Control experiments usingAgrotis segetum granulosis virus againstAgrotis ipsilon [Lep.: Noctuidae] on tobacco seedlings in Northern Pakistan

Agrotis segetum Schiff. granulosis virus propagated in Denmark was applied against released 2nd instar larvae ofAgrotis ipsilon (Hfn.) in tobacco plots in nurseries at Peshawar and Bhurbun (Murree), Northern Pakistan. Nursery bed plots were isolated from the surroundings by net roof and plastic sheets. Granulosis virus concentrations used were 5×10⁷ and 10⁹ capsules per ml water, and 250 ml water per plot (1–4 m²). Reductions of cutworms as well as cutworm damages varied between 72 and 100% as compared to plots only treated with water. Addition of active coal to the GV did not increase reduction percentages. A possible effect of the GV could be traced one year after treatment.

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Résumé Le virus de la granulose d'Agrotis segetum Schiff. multiplié au Danemark a été appliqué contre le 2^e stade des chenilles deAgrotis ipsilon (Hfn.) dans des parcelles expérimentales à Peshawar et Bhurbun (Murree), Pakistan du nord. Les parcelles isolées avec des filets et des feuilles plastiques furent infestées artificiellement en chenilles. Les concentrations de GV utilisées furent de 5×10⁷ et 10⁹ granules par ml d'eau, 250 ml de la suspension préparée étant distribués par parcelle de 1 à 4 m². La réduction du nombre de chenilles et celui des plantes endommagées varie de 72 à 100% par rapport aux notations effectuées dans les parcelles traitées avec de l'eau pure. L'addition du charbon actif au GV n'augmente pas son effet. Une action du traitement a été retrouvée un an après l'application.

     

Vaccination uptake amongst older adults from minority ethnic backgrounds: A systematic review

BackgroundOlder adults from minority ethnic backgrounds are at increased risk of contracting COVID-19 and developing severe infection and have increased risk of mortality. Whilst an age-based vaccination approach prioritising older groups is being implemented worldwide, vaccine hesitancy is high amongst minority ethnic groups.Methods and findingsWe conducted a systematic review and convergent synthesis to systematically examine perceptions of vaccinations amongst older adults from minority ethnic backgrounds. We included studies that reported on perceptions, beliefs, and attitudes towards vaccinations in older adults aged ≥65 years from a minority ethnic background. We excluded studies of vaccinations in investigation or development, studies focused on specific medical conditions, studies where ethnic background or age group was unidentifiable, systematic reviews, editorials, and conference abstracts. We searched MEDLINE, Embase, Virtual Health Library, Web of Science, Cochrane Library, medRxiv, and PROSPERO databases from inception to 15 July 2021. Risk of bias for studies was assessed using the Mixed Methods Appraisal Tool. The quality of evidence of collective outcomes was estimated using the Grading of Recommendations Assessment, Development and Evaluation–Confidence in the Evidence from Reviews of Qualitative research (GRADE–CERQual) framework. A total of 28 eligible studies conducted between 1997 and 2020 were included in the final analysis (17 quantitative surveys, 8 focus group or interview studies, 2 mixed methods studies, and 1 case–control study). The majority were US studies in English or Spanish, except for 6 studies set in Hong Kong, 2 studies in Japan, 1 study in Brazil, and 1 multi-centre study (including China, Indonesia, Turkey, South Korea, Greece, UK, Brazil, and Nigeria). In total, 28,262 individuals with an estimated mean age of 69.8 years were included, 63.2% of whom were female. We summarised the common concepts and themes across studies and populations using a convergent synthesis analysis. Thirteen themes categorised as barriers or facilitators were identified and grouped into structural factors—healthcare provider and system related, patient related, and policy and operational—and were analysed by minority ethnic group. The main limitation of the study was the predominance of studies from the US and East Asia.ConclusionsIn this systematic review, we found that factors influencing vaccination uptake involve healthcare provider and system, patient-related, and governance-level factors that are specific to the older ethnic minority community being served. The evidence included in this review is supported by high or moderate certainty and can be translated to practice and policy. A tailored, multi-level approach combining increased education, access, and culturally competent discussions with trusted healthcare professionals to address health beliefs can maximise the potential impact of widespread vaccination policies.

In a systematic review, Dr. Cini Bhanu and colleagues investigate factors influencing vaccination uptake among older adults from minority ethnic backgrounds.     

Exploring the structural dynamics of the E.coli chaperonin GroEL using translation-libration-screw crystallographic refinement of intermediate states

Large rigid-body domain movements are critical to GroEL-mediated protein folding, especially apical domain elevation and twist associated with the formation of a folding chamber upon binding ATP and co-chaperonin GroES. Here, we have modeled the anisotropic displacements of GroEL domains from various crystallized states, unliganded GroEL, ATPgammaS-bound, ADP-AlFx/GroES-bound, and ADP/GroES bound, using translation-libration-screw (TLS) analysis. Remarkably, the TLS results show that the inherent motions of unliganded GroEL, a polypeptide-accepting state, are biased along the transition pathway that leads to the folding-active state. In the ADP-AlFx/GroES-bound folding-active state the dynamic modes of the apical domains become reoriented and coupled to the motions of bound GroES. The ADP/GroES complex exhibits these same motions, but they are increased in magnitude, potentially reflecting the decreased stability of the complex after nucleotide hydrolysis. Our results have allowed the visualization of the anisotropic molecular motions that link the static conformations previously observed by X-ray crystallography. Application of the same analyses to other macromolecules where rigid body motions occur may give insight into the large scale dynamics critical for function and thus has the potential to extend our fundamental understanding of molecular machines.     

Identification of a cis-acting replication element within the poliovirus coding region

The replication of poliovirus, a positive-stranded RNA virus, requires translation of the infecting genome followed by virus-encoded VPg and 3D polymerase-primed synthesis of a negative-stranded template. RNA sequences involved in the latter process are poorly defined. Since many sequences involved in picornavirus replication form RNA structures, we searched the genome, other than the untranslated regions, for predicted local secondary structural elements and identified a 61-nucleotide (nt) stem-loop in the region encoding the 2C protein. Covariance analysis suggested the structure was well conserved in the Enterovirus genus of the Picornaviridae. Site-directed mutagenesis, disrupting the structure without affecting the 2C product, destroyed genome viability and suggested that the structure was required in the positive sense for function. Recovery of revertant viruses suggested that integrity of the structure was critical for function, and analysis of replication demonstrated that nonviable mutants did not synthesize negative strands. Our conclusion, that this RNA secondary structure constitutes a novel poliovirus cis-acting replication element (CRE), is supported by the demonstration that subgenomic replicons bearing lethal mutations in the native structure can be restored to replication competence by the addition of a second copy of the 61-nt wild-type sequence at another location within the genome. This poliovirus CRE functionally resembles an element identified in rhinovirus type 14 (K. L. McKnight and S. M. Lemon, RNA 4:1569-1584, 1998) and the cardioviruses (P. E. Lobert, N. Escriou, J. Ruelle, and T. Michiels, Proc. Natl. Acad. Sci. USA 96:11560-11565, 1999) but differs in sequence, structure, and location. The functional role and evolutionary significance of CREs in the replication of positive-sense RNA viruses is discussed.     

Ras-Raf-Arf signaling critically depends on the Dmp1 transcription factor

Dmp1 prevents tumor formation by activating the Arf-p53 pathway. In cultured primary cells, the Dmp1 promoter was efficiently activated by oncogenic Ha-Ras(V12), but not by overexpressed c-Myc or E2F-1. Dmp1 promoter activation by Ras(V12) depended on Raf-MEK-ERK signaling. Induction of p19(Arf) and p21(Cip1) by oncogenic Raf was compromised in Dmp1-null cells, which were resistant to Raf-mediated premature senescence. A Ras(V12)-responsive element was mapped to the 5' leader sequence of the murine Dmp1 promoter, where endogenous Fos and Jun family proteins bind. Dmp1 promoter activation by Ras(V12) was strikingly impaired in c-Jun as well as in JunB knock-down cells, suggesting the critical role of Jun proteins in the activation of the Dmp1 promoter. A Ras(V12)-responsive element was mapped to the unique Dmp1/Ets site on the Arf promoter, where endogenous Dmp1 proteins bind upon oncogenic Raf activation. Therefore, activation of Arf by Ras/Raf signaling is indirectly mediated by Dmp1, explaining why Dmp1-null primary cells are highly susceptible to Ras-induced transformation. Our data indicate the presence of the novel Jun-Dmp1 pathway that directly links oncogenic Ras-Raf signaling and p19(Arf), independent of the classical cyclin D1/Cdk4-Rb-E2F pathway.     

The Nef protein of HIV-1 induces loss of cell surface costimulatory molecules CD80 and CD86 in APCs

The Nef protein of HIV-1 is essential for its pathogenicity and is known to down-regulate MHC expression on infected cell surfaces. We now show that Nef also redistributes the costimulatory molecules CD80 and CD86 away from the cell surface in the human monocytic U937 cell line as well as in mouse macrophages and dendritic cells. Furthermore, HIV-1-infected U937 cells and human blood-derived macrophages show a similar loss of cell surface CD80 and CD86. Nef colocalizes with MHC class I (MHCI), CD80, and CD86 in intracellular compartments, and binds to both mouse and human CD80 and CD86. Some Nef mutants defective in MHCI down-modulation, including one from a clinical isolate, remain capable of down-modulating CD80 and CD86. Nef-mediated loss of surface CD80/CD86 is functionally significant, because it leads to compromised activation of naive T cells. This novel immunomodulatory role of Nef may be of potential importance in explaining the correlations of macrophage-tropism and Nef with HIV-1 pathogenicity and immune evasion.