Fact or hypothesis: concomitant immunity in taeniid cestode infections

Sustained research efforts over the last 50 years have revealed a considerable amount of information about immunity to taeniid cestode infections in the parasites’ intermediate hosts. As a product of this research, a series of effective recombinant vaccines have been developed which have no parallel in any other group of parasitic organisms. There are, however, many important aspects relating to immunity that remain to be elucidated. Some concepts have come to be firmly held as facts and yet the supportive data are either conflicting or unconfirmed. This review considers the phenomenon of immunity to re-infection with taeniid cestodes in their intermediate hosts, examining carefully the nature of the evidence that is available to support conclusions that have been drawn in this area

GRSF1 regulates RNA processing in mitochondrial RNA granules.

Various specialized domains have been described in the cytosol and the nucleus; however, little is known about compartmentalization within the mitochondrial matrix. GRSF1 (G-rich sequence factor 1) is an RNA binding protein that was previously reported to localize in the cytosol. We found that an isoform of GRSF1 accumulates in discrete foci in the mitochondrial matrix. These foci are composed of nascent mitochondrial RNA and also contain RNase P, an enzyme that participates in mitochondrial RNA processing. GRSF1 was found to interact with RNase P and to be required for processing of both classical and tRNA-less RNA precursors. In its absence, cleavage of primary RNA transcripts is abnormal, leading to decreased expression of mitochondrially encoded proteins and mitochondrial dysfunction. Our findings suggest that the foci containing GRSF1 and RNase P correspond to sites where primary RNA transcripts converge to be processed. We have termed these large ribonucleoprotein structures "mitochondrial RNA granules.

Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability

PARN, a poly(A)-specific ribonuclease, binds the 5′ cap-structure of mRNA and initiates deadenylation-dependent decay. Eukaryotic initiation factor 4E (eIF4E) also binds to the cap structure, an interaction that is critical for initiating cap-dependent translation. The stability of various mRNA transcripts in human cell lines is reduced under conditions of serum starvation as determined by both functional and chemical half-lives. Serum starvation also leads to enhanced cap association by PARN. In contrast, the 5′ cap occupancy by eIF4E decreases under serum-deprivation, as does the translation of reporter transcripts. Further, we show that PARN is a phosphoprotein and that this modification can be modulated by serum status. Taken together, these data are consistent with a natural competition existing at the 5′ cap structure between PARN and eIF4E that may be regulated by changes in post-translational modifications. These phosphorylation-induced changes in the interplay of PARN and eIF4E may determine whether the mRNA is translated or decayed

Human mitochondrial ribosomes can switch structural tRNAs - but when and why?

High resolution cryoEM of mammalian mitoribosomes revealed the unexpected presence of mitochondrially encoded tRNA as a structural component of mitochondrial large ribosomal subunit (mt-LSU). Our previously published data identified that only mitochondrial (mt-) tRNA(Phe) and mt-tRNA(Val) can be incorporated into mammalian mt-LSU and within an organism there is no evidence of tissue specific variation. When mt-tRNA(Val) is limiting, human mitoribosomes can integrate mt-tRNA(Phe) instead to generate a translationally competent monosome. Here we discuss the possible reasons for and consequences of the observed plasticity of the structural mt-tRNA integration. We also indicate potential direction for further research that could help our understanding of the mechanistic and evolutionary aspects of this unprecedented system.This work was supported by the Wellcome Trust under Grant 096919/Z/11/Z and Medical Research Council UK under Grant MC_U105697135

Concentration of atomic hydrogen diffused into silicon in the temperature range 900–1300 °C

Boron-doped Czochralski silicon samples with [B]~1017 cm−3 have been heated at various temperatures in the range 800–1300 °C in an atmosphere of hydrogen and then quenched. The concentration of [H-B] pairs was measured by infrared localized vibrational mode spectroscopy. It was concluded that the solubility of atomic hydrogen is greater than [Hs] = 5.6 × 1018 exp( − 0.95 eV/kT)cm−3 at the temperatures investigated

Production of transmitochondrial cybrids containing naturally occurring pathogenic mtDNA variants

The human mitochondrial genome (mtDNA) encodes polypeptides that are critical for coupling oxidative phosphorylation. Our detailed understanding of the molecular processes that mediate mitochondrial gene expression and the structure–function relationships of the OXPHOS components could be greatly improved if we were able to transfect mitochondria and manipulate mtDNA in vivo. Increasing our knowledge of this process is not merely of fundamental importance, as mutations of the mitochondrial genome are known to cause a spectrum of clinical disorders and have been implicated in more common neurodegenerative disease and the ageing process. In organellar or in vitro reconstitution studies have identified many factors central to the mechanisms of mitochondrial gene expression, but being able to investigate the molecular aetiology of a limited number of cell lines from patients harbouring mutated mtDNA has been enormously beneficial. In the absence of a mechanism for manipulating mtDNA, a much larger pool of pathogenic mtDNA mutations would increase our knowledge of mitochondrial gene expression. Colonic crypts from ageing individuals harbour mutated mtDNA. Here we show that by generating cytoplasts from colonocytes, standard fusion techniques can be used to transfer mtDNA into rapidly dividing immortalized cells and, thereby, respiratory-deficient transmitochondrial cybrids can be isolated. A simple screen identified clones that carried putative pathogenic mutations in MTRNR1, MTRNR2, MTCOI and MTND2, MTND4 and MTND6. This method can therefore be exploited to produce a library of cell lines carrying pathogenic human mtDNA for further study

Theory of Umklapp-assisted recombination of bound excitons in Si:P

We present the calculations for the oscillator strength of the recombination of excitons bound to phosphorous donors in silicon. We show that the direct recombination of the bound exciton cannot account for the experimentally measured oscillator strength of the no-phonon line. Instead, the recombination process is assisted by an umklapp process of the donor electron state. We make use of the empirical pseudopotential method to evaluate the Umklapp-assisted recombination matrix element in second-order perturbation theory. Our result is in excellent agreement with the experiment. We also present two methods to improve the optical resolution of the optical detection of the spin state of a single nucleus in silicon.Comment: 9 pages, 6 EPS figures, Revtex

Home drinking during and post‐COVID ‐19: Why the silence on domestic violence?

There is a well‐established body of evidence demonstrating alcohol is a compounding factor increasing both the occurrence and the severity of domestic violence in intimate relationships. The COVID‐19 pandemic and associated public health measures such as lockdowns and social distancing have contributed to a rise in domestic violence. Yet, despite the closure of public drinking venues and substantial changes to the home drinking landscape, the role of alcohol in domestic violence has received little attention from both the alcohol and domestic violence fields. In this commentary, we argue that the pandemic has magnified existing silences across these fields, resulting in missed opportunities for intervention. The implications for home drinking in particular on domestic violence deserve greater focus in research and policy

Targeting of the cytosolic poly(A) binding protein PABPC1 to mitochondria causes mitochondrial translation inhibition

Mammalian mitochondria contain their own genome that is almost fully transcribed from both strands, generating polycistronic RNA units that are processed and matured. The mitochondrial mRNA is modified by oligo- or polyadenylation at the 3′ termini, but the exact function of this post-transcriptional addition is unclear. Current debate focuses on the role of polyadenylation in transcript stability. An equally likely function that has received little attention is that, as in the cytosol of eukaryotes, polyadenylation facilitates translation in the mitochondrion. To address this issue, we have targeted cytosolic proteins to the mitochondrion, a poly(A) specific 3′ exoribonuclease, mtPARN, and a poly(A)binding protein, mtPABP1. Removal of the 3′ adenylyl extensions had a variable effect on mt-mRNA steady-state levels, increasing (MTND1, 2, 5) or decreasing (MTCO1, 2, RNA14) certain species with minimal effect on others (RNA7, MTND3). Translation was markedly affected, but interpretation of this was complicated by the concomitant 3′ truncation of the open reading frame in most cases. Coating of the poly(A) tail by mtPABP1, however, did not lead to transcript decay but caused a marked inhibition of mitochondrial translation. These data are consistent with endogenous RNA-binding factor(s) interacting with the poly(A) to optimize mitochondrial protein synthesis

Human ERAL1 is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit

The bacterial Ras-like protein Era has been reported previously to bind 16S rRNA within the 30S ribosomal subunit and to play a crucial role in ribosome assembly. An orthologue of this essential GTPase ERAL1 (Era G-protein-like 1) exists in higher eukaryotes and although its exact molecular function and cellular localization is unknown, its absence has been linked to apoptosis. In the present study we show that human ERAL1 is a mitochondrial protein important for the formation of the 28S small mitoribosomal subunit. We also show that ERAL1 binds in vivo to the rRNA component of the small subunit [12S mt (mitochondrial)-rRNA]. Bacterial Era associates with a 3′ unstructured nonanucleotide immediately downstream of the terminal stem–loop (helix 45) of 16S rRNA. This site contains an AUCA sequence highly conserved across all domains of life, immediately upstream of the anti-Shine–Dalgarno sequence, which is conserved in bacteria. Strikingly, this entire region is absent from 12S mt-rRNA. We have mapped the ERAL1-binding site to a 33 nucleotide section delineating the 3′ terminal stem–loop region of 12S mt-rRNA. This loop contains two adenine residues that are reported to be dimethylated on mitoribosome maturation. Furthermore, and also in contrast with the bacterial orthologue, loss of ERAL1 leads to rapid decay of nascent 12S mt-rRNA, consistent with a role as a mitochondrial RNA chaperone. Finally, whereas depletion of ERAL1 leads to apoptosis, cell death occurs prior to any appreciable loss of mitochondrial protein synthesis or reduction in the stability of mitochondrial mRNA