Late Pleistocene pteropods, heteropods and planktonic foraminifera from the Caribbean Sea, Mediterranean Sea and Indian Ocean

Pteropods and heteropods (holoplanktonic gastropods) are an important component of the modern oceans; however, detailed information on their distribution in the fossil record is often based on poorly preserved specimens. This study presents the micropaleontological analysis of three exceptionally well-preserved Late Pleistocenemarine sediment cores from the eastern Caribbean Sea, westernMediterranean Sea and the Indian Ocean. This study presents the first stratigraphical record of heteropods in the Caribbean Sea and extends the known zonation of pteropods in the Mediterranean Sea. Distributions of pteropods, heteropods and planktonic foraminifera are presented with abundance and species richness data, as well as stratigraphical dates inferred from the oxygen isotope stratigraphy, argon-argon dating and biostratigraphy. The findings of this study greatly improve our understanding of holoplanktonic gastropod stratigraphy and ecology. Results reveal that the geographical range of heteropods, thought to be restricted to sub-tropical warm waters,may be much greater, including waters of sub-polar temperature. Heteropods were also found to be surprisingly abundant, potentially representing a more important part of the ocean food web than previously thought. Analysis revealed two species of holoplanktonic gastropod that are previously undescribed and indicate that the pteropod Heliconoides mermuysi (Cahuzac and Janssen 2010), known exclusively from the Moulin de Cabanes (Miocene),may have lived in theCaribbean Sea and Indian Ocean as recently as 4 kyr ago. These findings highlight the urgent need for increased research on holoplanktonic gastropods. The threat that current climate change and ocean acidification poses, particularly to the delicately shelled forms, means that some species may become extinct before they have even been fully ‘discovered’

Activation of Transfer RNA-Guanine Ribosyltransferase by Protein Kinase C

Transfer RNA-guanine ribosyltransferase (TGRase) irreversibly incorporates queuine into the first position in the anticodon of four tRNA isoacceptors. Rat brain protein kinase C (PKC) was shown to stimulate rat liver TG Rase activity, TGRase preparations derived from rat liver have been observed to decrease in activity over time in storage at -20 or -70°C, Contamination of the samples by phosphatases was indicated by a p-nitrophenylphosphate conversion test, The addition of micromolar concentrations of the phosphatase inhibitors sodium pyrophosphate and sodium fluoride into TGRase isolation buffers resulted in a greater return of TGRase activity than without these inhibitors, Inactive TGRase preparations were reactivated to their original activity with the addition of PKC, In assays combining both TGRase and PKC enzymes, inhibitors of protein kinase C (sphingosine, staurosporine, H-7 and calphostin C) all blocked the reactivation of TGRase, whereas activators of protein kinase C (calcium, diacylglycerol and phosphatidyl serine) increased the activity of TGRase, None of the PKC modulators affected TGRase activity directly, Alkaline phosphatase, when added to assays, decreased the activity of TGRase and also blocked the reactivation of TGRase with PKC, Denaturing PAGE and autoradiography was performed on TGRase isolates that had been labelled with 32P by PKC, The resulting strong 60 kDa band (containing the major site for phosphorylation) and weak 34.5 kDa band (containing the TGRase activity) are suggested to associate to make up a 104 kDa heterodimer that comprises the TGRase enzyme, This was corroberated by native and denaturing size-exclusion chromatography These results suggest that PKC-dependent phosphorylation of TGRase is tied to efficient enzymatic function and therefore control of the queuine modification of tRNA

The effect of FTO variation on increased osteoarthritis risk is mediated through body mass index : a mendelian randomisation study

Objective: Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. Methods: 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. Results: In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10−7). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. Conclusions: Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA

Molecular and functional correction of a deep intronic splicing mutation in CFTR by CRISPR-Cas9 gene editing

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The 10th most common mutation, c.3178-2477C>T (3849+10kb C>T), involves a cryptic, intronic splice site. This mutation was corrected in CF primary cells homozygous for this mutation by delivering pairs of guide RNAs (gRNAs) with Cas9 protein in ribonucleoprotein (RNP) complexes that introduce double-strand breaks to flanking sites to excise the 3849+10kb C>T mutation, followed by DNA repair by the non-homologous end-joining pathway, which functions in all cells of the airway epithelium. RNP complexes were delivered to CF basal epithelial cell by a non-viral, receptor-targeted nanocomplex comprising a formulation of targeting peptides and lipids. Canonical CFTR mRNA splicing was, thus, restored leading to the restoration of CFTR protein expression with concomitant restoration of electrophysiological function in airway epithelial air-liquid interface cultures. Off-target editing was not detected by Sanger sequencing of in silico-selected genomic sites with the highest sequence similarities to the gRNAs, although more sensitive unbiased whole genome sequencing methods would be required for possible translational developments. This approach could potentially be used to correct aberrant splicing signals in several other CF mutations and other genetic disorders where deep-intronic mutations are pathogenic

Exercise counselling and referral in cancer care: An international scoping survey of health care practitioners’ knowledge, practices, barriers, and facilitators

Purpose: Evidence supports the role of prescribed exercise for cancer survivors, yet few are advised to exercise by a healthcare practitioner (HCP). We sought to investigate the gap between HCPs’ knowledge and practice from an international perspective. Methods: An online questionnaire was administered to HCPs working in cancer care between February 2020 and February 2021. The questionnaire assessed knowledge, beliefs, and practices regarding exercise counselling and referral of cancer survivors to exercise programs. Results: The questionnaire was completed by 375 participants classified as medical practitioners (42 %), nurses (28 %), exercise specialists (14 %), and non-exercise allied health practitioners (16 %). Between 35 and 50 % of participants self-reported poor knowledge of when, how, and which cancer survivors to refer to exercise programs or professionals, and how to counsel based on exercise guidelines. Commonly reported barriers to exercise counselling were safety concerns, time constraints, cancer survivors being told to rest by friends and family, and not knowing how to screen people for suitability to exercise (40 – 48 %). Multivariable logistic regression models including age, gender, practitioner group, leisure-time physical activity, and recall of guidelines found significant effects for providing specific exercise advice (χ2(7) = 117.31, p \u3c .001), discussing the role of exercise in symptom management (χ2(7) = 65.13, p \u3c .001) and cancer outcomes (χ2(7) = 58.69, p \u3c .001), and referring cancer survivors to an exercise program or specialist (χ2(7) = 72.76, p \u3c .001). Conclusion: Additional education and practical support are needed to equip HCPs to provide cancer survivors with exercise guidelines, resources, and referrals to exercise specialists

The Extratropical Transition of Tropical Cyclones: Forecast Challenges, Current Understanding, and Future Directions

A significant number of tropical cyclones move into the midlatitudes and transform into extratropical cyclones. This process is generally referred to as extratropical transition (ET). During ET a cyclone frequently produces intense rainfall and strong winds and has increased forward motion, so that such systems pose a serious threat to land and maritime activities. Changes in the structure of a system as it evolves from a tropical to an extratropical cyclone during ET necessitate changes in forecast strategies. In this paper a brief climatology of ET is given and the challenges associated with forecasting extratropical transition are described in terms of the forecast variables (track, intensity, surface winds, precipitation) and their impacts (flooding, bush fires, ocean response). The problems associated with the numerical prediction of ET are discussed. A comprehensive review of the current understanding of the processes involved in ET is presented. Classifications of extratropical transition are described and potential vorticity thinking is presented as an aid to understanding ET. Further sections discuss the interaction between a tropical cyclone and the midlatitude environment, the role of latent heat release, convection and the underlying surface in ET, the structural changes due to frontogenesis, the mechanisms responsible for precipitation, and the energy budget during ET. Finally, a summary of the future directions for research into ET is given

Pitch Processing Sites in the Human Auditory Brain

Lateral Heschl's gyrus (HG), a subdivision of the human auditory cortex, is commonly believed to represent a general “pitch center,” responding selectively to the pitch of sounds, irrespective of their spectral characteristics. However, most neuroimaging investigations have used only one specialized pitch-evoking stimulus: iterated-ripple noise (IRN). The present study used a novel experimental design in which a range of different pitch-evoking stimuli were presented to the same listeners. Pitch sites were identified by searching for voxels that responded well to the range of pitch-evoking stimuli. The first result suggested that parts of the planum temporale are more relevant for pitch processing than lateral HG. In some listeners, pitch responses occurred elsewhere, such as the temporo-parieto-occipital junction or prefrontal cortex. The second result demonstrated a different pattern of response to the IRN and raises the possibility that features of IRN unrelated to pitch might contribute to the earlier results. In conclusion, it seems premature to assign special status to lateral HG solely on the basis of neuroactivation patterns. Further work should consider the functional roles of these multiple pitch processing sites within the proposed network