Defining the regulatory mechanisms of sigma factor RpoS degradation in Azotobacter vinelandii and Pseudomonas aeruginosa.

In several Gram-negative bacteria, the general stress response is mediated by the alternative sigma factor RpoS, a subunit of RNA polymerase that confers promoter specificity. In Escherichia coli, regulation of protein levels of RpoS involves the adaptor protein RssB, which binds RpoS for presenting it to the ClpXP protease for its degradation. However, in species from the Pseudomonadaceae family, RpoS is also degraded by ClpXP, but an adaptor has not been experimentally demonstrated. Here, we investigated the role of an E. coli RssB-like protein in two representative Pseudomonadaceae species such as Azotobacter vinelandii and Pseudomonas aeruginosa. In these bacteria, inactivation of the rssB gene increased the levels and stability of RpoS during exponential growth. Downstream of rssB lies a gene that encodes a protein annotated as an anti-sigma factor antagonist (rssC). However, inactivation of rssC in both A. vinelandii and P. aeruginosa also increased the RpoS protein levels, suggesting that RssB and RssC work together to control RpoS degradation. Furthermore, we identified an in vivo interaction between RssB and RpoS only in the presence of RssC using a bacterial three-hybrid system. We propose that both RssB and RssC are necessary for the ClpXP-dependent RpoS degradation during exponential growth in two species of the Pseudomonadaceae family.

Distinct trajectories of neuropsychiatric symptoms in the 12 months following traumatic brain injury (TBI): a TRACK-TBI study.

BACKGROUND: Neuropsychiatric symptoms are common after traumatic brain injury (TBI) and often resolve within 3 months post-injury. However, the degree to which individual patients follow this course is unknown. We characterized trajectories of neuropsychiatric symptoms over 12 months post-TBI. We hypothesized that a substantial proportion of individuals would display trajectories distinct from the group-average course, with some exhibiting less favorable courses. METHODS: Participants were level 1 trauma center patients with TBI (n = 1943), orthopedic trauma controls (n = 257), and non-injured friend controls (n = 300). Trajectories of six symptom dimensions (Depression, Anxiety, Fear, Sleep, Physical, and Pain) were identified using growth mixture modeling from 2 weeks to 12 months post-injury. RESULTS: Depression, Anxiety, Fear, and Physical symptoms displayed three trajectories: Stable-Low (86.2-88.6%), Worsening (5.6-10.9%), and Improving (2.6-6.4%). Among symptomatic trajectories (Worsening, Improving), lower-severity TBI was associated with higher prevalence of elevated symptoms at 2 weeks that steadily resolved over 12 months compared to all other groups, whereas higher-severity TBI was associated with higher prevalence of symptoms that gradually worsened from 3-12 months. Sleep and Pain displayed more variable recovery courses, and the most common trajectory entailed an average level of problems that remained stable over time (Stable-Average; 46.7-82.6%). Symptomatic Sleep and Pain trajectories (Stable-Average, Improving) were more common in traumatically injured groups. CONCLUSIONS: Findings illustrate the nature and rates of distinct neuropsychiatric symptom trajectories and their relationship to traumatic injuries. Providers may use these results as a referent for gauging typical v. atypical recovery in the first 12 months post-injury.

Follow-up for 3 years of a pediatric population diagnosed in 2018 with mother-to-child transmission of HIV in 8 Latin American countries in the PLANTAIDS cohort.

INTRODUCTION: The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. METHODOLOGY: Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). RESULTS: The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8-5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. CONCLUSIONS: It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.

Pentoxifylline Inhibits TNF-α/TGF-ß1-Induced Epithelial-Mesenchymal Transition via Suppressing the NF-κB Pathway and SERPINE1 Expression in CaSki Cells.

Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant organs (metastasis). The epithelial-mesenchymal transition (EMT) is a fundamental process of cancer metastasis. Inflammation can lead to tumor progression, EMT induction, and metastasis. The inflammatory microenvironment is a potent inducer of EMT; inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Transforming growth factor-beta (TGF-ß1) activate transcriptional factors such as STAT3, Snail, Smad, and the Nuclear Factor kappa light-chain-enhancer of activated beta cells (NF-κΒ), which drive EMT. Anti-inflammatory compounds may be an option in the disruption of EMT. PenToXifylline (PTX) possesses potent anti-inflammatory effects by inhibiting NF-κB activity. In addition, PTX exerts an anti-fibrotic effect by decreasing Smad2/3/4. We hypothesize that PTX could exert anti-EMT effects. CaSki human cervical tumor cells were exposed to TNF-α 10 ng/mL and TGF-ß1 alone or in combination for 5 days. Our results revealed that TNF-α and TGF-ß1 induced N-cadherin and Vimentin, confirming the induction of EMT. Furthermore, the combination of cytokines synergized the expression of mesenchymal proteins, enhanced IκBα and p65 phosphorylation, and upregulated Serpin family E member 1 (SERPINE1) mRNA. PTX pretreatment prior to the addition of TNF-α and TGF-ß1 significantly reduced N-cadherin and Vimentin levels. To our knowledge, this is the first time that this effect of PTX has been reported. Additionally, PTX reduced the phosphorylation of IκB-α and p65 and significantly decreased SERPINE1 expression, cell proliferation, migration, and invasion. In conclusion, PTX may counteract EMT in cervical cancer cells by decreasing the NF-κB and SERPINE1.

A Photoswitchable Ligand Targeting the ß1 -Adrenoceptor Enables Light-Control of the Cardiac Rhythm.

Catecholamine-triggered ß-adrenoceptor (ß-AR) signaling is essential for the correct functioning of the heart. Although both ß1 - and ß2 -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting ß1 -AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new strategy for the light-control of ß1 -AR activation by means of photoswitchable drugs with a high level of ß1 -/ß2 -AR selectivity. All reported molecules allow for an efficient real-time optical control of receptor function in vitro. Moreover, using confocal microscopy we demonstrate that the binding of our best hit, pAzo-2, can be reversibly photocontrolled. Strikingly, pAzo-2 also enables a dynamic cardiac rhythm management on living zebrafish larvae using light, thus highlighting the therapeutic and research potential of the developed photoswitches. Overall, this work provides the first proof of precise control of the therapeutic target ß1 -AR in native environments using light.

The impact of prenatal maternal stress due to potentially traumatic events on child temperament: A systematic review.

The objective of the current study was to complete a systematic review of the relationship between prenatal maternal stress due to potentially traumatic events (PTEs) and child temperament. Eligible studies through June 2020 were identified utilizing a search strategy in PubMed and PsycInfo. Included studies examined associations between prenatal maternal stress due to PTE and child temperament. Two independent coders extracted study characteristics and three coders assessed study quality. Of the 1969 identified studies, 20 met full inclusion criteria. Studies were classified on two dimensions: (1) disaster-related stress and (2) intimate partner violence during pregnancy. For disaster-related prenatal maternal stress, 75% (nine out of 12) of published reports found associations with increased child negative affectivity, 50% (five out of 10) also noted associations with lower effortful control/regulation, and 38% (three out of eight) found associations with lower positive affectivity. When considering prenatal intimate partner violence stress, 80% (four out of five) of published reports found associations with higher child negative affectivity, 67% (four out of six) found associations with lower effortful control/regulation, and 33% (one out of three) found associations with lower positive affectivity. Prenatal maternal stress due to PTEs may impact the offspring's temperament, especially negative affectivity. Mitigating the effects of maternal stress in pregnancy is needed in order to prevent adverse outcomes on the infant's socioemotional development.

Ultrabright Fluorescent Organic Nanoparticles Based on Small-Molecule Ionic Isolation Lattices*.

Ultrabright fluorescent nanoparticles (NPs) hold great promise for demanding bioimaging applications. Recently, extremely bright molecular crystals of cationic fluorophores were obtained by hierarchical coassembly with cyanostar anion-receptor complexes. These small-molecule ionic isolation lattices (SMILES) ensure spatial and electronic isolation to prohibit aggregation quenching of dyes. We report a simple, one-step supramolecular approach to formulate SMILES materials into NPs. Rhodamine-based SMILES NPs stabilized by glycol amphiphiles show high fluorescence quantum yield (30 %) and brightness per volume (5000 M-1 cm-1 /nm3 ) with 400 dye molecules packed into 16-nm particles, corresponding to a particle absorption coefficient of 4×107  M-1 cm-1 . UV excitation of the cyanostar component leads to higher brightness (>6000 M-1 cm-1 / nm3 ) by energy transfer to rhodamine emitters. Coated NPs stain cells and are thus promising for bioimaging.

Membrane curvature regulates ligand-specific membrane sorting of GPCRs in living cells.

The targeted spatial organization (sorting) of Gprotein-coupled receptors (GPCRs) is essential for their biological function and often takes place in highly curved membrane compartments such as filopodia, endocytic pits, trafficking vesicles or endosome tubules. However, the influence of geometrical membrane curvature on GPCR sorting remains unknown. Here we used fluorescence imaging to establish a quantitative correlation between membrane curvature and sorting of three prototypic class A GPCRs (the neuropeptide Y receptor Y2, the ß1 adrenergic receptor and the ß2 adrenergic receptor) in living cells. Fitting of a thermodynamic model to the data enabled us to quantify how sorting is mediated by an energetic drive to match receptor shape and membrane curvature. Curvature-dependent sorting was regulated by ligands in a specific manner. We anticipate that this curvature-dependent biomechanical coupling mechanism contributes to the sorting, trafficking and function of transmembrane proteins in general.

Evaluation of the cost-effectiveness of the treatment of uncomplicated severe acute malnutrition by lady health workers as compared to an outpatient therapeutic feeding programme in Sindh Province, Pakistan.

BACKGROUND: Due to the limited evidence of the cost-effectiveness of Community Health Workers (CHW) delivering treatment for severe acute malnutrition (SAM), there is a need to better understand the costs incurred by both implementing institutions and beneficiary households. This study assessed the costs and cost-effectiveness of treatment for cases of SAM without complications delivered by government-employed Lady Health Workers (LHWs) and complemented with non-governmental organisation (NGO) delivered outpatient facility-based care compared with NGO delivered outpatient facility-based care only alongside a two-arm randomised controlled trial conducted in Sindh Province, Pakistan. METHODS: An activity-based cost model was used, employing a societal perspective to include costs incurred by beneficiaries and the wider community. Costs were estimated through accounting records, interviews and informal group discussions. Cost-effectiveness was assessed for each arm relative to no intervention, and incrementally between the two interventions, providing information on both absolute and relative costs and effects. RESULTS: The cost per child recovered in outpatient facility-based care was similar to LHW-delivered care, at 363 USD and 382 USD respectively. An additional 146 USD was spent per additional child recovered by outpatient facilities compared to LHWs. Results of sensitivity analyses indicated considerable uncertainty in which strategy was most cost-effective due to small differences in cost and recovery rates between arms. The cost to the beneficiary household of outpatient facility-based care was double that of LHW-delivered care. CONCLUSIONS: Outpatient facility-based care was found to be slightly more cost-effective compared to LHW-delivered care, despite the potential for cost-effectiveness of CHWs managing SAM being demonstrated in other settings. The similarity of cost-effectiveness outcomes between the two models resulted in uncertainty as to which strategy was the most cost-effective. Similarity of costs and effectiveness between models suggests that whether it is appropriate to engage LHWs in substituting or complementing outpatient facilities may depend on population needs, including coverage and accessibility of existing services, rather than be purely a consideration of cost. Future research should assess the cost-effectiveness of LHW-delivered care when delivered solely by the government. TRIAL REGISTRATION: NCT03043352 , ClinicalTrials.gov. Retrospectively registered.

Costs and cost-efficiency of a mobile cash transfer to prevent child undernutrition during the lean season in Burkina Faso: a mixed methods analysis from the MAM'Out randomized controlled trial.

BACKGROUND: This study assessed the costs and cost-efficiency of a mobile cash transfer implemented in Tapoa Province, Burkina Faso in the MAM'Out randomized controlled trial from June 2013 to December 2014, using mixed methods and taking a societal perspective by including costs to implementing partners and beneficiary households. METHODS: Data were collected via interviews with implementing staff from the humanitarian agency and the private partner delivering the mobile money, focus group discussions with beneficiaries, and review of accounting databases. Costs were analyzed by input category and activity-based cost centers. cost-efficiency was analyzed by cost-transfer ratios (CTR) and cost per beneficiary. Qualitative analysis was conducted to identify themes related to implementing electronic cash transfers, and barriers to efficient implementation. RESULTS: The CTR was 0.82 from a societal perspective, within the same range as other humanitarian transfer programs; however the intervention did not achieve the same degree of cost-efficiency as other mobile transfer programs specifically. Challenges in coordination between humanitarian and private partners resulted in long wait times for beneficiaries, particularly in the first year of implementation. Sensitivity analyses indicated a potential 6% reduction in CTR through reducing beneficiary wait time by one-half. Actors reported that coordination challenges improved during the project, therefore inefficiencies likely would be resolved, and cost-efficiency improved, as the program passed the pilot phase. CONCLUSIONS: Despite the time required to establish trusting relationships among actors, and to set up a network of cash points in remote areas, this analysis showed that mobile transfers hold promise as a cost-efficient method of delivering cash in this setting. Implementation by local government would likely reduce costs greatly compared to those found in this study context, and improve cost-efficiency especially by subsidizing expansion of mobile money network coverage and increasing cash distribution points in remote areas which are unprofitable for private partners.

Cost-effectiveness of the treatment of uncomplicated severe acute malnutrition by community health workers compared to treatment provided at an outpatient facility in rural Mali.

BACKGROUND: The Malian Nutrition Division of the Ministry of Health and Action Against Hunger tested the feasibility of integrating treatment of severe acute malnutrition (SAM) into the existing Integrated Community Case Management package delivered by community health workers (CHWs). This study assessed costs and cost-effectiveness of CHW-delivered care compared to outpatient facility-based care. METHODS: Activity-based costing methods were used, and a societal perspective employed to include all relevant costs incurred by institutions, beneficiaries and communities. The intervention and control arm enrolled different numbers of children so a modelled scenario sensitivity analysis was conducted to assess the cost-effectiveness of the two arms, assuming equal numbers of children enrolled. RESULTS: In the base case, with unequal numbers of children in each arm, for CHW-delivered care, the cost per child treated was 244 USD and cost per child recovered was 259 USD. Outpatient facility-based care was less cost-effective at 442 USD per child and 501 USD per child recovered. The conclusions of the analysis changed in the modelled scenario sensitivity analysis, with outpatient facility-based care being marginally more cost-effective (cost per child treated is 188 USD, cost per child recovered is 214 USD), compared to CHW-delivered care. This suggests that achieving good coverage is a key factor influencing cost-effectiveness of CHWs delivering treatment for SAM in this setting. Per week of treatment, households receiving CHW-delivered care spent half of the time receiving treatment and three times less money compared with those receiving treatment from the outpatient facility. CONCLUSIONS: This study supports existing evidence that the delivery of treatment by CHWs is a cost-effective intervention, provided that good coverage is achieved. A major benefit of this strategy was the lower cost incurred by the beneficiary household when treatment is available in the community. Further research is needed on the implementation costs that would be incurred by the government to increase the operability of these results.

Promoting Diversity in the Clinical and Translational Research Workforce.

The positive impact of diversity in increasing the effectiveness of the research workforce has been undeniably demonstrated to be an essential element for achieving health equity. Diversity is also instrumental for the research workforce to advance discovery, eliminate health disparities, improve minority health and achieve effective patient-centered outcomes in the quest for better health. One of the sustainable ways to achieve diversity in the workforce is through training, education and career development of all interested individuals including minority, underserved, underrepresented and populations with special needs. A Hispanic public, academic health center, and a historically black private medical school, have joined efforts in this article to share their experiences in addressing diversity in the clinical and translational research workforce with grant support from the National Institutes of Health. The purpose of this paper is to describe how diversity has been achieved through a concerted effort to recruit and develop underrepresented junior faculty and doctoral candidates for successful careers in clinical and translational research focused on health disparities and minority health. We describe Initiatives designed to achieve diversity in recruitment and development of research teams, together with an evaluation of outcomes to determine the success of the program and its participants.

Bring Your Own Device and Nurse Managers' Decision Making.

The Bring Your Own Device phenomenon is important in the healthcare environment because this trend is changing the workplace in healthcare organizations, such as British Columbia. At present, there is little research that exists in Canada to provide a distinct understanding of the complexities and difficulties unique to this phenomenon within the nursing practice. This study focused on the experiences and perceptions of nurse managers regarding how they make decisions on the use of personal handheld devices in the workplace. Telephone interviews (N = 10) and qualitative descriptive analysis were used. Four major themes emerged: (1) management perspective, (2) opportunities, (3) disadvantages, and (4) solutions. Nurse managers and other executives in healthcare organizations and health information technology departments need to be aware of the practice and organizational implications of the Bring Your Own Device movement.

Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu(I) -catalyzed alkyne-azide cycloaddition and its strain-promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material.

Synthesis of an oligonucleotide-derivatized amphipol and its use to trap and immobilize membrane proteins.

Amphipols (APols) are specially designed amphipathic polymers that stabilize membrane proteins (MPs) in aqueous solutions in the absence of detergent. A8-35, a polyacrylate-based APol, has been grafted with an oligodeoxynucleotide (ODN). The synthesis, purification and properties of the resulting 'OligAPol' have been investigated. Grafting was performed by reacting an ODN carrying an amine-terminated arm with the carboxylates of A8-35. The use of OligAPol for trapping MPs and immobilizing them onto solid supports was tested using bacteriorhodopsin (BR) and the transmembrane domain of Escherichia coli outer membrane protein A (tOmpA) as model proteins. BR and OligAPol form water-soluble complexes in which BR remains in its native conformation. Hybridization of the ODN arm with a complementary ODN was not hindered by the assembly of OligAPol into particles, nor by its association with BR. BR/OligAPol and tOmpA/OligAPol complexes could be immobilized onto either magnetic beads or gold nanoparticles grafted with the complementary ODN, as shown by spectroscopic measurements, fluorescence microscopy and the binding of anti-BR and anti-tOmpA antibodies. OligAPols provide a novel, highly versatile approach to tagging MPs, without modifying them chemically nor genetically, for specific, reversible and targetable immobilization, e.g. for nanoscale applications.

Modulation of fluorescence signals from biomolecules along nanowires due to interaction of light with oriented nanostructures.

High aspect ratio nanostructures have gained increasing interest as highly sensitive platforms for biosensing. Here, well-defined biofunctionalized vertical indium arsenide nanowires are used to map the interaction of light with nanowires depending on their orientation and the excitation wavelength. We show how nanowires act as antennas modifying the light distribution and the emitted fluorescence. This work highlights an important optical phenomenon in quantitative fluorescence studies and constitutes an important step for future studies using such nanostructures.

Dimensional Assessment of Anxiety in Puerto Rican Patients: Evaluating Applicability of Psychological Questionnaires.

OBJECTIVE: A dimensional assessment model as a supplement to the diagnosis process could overcome the current pitfalls in classifying psychopathology in ethnic minorities. The aim of the study described herein was to examine a sample of Puerto Rican patients diagnosed with anxiety disorder in order to evaluate the psychometric properties of the specific scales that assess the following 3 domains: clinical symptoms, personality/trait, and affective style. METHODS: 80 subjects were recruited and interviewed using the Structured Clinical Interview for DSM-IV to identify the presence of anxiety disorders. Following this, various questionnaires assessing each proposed domain were administered to the participants. Reliability and validity of these questionnaires were examined using Cronbach's alpha and exploratory factor analysis. The effect of the individual items of the questionnaires on the overall reliability and validity was assessed using factor scores component matrix. RESULTS: Analyses revealed moderate to high reliability and validity scores within all 3 domains. The sample obtained moderate to high scores on the scales comprising clinical and personality/trait domains. CONCLUSION: The use of self-report scales in accordance with the proposed dimensional framework may be an effective way to supplement categorical diagnoses within the Hispanic population represented by this sample.

Covalent and stable CuAAC modification of silicon surfaces for control of cell adhesion.

Stable primary functionalization of metal surfaces plays a significant role in reliable secondary attachment of complex functional molecules used for the interfacing of metal objects and nanomaterials with biological systems. In principle, this can be achieved through chemical reactions either in the vapor or liquid phase. In this work, we compared these two methods for oxidized silicon surfaces and thoroughly characterized the functionalization steps by tagging and fluorescence imaging. We demonstrate that the vapor-phase functionalization only provided transient surface modification that was lost on extensive washing. For stable surface modification, a liquid-phase method was developed. In this method, silicon wafers were decorated with azides, either by silanization with (3-azidopropyl)triethoxysilane or by conversion of the amine groups of an aminopropylated surface by means of the azido-transfer reaction. Subsequently, D-amino acid adhesion peptides could be immobilized on the surface by use of Cu(I)-catalyzed click chemistry. This enabled the study of cell adhesion to the metal surface. In contrast to unmodified surfaces, the peptide-modified surfaces were able to maintain cell adhesion during significant flow velocities in a microflow reactor.

Synthesis of a Polyhistidine-bearing Amphipol and its Use for Immobilizing Membrane Proteins.

Amphipols (APols) are short amphipathic polymers that stabilize membrane proteins (MPs) in aqueous solutions. In the present study, A8-35, a polyacrylate-based APol, was grafted with hexahistidine tags (His6-tags). The synthesis and characterization of this novel functionalized APol, named HistAPol, are described. Its ability to immobilize MPs on nickel ion-bearing surfaces was tested using two complementary methods, immobilized metal affinity chromatography (IMAC) and surface plasmon resonance (SPR). Compared to a single His6-tag fused at one extremity of a MP, the presence of several His6-tags carried by the APol belt surrounding the transmembrane domain of a MP increases remarkably the affinity of the protein/APol complex for nickel ion-bearing SPR chips, whereas it does not show such a strong effect on an IMAC resin. HistAPol-mediated immobilization, which allows reversibility of the interaction and easy regeneration of the supports and dispenses with any genetic modification of the target protein, provides a novel, promising tool for attaching MPs onto solid supports while stabilizing them.

Thapsigargin--from Thapsia L. to mipsagargin.

The sesquiterpene lactone thapsigargin is found in the plant Thapsia garganica L., and is one of the major constituents of the roots and fruits of this Mediterranean species. In 1978, the first pharmacological effects of thapsigargin were established and the full structure was elucidated in 1985. Shortly after, the overall mechanism of the Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibition that leads to apoptosis was discovered. Thapsigargin has a potent antagonistic effect on the SERCA and is widely used to study Ca2+-signaling. The effect on SERCA has also been utilized in the treatment of solid tumors. A prodrug has been designed to target the blood vessels of cancer cells; the death of these blood vessels then leads to tumor necrosis. The first clinical trials of this drug were initiated in 2008, and the potent drug is expected to enter the market in the near future under the generic name Mipsagargin (G-202). This review will describe the discovery of the new drug, the on-going elucidation of the biosynthesis of thapsigargin in the plant and attempts to supply the global market with a novel potent anti-cancer drug.