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Analyses of multiple whole-genome sequences from the same species have revealed that differences in gene content can be substantial, particularly in prokaryotes. Such variation has led to the recognition of pangenomes, the complete set of genes present in a species – consisting of core genes, present in all individuals, and accessory genes whose presence is variable. Questions now arise about how pangenomes originate and evolve. We describe how gene content variation can arise as a result of the combination of several processes, including random drift, selection, gain/loss balance, and the influence of ecological and epistatic interactions. We believe that identifying the contributions of these processes to pangenomes will need novel theoretical approaches and empirical data. The genomes of individuals of the same species can display large amounts of variation in gene content, particularly in prokaryotes. We still do not understand the reasons behind this diversity. It is not clear to what extent the set of variable genes, the accessory genome, contributes to fitness. Different mechanisms can contribute to explain gene-content variation, including selection-dominated and random genetic drift-dominated processes. Variability in rates of gene gain and loss and fitness likely plays an important role in explaining pangenome variability. The distribution of these parameters will likely vary for different species. Multiple mechanisms likely contribute to gene content variation from neutral to selective, including gene gain/loss balance, gene-by-environment interactions, Black Queen dynamics and social interactions, and gene–gene interactions. The mechanisms that contribute to gene content diversity likely vary within and between species and could be themselves subject to evolution and selection. We are just starting to develop the theoretical toolkit required to describe and understand gene content variability and pangenomes. Understanding gene-content variation and evolution is important to understand microbial adaptation and associated processes, such as emergence of antimicrobial resistance and new pathogens. [ABSTRACT FROM AUTHOR]

No accepted phylogenetic scheme for prokaryotes emerged until the late 1970s. Prior to that, it was assumed that there was a phylogenetic tree uniting all prokaryotes, but no suitable data were available for its construction. For 20 years, through the 1980s and 1990s, rRNA phylogenies were the gold standard. However, beginning in the last decade, findings from genomic data have challenged this new consensus. Gene trees can conflict greatly, and strains of the same species can differ enormously in genome content. Horizontal gene transfer is now known to be a significant influence on genome evolution. The next decade is likely to resolve whether or not we retain the centuries-old metaphor of the tree for all of life. [Copyright &y& Elsevier]

Abstract: Cancer may act as the etiological agent for natural selection in some genes. This selective pressure would act to reduce the success of neoplastic lineages over normal cell lineages in individuals of reproductive age. In addition, human''s relatively larger brain and longer lifespan may have also acted as a selective force requiring new genotypes. One of the most important proteins in both processes is the fatty acid synthase (FAS) gene involved in fatty acid biosynthesis. A variety of other proteins, including PTEN, MAPK1, SREBP1, SREBP2 and PI are also involved in the regulation of fatty acid biosynthesis. We have specifically analysed variability in selective pressure across all these genes in human, mouse and other vertebrates. We have found that the FAS gene alone has signatures indicative of adaptive evolution. We did not find any signatures of adaptive evolution in any of the other proteins. In the FAS gene, we have detected an excess of non-synonymous over synonymous substitutions in approximately 6% of sites in the human lineage. Contrastingly, the substitution process at these sites in other available vertebrates and mammals indicates strong purifying selection. This is likely to reflect a functional shift in human FAS and correlates well with previously observed changes in FAS biochemical activities. We speculate that the role played by FAS either in cancer development or in human brain development has created this selective pressure, although we cannot rule out the various other functions of FAS. [Copyright &y& Elsevier]

Positive selection or adaptive evolution is thought to be responsible, at least some of the time, for the rapid accumulation of advantageous changes in protein-coding genes. The origin of new enzymatic functions, erection of barriers to heterospecific fertilization, and evasion of host response by pathogens, among other things, are thought to be instances of adaptive evolution. Detecting positive selection in protein-coding genes is fraught with difficulties. Saturation for sequence change, codon usage bias, ephemeral selection events and differential selective pressures on amino acids all contribute to the problem. A number of solutions have been proposed with varying degrees of success, however they suffer from limitations of not being accurate enough or being prohibitively computationally intensive. We have developed a character-based method of identifying lineages that undergo positive selection. In our method we assess the possibility that for each internal branch of a phylogenetic tree an event occurred that subsequently gave rise to a greater number of replacement substitutions than might be expected. We classify these replacement substitutions into two categories – whether they subsequently became invariable or changed again in at least one descendent lineage. The former situation indicates that the new character state is under strong selection to preserve its new identity (directional selection), while the latter situation indicates that there is a persistent pressure to change identity (non-directional selection). The method is fast and accurate, easy to implement, sensitive to short-lived selection events and robust with respect to sampling density and proportion of sites under the influence of positive selection. [Copyright &y& Elsevier]

Prokaryote pangenomes are influenced heavily by environmental factors and the opportunity for gene gain and loss events. As the field of pangenome analysis has expanded, so has the need to fully understand the complexity of how eco-evolutionary dynamics shape pangenomes. Here, we describe current models of pangenome evolution and discuss their suitability and accuracy. We suggest that pangenomes are dynamic entities under constant flux, highlighting the influence of two-way interactions between pangenome and environment. New classifications of core and accessory genes are also considered, underscoring the need for continuous evaluation of nomenclature in a fast-moving field. We conclude that future models of pangenome evolution should incorporate eco-evolutionary dynamics to fully encompass their dynamic, changeable nature. [ABSTRACT FROM AUTHOR]

The rate of protein evolution varies more than 1000-fold and, for the past 30 years, it was thought that the rate was determined by protein function. Drummond and co-workers have now shown that a single factor underlying mRNA expression, protein abundance and synonymous codon usage is the chief causal agent of protein evolutionary rate in yeast. It will be interesting to see whether this is shown to be a universal rule for all biological systems. [Copyright &y& Elsevier]

Relationships among prokaryotes and the origin of eukaryotes have both proven controversial, with results depending upon the gene sequences and methods used. Extensive horizontal gene transfer is one possible reason why inferring such deep phylogenetic relationships is difficult. In two recent papers, Lake and Rivera introduce new methods that can be used to reconstruct the genomic tree in the presence of horizontal gene transfers, but which suggest that a ring rather than a tree is a better representation of some parts of the history of life on Earth. [Copyright &y& Elsevier]

Horizontal transfer of genes has sometimes been viewed as a nuisance for the work of understanding the evolutionary history of lineages. Recent work has shown that clever analysis of inter-lineage gene transfer is productive and has tremendous explanatory power, in particular, for niche adaptation. These studies alter our perception of what are the fundamental units of evolution and selection. [ABSTRACT FROM AUTHOR]

To gain new insights into gene identity and gene expression in the bovine corpus luteum (CL) a directionally cloned CL cDNA library was constructed, screened with a total CL cDNA probe and clones representing abundant and rare mRNA transcripts isolated. The 5′-terminal DNA sequence of 960 cDNA clones, composed of 192 abundant and 768 rare mRNA transcripts was determined and clustered into 351 non-redundant expressed sequence tag (EST) groups. Bioinformatic analysis revealed that 309 (88%) of the ESTs showed significant homology to existing sequences in the protein and nucleotide public databases. Several previously unidentified bovine genes encoding proteins associated with key aspects of CL function including extracellular matrix remodelling, lipid metabolism/steroid biosynthesis and apoptosis, were identified. Forty-two (12%) of the ESTs showed homology with human or with other uncharacterised ESTs, some of these were abundantly expressed and may therefore play an important role in primary CL function. Tissue-specificity and temporal CL gene expression of selected clones previously unidentified in bovine CL tissue was also examined. The most interesting finds indicated that mRNA encoding squalene epoxidase was constitutively expressed in CL tissue throughout the oestrous cycle and 7-fold down-regulated (P<0.05) in late luteal tissue, concomitant with the disappearance of systemic progesterone, suggesting that de novo cholesterol biosynthesis plays an important role in steroidogenesis. The mRNA encoding the growth factor, insulin-like growth factor-binding protein-related protein 1 (IGFBP-rP1), remained constant during the oestrous cycle and was 1.8-fold up-regulated (P<0.05) in late luteal tissue implying a role in CL regression. [Copyright &y& Elsevier]

Background: The initial COVID-19 pandemic shutdown led to the canceling of elective surgeries throughout most of the USA and Canada.Objective: This survey was carried out on behalf of the Parkinson Study Group (PSG) to understand the impact of the shutdown on deep brain stimulation (DBS) practices in North America.Methods: A survey was distributed through RedCap® to the members of the PSG Functional Neurosurgical Working Group. Only one member from each site was asked to respond to the survey. Responses were collected from May 15 to June 6, 2020.Results: Twenty-three sites participated; 19 (83%) sites were from the USA and 4 (17%) from Canada. Twenty-one sites were academic medical centers. COVID-19 associated DBS restrictions were in place from 4 to 16 weeks. One-third of sites halted preoperative evaluations, while two-thirds of the sites offered limited preoperative evaluations. Institutional policy was the main contributor for the reported practice changes, with 87% of the sites additionally reporting patient-driven surgical delays secondary to pandemic concerns. Pre-post DBS associated management changes affected preoperative assessments 96%; electrode placement 87%; new implantable pulse generator (IPG) placement 83%; IPG replacement 65%; immediate postoperative DBS programming 74%; and routine DBS programming 91%.Conclusion: The COVID-19 pandemic related shutdown resulted in DBS practice changes in almost all North American sites who responded to this large survey. Information learned could inform development of future contingency plans to reduce patient delays in care under similar circumstances. [ABSTRACT FROM AUTHOR]

• Raman spectra for inks of Egyptian papyri dated 400 BCE and 1000 CE vary systematically with manuscript date. • Statistical analysis can provide date estimates for similar papyri to ± 120 years with 68% confidence. • Intrinsic variations in Raman spectra for different manuscripts limit accuracy of estimated dates. • Gaussian Mixture Modeling provides a statistical means for identifying carbon inks of similar character. • This methodology can constitute a strong indication of the antiquity and rough period for ancient inks. In the first study of its kind, we previously investigated Raman spectra of 17 papyri from the Columbia University Libraries collection, written in carbon-based black ink with well-established dates between 400 BCE and 1000 CE. Using a simple two-peak spectral model for the Raman spectrum of carbonaceous materials, we discovered small but statistically significant systematic variations in the spectral parameters with manuscript date. The purposes of this report are to present: (1) more-powerful statistical examinations of the correlation based on the two-peak spectral model and on a new three-peak model which includes spectral effects for amorphous carbon; (2) new data for additional ancient manuscripts, broadening the investigation; (3) a method for potentially exploiting the observed correlation to predict the dates of undated manuscripts of similar character; and (4) a hypothesis as to the underlying chemical basis of the observed spectral changes. We apply both linear and multiple linear regression analyses to the spectral models. We show that the three-peak model fits the experimental data much better than the two-peak model. Through the use of multiple linear regression, the three-peak model reduces significantly the overall correlation error. We find that our ability to predict dates for manuscripts that are similar to those of the study over the date range 400 BCE to 1000 CE is limited by intrinsic variations in the character of the pigments to about ± 118 years with 68% statistical confidence (or ± 236 years with 95% confidence). We confirm the observed correlation and prediction capabilities through a blind study of six additional ancient manuscripts and two late 19th- or early 20th-century fakes in the Columbia University collection. The data suggest that chemical degradation of amorphous carbon and chemical modification of graphitic crystals may both contribute to the observed spectral differences. This would also account for the magnitude of the variance in spectral character we observe, which possibly reflects differences in pigment manufacture processes as well as the effects of differences in chemical micro-environments after writing. The chemical degradation hypothesis receives additional support from previously unreported examination of two manuscripts from the collection of the Brooklyn Museum. The older of these, dated through conventional papyrological methods to 2323-2150 BCE, deviates from the linear regression models, but in a way consistent with chemical (i.e., non-linear) degradation. For comparison, we report Raman scattering for 8 different modern inks using the same protocol we developed for the ancient inks. Using statistical techniques based on Gaussian Mixture Modeling, we demonstrate differences between the spectral character of the inks of our base study and those prepared from modern reference pigments. This allows us to define a mathematical quantity that can distinguish between spectra of pigments that are spectrally similar to the ancient pigments studied here and those that are not. This new and non-destructive method produces a statistically robust indication of the antiquity and rough period (e.g., Ptolemaic, Roman, etc.) of the inks in question, if not the precise date. We hypothesize that the potential for greater precision is likely limited by the intrinsic variations in the spectral characteristics of the inks from manuscript to manuscript. [ABSTRACT FROM AUTHOR]

Objectives: Surgical treatment of odontoid fractures is recommended by many surgeons to prevent sudden neurologic injury or progressive myelopathy. Less aggressive approach to the treatment of odontoid fractures has been advocated by some authors especially in the elderly population. Very few reports have followed up patients' outcomes following conservative treatment of odontoid fractures. Here we evaluate the clinical and radiographic results of patients without myelopathy treated without surgery for an odontoid type fracture. Patients and methods: 101 patients with traumatic odontoid fracture admitted to the Pennsylvania State Hershey Medical Center between 1998 and 2008. Fractures were defined using a CT scan according to the Anderson-D'Alonzo Classification. Conservative treatment was pursued in appropriately selected patients. Results: Fifty-nine patients were selected to be treated in a cervical collar. Sixteen patients failed using radiographic evidence and continued neck pain. Fourteen patients went on to be surgically stabilized. The other two patients opted to continue with cervical orthosis and regular clinical evaluations. The Forty-three remaining patients had stable imaging studies and with no other complaints. None of the patients developed myelopathy symptoms during the follow-up period. Conclusions: Our results indicate that a select group of patients with odontoid fracture who are deemed stable on initial evaluation in a cervical orthosis may be effectively managed non-operatively. None of the patients who were managed conservatively had clinical worsening during the period of management. The decision to proceed with surgical treatment was based on failure of resolution of neck pain or worsening or concerning instability on imaging studies. However in many patients, even elderly patients in a surgical risks are greater, many odontoid fractures can be safely managed in a cervical orthosis. [ABSTRACT FROM AUTHOR]

Networks allow the investigation of evolutionary relationships that do not fit a tree model. They are becoming a leading tool for describing the evolutionary relationships between organisms, given the comparative complexities among genomes. [ABSTRACT FROM AUTHOR]