Thyroid hormone is essential for pituitary somatotropes and lactotropes.

PubMed

Stahl, J H; Kendall, S K; Brinkmeier, M L; Greco, T L; Watkins-Chow, D E; Campos-Barros, A; Lloyd, R V; Camper, S A

1999-04-01

Mice homozygous for a disruption in the alpha-subunit essential for TSH, LH, and FSH activity (alphaGsu-/-) exhibit hypothyroidism and hypogonadism similar to that observed in TSH receptor-deficient hypothyroid mice (hyt) and GnRH-deficient hypogonadal mutants (hpg). Although the five major hormone-producing cells of the anterior pituitary are present in alphaGsu-/- mice, the relative proportions of each cell type are altered dramatically. Thyrotropes exhibit hypertrophy and hyperplasia, and somatotropes and lactotropes are underrepresented. The size and number of gonadotropes in alphaGsu mutants are not remarkable in contrast to the hypertrophy characteristic of gonadectomized animals. The reduction in lactotropes is more severe in alphaGsu mutants (13-fold relative to wild-type) than in hyt or hpg mutants (4.5- and 1.5-fold, respectively). In addition, T4 replacement therapy of alphaGsu mutants restores lactotropes to near-normal levels, illustrating the importance of T4, but not alpha-subunit, for lactotrope proliferation and function. T4 replacement is permissive for gonadotrope hypertrophy in alphaGsu mutants, consistent with the role for T4 in the function of gonadotropes. This study reveals the importance of thyroid hormone in developing the appropriate proportions of anterior pituitary cell types.

An evolutionary analysis identifies a conserved pentapeptide stretch containing the two essential lysine residues for rice L-myo-inositol 1-phosphate synthase catalytic activity

PubMed Central

Basak, Papri; Maitra-Majee, Susmita; Das, Jayanta Kumar; Mukherjee, Abhishek; Ghosh Dastidar, Shubhra; Pal Choudhury, Pabitra

2017-01-01

A molecular evolutionary analysis of a well conserved protein helps to determine the essential amino acids in the core catalytic region. Based on the chemical properties of amino acid residues, phylogenetic analysis of a total of 172 homologous sequences of a highly conserved enzyme, L-myo-inositol 1-phosphate synthase or MIPS from evolutionarily diverse organisms was performed. This study revealed the presence of six phylogenetically conserved blocks, out of which four embrace the catalytic core of the functional protein. Further, specific amino acid modifications targeting the lysine residues, known to be important for MIPS catalysis, were performed at the catalytic site of a MIPS from monocotyledonous model plant, Oryza sativa (OsMIPS1). Following this study, OsMIPS mutants with deletion or replacement of lysine residues in the conserved blocks were made. Based on the enzyme kinetics performed on the deletion/replacement mutants, phylogenetic and structural comparison with the already established crystal structures from non-plant sources, an evolutionarily conserved peptide stretch was identified at the active pocket which contains the two most important lysine residues essential for catalytic activity. PMID:28950028

An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins

PubMed Central

Lange, Heike; Lisowsky, Thomas; Gerber, Jana; Mühlenhoff, Ulrich; Kispal, Gyula; Lill, Roland

2001-01-01

Biogenesis of Fe/S clusters involves a number of essential mitochondrial proteins. Here, we identify the essential Erv1p of Saccharomyces cerevisia mitochondria as a novel component that is specifically required for the maturation of Fe/S proteins in the cytosol, but not in mitochondria. Furthermore, Erv1p was found to be important for cellular iron homeostasis. The homologous mammalian protein ALR (‘augmenter of liver regeneration’), also termed hepatopoietin, can functionally replace defects in Erv1p and thus represents the mammalian orthologue of yeast Erv1p. Previously, a fragment of ALR was reported to exhibit an activity as an extracellular hepatotrophic growth factor. Both Erv1p and full-length ALR are located in the mitochondrial intermembrane space and represent the first components of this compartment with a role in the biogenesis of cytosolic Fe/S proteins. It is likely that Erv1p/ALR operates downstream of the mitochondrial ABC transporter Atm1p/ABC7/Sta1, which also executes a specific task in this essential biochemical process. PMID:11493598

An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins.

PubMed

Lange, H; Lisowsky, T; Gerber, J; Mühlenhoff, U; Kispal, G; Lill, R

2001-08-01

Biogenesis of Fe/S clusters involves a number of essential mitochondrial proteins. Here, we identify the essential Erv1p of Saccharomyces cerevisia mitochondria as a novel component that is specifically required for the maturation of Fe/S proteins in the cytosol, but not in mitochondria. Furthermore, Erv1p was found to be important for cellular iron homeostasis. The homologous mammalian protein ALR ('augmenter of liver regeneration'), also termed hepatopoietin, can functionally replace defects in Erv1p and thus represents the mammalian orthologue of yeast Erv1p. Previously, a fragment of ALR was reported to exhibit an activity as an extracellular hepatotrophic growth factor. Both Erv1p and full-length ALR are located in the mitochondrial intermembrane space and represent the first components of this compartment with a role in the biogenesis of cytosolic Fe/S proteins. It is likely that Erv1p/ALR operates downstream of the mitochondrial ABC transporter Atm1p/ABC7/Sta1, which also executes a specific task in this essential biochemical process.

Hormonal development therapy (HDT) in hypogonadism in long-term view.

PubMed

Heinz, Marlene

2010-04-01

Since the 1960s, oestrogen deficiency in hypogonadism in girls has been successfully treated by a sort of analogous application of the menopausal hormone replacement therapy (HRT) scheme, here however, to induce and support sexual development in puberty and adolescence. The essential distinction between goals, ways and means of the two distinct hormonal treatments caused by menopause and by hypogonadism in puberty also suggests that the latter treatment is more characteristic of defining hormonal development therapy (HDT). Moreover, specific HDT in hypogonadism is essential for longitudinal growth of girls, functions of female reproductive system, bone and lipid metabolism and the immune, central nervous and cardiovascular systems. By contrast, the aim of menopausal replacement therapy in elderly women is treating negative effects of physiological loss of oestrogens as hot flush, lacks of female well-being and osteoporosis, while in hypogonadal girls there is of course nothing that might be replaced eventually. Especially in cases of absolute oestrogen deficiency, as in Turner syndrome and in other cases of premature ovarian failure, HDT has to be started at the age of expected puberty. An international consensus suggests possibly lifelong HDT for the lasting support of female development and functions. However, neither reliable studies about possible risks and side effects of continuous hormonal therapy in adult women with hypogonadismus nor a more precise consensus have emerged yet. Emphasising the term HDT particularly aims at putting more effort in getting over these paucities simultaneously. Indications, hormonal therapy, dosage, application and timing in puberty are described in this article. Aspects of long-term hormonal treatment are critically discussed. Copyright 2010 Elsevier Ltd. All rights reserved.

Aconitase couples metabolic regulation to mitochondrial DNA maintenance.

PubMed

Chen, Xin Jie; Wang, Xiaowen; Kaufman, Brett A; Butow, Ronald A

2005-02-04

Mitochondrial DNA (mtDNA) is essential for cells to maintain respiratory competency and is inherited as a protein-DNA complex called the nucleoid. We have identified 22 mtDNA-associated proteins in yeast, among which is mitochondrial aconitase (Aco1p). We show that this Krebs-cycle enzyme is essential for mtDNA maintenance independent of its catalytic activity. Regulation of ACO1 expression by the HAP and retrograde metabolic signaling pathways directly affects mtDNA maintenance. When constitutively expressed, Aco1p can replace the mtDNA packaging function of the high-mobility-group protein Abf2p. Thus, Aco1p may integrate metabolic signals and mtDNA maintenance.

Influenza B virus M2 protein can functionally replace its influenza A virus counterpart in promoting virus replication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wanitchang, Asawin; Wongthida, Phonphimon; Jongkae

The M2 protein (AM2 and BM2) of influenza A and B viruses function as a proton channel essential for viral replication. They also carry a cytoplasmic tail whose functions are not fully delineated. It is currently unknown whether these proteins could be replaced functionally in a viral context. Here, we generated single-cycle influenza A viruses (scIAV-ΔHA) carrying various M2-2A-mCherry constructs in the segment 4 (HA) and evaluated their growth in complementing cells. Intriguingly, the scIAV-ΔHA carrying AM2 and that bearing BM2 grew comparably well in MDCK-HA cells. Furthermore, while the virus carrying chimeric B-AM2 in which the BM2 transmembrane fusedmore » with the AM2 cytoplasmic tail produced robust infection, the one bearing the AM2 transmembrane fused with the BM2 cytoplasmic tail (A-BM2) exhibited severely impaired growth. Altogether, we demonstrate that AM2 and BM2 are functionally interchangeable and underscore the role of compatibility between transmembrane and cytoplasmic tail of the M2 protein. -- Highlights: •Flu A M2 protein (AM2) can be functionally replaced by that of Flu B (BM2). •Both AM2 and BM2 with extended cytoplasmic tail are functional. •Compatibility between the ion channel and the cytoplasmic tail is critical for M2 function. •M2 with higher ion channel activity may augment influenza virus replication.« less

Pituitary cell differentiation from stem cells and other cells: toward restorative therapy for hypopituitarism?

PubMed

Willems, Christophe; Vankelecom, Hugo

2014-01-01

The pituitary gland, key regulator of our endocrine system, produces multiple hormones that steer essential physiological processes. Hence, deficient pituitary function (hypopituitarism) leads to severe disorders. Hypopituitarism can be caused by defective embryonic development, or by damage through tumor growth/resection and traumatic brain injury. Lifelong hormone replacement is needed but associated with significant side effects. It would be more desirable to restore pituitary tissue and function. Recently, we showed that the adult (mouse) pituitary holds regenerative capacity in which local stem cells are involved. Repair of deficient pituitary may therefore be achieved by activating these resident stem cells. Alternatively, pituitary dysfunction may be mended by cell (replacement) therapy. The hormonal cells to be transplanted could be obtained by (trans-)differentiating various kinds of stem cells or other cells. Here, we summarize the studies on pituitary cell regeneration and on (trans-)differentiation toward hormonal cells, and speculate on restorative therapies for pituitary deficiency.

Testosterone replacement therapy: role of pituitary and thyroid in diagnosis and treatment

PubMed Central

Crawford, Megan

2016-01-01

Crosstalk among hormones characterizes endocrine function, and assessment of the hypogonadal man should take that into consideration. In men for whom testosterone deficiency is a concern, initial evaluation should include a thorough history and physical exam in which other endocrinopathies are being considered. Hypogonadism can be associated with both pituitary and thyroid dysfunction, for which appropriate biochemical evaluation should be undertaken in certain clinical scenarios. If low serum testosterone is confirmed measurement of luteinizing and follicle stimulating hormones (LH and FSH respectively) is essential to establish whether the hypogonadism is primary or secondary. In secondary hypogonadism measurement of prolactin is always necessary, and measurement of other pituitary hormones, along with pituitary imaging, may be indicated. Checking thyroid function may also be enlightening, and can raise additional therapeutic considerations. Correction of other pituitary axes may attenuate the need for testosterone replacement therapy in some cases. PMID:28078216

How multi-partner endosymbioses function.

PubMed

Douglas, Angela E

2016-12-01

Various animals are associated with specific endosymbiotic microorganisms that provide the host with essential nutrients or confer protection against natural enemies. Genomic analyses of the many endosymbioses that are found in plant sap-feeding hemipteran insects have revealed independent acquisitions - and occasional replacements - of endosymbionts, such that many of these endosymbioses involve two or more microbial partners. In this Review, I discuss how partitioning of the genetic capacity for metabolic function between different endosymbionts has sustained nutritional function in multi-partner endosymbioses, and how the phenotypic traits of these endosymbionts can be shaped by co-evolutionary interactions with both co-occurring microbial taxa and the host, which often operate over long evolutionary timescales.

Folding and Function of a T4 Lysozyme Containing 10 Consecutive Alanines Illustrate the Redundancy of Information in an Amino Acid Sequence

NASA Astrophysics Data System (ADS)

Heinz, Dirk W.; Baase, Walt A.; Matthews, Brian W.

1992-05-01

Single and multiple Xaa -> Ala substitutions were constructed in the α-helix comprising residues 39-50 in bacteriophage T4 lysozyme. The variant with alanines at 10 consecutive positions (A40-49) folds normally and has activity essentially the same as wild type, although it is less stable. The crystal structure of this polyalanine mutant displays no significant change in the main-chain atoms of the helix when compared with the wild-type structure. The individual substitutions of the solvent-exposed residues Asn-40, Ser-44, and Glu-45 with alanine tend to increase the thermostability of the protein, whereas replacements of the buried or partially buried residues Lys-43 and Leu-46 are destabilizing. The melting temperature of the lysozyme in which Lys-43 and Leu-46 are retained and positions 40, 44, 45, 47, and 48 are substituted with alanine (i.e., A40-42/44-45/47-49) is increased by 3.1^circC relative to wild type at pH 3.0, but reduced by 1.6^circC at pH 6.7. In the case of the charged amino acids Glu-45 and Lys-48, the changes in melting temperature indicate that the putative salt bridge between these two residues contributes essentially nothing to the stability of the protein. The results clearly demonstrate that there is considerable redundancy in the sequence information in the polypeptide chain; not every amino acid is essential for folding. Also, further evidence is provided that the replacement of fully solvent-exposed residues within α-helices with alanines may be a general way to increase protein stability. The general approach may permit a simplification of the protein folding problem by retaining only amino acids proven to be essential for folding and replacing the remainder with alanine.

Digital Classrooms: A Multiple Case Study of Four Visually Impaired College Students' Challenges and Opportunities

ERIC Educational Resources Information Center

Malone, Jo Ann

2017-01-01

Access to the Internet and technology skills are essential to the success of college students. Electronic textbooks are replacing paper textbooks. Laptops are replacing pens, pencils, and paper. Electronic forms found on school websites are replacing long registration lines. Hyperlinks are replacing handouts, and face-to-face interaction with…

Essential oils for dairy calves: effects on performance, scours, rumen fermentation and intestinal fauna.

PubMed

Santos, F H R; De Paula, M R; Lezier, D; Silva, J T; Santos, G; Bittar, C M M

2015-06-01

The first cause of death of dairy calves is often diarrhea which is mainly caused by pathogenic bacteria, which can result in excessive use of antibiotics. However, facing the increase concern by the industry and consumers, the use of antibiotics not only to control pathogens, but also to manipulate growth, has become a challenge. Alternative additives, such essential oils, have the potential to decrease antibiotic use, without reducing performance or increasing mortality of dairy calves. The objective of this study was to evaluate the use of a commercial blend of essential oils, incorporated into the calf starter and/or milk replacer to monitor the effect on overall calf performance, fecal scores and rumen fermentation parameters. A total of 30 Holstein calves received 6 l/day of a liquid diet, consisting of a commercial milk replacer containing 20% CP : 15% fat (EE). Calves had free choice access to water and calf starter. Weaning occurred at week 8, and calves were followed until the 10th week of age. Calves were assigned to one of the three treatment groups in a randomized block design. (1) control without essential oils supplementation (C); (2) essential oils blend in the milk replacer at 400 mg/kg (MR) and (3) essential oils blend in the milk replacer (200 mg/kg) and starter feed (200 mg/kg) (MRS). From the 2nd week, calves were weighed and body measurements were taken, while concentrate intake and fecal scores were monitored daily. Blood samples were drawn weekly for determination of glucose and β-hydroxybutyrate. Fecal samples were collected weekly and analyzed for lactic acid bacteria and Enterobacteria; and ruminal fluid for determination of pH, short chain fatty acids, ammonia-N and counts of amylolytic and cellulolytic bacteria, and protozoa. Performance, fecal scores and intestines microorganisms were not affected by the essential oils supplementation. Ruminal and blood parameters were also not affected, with the exception the rumen ammonia-N concentration, with higher values when essential oils were supplemented in a combination of milk replacer and starter feed. Most of the evaluated parameters were affected by age of calves, mainly as a response to the increase in concentrate intake as animals' aged. Essential oils are promising substitutes for antibiotics. However, the dose and routes of administration deserve further studies, allowing a better animal performance and health to be achieved.

An enteric virus can replace the beneficial function of commensal bacteria

PubMed Central

Kernbauer, Elisabeth; Ding, Yi; Cadwell, Ken

2014-01-01

Intestinal microbial communities have profound effects on host physiology1. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined2,3. Here, we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germfree or antibiotics-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells (ILCs) observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signaling. Consistent with this observation, the IFNα receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of antibiotics-treatment in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity akin to commensal bacteria. PMID:25409145

Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle

PubMed Central

Stallmach, Robert; Kavishwar, Manoli; Withers-Martinez, Chrislaine; Hackett, Fiona; Collins, Christine R; Howell, Steven A; Yeoh, Sharon; Knuepfer, Ellen; Atid, Avshalom J; Holder, Anthony A; Blackman, Michael J

2015-01-01

The malaria parasite Plasmodium falciparum replicates in an intraerythrocytic parasitophorous vacuole (PV). The most abundant P. falciparum PV protein, called SERA5, is essential in blood stages and possesses a papain-like domain, prompting speculation that it functions as a proteolytic enzyme. Unusually however, SERA5 possesses a Ser residue (Ser596) at the position of the canonical catalytic Cys of papain-like proteases, and the function of SERA5 or whether it performs an enzymatic role is unknown. In this study, we failed to detect proteolytic activity associated with the Ser596-containing parasite-derived or recombinant protein. However, substitution of Ser596 with a Cys residue produced an active recombinant enzyme with characteristics of a cysteine protease, demonstrating that SERA5 can bind peptides. Using targeted homologous recombination in P. falciparum, we substituted Ser596 with Ala with no phenotypic consequences, proving that SERA5 does not perform an essential enzymatic role in the parasite. We could also replace an internal segment of SERA5 with an affinity-purification tag. In contrast, using almost identical targeting constructs, we could not truncate or C-terminally tag the SERA5 gene, or replace Ser596 with a bulky Arg residue. Our findings show that SERA5 plays an indispensable but non-enzymatic role in the P. falciparum blood-stage life cycle. PMID:25599609

Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

PubMed

Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

2014-08-12

The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

The evolution of functional hand replacement: From iron prostheses to hand transplantation

PubMed Central

Zuo, Kevin J; Olson, Jaret L

2014-01-01

The hand is an integral component of the human body, with an incredible spectrum of functionality. In addition to possessing gross and fine motor capabilities essential for physical survival, the hand is fundamental to social conventions, enabling greeting, grooming, artistic expression and syntactical communication. The loss of one or both hands is, thus, a devastating experience, requiring significant psychological support and physical rehabilitation. The majority of hand amputations occur in working-age males, most commonly as a result of work-related trauma or as casualties sustained during combat. For millennia, humans have used state-of-the-art technology to design clever devices to facilitate the reintegration of hand amputees into society. The present article provides a historical overview of the progress in replacing a missing hand, from early iron hands intended primarily for use in battle, to today’s standard body-powered and myoelectric prostheses, to revolutionary advancements in the restoration of sensorimotor control with targeted reinnervation and hand transplantation. PMID:25152647

The 10 Hz Frequency: A Fulcrum For Transitional Brain States.

PubMed

Garcia-Rill, E; D'Onofrio, S; Luster, B; Mahaffey, S; Urbano, F J; Phillips, C

A 10 Hz rhythm is present in the occipital cortex when the eyes are closed (alpha waves), in the precentral cortex at rest ( mu rhythm), in the superior and middle temporal lobe ( tau rhythm), in the inferior olive (projection to cerebellar cortex), and in physiological tremor (underlying all voluntary movement). These are all considered resting rhythms in the waking brain which are "replaced" by higher frequency activity with sensorimotor stimulation. That is, the 10 Hz frequency fulcrum is replaced on the one hand by lower frequencies during sleep, or on the other hand by higher frequencies during volition and cognition. The 10 Hz frequency fulcrum is proposed as the natural frequency of the brain during quiet waking, but is replaced by higher frequencies capable of permitting more complex functions, or by lower frequencies during sleep and inactivity. At the center of the transition shifts to and from the resting rhythm is the reticular activating system, a phylogenetically preserved area of the brain essential for preconscious awareness.

A replaceable liposomal aptamer for the ultrasensitive and rapid detection of biotin

NASA Astrophysics Data System (ADS)

Sung, Tzu-Cheng; Chen, Wen-Yih; Shah, Pramod; Chen, Chien-Sheng

2016-02-01

Biotin is an essential vitamin which plays an important role for maintaining normal physiological function. A rapid, sensitive, and simple method is necessary to monitor the biotin level. Here, we reported a replacement assay for the detection of biotin using a replaceable liposomal aptamer. Replacement assay is a competitive assay where a sample analyte replaces the labeled competitor of analyte out of its biorecognition element on a surface. It is user friendly and time-saving because of washing free. We used aptamer as a competitor, not a biorecognition element as tradition. To label aptamers, we used cholesterol-conjugated aptamers to tag signal-amplifying-liposomes. Without the need of conjugation procedure, aptamers can be easily incorporated into the surface of dye-encapsulating liposomes. Two aptamers as competitors of biotin, ST-21 and ST-21M with different affinities to streptavidin, were studied in parallel for the detection of biotin using replacement assays. ST-21 and ST-21M aptamers reached to limits of detection of 1.32 pg/80 μl and 0.47 pg/80 μl, respectively. The dynamic ranges of our assays using ST-21 and ST-21M aptamers were seven and four orders of magnitude, respectively. This assay can be completed in 20 minutes without washing steps. These results were overall better than previous reported assays.

Homologous gene replacement in Physarum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burland, T.G.; Pallotta, D.

1995-01-01

The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1more » in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.« less

Roles of the conserved cytoplasmic region and non-conserved carboxy-terminal region of SecE in Escherichia coli protein translocase.

PubMed

Kontinen, V P; Yamanaka, M; Nishiyama, K; Tokuda, H

1996-06-01

SecE, an essential membrane component of the Escherichia coli protein translocase, consists of 127 amino acid residues. Only a part of the second putative cytoplasmic region comprising some 13 residues is essential for the SecE function as long as the proper topological arrangement is retained. The Trp84 and Pro85 residues of this region are conserved in all eubacterial SecE homologues. The conservation of positively charged residues corresponding to Arg80 and Lys81 is also substantial. We deleted or replaced these residues to assess their roles in the SecE function. Deletion of the Arg80-Lys81 dipeptide did not abolish the SecE function whereas that of Trp84 or Pro85 caused a loss of the function. Strikingly, however, replacement of Pro85 with either Gly, Ser, or Ala, and that of Trp84 with Lys did not abolish the SecE function. These results indicate that the strong conservation of these residues does not reflect their obligatory requirement for the SecE function. A chimeric SecE possessing the cytoplasmic region of the E. coli SecE and the following region of the Bacillus subtilis SecE was able to form the translocation machinery together with SecA, SecY, and SecG. Although a Leu to Arg mutation at position 108 has been thought to cause a loss of signal recognition fidelity and thereby suppress a signal sequence defect, the same mutation at position 111 caused a complete loss of the function. The levels of SecY and SecG in the secEcsE501 mutant, which expresses SecE at a decreased level and is sensitive to low temperature, increased upon the expression of functional SecE derivatives, irrespective of the site of mutation, suggesting that the levels of SecY and SecG are co-operatively determined by the level of functional, but not non-functional, SecE. Based on these results, the SecE function in the translocase is discussed.

The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3

PubMed Central

Vidal, Valerie; Sacco, Sonia; Rocha, Ana Sofia; da Silva, Fabio; Panzolini, Clara; Dumontet, Typhanie; Doan, Thi Mai Phuong; Shan, Jingdong; Rak-Raszewska, Aleksandra; Bird, Tom; Vainio, Seppo; Martinez, Antoine; Schedl, Andreas

2016-01-01

Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life. PMID:27313319

Mapping and Engineering Functional Domains of the Assembly Activating Protein of Adeno-Associated Viruses.

PubMed

Tse, Longping V; Moller-Tank, Sven; Meganck, Rita M; Asokan, Aravind

2018-04-25

Adeno-associated viruses (AAV) encode a unique assembly activating protein (AAP) within their genome that is essential for capsid assembly. Studies to date have focused on establishing the role of AAP as a chaperone that mediates stability, nucleolar transport, and assembly of AAV capsid proteins. Here, we map structure-function correlates of AAP using secondary structure analysis followed by deletion and substitutional mutagenesis of specific domains, namely, the hydrophobic N-terminal domain (HR), conserved core (CC), proline-rich region (PRR), threonine/serine rich region (T/S) and basic region (BR). First, we establish that the centrally located PRR and T/S regions are flexible linker domains that can either be deleted completely or replaced by heterologous functional domains that enable ancillary functions such as fluorescent imaging or increased AAP stability. We also demonstrate that the C-terminal BR domains can be substituted with heterologous nuclear or nucleolar localization sequences that display varying ability to support AAV capsid assembly. Further, by replacing the BR domain with immunoglobulin (IgG) Fc domains, we assessed AAP complexation with AAV capsid subunits and demonstrate that the hydrophobic region (HR) and the conserved core (CC) in the AAP N-terminus are the sole determinants for viral protein (VP) recognition. However, VP recognition alone is not sufficient for capsid assembly. Our study sheds light on the modular structure-function correlates of AAP and provides multiple approaches to engineer AAP that might prove useful towards understanding and controlling AAV capsid assembly. Importance: Adeno-associated viruses (AAV) encode a unique assembly activating protein (AAP) within their genome that is essential for capsid assembly. Understanding how AAP acts as a chaperone for viral assembly could help improve efficiency and potentially control this process. Our studies reveal that AAP has a modular architecture, with each module playing a distinct role and can be engineered for carrying out new functions. Copyright © 2018 American Society for Microbiology.

Application of Zataria multiflora Boiss. and Cinnamon zeylanicum essential oils as two natural preservatives in cake.

PubMed

Kordsardouei, Habibe; Barzegar, Mohsen; Sahari, Mohamad Ali

2013-01-01

Oxidation of oils has an important effect on nutritional and organoleptic properties of foodstuffs. Nowadays, new tendency has created a necessity to use natural compounds such as essential oils for producing functional foods. In this study, antioxidant, antifungal, and organoleptic properties of Zataria multiflora Boiss. (ZMEO) and Cinnamon zeylanicum essential oils (CZEO) have been checked as two natural preservatives in the cakes. The antioxidant activity of essential oils were determined by measuring thiobarbituric, peroxide, and free fatty acid values of prepared cakes during 60 days storage at 25 ˚C. Antifungal properties of essential oils were determined and given as the ratio of colony number in samples containing ZMEO and CZEO to the control. Different concentrations of essential oils prevented oxidation rate and reducd preliminary and secondary oxidation products compared with butylate hydroxyanisole (BHA (100 and 200 ppm)) and control cakes. Moreover, ZMEO and CZEO at three concentrations (500, 1000, and 1500 ppm) reduced the fungal growth more than samples containing BHA (100 and 200 ppm) and the control. Our results showed that optimum concenteration of ZMEO and CZEO for using in the cakes was 500 ppm therefore it can be replaced instead of synthetic preservatives in foodstuffs.

Complex-valued multistate associative memory with nonlinear multilevel functions for gray-level image reconstruction.

PubMed

Tanaka, Gouhei; Aihara, Kazuyuki

2009-09-01

A widely used complex-valued activation function for complex-valued multistate Hopfield networks is revealed to be essentially based on a multilevel step function. By replacing the multilevel step function with other multilevel characteristics, we present two alternative complex-valued activation functions. One is based on a multilevel sigmoid function, while the other on a characteristic of a multistate bifurcating neuron. Numerical experiments show that both modifications to the complex-valued activation function bring about improvements in network performance for a multistate associative memory. The advantage of the proposed networks over the complex-valued Hopfield networks with the multilevel step function is more outstanding when a complex-valued neuron represents a larger number of multivalued states. Further, the performance of the proposed networks in reconstructing noisy 256 gray-level images is demonstrated in comparison with other recent associative memories to clarify their advantages and disadvantages.

Shoulder Arthroplasty, from Indications to Complications: What the Radiologist Needs to Know.

PubMed

Lin, Dana J; Wong, Tony T; Kazam, Jonathan K

2016-01-01

The replaced shoulder is increasingly encountered by the radiologist, both on a dedicated and incidental basis, in this era of the growing population of aging patients wishing to preserve their mobility and function. Knowledge of the normal biomechanics of the glenohumeral joint-particularly the function of the rotator cuff and the unique relationship of the humeral head to the glenoid-is essential for understanding the need for shoulder replacement and its subsequent complications, because the intent of shoulder arthroplasty is to approximate the normal joint as closely as possible. The most common indications for shoulder arthroplasty are osteoarthritis, inflammatory arthritis, proximal humerus fractures, irreparable rotator cuff tears, rotator cuff arthropathy, and avascular necrosis of the humeral head. Knowledge of the key imaging features of these indications helps facilitate a correlative understanding between the initial diagnosis and the choice of which type of arthroplasty is used-total shoulder arthroplasty, reverse total shoulder arthroplasty, or partial joint replacement (humeral head resurfacing arthroplasty or hemiarthroplasty). The preoperative requirements and usual postoperative appearance of each arthroplasty type are summarized, as well as the complications of shoulder arthroplasty, including those unique to or closely associated with each type of arthroplasty and those that can be encountered with any type of shoulder arthroplasty. ©RSNA, 2016.

Genetic analysis of neuronal ionotropic glutamate receptor subunits

PubMed Central

Granger, Adam J; Gray, John A; Lu, Wei; Nicoll, Roger A

2011-01-01

Abstract In the brain, fast, excitatory synaptic transmission occurs primarily through AMPA- and NMDA-type ionotropic glutamate receptors. These receptors are composed of subunit proteins that determine their biophysical properties and trafficking behaviour. Therefore, determining the function of these subunits and receptor subunit composition is essential for understanding the physiological properties of synaptic transmission. Here, we discuss and evaluate various genetic approaches that have been used to study AMPA and NMDA receptor subunits. These approaches have demonstrated that the GluA1 AMPA receptor subunit is required for activity-dependent trafficking and contributes to basal synaptic transmission, while the GluA2 subunit regulates Ca2+ permeability, homeostasis and trafficking to the synapse under basal conditions. In contrast, the GluN2A and GluN2B NMDA receptor subunits regulate synaptic AMPA receptor content, both during synaptic development and plasticity. Ongoing research in this field is focusing on the molecular interactions and mechanisms that control these functions. To accomplish this, molecular replacement techniques are being used, where native subunits are replaced with receptors containing targeted mutations. In this review, we discuss a single-cell molecular replacement approach which should arguably advance our physiological understanding of ionotropic glutamate receptor subunits, but is generally applicable to study of any neuronal protein. PMID:21768264

Genetic analysis of neuronal ionotropic glutamate receptor subunits.

PubMed

Granger, Adam J; Gray, John A; Lu, Wei; Nicoll, Roger A

2011-09-01

In the brain, fast, excitatory synaptic transmission occurs primarily through AMPA- and NMDA-type ionotropic glutamate receptors. These receptors are composed of subunit proteins that determine their biophysical properties and trafficking behaviour. Therefore, determining the function of these subunits and receptor subunit composition is essential for understanding the physiological properties of synaptic transmission. Here, we discuss and evaluate various genetic approaches that have been used to study AMPA and NMDA receptor subunits. These approaches have demonstrated that the GluA1 AMPA receptor subunit is required for activity-dependent trafficking and contributes to basal synaptic transmission, while the GluA2 subunit regulates Ca(2+) permeability, homeostasis and trafficking to the synapse under basal conditions. In contrast, the GluN2A and GluN2B NMDA receptor subunits regulate synaptic AMPA receptor content, both during synaptic development and plasticity. Ongoing research in this field is focusing on the molecular interactions and mechanisms that control these functions. To accomplish this, molecular replacement techniques are being used, where native subunits are replaced with receptors containing targeted mutations. In this review, we discuss a single-cell molecular replacement approach which should arguably advance our physiological understanding of ionotropic glutamate receptor subunits, but is generally applicable to study of any neuronal protein.

In silico molecular engineering for a targeted replacement in a tumor-homing peptide

PubMed Central

Zanuy, David; Flores-Ortega, Alejandra; Jiménez, Ana I.; Calaza, M. Isabel; Cativiela, Carlos; Nussinov, Ruth; Ruoslahti, Erkki; Alemán, Carlos

2009-01-01

A new amino acid has been designed as a replacement for arginine (Arg, R) to protect the tumor-homing pentapeptide CREKA from proteases. This amino acid, denoted (Pro)hArg, is characterized by a proline skeleton bearing a specifically oriented guanidinium side chain. This residue combines the ability of Pro to induce turn-like conformations with the Arg side-chain functionality. The conformational profile of the CREKA analogue incorporating this Arg substitute has been investigated by a combination of simulated annealing and Molecular Dynamics. Comparison of the results with those previously obtained for the natural CREKA shows that (Pro)hArg significantly reduces the conformational flexibility of the peptide. Although some changes are observed in the backbone···backbone and side chain···side chain interactions, the modified peptide exhibits a strong tendency to accommodate turn conformations centered at the (Pro)hArg residue and the overall shape of the molecule in the lowest energy conformations characterized for the natural and the modified peptide exhibit a high degree of similarity. In particular, the turn orients the backbone such that the Arg, Glu and Lys side chains face the same side of the molecule, which is considered essential for bioactivity. These results suggest that replacement of Arg by (Pro)hArg in CREKA may be useful in providing resistance against proteolytic enzymes while retaining conformational features which are essential for tumor-homing activity. PMID:19432404

Essential oils and herbal extracts as antimicrobial agents in cosmetic emulsion.

PubMed

Herman, Anna; Herman, Andrzej Przemysław; Domagalska, Beata Wanda; Młynarczyk, Andrzej

2013-06-01

The cosmetic industry adapts to the needs of consumers seeking to limit the use of preservatives and develop of preservative-free or self-preserving cosmetics, where preservatives are replaced by raw materials of plant origin. The aim of study was a comparison of the antimicrobial activity of extracts (Matricaria chamomilla, Aloe vera, Calendula officinalis) and essential oils (Lavandulla officinallis, Melaleuca alternifolia, Cinnamomum zeylanicum) with methylparaben. Extracts (2.5 %), essential oils (2.5 %) and methylparaben (0.4 %) were tested against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, Candida albicans ATCC 14053. Essentials oils showed higher inhibitory activity against tested microorganism strain than extracts and methylparaben. Depending on tested microorganism strain, all tested extracts and essential oils show antimicrobial activity 0.8-1.7 and 1-3.5 times stronger than methylparaben, respectively. This shows that tested extracts and essential oils could replace use of methylparaben, at the same time giving a guarantee of microbiological purity of the cosmetic under its use and storage.

The effects of n-3 fatty acid deficiency and repletion upon the fatty acid composition and function of the brain and retina.

PubMed

Connor, W E; Neuringer, M

1988-01-01

It is now apparent that both n-6 and n-3 fatty acids are essential for normal development in mammals, and that each has specific functions in the body. N-6 fatty acids are necessary primarily for growth, reproduction, and the maintenance of skin integrity, whereas n-3 fatty acids are involved in the development and function of the retina and cerebral cortex and perhaps other organs such as the testes. Fetal life and infancy are particularly critical for the nervous tissue development. Therefore, with respect to human nutrition, adequate amounts of omega-3 fatty acids should be provided during pregnancy, lactation and infancy, but probably throughout life. We estimate that adequate levels are provided by diets containing 6-8% kcals from linoleic acid and 1% from n-3 fatty acids (alpha-linolenic acid, EPA and DHA), resulting in a ratio of n-6 to n-3 fatty acids of 4:1 to 10:1. The essentiality of n-3 fatty acids resides in their presence as DHA in vital membranes of the photoreceptors of the retina and the synaptosomes and other subcellular membranes of the brain. The replacement of DHA in deficient animals by the n-6 fatty acid, 22:5, results in abnormal functioning of the membranes for reasons as yet to be ascertained. Most significant is the lability of fatty acid composition in the retinal and brain of deficient animals. Dietary fish oil, which contains EPA and DHA, will readily lead to a change in the composition of the membrane of retina and brain, fatty acids, with DHA replacing the n-6 fatty acid, 22:5. The interrelationships between the chemistry of neural and retinal membranes as affected by diet and their biological functioning provides an exciting prospect for future investigations.

Technology Roadmap Instrumentation, Control, and Human-Machine Interface to Support DOE Advanced Nuclear Energy Programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donald D Dudenhoeffer; Burce P Hallbert

Instrumentation, Controls, and Human-Machine Interface (ICHMI) technologies are essential to ensuring delivery and effective operation of optimized advanced Generation IV (Gen IV) nuclear energy systems. In 1996, the Watts Bar I nuclear power plant in Tennessee was the last U.S. nuclear power plant to go on line. It was, in fact, built based on pre-1990 technology. Since this last U.S. nuclear power plant was designed, there have been major advances in the field of ICHMI systems. Computer technology employed in other industries has advanced dramatically, and computing systems are now replaced every few years as they become functionally obsolete. Functionalmore » obsolescence occurs when newer, more functional technology replaces or supersedes an existing technology, even though an existing technology may well be in working order.Although ICHMI architectures are comprised of much of the same technology, they have not been updated nearly as often in the nuclear power industry. For example, some newer Personal Digital Assistants (PDAs) or handheld computers may, in fact, have more functionality than the 1996 computer control system at the Watts Bar I plant. This illustrates the need to transition and upgrade current nuclear power plant ICHMI technologies.« less

The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3.

PubMed

Vidal, Valerie; Sacco, Sonia; Rocha, Ana Sofia; da Silva, Fabio; Panzolini, Clara; Dumontet, Typhanie; Doan, Thi Mai Phuong; Shan, Jingdong; Rak-Raszewska, Aleksandra; Bird, Tom; Vainio, Seppo; Martinez, Antoine; Schedl, Andreas

2016-06-15

Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life. © 2016 Vidal et al.; Published by Cold Spring Harbor Laboratory Press.

Osteoblast and osteoclast behaviors in the turnover of attachment bones during medaka tooth replacement.

PubMed

Mantoku, Akiko; Chatani, Masahiro; Aono, Kazushi; Inohaya, Keiji; Kudo, Akira

2016-01-15

Tooth replacement in polyphyodont is a well-organized system for maintenance of homeostasis of teeth, containing the dynamic structural change in skeletal tissues such as the attachment bone, which is the supporting element of teeth. Histological analyses have revealed the character of tooth replacement, however, the cellular mechanism of how skeletal tissues are modified during tooth replacement is largely unknown. Here, we showed the important role of osteoblasts for controlling osteoclasts to modify the attachment bone during tooth replacement in medaka pharyngeal teeth, coupled with an osterix-DsRed/TRAP-GFP transgenic line to visualize osteoblasts and osteoclasts. In the turnover of the row of attachment bones, these bones were resorbed at the posterior side where most developed functional teeth were located, and generated at the anterior side where teeth were newly erupted, which caused continuous tooth replacement. In the cellular analysis, osteoclasts and osteoblasts were located at attachment bones separately, since mature osteoclasts were localized at the resorbing side and osteoblasts gathered at the generating side. To demonstrate the role of osteoclasts in tooth replacement, we established medaka made deficient in c-fms-a by TALEN. c-fms-a deficient medaka showed hyperplasia of attachment bones along with reduced bone resorption accompanied by a low number of TRAP-positive osteoclasts, indicating an important role of osteoclasts in the turnover of attachment bones. Furthermore, nitroreductase-mediated osteoblast-specific ablation induced disappearance of osteoclasts, indicating that osteoblasts were essential for maintenance of osteoclasts for the proper turnover. Taken together, our results suggested that the medaka attachment bone provides the model to understand the cellular mechanism for tooth replacement, and that osteoblasts act in the coordination of bone morphology by supporting osteoclasts. Copyright © 2015 Elsevier Inc. All rights reserved.

Strigolactone Biosynthesis in Medicago truncatula and Rice Requires the Symbiotic GRAS-Type Transcription Factors NSP1 and NSP2[W][OA

PubMed Central

Liu, Wei; Kohlen, Wouter; Lillo, Alessandra; Op den Camp, Rik; Ivanov, Sergey; Hartog, Marijke; Limpens, Erik; Jamil, Muhammad; Smaczniak, Cezary; Kaufmann, Kerstin; Yang, Wei-Cai; Hooiveld, Guido J.E.J.; Charnikhova, Tatsiana; Bouwmeester, Harro J.; Bisseling, Ton; Geurts, René

2011-01-01

Legume GRAS (GAI, RGA, SCR)-type transcription factors NODULATION SIGNALING PATHWAY1 (NSP1) and NSP2 are essential for rhizobium Nod factor-induced nodulation. Both proteins are considered to be Nod factor response factors regulating gene expression after symbiotic signaling. However, legume NSP1 and NSP2 can be functionally replaced by nonlegume orthologs, including rice (Oryza sativa) NSP1 and NSP2, indicating that both proteins are functionally conserved in higher plants. Here, we show that NSP1 and NSP2 are indispensable for strigolactone (SL) biosynthesis in the legume Medicago truncatula and in rice. Mutant nsp1 plants do not produce SLs, whereas in M. truncatula, NSP2 is essential for conversion of orobanchol into didehydro-orobanchol, which is the main SL produced by this species. The disturbed SL biosynthesis in nsp1 nsp2 mutant backgrounds correlates with reduced expression of DWARF27, a gene essential for SL biosynthesis. Rice and M. truncatula represent distinct phylogenetic lineages that split approximately 150 million years ago. Therefore, we conclude that regulation of SL biosynthesis by NSP1 and NSP2 is an ancestral function conserved in higher plants. NSP1 and NSP2 are single-copy genes in legumes, which implies that both proteins fulfill dual regulatory functions to control downstream targets after rhizobium-induced signaling as well as SL biosynthesis in nonsymbiotic conditions. PMID:22039214

Mobile Phone-Based Joint Angle Measurement for Functional Assessment and Rehabilitation of Proprioception

PubMed Central

Mourcou, Quentin; Fleury, Anthony; Diot, Bruno; Franco, Céline; Vuillerme, Nicolas

2015-01-01

Assessment of joint functional and proprioceptive abilities is essential for balance, posture, and motor control rehabilitation. Joint functional ability refers to the capacity of movement of the joint. It may be evaluated thereby measuring the joint range of motion (ROM). Proprioception can be defined as the perception of the position and of the movement of various body parts in space. Its role is essential in sensorimotor control for movement acuity, joint stability, coordination, and balance. Its clinical evaluation is commonly based on the assessment of the joint position sense (JPS). Both ROM and JPS measurements require estimating angles through goniometer, scoliometer, laser-pointer, and bubble or digital inclinometer. With the arrival of Smartphones, these costly clinical tools tend to be replaced. Beyond evaluation, maintaining and/or improving joint functional and proprioceptive abilities by training with physical therapy is important for long-term management. This review aims to report Smartphone applications used for measuring and improving functional and proprioceptive abilities. It identifies that Smartphone applications are reliable for clinical measurements and are mainly used to assess ROM and JPS. However, there is lack of studies on Smartphone applications which can be used in an autonomous way to provide physical therapy exercises at home. PMID:26583101

Replacement of C305 in heart/muscle-type isozyme of human carnitine palmitoyltransferase I with aspartic acid and other amino acids.

PubMed

Matsuo, Taisuke; Yamamoto, Atsushi; Yamamoto, Takenori; Otsuki, Kaoru; Yamazaki, Naoshi; Kataoka, Masatoshi; Terada, Hiroshi; Shinohara, Yasuo

2010-04-01

Liver- and heart/muscle-type isozymes of human carnitine palmitoyltransferase I (L- and M-CPTI, respectively) show a certain similarity in their amino acid sequences, and mutation studies on the conserved amino acids between these two isozymes often show essentially the same effects on their enzymatic properties. Earlier mutation studies on C305 in human M-CPTI and its counterpart residue, C304, in human L-CPTI showed distinct effects of the mutations, especially in the aspect of enzyme stability; however, simple comparison of these effects on the conserved Cys residue between L- and M-CPTI was difficult, because these studies were carried out using different expression systems and distinct amino acids as replacements. In the present study, we carried out mutation studies on the C305 in human M-CPTI using COS cells for the expression system. Our results showed that C305 was replaceable with aspartic acid but that substitution with other amino acids caused both loss of function and reduced expression.

Presence of Nosema ceranae associated with honeybee queen introductions.

PubMed

Muñoz, Irene; Cepero, Almudena; Pinto, Maria Alice; Martín-Hernández, Raquel; Higes, Mariano; De la Rúa, Pilar

2014-04-01

Microsporidiosis caused by Nosema species is one of the factors threatening the health of the honeybee (Apis mellifera), which is an essential element in agriculture mainly due to its pollination function. The dispersion of this pathogen may be influenced by many factors, including various aspects of beekeeping management such as introduction of queens with different origin. Herein we study the relation of the presence and distribution of Nosema spp. and the replacement of queens in honeybee populations settled on the Atlantic Canary Islands. While Nosema apis has not been detected, an increase of the presence and distribution of Nosema ceranae during the last decade has been observed in parallel with a higher frequency of foreign queens. On the other hand, a reduction of the number of N. ceranae positive colonies was observed on those islands with continued replacement of queens. We suggest that such replacement could help maintaining low rates of Nosema infection, but healthy queens native to these islands should be used in order to conserve local honeybee diversity. Copyright © 2014 Elsevier B.V. All rights reserved.

Computer-automated opponent for manned air-to-air combat simulations

NASA Technical Reports Server (NTRS)

Hankins, W. W., III

1979-01-01

Two versions of a real-time digital-computer program that operates a fighter airplane interactively against a human pilot in simulated air combat were evaluated. They function by replacing one of two pilots in the Langley differential maneuvering simulator. Both versions make maneuvering decisions from identical information and logic; they differ essentially in the aerodynamic models that they control. One is very complete, but the other is much simpler, primarily characterizing the airplane's performance (lift, drag, and thrust). Both models competed extremely well against highly trained U.S. fighter pilots.

Building vascular networks.

PubMed

Bae, Hojae; Puranik, Amey S; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A; Khademhosseini, Ali

2012-11-14

Only a few engineered tissues-skin, cartilage, bladder-have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology.

Building Vascular Networks

PubMed Central

Bae, Hojae; Puranik, Amey S.; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A.; Khademhosseini, Ali

2013-01-01

Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology. PMID:23152325

User's Manual for FSLIP-3, FLEXSTAB Loads Integration Program

NASA Technical Reports Server (NTRS)

Sims, R. L.

1981-01-01

The FSLIP program documentation and user's manual is presented. As a follow on program to the FLEXSTAB computer analysis system, the primary function of this FORTRAN IV program is to integrate panel pressure coefficients computed by FLEXSTAB to obtain total shear, bending, and torque airloads on various surfaces, summed relative to user specified axes. The program essentially replaces the ALOADS module in FLEXSTAB with expanded capabilities and flexibility. As such, FSLIP is generalized to work on any FLEXSTAB model or other pressure data if in a compatible format.

DISCOS- Current Status and Future Developments

NASA Astrophysics Data System (ADS)

Flohrer, T.; Lemmens, S.; Bastida Virgili, B.; Krag, H.; Klinkrad, H.; Parrilla, E.; Sanchez, N.; Oliveira, J.; Pina, F.

2013-08-01

We present ESA's Database and Information System Characterizing Objects in Space (DISCOS). DISCOS not only plays an essential role in the collision avoidance and re-entry prediction services provided by ESA's Space Debris Office, it is also providing input to numerous and very differently scoped engineering activities, within ESA and throughout industry. We introduce the central functionalities of DISCOS, present the available reporting capabilities, and describe selected data modelling features. Finally, we revisit the developments of the recent years and take a sneak preview of the on-going replacement of DISCOS web front-end.

Organic Functional Group Playing Card Deck

NASA Astrophysics Data System (ADS)

Welsh, Michael J.

2003-04-01

The recognition and identification of organic functional groups, while essential for chemistry and biology majors, is also very useful for non-science majors in the study of molecules in art and life. In order to make this task more palatable for the non-science major (art and communications students), the images of a traditional playing deck of cards (heart, spade, diamond, and club) have been replaced with four representations of common organic functional groups. The hierarchy rules for naming two groups in a molecule is loosely incorporated to represent the sequence (King, Queen, Jack, ?, Ace) of the deck. Students practice recognizing and identifying organic groups by playing simple card games of "Old Maid" and "Go Fish". To play games like "Poker" or "Gin", a student must not only recognize the functional groups, but also master a naming hierarchy for the organic groups.

Application of Zataria multiflora Boiss. and Cinnamon zeylanicum essential oils as two natural preservatives in cake

PubMed Central

Kordsardouei, Habibe; Barzegar, Mohsen; Sahari, Mohamad Ali

2013-01-01

Objective: Oxidation of oils has an important effect on nutritional and organoleptic properties of foodstuffs. Nowadays, new tendency has created a necessity to use natural compounds such as essential oils for producing functional foods. In this study, antioxidant, antifungal, and organoleptic properties of Zataria multiflora Boiss. (ZMEO) and Cinnamon zeylanicum essential oils (CZEO) have been checked as two natural preservatives in the cakes. Materials and Methods: The antioxidant activity of essential oils were determined by measuring thiobarbituric, peroxide, and free fatty acid values of prepared cakes during 60 days storage at 25 ˚C. Antifungal properties of essential oils were determined and given as the ratio of colony number in samples containing ZMEO and CZEO to the control. Results: Different concentrations of essential oils prevented oxidation rate and reducd preliminary and secondary oxidation products compared with butylate hydroxyanisole (BHA (100 and 200 ppm)) and control cakes. Moreover, ZMEO and CZEO at three concentrations (500, 1000, and 1500 ppm) reduced the fungal growth more than samples containing BHA (100 and 200 ppm) and the control. Conclusion: Our results showed that optimum concenteration of ZMEO and CZEO for using in the cakes was 500 ppm therefore it can be replaced instead of synthetic preservatives in foodstuffs. PMID:25050280

Heterologous RNA-silencing suppressors from both plant- and animal-infecting viruses support plum pox virus infection.

PubMed

Maliogka, Varvara I; Calvo, María; Carbonell, Alberto; García, Juan Antonio; Valli, Adrian

2012-07-01

HCPro, the RNA-silencing suppressor (RSS) of viruses belonging to the genus Potyvirus in the family Potyviridae, is a multifunctional protein presumably involved in all essential steps of the viral infection cycle. Recent studies have shown that plum pox potyvirus (PPV) HCPro can be replaced successfully by cucumber vein yellowing ipomovirus P1b, a sequence-unrelated RSS from a virus of the same family. In order to gain insight into the requirement of a particular RSS to establish a successful potyviral infection, we tested the ability of different heterologous RSSs from both plant- and animal-infecting viruses to substitute for HCPro. Making use of engineered PPV chimeras, we show that PPV HCPro can be replaced functionally by some, but not all, unrelated RSSs, including the NS1 protein of the mammal-infecting influenza A virus. Interestingly, the capacity of a particular RSS to replace HCPro does not correlate strictly with its RNA silencing-suppression strength. Altogether, our results suggest that not all suppression strategies are equally suitable for efficient escape of PPV from the RNA-silencing machinery. The approach followed here, based on using PPV chimeras in which an under-consideration RSS substitutes for HCPro, could further help to study the function of diverse RSSs in a 'highly sensitive' RNA-silencing context, such as that taking place in plant cells during the process of a viral infection.

Optimization of SDS exposure on preservation of ECM characteristics in whole organ decellularization of rat kidneys.

PubMed

He, M; Callanan, A; Lagaras, K; Steele, J A M; Stevens, M M

2017-08-01

Renal transplantation is well established as the optimal form of renal replacement therapy but is restricted by the limited pool of organs available for transplantation. The whole organ decellularisation approach is leading the way for a regenerative medicine solution towards bioengineered organ replacements. However, systematic preoptimization of both decellularization and recellularization parameters is essential prior to any potential clinical application and should be the next stage in the evolution of whole organ decellularization as a potential strategy for bioengineered organ replacements. Here we have systematically assessed two fundamental parameters (concentration and duration of perfusion) with regards to the effects of differing exposure to the most commonly used single decellularizing agent (sodium dodecyl sulphate/SDS) in the perfusion decellularization process for whole rat kidney ECM bioscaffolds, with findings showing improved preservation of both structural and functional components of the whole kidney ECM bioscaffold. Whole kidney bioscaffolds based on our enhanced protocol were successfully recellularized with rat primary renal cells and mesenchymal stromal cells. These findings should be widely applicable to decellularized whole organ bioscaffolds and their optimization in the development of regenerated organ replacements for transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1352-1360, 2017. © 2016 Wiley Periodicals, Inc.

Relative stability of radicals derived from artemisinin: A semiempirical and DFT study

NASA Astrophysics Data System (ADS)

Arantes, C.; de Araujo, M. T.; Taranto, A. G.; de M. Carneiro, J. W.

The semiempirical AM1 and PM3 methods, as well as the density functional (DFT/B3LYP) approach using the 6-31g(d) basis set, were employed to calculate the relative stability of intermediate radicals derived from artemisinin, a sesquiterpene lactone having an endoperoxide bridge that is essential for its antimalarial activity. The compounds studied have their nonperoxidic oxygen atom of the trioxane ring and/or the carbonyl group replaced by a CH2 unit. Relative stabilities were calculated by means of isodesmic equations using artemisinin as reference. It was found that replacement of oxygen atoms decreases the relative stability of the anionic radical intermediates. In contrast, for compounds with inverted stereochemistry the intermediate radicals were found to be more stable than those with the artemisinin-like stereochemistry. These relative stabilities may modulate the antimalarial potency. Radicals centered on carbon are always more stable than the corresponding radicals centered on oxygen.

Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases.

PubMed

Bukovsky, Antonin

2015-02-25

In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

Chemical composition and bioactivity of different oregano (Origanum vulgare) extracts and essential oil.

PubMed

Teixeira, Bárbara; Marques, António; Ramos, Cristina; Serrano, Carmo; Matos, Olívia; Neng, Nuno R; Nogueira, José M F; Saraiva, Jorge Alexandre; Nunes, Maria Leonor

2013-08-30

There is a growing interest in industry to replace synthetic chemicals by natural products with bioactive properties. Aromatic plants are excellent sources of bioactive compounds that can be extracted using several processes. As far as oregano is concerned, studies are lacking addressing the effect of extraction processes in bioactivity of extracts. This study aimed to characterise the in vitro antioxidant and antibacterial properties of oregano (Origanum vulgare) essential oil and extracts (in hot and cold water, and ethanol), and the chemical composition of its essential oil. The major components of oregano essential oil were carvacrol, β-fenchyl alcohol, thymol, and γ-terpinene. Hot water extract had the strongest antioxidant properties and the highest phenolic content. All extracts were ineffective in inhibiting the growth of the seven tested bacteria. In contrast, the essential oil inhibited the growth of all bacteria, causing greater reductions on both Listeria strains (L. monocytogenes and L. innocua). O. vulgare extracts and essential oil from Portuguese origin are strong candidates to replace synthetic chemicals used by the industry. © 2013 Society of Chemical Industry.

Genome Shrinkage and Loss of Nutrient-Providing Potential in the Obligate Symbiont of the Primitive Termite Mastotermes darwiniensis

PubMed Central

Huang, Charlie Ye; Arakawa, Gaku; Tokuda, Gaku; Lo, Nathan; Watanabe, Hirofumi

2012-01-01

Beneficial microbial associations with insects are common and are classified as either one or a few intracellular species that are vertically transmitted and reside intracellularly within specialized organs or as microbial assemblages in the gut. Cockroaches and termites maintain at least one if not both beneficial associations. Blattabacterium is a flavobacterial endosymbiont of nearly all cockroaches and the termite Mastotermes darwiniensis and can use nitrogenous wastes in essential amino acid and vitamin biosynthesis. Key changes during the evolutionary divergence of termites from cockroaches are loss of Blattabacterium, diet shift to wood, acquisition of a specialized hindgut microbiota, and establishment of advanced social behavior. Termite gut microbes collaborate to fix nitrogen, degrade lignocellulose, and produce nutrients, and the absence of Blattabacterium in nearly all termites suggests that its nutrient-provisioning role has been replaced by gut microbes. M. darwiniensis is a basal, extant termite that solely retains Blattabacterium, which would show evidence of relaxed selection if it is being supplanted by the gut microbiome. This termite-associated Blattabacterium genome is ∼8% smaller than cockroach-associated Blattabacterium genomes and lacks genes underlying vitamin and essential amino acid biosynthesis. Furthermore, the M. darwiniensis gut microbiome membership is more consistent between individuals and includes specialized termite gut-associated bacteria, unlike the more variable membership of cockroach gut microbiomes. The M. darwiniensis Blattabacterium genome may reflect relaxed selection for some of its encoded functions, and the loss of this endosymbiont in all remaining termite genera may result from its replacement by a functionally complementary gut microbiota. PMID:22020505

23 CFR 710.509 - Functional replacement of real property in public ownership.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Functional replacement of real property in public... Functional replacement of real property in public ownership. (a) General. When publicly owned real property...) Federal participation. Federal-aid funds may participate in functional replacement costs only if: (1...

Histone H2A is required for normal centromere function in Saccharomyces cerevisiae

PubMed Central

Pinto, Inés; Winston, Fred

2000-01-01

Histones are structural and functional components of the eukaryotic chromosome, and their function is essential for normal cell cycle progression. In this work, we describe the characterization of two Saccharomyces cerevisiae cold-sensitive histone H2A mutants. Both mutants contain single amino acid replacements of residues predicted to be on the surface of the nucleosome and in close contact with DNA. We show that these H2A mutations cause an increase-in-ploidy phenotype, an increased rate of chromosome loss, and a defect in traversing the G2–M phase of the cell cycle. Moreover, these H2A mutations show genetic interactions with mutations in genes encoding kinetochore components. Finally, chromatin analysis of these H2A mutants has revealed an altered centromeric chromatin structure. Taken together, these results strongly suggest that histone H2A is required for proper centromere–kinetochore function during chromosome segregation. PMID:10747028

Expanding the functional human mitochondrial DNA database by the establishment of primate xenomitochondrial cybrids

PubMed Central

Kenyon, Lesley; Moraes, Carlos T.

1997-01-01

The nuclear and mitochondrial genomes coevolve to optimize approximately 100 different interactions necessary for an efficient ATP-generating system. This coevolution led to a species-specific compatibility between these genomes. We introduced mitochondrial DNA (mtDNA) from different primates into mtDNA-less human cells and selected for growth of cells with a functional oxidative phosphorylation system. mtDNA from common chimpanzee, pigmy chimpanzee, and gorilla were able to restore oxidative phosphorylation in the context of a human nuclear background, whereas mtDNA from orangutan, and species representative of Old-World monkeys, New-World monkeys, and lemurs were not. Oxygen consumption, a sensitive index of respiratory function, showed that mtDNA from chimpanzee, pigmy chimpanzee, and gorilla replaced the human mtDNA and restored respiration to essentially normal levels. Mitochondrial protein synthesis was also unaltered in successful “xenomitochondrial cybrids.” The abrupt failure of mtDNA from primate species that diverged from humans as recently as 8–18 million years ago to functionally replace human mtDNA suggests the presence of one or a few mutations affecting critical nuclear–mitochondrial genome interactions between these species. These cellular systems provide a demonstration of intergenus mtDNA transfer, expand more than 20-fold the number of mtDNA polymorphisms that can be analyzed in a human nuclear background, and provide a novel model for the study of nuclear–mitochondrial interactions. PMID:9256447

Development of a ceramic surface replacement for the hip. An experimental Sialon model.

PubMed

Clarke, I C; Phillips, W; McKellop, H; Coster, I R; Hedley, A; Amstutz, H C

1979-01-01

The objective of this study was to investigate the design and fixation advantages of Sialon ceramic surface replacements implanted without acrylic bone cement. The biocompatibility and friction and wear properties of Sialon ceramic were compared with more conventional prosthetic materials such as stainless steel and alumina. A functional load-bearing canine hip surface replacement model was established to test Sialon femoral cups designed for fixation by bone ingrowth. The results of the polyethylene wear tests on highly polished ceramic and stainless steel counterfaces were essentially similar. These laboratory data indicated that the in-vivo polyethylene wear performance on metal or ceramic prosthetic surfaces could be expected to be indistinguishable, i.e. the ceramic/polyethylene combination would not offer any improved wear resistance in-vivo. It was found possible to get bone ingrowth into the macrokeying areas of the ceramic femoral cups but not into the microporous surfaces due to the presence of a fibrous membrane lining their internal surfaces. The biocompatability specimens also appeared to be invested with a fibrous membrane. Further studies are under way to determine the relationship between reaming procedures, micro motion at the interfaces and Sialon biocompatibility.

Cellular, ultrastructural and molecular analyses of epidermal cell development in the planarian Schmidtea mediterranea.

PubMed

Cheng, Li-Chun; Tu, Kimberly C; Seidel, Chris W; Robb, Sofia M C; Guo, Fengli; Sánchez Alvarado, Alejandro

2018-01-15

The epidermis is essential for animal survival, providing both a protective barrier and cellular sensor to external environments. The generally conserved embryonic origin of the epidermis, but the broad morphological and functional diversity of this organ across animals is puzzling. We define the transcriptional regulators underlying epidermal lineage differentiation in the planarian Schmidtea mediterranea, an invertebrate organism that, unlike fruitflies and nematodes, continuously replaces its epidermal cells. We find that Smed-p53, Sox and Pax transcription factors are essential regulators of epidermal homeostasis, and act cooperatively to regulate genes associated with early epidermal precursor cell differentiation, including a tandemly arrayed novel gene family (prog) of secreted proteins. Additionally, we report on the discovery of distinct and previously undescribed secreted organelles whose production is dependent on the transcriptional activity of soxP-3, and which we term Hyman vesicles. Copyright © 2017 Elsevier Inc. All rights reserved.

Nucleolus Precursor Bodies and Ribosome Biogenesis in Early Mammalian Embryos: Old Theories and New Discoveries.

PubMed

Fulka, Helena; Aoki, Fugaku

2016-06-01

In mammals, mature oocytes and early preimplantation embryos contain transcriptionally inactive structures termed nucleolus precursor bodies instead of the typical fibrillo-granular nucleoli. These nuclear organelles are essential and strictly of maternal origin. If they are removed from oocytes, the resulting embryos are unable to replace them and consequently fail to develop. Historically, nucleolus precursor bodies have been perceived as a passive repository site of nucleolar proteins that are required for embryos to form fully functional nucleoli. Recent results, however, contradict this long-standing dogma and show that these organelles are dispensable for nucleologenesis and ribosome biogenesis. In this article, we discuss the possible roles of nucleolus precursor bodies and propose how they might be involved in embryogenesis. Furthermore, we argue that these organelles are essential only shortly after fertilization and suggest that they might actively participate in centromeric chromatin establishment. © 2016 by the Society for the Study of Reproduction, Inc.

Different polyamine pathways from bacteria have replaced eukaryotic spermidine biosynthesis in ciliates Tetrahymena thermophila and Paramecium tetaurelia.

PubMed

Li, Bin; Kim, Sok Ho; Zhang, Yang; Hanfrey, Colin C; Elliott, Katherine A; Ealick, Steven E; Michael, Anthony J

2015-09-01

The polyamine spermidine is absolutely required for growth and cell proliferation in eukaryotes, due to its role in post-translational modification of essential translation elongation factor eIF5A, mediated by deoxyhypusine synthase. We have found that free-living ciliates Tetrahymena and Paramecium lost the eukaryotic genes encoding spermidine biosynthesis: S-adenosylmethionine decarboxylase (AdoMetDC) and spermidine synthase (SpdSyn). In Tetrahymena, they were replaced by a gene encoding a fusion protein of bacterial AdoMetDC and SpdSyn, present as three copies. In Paramecium, a bacterial homospermidine synthase replaced the eukaryotic genes. Individual AdoMetDC-SpdSyn fusion protein paralogues from Tetrahymena exhibit undetectable AdoMetDC activity; however, when two paralogous fusion proteins are mixed, AdoMetDC activity is restored and spermidine is synthesized. Structural modelling indicates a functional active site is reconstituted by sharing critical residues from two defective protomers across the heteromer interface. Paramecium was found to accumulate homospermidine, suggesting it replaces spermidine for growth. To test this concept, a budding yeast spermidine auxotrophic strain was found to grow almost normally with homospermidine instead of spermidine. Biosynthesis of spermidine analogue aminopropylcadaverine, but not exogenously provided norspermidine, correlated with some growth. Finally, we found that diverse single-celled eukaryotic parasites and multicellular metazoan Schistosoma worms have lost the spermidine biosynthetic pathway but retain deoxyhypusine synthase. © 2015 John Wiley & Sons Ltd.

Functionality of alternative protein in gluten-free product development.

PubMed

Deora, Navneet Singh; Deswal, Aastha; Mishra, Hari Niwas

2015-07-01

Celiac disease is an immune-mediated disease triggered in genetically susceptible individuals by ingested gluten from wheat, rye, barley, and other closely related cereal grains. The current treatment for celiac disease is life-long adherence to a strict gluten-exclusion diet. The replacement of gluten presents a significant technological challenge, as it is an essential structure-building protein, which is necessary for formulating high-quality baked goods. A major limitation in the production of gluten-free products is the lack of protein functionality in non-wheat cereals. Additionally, commercial gluten-free mixes usually contain only carbohydrates, which may significantly limit the amount of protein in the diet. In the recent past, various approaches are attempted to incorporate protein-based ingredients and to modify the functional properties for gluten-free product development. This review aims to the highlight functionality of the alternative protein-based ingredients, which can be utilized for gluten-free product development both functionally as well as nutritionally. © The Author(s) 2014.

Enabling access to new WHO essential medicines: the case for nicotine replacement therapies

PubMed Central

2010-01-01

Nicotine replacement therapies (NRT) are powerful tools for the successful treatment of nicotine addiction and tobacco use. The medicines are clinically effective, supported by the Framework Convention on Tobacco Control, and are now World Health Organization-approved essential medicines. Enabling global access to NRT remains a challenge given ongoing confusion and misperceptions about their efficacy, cost-effectiveness, and availability with respect to other tobacco control and public health opportunities. In this commentary, we review existing evidence and guidelines to make the case for global access to NRT highlighting the smoker's right to access treatment to sensibly address nicotine addiction. PMID:21092092

Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery

NASA Astrophysics Data System (ADS)

Rudolph, Karl Lenhard; Chang, Sandy; Millard, Melissa; Schreiber-Agus, Nicole; DePinho, Ronald A.

2000-02-01

Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.

Characterization of a nuclear localization signal in the foot-and-mouth disease virus polymerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez-Aparicio, Maria Teresa; Rosas, Maria Flora; Sobrino, Francisco, E-mail: fsobrino@cbm.uam.es

2013-09-15

We have experimentally tested whether the MRKTKLAPT sequence in FMDV 3D protein (residues 16 to 24) can act as a nuclear localization signal (NLS). Mutants with substitutions in two basic residues within this sequence, K18E and K20E, were generated. A decreased nuclear localization was observed in transiently expressed 3D and its precursor 3CD, suggesting a role of K18 and K20 in nuclear targeting. Fusion of MRKTKLAPT to the green fluorescence protein (GFP) increased the nuclear localization of GFP, which was not observed when GFP was fused to the 3D mutated sequences. These results indicate that the sequence MRKTKLAPT can bemore » functionally considered as a NLS. When introduced in a FMDV full length RNA replacements K18E and K20E led to production of revertant viruses that replaced the acidic residues introduced (E) by K, suggesting that the presence of lysins at positions 18 and 20 of 3D is essential for virus multiplication. - Highlights: • The FMDV 3D polymerase contains a nuclear localization signal. • Replacements K18E and K20E decrease nuclear localization of 3D and its precursor 3CD. • Fusion of the MRKTKLAPT 3D motif to GFP increases the nuclear localization of GFP. • Replacements K18E and K20E abolish the ability of MRKTKLAPT to relocate GFP. • RNAs harboring replacements K18E and K20E lead to recovery of revertant FMDVs.« less

The 10 Hz Frequency: A Fulcrum For Transitional Brain States

PubMed Central

Garcia-Rill, E.; D’Onofrio, S.; Luster, B.; Mahaffey, S.; Urbano, F. J.; Phillips, C.

2016-01-01

A 10 Hz rhythm is present in the occipital cortex when the eyes are closed (alpha waves), in the precentral cortex at rest (mu rhythm), in the superior and middle temporal lobe (tau rhythm), in the inferior olive (projection to cerebellar cortex), and in physiological tremor (underlying all voluntary movement). These are all considered resting rhythms in the waking brain which are “replaced” by higher frequency activity with sensorimotor stimulation. That is, the 10 Hz frequency fulcrum is replaced on the one hand by lower frequencies during sleep, or on the other hand by higher frequencies during volition and cognition. The 10 Hz frequency fulcrum is proposed as the natural frequency of the brain during quiet waking, but is replaced by higher frequencies capable of permitting more complex functions, or by lower frequencies during sleep and inactivity. At the center of the transition shifts to and from the resting rhythm is the reticular activating system, a phylogenetically preserved area of the brain essential for preconscious awareness. PMID:27547831

77 FR 24362 - Airworthiness Directives; Bombardier, Inc. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

... was prompted by reports of the air driven generator (ADG) failing to power essential buses during... essential buses which, in the event of an emergency, could prevent continued safe flight. DATES: This AD... prevent continued safe flight. This [TCCA] directive mandates the replacement of the ADG GCU. You may...

23 CFR 710.509 - Functional replacement of real property in public ownership.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Functional replacement is permitted under State law and the STD elects to provide it. (2) The property in... STD determination that functional replacement is in the public interest. (6) The real property is not...

23 CFR 710.509 - Functional replacement of real property in public ownership.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Functional replacement is permitted under State law and the STD elects to provide it. (2) The property in... STD determination that functional replacement is in the public interest. (6) The real property is not...

23 CFR 710.509 - Functional replacement of real property in public ownership.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Functional replacement is permitted under State law and the STD elects to provide it. (2) The property in... STD determination that functional replacement is in the public interest. (6) The real property is not...

Effectiveness of an interactive telerehabilitation system with home-based exercise training in patients after total hip or knee replacement: study protocol for a multicenter, superiority, no-blinded randomized controlled trial.

PubMed

Eichler, Sarah; Rabe, Sophie; Salzwedel, Annett; Müller, Steffen; Stoll, Josefine; Tilgner, Nina; John, Michael; Wegscheider, Karl; Mayer, Frank; Völler, Heinz

2017-09-21

Total hip or knee replacement is one of the most frequently performed surgical procedures. Physical rehabilitation following total hip or knee replacement is an essential part of the therapy to improve functional outcomes and quality of life. After discharge from inpatient rehabilitation, a subsequent postoperative exercise therapy is needed to maintain functional mobility. Telerehabilitation may be a potential innovative treatment approach. We aim to investigate the superiority of an interactive telerehabilitation intervention for patients after total hip or knee replacement, in comparison to usual care, regarding physical performance, functional mobility, quality of life and pain. This is an open, randomized controlled, multicenter superiority study with two prospective arms. One hundred and ten eligible and consenting participants with total knee or hip replacement will be recruited at admission to subsequent inpatient rehabilitation. After comprehensive, 3-week, inpatient rehabilitation, the intervention group performs a 3-month, interactive, home-based exercise training with a telerehabilitation system. For this purpose, the physiotherapist creates an individual training plan out of 38 different strength and balance exercises which were implemented in the system. Data about the quality and frequency of training are transmitted to the physiotherapist for further adjustment. Communication between patient and physiotherapist is possible with the system. The control group receives voluntary, usual aftercare programs. Baseline assessments are investigated after discharge from rehabilitation; final assessments 3 months later. The primary outcome is the difference in improvement between intervention and control group in 6-minute walk distance after 3 months. Secondary outcomes include differences in the Timed Up and Go Test, the Five-Times-Sit-to-Stand Test, the Stair Ascend Test, the Short-Form 36, the Western Ontario and McMaster Universities Osteoarthritis Index, the International Physical Activity Questionnaire, and postural control as well as gait and kinematic parameters of the lower limbs. Baseline-adjusted analysis of covariance models will be used to test for group differences in the primary and secondary endpoints. We expect the intervention group to benefit from the interactive, home-based exercise training in many respects represented by the study endpoints. If successful, this approach could be used to enhance the access to aftercare programs, especially in structurally weak areas. German Clinical Trials Register (DRKS), ID: DRKS00010009 . Registered on 11 May 2016.

DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

PubMed

Liu, Xiao; Dang, Yunkun; Matsu-Ura, Toru; He, Yubo; He, Qun; Hong, Christian I; Liu, Yi

2017-07-20

Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism. Published by Elsevier Inc.

Reovirus FAST Proteins Drive Pore Formation and Syncytiogenesis Using a Novel Helix-Loop-Helix Fusion-Inducing Lipid Packing Sensor

PubMed Central

Sarker, Muzaddid; de Antueno, Roberto; Langelaan, David N.; Parmar, Hiren B.; Shin, Kyungsoo; Rainey, Jan K.; Duncan, Roy

2015-01-01

Pore formation is the most energy-demanding step during virus-induced membrane fusion, where high curvature of the fusion pore rim increases the spacing between lipid headgroups, exposing the hydrophobic interior of the membrane to water. How protein fusogens breach this thermodynamic barrier to pore formation is unclear. We identified a novel fusion-inducing lipid packing sensor (FLiPS) in the cytosolic endodomain of the baboon reovirus p15 fusion-associated small transmembrane (FAST) protein that is essential for pore formation during cell-cell fusion and syncytiogenesis. NMR spectroscopy and mutational studies indicate the dependence of this FLiPS on a hydrophobic helix-loop-helix structure. Biochemical and biophysical assays reveal the p15 FLiPS preferentially partitions into membranes with high positive curvature, and this partitioning is impeded by bis-ANS, a small molecule that inserts into hydrophobic defects in membranes. Most notably, the p15 FLiPS can be functionally replaced by heterologous amphipathic lipid packing sensors (ALPS) but not by other membrane-interactive amphipathic helices. Furthermore, a previously unrecognized amphipathic helix in the cytosolic domain of the reptilian reovirus p14 FAST protein can functionally replace the p15 FLiPS, and is itself replaceable by a heterologous ALPS motif. Anchored near the cytoplasmic leaflet by the FAST protein transmembrane domain, the FLiPS is perfectly positioned to insert into hydrophobic defects that begin to appear in the highly curved rim of nascent fusion pores, thereby lowering the energy barrier to stable pore formation. PMID:26061049

[Indications and Borderline Indications for Medial Mobile Bearing Unicondylar Knee Replacement].

PubMed

Walker, T; Streit, M R; Streit, J; Gotterbarm, T; Aldinger, P R

2015-10-01

Beside the possibility of bicondylar knee replacement, patients with isolated anteromedial osteoarthritis also have the possibility of unicondylar knee replacement. Therefore some requirements are essential such as functionally intact cruciate and collateral ligaments, intact cartilage in the lateral compartment and an intraoperative flexion of more than 100°. An instability or contracture of the cruciate or collateral ligaments, a varus deformity more than 15°, a flexion deformity of more than 15°, an intraoperative flexion less than 100° as well as failed upper tibial osteotomy are seen as contraindications. In addition, a rheumatoid arthritis and a full thickness cartilage defect in the central part of the lateral compartment are seen as a contraindication because of the risk of a progression of the disease. With respect to these contraindications, excellent functional outcome and survival rates could be demonstrated in the long term. An expansion of these criteria, especially in patients with an insufficiency of the cruciate ligaments or after failed upper tibial osteotomy should only be done in certain cases after careful assessment of the benefits and risks. These patients should be informed about the lack of long-term results and the higher risk of complications. Quite commonly, the criteria of Kozinn and Scott are used for patient selection. These criteria were originally established for fixed-bearing prosthesis and have no relevance on mobile-bearing prosthesis. Criteria such as age, level of activity, weight, chondrocalcinosis and anterior knee pain have no effect on the clinical outcome or the long-term survival of a mobile-bearing prosthesis. Georg Thieme Verlag KG Stuttgart · New York.

Improvement of fatty acid profile and studio of rheological and technological characteristics in breads supplemented with flaxseed, soybean, and wheat bran flours.

PubMed

Osuna, Mariana B; Judis, María A; Romero, Ana M; Avallone, Carmen M; Bertola, Nora C

2014-01-01

Functional breads constitute an interesting alternative as vehicle of new essential fatty acids sources. The aim of this study was to improve the fatty acids (FA) profile of bakery products, producing breads with low saturated fatty acid (SFA) content and with high polyunsaturated fatty acid (PUFA) content, through partial substitution of wheat flour by other ingredients (soy flour, flax flour, and wheat bran) and to analyze the effect of this change on the technological, rheological, and sensorial characteristics of breads. Flaxseed flour (FF), soybeans flour (SF), or wheat bran (WB) was used to replace 50, 100, and 150 g kg(-1) of wheat flour (WF) in breads. FF or SF produced a decrease in monounsaturated and SFA and an increase of PUFA in these breads. Furthermore, breads replaced with FF presented considerable increase in the content of n3 FA, while, SF or WB contributed to rise of linoleic and oleic FA, respectively. The substitution percentage increase of FF, SF, or WB to formulation produced changes in the colour, rheological, textural, and technological characteristics of breads. This replacement resulted in improved lipid profile, being breads with 50 g kg(-1) SF, the better acceptance, baking features, and enhanced fatty acid profile.

Improvement of Fatty Acid Profile and Studio of Rheological and Technological Characteristics in Breads Supplemented with Flaxseed, Soybean, and Wheat Bran Flours

PubMed Central

Osuna, Mariana B.; Judis, María A.; Romero, Ana M.; Avallone, Carmen M.; Bertola, Nora C.

2014-01-01

Functional breads constitute an interesting alternative as vehicle of new essential fatty acids sources. The aim of this study was to improve the fatty acids (FA) profile of bakery products, producing breads with low saturated fatty acid (SFA) content and with high polyunsaturated fatty acid (PUFA) content, through partial substitution of wheat flour by other ingredients (soy flour, flax flour, and wheat bran) and to analyze the effect of this change on the technological, rheological, and sensorial characteristics of breads. Flaxseed flour (FF), soybeans flour (SF), or wheat bran (WB) was used to replace 50, 100, and 150 g kg−1 of wheat flour (WF) in breads. FF or SF produced a decrease in monounsaturated and SFA and an increase of PUFA in these breads. Furthermore, breads replaced with FF presented considerable increase in the content of n3 FA, while, SF or WB contributed to rise of linoleic and oleic FA, respectively. The substitution percentage increase of FF, SF, or WB to formulation produced changes in the colour, rheological, textural, and technological characteristics of breads. This replacement resulted in improved lipid profile, being breads with 50 g kg−1 SF, the better acceptance, baking features, and enhanced fatty acid profile. PMID:25478592

Ecological structure and function differs between habitats dominated by seagrasses and green seaweeds.

PubMed

Tuya, Fernando; Png-Gonzalez, Lydia; Riera, Rodrigo; Haroun, Ricardo; Espino, Fernando

2014-07-01

Marine vegetated habitats, e.g. seagrass meadows, deliver essential functions and services to coastal ecosystems and human welfare. Impacts induced by humans, however, have facilitated the replacement of seagrasses by alternative vegetation, e.g. green rhizophytic seaweeds. The implications of habitat shifts for ecosystem attributes and processes and the services they deliver remain poorly known. In this study, we compared ecosystem structure and function between Cymodocea nodosa seagrass meadows and bottoms dominated by Caulerpa prolifera, a green, native, rhizophytic seaweed, through 5 ecological proxies: (i) primary production (via community metabolism), (ii) composition and abundance of epifauna (a proxy for provision of habitat for epifauna), composition and abundance of (iii) small-sized (juvenile) and (iv) large-sized (adult) fishes (proxies for provision of habitat for fishes), and (v) sediment retention (a proxy for sediment stabilization). Four of these proxies were greater in C. nodosa seagrass meadows than in C. prolifera beds: gross primary productivity (∼1.4 times), the total abundance, species density and biomass of small-sized fishes (∼2.1, 1.3 and 1.3 times, respectively), the total abundance and species density of large-sized fishes (∼3.6 and 1.5 times, respectively), and sediment stabilization (∼1.4 times). In contrast, the total abundance and species density of epifauna was larger (∼3.1 and 1.7 times, respectively) in C. prolifera than in C. nodosa seagrass beds. These results suggest that ecosystem structure and function may differ if seagrasses are replaced by green rhizophytic seaweeds. Importantly, ecosystem functions may not be appropriate surrogates for one another. As a result, assessments of ecosystem services associated with ecosystem functions cannot be based on exclusively one service that is expected to benefit other services. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of essential histidine residues in the active site of Escherichia coli xylose (glucose) isomerase.

PubMed Central

Batt, C A; Jamieson, A C; Vandeyar, M A

1990-01-01

Two conserved histidine residues (His-101 and His-271) appear to be essential components in the active site of the enzyme xylose (glucose) isomerase (EC 5.3.1.5). These amino acid residues were targeted for mutagenesis on the basis of sequence homology among xylose isomerases isolated from Escherichia coli, Bacillus subtilis, Ampullariella sp. strain 3876, and Streptomyces violaceus-niger. Each residue was selectively replaced by site-directed mutagenesis and shown to be essential for activity. No measurable activity was observed for any mutations replacing either His-101 or His-271. Circular dichroism measurements revealed no significant change in the overall conformation of the mutant enzymes, and all formed dimers similar to the wild-type enzyme. Mutations at His-271 could be distinguished from those at His-101, since the former resulted in a thermolabile protein whereas no significant change in heat stability was observed for the latter. Based upon these results and structural data recently reported, we speculate that His-101 is the catalytic base mediating the reaction. Replacement of His-271 may render the enzyme thermolabile, since this residue appears to be a ligand for one of the metal ions in the active site of the enzyme. Images PMID:2405386

The Ω-loop lid domain of phosphoenolpyruvate carboxykinase is essential for catalytic function

PubMed Central

Johnson, Troy A.; Holyoak, Todd

2012-01-01

Phosphoenolpyruvate carboxykinase (PEPCK) is an essential metabolic enzyme operating in the gluconeogenesis and glyceroneogenesis pathways. Recent studies have demonstrated that the enzyme contains a mobile active site lid domain that transitions between an open/disorded conformation to a closed/ordered conformation as the enzyme progresses through the catalytic cycle. The understanding of how this mobile domain functions in catalysis is incomplete. Previous studies show that the closure of the lid domain stabilizes the reaction intermediate and protects the reactive intermediate from spurious protonation and thus contributes to the fidelity of the enzyme. In order to more fully investigate the roles of the lid domain in PEPCK function we created three mutations that replaced the 11-residue lid domain with one, two or three glycine residues. Kinetic analysis of the mutant enzymes demonstrates that none of the enzyme constructs exhibit any measurable kinetic activity resulting in a decrease in the catalytic parameters by at least 106. Structural characterization of the mutants in complexes representing the catalytic cycle suggest that the inactivity is due to a role for the lid domain in the formation of the fully closed state of the enzyme that is required for catalytic function. In the absence of the lid domain, the enzyme is unable to achieve the fully closed state and is rendered inactive despite possessing all of the residues and substrates required for catalytic function. This work demonstrates how enzyme catalytic function can be abolished through the alteration of conformational equilibria despite all elements required for chemical conversion of substrates to products remaining intact. PMID:23127136

Applications of CRISPR/Cas9 technology for targeted mutagenesis, gene replacement and stacking of genes in higher plants.

PubMed

Luo, Ming; Gilbert, Brian; Ayliffe, Michael

2016-07-01

Mutagenesis continues to play an essential role for understanding plant gene function and, in some instances, provides an opportunity for plant improvement. The development of gene editing technologies such as TALENs and zinc fingers has revolutionised the targeted mutation specificity that can now be achieved. The CRISPR/Cas9 system is the most recent addition to gene editing technologies and arguably the simplest requiring only two components; a small guide RNA molecule (sgRNA) and Cas9 endonuclease protein which complex to recognise and cleave a specific 20 bp target site present in a genome. Target specificity is determined by complementary base pairing between the sgRNA and target site sequence enabling highly specific, targeted mutation to be readily engineered. Upon target site cleavage, error-prone endogenous repair mechanisms produce small insertion/deletions at the target site usually resulting in loss of gene function. CRISPR/Cas9 gene editing has been rapidly adopted in plants and successfully undertaken in numerous species including major crop species. Its applications are not restricted to mutagenesis and target site cleavage can be exploited to promote sequence insertion or replacement by recombination. The multiple applications of this technology in plants are described.

A framework for geometry acquisition, 3-D printing, simulation, and measurement of head-related transfer functions with a focus on hearing-assistive devices

PubMed Central

Harder, Stine; Paulsen, Rasmus R.; Larsen, Martin; Laugesen, Søren; Mihocic, Michael; Majdak, Piotr

2017-01-01

Individual head-related transfer functions (HRTFs) are essential in applications like fitting hearing-assistive devices (HADs) for providing accurate sound localization performance. Individual HRTFs are usually obtained through intricate acoustic measurements. This paper investigates the use of a three-dimensional (3D) head model for acquisition of individual HRTFs. Two aspects were investigated; whether a 3D-printed model can replace measurements on a human listener and whether numerical simulations can replace acoustic measurements. For this purpose, HRTFs were acoustically measured for four human listeners and for a 3D printed head model of one of these listeners. Further, HRTFs were simulated by applying the finite element method to the 3D head model. The monaural spectral features and spectral distortions were very similar between re-measurements and between human and printed measurements, however larger deviations were observed between measurement and simulation. The binaural cues were in agreement among all HRTFs of the same listener, indicating that the 3D model is able to provide localization cues potentially accessible to HAD users. Hence, the pipeline of geometry acquisition, printing, and acoustic measurements or simulations, seems to be a promising step forward towards in-silico design of HADs. PMID:28239188

Site-directed mutagenesis of the regulatory light-chain Ca2+/Mg2+ binding site and its role in hybrid myosins

NASA Astrophysics Data System (ADS)

Reinach, Fernando C.; Nagai, Kiyoshi; Kendrick-Jones, John

1986-07-01

The regulatory light chains, small polypeptides located on the myosin head, regulate the interaction of myosin with actin in response to either Ca2+ or phosphorylation. The demonstration that the regulatory light chains on scallop myosin can be replaced by light chains from other myosins has allowed us to compare the functional capabilities of different light chains1, but has not enabled us to probe the role of features, such as the Ca2+/Mg2+ binding site, that are common to all of them. Here, we describe the use of site-directed mutagenesis to study the function of that site. We synthesized the chicken skeletal myosin light chain in Escherichia coli and constructed mutants with substitutions within the Ca2+/Mg2+ binding site. When the aspartate residues at the first and sixth Ca2+ coordination positions are replaced by uncharged alanines, the light chains have a reduced Ca2+ binding capacity but still bind to scallop myosin with high affinity. Unlike the wild-type skeletal light chain which inhibits myosin interaction with actin, the mutants activate it. Thus, an intact Ca2+/Mg2+ binding site in the N-terminal region of the light chain is essential for regulating the interaction of myosin with actin.

Importance of individual amino acids in the Switch I region in eEF2 studied by functional complementation in S. cerevisiae.

PubMed

Bartish, Galyna; Nygård, Odd

2008-05-01

Elongation factor 2 (eEF2) is a member of the G-protein super family. G-proteins undergo conformational changes associated with binding of the guanosine nucleotide and hydrolysis of the bound GTP. These structural rearrangements affects the Switch I region (also known as the Effector loop). We have studied the role of individual amino acids in the Switch I region (amino acids 25-73) of S. cerevisiae eEF2 using functional complementation in yeast. 21 point mutations in the Switch I region were created by site-directed mutagenesis. Mutants K49R, E52Q, A53G, F55Y, K60R, Q63A, T68S, I69M and A73G were functional while mutants R54H, F55N, D57A, D57E, D57S, R59K, R59M, Q63E, R65A, R65N, T68A and T68M were inactive. Expression of mutants K49R, A53G, Q63A, I69M and A73G was associated with markedly decreased growth rates and yeast cells expressing mutants A53G and I69M became temperature sensitive. The functional capacity of eEF2 in which the major part Switch I (amino acids T56 to I69) was converted into the homologous sequence found in EF-G from E. coli was also studied. This protein chimera could functionally replace yeast eEF2 in vivo. Yeast cells expressing this mutant grew extremely slowly, showed increased cell death and became temperature sensitive. The ability of the mutant to replace authentic eEF2 in vivo indicates that the structural rearrangement of Switch I necessary for eEF2 function is similar in eukaryotes and bacteria. The effect of two point mutations in the P-loop was also studied. Mutant A25G but not A25V could functionally replace yeast eEF2 even if cells expressing the mutant grew slowly. The A25G mutation converted the consensus sequences AXXXXGK[T/S] in eEF2 to the corresponding motif GXXXXGK[T/S] found in all other G-proteins, suggesting that the alanine found in the P-loop of peptidyltranslocases are not essential for function.

Effects of dietary supplementation of red pepper (Schinus terebinthifolius Raddi) essential oil on performance, small intestinal morphology and microbial counts of weanling pigs.

PubMed

Cairo, Pedro Leon Gomes; Gois, Franz Dias; Sbardella, Maicon; Silveira, Hebert; de Oliveira, Roberto Maciel; Allaman, Ivan Bezerra; Cantarelli, Vinicius Souza; Costa, Leandro Batista

2018-01-01

Many strategies, such as the antibiotic growth promoters, have been developed to improve intestinal health and performance of newly weaned piglets. Natural products such as essential oils have been scientifically recognized as growth enhancer feed additives for weanling pigs, replacing the antibiotics. Therefore, it has been hypothesized that Brazilian red pepper could replace performance-enhancing antibiotics also in weanling pig diets. However, one experiment was conducted to determine the effects of dietary Brazilian red pepper essential oil or antimicrobial growth promoter on intestinal health and growth performance of weanling pigs. No effects of treatments were observed on performance and organ weights (P > 0.05). Overall, both additives [red pepper essential oil (RPEO) or antibiotic (ANT)] increased gut Lactobacillus counts compared to negative control, as well as reduced villi density (P < 0.05). Animals fed diets containing 1.5 g kg -1 RPEO presented the lowest incidence of diarrhea (P < 0.05). Our findings suggested that essential oil from Brazilian red pepper or chlorohydroxyquinoline added in weanling pig diets affect gut microbiota and histology without affecting performance and organ weights. In addition, there was an indication that high doses of essential oil could reduce the incidence of diarrhea. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Effect of dietary fiber on properties and acceptance of meat products: a review.

PubMed

Talukder, Suman

2015-01-01

Meat is an important source of all essential nutritional components of our daily diet as it content most of the essential amino acids, fatty acids, vitamins, and minerals which are lack in plant based food, but it is devoid of dietary fiber, which is very essential component for normal physiological/biochemical process. During meat products processing, its functional values can be improved by supplementation of dietary fiber rich vegetative substances like cereal and pulse flour, vegetable and fruits pulp, etc. by this process, a significant proportion of required daily allowance of dietary fiber can be fulfilled for the frequent meat consumers. The consumption of meat products fortified with of dietary fiber can lead to the prevention of diseases like coronary heart disease, diabetes, irritable bowel disease, obesity, etc. On the other hand, the dietary fiber can effectively be incorporated in the processed meat products as binders, extender, and filler, they can significantly replace the unhealthy fat components from the products; increase acceptability by improving nutritional components, pH, water-holding capacity, emulsion stability, shear press value, sensory characters, etc. of finished products. Addition of dietary fiber in the meat products can increase the cooking yield therefore the economic gain as well.

Dissecting CNBP, a zinc-finger protein required for neural crest development, in its structural and functional domains.

PubMed

Armas, Pablo; Agüero, Tristán H; Borgognone, Mariana; Aybar, Manuel J; Calcaterra, Nora B

2008-10-17

Cellular nucleic-acid-binding protein (CNBP) plays an essential role in forebrain and craniofacial development by controlling cell proliferation and survival to mediate neural crest expansion. CNBP binds to single-stranded nucleic acids and displays nucleic acid chaperone activity in vitro. The CNBP family shows a conserved modular organization of seven Zn knuckles and an arginine-glycine-glycine (RGG) box between the first and second Zn knuckles. The participation of these structural motifs in CNBP biochemical activities has still not been addressed. Here, we describe the generation of CNBP mutants that dissect the protein into regions with structurally and functionally distinct properties. Mutagenesis approaches were followed to generate: (i) an amino acid replacement that disrupted the fifth Zn knuckle; (ii) N-terminal deletions that removed the first Zn knuckle and the RGG box, or the RGG box alone; and (iii) a C-terminal deletion that eliminated the three last Zn knuckles. Mutant proteins were overexpressed in Escherichia coli, purified, and used to analyze their biochemical features in vitro, or overexpressed in Xenopus laevis embryos to study their function in vivo during neural crest cell development. We found that the Zn knuckles are required, but not individually essential, for CNBP biochemical activities, whereas the RGG box is essential for RNA-protein binding and nucleic acid chaperone activity. Removal of the RGG box allowed CNBP to preserve a weak single-stranded-DNA-binding capability. A mutant mimicking the natural N-terminal proteolytic CNBP form behaved as the RGG-deleted mutant. By gain-of-function and loss-of-function experiments in Xenopus embryos, we confirmed the participation of CNBP in neural crest development, and we demonstrated that the CNBP mutants lacking the N-terminal region or the RGG box alone may act as dominant negatives in vivo. Based on these data, we speculate about the existence of a specific proteolytic mechanism for the regulation of CNBP biochemical activities during neural crest development.

Conceptualising time before surgery: The experience of patients waiting for hip replacement

PubMed Central

Johnson, Emma C.; Horwood, Jeremy; Gooberman-Hill, Rachael

2014-01-01

Interpretations of time underlie patients' experiences of illness and the way in which the National Health Service (NHS) is organised. In the NHS, achieving short waiting times for treatment is seen as important, and this is particularly evident in relation to chronic conditions where the time waiting in care from onset of symptoms to successful management can last months and years. One example of a chronic condition with high prevalence is osteoarthritis, estimated to affect 10% of people aged over 55 years in the UK. Osteoarthritis of the hip is particularly common, and treatments include exercise and medication. If these options do not provide enough relief from pain and functional difficulties, then joint replacement may be considered. With over 70,000 such operations conducted every year in England and Wales, processes relating to waiting times impact on many patients. This article explores how 24 patients with osteoarthritis experience time during the lead up to hip replacement surgery. We draw on data collected during longitudinal in-depth interviews with patients a median of 9.5 days before surgery and at two to four weeks post-operatively. Transcripts of audio-recorded interviews were imported into Atlas.ti® and inductive thematic analysis undertaken. Increasing pain and deterioration in function altered the experience of time during the journey towards hip replacement. Patients made essential changes to how they filled their days. They experienced lost and wasted time and faced disruption to the temporal order of their lives. A surgical date marked in the calendar became their focus. However, this date was not static, moving because of changing perceptions of duration and real-time alterations by the healthcare system. Findings highlight that patients' experience of time is complex and multi-dimensional and does not reflect the linear, monochronic conceptualisation of time embedded in the healthcare system. PMID:24997442

Conceptualising time before surgery: the experience of patients waiting for hip replacement.

PubMed

Johnson, Emma C; Horwood, Jeremy; Gooberman-Hill, Rachael

2014-09-01

Interpretations of time underlie patients' experiences of illness and the way in which the National Health Service (NHS) is organised. In the NHS, achieving short waiting times for treatment is seen as important, and this is particularly evident in relation to chronic conditions where the time waiting in care from onset of symptoms to successful management can last months and years. One example of a chronic condition with high prevalence is osteoarthritis, estimated to affect 10% of people aged over 55 years in the UK. Osteoarthritis of the hip is particularly common, and treatments include exercise and medication. If these options do not provide enough relief from pain and functional difficulties, then joint replacement may be considered. With over 70,000 such operations conducted every year in England and Wales, processes relating to waiting times impact on many patients. This article explores how 24 patients with osteoarthritis experience time during the lead up to hip replacement surgery. We draw on data collected during longitudinal in-depth interviews with patients a median of 9.5 days before surgery and at two to four weeks post-operatively. Transcripts of audio-recorded interviews were imported into Atlas.ti(®) and inductive thematic analysis undertaken. Increasing pain and deterioration in function altered the experience of time during the journey towards hip replacement. Patients made essential changes to how they filled their days. They experienced lost and wasted time and faced disruption to the temporal order of their lives. A surgical date marked in the calendar became their focus. However, this date was not static, moving because of changing perceptions of duration and real-time alterations by the healthcare system. Findings highlight that patients' experience of time is complex and multi-dimensional and does not reflect the linear, monochronic conceptualisation of time embedded in the healthcare system. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Friendly fire: redirecting herpes simplex virus-1 for therapeutic applications.

PubMed

Advani, S J; Weichselbaum, R R; Whitley, R J; Roizman, B

2002-09-01

Herpes simplex virus-1 (HSV-1) is a relatively large double-stranded DNA virus encoding at least 89 proteins with well characterized disease pathology. An understanding of the functions of viral proteins together with the ability to genetically engineer specific viral mutants has led to the development of attenuated HSV-1 for gene therapy. This review highlights the progress in creating attenuated genetically engineered HSV-1 mutants that are either replication competent (viral non-essential gene deleted) or replication defective (viral essential gene deleted). The choice between a replication-competent or -defective virus is based on the end-goal of the therapeutic intervention. Replication-competent HSV-1 mutants have primarily been employed as antitumor oncolytic viruses, with the lytic nature of the virus harnessed to destroy tumor cells selectively. In replacement gene therapy, replication-defective viruses have been utilized as delivery vectors. The advantages of HSV-1 vectors are that they infect quiescent and dividing cells efficiently and can encode for relatively large transgenes.

Facial Gunshot Wounds: Trends in Management

PubMed Central

Kaufman, Yoav; Cole, Patrick; Hollier, Larry H.

2009-01-01

Facial gunshot wounds, often comprising significant soft and bone tissue defects, pose a significant challenge for reconstructive surgeons. Whether resulting from assault, accident, or suicide attempt, a thorough assessment of the defects is essential for devising an appropriate tissue repair and replacement with a likely secondary revision. Immediately after injury, management is centered on advanced trauma life support with patient stabilization as the primary goal. Thorough examination along with appropriate imaging is critical for identifying any existing defects. Whereas past surgical management advocated delayed definitive treatment using serial debridement, today’s management favors use of more immediate reconstruction. Recent advances in microsurgical technique have shifted favor from local tissue advancement to distant free flap transfers, which improve cosmesis and function. This has resulted in a lower number of surgeries required to achieve reconstruction. Because of the diversity of injury and the complexity of facial gunshot injuries, a systematic algorithm is essential to help manage the different stages of healing and to ensure that the best outcome is achieved. PMID:22110801

2.4 Å resolution crystal structure of human TRAP1NM, the Hsp90 paralog in the mitochondrial matrix.

PubMed

Sung, Nuri; Lee, Jungsoon; Kim, Ji Hyun; Chang, Changsoo; Tsai, Francis T F; Lee, Sukyeong

2016-08-01

TRAP1 is an organelle-specific Hsp90 paralog that is essential for neoplastic growth. As a member of the Hsp90 family, TRAP1 is presumed to be a general chaperone facilitating the late-stage folding of Hsp90 client proteins in the mitochondrial matrix. Interestingly, TRAP1 cannot replace cytosolic Hsp90 in protein folding, and none of the known Hsp90 co-chaperones are found in mitochondria. Thus, the three-dimensional structure of TRAP1 must feature regulatory elements that are essential to the ATPase activity and chaperone function of TRAP1. Here, the crystal structure of a human TRAP1NM dimer is presented, featuring an intact N-domain and M-domain structure, bound to adenosine 5'-β,γ-imidotriphosphate (ADPNP). The crystal structure together with epitope-mapping results shows that the TRAP1 M-domain loop 1 contacts the neighboring subunit and forms a previously unobserved third dimer interface that mediates the specific interaction with mitochondrial Hsp70.

Effects of fire on small mammal communities in frequent-fire forests in California

USGS Publications Warehouse

Roberts, Susan L.; Kelt, Douglas A.; Van Wagtendonk, Jan W.; Miles, A. Keith; Meyer, Marc D.

2015-01-01

Fire is a natural, dynamic process that is integral to maintaining ecosystem function. The reintroduction of fire (e.g., prescribed fire, managed wildfire) is a critical management tool for protecting many frequent-fire forests against stand-replacing fires while restoring an essential ecological process. Understanding the effects of fire on forests and wildlife communities is important in natural resource planning efforts. Small mammals are key components of forest food webs and essential to ecosystem function. To investigate the relationship of fire to small mammal assemblages, we live trapped small mammals in 10 burned and 10 unburned forests over 2 years in the central Sierra Nevada, California. Small mammal abundance was higher in unburned forests, largely reflecting the greater proportion of closed-canopy species such as Glaucomys sabrinus in unburned forests. The most abundant species across the entire study area was the highly adaptable generalist species, Peromyscus maniculatus. Species diversity was similar between burned and unburned forests, but burned forests were characterized by greater habitat heterogeneity and higher small mammal species evenness. The use and reintroduction of fire to maintain a matrix of burn severities, including large patches of unburned refugia, creates a heterogeneous and resilient landscape that allows for fire-sensitive species to proliferate and, as such, may help maintain key ecological functions and diverse small mammal assemblages.

Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy.

PubMed

Beer, Meinrad; Weidemann, Frank; Breunig, Frank; Knoll, Anita; Koeppe, Sabrina; Machann, Wolfram; Hahn, Dietbert; Wanner, Christoph; Strotmann, Jörg; Sandstede, Jörn

2006-05-15

The present study evaluated the evolution of cardiac morphology, function, and late enhancement as a noninvasive marker of myocardial fibrosis, and their inter-relation during enzyme replacement therapy in patients with Fabry's disease using magnetic resonance imaging and color Doppler myocardial imaging. Late enhancement, which was present in up to 50% of patients, was associated with increased left ventricular mass, the failure of a significant regression of hypertrophy during enzyme replacement therapy, and worse segmental myocardial function. Late enhancement may predict the effect of enzyme replacement therapy on left ventricular mass and cardiac function.

Full-arch implant-retained prosthetics in general dental practice.

PubMed

Rosenbaum, Nigel

2012-03-01

The loss of all teeth from one or both dental arches is a significant disability affecting self-confidence, communication, masticatory function and aesthetics. Whilst missing teeth cannot be restored to the natural state, the development of a prosthetic dentition has been a goal of dental science throughout the centuries. Contemporary techniques allow for the replacement of missing dentition with fixed or removable solutions, solving many of the problems. Implant dentistry has transformed this area of medicine. This article provides dental practitioners with an overview of this important area of patient care. Dental practitioners in clinical practice will frequently see edentulism; a good understanding of the available options for rehabilitation is essential.

[Unusual infection complication of total hip arthroplasty].

PubMed

Jány, R; Vojtassák, J; Lisý, M; Almási, J

2005-01-01

Authors present the case history of a 66-year old patient after repeated reimplantations of the THA with a deep infect caused by a rare aetiological agent (Serratia marcescens) associated with a pyogenic sinus. They describe the disease history, therapeutic procedure, complications associated with the surgery as well as postoperative course after the reimplantation of a customized total hip replacement. In the conclusion they state that in case of an infected total hip arthroplasty the treatment is focused on the salvage of the infection process and preservation of the function of the affected limb. Of essential importance is surgical revision with a radical removal of necrotic tissues and hardware in combination with an intensive parenteral antibiotic administration.

Formation of Protoplasts from Resting Spores

PubMed Central

Fitz-James, Philip C.

1971-01-01

Coat-stripped spores suspended in hypertonic solutions and supplied with two essential cations can be converted into viable protoplasts by lysozyme digestion of both cortex and germ cell wall. Calcium ions are necessary to prevent membrane rupture, and magnesium ions are necessary for changes indicative of hydration of the core, particularily the nuclear mass. Since remnant spore coat covered such protoplasts of Bacillus subtilis and the germ cell wall of B. cereus spores is not lysozyme digestible, coatless spores of B. megaterium KM were more useful for these studies. Lysozyme digestion in cation-free environment produced a peculiar semi-refractile spore core free of a cortex but prone to rapid hydration and lytic changes on the addition of cations. Strontium could replace Ca2+ but Mn2+ could not replace Mg2+ in these digestions. When added to the spores, dipicolinic acid and other chelates appeared to compete with the membrane for the calcium needed for stabilization during lysozyme conversion to protoplasts. It is argued that calcium could function to stabilize the inner membrane anionic groups over the anhydrous dipicolinic acid-containing core of resting spores. Images PMID:4995380

Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival.

PubMed

Princiotta, M F; Schubert, U; Chen, W; Bennink, J R; Myung, J; Crews, C M; Yewdell, J W

2001-01-16

The proteasome is the primary protease used by cells for degrading proteins and generating peptide ligands for class I molecules of the major histocompatibility complex. Based on the properties of cells adapted to grow in the presence of the proteasome inhibitor 4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone (NLVS), it was proposed that proteasomes can be replaced by alternative proteolytic systems, particularly a large proteolytic complex with a tripeptidyl peptidase II activity. Here we show that NLVS-adapted cells retain sensitivity to a number of highly specific proteasome inhibitors with regard to antigenic peptide generation, accumulation of polyubiquitinated proteins, degradation of p53, and cell viability. In addition, we show that in the same assays (with a single minor exception), NLVS-adapted cells are about as sensitive as nonselected cells to Ala-Ala-Phe-chloromethylketone, a specific inhibitor of tripeptidyl peptidase II activity. Based on these findings, we conclude that proteasomes still have essential proteolytic functions in adapted cells that are not replaced by Ala-Ala-Phe-chloromethylketone-sensitive proteases.

Drosophila Glypicans Regulate Follicle Stem Cell Maintenance and Niche Competition.

PubMed

Su, Tsu-Yi; Nakato, Eriko; Choi, Pui Yee; Nakato, Hiroshi

2018-04-09

Adult stem cells reside in specialized microenvironments, called niches, which provide signals for stem cells to maintain their undifferentiated and self-renewing state. To maintain stem cell quality, several types of stem cells are known to be regularly replaced by progenitor cells through niche competition. However, the cellular and molecular bases for stem cell competition for niche occupancy are largely unknown. Here, we show that two Drosophila members of the glypican family of heparan sulfate proteoglycans (HSPGs), Dally and Dally-like (Dlp), differentially regulate follicle stem cell (FSC) maintenance and FSC competitiveness for niche occupancy. Lineage analyses of glypican mutant FSC clones showed that dally is essential for normal FSC maintenance. In contrast, dlp is a hyper-competitive mutation: dlp mutant FSC progenitors often eventually occupy the entire epithelial sheet. RNAi knockdown experiments showed that Dally and Dlp play both partially redundant and distinct roles in regulating Jak/Stat, Wg and Hh signaling in FSCs. The Drosophila FSC system offers a powerful genetic model to study the mechanisms by which HSPGs exert specific functions in stem cell replacement and competition. Copyright © 2018, Genetics.

Cellular FLIP can substitute for the herpes simplex virus type 1 latency-associated transcript gene to support a wild-type virus reactivation phenotype in mice

PubMed Central

Jin, Ling; Carpenter, Dale; Moerdyk-Schauwecker, Megan; Vanarsdall, Adam L; Osorio, Nelson; Hsiang, Chinhui; Jones, Clinton; Wechsler, Steven L

2010-01-01

Latency-associated transcript (LAT) deletion mutants of herpes simplex virus type 1 (HSV-1) have reduced reactivation phenotypes. Thus, LAT plays an essential role in the latency-reactivation cycle of HSV-1. We have shown that LAT has antiapoptosis activity and demonstrated that the chimeric virus, dLAT-cpIAP, resulting from replacing LAT with the baculovirus antiapoptosis gene cpIAP, has a wild-type HSV-1 reactivation phenotype in mice and rabbits. Thus, LAT can be replaced by an alternative antiapoptosis gene, confirming that LAT’s antiapoptosis activity plays an important role in the mechanism by which LAT enhances the virus’ reactivation phenotype. However, because cpIAP interferes with both of the major apoptosis pathways, these studies did not address whether LAT’s proreactivation phenotype function was due to blocking the extrinsic (Fas-ligand–, caspase-8–, or caspase-10–dependent pathway) or the intrinsic (mitochondria-, caspase-9–dependent pathway) pathway, or whether both pathways must be blocked. Here we constructed an HSV-1 LAT(−) mutant that expresses cellular FLIP (cellular FLICE-like inhibitory protein) under control of the LAT promoter and in place of LAT nucleotides 76 to 1667. Mice were ocularly infected with this mutant, designated dLAT-FLIP, and the reactivation phenotype was determined using the trigeminal ganglia explant model. dLAT-FLIP had a reactivation phenotype similar to wild-type virus and significantly higher than the LAT(−) mutant dLAT2903. Thus, the LAT function responsible for enhancing the reactivation phenotype could be replaced with an antiapoptosis gene that primarily blocks the extrinsic signaling apoptosis pathway. PMID:18989818

Optimizing the specificity of nucleic acid hybridization.

PubMed

Zhang, David Yu; Chen, Sherry Xi; Yin, Peng

2012-01-22

The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biological and biotechnological reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temperature. Here, we analytically derived the thermodynamic properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temperature, salt and concentration conditions. We rationally designed 'toehold exchange' probes that approximate these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogues with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg(2+) to 47 mM Mg(2+), and with nucleic acid concentrations from 1 nM to 5 µM. Experiments with RNA also showed effective single-base change discrimination.

Ribosomal proteins S12 and S13 function as control elements for translocation of the mRNA:tRNA complex.

PubMed

Cukras, Anthony R; Southworth, Daniel R; Brunelle, Julie L; Culver, Gloria M; Green, Rachel

2003-08-01

Translocation of the mRNA:tRNA complex through the ribosome is promoted by elongation factor G (EF-G) during the translation cycle. Previous studies established that modification of ribosomal proteins with thiol-specific reagents promotes this event in the absence of EF-G. Here we identify two small subunit interface proteins S12 and S13 that are essential for maintenance of a pretranslocation state. Omission of these proteins using in vitro reconstitution procedures yields ribosomal particles that translate in the absence of enzymatic factors. Conversely, replacement of cysteine residues in these two proteins yields ribosomal particles that are refractive to stimulation with thiol-modifying reagents. These data support a model where S12 and S13 function as control elements for the more ancient rRNA- and tRNA-driven movements of translocation.

A neuro-inspired model-based closed-loop neuroprosthesis for the substitution of a cerebellar learning function in anesthetized rats

NASA Astrophysics Data System (ADS)

Hogri, Roni; Bamford, Simeon A.; Taub, Aryeh H.; Magal, Ari; Giudice, Paolo Del; Mintz, Matti

2015-02-01

Neuroprostheses could potentially recover functions lost due to neural damage. Typical neuroprostheses connect an intact brain with the external environment, thus replacing damaged sensory or motor pathways. Recently, closed-loop neuroprostheses, bidirectionally interfaced with the brain, have begun to emerge, offering an opportunity to substitute malfunctioning brain structures. In this proof-of-concept study, we demonstrate a neuro-inspired model-based approach to neuroprostheses. A VLSI chip was designed to implement essential cerebellar synaptic plasticity rules, and was interfaced with cerebellar input and output nuclei in real time, thus reproducing cerebellum-dependent learning in anesthetized rats. Such a model-based approach does not require prior system identification, allowing for de novo experience-based learning in the brain-chip hybrid, with potential clinical advantages and limitations when compared to existing parametric ``black box'' models.

Osteoporosis: new hope for the future.

PubMed

Masi, L; Bilezikian, J P

1997-01-01

This article will review established and newer approaches to osteoporosis. With greater awareness of this major public health problem and highly sensitive, safe, and accurate measures of bone mass, it is now possible to identify women with osteoporosis well before they begin to suffer some of its devastating consequences. One of the most important approaches to therapy is prevention. Measures of importance relate to the establishment of peak bone mass in young adulthood. Along with issues of life style, adequate calcium intake looms as one of the important nutritional features of a program designed to establish peak bone mass. Calcium is also important later on in life to prevent bone loss and to help restore bone that might have been lost due to osteoporosis. Sufficient calcium intake is an essential component of any preventive regimen. New guidelines for optimal calcium intake are based upon the Consensus Development Conference that was held at the National Institutes of Health in June 1994. These guidelines recommended calcium intake somewhat higher than the official recommended dietary allowances (RDA) as published by the Food and Drug Administration. For women who are not yet menopausal as well as for those who are taking hormone replacement therapy (up to the age of 65) an intake of 1,000 mg daily is recommended. For women beyond the age of 65, as well as for women over 50 who choose not to take hormone replacement therapy, 1,500 mg of calcium a day are recommended. Along with sufficient calcium, it is important that vitamin D be sufficient in supply. Adequate vitamin D is essential for optimal dietary calcium absorption. In the United States, many factors are predisposing women to become less sufficient with respect to vitamin D stores. These factors include routine avoidance of sun, which is a major source of vitamin D; avoidance of milk, which is fortified with vitamin D; and physiological factors that make it more difficult for an older individual to activate vitamin D and to respond to it. Thus, along with adequate calcium, it is important that vitamin D stores are adequate. If vitamin D stores are inadequate or if they are marginal, a supplement regimen is usually advisable. Another helpful preventive measure is an exercise program. It is also important to minimize the likelihood of falling because hip fractures do not generally occur among those who do not fall. Attention to factors that may predispose an individual to fall, such as her balance, eyesight, stairs, and bathtubs that are difficult to get into and out of, are all items that need attention. The controversy surrounding hormone replacement therapy in postmenopausal women continues to be active. On the other hand, there is no question that estrogen replacement therapy in the menopausal years is a highly effective means to prevent bone loss. In its absence, women experience a 5- to 8-year period of accelerated bone loss-beyond what would be expected to occur as a function of age alone. Estrogen essentially prevents this bone loss, and it continues to be prevented for as long as estrogens are taken. Estrogen therapy has also been strongly associated with preventing deaths due to cardiovascular disease. In fact, recommendations for hormone replacement therapy are more compelling when cardiovascular risks are considered than those for osteoporosis alone. More women die of cardiovascular causes than any others, far exceeding the mortality associated with hip fracture. The controversy around estrogen replacement therapy specifically related to the increased risk of uterine cancer is essentially negated because a progestational agent is part of the regimen when the uterus is present. Breast cancer, however, continues to be a potential risk for those who take long-term estrogen therapy. (ABSTRACT TRUNCATED)

The impact of changes in LVEF and renal function on the prognosis of ICD patients after elective device replacement.

PubMed

Vandenberk, Bert; Robyns, Tomas; Garweg, Christophe; Floré, Vincent; Foulon, Stefaan; Voros, Gabor; Ector, Joris; Willems, Rik

2017-10-01

A proportion of patients with an implantable cardioverter-defibrillator (ICD) in prevention of sudden cardiac death will only receive their first appropriate ICD therapy (AT) after device replacement. Clinical reassessment at the time of replacement could be helpful to guide the decision to replace or not in the future. All patients with an ICD for primary or secondary prevention in ischemic (ICM) or nonischemic cardiomyopathy were included in a single-center retrospective registry. The association of changes in left ventricular ejection fraction (LVEF; cut-off at 35%), worsening renal function (decrease in estimated glomerular filtration rate > 15 mL/min), and worsening New York Heart Association class at elective device replacement with mortality and AT was analyzed using adjusted Cox regression analysis. A total of 238 (33%) out of 727 patients received elective device replacement (86.1% male, 74.4% ICM, 42.9% primary prevention). During this replacement 20.2% received a device upgrade. The mean time to replacement was 6.4 ± 2.0 years and mean follow-up after replacement was 3.4 ± 3.0 years. Of patients who did not receive AT before replacement 23.1% received their first AT after replacement. Worsening renal function (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.50-5.18) and a consistently LVEF ≤35% compared to a consistently LVEF >35% (HR 2.15, 95% CI 1.10-4.19) at the time of replacement were independent predictors of mortality. Independent predictors of first AT after replacement could not be identified. Although reassessment of LVEF and renal function at replacement can be helpful in predicting total mortality, the clinical utility to guide reimplantation seemed limited. Our experience indicates that approximately 25% of patients received their first AT only after replacement. © 2017 Wiley Periodicals, Inc.

Enzyme Replacement for Craniofacial Skeletal Defects and Craniosynostosis in Murine Hypophosphatasia

PubMed Central

Liu, Jin; Campbell, Cassie; Nam, Hwa Kyung; Caron, Alexandre; Yadav, Manisha C; Millán, José Luis; Hatch, Nan E.

2015-01-01

Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by deficient bone and tooth mineralization due to loss-of function mutations in the gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl−/− mice exhibit many characteristics seen in infantile HPP including long bone and tooth defects, vitamin B6 responsive seizures and craniosynostosis. Previous reports demonstrated that a mineral-targeted form of TNAP rescues long bone, verterbral and tooth mineralization defects in Alpl−/− mice. Here we report that enzyme replacement with mineral-targeted TNAP (asfotase-alfa) also prevents craniosynostosis (the premature fusion of cranial bones) and additional craniofacial skeletal abnormalities in Alpl−/− mice. Craniosynostosis, cranial bone volume and density, and craniofacial shape abnormalities were assessed by microsocopy, histology, digital caliper measurements and micro CT. We found that craniofacial shape defects, cranial bone mineralization and craniosynostosis were corrected in Alpl−/− mice injected daily subcutaneously starting at birth with recombinant enzyme. Analysis of Alpl−/− calvarial cells indicates that TNAP deficiency leads to aberrant osteoblastic gene expression and diminished proliferation. Some but not all of these cellular abnormalities were rescued by treatment with inorganic phosphate. These results confirm an essential role for TNAP in craniofacial skeletal development and demonstrate the efficacy of early postnatal mineral-targeted enzyme replacement for preventing craniofacial abnormalities including craniosynostosis in murine infantile HPP. PMID:25959417

A Review of Cell Adhesion Studies for Biomedical and Biological Applications.

PubMed

Khalili, Amelia Ahmad; Ahmad, Mohd Ridzuan

2015-08-05

Cell adhesion is essential in cell communication and regulation, and is of fundamental importance in the development and maintenance of tissues. The mechanical interactions between a cell and its extracellular matrix (ECM) can influence and control cell behavior and function. The essential function of cell adhesion has created tremendous interests in developing methods for measuring and studying cell adhesion properties. The study of cell adhesion could be categorized into cell adhesion attachment and detachment events. The study of cell adhesion has been widely explored via both events for many important purposes in cellular biology, biomedical, and engineering fields. Cell adhesion attachment and detachment events could be further grouped into the cell population and single cell approach. Various techniques to measure cell adhesion have been applied to many fields of study in order to gain understanding of cell signaling pathways, biomaterial studies for implantable sensors, artificial bone and tooth replacement, the development of tissue-on-a-chip and organ-on-a-chip in tissue engineering, the effects of biochemical treatments and environmental stimuli to the cell adhesion, the potential of drug treatments, cancer metastasis study, and the determination of the adhesion properties of normal and cancerous cells. This review discussed the overview of the available methods to study cell adhesion through attachment and detachment events.

A Review of Cell Adhesion Studies for Biomedical and Biological Applications

PubMed Central

Ahmad Khalili, Amelia; Ahmad, Mohd Ridzuan

2015-01-01

Cell adhesion is essential in cell communication and regulation, and is of fundamental importance in the development and maintenance of tissues. The mechanical interactions between a cell and its extracellular matrix (ECM) can influence and control cell behavior and function. The essential function of cell adhesion has created tremendous interests in developing methods for measuring and studying cell adhesion properties. The study of cell adhesion could be categorized into cell adhesion attachment and detachment events. The study of cell adhesion has been widely explored via both events for many important purposes in cellular biology, biomedical, and engineering fields. Cell adhesion attachment and detachment events could be further grouped into the cell population and single cell approach. Various techniques to measure cell adhesion have been applied to many fields of study in order to gain understanding of cell signaling pathways, biomaterial studies for implantable sensors, artificial bone and tooth replacement, the development of tissue-on-a-chip and organ-on-a-chip in tissue engineering, the effects of biochemical treatments and environmental stimuli to the cell adhesion, the potential of drug treatments, cancer metastasis study, and the determination of the adhesion properties of normal and cancerous cells. This review discussed the overview of the available methods to study cell adhesion through attachment and detachment events. PMID:26251901

The deca-GX3 proteins Yae1-Lto1 function as adaptors recruiting the ABC protein Rli1 for iron-sulfur cluster insertion

PubMed Central

Paul, Viktoria Désirée; Mühlenhoff, Ulrich; Stümpfig, Martin; Seebacher, Jan; Kugler, Karl G; Renicke, Christian; Taxis, Christof; Gavin, Anne-Claude; Pierik, Antonio J; Lill, Roland

2015-01-01

Cytosolic and nuclear iron-sulfur (Fe-S) proteins are involved in many essential pathways including translation and DNA maintenance. Their maturation requires the cytosolic Fe-S protein assembly (CIA) machinery. To identify new CIA proteins we employed systematic protein interaction approaches and discovered the essential proteins Yae1 and Lto1 as binding partners of the CIA targeting complex. Depletion of Yae1 or Lto1 results in defective Fe-S maturation of the ribosome-associated ABC protein Rli1, but surprisingly no other tested targets. Yae1 and Lto1 facilitate Fe-S cluster assembly on Rli1 in a chain of binding events. Lto1 uses its conserved C-terminal tryptophan for binding the CIA targeting complex, the deca-GX3 motifs in both Yae1 and Lto1 facilitate their complex formation, and Yae1 recruits Rli1. Human YAE1D1 and the cancer-related ORAOV1 can replace their yeast counterparts demonstrating evolutionary conservation. Collectively, the Yae1-Lto1 complex functions as a target-specific adaptor that recruits apo-Rli1 to the generic CIA machinery. DOI: http://dx.doi.org/10.7554/eLife.08231.001 PMID:26182403

Vestigialization of an Allosteric Switch: Genetic and Structural Mechanisms for the Evolution of Constitutive Activity in a Steroid Hormone Receptor

PubMed Central

Bridgham, Jamie T.; Keay, June; Ortlund, Eric A.; Thornton, Joseph W.

2014-01-01

An important goal in molecular evolution is to understand the genetic and physical mechanisms by which protein functions evolve and, in turn, to characterize how a protein's physical architecture influences its evolution. Here we dissect the mechanisms for an evolutionary shift in function in the mollusk ortholog of the steroid hormone receptors (SRs), a family of biologically essential transcription factors. In vertebrates, the activity of SRs allosterically depends on binding a hormonal ligand; in mollusks, however, the SR ortholog (called ER, because of high sequence similarity to vertebrate estrogen receptors) activates transcription in the absence of ligand and does not respond to steroid hormones. To understand how this shift in regulation evolved, we combined evolutionary, structural, and functional analyses. We first determined the X-ray crystal structure of the ER of the Pacific oyster Crassostrea gigas (CgER), and found that its ligand pocket is filled with bulky residues that prevent ligand occupancy. To understand the genetic basis for the evolution of mollusk ERs' unique functions, we resurrected an ancient SR progenitor and characterized the effect of historical amino acid replacements on its functions. We found that reintroducing just two ancient replacements from the lineage leading to mollusk ERs recapitulates the evolution of full constitutive activity and the loss of ligand activation. These substitutions stabilize interactions among key helices, causing the allosteric switch to become “stuck” in the active conformation and making activation independent of ligand binding. Subsequent changes filled the ligand pocket without further affecting activity; by degrading the allosteric switch, these substitutions vestigialized elements of the protein's architecture required for ligand regulation and made reversal to the ancestral function more complex. These findings show how the physical architecture of allostery enabled a few large-effect mutations to trigger a profound evolutionary change in the protein's function and shaped the genetics of evolutionary reversibility. PMID:24415950

Structural and Thermodynamic Consequences of the Replacement of Zinc with Environmental Metals on ERα-DNA Interactions

PubMed Central

Deegan, Brian J.; Bona, Anna M.; Bhat, Vikas; Mikles, David C.; McDonald, Caleb B.; Seldeen, Kenneth L.; Farooq, Amjad

2011-01-01

Estrogen receptor α (ERα) acts as a transcription factor by virtue of the ability of its DNA-binding (DB) domain, comprised of a tandem pair of zinc fingers, to recognize the estrogen response element (ERE) within the promoters of target genes. Herein, using an array of biophysical methods, we probe structural consequences of the replacement of zinc within the DB domain of ERα with various environmental metals and their effects on the thermodynamics of binding to DNA. Our data reveal that while the DB domain reconstituted with divalent ions of zinc, cadmium, mercury and cobalt binds to DNA with affinities in the nanomolar range, divalent ions of barium, copper, iron, lead, manganese, nickel and tin are unable to regenerate DB domain with DNA-binding potential though they can compete with zinc for coordinating the cysteine ligands within the zinc fingers. We also show that the metal-free DB domain is a homodimer in solution and that the binding of various metals only results in subtle secondary and tertiary structural changes, implying that metal-coordination may only be essential for DNA-binding. Collectively, our findings provide mechanistic insights into how environmental metals may modulate the physiological function of a key nuclear receptor involved in mediating a plethora of cellular functions central to human health and disease. PMID:22038807

[Tricuspid valve regurgitation : Indications and operative techniques].

PubMed

Lange, R; Piazza, N; Günther, T

2017-11-01

Functional tricuspid valve (TV) regurgitation secondary to left heart disease (e.g. mitral insufficiency and stenosis) is observed in 75% of the patients with TV regurgitation and is thus the most common etiology; therefore, the majority of patients who require TV surgery, undergo concomitant mitral and/or aortic valve surgery. Uncorrected moderate and severe TV regurgitation may persist or even worsen after mitral valve surgery, leading to progressive heart failure and death. Patients with moderate to severe TV regurgitation show a 3-year survival rate of 40%. Surgery is indicated in patients with severe TV regurgitation undergoing left-sided valve surgery and in patients with severe isolated primary regurgitation without severe right ventricular (RV) dysfunction. For patients requiring mitral valve surgery, tricuspid valve annuloplasty should be considered even in the absence of significant regurgitation, when severe annular dilatation (≥40 mm or >21 mm/m 2 ) is present. Functional TV regurgitation is primarily treated with valve reconstruction which carries a lower perioperative risk than valve replacement. Valve replacement is rarely required. Tricuspid valve repair with ring annuloplasty is associated with better survival and a lower reoperation rate than suture annuloplasty. Long-term results are not available. The severity of the heart insufficiency and comorbidities (e.g. renal failure and liver dysfunction) are the essential determinants of operative mortality and long-term survival. Tricuspid valve reoperations are rarely necessary and associated with a considerable mortality.

Special features of total knee replacement in hemophilia.

PubMed

Rodriguez-Merchan, Emerito Carlos

2013-12-01

Total knee replacement is an operation frequently needed by hemophilia patients, which greatly improves their quality of life. This operation, however, carries a higher risk of bleeding and infection for hemophiliacs than it does for osteoarthritis sufferers. It is advisable to implant prosthetic components using antibiotic-loaded cement. It is essential to maintain a level of 100% of the replacement clotting factor for 2 weeks. Hematological treatment must be established, depending on the patient's factor levels and other pharmacokinetic parameters such as recovery and half-life, optimal doses and treatment time. It is preferable to use general anesthesia due to the risk of spinal bleeding. The lifespan of total knee replacement in hemophilic patients is shorter than in patients with osteoarthritis because of the increased risk of infection.

Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria.

PubMed

Bershtein, Shimon; Serohijos, Adrian W R; Bhattacharyya, Sanchari; Manhart, Michael; Choi, Jeong-Mo; Mu, Wanmeng; Zhou, Jingwen; Shakhnovich, Eugene I

2015-10-01

Horizontal gene transfer (HGT) plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood. Here we performed inter-species replacement of the chromosomal folA gene, encoding an essential metabolic enzyme dihydrofolate reductase (DHFR), with orthologs from 35 other mesophilic bacteria. The orthologous inter-species replacements caused a marked drop (in the range 10-90%) in bacterial growth rate despite the fact that most orthologous DHFRs are as stable as E.coli DHFR at 37°C and are more catalytically active than E. coli DHFR. Although phylogenetic distance between E. coli and orthologous DHFRs as well as their individual molecular properties correlate poorly with growth rates, the product of the intracellular DHFR abundance and catalytic activity (kcat/KM), correlates strongly with growth rates, indicating that the drop in DHFR abundance constitutes the major fitness barrier to HGT. Serial propagation of the orthologous strains for ~600 generations dramatically improved growth rates by largely alleviating the fitness barriers. Whole genome sequencing and global proteome quantification revealed that the evolved strains with the largest fitness improvements have accumulated mutations that inactivated the ATP-dependent Lon protease, causing an increase in the intracellular DHFR abundance. In one case DHFR abundance increased further due to mutations accumulated in folA promoter, but only after the lon inactivating mutations were fixed in the population. Thus, by apparently distinguishing between self and non-self proteins, protein homeostasis imposes an immediate and global barrier to the functional integration of foreign genes by decreasing the intracellular abundance of their products. Once this barrier is alleviated, more fine-tuned evolution occurs to adjust the function/expression of the transferred proteins to the constraints imposed by the intracellular environment of the host organism.

Ssrp1a controls organogenesis by promoting cell cycle progression and RNA synthesis.

PubMed

Koltowska, Katarzyna; Apitz, Holger; Stamataki, Despina; Hirst, Elizabeth M A; Verkade, Heather; Salecker, Iris; Ober, Elke A

2013-05-01

Tightly controlled DNA replication and RNA transcription are essential for differentiation and tissue growth in multicellular organisms. Histone chaperones, including the FACT (facilitates chromatin transcription) complex, are central for these processes and act by mediating DNA access through nucleosome reorganisation. However, their roles in vertebrate organogenesis are poorly understood. Here, we report the identification of zebrafish mutants for the gene encoding Structure specific recognition protein 1a (Ssrp1a), which, together with Spt16, forms the FACT heterodimer. Focussing on the liver and eye, we show that zygotic Ssrp1a is essential for proliferation and differentiation during organogenesis. Specifically, gene expression indicative of progressive organ differentiation is disrupted and RNA transcription is globally reduced. Ssrp1a-deficient embryos exhibit DNA synthesis defects and prolonged S phase, uncovering a role distinct from that of Spt16, which promotes G1 phase progression. Gene deletion/replacement experiments in Drosophila show that Ssrp1b, Ssrp1a and N-terminal Ssrp1a, equivalent to the yeast homologue Pob3, can substitute Drosophila Ssrp function. These data suggest that (1) Ssrp1b does not compensate for Ssrp1a loss in the zebrafish embryo, probably owing to insufficient expression levels, and (2) despite fundamental structural differences, the mechanisms mediating DNA accessibility by FACT are conserved between yeast and metazoans. We propose that the essential functions of Ssrp1a in DNA replication and gene transcription, together with its dynamic spatiotemporal expression, ensure organ-specific differentiation and proportional growth, which are crucial for the forming embryo.

Blocking VEGF signaling delays development of replacement teeth in zebrafish.

PubMed

Crucke, J; Huysseune, A

2015-01-01

The dentition in zebrafish is extremely and richly vascularized, but the function of the vasculature, in view of the continuous replacement of the teeth, remains elusive. Through application of SU5416, a vascular endothelial growth factor receptor inhibitor, we studied the role of the blood vessels in the dentition of the zebrafish. We were unable to show an effect on the development of first-generation teeth as well as first tooth replacement. However, in juvenile fish, a delay was observed in the developmental state of the replacement tooth compared with what was expected based on the maturation state of the functional tooth. Furthermore, we observed a difference between treated and nontreated fish in the distance between blood vessels and developing replacement teeth. In conclusion, our results provide support for a nutritive, rather than an inductive, function of the vasculature in the process of tooth development and replacement. © International & American Associations for Dental Research 2014.

Development of micro-four-point probe in a scanning tunneling microscope for in situ electrical transport measurement.

PubMed

Ge, Jian-Feng; Liu, Zhi-Long; Gao, Chun-Lei; Qian, Dong; Liu, Canhua; Jia, Jin-Feng

2015-05-01

Electrons at surface may behave differently from those in bulk of a material. Multi-functional tools are essential in comprehensive studies on a crystal surface. Here, we developed an in situ microscopic four-point probe (4PP) transport measurement system on the basis of a scanning tunneling microscope (STM). In particular, convenient replacement between STM tips and micro-4PPs enables systematic investigations of surface morphology, electronic structure, and electrical transport property of a same sample surface. Performances of the instrument are demonstrated with high-quality STM images, tunneling spectra, and low-noise electrical I-V characteristic curves of a single-layer FeSe film grown on a conductive SrTiO3 surface.

Learning from regeneration research organisms: The circuitous road to scar free wound healing

PubMed Central

Erickson, Jami R.; Echeverri, Karen

2018-01-01

The skin is the largest organ in the body and plays multiple essential roles ranging from regulating temperature, preventing infection and ultimately defining who we are physically. It is a highly dynamic organ that constantly replaces the outermost cells throughout life. However, when faced with a major injury, human skin cannot restore a significant lesion to its original functionality, instead a reparative scar is formed. In contrast to this, many other species have the unique ability to regenerate full thickness skin without formation of scar tissue. Here we review recent advances in the field that shed light on how the skin cells in regenerative species react to injury to prevent scar formation versus scar forming humans. PMID:29179946

Laminin and Matrix metalloproteinase 11 regulate Fibronectin levels in the zebrafish myotendinous junction.

PubMed

Jenkins, Molly H; Alrowaished, Sarah S; Goody, Michelle F; Crawford, Bryan D; Henry, Clarissa A

2016-01-01

Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition. We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture. These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.

Urban chaos and replacement dynamics in nature and society

NASA Astrophysics Data System (ADS)

Chen, Yanguang

2014-11-01

Replacements resulting from competition are ubiquitous phenomena in both nature and society. The evolution of a self-organized system is always a physical process substituting one type of components for another type of components. A logistic model of replacement dynamics has been proposed in terms of technical innovation and urbanization, but it fails to arouse widespread attention in the academia. This paper is devoted to laying the foundations of general replacement principle by using analogy and induction. The empirical base of this study is urban replacement, including urbanization and urban growth. The sigmoid functions can be employed to model various processes of replacement. Many mathematical methods such as allometric scaling and head/tail breaks can be applied to analyzing the processes and patterns of replacement. Among varied sigmoid functions, the logistic function is the basic and the simplest model of replacement dynamics. A new finding is that replacement can be associated with chaos in a nonlinear system, e.g., urban chaos is just a part of replacement dynamics. The aim of developing replacement theory is at understanding complex interaction and conversion. This theory provides a new way of looking at urbanization, technological innovation and diffusion, Volterra-Lotka’s predator-prey interaction, man-land relation, and dynastic changes resulting from peasant uprising, and all that. Especially, the periodic oscillations and chaos of replacement dynamics can be used to explain and predict the catastrophic occurrences in the physical and human systems.

2.4 Å resolution crystal structure of human TRAP1 NM , the Hsp90 paralog in the mitochondrial matrix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, Nuri; Lee, Jungsoon; Kim, Ji-Hyun

2016-07-13

TRAP1 is an organelle-specific Hsp90 paralog that is essential for neoplastic growth. As a member of the Hsp90 family, TRAP1 is presumed to be a general chaperone facilitating the late-stage folding of Hsp90 client proteins in the mitochondrial matrix. Interestingly, TRAP1 cannot replace cytosolic Hsp90 in protein folding, and none of the known Hsp90 co-chaperones are found in mitochondria. Thus, the three-dimensional structure of TRAP1 must feature regulatory elements that are essential to the ATPase activity and chaperone function of TRAP1. Here, the crystal structure of a human TRAP1 NMdimer is presented, featuring an intact N-domain and M-domain structure, boundmore » to adenosine 5'-β,γ-imidotriphosphate (ADPNP). The crystal structure together with epitope-mapping results shows that the TRAP1 M-domain loop 1 contacts the neighboring subunit and forms a previously unobserved third dimer interface that mediates the specific interaction with mitochondrial Hsp70.« less

Window Of Opportunity: Estrogen As A Treatment For Ischemic Stroke✰

PubMed Central

Liu, Ran; Yang, Shao-Hua

2013-01-01

The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue plasminogen activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the “critical period” and newly emerged “biomarkers window” hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials. PMID:23340160

Man and His Environment

ERIC Educational Resources Information Center

Coale, Ansley J.

1970-01-01

Discusses economic factors as the essential causes of world environment deterioration. Presents case for critical and prompt action in prevention of natural resource exhaustion and pollution, particularly by means of replacement level, population control, and consequent economic organization. (JM)

Preoperative Education for Hip and Knee Replacement: Never Stop Learning.

PubMed

Edwards, Paul K; Mears, Simon C; Lowry Barnes, C

2017-09-01

Participation in alternative payment models has focused efforts to improve outcomes and patient satisfaction while also lowering cost for elective hip and knee replacement. The purpose of this review is to determine if preoperative education classes for elective hip and knee replacement achieve these goals. Recent literature demonstrates that patients who attend education classes prior to surgery have decreased anxiety, better post-operative pain control, more realistic expectations of surgery, and a better understanding of their surgery. As a result, comprehensive clinical pathways incorporating a preoperative education program for elective hip and knee replacement lead to lower hospital length of stay, higher home discharge, lower readmission, and improved cost. In summary, we report convincing evidence that preoperative education classes are an essential element to successful participation in alternative payment models such as the Bundle Payment Care Initiative.

Neurocognitive functions after beating heart mitral valve replacement without cross-clamping the aorta.

PubMed

Cicekcioglu, Ferit; Ozen, Anil; Tuluce, Hicran; Tutun, Ufuk; Parlar, Ali Ihsan; Kervan, Umit; Karakas, Sirel; Katircioglu, Salih Fehmi

2008-01-01

Although neurologic outcome after cardiac surgery is well-established, neurocognitive functions after beating heart mitral valve replacement still needs to be elucidated. The aim of this study was to compare preoperative and postoperative neurocognitive functions in patients who underwent beating heart mitral valve replacement on cardiopulmonary bypass without cross-clamping the aorta. The prospective study included 25 consecutive patients who underwent mitral valve replacement. The operations were carried out on a beating heart method using normothermic cardiopulmonary bypass without cross-clamping the aorta. All patients were evaluated preoperatively (E1) and postoperatively (at sixth day [E2] and second month [E3]) for neurocognitive functions. Neurologic deficit was not observed in the postoperative period. Comparison of the neurocognitive test results, between the preoperative and postoperative assessment for both hemispheric cognitive functions, demonstrated that no deterioration occurred. In the three subsets of left hemispheric cognitive function test evaluation, total verbal learning, delayed recall, and recognition, significant improvements were detected at the postoperative second month (E3) compared to the preoperative results (p = 0.005, 0.01, and 0.047, respectively). Immediate recall and retention were significantly improved within the first postoperative week (E2) when compared to the preoperative results (p = 0.05 and 0.05, respectively). The technique of mitral valve replacement with normothermic cardiopulmonary bypass without cross-clamping of the aorta may be safely used for majority of patients requiring mitral valve replacement without causing deterioration in neurocognitive functions.

Unique method of tooth replacement in durophagous placodont marine reptiles, with new data on the dentition of Chinese taxa

PubMed Central

Neenan, James M; Li, Chun; Rieppel, Olivier; Bernardini, Federico; Tuniz, Claudio; Muscio, Giuseppe; Scheyer, Torsten M

2014-01-01

The placodonts of the Triassic period (˜252–201 mya) represent one of the earliest and most extreme specialisations to a durophagous diet of any known reptile group. Exceptionally enlarged crushing tooth plates on the maxilla, dentary and palatine cooperated to form functional crushing areas in the buccal cavity. However, the extreme size of these teeth, combined with the unusual way they occluded, constrained how replacement occurred. Using an extensive micro-computed tomographic dataset of 11 specimens that span all geographic regions and placodont morphotypes, tooth replacement patterns were investigated. In addition, the previously undescribed dental morphologies and formulae of Chinese taxa are described for the first time and incorporated into the analysis. Placodonts have a unique tooth replacement pattern and results follow a phylogenetic trend. The plesiomorphic Placodus species show many replacement teeth at various stages of growth, with little or no discernible pattern. On the other hand, the more derived cyamodontoids tend to have fewer replacement teeth growing at any one time, replacing teeth unilaterally and/or in functional units, thus maintaining at least one functional crushing area at all times. The highly derived placochelyids have fewer teeth and, as a result, only have one or two replacement teeth in the upper jaw. This supports previous suggestions that these taxa had an alternative diet to other placodonts. Importantly, all specimens show at least one replacement tooth growing at the most posterior palatine tooth plates, indicating increased wear at this point and thus the most efficient functional crushing area. PMID:24517163

Improving Software Sustainability: Lessons Learned from Profiles in Science.

PubMed

Gallagher, Marie E

2013-01-01

The Profiles in Science® digital library features digitized surrogates of historical items selected from the archival collections of the U.S. National Library of Medicine as well as collaborating institutions. In addition, it contains a database of descriptive, technical and administrative metadata. It also contains various software components that allow creation of the metadata, management of the digital items, and access to the items and metadata through the Profiles in Science Web site [1]. The choices made building the digital library were designed to maximize the sustainability and long-term survival of all of the components of the digital library [2]. For example, selecting standard and open digital file formats rather than proprietary formats increases the sustainability of the digital files [3]. Correspondingly, using non-proprietary software may improve the sustainability of the software--either through in-house expertise or through the open source community. Limiting our digital library software exclusively to open source software or to software developed in-house has not been feasible. For example, we have used proprietary operating systems, scanning software, a search engine, and office productivity software. We did this when either lack of essential capabilities or the cost-benefit trade-off favored using proprietary software. We also did so knowing that in the future we would need to replace or upgrade some of our proprietary software, analogous to migrating from an obsolete digital file format to a new format as the technological landscape changes. Since our digital library's start in 1998, all of its software has been upgraded or replaced, but the digitized items have not yet required migration to other formats. Technological changes that compelled us to replace proprietary software included the cost of product licensing, product support, incompatibility with other software, prohibited use due to evolving security policies, and product abandonment. Sometimes these changes happen on short notice, so we continually monitor our library's software for signs of endangerment. We have attempted to replace proprietary software with suitable in-house or open source software. When the replacement involves a standalone piece of software with a nearly equivalent version, such as replacing a commercial HTTP server with an open source HTTP server, the replacement is straightforward. Recently we replaced software that functioned not only as our search engine but also as the backbone of the architecture of our Web site. In this paper, we describe the lessons learned and the pros and cons of replacing this software with open source software.

Compatibility of the totally replaced hip. Reduction of wear by amorphous diamond coating.

PubMed

Santavirta, Seppo

2003-12-01

Particulate wear debris in totally replaced hips causes adverse local host reactions. The extreme form of such a reaction, aggressive granulomatosis, was found to be a distinct condition and different from simple aseptic loosening. Reactive and adaptive tissues around the totally replaced hip were made of proliferation of local fibroblast like cells and activated macrophages. Methylmethacrylate and high-molecular-weight polyethylene were shown to be essentially immunologically inert implant materials, but in small particulate form functioned as cellular irritants initiating local biological reactions leading to loosening of the implants. Chromium-cobalt-molybdenum is the most popular metallic implant material; it is hard and tough, and the bearings of this metal are partially self-polishing. In total hip implants, prerequisites for longevity of the replaced hip are good biocompatibility of the materials and sufficient tribological properties of the bearings. The third key issue is that the bearing must minimize frictional shear at the prosthetic bone-implant interface to be compatible with long-term survival. Some of the approaches to meet these demands are alumina-on-alumina and metal-on-metal designs, as well as the use of highly crosslinked polyethylene for the acetabular component. In order to avoid the wear-based deleterious properties of the conventional total hip prosthesis materials or coatings, the present work included biological and tribological testing of amorphous diamond. Previous experiments had demonstrated that a high adhesion of tetrahedral amorphous carbon coatings to a substrate can be achieved by using mixing layers or interlayers. Amorphous diamond was found to be biologically inert, and simulator testing indicated excellent wear properties for conventional total hip prostheses, in which either the ball or both bearing surfaces were coated with hydrogen-free tetrahedral amorphous diamond films. Simulator testing with such total hip prostheses showed no measurable wear or detectable delamination after 15,000,000 test cycles corresponding to 15 years of clinical use. The present work clearly shows that wear is one of the basic problems with totally replaced hips. Diamond coating of the bearing surfaces appears to be an attractive solution to improve longevity of the totally replaced hip.

Identification of a basic helix-loop-helix-type transcription regulator gene in Aspergillus oryzae by systematically deleting large chromosomal segments.

PubMed

Jin, Feng Jie; Takahashi, Tadashi; Machida, Masayuki; Koyama, Yasuji

2009-09-01

We previously developed two methods (loop-out and replacement-type recombination) for generating large-scale chromosomal deletions that can be applied to more effective chromosomal engineering in Aspergillus oryzae. In this study, the replacement-type method is used to systematically delete large chromosomal DNA segments to identify essential and nonessential regions in chromosome 7 (2.93 Mb), which is the smallest A. oryzae chromosome and contains a large number of nonsyntenic blocks. We constructed 12 mutants harboring deletions that spanned 16- to 150-kb segments of chromosome 7 and scored phenotypic changes in the resulting mutants. Among the deletion mutants, strains designated Delta5 and Delta7 displayed clear phenotypic changes involving growth and conidiation. In particular, the Delta5 mutant exhibited vigorous growth and conidiation, potentially beneficial characteristics for certain industrial applications. Further deletion analysis allowed identification of the AO090011000215 gene as the gene responsible for the Delta5 mutant phenotype. The AO090011000215 gene was predicted to encode a helix-loop-helix binding protein belonging to the bHLH family of transcription factors. These results illustrate the potential of the approach for identifying novel functional genes.

Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival

PubMed Central

Princiotta, Michael F.; Schubert, Ulrich; Chen, Weisan; Bennink, Jack R.; Myung, Jayhyuk; Crews, Craig M.; Yewdell, Jonathan W.

2001-01-01

The proteasome is the primary protease used by cells for degrading proteins and generating peptide ligands for class I molecules of the major histocompatibility complex. Based on the properties of cells adapted to grow in the presence of the proteasome inhibitor 4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone (NLVS), it was proposed that proteasomes can be replaced by alternative proteolytic systems, particularly a large proteolytic complex with a tripeptidyl peptidase II activity. Here we show that NLVS-adapted cells retain sensitivity to a number of highly specific proteasome inhibitors with regard to antigenic peptide generation, accumulation of polyubiquitinated proteins, degradation of p53, and cell viability. In addition, we show that in the same assays (with a single minor exception), NLVS-adapted cells are about as sensitive as nonselected cells to Ala-Ala-Phe-chloromethylketone, a specific inhibitor of tripeptidyl peptidase II activity. Based on these findings, we conclude that proteasomes still have essential proteolytic functions in adapted cells that are not replaced by Ala-Ala-Phe-chloromethylketone-sensitive proteases. PMID:11149939

Patient selection for transcatheter aortic valve replacement: A combined clinical and multimodality imaging approach

PubMed Central

Cocchia, Rosangela; D’Andrea, Antonello; Conte, Marianna; Cavallaro, Massimo; Riegler, Lucia; Citro, Rodolfo; Sirignano, Cesare; Imbriaco, Massimo; Cappelli, Maurizio; Gregorio, Giovanni; Calabrò, Raffaele; Bossone, Eduardo

2017-01-01

Transcatheter aortic valve replacement (TAVR) has been validated as a new therapy for patients affected by severe symptomatic aortic stenosis who are not eligible for surgical intervention because of major contraindication or high operative risk. Patient selection for TAVR should be based not only on accurate assessment of aortic stenosis morphology, but also on several clinical and functional data. Multi-Imaging modalities should be preferred for assessing the anatomy and the dimensions of the aortic valve and annulus before TAVR. Ultrasounds represent the first line tool in evaluation of this patients giving detailed anatomic description of aortic valve complex and allowing estimating with enough reliability the hemodynamic entity of valvular stenosis. Angiography should be used to assess coronary involvement and plan a revascularization strategy before the implant. Multislice computed tomography play a central role as it can give anatomical details in order to choice the best fitting prosthesis, evaluate the morphology of the access path and detect other relevant comorbidities. Cardiovascular magnetic resonance and positron emission tomography are emergent modality helpful in aortic stenosis evaluation. The aim of this review is to give an overview on TAVR clinical and technical aspects essential for adequate selection. PMID:28400918

Programming of the complex logarithm function in the solution of the cracked anisotropic plate loaded by a point force

NASA Astrophysics Data System (ADS)

Zaal, K. J. J. M.

1991-06-01

In programming solutions of complex function theory, the complex logarithm function is replaced by the complex logarithmic function, introducing a discontinuity along the branch cut into the programmed solution which was not present in the mathematical solution. Recently, Liaw and Kamel presented their solution of the infinite anisotropic centrally cracked plate loaded by an arbitrary point force, which they used as Green's function in a boundary element method intended to evaluate the stress intensity factor at the tip of a crack originating from an elliptical home. Their solution may be used as Green's function of many more numerical methods involving anisotropic elasticity. In programming applications of Liaw and Kamel's solution, the standard definition of the logarithmic function with the branch cut at the nonpositive real axis cannot provide a reliable computation of the displacement field for Liaw and Kamel's solution. Either the branch cut should be redefined outside the domain of the logarithmic function, after proving that the domain is limited to a part of the plane, or the logarithmic function should be defined on its Riemann surface. A two dimensional line fractal can provide the link between all mesh points on the plane essential to evaluate the logarithm function on its Riemann surface. As an example, a two dimensional line fractal is defined for a mesh once used by Erdogan and Arin.

State of the art in fluid and volume therapy : A user-friendly staged concept. English version.

PubMed

Rehm, M; Hulde, N; Kammerer, T; Meidert, A S; Hofmann-Kiefer, K

2017-04-10

Adequate intraoperative infusion therapy is essential for the perioperative outcome of a patient. Both hypo- and hypervolemia can lead to an increased rate of perioperative complications and to a worse outcome. Perioperative infusion therapy should therefore be needs-based. The primary objective is the maintenance of preoperative normovolemia using a rational infusion strategy. Perioperative fluid losses should be differentiated from volume losses due to surgical bleeding or protein losses into the interstitial space. Fluid loss via urine excretion or insensible perspiration (0.5-1.0 ml/kg/h) should be replaced with balanced, isooncotic, crystalloid infusion solutions in a ratio of 1:1. Volume therapy stage 1: intraoperative volume losses up to a blood loss corresponding to 20% of the patient's total blood volume are compensated for by balanced crystalloids in a ratio of 4-5:1. Stage 2: blood losses exceeding this level are to be treated with isooncotic colloids (preferably balanced) in a 1:1 ratio. In this regard taking into consideration the contraindications, e. g., sepsis, burns, critical illness (usually patients in the intensive care unit), impaired renal function or renal replacement therapy, intracranial hemorrhage, or severe coagulopathy, artificial colloids such as hydroxyethyl starch (HES) can be used perioperatively for volume replacement. Stage 3: if an allogeneic blood transfusion is indicated, blood and blood products are applied in a differentiated manner.

A single amino acid substitution in the variable region of the light chain specifically blocks immunoglobulin secretion.

PubMed Central

Dul, J L; Argon, Y

1990-01-01

Although immunoglobulin light chains are usually secreted in association with heavy chains, free light chains can be secreted by lymphocytes. To identify the structural features of light chains that are essential for their secretion, we mutated a conserved sequence in the variable domain of a lambda I light chain. The effects of the mutations on secretion were assayed by transient expression in COS-1 cells. One mutant (AV60), which replaced Ala-60 with Val, was secreted as efficiently as wild-type lambda I by transfected COS-1 cells. This result was not surprising because secreted lambda II chains contain valine in this position. However, a second lambda I mutant (AV60FS62), which replaced Phe-62 with Ser as well as Ala-60 with Val, was not secreted. This mutant was arrested in the endoplasmic reticulum, as judged by immunofluorescence and by its association with a lumenal endoplasmic reticulum protein, immunoglobulin heavy chain binding protein (BiP). The defect in secretion was not due to gross misfolding of the lambda I chain, since cells cotransfected with AV60FS62 and an immunoglobulin heavy chain gene produced functional antigen-binding antibodies. These assembled IgM molecules were still not secreted. Hence, the replacement of Phe-62 with Ser specifically affects a determinant on the lambda I light chain that is necessary for the intracellular transport of this molecule. Images PMID:2122454

(Re)Building a Kidney

PubMed Central

Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

2017-01-01

(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

Functional characterizations of malonyl-CoA:acyl carrier protein transacylase (MCAT) in Eimeria tenella.

PubMed

Sun, Mingfei; Zhu, Guan; Qin, Zonghua; Wu, Caiyan; Lv, Minna; Liao, Shenquan; Qi, Nanshan; Xie, Mingquan; Cai, Jianping

2012-07-01

Eimeria tenella, an apicomplexan parasite in chickens, possesses an apicoplast and its associated metabolic pathways including the Type II fatty acid synthesis (FAS II). Malonyl-CoA:acyl-carry protein transacylase (MCAT) encoded by the fabD gene is one of the essential enzymes in the FAS II system. In the present study, the entire E. tenella MCAT gene (EtfabD) was cloned and sequenced. Immunolabeling located this protein in the apicoplast organelle in coccidial sporozoites. Functional replacement of the fabD gene with amber mutation of E. coli temperature-sensitive LA2-89 strain by E. tenella EtMCAT demonstrated that EcFabD and EtMCAT perform the same biochemical function. The recombinant EtMCAT protein was expressed and its general biochemical features were also determined. An alkaloid natural product corytuberine (CAS: 517-56-6) could specifically inhibit the EtMCAT activity (IC(50)=16.47μM), but the inhibition of parasite growth in vitro by corytuberine was very weak (the predicted MIC(50)=0.65mM). Copyright © 2012 Elsevier B.V. All rights reserved.

Evolution of Fe/S cluster biogenesis in the anaerobic parasite Blastocystis

PubMed Central

Tsaousis, Anastasios D.; Ollagnier de Choudens, Sandrine; Gentekaki, Eleni; Long, Shaojun; Gaston, Daniel; Stechmann, Alexandra; Vinella, Daniel; Py, Béatrice; Fontecave, Marc; Barras, Frédéric; Lukeš, Julius; Roger, Andrew J.

2012-01-01

Iron/sulfur cluster (ISC)-containing proteins are essential components of cells. In most eukaryotes, Fe/S clusters are synthesized by the mitochondrial ISC machinery, the cytosolic iron/sulfur assembly system, and, in photosynthetic species, a plastid sulfur-mobilization (SUF) system. Here we show that the anaerobic human protozoan parasite Blastocystis, in addition to possessing ISC and iron/sulfur assembly systems, expresses a fused version of the SufC and SufB proteins of prokaryotes that it has acquired by lateral transfer from an archaeon related to the Methanomicrobiales, an important lineage represented in the human gastrointestinal tract microbiome. Although components of the Blastocystis ISC system function within its anaerobic mitochondrion-related organelles and can functionally replace homologues in Trypanosoma brucei, its SufCB protein has similar biochemical properties to its prokaryotic homologues, functions within the parasite’s cytosol, and is up-regulated under oxygen stress. Blastocystis is unique among eukaryotic pathogens in having adapted to its parasitic lifestyle by acquiring a SUF system from nonpathogenic Archaea to synthesize Fe/S clusters under oxygen stress. PMID:22699510

DOE Office of Scientific and Technical Information (OSTI.GOV)

Draelos, Timothy John; Dautenhahn, Nathan; Schroeppel, Richard Crabtree

The security of the widely-used cryptographic hash function SHA1 has been impugned. We have developed two replacement hash functions. The first, SHA1X, is a drop-in replacement for SHA1. The second, SANDstorm, has been submitted as a candidate to the NIST-sponsored SHA3 Hash Function competition.

What is the best approach to tailoring hydrocortisone dose to meet patient needs in 2012?

PubMed

Debono, Miguel; Ross, Richard J

2013-05-01

Cortisol is an essential stress hormone and replacement with oral hydrocortisone is lifesaving in patients with adrenal insufficiency. Cortisol has a diurnal rhythm regulated by the central body clock and this rhythm is a metabolic signal for peripheral tissue clocks. Loss of cortisol rhythmicity is associated with fatigue, depression and insulin resistance. A general principle in endocrinology is to replace hormones to replicate physiological concentrations; however, the pharmacokinetics of oral immediate-release hydrocortisone make it impossible to fully mimic the cortisol rhythm and patients still have an increased morbidity and mortality despite replacement. Traditionally, physicians have replaced hydrocortisone with a total daily dose based on the diurnal 24-h cortisol production rate with hydrocortisone given twice or thrice daily, with the highest dose first thing in the morning. Monitoring treatment and dose titration has been much debated with some clinicians using cortisol day curves and others relying on clinical symptoms. The main challenge is that there is no established biomarker of cortisol activity. In addressing the clinical question, we have taken the view that an understanding of the cortisol circadian rhythm and hydrocortisone pharmacokinetics is essential when tailoring hydrocortisone dose. Using this approach, we have developed a thrice daily, weight-related, dosing regimen and a pharmacokinetic and clinical method to monitor treatment. Our argument for replicating the cortisol circadian rhythm is based on the observation that disruption of the rhythm is associated with ill health, and the few studies that have compared different treatment regimens. Further studies are required to definitively test the benefits of replacing the cortisol circadian rhythm in patients with adrenal insufficiency. © 2012 Blackwell Publishing Ltd.

Are WHO/UNAIDS/UNICEF-recommended replacement milks for infants of HIV-infected mothers appropriate in the South African context?

PubMed Central

Papathakis, P. C.; Rollins, N. C.

2004-01-01

OBJECTIVE: Little is known about the nutritional adequacy and feasibility of breastmilk replacement options recommended by WHO/UNAIDS/UNICEF. The study aim was to explore suitability of the 2001 feeding recommendations for infants of HIV-infected mothers for a rural region in KwaZulu Natal, South Africa specifically with respect to adequacy of micronutrients and essential fatty acids, cost, and preparation times of replacement milks. METHODS: Nutritional adequacy, cost, and preparation time of home-prepared replacement milks containing powdered full cream milk (PM) and fresh full cream milk (FM) and different micronutrient supplements (2 g UNICEF micronutrient sachet, government supplement routinely available in district public health clinics, and best available liquid paediatric supplement found in local pharmacies) were compared. Costs of locally available ingredients for replacement milk were used to calculate monthly costs for infants aged one, three, and six months. Total monthly costs of ingredients of commercial and home-prepared replacement milks were compared with each other and the average monthly income of domestic or shop workers. Time needed to prepare one feed of replacement milk was simulated. FINDINGS: When mixed with water, sugar, and each micronutrient supplement, PM and FM provided <50% of estimated required amounts for vitamins E and C, folic acid, iodine, and selenium and <75% for zinc and pantothenic acid. PM and FM made with UNICEF micronutrient sachets provided 30% adequate intake for niacin. FM prepared with any micronutrient supplement provided no more than 32% vitamin D. All PMs provided more than adequate amounts of vitamin D. Compared with the commercial formula, PM and FM provided 8-60% of vitamins A, E, and C, folic acid, manganese, zinc, and iodine. Preparations of PM and FM provided 11% minimum recommended linoleic acid and 67% minimum recommended alpha-linolenic acid per 450 ml mixture. It took 21-25 minutes to optimally prepare 120 ml of replacement feed from PM or commercial infant formula and 30-35 minutes for the fresh milk preparation. PM or FM cost approximately 20% of monthly income averaged over the first six months of life; commercial formula cost approximately 32%. CONCLUSION: No home-prepared replacement milks in South Africa meet all estimated micronutrient and essential fatty acid requirements of infants aged <6 months. Commercial infant formula is the only replacement milk that meets all nutritional needs. Revisions of WHO/UNAIDS/UNICEF HIV and infant feeding course replacement milk options are needed. If replacement milks are to provide total nutrition, preparations should include vegetable oils, such as soybean oil, as a source of linoleic and alpha-linolenic acids, and additional vitamins and minerals. PMID:15112004

Bicarbonate may Be required for ligation of manganese in the oxygen-evolving complex of photosystem II.

PubMed

Klimov, V V; Hulsebosch, R J; Allakhverdiev, S I; Wincencjusz, H; van Gorkom, H J; Hoff, A J

1997-12-23

It was previously shown in the photosystem II membrane preparation DT-20 that photoxidation of the oxygen-evolving manganese cluster was blocked by 0.1 mM formate, unless 0.2 mM bicarbonate was present as well [Wincencjusz, H., Allakhverdiev, S. I., Klimov, V. V., and Van Gorkom, H. J. (1996) Biochim. Biophys. Acta 1273, 1-3]. Here it is shown by measurements of EPR signal II that oxidation of the secondary electron donor, YZ, is not inhibited. However, the reduction of is greatly slowed and occurs largely by back reaction with reduced acceptors. Bicarbonate is shown to prevent the loss of fast electron donation to . The release of about one or two free Mn2+ per photosystem II during formate treatment, and the fact that these effects are mimicked by Mn-depletion, suggests that formate may act by replacing a bicarbonate which is essential for Mn binding. Irreversible light-induced rebinding in an EPR-silent form of Mn2+ that was added to Mn-depleted DT-20 was indeed found to depend on the presence of bicarbonate, as did the reconstitution in such material of both the fast electron donation to and the UV absorbance changes characteristic of a functional oxygen-evolving complex. It is concluded that bicarbonate may be an essential ligand of the functional Mn cluster.

OPTIMIZING POTENTIAL GREEN REPLACEMENT CHEMICALS – BALANCING FUNCTION AND RISK

EPA Science Inventory

An important focus of green chemistry is the design of new chemicals that are inherently less toxic than the ones they might replace, but still retain required functional properties. A variety of methods exist to measure or model both functional and toxicity surrogates that could...

Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62.

PubMed

Kim, Seong K; Shakya, Akhalesh K; Kim, Seongman; O'Callaghan, Dennis J

2016-01-15

The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for trans-activation, including an acidic trans-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT trans-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its trans-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold) trans-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited trans-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to trans-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly, trans-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication. The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral trans-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for trans-activation mediated by the acidic trans-activation domain (TAD). The TADs of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with cellular Mediator 25 in bimolecular complementation assays. The interaction of the IE62 SRT with nucleolar-ribosomal protein EAP resulted in the formation of globular structures within the nucleus. Understanding the mechanisms by which the TAD and SRT of IE62 contribute to the function of this essential regulatory protein is important in understanding the gene program of this human pathogen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62

PubMed Central

Shakya, Akhalesh K.; Kim, Seongman; O'Callaghan, Dennis J.

2015-01-01

ABSTRACT The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for trans-activation, including an acidic trans-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT trans-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its trans-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold) trans-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited trans-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to trans-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly, trans-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication. IMPORTANCE The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral trans-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for trans-activation mediated by the acidic trans-activation domain (TAD). The TADs of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with cellular Mediator 25 in bimolecular complementation assays. The interaction of the IE62 SRT with nucleolar-ribosomal protein EAP resulted in the formation of globular structures within the nucleus. Understanding the mechanisms by which the TAD and SRT of IE62 contribute to the function of this essential regulatory protein is important in understanding the gene program of this human pathogen. PMID:26537679

Functional importance of evolutionally conserved Tbx6 binding sites in the presomitic mesoderm-specific enhancer of Mesp2.

PubMed

Yasuhiko, Yukuto; Kitajima, Satoshi; Takahashi, Yu; Oginuma, Masayuki; Kagiwada, Harumi; Kanno, Jun; Saga, Yumiko

2008-11-01

The T-box transcription factor Tbx6 controls the expression of Mesp2, which encodes a basic helix-loop-helix transcription factor that has crucial roles in somitogenesis. In cultured cells, Tbx6 binding to the Mesp2 enhancer region is essential for the activation of Mesp2 by Notch signaling. However, it is not known whether this binding is required in vivo. Here we report that an Mesp2 enhancer knockout mouse bearing mutations in two crucial Tbx6 binding sites does not express Mesp2 in the presomitic mesoderm. This absence leads to impaired skeletal segmentation identical to that reported for Mesp2-null mice, indicating that these Tbx6 binding sites are indispensable for Mesp2 expression. T-box binding to the consensus sequences in the Mesp2 upstream region was confirmed by chromatin immunoprecipitation assays. Further enhancer analyses indicated that the number and spatial organization of the T-box binding sites are critical for initiating Mesp2 transcription via Notch signaling. We also generated a knock-in mouse in which the endogenous Mesp2 enhancer was replaced by the core enhancer of medaka mespb, an ortholog of mouse Mesp2. The homozygous enhancer knock-in mouse was viable and showed normal skeletal segmentation, indicating that the medaka mespb enhancer functionally replaced the mouse Mesp2 enhancer. These results demonstrate that there is significant evolutionary conservation of Mesp regulatory mechanisms between fish and mice.

Recent Patents and Designs on Hip Replacement Prostheses

PubMed Central

Derar, H; Shahinpoor, M

2015-01-01

Hip replacement surgery has gone through tremendous evolution since the first procedure in 1840. In the past five decades the advances that have been made in technology, advanced and smart materials innovations, surgical techniques, robotic surgery and methods of fixations and sterilization, facilitated hip implants that undergo multiple design revolutions seeking the least problematic implants and a longer survivorship. Hip surgery has become a solution for many in need of hip joint remedy and replacement across the globe. Nevertheless, there are still long-term problems that are essential to search and resolve to find the optimum implant. This paper reviews several recent patents on hip replacement surgery. The patents present various designs of prostheses, different materials as well as methods of fixation. Each of the patents presents a new design as a solution to different issues ranging from the longevity of the hip prostheses to discomfort and inconvenience experienced by patients in the long-term. PMID:25893020

Microstructural characterization of catalysis product of nanocement based materials: A review

NASA Astrophysics Data System (ADS)

Sutan, Norsuzailina Mohamed; Izaitul Akma Ideris, Nur; Taib, Siti Noor Linda; Lee, Delsye Teo Ching; Hassan, Alsidqi; Kudnie Sahari, Siti; Mohamad Said, Khairul Anwar; Rahman Sobuz, Habibur

2018-03-01

Cement as an essential element for cement-based products contributed to negative environmental issues due to its high energy consumption and carbon dioxide emission during its production. These issues create the need to find alternative materials as partial cement replacement where studies on the potential of utilizing silica based materials as partial cement replacement come into picture. This review highlights the effectiveness of microstructural characterization techniques that have been used in the studies that focus on characterization of calcium hydroxide (CH) and calcium silicate hydrate (C-S-H) formation during hydration process of cement-based product incorporating nano reactive silica based materials as partial cement replacement. Understanding the effect of these materials as cement replacement in cement based product focusing on the microstructural development will lead to a higher confidence in the use of industrial waste as a new non-conventional material in construction industry that can catalyse rapid and innovative advances in green technology.

Essential role of the NH2-terminal WD/EPF motif in the phosphorylation-activated protective function of mammalian Hsp27.

PubMed

Thériault, Jimmy R; Lambert, Herman; Chávez-Zobel, Aura T; Charest, Gabriel; Lavigne, Pierre; Landry, Jacques

2004-05-28

Hsp27 is expressed at high levels after mild heat shock and contributes to making cells extremely resistant to subsequent treatments. The activity of the protein is regulated at the transcriptional level, but also by phosphorylation, which occurs rapidly during stress and is responsible for causing the dissociation of large 700-kDa Hsp27 oligomers into dimers. We investigated the mechanism by which phosphorylation and oligomerization modulate the protective activity of Chinese hamster Hsp27. In contrast to oligomer dissociation, which only required Ser90 phosphorylation, activation of Hsp27 thermoprotective activity required the phosphorylation of both Ser90 and Ser15. Replacement of Ser90 by Ala90, which prevented the dissociation of the oligomer upon stress, did cause a severe defect in the protective activity. Dissociation was, however, not a sufficient condition to activate the protein because replacement of Ser15 by Ala15, which caused little effect in the oligomeric organization of the protein, also yielded an inactive protein. Analyzes of mutants with short deletions in the NH2 terminus identified the Hsp27 WD/EPF or PF-rich domain as essential for protection, maintenance of the oligomeric structure, and in vitro chaperone activity of the protein. In light of a three-dimensional model of Hsp27 based on the crystallographic structure of wheat Hsp16.9, we propose that the conserved WD/EPF motif of mammalian Hsp27 mediates important intramolecular interactions with hydrophic surfaces of the alpha-crystallin domain of the protein. These interactions are destabilized by Ser90 phosphorylation, making the motif free to interact with heterologous molecular targets upon the additional phosphorylation of the nearby Ser15.

Hibiscus Chlorotic Ringspot Virus Coat Protein Is Essential for Cell-to-Cell and Long-Distance Movement but Not for Viral RNA Replication

PubMed Central

Niu, Shengniao; Gil-Salas, Francisco M.; Tewary, Sunil Kumar; Samales, Ashwin Kuppusamy; Johnson, John; Swaminathan, Kunchithapadam; Wong, Sek-Man

2014-01-01

Hibiscus chlorotic ringspot virus (HCRSV) is a member of the genus Carmovirus in the family Tombusviridae. In order to study its coat protein (CP) functions on virus replication and movement in kenaf (Hibiscus cannabinus L.), two HCRSV mutants, designated as p2590 (A to G) in which the first start codon ATG was replaced with GTG and p2776 (C to G) in which proline 63 was replaced with alanine, were constructed. In vitro transcripts of p2590 (A to G) were able to replicate to a similar level as wild type without CP expression in kenaf protoplasts. However, its cell-to-cell movement was not detected in the inoculated kenaf cotyledons. Structurally the proline 63 in subunit C acts as a kink for β-annulus formation during virion assembly. Progeny of transcripts derived from p2776 (C to G) was able to move from cell-to-cell in inoculated cotyledons but its long-distance movement was not detected. Virions were not observed in partially purified mutant virus samples isolated from 2776 (C to G) inoculated cotyledons. Removal of the N-terminal 77 amino acids of HCRSV CP by trypsin digestion of purified wild type HCRSV virions resulted in only T = 1 empty virus-like particles. Taken together, HCRSV CP is dispensable for viral RNA replication but essential for cell-to-cell movement, and virion is required for the virus systemic movement. The proline 63 is crucial for HCRSV virion assembly in kenaf plants and the N-terminal 77 amino acids including the β-annulus domain is required in T = 3 assembly in vitro. PMID:25402344

Molecular analysis of functional redundancy among anti-apoptotic Bcl-2 proteins and its role in cancer cell survival.

PubMed

Eichhorn, Joshua M; Alford, Sarah E; Sakurikar, Nandini; Chambers, Timothy C

2014-04-01

Bcl-2 family proteins act as essential regulators and mediators of intrinsic apoptosis. Several lines of evidence suggest that the anti-apoptotic members of the family, including Bcl-2, Bcl-xL and Mcl-1, exhibit functional redundancy. However, the current evidence is largely indirect, and based mainly on pharmacological data using small-molecule inhibitors. In order to study compensation and redundancy of anti-apoptotic Bcl-2 proteins at the molecular level, we used a combined knockdown/overexpression strategy to essentially replace the function of one member with another. The results show that HeLa cells are strictly dependent on Mcl-1 for survival and correspondingly refractory to the Bcl-2/Bcl-xL inhibitor ABT-263, and remain resistant to ABT-263 in the context of Bcl-xL overexpression because endogenous Mcl-1 continues to provide the primary guardian role. However, if Mcl-1 is knocked down in the context of Bcl-xL overexpression, the cells become Bcl-xL-dependent and sensitive to ABT-263. We also show that Bcl-xL compensates for loss of Mcl-1 by sequestration of two key pro-apoptotic Bcl-2 family members, Bak and Bim, normally bound to Mcl-1, and that Bim is essential for cell death induced by Mcl-1 knockdown. To our knowledge, this is the first example where cell death induced by loss of Mcl-1 was rescued by the silencing of a single BH3-only Bcl-2 family member. In colon carcinoma cell lines, Bcl-xL and Mcl-1 also play compensatory roles, and Mcl-1 knockdown sensitizes cells to ABT-263. The results, obtained employing a novel strategy of combining knockdown and overexpression, provide unique molecular insight into the mechanisms of compensation by pro-survival Bcl-2 family proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

A single-cysteine mutant and chimeras of essential Leishmania Erv can complement the loss of Erv1 but not of Mia40 in yeast.

PubMed

Specht, Sandra; Liedgens, Linda; Duarte, Margarida; Stiegler, Alexandra; Wirth, Ulrike; Eberhardt, Maike; Tomás, Ana; Hell, Kai; Deponte, Marcel

2018-05-01

Mia40/CHCHD4 and Erv1/ALR are essential for oxidative protein folding in the mitochondrial intermembrane space of yeast and mammals. In contrast, many protists, including important apicomplexan and kinetoplastid parasites, lack Mia40. Furthermore, the Erv homolog of the model parasite Leishmania tarentolae (LtErv) was shown to be incompatible with Saccharomyces cerevisiae Mia40 (ScMia40). Here we addressed structure-function relationships of ScErv1 and LtErv as well as their compatibility with the oxidative protein folding system in yeast using chimeric, truncated, and mutant Erv constructs. Chimeras between the N-terminal arm of ScErv1 and a variety of truncated LtErv constructs were able to rescue yeast cells that lack ScErv1. Yeast cells were also viable when only a single cysteine residue was replaced in LtErv C17S . Thus, the presence and position of the C-terminal arm and the kinetoplastida-specific second (KISS) domain of LtErv did not interfere with its functionality in the yeast system, whereas a relatively conserved cysteine residue before the flavodomain rendered LtErv incompatible with ScMia40. The question whether parasite Erv homologs might also exert the function of Mia40 was addressed in another set of complementation assays. However, neither the KISS domain nor other truncated or mutant LtErv constructs were able to rescue yeast cells that lack ScMia40. The general relevance of Erv and its candidate substrate small Tim1 was analyzed for the related parasite L. infantum. Repeated unsuccessful knockout attempts suggest that both genes are essential in this human pathogen and underline the potential of mitochondrial protein import pathways for future intervention strategies. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Reducing Sodium in Foods: The Effect on Flavor

PubMed Central

Liem, Djin Gie; Miremadi, Fatemeh; Keast, Russell S. J.

2011-01-01

Sodium is an essential micronutrient and, via salt taste, appetitive. High consumption of sodium is, however, related to negative health effects such as hypertension, cardiovascular diseases and stroke. In industrialized countries, about 75% of sodium in the diet comes from manufactured foods and foods eaten away from home. Reducing sodium in processed foods will be, however, challenging due to sodium’s specific functionality in terms of flavor and associated palatability of foods (i.e., increase of saltiness, reduction of bitterness, enhancement of sweetness and other congruent flavors). The current review discusses the sensory role of sodium in food, determinants of salt taste perception and a variety of strategies, such as sodium replacers (i.e., potassium salts) and gradual reduction of sodium, to decrease sodium in processed foods while maintaining palatability. PMID:22254117

Learning from regeneration research organisms: The circuitous road to scar free wound healing.

PubMed

Erickson, Jami R; Echeverri, Karen

2018-01-15

The skin is the largest organ in the body and plays multiple essential roles ranging from regulating temperature, preventing infection and ultimately defining who we are physically. It is a highly dynamic organ that constantly replaces the outermost cells throughout life. However, when faced with a major injury, human skin cannot restore a significant lesion to its original functionality, instead a reparative scar is formed. In contrast to this, many other species have the unique ability to regenerate full thickness skin without formation of scar tissue. Here we review recent advances in the field that shed light on how the skin cells in regenerative species react to injury to prevent scar formation versus scar forming humans. Copyright © 2017 Elsevier Inc. All rights reserved.

The versatile subepithelial connective tissue graft: a literature update.

PubMed

Karthikeyan, B V; Khanna, Divya; Chowdhary, Kamedh Yashawant; Prabhuji, M Lv

2016-01-01

Harmony between hard and soft tissue morphologies is essential for form, function, and a good esthetic outlook. Replacement grafts for correction of soft tissue defects around the teeth have become important to periodontal plastic and implant surgical procedures. Among a multitude of surgical techniques and graft materials reported in literature, the subepithelial connective tissue graft (SCTG) has gained wide popularity and acceptance. The purpose of this article is to acquaint clinicians with the current understanding of the versatile SCTG. Key factors associated with graft harvesting as well as applications, limitations, and complications of SCTGs are discussed. This connective tissue has shown excellent short- and long-term stability, is easily available, and is economical to use. The SCTG should be considered as an alternative in all periodontal reconstruction surgeries.

Increasing and stabilizing β-sheet structure of maize zein causes improvement in its rheological properties.

PubMed

Mejia, Carla D; Gonzalez, David C; Mauer, Lisa J; Campanella, Osvaldo H; Hamaker, Bruce R

2012-03-07

Wheat gluten proteins are considered to have the unique ability to form viscoelastic matrices that are essential for breadmaking. This study shows that maize seed storage protein (zein), if properly treated, can be made to function similarly to gluten at the protein secondary structure level with concomitant improved viscoelasticity. Here, we propose the concept of a small amount of coprotein (high molecular weight glutenin or casein) acting to stabilize a build-up of β-sheet structure in a zein-based dough, thus creating a viscoelastic matrix that is retained over time. This discovery is relevant to the need for gluten replacement viscoelastic proteins for wheat intolerant individuals and as well opens possibilities of creating wheatlike cereal varieties that could more cheaply substitute for wheat imports in developing countries.

Optimizing the specificity of nucleic acid hybridization

PubMed Central

Zhang, David Yu; Chen, Sherry Xi; Yin, Peng

2014-01-01

The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biological and biotechnological reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temperature. Here, we analytically derived the thermodynamic properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temperature, salt and concentration conditions. We rationally designed ‘toehold exchange’ probes that approximate these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogues with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg2+ to 47 mM Mg2+, and with nucleic acid concentrations from 1 nM to 5 μM. Experiments with RNA also showed effective single-base change discrimination. PMID:22354435

Expansion of the aspartate [beta]-semialdehyde dehydrogenase family: the first structure of a fungal ortholog

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arachea, B.T.; Liu, X.; Pavlovsky, A.G.

2010-08-13

The enzyme aspartate semialdehyde dehydrogenase (ASADH) catalyzes a critical transformation that produces the first branch-point intermediate in an essential microbial amino-acid biosynthetic pathway. The first structure of an ASADH isolated from a fungal species (Candida albicans) has been determined as a complex with its pyridine nucleotide cofactor. This enzyme is a functional dimer, with a similar overall fold and domain organization to the structurally characterized bacterial ASADHs. However, there are differences in the secondary-structural elements and in cofactor binding that are likely to cause the lower catalytic efficiency of this fungal enzyme. Alterations in the dimer interface, through deletion ofmore » a helical subdomain and replacement of amino acids that participate in a hydrogen-bonding network, interrupt the intersubunit-communication channels required to support an alternating-site catalytic mechanism. The detailed functional information derived from this new structure will allow an assessment of ASADH as a possible target for antifungal drug development.« less

Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae

PubMed Central

Specht, Sebastian; Miller, Stephanie B.M.

2011-01-01

The aggregation of proteins inside cells is an organized process with cytoprotective function. In Saccharomyces cerevisiae, aggregating proteins are spatially sequestered to either juxtanuclear or peripheral sites, which target distinct quality control pathways for refolding and degradation. The cellular machinery driving the sequestration of misfolded proteins to these sites is unknown. In this paper, we show that one of the two small heat shock proteins of yeast, Hsp42, is essential for the formation of peripheral aggregates during physiological heat stress. Hsp42 preferentially localizes to peripheral aggregates but is largely absent from juxtanuclear aggregates, which still form in hsp42Δ cells. Transferring the amino-terminal domain of Hsp42 to Hsp26, which does not participate in aggregate sorting, enables Hsp26 to replace Hsp42 function. Our data suggest that Hsp42 acts via its amino-terminal domain to coaggregate with misfolded proteins and perhaps link such complexes to further sorting factors. PMID:22065637

A Review of Selected Models.

DTIC Science & Technology

1982-02-01

evacuation, essential maintenance, transportation, decontamination, and field services (i.e., replacements, graves registration, finance , etc.). 2...such logic through the tactical decision rules input by the user. With such a device, the UNICORN nuclear weapons 78 -T -- : I-, -- r, Pow- allocation

Tensor voting for image correction by global and local intensity alignment.

PubMed

Jia, Jiaya; Tang, Chi-Keung

2005-01-01

This paper presents a voting method to perform image correction by global and local intensity alignment. The key to our modeless approach is the estimation of global and local replacement functions by reducing the complex estimation problem to the robust 2D tensor voting in the corresponding voting spaces. No complicated model for replacement function (curve) is assumed. Subject to the monotonic constraint only, we vote for an optimal replacement function by propagating the curve smoothness constraint using a dense tensor field. Our method effectively infers missing curve segments and rejects image outliers. Applications using our tensor voting approach are proposed and described. The first application consists of image mosaicking of static scenes, where the voted replacement functions are used in our iterative registration algorithm for computing the best warping matrix. In the presence of occlusion, our replacement function can be employed to construct a visually acceptable mosaic by detecting occlusion which has large and piecewise constant color. Furthermore, by the simultaneous consideration of color matches and spatial constraints in the voting space, we perform image intensity compensation and high contrast image correction using our voting framework, when only two defective input images are given.

Nursing essential principles: continuous renal replacement therapy.

PubMed

Richardson, Annette; Whatmore, Jayne

2015-01-01

This article aims to guide critical care nurses with the care and management of patients on continuous renal replacement therapy (CRRT). CRRT, a highly specialized therapy involving complex nursing care, is used widely in the intensive care unit to treat patients with acute kidney injury. A literature search was conducted using CINAHL, Medline from PubMed and BNI using the search terms CRRT or continuous veno-venous haemofiltration and nursing or nurses from 2000 onwards and limited to the English language. The appraised evidence and expert opinion is used in this article. Four essential nursing principles for CRRT are reviewed (1) the importance of continuous assessment of the indications to influence the appropriate mode; (2) ensuring good vascular access; (3) the avoidance of unnecessary interruptions and (4) the prevention of complications. The identified four essential nursing principles provide guidance on this complex aspects of nursing practice. Specific nursing research to guide the care and management of this therapy is limited so should be explored in the future. Critical care nurses caring for and managing patients on CRRT require an understanding of how to deliver safe CRRT. © 2014 British Association of Critical Care Nurses.

EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.

PubMed

Dong, Yixin; Isono, Kyo-Ichi; Ohbo, Kazuyuki; Endo, Takaho A; Ohara, Osamu; Maekawa, Mamiko; Toyama, Yoshiro; Ito, Chizuru; Toshimori, Kiyotaka; Helin, Kristian; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Yamagata, Kazutsune; Kitabayashi, Issay; Koseki, Haruhiko

2017-10-01

Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome. Copyright © 2017 American Society for Microbiology.

Femoral offset: anatomical concept, definition, assessment, implications for preoperative templating and hip arthroplasty.

PubMed

Lecerf, G; Fessy, M H; Philippot, R; Massin, P; Giraud, F; Flecher, X; Girard, J; Mertl, P; Marchetti, E; Stindel, E

2009-05-01

BACKGROUND OBJECTIVE: Femoral offset is supposed to influence the results of hip replacement but little is known about the accurate method of measure and the true effect of offset modifications. This article is a collection of independent anatomic, radiological and clinical works, which purpose is to assess knowledge of the implications of femoral offset for preoperative templating and total hip arthroplasty. There is a strong correlation between femoral offset, abductors lever arm and hip abductor strength. Hip lateralization is independent of the femoral endomedullary characteristics. The abductors lever arm is highly correlated to the gluteus medius activation angle. There were correlations between femoral offset and endomedullary shape. The hip center was high and medial for stovepipe metaphysis while it was lower and lateralized for champagne - flute upper femur. A study was performed to compare the femoral offset measured by X-ray and CT-scan in 50 patients, demonstrated that plain radiography underestimates offset measurement. The 2D templating cannot appreciate the rotation of the lower limb. Taking into account the horizontal plane is essential to obtain proper 3D planning of the femoral offset. A randomized study was designed to compare femoral offset measurements after hip resurfacing and total hip arthroplasty. This study underlined hip resurfacing reduced the femoral offset, while hip replacement increased offset. However, the reduction of femoral offset after hip resurfacing does not affect the function. A pilot study was designed to assess the results of 120 hip arthroplasties with a modular femoral neck. This study showed that the use of a modular collar ensures an easier restoration of the femoral offset. A cohort of high offset stems (Lubinus 117 degrees) was retrospectively assessed. The survival rate was slightly lower that the standard design reported in the Swedish register. Finally, the measurement of offset and leg length was assessed with the help of computer assistance. The software changed the initial schedule (obtained by templating) in 29%. Therefore, femoral offset restoration is essential to improve function and longevity of hip arthroplasty. CT-scan is more accurate than plain radiography to assess femoral offset. Hip resurfacing decreases offset without effect on function. Modular neck and computer assistance may improve intraoperative calculation and reproduction of femoral offset. Increasing offset with a standard cemented design may decrease long-term fixation. Level IV: Retrospective or historical series.

Xanthomonas campestris RpfB is a Fatty Acyl-CoA Ligase Required to Counteract the Thioesterase Activity of the RpfF Diffusible Signal Factor (DSF) Synthase

PubMed Central

Bi, Hongkai; Yu, Yonghong; Dong, Huijuan; Wang, Haihong; Cronan, John E.

2014-01-01

SUMMARY In Xanthomonas campestris pv. campestris (Xcc), the proteins encoded by the rpf (regulator of pathogenicity factor) gene cluster produce and sense a fatty acid signal molecule called diffusible signaling factor (DSF, 2(Z)-11-methyldodecenoic acid). RpfB was reported to be involved in DSF processing and was predicted to encode an acyl-CoA ligase. We report that RpfB activates a wide range of fatty acids to their CoA esters in vitro. Moreover, RpfB can functionally replace the paradigm bacterial acyl-CoA ligase, Escherichia coli FadD, in the E. coli β-oxidation pathway and deletion of RpfB from the Xcc genome results in a strain unable to utilize fatty acids as carbon sources. An essential RpfB function in the pathogenicity factor pathway was demonstrated by the properties of a strain deleted for both the rpfB and rpfC genes. The ΔrpfB ΔrpfC strain grew poorly and lysed upon entering stationary phase. Deletion of rpfF, the gene encoding the DSF synthetic enzyme, restored normal growth to this strain. RpfF is a dual function enzyme that synthesizes DSF by dehydration of a 3-hydroxyacyl-acyl carrier protein (ACP) fatty acid synthetic intermediate and also cleaves the thioester bond linking DSF to ACP. However, the RpfF thioesterase activity is of broad specificity and upon elimination of its RpfC inhibitor RpfF attains maximal activity and its thioesterase activity proceeds to block membrane lipid synthesis by cleavage of acyl-ACP intermediates. This resulted in release of the nascent acyl chains to the medium as free fatty acids. This lack of acyl chains for phospholipid synthesis results in cell lysis unless RpfB is present to counteract the RpfF thioesterase activity by catalyzing uptake and activation of the free fatty acids to give acyl-CoAs that can be utilized to restore membrane lipid synthesis. Heterologous expression of a different fatty acid activating enzyme, the Vibrio harveyi acyl-ACP synthetase, replaced RpfB in counteracting the effects of high level RpfF thioesterase activity indicating that the essential role of RpfB is uptake and activation of free fatty acids. PMID:24866092

Analysis of NFU-1 metallocofactor binding-site substitutions-impacts on iron-sulfur cluster coordination and protein structure and function.

PubMed

Wesley, Nathaniel A; Wachnowsky, Christine; Fidai, Insiya; Cowan, J A

2017-11-01

Iron-sulfur (Fe/S) clusters are ancient prosthetic groups found in numerous metalloproteins and are conserved across all kingdoms of life due to their diverse, yet essential functional roles. Genetic mutations to a specific subset of mitochondrial Fe/S cluster delivery proteins are broadly categorized as disease-related under multiple mitochondrial dysfunction syndrome (MMDS), with symptoms indicative of a general failure of the metabolic system. Multiple mitochondrial dysfunction syndrome 1 (MMDS1) arises as a result of the missense mutation in NFU1, an Fe/S cluster scaffold protein, which substitutes a glycine near the Fe/S cluster-binding pocket to a cysteine (p.Gly208Cys). This substitution has been shown to promote protein dimerization such that cluster delivery to NFU1 is blocked, preventing downstream cluster trafficking. However, the possibility of this additional cysteine, located adjacent to the cluster-binding site, serving as an Fe/S cluster ligand has not yet been explored. To fully understand the consequences of this Gly208Cys replacement, complementary substitutions at the Fe/S cluster-binding pocket for native and Gly208Cys NFU1 were made, along with six other variants. Herein, we report the results of an investigation on the effect of these substitutions on both cluster coordination and NFU1 structure and function. The data suggest that the G208C substitution does not contribute to cluster binding. Rather, replacement of the glycine at position 208 changes the oligomerization state as a result of global structural alterations that result in the downstream effects manifest as MMDS1, but does not perturb the coordination chemistry of the Fe-S cluster. © 2017 Federation of European Biochemical Societies.

Myelin damage and repair in pathologic CNS: challenges and prospects

PubMed Central

Alizadeh, Arsalan; Dyck, Scott M.; Karimi-Abdolrezaee, Soheila

2015-01-01

Injury to the central nervous system (CNS) results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes and molecular reorganizations that collectively result in axonal dysfunction, degeneration and loss of sensory and motor functions. Endogenous adult oligodendrocyte precursor cells and neural stem/progenitor cells contribute to the replacement of oligodendrocytes, however, the extent and quality of endogenous remyelination is suboptimal. Emerging evidence indicates that optimal remyelination is restricted by multiple factors including (i) low levels of factors that promote oligodendrogenesis; (ii) cell death among newly generated oligodendrocytes, (iii) inhibitory factors in the post-injury milieu that impede remyelination, and (iv) deficient expression of key growth factors essential for proper re-construction of a highly organized myelin sheath. Considering these challenges, over the past several years, a number of cell-based strategies have been developed to optimize remyelination therapeutically. Outcomes of these basic and preclinical discoveries are promising and signify the importance of remyelination as a mechanism for improving functions in CNS injuries. In this review, we provide an overview on: (1) the precise organization of myelinated axons and the reciprocal axo-myelin interactions that warrant properly balanced physiological activities within the CNS; (2) underlying cause of demyelination and the structural and functional consequences of demyelination in axons following injury and disease; (3) the endogenous mechanisms of oligodendrocyte replacement; (4) the modulatory role of reactive astrocytes and inflammatory cells in remyelination; and (5) the current status of cell-based therapies for promoting remyelination. Careful elucidation of the cellular and molecular mechanisms of demyelination in the pathologic CNS is a key to better understanding the impact of remyelination for CNS repair. PMID:26283909

Dynamic biomechanical examination of the lumbar spine with implanted total spinal segment replacement (TSSR) utilizing a pendulum testing system.

PubMed

Daniels, Alan H; Paller, David J; Koruprolu, Sarath; Palumbo, Mark A; Crisco, Joseph J

2013-01-01

Biomechanical investigations of spinal motion preserving implants help in the understanding of their in vivo behavior. In this study, we hypothesized that the lumbar spine with implanted total spinal segment replacement (TSSR) would exhibit decreased dynamic stiffness and more rapid energy absorption compared to native functional spinal units under simulated physiologic motion when tested with the pendulum system. Five unembalmed, frozen human lumbar functional spinal units were tested on the pendulum system with axial compressive loads of 181 N, 282 N, 385 N, and 488 N before and after Flexuspine total spinal segment replacement implantation. Testing in flexion, extension, and lateral bending began by rotating the pendulum to 5°; resulting in unconstrained oscillatory motion. The number of rotations to equilibrium was recorded and bending stiffness (N-m/°) was calculated and compared for each testing mode. The total spinal segment replacement reached equilibrium with significantly fewer cycles to equilibrium compared to the intact functional spinal unit at all loads in flexion (p<0.011), and at loads of 385 N and 488 N in lateral bending (p<0.020). Mean bending stiffness in flexion, extension, and lateral bending increased with increasing load for both the intact functional spinal unit and total spinal segment replacement constructs (p<0.001), with no significant differences in stiffness between the intact functional spinal unit and total spinal segment replacement in any of the test modes (p>0.18). Lumbar functional spinal units with implanted total spinal segment replacement were found to have similar dynamic bending stiffness, but absorbed energy at a more rapid rate than intact functional spinal units during cyclic loading with an unconstrained pendulum system. Although the effects on clinical performance of motion preserving devices is not fully known, these results provide further insight into the biomechanical behavior of this device under approximated physiologic loading conditions.

Dynamic Biomechanical Examination of the Lumbar Spine with Implanted Total Spinal Segment Replacement (TSSR) Utilizing a Pendulum Testing System

PubMed Central

Daniels, Alan H.; Paller, David J.; Koruprolu, Sarath; Palumbo, Mark A.; Crisco, Joseph J.

2013-01-01

Background Biomechanical investigations of spinal motion preserving implants help in the understanding of their in vivo behavior. In this study, we hypothesized that the lumbar spine with implanted total spinal segment replacement (TSSR) would exhibit decreased dynamic stiffness and more rapid energy absorption compared to native functional spinal units under simulated physiologic motion when tested with the pendulum system. Methods Five unembalmed, frozen human lumbar functional spinal units were tested on the pendulum system with axial compressive loads of 181 N, 282 N, 385 N, and 488 N before and after Flexuspine total spinal segment replacement implantation. Testing in flexion, extension, and lateral bending began by rotating the pendulum to 5°; resulting in unconstrained oscillatory motion. The number of rotations to equilibrium was recorded and bending stiffness (N-m/°) was calculated and compared for each testing mode. Results The total spinal segment replacement reached equilibrium with significantly fewer cycles to equilibrium compared to the intact functional spinal unit at all loads in flexion (p<0.011), and at loads of 385 N and 488 N in lateral bending (p<0.020). Mean bending stiffness in flexion, extension, and lateral bending increased with increasing load for both the intact functional spinal unit and total spinal segment replacement constructs (p<0.001), with no significant differences in stiffness between the intact functional spinal unit and total spinal segment replacement in any of the test modes (p>0.18). Conclusions Lumbar functional spinal units with implanted total spinal segment replacement were found to have similar dynamic bending stiffness, but absorbed energy at a more rapid rate than intact functional spinal units during cyclic loading with an unconstrained pendulum system. Although the effects on clinical performance of motion preserving devices is not fully known, these results provide further insight into the biomechanical behavior of this device under approximated physiologic loading conditions. PMID:23451222

Selenium. Role of the Essential Metalloid in Health

PubMed Central

Kurokawa, Suguru; Berry, Marla J.

2015-01-01

Selenium is an essential micronutrient in mammals, but is also recognized as toxic in excess. It is a non-metal with properties that are intermediate between the chalcogen elements sulfur and tellurium. Selenium exerts its biological functions through selenoproteins. Selenoproteins contain selenium in the form of the 21st amino acid, selenocysteine (Sec), which is an analog of cysteine with the sulfur-containing side chain replaced by a Se-containing side chain. Sec is encoded by the codon UGA, which is one of three termination codons for mRNA translation in non-selenoprotein genes. Recognition of the UGA codon as a Sec insertion site instead of stop requires a Sec insertion sequence (SECIS) element in selenoprotein mRNAs and a unique selenocysteyl-tRNA, both of which are recognized by specialized protein factors. Unlike the 20 standard amino acids, Sec is biosynthesized from serine on its tRNA. Twenty-five selenoproteins are encoded in the human genome. Most of the selenoprotein genes were discovered by bioinformatics approaches, searching for SECIS elements downstream of in-frame UGA codons. Sec has been described as having stronger nucleophilic and electrophilic properties than cysteine, and Sec is present in the catalytic site of all selenoenzymes. Most selenoproteins, whose functions are known, are involved in redox systems and signaling pathways. However, several selenoproteins are not well characterized in terms of their function. The selenium field has grown dramatically in the last few decades, and research on selenium biology is providing extensive new information regarding its importance for human health. PMID:24470102

Domain-swapping analysis of FtsI, FtsL, and FtsQ, bitopic membrane proteins essential for cell division in Escherichia coli.

PubMed Central

Guzman, L M; Weiss, D S; Beckwith, J

1997-01-01

FtsI, FtsL, and FtsQ are three membrane proteins required for assembly of the division septum in the bacterium Escherichia coli. Cells lacking any of these three proteins form long, aseptate filaments that eventually lyse. FtsI, FtsL, and FtsQ are not homologous but have similar overall structures: a small cytoplasmic domain, a single membrane-spanning segment (MSS), and a large periplasmic domain that probably encodes the primary functional activities of these proteins. The periplasmic domain of FtsI catalyzes transpeptidation and is involved in the synthesis of septal peptidoglycan. The precise functions of FtsL and FtsQ are not known. To ask whether the cytoplasmic domain and MSS of each protein serve only as a membrane anchor or have instead a more sophisticated function, we have used molecular genetic techniques to swap these domains among the three Fts proteins and one membrane protein not involved in cell division, MalF. In the cases of FtsI and FtsL, replacement of the cytoplasmic domain and/or MSS resulted in the loss of the ability to support cell division. For FtsQ, MSS swaps supported cell division but cytoplasmic domain swaps did not. We discuss several potential interpretations of these results, including that the essential domains of FtsI, FtsL, and FtsQ have a role in regulating the localization and/or activity of these proteins to ensure that septum formation occurs at the right place in the cell and at the right time during the division cycle. PMID:9260951

75 FR 23579 - Airworthiness Directives; DASSAULT AVIATION Model FALCON 900EX and MYSTERE-FALCON 900 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... asymmetry detection system to verify proper functioning, and repair if necessary; repetitive replacement of... detection system to verify proper functioning, and repair if necessary; repetitive replacement of the...

SAR of α7 nicotinic receptor agonists derived from tilorone: exploration of a novel nicotinic pharmacophore.

PubMed

Schrimpf, Michael R; Sippy, Kevin B; Briggs, Clark A; Anderson, David J; Li, Tao; Ji, Jianguo; Frost, Jennifer M; Surowy, Carol S; Bunnelle, William H; Gopalakrishnan, Murali; Meyer, Michael D

2012-02-15

The well-known interferon-inducer tilorone was found to possess potent affinity for the agonist site of the α7 neuronal nicotinic receptor (K(i)=56 nM). SAR investigations determined that both basic sidechains are essential for potent activity, however active monosubstituted derivatives can also be prepared if the flexible sidechains are replaced with conformationally rigidified cyclic amines. Analogs in which the fluorenone core is replaced with either dibenzothiophene-5,5-dioxide or xanthenone also retain potent activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

21 CFR 870.3925 - Replacement heart valve.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

21 CFR 870.3925 - Replacement heart valve.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

21 CFR 870.3925 - Replacement heart valve.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

21 CFR 870.3925 - Replacement heart valve.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

21 CFR 870.3925 - Replacement heart valve.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

Mechanical drive for blood pump

DOEpatents

Bifano, N.J.; Pouchot, W.D.

1975-07-29

This patent relates to a highly efficient blood pump to be used as a replacement for a ventricle of the human heart to restore people disabled by heart disease. The mechanical drive of the present invention is designed to operate in conjunction with a thermoelectric converter power source. The mechanical drive system essentially converts the output of a rotary power into pulsatile motion so that the power demand from the thermoelectric converter remains essentially constant while the blood pump output is pulsed. (auth)

Monitoring the vaccine cold chain.

PubMed

Cheriyan, E

1993-11-01

Maintaining the vaccine cold chain is an essential part of a successful immunisation programme. A continuous electronic temperature monitor helped to identify breaks in the cold chain in the community and the study led to the issue of proper guidelines and replacement of faulty equipment.

Convergent Cognition

ERIC Educational Resources Information Center

Rich, Peter J.; Leatham, Keith R.; Wright, Geoffrey A.

2013-01-01

In an attempt to address shortcomings revealed in international assessments and lamented in legislation, many schools are reducing or eliminating elective courses, applying the rationale that replacing "non-essential" subjects with core subjects, such as mathematics and language arts, will better position students in the global market. However,…

Structure, attachment, replacement and growth of teeth in bluefish, Pomatomus saltatrix (Linnaeus, 1776), a teleost with deeply socketed teeth.

PubMed

Bemis, William E; Giuliano, Anne; McGuire, Betty

2005-01-01

Tooth replacement poses many questions about development, pattern formation, tooth attachment mechanisms, functional morphology and the evolution of vertebrate dentitions. Although most vertebrate species have polyphyodont dentitions, detailed knowledge of tooth structure and replacement is poor for most groups, particularly actinopterygians. We examined the oral dentition of the bluefish, Pomatomus saltatrix, a pelagic and coastal marine predator, using a sample of 50 individuals. The oral teeth are located on the dentary and premaxillary bones, and we scored each tooth locus in the dentary and premaxillary bones using a four-part functional classification: absent (A), incoming (I), functional (F=fully ankylosed) or eroding (E). The homodont oral teeth of Pomatomus are sharp, deeply socketed and firmly ankylosed to the bone of attachment. Replacement is intraosseus and occurs in alternate tooth loci with long waves of replacement passing from rear to front. The much higher percentage of functional as opposed to eroding teeth suggests that replacement rates are low but that individual teeth are quickly lost once erosion begins. Tooth number increases ontogenetically, ranging from 15-31 dentary teeth and 15-39 premaxillary teeth in the sample studied. Teeth increase in size with every replacement cycle. Remodeling of the attachment bone occurs continuously to accommodate growth. New tooth germs originate from a discontinuous dental lamina and migrate from the lingual (dentary) or labial (premaxillary) epithelium through pores in the bone of attachment into the resorption spaces beneath the existing teeth. Pomatomus shares unique aspects of tooth replacement with barracudas and other scombroids and this supports the interpretation that Pomatomus is more closely related to scombroids than to carangoids.

Modeling sensitive elasmobranch habitats

NASA Astrophysics Data System (ADS)

Pennino, M. Grazia; Muñoz, Facundo; Conesa, David; López-Quílez, Antonio; Bellido, José Marí; a

2013-10-01

Basic information on the distribution and habitat preferences of ecologically important species is essential for their management and protection. In the Mediterranean Sea there is increasing concern over elasmobranch species because their biological (ecological) characteristics make them highly vulnerable to fishing pressure. Their removal could affect the structure and function of marine ecosystems, inducing changes in trophic interactions at the community level due to the selective elimination of predators or prey species, competitors and species replacement. In this study Bayesian hierarchical spatial models are used to map the sensitive habitats of the three most caught elasmobranch species (Galeus melastomus, Scyliorhinus canicula, Etmopterus spinax) in the western Mediterranean Sea, based on fishery-dependent bottom trawl data. Results show that habitats associated with hard substrata and sandy beds, mainly in deep waters and with a high seabed gradient, have a greater probability registering the presence of the studied species than those associated with muddy shallow waters. Temperature and chlorophyll-α concentration show a negative relationship with S. canicula occurrence. Our results identify some of the sensitive habitats for elasmobranchs in the western Mediterranean Sea (GSA06 South), providing essential and easy-to-use interpretation tools, such as predictive distribution maps, with the final aim of improving management and conservation of these vulnerable species.

Battle of oral anticoagulants in the field of atrial fibrillation scrutinized from a clinical practice (the real world) perspective

PubMed Central

2011-01-01

Warfarin has a long history of benefit and has become the gold standard medication for the prevention of ischemic stroke in patients with atrial fibrillation. Nevertheless, it is far from perfect and there is no doubt that new drugs must be found to replace warfarin. The new oral anticoagulants that are on the market or awaiting approval or under research offer some benefits but not enough to replace warfarin until results of additional studies can show an adequate balance between effectiveness/safety and cost/benefit. There are several issues concerning the new oral anticoagulants. It is essential that the effect of any anticoagulant can be measured in plasma. But to date, there is no test to assess the effect or therapeutic range for the new oral anticoagulants. There is no antidote to neutralize the action of the new drugs in cases of bleeding or when acute surgical intervention is necessary. Dabigatran requires dose adjustment in patients with moderate renal impairment and is contraindicated in patients with severe renal failure. Rivaroxaban should be used with caution in patients with severe renal impairment. Apixaban excretion is also partly dependent on renal function, although the impact of renal insufficiency has not yet been determined. How anticoagulant bridging can be done before surgery has not yet been established. In conclusion, although thousands of patients have been treated in phase III studies, additional data are necessary before conclusions can be drawn on the potential for these new anticoagulant drugs to replace warfarin in patients with atrial fibrillation. PMID:21794130

An investigation of the validity of six measures of physical function in people awaiting joint replacement surgery of the hip or knee.

PubMed

Gill, Stephen D; de Morton, Natalie A; Mc Burney, Helen

2012-10-01

To assess and compare the validity of six physical function measures in people awaiting hip or knee joint replacement. Eighty-two people awaiting hip or knee replacement were assessed using six physical function measures including the WOMAC Function scale, SF-36 Physical Function scale, SF-36 Physical Component Summary scale, Patient Specific Functional Scale, 30-second chair stand test, and 50-foot timed walk. Validity was assessed using a head-to-head comparison design. Convergent validity was demonstrated with significant correlations between most measures (Spearman's rho 0.22 to 0.71). The Patient Specific Functional Scale had the lowest correlations with other measures of physical function. Discriminant validity was demonstrated with low correlations between mental health and physical function scores (Spearman's rho -0.12 to 0.33). Only the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated known groups validity when scores for participants who walked with a gait aid were compared with those who did not. Standardized response means and Guyatt's responsiveness indexes indicated that the SF-36 was the least responsive measure. For those awaiting joint replacement surgery of the hip or knee, the current investigation found that the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated the most evidence of validity. The Patient Specific Functional Scale might complement other measures by capturing a different aspect of physical function.

Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential.

PubMed

Thompson, Brian R; Metzger, Joseph M

2014-09-01

The cardiac sarcomere is the functional unit for myocyte contraction. Ordered arrays of sarcomeric proteins, held in stoichiometric balance with each other, respond to calcium to coordinate contraction and relaxation of the heart. Altered sarcomeric structure-function underlies the primary basis of disease in multiple acquired and inherited heart disease states. Hypertrophic and restrictive cardiomyopathies are caused by inherited mutations in sarcomeric genes and result in altered contractility. Ischemia-mediated acidosis directly alters sarcomere function resulting in decreased contractility. In this review, we highlight the use of acute genetic engineering of adult cardiac myocytes through stoichiometric replacement of sarcomeric proteins in these disease states with particular focus on cardiac troponin I. Stoichiometric replacement of disease causing mutations has been instrumental in defining the molecular mechanisms of hypertrophic and restrictive cardiomyopathy in a cellular context. In addition, taking advantage of stoichiometric replacement through gene therapy is discussed, highlighting the ischemia-resistant histidine-button, A164H cTnI. Stoichiometric replacement of sarcomeric proteins offers a potential gene therapy avenue to replace mutant proteins, alter sarcomeric responses to pathophysiologic insults, or neutralize altered sarcomeric function in disease. © 2014 Wiley Periodicals, Inc.

Total ankle replacement systems available in the United States.

PubMed

Coetzee, J Chris; Deorio, James K

2010-01-01

Ankle replacement continues to be a viable option for treating patients with ankle arthritis. Over the past 10 years, there has been a significant increase in the number of ankle replacement systems available for use. Current controversy centers on whether fixed- or mobile-bearing devices are most advantageous. Most total ankle systems used outside the United States are mobile-bearing devices, whereas ankle replacement systems used in the United States are all essentially fixed-bearing devices. Not all ankles with degenerative changes are amenable to replacement surgery, and several exclusion criteria are well documented. Ankle replacement is especially complicated because of the ankle's proximity to the foot and the important role that the balance and alignment of the foot play in the success of the ankle replacement. Foot deformities should be treated before or at the time of ankle replacement surgery. Ignoring foot deformities can lead to failure of the ankle replacement. It is also of paramount importance to consider the stability of the ankle ligaments. An unstable ankle with a varus or valgus deformity of more than 20 degrees is probably not amenable to ankle replacement. There are currently no reliable options to predictably reconstruct the lateral or medial ligaments in these severe deformities. It is important to be aware of the ankle replacement systems currently available in the United States and understand the key features of each design. Devices approved by the US Food and Drug Administration, a device that is awaiting approval, and a device that is being evaluated by the Food and Drug Administration in a prospective randomized clinical trial are discussed, along with an objective comparison of fixed- and mobile-bearing devices.

[Clinical study on patellar replacement in total knee arthroplasty].

PubMed

Bao, Liang; Gao, Zhihui; Shi, Xiaoqiang; Fang, Xiaomin; Jin, Qunhua

2013-01-01

To evaluate the influence of patellar replacement on total knee arthroplasty by comparing with non patellar replacement. Between September 2010 and November 2010, 63 patients (63 knees) with osteoarthritis who met the selection criteria and underwent total knee arthroplasty, were randomly divided into 2 groups: patellar replacement in 32 cases (replacement group), non patellar replacement in 31 cases (non patellar replacement group). There was no significant difference in gender, age, disease duration, osteoarthritis grading, the clinical and functional scores of American Knee Society Score (KSS), the patellar tilt angle, tibiofemoral angle, and patellar ligament ratio between 2 groups (P > 0.05), they were comparable. After 6 weeks, 3, 6, and 12 months of operation, clinical and imaging evaluation methods were used to assessment the effectiveness. Primary healing of incision was obtained in all patients of 2 groups. Deep venous thrombosis occurred in 6 cases of replacement group and in 8 cases of non patellar replacement group. All patients were followed up 12 months. The postoperative incidence of anterior knee pain in replacement group was significantly lower than that in non patellar replacement group (P < 0.05) at 3, 6, and 12 months after operation. No significant difference was found in the postoperative KSS clinical score between 2 groups at each time point (P > 0.05). The joint function score of the replacement group was significantly higher than that of the non patellar replacement group at the other time point (P < 0.05) except the score at 6 weeks and 3 months. Significant difference was found in the patella score between 2 groups at 12 months (P < 0.05), but no significant difference at the other time points (P > 0.05). X-ray film showed no patellar fracture and dislocation, or loosening and breakage of internal fixation. At 12 months after operation, the tibiofemoral angle, the patellar ligament ratio, and the patellar tilt angle showed no significant difference between 2 groups (P > 0.05). Patella replacement can improve knee function score and the patella score, and reduce the incidence of postoperative anterior knee pain.

Landscape restoration supports genetic connectivity among populations of a keystone species

USDA-ARS?s Scientific Manuscript database

Background/Question/Methods: Restoration of habitats that minimize dispersal costs could be essential for supporting population connectivity and the recovery of wildlife species. In the Chihuahuan Desert of southern New Mexico, grasslands have been replaced with shrubs due to overgrazing, drought, ...

The Wise Bus Buyer.

ERIC Educational Resources Information Center

Dervarics, Charles

1993-01-01

School transportation experts consider the following essential rules in purchasing school buses: know your geography; know federal and state regulations; write specifications carefully; plan for replacement and growth; check out prospective bidders; keep up with recent trends; and remain flexible. New Jersey enacted a law last year requiring seat…

An invasive social insect overcomes genetic load at the sex locus.

PubMed

Gloag, Rosalyn; Ding, Guiling; Christie, Joshua R; Buchmann, Gabriele; Beekman, Madeleine; Oldroyd, Benjamin P

2016-11-07

Some invasive hymenopteran social insects found new populations with very few reproductive individuals. This is despite the high cost of founder effects for such insects, which generally require heterozygosity at a single locus-the complementary sex determiner, csd-to develop as females. Individuals that are homozygous at csd develop as either infertile or subfertile diploid males or not at all. Furthermore, diploid males replace the female workers that are essential for colony function. Here we document how the Asian honey bee (Apis cerana) overcame the diploid male problem during its invasion of Australia. Natural selection prevented the loss of rare csd alleles due to genetic drift and corrected the skew in allele frequencies caused by founder effects to restore high average heterozygosity. Thus, balancing selection can alleviate the genetic load at csd imposed by severe bottlenecks, and so facilitate invasiveness.

Development and regeneration of vestibular hair cells in mammals.

PubMed

Burns, Joseph C; Stone, Jennifer S

2017-05-01

Vestibular sensation is essential for gaze stabilization, balance, and perception of gravity. The vestibular receptors in mammals, Type I and Type II hair cells, are located in five small organs in the inner ear. Damage to hair cells and their innervating neurons can cause crippling symptoms such as vertigo, visual field oscillation, and imbalance. In adult rodents, some Type II hair cells are regenerated and become re-innervated after damage, presenting opportunities for restoring vestibular function after hair cell damage. This article reviews features of vestibular sensory cells in mammals, including their basic properties, how they develop, and how they are replaced after damage. We discuss molecules that control vestibular hair cell regeneration and highlight areas in which our understanding of development and regeneration needs to be deepened. Copyright © 2016 Elsevier Ltd. All rights reserved.

High‐Volume Processed, ITO‐Free Superstrates and Substrates for Roll‐to‐Roll Development of Organic Electronics

PubMed Central

Hösel, Markus; Angmo, Dechan; Søndergaard, Roar R.; dos Reis Benatto, Gisele A.; Carlé, Jon E.; Jørgensen, Mikkel

2014-01-01

The fabrication of substrates and superstrates prepared by scalable roll‐to‐roll methods is reviewed. The substrates and superstrates that act as the flexible carrier for the processing of functional organic electronic devices are an essential component, and proposals are made about how the general availability of various forms of these materials is needed to accelerate the development of the field of organic electronics. The initial development of the replacement of indium‐tin‐oxide (ITO) for the flexible carrier materials is described and a description of how roll‐to‐roll processing development led to simplification from an initially complex make‐up to higher performing materials through a more simple process is also presented. This process intensification through process simplification is viewed as a central strategy for upscaling, increasing throughput, performance, and cost reduction. PMID:27980893

48 CFR 252.237-7023 - Continuation of Essential Contractor Services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... prescribed in 237.7603, use the following clause: Continuation of Mission Essential Functions (Date) (a) The... contractor services in support of mission-essential functions. The contractor-provided services that have been determined to be essential contractor services in support of mission-essential functions are...

Species replacement by a nonnative salmonid alters ecosystem function by reducing prey subsidies that support riparian spiders

USGS Publications Warehouse

Benjamin, J.R.; Fausch, K.D.; Baxter, C.V.

2011-01-01

Replacement of a native species by a nonnative can have strong effects on ecosystem function, such as altering nutrient cycling or disturbance frequency. Replacements may cause shifts in ecosystem function because nonnatives establish at different biomass, or because they differ from native species in traits like foraging behavior. However, no studies have compared effects of wholesale replacement of a native by a nonnative species on subsidies that support consumers in adjacent habitats, nor quantified the magnitude of these effects. We examined whether streams invaded by nonnative brook trout (Salvelinus fontinalis) in two regions of the Rocky Mountains, USA, produced fewer emerging adult aquatic insects compared to paired streams with native cutthroat trout (Oncorhynchus clarkii), and whether riparian spiders that depend on these prey were less abundant along streams with lower total insect emergence. As predicted, emergence density was 36% lower from streams with the nonnative fish. Biomass of brook trout was higher than the cutthroat trout they replaced, but even after accounting for this difference, emergence was 24% lower from brook trout streams. More riparian spiders were counted along streams with greater total emergence across the water surface. Based on these results, we predicted that brook trout replacement would result in 6-20% fewer spiders in the two regions. When brook trout replace cutthroat trout, they reduce cross-habitat resource subsidies and alter ecosystem function in stream-riparian food webs, not only owing to increased biomass but also because traits apparently differ from native cutthroat trout. ?? 2011 Springer-Verlag.

Engineering botulinum neurotoxin domains for activation by toxin light chain.

PubMed

Stancombe, Patrick R; Masuyer, Geoffrey; Birch-Machin, Ian; Beard, Matthew; Foster, Keith A; Chaddock, John A; Acharya, K Ravi

2012-02-01

Targeted secretion inhibitors (TSI) are a new class of biopharmaceuticals designed from a botulinum neurotoxin protein scaffold. The backbone consists of the 50-kDa endopeptidase light chain and translocation domain (N-terminal portion of the heavy chain), lacks neuronal toxicity, but retains the ability to target cytoplasmic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. TSI are produced as single-chain proteins and then cleaved post-translationally to generate functional heterodimers. Precise proteolytic cleavage is essential to activate the protein to a dichain form. TSI are themselves highly specific proteases. We have exploited this activity to create self-activating enzymes by replacing the native proteolytic site with a substrate SNARE peptide for the TSI protease. We have also created cross-activating backbones. By replacing the proteolytic activation site in one backbone with the substrate SNARE peptide for another serotype, controlled activation is achieved. SNARE peptides encompassing the whole of the coiled-coil region enabled complete activation and assembly of the dichain backbone. These engineered TSI backbones are capable of translocating their enzymatic domains to target intracellular SNARE proteins. They are also investigative tools with which to further the understanding of endopeptidase activity of light chain in SNARE interactions. © 2011 Syntaxin Ltd. Journal compilation © 2011 FEBS.

30 CFR 822.11 - Essential hydrologic functions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Essential hydrologic functions. 822.11 Section... IN ALLUVIAL VALLEY FLOORS § 822.11 Essential hydrologic functions. (a) The operator of a surface coal... throughout the mining and reclamation process the essential hydrologic functions of an alluvial valley floor...

The Radical SAM enzyme NirJ catalyzes the removal of two propionate side chains during heme d1 biosynthesis.

PubMed

Boss, Linda; Oehme, Ramona; Billig, Susan; Birkemeyer, Claudia; Layer, Gunhild

2017-12-01

Heme d 1 is a modified tetrapyrrole playing an important role in denitrification by acting as the catalytically essential cofactor in the cytochrome cd 1 nitrite reductase of many denitrifying bacteria. In the course of heme d 1 biosynthesis, the two propionate side chains on pyrrole rings A and B of the intermediate 12,18-didecarboxysiroheme are removed from the tetrapyrrole macrocycle. In the final heme d 1 molecule, the propionate groups are replaced by two keto functions. Although it was speculated that the Radical S-adenosyl-l-methionine (SAM) enzyme NirJ might be responsible for the removal of the propionate groups and introduction of the keto functions, this has not been shown experimentally, so far. Here, we demonstrate that NirJ is a Radical SAM enzyme carrying two iron-sulfur clusters. While the N-terminal [4Fe-4S] cluster is essential for the initial SAM cleavage reaction, it is not required for substrate binding. NirJ tightly binds its substrate 12,18-didecarboxysiroheme and, thus, can be purified in complex with the substrate. By using the purified NirJ/substrate complex in an in vitro enzyme activity assay, we show that NirJ indeed catalyzes the removal of the two propionate side chains under simultaneous SAM cleavage. However, under the reaction conditions employed, no keto group formation is observed indicating that an additional cofactor or enzyme is needed for this reaction. © 2017 Federation of European Biochemical Societies.

Calcium binding and transport by coenzyme Q.

PubMed

Bogeski, Ivan; Gulaboski, Rubin; Kappl, Reinhard; Mirceski, Valentin; Stefova, Marina; Petreska, Jasmina; Hoth, Markus

2011-06-22

Coenzyme Q10 (CoQ10) is one of the essential components of the mitochondrial electron-transport chain (ETC) with the primary function to transfer electrons along and protons across the inner mitochondrial membrane (IMM). The concomitant proton gradient across the IMM is essential for the process of oxidative phosphorylation and consequently ATP production. Cytochrome P450 (CYP450) monoxygenase enzymes are known to induce structural changes in a variety of compounds and are expressed in the IMM. However, it is unknown if CYP450 interacts with CoQ10 and how such an interaction would affect mitochondrial function. Using voltammetry, UV-vis spectrometry, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), fluorescence microscopy and high performance liquid chromatography-mass spectrometry (HPLC-MS), we show that both CoQ10 and its analogue CoQ1, when exposed to CYP450 or alkaline media, undergo structural changes through a complex reaction pathway and form quinone structures with distinct properties. Hereby, one or both methoxy groups at positions 2 and 3 on the quinone ring are replaced by hydroxyl groups in a time-dependent manner. In comparison with the native forms, the electrochemically reduced forms of the new hydroxylated CoQs have higher antioxidative potential and are also now able to bind and transport Ca(2+) across artificial biomimetic membranes. Our results open new perspectives on the physiological importance of CoQ10 and its analogues, not only as electron and proton transporters, but also as potential regulators of mitochondrial Ca(2+) and redox homeostasis.

The family of light-harvesting-related proteins (LHCs, ELIPs, HLIPs): was the harvesting of light their primary function?

PubMed

Montané, M H; Kloppstech, K

2000-11-27

Light-harvesting complex proteins (LHCs) and early light-induced proteins (ELIPs) are essential pigment-binding components of the thylakoid membrane and are encoded by one of the largest and most complex higher plant gene families. The functional diversification of these proteins corresponded to the transition from extrinsic (phycobilisome-based) to intrinsic (LHC-based) light-harvesting antenna systems during the evolution of chloroplasts from cyanobacteria, yet the functional basis of this diversification has been elusive. Here, we propose that the original function of LHCs and ELIPs was not to collect light and to transfer its energy content to the reaction centers but to disperse the absorbed energy of light in the form of heat or fluorescence. These energy-dispersing proteins are believed to have originated in cyanobacteria as one-helix, highly light-inducible proteins (HLIPs) that later acquired four helices through two successive gene duplication steps. We suggest that the ELIPs arose first in this succession, with a primary function in energy dispersion for protection of photosynthetic pigments from photo-oxidation. We consider the LHC I and II families as more recent and very successful evolutionary additions to this family that ultimately attained a new function, thereby replacing the ancestral extrinsic light-harvesting system. Our model accounts for the non-photochemical quenching role recently shown for higher plant psbS proteins.

Degradation of Beta-Cloth Covering for a Battery Orbital Replacement Unit in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Gaier, James R.; Baldwin, Sammantha; Folz, Angela D.; Waters, Deborah L.; Loos, Alyssa

2016-01-01

Samples from the B-cloth cover for a battery orbit replaceable unit from the International Space Station were characterized using optical and electron microscopy, UV-vis-NIR spectrophotometry, and x-ray energy dispersive spectroscopy. Results showed that in areas where the fabric was exposed to solar radiation the absorptance increased by as much as 20 percent, and the peak difference was in the ultraviolet, indicating that the increased absorptance may have been due to radiation. The emissivity of the material over a temperature range of 300 - 700 K was essentially unchanged.

Degradation of Beta Cloth Covering for a Battery Orbital Replacement Unit in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Gaier, James R.; Waters, Deborah L.; Baldwin, Sammantha; Folz, Angela D.; Loos, Alyssa

2016-01-01

Samples from the beta cloth cover for a battery orbit replaceable unit from the International Space Station (ISS) were characterized using optical and electron microscopy, UV-vis-NIR spectrophotometry, and x-ray energy dispersive spectroscopy. Results showed that in areas where the fabric was exposed to solar radiation the absorptance increased by as much as 20 percent, and the peak difference was in the ultraviolet, indicating that the increased absorptance may have been due to radiation. The emissivity of the material over a temperature range of 300 to 700 K was essentially unchanged.

Health reform through tax reform: a primer.

PubMed

Furman, Jason

2008-01-01

Tax incentives for employer-sponsored insurance and other medical spending cost about $200 billion annually and have pervasive effects on coverage and costs. This paper surveys a range of proposals to reform health care, either by adding new tax incentives or by limiting or replacing the existing tax incentives. Replacing the current tax preference for insurance with an income-related, refundable tax credit has the potential to expand coverage and reduce inefficient spending at no net federal cost. But such an approach by itself would entail substantial risks, so complementary reforms to the insurance market are essential to ensure success.

Medicaid prescription limits: policy trends and comparative impact on utilization.

PubMed

Lieberman, Daniel A; Polinski, Jennifer M; Choudhry, Niteesh K; Avorn, Jerry; Fischer, Michael A

2016-01-15

Medicaid programs face growing pressure to control spending. Despite evidence of clinical harms, states continue to impose policies limiting the number of reimbursable prescriptions (caps). We examined the recent use of prescription caps by Medicaid programs and the impact of policy implementation on prescription utilization. We identified Medicaid cap policies from 2001-2010. We classified caps as applying to all prescriptions (overall caps) or only branded prescriptions (brand caps). Using state-level, aggregate prescription data, we developed interrupted time-series analyses to evaluate the impact of implementing overall caps and brand caps in a subset of states with data available before and after cap initiation. For overall caps, we examined the use of essential medications, which were classified as preventive or as providing symptomatic benefit. For brand caps, we examined the use of all branded drugs as well as branded and generic medications among classes with available generic replacements. The number of states with caps increased from 12 in 2001 to 20 in 2010. Overall cap implementation (n = 3) led to a 0.52% (p < 0.001) annual decrease in the proportion of essential prescriptions but no change in cost. For preventive essential medications, overall caps led to a 1.12% (p = 0.001) annual decrease in prescriptions (246,000 prescriptions annually) and a 1.20% (p < 0.001) decrease in spending (-$12.2 million annually), but no decrease in symptomatic essential medication use. Brand cap implementation (n = 6) led to an immediate 2.29% (p = 0.16) decrease in branded prescriptions and 1.26% (p = 0.025) decrease in spending. For medication classes with generic replacements, the decrease in branded prescriptions (0.74%, p = 0.003) approximately equaled the increase in generics (0.79%, p = 0.009), with estimated savings of $17.4 million. An increasing number of states are using prescription caps, with mixed results. Overall caps decreased the use of preventive but not symptomatic essential medications, suggesting that patients assign higher priority to agents providing symptomatic benefit when faced with reimbursement limits. Among medications with generic replacements, brand caps shifted usage from branded drugs to generics, with considerable savings. Future research should analyze the patient-level impact of these policies to measure clinical outcomes associated with these changes.

Five Residues in the Apical Loop of the Respiratory Syncytial Virus Fusion Protein F2 Subunit are Critical for its Fusion Activity.

PubMed

Hicks, Stephanie N; Chaiwatpongsakorn, Supranee; Costello, Heather M; McLellan, Jason S; Ray, William; Peeples, Mark E

2018-05-09

The respiratory syncytial virus (RSV) fusion (F) protein is a trimeric, membrane-anchored glycoprotein capable of mediating both viral-target cell membrane fusion to initiate infection and cell-cell fusion, even in the absence of the attachment glycoprotein. The F protein is initially expressed in a precursor form, whose functional capabilities are activated by proteolysis at two sites between the F 1 and F 2 subunits. This cleavage results in expression of the metastable and high-energy prefusion conformation. To mediate fusion, the F protein is triggered by an unknown stimulus, causing the F 1 subunit to refold dramatically while F 2 changes minimally. Hypothesizing that the most likely site for interaction with a target-cell component would be the top, or apex, of the protein, we determined the importance of the residues in the apical loop of F 2 by scanning mutagenesis. Five residues were not important, two were of intermediate importance, and all four lysines and one isoleucine were essential. Alanine replacement did not result in the loss of pre-F conformation for any of these mutants. Each of the four lysines required its specific charge for fusion function. Alanine replacement of the three essential lysines on the ascent to the apex hindered fusion following a forced fusion event, suggesting they are involved in refolding. Alanine mutation at Ile64, also on the ascent to the apex, and Lys75, did not prevent fusion following forced triggering, suggesting they are not involved in refolding and may instead be involved in the natural triggering of the F protein. IMPORTANCE RSV infects virtually every child by the age of 3, causing nearly 33 million acute lower respiratory infections (ALRI) worldwide each year in children younger than 5 (Nair H, et al. 2010. Lancet 375:1545-55). RSV is also the second leading cause of respiratory related death in the elderly (Falsey AR, Walsh EE. 2005. Drugs Aging 22:577-87; Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. 2005. N Engl J Med 352:1749-1759). The monoclonal antibody palivizumab is approved for prophylactic use in some at-risk infants, but healthy infants remain unprotected. Furthermore, its expense limits its use primarily to developed countries. No vaccine or effective small-molecule drug is approved for preventing disease or treating infection (Costello HM, Ray W, Chaiwatpongsakorn S, Peeples ME. 2012. 12:110-128). The essential residues identified in the apical domain of F 2 are adjacent to the apical portion of F 1 which, upon triggering, refolds into the long heptad repeat A (HRA) with the fusion peptide at its N-terminus. These essential residues in F 2 are likely involved in triggering and/or refolding of the F protein and as such may be ideal targets for antiviral drug development. Copyright © 2018 American Society for Microbiology.

Characterization of Chlamydomonas Ribulose-1,5-bisphosphate carboxylase/oxygenase variants mutated at residues that are post-translationally modified.

PubMed

Rasineni, Girish Kumar; Loh, Pek Chin; Lim, Boon Hoe

2017-02-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the chloroplast enzyme that fixes CO 2 in photosynthesis, but the enzyme also fixes O 2 , which leads to the wasteful photorespiratory pathway. If we better understand the structure-function relationship of the enzyme, we might be able to engineer improvements. When the crystal structure of Chlamydomonas Rubisco was solved, four new posttranslational modifications were observed which are not present in other species. The modifications were 4-hydroxylation of the conserved Pro-104 and 151 residues, and S-methylation of the variable Cys-256 and 369 residues, which are Phe-256 and Val-369 in land plants. Because the modifications were only observed in Chlamydomonas Rubisco, they might account for the differences in kinetic properties between the algal and plant enzymes. Site-directed mutagenesis and chloroplast transformation have been used to test the essentiality of these modifications by replacing each of the residues with alanine (Ala). Biochemical analyses were done to determine the specificity factors and kinetic constants. Replacing the modified-residues in Chlamydomonas Rubisco affected the enzyme's catalytic activity. Substituting hydroxy-Pro-104 and methyl-Cys-256 with alanine influenced Rubisco catalysis. This is the first study on these posttranslationally-modified residues in Rubisco by genetic engineering. As these forms of modifications/regulation are not available in plants, the modified residues could be a means to modulate Rubisco activity. With a better understanding of Rubisco structure-function, we can define targets for improving the enzyme. Copyright © 2016 Elsevier B.V. All rights reserved.

Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: a pilot study.

PubMed

Mignani, Renzo; Panichi, Vincenzo; Giudicissi, Antonio; Taccola, Daniele; Boscaro, Francesca; Feletti, Carlo; Moneti, Gloriano; Cagnoli, Leonardo

2004-04-01

We sought to assess the safety and efficacy of enzyme replacement therapy (ERT) with recombinant human-alpha-galactosidase A (rh-alpha-Gal A) in kidney transplant recipients with Fabry disease, a previously unstudied population. Three male kidney transplant recipients with biochemically, genetically, and histologically confirmed Fabry disease and documented Fabry myocardiopathy received the rh-alpha-Gal A, agalsidase beta, 1 mg/kg of body weight every 2 weeks by intravenous infusion and were monitored biochemically, clinically, and electrocardiographically and echocardiographically for 18 months. Patients showed biochemical, clinical/functional, and morphologic response to ERT. Plasma globotriaosylceramide decreased 23% to 50%. Extremity pain resolved within 2 months in the patient with this manifestation. On echocardiography, left ventricular mass, end diastolic diameter (EDD), and cardiac contractility, shown by ejection fraction (EF), improved in 2 of the 3 patients receiving essentially all planned infusions. EDD and EF remained basically stable, but cardiac morphologic abnormalities progressed in the other patient, who had a 5-month interruption in ERT after the initial month. Mild mitral insufficiency persisted in all patients, as did atrial fibrillation in the affected individual. After a combined total of 116 infusions, no treatment-related adverse event, intolerance, or seroconversion was seen. Renal function remained stable and the immunosuppression regimen unchanged in all patients. Our pilot study provides preliminary evidence that ERT with agalsidase beta, 1 mg/kg every 2 weeks, is safe and often effective against extra-renal manifestations in kidney transplant patients with Fabry disease. Studies with longer courses of this and higher doses of ERT are merited in this population.

Hypophosphatasia - pathophysiology and treatment.

PubMed

Millán, José Luis; Plotkin, Horacio

2012-09-01

Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) in the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). The disease has been classified according to patient age when the first signs and symptoms manifest; i.e., perinatal, infantile, childhood, adult HPP. Other types include odonto HPP and perinatal benign. Babies with the perinatal/infantile forms of HPP often die with severe rickets and respiratory insufficiency and sometimes hypercalcemia and vitamin B 6 -responsive seizures. The primary biochemical defect in HPP is a deficiency of TNAP activity that leads to elevated circulating levels of substrates, in particular inorganic pyrophosphate (PP i ), a potent calcification inhibitor. To-date, the management of HPP has been essentially symptomatic or orthopedic. However, enzyme replacement therapy with mineral-targeting TNAP (sALP-FcD 10 , also known as ENB-0040 or asfotase alfa) has shown promising results in a mouse model of HPP ( Alpl -/- mice). Administration of mineral-targeting TNAP from birth increased survival and prevented the seizures, rickets, as well as all the tooth abnormalities, including dentin, acellular cementum, and enamel defects in this model of severe HPP. Clinical trials using mineral-targeting TNAP in children 3 years of age or younger with life-threatening HPP was associated with healing of the skeletal manifestations of HPP as well as improved respiratory and motor function. Improvement is still being observed in the patients receiving continued asfotase alfa therapy, with more than 3 years of treatment in some children. Enzyme replacement therapy with asfotase alfa has to-date been successful in patients with life-threatening HPP.

Hypophosphatasia - pathophysiology and treatment

PubMed Central

Millán, José Luis; Plotkin, Horacio

2013-01-01

English Summary Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) in the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). The disease has been classified according to patient age when the first signs and symptoms manifest; i.e., perinatal, infantile, childhood, adult HPP. Other types include odonto HPP and perinatal benign. Babies with the perinatal/infantile forms of HPP often die with severe rickets and respiratory insufficiency and sometimes hypercalcemia and vitamin B6-responsive seizures. The primary biochemical defect in HPP is a deficiency of TNAP activity that leads to elevated circulating levels of substrates, in particular inorganic pyrophosphate (PPi), a potent calcification inhibitor. To-date, the management of HPP has been essentially symptomatic or orthopedic. However, enzyme replacement therapy with mineral-targeting TNAP (sALP-FcD10, also known as ENB-0040 or asfotase alfa) has shown promising results in a mouse model of HPP (Alpl−/− mice). Administration of mineral-targeting TNAP from birth increased survival and prevented the seizures, rickets, as well as all the tooth abnormalities, including dentin, acellular cementum, and enamel defects in this model of severe HPP. Clinical trials using mineral-targeting TNAP in children 3 years of age or younger with life-threatening HPP was associated with healing of the skeletal manifestations of HPP as well as improved respiratory and motor function. Improvement is still being observed in the patients receiving continued asfotase alfa therapy, with more than 3 years of treatment in some children. Enzyme replacement therapy with asfotase alfa has to-date been successful in patients with life-threatening HPP. PMID:25254037

Cell response to quasi-monochromatic light with different coherence

NASA Astrophysics Data System (ADS)

Budagovsky, A. V.; Solovykh, N. V.; Budagovskaya, O. N.; Budagovsky, I. A.

2015-04-01

The problem of the light coherence effect on the magnitude of the photoinduced cell response is discussed. The origins of ambiguous interpretation of the known experimental results are considered. Using the biological models, essentially differing in anatomy, morphology and biological functions (acrospires of radish, blackberry microsprouts cultivated in vitro, plum pollen), the effect of statistical properties of quasi-monochromatic light (λmax = 633 nm) on the magnitude of the photoinduced cell response is shown. It is found that for relatively low spatial coherence, the cell functional activity changes insignificantly. The maximal enhancement of growing processes (stimulating effect) is observed when the coherence length Lcoh and the correlation radius rcor are greater than the cell size, i.e., the entire cell fits into the field coherence volume. In this case, the representative indicators (germination of seeds and pollen, the spears length) exceeds those of non-irradiated objects by 1.7 - 3.9 times. For more correct assessment of the effect of light statistical properties on photocontrol processes, it is proposed to replace the qualitative description (coherent - incoherent) with the quantitative one, using the determination of spatial and temporal correlation functions and comparing them with the characteristic dimensions of the biological structures, e.g., the cell size.

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs

PubMed Central

Wang, Bo; Patnaik, Sourav S.; Brazile, Bryn; Butler, J. Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

2016-01-01

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications. PMID:27480586

Escherichia coli K-12 and B contain functional bacteriophage P2 ogr genes.

PubMed Central

Slettan, A; Gebhardt, K; Kristiansen, E; Birkeland, N K; Lindqvist, B H

1992-01-01

The bacteriophage P2 ogr gene encodes an essential 72-amino-acid protein which acts as a positive regulator of P2 late transcription. A P2 ogr deletion phage, which depends on the supply of Ogr protein in trans for lytic growth on Escherichia coli C, has previously been constructed. E. coli B and K-12 were found to support the growth of the ogr-defective P2 phage because of the presence of functional ogr genes located in cryptic P2-like prophages in these strains. The cryptic ogr genes were cloned and sequenced. Compared with the P2 wild-type ogr gene, the ogr genes in the B and K-12 strains are conserved, containing mostly silent base substitutions. One of the base substitutions in the K-12 ogr gene results in replacement of an alanine with valine at position 57 in the Ogr protein but does not seem to affect the function of Ogr as a transcriptional activator. The cryptic ogr genes are constitutively transcribed, apparently at a higher level than the wild-type ogr gene in a P2 lysogen. Images PMID:1597424

Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy

PubMed Central

Sauer, Aisha V.; Morbach, Henner; Brigida, Immacolata; Ng, Yen-Shing; Aiuti, Alessandro; Meffre, Eric

2012-01-01

Adenosine deaminase (ADA) gene defects are among the most common causes of SCID. Restoration of purine metabolism and immune functions can be achieved by enzyme replacement therapy, or more effectively by bone marrow transplant or HSC gene therapy (HSC-GT). However, autoimmune complications and autoantibody production, including anti-nuclear antibodies (ANAs), frequently occur in ADA-SCID patients after treatment. To assess whether ADA deficiency affects the establishment of B cell tolerance, we tested the reactivity of recombinant antibodies isolated from single B cells of ADA-SCID patients before and after HSC-GT. We found that before HSC-GT, new emigrant/transitional and mature naive B cells from ADA-SCID patients contained more autoreactive and ANA-expressing clones, indicative of defective central and peripheral B cell tolerance checkpoints. We further observed impaired B cell receptor (BCR) and TLR functions in B cells after ADA inhibition, which may underlie the defects in B cell tolerance. Strikingly, after HSC-GT, ADA-SCID patients displayed quasi-normal early B cell tolerance checkpoints, as evidenced by restored removal of developing autoreactive and ANA-expressing B cells. Hence, ADA plays an essential role in controlling autoreactive B cell counterselection by regulating BCR and TLR functions. PMID:22622038

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

PubMed

Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

2015-01-01

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

Formation of a successional dental lamina in the zebrafish (Danio rerio): support for a local control of replacement tooth initiation.

PubMed

Huysseune, Ann

2006-01-01

In order to test whether the formation of a replacement tooth bud in a continuously replacing dentition is linked to the functional state of the tooth predecessor, I examined the timing of development of replacement teeth with respect to their functional predecessors in the pharyngeal dentition of the zebrafish. Observations based on serial semithin sections of ten specimens, ranging in age from four week old juveniles to adults, indicate that (i) a replacement tooth germ develops at the distal end of an epithelial structure, called the successional dental lamina, budding off from the crypt epithelium surrounding the erupted part of a functional tooth; (ii) there appears to be a developmental link between the eruption of a tooth and the formation of a successional dental lamina and (iii) there can be a time difference between successional lamina formation and initiation of the new tooth germ, i.e., the successional dental lamina can remain quiescent for some time. The data suggest that the formation of a successional lamina and the differentiation of a replacement tooth germ from this lamina, are two distinct phases of a process and possibly under a different control. The strong spatio-temporal coincidence of eruption of a tooth and development of a successional dental lamina is seen as evidence for a local control over tooth replacement.

Teaching Marketing Strategy: Using Resource-Advantage Theory as an Integrative Theoretical Foundation

ERIC Educational Resources Information Center

Hunt, Shelby D.; Madhavaram, Sreedhar

2006-01-01

Knowledge of marketing strategy is essential for marketing majors. To supplement and/or replace the traditional lecture-discussion approach, several pedagogical vehicles have been recommended to teach marketing strategy, including the analytic hierarchy process; career-planning cases; computer-assisted, simulated marketing cases; experiential…

Data Release Summary Statement

Atmospheric Science Data Center

2016-11-14

... of the CALIPSO data products includes new versions of its standard Level1 and Level2 lidar data. The V4.10 CALIOP Level 2 data products ... essential ancillary data sets. The GTOPO30 Digital Elevation Model (DEM) used in V4.00 has been replaced by a substantially more accurate ...

48 CFR 2052.215-70 - Key personnel.

Code of Federal Regulations, 2013 CFR

2013-10-01

... are considered to be essential to the successful performance of the work hereunder: * The contractor agrees that personnel may not be removed from the contract work or replaced without compliance with..., or is expected to become, unavailable for work under this contract for a continuous period exceeding...

Advances in Support of the CMAQ Bidirectional Science Option for the Estimation of Ammonia Flux from Agricultural cropland

EPA Science Inventory

Proposed Session: Emissions Inventories, Models and processes: Last year a new CMAQ bidirectional option for the estimation of ammonia flux (emission and deposition) was released. This option essentially replaces NEI crop ammonia emissions with emissions calculated dynamically...

Dry-extrusion of asian carp to supplement natural methionine in organic poultry production

USDA-ARS?s Scientific Manuscript database

Methionine, a sulfur containing amino acid, is essential for healthy poultry production. Synthetic methionine is commonly used as a supplement in conventional poultry. However, for organic poultry, a natural, cost effective source of methionine that can replace synthetic methionine is unavailable. I...

Glutamate 90 at the Luminal Ion Gate of Sarcoplasmic Reticulum Ca2+-ATPase Is Critical for Ca2+ Binding on Both Sides of the Membrane*

PubMed Central

Clausen, Johannes D.; Andersen, Jens Peter

2010-01-01

The roles of Ser72, Glu90, and Lys297 at the luminal ends of transmembrane helices M1, M2, and M4 of sarcoplasmic reticulum Ca2+-ATPase were examined by transient and steady-state kinetic analysis of mutants. The dependence on the luminal Ca2+ concentration of phosphorylation by Pi (“Ca2+ gradient-dependent E2P formation”) showed a reduction of the apparent affinity for luminal Ca2+ in mutants with alanine or leucine replacement of Glu90, whereas arginine replacement of Glu90 or Ser72 allowed E2P formation from Pi even at luminal Ca2+ concentrations much too small to support phosphorylation in wild type. The latter mutants further displayed a blocked dephosphorylation of E2P and an increased rate of conversion of the ADP-sensitive E1P phosphoenzyme intermediate to ADP-insensitive E2P as well as insensitivity of the E2·BeF3− complex to luminal Ca2+. Altogether, these findings, supported by structural modeling, indicate that the E2P intermediate is stabilized in the mutants with arginine replacement of Glu90 or Ser72, because the positive charge of the arginine side chain mimics Ca2+ occupying a luminally exposed low affinity Ca2+ site of E2P, thus identifying an essential locus (a “leaving site”) on the luminal Ca2+ exit pathway. Mutants with alanine or leucine replacement of Glu90 further displayed a marked slowing of the Ca2+ binding transition as well as slowing of the dissociation of Ca2+ from Ca2E1 back toward the cytoplasm, thus demonstrating that Glu90 is also critical for the function of the cytoplasmically exposed Ca2+ sites on the opposite side of the membrane relative to where Glu90 is located. PMID:20421308

ReplacementMatrix: a web server for maximum-likelihood estimation of amino acid replacement rate matrices.

PubMed

Dang, Cuong Cao; Lefort, Vincent; Le, Vinh Sy; Le, Quang Si; Gascuel, Olivier

2011-10-01

Amino acid replacement rate matrices are an essential basis of protein studies (e.g. in phylogenetics and alignment). A number of general purpose matrices have been proposed (e.g. JTT, WAG, LG) since the seminal work of Margaret Dayhoff and co-workers. However, it has been shown that matrices specific to certain protein groups (e.g. mitochondrial) or life domains (e.g. viruses) differ significantly from general average matrices, and thus perform better when applied to the data to which they are dedicated. This Web server implements the maximum-likelihood estimation procedure that was used to estimate LG, and provides a number of tools and facilities. Users upload a set of multiple protein alignments from their domain of interest and receive the resulting matrix by email, along with statistics and comparisons with other matrices. A non-parametric bootstrap is performed optionally to assess the variability of replacement rate estimates. Maximum-likelihood trees, inferred using the estimated rate matrix, are also computed optionally for each input alignment. Finely tuned procedures and up-to-date ML software (PhyML 3.0, XRATE) are combined to perform all these heavy calculations on our clusters. http://www.atgc-montpellier.fr/ReplacementMatrix/ olivier.gascuel@lirmm.fr Supplementary data are available at http://www.atgc-montpellier.fr/ReplacementMatrix/

Functional substitution for TAF(II)250 by a retroposed homolog that is expressed in human spermatogenesis.

PubMed

Wang, P Jeremy; Page, David C

2002-09-15

TAF(II)250, the largest subunit of the general transcription factor TFIID, is expressed from the human X chromosome, at least in somatic cells. In male meiosis, however, the sex chromosomes are transcriptionally silenced, while the autosomes remain active. How then are protein-encoding genes transcribed during human male meiosis? Here we present a novel autosomal human gene, TAF1L, which is homologous to TAF(II)250 and is expressed specifically in the testis, apparently in germ cells. We hypothesize that during male meiosis, transcription of protein-encoding genes relies upon TAF1L as a functional substitute for TAF(II)250. Like TAF(II)250, the human TAF1L protein can bind directly to TATA-binding protein, an essential component of TFIID. Most importantly, transfection with human TAF1L rescued the temperature-sensitive lethality of a hamster cell line mutant in TAF(II)250. TAF1L lacks introns and evidently arose by retroposition of a processed TAF(II)250 mRNA during primate evolution. The observation that TAF1L can functionally replace TAF(II)250 provides experimental support for the hypothesis that during male meiosis, autosomes provide cellular functions usually supplied by the X chromosome in somatic cells.

Twin Attributes of Tyrosyl-tRNA Synthetase of Leishmania donovani: A HOUSEKEEPING PROTEIN TRANSLATION ENZYME AND A MIMIC OF HOST CHEMOKINE.

PubMed

Anand, Sneha; Madhubala, Rentala

2016-08-19

Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes essential for protein synthesis. Apart from their parent aminoacylation activity, several aaRSs perform non-canonical functions in diverse biological processes. The present study explores the twin attributes of Leishmania tyrosyl-tRNA synthetase (LdTyrRS) namely, aminoacylation, and as a mimic of host CXC chemokine. Leishmania donovani is a protozoan parasite. Its genome encodes a single copy of tyrosyl-tRNA synthetase. We first tested the canonical aminoacylation role of LdTyrRS. The recombinant protein was expressed, and its kinetic parameters were determined by aminoacylation assay. To study the physiological role of LdTyrRS in Leishmania, gene deletion mutations were attempted via targeted gene replacement. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. LdTyrRS appears to be an essential gene as the chromosomal null mutants did not survive. Our data also highlights the non-canonical function of L. donovani tyrosyl-tRNA synthetase. We show that LdTyrRS protein is present in the cytoplasm and exits from the parasite cytoplasm into the extracellular medium. The released LdTyrRS functions as a neutrophil chemoattractant. We further show that LdTyrRS specifically binds to host macrophages with its ELR (Glu-Leu-Arg) peptide motif. The ELR-CXCR2 receptor interaction mediates this binding. This interaction triggers enhanced secretion of the proinflammatory cytokines TNF-α and IL-6 by host macrophages. Our data indicates a possible immunomodulating role of LdTyrRS in Leishmania infection. This study provides a platform to explore LdTyrRS as a potential target for drug development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Rapid formin-mediated actin-filament elongation is essential for polarized plant cell growth.

PubMed

Vidali, Luis; van Gisbergen, Peter A C; Guérin, Christophe; Franco, Paula; Li, Ming; Burkart, Graham M; Augustine, Robert C; Blanchoin, Laurent; Bezanilla, Magdalena

2009-08-11

Formins are present in all eukaryotes and are essential for the creation of actin-based structures responsible for diverse cellular processes. Because multicellular organisms contain large formin gene families, establishing the physiological functions of formin isoforms has been difficult. Using RNAi, we analyzed the function of all 9 formin genes within the moss Physcomitrella patens. We show that plants lacking class II formins (For2) are severely stunted and composed of spherical cells with disrupted actin organization. In contrast, silencing of all other formins results in normal elongated cell morphology and actin organization. Consistent with a role in polarized growth, For2 are apically localized in growing cells. We show that an N-terminal phosphatase tensin (PTEN)-like domain mediates apical localization. The PTEN-like domain is followed by a conserved formin homology (FH)1-FH2 domain, known to promote actin polymerization. To determine whether apical localization of any FH1-FH2 domain mediates polarized growth, we performed domain swapping. We found that only the class II FH1-FH2, in combination with the PTEN-like domain, rescues polarized growth, because it cannot be replaced with a similar domain from a For1. We used in vitro polymerization assays to dissect the functional differences between these FH1-FH2 domains. We found that both the FH1 and the FH2 domains from For2 are required to mediate exceptionally rapid rates of actin filament elongation, much faster than any other known formin. Thus, our data demonstrate that rapid rates of actin elongation are critical for driving the formation of apical filamentous actin necessary for polarized growth.

Recurrent pannus formation causing prosthetic aortic valve dysfunction: Is excision without valve re-replacement applicable?

PubMed Central

2012-01-01

Prosthetic valve dysfunction at aortic position is commonly caused by pannus formation. The exact etiology is not known. It arises from ventricular aspect of the prosthesis encroaching its leaflets causing stenosis or it may remain localized causing left ventricular outflow tract obstruction without affecting valve function. The difference in location entails different approaches in management. Such a pathology requires surgical excision of the pannus with or without valve re-replacement. A recurrent pannus was observed in a female patient who needed repeated surgical intervention to excise a localized pannus without re-replacement of a well functioning prosthetic valve. Management of our case presents several questions, whether recurrence of pannus is caused by sparing the prosthetic valve, is it simply an exaggeration of an inflammatory healing process in certain individuals or is it ideal to re-replace the valve despite a well preserved function. PMID:22747790

Recurrent pannus formation causing prosthetic aortic valve dysfunction: is excision without valve re-replacement applicable?

PubMed

Darwazah, Ahmad K

2012-06-29

Prosthetic valve dysfunction at aortic position is commonly caused by pannus formation. The exact etiology is not known. It arises from ventricular aspect of the prosthesis encroaching its leaflets causing stenosis or it may remain localized causing left ventricular outflow tract obstruction without affecting valve function.The difference in location entails different approaches in management. Such a pathology requires surgical excision of the pannus with or without valve re-replacement.A recurrent pannus was observed in a female patient who needed repeated surgical intervention to excise a localized pannus without re-replacement of a well functioning prosthetic valve.Management of our case presents several questions, whether recurrence of pannus is caused by sparing the prosthetic valve, is it simply an exaggeration of an inflammatory healing process in certain individuals or is it ideal to re-replace the valve despite a well preserved function.

Autotransplantation of a mandibular third molar: a case report with 5 years of follow-up.

PubMed

Chagas e Silva, Mauro Henrique; Lacerda, Mariane Floriano Lopes Santos; Chaves, Maria das Graças Afonso Miranda; Campos, Celso Neiva

2013-01-01

This paper describes the autologous transplantation of a mandibular right third molar to replace the residual roots of the second molar in the same quadrant, preserving function and aesthetics. A 5-year clinical and radiographic follow-up was undertaken. After transplantation, the donor tooth received endodontic treatment and placement of calcium hydroxide, which was periodically replaced every 3 months until the filling of the root canals, totalizing a period of 1-year, when apical closure was confirmed. The tooth was in perfect functional and aesthetic conditions 5 years after beginning of treatment. Autotransplantation is a feasible option for replacing missing teeth when a donor tooth is available. The autotransplantation of a right mandibular third molar with compromised function and aesthetics to replace the residual roots resulting from coronal destruction due to extensive carious lesion of the second molar in the same quadrant was a viable treatment alternative.

Playing RNase P evolution: swapping the RNA catalyst for a protein reveals functional uniformity of highly divergent enzyme forms.

PubMed

Weber, Christoph; Hartig, Andreas; Hartmann, Roland K; Rossmanith, Walter

2014-08-01

The RNase P family is a diverse group of endonucleases responsible for the removal of 5' extensions from tRNA precursors. The diversity of enzyme forms finds its extremes in the eukaryal nucleus where RNA-based catalysis by complex ribonucleoproteins in some organisms contrasts with single-polypeptide enzymes in others. Such structural contrast suggests associated functional differences, and the complexity of the ribonucleoprotein was indeed proposed to broaden the enzyme's functionality beyond tRNA processing. To explore functional overlap and differences between most divergent forms of RNase P, we replaced the nuclear RNase P of Saccharomyces cerevisiae, a 10-subunit ribonucleoprotein, with Arabidopsis thaliana PRORP3, a single monomeric protein. Surprisingly, the RNase P-swapped yeast strains were viable, displayed essentially unimpaired growth under a wide variety of conditions, and, in a certain genetic background, their fitness even slightly exceeded that of the wild type. The molecular analysis of the RNase P-swapped strains showed a minor disturbance in tRNA metabolism, but did not point to any RNase P substrates or functions beyond that. Altogether, these results indicate the full functional exchangeability of the highly dissimilar enzymes. Our study thereby establishes the RNase P family, with its combination of structural diversity and functional uniformity, as an extreme case of convergent evolution. It moreover suggests that the apparently gratuitous complexity of some RNase P forms is the result of constructive neutral evolution rather than reflecting increased functional versatility.

23 CFR 710.509 - Functional replacement of real property in public ownership.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 23 Highways 1 2012-04-01 2012-04-01 false Functional replacement of real property in public ownership. 710.509 Section 710.509 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT RIGHT-OF-WAY AND REAL ESTATE Property Acquisition Alternatives § 710.509...

A search for new glucophores by isosteric replacement of carboxylic function.

PubMed

Polański, J; Jarzembek, K; Łysiak, V

2000-11-01

We used arylsulfonylalkanoic acids as parent structures for designing new potential sweeteners. The Kohonen maps of the molecular electrostatic potential of the possible bioisosteric replacements of carboxylic function have been simulated and used for the selection of the potential synthetic targets which are now under synthesis.

Ribosomal Protein Rps26 Influences 80S Ribosome Assembly in Saccharomyces cerevisiae.

PubMed

Belyy, Alexander; Levanova, Nadezhda; Tabakova, Irina; Rospert, Sabine; Belyi, Yury

2016-01-01

The eukaryotic ribosome consists of a small (40S) and a large (60S) subunit. Rps26 is one of the essential ribosomal proteins of the 40S subunit and is encoded by two almost identical genes, RPS26a and RPS26b. Previous studies demonstrated that Rps26 interacts with the 5' untranslated region of mRNA via the eukaryote-specific 62-YXXPKXYXK-70 (Y62-K70) motif. Those observations suggested that this peptide within Rps26 might play an important and specific role during translation initiation. By using alanine-scanning mutagenesis and engineered strains of the yeast Saccharomyces cerevisiae, we found that single amino acid substitutions within the Y62-K70 motif of Rps26 did not affect the in vivo function of the protein. In contrast, complete deletion of the Y62-K70 segment was lethal. The simultaneous replacement of five conserved residues within the Y62-K70 segment by alanines resulted in growth defects under stress conditions and produced distinct changes in polysome profiles that were indicative of the accumulation of free 60S subunits. Human Rps26 (Rps26-Hs), which displays significant homology with yeast Rps26, supported the growth of an S. cerevisiae Δrps26a Δrps26b strain. However, the Δrps26a Δrps26b double deletion strain expressing Rps26-Hs displayed substantial growth defects and an altered ratio of 40S/60S ribosomal subunits. The combined data strongly suggest that the eukaryote-specific motif within Rps26 does not play a specific role in translation initiation. Rather, the data indicate that Rps26 as a whole is necessary for proper assembly of the 40S subunit and the 80S ribosome in yeast. IMPORTANCE Rps26 is an essential protein of the eukaryotic small ribosomal subunit. Previous experiments demonstrated an interaction between the eukaryote-specific Y62-K70 segment of Rps26 and the 5' untranslated region of mRNA. The data suggested a specific role of the Y62-K70 motif during translation initiation. Here, we report that single-site substitutions within the Y62-K70 peptide did not affect the growth of engineered yeast strains, arguing against its having a critical role during translation initiation via specific interactions with the 5' untranslated region of mRNA molecules. Only the simultaneous replacement of five conserved residues within the Y62-K70 fragment or the replacement of the yeast protein with the human homolog resulted in growth defects and caused significant changes in polysome profiles. The results expand our knowledge of ribosomal protein function and suggest a role of Rps26 during ribosome assembly in yeast.

A COTS-Based Replacement Strategy for Aging Avionics Computers

DTIC Science & Technology

2001-12-01

Communication Control Unit. A COTS-Based Replacement Strategy for Aging Avionics Computers COTS Microprocessor Real Time Operating System New Native Code...Native Code Objec ts Native Code Thread Real - Time Operating System Legacy Function x Virtual Component Environment Context Switch Thunk Add-in Replace

High prevalence of iatrogenic hyperthyroidism in elderly patients with atrial fibrillation in an anticoagulation clinic.

PubMed

Krishnan, Sandeep Kumar; Dohrmann, Mary L; Brietzke, Stephen A; Fleming, David A; Flaker, Greg C

2011-01-01

In elderly patients with established atrial fibrillation (AF) who are receiving thyroid replacement, regular testing for thyroid function is often not performed, placing the patient at risk for iatrogenic hyperthyroidism. Of 215 patients followed in an anticoagulation clinic, 41 were receiving thyroid replacement and 15 of these were found to have hyperthyroidism. Eight had documented AF coincident with abnormal thyroid function. In addition, only 22 patients on thyroid replacement had an annual TSH. In conclusion, iatrogenic hyperthyroidism may frequently be missed in AF patients because of inadequate monitoring of serum TSH. Thyroid replacement is common in elderly patients with AF followed in an anticoagulation clinic. Laboratory evidence of hyperthyroidism occurred in 37%, usually in patients with higher doses of thyroid replacement, and often associated with AF. The frequency of iatrogenic hyperthyroidism may be underestimated in patients with AF since many patients who receive thyroid replacement therapy are not monitored regularly with serum TSH.

Membrane Lipid Replacement for chronic illnesses, aging and cancer using oral glycerolphospholipid formulations with fructooligosaccharides to restore phospholipid function in cellular membranes, organelles, cells and tissues.

PubMed

Nicolson, Garth L; Ash, Michael E

2017-09-01

Membrane Lipid Replacement is the use of functional, oral supplements containing mixtures of cell membrane glycerolphospholipids, plus fructooligosaccharides (for protection against oxidative, bile acid and enzymatic damage) and antioxidants, in order to safely replace damaged, oxidized, membrane phospholipids and restore membrane, organelle, cellular and organ function. Defects in cellular and intracellular membranes are characteristic of all chronic medical conditions, including cancer, and normal processes, such as aging. Once the replacement glycerolphospholipids have been ingested, dispersed, complexed and transported, while being protected by fructooligosaccharides and several natural mechanisms, they can be inserted into cell membranes, lipoproteins, lipid globules, lipid droplets, liposomes and other carriers. They are conveyed by the lymphatics and blood circulation to cellular sites where they are endocytosed or incorporated into or transported by cell membranes. Inside cells the glycerolphospholipids can be transferred to various intracellular membranes by lipid globules, liposomes, membrane-membrane contact or by lipid carrier transfer. Eventually they arrive at their membrane destinations due to 'bulk flow' principles, and there they can stimulate the natural removal and replacement of damaged membrane lipids while undergoing further enzymatic alterations. Clinical trials have shown the benefits of Membrane Lipid Replacement in restoring mitochondrial function and reducing fatigue in aged subjects and chronically ill patients. Recently Membrane Lipid Replacement has been used to reduce pain and other symptoms as well as removing hydrophobic chemical contaminants, suggesting that there are additional new uses for this safe, natural medicine supplement. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Introducing Optical Concepts in Electrical Engineering.

ERIC Educational Resources Information Center

Daneshvar, K.; Coleman, R.

The expansion in the fields of optical engineering and optoelectronics has made it essential to introduce optical engineering concepts into undergraduate courses and curricula. Because of limits on the number of course requirements for the BS degree, it is not clear how these topics should be introduced without replacing some of the traditional…

Air Age Education. Aviation Career Awareness Program.

ERIC Educational Resources Information Center

Petrie, Edwin T.

Described is a program designed to help introduce the broad scope of occupational careers available with general aviation. The program is designed to aid the teacher in presenting the basic principles of flight, essential facts about general aviation as well as its occupational opportunities. It replaces previous elementary student materials, and…

From Concept to Reality in Implementing the Knowledge Triangle

ERIC Educational Resources Information Center

Sjoer, Ellen; Nørgaard, Bente; Goossens, Marc

2016-01-01

The concept of Knowledge Triangle (KT) links together research, education and innovation and replaces the traditional "one way" flow of knowledge, essentially from research to education, by a "both ways" circular motion between all the corners of a triangle that, besides research and education, also includes innovation, the…

CALIOP V4.10 L1 & L2 Release Announcement

Atmospheric Science Data Center

2016-11-14

... CALIPSO mission announces the release of new versions of its standard Level 1 and Level 2 lidar data products.  These products are ... essential ancillary data sets. The GTOPO30 Digital Elevation Model (DEM) used in V4.00 has been replaced by a substantially more accurate ...

Dry-extrusion of Asian Carp to supplement natural methionine for organic poultry production

USDA-ARS?s Scientific Manuscript database

Methionine, a sulfur containing amino acid, is essential for healthy poultry production. Synthetic methionine is commonly used as a supplement in conventional poultry. However, for organic poultry in the United States, a natural, cost effective source of methionine that can replace synthetic methion...

Replacing State Appropriations with Alternative Revenue Sources: The Case of Voluntary Support

ERIC Educational Resources Information Center

Cheslock, John J.; Gianneschi, Matt

2008-01-01

Public higher education's changing financial environment is well documented. Facing shrinking budgets, competing priorities, public resistance to increasing state levies, and prohibitions on deficit spending, state legislators more and more often find themselves in the unenviable position of debating the relative essentiality of state services,…

Canadian Postcolonialism: Recovering British Roots

ERIC Educational Resources Information Center

Doughty, Howard A.

2005-01-01

The field of Postcolonial Studies is one of the academic fashions that has arisen in an attempt to amend or replace radical theories of social power since the alleged discrediting of Marxism. The Canadian case is more ambiguous. Postcolonialism, already an essentially contested concept, is especially conflicted where Canada is concerned. Canada…

Unilateral total hip replacement patients with symptomatic leg length inequality have abnormal hip biomechanics during walking.

PubMed

Li, Junyan; McWilliams, Anthony B; Jin, Zhongmin; Fisher, John; Stone, Martin H; Redmond, Anthony C; Stewart, Todd D

2015-06-01

Symptomatic leg length inequality accounts for 8.7% of total hip replacement related claims made against the UK National Health Service Litigation authority. It has not been established whether symptomatic leg length inequality patients following total hip replacement have abnormal hip kinetics during gait. Hip kinetics in 15 unilateral total hip replacement patients with symptomatic leg length inequality during gait was determined through multibody dynamics and compared to 15 native hip healthy controls and 15 'successful' asymptomatic unilateral total hip replacement patients. More significant differences from normal were found in symptomatic leg length inequality patients than in asymptomatic total hip replacement patients. The leg length inequality patients had altered functions defined by lower gait velocity, reduced stride length, reduced ground reaction force, decreased hip range of motion, reduced hip moment and less dynamic hip force with a 24% lower heel-strike peak, 66% higher mid-stance trough and 37% lower toe-off peak. Greater asymmetry in hip contact force was also observed in leg length inequality patients. These gait adaptions may affect the function of the implant and other healthy joints in symptomatic leg length inequality patients. This study provides important information for the musculoskeletal function and rehabilitation of symptomatic leg length inequality patients. Copyright © 2015. Published by Elsevier Ltd.

Evaluation of two milk replacers fed to hand-reared cheetah cubs (Acinonyx jubatus): nutrient composition, apparent total tract digestibility, and comparison to maternal cheetah milk.

PubMed

Bell, Katherine M; Rutherfurd, Shane M; Cottam, Yvette H; Hendriks, Wouter H

2011-01-01

Commercially prepared milk replacers are frequently used to provide the sole source of nutrition for hand-reared cheetah cubs (Acinonyx jubatus). The nutrient composition of two commonly used milk replacers was determined. Using titanium dioxide as an indigestible marker, nutrient digestibility was calculated from the analyses of fecal samples collected from each cub (n = 4 on formula 1, and n = 2 on formula 2). Mean apparent total tract digestibility for both formulas was >90% for all nutrients analyzed (crude protein, amino acids, crude fat (CF), and dry matter). However, the total CF content and the concentration of the essential fatty acids, such as α-linolenic, linolenic, and arachidonic acid, of both formulas was lower than reported for maternal cheetah milk. Additionally, one formula contained a comparatively high amount of carbohydrate, at the expense of protein. Although data were lacking for cheetah maternal milk, comparison with domestic cat milk revealed high concentrations of a number of minerals (K, Fe, Zn, and Cu), while vitamin D(3) was not detected in one formula. Both formulas were low in the majority of essential amino acids compared with domestic cat maternal milk. Despite their apparently high digestibility, neither formula was complete or balanced in terms of nutrient concentrations and ratios when maternal cheetah milk and/or the requirements established for growth in domestic cats were used as estimates of ideal. On this basis, although all cubs in this study were healthy and maintained good body conditions for the duration of the trial, the results of dietary analyses indicate that these milk replacers may not provide optimal nutrition for growth in cheetah cubs when used for extended periods. © 2010 Wiley-Liss, Inc.

Engineering the genomes of wild insect populations: challenges, and opportunities provided by synthetic Medea selfish genetic elements

PubMed Central

Chen, Chun-Hong; Ward, Catherine M.; Huang, Haixia; Su, Jessica T.; Guo, Ming

2013-01-01

Advances in insect transgenesis and our knowledge of insect physiology and genomics are making it possible to create transgenic populations of beneficial or pest insects that express novel traits. There are contexts in which we may want the transgenes responsible for these traits to spread so that all individuals within a wild population carry them, a process known as population replacement. Transgenes of interest are unlikely to confer an overall fitness benefit on those who carry them. Therefore, an essential component of any population replacement strategy is the presence of a drive mechanism that will ensure the spread of linked transgenes. We discuss contexts in which population replacement might be desirable and the requirements a drive system must satisfy to be both effective and safe. We then describe the creation of synthetic Medea elements, the first selfish genetic elements synthesized de novo, with the capability of driving population replacement, in this case in Drosophila. The strategy used to create Drosophila Medea is applicable to a number of other insect species and the Medea system satisfies key requirements for scientific and social acceptance. Finally, we highlight several challenges to implementing population replacement in the wild. PMID:20570677

Laparoscopic gastric bypass in patients on thyroid replacement therapy for subnormal thyroid function - prevalence and short-term outcome.

PubMed

Szomstein, Samuel; Avital, Shmuel; Brasesco, Oscar; Mehran, Amir; Cabral, Jose M; Rosenthal, Raul

2004-01-01

Hypothyroidism is associated with increased body weight. Weight gain may occur despite normal levels of serum thyroid stimulating hormone (TSH) and thyroxine (T4) achieved by replacement therapy. We evaluated the prevalence of patients on thyroid replacement for subnormal thyroid function who were operated on for morbid obesity and monitored their postoperative weight loss pattern. Data was identified from a prospectively accrued database of patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) or laparoscopic adjustable gastric banding (LAGB) for morbid obesity from February 2000 to November 2001. All patients with subnormal thyroid function, diagnosed by past thyroid function tests and treated by an endocrinologist, who were on thyroid replacement therapy, were identified; 5 of these were matched for age, gender, preoperative body mass index (BMI) and surgical procedure (LRYGBP) to 5 non-hypothyroid patients. Weight loss at 3 and 9 months after surgery was compared between the 2 groups. 192 patients underwent LRYGBP (n=155) or LAGB (n=37). Of the 21 patients (10.9%) on thyroid replacement identified, 14 were primary, 4 were postablative, and 3 were post-surgical; 17 underwent LRYGBP. All patients had normal preoperative serum levels of TSH and T4. Comparison of the 2 matched groups of patients revealed no difference in weight loss at 3 and 9 months after surgery (P=1.0). The prevalence of euthyroid patients on thyroid replacement for subnormal thyroid function who undergo surgical intervention for morbid obesity is high. Short-term weight loss in these patients is comparable to normal thyroid patients. Longer follow-up may be necessary to demonstrate the weight loss pattern in this group.

Development and applications of 3-dimensional integration nanotechnologies.

PubMed

Kim, Areum; Choi, Eunmi; Son, Hyungbin; Pyo, Sung Gyu

2014-02-01

Unlike conventional two-dimensional (2D) planar structures, signal or power is supplied through through-silicon via (TSV) in three-dimensional (3D) integration technology to replace wires for binding the chip/wafer. TSVs have becomes an essential technology, as they satisfy Moore's law. This 3D integration technology enables system and sensor functions at a nanoscale via the implementation of a highly integrated nano-semiconductor as well as the fabrication of a single chip with multiple functions. Thus, this technology is considered to be a new area of development for the systemization of the nano-bio area. In this review paper, the basic technology required for such 3D integration is described and methods to measure the bonding strength in order to measure the void occurring during bonding are introduced. Currently, CMOS image sensors and memory chips associated with nanotechnology are being realized on the basis of 3D integration technology. In this paper, we intend to describe the applications of high-performance nano-biosensor technology currently under development and the direction of development of a high performance lab-on-a-chip (LOC).

Wld S protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice.

PubMed

Conforti, Laura; Wilbrey, Anna; Morreale, Giacomo; Janeckova, Lucie; Beirowski, Bogdan; Adalbert, Robert; Mazzola, Francesca; Di Stefano, Michele; Hartley, Robert; Babetto, Elisabetta; Smith, Trevor; Gilley, Jonathan; Billington, Richard A; Genazzani, Armando A; Ribchester, Richard R; Magni, Giulio; Coleman, Michael

2009-02-23

The slow Wallerian degeneration (Wld(S)) protein protects injured axons from degeneration. This unusual chimeric protein fuses a 70-amino acid N-terminal sequence from the Ube4b multiubiquitination factor with the nicotinamide adenine dinucleotide-synthesizing enzyme nicotinamide mononucleotide adenylyl transferase 1. The requirement for these components and the mechanism of Wld(S)-mediated neuroprotection remain highly controversial. The Ube4b domain is necessary for the protective phenotype in mice, but precisely which sequence is essential and why are unclear. Binding to the AAA adenosine triphosphatase valosin-containing protein (VCP)/p97 is the only known biochemical property of the Ube4b domain. Using an in vivo approach, we show that removing the VCP-binding sequence abolishes axon protection. Replacing the Wld(S) VCP-binding domain with an alternative ataxin-3-derived VCP-binding sequence restores its protective function. Enzyme-dead Wld(S) is unable to delay Wallerian degeneration in mice. Thus, neither domain is effective without the function of the other. Wld(S) requires both of its components to protect axons from degeneration.

Budding yeast mms4 is epistatic with rad52 and the function of Mms4 can be replaced by a bacterial Holliday junction resolvase.

PubMed

Odagiri, Nao; Seki, Masayuki; Onoda, Fumitoshi; Yoshimura, Akari; Watanabe, Sei; Enomoto, Takemi

2003-03-01

MMS4 of Saccharomyces cerevisiae was originally identified as the gene responsible for one of the collection of methyl methanesulfonate (MMS)-sensitive mutants, mms4. Recently it was identified as a synthetic lethal gene with an SGS1 mutation. Epistatic analyses revealed that MMS4 is involved in a pathway leading to homologous recombination requiring Rad52 or in the recombination itself, in which SGS1 is also involved. MMS sensitivity of mms4 but not sgs1, was suppressed by introducing a bacterial Holliday junction (HJ) resolvase, RusA. The frequencies of spontaneously occurring unequal sister chromatid recombination (SCR) and loss of marker in the rDNA in haploid mms4 cells and interchromosomal recombination between heteroalleles in diploid mms4 cells were essentially the same as those of wild-type cells. Although UV- and MMS-induced interchromosomal recombination was defective in sgs1 diploid cells, hyper-induction of interchromosomal recombination was observed in diploid mms4 cells, indicating that the function of Mms4 is dispensable for this type of recombination.

Primary hypothyroidism in the community: Lower daily dosages of levothyroxine replacement therapy for Asian patients.

PubMed

Tan, Ngiap Chuan; Chew, Rong Quan; Koh, Yi Ling Eileen; Subramanian, Reena Chandini; Sankari, Usha; Meyappan, Meykkumar; Cho, Li Wei

2017-02-01

The goal of treatment in patients with primary hypothyroidism is to attain euthyroidism guided by the stipulated thyroid-stimulating hormone (TSH) levels range so as to minimize any potential long-term adverse effects. However, various factors may result in their Levothyroxine (T4) under and over-replacement.Our study aimed to evaluate the mean daily dose of L-T4 replacement for Asian patients with primary hypothyroidism. The secondary aims were to determine the proportion of those who were either over or under-replaced, and the factors associated with their thyroid function status and replacement adherence.Data collected using questionnaire survey from targeted patients managed in a typical public primary care center in Singapore: socio-demographic characteristics, clinical parameters, laboratory investigations, mean daily L-T4-replacement doses, and replacement regimens. The thyroid status of patients was classified based on thyroid function investigations.Complete data of 229 patients were analyzed. A total of 59.8% of patients had TSH within the normal range, 27.5% and 12.7% were under and over-replaced, respectively. About 60% of Asian patients with primary hypothyroidism achieved normal TSH status requiring average of 1.1 μg of daily L-T4/kgBW (kg body weight). Subjects who were over-replaced had a higher daily L-T4 dose/kgBW when compared to the euthyroid and the under replaced groups. Those with L-T4 over-replacement were largely due to excessive dosage. Patients who were younger, from lower socioeconomic strata, and higher BMI were more likely to be over or under-replaced.Majority of Asian patients with hypothyroidism required replacement of 1.1 μg of daily L-T4/kgBW. Their thyroid status was influenced by demographic and dosing factors.

Replacement Behaviors for Identified Functions of Challenging Behaviors

ERIC Educational Resources Information Center

Matson, Johnny L.; Shoemaker, Mary E.; Sipes, Megan; Horovitz, Max; Worley, Julie A.; Kozlowski, Alison M.

2011-01-01

Functional assessment has become a major feature of learning-based research. A critical element of the majority of these studies includes not only methods and procedures to identify the cause of the challenging behavior, but to establish replacement treatment methods. By far the most common intervention in the 176 studies we reviewed was…

Ross procedure for ascending aortic replacement.

PubMed

Elkins, R C; Lane, M M; McCue, C

1999-06-01

Patients with aortic valve disease and aneurysm or dilatation of the ascending aorta require both aortic valve replacement and treatment of their ascending aortic disease. In children and young adults, the Ross operation is preferred when the aortic valve requires replacement, but the efficacy of extending this operation to include replacement of the ascending aorta or reduction of the dilated aorta has not been tested. We reviewed the medical records of 18 (5.9%) patients with aortic valve disease and an ascending aortic aneurysm and 26 (8.5%) patients with dilation of the ascending aorta, subgroups of 307 patients who had a Ross operation between August 1986 and February 1998. We examined operative and midterm results, including recent echocardiographic assessment of autograft valve function and ability of the autograft root and ascending aortic repair or replacement to maintain normal structural integrity. There was one operative death (2%) related to a perioperative stroke. Forty-two of 43 survivors have normal autograft valve function, with trace to mild autograft valve insufficiency, and one patient has moderate insufficiency at the most recent echocardiographic evaluation. None of the patients has dilatation of the autograft root or of the replaced or reduced ascending aorta. Early results with extension of the Ross operation to include replacement of an ascending aortic aneurysm or vertical aortoplasty for reduction of a dilated ascending aorta are excellent, with autograft valve function equal to that seen in similar patients without ascending aortic disease.

Nutritional and medicinal aspects of D-amino acids.

PubMed

Friedman, Mendel; Levin, Carol E

2012-05-01

This paper reviews and interprets a method for determining the nutritional value of D-amino acids, D-peptides, and amino acid derivatives using a growth assay in mice fed a synthetic all-amino acid diet. A large number of experiments were carried out in which a molar equivalent of the test compound replaced a nutritionally essential amino acid such as L-lysine (L-Lys), L-methionine (L-Met), L-phenylalanine (L-Phe), and L-tryptophan (L-Trp) as well as the semi-essential amino acids L-cysteine (L-Cys) and L-tyrosine (L-Tyr). The results show wide-ranging variations in the biological utilization of test substances. The method is generally applicable to the determination of the biological utilization and safety of any amino acid derivative as a potential nutritional source of the corresponding L-amino acid. Because the organism is forced to use the D-amino acid or amino acid derivative as the sole source of the essential or semi-essential amino acid being replaced, and because a free amino acid diet allows better control of composition, the use of all-amino-acid diets for such determinations may be preferable to protein-based diets. Also covered are brief summaries of the widely scattered literature on dietary and pharmacological aspects of 27 individual D-amino acids, D-peptides, and isomeric amino acid derivatives and suggested research needs in each of these areas. The described results provide a valuable record and resource for further progress on the multifaceted aspects of D-amino acids in food and biological samples.

Concordance and discordance between taxonomic and functional homogenization: responses of soil mite assemblages to forest conversion.

PubMed

Mori, Akira S; Ota, Aino T; Fujii, Saori; Seino, Tatsuyuki; Kabeya, Daisuke; Okamoto, Toru; Ito, Masamichi T; Kaneko, Nobuhiro; Hasegawa, Motohiro

2015-10-01

The compositional characteristics of ecological assemblages are often simplified; this process is termed "biotic homogenization." This process of biological reorganization occurs not only taxonomically but also functionally. Testing both aspects of homogenization is essential if ecosystem functioning supported by a diverse mosaic of functional traits in the landscape is concerned. Here, we aimed to infer the underlying processes of taxonomic/functional homogenization at the local scale, which is a scale that is meaningful for this research question. We recorded species of litter-dwelling oribatid mites along a gradient of forest conversion from a natural forest to a monoculture larch plantation in Japan (in total 11 stands), and collected data on the functional traits of the recorded species to quantify functional diversity. We calculated the taxonomic and functional β-diversity, an index of biotic homogenization. We found that both the taxonomic and functional β-diversity decreased with larch dominance (stand homogenization). After further deconstructing β-diversity into the components of turnover and nestedness, which reflect different processes of community organization, a significant decrease in the response to larch dominance was observed only for the functional turnover. As a result, there was a steeper decline in the functional β-diversity than the taxonomic β-diversity. This discordance between the taxonomic and functional response suggests that species replacement occurs between species that are functionally redundant under environmental homogenization, ultimately leading to the stronger homogenization of functional diversity. The insights gained from community organization of oribatid mites suggest that the functional characteristics of local assemblages, which support the functionality of ecosystems, are of more concern in human-dominated forest landscapes.

Wildland fire effects in silviculturally treated vs. untreated stands of New Mexico and Arizona

Treesearch

Douglas S. Cram; Terrell T. Baker; Jon C. Boren

2006-01-01

Stand-replacement fires, particularly in ponderosa pine (Pinus ponderosa) forests, have replaced highfrequency, low-intensity historical fire regimes. We examined whether forest stands treated recently using silvicultural practices would be (1) less susceptible to stand-replacing crownfires, and (2) more ecologically and functionally resilient...

Functionality of Inulin as a Sucrose Replacer in Cookie Baking

USDA-ARS?s Scientific Manuscript database

Inulin was evaluated as a sucrose replacer for healthy cookie production with benefits of low glycemic impact and prebiotic soluble fiber. Sucrose (as a reference) and three inulin products of different concentrations (as soluble fibers) were used to explore the effects of sugar-replacer type on so...

Cholecalciferol treatment downregulates renin-angiotensin system and improves endothelial function in essential hypertensive patients with hypovitaminosid D.

PubMed

Carrara, Davide; Bruno, Rosa Maria; Bacca, Alessandra; Taddei, Stefano; Duranti, Emiliano; Ghiadoni, Lorenzo; Bernini, Giampaolo

2016-11-01

Vitamin D deficiency is related to an increased prevalence of cardiovascular disease. Renin-angiotensin-aldosterone system suppression and vascular dysfunction are considered among the main mechanisms implicated in this association. However, interventional studies demonstrating that vitamin D replacement reduces circulating renin-angiotensin-aldosterone components and improves vascular function in humans are still lacking. Thirty-three consecutive patients with essential hypertension and hypovitaminosis D underwent therapy with cholecalciferol 50 000 IU/week orally for 8 weeks. Thirty-three hypertensive patients with normal vitamin D levels and 20 normotensive individuals were also enrolled as control groups. At baseline and at the end of the study, we evaluated plasma renin activity, circulating renin, angiotensin II, aldosterone and plasma vitamin D levels. Endothelial function [flow-mediated dilation (FMD)], carotid-femoral pulse wave velocity and augmentation index, peripheral and central blood pressure were also acquired. After 8-week cholecalciferol administration, all treated patients normalized plasma 25(OH)D values. Furthermore, a reduction in plasma levels of plasma renin activity (1.17 ± 0.3 vs 1.51 ± 0.4 ng/ml per h, P = 0.02), renin (13.4 ± 1.7 vs 19.2 ± 2.9 pg/ml, P < 0.001), angiotensin II (11.6 ± 1.6 vs 15.8 ± 2.7 pg/ml, P = 0.02) was observed at the end of the study. FMD was significantly increased after cholecalciferol treatment (4.4 ± 2.6 vs 3.3 ± 2.1%, P < 0.05), in the absence of changes of brachial artery diameter and endothelium-independent vasodilation. Carotid-femoral pulse wave velocity and augmentation index were not modified, as well peripheral and central blood pressure. The restoration of normal vitamin D levels after 8-week cholecalciferol treatment is able to inhibit peripheral renin-angiotensin system and improve FMD in essential hypertensive patients with hypovitaminosis D.

Natural shorelines promote the stability of fish communities in an urbanized coastal system.

PubMed

Scyphers, Steven B; Gouhier, Tarik C; Grabowski, Jonathan H; Beck, Michael W; Mareska, John; Powers, Sean P

2015-01-01

Habitat loss and fragmentation are leading causes of species extinctions in terrestrial, aquatic and marine systems. Along coastlines, natural habitats support high biodiversity and valuable ecosystem services but are often replaced with engineered structures for coastal protection or erosion control. We coupled high-resolution shoreline condition data with an eleven-year time series of fish community structure to examine how coastal protection structures impact community stability. Our analyses revealed that the most stable fish communities were nearest natural shorelines. Structurally complex engineered shorelines appeared to promote greater stability than simpler alternatives as communities nearest vertical walls, which are among the most prevalent structures, were most dissimilar from natural shorelines and had the lowest stability. We conclude that conserving and restoring natural habitats is essential for promoting ecological stability. However, in scenarios when natural habitats are not viable, engineered landscapes designed to mimic the complexity of natural habitats may provide similar ecological functions.

Crossroads of Wnt and Hippo in epithelial tissues.

PubMed

Bernascone, Ilenia; Martin-Belmonte, Fernando

2013-08-01

Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of transition metal exporters in virulence: the example of Neisseria meningitidis.

PubMed

Guilhen, Cyril; Taha, Muhamed-Kheir; Veyrier, Frédéric J

2013-01-01

Transition metals such as iron, manganese, and zinc are essential micronutrients for bacteria. However, at high concentration, they can generate non-functional proteins or toxic compounds. Metal metabolism is therefore regulated to prevent shortage or overload, both of which can impair cell survival. In addition, equilibrium among these metals has to be tightly controlled to avoid molecular replacement in the active site of enzymes. Bacteria must actively maintain intracellular metal concentrations to meet physiological needs within the context of the local environment. When intracellular buffering capacity is reached, they rely primarily on membrane-localized exporters to maintain metal homeostasis. Recently, several groups have characterized new export systems and emphasized their importance in the virulence of several pathogens. This article discusses the role of export systems as general virulence determinants. Furthermore, it highlights the contribution of these exporters in pathogens emergence with emphasis on the human nasopharyngeal colonizer Neisseria meningitidis.

Cytoplasmic Dynein Regulation by Subunit Heterogeneity and Its Role in Apical Transport

PubMed Central

Tai, Andrew W.; Chuang, Jen-Zen; Sung, Ching-Hwa

2001-01-01

Despite the existence of multiple subunit isoforms for the microtubule motor cytoplasmic dynein, it has not yet been directly shown that dynein complexes with different compositions exhibit different properties. The 14-kD dynein light chain Tctex-1, but not its homologue RP3, binds directly to rhodopsin's cytoplasmic COOH-terminal tail, which encodes an apical targeting determinant in polarized epithelial Madin-Darby canine kidney (MDCK) cells. We demonstrate that Tctex-1 and RP3 compete for binding to dynein intermediate chain and that overexpressed RP3 displaces endogenous Tctex-1 from dynein complexes in MDCK cells. Furthermore, replacement of Tctex-1 by RP3 selectively disrupts the translocation of rhodopsin to the MDCK apical surface. These results directly show that cytoplasmic dynein function can be regulated by its subunit composition and that cytoplasmic dynein is essential for at least one mode of apical transport in polarized epithelia. PMID:11425878

Biology's built-in Faraday cages

NASA Astrophysics Data System (ADS)

Klee, Maurice M.

2014-05-01

Biological fluids are water-based, ionic conductors. As such, they have both high relative dielectric constants and substantial conductivities, meaning they are lossy dielectrics. These fluids contain charged molecules (free charges), whose movements play roles in essentially all cellular processes from metabolism to communication with other cells. Using the problem of a point source in air above a biological fluid of semi-infinite extent, the bound charges in the fluid are shown to perform the function of a fast-acting Faraday cage, which protects the interior of the fluid from external electric fields. Free charges replace bound charges in accordance with the fluid's relaxation time, thereby providing a smooth transition between the initial protection provided by the bound charges and the steady state protection provided by the free charges. The electric fields within the biological fluid are thus small for all times just as they would be inside a classical Faraday cage.

Visibility analysis of fire lookout towers in the Boyabat State Forest Enterprise in Turkey.

PubMed

Kucuk, Omer; Topaloglu, Ozer; Altunel, Arif Oguz; Cetin, Mehmet

2017-07-01

For a successful fire suppression, it is essential to detect and intervene forest fires as early as possible. Fire lookout towers are crucial assets in detecting forest fires, in addition to other technological advancements. In this study, we performed a visibility analysis on a network of fire lookout towers currently operating in a relatively fire-prone region in Turkey's Western Black Sea region. Some of these towers had not been functioning properly; it was proposed that these be taken out of the grid and replaced with new ones. The percentage of visible areas under the current network of fire lookout towers was 73%; it could rise to 81% with the addition of newly proposed towers. This study was the first research to conduct a visibility analysis of current and newly proposed fire lookout towers in the Western Black Sea region and focus on its forest fire problem.

Natural Shorelines Promote the Stability of Fish Communities in an Urbanized Coastal System

PubMed Central

Scyphers, Steven B.; Gouhier, Tarik C.; Grabowski, Jonathan H.; Beck, Michael W.; Mareska, John; Powers, Sean P.

2015-01-01

Habitat loss and fragmentation are leading causes of species extinctions in terrestrial, aquatic and marine systems. Along coastlines, natural habitats support high biodiversity and valuable ecosystem services but are often replaced with engineered structures for coastal protection or erosion control. We coupled high-resolution shoreline condition data with an eleven-year time series of fish community structure to examine how coastal protection structures impact community stability. Our analyses revealed that the most stable fish communities were nearest natural shorelines. Structurally complex engineered shorelines appeared to promote greater stability than simpler alternatives as communities nearest vertical walls, which are among the most prevalent structures, were most dissimilar from natural shorelines and had the lowest stability. We conclude that conserving and restoring natural habitats is essential for promoting ecological stability. However, in scenarios when natural habitats are not viable, engineered landscapes designed to mimic the complexity of natural habitats may provide similar ecological functions. PMID:26039407

Bioreactors as engineering support to treat cardiac muscle and vascular disease.

PubMed

Massai, Diana; Cerino, Giulia; Gallo, Diego; Pennella, Francesco; Deriu, Marco A; Rodriguez, Andres; Montevecchi, Franco M; Bignardi, Cristina; Audenino, Alberto; Morbiducci, Umberto

2013-01-01

Cardiovascular disease is the leading cause of morbidity and mortality in the Western World. The inability of fully differentiated, load-bearing cardiovascular tissues to in vivo regenerate and the limitations of the current treatment therapies greatly motivate the efforts of cardiovascular tissue engineering to become an effective clinical strategy for injured heart and vessels. For the effective production of organized and functional cardiovascular engineered constructs in vitro, a suitable dynamic environment is essential, and can be achieved and maintained within bioreactors. Bioreactors are technological devices that, while monitoring and controlling the culture environment and stimulating the construct, attempt to mimic the physiological milieu. In this study, a review of the current state of the art of bioreactor solutions for cardiovascular tissue engineering is presented, with emphasis on bioreactors and biophysical stimuli adopted for investigating the mechanisms influencing cardiovascular tissue development, and for eventually generating suitable cardiovascular tissue replacements.

Regional analgesia for improvement of long-term functional outcome after elective large joint replacement.

PubMed

Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

2015-08-13

Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low.Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) - 2.23 to 10.21; P value = 0.21, 3 studies, 140 participants, very low quality evidence).We did not perform further analyses because immediate adverse effects were not part of the explicit outcomes of any of these typically small studies, and long-term adverse events after regional anaesthesia are rare.None of the included studies elicited or reported long-term adverse effects like persistent nerve damage. More high-quality studies are needed to establish the effects of regional analgesia on function after major joint replacement, as well as on the risk of adverse events (falls).

Supportability Technologies for Future Exploration Missions

NASA Technical Reports Server (NTRS)

Watson, Kevin; Thompson, Karen

2007-01-01

Future long-duration human exploration missions will be challenged by resupply limitations and mass and volume constraints. Consequently, it will be essential that the logistics footprint required to support these missions be minimized and that capabilities be provided to make them highly autonomous from a logistics perspective. Strategies to achieve these objectives include broad implementation of commonality and standardization at all hardware levels and across all systems, repair of failed hardware at the lowest possible hardware level, and manufacture of structural and mechanical replacement components as needed. Repair at the lowest hardware levels will require the availability of compact, portable systems for diagnosis of failures in electronic systems and verification of system functionality following repair. Rework systems will be required that enable the removal and replacement of microelectronic components with minimal human intervention to minimize skill requirements and training demand for crews. Materials used in the assembly of electronic systems (e.g. solders, fluxes, conformal coatings) must be compatible with the available repair methods and the spacecraft environment. Manufacturing of replacement parts for structural and mechanical applications will require additive manufacturing systems that can generate near-net-shape parts from the range of engineering alloys employed in the spacecraft structure and in the parts utilized in other surface systems. These additive manufacturing processes will need to be supported by real-time non-destructive evaluation during layer-additive processing for on-the-fly quality control. This will provide capabilities for quality control and may serve as an input for closed-loop process control. Additionally, non-destructive methods should be available for material property determination. These nondestructive evaluation processes should be incorporated with the additive manufacturing process - providing an in-process capability to ensure that material deposited during layer-additive processing meets required material property criteria.

Fate of the Molar Dental Lamina in the Monophyodont Mouse

PubMed Central

Dosedělová, Hana; Dumková, Jana; Lesot, Hervé; Glocová, Kristýna; Kunová, Michaela; Tucker, Abigail S.; Veselá, Iva; Krejčí, Pavel; Tichý, František; Hampl, Aleš; Buchtová, Marcela

2015-01-01

The successional dental lamina (SDL) plays an essential role in the development of replacement teeth in diphyodont and polyphyodont animals. A morphologically similar structure, the rudimental successional dental lamina (RSDL), has been described in monophyodont (only one tooth generation) lizards on the lingual side of the developing functional tooth. This rudimentary lamina regresses, which has been proposed to play a role in preventing the formation of future generations of teeth. A similar rudimentary lingual structure has been reported associated with the first molar in the monophyodont mouse, and we show that this structure is common to all murine molars. Intriguingly, a lingual lamina is also observed on the non-replacing molars of other diphyodont mammals (pig and hedgehog), initially appearing very similar to the successional dental lamina on the replacing teeth. We have analyzed the morphological as well as ultrastructural changes that occur during the development and loss of this molar lamina in the mouse, from its initiation at late embryonic stages to its disappearance at postnatal stages. We show that loss appears to be driven by a reduction in cell proliferation, down-regulation of the progenitor marker Sox2, with only a small number of cells undergoing programmed cell death. The lingual lamina was associated with the dental stalk, a short epithelial connection between the tooth germ and the oral epithelium. The dental stalk remained in contact with the oral epithelium throughout tooth development up to eruption when connective tissue and numerous capillaries progressively invaded the dental stalk. The buccal side of the dental stalk underwent keratinisation and became part of the gingival epithelium, while most of the lingual cells underwent programmed cell death and the tissue directly above the erupting tooth was shed into the oral cavity. PMID:26010446

Replacement of the double bond of antitubulin chalcones with triazoles and tetrazoles: Synthesis and biological evaluation.

PubMed

Mesenzani, Ornella; Massarotti, Alberto; Giustiniano, Mariateresa; Pirali, Tracey; Bevilacqua, Valentina; Caldarelli, Antonio; Canonico, Pierluigi; Sorba, Giovanni; Novellino, Ettore; Genazzani, Armando A; Tron, Gian Cesare

2011-01-15

In the chalcone scaffold, it is thought that the double bond is an important structural linker but it is likely not essential for the interaction with tubulin. Yet, it may be a potential site of metabolic degradation and interaction with biological nucleophiles. In this letter, we have replaced this olefinic portion of chalcones with two metabolically stable and chemically inert heterocyclic rings, namely triazole or tetrazole. Yet, our biologic data suggest that, unlike in other antitubulinic structures, the olephinic ring might not be merely a structural linker. Copyright © 2010 Elsevier Ltd. All rights reserved.

A prospective study on the risk of glove fingertip contamination during draping in joint replacement surgery.

PubMed

Makki, D; Deierl, K; Pandit, A; Trakru, S

2014-09-01

The aim of this prospective study was to investigate the risk of contamination of surgical gloves during preparation and draping in joint replacement surgery. During 46 hip and knee replacement procedures, the gloves of orthopaedic consultants (n=5) and registrars (n=3) were assessed for contamination immediately after draping by impression of gloved fingers on blood agar. Contamination was evaluated by the surgeon's grade, the type of procedure, the role of the assistant and the dominance of the hand. A total of 125 pairs of top gloves were examined (79 pairs from registrars and 46 pairs from consultants). Bacterial contamination was isolated on 19 pairs (15.2%) (16 pairs from registrars and 3 pairs from consultants, p=0.04). Coagulase negative staphylococci were the main isolates and contamination was considered low in all cases (1-5 colonies). Contamination was seen more on the dominant hand (16 gloves from dominant hands and 6 from non-dominant hands, p=0.04), on the index finger and thumb. More contaminated gloves were seen in hip arthroplasty procedures (16 pairs from total hip replacements vs 3 pairs from total knee replacements, p=0.02). Contamination of glove fingertips during draping in joint replacement procedures is more likely to occur among junior surgeons, in hip rather than knee arthroplasty procedures and on the dominant hand. It is therefore essential that surgeons of different grades replace gloves used in draping to avoid exposing patients to the risk of infection.

The influence of optimism on functionality after total hip replacement surgery.

PubMed

Balck, Friedrich; Lippmann, Maike; Jeszenszky, Csilla; Günther, Klaus-Peter; Kirschner, Stephan

2016-08-01

Among other factors, optimism has been shown to significantly influence the course of some diseases (cancer, HIV, coronary heart disease). This study investigated whether optimism of a patient before a total hip replacement can predict the functionality of the lower limbs 3 and 6 months after surgery. A total of 325 patients took part in the study (age: 58.7 years; w: 55%). The functionality was measured with the Western Ontario and McMaster Universities arthrosis index, and optimism with the Life Orientation Test. To analyse the influences of age, gender and optimism, general linear models were calculated. In optimistic patients, functionality improved significantly over time. The study showed a clear influence of dispositional optimism on the recovery after total hip replacement in the first 3 months after surgery. © The Author(s) 2015.

Amphibole and hercynite spinel in Shergotty and Zagami Magmatic water, depth of crystallization, and metasomatism

NASA Technical Reports Server (NTRS)

Treiman, A. H.

1985-01-01

Amphibole and spinel occur in the Shergotty and Zagami meteorites only in magmatic inclusions in pigeonite. The trapped magma is essentially identical to the parental magmas for Shergotty and Zagami. The amphibole is a kaersutite with minimal halogen content; by inference, it must have been hydrous. If so, the Shergotty and Zagami melts contained at least 0.2 wt pct H2O and were probably H2O-undersaturated. Pressures in excess of 1 kilobar seem necessary for the formation of amphibole. Spinel replaces magnetite in the inclusions, and olivine replaces magnetite elsewhere in the meteorites. To stabilize spinel, the melt in the inclusions must have become enriched in Al during fractionation, possibly because the small volume of the inclusions made nucleation of plagioclase unlikely. Pervasive replacement of magnetite through reduction reactions suggests that Shergotty and Zagami interacted with hydrogen-rich fluids during their cooling.

Cine film replacement: digital archival requirements and remaining obstacles.

PubMed

Holmes, D R; Wondrow, M A; Bell, M R; Nissen, S E; Cusma, J T

1998-07-01

The acceptance of the Digital Imaging and Communication in Medicine (DICOM) standard and the Compact Disk-Recordable (CD-R) as the interchange medium have been critical developments for laboratories that need to move forward on the cine replacement front, while at the same time retain a means to communicate with other centers. One remaining essential component which has not been satisfactorily addressed is the issue of how digital image data should be archived within an institution. Every laboratory must consider the diverse issues which affect the choice of a digital archiving system. These factors include technical and economic issues, along with the clinical routines prevailing in their laboratory. A complete understanding of the issues will lead to the formulation of multiple options which may prove acceptable and will help to overcome the last obstacle which remains for the complete replacement of cine film in the cardiac catheterization laboratory.

It takes a village: Stakeholder participation is essential to transforming science.

PubMed

Sullivan, Kristie

2016-10-01

Efforts toward replacing the use of animals in toxicology testing have begun to make significant headway in the last several years, due to co-operative and pragmatic efforts on the part of many stakeholders, and the public pressure that non-governmental advocacy organisations represent. Science-focused advocacy organisations have a unique role to play in these efforts, as they often have flexibility to adapt quickly to keep a project going and forge connections among different kinds of stakeholders to help encourage buy-in. This year, meaningful progress has been made, especially in regulatory laws and policies, which will lead to the replacement of animals in toxicology testing. In order to keep this momentum, we need to measure progress -- but this requires improved transparency and regular reporting of animal use. In addition, we should consider how strategies that have successfully reduced and replaced animal use in toxicology can be applied to basic biomedical research practices. 2016 FRAME.

The Role of the Replacement Behavior in Function-Based Intervention

ERIC Educational Resources Information Center

Reeves, Linda M.; Ferro, Jolenea B.; Umbreit, John; Liaupsin, Carl J.

2017-01-01

Three students with autism spectrum disorder (ASD) who displayed off-task behavior participated in a two-phase study. In Phase 1, a functional behavioral assessment (FBA) was conducted for each student. In addition, an assessment of each student's ability to perform the replacement behavior identified that none of the participants was able to do…

Mini-Journal Inquiry Laboratory: A Case Study in a General Chemistry Kinetics Experiment

ERIC Educational Resources Information Center

Zhao, Ningfeng; Wardeska, Jeffrey G.

2011-01-01

The mini-journal curriculum for undergraduate science laboratories mirrors the format of scientific literature and helps students improve their learning through direct scientific practices. The lab embodies the essential features of scientific inquiry and replaces the traditional "cookbook" lab to engage students in active learning. A case study…

33 CFR 157.12c - Construction, maintenance, security, calibration, and training.

Code of Federal Regulations, 2011 CFR

2011-07-01

... RELATING TO TANK VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12c Construction... designed to ensure that user access is restricted to essential controls. Access beyond these controls must... of a design that only the manufacturer or the manufacturer's agent can replace the seals or reset the...

33 CFR 157.12c - Construction, maintenance, security, calibration, and training.

Code of Federal Regulations, 2012 CFR

2012-07-01

... RELATING TO TANK VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12c Construction... designed to ensure that user access is restricted to essential controls. Access beyond these controls must... of a design that only the manufacturer or the manufacturer's agent can replace the seals or reset the...

33 CFR 157.12c - Construction, maintenance, security, calibration, and training.

Code of Federal Regulations, 2014 CFR

2014-07-01

... RELATING TO TANK VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12c Construction... designed to ensure that user access is restricted to essential controls. Access beyond these controls must... of a design that only the manufacturer or the manufacturer's agent can replace the seals or reset the...

33 CFR 157.12c - Construction, maintenance, security, calibration, and training.

Code of Federal Regulations, 2010 CFR

2010-07-01

... RELATING TO TANK VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12c Construction... designed to ensure that user access is restricted to essential controls. Access beyond these controls must... of a design that only the manufacturer or the manufacturer's agent can replace the seals or reset the...

The Language of Coping: Understanding Filipino Geriatric Patients' Hemodialysis Lived Experiences

ERIC Educational Resources Information Center

de Guzman, Allan B.; Chy, Mark Anthony S.; Concepcion, April Faye P.; Conferido, Alvin John C.; Coretico, Kristine I.

2009-01-01

The majority of patients with chronic kidney disease (CKD) are undergoing maintenance hemodialysis. Hemodialysis is a process of removing metabolic waste, other poisons, and excess fluids from the blood and replacing essential blood constituents through a dialysis machine. With hemodialysis causing stress not only to physical status but also to…

An overview of live attenuated recombinant pseudorabies viruses for use as novel vaccines

USDA-ARS?s Scientific Manuscript database

Pseudorabies virus (PRV) is a double-stranded, DNA-based swine virus with a genome approximating 150 kb in size. In cell culture, PRV has many non-essential genes which can be replaced with genes encoding heterologous antigens but without deleterious effects on virus propagation. Recombinant PRVs ex...

Changing Images of the Inclined Plane: A Case Study of a Revolution in American Science Education

ERIC Educational Resources Information Center

Turner, Steven C.

2012-01-01

Between 1880 and 1920 the way science was taught in American High Schools changed dramatically. The old "lecture/demonstration" method, where information was presented to essentially passive students, was replaced by the "laboratory" method, where students performed their own experiments in specially constructed student laboratories. National…

Quinovosamycins: New tunicamycin-type antibiotics in which the alpha, beta-1", 11'-linked N-acetylglucosamine residue is replaced by N-acetylquinovosamine.

USDA-ARS?s Scientific Manuscript database

Tunicamycins (TUN) are potent inhibitors of polyprenyl phosphate N-acetylhexosamine 1-phosphate transferases (PPHP), including essential eukaryotic GPT enzymes and bacterial HexNAc 1-P translocases. Hence, TUN blocks the formation of eukaryotic N-glycoproteins and the assembly of bacterial call wall...

An anion substitution route to low loss colossal dielectric CaCu{sub 3}Ti{sub 4}O{sub 12}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Andrew E.; Calvarese, T.G.; Sleight, A.W.

2009-02-15

An anion substitution route was utilized for lowering the dielectric loss in CaCu{sub 3}Ti{sub 4}O{sub 12} (CCTO) by partial replacement of oxygen by fluorine. This substitution reduced the dielectric loss, and retained a high dielectric constant that was essentially temperature independent from 25 to 200 deg. C. In particular, CaCu{sub 3}Ti{sub 4}O{sub 11.7}F{sub 0.3} exhibited a giant dielectric constant over 6000 and low dielectric loss below 0.075 at 100 kHz within a temperature range of 25-200 deg. C. Fluorine analysis confirmed the presence of fluorine in all samples measured. - Grapical Abstract: An anion substitution route was utilized for loweringmore » the dielectric loss in CaCu{sub 3}Ti{sub 4}O{sub 12} (CCTO) by partial replacement of oxygen by fluorine. This substitution, confirmed by fluorine analysis, reduced tan {delta}, and retained a high dielectric constant that was essentially temperature independent from 25 to 200 deg. C at 100 kHz.« less

Improvement in the assessment of wear of total knee replacements using coordinate-measuring machine techniques.

PubMed

Blunt, L A; Bills, P J; Jiang, X-Q; Chakrabarty, G

2008-04-01

Total joint replacement is one of the most common elective surgical procedures performed worldwide, with an estimate of 1.5x 10(6) operations performed annually. Currently joint replacements are expected to function for 10-15 years; however, with an increase in life expectancy, and a greater call for knee replacement due to increased activity levels, there is a requirement to improve their function to offer longer-term improved quality of life for patients. Wear analysis of total joint replacements has long been an important means in determining failure mechanisms and improving longevity of these devices. The effectiveness of the coordinate-measuring machine (CMM) technique for assessing volumetric material loss during simulated life testing of a replacement knee joint has been proved previously by the present authors. The purpose of the current work is to present an improvement to this method for situations where no pre-wear data are available. To validate the method, simulator tests were run and gravimetric measurements taken throughout the test, such that the components measured had a known wear value. The implications of the results are then discussed in terms of assessment of joint functionality and development of standardized CMM-based product standards. The method was then expanded to allow assessment of clinically retrieved bearings so as to ascertain a measure of true clinical wear.

Nutritional value of raw Canavalia ensiformis and its utilization as partial replacement for soybean meal in the diet of Clarias gariepinus (Burchell, 1822) fingerlings.

PubMed

Solomon, Shola G; Okomoda, Victor T; Oguche, Obekpa

2018-01-01

The nutritional value of raw Jack bean meal ( Canavalia ensiformis ) as a partial substitute for soybeans meal was investigated in this study. Preliminary investigation on nutrient composition revealed that lysine, histidine, and phenylalanine were significantly higher in C .  ensiformis seed meal compared to soybean meal. However, crude protein and other essential amino acids were significantly lower. Feeding trial was then conducted to investigate the effect of replacing about 40% soybeans meal (at 58.8% inclusion) with C .  ensiformis in the diet of Clarias gariepinus . The result obtained after 56 days revealed that fingerlings could tolerate up to 20% replacement without significant effect on growth and nutrient utilization. Beyond this, growth was significantly reduced. Survivals of the fish also follow a similar trend as stated above. It was concluded that dietary inclusion of raw C .  ensiform meal should not be beyond 11% (or 20% replacement for soybeans meal included at 58.8%) in the diet of C .  gariepinus .

Increasing intake of essential fatty acids from milk replacer benefits performance, immune responses, and health of preweaned Holstein calves.

PubMed

Garcia, M; Shin, J H; Schlaefli, A; Greco, L F; Maunsell, F P; Thatcher, W W; Santos, J E P; Staples, C R

2015-01-01

The objective was to evaluate the effect of feeding increasing amounts of essential fatty acids (FA) in milk replacer (MR) during the first 60 d of life on growth, health, and immunity of Holstein calves. Calves were born from dams fed low concentrations of total and essential FA during the lasT2 mo of pregnancy. Newborn calves were blocked by sex and parity of the dam and assigned randomly to receive 1 of 4 MR treatments (T). Hydrogenated coconut oil and soybean oil were mixed with emulsifier and commercial MR powder to prepare the following 4 MR containing 0.119 and 0.007 (T1), 0.187 and 0.017 (T2), 0.321 and 0.036 (T3), and 0.593 and 0.076 (T4) g of intake per kg of metabolic body weight (BW(0.75)) of linoleic acid and α-linolenic acid, respectively. At 30 d of life, concentrations of essential FA (linoleic acid and α-linolenic acid) in liver increased, whereas concentrations of C12:0, C14:0, C16:0, and C20:3n-9 decreased linearly with increasing intake of essential FA. Body weight gain and feed efficiency were optimized when male calves consumed T2, whereas gain by female calves tended to increase linearly with increasing intake of essential FA during the first 30 d of age. However, these responses to treatment were not maintained after initiation of concentrate feeding at 31 d of life. Over the 60-d preweaning period, wither and hip heights were improved in both sexes as intake of essential FA increased up to T3. Some measures of health and immunity were affected by replacing some coconut oil with soybean oil. Severity of diarrhea tended to decrease linearly; plasma concentrations of haptoglobin during diarrhea were lower in T2, T3, and T4; phagocytosis by blood neutrophils tended to peak for calves fed T2; in vitro proliferation of stimulated blood lymphocytes was greater for calves fed T2; in vitro stimulated blood cells produced more IFN-γ (up to T3 for males and T2 for females), concentrations of serum IgG against ovalbumin injections were increased in males fed T2 or T3; and skin-fold thickness increased in response to an intradermal antigen injection of all calves fed up to T4. Across sex and under the conditions of the present study, mean daily intakes of linoleic acid between 3 to 5g/d and intakes of α-linolenic acid between 0.3 and 0.6g/d during the first 30 d of life promoted growth of preweaned Holstein calves, possibly by improving their immune status. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Evolution subverting essentiality: Dispensability of the cell attachment Arg-Gly-Asp motif in multiply passaged foot-and-mouth disease virus

PubMed Central

Martínez, Miguel A.; Verdaguer, Nuria; Mateu, Mauricio G.; Domingo, Esteban

1997-01-01

Aphthoviruses use a conserved Arg-Gly-Asp triplet for attachment to host cells and this motif is believed to be essential for virus viability. Here we report that this triplet—which is also a widespread motif involved in cell-to-cell adhesion—can become dispensable upon short-term evolution of the virus harboring it. Foot-and-mouth disease virus (FMDV), which was multiply passaged in cell culture, showed an altered repertoire of antigenic variants resistant to a neutralizing monoclonal antibody. The altered repertoire includes variants with substitutions at the Arg-Gly-Asp motif. Mutants lacking this sequence replicated normally in cell culture and were indistinguishable from the parental virus. Studies with individual FMDV clones indicate that amino acid replacements on the capsid surface located around the loop harboring the Arg-Gly-Asp triplet may mediate in the dispensability of this motif. The results show that FMDV quasispecies evolving in a constant biological environment have the capability of rendering totally dispensable a receptor recognition motif previously invariant, and to ensure an alternative pathway for normal viral replication. Thus, variability of highly conserved motifs, even those that viruses have adapted from functional cellular motifs, can contribute to phenotypic flexibility of RNA viruses in nature. PMID:9192645

Fundamental reform of payment for adult primary care: comprehensive payment for comprehensive care.

PubMed

Goroll, Allan H; Berenson, Robert A; Schoenbaum, Stephen C; Gardner, Laurence B

2007-03-01

Primary care is essential to the effective and efficient functioning of health care delivery systems, yet there is an impending crisis in the field due in part to a dysfunctional payment system. We present a fundamentally new model of payment for primary care, replacing encounter-based imbursement with comprehensive payment for comprehensive care. Unlike former iterations of primary care capitation (which simply bundled inadequate fee-for-service payments), our comprehensive payment model represents new investment in adult primary care, with substantial increases in payment over current levels. The comprehensive payment is directed to practices to include support for the modern systems and teams essential to the delivery of comprehensive, coordinated care. Income to primary physicians is increased commensurate with the high level of responsibility expected. To ensure optimal allocation of resources and the rewarding of desired outcomes, the comprehensive payment is needs/risk-adjusted and performance-based. Our model establishes a new social contract with the primary care community, substantially increasing payment in return for achieving important societal health system goals, including improved accessibility, quality, safety, and efficiency. Attainment of these goals should help offset and justify the costs of the investment. Field tests of this and other new models of payment for primary care are urgently needed.

Aspartate Biosynthesis Is Essential for the Growth of Streptococcus thermophilus in Milk, and Aspartate Availability Modulates the Level of Urease Activity▿

PubMed Central

Arioli, Stefania; Monnet, Christophe; Guglielmetti, Simone; Parini, Carlo; De Noni, Ivano; Hogenboom, Johannes; Halami, Prakash M.; Mora, Diego

2007-01-01

We investigated the carbon dioxide metabolism of Streptococcus thermophilus, evaluating the phenotype of a phosphoenolpyruvate carboxylase-negative mutant obtained by replacement of a functional ppc gene with a deleted and inactive version, Δppc. The growth of the mutant was compared to that of the parent strain in a chemically defined medium and in milk, supplemented or not with l-aspartic acid, the final product of the metabolic pathway governed by phosphoenolpyruvate carboxylase. It was concluded that aspartate present in milk is not sufficient for the growth of S. thermophilus. As a consequence, phosphoenolpyruvate carboxylase activity was considered fundamental for the biosynthesis of l-aspartic acid in S. thermophilus metabolism. This enzymatic activity is therefore essential for growth of S. thermophilus in milk even if S. thermophilus was cultured in association with proteinase-positive Lactobacillus delbrueckii subsp. bulgaricus. It was furthermore observed that the supplementation of milk with aspartate significantly affected the level of urease activity. Further experiments, carried out with a pureI-gusA recombinant strain, revealed that expression of the urease operon was sensitive to the aspartate concentration in milk and to the cell availability of glutamate, glutamine, and ammonium ions. PMID:17660309

Fundamental Reform of Payment for Adult Primary Care: Comprehensive Payment for Comprehensive Care

PubMed Central

Berenson, Robert A.; Schoenbaum, Stephen C.; Gardner, Laurence B.

2007-01-01

Primary care is essential to the effective and efficient functioning of health care delivery systems, yet there is an impending crisis in the field due in part to a dysfunctional payment system. We present a fundamentally new model of payment for primary care, replacing encounter-based imbursement with comprehensive payment for comprehensive care. Unlike former iterations of primary care capitation (which simply bundled inadequate fee-for-service payments), our comprehensive payment model represents new investment in adult primary care, with substantial increases in payment over current levels. The comprehensive payment is directed to practices to include support for the modern systems and teams essential to the delivery of comprehensive, coordinated care. Income to primary physicians is increased commensurate with the high level of responsibility expected. To ensure optimal allocation of resources and the rewarding of desired outcomes, the comprehensive payment is needs/risk-adjusted and performance-based. Our model establishes a new social contract with the primary care community, substantially increasing payment in return for achieving important societal health system goals, including improved accessibility, quality, safety, and efficiency. Attainment of these goals should help offset and justify the costs of the investment. Field tests of this and other new models of payment for primary care are urgently needed. PMID:17356977

Differential Expression of Histone H3.3 Genes and Their Role in Modulating Temperature Stress Response in Caenorhabditis elegans.

PubMed

Delaney, Kamila; Mailler, Jonathan; Wenda, Joanna M; Gabus, Caroline; Steiner, Florian A

2018-04-10

Replication-independent variant histones replace canonical histones in nucleosomes and act as important regulators of chromatin function. H3.3 is a major variant of histone H3 that is remarkably conserved across all taxa and is distinguished from canonical H3 by just four key amino acids. Most genomes contain two or more genes expressing H3.3, and complete loss of the protein usually causes sterility or embryonic lethality. Here we investigated the developmental expression pattern of the five Caenorhabditis elegans H3.3 homologues and identified two previously uncharacterized homologues to be restricted to the germ line. We demonstrate an essential role for the conserved histone chaperone HIRA in the nucleosomal loading of all H3.3 variants. This requirement can be bypassed by mutation of the H3.3-specific residues to those found in H3. Analysis of H3.3 knockout mutants revealed a surprising absence of developmental phenotypes. While removal of all H3.3 homologues did not result in lethality, it led to reduced fertility and viability in response to high temperature stress. Our results thus show that H3.3 is non-essential in C. elegans , but is critical for ensuring adequate response to stress. Copyright © 2018, Genetics.

Physiological Implications of Myocardial Scar Structure

PubMed Central

Richardson, WJ; Clarke, SA; Quinn, TA; Holmes, JW

2016-01-01

Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following an MI, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction. PMID:26426470

Epithelial-Mesenchymal Interactions in Urinary Bladder and Small Intestine and How to Apply Them in Tissue Engineering.

PubMed

Jerman, Urška Dragin; Kreft, Mateja Erdani; Veranič, Peter

2015-12-01

Reciprocal interactions between the epithelium and mesenchyme are essential for the establishment of proper tissue morphology during organogenesis and tissue regeneration as well as for the maintenance of cell differentiation. With this review, we highlight the importance of epithelial-mesenchymal cross talk in healthy tissue and further discuss its significance in engineering functional tissues in vitro. We focus on the urinary bladder and small intestine, organs that are often compromised by disease and are as such in need of research that would advance effective treatment or tissue replacement. To date, the understanding of epithelial-mesenchymal reciprocal interactions has enabled the development of in vitro biomimetic tissue equivalents that have provided many possibilities in treating defective, damaged, or even cancerous tissues. Although research of the past several years has advanced the field of bladder and small intestine tissue engineering, one must be aware of its current limitations in successfully and above all safely introducing tissue-engineered constructs into clinical practice. Special attention is in particular needed when treating cancerous tissues, as initially successful tumor excision and tissue reconstruction may later on result in cancer recurrence due to oncogenic signals originating from an altered stroma. Recent rather poor outcomes in pioneering clinical trials of bladder reconstructions should serve as a reminder that recreating a functional organ to replace a dysfunctional one is an objective far more difficult to reach than initially foreseen. When considering effective tissue engineering approaches for diseased tissues in humans, it is imperative to introduce animal models with dysfunctional or, even more importantly, cancerous organs, which would greatly contribute to predicting possible complications and, hence, reducing risks when translating to the clinic.

Replacement of Ser108 in Plasmodium falciparum enolase results in weak Mg(II) binding: role of a parasite-specific pentapeptide insert in stabilizing the active conformation of the enzyme.

PubMed

Dutta, Sneha; Mukherjee, Debanjan; Jarori, Gotam K

2015-06-01

A distinct structural feature of Plasmodium falciparum enolase (Pfeno) is the presence of a five amino acid insert -104EWGWS108- that is not found in host enolases. Its conservation among apicomplexan enolases has raised the possibility of its involvement in some important physiological function(s). Deletion of this sequence is known to lower k(cat)/K(m), increase K(a) for Mg(II) and convert dimer into monomers (Vora HK, Shaik FR, Pal-Bhowmick I, Mout R & Jarori GK (2009) Arch Biochem Biophys 485, 128-138). These authors also raised the possibility of the formation of an H-bond between Ser108 and Leu49 that could stabilize the apo-Pfeno in an active closed conformation that has high affinity for Mg(II). Here, we examined the effect of replacement of Ser108 with Gly/Ala/Thr on enzyme activity, Mg(II) binding affinity, conformational states and oligomeric structure and compared it with native recombinant Pfeno. The results obtained support the view that Ser108 is likely to be involved in the formation of certain crucial H-bonds with Leu49. The presence of these interactions can stabilize apo-Pfeno in an active closed conformation similar to that of Mg(II) bound yeast enolase. As predicted, S108G/A-Pfeno variants (where Ser108-Leu49 H-bonds are likely to be disrupted) were found to exist in an open conformation and had low affinity for Mg(II). They also required Mg(II) induced conformational changes to acquire the active closed conformational state essential for catalysis. The possible physiological relevance of apo-Pfeno being in such an active state is discussed. © 2015 FEBS.

A virally inactivated functional growth factor preparation from human platelet concentrates.

PubMed

Su, C-Y; Kuo, Y P; Lin, Y C; Huang, C-T; Tseng, Y H; Burnouf, T

2009-08-01

Human platelet growth factors (HPGF) are essential for tissue regeneration and may replace fetal bovine serum (FBS) in cell therapy. No method for the manufacture of standardized virally inactivated HPGF has been developed yet. Platelet concentrates (PC) were subjected to solvent/detergent (S/D) treatment (1% TnBP/1% Triton X-45), oil extraction, hydrophobic interaction chromatography and sterile filtration. Platelet-derived growth factor (PDGF)-AB, -BB and -AA, transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1) and vascular endothelium growth factor (VEGF) were measured by ELISA. Composition in proteins and lipids was determined, protein profiles were obtained by SDS-PAGE, and TnBP and Triton X-45 were assessed by gas chromatography and high-performance liquid chromatography, respectively. Cell growth promoting activity of HPGF was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay using human embryonic kidney (HEK293A) fibroblast and Statens Seruminstitute rabbit corneal (SIRC) epithelial cell lines. The GF preparation contained a mean of 16.66, 2.04, 1.53, 72.19, 0.33, 48.59 and 0.44 ng/ml of PDGF-AB, -BB, -AA, TGF-beta1, EGF, IGF-1 and VEGF, respectively. The protein profile was typical of platelet releasates and had less than 2 p.p.m. of residual S/D agents. MTS assay of HEK293A and SIRC cultures showed that the GF preparation at 10% and 0.1% (v/v), respectively, could successfully replace 10% FBS for cell proliferation. Cell-stimulating activity of HPGF on HEK293A was over twice that of PC releasates. STANDARDIZED and functional virally inactivated HPGF can be prepared from human PC for possible applications in cell therapy and regenerative medicine.

Effects of vulture exclusion on carrion consumption by facultative scavengers.

PubMed

Hill, Jacob E; DeVault, Travis L; Beasley, James C; Rhodes, Olin E; Belant, Jerrold L

2018-03-01

Vultures provide an essential ecosystem service through removal of carrion, but globally, many populations are collapsing and several species are threatened with extinction. Widespread declines in vulture populations could increase the availability of carrion to other organisms, but the ways facultative scavengers might respond to this increase have not been thoroughly explored. We aimed to determine whether facultative scavengers increase carrion consumption in the absence of vulture competition and whether they are capable of functionally replacing vultures in the removal of carrion biomass from the landscape. We experimentally excluded 65 rabbit carcasses from vultures during daylight hours and placed an additional 65 carcasses that were accessible to vultures in forested habitat in South Carolina, USA during summer (June-August). We used motion-activated cameras to compare carrion use by facultative scavenging species between the experimental and control carcasses. Scavenging by facultative scavengers did not increase in the absence of competition with vultures. We found no difference in scavenger presence between control carcasses and those from which vultures were excluded. Eighty percent of carcasses from which vultures were excluded were not scavenged by vertebrates, compared to 5% of carcasses that were accessible to vultures. At the end of the 7-day trials, there was a 10.1-fold increase in the number of experimental carcasses that were not fully scavenged compared to controls. Facultative scavengers did not functionally replace vultures during summer in our study. This finding may have been influenced by the time of the year in which the study took place, the duration of the trials, and the spacing of carcass sites. Our results suggest that under the warm and humid conditions of our study, facultative scavengers would not compensate for loss of vultures. Carcasses would persist longer in the environment and consumption of carrion would likely shift from vertebrates to decomposers. Such changes could have substantial implications for disease transmission, nutrient cycling, and ecosystem functioning.

KARP-1 works as a heterodimer with Ku70, but the function of KARP-1 cannot perfectly replace that of Ku80 in DSB repair

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koike, Manabu, E-mail: m_koike@nirs.go.jp; Yutoku, Yasutomo; Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522

2011-10-01

Ku, the heterodimer of Ku70 and Ku80, plays an essential role in the DNA double-strand break (DSB) repair pathway, i.e., non-homologous end-joining (NHEJ). Two isoforms of Ku80 encoded by the same genes, namely, Ku80 and KARP-1 are expressed and function in primate cells, but not in rodent cells. Ku80 works as a heterodimer with Ku70. However, it is not yet clear whether KARP-1 forms a heterodimer with Ku70 and works as a heterodimer. Although KARP-1 appears to work in NHEJ, its physiological role remains unclear. In this study, we established and characterized EGFP-KARP-1-expressing xrs-6 cell lines, EGFP-KARP-1/xrs-6. We found thatmore » nuclear localization signal (NLS) of KARP-1 is localized in the C-terminal region. Our data showed that KARP-1 localizes within the nucleus in NLS-dependent and NLS-independent manner and forms a heterodimer with Ku70, and stabilizes Ku70. On the other hand, EGFP-KARP-1 could not perfectly complement the radiosensitivity and DSB repair activity of Ku80-deficient xrs-6 cells. Furthermore, KARP-1 could not accumulate at DSBs faster than Ku80, although EGFP-KARP-1 accumulates at DSBs. Our data demonstrate that the function of KARP-1 could not perfectly replace that of Ku80 in DSB repair, although KARP-1 has some biochemical properties, which resemble those of Ku80, and works as a heterodimer with Ku70. On the other hand, the number of EGFP-KARP-1-expressing xrs-6 cells showing pan-nuclear {gamma}-H2AX staining significantly increases following X-irradiation, suggesting that KARP-1 may have a novel role in DSB response.« less

Integrated Systems Mitigate Land Degradation and Improve Agricultural System Sustainability

NASA Astrophysics Data System (ADS)

Landblom, Douglas; Senturklu, Songul; Cihacek, Larry; Brevik, Eric

2017-04-01

Rain-fed agricultural production supported by exogenous inputs is not sustainable because a continuous influx of expensive inputs (fertilizer, chemicals, fossil fuel, labor, tillage, and other) is required. Alternatives to traditional management allow natural occurring dynamic soil processes to provide the necessary microbial activity that supports nutrient cycling in balance with nature. Research designed to investigate the potential for integrated systems to replace expensive inputs has shown that healthy soils rich in soil organic matter (SOM) are the foundation upon which microbial nutrient cycling can reduce and eventually replace expensive fertilizer. No-till seed placement technology effectively replaces multiple-pass cultivation conserving stored soil water in semi-arid farming systems. In multi-crop rotations, cool- and warm-season crops are grown in sequence to meet goals of the integrated farming and ranching system, and each crop in the rotation complements the subsequent crop by supplying a continuous flow of essential SOM for soil nutrient cycling. Grazing animals serve an essential role in the system's sustainability as non-mechanized animal harvesters that reduce fossil fuel consumption and labor, and animal waste contributes soil nutrients to the system. Integrated systems' complementarity has contributed to greater soil nutrient cycling and crop yields, fertilizer reduction or elimination, greater yearling steer grazing net return, reduced cow wintering costs grazing crop residues, increased wildlife sightings, and reduced environmental footprint. Therefore, integrating crop and animal systems can reverse soil quality decline and adopting non-traditional procedures has resulted in a wider array of opportunities for sustainable agriculture and profitability.

The crystal structure of TrxA(CACA): Insights into the formation of a [2Fe-2S] iron–sulfur cluster in an Escherichia coli thioredoxin mutant

PubMed Central

Collet, Jean-Francois; Peisach, Daniel; Bardwell, James C.A.; Xu, Zhaohui

2005-01-01

Escherichia coli thioredoxin is a small monomeric protein that reduces disulfide bonds in cytoplasmic proteins. Two cysteine residues present in a conserved CGPC motif are essential for this activity. Recently, we identified mutations of this motif that changed thioredoxin into a homodimer bridged by a [2Fe-2S] iron–sulfur cluster. When exported to the periplasm, these thioredoxin mutants could restore disulfide bond formation in strains lacking the entire periplasmic oxidative pathway. Essential for the assembly of the iron–sulfur was an additional cysteine that replaced the proline at position three of the CGPC motif. We solved the crystalline structure at 2.3 Å for one of these variants, TrxA(CACA). The mutant protein crystallized as a dimer in which the iron–sulfur cluster is replaced by two intermolecular disulfide bonds. The catalytic site, which forms the dimer interface, crystallized in two different conformations. In one of them, the replacement of the CGPC motif by CACA has a dramatic effect on the structure and causes the unraveling of an extended α-helix. In both conformations, the second cysteine residue of the CACA motif is surface-exposed, which contrasts with wildtype thioredoxin where the second cysteine of the CXXC motif is buried. This exposure of a pair of vicinal cysteine residues apparently allows thioredoxin to acquire an iron–sulfur cofactor at its active site, and thus a new activity and mechanism of action. PMID:15987909

The crystal structure of TrxA(CACA): Insights into the formation of a [2Fe-2S] iron-sulfur cluster in an Escherichia coli thioredoxin mutant.

PubMed

Collet, Jean-Francois; Peisach, Daniel; Bardwell, James C A; Xu, Zhaohui

2005-07-01

Escherichia coli thioredoxin is a small monomeric protein that reduces disulfide bonds in cytoplasmic proteins. Two cysteine residues present in a conserved CGPC motif are essential for this activity. Recently, we identified mutations of this motif that changed thioredoxin into a homodimer bridged by a [2Fe-2S] iron-sulfur cluster. When exported to the periplasm, these thioredoxin mutants could restore disulfide bond formation in strains lacking the entire periplasmic oxidative pathway. Essential for the assembly of the iron-sulfur was an additional cysteine that replaced the proline at position three of the CGPC motif. We solved the crystalline structure at 2.3 Angstroms for one of these variants, TrxA(CACA). The mutant protein crystallized as a dimer in which the iron-sulfur cluster is replaced by two intermolecular disulfide bonds. The catalytic site, which forms the dimer interface, crystallized in two different conformations. In one of them, the replacement of the CGPC motif by CACA has a dramatic effect on the structure and causes the unraveling of an extended alpha-helix. In both conformations, the second cysteine residue of the CACA motif is surface-exposed, which contrasts with wildtype thioredoxin where the second cysteine of the CXXC motif is buried. This exposure of a pair of vicinal cysteine residues apparently allows thioredoxin to acquire an iron-sulfur cofactor at its active site, and thus a new activity and mechanism of action.

The role of cardiovascular magnetic resonance in the assessment of severe aortic stenosis and in post-procedural evaluation following transcatheter aortic valve implantation and surgical aortic valve replacement.

PubMed

Musa, Tarique Al; Plein, Sven; Greenwood, John P

2016-06-01

Degenerative aortic stenosis (AS) is the most common valvular disease in the western world with a prevalence expected to double within the next 50 years. International guidelines advocate the use of cardiovascular magnetic resonance (CMR) as an investigative tool, both to guide diagnosis and to direct optimal treatment. CMR is the reference standard for quantifying both left and right ventricular volumes and mass, which is essential to assess the impact of AS upon global cardiac function. Given the ability to image any structure in any plane, CMR offers many other diagnostic strengths including full visualisation of valvular morphology, direct planimetry of orifice area, the quantification of stenotic jets and in particular, accurate quantification of valvular regurgitation. In addition, CMR permits reliable and accurate measurements of the aortic root and arch which can be fundamental to appropriate patient management. There is a growing evidence base to indicate tissue characterisation using CMR provides prognostic information, both in asymptomatic AS patients and those undergoing intervention. Furthermore, a number of current clinical trials will likely raise the importance of CMR in routine patient management. This article will focus on the incremental value of CMR in the assessment of severe AS and the insights it offers following valve replacement.

A single amino acid limits the substrate specificity of Thermus thermophilus uridine-cytidine kinase to cytidine.

PubMed

Tomoike, Fumiaki; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

2011-05-31

The salvage pathways of nucleotide biosynthesis are more diverse and are less well understood as compared with de novo pathways. Uridine-cytidine kinase (UCK) is the rate-limiting enzyme in the pyrimidine-nucleotide salvage pathway. In this study, we have characterized a UCK homologue of Thermus thermophilus HB8 (ttCK) biochemically and structurally. Unlike other UCKs, ttCK had substrate specificity toward only cytidine and showed no inhibition by UTP, suggesting uridine does not bind to ttCK as substrate. Structural analysis revealed that the histidine residue located near the functional group at position 4 of cytidine or uridine in most UCKs is substituted with tyrosine, Tyr93, in ttCK. Replacement of Tyr93 by histidine or glutamine endowed ttCK with phosphorylation activity toward uridine. These results suggested that a single amino acid residue, Tyr93, gives cytidine-limited specificity to ttCK. However, replacement of Tyr93 by Phe or Leu did not change the substrate specificity of ttCK. Therefore, we conclude that a residue at this position is essential for the recognition of uridine by UCK. In addition, thymidine phosphorylase from T. thermophilus HB8 was equally active with thymidine and uridine, which indicates that this protein is the sole enzyme metabolizing uridine in T. Thermophilus HB8. On the basis of these results, we discuss the pyrimidine-salvage pathway in T. thermophilus HB8.

75 FR 42790 - Exelon Generation Company, LLC; Clinton Power Station; Environmental Assessment and Finding of No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-22

... functions, and replace a Mechanical Maintenance person with a NLO. The regulation at 10 CFR 50.54(q) states... assigned other functions, and replace a Mechanical Maintenance person with a NLO. According to the licensee... to plant personnel work assignments. No changes will be made to plant buildings or the site property...

Correlation between plasma N-terminal pro-brain natriuretic peptide levels and changes in New York Heart Association functional class, left atrial size, left ventricular size and function after mitral and/or aortic valve replacement.

PubMed

Elasfar, Abdelfatah

2012-01-01

Elevated plasma brain natriuretic peptide (BNP) levels have been demonstrated in patients with chronic valvular disease. We designed the present study to assess whether changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels after mitral, aortic and double mitral and aortic valve replacement reflect changes in heart failure (HF) symptoms including New York Heart Association (NYHA) class and changes in left atrium (LA) size, left ventricle (LV) size and LV function. A prospective observational nonrandomized study among consecutive patients undergoing mitral and/or aortic valve replacement in our center. The study population consisted of 24 patients (mean [SD] age of 55.3 [16.2] years, 58% were males) who underwent surgical mitral valve replacement (12 patients), aortic valve replacement (8 patients) and combined mitral and aortic valve replacement (4 patients). NT-proBNP measurements, transthoracic echocardiography and NYHA class assessments were performed before and 6 months after surgery. The decrease in NT-proBNP was associated with decrease in left atrial dimension (r = 0.73, P < .002), LV end-diastolic dimension (r=0.65, P=.001), LV end-systolic dimension (r=0.53, P=.036), and increase in ejection fraction (r=-0.65, P=.001) after 6 months postoperatively. Furthermore, a decreasing NT-proBNP was associated with improvement in NYHA class. NT-proBNP levels after mitral, aortic and double valve replacement correlates with changes in HF manifestations as well as changes in LA size and LV dimension and function. Thus, we hypothesize that interval measurement of the NT-proBNP level at clinic visits can allow early detection of any clinical deterioration as well as the possibility of assessment of the long-term outcome of those patients.

Protein domains of unknown function are essential in bacteria.

PubMed

Goodacre, Norman F; Gerloff, Dietlind L; Uetz, Peter

2013-12-31

More than 20% of all protein domains are currently annotated as "domains of unknown function" (DUFs). About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs. Evolutionary conservation suggests that many of these DUFs are important. Here we show that 355 essential proteins in 16 model bacterial species contain 238 DUFs, most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. We suggest that experimental research should focus on conserved and essential DUFs (eDUFs) for functional analysis given their important function and wide taxonomic distribution, including bacterial pathogens. The functional units of proteins are domains. Typically, each domain has a distinct structure and function. Genomes encode thousands of domains, and many of the domains have no known function (domains of unknown function [DUFs]). They are often ignored as of little relevance, given that many of them are found in only a few genomes. Here we show that many DUFs are essential DUFs (eDUFs) based on their presence in essential proteins. We also show that eDUFs are often essential even if they are found in relatively few genomes. However, in general, more common DUFs are more often essential than rare DUFs.

The association between radiographic severity and pre-operative function in patients undergoing primary knee replacement for osteoarthritis.

PubMed

Dowsey, Michelle M; Dieppe, Paul; Lohmander, Stefan; Castle, David; Liew, Danny; Choong, Peter F M

2012-12-01

To determine the association between radiographic osteoarthritis (OA) and pre-operative function in patients undergoing primary knee replacement. Single centre study examining pre-operative outcomes in a consecutive series of 525 patients who underwent primary knee replacement for OA between January 2006 and December 2007. Pre-operative data included: demographics, American Society of Anaesthesiologists (ASA) status and OA in the contralateral knee. The International Knee Society (IKS) rating and Short Form-12 (SF-12) were recorded for each patient. Pre-operative radiographs were read by a single observer for Kellgren and Lawrence (K&L) grading and Osteoarthritis Research Society International (OARSI) atlas features. Multiple linear regression was used to assess the strength of associations between radiographic OA severity and function, adjusting for clinically relevant variables. Lateral tibiofemoral osteophyte grade was an independent predictor of pre-operative function as determined by the functional sub-scale of the IKS in patients undergoing primary knee replacement (coefficient=2.58, p=0.033). No associations were evident between pre-operative function and modified K&L, joint space narrowing, Ahlbäck attrition and coronal plane deformity. Other statistically significant predictors of poorer pre-operative function included: advancing age, female gender, knee pain and poorer SF-12 mental component summary scores which including osteophyte grade accounted for 24.6% of the variation in functional scores, (r=0.496). Osteophytes in the lateral compartment of the knee were associated with pre-operative function in patients with advanced knee OA. Further studies are required which examine individual radiographic features specifically in patients with advanced knee OA to determine their relationship to pre-operative pain and function. Copyright © 2012 Elsevier B.V. All rights reserved.

Engineering the genomes of wild insect populations: challenges, and opportunities provided by synthetic Medea selfish genetic elements.

PubMed

Hay, Bruce A; Chen, Chun-Hong; Ward, Catherine M; Huang, Haixia; Su, Jessica T; Guo, Ming

2010-10-01

Advances in insect transgenesis and our knowledge of insect physiology and genomics are making it possible to create transgenic populations of beneficial or pest insects that express novel traits. There are contexts in which we may want the transgenes responsible for these traits to spread so that all individuals within a wild population carry them, a process known as population replacement. Transgenes of interest are unlikely to confer an overall fitness benefit on those who carry them. Therefore, an essential component of any population replacement strategy is the presence of a drive mechanism that will ensure the spread of linked transgenes. We discuss contexts in which population replacement might be desirable and the requirements a drive system must satisfy to be both effective and safe. We then describe the creation of synthetic Medea elements, the first selfish genetic elements synthesized de novo, with the capability of driving population replacement, in this case in Drosophila. The strategy used to create Drosophila Medea is applicable to a number of other insect species and the Medea system satisfies key requirements for scientific and social acceptance. Finally, we highlight several challenges to implementing population replacement in the wild. Copyright 2010 Elsevier Ltd. All rights reserved.

Leaving Moderate Tricuspid Valve Regurgitation Alone at the Time of Pulmonary Valve Replacement: A Worthwhile Approach.

PubMed

Kogon, Brian; Mori, Makoto; Alsoufi, Bahaaldin; Kanter, Kirk; Oster, Matt

2015-06-01

Pulmonary valve disruption in patients with tetralogy of Fallot and congenital pulmonary stenosis often results in pulmonary insufficiency, right ventricular dilation, and tricuspid valve regurgitation. Management of functional tricuspid regurgitation at the time of subsequent pulmonary valve replacement remains controversial. Our aims were to (1) analyze tricuspid valve function after pulmonary valve replacement through midterm follow-up and (2) determine the benefits, if any, of concomitant tricuspid annuloplasty. Thirty-five patients with tetralogy of Fallot or congenital pulmonary stenosis were analyzed. All patients had been palliated in childhood by disrupting the pulmonary valve, and all patients had at least moderate tricuspid valve regurgitation at the time of subsequent pulmonary valve replacement. Preoperative and serial postoperative echocardiograms were analyzed. Pulmonary and tricuspid regurgitation, along with right ventricular dilation and dysfunction were scored as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Right ventricular volume and area were also calculated. Comparisons were made between patients who underwent pulmonary valve replacement alone and those who underwent concomitant tricuspid valve annuloplasty. At 1 month after pulmonary valve replacement, there were significant reductions in pulmonary valve regurgitation (mean 3 vs 0.39, p < 0.0001), tricuspid valve regurgitation (mean 2.33 vs 1.3, p < 0.0001), and in right ventricular dilation, volume, and area. There was no difference in the degree of tricuspid regurgitation 1 month postoperatively between patients who underwent concomitant tricuspid annuloplasty and those who underwent pulmonary valve replacement alone (mean 1.31 vs 1.29, p = 0.81). However, at latest follow-up (mean 7.0 ± 2.8 years), the degree of tricuspid regurgitation was significantly higher in the concomitant annuloplasty group (mean 1.87 vs 1.12, p = 0.005). In patients with at least moderate tricuspid valve regurgitation, significant improvement in tricuspid valve function and right ventricular size occurs in the first postoperative month after pulmonary valve replacement, irrespective of concomitant tricuspid valve annuloplasty. The tricuspid valve appears to function better over the midterm if annuloplasty is not performed. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The rapidly evolving centromere-specific histone has stringent functional requirements in Arabidopsis thaliana.

PubMed

Ravi, Maruthachalam; Kwong, Pak N; Menorca, Ron M G; Valencia, Joel T; Ramahi, Joseph S; Stewart, Jodi L; Tran, Robert K; Sundaresan, Venkatesan; Comai, Luca; Chan, Simon W-L

2010-10-01

Centromeres control chromosome inheritance in eukaryotes, yet their DNA structure and primary sequence are hypervariable. Most animals and plants have megabases of tandem repeats at their centromeres, unlike yeast with unique centromere sequences. Centromere function requires the centromere-specific histone CENH3 (CENP-A in human), which replaces histone H3 in centromeric nucleosomes. CENH3 evolves rapidly, particularly in its N-terminal tail domain. A portion of the CENH3 histone-fold domain, the CENP-A targeting domain (CATD), has been previously shown to confer kinetochore localization and centromere function when swapped into human H3. Furthermore, CENP-A in human cells can be functionally replaced by CENH3 from distantly related organisms including Saccharomyces cerevisiae. We have used cenh3-1 (a null mutant in Arabidopsis thaliana) to replace endogenous CENH3 with GFP-tagged variants. A H3.3 tail domain-CENH3 histone-fold domain chimera rescued viability of cenh3-1, but CENH3's lacking a tail domain were nonfunctional. In contrast to human results, H3 containing the A. thaliana CATD cannot complement cenh3-1. GFP-CENH3 from the sister species A. arenosa functionally replaces A. thaliana CENH3. GFP-CENH3 from the close relative Brassica rapa was targeted to centromeres, but did not complement cenh3-1, indicating that kinetochore localization and centromere function can be uncoupled. We conclude that CENH3 function in A. thaliana, an organism with large tandem repeat centromeres, has stringent requirements for functional complementation in mitosis.

Cell response to quasi-monochromatic light with different coherence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budagovsky, A V; Solovykh, N V; Budagovskaya, O N

The problem of the light coherence effect on the magnitude of the photoinduced cell response is discussed. The origins of ambiguous interpretation of the known experimental results are considered. Using the biological models, essentially differing in anatomy, morphology and biological functions (acrospires of radish, blackberry microsprouts cultivated in vitro, plum pollen), the effect of statistical properties of quasi-monochromatic light (λ{sub max} = 633 nm) on the magnitude of the photoinduced cell response is shown. It is found that for relatively low spatial coherence, the cell functional activity changes insignificantly. The maximal enhancement of growing processes (stimulating effect) is observed whenmore » the coherence length L{sub coh} and the correlation radius r{sub cor} are greater than the cell size, i.e., the entire cell fits into the field coherence volume. In this case, the representative indicators (germination of seeds and pollen, the spears length) exceeds those of non-irradiated objects by 1.7 – 3.9 times. For more correct assessment of the effect of light statistical properties on photocontrol processes, it is proposed to replace the qualitative description (coherent – incoherent) with the quantitative one, using the determination of spatial and temporal correlation functions and comparing them with the characteristic dimensions of the biological structures, e.g., the cell size. (biophotonics)« less

Mutational analysis of polyomavirus small-T-antigen functions in productive infection and in transformation.

PubMed Central

Martens, I; Nilsson, S A; Linder, S; Magnusson, G

1989-01-01

The function of polyomavirus small T antigen in productive infection and in transformation was studied. Transfection of permissive mouse cells with mixtures of mutants that express only one type of T antigen showed that small T antigen increased large-T-antigen-dependent viral DNA synthesis approximately 10-fold. Under the same conditions, small T antigen was also essential for the formation of infectious virus particles. To analyze these activities of small T antigen, mutants producing protein with single amino acid replacements were constructed. Two mutants, bc1073 and bc1075, were characterized. Although both mutations led to the substitution of amino acid residues of more than one T antigen, the phenotype of both mutants was associated with alterations of the small T antigen. Both mutant proteins had lost their activity in the maturation of infectious virus particles. The bc1075 but not the bc1073 small T antigen had also lost its ability to stimulate viral DNA synthesis in mouse 3T6 cells. Finally, both mutants retained a third activity of small T antigen: to confer on rat cells also expressing middle T antigen the ability to grow efficiently in semisolid medium. The phenotypes of the mutants in these three assays suggest that small T antigen has at least three separate functions. Images PMID:2704075

Mutational analysis of polyomavirus small-T-antigen functions in productive infection and in transformation.

PubMed

Martens, I; Nilsson, S A; Linder, S; Magnusson, G

1989-05-01

The function of polyomavirus small T antigen in productive infection and in transformation was studied. Transfection of permissive mouse cells with mixtures of mutants that express only one type of T antigen showed that small T antigen increased large-T-antigen-dependent viral DNA synthesis approximately 10-fold. Under the same conditions, small T antigen was also essential for the formation of infectious virus particles. To analyze these activities of small T antigen, mutants producing protein with single amino acid replacements were constructed. Two mutants, bc1073 and bc1075, were characterized. Although both mutations led to the substitution of amino acid residues of more than one T antigen, the phenotype of both mutants was associated with alterations of the small T antigen. Both mutant proteins had lost their activity in the maturation of infectious virus particles. The bc1075 but not the bc1073 small T antigen had also lost its ability to stimulate viral DNA synthesis in mouse 3T6 cells. Finally, both mutants retained a third activity of small T antigen: to confer on rat cells also expressing middle T antigen the ability to grow efficiently in semisolid medium. The phenotypes of the mutants in these three assays suggest that small T antigen has at least three separate functions.

Escherichia coli F1Fo-ATP synthase with a b/δ fusion protein allows analysis of the function of the individual b subunits.

PubMed

Gajadeera, Chathurada S; Weber, Joachim

2013-09-13

The "stator stalk" of F1Fo-ATP synthase is essential for rotational catalysis as it connects the nonrotating portions of the enzyme. In Escherichia coli, the stator stalk consists of two (identical) b subunits and the δ subunit. In mycobacteria, one of the b subunits and the δ subunit are replaced by a b/δ fusion protein; the remaining b subunit is of the shorter b' type. In the present study, it is shown that it is possible to generate a functional E. coli ATP synthase containing a b/δ fusion protein. This construct allowed the analysis of the roles of the individual b subunits. The full-length b subunit (which in this case is covalently linked to δ in the fusion protein) is responsible for connecting the stalk to the catalytic F1 subcomplex. It is not required for interaction with the membrane-embedded Fo subcomplex, as its transmembrane helix can be removed. Attachment to Fo is the function of the other b subunit which in turn has only a minor (if any at all) role in binding to δ. Also in E. coli the second b subunit can be shortened to a b' type.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

PubMed

Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Crystal structures of the F and pSLT plasmid TraJ N-terminal regions reveal similar homodimeric PAS folds with functional interchangeability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Jun; Wu, Ruiying; Adkins, Joshua N.

2014-09-16

In the F-family of conjugative plasmids, TraJ is an essential transcriptional activator of the tra operon that encodes most of the proteins required for conjugation. Here we report for the first time the X-ray crystal structures of the TraJ N-terminal regions from the prototypic F plasmid (TraJF11-130) and from the Salmonella virulence plasmid pSLT (TraJpSLT 1-128). Both proteins form similar homodimeric Per-ARNT-Sim (PAS) fold structures. Mutational analysis reveals that the observed dimeric interface is critical for TraJF transcriptional activation, indicating that dimerization of TraJ is required for its in vivo function. An artificial ligand (oxidized dithiothreitol) occupies a cavity inmore » the TraJF dimer interface, while a smaller cavity in corresponding region of the TraJpSLT structure lacks a ligand. Gas chromatography/mass spectrometry-electron ionization analysis of dithiothreitol-free TraJF suggests indole may be the natural TraJ ligand; however, disruption of the indole biosynthetic pathway does not affect TraJF function. Heterologous PAS domains from pSLT and R100 TraJ can functionally replace the TraJF PAS domain, suggesting that TraJ allelic specificity is mediated by the region C-terminal to the PAS domain.« less

Structural and functional characterization of phosphomimetic mutants of cytochrome c at threonine 28 and serine 47.

PubMed

Guerra-Castellano, Alejandra; Díaz-Moreno, Irene; Velázquez-Campoy, Adrián; De la Rosa, Miguel A; Díaz-Quintana, Antonio

2016-04-01

Protein function is frequently modulated by post-translational modifications of specific residues. Cytochrome c, in particular, is phosphorylated in vivo at threonine 28 and serine 47. However, the effect of such modifications on the physiological functions of cytochrome c - namely, the transfer of electrons in the respiratory electron transport chain and the triggering of programmed cell death - is still unknown. Here we replace each of these two residues by aspartate, in order to mimic phosphorylation, and report the structural and functional changes in the resulting cytochrome c variants. We find that the T28D mutant causes a 30-mV decrease on the midpoint redox potential and lowers the affinity for the distal site of Arabidopsis thaliana cytochrome c1 in complex III. Both the T28D and S47D variants display a higher efficiency as electron donors for the cytochrome c oxidase activity of complex IV. In both protein mutants, the peroxidase activity is significantly higher, which is related to the ability of cytochrome c to leave the mitochondria and reach the cytoplasm. We also find that both mutations at serine 47 (S47D and S47A) impair the ability of cytoplasmic cytochrome c to activate the caspases cascade, which is essential for triggering programmed cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

PubMed Central

Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

A prospective study on the risk of glove fingertip contamination during draping in joint replacement surgery

PubMed Central

Deierl, K; Pandit, A; Trakru, S

2014-01-01

Introduction The aim of this prospective study was to investigate the risk of contamination of surgical gloves during preparation and draping in joint replacement surgery. Methods During 46 hip and knee replacement procedures, the gloves of orthopaedic consultants (n=5) and registrars (n=3) were assessed for contamination immediately after draping by impression of gloved fingers on blood agar. Contamination was evaluated by the surgeon’s grade, the type of procedure, the role of the assistant and the dominance of the hand. Results A total of 125 pairs of top gloves were examined (79 pairs from registrars and 46 pairs from consultants). Bacterial contamination was isolated on 19 pairs (15.2%) (16 pairs from registrars and 3 pairs from consultants, p=0.04). Coagulase negative staphylococci were the main isolates and contamination was considered low in all cases (1–5 colonies). Contamination was seen more on the dominant hand (16 gloves from dominant hands and 6 from non-dominant hands, p=0.04), on the index finger and thumb. More contaminated gloves were seen in hip arthroplasty procedures (16 pairs from total hip replacements vs 3 pairs from total knee replacements, p=0.02). Conclusions Contamination of glove fingertips during draping in joint replacement procedures is more likely to occur among junior surgeons, in hip rather than knee arthroplasty procedures and on the dominant hand. It is therefore essential that surgeons of different grades replace gloves used in draping to avoid exposing patients to the risk of infection. PMID:25198974

Four possible types of pulses for self-induced transparency

NASA Technical Reports Server (NTRS)

Lee, C. T.

1974-01-01

Four types of steady-state solutions were derived for the coupled Maxwell-Bloch equations which describe highly intense pulse propagation in a resonant medium. Essential in the derivation procedures is the replacement of the usual slowly varying envelope approximation with an alternative procedure, the omission of possible nonresonant losses, and the assumption that the relaxation times are infinite.

Searing the rhizosphere: belowground impacts of prescribed fires.

Treesearch

Jonathan Thompson

2006-01-01

A century of fire suppression has resulted in dense fuel loads within the dry pine forests of eastern Oregon . To alleviate the risk of stand-replacing wildfire, forest managers are using prescribed fire and thinning treatments. Until recently, the impact of these fuel treatments on soil productivity has been largely unknown. Such information is essential for making...

Five Essential Reasons to Keep Naptime in the Early Childhood Curriculum

ERIC Educational Resources Information Center

Desjean-Perrotta, Blanche

2008-01-01

Many early childhood educators are faced with ever-increasing pressure by families, administrators, and policymakers to replace components of their programs deemed to be a waste of time, such as naptime or playtime, with what are considered to be more academic activities. A large body of literature supports the inclusion of play in an early…

75 FR 19213 - Use of Ozone-Depleting Substances; Removal of Essential-Use Designation (Flunisolide, etc.)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

... the early 1930s as a replacement for hazardous materials then used in refrigeration, such as sulfur... FDA regulations on labeling for use during pregnancy require the classification of each drug product under one of five pregnancy categories (A, B, C, D, or X) on the basis of risk of reproductive and...

Black aorta in a patient with alkaptonuria (ochronosis).

PubMed

Concistrè, Giovanni; Fiorani, Brenno; Ranocchi, Federico; Casali, Giovanni; Loforte, Antonio; Musumeci, Francesco

2011-06-01

A rare cause of valvular heart disease is the deposition of foreign material in the valvular tissues, including material accumulating as a result of inborn errors of metabolism of the essential amino acids. Alkaptonuria can result in accumulation of homogentisic acid. We report the case of a patient with alkaptonuria undergoing surgery for aortic valve replacement.

Population Bulletin, Vol. 33, No. 3. What Will a ZPG Society Be Like?

ERIC Educational Resources Information Center

Day, Lincoln H.

This Bulletin explores the implications of a population with essentially zero growth and an unchanging, or stationary, age-sex structure--a likely prospect for at least the approximately 26 countries, containing a quarter of the world's population, who were at or below replacement level fertility by early 1978. The only certain demographic…

Taurine supplemented plant protein based diets with alternative lipid sources for juvenile sea bream, sparus aurata

USDA-ARS?s Scientific Manuscript database

Two lipid sources were evaluated as fish oil replacements in fishmeal free, plant protein based diets for juvenile gilthead sea bream, Sparus aurata. A twelve week feeding study was undertaken to examine the performance of fish fed the diets with different sources of essential fatty acids (canola o...

Regional analgesia for improvement of long-term functional outcome after elective large joint replacement

PubMed Central

Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

2015-01-01

Background Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. Objectives To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. Search methods We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. Selection criteria We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. Data collection and analysis We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. Main results We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low. Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) − 2.23 to 10.21; P value = 0.21, 3 studies, 140 participants, very low quality evidence). We did not perform further analyses because immediate adverse effects were not part of the explicit outcomes of any of these typically small studies, and long-term adverse events after regional anaesthesia are rare. None of the included studies elicited or reported long-term adverse effects like persistent nerve damage. Authors’ conclusions More high-quality studies are needed to establish the effects of regional analgesia on function after major joint replacement, as well as on the risk of adverse events (falls). PMID:26269416

[Retrospective study about periodontal ligament healing of replanted permanent teeth in children].

PubMed

Bai, J; Zhao, Y M; Qin, M

2015-04-18

To analyze the prognosis about periodontal ligament healing of replanted permanent teeth in children and to examine the associated factors. The sample consisted of 49 children with 61 avulsed permanent teeth, whose injuries had been managed in the period from 2000 to 2012. The clinical data of replanted teeth were collected, and the follow-up period was no less than 12 months. The factors were analyzed in relation to postoperative outcomes, classified as functional periodontal healing (FH), infection-related (inflammatory) resorption (IRR) and replacement resorption (RR). The functional healing rate was 23.0%, while replacement resorption rate was 72.1%. The replacement resorption (ankylosis) was usually observed earlier by clinical examination than by radiographic examination. 86.0% (40/47) resorptive processes were diagnosed within the first year. Physiological storages, such as milk, saline and saliva were significantly better to periodontal ligament healing than nonphysiological storages, such as tap water and sterilizing solutions (chloramine and alcohol). Functional healing was found significantly more frequent in canines and premolars. The factor significantly affecting periodontal ligament healing is storage medium. Replacement resorption is the most common type of root resorption. The replacement resorption diagnosis must combine the radiographic examination with the clinical examination. It is better to follow up more than 1 year after tooth replantation.

The conserved Phe GH5 of importance for hemoglobin intersubunit contact is mutated in gadoid fish

PubMed Central

2014-01-01

Background Functionality of the tetrameric hemoglobin molecule seems to be determined by a few amino acids located in key positions. Oxygen binding encompasses structural changes at the interfaces between the α1β2 and α2β1 dimers, but also subunit interactions are important for the oxygen binding affinity and stability. The latter packing contacts include the conserved Arg B12 interacting with Phe GH5, which is replaced by Leu and Tyr in the αA and αD chains, respectively, of birds and reptiles. Results Searching all known hemoglobins from a variety of gnathostome species (jawed vertebrates) revealed the almost invariant Arg B12 coded by the AGG triplet positioned at an exon-intron boundary. Rare substitutions of Arg B12 in the gnathostome β globins were found in pig, tree shrew and scaled reptiles. Phe GH5 is also highly conserved in the β globins, except for the Leu replacement in the β1 globin of five marine gadoid species, gilthead seabream and the Comoran coelacanth, while Cys and Ile were found in burbot and yellow croaker, respectively. Atlantic cod β1 globin showed a Leu/Met polymorphism at position GH5 dominated by the Met variant in northwest-Atlantic populations that was rarely found in northeast-Atlantic cod. Site-specific analyses identified six consensus codons under positive selection, including 122β(GH5), indicating that the amino acid changes identified at this position may offer an adaptive advantage. In fact, computational mutation analysis showed that the replacement of Phe GH5 with Leu or Cys decreased the number of van der Waals contacts essentially in the deoxy form that probably causes a slight increase in the oxygen binding affinity. Conclusions The almost invariant Arg B12 and the AGG codon seem to be important for the packing contacts and pre-mRNA processing, respectively, but the rare mutations identified might be beneficial. The Leu122β1(GH5)Met and Met55β1(D6)Val polymorphisms in Atlantic cod hemoglobin modify the intradimer contacts B12-GH5 and H2-D6, while amino acid replacements at these positions in avian hemoglobin seem to be evolutionary adaptive in air-breathing vertebrates. The results support the theory that adaptive changes in hemoglobin functions are caused by a few substitutions at key positions. PMID:24655798

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism

PubMed Central

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K.; Vivekanandan, Muthupillai

2016-01-01

Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations. PMID:27042409

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism.

PubMed

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K; Vivekanandan, Muthupillai

2016-01-01

Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

Hierarchy revealed in the specification of three skeletal fates by Sox9 and Runx2.

PubMed

Eames, B Frank; Sharpe, Paul T; Helms, Jill A

2004-10-01

Across vertebrates, there are three principal skeletal tissues: bone, persistent cartilage, and replacement cartilage. Although each tissue has a different evolutionary history and functional morphology, they also share many features. For example, they function as structural supports, they are comprised of cells embedded in collagen-rich extracellular matrix, and they derive from a common embryonic stem cell, the osteochondroprogenitor. Occasionally, homologous skeletal elements can change tissue type through phylogeny. Together, these observations raise the possibility that skeletal tissue identity is determined by a shared set of genes. Here, we show that misexpression of either Sox9 or Runx2 can substitute bone with replacement cartilage or can convert persistent cartilage into replacement cartilage and vice versa. Our data also suggest that these transcription factors function in a molecular hierarchy in which chondrogenic factors dominate. We propose a binary molecular code that determines whether skeletal tissues form as bone, persistent cartilage, or replacement cartilage. Finally, these data provide insights into the roles that master regulatory genes play during evolutionary change of the vertebrate skeleton.

Enzyme replacement therapy of Fabry disease.

PubMed

Clarke, Joe T R; Iwanochko, R Mark

2005-08-01

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A and results in pain, progressive renal impairment, cardiomyopathy, and cerebrovascular disease. The results of two major randomized, double-blind, placebo-controlled clinical trials and open-label extensions have shown that replacement of the deficient enzyme with either of two preparations of recombinant human alpha-galactosidase A, agalsidase-alfa, and agalsidase-beta is safe. Biweekly i.v. infusions of 0.2 mg/kg of agalsidase-alfa were associated with a significant decrease in pain and stabilization of renal function. Biweekly infusions of 1 mg/kg of agalsidase-beta were associated with virtually complete clearing of accumulated glycolipid substrate from renal and cutaneous capillary endothelial cells. Several smaller, open-label studies, along with observations made in the course of monitoring large numbers of patients on enzyme replacement therapy, indicated that treatment stabilizes renal function and produces significant improvements in myocardial mass and function. Treatment of Fabry disease by enzyme replacement has a significant impact on at least some serious complications of the disease.

Naturally Occurring Differences in CENH3 Affect Chromosome Segregation in Zygotic Mitosis of Hybrids

PubMed Central

Maheshwari, Shamoni; Tan, Ek Han; West, Allan; Franklin, F. Chris H.; Comai, Luca

2015-01-01

The point of attachment of spindle microtubules to metaphase chromosomes is known as the centromere. Plant and animal centromeres are epigenetically specified by a centromere-specific variant of Histone H3, CENH3 (a.k.a. CENP-A). Unlike canonical histones that are invariant, CENH3 proteins are accumulating substitutions at an accelerated rate. This diversification of CENH3 is a conundrum since its role as the key determinant of centromere identity remains a constant across species. Here, we ask whether naturally occurring divergence in CENH3 has functional consequences. We performed functional complementation assays on cenh3-1, a null mutation in Arabidopsis thaliana, using untagged CENH3s from increasingly distant relatives. Contrary to previous results using GFP-tagged CENH3, we find that the essential functions of CENH3 are conserved across a broad evolutionary landscape. CENH3 from a species as distant as the monocot Zea mays can functionally replace A. thaliana CENH3. Plants expressing variant CENH3s that are fertile when selfed show dramatic segregation errors when crossed to a wild-type individual. The progeny of this cross include hybrid diploids, aneuploids with novel genetic rearrangements and haploids that inherit only the genome of the wild-type parent. Importantly, it is always chromosomes from the plant expressing the divergent CENH3 that missegregate. Using chimeras, we show that it is divergence in the fast-evolving N-terminal tail of CENH3 that is causing segregation errors and genome elimination. Furthermore, we analyzed N-terminal tail sequences from plant CENH3s and discovered a modular pattern of sequence conservation. From this we hypothesize that while the essential functions of CENH3 are largely conserved, the N-terminal tail is evolving to adapt to lineage-specific centromeric constraints. Our results demonstrate that this lineage-specific evolution of CENH3 causes inviability and sterility of progeny in crosses, at the same time producing karyotypic variation. Thus, CENH3 evolution can contribute to postzygotic reproductive barriers. PMID:25622028

Effects of balance and proprioceptive training on total hip and knee replacement rehabilitation: A systematic review and meta-analysis.

PubMed

Domínguez-Navarro, Fernando; Igual-Camacho, Celedonia; Silvestre-Muñoz, Antonio; Roig-Casasús, Sergio; Blasco, José María

2018-05-01

Balance and proprioceptive deficits are frequently persistent after total joint replacement, limiting functionality and involving altered movement patterns and difficulties in walking and maintaining postural control among patients. The goal of this systematic review was to evaluate the short- and mid-term effects of proprioceptive and balance training for patients undergoing total knee and hip replacement. This is a systematic review of literature. MEDLINE, Embase, Cochrane Library, PEDro, and Scopus were the databases searched. The review included randomized clinical trials in which the experimental groups underwent a training aimed at improving balance and proprioception, in addition to conventional care. The studies had to assess at least one of the following outcomes: self-reported functionality or balance (primary outcomes), knee function, pain, falls, or quality of life. Eight trials were included, involving 567 participants. The quantitative synthesis found a moderate to high significant effect of balance and proprioceptive trainings on self-reported functionality and balance after total knee replacement. The effects were maintained at mid-term in terms of balance alone. Conversely, preoperative training did not enhance outcomes after total hip arthroplasty. The synthesis showed that, in clinical terms, balance trainings are a convenient complement to conventional physiotherapy care to produce an impact on balance and functionality after knee replacement. If outcomes such as improvement in pain, knee range of movement, or patient quality of life are to be promoted, it would be advisable to explore alternative proposals specifically targeting these goals. Further research is needed to confirm or discard the current evidence ultimately, predominantly in terms of the effects on the hips and those yielded by preoperative interventions. Copyright © 2018 Elsevier B.V. All rights reserved.

Fungicidal activity of essential oils of Cinnamomum zeylanicum (L.) and Syzygium aromaticum (L.) Merr et L.M. Perry against crown rot and anthracnose pathogens isolated from banana.

PubMed

Ranasinghe, L; Jayawardena, B; Abeywickrama, K

2002-01-01

To develop a post-harvest treatment system against post-harvest fungal pathogens of banana using natural products. Colletotrichum musae was isolated and identified as the causative agent responsible for anthracnose peel blemishes while three fungi, namely Lasiodiplodia theobromae, C. musae and Fusarium proliferatum, were identified as causative agents responsible for crown rot. During the liquid bioassay, cinnamon [Cinnamomum zeylanicum (L.)] leaf, bark and clove [Syzygium aromaticum (L.)] oils were tested against the anthracnose and crown rot pathogens. The test oils were fungistatic and fungicidal against the test pathogens within a range of 0.03-0.11% (v/v). Cinnamon and clove essential oils could be used as antifungal agents to manage post harvest fungal diseases of banana. Cinnamon and clove essential oil could be used as alternative post-harvest treatments on banana. Banana treated with essential oil is chemically safe and acceptable to consumers. Benomyl (Benlate), which is currently used to manage fungal pathogens, can cause adverse health effects and could be replaced with volatile essential oils.

Ribosomal Protein Rps26 Influences 80S Ribosome Assembly in Saccharomyces cerevisiae

PubMed Central

Belyy, Alexander; Levanova, Nadezhda; Tabakova, Irina; Rospert, Sabine

2016-01-01

ABSTRACT The eukaryotic ribosome consists of a small (40S) and a large (60S) subunit. Rps26 is one of the essential ribosomal proteins of the 40S subunit and is encoded by two almost identical genes, RPS26a and RPS26b. Previous studies demonstrated that Rps26 interacts with the 5′ untranslated region of mRNA via the eukaryote-specific 62-YXXPKXYXK-70 (Y62–K70) motif. Those observations suggested that this peptide within Rps26 might play an important and specific role during translation initiation. By using alanine-scanning mutagenesis and engineered strains of the yeast Saccharomyces cerevisiae, we found that single amino acid substitutions within the Y62–K70 motif of Rps26 did not affect the in vivo function of the protein. In contrast, complete deletion of the Y62–K70 segment was lethal. The simultaneous replacement of five conserved residues within the Y62–K70 segment by alanines resulted in growth defects under stress conditions and produced distinct changes in polysome profiles that were indicative of the accumulation of free 60S subunits. Human Rps26 (Rps26-Hs), which displays significant homology with yeast Rps26, supported the growth of an S. cerevisiae Δrps26a Δrps26b strain. However, the Δrps26a Δrps26b double deletion strain expressing Rps26-Hs displayed substantial growth defects and an altered ratio of 40S/60S ribosomal subunits. The combined data strongly suggest that the eukaryote-specific motif within Rps26 does not play a specific role in translation initiation. Rather, the data indicate that Rps26 as a whole is necessary for proper assembly of the 40S subunit and the 80S ribosome in yeast. IMPORTANCE Rps26 is an essential protein of the eukaryotic small ribosomal subunit. Previous experiments demonstrated an interaction between the eukaryote-specific Y62–K70 segment of Rps26 and the 5′ untranslated region of mRNA. The data suggested a specific role of the Y62–K70 motif during translation initiation. Here, we report that single-site substitutions within the Y62–K70 peptide did not affect the growth of engineered yeast strains, arguing against its having a critical role during translation initiation via specific interactions with the 5′ untranslated region of mRNA molecules. Only the simultaneous replacement of five conserved residues within the Y62–K70 fragment or the replacement of the yeast protein with the human homolog resulted in growth defects and caused significant changes in polysome profiles. The results expand our knowledge of ribosomal protein function and suggest a role of Rps26 during ribosome assembly in yeast. PMID:27303706

[Rational therapy of patients with essential hypertension and abdominal obesity with concomitant subclinical hypothyroidism].

PubMed

Pligovka, V M

2014-11-01

It was determined the characteristics of lipid status of patients with essential hypertension, abdominal obesity with concomitant subclinical hypothyroidism--mostly increased levels of total and LDL cholesterol. In assessing the effectiveness of statin therapy in combination with levothyroxine replacement therapy compared with statin monotherapy, combination therapy showed the best result in terms of achievement of target levels of both total cholesterol and LDL. The obtained results allow us to recommend the use of combination therapy for patients with hypertension, abdominal obesity with concomitant subclinical hypothyroidism in order to achieve the target values of LDL and thus to reduce the cardiovascular risk of these patients.

Threonine-4 of mammalian RNA polymerase II CTD is targeted by Polo-like kinase 3 and required for transcriptional elongation

PubMed Central

Hintermair, Corinna; Heidemann, Martin; Koch, Frederic; Descostes, Nicolas; Gut, Marta; Gut, Ivo; Fenouil, Romain; Ferrier, Pierre; Flatley, Andrew; Kremmer, Elisabeth; Chapman, Rob D; Andrau, Jean-Christophe; Eick, Dirk

2012-01-01

Eukaryotic RNA polymerase II (Pol II) has evolved an array of heptad repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the carboxy-terminal domain (CTD) of the large subunit (Rpb1). Differential phosphorylation of Ser2, Ser5, and Ser7 in the 5′ and 3′ regions of genes coordinates the binding of transcription and RNA processing factors to the initiating and elongating polymerase complexes. Here, we report phosphorylation of Thr4 by Polo-like kinase 3 in mammalian cells. ChIPseq analyses indicate an increase of Thr4-P levels in the 3′ region of genes occurring subsequently to an increase of Ser2-P levels. A Thr4/Ala mutant of Pol II displays a lethal phenotype. This mutant reveals a global defect in RNA elongation, while initiation is largely unaffected. Since Thr4 replacement mutants are viable in yeast we conclude that this amino acid has evolved an essential function(s) in the CTD of Pol II for gene transcription in mammalian cells. PMID:22549466

Probing transcription-specific outputs of β-catenin in vivo

PubMed Central

Valenta, Tomas; Gay, Max; Steiner, Sarah; Draganova, Kalina; Zemke, Martina; Hoffmans, Raymond; Cinelli, Paolo; Aguet, Michel; Sommer, Lukas; Basler, Konrad

2011-01-01

β-Catenin, apart from playing a cell-adhesive role, is a key nuclear effector of Wnt signaling. Based on activity assays in Drosophila, we generated mouse strains where the endogenous β-catenin protein is replaced by mutant forms, which retain the cell adhesion function but lack either or both of the N- and the C-terminal transcriptional outputs. The C-terminal activity is essential for mesoderm formation and proper gastrulation, whereas N-terminal outputs are required later during embryonic development. By combining the double-mutant β-catenin with a conditional null allele and a Wnt1-Cre driver, we probed the role of Wnt/β-catenin signaling in dorsal neural tube development. While loss of β-catenin protein in the neural tube results in severe cell adhesion defects, the morphology of cells and tissues expressing the double-mutant form is normal. Surprisingly, Wnt/β-catenin signaling activity only moderately regulates cell proliferation, but is crucial for maintaining neural progenitor identity and for neuronal differentiation in the dorsal spinal cord. Our model animals thus allow dissecting signaling and structural functions of β-catenin in vivo and provide the first genetic tool to generate cells and tissues that entirely and exclusively lack canonical Wnt pathway activity. PMID:22190459

Down-Regulating γ-Gliadins in Bread Wheat Leads to Non-Specific Increases in Other Gluten Proteins and Has No Major Effect on Dough Gluten Strength

PubMed Central

Pistón, Fernando; Gil-Humanes, Javier; Rodríguez-Quijano, Marta; Barro, Francisco

2011-01-01

Background Gliadins are a major component of gluten proteins but their role in the mixing of dough is not well understood because their contribution to wheat flour functional properties are not as clear as for the glutenin fraction. Methodology/Principal Findings Transgenic lines of bread wheat with γ-gliadins suppressed by RNAi are reported. The effects on the gluten protein composition and on technological properties of flour were analyzed by RP-HPLC, by sodium dodecyl sulfate sedimentation (SDSS) test and by Mixograph analysis. The silencing of γ-gliadins by RNAi in wheat lines results in an increase in content of all other gluten proteins. Despite the gluten proteins compensation, in silico analysis of amino acid content showed no difference in the γ-gliadins silenced lines. The SDSS test and Mixograph parameters were slightly affected by the suppression of γ-gliadins. Conclusions/Significance Therefore, it is concluded that γ-gliadins do not have an essential functional contribution to the bread-making quality of wheat dough, and their role can be replaced by other gluten proteins. PMID:21935456

Shp2–Mitogen-Activated Protein Kinase Signaling Drives Proliferation during Zebrafish Embryo Caudal Fin Fold Regeneration

PubMed Central

Hale, Alexander James

2017-01-01

ABSTRACT Regeneration of the zebrafish caudal fin following amputation occurs through wound healing, followed by formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. We show that ptpn11a−/− ptpn11b−/− zebrafish embryos, lacking functional Shp2, fail to regenerate their caudal fin folds. Rescue experiments indicated that Shp2a has a functional signaling role, requiring its catalytic activity and SH2 domains but not the two C-terminal tyrosine phosphorylation sites. Surprisingly, expression of Shp2a variants with increased and reduced catalytic activity, respectively, rescued caudal fin fold regeneration to similar extents. Expression of mmp9 and junbb, indicative of formation of the wound epidermis and distal blastema, respectively, suggested that these processes occurred in ptpn11a−/− ptpn11b−/− zebrafish embryos. However, cell proliferation and MAPK phosphorylation were reduced. Pharmacological inhibition of MEK1 in wild-type zebrafish embryos phenocopied loss of Shp2. Our results suggest an essential role for Shp2a–mitogen-activated protein kinase (MAPK) signaling in promoting cell proliferation during zebrafish embryo caudal fin fold regeneration. PMID:29203641

The ecdysis triggering hormone system is essential for successful moulting of a major hemimetabolous pest insect, Schistocerca gregaria

PubMed Central

Lenaerts, Cynthia; Cools, Dorien; Verdonck, Rik; Verbakel, Lina; Vanden Broeck, Jozef; Marchal, Elisabeth

2017-01-01

Insects are enclosed in a rigid exoskeleton, providing protection from desiccation and mechanical injury. To allow growth, this armour needs to be replaced regularly in a process called moulting. Moulting entails the production of a new exoskeleton and shedding of the old one and is induced by a pulse in ecdysteroids, which activates a peptide-mediated signalling cascade. In Holometabola, ecdysis triggering hormone (ETH) is the key factor in this cascade. Very little functional information is available in Hemimetabola, which display a different kind of development characterized by gradual changes. This paper reports on the identification of the ETH precursor and the pharmacological and functional characterisation of the ETH receptor in a hemimetabolous pest species, the desert locust, Schistocerca gregaria. Activation of SchgrETHR by SchgrETH results in an increase of both Ca2+ and cyclic AMP, suggesting that SchgrETHR displays dual coupling properties in an in vitro cell-based assay. Using qRT-PCR, an in-depth profiling study of SchgrETH and SchgrETHR transcripts was performed. Silencing of SchgrETH and SchgrETHR resulted in lethality at the expected time of ecdysis, thereby showing their crucial role in moulting. PMID:28417966

[French guidelines on electroencephalogram].

PubMed

André-Obadia, N; Sauleau, P; Cheliout-Heraut, F; Convers, P; Debs, R; Eisermann, M; Gavaret, M; Isnard, J; Jung, J; Kaminska, A; Kubis, N; Lemesle, M; Maillard, L; Mazzola, L; Michel, V; Montavont, A; N'Guyen, S; Navarro, V; Parain, D; Perin, B; Rosenberg, S D; Sediri, H; Soufflet, C; Szurhaj, W; Taussig, D; Touzery-de Villepin, A; Vercueil, L; Lamblin, M D

2014-12-01

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows control tests when follow-up is necessary, even at the patient's bedside. Faced with the advances in knowledge, techniques and indications, the Société de Neurophysiologie Clinique de Langue Française (SNCLF) and the Ligue Française Contre l'Épilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and underline proposals for writing an EEG report. Some questions could not be answered by the review of the literature; in those cases, an expert advice was given by the working and reading groups in addition to the guidelines. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Class-Switch Recombination in the Absence of the IgH 3' Regulatory Region.

PubMed

Kim, Ahrom; Han, Li; Santiago, Gabriel E; Verdun, Ramiro E; Yu, Kefei

2016-10-01

The ∼28-kb 3' regulatory region (3'RR), which is located at the most distal 3' region of the Ig H chain locus, has multiple regulatory functions that control IgH expression, class-switch recombination (CSR), and somatic hypermutation. In this article, we report that deletion of the entire 3'RR in a mouse B cell line that is capable of robust cytokine-dependent CSR to IgA results in reduced, but not abolished, CSR. These data suggest that 3'RR is not absolutely required for CSR and, thus, is not essential for targeting activation-induced cytidine deaminase to S regions, as was suggested. Moreover, replacing 3'RR with a DNA fragment including only its four DNase I hypersensitive sites (lacking the large spacer regions) restores CSR to a level equivalent to or even higher than in wild-type cells, suggesting that the four hypersensitive sites contain most of the CSR-promoting functions of 3'RR. Stimulated cells express abundant germline transcripts, with the presence or absence of 3'RR, providing evidence that 3'RR has a role in promoting CSR that is unique from enhancing S region transcription. Copyright © 2016 by The American Association of Immunologists, Inc.

An Enhanced Lightweight Anonymous Authentication Scheme for a Scalable Localization Roaming Service in Wireless Sensor Networks.

PubMed

Chung, Youngseok; Choi, Seokjin; Lee, Youngsook; Park, Namje; Won, Dongho

2016-10-07

More security concerns and complicated requirements arise in wireless sensor networks than in wired networks, due to the vulnerability caused by their openness. To address this vulnerability, anonymous authentication is an essential security mechanism for preserving privacy and providing security. Over recent years, various anonymous authentication schemes have been proposed. Most of them reveal both strengths and weaknesses in terms of security and efficiency. Recently, Farash et al. proposed a lightweight anonymous authentication scheme in ubiquitous networks, which remedies the security faults of previous schemes. However, their scheme still suffers from certain weaknesses. In this paper, we prove that Farash et al.'s scheme fails to provide anonymity, authentication, or password replacement. In addition, we propose an enhanced scheme that provides efficiency, as well as anonymity and security. Considering the limited capability of sensor nodes, we utilize only low-cost functions, such as one-way hash functions and bit-wise exclusive-OR operations. The security and lightness of the proposed scheme mean that it can be applied to roaming service in localized domains of wireless sensor networks, to provide anonymous authentication of sensor nodes.

Bioinks for 3D bioprinting: an overview.

PubMed

Gungor-Ozkerim, P Selcan; Inci, Ilyas; Zhang, Yu Shrike; Khademhosseini, Ali; Dokmeci, Mehmet Remzi

2018-05-01

Bioprinting is an emerging technology with various applications in making functional tissue constructs to replace injured or diseased tissues. It is a relatively new approach that provides high reproducibility and precise control over the fabricated constructs in an automated manner, potentially enabling high-throughput production. During the bioprinting process, a solution of a biomaterial or a mixture of several biomaterials in the hydrogel form, usually encapsulating the desired cell types, termed the bioink, is used for creating tissue constructs. This bioink can be cross-linked or stabilized during or immediately after bioprinting to generate the final shape, structure, and architecture of the designed construct. Bioinks may be made from natural or synthetic biomaterials alone, or a combination of the two as hybrid materials. In certain cases, cell aggregates without any additional biomaterials can also be adopted for use as a bioink for bioprinting processes. An ideal bioink should possess proper mechanical, rheological, and biological properties of the target tissues, which are essential to ensure correct functionality of the bioprinted tissues and organs. In this review, we provide an in-depth discussion of the different bioinks currently employed for bioprinting, and outline some future perspectives in their further development.

An Enhanced Lightweight Anonymous Authentication Scheme for a Scalable Localization Roaming Service in Wireless Sensor Networks

PubMed Central

Chung, Youngseok; Choi, Seokjin; Lee, Youngsook; Park, Namje; Won, Dongho

2016-01-01

More security concerns and complicated requirements arise in wireless sensor networks than in wired networks, due to the vulnerability caused by their openness. To address this vulnerability, anonymous authentication is an essential security mechanism for preserving privacy and providing security. Over recent years, various anonymous authentication schemes have been proposed. Most of them reveal both strengths and weaknesses in terms of security and efficiency. Recently, Farash et al. proposed a lightweight anonymous authentication scheme in ubiquitous networks, which remedies the security faults of previous schemes. However, their scheme still suffers from certain weaknesses. In this paper, we prove that Farash et al.’s scheme fails to provide anonymity, authentication, or password replacement. In addition, we propose an enhanced scheme that provides efficiency, as well as anonymity and security. Considering the limited capability of sensor nodes, we utilize only low-cost functions, such as one-way hash functions and bit-wise exclusive-OR operations. The security and lightness of the proposed scheme mean that it can be applied to roaming service in localized domains of wireless sensor networks, to provide anonymous authentication of sensor nodes. PMID:27739417

Integration of plastids with their hosts: Lessons learned from dinoflagellates

PubMed Central

Dorrell, Richard G.; Howe, Christopher J.

2015-01-01

After their endosymbiotic acquisition, plastids become intimately connected with the biology of their host. For example, genes essential for plastid function may be relocated from the genomes of plastids to the host nucleus, and pathways may evolve within the host to support the plastid. In this review, we consider the different degrees of integration observed in dinoflagellates and their associated plastids, which have been acquired through multiple different endosymbiotic events. Most dinoflagellate species possess plastids that contain the pigment peridinin and show extreme reduction and integration with the host biology. In some species, these plastids have been replaced through serial endosymbiosis with plastids derived from a different phylogenetic derivation, of which some have become intimately connected with the biology of the host whereas others have not. We discuss in particular the evolution of the fucoxanthin-containing dinoflagellates, which have adapted pathways retained from the ancestral peridinin plastid symbiosis for transcript processing in their current, serially acquired plastids. Finally, we consider why such a diversity of different degrees of integration between host and plastid is observed in different dinoflagellates and how dinoflagellates may thus inform our broader understanding of plastid evolution and function. PMID:25995366

Integration of plastids with their hosts: Lessons learned from dinoflagellates.

PubMed

Dorrell, Richard G; Howe, Christopher J

2015-08-18

After their endosymbiotic acquisition, plastids become intimately connected with the biology of their host. For example, genes essential for plastid function may be relocated from the genomes of plastids to the host nucleus, and pathways may evolve within the host to support the plastid. In this review, we consider the different degrees of integration observed in dinoflagellates and their associated plastids, which have been acquired through multiple different endosymbiotic events. Most dinoflagellate species possess plastids that contain the pigment peridinin and show extreme reduction and integration with the host biology. In some species, these plastids have been replaced through serial endosymbiosis with plastids derived from a different phylogenetic derivation, of which some have become intimately connected with the biology of the host whereas others have not. We discuss in particular the evolution of the fucoxanthin-containing dinoflagellates, which have adapted pathways retained from the ancestral peridinin plastid symbiosis for transcript processing in their current, serially acquired plastids. Finally, we consider why such a diversity of different degrees of integration between host and plastid is observed in different dinoflagellates and how dinoflagellates may thus inform our broader understanding of plastid evolution and function.

Emerging trends in nutraceutical applications of whey protein and its derivatives.

PubMed

Patel, Seema

2015-11-01

The looming food insecurity demands the utilization of nutrient-rich residues from food industries as value-added products. Whey, a dairy industry waste has been characterized to be excellent nourishment with an array of bioactive components. Whey protein comprises 20 % of total milk protein and it is rich in branched and essential amino acids, functional peptides, antioxidants and immunoglobulins. It confers benefits against a wide range of metabolic diseases such as cardiovascular complications, hypertension, obesity, diabetes, cancer and phenylketonuria. The protein has been validated to boost recovery from resistance exercise-injuries, stimulate gut physiology and protect skin against detrimental radiations. Apart from health invigoration, whey protein has proved its suitability as fat replacer and emulsifier. Further, its edible and antimicrobial packaging potential renders its highly desirable in food as well as pharmaceutical sectors. Considering the enormous nutraceutical worth of whey protein, this review emphasizes on its established and emerging biological roles. Present and future scopes in food processing and dietary supplement formulation are discussed. Associated hurdles are identified and how technical advancement might augment its applications are explored. This review is expected to provide valuable insight on whey protein-fortified functional foods, associated technical hurdles and scopes of improvement.

Incorporation of an aldehyde function in oligonucleotides.

PubMed

Tilquin, J M; Dechamps, M; Sonveaux, E

2001-01-01

A nucleotide-like phosphoramidite building block that has the nucleic base replaced by the tert-butyldimethylsilyl-protected styrene glycol was synthesized. After the automatic synthesis of an oligonucleotide incorporating this synthon, the benzaldehyde function was generated by fluoride deprotection and oxidation by sodium periodate. In a similar manner, an oligonucleotide where a nucleic base was replaced by the (CH2)8CH=O chain was synthesized and conjugated with biotin derivatives.

Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease

PubMed Central

Fervenza, Fernando C; Torra, Roser; Warnock, David G

2008-01-01

Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of α-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human α-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed. PMID:19707461

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

NASA Astrophysics Data System (ADS)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

Pharmacokinetic analysis of cloxacillin loss in children undergoing major surgery with massive bleeding.

PubMed Central

Levy, M; Egersegi, P; Strong, A; Tessoro, A; Spino, M; Bannatyne, R; Fear, D; Posnick, J C; Koren, G

1990-01-01

To determine the magnitude of cloxacillin loss during surgical procedures involving significant blood loss and high fluid replacement, we compared the pharmacokinetics of cloxacillin in children during craniomaxillofacial surgery with the disposition of the drug in healthy young adult volunteers with intact circulation. Blood loss during craniofacial operations may exceed blood volume, in some cases by as much as three times. Hemodynamic replacement with electrolyte solutions and blood products, which do not contain the drug, further dilute cloxacillin concentrations. In the patients that we studied, mean drug loss was estimated at 71%. Cloxacillin concentrations in serum fell below the lower range of the MIC for Staphylococcus aureus during significant portions of the surgical procedures. Thus, the traditional dosing of cloxacillin during prolonged operations with massive blood loss is inadequate. A more frequent dosing interval or priming of all replacement fluids with the drug may be required to maintain therapeutic levels. Our findings suggest that massive blood loss is likely to have a dramatic effect on the level of any drug with a small distribution volume. If such a drug is essential to the patient's well-being (e.g., antibiotics, antiarrhythmics, and anticonvulsants), it must be replaced promptly. PMID:2393274

Resolution of non-alcoholic steatohepatitis after growth hormone replacement in a pediatric liver transplant patient with panhypopituitarism.

PubMed

Gilliland, Thomas; Dufour, Sylvie; Shulman, Gerald I; Petersen, Kitt Falk; Emre, Sukru H

2016-12-01

NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency. Refractory NAFLD in panhypopituitarism may be amenable to GH replacement. Here, we report a pediatric case of NASH secondary to panhypopituitarism from craniopharyngioma, which recurred by 11 months after LDLT. Despite low-dose GH replacement, the patient remained GH deficient. Pubertal dosed GH therapy led to rapid and complete resolution of hepatic steatosis, which we tracked using serial 1 H MRS. Pediatric patients with NASH cirrhosis secondary to panhypopituitarism can be good candidates for liver transplantation, but hormone deficiencies predispose to recurrence after transplant. High-dose GH replacement should be considered in pediatric patients with GH deficiency and recurrent disease. A multidisciplinary team approach is essential for successful outcomes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Conformation of the N-terminal ectodomain elicits different effects on DUOX function: a potential impact on congenital hypothyroidism caused by a H2O2 production defect.

PubMed

Louzada, Ruy Andrade; Corre, Raphaël; Ameziane-El-Hassani, Rabii; Hecht, Fabio; Cazarin de Menezes, Juliana; Buffet, Camille; Carvalho, Denise P; Dupuy, Corinne

2018-05-30

Dual oxidases (DUOX1 and DUOX2) were initially identified as H2O2 sources involved in thyroid hormone synthesis. Congenital hypothyroidism (CH) resulting essentially from inactivating mutations of the DUOX2 gene highlighted that DUOX2 is the major H2O2 provider to thyroperoxidase. The role of DUOX1 in the thyroid remains unknown. A recent study suggests that it could compensate for the DUOX2 deficiency in CH. Both DUOX and their maturation factors DUOXA form a stable complex at the cell surface, which is fundamental for their respective enzymatic activity. Recently, intra- and intermolecular disulfide bridges were identified that are essential for the structure and the function of the complex DUOX2-DUOXA2. In this study, we investigated the involvement of cysteine residues conserved in DUOX1 towards the formation of disulfide bridges, which could be important for the function of the DUOX1-DUOXA1 complex. To analyse the role of these cysteine residues in both the targeting and function of dual oxidase, different human DUOX1 mutants were constructed, where the cysteine residues were replaced with glycine. The effect of these mutations on the cell surface expression and H2O2-generating activity of the complex DUOX1-DUOXA1 was analysed. Mutations of two cysteine residues (cys-118 and cys-1165), involved in the formation of the intramolecular disulfide bridge between the N-terminal ectodomain and one of the extracellular loops, mildly altered the function and the targeting of DUOX1, while this bridge is crucial for DUOX2 function. Unlike DUOXA2, with respect to DUOX2, the stability of the maturation factor DUOXA1 is not dependent on the oxidative folding of DUOX1. Only mutation of cys-579 induced a strong alteration of both targeting and function of the oxidase by preventing the covalent interaction between DUOX1 and DUOXA1 Conclusion: It is an intermolecular disulfide bridge and not an intramolecular disulfide bridge that is important in both the trafficking and H2O2-generating activity of the DUOX1-DUOXA1 complex.

The Principals' Perspective of Sustainable Partnerships in New York City's New School Initiative

ERIC Educational Resources Information Center

Klein, Robert

2010-01-01

New York City's Mayor Michael Bloomberg and school's Chancellor Joel Klein made the creation of new schools an essential part of their Children First reform policy. In September 2002, 13 high schools opened replacing the lowest performing large high schools throughout the City. As of 2010, more than 400 new district and charter schools are in…

Decadal-Scale Reduction in Forest Net Ecosystem Production Following Insect Defoliation Contrasts with Short-Term Impacts of Prescribed Fires

Treesearch

Kenneth L. Clark; Heidi J. Renninger; Nicholas Skowronski; Michael Gallagher; Karina V.R.  Schäfer

2018-01-01

Understanding processes underlying forest carbon dynamics is essential for accurately predicting the outcomes of non-stand-replacing disturbance in intermediate-age forests. We quantified net ecosystem production (NEP), aboveground net primary production (ANPP), and the dynamics of major carbon (C) pools before and during the decade following invasive insect...

State Policies and Practices in Behavior Supports for Persons with Intellectual and Developmental Disabilities in the United States: A National Survey

ERIC Educational Resources Information Center

Rotholz, David A.; Moseley, Charles R.; Carlson, Kinsey B.

2013-01-01

Providing effective behavioral supports to decrease challenging behavior and replace it with appropriate alternative skills is essential to meeting the needs of many individuals with intellectual and developmental disabilities (IDD). It is also necessary for fulfilling the requirements of Medicaid-funded individual support plans and is important…

Lasers in automobile production

NASA Astrophysics Data System (ADS)

Pizzi, P.

There is a trend in mechanical equipment to replace complicated mechanical components with electronics, especially microprocessors, laser technology represents an important new tool. The effects of laser technology can be seen in production systems concerned with cutting, welding, heat treatment, and the alloying of mechanical components. Applications in the automobile industry today are not very widespread and are concerned essentially with welding and cutting.

Intestinal irony: how probiotic bacteria outcompete bad bugs.

PubMed

Weiss, Guenter

2013-07-17

In this issue of Cell Host & Microbe, Deriu et al. present a mechanistic explanation underlying the benefits of certain probiotic bacteria. Intestinal bacteria compete for the essential nutrient iron, leading to replacement of pathogenic Salmonella by the probiotic Escherichia coli Nissle, which is better equipped with iron acquisition systems, and resolution of infectious colitis. Copyright © 2013 Elsevier Inc. All rights reserved.

77 FR 30988 - Endangered and Threatened Wildlife and Plants; Designation of Critical Habitat for the Cumberland...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... revised totals. The data in this table replaces the data provided in table 3 of the proposed rule at 76 FR... that we designate or revise critical habitat based upon the best scientific data available, after... educational benefits of mapping areas containing essential features that aid in the recovery of the listed...

Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli

PubMed Central

Napolitano, Michael G.; Landon, Matthieu; Gregg, Christopher J.; Lajoie, Marc J.; Govindarajan, Lakshmi; Mosberg, Joshua A.; Kuznetsov, Gleb; Goodman, Daniel B.; Vargas-Rodriguez, Oscar; Isaacs, Farren J.; Söll, Dieter; Church, George M.

2016-01-01

The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes. We readily replaced 110 AGR codons with the synonymous CGU codons, but the remaining 13 “recalcitrant” AGRs required diversification to identify viable alternatives. Successful replacement codons tended to conserve local ribosomal binding site-like motifs and local mRNA secondary structure, sometimes at the expense of amino acid identity. Based on these observations, we empirically defined metrics for a multidimensional “safe replacement zone” (SRZ) within which alternative codons are more likely to be viable. To evaluate synonymous and nonsynonymous alternatives to essential AGRs further, we implemented a CRISPR/Cas9-based method to deplete a diversified population of a wild-type allele, allowing us to evaluate exhaustively the fitness impact of all 64 codon alternatives. Using this method, we confirmed the relevance of the SRZ by tracking codon fitness over time in 14 different genes, finding that codons that fall outside the SRZ are rapidly depleted from a growing population. Our unbiased and systematic strategy for identifying unpredicted design flaws in synthetic genomes and for elucidating rules governing codon choice will be crucial for designing genomes exhibiting radically altered genetic codes. PMID:27601680

The crystal structure of TrxA(CACA): Insights into the formation of a [2Fe-2S] iron-sulfur cluster in an Escherichia coli thioredoxin mutant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collet, Jean-Francois; Peisach, Daniel; Bardwell, James C.A.

2010-07-13

Escherichia coli thioredoxin is a small monomeric protein that reduces disulfide bonds in cytoplasmic proteins. Two cysteine residues present in a conserved CGPC motif are essential for this activity. Recently, we identified mutations of this motif that changed thioredoxin into a homodimer bridged by a [2Fe-2S] iron-sulfur cluster. When exported to the periplasm, these thioredoxin mutants could restore disulfide bond formation in strains lacking the entire periplasmic oxidative pathway. Essential for the assembly of the iron-sulfur was an additional cysteine that replaced the proline at position three of the CGPC motif. We solved the crystalline structure at 2.3 {angstrom} formore » one of these variants, TrxA(CACA). The mutant protein crystallized as a dimer in which the iron-sulfur cluster is replaced by two intermolecular disulfide bonds. The catalytic site, which forms the dimer interface, crystallized in two different conformations. In one of them, the replacement of the CGPC motif by CACA has a dramatic effect on the structure and causes the unraveling of an extended {alpha}-helix. In both conformations, the second cysteine residue of the CACA motif is surface-exposed, which contrasts with wildtype thioredoxin where the second cysteine of the CXXC motif is buried. This exposure of a pair of vicinal cysteine residues apparently allows thioredoxin to acquire an iron-sulfur cofactor at its active site, and thus a new activity and mechanism of action.« less

Theoretical Impact of Replacing Whole Cow's Milk by Young-Child Formula on Nutrient Intakes of UK Young Children: Results of a Simulation Study.

PubMed

Eussen, Simone R B M; Pean, Josephine; Olivier, Leanne; Delaere, Fabien; Lluch, Anne

2015-01-01

Research into the role of young-child formulae (YCF) in a child's diet is limited and there is no consensual recommendation on its use. We evaluated the theoretical nutritional impact of replacing the existing practice of consuming cow's milk by YCF. From the UK Diet and Nutrition Survey of Infants and Young Children, whole cow's milk consumers, aged 12-18 months (n = 591) were selected for simulation scenarios. In Scenario 1, we tested the replacement of all whole cow's milk (434 ± 187 ml/day) by a matching volume of YCF, and in Scenario 2, all whole cow's milk was replaced by the on-pack recommended daily intake of 300 ml. Nutrient intakes before and after simulation scenarios were compared and evaluated against nutrient recommendations. Intakes of protein and saturated fatty acids were significantly decreased, whereas essential fatty acid intakes were increased. The prevalence of nutrient inadequacy before simulation was 95.2% for vitamin D and 53.8% for iron. After simulation, inadequacy decreased to 4.9% (Scenario 1) and 0% (Scenario 2) for vitamin D and to 2.7% (Scenario 1) and 1.1% (Scenario 2) for iron. Replacement of habitual cow's milk intake by a matching volume or 300 ml of YCF may lead to nutritional intakes more in line with recommendations in young children. © 2015 S. Karger AG, Basel.

Competition, coinfection and strain replacement in models of Bordetella pertussis.

PubMed

Nicoli, Emily J; Ayabina, Diepreye; Trotter, Caroline L; Turner, Katherine M E; Colijn, Caroline

2015-08-01

Pertussis, or whooping cough, is an important respiratory infection causing considerable infant mortality worldwide. Recently, incidence has risen in countries with strong vaccine programmes and there are concerns about antigenic shift resulting in vaccine evasion. Interactions between pertussis and non-vaccine-preventable strains will play an important role in the evolution and population dynamics of pertussis. In particular, if we are to understand the role strain replacement plays in vaccinated settings, it will be essential to understand how strains or variants of pertussis interact. Here we explore under what conditions we would expect strain replacement to be of concern in pertussis. We develop a dynamic transmission model that allows for coinfection between Bordetella pertussis (the main causative agent of pertussis) and a strain or variant unaffected by the vaccine. We incorporate both neutrality (in the sense of ecological/population genetic neutrality) and immunity into the model, leaving the specificity of the immune response flexible. We find that strain replacement may be considerable when immunity is non-specific. This is in contrast to previous findings where neutrality was not considered. We conclude that the extent to which models reflect ecological neutrality can have a large impact on conclusions regarding strain replacement. This will likely have onward consequences for estimates of vaccine efficacy and cost-effectiveness. Copyright © 2015 Elsevier Inc. All rights reserved.

A meta-analysis of functional group responses to forest recovery outside of the tropics.

PubMed

Spake, Rebecca; Ezard, Thomas H G; Martin, Philip A; Newton, Adrian C; Doncaster, C Patrick

2015-12-01

Both active and passive forest restoration schemes are used in degraded landscapes across the world to enhance biodiversity and ecosystem service provision. Restoration is increasingly also being implemented in biodiversity offset schemes as compensation for loss of natural habitat to anthropogenic development. This has raised concerns about the value of replacing old-growth forest with plantations, motivating research on biodiversity recovery as forest stands age. Functional diversity is now advocated as a key metric for restoration success, yet it has received little analytical attention to date. We conducted a meta-analysis of 90 studies that measured differences in species richness for functional groups of fungi, lichens, and beetles between old-growth control and planted or secondary treatment forests in temperate, boreal, and Mediterranean regions. We identified functional-group-specific relationships in the response of species richness to stand age after forest disturbance. Ectomycorrhizal fungi averaged 90 years for recovery to old-growth values (between 45 years and unrecoverable at 95% prediction limits), and epiphytic lichens took 180 years to reach 90% of old-growth values (between 140 years and never for recovery to old-growth values at 95% prediction limits). Non-saproxylic beetle richness, in contrast, decreased as stand age of broadleaved forests increased. The slow recovery by some functional groups essential to ecosystem functioning makes old-growth forest an effectively irreplaceable biodiversity resource that should be exempt from biodiversity offsetting initiatives. © 2015 The Authors Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

SCIENCE BRIEF: REHABILITATION OF WASTEWATER COLLECTION SYSTEMS

EPA Science Inventory

System rehabilitation is the application of infrastructure repair, renewal and replacement technologies in order to reinstate functionality of a wastewater system or subsystem. The proper balance of the repair, renewal, and replacement depends on the condition assessment, the lif...

Structural requirements for thioester bond formation in human complement component C3. Reassessment of the role of thioester bond integrity on the conformation of C3.

PubMed

Isaac, L; Isenman, D E

1992-05-15

A unique thioester bond, formed between the side chains of neighboring C and Q residues, is present in complement components C3 and C4 and the protease inhibitor alpha 2-macroglobulin. This structure is essential for mediating covalent attachment to target acceptors and also for maintaining these proteins in their native conformation. An examination of the residues in the immediate vicinity of the C and Q reveals a very high degree of sequence similarity among the three proteins which crosses species barriers. The following is the sequence flanking the thioester residues in C3, the highly conserved amino acids being underlined and the the thioester-forming residues being indicated by italics: 1005V-T-P-S-G-C-G-E-Q-N-M-I-G-M-T-P-T1021. Through a site-directed mutagenesis and cDNA expression approach, we have examined the importance of the conserved amino acids in the formation, stability, and function of the thioester bond in C3. The behavior of the mutants fell into three categories. The potential loss in peptide backbone flexibility by the replacement of G1009 by A or S was permissive to thioester formation and function as was replacement of M1015 by the still fairly bulky residue F. In contrast, replacement of M1015 by A resulted in an alpha-chain which was highly unstable toward proteolytic degradation. The third category, which included mutant molecules P1007G, P1020G, E1012Q, and Q1013N, displayed an unusual phenotype in which both the autolytic fragmentation and the hemolytic activity characteristics of thioester-intact molecules were absent. However, like their wildtype counterpart, these molecules retained the ability to be cleaved by C3 convertase (C4b2a), a conformation-dependent property that is normally lost in the conversion of native C3 to thioester-hydrolyzed C3(H2O). Since an identical functional profile was obtained when the thioester was deliberately prevented from forming in the mutant C1010A, we conclude that if a stable thioester fails to form during biosynthesis, at least parts of the mature protein can adopt a more native-like conformation than is the case when the thioester is first formed and then hydrolyzed in the mature protein. In view of these new findings, the interpretation of the previously observed correlation between the loss of thioester integrity and the adoption of a C3b-like conformation must be reassessed.

Long-term auxological and pubertal outcome of patients with hereditary insulin-like growth factor-I deficiency (Laron and growth hormone-gene deletion syndrome) treated with recombinant human insulin-like growth factor-I.

PubMed

Messina, M F; Arrigo, T; Valenzise, M; Ghizzoni, L; Caruso-Nicoletti, M; Zucchini, S; Chiabotto, P; Crisafulli, G; Zirilli, G; De Luca, F

2011-04-01

GH-IGF-I axis is mainly involved in the complex process of somatic growth but emerging evidence suggests that it also influences hypothalamic-pituitary-gonadal (HPG) function. We report some data regarding long-term auxological and pubertal outcome of five female patients with hereditary forms of GH-IGF-I deficiency (Laron and GH-gene deletion syndrome) and a mean age of 23.4±5.3 yr (range 19-32). All the patients received recombinant human IGF-I (rhIGF-I, Pharmacia and Upjohn, Stockholm, Sweden, and rhIGF-I, Genentech, San Francisco, CA, USA) from a mean age of 8.6 yr (range 3.2-14.2) up to the final height. Final height was very disappointing (≤ -5.0 SD scores) and lower than target height in all the patients. Pubertal onset was delayed in most of them but menarche occurred spontaneously in all the patients. Median age at menarche was 15.1 yr. Menstrual cycles were regular for several years. Median duration of gynecological follow- up was 8.3 yr with the longest span of 17.2 yr. We can assert that GH-IGF-I axis has an essential role in promoting linear growth in humans and its physiological action cannot be replaced by pharmacological treatment in most patients with hereditary forms of IGF-I insufficiency as demonstrated by their subnormal final height. Our clinical observations can also support an essential role of IGF-I in genitalia growth but not in the function of HPG axis as demonstrated by the maintenance of regular menstrual cycles in the presence of subnormal levels of IGF-I after treatment discontinuation.

Spermidine promotes Bacillus subtilis biofilm formation by activating expression of the matrix regulator slrR.

PubMed

Hobley, Laura; Li, Bin; Wood, Jennifer L; Kim, Sok Ho; Naidoo, Jacinth; Ferreira, Ana Sofia; Khomutov, Maxim; Khomutov, Alexey; Stanley-Wall, Nicola R; Michael, Anthony J

2017-07-21

Ubiquitous polyamine spermidine is not required for normal planktonic growth of Bacillus subtilis but is essential for robust biofilm formation. However, the structural features of spermidine required for B. subtilis biofilm formation are unknown and so are the molecular mechanisms of spermidine-stimulated biofilm development. We report here that in a spermidine-deficient B. subtilis mutant, the structural analogue norspermidine, but not homospermidine, restored biofilm formation. Intracellular biosynthesis of another spermidine analogue, aminopropylcadaverine, from exogenously supplied homoagmatine also restored biofilm formation. The differential ability of C-methylated spermidine analogues to functionally replace spermidine in biofilm formation indicated that the aminopropyl moiety of spermidine is more sensitive to C -methylation, which it is essential for biofilm formation, but that the length and symmetry of the molecule is not critical. Transcriptomic analysis of a spermidine-depleted B. subtilis speD mutant uncovered a nitrogen-, methionine-, and S -adenosylmethionine-sufficiency response, resulting in repression of gene expression related to purine catabolism, methionine and S -adenosylmethionine biosynthesis and methionine salvage, and signs of altered membrane status. Consistent with the spermidine requirement in biofilm formation, single-cell analysis of this mutant indicated reduced expression of the operons for production of the exopolysaccharide and TasA protein biofilm matrix components and SinR antagonist slrR Deletion of sinR or ectopic expression of slrR in the spermidine-deficient Δ speD background restored biofilm formation, indicating that spermidine is required for expression of the biofilm regulator slrR Our results indicate that spermidine functions in biofilm development by activating transcription of the biofilm matrix exopolysaccharide and TasA operons through the regulator slrR . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The pnk/pnl gene (ORF 86) of Autographa californica nucleopolyhedrovirus is a non-essential, immediate early gene.

PubMed

Durantel, D; Croizier, L; Ayres, M D; Croizier, G; Possee, R D; López-Ferber, M

1998-03-01

Autographa californica nucleopolyhedrovirus (AcMNPV) ORF 86, located within the HindIII C fragment, potentially encodes a protein which shares sequence similarity with two T4 bacteriophage gene products, RNA ligase and polynucleotide kinase. This AcMNPV gene has been designated pnk/pnl but has yet to be assigned a function in virus replication. It has been classified as an immediate early virus gene, since the promoter was active in uninfected insect cells and mRNA transcripts were detectable from 4 to 48 h post-infection and in the presence of cycloheximide or aphidicolin in virus-infected cells. The extremities of the transcript have been mapped by primer extension and 3' RACE-PCR to positions -18 from the translational start codon and +15 downstream of the stop codon. The function of pnk/pnl was investigated by producing a recombinant virus (Acdel86lacZ) with the coding region replaced with that of lacZ. This virus replicated normally in Spodoptera frugiperda (Sf 21) cells, indicating that pnk/pnl is not essential for propagation in these cells. Virus protein production in Acdel86lacZ-infected Sf 21 cells also appeared to be unaffected, with normal synthesis of the IE-1, GP64, VP39 and polyhedrin proteins. Shut-down of host protein synthesis was not abolished in recombinant infection. When other baculovirus genomes were examined for the presence of pnk/pnl by restriction enzyme digestion and PCR, a deletion was found in AcMNPV 1.2, Galleria mellonella NPV (GmMNPV) and Bombyx mori NPV (BmNPV), suggesting that in many isolates this gene has either never been acquired or has been lost during genome evolution. This is one of the first baculovirus immediate early genes that appears to be nonessential for virus survival.

Functional Analysis of Vaccinia Virus B5R Protein: Essential Role in Virus Envelopment Is Independent of a Large Portion of the Extracellular Domain

PubMed Central

Herrera, Elizabeth; del Mar Lorenzo, María; Blasco, Rafael; Isaacs, Stuart N.

1998-01-01

Vaccinia virus has two forms of infectious virions: the intracellular mature virus and the extracellular enveloped virus (EEV). EEV is critical for cell-to-cell and long-range spread of the virus. The B5R open reading frame (ORF) encodes a membrane protein that is essential for EEV formation. Deletion of the B5R ORF results in a dramatic reduction of EEV, and as a consequence, the virus produces small plaques in vitro and is highly attenuated in vivo. The extracellular portion of B5R is composed mainly of four domains that are similar to the short consensus repeats (SCRs) present in complement regulatory proteins. To determine the contribution of these putative SCR domains to EEV formation, we constructed recombinant vaccinia viruses that replaced the wild-type B5R gene with a mutated gene encoding a B5R protein lacking the SCRs. The resulting recombinant viruses produced large plaques, indicating efficient cell-to-cell spread in vitro, and gradient centrifugation of supernatants from infected cells confirmed that EEV was formed. In contrast, phalloidin staining of infected cells showed that the virus lacking the SCR domains was deficient in the induction of thick actin bundles. Thus, the highly conserved SCR domains present in the extracellular portion of the B5R protein are dispensable for EEV formation. This indicates that the B5R protein is a key viral protein with multiple functions in the process of virus envelopment and release. In addition, given the similarity of the extracellular domain to complement control proteins, the B5R protein may be involved in viral evasion from host immune responses. PMID:9420227

In Search of Mechanisms Associated with Mesenchymal Stem Cell-Based Therapies for Acute Kidney Injury

PubMed Central

de Almeida, Danilo C; Donizetti-Oliveira, Cassiano; Barbosa-Costa, Priscilla; Origassa, Clarice ST; Câmara, Niels OS

2013-01-01

Acute kidney injury (AKI) is classically described as a rapid loss of kidney function. AKI affects more than 15% of all hospital admissions and is associated with elevated mortality rates. Although many advances have occurred, intermittent or continuous renal replacement therapies are still considered the best options for reversing mild and severe AKI syndrome. For this reason, it is essential that innovative and effective therapies, without side effects and complications, be developed to treat AKI and the end-stages of renal disease. Mesenchymal stem cell (MSC) based therapies have numerous advantages in helping to repair inflamed and damaged tissues and are being considered as a new alternative for treating kidney injuries. Numerous experimental models have shown that MSCs can act via differentiation-independent mechanisms to help renal recovery. Essentially, MSCs can secrete a pool of cytokines, growth factors and chemokines, express enzymes, interact via cell-to-cell contacts and release bioagents such as microvesicles to orchestrate renal protection. In this review, we propose seven distinct properties of MSCs which explain how renoprotection may be conferred: 1) anti-inflammatory; 2) pro-angiogenic; 3) stimulation of endogenous progenitor cells; 4) anti-apoptotic; 5) anti-fibrotic; 6) anti-oxidant; and 7) promotion of cellular reprogramming. In this context, these mechanisms, either individually or synergically, could induce renal protection and functional recovery. This review summarises the most important effects and benefits associated with MSC-based therapies in experimental renal disease models and attempts to clarify the mechanisms behind the MSC-related renoprotection. MSCs may prove to be an effective, innovative and affordable treatment for moderate and severe AKI. However, more studies need to be performed to provide a more comprehensive global understanding of MSC-related therapies and to ensure their safety for future clinical applications. PMID:24353358

Characterization of human pre-elafin mutants: full antipeptidase activity is essential to preserve lung tissue integrity in experimental emphysema.

PubMed

Doucet, Alain; Bouchard, Dominique; Janelle, Marie France; Bellemare, Audrey; Gagné, Stéphane; Tremblay, Guy M; Bourbonnais, Yves

2007-08-01

Pre-elafin is a tight-binding inhibitor of neutrophil elastase and myeloblastin; two enzymes thought to contribute to tissue damage in lung emphysema. Previous studies have established that pre-elafin is also an effective anti-inflammatory molecule. However, it is not clear whether both functions are linked to the antipeptidase activity of pre-elafin. As a first step toward elucidating the structure/function relationship of this protein, we describe here the construction and characterization of pre-elafin variants with attenuated antipeptidase potential. In these mutants, the P1' methionine residue of the inhibitory loop is replaced by either a lysine (pre-elafinM25K) or a glycine (pre-elafinM25G) residue. Both mutated variants are stable and display biochemical properties undistinguishable from WT (wild-type) pre-elafin. However, compared with WT pre-elafin, their inhibitory constants are increased by one to four orders of magnitude toward neutrophil elastase, myeloblastin and pancreatic elastase, depending on the variants and enzymes tested. As suggested by molecular modelling, this attenuated inhibitory potential correlates with decreased van der Waals interactions between the variants and the enzymes S1' subsite. In elastase-induced experimental emphysema in mice, only WT pre-elafin protected against tissue destruction, as assessed by the relative airspace enlargement measured using lung histopathological sections. Pre-elafin and both mutants prevented transient neutrophil alveolitis. However, even the modestly affected pre-elafinM25K mutant, as assayed in vitro with small synthetic substrates, was a poor inhibitor of the neutrophil elastase and myeloblastin elastolytic activity measured with insoluble elastin. We therefore conclude that full antipeptidase activity of pre-elafin is essential to protect against lung tissue lesions in this experimental model.

Ethnicity and patient's perception of risk in joint replacement surgery.

PubMed

Gandhi, Rajiv; Razak, Fahad; Davey, J Roderick; Mahomed, Nizar N

2008-08-01

Despite much evidence showing racial disparities in the use of surgical procedures, it is unknown whether ethnicity affects perception of surgical risk. We surveyed 1609 patients undergoing primary hip or knee replacement surgery. Relevant covariates including demographic data, body mass index (BMI), sex, comorbidities, education, and ethnicity were recorded. Pain and joint functional status were assessed at baseline and at 1-year followup with the Western Ontario McMaster University Osteoarthritis Index (WOMAC) pain and function scores. Risk perception was assessed with 3 survey questions. Non-European patients had greater functional disability and pain prior to surgery and demonstrated significantly greater perception of risk than European patients (p < 0.001). Independent of other covariates, non-European ethnicity was an independent predictor of a greater perception of risk (p < 0.05). Patient ethnicity is an important factor to consider in understanding a patient's perception of risk in joint replacement surgery.

Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model

PubMed Central

Ono, Mitsuaki; Oshima, Masamitsu; Ogawa, Miho; Sonoyama, Wataru; Hara, Emilio Satoshi; Oida, Yasutaka; Shinkawa, Shigehiko; Nakajima, Ryu; Mine, Atsushi; Hayano, Satoru; Fukumoto, Satoshi; Kasugai, Shohei; Yamaguchi, Akira; Tsuji, Takashi; Kuboki, Takuo

2017-01-01

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine. PMID:28300208

Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output.

PubMed

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1998-01-01

To determine whether prolonged (chronic) resuscitation has any beneficial effects on cardiac output and hepatocellular function after trauma-hemorrhage and acute fluid replacement. Acute fluid resuscitation after trauma-hemorrhage restores but does not maintain the depressed hepatocellular function and cardiac output. Male Sprague-Dawley rats underwent a 5-cm laparotomy (i.e., trauma was induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer's lactate (RL). The animals were acutely resuscitated with RL using 4 times the volume of maximum bleed-out over 60 minutes, followed by chronic resuscitation of 0, 5, or 10 mL/kg/hr RL for 20 hours. Hepatocellular function was determined by an in vivo indocyanine green clearance technique. Hepatic microvascular blood flow was assessed by laser Doppler flowmetry. Plasma levels of interleukin-6 (IL-6) were determined by bioassay. Chronic resuscitation with 5 mL/kg/hr RL, but not with 0 or 10 mL/kg/hr RL, restored cardiac output, hepatocellular function, and hepatic microvascular blood flow at 20 hours after hemorrhage. The regimen above also reduced plasma IL-6 levels. Because chronic resuscitation with 5 mL/kg/hr RL after trauma-hemorrhage and acute fluid replacement restored hepatocellular function and hepatic microvascular blood flow and decreased plasma levels of IL-6, we propose that chronic fluid resuscitation in addition to acute fluid replacement should be routinely used in experimental studies of trauma-hemorrhage.

Tooth replacement and putative odontogenic stem cell niches in pharyngeal dentition of medaka (Oryzias latipes).

PubMed

Abduweli, Dawud; Baba, Otto; Tabata, Makoto J; Higuchi, Kazunori; Mitani, Hiroshi; Takano, Yoshiro

2014-04-01

The small-sized teleost fish medaka, Oryzias latipes, has as many as 1000 pharyngeal teeth undergoing continuous replacement. In this study, we sought to identify the tooth-forming units and determine its replacement cycles, and further localize odontogenic stem cell niches in the pharyngeal dentition of medaka to gain insights into the mechanisms whereby continuous tooth replacement is maintained. Three-dimensional reconstruction of pharyngeal epithelium and sequential fluorochrome labeling of pharyngeal bones and teeth indicated that the individual functional teeth and their successional teeth were organized in families, each comprising up to five generations of teeth and successional tooth germs, and that the replacement cycle of functional teeth was approximately 4 weeks. BrdU label/chase experiments confirmed the existence of clusters of label-retaining epithelial cells at the posterior end of each tooth family where the expression of pluripotency marker Sox2 was confirmed by in situ hybridization. Label-retaining cells were also identified in the mesoderm immediately adjacent to the posterior end of each tooth family. These data suggest the importance of existence of slow-cycling dental epithelial cells and Sox2 expressions at the posterior end of each tooth family to maintain continuous tooth formation and replacement in the pharyngeal dentition of medaka.

Molecular and Mutational Analysis of a Gelsolin-Family Member Encoded by the Flightless I Gene of Drosophila Melanogaster

PubMed Central

de-Couet, H. G.; Fong, KSK.; Weeds, A. G.; McLaughlin, P. J.; Miklos, GLG.

1995-01-01

The flightless locus of Drosophila melanogaster has been analyzed at the genetic, molecular, ultrastructural and comparative crystallographic levels. The gene encodes a single transcript encoding a protein consisting of a leucine-rich amino terminal half and a carboxyterminal half with high sequence similarity to gelsolin. We determined the genomic sequence of the flightless landscape, the breakpoints of four chromosomal rearrangements, and the molecular lesions in two lethal and two viable alleles of the gene. The two alleles that lead to flight muscle abnormalities encode mutant proteins exhibiting amino acid replacements within the S1-like domain of their gelsolin-like region. Furthermore, the deduced intronexon structure of the D. melanogaster gene has been compared with that of the Caenorhabditis elegans homologue. Furthermore, the sequence similarities of the flightless protein with gelsolin allow it to be evaluated in the context of the published crystallographic structure of the S1 domain of gelsolin. Amino acids considered essential for the structural integrity of the core are found to be highly conserved in the predicted flightless protein. Some of the residues considered essential for actin and calcium binding in gelsolin S1 and villin V1 are also well conserved. These data are discussed in light of the phenotypic characteristics of the mutants and the putative functions of the protein. PMID:8582612

Studies of Inhibitory Mechanisms of Propeptide-Like Cysteine Protease Inhibitors

PubMed Central

Nga, Bui T. T.; Takeshita, Yuki; Yamamoto, Misa; Yamamoto, Yoshimi

2014-01-01

Mouse cytotoxic T-lymphocyte antigen-2α (CTLA-2α), Drosophila CTLA-2-like protein (crammer), and Bombyx cysteine protease inhibitor (BCPI) belong to a novel family of cysteine protease inhibitors (I29). Their inhibitory mechanisms were studied comparatively. CTLA-2α contains a cysteine residue (C75), which is essential for its inhibitory potency. The CTLA-2α monomer was converted to a disulfide-bonded dimer in vitro and in vivo. The dimer was fully inhibitory, but the monomer, which possessed a free thiol residue, was not. A disulfide-bonded CTLA-2α/cathepsin L complex was isolated, and a cathepsin L subunit with a molecular weight of 24,000 was identified as the interactive enzyme protein. Crammer also contains a cysteine residue (C72). Both dimeric and monomeric forms of crammer were inhibitory. A crammer mutant with Cys72 to alanine (C72A) was fully inhibitory, while the replacement of Gly73 with alanine (G73A) caused a significant loss in inhibitory potency, which suggests a different inhibition mechanism from CTLA-2α. BCPI does not contain cysteine residue. C-terminal region (L77-R80) of BCPI was essential for its inhibitory potency. CTLA-2α was inhibitory in the acidic pH condition but stabilized cathepsin L under neutral pH conditions. The different inhibition mechanisms and functional considerations of these inhibitors are discussed. PMID:25045530

Hip Abductor Strengthening Improves Physical Function Following Total Knee Replacement: One-Year Follow-Up of a Randomized Pilot Study.

PubMed

Harikesavan, Karvannan; Chakravarty, Raj D; Maiya, Arun G; Hegde, Sanjay P; Y Shivanna, Shivakumar

2017-01-01

Total knee replacement (TKR) is the commonest surgical procedure for patients with severe pain and impaired physical function following end stage knee osteoarthritis. The hip abductors are well renowned in stabilization of the trunk and hip during walking, maintaining the lower limb position, and transferring the forces from the lower limbs to the pelvis. To assess the efficacy of hip abductor strengthening exercise on functional outcome using performance based outcome measures following total knee replacement. An observer blinded randomized pilot trial design was conducted at Manipal hospital, Bangalore, India. Participants designated for elective TKR were randomized to experimental group hip abductor strengthening along with standard rehabilitation (n=10) or control group standard rehabilitation alone (n=10). Participants followed for one year to assess physical function using performance based outcomes, such as timed up and go test, single leg stance test, six minute walk test, knee extensor strength and hip abductor strength. Eighteen participants with a mean age of 63.1 ± 5.5 years (8 Males and 10 Females) completed the study. Improvement in hip abduction strength, single leg stand test was superior in hip abductor strengthening group at 3 months and 1 year when compared to standard rehabilitation alone. Hip abductor strengthening showed superior improvements in single leg stance test and six minute walk test. Hip abductor strengthening exercises has the potential to improve physical function following total knee replacement.

Hip Abductor Strengthening Improves Physical Function Following Total Knee Replacement: One-Year Follow-Up of a Randomized Pilot Study

PubMed Central

Harikesavan, Karvannan; Chakravarty, Raj D.; Maiya, Arun G; Hegde, Sanjay P.; Y. Shivanna, Shivakumar

2017-01-01

Background: Total knee replacement (TKR) is the commonest surgical procedure for patients with severe pain and impaired physical function following end stage knee osteoarthritis. The hip abductors are well renowned in stabilization of the trunk and hip during walking, maintaining the lower limb position, and transferring the forces from the lower limbs to the pelvis. Objective: To assess the efficacy of hip abductor strengthening exercise on functional outcome using performance based outcome measures following total knee replacement. Methods: An observer blinded randomized pilot trial design was conducted at Manipal hospital, Bangalore, India. Participants designated for elective TKR were randomized to experimental group hip abductor strengthening along with standard rehabilitation (n=10) or control group standard rehabilitation alone (n=10). Participants followed for one year to assess physical function using performance based outcomes, such as timed up and go test, single leg stance test, six minute walk test, knee extensor strength and hip abductor strength. Result: Eighteen participants with a mean age of 63.1 ± 5.5 years (8 Males and 10 Females) completed the study. Improvement in hip abduction strength, single leg stand test was superior in hip abductor strengthening group at 3 months and 1 year when compared to standard rehabilitation alone. Conclusion: Hip abductor strengthening showed superior improvements in single leg stance test and six minute walk test. Hip abductor strengthening exercises has the potential to improve physical function following total knee replacement. PMID:28567148

Transverse joint configuration development and testing for a modular bridge deck replacement system.

DOT National Transportation Integrated Search

2011-03-01

According to the 2009 Report Card for Americas Infrastructure, one in four of the nations bridges are listed as : structurally deficient of functionally obsolete, establishing a dire need for new and innovative repair and replacement : techniqu...

Physiotherapy rehabilitation after total knee or hip replacement: an evidence-based analysis.

PubMed

2005-01-01

The objective of this health technology policy analysis was to determine, where, how, and when physiotherapy services are best delivered to optimize functional outcomes for patients after they undergo primary (first-time) total hip replacement or total knee replacement, and to determine the Ontario-specific economic impact of the best delivery strategy. The objectives of the systematic review were as follows: To determine the effectiveness of inpatient physiotherapy after discharge from an acute care hospital compared with outpatient physiotherapy delivered in either a clinic-based or home-based setting for primary total joint replacement patientsTo determine the effectiveness of outpatient physiotherapy delivered by a physiotherapist in either a clinic-based or home-based setting in addition to a home exercise program compared with a home exercise program alone for primary total joint replacement patientsTo determine the effectiveness of preoperative exercise for people who are scheduled to receive primary total knee or hip replacement surgery Total hip replacements and total knee replacements are among the most commonly performed surgical procedures in Ontario. Physiotherapy rehabilitation after first-time total hip or knee replacement surgery is accepted as the standard and essential treatment. The aim is to maximize a person's functionality and independence and minimize complications such as hip dislocation (for hip replacements), wound infection, deep vein thrombosis, and pulmonary embolism. THE THERAPY: The physiotherapy rehabilitation routine has 4 components: therapeutic exercise, transfer training, gait training, and instruction in the activities of daily living. Physiotherapy rehabilitation for people who have had total joint replacement surgery varies in where, how, and when it is delivered. In Ontario, after discharge from an acute care hospital, people who have had a primary total knee or hip replacement may receive inpatient or outpatient physiotherapy. Inpatient physiotherapy is delivered in a rehabilitation hospital or specialized hospital unit. Outpatient physiotherapy is done either in an outpatient clinic (clinic-based) or in the person's home (home-based). Home-based physiotherapy may include practising an exercise program at home with or without supplemental support from a physiotherapist. Finally, physiotherapy rehabilitation may be administered at several points after surgery, including immediately postoperatively (within the first 5 days) and in the early recovery period (within the first 3 months) after discharge. There is a growing interest in whether physiotherapy should start before surgery. A variety of practises exist, and evidence regarding the optimal pre- and post-acute course of rehabilitation to obtain the best outcomes is needed. The Medical Advisory Secretariat used its standard search strategy, which included searching the databases of Ovid MEDLINE, CINHAL, EMBASE, Cochrane Database of Systematic Reviews, and PEDro from 1995 to 2005. English-language articles including systematic reviews, randomized controlled trials (RCTs), non-RCTs, and studies with a sample size of greater than 10 patients were included. Studies had to include patients undergoing primary total hip or total knee replacement, aged 18 years of age or older, and they had to have investigated one of the following comparisons: inpatient rehabilitation versus outpatient (clinic- or home-based therapy) rehabilitation, land-based post-acute care physiotherapy delivered by a physiotherapist compared with patient self-administered exercise and a land-based exercise program before surgery. The primary outcome was postoperative physical functioning. Secondary outcomes included the patient's assessment of therapeutic effect (overall improvement), perceived pain intensity, health services utilization, treatment side effects, and adverse events The quality of the methods of the included studies was assessed using the criteria outlined in the Cochrane Musculoskeletal Injuries Group Quality Assessment Tool. After this, a summary of the biases threatening study validity was determined. Four methodological biases were considered: selection bias, performance bias, attrition bias, and detection bias. A meta-analysis was conducted when adequate data were available from 2 or more studies and where there was no statistical or clinical heterogeneity among studies. The GRADE system was used to summarize the overall quality of evidence. The search yielded 422 citations; of these, 12 were included in the review including 10 primary studies (9 RCTs, 1 non-RCT) and 2 systematic reviews. The Medical Advisory Secretariat review included 2 primary studies (N = 334) that examined the effectiveness of an inpatient physiotherapy rehabilitation program compared with an outpatient home-based physiotherapy program on functional outcomes after total knee or hip replacement surgery. One study, available only as an abstract, found no difference in functional outcome at 1 year after surgery (TKR or THR) between the treatments. The other study was an observational study that found that patients who are younger than 71 years of age on average, who do not live alone, and who do not have comorbid illnesses recover adequate function with outpatient home-based physiotherapy. However results were only measured up to 3 months after surgery, and the outcome measure they used is not considered the best one for physical functioning. Three primary studies (N = 360) were reviewed that tested the effectiveness of outpatient home-based or clinic-based physiotherapy in addition to a self-administered home exercise program, compared with a self-administered exercise program only or in addition to using another therapy (phone calls or continuous passive movement), on postoperative physical functioning after primary TKR surgery. Two of the studies reported no difference in change from baseline in flexion range of motion between those patients receiving outpatient or home-based physiotherapy and doing a home exercise program compared with patients who did a home exercise program only with or without continuous passive movement. The other study reported no difference in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores between patients receiving clinic-based physiotherapy and practising a home exercise program and those who received monitoring phone calls and did a home exercise program after TKR surgery. The Medical Advisory Secretariat reviewed two systematic reviews evaluating the effects of preoperative exercise on postoperative physical functioning. One concluded that preoperative exercise is not effective in improving functional recovery or pain after TKR and any effects after THR could not be adequately determined. The other concluded that there was inconclusive evidence to determine the benefits of preoperative exercise on functional recovery after TKR. Because 2 primary studies were added to the published literature since the publication of these systematic reviews the Medical Advisory Secretariat revisited the question of effectiveness of a preoperative exercise program for patients scheduled for TKR ad THR surgery. The Medical Advisory Secretariat also reviewed 3 primary studies (N = 184) that tested the effectiveness of preoperative exercise beginning 4-6 weeks before surgery on postoperative outcomes after primary TKR surgery. All 3 studies reported negative findings with regard to the effectiveness of preoperative exercise to improve physical functioning after TKR surgery. However, 2 failed to show an effect of the preoperative exercise program before surgery in those patients receiving preoperative exercise. The third study did not measure functional outcome immediately before surgery in the preoperative exercise treatment group; therefore the study's authors could not document an effect of the preoperative exercise program before surgery. Regarding health services utilization, 2 of the studies did not find significant differences in either the length of the acute care hospital stay or the inpatient rehabilitation care setting between patients treated with a preoperative exercise program and those not treated. The third study did not measure health services utilization. These results must be interpreted within the limitations and the biases of each study. Negative results do not necessarily support a lack of treatment effect but may be attributed to a type II statistical error. Finally, the Medical Advisory Secretariat reviewed 2 primary studies (N = 136) that examined the effectiveness of preoperative exercise on postoperative functional outcomes after primary THR surgery. One study did not support the effectiveness of an exercise program beginning 8 weeks before surgery. However, results from the other did support the effectiveness of an exercise program 8 weeks before primary THR surgery on pain and functional outcomes 1 week before and 3 weeks after surgery. Based on the evidence, the Medical Advisory Secretariat reached the following conclusions with respect to physiotherapy rehabilitation and physical functioning 1 year after primary TKR or THR surgery: There is high-quality evidence from 1 large RCT to support the use of home-based physiotherapy instead of inpatient physiotherapy after primary THR or TKR surgery.There is low-to-moderate quality evidence from 1 large RCT to support the conclusion that receiving a monitoring phone call from a physiotherapist and practising home exercises is comparable to receiving clinic-based physiotherapy and practising home exercises for people who have had primary TKR surgery. However, results may not be generalizable to those who have had THR surgery.There is moderate evidence to suggest that an exercise program beginning 4 to 6 weeks before primary TKR surgery is not effective. (ABSTRACT TRUNCATED)

Evaluation of novel micronized encapsulated essential oil-containing phosphate and lactate blends for growth inhibition of Listeria monocytogenes and Salmonella on poultry bologna, pork ham, and roast beef ready-to-eat deli loaves.

PubMed

Casco, G; Taylor, T M; Alvarado, C

2015-04-01

Essential oils and their constituents are reported to possess potent antimicrobial activity, but their use in food processing is limited because of low solubility in aqueous systems and volatilization during processing. Two proprietary noncommercial essential oil-containing phosphate blends were evaluated for antimicrobial activity against Salmonella enterica cocktail (SC)-and Listeria monocytogenes (Lm)-inoculated deli meat products made from pork, poultry, or beef. Four treatments were tested on restructured cured pork ham, emulsified chicken bologna, and restructured beef loaf: nonencapsulated essential oil with phosphate version 1 at 0.45% of final batch (EOV145; chicken and pork, or EEOV245 beef), micronized encapsulated essential oil with phosphate version 2 at 0.60% of final batch (EEOV260), a 2.0% potassium lactate (PL) control, and a negative control (CN) with no applied antimicrobial agent. Compared with the CN, none of the antimicrobial agents (EEOV260, EOV145, PL) successfully limited Lm or SC growth to <2.0 log cycles over 49 days or 35 days of refrigerated storage, respectively. The PL and EEOV260-treated ham loaves did show Lm growth limiting ability of up to 1 log cycle by days 35 and 42. On formed roast beef, the EEOV260 was able to extend the lag phase and inhibited the growth of Lm in the same manner as the PL. For SC-treated samples, the following effects were observed: in poultry bologna treated with EEOV260, a lag-phase extension was observed through 35 days of storage compared with the other samples. For pork deli loaves, the EEOV260 inhibited growth of SC at days 21 and 28 to the same level of efficacy as PL (0.5 log cycle). In roast beef samples, on day 35, the SC growth was inhibited ca. 0.5 log CFU/g by EEOV260 when compared with the CN. In conclusion the EEOV260 can function to replace PL to limit Salmonella and Lm growth in ready-to-eat deli products. Further testing is needed to ensure consumer acceptability.

Three-dimensional structure of E. Coli purine nucleoside phosphorylase at 0.99 Å resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timofeev, V. I., E-mail: tostars@mail.ru; Abramchik, Yu. A., E-mail: ugama@yandex.ru; Zhukhlistova, N. E., E-mail: inna@ns.crys.ras.ru

2016-03-15

Purine nucleoside phosphorylases (PNPs) catalyze the reversible phosphorolysis of nucleosides and are key enzymes involved in nucleotide metabolism. They are essential for normal cell function and can catalyze the transglycosylation. Crystals of E. coli PNP were grown in microgravity by the capillary counterdiffusion method through a gel layer. The three-dimensional structure of the enzyme was determined by the molecular-replacement method at 0.99 Å resolution. The structural features are considered, and the structure of E. coli PNP is compared with the structures of the free enzyme and its complexes with purine base derivatives established earlier. A comparison of the environment ofmore » the purine base in the complex of PNP with formycin A and of the pyrimidine base in the complex of uridine phosphorylase with thymidine revealed the main structural features of the base-binding sites. Coordinates of the atomic model determined with high accuracy were deposited in the Protein Data Bank (PDB-ID: 4RJ2).« less

Optimization of a Bioluminescence Resonance Energy Transfer-Based Assay for Screening of Trypanosoma cruzi Protein/Protein Interaction Inhibitors.

PubMed

Mild, Jesica G; Fernandez, Lucia R; Gayet, Odile; Iovanna, Juan; Dusetti, Nelson; Edreira, Martin M

2018-05-01

Chagas disease, a parasitic disease caused by Trypanosoma cruzi, is a major public health burden in poor rural populations of Central and South America and a serious emerging threat outside the endemic region, since the number of infections in non-endemic countries continues to rise. In order to develop more efficient anti-trypanosomal treatments to replace the outdated therapies, new molecular targets need to be explored and new drugs discovered. Trypanosoma cruzi has distinctive structural and functional characteristics with respect to the human host. These exclusive features could emerge as interesting drug targets. In this work, essential and differential protein-protein interactions for the parasite, including the ribosomal P proteins and proteins involved in mRNA processing, were evaluated in a bioluminescence resonance energy transfer-based assay as a starting point for drug screening. Suitable conditions to consider using this simple and robust methodology to screening compounds and natural extracts able to inhibit protein-protein interactions were set in living cells and lysates.

MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.

PubMed

Posavec Marjanović, Melanija; Hurtado-Bagès, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Hélène; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M; Ahel, Ivan; Ladurner, Andreas G; Yanes, Oscar; Bouvet, Philippe; Suelves, Mònica; Teperino, Raffaele; Pospisilik, J Andrew; Buschbeck, Marcus

2017-11-01

Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD + -derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD + consumption. The resultant accumulation of the NAD + precursor NMN allows for maintenance of mitochondrial NAD + pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD + consumption and establishing a buffer of NAD + precursors in differentiated cells.

Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

PubMed Central

Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R.

2016-01-01

Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients. PMID:27725636

Dampened STING-Dependent Interferon Activation in Bats.

PubMed

Xie, Jiazheng; Li, Yang; Shen, Xurui; Goh, Geraldine; Zhu, Yan; Cui, Jie; Wang, Lin-Fa; Shi, Zheng-Li; Zhou, Peng

2018-03-14

Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir. Copyright © 2018 Elsevier Inc. All rights reserved.

Phosphorylated ubiquitin chain is the genuine Parkin receptor

PubMed Central

Okatsu, Kei; Koyano, Fumika; Kimura, Mayumi; Kosako, Hidetaka; Saeki, Yasushi

2015-01-01

PINK1 selectively recruits Parkin to depolarized mitochondria for quarantine and removal of damaged mitochondria via ubiquitylation. Dysfunction of this process predisposes development of familial recessive Parkinson’s disease. Although various models for the recruitment process have been proposed, none of them adequately explain the accumulated data, and thus the molecular basis for PINK1 recruitment of Parkin remains to be fully elucidated. In this study, we show that a linear ubiquitin chain of phosphomimetic tetra-ubiquitin(S65D) recruits Parkin to energized mitochondria in the absence of PINK1, whereas a wild-type tetra-ubiquitin chain does not. Under more physiologically relevant conditions, a lysosomal phosphorylated polyubiquitin chain recruited phosphomimetic Parkin to the lysosome. A cellular ubiquitin replacement system confirmed that ubiquitin phosphorylation is indeed essential for Parkin translocation. Furthermore, physical interactions between phosphomimetic Parkin and phosphorylated polyubiquitin chain were detected by immunoprecipitation from cells and in vitro reconstitution using recombinant proteins. We thus propose that the phosphorylated ubiquitin chain functions as the genuine Parkin receptor for recruitment to depolarized mitochondria. PMID:25847540

cipC is important for Aspergillus fumigatus virulence.

PubMed

Canela, Heliara Maria Spina; Takami, Luciano Akira; da Silva Ferreira, Márcia Eliana

2017-02-01

Aspergillus fumigatus is the main causative agent of invasive aspergillosis, a disease that affects immunocompromised patients and has a high mortality rate. We previously observed that the transcription of a cipC-like gene was increased when A. fumigatus encountered an increased CO 2 concentration, as occurs during the infection process. CipC is a protein of unknown function that might be associated with fungal pathogenicity. In this study, the cipC gene was disrupted in A. fumigatus to evaluate its importance for fungal pathogenicity. The gene was replaced, and the germination, growth phenotype, stress responses, and virulence of the resultant mutant were assessed. Although cipC was not essential, its deletion attenuated A. fumigatus virulence in a low-dose murine infection model, suggesting the involvement of the cipC gene in the virulence of this fungus. This study is the first to disrupt the cipC gene in A. fumigatus. © 2017 APMIS. Published by John Wiley & Sons Ltd.

[Legal repercussions of Clinical Ethics Committees reports].

PubMed

Couceiro V, Azucena; Beca I, Juan Pablo

2006-04-01

Clinical Ethics Committees and Research Ethics Committees have their own specific roles. The Clinical Ethics Committee's pronouncements have an advisory function, whereas Research Ethics Committees' decisions are binding. This article analyzes the legal impact of the Clinical Ethics Committees' reports. Legal and medical reasoning share the same practical nature. Both can have several correct answers to the same situation. Clinical Ethics Committees deliberate about these alternatives and analyze the involved values. Their conclusions are non-compulsory recommendations. They do not replace nor diminish the doctor's personal responsibility. Even though the Clinical Ethics Committees' reports are not binding, they constitute a sort of "expert's opinion", expressed by qualified professionals, who assume their own professional responsibility as advisors. The members' behavior is necessarily subject to constitutional and legal regulations. When judges review the Clinical Ethics Committee's reports, they must realize that their nature is advisory, and also consider them an essential element to reduce the gap between the medical and legal fields. In this way, the problem of increasingly transforming medicine into a legal issue can be prevented.

Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES.

PubMed

Pfeiffer, Martin J; Quaranta, Roberto; Piccini, Ilaria; Fell, Jakob; Rao, Jyoti; Röpke, Albrecht; Seebohm, Guiscard; Greber, Boris

2018-01-30

Master cell fate determinants are thought to induce specific cell lineages in gastrulation by orchestrating entire gene programs. The T-box transcription factor EOMES (eomesodermin) is crucially required for the development of the heart-yet it is equally important for endoderm specification suggesting that it may act in a context-dependent manner. Here, we define an unrecognized interplay between EOMES and the WNT signaling pathway in controlling cardiac induction by using loss and gain-of-function approaches in human embryonic stem cells. Dose-dependent EOMES induction alone can fully replace a cocktail of signaling molecules otherwise essential for the specification of cardiogenic mesoderm. Highly efficient cardiomyocyte programming by EOMES mechanistically involves autocrine activation of canonical WNT signaling via the WNT3 ligand, which necessitates a shutdown of this axis at a subsequent stage. Our findings provide insights into human germ layer induction and bear biotechnological potential for the robust production of cardiomyocytes from engineered stem cells.

Recent patents on microbial proteases for the dairy industry.

PubMed

Feijoo-Siota, Lucía; Blasco, Lucía; Rodríguez-Rama, José Luis; Barros-Velázquez, Jorge; Miguel, Trinidad de; Sánchez-Pérez, Angeles; Villa, Tomás G

2014-01-01

This paper reviews the general characteristics of exo and endopeptidases of microbial origin currently used in the milk industry. It also includes recent patents developed either to potentiate the enzymatic activity or to improve the resulting milk derivatives. The main application of these proteases is in the cheese-making industry. Although this industry preferentially uses animal rennets, and in particular genetically engineered chymosins, it also utilizes milk coagulants of microbial origin. Enzymes derived from Rhizomucor miehei, Rhizomucor pusillus and Cryphonectria parasitica are currently used to replace the conventional milk-clotting enzymes. In addition, the dairy industry uses microbial endo and exoproteases for relatively new applications, such as debittering and flavor generation in cheese, accelerated cheese ripening, manufacture of protein hydrolysates with improved functional properties, and production of enzyme-modified cheeses. Lactic acid bacteria play an essential role in these processes, hence these bacteria and the proteases they produce are currently being investigated by the dairy industry and are the subject of many of their patent applications.

Bioengineered Lacrimal Gland Organ Regeneration in Vivo

PubMed Central

Hirayama, Masatoshi; Tsubota, Kazuo; Tsuji, Takashi

2015-01-01

The lacrimal gland plays an important role in maintaining a homeostatic environment for healthy ocular surfaces via tear secretion. Dry eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye disorders and causes ocular discomfort, significant visual disturbances, and a reduced quality of life. Current therapies for dry eye disease, including artificial tear eye drops, are transient and palliative. The lacrimal gland, which consists of acini, ducts, and myoepithelial cells, develops from its organ germ via reciprocal epithelial-mesenchymal interactions during embryogenesis. Lacrimal tissue stem cells have been identified for use in regenerative therapeutic approaches aimed at restoring lacrimal gland functions. Fully functional organ replacement, such as for tooth and hair follicles, has also been developed via a novel three-dimensional stem cell manipulation, designated the Organ Germ Method, as a next-generation regenerative medicine. Recently, we successfully developed fully functional bioengineered lacrimal gland replacements after transplanting a bioengineered organ germ using this method. This study represented a significant advance in potential lacrimal gland organ replacement as a novel regenerative therapy for dry eye disease. In this review, we will summarize recent progress in lacrimal regeneration research and the development of bioengineered lacrimal gland organ replacement therapy. PMID:26264034

Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

PubMed

Zappitelli, Michael; Goldstein, Stuart L; Symons, Jordan M; Somers, Michael J G; Baum, Michelle A; Brophy, Patrick D; Blowey, Douglas; Fortenberry, James D; Chua, Annabelle N; Flores, Francisco X; Benfield, Mark R; Alexander, Steven R; Askenazi, David; Hackbarth, Richard; Bunchman, Timothy E

2008-12-01

Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories. Retrospective database study. Multicenter study in pediatric critical care units. Patients with acute kidney injury (estimated glomerular filtration rate < 75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. None. Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis. One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed < 1 g/kg/day protein; 23% never attained > 1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was > 2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of > 2 g/kg/day in > or = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05). Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

Analysis and separation of residues important for the chemoattractant and antimicrobial activities of beta-defensin 3.

PubMed

Taylor, Karen; Clarke, David J; McCullough, Bryan; Chin, Wutharath; Seo, Emily; Yang, De; Oppenheim, Joost; Uhrin, Dusan; Govan, John R W; Campopiano, Dominic J; MacMillan, Derek; Barran, Perdita; Dorin, Julia R

2008-03-14

beta-Defensins are important in mammalian immunity displaying both antimicrobial and chemoattractant activities. Three canonical disulfide intramolecular bonds are believed to be dispensable for antimicrobial activity but essential for chemoattractant ability. However, here we show that HBD3 (human beta-defensin 3) alkylated with iodoactemide and devoid of any disulfide bonds is still a potent chemoattractant. Furthermore, when the canonical six cysteine residues are replaced with alanine, the peptide is no longer active as a chemoattractant. These findings are replicated by the murine ortholog Defb14. We restore the chemoattractant activity of Defb14 and HBD3 by introduction of a single cysteine in the fifth position (Cys V) of the beta-defensin six cysteine motif. In contrast, a peptide with a single cysteine at the first position (Cys I) is inactive. Moreover, a range of overlapping linear fragments of Defb14 do not act as chemoattractants, suggesting that the chemotactic activity of this peptide is not dependent solely on an epitope surrounding Cys V. Full-length peptides either with alkylated cysteine residues or with cysteine residues replaced with alanine are still strongly antimicrobial. Defb14 peptide fragments were also tested for antimicrobial activity, and peptides derived from the N-terminal region display potent antimicrobial activity. Thus, the chemoattractant and antimicrobial activities of beta-defensins can be separated, and both of these functions are independent of intramolecular disulfide bonds. These findings are important for further understanding of the mechanism of action of defensins and for therapeutic design.

Structure-activity relationships of sialogogic heptapeptides analogous to physalaemin.

PubMed

Gao, C; Abe, K

2000-05-01

The rationale behind this study was to determine in detail which amino acids in physalaemin are crucial to its sialogogue activity, with a view of synthesizing new sialogogues which might be of use in the treatment of dry mouth. With the progressive elimination of amino acids, one by one, from the C- and N-terminal regions, 126 heptapeptides were newly synthesized by the multipin peptide method, for comparison with II naturally occurring tachykinins. The C-terminal amide in position II was essential for salivation, but not the pyrolidine group or the N-terminal amino acid residues in positions I to 4. In 18 heptapeptides in which M in position II (MII) was replaced by another amino acid, one by one, none caused salivation. In 18 heptapeptides, in which L10 or G9 was replaced, three peptides caused salivation but none had significantly increased secretory activities. In 18 heptapeptides in which Y8 was replaced, four caused salivation but only one (I) had significantly increased secretory activity. In 18 heptapeptides in which F7 was replaced, only Y caused salivation but with significantly reduced secretory activity. In contrast, in 18 heptapeptides in which K6 and N5 were replaced, most caused salivation and some of them had significantly increased secretory activities. It is concluded that the sequence FYGLM-NH2 conserved in the C-terminal region of physalaemin is optimal, that amides in position II and F7 are very important for salivation, but that K6 and N5 can be replaced by some other amino acids, resulting in increased secretory activities.

Rapid battery depletion and loss of therapy due to a short circuit in bipolar DBS for essential tremor.

PubMed

Allert, Niels; Barbe, Michael Thomas; Timmermann, Lars; Coenen, Volker Arnd

2017-05-01

Technical dysfunctions have been reported reducing efficacy of deep brain stimulation (DBS). Here, we report on an essential-tremor patient in whom a short circuit in bipolar DBS resulted not only in unilateral loss of therapy but also in high current flow and thereby rapid decline of the impulse-generator battery voltage from 2.83 V a week before the event to 2.54 V, indicating the need for an impulse-generator replacement. Immediate re-programming restored therapeutic efficacy. Moreover, the reduction in current flow allowed the battery voltage to recover without immediate surgical intervention to 2.81 V a week later.

Quantifying legacies of clearcut on carbon fluxes and biomass carbon stock in northern temperate forests

Treesearch

W. Wang; J. Xiao; S. V. Ollinger; J. Chen; A. Noormets

2014-01-01

Stand-replacing disturbances including harvests have substantial impacts on forest carbon (C) fluxes and stocks. The quantification and simulation of these effects is essential for better understanding forest C dynamics and informing forest management 5 in the context of global change. We evaluated the process-based forest ecosystem model, PnET-CN, for how well and by...

Solving bezel reliability and CRT obsolescence

NASA Astrophysics Data System (ADS)

Schwartz, Richard J.; Bowen, Arlen R.; Knowles, Terry

2003-09-01

Scientific Research Corporation designed a Smart Multi-Function Color Display with Positive Pilot Feedback under the funding of an U. S. Navy Small Business Innovative Research program. The Smart Multi-Function Color Display can replace the obsolete monochrome Cathode Ray Tube display currently on the T-45C aircraft built by Boeing. The design utilizes a flat panel color Active Matrix Liquid Crystal Display and TexZec's patented Touch Thru Metal bezel technology providing both visual and biomechanical feedback to the pilot in a form, fit, and function replacement to the current T-45C display. Use of an existing color AMLCD, requires the least adaptation to fill the requirements of this application, thereby minimizing risk associated with developing a new display technology and maximizing the investment in improved user interface technology. The improved user interface uses TexZec's Touch Thru Metal technology to eliminate all of the moving parts that traditionally have limited Mean-Time-Between-Failure. The touch detection circuit consists of Commercial-Off-The-Shelf components, creating touch detection circuitry, which is simple and durable. This technology provides robust switch activation and a high level of environmental immunity, both mechanical and electrical. Replacement of all the T-45C multi-function displays with this design will improve the Mean-Time-Between-Failure and drastically reduce display life cycle costs. The design methodology described in this paper can be adapted to any new or replacement display.

Bioartificial organ support for hepatic, renal, and hematologic failure.

PubMed

Maguire, P J; Stevens, C; Humes, H D; Shander, A; Halpern, N A; Pastores, S M

2000-10-01

The current strategy to the treatment of SIRS and MODS uses a multidisciplinary approach that emphasizes supportive therapy. Herein, we have presented a futuristic approach that focuses on replacing the function of failed organs using bioartificial technology (Table 1). Bioartificial organ technology may allow the intensivist to provide physiologic organ replacement either as a bridge to transplantation or as a "time-buying" element until native organs that have become acutely dysfunctional or nonfunctional in a variety of clinical settings, can recover their function or regenerate their mass. As bioartificial organ technology matures, it is conceivable as an ultimate goal that non-immunogenic bioartificial organs would be miniaturized or redesigned and acutely placed within the intracorporeal space as replacement organs.

The Cost of Joint Replacement: Comparing Two Approaches to Evaluating Costs of Total Hip and Knee Arthroplasty.

PubMed

Palsis, John A; Brehmer, Thomas S; Pellegrini, Vincent D; Drew, Jacob M; Sachs, Barton L

2018-02-21

In an era of mandatory bundled payments for total joint replacement, accurate analysis of the cost of procedures is essential for orthopaedic surgeons and their institutions to maintain viable practices. The purpose of this study was to compare traditional accounting and time-driven activity-based costing (TDABC) methods for estimating the total costs of total hip and knee arthroplasty care cycles. We calculated the overall costs of elective primary total hip and total knee replacement care cycles at our academic medical center using traditional and TDABC accounting methods. We compared the methods with respect to the overall costs of hip and knee replacement and the costs for each major cost category. The traditional accounting method resulted in higher cost estimates. The total cost per hip replacement was $22,076 (2014 USD) using traditional accounting and was $12,957 using TDABC. The total cost per knee replacement was $29,488 using traditional accounting and was $16,981 using TDABC. With respect to cost categories, estimates using traditional accounting were greater for hip and knee replacement, respectively, by $3,432 and $5,486 for personnel, by $3,398 and $3,664 for space and equipment, and by $2,289 and $3,357 for indirect costs. Implants and consumables were derived from the actual hospital purchase price; accordingly, both methods produced equivalent results. Substantial cost differences exist between accounting methods. The focus of TDABC only on resources used directly by the patient contrasts with the allocation of all operating costs, including all indirect costs and unused capacity, with traditional accounting. We expect that the true costs of hip and knee replacement care cycles are likely somewhere between estimates derived from traditional accounting methods and TDABC. TDABC offers patient-level granular cost information that better serves in the redesign of care pathways and may lead to more strategic resource-allocation decisions to optimize actual operating margins.

How perceived feelings of "wellness" influence the decision-making of people with predialysis chronic kidney disease.

PubMed

Campbell-Crofts, Sandra; Stewart, Glenn

2018-04-01

To identify the subjective meanings attached to decisions made by people living with chronic kidney disease as they consider their transition to renal replacement therapy. Within the challenging world of chronic illness, people draw upon their temporal life experiences to help them make the best or most balanced primary healthcare decisions. Understanding the risks and benefits associated with these decisions has been an area of intense interest in health research. An exploratory qualitative descriptive design. A convenience sample of twelve people, at stages 3B to 5 of chronic kidney disease, attending two predialysis renal clinics in Sydney, Australia, consented to be interviewed. The semi-structured interviews centred on their decision-making experiences as they considered their transition to renal replacement therapy. Three themes emerged from participant narratives which have been framed into the following questions: (i) Do I need renal replacement therapy? (ii) What is the "right" renal replacement therapy for me? and (iii) When should I start renal replacement therapy? Decisions about the transition to renal replacement therapy were impacted upon by the participants' perceived feelings of wellness and the belief that renal replacement therapy would not be needed at any time in the foreseeable future. This study highlights the importance of optimising person-centred care and raises important issues for the education and management of people with chronic kidney disease in the predialysis stages of the illness. In order to facilitate the transition to renal replacement therapy, renal clinicians have a responsibility to more fully understand the patient journey during the predialysis stages of chronic kidney disease. A clearer understanding of patients' perceptions and decision-making experiences creates a space for mutual understanding. This is essential for the future development and implementation of collaborative, person-centred educational strategies and long-term renal healthcare outcomes. © 2017 John Wiley & Sons Ltd.

Semantic Factors Predict the Rate of Lexical Replacement of Content Words

PubMed Central

Vejdemo, Susanne; Hörberg, Thomas

2016-01-01

The rate of lexical replacement estimates the diachronic stability of word forms on the basis of how frequently a proto-language word is replaced or retained in its daughter languages. Lexical replacement rate has been shown to be highly related to word class and word frequency. In this paper, we argue that content words and function words behave differently with respect to lexical replacement rate, and we show that semantic factors predict the lexical replacement rate of content words. For the 167 content items in the Swadesh list, data was gathered on the features of lexical replacement rate, word class, frequency, age of acquisition, synonyms, arousal, imageability and average mutual information, either from published databases or gathered from corpora and lexica. A linear regression model shows that, in addition to frequency, synonyms, senses and imageability are significantly related to the lexical replacement rate of content words–in particular the number of synonyms that a word has. The model shows no differences in lexical replacement rate between word classes, and outperforms a model with word class and word frequency predictors only. PMID:26820737

Chimeric bovine respiratory syncytial virus with attachment and fusion glycoproteins replaced by bovine parainfluenza virus type 3 hemagglutinin-neuraminidase and fusion proteins.

PubMed

Stope, M B; Karger, A; Schmidt, U; Buchholz, U J

2001-10-01

Chimeric bovine respiratory syncytial viruses (BRSV) expressing glycoproteins of bovine parainfluenza virus type 3 (BPIV-3) instead of BRSV glycoproteins were generated from cDNA. In the BRSV antigenome cDNA, the open reading frames of the major BRSV glycoproteins, attachment protein G and fusion protein F, were replaced individually or together by those of the BPIV-3 hemagglutinin-neuraminidase (HN) and/or fusion (F) glycoproteins. Recombinant virus could not be recovered from cDNA when the BRSV F open reading frame was replaced by the BPIV-3 F open reading frame. However, cDNA recovery of the chimeric virus rBRSV-HNF, with both glycoproteins replaced simultaneously, and of the chimeric virus rBRSV-HN, with the BRSV G protein replaced by BPIV-3 HN, was successful. The replication rates of both chimeras were similar to that of standard rBRSV. Moreover, rBRSV-HNF was neutralized by antibodies specific for BPIV-3, but not by antibodies specific to BRSV, demonstrating that the BRSV glycoproteins can be functionally replaced by BPIV-3 glycoproteins. In contrast, rBRSV-HN was neutralized by BRSV-specific antisera, but not by BPIV-3 specific sera, showing that infection of rBRSV-HN is mediated by BRSV F. Hemadsorption of cells infected with rBRSV-HNF and rBRSV-HN proved that BPIV-3 HN protein expressed by rBRSV is functional. Colocalization of the BPIV-3 glycoproteins with BRSV M protein was demonstrated by confocal laser scan microscopy. Moreover, protein analysis revealed that the BPIV-3 glycoproteins were present in chimeric virions. Taken together, these data indicate that the heterologous glycoproteins were not only expressed but were incorporated into the envelope of recombinant BRSV. Thus, the envelope glycoproteins derived from a member of the Respirovirus genus can together functionally replace their homologs in a Pneumovirus background.

Engineered disc-like angle-ply structures for intervertebral disc replacement.

PubMed

Nerurkar, Nandan L; Sen, Sounok; Huang, Alice H; Elliott, Dawn M; Mauck, Robert L

2010-04-15

To develop a construction algorithm in which electrospun nanofibrous scaffolds are coupled with a biocompatible hydrogel to engineer a mesenchymal stem cell (MSC)-based disc replacement. To engineer a disc-like angle-ply structure (DAPS) that replicates the multiscale architecture of the intervertebral disc. Successful engineering of a replacement for the intervertebral disc requires replication of its mechanical function and anatomic form. Despite many attempts to engineer a replacement for ailing and degenerated discs, no prior study has replicated the multiscale hierarchical architecture of the native disc, and very few have assessed the mechanical function of formed neo-tissues. A new algorithm for the construction of a disc analogue was developed, using agarose to form a central nucleus pulposus (NP) and oriented electrospun nanofibrous scaffolds to form the anulus fibrosus region (AF). Bovine MSCs were seeded into both regions and biochemical, histologic, and mechanical maturation were evaluated with in vitro culture. We show that mechanical testing in compression and torsion, loading methods commonly used to assess disc mechanics, reveal equilibrium and time-dependent behaviors that are qualitatively similar to native tissue, although lesser in magnitude. Further, we demonstrate that cells seeded into both AF and NP regions adopt distinct morphologies that mirror those seen in native tissue, and that, in the AF region, this ordered community of cells deposit matrix that is organized in an angle-ply configuration. Finally, constructs demonstrate functional development with long-term in vitro culture. These findings provide a new approach for disc tissue engineering that replicates multi-scale form and function of the intervertebral disc, providing a foundation from which to build a multi-scale, biologic, anatomically and hierarchically relevant composite disc analogue for eventual disc replacement.

Assuring safety without animal testing: the case for the human testis in vitro.

PubMed

Chapin, Robert E; Boekelheide, Kim; Cortvrindt, Rita; van Duursen, Majorie B M; Gant, Tim; Jegou, Bernard; Marczylo, Emma; van Pelt, Ans M M; Post, Janine N; Roelofs, Maarke J E; Schlatt, Stefan; Teerds, Katja J; Toppari, Jorma; Piersma, Aldert H

2013-08-01

From 15 to 17 June 2011, a dedicated workshop was held on the subject of in vitro models for mammalian spermatogenesis and their applications in toxicological hazard and risk assessment. The workshop was sponsored by the Dutch ASAT initiative (Assuring Safety without Animal Testing), which aims at promoting innovative approaches toward toxicological hazard and risk assessment on the basis of human and in vitro data, and replacement of animal studies. Participants addressed the state of the art regarding human and animal evidence for compound mediated testicular toxicity, reviewed existing alternative assay models, and brainstormed about future approaches, specifically considering tissue engineering. The workshop recognized the specific complexity of testicular function exemplified by dedicated cell types with distinct functionalities, as well as different cell compartments in terms of microenvironment and extracellular matrix components. This complexity hampers quick results in the realm of alternative models. Nevertheless, progress has been achieved in recent years, and innovative approaches in tissue engineering may open new avenues for mimicking testicular function in vitro. Although feasible, significant investment is deemed essential to be able to bring new ideas into practice in the laboratory. For the advancement of in vitro testicular toxicity testing, one of the most sensitive end points in regulatory reproductive toxicity testing, such an investment is highly desirable. Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Multiple Resting-State Networks Are Associated With Tremors and Cognitive Features in Essential Tremor.

PubMed

Fang, Weidong; Chen, Huiyue; Wang, Hansheng; Zhang, Han; Liu, Mengqi; Puneet, Munankami; Lv, Fajin; Cheng, Oumei; Wang, Xuefeng; Lu, Xiurong; Luo, Tianyou

2015-12-01

The heterogeneous clinical features of essential tremor indicate that the dysfunctions of this syndrome are not confined to motor networks, but extend to nonmotor networks. Currently, these neural network dysfunctions in essential tremor remain unclear. In this study, independent component analysis of resting-state functional MRI was used to study these neural network mechanisms. Thirty-five essential tremor patients and 35 matched healthy controls with clinical and neuropsychological tests were included, and eight resting-state networks were identified. After considering the structure and head-motion factors and testing the reliability of the selected resting-state networks, we assessed the functional connectivity changes within or between resting-state networks. Finally, image-behavior correlation analysis was performed. Compared to healthy controls, essential tremor patients displayed increased functional connectivity in the sensorimotor and salience networks and decreased functional connectivity in the cerebellum network. Additionally, increased functional network connectivity was observed between anterior and posterior default mode networks, and a decreased functional network connectivity was noted between the cerebellum network and the sensorimotor and posterior default mode networks. Importantly, the functional connectivity changes within and between these resting-state networks were correlated with the tremor severity and total cognitive scores of essential tremor patients. The findings of this study provide the first evidence that functional connectivity changes within and between multiple resting-state networks are associated with tremors and cognitive features of essential tremor, and this work demonstrates a potential approach for identifying the underlying neural network mechanisms of this syndrome. © 2015 International Parkinson and Movement Disorder Society.

Twin Valve Caval Stent for Functional Replacement of Incompetent Tricuspid Valve: A Feasibility Animal Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sochman, Jan, E-mail: jan.sochman@medicon.cz; Peregrin, Jan H., E-mail: jape@medicon.cz; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu

Objective: To evaluate feasibility of a twin valve caval stent (TVCS) for functional replacement of an incompetent tricuspid valve (TV) in an acute animal study. Methods: One swine and three sheep were used in the study. TVCS placement was tested in a swine with a normal TV. TVCS function was tested in three sheep with TV regurgitation created by papillary muscle avulsion. Cardiac angiograms and pressure measurements were used to evaluate TVCS function. Two sheep were studied after fluid overload. Results: TVCS was percutaneously placed properly at the central portions of the superior vena cava (SVC) and inferior vena cavamore » (IVC) in the swine. Papillary muscle avulsion in three sheep caused significant tricuspid regurgitation with massive reflux into the right atrium (RA) and partial reflux into the SVC and IVC. TVCS placement eliminated reflux into the SVC and IVC. After fluid overload, there was enlargement of the right ventricle and RA and significant increase in right ventricle, RA, SVC, and IVC pressures, but no reflux into the IVC and SVC. Conclusion: The results of this feasibility study justify detailed evaluation of TVCS insertion for functional chronic replacement of incompetent TV.« less

The reprogramming factor nuclear receptor subfamily 5, group A, member 2 cannot replace octamer-binding transcription factor 4 function in the self-renewal of embryonic stem cells.

PubMed

Choi, Kyeng-Won; Oh, Hye-Rim; Lee, Jaeyoung; Lim, Bobae; Han, Yong-Mahn; Oh, Junseo; Kim, Jungho

2014-02-01

Although octamer-binding transcription factor 4 (Oct-4) is one of the most intensively studied factors in mammalian development, no cellular genes capable of replacing Oct-4 function in embryonic stem (ES) cells have been found. Recent data show that nuclear receptor subfamily 5, group A, member 2 (Nr5a2) is able to replace Oct-4 function in the reprogramming process; however, it is unclear whether Nr5a2 can replace Oct-4 function in ES cells. In this study, the ability of Nr5a2 to maintain self-renewal and pluripotency in ES cells was investigated. Nr5a2 localized to the nucleus in ES cells, similarly to Oct-4. However, expression of Nr5a2 failed to rescue the stem cell phenotype or to maintain the self-renewal ability of ES cells. Furthermore, as compared with Oct-4-expressing ES cells, Nr5a2-expressing ES cells showed a reduced number of cells in S-phase, did not expand normally, and did not remain in an undifferentiated state. Ectopic expression of Nr5a2 in ES cells was not able to activate transcription of ES cell-specific genes, and gene expression profiling demonstrated differences between Nr5a2-expressing and Oct-4-expressing ES cells. In addition, Nr5a2-expressing ES cells were not able to form teratomas in nude mice. Taken together, these results strongly suggest that the gene regulation properties of Nr5a2 and Oct-4 and their abilities to confer self-renewal and pluripotency of ES cells differ. The present study provides strong evidence that Nr5a2 cannot replace Oct-4 function in ES cells. © 2013 FEBS.

Equivalency of Galápagos giant tortoises used as ecological replacement species to restore ecosystem functions.

PubMed

Hunter, Elizabeth A; Gibbs, James P; Cayot, Linda J; Tapia, Washington

2013-08-01

Loss of key plant-animal interactions (e.g., disturbance, seed dispersal, and herbivory) due to extinctions of large herbivores has diminished ecosystem functioning nearly worldwide. Mitigating for the ecological consequences of large herbivore losses through the use of ecological replacements to fill extinct species' niches and thereby replicate missing ecological functions has been proposed. It is unknown how different morphologically and ecologically a replacement can be from the extinct species and still provide similar functions. We studied niche equivalency between 2 phenotypes of Galápagos giant tortoises (domed and saddlebacked) that were translocated to Pinta Island in the Galápagos Archipelago as ecological replacements for the extinct saddlebacked giant tortoise (Chelonoidis abingdonii). Thirty-nine adult, nonreproductive tortoises were introduced to Pinta Island in May 2010, and we observed tortoise resource use in relation to phenotype during the first year following release. Domed tortoises settled in higher, moister elevations than saddlebacked tortoises, which favored lower elevation arid zones. The areas where the tortoises settled are consistent with the ecological conditions each phenotype occupies in its native range. Saddlebacked tortoises selected areas with high densities of the arboreal prickly pear cactus (Opuntia galapageia) and mostly foraged on the cactus, which likely relied on the extinct saddlebacked Pinta tortoise for seed dispersal. In contrast, domed tortoises did not select areas with cactus and therefore would not provide the same seed-dispersal functions for the cactus as the introduced or the original, now extinct, saddlebacked tortoises. Interchangeability of extant megaherbivores as replacements for extinct forms therefore should be scrutinized given the lack of equivalency we observed in closely related forms of giant tortoises. Our results also demonstrate the value of trial introductions of sterilized individuals to test niche equivalency among candidate analog species. © 2013 Society for Conservation Biology.

Current state of micro-robots/devices as substitutes for screening colonoscopy: assessment based on technology readiness levels.

PubMed

Tapia-Siles, Silvia C; Coleman, Stuart; Cuschieri, Alfred

2016-02-01

Previous reports have described several candidates, which have the potential to replace colonoscopy, but to date, there is still no device capable of fully replacing flexible colonoscopy in the management of colonic disorders and for mass adult population screening for asymptomatic colorectal cancer. NASA developed the TRL methodology to describe and define the stages of development before use and marketing of any device. The definitions of the TRLS used in the present review are those formulated by "The US Department of Defense Technology Readiness Assessment Guidance" but adapted to micro-robots for colonoscopy. All the devices included are reported in scientific literature. They were identified by a systematic search in Web of Science, PubMed and IEEE Xplore amongst other sources. Devices that clearly lack the potential for full replacement of flexible colonoscopy were excluded. The technological salient features of all the devices included for assessment are described briefly, with particular focus on device propulsion. The devices are classified according to the TRL criteria based on the reported information. An analysis is next undertaken of the characteristics and salient features of the devices included in the review: wireless/tethered devices, data storage-transmission and navigation, additional functionality, residual technology challenges and clinical and socio-economical needs. Few devices currently possess the required functionality and performance to replace the conventional colonoscopy. The requirements, including functionalities which favour the development of a micro-robot platform to replace colonoscopy, are highlighted.

Physicochemical and functional properties of micronized jincheng orange by-products (Citrus sinensis Osbeck) dietary fiber and its application as a fat replacer in yogurt.

PubMed

Yi, Tian; Huang, Xingjian; Pan, Siyi; Wang, Lufeng

2014-08-01

Orange by-products from juice extraction are generally discarded or used in animal feed due to their low market value. However, orange by-products show potential as dietary fiber (DF) and fat replacers in products such as yogurt. This study assessed the benefits of using orange by-products in DF-enriched materials such as DF powders (OP) and micronized DF with ball-milling (MDF). The study also investigated the effects of adding different levels of OP and MDF on the quality of low-fat yogurt. Results show that MDF showed better physicochemical and functional properties than OP, and that 2% MDF as a fat replacer in yogurt retained most of the textural and sensory properties of full-fat yogurt. Therefore, this study showed that MDF is a promising alternative as a fat replacer in low-fat yogurt, without sacrificing good taste and other qualities of full-fat yogurt.

Solid-State Thyratron Replacement. Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roth, Ian

2017-12-12

Under this SBIR, DTI developed a solid-state switch as an alternative to legacy thyratron equipment. Our Phase II objective was to make a solid-state thyratron replacement that would provide equivalent or better performance, much higher reliability (at least a 20 year lifetime, compared to a thyratron’s two-year lifetime) and would sell for ~3x the cost of a thyratron, or less than $40k. We were successful in building a solid-state switch which could reliably function as a thyratron replacement. The unit was designed to directly replace the thyratrons currently being used at SLAC’s Linac Coherent Light Source (LCLS), and was builtmore » in a tank that was small enough to fit into the existing thyratron cabinet, providing a true form-fit-function replacement path. We tested the switch at the full operating specifications: 48 kV, 6.3 kA, and 1 µs risetime. We also demonstrated a peak-to-peak pulse jitter of 1.5 ns, which is five times shorter than is typical for thyratrons. This lower jitter would improve the performance of the LCLS beam. The predicted reliability is more than 80 years, which is 40 times greater than a thyratron.« less

ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy?

PubMed Central

Buscà, Roser; Pouysségur, Jacques; Lenormand, Philippe

2016-01-01

The MAP kinase signaling cascade Ras/Raf/MEK/ERK has been involved in a large variety of cellular and physiological processes that are crucial for life. Many pathological situations have been associated to this pathway. More than one isoform has been described at each level of the cascade. In this review we devoted our attention to ERK1 and ERK2, which are the effector kinases of the pathway. Whether ERK1 and ERK2 specify functional differences or are in contrast functionally redundant, constitutes an ongoing debate despite the huge amount of studies performed to date. In this review we compiled data on ERK1 vs. ERK2 gene structures, protein sequences, expression levels, structural and molecular mechanisms of activation and substrate recognition. We have also attempted to perform a rigorous analysis of studies regarding the individual roles of ERK1 and ERK2 by the means of morpholinos, siRNA, and shRNA silencing as well as gene disruption or gene replacement in mice. Finally, we comment on a recent study of gene and protein evolution of ERK isoforms as a distinct approach to address the same question. Our review permits the evaluation of the relevance of published studies in the field especially when measurements of global ERK activation are taken into account. Our analysis favors the hypothesis of ERK1 and ERK2 exhibiting functional redundancy and points to the concept of the global ERK quantity, and not isoform specificity, as being the essential determinant to achieve ERK function. PMID:27376062

Replacement predictions for drinking water networks through historical data.

PubMed

Malm, Annika; Ljunggren, Olle; Bergstedt, Olof; Pettersson, Thomas J R; Morrison, Gregory M

2012-05-01

Lifetime distribution functions and current network age data can be combined to provide an assessment of the future replacement needs for drinking water distribution networks. Reliable lifetime predictions are limited by a lack of understanding of deterioration processes for different pipe materials under varied conditions. An alternative approach is the use of real historical data for replacement over an extended time series. In this paper, future replacement needs are predicted through historical data representing more than one hundred years of drinking water pipe replacement in Gothenburg, Sweden. The verified data fits well with commonly used lifetime distribution curves. Predictions for the future are discussed in the context of path dependence theory. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ross operation in children: late results.

PubMed

Elkins, R C; Lane, M M; McCue, C

2001-11-01

Although the Ross operation has become the accepted aortic valve replacement in children, the long-term fate of the pulmonary autograft valve remains unknown. To assess mid-term and late results of autograft valve durability, patient survival and valve-related morbidity, a retrospective review of patients (age range: 3 days to 17 years) having a Ross operation between November 1986 and May 2001 were reviewed. Medical records and patient contacts with all but two of 167 current survivors of 178 consecutive patients having an aortic valve replacement as a Ross operation have been completed during the past two years. The most recent echocardiographic evaluation was reviewed for autograft valve and homograft valve function. Operative mortality was 4.5% (8/178), with three late deaths (two were non-valve-related) for an actuarial survival of 92+/-3% at 12 years. Actuarial freedom from autograft valve degeneration (reoperation or severe insufficiency of autograft valve or valve-related death) was 90+/-4% at 12 years. Autograft valve degeneration was not affected by technique of insertion (141 root replacement, 37 intra-aortic), aortic valve morphology (157 bicuspid or unicuspid, 26 tricuspid), or age at operation. Autograft valve degeneration was worse in patients with a primary lesion of aortic insufficiency than in those with aortic stenosis (p = 0.03). Autograft valve reoperation was required in 12 patients, with autograft valve replacement in seven. Actuarial freedom from autograft replacement was 93+/-3% at 12 years. Homograft valve replacement was required in seven patients, with actuarial freedom from replacement of 90+/-4% at 12 years. Eight additional patients have homograft valve obstruction (gradient > or =50 mmHg), and seven have severe pulmonary insufficiency. Survival and freedom from aortic valve replacement are excellent in children. Homograft valve late function remains a concern, and efforts to improve homograft durability should be encouraged.

Prioritization Methodology for Chemical Replacement

NASA Technical Reports Server (NTRS)

Cruit, W.; Schutzenhofer, S.; Goldberg, B.; Everhart, K.

1993-01-01

This project serves to define an appropriate methodology for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semiquantitative approach derived from quality function deployment techniques (QFD Matrix). This methodology aims to weigh the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives. The results are being implemented as a guideline for consideration for current NASA propulsion systems.

[The importance of C-terminal aspartic acid residue (D141) to the antirestriction activity of the ArdB (R64) protein].

PubMed

Kudryavtseva, A A; Osetrova, M S; Livinyuk, V Ya; Manukhov, I V; Zavilgelsky, G B

2017-01-01

Antirestriction proteins of the ArdB/KlcA family are specific inhibitors of restriction (endonuclease) activity of type-I restriction/modification enzymes. The effect of conserved amino acid residues on the antirestriction activity of the ArdB protein encoded by the transmissible R64 (IncI1) plasmid has been investigated. An analysis of the amino acid sequences of ArdB homologues demonstrated the presence of four groups of conserved residues ((1) R16, E32, and W51; (2) Y46 and G48; (3) S81, D83 and E132, and (4) N77, L(I)140, and D141) on the surface of the protein globule. Amino acid residues of the fourth group showed a unique localization pattern with the terminal residue protruding beyond the globule surface. The replacement of two conserved amino acids (D141 and N77) located in the close vicinity of each other on the globule surface showed that the C-terminal D141 is essential for the antirestriction activity of ArdB. The deletion of this residue, as well as replacement by a hydrophobic threonine residue (D141T), completely abolished the antirestriction activity of ArdB. The synonymous replacement of D141 by a glutamic acid residue (D141E) caused an approximately 30-fold decrease of the antirestriction activity of ArdB, and the point mutation N77A caused an approximately 20-fold decrease in activity. The residues D141 and N77 located on the surface of the protein globule are presumably essential for the formation of a contact between ArdB and a currently unknown factor that modulates the activity of type-I restriction/modification enzymes.

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals.

PubMed

Coker, Robert H; Miller, Sharon; Schutzler, Scott; Deutz, Nicolaas; Wolfe, Robert R

2012-12-11

Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly. In the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR) would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR). We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day): 1) EAAMR or a 2) competitive meal replacement (CMR) in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR. By design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR. The provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

Effects of two-year testosterone replacement therapy on cognition, emotions and quality of life in young and middle-aged hypogonadal men.

PubMed

Lašaitė, L; Čeponis, J; Preikša, R T; Žilaitienė, B

2017-04-01

The aim of the study was to examine the effects of two-year testosterone replacement therapy on cognitive functioning, emotional state and quality of life in young and middle-aged men with hypogonadotropic hypogonadism. Nineteen males diagnosed with hypogonadotropic hypogonadism participated in the study. Cognitive functions were assessed by Trail Making Test and Digit Span Test of Wechsler Adult Intelligence Scale. Emotional state was evaluated by Profile of Mood States. Quality of life was evaluated by WHO Brief Quality of Life Questionnaire. Changes after two-year testosterone replacement therapy were detected in Trail Making A (42.9 ± 22.3 vs. 36.2 ± 22.5, p = .050) and B (90.6 ± 55.3 vs. 65.6 ± 21.4, p = .025) tests, showing improvement in attention and visual scanning abilities, executive function and psychomotor speed, as well as in Digit Span Test forward score (5.4 ± 2.0 vs. 6.1 ± 2.6, p = .046), showing improvement in attention capacity and psychomotor speed. No significant differences were observed in emotional state and quality of life. In conclusion, beneficial effect in cognitive functioning (improved attention and visual scanning ability, executive function and psychomotor speed), but not in emotional state and quality of life, was observed in young and middle-aged hypogonadal men after two-year testosterone replacement therapy. © 2016 Blackwell Verlag GmbH.

Early self-managed focal sensorimotor rehabilitative training enhances functional mobility and sensorimotor function in patients following total knee replacement: a controlled clinical trial.

PubMed

Moutzouri, Maria; Gleeson, Nigel; Coutts, Fiona; Tsepis, Elias; John, Gliatis

2018-02-01

To assess the effects of early self-managed focal sensorimotor training compared to functional exercise training after total knee replacement on functional mobility and sensorimotor function. A single-blind controlled clinical trial. University Hospital of Rion, Greece. A total of 52 participants following total knee replacement. The primary outcome was the Timed Up and Go Test and the secondary outcomes were balance, joint position error, the Knee Outcome Survey Activities of Daily Living Scale, and pain. Patients were assessed on three separate occasions (presurgery, 8 weeks post surgery, and 14 weeks post surgery). Participants were randomized to either focal sensorimotor exercise training (experimental group) or functional exercise training (control group). Both groups received a 12-week home-based programme prescribed for 3-5 sessions/week (35-45 minutes). Consistently greater improvements ( F 2,98  = 4.3 to 24.8; P < 0.05) in group mean scores favour the experimental group compared to the control group: Timed Up and Go (7.8 ± 2.9 seconds vs. 4.6 ± 2.6 seconds); balance (2.1 ± 0.9° vs. 0.7 ± 1.2°); joint position error (13.8 ± 7.3° vs. 6.2 ± 9.1°); Knee Outcome Survey Activities of Daily Living Scale (44.2 ± 11.3 vs. 26.1 ± 11.4); and pain (5.9 ± 1.3 cm vs. 4.6 ± 1.1 cm). Patterns of improvement for the experimental group over time were represented by a relative effect size range of 1.3-6.5. Overall, the magnitude of improvements in functional mobility and sensorimotor function endorses using focal sensorimotor training as an effective mode of rehabilitation following knee replacement.

Functional outcomes of outpatient balance training following total knee replacement in patients with knee osteoarthritis: a randomized controlled trial.

PubMed

Liao, Chun-De; Lin, Li-Fong; Huang, Yi-Ching; Huang, Shih-Wei; Chou, Lin-Chuan; Liou, Tsan-Hon

2015-09-01

To evaluate whether balance training after total knee replacement surgery improves functional outcomes and to determine whether postoperative balance is associated with mobility. A prospective intervention study and randomized controlled trial with an intention-to-treat analysis. The rehabilitation center of a university-based teaching hospital. A total of 130 patients with knee osteoarthritis who had undergone total knee replacement surgery were recruited to attend an outpatient rehabilitation program. They were randomly allocated to additional balance rehabilitation and functional rehabilitation groups. During the eight-week outpatient rehabilitation program, both groups received general functional training. Patients in the balance rehabilitation group received an additional balance-based rehabilitation program. The functional reach test, single-leg stance test, 10-m walk test, Timed Up and Go Test, timed chair-stand test, stair-climb test, and Western Ontario and McMaster Universities Osteoarthritis Index were measured at baseline, eight weeks (T(1)), and 32 weeks (T(2)). The balance rehabilitation group patients demonstrated significant improvement in the results of the functional reach test at T(1) (37.6 ±7.8 cm) and T(2) (39.3 ±9.7 cm) compared with the baseline assessment (11.5 ±2.9 cm) and Timed Up and Go Test at T(1) (8.9 ±1.2 seconds) and T(2) (8.0 ±1.9 seconds) compared with the baseline assessment (12.5 ±1.8 seconds). Moreover, the balance rehabilitation group patients exhibited significantly greater improvements in balance and mobility than did the functional rehabilitation group patients (all P < 0.001). Furthermore, improved balance was significantly associated with improved mobility at T(2). Postoperative outpatient rehabilitation with balance training improves the balance, mobility, and functional outcomes in patients with knee osteoarthritis after total knee replacement. © The Author(s) 2014.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oberhardt, Matthew A.; Zarecki, Raphy; Reshef, Leah

Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such enzymes is an important open question in biology. Here we develop a genome-wide method, PROPER, that uses a permissive PSI-BLAST approach to predict promiscuous activities of metabolic genes. Enzyme promiscuity is typically studied experimentally using multicopy suppression, in which over-expression of a promiscuous ‘replacer’ gene rescues lethality caused by inactivation of a ‘target’ gene. We use PROPER to predict multicopy suppression in Escherichia coli, achieving highly significant overlap with published cases (hypergeometric p = 4.4e-13). We then validate three novel predictedmore » target-replacer gene pairs in new multicopy suppression experiments. We next go beyond PROPER and develop a network-based approach, GEM-PROPER, that integrates PROPER with genome-scale metabolic modeling to predict promiscuous replacements via alternative metabolic pathways. GEM-PROPER predicts a new indirect replacer (thiG) for an essential enzyme (pdxB) in production of pyridoxal 5’-phosphate (the active form of Vitamin B 6), which we validate experimentally via multicopy suppression. Here, we perform a structural analysis of thiG to determine its potential promiscuous active site, which we validate experimentally by inactivating the pertaining residues and showing a loss of replacer activity. Thus, this study is a successful example where a computational investigation leads to a network-based identification of an indirect promiscuous replacement of a key metabolic enzyme, which would have been extremely difficult to identify directly.« less

40 CFR 86.1806-01 - On-board diagnostics.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-board diagnostic system during the certification process, that functions properly on low-sulfur gasoline... equipped. (1) A catalyst is replaced with a deteriorated or defective catalyst, or an electronic simulation... oxygen sensor is replaced with a deteriorated or defective oxygen sensor, or an electronic simulation of...

Comparison of antimicrobial activity of essential oils, plant extracts and methylparaben in cosmetic emulsions: 2 months study.

PubMed

Herman, Anna

2014-09-01

The aim of the study was to compare the preservative effectiveness of plant extracts (Matricaria chamomilla, Aloe vera, Calendula officinalis) and essential oils (Lavandulla officinalis, Melaleuca alternifolia, Cinnamomum zeylanicum) with methylparaben in cosmetic emulsions against skin microflora during 2 months of application by volunteers. Cosmetic emulsions with extracts (2.5 %), essential oils (2.5 %), methylparaben (0.4 %) or placebo were tested by 40 volunteers during 2 months of treatment. In order to determine microbial purity of the emulsions, the samples were taken after 0, 2, 4, 6 and 8 weeks of application. Throughout the trial period it was revealed that only cinnamon oil completely inhibited the growth of bacteria, yeast and mould, as compared to all other essential oils, plant extracts and methylparaben in the tested emulsions. This result shows that cinnamon oil could successfully replace the use of methylparaben in cosmetics, at the same time ensuring microbiological purity of a cosmetic product under its in-use and storage conditions.

Seismic interferometry by crosscorrelation and by multidimensional deconvolution: a systematic comparison

NASA Astrophysics Data System (ADS)

Wapenaar, Kees; van der Neut, Joost; Ruigrok, Elmer; Draganov, Deyan; Hunziker, Juerg; Slob, Evert; Thorbecke, Jan; Snieder, Roel

2010-05-01

In recent years, seismic interferometry (or Green's function retrieval) has led to many applications in seismology (exploration, regional and global), underwater acoustics and ultrasonics. One of the explanations for this broad interest lies in the simplicity of the methodology. In passive data applications a simple crosscorrelation of responses at two receivers gives the impulse response (Green's function) at one receiver as if there were a source at the position of the other. In controlled-source applications the procedure is similar, except that it involves in addition a summation along the sources. It has also been recognized that the simple crosscorrelation approach has its limitations. From the various theoretical models it follows that there are a number of underlying assumptions for retrieving the Green's function by crosscorrelation. The most important assumptions are that the medium is lossless and that the waves are equipartitioned. In heuristic terms the latter condition means that the receivers are illuminated isotropically from all directions, which is for example achieved when the sources are regularly distributed along a closed surface, the sources are mutually uncorrelated and their power spectra are identical. Despite the fact that in practical situations these conditions are at most only partly fulfilled, the results of seismic interferometry are generally quite robust, but the retrieved amplitudes are unreliable and the results are often blurred by artifacts. Several researchers have proposed to address some of the shortcomings by replacing the correlation process by deconvolution. In most cases the employed deconvolution procedure is essentially 1-D (i.e., trace-by-trace deconvolution). This compensates the anelastic losses, but it does not account for the anisotropic illumination of the receivers. To obtain more accurate results, seismic interferometry by deconvolution should acknowledge the 3-D nature of the seismic wave field. Hence, from a theoretical point of view, the trace-by-trace process should be replaced by a full 3-D wave field deconvolution process. Interferometry by multidimensional deconvolution is more accurate than the trace-by-trace correlation and deconvolution approaches but the processing is more involved. In the presentation we will give a systematic analysis of seismic interferometry by crosscorrelation versus multi-dimensional deconvolution and discuss applications of both approaches.

Properties of genes essential for mouse development

PubMed Central

Kabir, Mitra; Barradas, Ana; Tzotzos, George T.; Hentges, Kathryn E.

2017-01-01

Essential genes are those that are critical for life. In the specific case of the mouse, they are the set of genes whose deletion means that a mouse is unable to survive after birth. As such, they are the key minimal set of genes needed for all the steps of development to produce an organism capable of life ex utero. We explored a wide range of sequence and functional features to characterise essential (lethal) and non-essential (viable) genes in mice. Experimental data curated manually identified 1301 essential genes and 3451 viable genes. Very many sequence features show highly significant differences between essential and viable mouse genes. Essential genes generally encode complex proteins, with multiple domains and many introns. These genes tend to be: long, highly expressed, old and evolutionarily conserved. These genes tend to encode ligases, transferases, phosphorylated proteins, intracellular proteins, nuclear proteins, and hubs in protein-protein interaction networks. They are involved with regulating protein-protein interactions, gene expression and metabolic processes, cell morphogenesis, cell division, cell proliferation, DNA replication, cell differentiation, DNA repair and transcription, cell differentiation and embryonic development. Viable genes tend to encode: membrane proteins or secreted proteins, and are associated with functions such as cellular communication, apoptosis, behaviour and immune response, as well as housekeeping and tissue specific functions. Viable genes are linked to transport, ion channels, signal transduction, calcium binding and lipid binding, consistent with their location in membranes and involvement with cell-cell communication. From the analysis of the composite features of essential and viable genes, we conclude that essential genes tend to be required for intracellular functions, and viable genes tend to be involved with extracellular functions and cell-cell communication. Knowledge of the features that are over-represented in essential genes allows for a deeper understanding of the functions and processes implemented during mammalian development. PMID:28562614

[Tachycardia detection in implantable cardioverter-defibrillators by Sorin/LivaNova : Algorithms, pearls and pitfalls].

PubMed

Kolb, Christof; Ocklenburg, Rolf

2016-09-01

For physicians involved in the treatment of patients with implantable cardioverter-defibrillators (ICDs) the knowledge of tachycardia detection algorithms is of paramount importance. This knowledge is essential for adequate device selection during de-novo implantation, ICD replacement, and for troubleshooting during follow-up. This review describes tachycardia detection algorithms incorporated in ICDs by Sorin/LivaNova and analyses their strengths and weaknesses.

Acoustic Evaluation of Sanders Associates ACODAC Sensors

DTIC Science & Technology

1983-03-01

this securing technique because of its susceptibility to in-band resonances. Although this unit was primarily submitted for sensor flow- noise evaluation...of this sensor and prepare it for the required flow- noise evaluation by replacing the defective geophones in the cosine channel. For completeness...channels displayed essentially flat response with a low frequency roll off starting at about 20 Hz and an upper resonance at 3300 Hz. The sensitivity

A radially resolved kinetic model for nonlocal electron ripple diffusion losses in tokamaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, Scott

A relatively simple radially resolved kinetic model is applied to the ripple diffusion problem for electrons in tokamaks. The distribution function f(r,v) is defined on a two-dimensional grid, where r is the radial coordinate and v is the velocity coordinate. Particle transport in the radial direction is from ripple and banana diffusion and transport in the velocity direction is described by the Fokker-Planck equation. Particles and energy are replaced by source functions that are adjusted to maintain a constant central density and temperature. The relaxed profiles of f(r,v) show that the electron distribution function at the wall contains suprathermal electronsmore » that have diffused from the interior that enhance ripple transport. The transport at the periphery is therefore nonlocal. The energy replacement times from the computational model are near to the experimental replacement times for tokamak discharges in the compilation by Pfeiffer and Waltz [Nucl. Fusion 19, 51 (1979)].« less

Replacement of all arginine residues with canavanine in MazF-bs mRNA interferase changes its specificity.

PubMed

Ishida, Yojiro; Park, Jung-Ho; Mao, Lili; Yamaguchi, Yoshihiro; Inouye, Masayori

2013-03-15

Replacement of a specific amino acid residue in a protein with nonnatural analogues is highly challenging because of their cellular toxicity. We demonstrate for the first time the replacement of all arginine (Arg) residues in a protein with canavanine (Can), a toxic Arg analogue. All Arg residues in the 5-base specific (UACAU) mRNA interferase from Bacillus subtilis (MazF-bs(arg)) were replaced with Can by using the single-protein production system in Escherichia coli. The resulting MazF-bs(can) gained a 6-base recognition sequence, UACAUA, for RNA cleavage instead of the 5-base sequence, UACAU, for MazF-bs(arg). Mass spectrometry analysis confirmed that all Arg residues were replaced with Can. The present system offers a novel approach to create new functional proteins by replacing a specific amino acid in a protein with its analogues.

Applying machine learning to pattern analysis for automated in-design layout optimization

NASA Astrophysics Data System (ADS)

Cain, Jason P.; Fakhry, Moutaz; Pathak, Piyush; Sweis, Jason; Gennari, Frank; Lai, Ya-Chieh

2018-04-01

Building on previous work for cataloging unique topological patterns in an integrated circuit physical design, a new process is defined in which a risk scoring methodology is used to rank patterns based on manufacturing risk. Patterns with high risk are then mapped to functionally equivalent patterns with lower risk. The higher risk patterns are then replaced in the design with their lower risk equivalents. The pattern selection and replacement is fully automated and suitable for use for full-chip designs. Results from 14nm product designs show that the approach can identify and replace risk patterns with quantifiable positive impact on the risk score distribution after replacement.

Novel Highly Porous Metal Technology in Artificial Hip and Knee Replacement: Processing Methodologies and Clinical Applications

NASA Astrophysics Data System (ADS)

Muth, John; Poggie, Matthew; Kulesha, Gene; Michael Meneghini, R.

2013-02-01

Hip and knee replacement can dramatically improve a patient's quality of life through pain relief and restored function. Fixation of hip and knee replacement implants to bone is critical to the success of the procedure. A variety of roughened surfaces and three-dimensional porous surfaces have been used to enhance biological fixation on orthopedic implants. Recently, highly porous metals have emerged as versatile biomaterials that may enhance fixation to bone and are suitable to a number of applications in hip and knee replacement surgery. This article provides an overview of several processes used to create these implant surfaces.

Esophageal replacement.

PubMed

Kunisaki, Shaun M; Coran, Arnold G

2017-04-01

This article focuses on esophageal replacement as a surgical option for pediatric patients with end-stage esophageal disease. While it is obvious that the patient׳s own esophagus is the best esophagus, persisting with attempts to retain a native esophagus with no function and at all costs are futile and usually detrimental to the overall well-being of the child. In such cases, the esophagus should be abandoned, and the appropriate esophageal replacement is chosen for definitive reconstruction. We review the various types of conduits used for esophageal replacement and discuss the unique advantages and disadvantages that are relevant for clinical decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of leptin deficiency and replacement on cerebellar response to food-related cues

PubMed Central

Berman, Steven M.; Paz-Filho, Gilberto; Wong, Ma-Li; Kohno, Milky; Licinio, Julio; London, Edythe D.

2013-01-01

Leptin affects eating behavior partly by altering the response of the brain to food-related stimuli. Effects of leptin on brain structure have been observed in the cerebellum, where leptin receptors are most densely expressed, but the function of leptin in the cerebellum remains unclear. We performed a nonrandomized, prospective interventional study of three adults with genetically-mediated leptin deficiency. FMRI was recorded three times each year during years 5 and 6 of leptin replacement treatment. Session one of each year occurred after 10 months of continuous daily replacement, session two after 33–37 days without leptin, and session three 14–23 days after daily replacement was restored. Statistical parametric mapping software (SPM5) was employed to contrast the fMRI blood-oxygenation level-dependent response to images of high-calorie foods versus images of brick walls. Covariate analyses quantified the effects of the duration of leptin replacement and concomitant changes in body mass on the cerebral responses. Longer duration of replacement was associated with more activation by food images in a ventral portion of the posterior lobe of the cerebellum, while simultaneous decreases in body mass were associated with decreased activation in a more dorsal portion of the same lobe. These findings indicate that leptin replacement reversibly alters neural function within the posterior cerebellum, and modulates plasticity-dependent brain physiology in response to food cues. The results suggest an underexplored role for the posterior cerebellum in the regulation of leptin-mediated processes related to food intake. PMID:22576622

The Essential Gene EMB1611 Maintains Shoot Apical Meristem Function During Arabidopsis Development

USDA-ARS?s Scientific Manuscript database

The Arabidopsis thaliana genome contains hundreds of genes essential for seed development. Because null mutations in these genes cause embryo lethality, their specific molecular and developmental functions are largely unknown. Here, we identify a role for EMB1611/MEE22, an essential gene in Arabidop...

21 CFR 874.3495 - Total ossicular replacement prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Total ossicular replacement prosthesis. 874.3495 Section 874.3495 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... be implanted for the total functional reconstruction of the ossicular chain and facilitates the...

21 CFR 874.3450 - Partial ossicular replacement prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Partial ossicular replacement prosthesis. 874.3450 Section 874.3450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... be implanted for the functional reconstruction of segments of the ossicular chain and facilitates the...

Reiter during maintenance tasks in the FGB

NASA Image and Video Library

2006-08-10

ISS013-E-65721 (10 Aug. 2006) --- European Space Agency (ESA) astronaut Thomas Reiter, Expedition 13 flight engineer, replaces the number two replaceable pump panel (SPN) in the number one loop (VGK1) of the International Space Station's Zarya functional cargo block (FGB) thermal control system with a new spare from stowage.

21 CFR 874.3495 - Total ossicular replacement prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Total ossicular replacement prosthesis. 874.3495 Section 874.3495 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... be implanted for the total functional reconstruction of the ossicular chain and facilitates the...

21 CFR 874.3450 - Partial ossicular replacement prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Partial ossicular replacement prosthesis. 874.3450 Section 874.3450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... be implanted for the functional reconstruction of segments of the ossicular chain and facilitates the...

Reduced Toxicity, High Performance Monopropellant at the U.S. Air Force Research Laboratory

NASA Astrophysics Data System (ADS)

Hawkins, T. W.; Brand, A. J.; McKay, M. B.; Tinnirello, M.

2010-09-01

Current programs are aiming to develop reduced toxicity monopropellant formulations to replace spacecraft hydrazine monopropellant. The Air Force Research Laboratory's(AFRL's) approach to replacing hydrazine is the synthesis and development of energetic compounds/formulations with substantially less vapor toxicity and superior performance(specific impulse and density). Characterization and testing of these high energy density materials is an essential part of the screening process for viable advanced propellants. Hazardous handling characteristics, undesirable physical properties or unacceptable sensitivity behaviors must also be identified and/or modified to further development by a potential user. AFRL has successfully identified a novel monopropellant(designated AF-M315E) that shows great promise as an avenue toward replacement of hydrazine monopropellant for spacecraft propulsion. Hazard and safety/sensitivity, stability, and toxicity studies have been conducted on the monopropellant and will be described. The results from AF-M315E indicate that a >50% improvement in propulsion system performance over hydrazine is achievable while simultaneously providing a safer environment for the general public, ground personnel, crews and flight participants.

A hydrogen-bonding network modulating enzyme function: asparagine-194 and tyrosine-225 of Escherichia coli aspartate aminotransferase.

PubMed

Yano, T; Mizuno, T; Kagamiyama, H

1993-02-23

The electron distribution within the coenzyme or coenzyme-substrate conjugate needs to be properly regulated during the catalytic process of aspartate aminotransferase (AspAT). Asn194 and Tyr225 may function in regulating the electron distribution through hydrogen-bonding to O(3') of the coenzyme, pyridoxal 5'-phosphate (PLP) or pyridoxamine 5'-phosphate (PMP). The roles of Tyr225 have already been explored by site-directed mutagenesis (Inoue et al., 1991; Goldberg et al., 1991). In the present studies, the mutant enzymes Asn194-->Ala and Asn194-->Ala + Tyr225-->Phe were analyzed kinetically and spectroscopically and were compared with the wild-type and Tyr225-->Phe enzymes. The kinetic studies showed that Asn194 is not essential for AspAT catalysis, although the Kd values for the substrates were increased by 10- to 50-fold upon the replacement of Asn194. The measurements of the absorption and fluorescence excitation spectra revealed that the ratio of an enolimine to a ketoenamine form was considerably increased as a tautomeric form of the protonated PLP in the active site of the double mutant enzyme. The pH-pKd relationship for the binding of maleate to AspAT could be explained by a simple thermodynamic cycle where only one ionizing group (the imine nitrogen of the internal aldimine bond) affects the binding of maleate. The analyses of the pH-pKd curves for the wild-type and mutant enzymes showed that (i) the hydrogen bond between O(3') of PLP and Asn194 is weakened by the binding of maleate to AspAT, while the hydrogen bond between O(3') and Tyr225 is not changed, and that (ii) the replacement of Asn194 causes some effect hampering the binding of maleate.(ABSTRACT TRUNCATED AT 250 WORDS)

Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus.

PubMed

Merceron, Christophe; Mangiavini, Laura; Robling, Alexander; Wilson, Tremika LeShan; Giaccia, Amato J; Shapiro, Irving M; Schipani, Ernestina; Risbud, Makarand V

2014-01-01

The intervertebral disc (IVD) is one of the largest avascular organs in vertebrates. The nucleus pulposus (NP), a highly hydrated and proteoglycan-enriched tissue, forms the inner portion of the IVD. The NP is surrounded by a multi-lamellar fibrocartilaginous structure, the annulus fibrosus (AF). This structure is covered superior and inferior side by cartilaginous endplates (CEP). The NP is a unique tissue within the IVD as it results from the differentiation of notochordal cells, whereas, AF and CEP derive from the sclerotome. The hypoxia inducible factor-1α (HIF-1α) is expressed in NP cells but its function in NP development and homeostasis is largely unknown. We thus conditionally deleted HIF-1α in notochordal cells and investigated how loss of this transcription factor impacts NP formation and homeostasis at E15.5, birth, 1 and 4 months of age, respectively. Histological analysis, cell lineage studies, and TUNEL assay were performed. Morphologic changes of the mutant NP cells were identified as early as E15.5, followed, postnatally, by the progressive disappearance and replacement of the NP with a novel tissue that resembles fibrocartilage. Notably, lineage studies and TUNEL assay unequivocally proved that NP cells did not transdifferentiate into chondrocyte-like cells but they rather underwent massive cell death, and were completely replaced by a cell population belonging to a lineage distinct from the notochordal one. Finally, to evaluate the functional consequences of HIF-1α deletion in the NP, biomechanical testing of mutant IVD was performed. Loss of the NP in mutant mice significantly reduced the IVD biomechanical properties by decreasing its ability to absorb mechanical stress. These findings are similar to the changes usually observed during human IVD degeneration. Our study thus demonstrates that HIF-1α is essential for NP development and homeostasis, and it raises the intriguing possibility that this transcription factor could be involved in IVD degeneration in humans.

Metal Organic Framework-Templated Chemiresistor: Sensing Type Transition from P-to-N Using Hollow Metal Oxide Polyhedron via Galvanic Replacement.

PubMed

Jang, Ji-Soo; Koo, Won-Tae; Choi, Seon-Jin; Kim, Il-Doo

2017-08-30

Facile synthesis of porous nanobuilding blocks with high surface area and uniform catalyst functionalization has always been regarded as an essential requirement for the development of highly sensitive and selective chemical sensors. Metal-organic frameworks (MOFs) are considered as one of the most ideal templates due to their ability to encapsulate ultrasmall catalytic nanoparticles (NPs) in microporous MOF structures in addition to easy removal of the sacrificial MOF scaffold by calcination. Here, we introduce a MOFs derived n-type SnO 2 (n-SnO 2 ) sensing layer with hollow polyhedron structures, obtained from p-n transition of MOF-templated p-type Co 3 O 4 (p-Co 3 O 4 ) hollow cubes during galvanic replacement reaction (GRR). In addition, the Pd NPs encapsulated in MOF and residual Co 3 O 4 clusters partially remained after GRR led to uniform functionalization of efficient cocatalysts (PdO NPs and p-Co 3 O 4 islands) on the porous and hollow polyhedron SnO 2 structures. Due to high gas accessibility through the meso- and macrosized pores in MOF-templated oxides and effective modulation of electron depletion layer assisted by the creation of numerous p-n junctions, the GRR-treated SnO 2 structures exhibited 21.9-fold higher acetone response (R air /R gas = 22.8 @ 5 ppm acetone, 90%RH) compared to MOF-templated p-Co 3 O 4 hollow structures. To the best of our knowledge, the selectivity and response amplitudes reported here for the detection of acetone are superior to those MOF derived metal oxide sensing layers reported so far. Our results demonstrate that highly active MOF-derived sensing layers can be achieved via p-n semiconducting phase transition, driven by a simple and versatile GRR process combined with MOF templating route.

Prosthetic knee design by simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hollerbach, K; Hollister, A

1999-07-30

Although 150,000 total knee replacement surgeries are performed annually in North America, current designs of knee prostheses have mechanical problems that include a limited range of motion, abnormal gait patterns, patellofemoral joint dysfunction, implant loosening or subsidence, and excessive wear. These problems fall into three categories: failure to reproduce normal joint kinematics, which results in altered limb function; bone-implant interface failure; and material failure. Modern computer technology can be used to design, prototype, and test new total knee implants. The design team uses the full range of CAD-CAM to design and produce implant prototypes for mechanical and clinical testing. Closermore » approximation of natural knee kinematics and kinetics is essential for improved patient function and diminished implant loads. Current knee replacement designs are based on 19th Century theories that the knee moves about a variable axis of rotation. Recent research has shown, however, that knee motion occurs about two fixed, offset axes of rotation. These aces are not perpendicular to the long axes of the bones or to each other, and the axes do not intersect. Bearing surfaces of mechanisms that move about axes of rotation are surfaces of revolution of those axes which advanced CAD technology can produce. Solids with surfaces of revolution for the two axes of rotation for the knee have been made using an HP9000 workstation and Structural Ideas Master Series CAD software at ArthroMotion. The implant's CAD model should closely replicate movements of the normal knee. The knee model will have a range of flexion-extension (FE) from -5 to 120 degrees. Movements include varus, valgus, internal and external rotation, as well as flexion and extension. The patellofemoral joint is aligned perpendicular to the FE axis and replicates the natural joint more closely than those of existing prostheses. The bearing surfaces will be more congruent than current designs and should generate lower stresses in the materials.« less

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

PubMed Central

Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

2017-01-01

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

Prioritization methodology for chemical replacement

NASA Technical Reports Server (NTRS)

Goldberg, Ben; Cruit, Wendy; Schutzenhofer, Scott

1995-01-01

This methodology serves to define a system for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semi quantitative approach derived from quality function deployment techniques (QFD Matrix). QFD is a conceptual map that provides a method of transforming customer wants and needs into quantitative engineering terms. This methodology aims to weight the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives.

Effects of Kaolin Clay on the Mechanical Properties of Asphaltic Concrete AC14

NASA Astrophysics Data System (ADS)

Abdullah, M. E.; Ramadhansyah, P. J.; Rafsanjani, M. H.; Norhidayah, A. H.; Yaacob, H.; Hainin, M. R.; Warid, M. N. Mohd; Satar, M. K. I. Mohd; Aziz, Md Maniruzzaman A.; Mashros, N.

2018-04-01

This study investigated the effect of kaolin clay on the mechanical properties of asphaltic concrete AC14 through Marshall Stability, resilient modulus, and dynamic creep tests. Four replacement levels of kaolin clay (2%, 4%, 6%, and 8% by weight of the binder) were considered. Kaolin clay functioned as an effective filler replacement material to increase the mechanical properties of asphalt mixtures. Asphaltic concrete with 2% to 4% kaolin clay replacement level exhibited excellent performance with good stability, resilient modulus, and creep stiffness.

'Emerging technologies for the changing global market' - Prioritization methodology for chemical replacement

NASA Technical Reports Server (NTRS)

Cruit, Wendy; Schutzenhofer, Scott; Goldberg, Ben; Everhart, Kurt

1993-01-01

This project served to define an appropriate methodology for effective prioritization of technology efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semiquantitative approach derived from quality function deployment techniques (QFD Matrix). This methodology aims to weight the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives. The results will be implemented as a guideline for consideration for current NASA propulsion systems.

Description of the rates, trends and surgical burden associated with revision for prosthetic joint infection following primary and revision knee replacements in England and Wales: an analysis of the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

PubMed

Lenguerrand, Erik; Whitehouse, Michael R; Beswick, Andrew D; Toms, Andrew D; Porter, Martyn L; Blom, Ashley W

2017-07-10

To describe the prevalence rates of revision surgery for the treatment of prosthetic joint infection (PJI) for patients undergoing knee replacement, their time trends, the cumulative incidence function of revision for PJI and estimate the burden of PJI at health service level. We analysed revision knee replacements performed due to a diagnosis of PJI and the linked index procedures recorded in the National Joint Registry from 2003 to 2014 for England and Wales. The cohort analysed consisted of 679 010 index primary knee replacements, 33 920 index revision knee replacements and 8247 revision total knee replacements performed due to a diagnosis of PJI. The prevalence rates, their time trends investigated by time from index surgery to revision for PJI, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression. The incidence of revision total knee replacement due to PJI at 2 years was 3.2/1000 following primary and 14.4/1000 following revision knee replacement, respectively. The prevalence of revision due to PJI in the 3 months following primary knee replacement has risen by 2.5-fold (95% CI 1.2 to 5.3) from 2005 to 2013 and 7.5-fold (95% CI 1.0 to 56.1) following revision knee replacement. Over 1000 procedures per year are performed as a consequence of knee PJI, an increase of 2.8 from 2005 to 2013. Overall, 75% of revisions were two-stage with an increase in use of single-stage from 7.9% in 2005 to 18.8% in 2014. Although the risk of revision due to PJI following knee replacement is low, it is rising, and coupled with the established and further predicted increased incidence of both primary and revision knee replacements, this represents an increasing and substantial treatment burden for orthopaedic service delivery in England and Wales. This has implications for future service design and the funding of individual and specialist centres. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Description of the rates, trends and surgical burden associated with revision for prosthetic joint infection following primary and revision knee replacements in England and Wales: an analysis of the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man

PubMed Central

Lenguerrand, Erik; Whitehouse, Michael R; Beswick, Andrew D; Toms, Andrew D; Porter, Martyn L; Blom, Ashley W

2017-01-01

Objectives To describe the prevalence rates of revision surgery for the treatment of prosthetic joint infection (PJI) for patients undergoing knee replacement, their time trends, the cumulative incidence function of revision for PJI and estimate the burden of PJI at health service level. Design We analysed revision knee replacements performed due to a diagnosis of PJI and the linked index procedures recorded in the National Joint Registry from 2003 to 2014 for England and Wales. The cohort analysed consisted of 679 010 index primary knee replacements, 33 920 index revision knee replacements and 8247 revision total knee replacements performed due to a diagnosis of PJI. The prevalence rates, their time trends investigated by time from index surgery to revision for PJI, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression. Results The incidence of revision total knee replacement due to PJI at 2 years was 3.2/1000 following primary and 14.4/1000 following revision knee replacement, respectively. The prevalence of revision due to PJI in the 3 months following primary knee replacement has risen by 2.5-fold (95% CI 1.2 to 5.3) from 2005 to 2013 and 7.5-fold (95% CI 1.0 to 56.1) following revision knee replacement. Over 1000 procedures per year are performed as a consequence of knee PJI, an increase of 2.8 from 2005 to 2013. Overall, 75% of revisions were two-stage with an increase in use of single-stage from 7.9% in 2005 to 18.8% in 2014. Conclusions Although the risk of revision due to PJI following knee replacement is low, it is rising, and coupled with the established and further predicted increased incidence of both primary and revision knee replacements, this represents an increasing and substantial treatment burden for orthopaedic service delivery in England and Wales. This has implications for future service design and the funding of individual and specialist centres. PMID:28698316

Geranylgeranyl diphosphate synthases from Scoparia dulcis and Croton sublyratus. cDNA cloning, functional expression, and conversion to a farnesyl diphosphate synthase.

PubMed

Kojima, N; Sitthithaworn, W; Viroonchatapan, E; Suh, D Y; Iwanami, N; Hayashi, T; Sankaw, U

2000-07-01

cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene producing plants, Scoparia dulcis and Croton sublyratus, were isolated using the homology-based polymerase chain reaction method. Both cloned genes showed high amino acid sequence homology (60-70%) to other plant GGPPSs and contained highly conserved aspartate-rich motifs. The obtained clones were functionally expressed in Escherichia coli and showed sufficient GGPPS activity to catalyze the condensation of farnesyl diphosphate (FPP) and isopentenyl diphosphate to form geranylgeranyl diphosphate. To investigate the factor determining the product chain length of plant GGPPSs, S. dulcis GGPPS mutants in which either the small amino acids at the fourth and fifth positions before the first aspartate-rich motif (FARM) were replaced with aromatic amino acids or in which two additional amino acids in FARM were deleted were constructed. Both mutants behaved like FPPS-like enzymes and almost exclusively produced FPP when dimethylallyl diphosphate was used as a primer substrate, and failed to accept FPP as a primer substrate. These results indicate that both small amino acids at the fourth and fifth positions before FARM and the amino acid insertion in FARM play essential roles in product length determination in plant GGPPSs.

Probing transcription-specific outputs of β-catenin in vivo.

PubMed

Valenta, Tomas; Gay, Max; Steiner, Sarah; Draganova, Kalina; Zemke, Martina; Hoffmans, Raymond; Cinelli, Paolo; Aguet, Michel; Sommer, Lukas; Basler, Konrad

2011-12-15

β-Catenin, apart from playing a cell-adhesive role, is a key nuclear effector of Wnt signaling. Based on activity assays in Drosophila, we generated mouse strains where the endogenous β-catenin protein is replaced by mutant forms, which retain the cell adhesion function but lack either or both of the N- and the C-terminal transcriptional outputs. The C-terminal activity is essential for mesoderm formation and proper gastrulation, whereas N-terminal outputs are required later during embryonic development. By combining the double-mutant β-catenin with a conditional null allele and a Wnt1-Cre driver, we probed the role of Wnt/β-catenin signaling in dorsal neural tube development. While loss of β-catenin protein in the neural tube results in severe cell adhesion defects, the morphology of cells and tissues expressing the double-mutant form is normal. Surprisingly, Wnt/β-catenin signaling activity only moderately regulates cell proliferation, but is crucial for maintaining neural progenitor identity and for neuronal differentiation in the dorsal spinal cord. Our model animals thus allow dissecting signaling and structural functions of β-catenin in vivo and provide the first genetic tool to generate cells and tissues that entirely and exclusively lack canonical Wnt pathway activity. © 2011 by Cold Spring Harbor Laboratory Press

Simultaneous bilateral total knee and ankle arthroplasty as a single surgical procedure.

PubMed

Pagenstert, Geert; Hintermann, Beat

2011-10-13

Simultaneous osteoarthritis (OA) of the ankle joint complicates primary total knee arthroplasty (TKA). In such cases, rehabilitation of TKA is limited by debilitating ankle pain, but varus or valgus ankle arthritis may even compromise placement of knee prosthetic components. We present a patient with simultaneous bilateral valgus and patellofemoral OA of the knees and bilateral varus OA of the ankle joints that equally contributed to overall disability. This 63 years old, motivated and otherwise healthy patient was treated by simultaneous bilateral total knee and ankle arthroplasty (quadruple total joint arthroplasty, TJA) during the same anesthesia. Two years outcome showed excellent alignment and function of all four replaced joints. Postoperative time for rehabilitation, back to work (6th week) and hospital stay (12 days) of this special patient was markedly reduced compared to the usual course of separate TJA. Simultaneous quadruple TJA in equally disabling OA of bilateral deformed knees and ankles resulted in a better functional outcome and faster recovery compared to the average reported results after TKA and TAA in literature. However, careful preoperative planning, extensive patient education, and two complete surgical teams were considered essential for successful performance. To the best of our knowledge this is the first case report in literature about quadruple major total joint arthroplasty implanted during the same anesthesia in the same patient.

An adaptation to life in acid through a novel mevalonate pathway

DOE PAGES

Vinokur, Jeffrey M.; Cummins, Matthew C.; Korman, Tyler P.; ...

2016-12-22

Here, extreme acidophiles are capable of growth at pH values near zero. Sustaining life in acidic environments requires extensive adaptations of membranes, proton pumps, and DNA repair mechanisms. Here we describe an adaptation of a core biochemical pathway, the mevalonate pathway, in extreme acidophiles. Two previously known mevalonate pathways involve ATP dependent decarboxylation of either mevalonate 5-phosphate or mevalonate 5-pyrophosphate, in which a single enzyme carries out two essential steps: (1) phosphorylation of the mevalonate moiety at the 3-OH position and (2) subsequent decarboxylation. We now demonstrate that in extreme acidophiles, decarboxylation is carried out by two separate steps: previouslymore » identified enzymes generate mevalonate 3,5-bisphosphate and a new decarboxylase we describe here, mevalonate 3,5-bisphosphate decarboxylase, produces isopentenyl phosphate. Why use two enzymes in acidophiles when one enzyme provides both functionalities in all other organisms examined to date? We find that at low pH, the dual function enzyme, mevalonate 5-phosphate decarboxylase is unable to carry out the first phosphorylation step, yet retains its ability to perform decarboxylation. We therefore propose that extreme acidophiles had to replace the dual-purpose enzyme with two specialized enzymes to efficiently produce isoprenoids in extremely acidic environments.« less

An adaptation to life in acid through a novel mevalonate pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vinokur, Jeffrey M.; Cummins, Matthew C.; Korman, Tyler P.

Here, extreme acidophiles are capable of growth at pH values near zero. Sustaining life in acidic environments requires extensive adaptations of membranes, proton pumps, and DNA repair mechanisms. Here we describe an adaptation of a core biochemical pathway, the mevalonate pathway, in extreme acidophiles. Two previously known mevalonate pathways involve ATP dependent decarboxylation of either mevalonate 5-phosphate or mevalonate 5-pyrophosphate, in which a single enzyme carries out two essential steps: (1) phosphorylation of the mevalonate moiety at the 3-OH position and (2) subsequent decarboxylation. We now demonstrate that in extreme acidophiles, decarboxylation is carried out by two separate steps: previouslymore » identified enzymes generate mevalonate 3,5-bisphosphate and a new decarboxylase we describe here, mevalonate 3,5-bisphosphate decarboxylase, produces isopentenyl phosphate. Why use two enzymes in acidophiles when one enzyme provides both functionalities in all other organisms examined to date? We find that at low pH, the dual function enzyme, mevalonate 5-phosphate decarboxylase is unable to carry out the first phosphorylation step, yet retains its ability to perform decarboxylation. We therefore propose that extreme acidophiles had to replace the dual-purpose enzyme with two specialized enzymes to efficiently produce isoprenoids in extremely acidic environments.« less

Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) oxidase (tNOX) of the HeLa cell surface

NASA Technical Reports Server (NTRS)

Chueh, Pin-Ju; Kim, Chinpal; Cho, NaMi; Morre, Dorothy M.; Morre, D. James

2002-01-01

NOX proteins are growth-related cell surface proteins that catalyze both hydroquinone or NADH oxidation and protein disulfide interchange and exhibit prion-like properties. The two enzymatic activities alternate to generate a regular period length of about 24 min. Here we report the expression, cloning, and characterization of a tumor-associated NADH oxidase (tNOX). The cDNA sequence of 1830 bp is located on gene Xq25-26 with an open reading frame encoding 610 amino acids. The activities of the bacterially expressed tNOX oscillate with a period length of 22 min as is characteristic of tNOX activities in situ. The activities are inhibited completely by capsaicin, which represents a defining characteristic of tNOX activity. Functional motifs identified by site-directed mutagenesis within the C-terminal portion of the tNOX protein corresponding to the processed plasma membrane-associated form include quinone (capsaicin), copper and adenine nucleotide binding domains, and two cysteines essential for catalytic activity. Four of the six cysteine to alanine replacements retained enzymatic activity, but the period lengths of the oscillations were increased. A single protein with two alternating enzymatic activities indicative of a time-keeping function is unprecedented in the biochemical literature.

Ortholog-based screening and identification of genes related to intracellular survival.

PubMed

Yang, Xiaowen; Wang, Jiawei; Bing, Guoxia; Bie, Pengfei; De, Yanyan; Lyu, Yanli; Wu, Qingmin

2018-04-20

Bioinformatics and comparative genomics analysis methods were used to predict unknown pathogen genes based on homology with identified or functionally clustered genes. In this study, the genes of common pathogens were analyzed to screen and identify genes associated with intracellular survival through sequence similarity, phylogenetic tree analysis and the λ-Red recombination system test method. The total 38,952 protein-coding genes of common pathogens were divided into 19,775 clusters. As demonstrated through a COG analysis, information storage and processing genes might play an important role intracellular survival. Only 19 clusters were present in facultative intracellular pathogens, and not all were present in extracellular pathogens. Construction of a phylogenetic tree selected 18 of these 19 clusters. Comparisons with the DEG database and previous research revealed that seven other clusters are considered essential gene clusters and that seven other clusters are associated with intracellular survival. Moreover, this study confirmed that clusters screened by orthologs with similar function could be replaced with an approved uvrY gene and its orthologs, and the results revealed that the usg gene is associated with intracellular survival. The study improves the current understanding of intracellular pathogens characteristics and allows further exploration of the intracellular survival-related gene modules in these pathogens. Copyright © 2018. Published by Elsevier B.V.

Birth, death, and replacement of karyopherins in Drosophila.

PubMed

Phadnis, Nitin; Hsieh, Emily; Malik, Harmit S

2012-05-01

Nucleocytoplasmic transport is a broadly conserved process across eukaryotes. Despite its essential function and conserved mechanism, components of the nuclear transport apparatus have been implicated in genetic conflicts in Drosophila, especially in the male germ line. The best understood case is represented by a truncated RanGAP gene duplication that is part of the segregation distorter system in Drosophila melanogaster. Consistent with the hypothesis that the nuclear transport pathway is at the heart of mediating genetic conflicts, both nucleoporins and directionality imposing components of nuclear transport have previously been shown to evolve under positive selection. Here, we present a comprehensive phylogenomic analysis of importins (karyopherins) in Drosophila evolution. Importins are adaptor molecules that physically mediate the transport of cargo molecules and comprise the third component of the nuclear transport apparatus. We find that importins have been repeatedly gained and lost throughout various stages of Drosophila evolution, including two intriguing examples of an apparently coincident loss and gain of nonorthologous and noncanonical importin-α. Although there are a few signatures of episodic positive selection, genetic innovation in importin evolution is more evident in patterns of recurrent gene birth and loss specifically for function in Drosophila testes, which is consistent with their role in supporting host genomes defense against segregation distortion.

Recommendations for fitness for work medical evaluations in chronic respiratory patients. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR).

PubMed

Martínez González, Cristina; González Barcala, Francisco Javier; Belda Ramírez, José; González Ros, Isabel; Alfageme Michavila, Inmaculada; Orejas Martínez, Cristina; González Rodríguez-Moro, José Miguel; Rodríguez Portal, José Antonio; Fernández Álvarez, Ramón

2013-11-01

Chronic respiratory diseases often cause impairment in the functions and/or structure of the respiratory system, and impose limitations on different activities in the lives of persons who suffer them. In younger patients with an active working life, these limitations can cause problems in carrying out their normal work. Article 41 of the Spanish Constitution states that «the public authorities shall maintain a public Social Security system for all citizens guaranteeing adequate social assistance and benefits in situations of hardship». Within this framework is the assessment of fitness for work, as a dual-nature process (medico-legal) that aims to determine whether it is appropriate or not to recognise a person's right to receive benefits which replace the income that they no longer receive as they cannot carry out their work, due to loss of health. The role of the pulmonologist is essential in evaluating the diagnosis, treatment, prognosis and functional capacity of respiratory patients. These recommendations seek to bring the complex setting of fitness for work evaluation to pulmonologists and thoracic surgeons, providing action guidelines that allow them to advise their own patients about their incorporation into working life. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Switching PD-based sliding mode control for hovering of a tilting-thruster underwater robot.

PubMed

Jin, Sangrok; Bak, Jeongae; Kim, Jongwon; Seo, TaeWon; Kim, Hwa Soo

2018-01-01

This paper presents a switching PD-based sliding mode control (PD-SMC) method for the 6-degree-of-freedom (DOF) hovering motion of the underwater robot with tilting thrusters. Four thrusters of robot can be tilted simultaneously in the horizontal and vertical directions, and the 6-DOF motion is achieved by switching between two thruster configurations. Therefore, the tilting speed of thruster becomes the most essential parameter to determine the stability of hovering motion. Even though the previous PD control ensures stable hovering motion within a certain ranges of tilting speed, a PD-SMC is suggested in this paper by combining PD control with sliding mode control in order to achieve acceptable hovering performance even at the much lower tilting speeds. Also, the sign function in the sliding mode control is replaced by a sigmoid function to reduce undesired chattering. Simulations show that while PD control is effective only for tilting duration of 600 ms, the PD-based sliding mode control can guarantee the stable hovering motion of underwater robot even for the tilting duration of up to 1500 ms. Extensive experimental results confirm the hovering performance of the proposed PD-SMC method is much superior to that of PD method for much larger tilting durations.

Establishing the framework to support bioartificial heart fabrication using fibrin-based three-dimensional artificial heart muscle.

PubMed

Hogan, Matthew; Mohamed, Mohamed; Tao, Ze-Wei; Gutierrez, Laura; Birla, Ravi

2015-02-01

Only 3000 heart transplants are performed in the USA every year, leaving some 30 000-70 000 Americans without proper care. Current treatment modalities for heart failure have saved many lives yet still do not correct the underlying problems of congestive heart failure. Tissue engineering represents a potential field of study wherein a combination of cells, scaffolds, and/or bioreactors can be utilized to create constructs to mimic, replace, and/or repair defective tissue. The focus of this study was to generate a bioartificial heart (BAH) model using artificial heart muscle (AHM), composed of fibrin gel and neonatal rat cardiac myocytes, and a decellularized scaffold, formed by subjecting an adult rat heart to a series of decellularization solutions. By suturing the AHM around the outside of the decellularized heart and culturing while suspended in media, we were able to retain functional cardiac cells on the scaffold as evinced by visible contractility. Observed contractility rate was correlated with biopotential measurements to confirm essential functionality of cardiac constructs. Cross-sections of the BAH show successful decellularization of the scaffold and contiguous cell-rich AHM around the perimeter of the heart. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Conciliation biology: the eco-evolutionary management of permanently invaded biotic systems

PubMed Central

Carroll, Scott P

2011-01-01

Biotic invaders and similar anthropogenic novelties such as domesticates, transgenics, and cancers can alter ecology and evolution in environmental, agricultural, natural resource, public health, and medical systems. The resulting biological changes may either hinder or serve management objectives. For example, biological control and eradication programs are often defeated by unanticipated resistance evolution and by irreversibility of invader impacts. Moreover, eradication may be ill-advised when nonnatives introduce beneficial functions. Thus, contexts that appear to call for eradication may instead demand managed coexistence of natives with nonnatives, and yet applied biologists have not generally considered the need to manage the eco-evolutionary dynamics that commonly result from interactions of natives with nonnatives. Here, I advocate a conciliatory approach to managing systems where novel organisms cannot or should not be eradicated. Conciliatory strategies incorporate benefits of nonnatives to address many practical needs including slowing rates of resistance evolution, promoting evolution of indigenous biological control, cultivating replacement services and novel functions, and managing native–nonnative coevolution. Evolutionary links across disciplines foster cohesion essential for managing the broad impacts of novel biotic systems. Rather than signaling defeat, conciliation biology thus utilizes the predictive power of evolutionary theory to offer diverse and flexible pathways to more sustainable outcomes. PMID:25567967

Management of methicillin-resistant Staphylococcus aureus bacteremia.

PubMed

Cosgrove, Sara E; Fowler, Vance G

2008-06-01

Staphylococcus aureus bacteremia and endocarditis are serious infections that demand prompt clinical attention to ensure good outcomes. Of foremost importance is identifying and managing the source of infection and any associated complications. Evaluation for the presence of cardiac involvement is essential because inadequately managed S. aureus endocarditis is life threatening. Thus, physicians must aggressively negotiate treatment paths, considering whether the S. aureus bacteremia is complicated, whether foreign sources of infection should be removed or replaced, and whether surgical intervention is necessary. Selection of an antibiotic treatment is also an essential factor for optimal management. The increasing prevalence of methicillin-resistant S. aureus (MRSA) infections has created a tremendous demand for effective and safe antimicrobial agents other than the historic anti-MRSA agent vancomycin.

Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours.

PubMed

Masugi-Tokita, M; Yoshida, T; Kageyama, S; Kawata, M; Kawauchi, A

2018-03-01

Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localised to presynaptic active zones of the mammalian central nervous system. We previously reported that mGluR7 is essential for intermale aggression and amygdala-dependent fear learning. To elucidate the role of mGluR7 in the neuroendocrine system, we performed biochemical analyses and found a significant reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone replacement restored intermale aggressive behaviour in castrated wild-type mice to the level of gonadally intact wild-type mice. However, given the same dosage of testosterone replacement, mGluR7 KO mice showed almost no aggressive behaviour. These results indicate that reduction of plasma testosterone is unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social investigating behaviour of intact mGluR7 KO mice also differed from that of wild-type mice; e.g. the KO mice showing less frequent anogenital sniffing and more frequent grooming behaviour. Testosterone replacement increased anogenital sniffing and grooming behaviour in castrated mGluR7 KO mice, while the differences were still present between castrated wild-type mice and KO mice after both underwent testosterone replacement. These results imply that reduction of plasma testosterone may partially inhibit social investigating behaviours in intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal vesicles than those of castrated wild-type mice, although seminal vesicle weights were normal in intact mice. These observations suggest that, besides testicular testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice, and indicate a critical role of mGluR7 in the endocrine system. Taken together, our findings demonstrate that mGluR7 is essential for the regulation of the endocrine system, in addition to innate behaviours such as intermale aggression and fear response. © 2018 British Society for Neuroendocrinology.

Isotemporal Substitution of Sedentary Behavior and Physical Activity on Function.

PubMed

Lerma, Nicholas L; Cho, Chi C; Swartz, Ann M; Miller, Nora E; Keenan, Kevin G; Strath, Scott J

2018-04-01

The amount of time spent in sedentary behaviors (SB) progressively increases with age, while reducing time spent in light-intensity physical activity (LPA) and moderate- to vigorous-intensity physical activity (MVPA). These trajectories in PA and SB are linked to accelerated reductions in physical functioning. This study aimed to examine the association of substituting SB time with LPA and MVPA on physical function in older adults. Ninety-one older adults (mean age, 70.7 ± 10.2 yr) wore a hip-mounted accelerometer to measure SB, LPA, and MVPA time. Measures of physical function included a 400-m walk test (400W), the usual gait speed (UGS), the five times sit-to-stand (5xSTS) test, and the short physical performance battery (SPPB). Isotemporal substitution regression modeling was performed to assess the relationship of replacing the amount of time spent in one activity for another. Replacing 30 min·d of SB with LPA was associated with a significant improvement in 400W (P = 0.0497), whereas MVPA resulted in a significant improvement (P < 0.01) in 400W, UGS, 5xSTS, and SPPB. Replacing 60 min·d of SB with 10 min·d of MVPA and 50 min·d of LPA was associated with significant improvements in the 400W, UGS, and 5xSTS (P < 0.05). Meanwhile, as little as 5 min·d of MVPA and 55 min·d of LPA were linked to a 78% increased odds of scoring with good function in the SPPB (P = 0.0247). Replacing SB with LPA was linked to a significant improvement in the 400W, but not the other brief functional measures. Mixed doses of LPA and MVPA may add flexibility to interventions targeting reductions of SB in older adults for clinically relevant improvements in physical function.

Should patients with Björk-Shiley valves undergo prophylactic replacement?

PubMed

Birkmeyer, J D; Marrin, C A; O'Connor, G T

1992-08-29

About 85,000 patients have undergone replacement of diseased heart valves with prosthetic Björk-Shiley convexo-concave (CC) valves. These valves are prone to fracture of the outlet strut, which leads to acute valve failure that is usually fatal. Should patients with these valves undergo prophylactic replacement to avoid fracture? The incidence of strut fracture varies between 0% and 1.5% per year, depending on valve opening angle (60 degrees or 70 degrees), diameter (less than 29 mm or greater than or equal to 29 mm), and location (aortic or mitral). Other factors include the patient's life expectancy and the expected morbidity and mortality associated with reoperation. We have used decision analysis to identify the patients most likely to benefit from prophylactic reoperation. The incidence of outlet strut fracture was estimated from the data of three large studies on CC valves, and stratified by opening angle, diameter, and location. A Markov decision analysis model was used to estimate life expectancy for patients undergoing prophylactic valve replacement and for those not undergoing reoperation. Prophylactic valve replacement does not benefit patients with CC valves that have low strut fracture risks (60 degrees aortic valves and less than 29 mm, 60 degrees mitral valves). For most patients with CC valves that have high strut fracture risks (greater than or equal to 29 mm, 70 degrees CC), prophylactic valve replacement increases life expectancy. However, elderly patients with such valves benefit from prophylactic reoperation only if the risk of operative mortality is low. Patient age and operative risk are most important in recommendations for patients with CC valves that have intermediate strut fracture risks (less than 29 mm, 70 degrees valves and greater than or equal to 29 mm, 60 degrees mitral valves). For all patients and their doctors facing the difficult decision on whether to replace CC valves, individual estimates of operative mortality risk that take account of both patient-specific and institution-specific factors are essential.

Larvicidal Activity of Essential Oils of Five Apiaceae Taxa and Some of Their Main Constituents Against Culex quinquefasciatus.

PubMed

Pavela, Roman; Maggi, Filippo; Cianfaglione, Kevin; Bruno, Maurizio; Benelli, Giovanni

2018-01-01

Apiaceae are aromatic herbs producing essential oils which are used on an industrial scale for various purposes. Notably, Apiaceae essential oils may replace synthetic insecticides keeping most of their efficacy and avoiding environmental pollution and human poisoning. In the present work, we explored the insecticidal potential of the essential oils from five Apiaceae taxa, namely Sison amomum, Echinophora spinosa, Heracleum sphondylium subsp. sphondylium, Heracleum sphondylium subsp. ternatum, and Trachyspemum ammi, as well as their major constituents (sabinene, p-cymene, terpinolene, myristicin, and thymol), against the filariasis vector Culex quinquefasciatus. For the purpose, the essential oils were obtained by hydrodistillation and their composition was achieved by gas chromatography/mass spectrometry (GC/MS). Their acute toxicity on third instar larvae of C. quinquefasciatus was determined. The two most active essential oils were those from T. ammi fruits and E. spinosa roots, showing LC 50 below 20 μl/l and LD 90 below 50 μl/l. These oils were dominated by the monoterpene phenol thymol and the phenylpropanoid myristicin, respectively, which showed the strongest larvicidal activity (LC 50 of 15.1 and 16.3 μl/l, respectively) among the pure compounds tested. These results showed that Apiaceae may be useful as source of larvicidal compounds to be used for the development of cheap, effective and eco-friendly insecticidal formulations. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Evaluation of COSHH essentials: methylene chloride, isopropanol, and acetone exposures in a small printing plant.

PubMed

Lee, Eun Gyung; Harper, Martin; Bowen, Russell B; Slaven, James

2009-07-01

The current study evaluated the Control of Substances Hazardous to Health (COSHH) Essentials model for short-term task-based exposures and full-shift exposures using measured concentrations of three volatile organic chemicals at a small printing plant. A total of 188 exposure measurements of isopropanol and 187 measurements of acetone were collected and each measurement took approximately 60 min. Historically, collected time-weighted average concentrations (seven results) were evaluated for methylene chloride. The COSHH Essentials model recommended general ventilation control for both isopropanol and acetone. There was good agreement between the task-based exposure measurements and the COSHH Essentials predicted exposure range (PER) for cleaning and print preparation with isopropanol and for cleaning with acetone. For the other tasks and for full-shift exposures, agreement between the exposure measurements and the PER was either moderate or poor. However, for both isopropanol and acetone, our findings suggested that the COSHH Essentials model worked reasonably well because the probabilities of short-term exposure measurements exceeding short-term occupational exposure limits (OELs) or full-shift exposures exceeding the corresponding full-shift OELs were <0.05 under the recommended control strategy. For methylene chloride, the COSHH Essentials recommended containment control but a follow-up study was not able to be performed because it had already been replaced with a less hazardous substance (acetone). This was considered a more acceptable alternative to increasing the level of control.

Taste function in xerostomia before and after treatment with a saliva substitute containing carboxymethylcellulose.

PubMed

Temmel, Andreas F P; Quint, Christian; Schickinger-Fischer, Bettina; Hummel, Thomas

2005-04-01

The feeling of a dry mouth may affect individual dietary habits, nutritional status, oral hygiene, speech, and gustatory sensitivity. The present study aimed to specifically investigate gustatory function before and after saliva replacement therapy. Whole-mouth gustatory function was assessed in 25 patients suffering from xerostomia (6 male, 19 female; age range 42-82 years) before and after 4 to 6 weeks of saliva replacement therapy using a preparation containing carboxymethylcellulose. The results were compared with those from healthy controls matched for age and sex (6 male, 19 female; age range 42-82 years). Using a whole-mouth test, gustatory function was assessed for sucrose, citric acid, sodium chloride, and caffeine. All subjects detected the four taste qualities at the highest concentration. However, the patients with xerostomia had lower scores in the gustatory test compared with the healthy controls (p < .001). No correlation was found between gustatory scores and the duration or severity of the disorder. Therapy had no effect on measured gustatory function (p = .33); however, saliva replacement led to a significant improvement in other xerostomia-related symptoms (p < .001). This study confirms previous work indicating that xerostomia is accompanied by decreased gustatory sensitivity. Lubricants based on carboxymethylcellulose may have a positive effect on some of the symptoms of xerostomia. However, these "simple" lubricants based on carboxymethylcellulose have little or no effect on whole-mouth gustatory function.

Integrable RCS as a Proposed Replacement for Fermilab Booster

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eldred, Jeffrey; Valishev, Alexander

2017-03-07

Integrable optics is an innovation in particle accelerator design that potentially enables a greater betatron tune spread and damps collective instabilities. An integrable rapid-cycling synchrotron (RCS) would be an effective replacement for the Fermilab Booster, as part of a plan to reach multi-MW beam power at 120 GeV for the Fermilab high-energy neutrino program. We provide an example integrable lattice with features of a modern RCS - dispersion-free drifts, low momentum compaction factor, superperiodicity, chromaticity correction, bounded beta functions, and separate-function magnets.

[Phonological characteristics and rehabilitation training of abnormal velar in children with functional articulation disorders].

PubMed

Lina, Xu; Feng, Li; Yanyun, Zhang; Nan, Gao; Mingfang, Hu

2016-12-01

To explore the phonological characteristics and rehabilitation training of abnormal velar in patients with functional articulation disorders (FAD). Eighty-seven patients with FAD were observed of the phonological characteristics of velar. Seventy-two patients with abnormal velar accepted speech training. The correlation and simple linear regression analysis were carried out on abnormal velar articulation and age. The articulation disorder of /g/ mainly showed replacement by /d/, /b/ or omission. /k/ mainly showed replacement by /d/, /t/, /g/, /p/, /b/. /h/ mainly showed replacement by /g/, /f/, /p/, /b/ or omission. The common erroneous articulation forms of /g/, /k/, /h/ were fronting of tongue and replacement by bilabial consonants. When velar combined with vowels contained /a/ and /e/, the main error was fronting of tongue. When velar combined with vowels contained /u/, the errors trended to be replacement by bilabial consonants. After 3 to 10 times of speech training, the number of erroneous words decreased to (6.24±2.61) from (40.28±6.08) before the speech training was established, the difference was statistically significant (Z=-7.379, P=0.000). The number of erroneous words was negatively correlated with age (r=-0.691, P=0.000). The result of simple linear regression analysis showed that the determination coefficient was 0.472. The articulation disorder of velar mainly shows replacement, varies with the vowels. The targeted rehabilitation training hereby established is significantly effective. Age plays an important role in the outcome of velar.

Fine tuning of the spectral properties of LH2 by single amino acid residues.

PubMed

Silber, Martina V; Gabriel, Günther; Strohmann, Brigitte; Garcia-Martin, Adela; Robert, Bruno; Braun, Paula

2008-05-01

The peripheral light-harvesting complex, LH2, of Rhodobacter sphaeroides consists of an assembly of membrane-spanning alpha and beta polypeptides which assemble the photoactive bacteriochlorophyll and carotenoid molecules. In this study we systematically investigated bacteriochlorophyll-protein interactions and their effect on functional bacteriochlorophyll assembly by site-directed mutations of the LH2 alpha-subunit. The amino acid residues, isoleucine at position -1 and serine at position -4 were replaced by 12 and 13 other residues, respectively. All residues replacing isoleucine at position -1 supported the functional assembly of LH2. The replacement of isoleucine by glycine, glutamine or asparagine, however, produced LH2 complex with significantly altered spectral properties in comparison to LH2 WT. As indicated by resonance Raman spectroscopy extensive rearrangement of the bacteriochlorophyll-B850 macrocycle(s) took place in LH2 in which isoleucine -1 was replaced by glycine. The replacement results in disruption of the H-bond between the C3 acetyl groups and the aromatic residues +13/+14 without affecting the H-bond involving the C13(1) keto group. In contrast, nearly all amino acid replacements of serine at position -4 resulted in shifting of the bacteriochlorophyll-B850 red most absorption maximum. Interestingly, the extent of shifting closely correlated with the volume of the residue at position -4. These results illustrate that fine tuning of the spectral properties of the bacteriochlorophyll-B850 molecules depend on their packing with single amino acid residues at distinct positions.

Comparative Study of Surface Chemical Composition and Oxide Layer Modification upon Oxygen Plasma Cleaning and Piranha Etching on a Novel Low Elastic Modulus Ti25Nb21Hf Alloy

NASA Astrophysics Data System (ADS)

Paredes, Virginia; Salvagni, Emiliano; Rodríguez-Castellón, Enrique; Manero, José María

2017-08-01

Metals are widely employed for many biological artificial replacements, and it is known that the quality and the physical/chemical properties of the surface are crucial for the success of the implant. Therefore, control over surface implant materials and their elastic moduli may be crucial to avoid undesired effects. In this study, surface modification upon cleaning and activation of a low elastic modulus Ti alloy (Ti25Hf21Nb) was investigated. Two different methods, oxygen plasma (OP) cleaning and piranha (PI) solution, were studied and compared. Both surface treatments were effective for organic contaminant removal and to increase the Ti-oxide layer thickness rather than other metal-oxides present at the surface, which is beneficial for biocompatibility of the material. Furthermore, both techniques drastically increased hydrophilicity and introduced oxidation and hydroxylation (OH)-functional groups at the surface that may be beneficial for further chemical modifications. However, these treatments did not alter the surface roughness and bulk material properties. The surfaces were fully characterized in terms of surface roughness, wettability, oxide layer composition, and hydroxyl surface density through analytical techniques (interferometry, X-ray photoelectron spectroscopy (XPS), contact angle, and zinc complexation). These findings provide essential information when planning surface modifications for cleanliness, oxide layer thickness, and surface hydroxyl density, as control over these factors is essential for many applications, especially in biomaterials.

Bioregenerative life support: not a picnic

NASA Technical Reports Server (NTRS)

Knott, W. M.

1998-01-01

If humans are to live permanently in space, regenerative life support systems are an enabling technology and must replace the picnic approach of taking all supplies required for each mission. These systems are classified by technologies as either physical/chemical or bioregenerative. Both of these system-types can recycle water, remove carbon dioxide, produce oxygen, and recover essential elements from waste products. Bioregenerative can also produce food, thus, making it essential if humans are to exist in space independent of earth. A solely bioregenerative life support system includes plants as a biomass production module and microbial organisms in bioreactors as a resource recovery module. In the Advanced Life Support Program, bioregenerative life support systems are being investigated through a research and technology development project which includes large scale testing as part of the Breadboard Project and human tests conducted in the soon to be constructed BioPlex facility. Research and technology development efforts are directed toward optimizing biomass productivity in controlled chambers by developing light weight, energy efficient, and automated systems; recycling liquid and solid wastes; baselining the operation of bioreactors; determining system microbial stability; assessing chemical contamination; and building models required for long term system operations. The program will include space flight studies in the near future to determine if these life support technologies will function in microgravity. When a bioregenerative system is finally incorporated into a mission, the conversion from a picnic and resupply mentality to permanent recycling and independence from earth will be complete.

Autophagy-Associated Protein SmATG12 Is Required for Fruiting-Body Formation in the Filamentous Ascomycete Sordaria macrospora

PubMed Central

Werner, Antonia; Herzog, Britta; Frey, Stefan; Pöggeler, Stefanie

2016-01-01

In filamentous fungi, autophagy functions as a catabolic mechanism to overcome starvation and to control diverse developmental processes under normal nutritional conditions. Autophagy involves the formation of double-membrane vesicles, termed autophagosomes that engulf cellular components and bring about their degradation via fusion with vacuoles. Two ubiquitin-like (UBL) conjugation systems are essential for the expansion of the autophagosomal membrane: the UBL protein ATG8 is conjugated to the lipid phosphatidylethanolamine and the UBL protein ATG12 is coupled to ATG5. We recently showed that in the homothallic ascomycete Sordaria macrospora autophagy-related genes encoding components of the conjugation systems are required for fruiting-body development and/or are essential for viability. In the present work, we cloned and characterized the S. macrospora (Sm)atg12 gene. Two-hybrid analysis revealed that SmATG12 can interact with SmATG7 and SmATG3. To examine its role in S. macrospora, we replaced the open reading frame of Smatg12 with a hygromycin resistance cassette and generated a homokaryotic ΔSmatg12 knockout strain, which displayed slower vegetative growth under nutrient starvation conditions and was unable to form fruiting bodies. In the hyphae of S. macrospora EGFP-labeled SmATG12 was detected in the cytoplasm and as punctate structures presumed to be phagophores or phagophore assembly sites. Delivery of EGFP-labelled SmATG8 to the vacuole was entirely dependent on SmATG12. PMID:27309377

Autophagy-Associated Protein SmATG12 Is Required for Fruiting-Body Formation in the Filamentous Ascomycete Sordaria macrospora.

PubMed

Werner, Antonia; Herzog, Britta; Frey, Stefan; Pöggeler, Stefanie

2016-01-01

In filamentous fungi, autophagy functions as a catabolic mechanism to overcome starvation and to control diverse developmental processes under normal nutritional conditions. Autophagy involves the formation of double-membrane vesicles, termed autophagosomes that engulf cellular components and bring about their degradation via fusion with vacuoles. Two ubiquitin-like (UBL) conjugation systems are essential for the expansion of the autophagosomal membrane: the UBL protein ATG8 is conjugated to the lipid phosphatidylethanolamine and the UBL protein ATG12 is coupled to ATG5. We recently showed that in the homothallic ascomycete Sordaria macrospora autophagy-related genes encoding components of the conjugation systems are required for fruiting-body development and/or are essential for viability. In the present work, we cloned and characterized the S. macrospora (Sm)atg12 gene. Two-hybrid analysis revealed that SmATG12 can interact with SmATG7 and SmATG3. To examine its role in S. macrospora, we replaced the open reading frame of Smatg12 with a hygromycin resistance cassette and generated a homokaryotic ΔSmatg12 knockout strain, which displayed slower vegetative growth under nutrient starvation conditions and was unable to form fruiting bodies. In the hyphae of S. macrospora EGFP-labeled SmATG12 was detected in the cytoplasm and as punctate structures presumed to be phagophores or phagophore assembly sites. Delivery of EGFP-labelled SmATG8 to the vacuole was entirely dependent on SmATG12.

Complications in implant dentistry

PubMed Central

Hanif, Ayesha; Qureshi, Saima; Sheikh, Zeeshan; Rashid, Haroon

2017-01-01

After tooth loss, an individual may seek tooth replacement so that his/her function and esthetics could be restored. Clinical prosthodontics, during the past decade, has significantly improved and developed according to the advancements in the science and patient's demands and needs. Conventional options in prosthodontics for substituting a missing single tooth include the removable partial denture, partial and full coverage bridgework, and resin-bonded bridgework. Dental implants have gained increasing popularity over the years as they are capable of restoring the function to near normal in both partial and completely edentulous arches. With substantial evidence available, fixed implant-supported prosthesis are fully acknowledged as a reliable treatment option for the replacement of single or multiple missing teeth nowadays. While dental implants are increasingly becoming the choice of replacement for missing teeth, the impediments associated with them are progressively emerging too. PMID:28435381