Meeting – Influenza: Translating basic insights

June 7, 2010

Influenza: Translating basic insights December 2-4 2010, Washington Marriott Hotel, Washington D.C.

Given the recent influenza pandemic, the last 12 months have seen a flurry of activity in the area of flu research. New insights are being gained about the biology of the virus, the host immune response, and the ability of the virus to overcome species barriers and host-immune defenses. The broader goal of influenza research is to extrapolate these basic insights for better control of disease, and to develop better vaccines and anti-viral therapeutics. This meeting aims to foster interactions among a broad group of scientists studying the influenza virus from multiple perspectives including: the virus itself, the host response to viral infection, the clinical manifestations of pandemic and seasonal influenza, as well as those scientists actively working to develop better vaccines and therapeutics in an industrial setting.

Postnatal Neural Development – Music

March 15, 2010

How does the brain develop the specialization associated with music recognition? This recent PNAS paper uses the non-invasive functional Magnetic Resonant Imaging (fMRI) technique to study newborn response to music and identifies specific regions of the brain that are activated.

Functional specializations for music processing in the human newborn brain. Perani D, Saccuman MC, Scifo P, Spada D, Andreolli G, Rovelli R, Baldoli C, Koelsch S. Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4758-63. Epub 2010 Feb 22. PMID: 20176953

In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody, and harmony as well as structure and meaning emerging from musical sequences. It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints. One way to address this question is to examine how these systems function at birth, when auditory experience is minimal. We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts. Altered versions either included changes of the tonal key or were permanently dissonant. Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex. During presentation of the altered excerpts, hemodynamic responses were significantly reduced in the rig1ht auditory cortex, and activations emerged in the left inferior frontal cortex and limbic structures. These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours. Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance.

If you are interested in the technique of fMRI, look also at this recent international collaborative project to establish a standard dataset of resting state of adult fMRI scans. Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4734-9. Epub 2010 Feb 22.PMID: 20176931

(More? UNSW EmbryologyPostnatal Neural | Magnetic Resonance Imaging)

Liver Development – Pregnancy and Aging

March 15, 2010

As you age, you gradually loose the capacity to regenerate many tissues. The liver which has important digestive, metabolic, hormonal and other roles, is one of these tissues. This Genes & Development paper looks in mice at the ability of the liver to redevelop and identifies pregnancy as a key regulator of regenerative capacity. Suggesting that therapies that mimic pregnancy may aid liver redevelopment.

Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch. Yuval Gielchinsky, Neri Laufer, Efi Weitman, Rinat Abramovitch, Zvi Granot, Yehudit Bergman, and Eli Pikarsky Genes Dev. 2010;24 543-548

Regenerative capacity is progressively lost with age. Here we show that pregnancy markedly improved liver regeneration in aged mice concomitantly with inducing a switch from proliferation-based liver regeneration to a regenerative process mediated by cell growth. We found that the key mediator of this switch was the Akt/mTORC1 pathway; its inhibition blocked hypertrophy, while increasing proliferation. Moreover, pharmacological activation of this pathway sufficed to induce the hypertrophy module, mimicking pregnancy. This treatment dramatically improved hepatic regenerative capacity and survival of old mice. Thus, cell growth-mediated mass reconstitution, which is relatively resistant to the detrimental effects of aging, is employed in a physiological situation and holds potential as a therapeutic strategy for ameliorating age-related functional deterioration.

(More? UNSW Embryology Gastrointestinal Tract – Liver)

Diabetes & Pregnancy Meeting Salzburg, Austria March 24-26, 2011

February 24, 2010

The 6th International Symposium on Diabetes & Pregnancy (DIP) Salzburg, Austria March 24-26, 2011

The field of diabetes and pregnancy has come of age. From the conception of the terminology ‘gestational diabetes’ and ‘diabetes in pregnancy’ to the creation of an entire subspecialty, this Symposium documents the ‘gestation’ of the field.
This Symposium not only documents the past 80+ years of progress in the field of diabetes and pregnancy, but also presents the most up-to-date tools, techniques and management protocols to ensure the optimal outcome of pregnancies complicated by diabetes. In addition, the areas that remain controversial, such as screening and diagnosis, will be discussed in detail to enable participants to come to an opinion while waiting for the evidence to validate many of the expert opinions presented.
The latest theories and literature on the immunology of Type 1 diabetes will also be included, giving us hope that the near future holds the answers to prevention of this disease. Until there is a cure for diabetes, we must continually take on the weight of astutely diagnosing diabetes and treating all pregnant women who are at risk of an untoward outcome of pregnancy.
The faculty is comprised of renowned professionals and practitioners, who will present based on evidence as well as clinical experience.
In addition, this Symposium provides an international approach to enhancing the quality of care for women with diabetes in pregnancy, and answers for the clinician to enable delivery of optimal care for all pregnancies complicated by diabetes.

(More? UNSW Embryology Abnormal Development – Maternal Diabetes | Endocrine Development – Pancreas)

Ovarian cancer in Australia an overview, 2010

February 23, 2010

A new report by the Australian Institute of Health and Welfare – Ovarian cancer in Australia an overview, 2010. The report shows that in 2006, there were 1,226 cases of ovarian cancer diagnosed in Australia, which equates to an average of three women being diagnosed with the disease every day. Between 1982 and 2006, although the overall number of cases increased (largely due to a growing and ageing population) the incidence rate dropped slightly from 12.4 to 10.7 per 100,000 women. The report shows that 40% of women who were diagnosed with ovarian cancer between 2000 and 2006 were alive five years after their diagnosis. This is in contrast to those diagnosed between 1982 and 1987, when only 33% were alive five years after their diagnosis.

Ovarian cancer was the most common cause of gynaecological cancer death and the sixth most common cause of cancer-related death among women in 2006. Almost 800 Australian women, an average of two per day, died from ovarian cancer in 2006. One in 77 women will be diagnosed with ovarian cancer by the time they reach the age of 85. Although the prognosis for women diagnosed with ovarian cancer was relatively poor compared with a number of other cancers, the prognosis has improved over time. These and other data in this report provide a comprehensive picture of ovarian cancer in Australia including how ovarian cancer rates differ by age, Indigenous status, country of birth, socioeconomic status and geographical area.

Report webpage | Report PDF

(More? UNSW EmbryologyOvary Development | Medline Plus – Ovarian Cancer)

Retraction of the paper (MMR) vaccine and an autism-like disorder

February 4, 2010

The Lancet has finally retracted, more than 10 years after it first published, a paper that linked MMR vaccine and an autism-like disorder. This original paper led to a huge health concern amongst parents and shows how misinformation in medicine can not only affect health care but also have long term scientific consequences.

Following the judgment of the UK General Medical Council’s Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al 1 are incorrect, contrary to the findings of an earlier investigation. 2 In particular, the claims in the original paper that children were “consecutively referred” and that investigations were “approved” by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published….

Retraction—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children

See also BMJ Why did the Lancet take so long? | Reflections on investigating Wakefield

Vitamin A and Hirschsprung disease

February 3, 2010

This recent Development paper identifies a potential non-genetic risk for Hirschsprung disease. During development neural crest cells migrate into the developing gastrointestinal tract wall forming the enteric nervous system required for smoth muscle peristaltic contractility. In Hirschsprung disease  failure of neural crest cell migration leaves sections of the bowel without neurons (aganglionic). Excess retinoic acid though has also been identified as a teratogenic factor.

Hirschsprung disease is a serious disorder of enteric nervous system (ENS) development caused by the failure of ENS precursor migration into the distal bowel. We now demonstrate that retinoic acid (RA) is crucial for GDNF-induced ENS precursor migration, cell polarization and lamellipodia formation, and that vitamin A depletion causes distal bowel aganglionosis in serum retinol-binding-protein-deficient (Rbp4(-/-)) mice. Ret heterozygosity increases the incidence and severity of distal bowel aganglionosis induced by vitamin A deficiency in Rbp4(-/-) animals. Furthermore, RA reduces phosphatase and tensin homolog (Pten) accumulation in migrating cells, whereas Pten overexpression slows ENS precursor migration. Collectively, these data support the hypothesis that vitamin A deficiency is a non-genetic risk factor that increases Hirschsprung disease penetrance and expressivity, suggesting that some cases of Hirschsprung disease might be preventable by optimizing maternal nutrition.

Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation. Fu M, Sato Y, Lyons-Warren A, Zhang B, Kane MA, Napoli JL, Heuckeroth RO. Development. 2010 Feb;137(4):631-40. PMID: 20110328

(More? UNSW EmbryologyGastrointestinal Tract Abnormalities | Neural Crest Abnormalities)

Pregnancy Changes in Patients with Multiple Sclerosis

February 1, 2010

Pregnancy has been previously associated with the reduced activity of multiple sclerosis (MS) in patients. This recent PLOS One paper has initially attempted to identify at the molecular level the potential changes that occur during pregnancy that could lead to this disease reducing effect.

Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1.

Gilli F, Lindberg RLP, Valentino P, Marnetto F, Malucchi S, et al. (2010) Learning from Nature: Pregnancy Changes the Expression of Inflammation-Related Genes in Patients with Multiple Sclerosis. PLoS ONE 5(1): e8962. doi:10.1371/journal.pone.0008962

Effectiveness of Common Household Cleaning Agents in Reducing the Viability of Human Influenza A/H1N1

February 1, 2010

Some viruses and their associated infection hyperthermia are known teratogens. This recent PLOS One paper studied the actions of commercially available cleaning agents with some common household cleaning agents for viral inactivation and found that both had similar results. This would be useful information in the case of an Influenza pandemic, such as that seen with the  Human Influenza A/H1N1 virus.

Active ingredients in a number of the cleaning agents, wipes, and tissues tested were able to rapidly render influenza virus nonviable, as determined by plaque assay. Commercially available wipes with a claimed antiviral or antibacterial effect killed or reduced virus infectivity, while nonmicrobiocidal wipes and those containing only low concentrations (<5%) of surfactants showed lower anti-influenza activity. Importantly, however, our findings indicate that it is possible to use common, low-technology agents such as 1% bleach, 10% malt vinegar, or 0.01% washing-up liquid to rapidly and completely inactivate influenza virus. Thus, in the context of the ongoing pandemic, and especially in low-resource settings, the public does not need to source specialized cleaning products, but can rapidly disinfect potentially contaminated surfaces with agents readily available in most homes.

Greatorex JS, Page RF, Curran MD, Digard P, Enstone JE, et al. (2010) Effectiveness of Common Household Cleaning Agents in Reducing the Viability of Human Influenza A/H1N1. PLoS ONE 5(2): e8987. doi:10.1371/journal.pone.0008987

(More? UNSW Embryology Abnormal Development – Viral Infection | Abnormal Development – Maternal Hyperthermia)

Abnormal Development – Illegal Drugs – Cocaine

January 27, 2010

This recent PNAS paper uses a nonhuman primate model of fetal brain development in combination with non-invasive PET and MRI analysis. The study shows that in addition to the known effects of cocaine on placental circulation there was also a detectable direct pharmacological effect to the developing fetal brain.

Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third-trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (∼100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine’s effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine are influenced by the state of pregnancy. Our findings have clinical implications because they imply that the adverse effects of prenatal cocaine exposure to the newborn child include not only cocaine’s deleterious effects to the placental circulation, but also cocaine’s direct pharmacological effect to the developing fetal brain.

Cocaine is pharmacologically active in the nonhuman primate fetal brain. Benveniste H, Fowler JS, Rooney WD, Scharf BA, Backus WW, Izrailtyan I, Knudsen GM, Hasselbalch SG, Volkow ND. Proc Natl Acad Sci U S A. 2010 Jan 4. [Epub ahead of print] PMID: 20080687

More? UNSW EmbryologyAbnormal Development – Illegal Drugs | Neural System Development