An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis.

Myeloid cells are known to suppress antitumour immunity1. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells. Consequentially, depletion of basophils profoundly reduced tumour burden and normalized myelopoiesis. We subsequently initiated a clinical trial of the IL-4Rα blocking antibody dupilumab2-5 given in conjunction with PD-1/PD-L1 checkpoint blockade in patients with relapsed or refractory NSCLC who had progressed on PD-1/PD-L1 blockade alone (ClinicalTrials.gov identifier NCT05013450 ). Dupilumab supplementation reduced circulating monocytes, expanded tumour-infiltrating CD8 T cells, and in one out of six patients, drove a near-complete clinical response two months after treatment. Our study defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer, identifies a novel combination therapy for immune checkpoint blockade in humans, and highlights cancer as a systemic malady that requires therapeutic strategies beyond the primary disease site.

Engineering Escherichia coli for increased Und-P availability leads to material improvements in glycan expression technology.

BACKGROUND: Bacterial surface glycans are assembled by glycosyltransferases (GTs) that transfer sugar monomers to long-chained lipid carriers. Most bacteria employ the 55-carbon chain undecaprenyl phosphate (Und-P) to scaffold glycan assembly. The amount of Und-P available for glycan synthesis is thought to be limited by the rate of Und-P synthesis and by competition for Und-P between phosphoglycosyl transferases (PGTs) and GTs that prime glycan assembly (which we collectively refer to as PGT/GTs). While decreasing Und-P availability disrupts glycan synthesis and promotes cell death, less is known about the effects of increased Und-P availability. RESULTS: To determine if cells can maintain higher Und-P levels, we first reduced intracellular competition for Und-P by deleting all known non-essential PGT/GTs in the Gram-negative bacterium Escherichia coli (hereafter called ΔPGT/GT cells). We then increased the rate of Und-P synthesis in ΔPGT/GT cells by overexpressing the Und-P(P) synthase uppS from a plasmid (puppS). Und-P quantitation revealed that ΔPGT/GT/puppS cells can be induced to maintain 3-fold more Und-P than wild type cells. Next, we determined how increasing Und-P availability affects glycan expression. Interestingly, increasing Und-P availability increased endogenous and recombinant glycan expression. In particular, ΔPGT/GT/puppS cells could be induced to express 7-fold more capsule from Streptococcus pneumoniae serotype 4 than traditional E. coli cells used to express recombinant glycans. CONCLUSIONS: We demonstrate that the biotechnology standard bacterium E. coli can be engineered to maintain higher levels of Und-P. The results also strongly suggest that Und-P pathways can be engineered to increase the expression of potentially any Und-P-dependent polymer. Given that many bacterial glycans are central to the production of vaccines, diagnostics, and therapeutics, increasing Und-P availability should be a foremost consideration when designing bacterial glycan expression systems.

Tracking Colanic Acid Repeat Unit Formation from Stepwise Biosynthesis Inactivation in Escherichia coli.

Colanic acid is a glycopolymer loosely associated with the outer membrane of Escherichia coli that plays a role in pathogen survival. For nearly six decades since its discovery, the functional identities of the enzymes necessary to synthesize colanic acid have yet to be assessed in full. Herein, we developed a method for detecting the lipid-linked intermediates from each step of colanic acid biosynthesis in E. coli. The accumulation of each enzyme product was made possible by inactivating sequential genes involved in colanic acid biosynthesis and upregulating the colanic acid operon by inducing rcsA transcription. LC-MS analysis revealed that these accumulated materials were consistent with the well-documented composition analysis. Recapitulating the native bioassembly of colanic acid enabled us to identify the functional roles of the last two enzymes, WcaL and WcaK, associated with the formation of the lipid-linked oligosaccharide repeating unit of colanic acid. Importantly, biochemical evidence is provided for the formation of the final glycosylation hexasaccharide product formed by WcaL and the addition of a pyruvate moiety to form a pyruvylated hexasaccharide by WcaK. These findings provide insight into the development of methods for the identification of enzyme functions during cell envelope synthesis.

General Utilization of Fluorescent Polyisoprenoids with Sugar Selective Phosphoglycosyltransferases.

The protective surfaces of bacteria are comprised of polysaccharides and are involved in host invasion and colonization, host immune system evasion, and antibacterial resistance. A major barrier to our fundamental understanding of these complex surface polysaccharides lies in the tremendous diversity in glycan composition among bacterial species. The polyisoprenoid bactoprenyl phosphate (or undecaprenyl phosphate) is an essential lipid carrier necessary for early stages of glycopolymer assembly. Because of the ubiquity of bactoprenyl phosphate in these critical processes, molecular probes appended to this lipid carrier simplify identification of enzymatic roles during polysaccharide bioassembly. A limited number of these probes exist in the literature or have been assessed with such pathways, and the limits of their use are not currently known. Herein, we devise an efficient method for producing fluorescently modified bactoprenyl probes. We further expand our previous efforts utilizing 2-nitrileaniline and additionally prepare nitrobenzoxadizol-tagged bactoprenyl phosphate for the first time. We then assess the enzyme promiscuity of these two probes utilizing four well-characterized initiating phosphoglycosyltransferases: CPS2E (Streptococcus pneumoniae), WbaP (Salmonella enterica), WecA (Escherichia coli), and WecP (Aeromonas hydrophilia). Both probes serve as substrates for these enzymes and could be readily used to investigate a wide range of bacterial glycoassembly pathways. Interestingly, we have also identified unique solubility requirements for the nitrobenzoxadizol moiety for efficient enzymatic utilization that was not observed for the 2-nitrileaniline.

Diffusible Signal Factors Act through AraC-Type Transcriptional Regulators as Chemical Cues To Repress Virulence of Enteric Pathogens.

Successful colonization by enteric pathogens is contingent upon effective interactions with the host and the resident microbiota. These pathogens thus respond to and integrate myriad signals to control virulence. Long-chain fatty acids repress the virulence of the important enteric pathogens Salmonella enterica and Vibrio cholerae by repressing AraC-type transcriptional regulators in pathogenicity islands. While several fatty acids are known to be repressive, we show here that cis-2-unsaturated fatty acids, a rare chemical class used as diffusible signal factors (DSFs), are highly potent inhibitors of virulence functions. We found that DSFs repressed virulence gene expression of enteric pathogens by interacting with transcriptional regulators of the AraC family. In Salmonella enterica serovar Typhimurium, DSFs repress the activity of HilD, an AraC-type activator essential to the induction of epithelial cell invasion, by both preventing its interaction with target DNA and inducing its rapid degradation by Lon protease. cis-2-Hexadecenoic acid (c2-HDA), a DSF produced by Xylella fastidiosa, was the most potent among those tested, repressing the HilD-dependent transcriptional regulator hilA and the type III secretion effector sopB >200- and 68-fold, respectively. Further, c2-HDA attenuated the transcription of the ToxT-dependent cholera toxin synthesis genes of V. cholerae c2-HDA significantly repressed invasion gene expression by Salmonella in the murine colitis model, indicating that the HilD-dependent signaling pathway functions within the complex milieu of the animal intestine. These data argue that enteric pathogens respond to DSFs as interspecies signals to identify appropriate niches in the gut for virulence activation, which could be exploited to control the virulence of enteric pathogens.

Pharmacists' Knowledge and Practices Surrounding Expedited Partner Therapy for Chlamydia trachomatis, New York City, 2012 and 2014.

BACKGROUND: Health care providers in New York City can prescribe treatment for Chlamydia trachomatis (Ct) for a patient's partner without the partner having a medical evaluation ("prescription-expedited partner therapy" [EPT]), and use of prescription-EPT is common. However, there is little known about pharmacists' knowledge and practices surrounding EPT. METHODS: Two cross-sectional surveys, in 2012 and 2014, were conducted with representative samples of supervising pharmacists in NYC neighborhoods with high rates of Ct infection. RESULTS: In both survey years, the majority of pharmacists who agreed to participate returned a survey (2012: 81% [83/103], 2014: 61% [106/173]), and pharmacist and pharmacy characteristics were similar across the 2 surveys. Pharmacists' EPT-related knowledge and practice was generally low, with little change between 2012 and 2014. In both years, fewer than half of pharmacists knew EPT was legal (2012, 46%; 2014, 42%). There were even decreases in specific content knowledge; in 2014, significantly fewer of the pharmacists who knew EPT was legal, knew that the initials "EPT" must be written in the body of the prescription (2012: 58%; 2014: 36%, P < 0.05). Most pharmacists in both survey years reported they had never received an EPT prescription, and those who had reported only infrequent receipt. CONCLUSIONS: NYC pharmacists had low levels of knowledge and familiarity with EPT law and reported infrequent receipt of EPT prescriptions. Pharmacists and providers should be further educated about EPT laws and regulations so that prescription-EPT use can be accurately monitored, and to assure the success of this partner treatment strategy.

The study of deep-sea cephalopods.

"Deep-sea" cephalopods are here defined as cephalopods that spend a significant part of their life cycles outside the euphotic zone. In this chapter, the state of knowledge in several aspects of deep-sea cephalopod research are summarized, including information sources for these animals, diversity and general biogeography and life cycles, including reproduction. Recommendations are made for addressing some of the remaining knowledge deficiencies using a variety of traditional and more recently developed methods. The types of oceanic gear that are suitable for collecting cephalopod specimens and images are reviewed. Many groups of deep-sea cephalopods require taxonomic reviews, ideally based on both morphological and molecular characters. Museum collections play a vital role in these revisions, and novel (molecular) techniques may facilitate new use of old museum specimens. Fundamental life-cycle parameters remain unknown for many species; techniques developed for neritic species that could potentially be applied to deep-sea cephalopods are discussed. Reproductive tactics and strategies in deep-sea cephalopods are very diverse and call for comparative evolutionary and experimental studies, but even in the twenty-first century, mature individuals are still unknown for many species. New insights into diet and trophic position have begun to reveal a more diverse range of feeding strategies than the typically voracious predatory lifestyle known for many cephalopods. Regular standardized deep-sea cephalopod surveys are necessary to provide insight into temporal changes in oceanic cephalopod populations and to forecast, verify and monitor the impacts of global marine changes and human impacts on these populations.

Chemoenzymatic Preparation of a Campylobacter jejuni Lipid-Linked Heptasaccharide on an Azide-Linked Polyisoprenoid.

Complex poly- and oligosaccharides on the surface of bacteria provide a unique fingerprint to different strains of pathogenic and symbiotic microbes that could be exploited for therapeutics or sensors selective for specific glycans. To discover reagents that can selectively interact with specific bacterial glycans, a system for both the chemoenzymatic preparation and immobilization of these materials would be ideal. Bacterial glycans are typically synthesized in nature on the C55 polyisoprenoid bactoprenyl (or undecaprenyl) phosphate. However, this long-chain isoprenoid can be difficult to work with in vitro. Here, we describe the addition of a chemically functional benzylazide tag to polyisoprenoids. We have found that both the organic-soluble and water-soluble benzylazide isoprenoid can serve as a substrate for the well-characterized system responsible for Campylobacter jejuni N-linked heptasaccharide assembly. Using the organic-soluble analogue, we demonstrate the use of an N-acetyl-glucosamine epimerase that can be used to lower the cost of glycan assembly, and using the water-soluble analogue, we demonstrate the immobilization of the C. jejuni heptasaccharide on magnetic beads. These conjugated beads are then shown to interact with soybean agglutinin, a lectin known to interact with N-acetyl-galactosamine in the C. jejuni heptasaccharide. The methods provided could be used for a wide variety of applications including the discovery of new glycan-interacting partners.

Pharmacological Interventions for Sialorrhoea in People with Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background/objectives: Sialorrhoea is a common non motor complication experienced by people with Parkinson's disease (PD). Despite its prevalence there is conflicting evidence on how to effectively treat it. Our aim was to establish the efficacy and safety outcomes of pharmacological interventions used to treat sialorrhoea in people with idiopathic PD. Methods: We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42016042470). We searched seven electronic databases from inception until July 2022. Quantitative synthesis was performed where data allowed using random effects models. Results: From 1374 records we included 13 studies (n = 405 participants). Studies were conducted in Europe, North America and China. There was marked heterogeneity in the interventions used, follow up times and outcome measures investigated. The main source of risk of bias identified was reporting bias. Five studies were included in the quantitative synthesis. Summary estimates showed administration of botulinum toxin significantly reduced saliva production, improved patient reported functional outcomes and was associated with an increase in adverse events. Conclusion: Sialorrhoea in PD is an important condition, but current data does not allow for strong recommendations on optimal pharmacological treatments. There is significant heterogeneity in outcomes measures used to evaluate the burden of sialorrhoea with lack of consensus on what constitutes clinically meaningful change. More research is required to better understand the underlying mechanism and potential treatments of sialorrhoea in idiopathic PD.

Exploring Music Therapists' Experiences With and Perceptions About Copyrighted Music: A Thematic Analysis.

Patient-preferred music is often copyrighted music; prior research, however, has paid scant attention to music therapists' understanding and use of copyrighted music. To fill a gap in the literature, this exploratory study sought to understand music therapists' experiences and perceptions about permissible therapeutic uses of copyrighted music. Semi-structured interviews were conducted with 18 board-certified music therapists working in the United States. Collectively, these participants had over 300 years of professional experience. The interview transcripts were analyzed using an inductive approach to thematic analysis. Five main themes were identified: (1) copyright concerns created a complex psychological burden; (2) therapeutic needs warranted use of copyrighted music; (3) perceptions varied on permissible therapeutic practices using copyrighted music; (4) varied sources informed an understanding of copyright law; and (5) copyright clarity was needed to reduce the psychological burden. These themes suggest that psychological stress was produced by copyright uncertainty coupled with attempts by participants to satisfy diverse interests and protect multiple stakeholders, including patients, employers, their profession, and the law. Our findings suggest that a lack of clarity about permissible uses of copyrighted music can complicate music therapists' decision-making about appropriate therapeutic interventions. Clarity on permissible therapeutic uses of music could yield benefits for music therapists, patients, and the community.

Two new species of Iridoteuthis (Cephalopoda: Sepiolidae: Heteroteuthinae) from the southwest Pacific, with a redescription of Stoloteuthis maoria (Dell, 1959).

Examination of the Stoloteuthis maoria (Dell, 1959) type specimens held in the Museum of New Zealand, Te Papa Tongarewa revealed that the two female paratypes were not conspecific with the S. maoria holotype male and belong to the genus Iridoteuthis Naef, 1912. Based on this finding, Stoloteuthis maoria is redescribed here to properly define the male and female characters. Its occurrence in Australian waters is formally recognised for the first time; the species was known previously only from New Zealand. The Iridoteuthis taxon was found to be new and is described as I. merlini, n. sp. Like S. maoria, this new species occurs in New Zealand and southern Australia. A second new Iridoteuthis from New Zealand was also discovered among the Te Papa collection and is described here as I. lophia, n. sp. The sucker pedicels in males of this latter species are highly and uniquely modified.

Copyright as a Barrier to Music Therapy Telehealth Interventions: Qualitative Interview Study.

BACKGROUND: Music therapy is a multifaceted discipline that harnesses the power of music to treat a wide range of patient populations. A therapist who plays music in a private room for a patient is not subject to copyright restrictions on public performances. However, in the wake of the COVID-19 pandemic, music therapy is no longer strictly confined to the face-to-face setting. This study explores music therapists' perceptions of copyright law with respect to their ability to provide mediated services to their clients. OBJECTIVE: The objectives of our study were two-fold. The first was to investigate whether concerns about copyright law are hampering the diffusion of telehealth innovations, and the second was whether these concerns are causing music therapists to avoid therapeutically beneficial telehealth interventions. METHODS: Semistructured interviews were conducted with credentialed music therapists (n=18) in the United States between May 2020 and June 2020. With participants' consent, we used video conference technology to record and transcribe the in-depth interviews. The median interview length was 45 (SD 16.37) minutes. This theoretically informed study employed thematic analysis of the interview data. RESULTS: The COVID-19 pandemic accelerated the adoption of telehealth interventions to facilitate therapy outside of private face-to-face environments: environments where music therapy practices are largely shielded from copyright infringement concerns. Five main themes emerged, including therapists' uncertainty about permissible uses of music and therapists' erring on the side of caution causing lost opportunities for care. Our interview data suggest music therapists have altered telehealth interventions in suboptimal ways to avoid copyright liability in a physically distanced environment. CONCLUSIONS: Some music therapists "drag their feet" on offering therapeutically appropriate telehealth services to clients because of copyright concerns. Our findings suggest innovative mediated therapies were shied away from or abandoned. These findings offer a novel contribution to the public health literature by highlighting copyright law as an unexpected and unwelcome barrier to the diffusion of music therapy practices in technology-mediated settings.

Lipopolysaccharide Is a 4-Aminoarabinose Donor to Exogenous Polyisoprenyl Phosphates through the Reverse Reaction of the Enzyme ArnT.

Modification of the lipid A portion of LPS with cationic monosaccharides provides resistance to polymyxins, which are often employed as a last resort to treat multidrug-resistant bacterial infections. Here, we describe the use of fluorescent polyisoprenoids, liquid chromatography-mass spectrometry, and bacterial genetics to probe the activity of membrane-localized proteins that utilize the 55-carbon lipid carrier bactoprenyl phosphate (BP). We have discovered that a substantial background reaction occurs when B-strain E. coli cell membrane fractions are supplemented with exogenous BP. This reaction involves proteins associated with the arn operon, which is necessary for the covalent modification of lipid A with the cationic 4-aminoarabinose (Ara4N). Using a series of arn operon gene deletion mutants, we identified that the modification was dependent on ArnC, which is responsible for forming BP-linked Ara4N, or ArnT, which transfers Ara4N to lipid A. Surprisingly, we found that the majority of the Ara4N-modified isoprenoid was due to the reverse reaction catalyzed by ArnT and demonstrate this using heat-inactivated membrane fractions, isolated lipopolysaccharide fractions, and analyses of a purified ArnT. This work provides methods that will facilitate thorough and rapid investigation of bacterial outer membrane remodeling and the evaluation of polyisoprenoid precursors required for covalent glycan modifications.

Making the Enterobacterial Common Antigen Glycan and Measuring Its Substrate Sequestration.

The enterobacterial common antigen (ECA), a three-sugar repeat unit polysaccharide produced by Enterobacteriaceae family members, impacts bacterial outer membrane permeability, and its biosynthesis affects the glycan landscape of the organism. ECA synthesis impacts the production of other polysaccharides by reducing the availability of shared substrates, the most notable of which is the 55-carbon polyisoprenoid bactoprenyl phosphate (BP), which serves as a carrier for the production of numerous bacterial glycans including ECA, peptidoglycan, O-antigen, and more. Here, using a combination of in vitro enzymatic synthesis and liquid chromatography-mass spectrometry (LC-MS) analysis of bacterial lysates, we provide biochemical evidence for the effect on endogenous polyisoprenoid pools from cell culture that arises from glycan pathway disruption. In this work, we have cloned and expressed each gene involved in ECA repeat unit biosynthesis and reconstituted the pathway in vitro, providing LC-MS characterized standards for the investigation of cellular glycan-linked intermediates and BP. We then generated ECA deficient mutants in genes associated with production of the polysaccharide, which we suspected would accumulate materials identical to our standards. We found that indeed accumulated products from these cells were indistinguishable from our enzymatically prepared standards, and moreover we observed a concomitant decrease in cellular BP levels with each mutant. This work provides the first direct biochemical evidence for the sequestration of BP upon the genetic disruption of glycan biosynthesis pathways in bacteria. This work also provides methods for the direct assessment of both the ECA glycan, and a new understanding of the dynamic interdependence of the bacterial polysaccharide repertoire.

Children's magazines: reading resources or food marketing tools?

OBJECTIVE: Magazines targeted at children under 12 years old are growing in popularity; past studies have asserted that food items are rarely exposed, but methodological issues may have covered the true extent of covert promotion. The primary purpose of the present study was to quantify the nature and extent of the promotion of branded food products in Australian children's magazines. DESIGN: We conducted a content analysis of possible food promotions in seven top-selling Australian children's magazines published in 2005. In addition to regular food advertisements, the number of advertisements for premiums, editorials, puzzles or games, competitions and branded non-food promotions by food companies was recorded. Category frequencies are reported with a detailed description of the promotions present during September 2005. RESULTS: Only fifty-eight out of the 444 items identified could be classed as regular food advertisements. Several advertisements appeared to be in breach of codes regarding advertising to children and premiums. CONCLUSIONS: The pervasiveness of covert food marketing in the present study was contrary to previous findings and raises questions about the effectiveness of legal restrictions and self-regulation of advertising in protecting children from commercial food messages that may not be regarded as advertising.

New bobtail squid (Sepiolidae: Sepiolinae) from the Ryukyu islands revealed by molecular and morphological analysis.

Bobtail squid are emerging models for host-microbe interactions, behavior, and development, yet their species diversity and distribution remain poorly characterized. Here, we combine mitochondrial and transcriptome sequences with morphological analysis to describe three species of bobtail squid (Sepiolidae: Sepiolinae) from the Ryukyu archipelago, and compare them with related taxa. One Ryukyuan type was previously unknown, and is described here as Euprymna brenneri sp. nov. Another Ryukyuan type is morphologically indistinguishable from Sepiola parva Sasaki, 1913. Molecular analyses, however, place this taxon within the genus Euprymna Steenstrup, 1887, and additional morphological investigation led to formal rediagnosis of Euprymna and reassignment of this species as Euprymna parva comb. nov. While no adults from the third Ryukyuan type were found, sequences from hatchlings suggest a close relationship with E. pardalota Reid, 2011, known from Australia and East Timor. The broadly sampled transcriptomes reported here provide a foundation for future phylogenetic and comparative studies.

The first global deep-sea stable isotope assessment reveals the unique trophic ecology of Vampire Squid Vampyroteuthis infernalis (Cephalopoda).

Vampyroteuthis infernalis Chun, 1903, is a widely distributed deepwater cephalopod with unique morphology and phylogenetic position. We assessed its habitat and trophic ecology on a global scale via stable isotope analyses of a unique collection of beaks from 104 specimens from the Atlantic, Pacific and Indian Oceans. Cephalopods typically are active predators occupying a high trophic level (TL) and exhibit an ontogenetic increase in δ15N and TL. Our results, presenting the first global comparison for a deep-sea invertebrate, demonstrate that V. infernalis has an ontogenetic decrease in δ15N and TL, coupled with niche broadening. Juveniles are mobile zooplanktivores, while larger Vampyroteuthis are slow-swimming opportunistic consumers and ingest particulate organic matter. Vampyroteuthis infernalis occupies the same TL (3.0-4.3) over its global range and has a unique niche in deep-sea ecosystems. These traits have enabled the success and abundance of this relict species inhabiting the largest ecological realm on the planet.

Skills, knowledge, and attitudes expected of a newly-graduated mental health nurse in an inpatient setting.

Mental health nurses (MHN) are at the forefront of care and treatment within acute inpatient settings. Research suggests that newly-graduated MHN are unsure about the skills and knowledge that they are expected to possess, and are expected to practice at a level that they are not prepared for in their undergraduate courses; however, research focusing on competencies for newly-graduated MHN is scarce. This study aimed to identify competencies expected of newly-graduated MHN working in a regional mental health facility in New South Wales, Australia. Eight registered nurses (with varying levels of experience) participated in individual semistructured interviews. Four themes were identified, and termed: communication, safety, self-awareness, and treatment. Within these four themes, 14 competencies were described that detail clear aims for new graduates, provide a better understanding of mental health nursing, and promote specialized and competent practice in mental health.

A new pygmy squid, Idiosepius hallami n. sp. (Cephalopoda: Idiosepiidae) from eastern Australia and elevation of the southern endemic 'notoides' clade to a new genus, Xipholeptos n. gen.

A new species of pygmy squid, Idiosepius hallami n. sp., is described from eastern Australia. It differs from I. notoides Berry, 1921 and I. pygmaeus Steenstrup, 1881 (also found in Australian waters) in a number of traits, including the number of club suckers, shape of the funnel-mantle locking apparatus and the modification of the male hectocotylus. Mitochondrial DNA markers (12S rRNA, 16S rRNA and cytochrome c oxidase subunit 1) indicate that it is also distinct on a molecular level. The new Australian species is also recognised as the taxon from Stradbroke I., Queensland for which the entire mitochondrial genome has been sequenced (Hall et al. 2014). Idiosepius hallami n. sp. is compared with all nominal Idiosepius Steenstrup, 1881 and a current summary of Idiosepius systematics is provided as a basis for future studies. Based on our analyses, we propose the elevation of the 'notoides' clade to the new genus Xipholeptos n. gen., retaining Idiosepius as the genetic epithet for all other nominal idiosepiids. This is supported by: monophyly of the two lineages based on molecular data sets, the level of sequence divergence between these lineages, and morphological differences. The 'notoides' clade is endemic to southern Australia and its basal phylogenetic position suggests that the family may have originated in the Australasian region. Idiosepiids are found in seagrass beds and among mangroves-among the most threatened ecosystems in the world.