Thyroid Hormone Receptors and Resistance to Thyroid Hormone Disorders

Thyroid hormone action is predominantly mediated by thyroid hormone receptors (THRs), which are encoded by the thyroid hormone receptor α (THRA) and thyroid hormone receptor β (THRB) genes. Patients with mutations in THRB present with resistance to thyroid hormone β (RTHβ), which is a disorder characterized by elevated levels of thyroid hormone, normal or elevated levels of TSH and goitre.

Mechanistic insights about the contributions of THRβ to various processes, including colour vision, development of the cochlea and the cerebellum, and normal functioning of the adult liver and heart, have been obtained by either introducing human THRB mutations into mice or by deletion of the mouse Thrb gene. The introduction of the same mutations that mimic human THRβ alterations into the mouse Thra and Thrb genes resulted in distinct phenotypes, which suggests that THRA and THRB might have non-overlapping functions in human physiology.

These studies also suggested that THRA mutations might not be lethal. Seven patients with mutations in THRα have since been described. These patients have RTHα and presented with major abnormalities in growth and gastrointestinal function. The hypothalamic–pituitary–thyroid axis in these individuals is minimally affected, which suggests that the central T3 feedback loop is not impaired in patients with RTHα, in stark contrast to patients with RTHβ.

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Overview of tissues and homeostatic functions affected in RTHα and RTHβ.

Source: NatureReviewsEndocrinology

'Breast Cancer Gene' BRCA1 Linked to Aggressive Uterine Cancer

Mutations in women's BRCA genes, which are linked to both breast cancer and ovarian cancer, may also increase their risk of developing a particularly deadly form of uterine cancer, a new study finds.

The BRCA1 and BRCA2 genes are sometimes referred to as the "breast cancer genes" because women who have a mutation in one or both of these genes face a much greater risk of developing breast and/or ovarian cancer than women without mutations in these genes.

But previous studies have also suggested that women with a BRCA1 or BRCA2 mutation may also be more likely to develop a type of uterine cancer called uterine serous carcinoma, said Dr. Noah Kauff, director of clinical cancer genetics at the Duke Cancer Institute in North Carolina and the senior author of the new study.

Read more: 'Breast Cancer Gene' BRCA1 Linked to Aggressive Uterine Cancer

SebastianKaulitzki | Shutterstock

Source: livescience

Antimicrobial resistance: a collection of reviews and research papers from Nature journals

Resistance to antimicrobials is a global problem of increasing importance. Pathogens rapidly develop mutations that render current treatments ineffective. For example, resistance to carbapenems, one of the ‘last lines’ of antibiotics, is widespread and has been observed in numerous countries; resistance to artemisinin, the gold standard in malaria treatment, has also emerged. Our current arsenal of antimicrobial agents thus has a limited lifespan and new drugs are urgently needed. Tackling this resistance will require a deep understanding of microbial infections and the mechanisms through which resistance arises, as well as concerted efforts between academia and industry aimed at developing novel antimicrobial agents.

This collection consists of Reviews, Research articles, and News and Comment articles from several Nature journals, describing how antibiotic resistance emerges and detailing strategies through which new antimicrobial compounds are being discovered.

Read more: Antimicrobial resistance: a collection of reviews and research papers from Nature journals

Source: nature

Recent Progress in Genome Editing

Researchers develop a CRISPR-based technique that efficiently corrects point mutations without cleaving DNA.

Most genetic diseases in humans are caused by point mutations—single base errors in the DNA sequence. However, current genome-editing methods cannot efficiently correct these mutations in cells, and often cause random nucleotide insertions or deletions (indels) as a byproduct. Now, researchers at Harvard University have modified CRISPR/Cas9 technology to get around these problems, creating a new “base editor,” described today (April 20) in Nature, which permanently and efficiently converts cytosine (C) to uracil (U) bases with low error in human and mouse cell lines.

“There are a lot of genetic diseases where you would want, in essence, to swap bases in and out,” said Jacob Corn, scientific director of the Innovative Genomics Initiative at the University of California, Berkeley, who was not involved in the research. “Trying to get this to work is one of the big challenges in the field, and I think this is a really exciting approach.”

Read more: Recent Progress in Genome Editing

Illustration of DNA ligase, one of the cell proteins involved in repairing double-strand breaks in
DNAWIKIMEDIA; WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS

Source: wikimedia