Cilia are made up of gene products too

We have discussed gene loss in the host and its relationship with viral pathogens earlier concerning C9 and the TCP. Despite its fame and obvious importance to chicken health, the loss of C9 seems to have had zero impact in the almost one-year period in which the "Birth and Death in the Terminal Complement Pathway" article has been live on the internet, PubMed and the well-read journal Molecular Immunology. The complicated lives of the rich and powerful are hard to comprehend. So looking at less well-known and hard-to-study genes seems a better bet, given the multi-citation success of PLGRKT. 

Hopefully, the pandemic of the century (Covid-19) is done and dusted. Let's pray to the Supreme Lord Krishna to ensure it was indeed the PoTC (Pandemic of the Century) and move ahead with our lives. However, that would mean another PoTC is due in the next century, and if covid has taught us anything, you can never be too prepared to deal with it. So it is natural for us to continue working on increasing our knowledge to deal with the next PoTC. While most of us were hiding, scared in our homes, the brave few were working round the clock on a war footing to stop covid. One such covid warrior is Lisa A. Chakrabarti from the Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France. 

In their paper titled "SARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance" published in Nature Communications, Robinot and Hubert et al. use "a reconstructed human bronchial epithelium model" to study the structural and functional consequences of SARS-CoV-2 infection. They find "rapid loss of the ciliary layer" using their robust assay procedure. Several other prominent studies have found that the cilia are affected by viral infections such as the one caused by SARS-CoV-2. Interestingly, these changes to the epithelium have also been identified using golden Syrian hamsters as a model. The study titled "Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters" by Bryche et al. finds "massive damage of the olfactory epithelium as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection". Based on these studies, it has been suggested that the loss of odour detection experienced by many of the covid infected individuals is due to the loss of the cilia. The tiny cilia lining the epithelia seem to have a prominent role when it comes to mighty viral pathogens. 

When Buddhabhushan et al. found that genes that code for parts of the ciliary apparatus are lost in chicken and a few other bird species, it was an interesting find from the perspective of how they may differ in their susceptibility to pathogens. It would also be possible that the change in the cilia could alter the ability to smell things. The prevalence of olfactory receptor genes has been linked to differences in the sense of smell among birds. Hence, a follow-up to the study titled "Avian olfactory receptor gene repertoires: evidence for a well-developed sense of smell in birds?" could focus on unorthodox genes such as those identified by  Buddhabhushan et al. Very little research has been conducted to date on the functions of the genes WDR93 and CFAP46. While it is known that they are part of the central apparatus projection D (C1d), the role of these genes in host-pathogen interaction is unclear. Two or three papers briefly suggest a role for WDR93 in dealing with pathogens. Further experimental work will need to decode the relevance using extensive experimental approaches.

Experimental studies of the cilia and their functionality have been challenging due to the lack of high throughput assays and the difficulties involved in the study of cilia. The recent pandemic has helped refocus efforts on studying cilia for its motility using cell culture approaches. A recent paper published in the journal Royal Society Open Science provides a very useful software resource to perform automated measurements of ciliary motility. The paper titled "Assessing motile cilia coverage and beat frequency in mammalian in vitro cell culture tissues" presents "a novel and open-source method" to "fully characterize cilia beating frequency and motile cilia coverage in an automated fashion without user intervention". The technical advancements involved in this manuscript involve the use of several image analysis methods and results in a GUI-based tool called Canvas. All publications in the journal Royal Society Open Science publish the peer review report online and is available on the Web of Science with citable doi's. So it is possible to see how many reviewers were involved and what comments were raised by them.

In the genetics section of the journal, the most recent article is about the evolution of the gene ADH7 and its link with diet. 

1. The dataset spanning seven orders consists of 59 mammalian species: 27 bat, nine treeshrew, 11 rodent, four opossum and eight additional small to mid-sized mammal species in Central and South America, the Caribbean, as well as Southeast Asia.
2. The sequences were obtained using target capture plus massive parallel sequencing, or Sanger sequencing following PCR amplification of exon 7.
3. The authors find high concordance in the sequences generated by these two methods. The only differences between the two sequencing methods seem to be a result of SNP's and inter-individual variation.
4. The HybPiper pipeline is also used to recover the gene sequences and assemble them into full-length gene sequences.
5. Interestingly, the authors find the presence of multiple copies of the ADH7 gene and note: "The presence of a second ADH7 gene in bats was not known at the time we designed the baits for our target capture sequencing, complicating our assembly pipeline. As expected with short-read sequencing data, attempts to fully assemble these paralogues separately from our reads were not successful; however, variation in bat ADH7 sequences at site 294 could be determined by visually inspecting the mapped shorts reads in IGV"
6. The full dataset consisting of the following was compiled:
1. 59 mammalian species new data
2. 85 ADH7 sequences curated in a previous study (Genetic evidence of widespread variation in ethanol metabolism among mammals: revisiting the ‘myth' of natural intoxication)
3. 30 sequences newly mined from NCBI
7. After the dataset was compiled, model testing was done with a phylogenetic correction to test "if a frugivorous and/or nectarivorous diet correlates with"
1. retention/pseudogenization; n = 166
2. presence of a substitution at site 294 (yes/no) as a binary dependent variable (n = 133)
8. For testing the hypothesis, the following Phylogenetic generalized linear models (PGLM) were used:
1. The maximum penalized likelihood estimation (MPLE) and 
2. The IG10 method

The two main results from tests done on these data are:

1. Diet and putative functional variation at site 294
2. Diet and putative gene functionality

Finally, the authors discuss the interpretation of the two predictions made by them:

1. Primarily frugivorous and/or nectarivorous species will have substitutions at site 294 to valine or to other amino acids with similar physical and chemical properties, i.e. hydrophobic nature and a large side chain
2. The ADH7 genes of highly insectivorous, carnivorous/sanguinivorous or herbivorous species will be pseudogenized due to relaxed selection, as they are less likely to be exposed to dietary ethanol

Both this ADH7 paper and the previous one published in Biology Letters share several authors, such as Amanda D. Melin from the University of Calgary, Canada. The Biology Letters paper has seen a great deal of popularity in the media due to its links with animal intoxication. In terms of methodology, both papers are rather similar. However, the authors do spend a considerable amount of time and effort to estimate gene loss timing using the Meredith et al. method in the first paper. Given the sensitivity of the Meredith method to the set of species used in estimating the gene loss timing, its use is not as widespread as it might have been if the estimates were robust. Moreover, some of the assumptions used to estimate the time of gene loss are not true in most cases. All of these articles are published by journals of the Royal Society and are part of Open Science. What is Open Science?

The benefits of Open Science are described in this short video from the Royal Society. 

Many open-access journals are actually predatory and are known to entrap unsuspecting scientists, especially from low- and middle-income countries (LMICs). So how to know if a journal is predatory? Some brilliant folk have come up with useful criteria to identify predatory journals. However, as they note in their article, it can be very tricky to distinguish between predatory and legitimate journals. Royal Society Open Science has various read and publish agreements with major universities worldwide to cover the article processing charges. So in some cases, the authors from these universities are assured by the university that this is not deemed a predatory journal by them. Based on this reasoning, it would appear Royal Society Open Science is not a predatory journal, and the publication of the article titled "Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds" by Buddhabhushan et al. may not be an example of entrapment of unsuspecting entities.