Lim homeobox genes in the Ctenophore Mnemiopsis leidyi: the evolution of neural cell type specification

<p>Abstract</p> <p>Background</p> <p>Nervous systems are thought to be important to the evolutionary success and diversification of metazoans, yet little is known about the origin of simple nervous systems at the base of the animal tree. Recent data suggest that ctenophores, a group of macroscopic pelagic marine invertebrates, are the most ancient group of animals that possess a definitive nervous system consisting of a distributed nerve net and an apical statocyst. This study reports on details of the evolution of the neural cell type specifying transcription factor family of LIM homeobox containing genes (Lhx), which have highly conserved functions in neural specification in bilaterian animals.</p> <p>Results</p> <p>Using next generation sequencing, the first draft of the genome of the ctenophore <it>Mnemiopsis leidyi </it>has been generated. The Lhx genes in all animals are represented by seven subfamilies (<it>Lhx1/5, Lhx3/4, Lmx, Islet, Lhx2/9, Lhx6/8</it>, and <it>LMO</it>) of which four were found to be represented in the ctenophore lineage (<it>Lhx1/5, Lhx3/4, Lmx</it>, and <it>Islet</it>). Interestingly, the ctenophore Lhx gene complement is more similar to the sponge complement (sponges do not possess neurons) than to either the cnidarian-bilaterian or placozoan Lhx complements. Using whole mount <it>in situ </it>hybridization, the Lhx gene expression patterns were examined and found to be expressed around the blastopore and in cells that give rise to the apical organ and putative neural sensory cells.</p> <p>Conclusion</p> <p>This research gives us a first look at neural cell type specification in the ctenophore <it>M. leidyi</it>. Within <it>M. leidyi</it>, Lhx genes are expressed in overlapping domains within proposed neural cellular and sensory cell territories. These data suggest that Lhx genes likely played a conserved role in the patterning of sensory cells in the ancestor of sponges and ctenophores, and may provide a link to the expression of Lhx orthologs in sponge larval photoreceptive cells. Lhx genes were later co-opted into patterning more diversified complements of neural and non-neural cell types in later evolving animals.</p

Expression of multiple Sox genes through embryonic development in the ctenophore Mnemiopsis leidyi is spatially restricted to zones of cell proliferation

Background: The Sox genes, a family of transcription factors characterized by the presence of a high mobility group (HMG) box domain, are among the central groups of developmental regulators in the animal kingdom. They are indispensable in progenitor cell fate determination, and various Sox family members are involved in managing the critical balance between stem cells and differentiating cells. There are 20 mammalian Sox genes that are divided into five major groups (B, C, D, E, and F). True Sox genes have been identified in all animal lineages but not outside Metazoa, indicating that this gene family arose at the origin of the animals. Whole-genome sequencing of the lobate ctenophore Mnemiopsis leidyi allowed us to examine the full complement and expression of the Sox gene family in this early-branching animal lineage. Results: Our phylogenetic analyses of the Sox gene family were generally in agreement with previous studies and placed five of the six Mnemiopsis Sox genes into one of the major Sox groups: SoxB (MleSox1), SoxC (MleSox2), SoxE (MleSox3, MleSox4), and SoxF (MleSox5), with one unclassified gene (MleSox6). We investigated the expression of five out of six Mnemiopsis Sox genes during early development. Expression patterns determined through in situ hybridization generally revealed spatially restricted Sox expression patterns in somatic cells within zones of cell proliferation, as determined by EdU staining. These zones were located in the apical sense organ, upper tentacle bulbs, and developing comb rows in Mnemiopsis, and coincide with similar zones identified in the cydippid ctenophore Pleurobrachia. Conclusions: Our results are consistent with the established role of multiple Sox genes in the maintenance of stem cell pools. Both similarities and differences in juvenile cydippid stage expression patterns between Mnemiopsis Sox genes and their orthologs from Pleurobrachia highlight the importance of using multiple species to characterize the evolution of development within a given phylum. In light of recent phylogenetic evidence that Ctenophora is the earliest-branching animal lineage, our results are consistent with the hypothesis that the ancient primary function of Sox family genes was to regulate the maintenance of stem cells and function in cell fate determination

Expression of multiple Sox genes through embryonic development in the ctenophore Mnemiopsis leidyi is spatially restricted to zones of cell proliferation

Background: The Sox genes, a family of transcription factors characterized by the presence of a high mobility group (HMG) box domain, are among the central groups of developmental regulators in the animal kingdom. They are indispensable in progenitor cell fate determination, and various Sox family members are involved in managing the critical balance between stem cells and differentiating cells. There are 20 mammalian Sox genes that are divided into five major groups (B, C, D, E, and F). True Sox genes have been identified in all animal lineages but not outside Metazoa, indicating that this gene family arose at the origin of the animals. Whole-genome sequencing of the lobate ctenophore Mnemiopsis leidyi allowed us to examine the full complement and expression of the Sox gene family in this early-branching animal lineage. Results: Our phylogenetic analyses of the Sox gene family were generally in agreement with previous studies and placed five of the six Mnemiopsis Sox genes into one of the major Sox groups: SoxB (MleSox1), SoxC (MleSox2), SoxE (MleSox3, MleSox4), and SoxF (MleSox5), with one unclassified gene (MleSox6). We investigated the expression of five out of six Mnemiopsis Sox genes during early development. Expression patterns determined through in situ hybridization generally revealed spatially restricted Sox expression patterns in somatic cells within zones of cell proliferation, as determined by EdU staining. These zones were located in the apical sense organ, upper tentacle bulbs, and developing comb rows in Mnemiopsis, and coincide with similar zones identified in the cydippid ctenophore Pleurobrachia. Conclusions: Our results are consistent with the established role of multiple Sox genes in the maintenance of stem cell pools. Both similarities and differences in juvenile cydippid stage expression patterns between Mnemiopsis Sox genes and their orthologs from Pleurobrachia highlight the importance of using multiple species to characterize the evolution of development within a given phylum. In light of recent phylogenetic evidence that Ctenophora is the earliest-branching animal lineage, our results are consistent with the hypothesis that the ancient primary function of Sox family genes was to regulate the maintenance of stem cells and function in cell fate determination.publishedVersionPeer Reviewe

The use of two-dimensional shear wave elastography in people with obesity for the assessment of liver fibrosis in non-alcoholic fatty liver disease

Obesity is associated with significant comorbidities, including non-alcoholic fatty liver disease (NAFLD). Given its potential to progress to advanced liver disease, monitoring the extent and progress of liver fibrosis and assessing its fibrosis stage are essential. Although liver biopsy is considered to be the gold standard for liver fibrosis staging, it is an invasive procedure with risk of complications. Considering the rising prevalence of obesity and NAFLD globally, developing non-invasive diagnostic methods is a priority. Transient elastography (TE) is increasingly being used to assess the severity of liver disease. However, in the presence of severe obesity, the increased thickness of subcutaneous adipose tissue and changes in anatomy may affect its diagnostic accuracy. Two-dimensional shear wave elastography (2D-SWE) assesses the liver stiffness in real time along with simultaneous anatomic B-mode ultrasound imaging and allows selection of the region of interest. This would suggest that 2D-SWE has several advantages over TE in patients with severe obesity. The purpose of this review is to examine the current literature addressing the use of 2D-SWE in the assessment of liver fibrosis in patients with NAFLD. This review also examines the evidence on the use of 2D-SWE in patients with obesity and NAFLD and compares it to TE as a novel and non-invasive method of assessing liver fibrosis

The relationship between self-reported sensory experiences and autistic traits in the general population:a mixed methods analysis

There have been few examples of inductive research in sensory reactivity, particularly in relation to autistic traits among the general population. This study used a mixed methods approach to explore the nature of sensory experiences among people with different levels of autistic traits. Participants completed the Glasgow Sensory Questionnaire and the Autism Spectrum Quotient. Both quantitative and qualitative analyses were performed on the data. Responses to the open questions were analyzed as part of this study, and the closed questionnaire data have been reported elsewhere. Data were coded and responses quantitatively compared by group. In addition, data were qualitatively analyzed using a general inductive approach, which resulted in two themes: “problematic sensory experiences” and “calming sensory experiences.” Results show that coping mechanisms and certain aspects of the sensory experience vary according to autistic trait level, and provide insight into the nature of sensory reactivity across the general population

Recent Cases

If the instant case, rather than Northway, is to become the accepted rule in the area of discounting, consumers and state lenders will be protected while the national bank-lenders will be burdened only slightly, if at all. National banks located in states that permit state lenders to discount loans at the maximum rate, with-out regard to the actual yield, will not be affected. National banks located in states that permit state lenders to discount only to the extent that the actual yield is within the statutory maximum will need to change their practices merely by charging the statutory rate only when it becomes due, or by charging a lower rate in advance that yields an effective rate not in excess of the maximum. Furthermore, the impact of the instant decision on national banks will be practically limited to consumer loans, because of the usual exemption of corporations from usury laws and of section 85\u27s higher alternative rate for business or agricultural loans. This limited restriction on the national banks will be justified by its beneficent effect on the borrower and on the competing state lenders, who have always been subject to the state restrictions. Linda A. Bunsey ======================= With the instant decision, federal defamation law has advanced within the space of ten years from no constitutional privilege, even for the press in defending against a public person, to the realized prospect of a constitutional privilege so sweeping that it prevents recovery of an element of damages by a public person who has been defamed by an individual. Specifically, the instant court\u27s holding completes a four-part scheme for liability and damages in defamation actions: under Supreme Court decisions, a private figure must prove negligence to receive compensatory damages and actual malice to receive punitive damages, and a public figure must prove actual malice to recover compensatory damages; under the instant decision, a public figure is almost totally precluded from recovering punitive damages. As the Sullivan Court in large measure adopted the minority position concerning fair comment and liability, so too the Maheu court in large measure adopted the minority position concerning punitive damages. Nevertheless, the instant decision was solidly based: the court fully considered the Supreme Court\u27s prior concerns with encouraging debate and discouraging self-censorship, shielding reputation and privacy, and, most importantly, scrutinizing the need for punitive damages. David M. Thompson ============================ In rejecting the State\u27s reliance upon the stated rule of the Brady trilogy and Tollett, the instant Court noted the suggestion originally made in a McMann footnote that an exception might exist if the applicable state law permitted appeal from adverse pretrial rulings despite a subsequent guilty plea. Under New York procedure, a defendant who chooses to plead guilty does not deliberately by-pass state appellate review of certain constitutional claims, and the State acquires no legitimate expectation of finality in the ensuing conviction. As to these constitutional claims, the plea does not constitute a break in the chain, but operates merely as a procedural device to secure review of the adverse pretrial ruling without the necessity of a time-consuming and expensive trial. The Court held that because the respondent\u27s guilty plea was entered in reliance upon a guarantee of the availability of further appellate review of his constitutional claims, it was essentially different from guilty pleas entered in other states that result in an absolute conviction and a waiver of all further state review. Charles K. Campbell, Jr. ======================================== In determining whether the challenged statute met the procedural requirements of the fourteenth amendment, the instant Court looked to the statutory safeguards protecting the debtor\u27s property interest in the absence of prior notice and hearing. Comparing the instant statute to the Fuentes statutes, the Court asserted that the same constitutional infirmities were present. Each statute allowed the seizure of property without prior notice and opportunity for a hearing by the issuance of a writ by a court clerk after the filing of an affidavit containing conclusory allegations. The instant Court restated its belief set forth in Sniadach and Fuentes that even a temporary deprivation of property does not put the seizure beyond scrutiny under due process requirements. The Court then asserted that the Georgia statute had none of the saving characteristics of the Louisiana sequestration statute upheld in Mitchell. According to the Court, the Mitchell statute survived challenge because of the presence of safeguards which imposed judicial control over the process of issuance of the writ; required the creditor\u27s affidavit to contain factual allegations; and provided for an immediate post-seizure hearing at which the debtor could seek dissolution of the writ. Keith B. Simmons ============================== The instant court rejected arguments based mainly on the vague wording of the statute and relied on two basic policies-(1)to compel pro rata distributions of unneeded funds that will be taxable to shareholders and (2) to avoid constructions that lead to inconsistent results in similar fact situations. Also, the court seemed to contemplate two theories of liability available to the Commissioner-first, that the corporation was availed of by permitting funds not used in the redemption to remain accumulated, and secondly, that the corporation was availed of through the redemption itself. The arguments based on the equivalency of the phrases to accumulate and to remain accumulated , the purpose of Congress to reach any corporation with an undue accumulation, and the relevance of past accumulations, plus the remand for determination of whether an unreasonable accumulation actually occurred, relate to the first theory. Other arguments used by the court relate more to the second theory-the repeated idea that preferential distribution of unneeded funds is not a congressionally approved method of abating the penalty tax with respect to those funds, the mention of corporations formed for the proscribed purpose that may be liable without regard to actual accumulation, and especially the concluding statement that the judgment concerning 1967 made liability in 1968 apparent. Thomas C. Hundle

Probing Red Giant Atmospheres with Gravitational Microlensing

Gravitational microlensing provides a new technique for studying the surfaces of distant stars. Microlensing events are detected in real time and can be followed up with precision photometry and spectroscopy. This method is particularly adequate for studying red giants in the Galactic bulge. Recently we developed an efficient method capable of computing the lensing effect for thousands of frequencies in a high-resolution stellar spectrum. Here we demonstrate the effects of microlensing on synthesized optical spectra of red giant model atmospheres. We show that different properties of the stellar surface can be recovered from time-dependent photometry and spectroscopy of a point-mass microlensing event with a small impact parameter. In this study we concentrate on center-to-limb variation of spectral features. Measuring such variations can reveal the depth structure of the atmosphere of the source star.Comment: 23 pages with 11 Postscript figures, submitted to ApJ; Section 2 expanded, references added, text revise

Analysis of in-hospital mortality among people with and without diabetes in South Western Sydney public hospitals (2014-2017)

Background: Diabetes is a major public health problem affecting about 1.4 million Australians, especially in South Western Sydney, a hotspot of diabetes with higher than average rates for hospitalisations. The current understanding of the international burden of diabetes and related complications is poor and data on hospital outcomes and/or what common factors influence mortality rate in people with and without diabetes in Australia using a representative sample is lacking. This study determined in-hospital mortality rate and the factors associated among people with and without diabetes. Methods: Retrospective data for 554,421 adult inpatients was extracted from the population-based New South Wales (NSW) Admitted Patient Data over 3 financial years (from 1 July 2014–30 June 2015 to 1 July 2016–30 June 2017). The in-hospital mortality per 1000 admitted persons, standardised mortality ratios (SMR) were calculated. Binary logistic regression was performed, adjusting for potential covariates and co-morbidities for people with and without diabetes over three years. Results: Over three years, 8.7% (48,038 people) of admissions involved people with diabetes. This increased from 8.4% in 2014–15 to 8.9% in 2016–17 (p = 0.007). Across all age groups, in-hospital mortality rate was significantly greater in people with diabetes (20.6, 95% Confidence intervals CI 19.3–21.9 per 1000 persons) than those without diabetes (11.8, 95%CI 11.5–12.1) and more in men than women (23.1, 95%CI 21.2–25.0 vs 17.9, 95%CI 16.2–19.8) with diabetes. The SMR for those with and without diabetes were 3.13 (95%CI 1.78–4.48) and 1.79 (95%CI 0.77–2.82), respectively. There were similarities in the factors associated with in hospital mortality in both groups including: older age (> 54 years), male sex, marital status (divorced/widowed), length of stay in hospital (staying longer than 4 days), receiving intensive care in admission and being admitted due to primary respiratory and cardiovascular diagnoses. The odds of death in admission was increased in polymorbid patients without diabetes (28.68, 95%CI 23.49–35.02) but not in those with diabetes. Conclusions: In-patients with diabetes continue to have higher mortality rates than those without diabetes and the Australian population. Overall, similar factors influenced mortality rate in people with and without diabetes, but significantly more people with diabetes had two or more co-morbidities, suggesting that hospital mortality may be driven by those with pre-existing health/comorbidities. Urgent measures in primary care to prevent admissions among people with multiple co-morbidities are needed

Factors associated with long intensive care unit (ICU) admission among inpatients with and without diabetes in South Western Sydney public hospitals using the New South Wales admission patient data collection (2014-2017)

Despite a campaign of effective educational interventions targeting knowledge, attitudes, and prevention, Human Immunodeficiency-Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) continues to be a significant public health issue in India, with Mizoram reporting the highest HIV/AIDS cases in 2018–2019. In this study, we extracted Mizoram state from the National Family Health Survey Fourth Series (NFHS-4) 2015–2016 datasets and investigated factors associated with respondents’ knowledge, attitudes, and prevention towards HIV/AIDS. The sample included 3555 adults aged 15–49 years residing in Mizoram, North-east India. Respondents who reported having ever heard of HIV/AIDS was 98%. Multivariate analysis indicated that the probability of having inadequate knowledge of HIV/AIDS was higher among those with no schooling, who were illiterate, of non-Christian faiths, belonging to backward tribes or caste, from poor households, and those who lived in rural areas, not exposed to media. The odds of mother-to-child transmission (PMTCT) of HIV/AIDS transmission was high among females (AOR = 3.12, 95% CI 2.34–4.16), respondents aged 35–39 years (AOR = 1.74, 95% CI 1.05–2.87) and those belonging to other backward class. The HIV/AIDS knowledge of respondents was found to be encouraging as the majority (98%) were considered to have a good level of understanding of the condition. An educational intervention to reduce the number of adults 15–49 years infected with HIV/AIDS in Mizoram should target those from low socioeconomic groups, those from non-Christian religions, and those from other backward classes