Diverse origins of near-identical antifreeze proteins in unrelated fish lineages provide insights into evolutionary mechanisms of new gene birth and protein sequence convergence.

Determining the origins of novel genes and the genetic mechanisms underlying the emergence of new functions is challenging yet crucial for understanding evolutionary innovations. The novel fish antifreeze proteins, exemplifying convergent evolution, represent excellent opportunities to investigate the evolutionary origins and pathways of new genes. Particularly notable is the near-identical type I antifreeze proteins (AFPI) in four phylogenetically divergent fish taxa. This study tested the hypothesis of protein sequence convergence beyond functional convergence in three unrelated AFPI-bearing fish lineages, revealing different paths by which a similar protein arose from diverse genomic resources. Comprehensive comparative analyses of de novo sequenced genome of the winter flounder and grubby sculpin, available high-quality genome of the cunner, and those of 14 other relevant species found that the near-identical AFPI originated from a distinct genetic precursor in each lineage, and independently evolved coding regions for the novel ice-binding protein while retaining sequence identity in the regulatory regions with their respective ancestor. The deduced evolutionary processes and molecular mechanisms is consistent with the Innovation-Amplification-Divergence (IAD) model applicable to AFPI formation in all three lineages, a new Duplication-Degeneration-Divergence (DDD) model we propose for the sculpin lineage, and a DDD model with gene fission for the cunner lineage. This investigation illustrates the multiple ways by which a novel functional gene with sequence convergence at the protein level could evolve across divergent species, advancing our understanding of the mechanistic intricacies in new gene formation.

Genomics of cold adaptations in the Antarctic notothenioid fish radiation.

Numerous novel adaptations characterise the radiation of notothenioids, the dominant fish group in the freezing seas of the Southern Ocean. To improve understanding of the evolution of this iconic fish group, here we generate and analyse new genome assemblies for 24 species covering all major subgroups of the radiation, including five long-read assemblies. We present a new estimate for the onset of the radiation at 10.7 million years ago, based on a time-calibrated phylogeny derived from genome-wide sequence data. We identify a two-fold variation in genome size, driven by expansion of multiple transposable element families, and use the long-read data to reconstruct two evolutionarily important, highly repetitive gene family loci. First, we present the most complete reconstruction to date of the antifreeze glycoprotein gene family, whose emergence enabled survival in sub-zero temperatures, showing the expansion of the antifreeze gene locus from the ancestral to the derived state. Second, we trace the loss of haemoglobin genes in icefishes, the only vertebrates lacking functional haemoglobins, through complete reconstruction of the two haemoglobin gene clusters across notothenioid families. Both the haemoglobin and antifreeze genomic loci are characterised by multiple transposon expansions that may have driven the evolutionary history of these genes.

Differentiation between normal and abnormal kidneys using 99mTc-DMSA SPECT with deep learning in paediatric patients.

AIM: To investigate the feasibility of using deep learning (DL) to differentiate normal from abnormal (or scarred) kidneys using technetium-99m dimercaptosuccinic acid (99mTc-DMSA) single-photon-emission computed tomography (SPECT) in paediatric patients. MATERIAL AND METHODS: Three hundred and one 99mTc-DMSA renal SPECT examinations were reviewed retrospectively. The 301 patients were split randomly into 261, 20, and 20 for training, validation, and testing data, respectively. The DL model was trained using three-dimensional (3D) SPECT images, two-dimensional (2D) maximum intensity projections (MIPs), and 2.5-dimensional (2.5D) MIPs (i.e., transverse, sagittal, and coronal views). Each DL model was trained to determine renal SPECT images into either normal or abnormal. Consensus reading results by two nuclear medicine physicians served as the reference standard. RESULTS: The DL model trained by 2.5D MIPs outperformed that trained by either 3D SPECT images or 2D MIPs. The accuracy, sensitivity, and specificity of the 2.5D model for the differentiation between normal and abnormal kidneys were 92.5%, 90% and 95%, respectively. CONCLUSION: The experimental results suggest that DL has the potential to differentiate normal from abnormal kidneys in children using 99mTc-DMSA SPECT imaging.

Novel mitochondrial genome rearrangements including duplications and extensive heteroplasmy could underlie temperature adaptations in Antarctic notothenioid fishes.

Mitochondrial genomes are known for their compact size and conserved gene order, however, recent studies employing long-read sequencing technologies have revealed the presence of atypical mitogenomes in some species. In this study, we assembled and annotated the mitogenomes of five Antarctic notothenioids, including four icefishes (Champsocephalus gunnari, C. esox, Chaenocephalus aceratus, and Pseudochaenichthys georgianus) and the cold-specialized Trematomus borchgrevinki. Antarctic notothenioids are known to harbor some rearrangements in their mt genomes, however the extensive duplications in icefishes observed in our study have never been reported before. In the icefishes, we observed duplications of the protein coding gene ND6, two transfer RNAs, and the control region with different copy number variants present within the same individuals and with some ND6 duplications appearing to follow the canonical Duplication-Degeneration-Complementation (DDC) model in C. esox and C. gunnari. In addition, using long-read sequencing and k-mer analysis, we were able to detect extensive heteroplasmy in C. aceratus and C. esox. We also observed a large inversion in the mitogenome of T. borchgrevinki, along with the presence of tandem repeats in its control region. This study is the first in using long-read sequencing to assemble and identify structural variants and heteroplasmy in notothenioid mitogenomes and signifies the importance of long-reads in resolving complex mitochondrial architectures. Identification of such wide-ranging structural variants in the mitogenomes of these fishes could provide insight into the genetic basis of the atypical icefish mitochondrial physiology and more generally may provide insights about their potential role in cold adaptation.

Environmental DNA from Marine Waters and Substrates: Protocols for Sampling and eDNA Extraction.

Environmental DNA (eDNA) analysis has emerged in recent years as a powerful tool for the detection, monitoring, and characterization of aquatic metazoan communities, including vulnerable species. The rapid rate of adopting the eDNA approach across diverse habitats and taxonomic groups attests to its value for a wide array of investigative goals, from understanding natural or changing biodiversity to informing on conservation efforts at local and global scales. Regardless of research objectives, eDNA workflows commonly include the following essential steps: environmental sample acquisition, processing and preservation of samples, and eDNA extraction, followed by eDNA sequencing library preparation, high-capacity sequencing and sequence data analysis, or other methods of genetic detection. In this chapter, we supply instructional details for the early steps in the workflow to facilitate researchers considering adopting eDNA analysis to address questions in marine environments. Specifically, we detail sampling, preservation, extraction, and quantification protocols for eDNA originating from marine water, shallow substrates, and deeper sediments. eDNA is prone to degradation and loss, and to contamination through improper handling; these factors crucially influence the outcome and validity of an eDNA study. Thus, we also provide guidance on avoiding these pitfalls. Following extraction, purified eDNA is often sequenced on massively parallel sequencing platforms for comprehensive faunal diversity assessment using a metabarcoding or metagenomic approach, or for the detection and quantification of specific taxa by qPCR methods. These components of the workflow are project-specific and thus not included in this chapter. Instead, we briefly touch on the preparation of eDNA libraries and discuss comparisons between sequencing approaches to aid considerations in project design.

Propagation of a De Novo Gene under Natural Selection: Antifreeze Glycoprotein Genes and Their Evolutionary History in Codfishes.

The de novo birth of functional genes from non-coding DNA as an important contributor to new gene formation is increasingly supported by evidence from diverse eukaryotic lineages. However, many uncertainties remain, including how the incipient de novo genes would continue to evolve and the molecular mechanisms underlying their evolutionary trajectory. Here we address these questions by investigating evolutionary history of the de novo antifreeze glycoprotein (AFGP) gene and gene family in gadid (codfish) lineages. We examined AFGP phenotype on a phylogenetic framework encompassing a broad sampling of gadids from freezing and non-freezing habitats. In three select species representing different AFGP-bearing clades, we analyzed all AFGP gene family members and the broader scale AFGP genomic regions in detail. Codon usage analyses suggest that motif duplication produced the intragenic AFGP tripeptide coding repeats, and rapid sequence divergence post-duplication stabilized the recombination-prone long repetitive coding region. Genomic loci analyses support AFGP originated once from a single ancestral genomic origin, and shed light on how the de novo gene proliferated into a gene family. Results also show the processes of gene duplication and gene loss are distinctive in separate clades, and both genotype and phenotype are commensurate with differential local selective pressures.

Effects of warming rates on physiological and molecular components of response to CTMax heat stress in the Antarctic fish Harpagifer antarcticus.

Maximum and minimum Critical thermal limits (CTMax and CTMin) have been studied extensively to assess thermal tolerance in ectotherms by means of ramping assays. Notothenioid fish have been proposed as particularly sensitive to temperature increases related to global climate change. However, there are large gaps in our understanding of the thermal responses of these extreme cold-adapted fish in assays with heating rates. We evaluated the effects of two commonly used heating rates (0.3 and 1 °C/min) on the cellular stress responses in the intertidal Antarctic fish Harpagifer antarcticus immediately after CTMax was reached, and at 2 and 4 h of recovery time in ambient water. We compared CTMax values, the relative transcript expression of genes relvant to heat shock response (Hsc70, Hsp70, Grp78), hypoxia (Hif1-α, LDHa, GR), ubiquitination (Ube2), and apoptosis (SMAC/DIABLO), and five plasma parameters - glucose, lactate, total protein, osmolality and cortisol. CTMax values between the two heating rates are not significantly different, and both rates elicited a similar stress response at molecular and physiological levels. We found a lack of up-regulated response of heat shock proteins, consistent with other Antarctic notothenioids. The general transcriptional pattern trended to downregulation, which was more evident in the slower 0.3 °C/min rate, and instances of upregulation were mainly related to ubiquitination. The faster 1 °C/min rate, rarely used for Antarctic fish, can be suitable for studying cold-adapted stenothermic fish without overestimating thermal tolerance or inducing damage from longer heat exposure.

Effect of glucocorticoid therapy on the prognosis of patients with severe and critical COVID-19: a single-center retrospective cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has elevated mortality in severe and critical patients globally. This study examined the effect of glucocorticoids (GCS) on the time of virus clearance and absorption of lung lesions in severe and critical COVID-19 patients. PATIENTS AND METHODS: Severe and critical COVID-19 cases diagnosed in Wuhan Pulmonary Hospital from January 7 to February 10, 2020 were analyzed. The generalized linear model was utilized to assess the effects of GCS therapy on the times of nucleic acid test turning negative and improved pulmonary imaging, respectively. RESULTS: Of 66 patients, 51 (77.3%) and 15 (22.7%) were severe and critical cases, respectively, and aged 62 ± 11 years. A total of 58 patients (87.9%) tested negative, and 56 (84.8%) showed improved lung imaging. Age, thrombocytopenia, CD8 + T cell count, course of GCS therapy, and total dose were correlated with the time of nucleic acid test turning negative (p < 0.05), and sex was correlated with the time of initial pulmonary imaging improvement (p < 0.05). The time of nucleic acid test turning negative in individuals with GCS therapy course ≤ 10 days was shorter than that of the GCS therapy course > 10 days group (p=0.001). No statistical difference was found in the dose, course of GCS, and initial time of improved lung imaging. CONCLUSIONS: Increasing the dose of GCS and prolonging the course of treatment do not shorten the time of nucleic acid test turning negative or improved absorption of pulmonary lesions. Thus, the rational use of GCS is particularly important.

Reducing scan time of paediatric 99mTc-DMSA SPECT via deep learning.

AIM: To investigate the feasibility of reducing the scan time of paediatric technetium 99m (99mTc) dimercaptosuccinic acid (DMSA) single-photon-emission computed tomographic (SPECT) using a deep learning (DL) method. MATERIAL AND METHODS: A total of 112 paediatric 99mTc-DMSA renal SPECT scans were analysed retrospectively. Of the 112 examinations, 88 (84 for training and four for validation) were used to train a DL-based model that could generate full-acquisition-time reconstructed SPECT images from half-time acquisition. The remaining 24 examinations were used to evaluate the performance of the trained model. RESULTS: DL-based SPECT images obtained from half-time acquisition have image quality similar to the standard clinical SPECT images obtained from full-acquisition-time acquisition. Moreover, the accuracy, sensitivity and specificity of the DL-based SPECT images for detection of affected kidneys were 91.7%, 83.3%, and 100%, respectively. CONCLUSION: These preliminary results suggest that DL has the potential to reduce the scan time of paediatric 99mTc-DMSA SPECT imaging while maintaining diagnostic accuracy.

Antarctic ecosystems in transition - life between stresses and opportunities.

Important findings from the second decade of the 21st century on the impact of environmental change on biological processes in the Antarctic were synthesised by 26 international experts. Ten key messages emerged that have stakeholder-relevance and/or a high impact for the scientific community. They address (i) altered biogeochemical cycles, (ii) ocean acidification, (iii) climate change hotspots, (iv) unexpected dynamism in seabed-dwelling populations, (v) spatial range shifts, (vi) adaptation and thermal resilience, (vii) sea ice related biological fluctuations, (viii) pollution, (ix) endangered terrestrial endemism and (x) the discovery of unknown habitats. Most Antarctic biotas are exposed to multiple stresses and considered vulnerable to environmental change due to narrow tolerance ranges, rapid change, projected circumpolar impacts, low potential for timely genetic adaptation, and migration barriers. Important ecosystem functions, such as primary production and energy transfer between trophic levels, have already changed, and biodiversity patterns have shifted. A confidence assessment of the degree of 'scientific understanding' revealed an intermediate level for most of the more detailed sub-messages, indicating that process-oriented research has been successful in the past decade. Additional efforts are necessary, however, to achieve the level of robustness in scientific knowledge that is required to inform protection measures of the unique Antarctic terrestrial and marine ecosystems, and their contributions to global biodiversity and ecosystem services.

Evolution of chaperome gene expression and regulatory elements in the antarctic notothenioid fishes.

Confined within the cold-stable Southern Ocean, Antarctic notothenioid fishes have undergone an evolutionary loss of the inducible heat shock response (HSR), while facing perpetual low-temperature challenges to cellular proteostasis. This study examines how evolution in chronic cold has affected the shared cellular apparatus that mediates proteostasis under normal and heat stressed states. To deduce Antarctic-specific changes, we compared native expression levels across the full suite of chaperome genes and assessed the structural integrity of two crucial HSR regulators - Heat Shock Factor 1 (HSF1) that activates HSR, and heat shock elements (HSEs), the binding sites for HSF1 - between Antarctic fishes and the basal temperate notothenioid Eleginops maclovinus. Native expression levels of Antarctic fish chaperomes showed very modest changes overall, contrary to the common view of constitutive upregulation in the cold. Only a few cytosolic HSP70 genes showed greater transcription, with only the ancestrally-inducible HSPA6 strongly upregulated across all Antarctic species. Additionally, the constant cold has apparently not relaxed the selective pressures on maintaining HSF1 and HSEs in Antarctic fish. Instead, we found HSF1 experienced intensified selective pressure, with conserved sequence changes in Antarctic species suggesting optimization for non-heat-stress functional roles. HSEs of the HSP70 gene family have largely remained conserved in canonical sequence motifs and copy numbers as in E. maclovinus, showing limited impact of relaxed selective pressure. This study shows that evolution in chronic cold has led to both subtle and distinctive changes in the cellular apparatus for proteostasis and HSR, with functional consequences amenable to experimental evaluation.

A tale of two genes: divergent evolutionary fate of haptoglobin and hemopexin in hemoglobinless Antarctic icefishes.

The evolution of Antarctic notothenioid fishes in the isolated freezing Southern Ocean has led to remarkable trait gains and losses. One of the most extraordinary was the loss of the major oxygen carrier hemoglobin (Hb) in the icefishes (family Channichthyidae). Although the mechanisms of this loss and the resulting compensatory changes have been well studied, the impact of Hb loss on the network of genes that once supported its recycling and disposal has remained unexplored. Here, we report the functional fate and underlying molecular changes of two such key Hb-supporting proteins across the icefish family - haptoglobin (Hp) and hemopexin (Hx), crucial in removing cytotoxic free Hb and heme, respectively. Hp plays a critical role in binding free Hb for intracellular recycling and absent its primary client, icefish Hp transcription is now vanishingly little, and translation into a functional protein is nearly silenced. Hp genotype degeneration has manifested in separate lineages of the icefish phylogeny with three distinct nonsense mutations and a deletion frame shift, as well as mutated polyadenylation signal sequences. Thus, Hb loss appears to have diminished selective constraint on Hp maintenance, resulting in its stochastic, co-evolutionary drift towards extinction. Hx binds free heme for iron recycling in hepatocytes. In contrast to Hp, Hx genotype integrity is preserved in the icefishes and transcription occurs at levels comparable to those in the red-blooded notothenioids. The persistence of Hx likely owes to continued selective pressure for its function from mitochondrial and non-Hb cellular hemoproteins.

Molecular mechanism and history of non-sense to sense evolution of antifreeze glycoprotein gene in northern gadids.

A fundamental question in evolutionary biology is how genetic novelty arises. De novo gene birth is a recently recognized mechanism, but the evolutionary process and function of putative de novo genes remain largely obscure. With a clear life-saving function, the diverse antifreeze proteins of polar fishes are exemplary adaptive innovations and models for investigating new gene evolution. Here, we report clear evidence and a detailed molecular mechanism for the de novo formation of the northern gadid (codfish) antifreeze glycoprotein (AFGP) gene from a minimal noncoding sequence. We constructed genomic DNA libraries for AFGP-bearing and AFGP-lacking species across the gadid phylogeny and performed fine-scale comparative analyses of the AFGP genomic loci and homologs. We identified the noncoding founder region and a nine-nucleotide (9-nt) element therein that supplied the codons for one Thr-Ala-Ala unit from which the extant repetitive AFGP-coding sequence (cds) arose through tandem duplications. The latent signal peptide (SP)-coding exons were fortuitous noncoding DNA sequence immediately upstream of the 9-nt element, which, when spliced, supplied a typical secretory signal. Through a 1-nt frameshift mutation, these two parts formed a single read-through open reading frame (ORF). It became functionalized when a putative translocation event conferred the essential cis promoter for transcriptional initiation. We experimentally proved that all genic components of the extant gadid AFGP originated from entirely nongenic DNA. The gadid AFGP evolutionary process also represents a rare example of the proto-ORF model of de novo gene birth where a fully formed ORF existed before the regulatory element to activate transcription was acquired.

Morphological study of myelinated and unmyelinated fibres in the sacrococcygeal dorsal roots of the rat.

BACKGROUND: The number and calibre of myelinated and unmyelinated fibres of the sacrococcygeal dorsal roots innervating the tail of rats were studied by means of light and electron microscopy. MATERIALS AND METHODS: There were an estimated total of 12,500 myelinated and 25,500 unmyelinated dorsal root fibres innervating the tail of a rat. RESULTS: The results showed that from the second sacral (S2) to the fourth sacral (S4) segment, the fibre diameter spectrum of myelinated fibres within each dorsal root was bimodal with two peaks at 5 microns and 10 microns, respectively. The first sacral (S1) segment was composed of numerous smaller-size myelinated fibres, thus forming a right-skewed distribution. The coccygeal (Co) segments showed a unimodal distribution peaking at 10 microns for the first (Co1) segment and gradually shifting to 7 microns for the third (Co3) segment. Overall, there was a continuous relative increase of the larger vs. the smaller myelinated fibres from the sacral to coccygeal segments. The fibre diameter of unmyelinated fibres of all these roots was unimodal with a single peak at 0.5 microns. The ratio of unmy- elinated to myelinated fibre numbers was on average 2.83 for the S1-S2 roots, 1.66 for the S3-S4 roots, and 1.24 for the coccygeal roots. CONCLUSIONS: The comparison of the left- and right-side nerve fibres show that there was no significant difference, thus implying a symmetrical sensory innervation of the rat's tail.

Controlling Liquid-Liquid Phase Separation of Cold-Adapted Crystallin Proteins from the Antarctic Toothfish.

Liquid-liquid phase separation (LLPS) of proteins is important to a variety of biological processes both functional and deleterious, including the formation of membraneless organelles, molecular condensations that sequester or release molecules in response to stimuli, and the early stages of disease-related protein aggregation. In the protein-rich, crowded environment of the eye lens, LLPS manifests as cold cataract. We characterize the LLPS behavior of six structural γ-crystallins from the eye lens of the Antarctic toothfish Dissostichus mawsoni, whose intact lenses resist cold cataract in subzero waters. Phase separation of these proteins is not strongly correlated with thermal stability, aggregation propensity, or cross-species chaperone protection from heat denaturation. Instead, LLPS is driven by protein-protein interactions involving charged residues. The critical temperature of the phase transition can be tuned over a wide temperature range by selective substitution of surface residues, suggesting general principles for controlling this phenomenon, even in compactly folded proteins.

Evolution in chronic cold: varied loss of cellular response to heat in Antarctic notothenioid fish.

BACKGROUND: Confined within the freezing Southern Ocean, the Antarctic notothenioids have evolved to become both cold adapted and cold specialized. A marked signature of cold specialization is an apparent loss of the cellular heat shock response (HSR). As the HSR has been examined in very few notothenioid species to-date, it remains unknown whether HSR loss pervades the Antarctic radiation, or whether the broader cellular responses to heat stress has sustained similar loss. Understanding the evolutionary status of these responses in this stenothermal taxon is crucial for evaluating its adaptive potential to ocean warming under climate change. RESULTS: In this study, we used an acute heat stress protocol followed by RNA-Seq analyses to study the evolution of cellular-wide transcriptional responses to heat stress across three select notothenioid lineages - the basal temperate and nearest non-Antarctic sister species Eleginops maclovinus serving as ancestral proxy, the cryopelagic Pagothenia borchgrevinki and the icefish Chionodraco rastrospinosus representing cold-adapted red-blooded and hemoglobinless Antarctic notothenioids respectively. E. maclovinus displayed robust cellular stress responses including the ER Unfolded Protein Response and the cytosolic HSR, cementing the HSR as a plesiomorphy that preceded Antarctic notothenioid radiation. While the transcriptional response to heat stress was minimal in P. borchgrevinki, C. rastrospinosus exhibited robust responses in the broader cellular networks especially in inflammatory responses despite lacking the classic HSR and UPR. CONCLUSION: The disparate patterns observed in these two archetypal Antarctic species indicate the evolutionary status in cellular ability to mitigate acute heat stress varies even among Antarctic lineages, which may affect their adaptive potential in coping with a warming world.

Reconstruction of the repetitive antifreeze glycoprotein genomic loci in the cold-water gadids Boreogadus saida and Microgadus tomcod.

Antifreeze glycoproteins (AFGPs) are a novel evolutionary innovation in members of the northern cod fish family (Gadidae), crucial in preventing death from inoculative freezing by environmental ice in their frigid Arctic and sub-Arctic habitats. However, the genomic origin and molecular mechanism of evolution of this novel life-saving adaptive genetic trait remained to be definitively determined. To this end, we constructed large insert genomic DNA BAC (bacterial artificial chromosome) libraries for two AFGP-bearing gadids, the high-Arctic polar cod Boreogadus saida and the cold-temperate Atlantic tomcod Microgadus tomcod, to isolate and sequence their AFGP genomic regions for fine resolution evolutionary analyses. The BAC library construction encountered poor cloning efficiency initially, which we resolved by pretreating the agarose-embedded erythrocyte DNA with a cationic detergent, a method that may be of general use to BAC cloning for teleost species and/or where erythrocytes are the source of input DNA. The polar cod BAC library encompassed 92,160 clones with an average insert size of 94.7 kbp, and the Atlantic tomcod library contained 73,728 clones with an average insert size of 89.6 kbp. The genome sizes of B. saida and M. tomcod were estimated by cell flow cytometry to be 836 Mbp and 645 Mbp respectively, thus their BAC libraries have approximately 10- and 9.7-fold genome coverage respectively. The inclusiveness and depth of coverage were empirically confirmed by screening the libraries with three housekeeping genes. The BAC clones that mapped to the AFGP genomic loci of the two gadids were then isolated by screening the BAC libraries with gadid AFGP gene probes. Eight minimal tiling path (MTP) clones were identified for B. saida, sequenced, and assembled. The B. saida AFGP locus reconstruction produced both haplotypes, and the locus comprises three distinct AFGP gene clusters, containing a total of 16 AFGP genes and spanning a combined distance of 512 kbp. The M. tomcod AFGP locus is much smaller at approximately 80 kbp, and contains only three AFGP genes. Fluorescent in situ hybridization with an AFGP gene probe showed the AFGP locus in both species occupies a single chromosomal location. The large AFGP locus with its high gene dosage in B. saida is consistent with its chronically freezing high Arctic habitats, while the small gene family in M. tomcod correlates with its milder habitats in lower latitudes. The results from this study provided the data for fine resolution sequence analyses that would yield insight into the molecular mechanisms and history of gadid AFGP gene evolution driven by northern hemisphere glaciation.

Viral activity and outcome of hepatitis B surface antigen-positive grafts in deceased liver transplantation.

Indications of liver transplantation are extensive, but deceased donation does not meet the demand. Hepatitis B surface antigen (HBsAg)-positive grafts used to be discarded in the past. The aim of this study was to examine viral activity and outcome of HBsAg-positive deceased grafts transplanted to HBsAg-positive recipients. Eleven HBsAg-positive deceased grafts were transplanted to HBsAg-positive patients with acute liver failure (3 patients), hepatocellular carcinoma (6 patients) and repeatedly bleeding varices (2 patients). Postoperatively, hepatitis B virus (HBV) infection was treated by a combination of antiviral nucleoside and nucleotide analogues. HBV DNA and HBsAg were measured periodically. The median (interquartile) model of end-stage liver disease score for the recipients was 19 (16-32) with a range from 11 to 40. HBV DNA was detected in 6 patients with a range from 61 to 1083 IU/mL before transplantation. After transplantation, HBV DNA was detected in 4 patients in the first month and 2 patients in the 6th month and became undetectable for all patients at end of the first year. The quantitative HBsAg ranged from 0.86 to 241.1 IU/mL at 6 months and 0.34 to 238.5 IU/mL at 24 months (P = .135). Three of the patients died in the early phase, and the other patients were followed up for 40.0 ± 19.2 months with normal liver function. In conclusion, HBsAg-positive deceased liver grafts function well with minimal viral activity under treatment of combined antiviral nucleoside and nucleotide analogues. Use of HBsAg-positive deceased grafts is feasible and increases the donor pool to rescue dying patients.