Melissa Gómez
Dec 1, 2020; 61:1658-1674
Research Articles

Xanthophyllomyces dendrorhous is a basidiomycete yeast that produces carotenoids, mainly astaxanthin. Astaxanthin is an organic pigment of commercial interest due to its antioxidant and coloring properties. X. dendrorhous has a functional SREBP pathway, and the Sre1 protein is the SREBP homolog in this yeast. However, how sterol regulatory element (Sre)1 promotes the biosynthesis of sterols and carotenoids in X. dendrorhous is unknown. In this work, comparative RNA-sequencing analysis between modified X. dendrorhous strains that have an active Sre1 protein and the WT was performed to identify Sre1-dependent genes. In addition, Sre1 direct target genes were identified through ChIP combined with lambda exonuclease digestion (ChIP-exo) assays. SRE motifs were detected in the promoter regions of several Sre1 direct target genes and were consistent with the SREs described in other yeast species. Sre1 directly regulates genes related to ergosterol biosynthesis as well as genes related to the mevalonate (MVA) pathway, which synthesizes the building blocks of isoprenoids, including carotenoids. Two carotenogenic genes, crtE and crtR, were also identified as Sre1 direct target genes. Thus, carotenogenesis in X. dendrorhous is regulated by Sre1 through the regulation of the MVA pathway and the regulation of the crtE and crtR genes. As the crtR gene encodes a cytochrome P450 reductase, Sre1 regulates pathways that include cytochrome P450 enzymes, such as the biosynthesis of carotenoids and sterols. These results demonstrate that Sre1 is a sterol master regulator that is conserved in X. dendrorhous.

The planned action signals growing regulatory scrutiny of Walmart-owned Flipkart and Amazon when their sales are rapidly growing in India's $70 billion (roughly Rs. 5,93,614 crore) e-commerce market. An Indian antitrust investigation also found the two companies breached laws by favouring select sellers,

To attract infrastructure investment to meet national goals for providing electricity to consumers, India needs continued macroeconomic stability as well as an improved policy and regulatory environment.

Pleiotropy, measured as expression breadth across tissues, is one of the best predictors for protein sequence and expression conservation. In this study, we investigated its effect on the evolution of cis-regulatory elements (CREs). To this end, we carefully reanalyzed the Epigenomics Roadmap data for nine fetal tissues, assigning a measure of pleiotropic degree to nearly half a million CREs. To assess the functional conservation of CREs, we generated ATAC-seq and RNA-seq data from humans and macaques. We found that more pleiotropic CREs exhibit greater conservation in accessibility, and the mRNA expression levels of the associated genes are more conserved. This trend of higher conservation for higher degrees of pleiotropy persists when analyzing the transcription factor binding repertoire. In contrast, simple DNA sequence conservation of orthologous sites between species tends to be even lower for pleiotropic CREs than for species-specific CREs. Combining various lines of evidence, we propose that the lack of sequence conservation in functionally conserved pleiotropic CREs is owing to within-element compensatory evolution. In summary, our findings suggest that pleiotropy is also a good predictor for the functional conservation of CREs, even though this is not reflected in the sequence conservation of pleiotropic CREs.

Thermoregulation, responsible for maintaining a stable core temperature during wide fluctuations in external and internal thermal environments, is an iconic homeostatic process. However, we suggest that despite its fundamental physiological significance, the potential for required cool housing temperatures and thermoregulatory mechanisms to influence the interpretation of experimental data is not sufficiently appreciated. Moreover, although it is generally assumed that the major thermoregulatory pathways are well understood, here we discuss new research that suggests otherwise and reveals the emergence of a new wave of exciting ideas for this "old" field of research.

[¹⁷⁷Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [¹⁷⁷Lu]Lu-PSMA-617 at a major U.S. academic center. Methods: Patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [¹⁷⁷Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer–associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated. Results: All 76 patients with PSMA-positive mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0–6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3–16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer–associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046). Conclusion: [¹⁷⁷Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence–based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted.

Olivia Friett, editor of Medical Plastics News takes a look at the current regulatory landscape.

Regulatory experts LFH Regulatory have announced their attendance at MEDICA 2024 to provide insights and support to healthcare innovators facing the complexities of the UK and EU markets.

<p>On 3^&nbsp;June 2024,&nbsp;Resolution&nbsp;RDC No. 876 was published in Brazil in the Official Journal of the Union (DOU)[1],&nbsp;modifying the current regulations regarding the post-registration of biological products (RDC 413/2020).</p>

<p> <b>23rd Regulatory Affairs Conference 202</b><b>5</b><br /> <b>27</b><b>‒</b><b>28 February 2025</b><br /> Hilton Amsterdam Airport Schiphol<br />Amsterdam, The Netherlands</p>

More than 15 generic medications, including injectables and tablets, have been debarred since January by Tamil Nadu Medical Services Corporation (TNMSC).

The recent reprimand by the Supreme Court against Patanjali Ayurved highlights a troubling pattern of disregard for regulatory standards and ethical advertising practices.

Two Hyderabad-based drug companies, Natco Pharma and Hetero have received approval for the sale of Hepatitis- C drug from the Drugs Controller General of India (DCGI).

The Health Ministry has notified the Medical Devices Rule, 2017 in which manufacturers of medical devices will be required to meet risk proportionate regulatory requirements.

Regulation, compliance, and price pressure are slowing access to potentially life-saving new medicines, and undermining industry confidence in the current listing process.

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The Appellant filed an (offline) RTI application dated 24.03.2023 seeking the following information:

"1- क्या भारतीय बीमा कंपनी को लाइसेस दे ने पर आई आर०डी० ए०आई०द्वारा प्रमाण-पत्र/लाईतेस के ननलम्वन के ललये कोई ननश्चित ननयम व शते है ।

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2- क्या भारतीय बीमा कंपनी के आईआरडीएआई लाइसेस आवेदन में हे रफेर प्रथाओ मे ललप्त होना भी एक ननयम की शते भी प्रमाण-पत्र के ननलम्वन के सालमल है ।

3- क्या आईडीआरडीएआई द्वारा मामले की पूछताछ के ललये ककसी जांि अधिकारी / जााँय अधिकाररयो की टीम को ननयुक्त करता है । 4- क्या जांि अधिकारी को जांि ररपोटट प्रस्तुत करने के ललये ककतनी समय सीमा ननिाटररत है।

The crypto firm added that elevated interest rates, inflationary pressures, and tightening liquidity have created a more “cautious macroeconomic environment”

Recently, the new IRDAI Chairman Debasish Panda had said it was time life insurers re-entered the health vertical

The policy initiatives of recall guidelines, good distribution practices and the use of similar brand-names either lack the force of law or are poorly thought through

National Bureau of Economic Research

As the nutraceutical landscape grows, experts call for clarity in the manufacturing debate

Inadequate capacity for drug regulation, need for advanced testing facilities, lack of strong framework for monitoring quality compliance among policy challenges, says report

The Association for Gold Excellence and Standards will frame good practices to be followed by the entire value chain of the industry, including bullion, jewellery manufacturers and retailers

The European Union is working on new rules and controls that crypto companies will have to comply with

Constellation Energy will continue to pursue deals to develop data centres on the sites of its U.S. power plants, days after federal regulators dealt a blow to the so-called co-located arrangements, company executives said

Datum Intelligence estimates Flipkart had a 32% market share and Amazon a 24% share last year in Indian e-commerce, which roughly accounts for 8% of the $834 billion retail sector

Current district judge is viewed as reliably conservative, deferent to presidential power

WASHINGTON (April 28, 2020) —  Today, the U.S. Environmental Protection Agency’s (EPA) Science Advisory Board (SAB) transmitted its official advice and comments to EPA Administrator Wheeler on the Strengthening Transparency in Regulatory Science proposed rule.

Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering–based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation.

The Government has this afternoon published the Enterprise and Regulatory Reform Bill which will, if passed, introduce some of the tribunal and dispute resolution measures previously announced (see HR ...

Across India, reducing regulatory cholesterol is one thing. But suspending all laws, rules and regulations are like throwing the baby with the bathwater.

The FDI Regulatory Restrictiveness Index (FDI Index) measures statutory restrictions on foreign direct investment in 68 countries, including all OECD and G20 countries, and covers 22 sectors.

This review of Colombia by the OECD Working Party on Private Pensions examines Colombia’s position with respect to core principles related to pension systems.

This report summarises the legal and regulatory framework for transparency and exchange of information for tax purposes in Luxembourg.

This paper examines how three multilateral environmental agreements (MEAs) incorporate transparency into their regulatory regimes: CITES (endangered species, especially tropical timber), the Basel Convention (hazardous e-waste), and the Kimberley Process (conflict diamonds)

This paper proposes a new measure of stringency to measure the consequences of environmental regulations on investment, labour demand, and patterns of international trade that would be based on emissions data and which could be constructed separately for different pollutants.

The aim of this workshop was to present recent developments in implementing Regulatory Impact Assessment in the Czech Republic as well as to enable an exposure to different approaches in some leading OECD countries.

This Guide provides concrete recommendations of high impact reforms to simplify the processes of business start ups, construction permits, property registration, procurement, and to upgrade regulatory transparency and efficiency in the management of formalities in Mexico.

This report summarises the results of the survey on regulatory enforcement and inspections conducted among OECD countries in 2012. The report draws some general conclusions from this survey and provides theoretical background on the topic. It also suggests some recommendations for organising and reforming inspections.