Novel Strain Research Articles

Optimization, and biological evaluation of 3-O-β-chacotriosyl betulinic acid amide derivatives as novel small-molecule Omicron

SARS-CoV-2 Omicron viruses possess a high antigenic shift, and the approved anti-SARS-CoV-2 drugs are extremely limited, which makes the development of new antiviral drugs for the clinical treatment and prevention of SARS-CoV-2 outbreaks imperative. We have previously discovered a new series of markedly potent small-molecule inhibitors of SARS-CoV-2 virus entry, exampled by the hit compound 2. Here, we report a further study of bioisosteric replacement of the eater linker at the C-17 position of 2 with a variety of aromatic amine moieties, followed by a focused structure-activity relationship study, leading to the discovery of a series of novel 3-O-β-chacotriosyl BA amide derivatives as small-molecule Omicron fusion inhibitors with improved potency and selectivity index. Particularly, our medicinal chemistry efforts have resulted in a potent, and efficacious lead compound S-10 with appreciable pharmacokinetic properties, which exhibited broad-spectrum potency against Omicron and other variants with EC50 values ranging from 0.82 to 5.45 μM. Mutagenesis studies confirmed that inhibition of Omicron viral entry was mediated by the direct interaction with S in the prefusion state. These results reveal that S-10 is suitable for further optimization as Omicron fusion inhibitors, with the potential to be developed as therapeutic agents for the treatment and control of SARS-CoV-2 ant its variants infections.

Combination adjuvants and antigens provide heterosubtypic protection against lethal influenza infection.

Abstract Influenza A virus (IAV) is a negative strand RNA virus that undergoes antigenic drift and shift, leading to serologically distinct strains that can cause tens of thousands of deaths annually in the US. The wide variety of hemagglutinin (HA) and neuraminidase (NA) proteins necessitates yearly reformulation of the vaccine to protect against novel seasonal and pandemic strains. Current IAV vaccines do not contain adjuvants, however, immune modulators such as pattern recognition receptor (PRR) agonists may enhance antigen presentation to T cells and provide broader protection against IAV strains that differ in HA and NA outer coat proteins. We set out to investigate whether TLR4 (lipopolysaccharide) and TLR3 (poly IC) agonists in combination with HA (H3N2) and nucleoprotein (NP) or NP and matrix (M1) proteins could provide protection against lethal challenge with mismatched IAV strain H1N1. Mice given H3 and NP with LPS + pIC in a prime/boost strategy demonstrated 80% survival after heterosubtypic H1N1 challenge while H3 + NP in PBS showed 20% survival. Similar results were seen using LPS + pIC in combination with NP and M1 protein with 90% survival. High endpoint titers of anti-NP antibodies (that also bound H1N1 virus) correlated with heterosubtypic protection suggesting a role for non-neutralizing antibodies in promoting survival. In addition, LPS and pIC enhanced dendritic cell (DC) function in vitro and increased migratory monocyte DC in the lymph node in vivo, coupled with early upregulation of T cell marker CD69. This strategy may provide increased efficacy over current IAV vaccines by inducing non-neutralizing antibodies and enhanced T cell responses to internal proteins. Supported by Trudeau Institute and Clarkson University.

An Orf-Virus (ORFV)-Based Vector Expressing a Consensus H1 Hemagglutinin Provides Protection against Diverse Swine Influenza Viruses.

Influenza A viruses (IAV-S) belonging to the H1 subtype are endemic in swine worldwide. Antigenic drift and antigenic shift lead to a substantial antigenic diversity in circulating IAV-S strains. As a result, the most commonly used vaccines based on whole inactivated viruses (WIVs) provide low protection against divergent H1 strains due to the mismatch between the vaccine virus strain and the circulating one. Here, a consensus coding sequence of the full-length of HA from H1 subtype was generated in silico after alignment of the sequences from IAV-S isolates obtained from public databases and was delivered to pigs using the Orf virus (ORFV) vector platform. The immunogenicity and protective efficacy of the resulting ORFVΔ121conH1 recombinant virus were evaluated against divergent IAV-S strains in piglets. Virus shedding after intranasal/intratracheal challenge with two IAV-S strains was assessed by real-time RT-PCR and virus titration. Viral genome copies and infectious virus load were reduced in nasal secretions of immunized animals. Flow cytometry analysis showed that the frequency of T helper/memory cells, as well as cytotoxic T lymphocytes (CTLs), were significantly higher in the peripheral blood mononuclear cells (PBMCs) of the vaccinated groups compared to unvaccinated animals when they were challenged with a pandemic strain of IAV H1N1 (CA/09). Interestingly, the percentage of T cells was higher in the bronchoalveolar lavage of vaccinated animals in relation to unvaccinated animals in the groups challenged with a H1N1 from the gamma clade (OH/07). In summary, delivery of the consensus HA from the H1 IAV-S subtype by the parapoxvirus ORFV vector decreased shedding of infectious virus and viral load of IAV-S in nasal secretions and induced cellular protective immunity against divergent influenza viruses in swine.

Identification of broad-spectrum neutralizing antibodies against influenza A virus and evaluation of their prophylactic efficacy in mice

Influenza A virus continuously infects humans and the antigenic shifts of this respiratory virus enable it to cross the species barrier, threatening public health with the risk of pandemics. Broadly neutralizing antibodies (bnAbs) that target the antigenic surface glycoprotein, hemagglutinin (HA), of influenza A virus protect against various subtypes of the virus. Here, we screened a human scFv library, through phage display and panning against recombinant HA proteins, to discover human monoclonal antibodies (mAbs) that are broadly active. Consequently, two human mAbs, named G1 and G2, were identified, which target the HA proteins of the H1N1 and H3N2 subtypes, respectively. G1 was shown to have broad binding ability to different HA subtypes of group 1. By contrast, G2 had higher binding affinity but sensed exclusively H3 subtype-derived HAs. In a cell culture-based virus-neutralizing assay, both G1 and G2 efficiently suppressed infection of the parental influenza A viruses of H1N1 and H3N2 subtypes. Mode-of-action studies showed that the G1 antibody blocked HA2-mediated membrane fusion. Meanwhile, G2 inhibited HA1-mediated viral attachment to host cells. It is noteworthy that both antibodies elicited antibody-dependent cellular cytotoxicity (ADCC) activities by recruiting FcγRIIIA-expressing effector cells. In mouse challenge models, single-shot, intraperitoneal administration of chimeric G1 and G2 antibodies with the mouse IgG constant region completely protected mice from viral infections at doses above 10 and 1 mg/kg, respectively. The newly identified bnAbs, G1 and G2, could provide insight into the development of broad-spectrum antivirals against future pandemic influenza A virus involving group 1- or H3-subtyped strains.

Improvement influenza vaccine immune responses with traditional Chinese medicine and its active ingredients.

The current influenza vaccines are unable to provide effective protection in many cases, like influenza viruses strain antigenic drift or shift, and the influenza continues to cause significant annual morbidity and mortality. Improving the immune response to influenza vaccination is an unmet need. Traditional Chinese medicine (TCM) and its active ingredients are commonly known to have immunomodulatory properties. We therefore compared influenza vaccination alone or formulated with Astragali Radix (Huangqi in Chinese), and several representative ingredients of TCM, including lentinan (polysaccharide), panax notoginseng saponins (saponin), breviscapine (flavone), andrographolide (terpenoid), and a Chinese herbal compound (kangai) for their potential to enhance immune responses to influenza vaccine in mice. We found that all these TCM-adjuvants were able to increase hemagglutination inhibition (HAI) antibody titers, splenocyte proliferation, splenic T cell differentiation, bone marrow dendritic cell maturity, and both Th1 and Th2 cytokine secretion of influenza vaccine to varying degrees, and that had the characteristics of no excessive inflammatory responses and bidirectional regulation simultaneously. Taken together, our findings show that Astragali Radix exerts a more comprehensive effect on vaccine immunity, on both innate and adaptive immunity. The effects of lentinan and andrographolide on adaptive immunity were more significant, while the effects of breviscapine on innate immunity were stronger, and the other two TCM adjuvants were weaker. As the first report of a comprehensive evaluation of TCM adjuvants in influenza vaccines, the results suggest that TCM and their active ingredients are good candidates for enhancing the immune response of influenza vaccines, and that suitable TCMs can be selected based on the adjuvant requirements of different vaccines.

Emerging and re-emerging viral diseases, predisposing risk factors, and implications of international travel: a call for action for increasing vigilance and imposing restrictions under the current threats of recently emerging multiple Omicron subvariants.

Emerging and re-emerging viral diseases, predisposing risk factors, and implications of international travel: a call for action for increasing vigilance and imposing restrictions under the current threats of recently emerging multiple Omicron subvariants.

Human death due to H5N1 amid the COVID-19 pandemic and Mpox outbreak: A call for action.

Human death due to H5N1 amid the COVID-19 pandemic and Mpox outbreak: A call for action.

Avian influenza (H5N1) virus, epidemiology and its effects on backyard poultry in Indonesia: a review.

Avian influenza (AI) is a zoonotic viral endemic disease that affects poultry, swine, and mammals, including humans. Highly pathogenic avian influenza (HPAI) is caused by influenza type A virus subtypes H5, and H7 which are naturally carried by a wild bird and often affect domestic poultry. Avian influenza (AI) is a major problem worldwide that causes significant economic losses in the poultry sector. Since 2003, the widespread H5N1 HPAI in poultry has led to high mortalities resulting in huge economic losses in the poultry sector in Indonesia. Domestic poultry is a key source of income that contributes to economic growth, both directly and indirectly, by reducing poverty among the people living in rural communities. Furthermore, in many developing countries, including Indonesia, rural people meet a portion of their food needs through backyard poultry. Nevertheless, this sector is strongly affected by biosecurity hazards, particularly in Indonesia by HPAI infections. Avian influenza (AI), subtype H5N1 has zoonotic significance, posing major risks to public health and poultry. Due to close interaction between wild migratory birds and ducks, the domestic poultry sector in Indonesia is directly affected by this virus. This virus continues to be ubiquitous in Indonesia as a result of the unpredictable mutations produced by antigenic drift and shift, which can persist from a few days to several years. In this review, the epidemiology and impact, of highly pathogenic avian influenza H5N1 subtype virus infection on backyard poultry in Indonesia were discussed.

The Epidemiological surveillance of Human Papillomavirus (HPV) genotypes in oral and genital tracts and the impact of HPV vaccination on male university students from Rio de Janeiro state, Brazil

Introduction: Human Papillomavirus (HPV) infections are of significant concern in men, given its potential impact on their health and the risk of transmission to partners. Understanding and addressing this infection in men is crucial to evaluate the effectiveness of vaccination in reducing HPV-related diseases. Objective: To assess the impact of HPV vaccination, potential genotype shifts, and adverse effects, through a prospective study conducted with male university students. Methods:The study involved 286 volunteers who were examined at Sexually Transmitted Disease Clinics at the Universidade Federal Fluminense in Niterói, Rio de Janeiro, Brazil. The HPV prevalence was evaluated using generic PCR, genotyped by DNA microarray and monitored adverse effects. Results: The findings of this study revealed the absence of moderate or severe adverse effects. Genetic shifts were observed, including the disappearance of oncogenic HPV types 16 and 18. Surprisingly, even after completing the full vaccine regimen, students still harbored HPV11 in the oral tract. Furthermore, persistent HPV 6 and 11 infections were identified in three students, who had pre-existing infections prior to vaccination, at the follow-up visit. Multivariate analysis uncovered independent associations, notably an increased risk of HPV infection in the oral tract among men who have sex with men. HPV prevalence rates remained low both before and after the vaccination scheme (T0: 14.7%, T1: 8.7%). Even after the full vaccination scheme, the prevalence remained similar at T2 (14.6%), with no statistically significant differences recorded. HPV11 emerged as the most prevalent type throughout the study, followed by HPV6. Vaccine genotypes were detected in a significant proportion of samples at T0 (85.4%), T1 (89.5%), and T2 (100%). Conclusion: Overall, this study suggests that vaccination may represent a promising approach to reducing HPV-related health risks. These findings shed light on the potential benefits and challenges of HPV vaccination, emphasizing the need for continued monitoring and vaccination efforts.

The convergent evolution of influenza A virus: Implications, therapeutic strategies and what we need to know

Influenza virus infection, more commonly known as the ‘cold flu’, is an etiological agent that gives rise to recurrent annual flu and many pandemics. Dated back to the 1918- Spanish Flu, the influenza infection has caused the loss of many human lives and significantly impacted the economy and daily lives. Influenza virus can be classified into four different genera: influenza A-D, with the former two, influenza A and B, relevant to humans. The capacity of antigenic drift and shift in Influenza A has given rise to many novel variants, rendering vaccines and antiviral therapies useless. In light of the emergence of a novel betacoronavirus, the SARS-CoV-2, unravelling the underpinning mechanisms that support the recurrent influenza epidemics and pandemics is essential. Given the symptom similarities between influenza and covid infection, it is crucial to reiterate what we know about the influenza infection. This review aims to describe the origin and evolution of influenza infection. Apart from that, the risk factors entail the implication of co-infections, especially regarding the COVID-19 pandemic is further discussed. In addition, antiviral strategies, including the potential of drug repositioning, are discussed in this context. The diagnostic approach is also critically discussed in an effort to understand better and prepare for upcoming variants and potential influenza pandemics in the future. Lastly, this review encapsulates the challenges in curbing the influenza spread and provides insights for future directions in influenza management.

Outdoor light at night, genetic predisposition and type 2 diabetes mellitus: A prospective cohort study

BackgroundAccording to animal and human epidemiologic studies, exposure to outdoor light at night (LAN) may cause circadian disruption, which may disturb sleep quality and lead to incident type 2 diabetes mellitus (T2DM). MethodsWe followed 283,374 persons from 2006 through 2020. Outdoor LAN exposure was estimated using satellite data for individual address with 500 m2 scale buffer during follow-up. Incidence of T2DM was confirmed by hospital inpatient records. We identified potential confounders by a directed acyclic graph, including demographic, genetic, individual and regional level socioeconomic status, and environmental risk factors, and calculated hazard ratios (HRs) and 95% confidence intervals (CIs) through time-varying Cox proportional hazard model. Furthermore, we examined the association of outdoor LAN with a defined health sleep scores and moderation of genetic predisposition and shift work on the relationship of outdoor LAN and incident T2DM. ResultsWe identified 7,775 incident T2DM cases over 3,027,505 person-years. Higher outdoor LAN exposures were significantly associated with higher risk of T2DM. The estimated HR for incident T2DM with an interquartile range (IQR: 11.22 nW/cm2/sr) increase in outdoor LAN was 1.05 (95%CI: 1.01, 1.09) in the fully adjusted model. Participants who lived in the highest quarter of outdoor LAN area were more likely to develop T2DM (HR: 1.14,95%CI: 1.02, 1.27). Besides, those who were exposed to higher levels of outdoor LAN had poorer sleep quality. No moderation role of PRS on outdoor LAN-induced T2DM observed both on the multiplicated and additive scale. The hazards of outdoor LAN were observed in those who never owned a night shift work. ConclusionAlthough further work is required to clarify potential mechanisms, our findings indicate that exposure to residential outdoor LAN may contribute to T2DM risk and low sleep quality.

Whole genome resequencing identifies local adaptation associated with environmental variation for redband trout.

Aquatic ectotherms are predicted to harbour genomic signals of local adaptation resulting from selective pressures driven by the strong influence of climate conditions on body temperature. We investigated local adaptation in redband trout (Oncorhynchus mykiss gairdneri) using genome scans for 547 samples from 11 populations across a wide range of habitats and thermal gradients in the interior Columbia River. We estimated allele frequencies for millions of single nucleotide polymorphism loci (SNPs) across populations using low-coverage whole genome resequencing, and used population structure outlier analyses to identify genomic regions under divergent selection between populations. Twelve genomic regions showed signatures of local adaptation, including two regions associated with genes known to influence migration and developmental timing in salmonids (GREB1L, ROCK1, SIX6). Genotype-environment association analyses indicated that diurnal temperature variation was a strong driver of local adaptation, with signatures of selection driven primarily by divergence of two populations in the northern extreme of the subspecies range. We also found evidence for adaptive differences between high-elevation desert vs. montane habitats at a smaller geographical scale. Finally, we estimated vulnerability of redband trout to future climate change using ecological niche modelling and genetic offset analyses under two climate change scenarios. These analyses predicted substantial habitat loss and strong genetic shifts necessary for adaptation to future habitats, with the greatest vulnerability predicted for high-elevation desert populations. Our results provide new insight into the complexity of local adaptation in salmonids, and important predictions regarding future responses of redband trout to climate change.

VIRUS: EVOLUSI, GENETIKA, DRIFT DAN SHIFT ANTIGEN

Viral evolution is a subdiscipline of evolutionary biology and virology that focuses on the evolution of viruses. Many viruses, especially RNA viruses, have relatively high mutation rates and short production durations (on the order of one point mutation or more per genome per round of replication). The rapid pace of viral mutation paired with natural selection enables viruses to rapidly adapt to changes in the host environment, despite the fact that the majority of viral mutations offer little benefit and frequently prove to be harmful. Additionally, because viruses often make several copies in an infected host, altered genes can be rapidly transmitted to a large number of offspring. The high mutation rates of RNA viruses, which are the result of an error-prone RNA-dependent RNA polymerase, make them a veritable gold mine for researchers interested in discovering evolutionary novelty and developing new methods to study evolution in action. There are two different forms of genetic changes: antigenic drift and antigenic shift. This article covers briefly the evolution of viruses in terms of genetic variation.

SitePath: a visual tool to identify polymorphism clades and help find fixed and parallel mutations

BackgroundIdentifying polymorphism clades on phylogenetic trees could help detect punctual mutations that are associated with viral functions. With visualization tools coloring the tree, it is easy to visually find clades where most sequences have the same polymorphism state. However, with the fast accumulation of viral sequences, a computational tool to automate this process is urgently needed.ResultsHere, by implementing a branch-and-bound-like search method, we developed an R package named sitePath to identify polymorphism clades automatically. Based on the identified polymorphism clades, fixed and parallel mutations could be inferred. Furthermore, sitePath also integrated visualization tools to generate figures of the calculated results. In an example with the influenza A virus H3N2 dataset, the detected fixed mutations coincide with antigenic shift mutations. The highly specificity and sensitivity of sitePath in finding fixed mutations were achieved for a range of parameters and different phylogenetic tree inference software.ConclusionsThe result suggests that sitePath can identify polymorphism clades per site. The clustering of sequences on a phylogenetic tree can be used to infer fixed and parallel mutations. High-quality figures of the calculated results could also be generated by sitePath.

Avian influenza (H5N1) virus, epidemiology and its effects on backyard poultry in Indonesia: a review.

Avian influenza (AI) is a zoonotic viral endemic disease that affects poultry, swine, and mammals, including humans. Highly pathogenic avian influenza (HPAI) is caused by influenza type A virus subtypes H5, and H7 which are naturally carried by a wild bird and often affect domestic poultry. Avian influenza (AI) is a major problem worldwide that causes significant economic losses in the poultry sector. Since 2003, the widespread H5N1 HPAI in poultry has led to high mortalities resulting in huge economic losses in the poultry sector in Indonesia. Domestic poultry is a key source of income that contributes to economic growth, both directly and indirectly, by reducing poverty among the people living in rural communities. Furthermore, in many developing countries, including Indonesia, rural people meet a portion of their food needs through backyard poultry. Nevertheless, this sector is strongly affected by biosecurity hazards, particularly in Indonesia by HPAI infections. Avian influenza (AI), subtype H5N1 has zoonotic significance, posing major risks to public health and poultry. Due to close interaction between wild migratory birds and ducks, the domestic poultry sector in Indonesia is directly affected by this virus. This virus continues to be ubiquitous in Indonesia as a result of the unpredictable mutations produced by antigenic drift and shift, which can persist from a few days to several years. In this review, the epidemiology and impact, of highly pathogenic avian influenza H5N1 subtype virus infection on backyard poultry in Indonesia were discussed.

A Novel Fusion Partner in a Case of Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement

Abstract Introduction/Objective Myeloid/lymphoid neoplasms with rearrangement of FGFR1 are uncommon and heterogeneous group of hematological malignancies that may present as myeloproliferative neoplasm, acute myeloid leukemia, T or B lymphoblastic lymphoma/leukemia, or mixed phenotypic acute leukemia. Patients can present with lymphadenopathy, mediastinal mass, or systemic symptoms. Eosinophilia is common in peripheral blood or bone marrow. Several chromosomal rearrangements and fusion genes have been described with FGFR1 rearrangement and all of them encode an aberrant tyrosine kinase. Tyrosine kinase inhibitors may offer a prospective therapeutic approach although specific targeted therapies have yet to be established. Methods/Case Report We present a case of a 14-year-old male who presented with rapid neck pain and swelling. Imaging revealed a 15 x 8 x 6 cm neck mass extending into the anterior mediastinum. Laboratory evaluation revealed anemia, thrombocytopenia, and leukocytosis (41.7 K/mm3), with absolute eosinophilia and blasts of 50%. Flow cytometry of peripheral blood demonstrated a population of T-lymphoblasts comprising about 60% of the cellularity with dim CD45, cytoplasmic CD3, CD7, TdT, CD38, CD4, CD5, CD10, and CD15, supporting T-lymphoblastic leukemia/lymphoma. The patient received induction chemotherapy, and subsequent bone marrow biopsy showed morphologic remission. Six weeks from diagnosis, the patient developed a gluteal mass with an atypical T-cell infiltrate that was negative for TdT; and at 15 weeks from diagnosis, developed an enlarging abdominal mass, also with an atypical T-cell infiltrate also negative for TdT and CD1a. At that time molecular diagnostic studies of the abdominal wall mass discovered a previously unpublished ATG16L1-FGFR1 fusion, supporting myeloid/lymphoid neoplasm with FGFR1 rearrangement, T-lymphoblastic leukemia/lymphoma. Results (if a Case Study enter NA) NA. Conclusion Although a variety of translocations have been identified with FGFR1 rearrangement, the novel fusion partner ATG16L1 has not been previously reported. The case also illustrates an unusual extramedullary recurrence of the T-cell lymphoblastic leukemia/lymphoma with significant antigenic shift including loss of TdT and CD1a.

Inhibition of KIF20A suppresses the replication of influenza A virus by inhibiting viral entry.

The influenza A virus (IAV) has caused several pandemics, and therefore there are many ongoing efforts to identify novel antiviral therapeutic strategies including vaccines and antiviral drugs. However, influenza viruses continuously undergo antigenic drift and shift, resulting in the emergence of mutated viruses. In turn, this decreases the efficiency of existing vaccines and antiviral drugs to control IAV infection. Therefore, this study sought to identify alternative therapeutic strategies targeting host cell factors rather than viruses to avoid infection by mutated viruses. Particularly, we investigated the role of KIF20A that is one of kinesin superfamily proteins in the replication of IAV. The KIF20A increased viral protein levels in IAV-infected cells by regulating the initial entry stage during viral infection. Furthermore, the KIF20A inhibitor significantly suppressed viral replication, which protected mice from morbidity and mortality. Therefore, our findings demonstrated that KIF20A is highly involved in the viral replication process and viral propagation both in vitro and in vivo, and could thus be used as a target for the development of novel antiviral drugs.

Dual ancestries and ecologies of the Late Glacial Palaeolithic in Britain

Genetic investigations of Upper Palaeolithic Europe have revealed a complex and transformative history of human population movements and ancestries, with evidence of several instances of genetic change across the European continent in the period following the Last Glacial Maximum (LGM). Concurrent with these genetic shifts, the post-LGM period is characterized by a series of significant climatic changes, population expansions and cultural diversification. Britain lies at the extreme northwest corner of post-LGM expansion and its earliest Late Glacial human occupation remains unclear. Here we present genetic data from Palaeolithic human individuals in the United Kingdom and the oldest human DNA thus far obtained from Britain or Ireland. We determine that a Late Upper Palaeolithic individual from Gough's Cave probably traced all its ancestry to Magdalenian-associated individuals closely related to those from sites such as El Mirón Cave, Spain, and Troisième Caverne in Goyet, Belgium. However, an individual from Kendrick's Cave shows no evidence of having ancestry related to the Gough’s Cave individual. Instead, the Kendrick’s Cave individual traces its ancestry to groups who expanded across Europe during the Late Glacial and are represented at sites such as Villabruna, Italy. Furthermore, the individuals differ not only in their genetic ancestry profiles but also in their mortuary practices and their diets and ecologies, as evidenced through stable isotope analyses. This finding mirrors patterns of dual genetic ancestry and admixture previously detected in Iberia but may suggest a more drastic genetic turnover in northwestern Europe than in the southwest.

Compensatory Genetic and Transcriptional Cytonuclear Coordination in Allopolyploid Lager Yeast (Saccharomyces pastorianus).

Cytonuclear coordination between biparental-nuclear genomes and uniparental-cytoplasmic organellar genomes in plants is often resolved by genetic and transcriptional cytonuclear responses. Whether this mechanism also acts in allopolyploid members of other kingdoms is not clear. Additionally, cytonuclear coordination of interleaved allopolyploid cells/individuals within the same population is underexplored. The yeast Saccharomyces pastorianus provides the opportunity to explore cytonuclear coevolution during different growth stages and from novel dimensions. Using S. pastorianus cells from multiple growth stages in the same environment, we show that nuclear mitochondria-targeted genes have undergone both asymmetric gene conversion and growth stage-specific biased expression favoring genes from the mitochondrial genome donor (Saccharomyces eubayanus). Our results suggest that cytonuclear coordination in allopolyploid lager yeast species entails an orchestrated and compensatory genetic and transcriptional evolutionary regulatory shift. The common as well as unique properties of cytonuclear coordination underlying allopolyploidy between unicellular yeasts and higher plants offers novel insights into mechanisms of cytonuclear evolution associated with allopolyploid speciation.

Confirmation of physiological race of Bipolaris maydis causing maydis leaf blight of maize in India

Maydis leaf blight (MLB) incited by Bipolaris maydis occurs in most of the maize growing regions. Present study revealed morphological divergence among 74 isolates of B. maydis collected from geographically distant places of India. Based on morpho-cultural features clustered by R software, 25 representative isolates of B. maydis were used for race identification. The internal transcribed spacer (ITS) sequence further confirmed the isolates as B. maydis. In recent concept, variation in disease incidence and infectivity denotes genetic shift in the pathogen or introduction of new pathogenic race(s) through germplasm exchange. For unveiling Indian race(s) of B. maydis, present exploration was made. Four genetically divergent maize genotypes with cytoplasmic male sterility (CMS), viz. -C (MGU- 161QPV-C), -T (MGU- 345PV-T), -S (MGU-150Q-S) and CM-119 (fertile cytoplasm) were assessed using 25 isolates of B. maydis during kharif 2018-19 at ICAR-IARI, New Delhi. The genotype MGU-161QPV-C associated with CMS-C was highly resistant followed by MGU-345PV-T (CMS-T) and MGU-150Q-S (CMS-S), whereas CM-119 showed high susceptibility. Present outcome confirmed prevalence of race 'O' of B. maydis in India and eliminated uncertainty about occurrence of other races, i.e. T and C.