Gene losses in the common vampire bat illuminate molecular adaptations to blood feeding

Feeding exclusively on blood, vampire bats represent the only obligate sanguivorous lineage among mammals. To uncover genomic changes associated with adaptations to this unique dietary specialization, we generated a new haplotype-resolved reference-quality genome of the common vampire bat (Desmodus rotundus) and screened 26 bat species for genes that were specifically lost in the vampire bat lineage. We discovered previously-unknown gene losses that relate to metabolic and physiological changes, such as reduced insulin secretion (FFAR1, SLC30A8), limited glycogen stores (PPP1R3E), and a distinct gastric physiology (CTSE). Other gene losses likely reflect the biased nutrient composition (ERN2, CTRL) and distinct pathogen diversity of blood (RNASE7). Interestingly, the loss of REP15 likely helped vampire bats to adapt to high dietary iron levels by enhancing iron excretion and the loss of the 24S-hydroxycholesterol metabolizing enzyme CYP39A1 could contribute to their exceptional cognitive abilities. Finally, losses of key cone phototransduction genes (PDE6H, PDE6C) suggest that these strictly-nocturnal bats completely lack cone-based vision. These findings enhance our understanding of vampire bat biology and the genomic underpinnings of adaptations to sanguivory.

Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells

The stomach is an ideal organ to study because the gastric juice kills most of the swallowed microbes and, thus, creates rather similar milieu among individuals. Combined with a rather easy access to gastric juice, gastric physiology was among the first areas to be studied. During the last century, a rather complete understanding of the regulation of gastric acidity was obtained, establishing the central role of gastrin and the histamine producing enterochromaffin-like (ECL) cell. Similarly, the close connection between regulation of function and proliferation became evident, and, furthermore, that chronic overstimulation of a cell with the ability to proliferate, results in tumour formation. The ECL cell has long been acknowledged to give rise to neuroendocrine tumours (NETs), but not to play any role in carcinogenesis of gastric adenocarcinomas. However, when examining human gastric adenocarcinomas with the best methods presently available (immunohistochemistry with increased sensitivity and in-situ hybridization), it became clear that many of these cancers expressed neuroendocrine markers, suggesting that some of these tumours were of neuroendocrine, and more specifically, ECL cell origin. Thus, the ECL cell and its main regulator, gastrin, are central in human gastric carcinogenesis, which make new possibilities in prevention, prophylaxis, and treatment of this cancer.

Equine gastric ulcer syndrome in foals

Equine gastric ulcer syndrome (EGUC) is a common problem in foals. Gastric physiology differs between foals and adult horses, and the risk of EGUS also depends on age and other factors. This article aims to review what we know about EGUS in foals and provide some guidelines about the detection, management and prevention of EGUS in clinical practice.

Gfral-expressing Neurons Suppress Food Intake via Aversive Pathways

To determine the function and mechanisms of action for hindbrain neurons that express GFRAL, the receptor for the anorexigenic peptide, GDF-15, we generated Gfralcre and conditional GfralCreERT mice. While signals of infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, the artificial activation of GfralCre- expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). Additionally, activation of the smaller population of GFRAL neurons captured by the GfralCreERT allele decreased gastric emptying and produced a CTA without suppressing food intake, suggesting that GFRAL neurons primarily modulate gastric physiology and stimulate aversive responses. GFRAL neurons most strongly innervated the parabrachial nucleus (PBN), where they targeted CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated, pathophysiologic signals to the aversive suppression of nutrient uptake and absorption.

Gastroretentive Mucoadhesive Microsphere for the Management of Gastric Infection

Gastric infections are mostly triggered by Helicobacter pylori (H. pylori), a fungus that colonizes the stomach mucosa of more than 50% of the inhabitants of the world. Chronic H. Pylori diseasewas associated with stomach diseases such as peptic ulcer, chronic gastritis and stomach adenoc arcinoma. Current therapy for eradication relies on antibiotic-based therapies that are ineffective in about 20% of patients. Traditional method constraints optimize the creation of new techniques for fast, consistent and cost-effective H diagnosis. Infection with pylori. Wide-ranging study has been carried out over the previous few centuries to create a type of gastro-retentive dosage (GRDF). This sort of dosage form can advance the delivery and efficiency of stomach-active medicines because the GRDF enables the medication to remain in the stomach for a sufficient time period. Various methods were used to develop effective GRDFs such as high-density systems, low-density systems, swelling and expansion systems, hydrodynamically balanced systems, superporous hydrogels,. However, there are both merits and demerits in these kinds of schemes. Intra-individual and inter-individual dissimilarities are obstacles to the growth of effective GRDFs in gastric physiology. Examples of these individual differences include gastric pH and gastric motility that have a notable effect on the moment of stomach retention and delivery of drugs. Some of these obstacles can be overcome by developing a novel mucoadhesive microsphere. The mucoadhesive microsphere is characterized by close contact of the MDF with the mucosal layer, thereby increasing the localized absorption of the drug. H2Receptor antagonists (H2RAs) have become first-line therapy for acid related peptic disease and GRDF especially designed for H2RAs and drugs against H. pylori, including specific targeting systems and leading to a marked development in the quality of life for a large number of patients. In this relationship, new formulations with improved absorption, improved bioavailability and improved acid-suppressing regimens are welcome Keywords: H. pylori, gastro-retentive dosage, mucoadhesive microsphere

The Enterochromaffin-like [ECL] Cell—Central in Gastric Physiology and Pathology

Background: Studies on the regulation of gastric and pancreatic secretion began more than 100 years ago. Secretin was the first hormone postulated to exist, initiating the field of endocrinology. Gastrin produced in the antral mucosa was the second postulated hormone, and together with histamine and acetylcholine, represent the three major gastric acid secretagogues known since 1920. For a long time, the mast cell was the only recognized histamine-producing cell in the oxyntic mucosa and, in the mid-1980s, the ECL cell was recognized as the cell producing histamine, taking part in the regulation of gastric acid secretion. Methods: This review is based upon literature research and personal knowledge. Results: The ECL cell carries the gastrin receptor, and gastrin regulates its function (histamine release) as well as proliferation. Long-term hypergastrinemia results in gastric neoplasia of variable malignancies, implying that gastric hypoacidity resulting in increased gastrin release will induce gastric neoplasia, including gastric cancer. Conclusions: The trophic effect of gastrin on the ECL cell has implications to the treatment with inhibitors of acid secretion.