ganglion (DRG) neurons cultured from Long-Evans rats. Whole-cell voltage-clamp recordings were performed at 32 to 34°C in both HEK cell lines and DRG neurons. The recordings were taken after a 10-minute application of EtOH or protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate [PMA]). We recorded T-type Ca²⁺ currents (T-currents) from 3 channel isoforms (CaV3.1, CaV3.2, and CaV3.3) before and during administration of EtOH. We found that only 1 isoform, CaV3.2, was significantly affected by EtOH. EtOH reduced current density as well as producing a hyperpolarizing shift in steady-state inactivation of both CaV3.2 currents from HEK 293 cell lines and in native T-currents from DRG neurons that are known to be enriched in CaV3.2. A myristoylated PKC peptide inhibitor (MPI) blocked the major EtOH effects, in both the cell lines and the DRG neurons. However, PMA effects were more complex. Lower concentration PMA (100 nM) replicated the major effects of EtOH, while higher concentration PMA (1 μM) did not, suggesting that the EtOH effects operate through activation of PKC and were mimicked by lower concentration of PMA. EtOH primarily affects the CaV3.2 isoform of T-type Ca²⁺ channels acting through PKC, highlighting a novel target and mechanism for EtOH effects on excitable membranes.