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"Soman, David"
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\"A child's solitary day at the playground turns into a park-wide adventure as he learns how to play with nine new friends\"-- Provided by publisher.
Book
Depletion of aneuploid cells in human embryos and gastruloids
Chromosomal instability leading to aneuploidy is pervasive in early human embryos
1
,
2
–
3
and is considered as a major cause of infertility and pregnancy wastage
4
,
5
. Here we provide several lines of evidence that blastocysts containing aneuploid cells are worthy of in vitro fertilization transfer. First, we show clinically that aneuploid embryos can lead to healthy births, suggesting the presence of an in vivo mechanism to eliminate aneuploidy. Second, early development and cell specification modelled in micropatterned human ‘gastruloids’ grown in confined geometry show that aneuploid cells are depleted from embryonic germ layers, but not from extraembryonic tissue, by apoptosis in a bone morphogenetic protein 4 (BMP4)-dependent manner. Third, a small percentage of euploid cells rescues embryonic tissue in mosaic gastruloids when mixed with aneuploid cells. Finally, single-cell RNA-sequencing analysis of early human embryos revealed a decline of aneuploidy beginning on day 3. Our findings challenge two current dogmas: that a single trophectoderm biopsy at blastocyst stage to perform prenatal genetic testing can accurately determine the chromosomal make-up of a human embryo, and that aneuploid embryos should be withheld from embryo transfer in association with in vitro fertilization.
Using gastruloids and human embryos, Yang et al. demonstrate that aneuploid embryos can still lead to healthy births due to elimination of aneuploid cells by apoptosis in a BMP4-dependent manner.
Journal Article
Three bears in a boat
Afraid to face their mother after breaking her beautiful blue seashell, three bears set out on an high seas adventure to try to find a replacement.
Book
Creation of a point-of-care therapeutics sensor using protein engineering, electrochemical sensing and electronic integration
Point-of-care sensors, which are low-cost and user-friendly, play a crucial role in precision medicine by providing quick results for individuals. Here, we transform the conventional glucometer into a 4-hydroxytamoxifen therapeutic biosensor in which 4-hydroxytamoxifen modulates the electrical signal generated by glucose oxidation. To encode the 4-hydroxytamoxifen signal within glucose oxidation, we introduce the ligand-binding domain of estrogen receptor-alpha into pyrroloquinoline quinone-dependent glucose dehydrogenase by constructing and screening a comprehensive protein insertion library. In addition to obtaining 4-hydroxytamoxifen regulatable engineered proteins, these results unveil the significance of both secondary and quaternary protein structures in propagation of conformational signals. By constructing an effective bioelectrochemical interface, we detect 4-hydroxytamoxifen in human blood samples as changes in the electrical signal and use this to develop an electrochemical algorithm to decode the 4-hydroxytamoxifen signal from glucose. To meet the miniaturization and signal amplification requirements for point-of-care use, we harness power from glucose oxidation to create a self-powered sensor. We also amplify the 4-hydroxytamoxifen signal using an organic electrochemical transistor, resulting in milliampere-level signals. Our work demonstrates a broad interdisciplinary approach to create a biosensor that capitalizes on recent innovations in protein engineering, electrochemical sensing, and electrical engineering.
Low-cost point-of-care sensors are vital for precision medicine. Here, the authors have repurposed a glucometer for breast cancer therapeutic detection capable of sensing tamoxifen in human blood, utilizing blood glucose to power and amplify the therapeutic signals
Journal Article
Ladybug Girl at the beach
Lulu, who likes to wear a ladybug costume, goes to the beach for the first time and makes sand castles, flies kites, and deals with her fear of the ocean.
Book
Associations of cereal grains intake with cardiovascular disease and mortality across 21 countries in Prospective Urban and Rural Epidemiology study: prospective cohort study
AbstractObjectiveTo evaluate the association between intakes of refined grains, whole grains, and white rice with cardiovascular disease, total mortality, blood lipids, and blood pressure in the Prospective Urban and Rural Epidemiology (PURE) study.DesignProspective cohort study.SettingPURE study in 21 countries.Participants148 858 participants with median follow-up of 9.5 years.ExposuresCountry specific validated food frequency questionnaires were used to assess intakes of refined grains, whole grains, and white rice.Main outcome measureComposite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios were estimated for associations of grain intakes with mortality, major cardiovascular events, and their composite by using multivariable Cox frailty models with random intercepts to account for clustering by centre.ResultsAnalyses were based on 137 130 participants after exclusion of those with baseline cardiovascular disease. During follow-up, 9.2% (n=12 668) of these participants had a composite outcome event. The highest category of intake of refined grains (≥350 g/day or about 7 servings/day) was associated with higher risk of total mortality (hazard ratio 1.27, 95% confidence interval 1.11 to 1.46; P for trend=0.004), major cardiovascular disease events (1.33, 1.16 to 1.52; P for trend<0.001), and their composite (1.28, 1.15 to 1.42; P for trend<0.001) compared with the lowest category of intake (<50 g/day). Higher intakes of refined grains were associated with higher systolic blood pressure. No significant associations were found between intakes of whole grains or white rice and health outcomes.ConclusionHigh intake of refined grains was associated with higher risk of mortality and major cardiovascular disease events. Globally, lower consumption of refined grains should be considered.
Journal Article
Ladybug Girl and her papa
Join Lulu and her papa as they spend a perfect day together. They take a hike complete with rock-skipping at the stream, make a delicious pancake breakfast, and build a birdhouse. Even hanging the laundry to dry is an adventure when Ladybug Girl is with Papa. This sweet story captures the everyday magic of the love between a little girl and her dad.
Book
Cyclic AMP–regulated exocytosis of Escherichia coli from infected bladder epithelial cells
The superficial bladder epithelium is a powerful barrier to urine and also serves as a regulator of bladder volume, which is achieved by apical exocytosis of specialized fusiform vesicles during distension of the bladder. We report that type 1 fimbriated uropathogenic
Escherichia coli
(UPEC) circumvents the bladder barrier by harboring in these Rab27b/CD63-positive and cAMP-regulatable fusiform vesicles within bladder epithelial cells (BECs). Incorporation of UPEC into BEC fusiform compartments enabled bacteria to escape elimination during voiding and to re-emerge in the urine as the bladder distended. Notably, treatment of UPEC-infected mice with a drug that increases intracellular cAMP and induces exocytosis of fusiform vesicles reduced the number of intracellular
E. coli
.
Journal Article
Ladybug Girl's day out with Grandpa
Lulu, who likes to dress in a ladybug costume, wants to learn everything when she visits the natural history museum with Grandpa, but as she moves from exhibit to exhibit, she discovers that sometimes you have to slow down to appreciate the wonder of what's around you.
Book
SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration
Reactive astrogliosis is a common pathological hallmark of CNS injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These
Srf
GFAP-ER
CKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory. However, the brains of
Srf
knockout mice exhibited neuroprotection against kainic-acid induced excitotoxic cell death. Relevant to human neurodegenerative diseases,
Srf
GFAP-ER
CKO astrocytes abrogate nigral dopaminergic neuron death and reduce β-amyloid plaques in mouse models of Parkinson’s and Alzheimer’s disease, respectively. Taken together, these findings establish SRF as a key molecular switch for the generation of reactive astrocytes with neuroprotective functions that attenuate neuronal injury in the setting of neurodegenerative diseases.
Journal Article