In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Ex Input:
We report a hereditary leukodystrophy in Standard Schnauzer puppies. Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures and ventral strabismus consistent with a diffuse intracranial lesion. Magnetic resonance imaging revealed a diffuse white matter disease without mass effect. Macroscopically, the cerebral white matter showed a gelatinous texture in the centrum semiovale. A mild hydrocephalus internus was noted. Histopathologically, a severe multifocal reduction of myelin formation and moderate diffuse edema without inflammation was detected leading to the diagnosis of leukodystrophy. Combined linkage analysis and homozygosity mapping in two related families delineated critical intervals of approximately 29 Mb. The comparison of whole genome sequence data of one affected Standard Schnauzer to 221 control genomes revealed a single private homozygous protein changing variant in the critical intervals, TSEN54:c.371G>A or p.(Gly124Asp). TSEN54 encodes the tRNA splicing endonuclease subunit 54. In humans, several variants in TSEN54 were reported to cause different types of pontocerebellar hypoplasia. The genotypes at the c.371G>A variant were perfectly associated with the leukodystrophy phenotype in 12 affected Standard Schnauzers and almost 1000 control dogs from different breeds. These results suggest that TSEN54:c.371G>A causes the leukodystrophy. The identification of a candidate causative variant enables genetic testing so that the unintentional breeding of affected Standard Schnauzers can be avoided in the future. Our findings extend the known genotype-phenotype correlation for TSEN54 variants. Various hereditary diseases of the cerebral white matter occur in humans and dogs. We describe a new leukodystrophy in Standard Schnauzers. Genetic mapping and whole genome sequence analysis identified a likely candidate causative variant in the TSEN54 gene encoding tRNA splicing endonuclease 54. These results provide new information about the role of TSEN54 in cell metabolism and the development of the central nervous system in the late gestational and early post-natal period. The affected dogs potentially represent a translational large animal model for similar leukoencephalopathies in human medicine. The clinical phenotype in Schnauzers included multifocal central nervous system signs. A holistic pathogenically driven understanding of disease initiation and perpetuation requires a solid analysis of the underlying genetics and characterization of the disease phenotype at the clinical and cellular as well as sub-cellular level. In contrast to the canine phenotype with a predominant manifestation in the cerebrum white matter, other TSEN54 variants in humans have been reported to result in a different pathological phenotype characterized by pontocerebellar hypoplasia. The differences between humans and dogs underscore the need for comparative analysis at the clinical, pathological and molecular level to understand species-specific protein mediated pathways, interactions and outcomes.

Ex Output:
TSEN54 missense variant in Standard Schnauzers with leukodystrophy Author summary


Ex Input:
Bacterial and viral infections occur early and recurrently in life and thereby impose a substantial disease burden. Besides causing clinical symptoms, a potential role of infection in the development of the asthma syndrome later in life has also been suggested. However, whether bacterial and viral infections unmask host factors in children at risk of asthma or whether they directly cause asthma remains unclear; both viewpoints could be justifi ed, but the underlying mechanisms are complex and poorly understood. Recently, the role of the bacterial microbiome has been emphasised. But data are still sparse and future studies are needed for defi nitive conclusions to be made. In this Review, we discuss present knowledge of viruses and bacteria that infect and colonise the respiratory tract and mucosal surfaces, including their timepoint of action, host factors related to infection, and their eff ect on childhood asthma. Childhood asthma could be the result of a combination of altered host susceptibility and infectious agents.

Ex Output:
Prenatal and childhood infections: implications for the development and treatment of childhood asthma


Ex Input:
The giant triton snail (Charonia tritonis) is one of the few natural predators of the adult Crown-of-Thorns starfish (COTS), a corallivore that has been damaging to many reefs in the Indo-Pacific. Charonia species have large salivary glands (SGs) that are suspected to produce either a venom and/or sulphuric acid which can immobilize their prey and neutralize the intrinsic toxic properties of COTS. To date, there is little information on the types of toxins produced by tritons. In this paper, the predatory behaviour of the C. tritonis is described. Then, the C. tritonis SG, which itself is made up of an anterior lobe (AL) and posterior lobe (PL), was analyzed using an integrated transcriptomics and proteomics approach, to identify putative toxin-and feeding-related proteins. A de novo transcriptome database and in silico protein analysis predicts that ~3800 proteins have features consistent with being secreted. A gland-specific proteomics analysis confirmed the presence of numerous SG-AL and SG-PL proteins, including those with similarity to cysteine-rich venom proteins. Sulfuric acid biosynthesis enzymes were identified, specific to the SG-PL. Our analysis of the C. tritonis SG (AL and PL) has provided a deeper insight into the biomolecular toolkit used for predation and feeding by C. tritonis. If a generalist predator evolves to a more a specialist diet, it is assumed that it would be accompanied by modifications of characters that permit greater efficiency in capturing specific prey species. These likely include foraging behaviors and search strategies with fine-tuned chemosensory systems, physiological processes associated with digestion and waste removal, and other features involved with prey capture 1 . Among predatory taxa the evolution of a specialized diet is likely to be strongly linked to the evolution of venoms used to subdue prey. Although the evolution of many of these characters may be difficult to trace for a species that has evolved a restricted diet, the evolution of venoms can be inferred from analyses of expression of genes encoding venom and digestion components 2, 3 . Marine organisms from a broad range of phyla, from bacteria and algae to invertebrates and vertebrates, are known to produce toxins with high chemical diversity, divergence of which is likely driven by speciation and diet 4-6 . Some examples include tetrodotoxins produced by bacteria found in the saliva of the blue-ringed octopus and puffer fish 7, 8 , potent pore-forming toxins produced by cnidarians 9 , okadaic acid produced by bacteria in marine sponges 10 , and saponins (steroidal and triterpenoid) that are produced by echinoderms 11 . Venoms, and in particular specific toxins, play multiple roles from foraging to defense and intraspecific conflict 12 . Although there are many species of predatory marine snails, studies of venom toxins have been restricted to species within the superfamily Conoidea 13 . These venomous marine cone snails synthesize a remarkable diversity of pharmacologically active small peptides (conotoxins) to enable prey capture, self-defense and intra-specific competition 14-16 . The potency and selective profiles of the conotoxins vary depending on species targets that may include various subtypes of voltage-and ligand-gated ion channels, G protein-coupled receptors and neurotransmitter transporters 17 . Gastropods of the superfamily Tonnoidea are effective predators and thought to capture prey through envenomation 18 . Within the Tonnoidea, several species in the Cassidae family of snails are specialist predators of echinoderms. The large paired and mono-lobed salivary gland (SG) of Cassidae family snails are known to be toxic and inject a strong acid or venomous saliva into their prey to paralyse them before consumption [19] [20] [21] . For example, Cassidae helmet shell snails secrete an acidic saliva to soften the body wall of their preferred prey, sea urchin 22, 23 , Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 6000 |

Ex Output:

Multiomics analysis of the giant triton snail salivary gland, a crown- of-thorns starfish predator OPEN