Quantifying local randomness in human DNA and RNA sequences using Erdös motifs.

In 1932, Paul Erdös asked whether a random walk constructed from a binary sequence can achieve the lowest possible deviation (lowest discrepancy), for the sequence itself and for all its subsequences formed by homogeneous arithmetic progressions. Although avoiding low discrepancy is impossible for infinite sequences, as recently proven by Terence Tao, attempts were made to construct such sequences with finite lengths. We recognize that such constructed sequences (we call these "Erdös sequences") exhibit certain hallmarks of randomness at the local level: they show roughly equal frequencies of short subsequences, and at the same time exclude trivial periodic patterns. For the human DNA we examine the frequency of a set of Erdös motifs of length-10 using three nucleotides-to-binary mappings. The particular length-10 Erdös sequence is derived from the length-11 Mathias sequence and is identical with the first 10 digits of the Thue-Morse sequence, underscoring the fact that both are deficient in periodicities. Our calculations indicate that: (1) the purine(A and G)/pyridimine(C and T) based Erdös motifs are greatly underrepresented in the human genome, (2) the strong(G and C)/weak(A and T) based Erdös motifs are slightly overrepresented, (3) the densities of the two are negatively correlated, (4) the Erdös motifs based on all three mappings being combined are slightly underrepresented, and (5) the strong/weak based Erdös motifs are greatly overrepresented in the human messenger RNA sequences.

Return of the Tbx5; lineage-tracing reveals ventricular cardiomyocyte-like precursors in the injured adult mammalian heart.

The single curative measure for heart failure patients is a heart transplantation, which is limited due to a shortage of donors, the need for immunosuppression and economic costs. Therefore, there is an urgent unmet need for identifying cell populations capable of cardiac regeneration that we will be able to trace and monitor. Injury to the adult mammalian cardiac muscle, often leads to a heart attack through the irreversible loss of a large number of cardiomyocytes, due to an idle regenerative capability. Recent reports in zebrafish indicate that Tbx5a is a vital transcription factor for cardiomyocyte regeneration. Preclinical data underscore the cardioprotective role of Tbx5 upon heart failure. Data from our earlier murine developmental studies have identified a prominent unipotent Tbx5-expressing embryonic cardiac precursor cell population able to form cardiomyocytes, in vivo, in vitro and ex vivo. Using a developmental approach to an adult heart injury model and by employing a lineage-tracing mouse model as well as the use of single-cell RNA-seq technology, we identify a Tbx5-expressing ventricular cardiomyocyte-like precursor population, in the injured adult mammalian heart. The transcriptional profile of that precursor cell population is closer to that of neonatal than embryonic cardiomyocyte precursors. Tbx5, a cardinal cardiac development transcription factor, lies in the center of a ventricular adult precursor cell population, which seems to be affected by neurohormonal spatiotemporal cues. The identification of a Tbx5-specific cardiomyocyte precursor-like cell population, which is capable of dedifferentiating and potentially deploying a cardiomyocyte regenerative program, provides a clear target cell population for translationally-relevant heart interventional studies.

Incidental thyroid C cell hyperplasia: clinical significance and implications in practice.

Incidental C cell hyperplasia (CCH) following thyroidectomy for other indications may rarely be encountered, which may raise concerns about its clinical significance and proper management. CCH can be classified as physiological (reactive) or neoplastic. Reactive CCH has no malignant potential and can be observed in association with many other thyroid diseases (including differentiated thyroid cancer); in contrast, neoplastic CCH should be considered as a preneoplastic stage in the spectrum of C cell disease, ultimately leading to the development of medullary thyroid cancer (MTC). Neoplastic CCH is commonly observed in patients with germ-line mutations in the RET oncogene (commonly in families with a history of hereditary MTC, i.e. familial MTC or multiple endocrine neoplasia type 2 (MEN2)). CCH should be considered in patients with hypercalcitoninemia without nodular thyroidopathy. Total thyroidectomy, which is commonly performed for the majority of thyroid diseases, is an adequate treatment and achieves cure, even in patients with neoplastic CCH. There is no role for cervical lymph node dissection in patients with pure CCH. In conclusion, reactive CCH has no malignant potential, in contrast to neoplastic CCH. Total thyroidectomy achieves cure of patients with CCH.