Southern ocean carbon and heat impact on climate.

The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

A split-tattoo randomized Q-switched neodymium-doped yttrium-aluminium-garnet laser trial comparing the efficacy of a novel three-pass, one-session method with a conventional method in the treatment of blue/black tattoos in darker skin types.

Tattoos with blue/black ink show good lightening of pigment after treatment with 1064 nm Q-switched (QS) neodymium-doped yttrium-aluminium-garnet (Nd:YAG) laser. In this randomized trial, we compared the efficacy of a novel three pass, one session procedure (R15 method) with a conventional method for treating blue/black tattoos in darker skin types. Tattoos were treated with 1064 nm QS Nd:YAG Laser with a spot size of 4 mm, fluence of 5 J/cm2 and frequency of 5 Hz. The tattoo pigment lightening was comparable with both methods. Thread-like tattoos had significantly better pigment lightening with fewer side effects than the broad band-like tattoos. We would like to recommend the R15 method of the QS Nd:YAG laser for thread-like tattoos, which can save patients' time, cut short the frequency of their hospital visits and, more importantly, decrease the cost involved in it.

Dual-energy CT-generated bone marrow oedema maps improve timely visualisation and recognition of acute lower extremity fractures.

AIM: To assesses whether utilising bone marrow oedema (BMO) maps improved fracture read times and reader confidence in a large series of acute lower extremity trauma dual-energy computed tomography (DECT) studies. MATERIALS AND METHODS: One hundred and six DECT studies, including 60 fracture cases and 46 non-fracture cases, were evaluated retrospectively in this cross-sectional study. Three-dimensional (3D) BMO maps were generated for each study and coded to display skeletal anatomy in blue and marrow oedema in green. Studies were interpreted by two readers in two timed stages (without and with BMO maps). Readers identified the number, anatomical location, and comminution of fractures. Reader confidence (five-point Likert scale) for fracture identification and anatomical regions where oedema was present was also recorded. RESULTS: Decreased read times (p<0.01) were observed when readers utilised BMO maps for their fracture search. The presence of oedema on BMO maps corresponded with associated fracture in 75.7% reads. No differences in reader confidence were observed as a result of using this BMO-guided technique (>95%, 5/5 for both readers with and without the aid of BMO maps). CONCLUSIONS: DECT BMO maps improve the speed of radiological identification of suspected acute lower extremity fractures with preserved reader confidence. It may help emergent detection of fractures, important for patient management and outcomes.

Oral supplementation of trans-cinnamaldehyde reduces uropathogenic Escherichia coli colonization in a mouse model.

Urinary tract infections (UTIs) in the United States result in more than 7 million hospital visits per year. Uropathogenic Escherichia coli (UPEC) is responsible for more than 80% of UTIs. Although antibiotics are the drug of choice to control UTIs, their repeated use has resulted in the emergence of antibiotic-resistant UPEC. Thus, there is a need for effective alternate strategies to control UPEC infections. This study investigated the efficacy of trans-cinnamaldehyde (TC), a food-grade molecule present in cinnamon, in reducing UPEC colonization and pathogenesis in the lower UTI. Female C57BL/6 mice (6-8 weeks old) were fed ad libitum with 0, 0·1, 0·2 and 0·4% TC containing mouse chow for 10 days. Following TC supplementation, animals were experimentally infected with UPEC by transurethral catheterization. Mice were euthanized on days 1, 2 and 4 postinfection, and the bladder, urethra and urine were collected for bacterial enumeration. Prophylactic TC supplementation significantly (P ≤ 0·05) reduced UPEC colonization in the urinary bladder and urethra compared to the control. Results indicate that TC could potentially be used as an oral supplement to control UPEC-associated lower UTIs, however, follow-up clinical trials are warranted. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we have demonstrated that oral supplementation of trans-cinnamaldehyde (TC) reduced uropathogenic Escherichia coli (UPEC)-associated lower urinary tract infection (UTI) in mice. Specifically, in-feed supplementation of TC significantly decreased UPEC populations in the urethra and bladder, thereby reducing the infectious load. These findings are particularly significant given the increase in incidence and prevalence of antibiotic-resistant UTIs. Our study offers new insights into the potential use of natural antimicrobials including TC, the active ingredient in cinnamon, as a nonantibiotic-based natural dietary intervention in the prophylaxis of lower UTIs.

Linear magnetoresistance caused by mobility fluctuations in n-doped Cd(3)As(2).

Cd(3)As(2) is a candidate three-dimensional Dirac semimetal which has exceedingly high mobility and nonsaturating linear magnetoresistance that may be relevant for future practical applications. We report magnetotransport and tunnel diode oscillation measurements on Cd(3)As(2), in magnetic fields up to 65 T and temperatures between 1.5 and 300 K. We find that the nonsaturating linear magnetoresistance persists up to 65 T and it is likely caused by disorder effects, as it scales with the high mobility rather than directly linked to Fermi surface changes even when approaching the quantum limit. From the observed quantum oscillations, we determine the bulk three-dimensional Fermi surface having signatures of Dirac behavior with a nontrivial Berry phase shift, very light effective quasiparticle masses, and clear deviations from the band-structure predictions. In very high fields we also detect signatures of large Zeeman spin splitting (g∼16).

Dichotomy between the Hole and Electron Behavior in Multiband Superconductor FeSe Probed by Ultrahigh Magnetic Fields.

Magnetoresistivity ρ(xx) and Hall resistivity ρ(xy) in ultrahigh magnetic fields up to 88 T are measured down to 0.15 K to clarify the multiband electronic structure in high-quality single crystals of superconducting FeSe. At low temperatures and high fields we observe quantum oscillations in both resistivity and the Hall effect, confirming the multiband Fermi surface with small volumes. We propose a novel approach to identify from magnetotransport measurements the sign of the charge carriers corresponding to a particular cyclotron orbit in a compensated metal. The observed significant differences in the relative amplitudes of the quantum oscillations between the ρ(xx) and ρ(xy) components, together with the positive sign of the high-field ρ(xy), reveal that the largest pocket should correspond to the hole band. The low-field magnetotransport data in the normal state suggest that, in addition to one hole and one almost compensated electron band, the orthorhombic phase of FeSe exhibits an additional tiny electron pocket with a high mobility.

Stem cells of the lamina propria of human oral mucosa and gingiva develop into mineralized tissues in vivo.

AIMS: To characterize the mineralized tissue formed constitutively in the supracalvarial region of scid mice by a primitive stem cell population (hOMSC) derived from the lamina propria of the human oral mucosa and gingiva. MATERIAL AND METHODS: Fibrin-hOMSC constructs were cultured for 14 days at which time point they were analysed for the expression of osteoblastic/cementoblastic markers and implanted between the skin and calvaria bones into scid mice. After 8 weeks, the animals were sacrificed and the implantation sites analysed. RESULTS: Two-week-old cultures of fibrin-hOMSC constructs expressed osteogenic/cementogenic markers at the gene level. Macroscopic and radiographic examinations revealed mineralized masses at the implantation sites of fibrin-hOMSC constructs. Histology, histochemistry and immunofluorescence showed mineralized masses consisting of avascular cellular and acellular matrices that stained positively for collagen, Ca, cementum attachment protein, cementum protein 1, bone sialoprotein, alkaline phosphatase, osteocalcin, amelogenin and ameloblastin. Positive anti-human nuclear antigen indicated the human origin of the cells. Atomic force microscopy depicted long prismatic structures organized in lamellar aggregates. CONCLUSIONS: Within the limitation of this study, the results indicate for the first time that fibrin-hOMSC constructs are endowed with the constitutive capacity to develop into mineralized tissues that exhibit certain similarities to cementum and bone.

Broad responses and attitudes to having music in surgery (the BRAHMS study) - a South African perspective.

BACKGROUND: Music is played in operating theatres (OTs) throughout the world, though controversy around its use exists. While some clinicians may find background music favourable to the theatre mood and a way to augment surgical performance, there is concern raised over its distracting and noise-creating properties. METHODS: In this prospective observational study, between August and December 2021, 110 surgeons and registrars in South Africa responded to a survey investigating the way they use music, and their perceptions and attitudes towards its effect on the OT environment. RESULTS: In this cohort, 66% were male, 29% were consultants and the most common age range was 30-39 years old. Eighty per cent of respondents reported that music was played at least "sometimes", with 74% reporting that they enjoyed it. Easy Listening was the most played and preferred genre followed by Top 40/Billboard hits. Overwhelmingly, respondents reported that background music in the OT improved temperament, focus, mood, and performance, though over a quarter felt it worsened communication. Thirty-one per cent of respondents reported that the choice of music depended on the type of operation, and 70% would turn music down or off during crises. Those who enjoyed music in their spare time were significantly more likely to enjoy music in the OT and perceive it positively. CONCLUSION: This study provides a window into the surgeons' use of and attitudes to intraoperative music in South Africa. While overall, music is viewed positively by this cohort, some concerns remain regarding communication and distractedness. Further interventional and qualitative studies would be useful.

Cementum protein 1 (CEMP1) induces a cementoblastic phenotype and reduces osteoblastic differentiation in periodontal ligament cells.

Cementum is a calcified tissue covering the tooth root surface, which functions as rigid tooth-anchoring structure. Periodontal ligament is a unique non-mineralized connective tissue, and is a source of mineralized tissue forming cells such as cementoblasts and osteoblasts. The CEMP1 is a novel cementum component the presence of which appears to be limited to cementoblasts and their progenitors. In order to understand the function of CEMP1, we investigated CEMP1 expression during the differentiation of human periodontal ligament cells. Immunomagnetically enriched alkaline phosphatase (ALP)-positive periodontal ligament cells preferentially expressed CEMP1. CEMP1 expression was reduced when periodontal ligament cells differentiated to osteoblasts in vitro. Over-expression of CEMP1 in periodontal ligament cells enhanced cementoblast differentiation and attenuated periodontal and osteoblastic phenotypes. Our data demonstrate for the first time that the CEMP1 is not only a marker protein for cementoblast-related cells, but it also regulates cementoblast commitment in periodontal ligament cells.

Soluble ECM promotes organotypic formation in lung alveolar model.

Micropatterned suspension culture creates consistently sized and shaped cell aggregates but has not produced organotypic structures from stable cells, thus restricting its use in accurate disease modeling. Here, we show that organotypic structure is achieved in hybrid suspension culture via supplementation of soluble extracellular matrix (ECM). We created a viable lung organoid from epithelial, endothelial, and fibroblast human stable cell lines in suspension culture. We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of lumen-like structures with airspace showing feasible gas exchange units, formation of branching, perfusable vasculature, and long-term 70-day maintenance of lumen structure. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We also demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.

Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy.

BACKGROUND: Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours. METHODS: The chemosensitivity of a series of 31 ovarian tumours, all previously treated with platinum-based chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP-TCA) and correlated with resistance gene expression measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array following extraction of mRNA from formalin-fixed paraffin-embedded tissue. The results were standardised against a housekeeping gene (PBGD), and assessed by multiple linear regression. RESULTS: Predictive multiple linear regression models were derived for four single agents (cisplatin, gemcitabine, topotecan, and treosulfan), and for the combinations of cisplatin+gemcitabine and treosulfan+gemcitabine. Particularly strong correlations were obtained for cisplatin, gemcitabine, topotecan, and treosulfan+gemcitabine. No individual gene expression showed direct correlation with activity in the ATP-TCA. Genes involved in DNA repair and apoptosis were strongly represented, with some drug pumps also involved. CONCLUSION: The chemosensitivity of ovarian cancer to drugs is related to the expression of genes involved in sensitivity and resistance mechanisms.

Characterization of recombinant human cementum protein 1 (hrCEMP1): primary role in biomineralization.

Cementum protein 1 (CEMP1) has been recently cloned, and in vitro experiments have shown functions as regulator of cementoblast behavior and inducer of differentiation of non-osteogenic cells toward a cementoblastic/osteoblastic phenotype. In this study, we have produced a full-length human recombinant CEMP1 protein in a human gingival fibroblast cell line. The purified protein (hrCEMP1) has a M(r) 50,000. Characterization of hrCEMP1 indicates that its secondary structure is mainly composed of beta-sheet (55%), where random coil and alpha helix conformations correspond to 35% and 10%, respectively. It was found that hrCEMP1 is N-glycosylated, phosphorylated and possesses strong affinity for hydroxyapatite. Even more important, our results show that hrCEMP1 plays a role during the biomineralization process by promoting octacalcium phosphate (OCP) crystal nucleation. These features make CEMP1 a very good candidate for biotechnological applications in order to achieve cementum and/or bone regeneration.

The smooth muscle cell. III. Elastin synthesis in arterial smooth muscle cell culture.

Primate arterial smooth muscle cells and skin fibroblasts were examined for their ability to synthesize elastin in culture. In the presence of the lathyrogen beta-aminopropionitrile, the smooth muscle cells incorporate [3H]lysine into a lysyl oxidase substrate that was present in the medium and associated with the cell layer. A component having a mol wt of 72,000 and an electrophoretic mobility similar to that of authentic tropoelastin was isolated from the labeled smooth muscle cells by coacervation and fractionation with organic solvents. In the absence of beta-aminopropionitrile, long-term cultures of smooth muscle cells incorporated [14C]lysine into desmosine and isodesmosine, the cross-link amino acids unique to elastin. In contrast, no desmosine formation occurred in the fibroblast cultures. These characteristics demonstrate that arterial smooth muscle cells are capable of synthesizing both soluble and cross-lined elastin in culture.

Internal modification of U2 small nuclear (sn)RNA occurs in nucleoli of Xenopus oocytes.

U2 small nuclear (sn)RNA contains a large number of posttranscriptionally modified nucleotides, including a 5' trimethylated guanosine cap, 13 pseudouridines, and 10 2'-O-methylated residues. Using Xenopus oocytes, we demonstrated previously that at least some of these modified nucleotides are essential for biogenesis of a functional snRNP. Here we address the subcellular site of U2 internal modification. Upon injection into the cytoplasm of oocytes, G-capped U2 that is transported to the nucleus becomes modified, whereas A-capped U2 that remains in the cytoplasm is not modified. Furthermore, by injecting U2 RNA into isolated nuclei or enucleated oocytes, we observe that U2 internal modifications occur exclusively in the nucleus. Analysis of the intranuclear localization of fluorescently labeled RNAs shows that injected wild-type U2 becomes localized to nucleoli and Cajal bodies. Both internal modification and nucleolar localization of U2 are dependent on the Sm binding site. An Sm-mutant U2 is targeted only to Cajal bodies. The Sm binding site can be replaced by a nucleolar localization signal derived from small nucleolar RNAs (the box C/D motif), resulting in rescue of internal modification as well as nucleolar localization. Analysis of additional chimeric U2 RNAs reveals a correlation between internal modification and nucleolar localization. Together, our results suggest that U2 internal modification occurs within the nucleolus.

Heterogeneity of normal human diploid fibroblasts: isolation and characterization of one phenotype.

Cultures of human diploid fibroblasts contain cells that respond to exposure to the first component of complement (C1) by initiating DNA synthesis and growth. The plasma membranes of these cells have specific binding sites for the C1q subcomponent of C1. A fluorescence-activated cell sorter was used to isolate a subset of cells with a high affinity for C1q, and the growth and synthesis activities of these high-affinity cells were studied after numerous replications in vitro. These cells synthesize DNA and grow faster than the parent cultures and low-affinity cells, and they produce two to three times as much protein. About 40 percent of their total protein synthesis activity is directed to collagen production, unusually high proportions of collagen types III and V being produced. These properties and the high affinity of the cells for C1q are retained for at least six cell transfers. This phenotype has the properties expected of fibroblasts in healing wounds and inflamed tissues.

HR-TEM and FT-Raman dataset of the caffeine interacted Phe-Phe peptide nanotube for possible sensing applications.

Sensing ability of caffeine interaction with Phe-Phe annotates (PNTs), is presented (Govindhan et al., 2017; Karthikeyan et al., 2014; Tavagnacco et al., 2013; Kennedy et al., 2011; Wang et al., 2017) [1-5] in this data set. Investigation of synthesized caffeine carrying peptide nanotubes are carried out by FT-Raman spectral analysis and high resolution transmission electron microscopy (HR-TEM). Particle size of the caffeine loaded PNTs is < 40 nm. The FT-Raman spectrum signals are enhanced in the region of 400-1700 cm-1. These data are ideal tool for the applications like biosensing and drug delivery research (DDS).

qSR: a quantitative super-resolution analysis tool reveals the cell-cycle dependent organization of RNA Polymerase I in live human cells.

We present qSR, an analytical tool for the quantitative analysis of single molecule based super-resolution data. The software is created as an open-source platform integrating multiple algorithms for rigorous spatial and temporal characterizations of protein clusters in super-resolution data of living cells. First, we illustrate qSR using a sample live cell data of RNA Polymerase II (Pol II) as an example of highly dynamic sub-diffractive clusters. Then we utilize qSR to investigate the organization and dynamics of endogenous RNA Polymerase I (Pol I) in live human cells, throughout the cell cycle. Our analysis reveals a previously uncharacterized transient clustering of Pol I. Both stable and transient populations of Pol I clusters co-exist in individual living cells, and their relative fraction vary during cell cycle, in a manner correlating with global gene expression. Thus, qSR serves to facilitate the study of protein organization and dynamics with very high spatial and temporal resolutions directly in live cell.

Nuclear retention elements of U3 small nucleolar RNA.

The processing and methylation of precursor rRNA is mediated by the box C/D small nucleolar RNAs (snoRNAs). These snoRNAs differ from most cellular RNAs in that they are not exported to the cytoplasm. Instead, these RNAs are actively retained in the nucleus where they assemble with proteins into mature small nucleolar ribonucleoprotein particles and are targeted to their intranuclear site of action, the nucleolus. In this study, we have identified the cis-acting sequences responsible for the nuclear retention of U3 box C/D snoRNA by analyzing the nucleocytoplasmic distributions of an extensive panel of U3 RNA variants after injection of the RNAs into Xenopus oocyte nuclei. Our data indicate the importance of two conserved sequence motifs in retaining U3 RNA in the nucleus. The first motif is comprised of the conserved box C' and box D sequences that characterize the box C/D family. The second motif contains conserved box sequences B and C. Either motif is sufficient for nuclear retention, but disruption of both motifs leads to mislocalization of the RNAs to the cytoplasm. Variant RNAs that are not retained also lack 5' cap hypermethylation and fail to associate with fibrillarin. Furthermore, our results indicate that nuclear retention of U3 RNA does not simply reflect its nucleolar localization. A fragment of U3 containing the box B/C motif is not localized to nucleoli but retained in coiled bodies. Thus, nuclear retention and nucleolar localization are distinct processes with differing sequence requirements.

Role of the box C/D motif in localization of small nucleolar RNAs to coiled bodies and nucleoli.

Small nucleolar RNAs (snoRNAs) are a large family of eukaryotic RNAs that function within the nucleolus in the biogenesis of ribosomes. One major class of snoRNAs is the box C/D snoRNAs named for their conserved box C and box D sequence elements. We have investigated the involvement of cis-acting sequences and intranuclear structures in the localization of box C/D snoRNAs to the nucleolus by assaying the intranuclear distribution of fluorescently labeled U3, U8, and U14 snoRNAs injected into Xenopus oocyte nuclei. Analysis of an extensive panel of U3 RNA variants showed that the box C/D motif, comprised of box C', box D, and the 3' terminal stem of U3, is necessary and sufficient for the nucleolar localization of U3 snoRNA. Disruption of the elements of the box C/D motif of U8 and U14 snoRNAs also prevented nucleolar localization, indicating that all box C/D snoRNAs use a common nucleolar-targeting mechanism. Finally, we found that wild-type box C/D snoRNAs transiently associate with coiled bodies before they localize to nucleoli and that variant RNAs that lack an intact box C/D motif are detained within coiled bodies. These results suggest that coiled bodies play a role in the biogenesis and/or intranuclear transport of box C/D snoRNAs.