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Advances in embryo culture platforms: novel approaches to improve preimplantation embryo development through modifications of the microenvironment

Posted: June 12, 2011 at 4:00 pm

BACKGROUND

The majority of research aimed at improving embryo development in vitro has focused on manipulation of the chemical environment, examining details such as energy substrate composition and impact of various growth factors or other supplements. In comparison, relatively little work has been done examining the physical requirements of preimplantation embryos and the role culture platforms or devices can play in influencing embryo development.

METHODS

Electronic searches were performed using keywords centered on embryo culture techniques using PUBMED through June 2010 and references were searched for additional research articles.

RESULTS

Various approaches to in vitro embryo culture that involve manipulations of the physical culture environment are emerging. Novel culture platforms being developed examine issues such as media volume and embryo spacing. Furthermore, methods to permit dynamic embryo culture with fluid flow and embryo movement are now available, and novel culture surfaces are being tested.

CONCLUSIONS

Although several factors remain to be studied to optimize efficiency, manipulations of the embryo culture microenvironment through novel culture devices may offer a means to improve embryo development in vitro. Reduced volume systems that reduce embryo spacing, such as the well-of-the-well approach, appear beneficial, although more work is needed to verify the source of their true benefit in human embryos. Emerging microfluidic technology appears to be a promising approach. However, along with the work on specialized culture surfaces, more information is required to determine the impact on human embryo development.

Recommendation and review posted by G. Smith

Secondary recurrent miscarriage and H-Y immunity

Posted: June 12, 2011 at 4:00 pm

BACKGROUND

Approximately half recurrent miscarriage (RM) cases remain unexplained after standard investigations. Secondary RM (SRM) is, in contrast to primary RM, preceded by a birth, which increases the transfer of fetal cells into the maternal circulation. Mothers of boys are often immunized against male-specific minor histocompatibility (H-Y) antigens, and H-Y immunity can cause graft-versus-host disease after stem-cell transplantation. We proposed the H-Y hypothesis that aberrant H-Y immunity is a causal factor for SRM.

METHODS

This is a critical review of the H-Y hypothesis based on own publications and papers identified by systematic PubMed and EMBASE searches.

RESULTS

SRM is more common after the birth of a boy and the subsequent live birth rate is reduced for SRM patients with a firstborn boy. The male:female ratio of children born prior and subsequent to SRM is 1.49 and 0.76 respectively. Maternal carriage of HLA-class II alleles presenting H-Y antigens to immune cells is associated with a reduced live birth rate and increased risk of obstetric complications in surviving pregnancies in SRM patients with a firstborn boy. In early pregnancy, both antibodies against HLA and H-Y antigens are increased in SRM patients compared with controls. Presence of these antibodies in early pregnancy is associated with a lower live birth rate and a low male:female ratio in subsequent live births, respectively. Births of boys are also associated with subsequent obstetric complications in the background population.

CONCLUSIONS

Epidemiological, immunogenetic and immunological studies support the hypothesis that aberrant maternal H-Y immune responses have a pathogenic role in SRM.

Recommendation and review posted by G. Smith

Happiness Protects Your Heart

Posted: June 12, 2011 at 4:00 pm

(HealthDay News) — People who are enthusiastic and content are less likely to develop heart disease than less happy people, researchers from Columbia University report.

In this prospective study of the relationship between happiness and heart disease, researchers concluded that if everyone did more of the things that made them happy, they could significantly reduce their risk of heart attack and angina.

“We were excited to discover in a large population-based sample of adults that the tendency to express positive emotion predicted fewer heart attacks across a period of 10 years,” said lead researcher Karina Davidson, director of Columbia’s Center for Behavioral Cardiovascular Health.

“The study suggests that those people who are happier have heart-protective outcomes,” she added.

Davidson speculated that several factors may combine to producing this effect. Happier people tend to sleep better and to practice more heart-healthy behaviors, she said.

“But they may also be physiologically different than those of us who are more unhappy,” Davidson said. Read more…

AyurGold for Healthy Blood

Recommendation and review posted by G. Smith

More on 4-benzyltoluene and the impact of melting point data curation and transparency

Posted: June 12, 2011 at 12:53 pm

There are many motivations for performing scientific research. One of these is the desire to advance public scientific knowledge.

This is a difficult concept to quantify or even qualitatively assess. One can try to use literature citations and impact factors but that captures only a small fraction of the true scientific impact. For example, one formal citation of our solubility dataset doesn’t represent the 100,000 anonymous solubility queries made directly to our database. And of these the actual impact will depend on exactly how the information was used. Egon Willighagen has identified this as a problem for the Chemistry Development Kit (CDK) as well: many more people use the CDK than reflected simply by the number of citations to the original paper.

There are a few of us who believe that curating chemistry data is a high impact activity. Antony Williams spends a considerable amount of time on this activity and frequently uncovers very serious errors from a number of data sources. Andrew Lang and I have put in a similar effort in collecting and curating solubility measurements openly – and recently (with Antony) we have been doing the same for melting points.

Although attempting to estimate the total impact of the curation activity isn’t really practical, we can look at a specific and representative example to capture the scope.

I recently exposed the situation with the melting point measurements of 4-benzyltoluene. In brief, the literature provided contradictory information that could not be resolved without performing an experiment. Although an exact measurement was not found, a limit was determined that ruled out all measurements except for one.

Ironically it turns out that the melting point of this compound is its most important property for industrial use! Derivatives of diphenylmethane were sought out to replace PCBs as electrical insulating oils for capacitors because of toxicity concerns. As described in this patent (US5134761), for this application one requires the oil to remain liquid down to -50 C. Another key requirement is the ability to absorb hydrogen gas liberated at the electrode surface (a solubility property). Since this is optimal for smaller alkyl groups on the rings, it places benzyltoluene isomers at the focal point of research for this application.

The patent states: “According to references, the melting points of the position isomers of benzyltoluenes are as follows…” but does not make a specific reference. However, by comparing the numbers with other sources we can presume that the reference is the Lemneck1954 paper I discussed previously.

The patent then uses these melting points to calculate the melting behavior of mixtures of these isomers, as they obtain without further purification from a Friedel-Crafts reaction.


If our results are correct and the melting point of 4-benzyltoluene is not +4.6 C but well below -15 C, then the calculated properties in the patent may be significantly in error as well. With the information available thus far from our experiments (UC-EXP266), we think it is unlikely that the +4.6 C value can be correct because we observed no solidification after 2 days at -15 C. The patent reports that solidification of some viscous mixtures took up to a full week but we did not observe an appreciable increase in viscosity for 4-benzyltoluene at -15 C. But in order to be sure we will first freeze the sample again below -40 C and let it warm up to -15 C in the freezer and confirm that it melts completely.


It is in light of this analysis that I make the case that open curation of melting point data is likely to be a high impact activity relative to the amount of time required to perform it. The problem is that errors such as these cascade through the scientific record and likely retard scientific progress by causing confusion and wasted effort. Consider the total cost in terms of research and legal fees for just one patent. As I discussed previously, consider the effect of compromised and contradictory data now known to exist within training sets on the pace of developing reliable melting point models (cascading down to solubility models dependent upon melting point predictions or measurements – and ultimately cascading to the efficiency of drug design).

It is important to note that the benefits of curation would be greatly diminished without the component of transparency. We are not claiming to provide a “trusted source” of melting point data. There is no such thing – and operating under the illusion of the trusted source model has resulted in the mess we are in now – with multiple melting point values for the same compound cascading and multiplying to different databases (a good and still unresolved example is benzylamine).

What we are doing is reporting all the sources we can use and marking some sources as DONOTUSE so they are not included in the calculation of the average – with an explanation. We never delete data so users can make informed choices and not be in a position of having to trust our judgement. If someone does not agree with me that failure to freeze after 2 days at -15 C does not necessarily rule out the +4.6 C value for the melting point for 4-benzyltoluene then they are free to use it.

Using a trusted source model, all values within a collection are equally valid. In the transparency model not all values are equal – we are justifiably more confident in a melting point value near -114 C for ethanol than for a melting point with a single source (like this compound).

And finally, an important factor for having an impact on science is discoverability. It is likely that someone doing research involving the melting behavior of 4-benzyltoluene would perform at least quick Google search. What they are likely to find is not just a simple number without provenance but rather a collection of results capturing the full subtlety of the situation under discussion. This is a natural outcome of working transparently.

Recommendation and review posted by G. Smith

ON/OFF (TEASER) Young Onset Parkinson’s Disease

Posted: June 10, 2011 at 12:17 pm


PROJECT: ON/OFF Living

Here is the original post:
ON/OFF (TEASER) Young Onset Parkinson’s Disease

Recommendation and review posted by Fredricko

ON/OFF (TEASER) Young Onset Parkinson's Disease

Posted: June 10, 2011 at 12:17 pm


PROJECT: ON/OFF Living

Here is the original post:
ON/OFF (TEASER) Young Onset Parkinson’s Disease

Recommendation and review posted by Fredricko


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