are gram-negative, obligate, intracellular bacteria carried by a majority of insect species worldwide. Here we use a
-infected
cell line and genome-wide RNA interference (RNAi) screening to identify ...host factors that influence
titer. By screening an RNAi library targeting 15,699 transcribed host genes, we identified 36 candidate genes that dramatically reduced
titer and 41 that increased
titer. Host gene knockdowns that reduced
titer spanned a broad array of biological pathways including genes that influenced mitochondrial function and lipid metabolism. In addition, knockdown of seven genes in the host ubiquitin and proteolysis pathways significantly reduced
titer. To test the
relevance of these results, we found that drug and mutant inhibition of proteolysis reduced levels of
in the
oocyte. The presence of
in either cell lines or oocytes dramatically alters the distribution and abundance of ubiquitinated proteins. Functional studies revealed that maintenance of
titer relies on an intact host Endoplasmic Reticulum (ER)-associated protein degradation pathway (ERAD). Accordingly, electron microscopy studies demonstrated that
is intimately associated with the host ER and dramatically alters the morphology of this organelle. Given
lack essential amino acid biosynthetic pathways, the reliance of
on high rates of host proteolysis via ubiquitination and the ERAD pathways may be a key mechanism for provisioning
with amino acids. In addition, the reliance of
on the ERAD pathway and disruption of ER morphology suggests a previously unsuspected mechanism for
'
potent ability to prevent RNA virus replication.
While a number of studies have identified host factors that influence endosymbiont titer, little is known concerning environmental influences on titer. Here we examined nutrient impact on maternally ...transmitted Wolbachia endosymbionts in Drosophila. We demonstrate that Drosophila reared on sucrose- and yeast-enriched diets exhibit increased and reduced Wolbachia titers in oogenesis, respectively. The yeast-induced Wolbachia depletion is mediated in large part by the somatic TOR and insulin signaling pathways. Disrupting TORC1 with the small molecule rapamycin dramatically increases oocyte Wolbachia titer, whereas hyper-activating somatic TORC1 suppresses oocyte titer. Furthermore, genetic ablation of insulin-producing cells located in the Drosophila brain abolished the yeast impact on oocyte titer. Exposure to yeast-enriched diets altered Wolbachia nucleoid morphology in oogenesis. Furthermore, dietary yeast increased somatic Wolbachia titer overall, though not in the central nervous system. These findings highlight the interactions between Wolbachia and germline cells as strongly nutrient-sensitive, and implicate conserved host signaling pathways by which nutrients influence Wolbachia titer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Surrogacy is growing worldwide. Although recently some countries have sought to ban it, between 2010 and 2014 the number of babies born to gestational surrogates having in vitro fertilization ...treatment in California doubled, and in Canada it grew by 35%. This work seeks to fill identified knowledge gaps about the similarities and differences in the practices and outcomes of gestational surrogacy, which in California operates on a commercial basis, whereas in Canada it is illegal to pay a surrogate. The paper focusses on the period from 2010 to 2014, for which comparable American and Canadian national assisted reproduction technology information exist.
A retrospective data analysis was performed using information on gestational surrogate multiple births obtained from the Centers for Disease Control and Prevention National Assisted Reproductive Technology Surveillance System (NASS) and Canada's Assisted Reproduction Registry-Better Outcomes Registry and Network (CARTR-BORN). Multiple birth rates and transfers of multiple embryos were compared using relative risk analysis. Adherence to voluntary American Society for Reproductive Medicine–Society for Assisted Reproductive Technology and Canadian Fertility and Andrology Society embryo transfer guidelines was modelled.
Among gestational surrogates, when donor ova embryos obtained from women aged less than 35 years were used, embryo transfer guideline adherence was 42% in California and 48% in Canada.
Regardless of where on the commercial/noncommercial boundary North American surrogates reside, they are more likely to receive more donor ova embryos per in vitro fertilization transfer than other in vitro fertilization patients. An altruistic desire to assist childless couples and individuals create families along with clinic practices seem to play major roles in treatment decisions privileging the transfer two or more embryos.
is an intracellular endosymbiont present in most arthropod and filarial nematode species. Transmission between hosts is primarily vertical, taking place exclusively through the female germ line, ...although horizontal transmission has also been documented. The results of several studies indicate that
spp. can undergo transfer between somatic and germ line cells during nematode development and in adult flies. However, the mechanisms underlying horizontal cell-to-cell transfer remain largely unexplored. Here, we establish a tractable system for probing horizontal transfer of
cells between
cells in culture using fluorescence
hybridization (FISH). First, we show that horizontal transfer is independent of cell-to-cell contact and can efficiently take place through the culture medium within hours. Further, we demonstrate that efficient transfer utilizes host cell phagocytic and clathrin/dynamin-dependent endocytic machinery. Lastly, we provide evidence that this process is conserved between species, showing that horizontal transfer from mosquito to
cells takes place in a similar fashion. Altogether, our results indicate that
utilizes host internalization machinery during infection, and this mechanism is conserved across insect species.
Our work has broad implications for the control and treatment of tropical diseases.
can confer resistance against a variety of human pathogens in mosquito vectors. Elucidating the mechanisms of horizontal transfer will be useful for efforts to more efficiently infect nonnatural insect hosts with
as a biological control agent. Further, as
is essential for the survival of filarial nematodes, understanding horizontal transfer might provide new approaches to treating human infections by targeting
Finally, this work provides a key first step toward the genetic manipulation of
.
In January 2016, Melissa Cook, a California gestational surrogate experiencing a multiple-birth pregnancy following the in vitro fertilization (IVF) transfer of three embryos comprised of donor eggs ...and sperm provided by the intended father, went to the media when the intended father requested that she undergo a fetal reduction because twins were less expensive to raise than triplets. Much of the legal interest in this case to date has centered on the enforceability of surrogacy contracts. However, the Cook case also raises troubling issues about fertility treatment practices involving gestational surrogates, twin preference, and third-party reproduction medical decision-making. This paper focuses on multiple-embryo transfers in the context of US surrogacy arrangements. Offering an original analysis of data obtained from the US national-assisted reproduction registry, it examines single- and multiple-embryo transfer trends over a 12-year period (2003 to 2014). Findings reveal that recommended guidelines were followed in fewer than 42% of the cases in 2014. The paper argues that ensuring equitable medical treatment for all recipients of IVF requires the adoption of treatment guidelines tailored to, and offering protections for, specific patient groups, and that, once in place, guidelines must be robustly implemented.
The impacts of the molecular weight (MW), viscosity, and solubility of β-glucan on the rate of in vitro starch digestion and estimated glycemic index (GI) were evaluated. Extracted oat starch and ...β-glucan suspensions with high, medium, and low MW were heated to gelatinize the starch. The viscosity increased and the solubility decreased with an increase in the MW of β-glucan. The in vitro starch hydrolysis of the mixtures and a control, white bread, increased as the digestion time increased. As the MW of β-glucan increased, the starch hydrolysis decreased during in vitro digestion. The in vitro estimated GI of the mixture without β-glucan, determined from the starch hydrolysis rate, was 88.3 for Jim and 80.0 for N979, which decreased to 68.4 and 66.8, respectively, with the inclusion of high-MW β-glucan. The estimated GI values were negatively correlated with the β-glucan peak and final viscosities (r = −0.81 and −0.82). These results illustrated the importance of viscosity attributed to the β-glucan MW on starch hydrolysis during in vitro digestion. These findings will help to develop new food products with a low GI by using oat β-glucan.
This paper raises some troubling questions about the fertility treatments provided to Canadian gestational surrogates, women not genetically related to the child that they carry. Using information ...published between 2003 and 2012 by Canada’s Assisted Reproduction Registry, the paper traces the growing incidence of births to gestational surrogates. The transfer of more than one embryo increases the chance of pregnancy and the incidence of multiple births, and while the incidence of multiple births has declined overall since 2010, gestational surrogates consistently experience a higher proportion of multiple births and experienced higher levels of multiple embryo transfers. In 2012, just 26% of gestational surrogates received a single embryo transfer compared to 47% of other in vitro fertilisation (IVF) patients. The paper suggests that renewed attention needs to be paid to the counselling provided to gestational surrogates and treatment consenting mechanisms used by IVF clinics and that review of the 2007 Canadian Medical Association surrogate treatment guidelines is warranted. Finally, the paper describes the difficulties in obtaining accurate data about Canadian assisted reproductive medicine. Without good data, it becomes far more difficult to identify the possibility of potentially harmful practices.
Cet article soulève des questions troublantes sur les traitements de la fécondité pratiqués sur les mères porteuses (femmes qui ne sont pas génétiquement apparentées à l’enfant qu’elles portent) canadiennes. En utilisant les informations publiées sur une période de dix ans (2003-2012) par le Registre canadien des techniques de procréation assistée, l’article révèle l’incidence croissante des naissances chez des mères porteuses. L’implantation de plus d’un embryon augmente les chances de grossesse et l’incidence de naissances multiples et, s’il est en général moins fréquent qu’elles donnent naissance à plus d’un enfant à la fois depuis 2010, les mères porteuses enregistrent systématiquement une proportion plus élevée de naissances multiples. En 2012, à peine 26% des mères porteuses avaient reçu l’implantation d’un seul embryon,contre 47% des autres patientes de la FIV. L’article suggère qu’il faut accorder davantage d’attention aux conseils prodigués aux mères porteuses et aux mécanismes de consentement au traitement utilisés par les cliniques de FIV. Il note aussi qu’il est nécessaire de réviser les directives de l’Association médicale canadienne sur le traitement des mères porteuses. Enfin, l’article décrit les difficultés rencontrées pour obtenir des données exactes sur la procréation médicalement assistée au Canada. Sans informations solides, il est beaucoup plus difficile de déceler la possibilité de pratiques potentiellement nuisibles.
Este artículo plantea algunas preguntas preocupantes acerca de los tratamientos de fertilidad proporcionados a madres gestantes (mujeres que no están emparentadas genéticamente con la criatura que llevan en el vientre) canadienses. Utilizando información publicada en un plazo de diez años (de 2003 a 2012) por el Registro Canadiense de Técnicas de Reproducción Asistida, el artículo rastrea la creciente incidencia de partos a madres gestantes. La transferencia de más de un embrión aumenta la probabilidad de embarazo y la incidencia de partos multiples y aunque la incidencia de dar a luz a más de un hijo a la vez ha disminuido en general desde el año 2010, las madres gestantes experimentan un mayor porcentaje de partos múltiples. En el año 2012, tan solo el 26% de las madres gestantes recibieron una transferencia de un único embrión, comparado con el 47% de otras pacientes de fertilización in vitro (FIV). El artículo sugiere que es necesario prestar atención renovada a la consejería brindada a madres gestantes y a los mecanismos utilizados por las clínicas de FIV para obtener consentimiento para el tratamiento, y que es necesario revisar las directrices de 2007 de la Asociación Médica Canadiense referentes al tratamiento de madres gestantes. Por último, el artículo describe las dificultades para obtener datos exactos sobre la medicina reproductiva asistida canadiense. Sin datos buenos, es mucho más difícil identificar la posibilidad de prácticas posiblemente dañinas.
This article considers the little studied role of local implementation staff and their institutional operational environment at the grassroots of a rural development intervention in Nepal. The study ...describes the challenges the implementing staff encounters in relation to the steering policies, project modalities, local communities, partners in government administration, and their personal motivations. It observes the ways in which the implementing individuals must collaborate with their partners and facilitate the planned changes in local institutions and individual behaviours. The findings indicate that much of the actual implementation process at the grassroots is determined by informal, improvised, and fuzzy institutional surroundings, quite different to designed or regulated governance environs. The ability to operate in these less-regulated environs determines many of the implementation outcomes at the grassroots. Researchers, managers and decision-makers would benefit from incorporating institutional bricolage to the analyses of development interventions.
The in vitro starch digestion rate and estimated glycemic index (GI) of oat flours and oat starches from typical and high β-glucan oat lines were evaluated along with the impact of heating on starch ...digestion. Flour from oat lines ('Jim', 'Paul', IA95, and N979 containing 4.0, 5.3, 7.4, and 7.7% β-glucan, respectively) was digested by pepsin and porcine pancreatin. To determine the impact of heating on starch digestion, oat slurries were prepared by mixing oat flour and water (1:8 ratio) and heating for 10 min prior to digestion. Viscosity, as measured on a Rapid Visco Analyzer, increased with increases in concentration and molecular weight of β-glucan. The in vitro starch digestion of oat flours and a control, white bread made from wheat flour, increased as the digestion time increased. Starch digestion of oat flour was slower than that of the control (p < 0.05). Heat treatment of oat-flour slurries increased the starch digestion from a range of 31–39% to a range of 52–64% measured after 180 min of in vitro digestion. There were no differences in starch digestibility among oat starches extracted from the different oat lines. The GI, estimated by starch hydrolysis of oat flours, ranged from 61 to 67, which increased to a range of 77–86 after heating. Oat-flour slurries prepared from IA95 and N979 lines with high β-glucan concentrations had lower GI values than did slurries made from Jim and Paul lines. Starch digestion was negatively correlated with β-glucan concentrations in heated oat-flour slurries (R 2 = 0.92). These results illustrate that the oat soluble fiber, β-glucan, slowed the rate of starch digestion. This finding will help to develop new food products with low GI by using oat β-glucan.
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