Disc Growth Research Articles

Abstract IA07: Hippo signaling in liver regeneration and liver tumors

Abstract The Hippo pathway is required for normal tissue growth during development, and it is also involved in regeneration in flies and mammals. Hyperactivation of the Hippo pathway effector YAP drives cell proliferation and malignancy of tumor cells, and YAP is frequently hyperactivated in a broad range of different human carcinomas. Thus, targeting the activity of YAP may inhibit cancer cells. However, how the Hippo pathway is regulated during development and what role it plays during normal growth, regeneration, and in cancer cells is poorly understood. My group uses genetic approaches in Drosophila and mice to unravel the function of the Hippo pathway in the growth and regeneration of imaginal discs and liver and in liver cancer. I will present our recent efforts towards these aims and discuss our findings in light of different growth control models. Citation Format: Georg Halder. Hippo signaling in liver regeneration and liver tumors [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr IA07.

Irregular emission cycles in the Oe star HD 60 848

We analyse the spectroscopic and photometric variability of the Oe star HD 60 848 over the last twenty five years. The spectra reveal recurrent, but irregular cycles of increased circumstellar emission lines. These cycles are highly asymmetric displaying a slow increase over about 6 years, followed by a fast decay within about 6 months. Our analysis focuses on the most recent cycle (2013 – 2020). The equivalent width and velocity separation of the emission peaks indicate variations of the outer disk radius by a factor ~ 2.2, although the variability appears more complex than expected from first principle relations for optically thin Keplerian disks. We observe a time delay between the variations of the strengths of He iλ 5876 on the one hand and Hα and Hβ on the other hand. We interpret this behaviour in a two-step disk growth scenario, where the disk first expands radially before its density increases. A difference in behaviour is also seen between Hα and the H i Paschen lines, with the latter displaying a more symmetric cycle, similar to the photometric variability. The rather fast decays of the Hα emission observed in 2001, 2009 and 2018 – 2019 suggest that the strong radiation field and early spectral type of the star lead to a faster dissipation of the disk than in later-type Be stars, as theoretically expected. We discuss X-ray observations of the star both during a high and a low-emission state. The X-ray spectrum is soft at both epochs, and the X-ray fluxes are only marginally different and remain consistent with the canonical LX/Lbol relation of O-type stars. These results indicate that the circumstellar decretion disk of HD 60 848 has essentially no impact on the star’s X-ray emission, and that the latter most likely arises inside the stellar wind.

Contribution of Hydrogen Cyanide to the Antagonistic Activity of Pseudomonas Strains Against Phytophthora infestans.

Plants face many biotic and abiotic challenges in nature; one of them is attack by disease-causing microbes. Phytophthora infestans, the causal agent of late blight is one of the most prominent pathogens of the potato responsible for multi-billion-dollar losses every year. We have previously reported that potato-associated Pseudomonas strains inhibited P. infestans at various developmental stages. A comparative genomics approach identified several factors putatively involved in this anti-oomycete activity, among which was the production of hydrogen cyanide (HCN). Here, we report the relative contribution of HCN emission to the overall anti-Phytophthora activity of two cyanogenic Pseudomonas strains, P. putida R32 and P. chlororaphis R47. To quantify this contribution, we generated HCN-negative mutants (Δhcn) and compared their activities to those of their respective wild types in different experiments assessing P. infestans mycelial growth, zoospore germination, and infection of potato leaf disks. Using in vitro experiments allowing only volatile-mediated interactions, we observed that HCN accounted for most of the mycelial growth inhibition (57% in R47 and 80% in R32). However, when allowing both volatile and diffusible compound-mediated interactions, HCN only accounted for 1% (R47) and 18% (R32) of mycelial growth inhibition. Likewise, both mutants inhibited zoospore germination in a similar way as their respective wild types. More importantly, leaf disk experiments showed that both wild-type and Δhcn strains of R47 and R32 were able to limit P. infestans infection to a similar extent. Our results suggest that while HCN is a major contributor to the in vitro volatile-mediated restriction of P. infestans mycelial growth, it does not play a major role in the inhibition of other disease-related features such as zoospore germination or infection of plant tissues.

Adolescent idiopathic scoliosis: The mechanobiology of differential growth.

Adolescent idiopathic scoliosis (AIS) has been linked to neurological, genetic, hormonal, microbial, and environmental cues. Physically, however, AIS is a structural deformation, hence an adequate theory of etiology must provide an explanation for the forces involved. Earlier, we proposed differential growth as a possible mechanism for the slow, three‐dimensional deformations observed in AIS. In the current perspective paper, the underlying mechanobiology of cells and tissues is explored. The musculoskeletal system is presented as a tensegrity‐like structure, in which the skeletal compressive elements are stabilized by tensile muscles, ligaments, and fasciae. The upright posture of the human spine requires minimal muscular energy, resulting in less compression, and stability than in quadrupeds. Following Hueter‐Volkmann Law, less compression allows for faster growth of vertebrae and intervertebral discs. The substantially larger intervertebral disc height observed in AIS patients suggests high intradiscal pressure, a condition favorable for notochordal cells; this promotes the production of proteoglycans and thereby osmotic pressure. Intradiscal pressure overstrains annulus fibrosus and longitudinal ligaments, which are then no longer able to remodel and grow, and consequently induce differential growth. Intradiscal pressure thus is proposed as the driver of AIS and may therefore be a promising target for prevention and treatment.

Characterization and functional analysis of chitinase family genes involved in nymph-adult transition of Sogatella furcifera.

Chitinase degrades chitin in the old epidermis or peritrophic matrix of insects, which ensures normal development and metamorphosis. In our previous work, we comprehensively studied the function of SfCht7 in Sogatella furcifera. However, the number and function of chitinase genes in S. furcifera remain unknown. Here, we identified 12 full-length chitinase transcripts from S. furcifera, which included nine chitinase (Cht), two imaginal disc growth factor (IDGF), and one endo-β-N-acetylglucosaminidase (ENGase) genes. Expression analysis results revealed that the expression levels of eight genes (SfCht3, SfCht5, SfCht6-1, SfCht6-2, SfCht7, SfCht8, SfCht10, and SfIDGF2) with similar transcript levels peaked prior to molting of each nymph and were highly expressed in the integument. Based on RNA interference (RNAi), description of the functions of each chitinase gene indicated that the silencing of SfCht5, SfCht10, and SfIDGF2 led to molting defects and lethality. RNAi inhibited the expressions of SfCht5, SfCht7, SfCht10, and SfIDGF2, which led to downregulated expressions of chitin synthase 1 (SfCHS1, SfCHS1a, and SfCHS1b) and four chitin deacetylase genes (SfCDA1, SfCDA2, SfCDA3, and SfCDA4), and caused a change in the expression level of two trehalase genes (TRE1 and TRE2). Furthermore, silencing of SfCht7 induced a significant decrease in the expression levels of three wing development-related genes (SfWG, SfDpp, and SfHh). In conclusion, SfCht5, SfCht7, SfCht10, and SfIDGF2 play vital roles in nymph-adult transition and are involved in the regulation of chitin metabolism, and SfCht7 is also involved in wing development; therefore, these genes are potential targets for control of S. furcifera.

An optimized step-by-step protocol for isolation of nucleus pulposus, annulus fibrosus, and end plate cells from the mouse intervertebral discs and subsequent preparation of high-quality intact total RNA.

Intervertebral disc degeneration is the most significant, and least understood, cause of chronic back pain, affecting almost one in seven individuals at some point of time. Each intervertebral disc has three components; central nucleus pulposus (NP), concentric layers of annulus fibrosus (AF), and a pair of end plate (EP) that connects the disc to the vertebral bodies. Understanding the molecular and cellular basis of intervertebral disc growth, health, and aging will generate significant information for developing therapeutic approaches. Rapid and efficient preparations of homogeneous and pure cells are crucial for meaningful and rigorous downstream analysis at the cellular, molecular, and biochemical level. Cross‐sample contamination may influence the interpretation of the results. In addition to altering gene expression, slow or delayed isolation procedures will also cause the degradation of cells and biomolecules that create a bias in the outcomes of the study. The mouse model system is extensively used to understand the intervertebral disc biology. Here we describe two protocols: (a) for efficient isolation of pure NP, AF, and EP cells from mouse lumbar intervertebral disc. We validated the purity of the NP and AF cells using Shh Cre/+; R26 mT/mG/+ dual‐fluorescent reporter mice where all NP cells are GPF+ve, and by the sensitive approach of qPCR analysis using TaqMan probes for Shh, and Brachyury as NP‐specific markers, Tenomodulin as AF‐specific marker, and Osteocalcin as bone‐specific marker. (b) For isolation of high‐quality intact RNA with RIN of 9.3 to 10 from disc cells. These methods will be useful for the rigorous analysis of NP and AF cells, and improve our understanding of intervertebral disc biology.

Muscle-derived Myoglianin regulates Drosophila imaginal disc growth.

Organ growth and size are finely tuned by intrinsic and extrinsic signaling molecules. In Drosophila, the BMP family member Dpp is produced in a limited set of imaginal disc cells and functions as a classic morphogen to regulate pattern and growth by diffusing throughout imaginal discs. However, the role of TGFβ/Activin-like ligands in disc growth control remains ill-defined. Here, we demonstrate that Myoglianin (Myo), an Activin family member, and a close homolog of mammalian Myostatin (Mstn), is a muscle-derived extrinsic factor that uses canonical dSmad2-mediated signaling to regulate wing size. We propose that Myo is a myokine that helps mediate an allometric relationship between muscles and their associated appendages.

The Dragonfly Edge-on Galaxies Survey: Shaping the Outer disk of NGC 4565 via Accretion

Abstract We present deep g- and r-band imaging of the well-known edge-on galaxy NGC 4565 (the “Needle Galaxy”), observed as part of the Dragonfly Edge-on Galaxies Survey. The 3σ local surface brightness contrast limit on 10″ scales is 28.616 ± 0.005 mag arcsec−2 for the r-band image and 28.936 ± 0.005 mag arcsec−2 for the g-band image. We trace the galaxy’s starlight in narrow slice profiles spanning over 90 kpc along the major axis (with bin sizes ranging from 1.7 × 0.5 to 1.7 × 7.8 kpc) to surface brightnesses below 29 mag arcsec−2. We confirm the previously observed asymmetric disk truncation in NGC 4565. In addition, the sharp northwest truncation turns over to a shallower component that coincides with a fan-like feature seen to wrap around the northwest disk limb. We propose that the fan may be a tidal ribbon and qualitatively replicate the fan with simple simulations, although alternative explanations of the fan and the disk’s asymmetry are shown to be possible. In any case, we conclude that there is strong evidence for accretion-based outer disk growth in NGC 4565.

Influence of Temperature Distribution on Radial Growth of Compressor Disks

Abstract For the next generation of aero-engines, manufacturers are planning to increase the overall compressor pressure ratio from the existing values around 50:1 to values of 70:1. The requirement to control the tight clearances between the blade tips and the casing overall engine-operating conditions is a challenge for the engine designer attempting to minimize tip-clearances losses. Accurate prediction of the tip clearance requires an accurate prediction of the radial growth of the compressor rotor, which depends on the temperature distribution of the disk. The flow in the rotating cavities between adjacent disks is buoyancy-driven, which creates a conjugate heat transfer problem: the disk temperature depends on the radial distribution of the Nusselt number, which in turn depends on the radial distribution of disk temperature. This paper focuses on calculating the radial growth of a simplified compressor disk in isolation from the other components. Calculations were performed using steady one-dimensional (1D) theoretical and two-dimensional numerical computations (2D finite element analysis (FEA)) for overall pressure ratios (OPRs) of 50:1, 60:1, and 70:1. At each pressure ratio, calculations were conducted for five different temperature distributions; the distribution based on an experimentally validated buoyancy model was used as the datum case, and the results from this were compared with those from linear, quadratic, cubic, and quartic power laws. The results show that the assumed distribution of disk temperature has a significant effect on the calculated disk growth, whereas the pressure ratio has only a relatively small effect. Good agreement between the growth calculated by the 1D theoretical model and the FEA suggests that the 1D model should be useful for design purposes. Although the results were obtained for steady-state conditions, a method is outlined for calculating the growth under transient conditions.

Drifting inwards in protoplanetary discs I Sticking of chondritic dust at increasing temperatures

Sticking properties rule the early phases of pebble growth in protoplanetary discs in which grains regularly travel from cold, water-rich regions to the warm inner part. This drift affects composition, grain size, morphology, and water content as grains experience ever higher temperatures. In this study we tempered chondritic dust under vacuum up to 1400 K. Afterwards, we measured the splitting tensile strength of millimetre-sized dust aggregates. The deduced effective surface energy starts out asγe= 0.07 J m−2. This value is dominated by abundant iron-oxides as measured by Mössbauer spectroscopy. Up to 1250 K,γecontinuously decreases by up to a factor five. Olivines dominate at higher temperature. Beyond 1300 K dust grains significantly grow in size. Theγeno longer decreases but the large grain size restricts the capability of growing aggregates. Beyond 1400 K aggregation is no longer possible. Overall, under the conditions probed, the stability of dust pebbles would decrease towards the star. In view of a minimum aggregate size required to trigger drag instabilities it becomes increasingly harder to seed planetesimal formation closer to a star.

Stellar migrations and metal flows – Chemical evolution of the thin disc of a simulated Milky Way analogous galaxy

ABSTRACTIn order to understand the roles of metal flows in galaxy formation and evolution, we analyse our self-consistent cosmological chemodynamical simulation of a Milky Way like galaxy during its thin-disc phase. Our simulated galaxy disc qualitatively reproduces the variation of the dichotomy in [α/Fe]–[Fe/H] at different Galactocentric distances as derived by APOGEE-DR16, as well as the stellar age distribution in [α/Fe]–[Fe/H] from APOKASC-2. The disc grows from the inside out, with a radial gradient in the star-formation rate during the entire phase. Despite the radial dependence, the outflow-to-infall ratio of metals in our simulated halo shows a time-independent profile scaling with the disc growth. The simulated disc undergoes two modes of gas inflow: (i) an infall of metal-poor and relatively low-[α/Fe] gas, and (ii) a radial flow where already chemically enriched gas moves inwards with an average velocity of ∼0.7 km s−1. Moreover, we find that stellar migrations mostly happen outwards, on typical time-scales of ∼5 Gyr. Our predicted radial metallicity gradients agree with the observations from APOGEE-DR16, and the main effect of stellar migrations is to flatten the radial metallicity profiles by 0.05 dex/kpc in the slopes. We also show that the effect of migrations can appear more important in [α/Fe] than in the [Fe/H]–age relation of thin-disc stars.

SDSS-IV MaNGA: Excavating the fossil record of stellar populations in spiral galaxies

ABSTRACT We perform a ‘fossil record’ analysis for ≈800 low-redshift spiral galaxies, using starlight applied to integral field spectroscopic observations from the SDSS-IV MaNGA survey to obtain fully spatially resolved high-resolution star formation histories (SFHs). From the SFHs, we are able to build maps indicating the present-day distribution of stellar populations of different ages in each galaxy. We find small negative mean age gradients in most spiral galaxies, especially at high stellar mass, which reflects the formation times of stellar populations at different galactocentric radii. We show that the youngest (<108.5 yr) populations exhibit significantly more extended distributions than the oldest (>109.5 yr), again with a strong dependence on stellar mass. By interpreting the radial profiles of ‘time slices’ as indicative of the size of the galaxy at the time those populations had formed, we are able to trace the simultaneous growth in mass and size of the spiral galaxies over the last 10 Gyr. Despite finding that the evolution of the measured light-weighted radius is consistent with inside-out growth in the majority of spiral galaxies, the evolution of an equivalent mass-weighted radius has changed little over the same time period. Since radial migration effects are likely to be small, we conclude that the growth of discs in spiral galaxies has occurred predominantly through an inside-out mode (with the effect greatest in high-mass galaxies), but this has not had anywhere near as much impact on the distribution of mass within spiral galaxies.

Imaginal Disc Growth Factor 6 (Idgf6) Is Involved in Larval and Adult Wing Development in Bactrocera correcta (Bezzi) (Diptera: Tephritidae).

In insects, imaginal disk growth factors (IDGFs), an important component of the glycoside hydrolase 18 (GH18) family of chitinases, have been reported to be associated with the maintenance of the cuticle and molting. However, there is little knowledge of their function. In this study, imaginal disk growth factor 6 (Idgf6), which is an Idgf, was first identified and cloned from the guava fruit fly Bactrocera correcta (Bezzi) (Diptera: Tephritidae), one of the most serious pest insects in South China and surrounding Southeast Asian countries. This gene encodes IDGF6 protein with a conserved domain similar to ChiA chitinases, the glycoside hydrolase 18 (GH18) family of chitinases, according to NCBI BLAST. Phylogenetic analysis indicated that all Idgf6s were highly conserved among similar species. Subsequent temporal expression profiling revealed that Idgf6 was highly expressed in both the late-pupal and mid-adult stages, suggesting that this gene plays a predominant role in pupal and adult development. Furthermore, RNA interference experiments against Idgf6 in B. correcta, which led to the specific decrease in Idgf6 expression, resulted in larval death as well as adult wing malformation. The direct effects of Idgf6 silencing on B. correcta indicated its important role in development, and Idgf6 might be further exploited as a novel insecticide target in the context of pest management.

Alphitonia excelsa (Fenzl) Benth. Leaf Extracts Inhibit the Growth of a Panel of Pathogenic Bacteria

Introduction: Alphitonia excelsa (Fenzl) Benth. is a large tree that is native to the east coast and northern regions of Australia. Decoctions and infusions produced from the leaves were used by the first Australians to treat a variety of bacterial diseases. Despite this, A. excelsa leaf extractions have not been rigorously examined for antibacterial properties against many pathogens. Methods: The antimicrobial activity of A. excelsa leaf extractions was investigated by disc diffusion and growth time course assays against a panel of pathogenic bacteria. The growth inhibitory activity was quantified by MIC determination. Toxicity was determined using the Artemia franciscana nauplii bioassay. Results: Polar to mid-polarity A. excelsa leaf solvent extractions inhibited the growth of a wide range of bacterial species. Growth of both gram positive and gram negative bacteria was inhibited by the A. excelsa leaf extracts to approximately the same extent. The methanolic extracts were the most potent growth inhibitor against all bacteria tested. The methanolic, aqueous and ethyl acetate A. excelsa leaf extracts were particularly potent inhibitors of P. mirabilis growth, with MIC values as low as 118μg/mL for the methanolic extract. A. hydrophilia, E. coli, K. pneumonia, S. marcenscens and B. cereus were also particularly susceptible to the methanolic extract, with MIC values generally substantially <1000 μg/mL. The antibacterial activity of the methanolic A. excelsa leaf extract was further investigated by growth time course assays which showed significant growth inhibition in cultures of P. mirabilis and B. cereus within 1 h of exposure. All extracts were determined to be nontoxic in the Artemia franciscana nauplii bioassay, indicating their safety for internal use as well as for topical uses. Conclusion: The lack of toxicity of the A. excelsa leaf extracts and their growth inhibitory bioactivity against a panel of pathogenic bacteria partially validate the traditional usage of this species to treat bacterial diseases and indicate their potential in the development of antiseptic agents.

Degenerate-disc infection study with contaminant control (DISC): a multicenter prospective case-control trial

BACKGROUNDA bacterial cause of disc degeneration has evoked several controversies and, if true, would lead to a major shift in treatment paradigm. Earlier studies analyzing the relationship of bacterial disc infection within a degenerative cohort featured prolonged cultures susceptible to contamination. The degenerate-disc infection study with contaminant control (DISC) trial aims to investigate this theory further by examining infection rates using a non-degenerative control cohort in comparison to a degenerative internal control cohort and a sham cohort (sampling only sterile paraspinal tissue). To our knowledge, the current study is the largest evaluating the growth of organisms (or possible contamination rate) in paraspinal tissue if prolonged cultures are performed. Protocols on methodology have been previously published. PURPOSE(1) To investigate the infection rates across cohorts (degenerative vs. nondegenerative control; paraspinal and/or disc controls vs. combined sampling cohorts) using stringent standardized aseptic surgical technique and laboratory processing. (2) To compare our findings to that of the literature and make a statement in support and/or against a possible contamination theory to positive cultures. STUDY DESIGNMulticenter, multisurgeon case-control trial. PATIENT SAMPLEIn all, 812 surgical samples were retrieved across a 3.5-year period (2013–2016) including 25 trauma controls (nondegenerative), 550 "disc and paraspinal” samples (degenerative cases with internal control), 190 disc-only samples (degenerative cases without internal control), and 46 paraspinal only controls (sham group). OUTCOME MEASURESGrowth and/or Contamination rate (%) per cohort. Chi-square of growth in disc versus paraspinal samples as a means of examining the distribution of false positive and contaminant growth. The impact of previous injections and/or surgery on positive disc or paraspinal growth. Correlation of Modic changes with positive growth rates analyzed with the Kruskal-Wallis Test. The distribution of species in positive samples were also analyzed. METHODSThe DISC trial is registered under Australian and New Zealand clinical trials registry—ACTRN12616000541404. Institutional ethics review was obtained (HREC northern sector 13/218) at the primary center and further centers (n=6) were recruited. Patients undergoing spinal surgery with discectomy were eligible for trial entry with tissue specimens obtained using strict aseptic technique for microbiological examination. All specimens were handled with sterile instruments only and by a fresh instrument to a sterile pot that was closed immediately. Separate pots were used for the disc and paraspinal tissue respectively with similar stringent processing during microbiological assessment. A cohort of the degenerative cases at one single institution also underwent an additional histopathological examination. RESULTSThere was an expected significant difference in gender and age associated with the non-degenerative control group (due to trauma patients) compared with other cohorts. There was a higher percentage of positive-growth in the control group in comparison to the disc and paraspinal and disc only groups across positive disc growth (48% vs. 27% vs. 17%, p<.001). A similar infection rate was observed in the paraspinal samples across the equivalent controls (44% vs. 36% vs. 37%, p=.739). There was a significant difference in the proportions of positive growth with a large proportion of false positives (growth in both disc and paraspinal samples; p<.001). There was no difference in true positive growth between the case and control groups (16.0 vs. 7.7%, p=.112). These trends were preserved across all cohorts and when stratifying by spinal segment (cervical or lumbar). There was no correlation between Modic changes and positive disc culture growth (p=.398, n=144 samples). Cutibacterium (formerly Propionibacterium) acnes was the most dominant pathogen isolated, representing between 50% and 70% of positive disc and paraspinal specimens, followed by staphylococcal species. CONCLUSIONSOur study failed to find a difference in true infection rates between the nondegenerative and degenerative disc populations. These findings are suggestive of a contamination theory and against a common infective etiology in the setting of discogenic back and neck pain. We believe the rationale for antibiotic therapy in the management of discogenic back pain warrants further evidence to establish efficacy.

Excess C/H in Protoplanetary Disk Gas from Icy Pebble Drift Across the CO Snowline

Abstract The atmospheric composition of giant planets carries the information of their formation history. Superstellar C/H ratios are seen in atmospheres of Jupiter, Saturn, and various giant exoplanets. Also, giant exoplanets show a wide range of C/O ratio. To explain these ratios, one hypothesis is that protoplanets accrete carbon-enriched gas when a large number of icy pebbles drift across the CO snowline. Here we report the first direct evidence of an elevated C/H ratio in disk gas. We use two thermo-chemical codes to model the 13C18O, C17O, and C18O (2−1) line spectra of the HD 163296 disk. We show that the gas inside the CO snowline (∼70 au) has a C/H ratio that is 1–2 times higher than the stellar value. This ratio exceeds the expected value substantially, as only 25%–60% of the carbon should be in gas at these radii. Although we cannot rule out the case of a normal C/H ratio inside 70 au, the most probable solution is an elevated C/H ratio that is 2–8 times higher than the expectation. Our model also shows that the gas outside 70 au has a C/H ratio that is 0.1× the stellar value. This picture of enriched C/H gas at the inner region and depleted gas at the outer region is consistent with numerical simulations of icy pebble growth and drift in protoplanetary disks. Our results demonstrate that the large-scale drift of icy pebble can occur in disks and may significantly change the disk gas composition for planet formation.

Proteomic Signature of Nucleus Pulposus in Fetal Intervertebral Disc.

Study DesignProfiling proteins expressed in the nucleus pulposus of fetal intervertebral disc (IVD).PurposeTo evaluate the molecular complexity of fetal IVDs not exposed to mechanical, traumatic, inflammatory, or infective insults to generate improved knowledge on disc homeostasis.Overview of LiteratureLow back pain is the most common musculoskeletal disorder, causing a significant reduction in the quality of life, and degenerative disc disorders mainly contribute to the increasing socioeconomic burden. Despite extensive research, the causative pathomechanisms behind degenerative disc disorders are poorly understood. Precise molecular studies on the intricate biological processes involved in maintaining normal disc homeostasis are needed.MethodsIVDs of nine fetal specimens obtained from medical abortions were used to dissect out the annulus fibrosus and nucleus pulposus under sterile operating conditions. Dissected tissues were transferred to sterile Cryovials and snap frozen in liquid nitrogen before transporting to the research laboratory for protein extraction and further liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Collected data were further analyzed using Gene Functional Classification Tool in DAVID and STRING databases.ResultsA total of 1,316 proteins were identified through LC-MS/MS analysis of nine fetal IVD tissues. Approximately 247 proteins present in at least four fetal discs were subjected to further bioinformatic analysis. The following 10 clusters of proteins were identified: collagens, ribosomal proteins, small leucine-rich proteins, matrilin and thrombospondin, annexins, protein disulfide isomerase family proteins and peroxiredoxins, tubulins, histones, hemoglobin, and prolyl 4-hydroxylase family proteins.ConclusionsThis study provides fundamental information on the proteome networks involved in the growth and development of healthy fetal discs in humans. Systematic cataloging of proteins involved in various structural and regulatory processes has been performed. Proteins expressed most abundantly (collagen type XIV alpha 1 chain, biglycan, matrilin 1, and thrombospondin 1) in their respective clusters also elucidate the possibility of utilizing these proteins for potential regenerative therapies.

Hall effect in protostellar disc formation and evolution

ABSTRACT The Hall effect is recently shown to be efficient in magnetized dense molecular cores and could lead to a bimodal formation of rotationally supported discs (RSDs) in the first core phase. However, how such Hall dominated systems evolve in the protostellar accretion phase remains unclear. We carry out 2D axisymmetric simulations including Hall effect and ohmic dissipation, with realistic magnetic diffusivities computed from our equilibrium chemical network. We find that Hall effect only becomes efficient when the large population of very small grains (VSGs: ≲100 Å) is removed from the standard Mathis–Rumpl–Nordsieck size distribution. With such an enhanced Hall effect, however, the bimodality of disc formation does not continue into the main accretion phase. The outer part of the initial ∼40 au disc formed in the anti-aligned configuration ($\boldsymbol {\Omega \cdot B}\lt 0$) flattens into a thin rotationally supported Hall current sheet as Hall effect moves the poloidal magnetic field radially inward relative to matter, leaving only the inner ≲10–20 au RSD. In the aligned configuration ($\boldsymbol {\Omega \cdot B}\gt 0$), disc formation is suppressed initially but a counter-rotating disc forms subsequently due to efficient azimuthal Hall drift. The counter-rotating disc first grows to ∼30 au as Hall effect moves the magnetic field radially outward, but only the inner ≲10 au RSD is long lived like in the anti-aligned case. Besides removing VSGs, cosmic ray ionization rate should be below a few 10−16 s−1 for Hall effect to be efficient in disc formation. We conclude that Hall effect produces small ≲10–20 au discs regardless of the polarity of the magnetic field, and that radially outward diffusion of magnetic fields remains crucial for disc formation and growth.

Methicillin-Resistant Staphylococcus Aureus Nasal Carriers among Laboratory Technical Staff of Tertiary Hospital in Eastern Nepal

Background Methicillin-resistant Staphylococcus aureus (MRSA) has been the leading cause of nosocomial and community infections worldwide. In particular, healthcare workers are at constant risk to develop MRSA carriage. There is a paucity of data regarding the epidemiology of MRSA in laboratory workers who are constantly in contact with these pathogens in almost every hospital. Objective This study was undertaken to identify the burden of MRSA nasal carriers and the antibiotic susceptibility pattern of the isolates among laboratory technical staff. Method Sterile nasal swabs were taken from 50 laboratory technical staff working in the Central and Emergency laboratory of BP Koirala Institute of Health Sciences (BPKIHS). Standard procedures were followed for isolation, identification and antibiotic sensitivity testing. Antibiotic susceptibility tests were performed using disc diffusion and growth on Oxacillin screen agar based on Clinical and Laboratory Standards Institute (CLSI) guidelines. Result Out of 50 isolates of Staphylococcus aureus, 44 (88%) were Methicillin-sensitive (MSSA) while six (12%) were Methicillin-resistant (MRSA). All 50 isolates of S. aureus were found resistant to Penicillin while all were found sensitive to Teicoplanin, Linezolid, and Levofloxacin. Only five (10%) were sensitive to Erythromycin while 49 (98%) were sensitive to both Amikacin and Gentamicin. However, none of the MRSA isolates were found sensitive to all tested antimicrobial agents. Conclusion This repertoire portrays the emergence of MRSA in laboratory workers which clearly indicates the necessity of complying with the sanitary and antibacterial guidelines and adhering to the rational use of antibiotics to prevent nosocomial infections.

The growth of bulges and discs in relatively H i-rich galaxies: indication from H i scaling relations

ABSTRACT We study the relation between the properties of the bulge/disc components and the H i mass fraction of galaxies. We find that at fixed stellar mass, disc colours are correlated with the H i mass fraction, while bulge colours are not. The lack of a correlation between the bulge colour and the H i mass fraction is regardless whether the bulges are pseudo, or whether the galaxies host bars or are interacting with a neighbour. There is no strong correlation between the colours of the discs and bulges either. These results suggest that the current total amount of H i is closely related to the formation of discs, but does not necessarily fuel the formation of (pseudo) bulges in an efficient way. We do not find evidence for the star formation in the discs to be quenched by the bulges.