Cover Image,Volume 20, Issue 4

The cover image, by Inmaculada Ruz‐Maldonado et al., is based on the Original Article LH‐21 and abnormal cannabidiol improve β‐cell function in isolated human and mouse islets through GPR55‐dependent and ‐independent signalling, DOI: 10.1111/dom.13180 .

     

Use of calcium hydroxylapatite (Radiesse?) for facial augmentation

Radiesse^® (Bioform Inc, USA) is a sterile, latex-free, non-pyrogenic, semi-solid, cohesive subdermal, injectable implant, whose principal component is synthetic calcium hydroxylapatite, a biocompatible material with over 20 years of use in medicine. The semi-solid nature of the product is created by suspending calcium hydroxylapatite microspheres of 25–45 microns diameter in a gel carrier of carboxymethylcellulose. The product has FDA approval for esthetic facial augmentation in the US. Such approval includes the long-lasting correction of moderate to severe facial wrinkles and folds and the treatment of facial fat loss due to immunodeficiency virus infection. Diverse facial regions can be injected in order to ameliorate or enhance some features: glabellar lines, subdermal support of the brows, malar and buccal fat pads, tear troughs, nasolabial folds, nose, lips, perioral region, marionette lines, oral commisures and chin among others, as well as saucerized acne scars. Other medical indications include nipple projection for nipple areolar reconstruction, urinary incontinence, vesicoureteral reflux, vocal cord augmentation, and use as a radiographic tissue marker. The average lasting result is from 12 to 18 months. Radiesse can be considered an effective soft-tissue filler for overall longevity, biocompatibility, and low rate of side effects.     

Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia

OBJECTIVE: The pathophysiology of gastroesophageal reflux disease (GERD) has been studied extensively in patients with long-segment Barrett's esophagus (LSBE), but few reports have explored GERD pathophysiology in patients who have short-segment Barrett's esophagus (SSBE) or intestinal metaplasia at the cardia (IMC). We aimed to compare clinical, endoscopic, histological, and functional features in patients with LSBE, SSBE, and IMC. METHODS: We identified 582 patients who had intestinal metaplasia at the squamocolumnar junction in the distal esophagus and divided them into three groups based on the extent of columnar-lined esophagus observed endoscopically: 1) patients with IMC who had no columnar-lined esophagus (i.e., the squamocolumnar and gastroesophageal junctions coincided), 2) patients with LSBE who had >3 cm of columnar-lined esophagus, and 3) patients with SSBE who had <3 cm of columnar-lined esophagus. All patients had esophageal manometric evaluation, and 24-h esophageal pH monitoring was performed to determine the extent of acid and bile (bilirubin) reflux. RESULTS: There were 174 patients with IMC, 155 with LSBE, and 25 with SSBE. Compared to patients with LSBE and SSBE, patients with IMC had significantly lower frequencies of GERD symptoms, hiatal hernia, and erosive esophagitis; significantly higher lower esophageal sphincter pressures; and significantly shorter durations of acid and bile reflux. Between patients with SSBE and LSBE, significant differences were found in the frequency of hiatal hernia and duration of acid reflux (both greater in the patients with LSBE). Also, dysplasia was significantly more frequent in patients with LSBE than in those with SSBE or IMC. CONCLUSION: GERD symptoms, signs, and physiological abnormalities are found more often in patients with Barrett's esophagus than in those with IMC, and the duration of acid reflux in patients with LSBE is greater than that in patients with SSBE. These findings suggest that the extent of intestinal metaplasia in the esophagus is related directly to the severity of underlying GERD.     

Neurogenic disorders of osmoregulation

The osmolality of body fluids is normally maintained within a narrow range. This constancy is achieved largely via hypothalamic osmoreceptors that regulate thirst and arginine vasopressin, the antidiuretic hormone (ADH). Anything that interferes with the full expression of either osmoregulatory function exposes the patient to the hazards of abnormal increases or decreases in plasma osmolality. Hyposmolarity is almost always due to a defect in water excretion. Increased intake may contribute to the problem but is rarely, if ever, a sufficient cause. Impaired water excretion can be due to a primary defect in the osmoregulation of ADH (inappropriate antidiuresis) or secondary to nonosmotic stimuli like hypovolemia or nausea. The two types differ in clinical presentation and treatment. Resetting of the ADH osmostat is commonly associated with resetting of the thirst osmostat. Hyperosmolarity is almost always due to deficient water intake. Excessive excretion may contribute to the problem but is never a sufficient cause. Impaired water intake can result from a defect in either the osmoregulation of thirst or the necessary motor responses. Thirst may be deficient because of primary osmoreceptor damage as in the syndrome of adipsic hypernatremia or secondary to nonomsotic influences on the set of the system. They are distinguishable by the clinical presentation as well as the type of ADH defects with which they are associated. So-called essential hypernatremia due to primary resetting of the osmostat has been postulated, but unambiguous evidence for such an entity has not yet been reported.     

Haplotype tagging reveals parallel formation of hybrid races in two butterfly species

Genetic variation segregates as linked sets of variants or haplotypes. Haplotypes and linkage are central to genetics and underpin virtually all genetic and selection analysis. Yet, genomic data often omit haplotype information due to constraints in sequencing technologies. Here, we present “haplotagging,” a simple, low-cost linked-read sequencing technique that allows sequencing of hundreds of individuals while retaining linkage information. We apply haplotagging to construct megabase-size haplotypes for over 600 individual butterflies (Heliconius erato and H. melpomene), which form overlapping hybrid zones across an elevational gradient in Ecuador. Haplotagging identifies loci controlling distinctive high- and lowland wing color patterns. Divergent haplotypes are found at the same major loci in both species, while chromosome rearrangements show no parallelism. Remarkably, in both species, the geographic clines for the major wing-pattern loci are displaced by 18 km, leading to the rise of a novel hybrid morph in the center of the hybrid zone. We propose that shared warning signaling (Müllerian mimicry) may couple the cline shifts seen in both species and facilitate the parallel coemergence of a novel hybrid morph in both comimetic species. Our results show the power of efficient haplotyping methods when combined with large-scale sequencing data from natural populations.

Understanding how changes in DNA sequence affect traits and shape the evolution of populations and species has been a defining goal in genetics and evolution (1–3). DNA is naturally organized in the genome as long molecules consisting of linked chromosome segments. Linkage is a core concept in genetics: in genetic mapping, geneticists map causal variants not by tracking the actual mutation but through many otherwise neutral and unremarkable linked variants. Likewise, the detection of selection relies on observing hitchhiking of linked variants rather than seeing the mutation itself. This recognition makes it all the more paradoxical that haplotype information is routinely omitted from most genomic studies as a technical compromise. Lacking haplotype information not only complicates analysis and ancestry reconstruction but also precludes detection of allele-specific expression (4) and chromosome rearrangements and reduces power to detect selective sweeps, even entirely missing them when multiple haplotypes sweep together (5). Instead of sequencing genomes as haplotypes, short-read sequencing produces 150-bp reads. Until long-read platforms become sufficiently accurate and affordable, this lack of haplotype context will continue to impact mapping and genomic studies, particularly those in nonmodel organisms.One way to simplify haplotype reconstruction and inference from sequencing data is to avoid discarding haplotype information in the first place. A promising emerging technique is linked-read (LR) sequencing (6–9), which preserves long-range information via molecular barcoding of long DNA molecules before sequencing. Individual short reads can then be linked via a shared barcode to reconstruct the original haplotype. However, existing options all suffer from high cost, poor scalability, and/or require custom sequencing primers or settings that have thus far prevented them from being applied as the default sequencing platform (SI Appendix, Tables S1 and S2). If LR sequencing could become scalable and affordable, it would significantly advance genetics by enabling the “haplotyping” of entire populations (i.e., the sequencing and systematic discovery of genomic variants as haplotypes in hundreds or even thousands of samples in model and nonmodel organisms alike).Here, we describe a solution called “haplotagging,” a simple and rapid protocol for LR sequencing. Importantly, haplotagging maintains full compatibility with standard Illumina sequencing and can easily scale to large populations with no extra costs. We demonstrate this in three steps. First, we show that direct haplotyping using haplotagging is robust in single human and mouse samples with known haplotypes (“phases”). Next, we show the feasibility of population haplotyping in 245 mice, even with very low-coverage LR sequencing. Finally, we apply haplotagging to investigate the emergence of a hybrid morph in a hybrid zone system in Ecuador featuring 670 individuals of two species of Heliconius butterflies.