A promoter-level mammalian expression atlas.

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy.

BACKGROUND: Africans exhibit great diversity in cytochrome P450 2B6 isoenzyme (CYP2B6), the major enzyme in efavirenz metabolism. AIM: We examined the frequency of two functional single nucleotide polymorphisms (SNPs) of the CYP2B6 pharmacogene in HIV-infected Nigerians on efavirenz-based antiretroviral therapy. The potential implications of the SNPs for HIV therapy were discussed. MATERIALS AND METHODS: A cross-sectional study conducted from July 2018 to December 2018 in a tertiary health facility in Nigeria. A random sample of a clinic cohort of HIV-infected adult Nigerians of different ethnicities was characterized for two key SNPs; CYP2B6:516G>, and CYP2B6:983T > C, defining the alleles CYP2B6*6 and CYP2B6*18, respectively. Hardy-Weinberg equilibrium was calculated to evaluate the genotype frequency distribution. RESULTS: Genotyping was successful for 262 (83%) of the 316 study participants. Of those with genotype results, mean age was 41 ± 8 years and 182 (69.5%) were female. The CYP2B6:516 G/G (extensive metabolizers), CYP2B6:516 G/T (intermediate metabolizers), and CYP2B6:516 T/T (poor metabolizers) genotype frequency was 35.9%, 46.6%, and 17.6%, respectively. Also, 88.9% and 11.1% of participants were carriers of the CYP2B6:983 T/T and CYP2B6:983 T/C (poor metabolizers) genotypes, respectively. There were no gender or age-related differences in the genotype distribution. The CYP2B6:516G >T allele frequencies showed no significant deviations from the Hardy-Weinberg equilibrium (P = 0.66). CONCLUSIONS: The intermediate metabolizer genotype was more common than the extensive and poor metabolizer genotypes in our study sample. We recommended further studies to investigate the risk of efavirenz underexposure and overexposure in carries of the extensive and poor metabolizer genotypes respectively in our patient population.

A survey of anesthetic preference and preoperative anxiety in hip and knee arthroplasty patients: the utility of the outpatient preoperative anesthesia appointment.

PURPOSE: The general public's perceptions of anesthesia and the risks associated with it may be skewed. The outpatient preoperative appointment with an anesthesiologist allows for patient education regarding different anesthetic options and counseling regarding anxiety related to anesthesia and surgery. This study investigates whether the preoperative appointment for hip and knee arthroplasty alters patient preference for general or spinal anesthesia and reduces patient anxiety. METHODS: Sixty-two patients undergoing hip or knee arthroplasty were administered two verbal questionnaires at the preoperative clinic. The first questionnaire was completed prior to meeting the anesthesiologist and addressed patient anesthetic preferences, previous anesthetic experiences, and perioperative anxiety and need for information using the Amsterdam Preoperative Anxiety and Information Scale (APAIS). The second questionnaire was completed immediately following the appointment and addressed the patient's anesthetic preference, reasons for any preference changes, and anxiety levels and need for information using the APAIS. The clinic anesthesiologist was blinded to the nature of the study. RESULTS: Following the clinic appointment, a significant decrease in patients wanting general anesthesia (from 48 to 18%, P < 0.001) and a significant increase in patients wanting spinal anesthesia (from 39 to 76%, 95%, P < 0.01) was noted. A significant decrease in overall anxiety and anxiety related to the patients' upcoming surgeries and need for information was also noted. CONCLUSIONS: The preoperative anesthesia meeting serves an important role in educating patients regarding anesthesia, and can influence patients' choice of anesthetic while also reducing overall patient anxiety.

Optical tweezers as a mathematically driven spatio-temporal potential generator.

The ability to create and manipulate spatio-temporal potentials is essential in the diverse fields of science and technology. Here, we introduce an optical feedback trap system based on high precision position detection and ultrafast feedback control of a Brownian particle in the optical tweezers to generate spatio-temporal virtual potentials of the desired shape in a controlled manner. As an application, we study the nonequilibrium fluctuation dynamics of the particle in a time-varying virtual harmonic potential and validate the Crooks fluctuation theorem in the highly nonequilibrium condition.

Bias in Before-After Studies: Narrative Overview for Anesthesiologists.

Before-after study designs are effective research tools and in some cases, have changed practice. These designs, however, are inherently susceptible to bias (ie, systematic errors) that are sometimes subtle but can invalidate their conclusions. This overview provides examples of before-after studies relevant to anesthesiologists to illustrate potential sources of bias, including selection/assignment, history, regression to the mean, test-retest, maturation, observer, retrospective, Hawthorne, instrumentation, attrition, and reporting/publication bias. Mitigating strategies include using a control group, blinding, matching before and after cohorts, minimizing the time lag between cohorts, using prospective data collection with consistent measuring/reporting criteria, time series data collection, and/or alternative study designs, when possible. Improved reporting with enforcement of the Enhancing Quality and Transparency of Health Research (EQUATOR) checklists will serve to increase transparency and aid in interpretation. By highlighting the potential types of bias and strategies to improve transparency and mitigate flaws, this overview aims to better equip anesthesiologists in designing and/or critically appraising before-after studies.

In silico screening for candidate chassis strains of free fatty acid-producing cyanobacteria.

BACKGROUND: Finding a source from which high-energy-density biofuels can be derived at an industrial scale has become an urgent challenge for renewable energy production. Some microorganisms can produce free fatty acids (FFA) as precursors towards such high-energy-density biofuels. In particular, photosynthetic cyanobacteria are capable of directly converting carbon dioxide into FFA. However, current engineered strains need several rounds of engineering to reach the level of production of FFA to be commercially viable; thus new chassis strains that require less engineering are needed. Although more than 120 cyanobacterial genomes are sequenced, the natural potential of these strains for FFA production and excretion has not been systematically estimated. RESULTS: Here we present the FFA SC (FFASC), an in silico screening method that evaluates the potential for FFA production and excretion of cyanobacterial strains based on their proteomes. A literature search allowed for the compilation of 64 proteins, most of which influence FFA production and a few of which affect FFA excretion. The proteins are classified into 49 orthologous groups (OGs) that helped create rules used in the scoring/ranking of algorithms developed to estimate the potential for FFA production and excretion of an organism. Among 125 cyanobacterial strains, FFASC identified 20 candidate chassis strains that rank in their FFA producing and excreting potential above the specifically engineered reference strain, Synechococcus sp. PCC 7002. We further show that the top ranked cyanobacterial strains are unicellular and primarily include Prochlorococcus (order Prochlorales) and marine Synechococcus (order Chroococcales) that cluster phylogenetically. Moreover, two principal categories of enzymes were shown to influence FFA production the most: those ensuring precursor availability for the biosynthesis of lipids, and those involved in handling the oxidative stress associated to FFA synthesis. CONCLUSION: To our knowledge FFASC is the first in silico method to screen cyanobacteria proteomes for their potential to produce and excrete FFA, as well as the first attempt to parameterize the criteria derived from genetic characteristics that are favorable/non-favorable for this purpose. Thus, FFASC helps focus experimental evaluation only on the most promising cyanobacteria.

Pre- or postoperative interscalene block and/or general anesthesia for arthroscopic shoulder surgery: a retrospective observational study.

PURPOSE: Arthroscopic shoulder surgery can be performed with an interscalene brachial plexus block (ISBPB) alone, ISBPB combined with general anesthesia (GA), or GA alone. Postoperative pain is typically managed with opioids; however, both GA and opioids have adverse effects which can delay discharge. This retrospective study compares the efficacy of four methods of anesthesia management for arthroscopic shoulder surgery. METHODS: Charts of all patients who underwent shoulder surgery by a single surgeon from 2012-2015 were categorized by analgesic regimen: GA only (n = 177), single-shot ISBPB only (n = 124), or pre- vs postoperative ISBPB combined with GA (ISBPB + GA [n = 72] vs GA + ISBPB [n = 52], respectively). The primary outcome measure was the time to discharge from the postanesthesia care unit (PACU). RESULTS: Mean (SD) time in the PACU ranged from 70.5 (39.9) min for ISBPB only to 111.2 (56.9) min for GA only. Use of ISBPB in any combination and regardless of timing resulted in significantly reduced PACU time, with a mean drop of 27.2 min (95% confidence interval [CI], 17.3 to 37.2; P < 0.001). The largest mean pairwise difference was between GA only and ISBPB only, with a mean difference of 40.7 min (95% CI, 25.5 to 55.8; P < 0.001). Use of ISBPB also reduced pain upon arrival at the PACU and, in some cases, upon discharge from the PACU (i.e., ISBPB only but not ISBPB + GA compared with GA). An ISBPB (alone or prior to GA) also reduced analgesic requirements. CONCLUSION: Previously reported benefits of an ISBPB for arthroscopic shoulder surgery are confirmed. Postoperative ISBPBs may also be beneficial for reducing pain and opioid requirements and could be targeted for patients in severe pain upon emergence. A sufficiently powered randomized-controlled trial could determine the relative efficacy, safety, and associated financial implications associated with each method.

Hi-Jack: a novel computational framework for pathway-based inference of host-pathogen interactions.

MOTIVATION: Pathogens infect their host and hijack the host machinery to produce more progeny pathogens. Obligate intracellular pathogens, in particular, require resources of the host to replicate. Therefore, infections by these pathogens lead to alterations in the metabolism of the host, shifting in favor of pathogen protein production. Some computational identification of mechanisms of host-pathogen interactions have been proposed, but it seems the problem has yet to be approached from the metabolite-hijacking angle. RESULTS: We propose a novel computational framework, Hi-Jack, for inferring pathway-based interactions between a host and a pathogen that relies on the idea of metabolite hijacking. Hi-Jack searches metabolic network data from hosts and pathogens, and identifies candidate reactions where hijacking occurs. A novel scoring function ranks candidate hijacked reactions and identifies pathways in the host that interact with pathways in the pathogen, as well as the associated frequent hijacked metabolites. We also describe host-pathogen interaction principles that can be used in the future for subsequent studies. Our case study on Mycobacterium tuberculosis (Mtb) revealed pathways in human-e.g. carbohydrate metabolism, lipids metabolism and pathways related to amino acids metabolism-that are likely to be hijacked by the pathogen. In addition, we report interesting potential pathway interconnections between human and Mtb such as linkage of human fatty acid biosynthesis with Mtb biosynthesis of unsaturated fatty acids, or linkage of human pentose phosphate pathway with lipopolysaccharide biosynthesis in Mtb. AVAILABILITY AND IMPLEMENTATION: Datasets and codes are available at http://cloud.kaust.edu.sa/Pages/Hi-Jack.aspx

Bioprospecting Red Sea Coastal Ecosystems for Culturable Microorganisms and Their Antimicrobial Potential.

Microorganisms that inhabit unchartered unique soil such as in the highly saline and hot Red Sea lagoons on the Saudi Arabian coastline, represent untapped sources of potentially new bioactive compounds. In this study, a culture-dependent approach was applied to three types of sediments: mangrove mud (MN), microbial mat (MM), and barren soil (BS), collected from Rabigh harbor lagoon (RHL) and Al-Kharrar lagoon (AKL). The isolated bacteria were evaluated for their potential to produce bioactive compounds. The phylogenetic characterization of 251 bacterial isolates based on the 16S rRNA gene sequencing, supported their assignment to five different phyla: Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Planctomycetes. Fifteen putative novel species were identified based on a 16S rRNA gene sequence similarity to other strain sequences in the NCBI database, being ≤98%. We demonstrate that 49 of the 251 isolates exhibit the potential to produce antimicrobial compounds. Additionally, at least one type of biosynthetic gene sequence, responsible for the synthesis of secondary metabolites, was recovered from 25 of the 49 isolates. Moreover, 10 of the isolates had a growth inhibition effect towards Staphylococcus aureus, Salmonella typhimurium and Pseudomonas syringae. We report the previously unknown antimicrobial activity of B. borstelensis, P. dendritiformis and M. salipaludis against all three indicator pathogens. Our study demonstrates the evidence of diverse cultured microbes associated with the Red Sea harbor/lagoon environments and their potential to produce antimicrobial compounds.

A novel mercuric reductase from the unique deep brine environment of Atlantis II in the Red Sea.

A unique combination of physicochemical conditions prevails in the lower convective layer (LCL) of the brine pool at Atlantis II (ATII) Deep in the Red Sea. With a maximum depth of over 2000 m, the pool is characterized by acidic pH (5.3), high temperature (68 °C), salinity (26%), low light levels, anoxia, and high concentrations of heavy metals. We have established a metagenomic dataset derived from the microbial community in the LCL, and here we describe a gene for a novel mercuric reductase, a key component of the bacterial detoxification system for mercuric and organomercurial species. The metagenome-derived gene and an ortholog from an uncultured soil bacterium were synthesized and expressed in Escherichia coli. The properties of their products show that, in contrast to the soil enzyme, the ATII-LCL mercuric reductase is functional in high salt, stable at high temperatures, resistant to high concentrations of Hg(2+), and efficiently detoxifies Hg(2+) in vivo. Interestingly, despite the marked functional differences between the orthologs, their amino acid sequences differ by less than 10%. Site-directed mutagenesis and kinetic analysis of the mutant enzymes, in conjunction with three-dimensional modeling, have identified distinct structural features that contribute to extreme halophilicity, thermostability, and high detoxification capacity, suggesting that these were acquired independently during the evolution of this enzyme. Thus, our work provides fundamental structural insights into a novel protein that has undergone multiple biochemical and biophysical adaptations to promote the survival of microorganisms that reside in the extremely demanding environment of the ATII-LCL.

Dragon TIS Spotter: an Arabidopsis-derived predictor of translation initiation sites in plants.

SUMMARY: In higher eukaryotes, the identification of translation initiation sites (TISs) has been focused on finding these signals in cDNA or mRNA sequences. Using Arabidopsis thaliana (A.t.) information, we developed a prediction tool for signals within genomic sequences of plants that correspond to TISs. Our tool requires only genome sequence, not expressed sequences. Its sensitivity/specificity is for A.t. (90.75%/92.2%), for Vitis vinifera (66.8%/94.4%) and for Populus trichocarpa (81.6%/94.4%), which suggests that our tool can be used in annotation of different plant genomes. We provide a list of features used in our model. Further study of these features may improve our understanding of mechanisms of the translation initiation. AVAILABILITY AND IMPLEMENTATION: Our tool is implemented as an artificial neural network. It is available as a web-based tool and, together with the source code, the list of features, and data used for model development, is accessible at http://cbrc.kaust.edu.sa/dts.

DAMPD: a manually curated antimicrobial peptide database.

The demand for antimicrobial peptides (AMPs) is rising because of the increased occurrence of pathogens that are tolerant or resistant to conventional antibiotics. Since naturally occurring AMPs could serve as templates for the development of new anti-infectious agents to which pathogens are not resistant, a resource that contains relevant information on AMP is of great interest. To that extent, we developed the Dragon Antimicrobial Peptide Database (DAMPD, http://apps.sanbi.ac.za/dampd) that contains 1232 manually curated AMPs. DAMPD is an update and a replacement of the ANTIMIC database. In DAMPD an integrated interface allows in a simple fashion querying based on taxonomy, species, AMP family, citation, keywords and a combination of search terms and fields (Advanced Search). A number of tools such as Blast, ClustalW, HMMER, Hydrocalculator, SignalP, AMP predictor, as well as a number of other resources that provide additional information about the results are also provided and integrated into DAMPD to augment biological analysis of AMPs.

Gambling demon and stopping-time fluctuation relation of a Brownian particle under a time-dependent trapping potential.

A gambling demon is an external agent that can terminate a time-dependent driving protocol when a certain observable of the system exceeds a prescribed threshold. The gambling demon is examined in detail both theoretically and experimentally in a Brownian particle system under a compressing potential trap. Insight for choosing an appropriate work threshold for stopping is discussed. The energetics and the distributions of the stopping positions and stopping times are measured in simulations to gain further understanding of the process. Furthermore, the nonstationary and far-from-equilibrium stochastic process in the action of the gambling demon allows us to examine in detail some fundamental issues in stochastic thermodynamics, such as irreversibility and stopping-time fluctuation relation. Paradoxical violation of the stopping-time fluctuation relation can be reconciled in terms of the entropy production associated with fast hidden internal degrees of freedom. All the simulation or theoretical results are confirmed experimentally.

Dragon PolyA Spotter: predictor of poly(A) motifs within human genomic DNA sequences.

MOTIVATION: Recognition of poly(A) signals in mRNA is relatively straightforward due to the presence of easily recognizable polyadenylic acid tail. However, the task of identifying poly(A) motifs in the primary genomic DNA sequence that correspond to poly(A) signals in mRNA is a far more challenging problem. Recognition of poly(A) signals is important for better gene annotation and understanding of the gene regulation mechanisms. In this work, we present one such poly(A) motif prediction method based on properties of human genomic DNA sequence surrounding a poly(A) motif. These properties include thermodynamic, physico-chemical and statistical characteristics. For predictions, we developed Artificial Neural Network and Random Forest models. These models are trained to recognize 12 most common poly(A) motifs in human DNA. Our predictors are available as a free web-based tool accessible at http://cbrc.kaust.edu.sa/dps. Compared with other reported predictors, our models achieve higher sensitivity and specificity and furthermore provide a consistent level of accuracy for 12 poly(A) motif variants. CONTACT: vladimir.bajic@kaust.edu.sa SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Importance of the genetic diversity within the Mycobacterium tuberculosis complex for the development of novel antibiotics and diagnostic tests of drug resistance.

Despite being genetically monomorphic, the limited genetic diversity within the Mycobacterium tuberculosis complex (MTBC) has practical consequences for molecular methods for drug susceptibility testing and for the use of current antibiotics and those in clinical trials. It renders some representatives of MTBC intrinsically resistant against one or multiple antibiotics and affects the spectrum and consequences of resistance mutations selected for during treatment. Moreover, neutral or silent changes within genes responsible for drug resistance can cause false-positive results with hybridization-based assays, which have been recently introduced to replace slower phenotypic methods. We discuss the consequences of these findings and propose concrete steps to rigorously assess the genetic diversity of MTBC to support ongoing clinical trials.

Conotoxins that confer therapeutic possibilities.

Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt(®); Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ω-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred.

Polymorphisms in isoniazid and prothionamide resistance genes of the Mycobacterium tuberculosis complex.

Sequence analyses of 74 strains that encompassed major phylogenetic lineages of the Mycobacterium tuberculosis complex revealed 10 polymorphisms in mshA (Rv0486) and four polymorphisms in inhA (Rv1484) that were not responsible for isoniazid or prothionamide resistance. Instead, some of these mutations were phylogenetically informative. This genetic diversity must be taken into consideration for drug development and for the design of molecular tests for drug resistance.

Impact of Fgd1 and ddn diversity in Mycobacterium tuberculosis complex on in vitro susceptibility to PA-824.

PA-824 is a promising drug candidate for the treatment of tuberculosis (TB). It is in phase II clinical trials as part of the first newly designed regimen containing multiple novel antituberculosis drugs (PA-824 in combination with moxifloxacin and pyrazinamide). However, given that the genes involved in resistance against PA-824 are not fully conserved in the Mycobacterium tuberculosis complex (MTBC), this regimen might not be equally effective against different MTBC genotypes. To investigate this question, we sequenced two PA-824 resistance genes (fgd1 [Rv0407] and ddn [Rv3547]) in 65 MTBC strains representing major phylogenetic lineages. The MICs of representative strains were determined using the modified proportion method in the Bactec MGIT 960 system. Our analysis revealed single-nucleotide polymorphisms in both genes that were specific either for several genotypes or for individual strains, yet none of these mutations significantly affected the PA-824 MICs (≤ 0.25 µg/ml). These results were supported by in silico modeling of the mutations identified in Fgd1. In contrast, "Mycobacterium canettii" strains displayed a higher MIC of 8 µg/ml. In conclusion, we found a large genetic diversity in PA-824 resistance genes that did not lead to elevated PA-824 MICs. In contrast, M. canettii strains had MICs that were above the plasma concentrations of PA-824 documented so far in clinical trials. As M. canettii is also intrinsically resistant against pyrazinamide, new regimens containing PA-824 and pyrazinamide might not be effective in treating M. canettii infections. This finding has implications for the design of multiple ongoing clinical trials.

Specialist early and immediate repair of post-laparoscopic cholecystectomy bile duct injuries is associated with an improved long-term outcome.

INTRODUCTION: A majority of bile duct injuries (BDI) sustained during laparoscopic cholecystectomy require formal surgical reconstruction, and traditionally this repair is performed late. We aimed to assess long-term outcomes after repair, focusing on our preferred early approach. METHODS: A total of 200 BDI patients [age 54(20-83); 64 male], followed up for median 60 (5-212) months were assessed for morbidity. Factors contributing to this were analyzed with a univariate and multivariate analysis. RESULTS: A total of 112 (56%) patients were repaired by specialist hepatobiliary surgeons [timing of repair: immediate, n = 28; early (<21 days), n = 43; and late (>21 days) n = 41], whereas 45 (22%) underwent repair by nonspecialist surgeons before specialist referral [immediate, n = 16; early, n = 26 and late, n = 03]. Outcomes after immediate and early repairs were comparable to late repairs when performed by specialists [recurrent cholangitis:11%, 12%, and 10%; P = 0.96, NS; re-stricture:18%,5%, and 29%; P = 0.01; nonsurgical intervention: 14%, 5%, and 24%; P<0.03; redo surgery: 4%, 2%, and 5%; P = 0.81, NS; overall morbidity: 21%, 14%, and 39%; P<0.02]. On multivariate analysis, immediate and early repairs done by nonspecialist surgeons were independent risk factors (P < 0.05) for recurrent cholangitis [50% and 27%], re-stricturing (75% and 61%), redo reconstructions (31% and 61%), and overall morbidity (75% and 84%). CONCLUSION: Immediate and early repair after BDI results in comparable, if not better long-term outcomes compared to late repair when performed by specialists.

Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment.

Despite intense efforts to develop non-cytotoxic anticancer treatments, effective agents are still not available. Therefore, novel apoptosis-inducing drug leads that may be developed into effective targeted cancer therapies are of interest to the cancer research community. Targeted cancer therapies affect specific aberrant apoptotic pathways that characterize different cancer types and, for this reason, it is a more desirable type of therapy than chemotherapy or radiotherapy, as it is less harmful to normal cells. In this regard, marine sponge derived metabolites that induce apoptosis continue to be a promising source of new drug leads for cancer treatments. A PubMed query from 01/01/2005 to 31/01/2011 combined with hand-curation of the retrieved articles allowed for the identification of 39 recently confirmed apoptosis-inducing anticancer lead compounds isolated from the marine sponge that are selectively discussed in this review.