Unexpected Observation of Disorder and Multiple Phase-Transition Pathways in Shock-Compressed Zr.

The response of materials under dynamic compression involves a complex interplay of various deformation mechanisms aimed at relieving shear stresses, yielding a remarkable diversity in material behavior. In this Letter, we utilize femtosecond x-ray diffraction coupled with nanosecond laser compression to reveal an intricate competition between multiple shear-relieving mechanisms within an elemental metal. Our observations in shocked-compressed single-crystal Zr indicate a disorder-mediated shear relaxation at lower pressures. Above the phase-transition pressure, we observe the increasing contribution of structural phase transition in relieving shear stress. We detect not one but three concurrent pathways during the transition from the hcp to a hex-3 structure. These complex dynamics are partially corroborated through multimillion-atom molecular dynamics simulations employing a machine-learned interatomic potential. Our observation of multiple concurrent pathways and disorder during shock compression underscore the far greater intricacies in the dynamic response of metals than previously assumed.

Material Flow Analysis and Occupational Exposure Assessment in Additive Manufacturing End-of-Life Material Management.

Additive manufacturing (AM) offers a variety of material manufacturing techniques for a wide range of applications across many industries. Most efforts at process optimization and exposure assessment for AM are centered around the manufacturing process. However, identifying the material allocation and potentially harmful exposures in end-of-life (EoL) management is equally crucial to mitigating environmental releases and occupational health impacts within the AM supply chain. This research tracks the allocation and potential releases of AM EoL materials within the US through a material flow analysis. Of the generated AM EoL materials, 58% are incinerated, 33% are landfilled, and 9% are recycled by weight. The generated data set was then used to examine the theoretical occupational hazards during AM EoL material management practices through generic exposure scenario assessment, highlighting the importance of ventilation and personal protective equipment at all stages of AM material management. This research identifies pollution sources, offering policymakers and stakeholders insights to shape pollution prevention and worker safety strategies within the US AM EoL management pathways.

Review of generic scenario environmental release and occupational exposure models used in chemical risk assessment.

Under the Toxic Substances Control Act (TSCA), the United States Environmental Protection Agency (USEPA) is required to determine whether a new chemical substance poses an unreasonable risk to human health or the environment before the chemical is manufactured in or imported into the United States. This manuscript provides a review of the process used to evaluate the risk associated with a chemical based on the scenarios and models used in the evaluation. Specifically, the Generic Scenarios and Emission Scenario Documents developed by the USEPA were reviewed, along with background documentation prepared by USEPA to identify the core elements of the environmental release and occupational exposure scenarios used to assess the risk of the chemical being evaluated. Additionally, this contribution provides an overview of methods used to model occupational exposures and environmental releases as part of the chemical evaluation process used in other jurisdictions, along with work being performed to improve these models. Finally, the alternative methods to evaluate occupational exposures and environmental releases that may be used as part of the decision-making process regarding a chemical are identified. The contribution provides a path forward for reducing the time required and improving the chemical evaluation of the unreasonable risk determination regarding the manufacture or import of a chemical.

Quantitative analysis of diffraction by liquids using a pink-spectrum X-ray source.

A new approach for performing quantitative structure-factor analysis and density measurements of liquids using X-ray diffraction with a pink-spectrum X-ray source is described. The methodology corrects for the pink beam effect by performing a Taylor series expansion of the diffraction signal. The mean density, background scale factor, peak X-ray energy about which the expansion is performed, and the cutoff radius for density measurement are estimated using the derivative-free optimization scheme. The formalism is demonstrated for a simulated radial distribution function for tin. Finally, the proposed methodology is applied to experimental data on shock compressed tin recorded at the Dynamic Compression Sector at the Advanced Photon Source, with derived densities comparing favorably with other experimental results and the equations of state of tin.

Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion.

Therapies using mesenchymal stromal cells (MSCs) to treat immune and inflammatory conditions are now at an exciting stage of development, with many MSC-based products progressing to phase II and III clinical trials. However, a major bottleneck in the clinical translation of allogeneic MSC therapies is the variable immunomodulatory properties of MSC products due to differences in their tissue source, donor heterogeneity and processes involved in manufacturing and banking. This variable functionality of MSC products likely contributes to the substantial inconsistency observed in the clinical outcomes of phase III trials of MSC therapies; several trials have failed to reach the primary efficacy endpoint. In this review, we discuss various strategies to consistently maintain or enhance the immunomodulatory potency of MSCs during ex vivo expansion, which will enable the manufacture of allogeneic MSC banks that have high potency and low variability. Biophysical and biochemical priming strategies, the use of culture additives such as heparan sulfates, and genetic modification can substantially enhance the immunomodulatory properties of MSCs during in vitro expansion. Furthermore, robust donor screening, the use of biomarkers to select for potent MSC subpopulations, and rigorous quality testing to improve the release criteria for MSC banks have the potential to reduce batch-to-batch heterogeneity and enhance the clinical efficacy of the final MSC product. Machine learning approaches to develop predictive models of individual patient response can enable personalized therapies and potentially establish correlations between in vitro potency measurements and clinical outcomes in human trials.

Heparin-Induced Thrombocytopenia: A Management Review for Nurses.

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse drug reaction that relies on quick assessment and treatment by the health care team to prevent poor outcomes. Nurses can play a critical role in recognizing disease, advocating for patients, and facilitating treatment by being familiar with current guideline recommendations and risk stratification approaches. The purpose of this article is to review management of HIT including pathogenesis, clinical presentation, current guideline recommendations for risk assessment, laboratory testing, and treatment, as well as discuss nonheparin anticoagulation options that may be ordered when HIT is suspected.

Characterization of a Giant PSI Supercomplex in the Symbiotic Dinoflagellate Symbiodiniaceae.

Symbiodiniaceae are symbiotic dinoflagellates that provide photosynthetic products to corals. Because corals are distributed across a wide range of depths in the ocean, Symbiodiniaceae species must adapt to various light environments to optimize their photosynthetic performance. However, as few biochemical studies of Symbiodiniaceae photosystems have been reported, the molecular mechanisms of photoadaptation in this algal family remain poorly understood. Here, to investigate the photosynthetic machineries in Symbiodiniaceae, we purified and characterized the PSI supercomplex from the genome-sequenced Breviolum minutum (formerly Symbiodinium minutum). Mass spectrometry analysis revealed 25 light-harvesting complexes (LHCs), including both LHCF and LHCR families, from the purified PSI-LHC supercomplex. Single-particle electron microscopy showed unique giant supercomplex structures of PSI that were associated with the LHCs. Moreover, the PSI-LHC supercomplex contained a significant amount of the xanthophyll cycle pigment diadinoxanthin. Upon high light treatment, B. minutum cells showed increased nonphotochemical quenching, which was correlated with the conversion of diadinoxanthin to diatoxanthin, occurring preferentially in the PSI-LHC supercomplex. The possible role of PSI-LHC in photoprotection in Symbiodiniaceae is discussed.

Structural determination of the large photosystem II-light-harvesting complex II supercomplex of Chlamydomonas reinhardtii using nonionic amphipol.

In photosynthetic organisms, photosystem II (PSII) is a large membrane protein complex, consisting of a pair of core complexes surrounded by an array of variable numbers of light-harvesting complex (LHC) II proteins. Previously reported structures of the PSII-LHCII supercomplex of the green alga Chlamydomonas reinhardtii exhibit significant structural heterogeneity, but recently improved purification methods employing ionic amphipol A8-35 have enhanced supercomplex stability, providing opportunities for determining a more intact structure. Herein, we present a 5.8 Å cryo-EM map of the C. reinhardtii PSII-LHCII supercomplex containing six LHCII trimers (C2S2M2L2). Utilizing a newly developed nonionic amphipol-based purification and stabilizing method, we purified the largest photosynthetic supercomplex to the highest percentage of the intact configuration reported to date. We found that the interprotein distances within the light-harvesting complex array in the green algal photosystem are larger than those previously observed in higher plants, indicating that the potential route of energy transfer in the PSII-LHCII supercomplex in green algae may be altered. Interestingly, we also observed an asymmetric PSII-LHCII supercomplex structure comprising C2S2M1L1 in the same sample. Moreover, we found a new density adjacent to the PSII core complex, attributable to a single-transmembrane helix. It was previously unreported in the cryo-EM maps of PSII-LHCII supercomplexes from land plants.

Ten antenna proteins are associated with the core in the supramolecular organization of the photosystem I supercomplex in Chlamydomonas reinhardtii.

Photosystem I (PSI) is a large pigment-protein complex mediating light-driven charge separation and generating a highly negative redox potential, which is eventually utilized to produce organic matter. In plants and algae, PSI possesses outer antennae, termed light-harvesting complex I (LHCI), which increase the energy flux to the reaction center. The number of outer antennae for PSI in the green alga Chlamydomonas reinhardtii is known to be larger than that of land plants. However, their exact number and location remain to be elucidated. Here, applying a newly established sample purification procedure, we isolated a highly pure PSI-LHCI supercomplex containing all nine LHCA gene products under state 1 conditions. Single-particle cryo-EM revealed the 3D structure of this supercomplex at 6.9 Å resolution, in which the densities near the PsaF and PsaJ subunits were assigned to two layers of LHCI belts containing eight LHCIs, whereas the densities between the PsaG and PsaH subunits on the opposite side of the LHCI belt were assigned to two extra LHCIs. Using single-particle cryo-EM, we also determined the 2D projection map of the lhca2 mutant, which confirmed the assignment of LHCA2 and LHCA9 to the densities between PsaG and PsaH. Spectroscopic measurements of the PSI-LHCI supercomplex suggested that the bound LHCA2 and LHCA9 proteins have the ability to increase the light-harvesting energy for PSI. We conclude that the PSI in C. reinhardtii has a larger and more distinct outer-antenna organization and higher light-harvesting capability than that in land plants.

Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia.

BACKGROUND AND PURPOSE: Although VEGF165 (vascular endothelial growth factor-165) is able to enhance both angiogenesis and neurogenesis, it also increases vascular permeability through the blood-brain barrier. Heparan sulfate (HS) sugars play important roles in regulating VEGF bioactivity in the pericellular compartment. Here we asked whether an affinity-purified VEGF165-binding HS (HS7) could augment endogenous VEGF activity during stroke recovery without affecting blood-brain barrier function. METHODS: Both rat brain endothelial cell line 4 and primary rat neural progenitor cells were used to evaluate the potential angiogenic and neurogenic effects of HS7 in vitro. For in vivo experiments, male Sprague-Dawley rats were subjected to 100 minutes of transient focal cerebral ischemia, then treated after 4 days with either PBS or HS7. One week later, infarct volume, behavioral sequelae, immunohistochemical markers of angiogenesis and neural stem cell proliferation were assessed. RESULTS: HS7 significantly enhanced VEGF165-mediated angiogenesis in rat brain endothelial cell line 4 brain endothelial cells, and increased the proliferation and differentiation of primary neural progenitor cells, both via the VEGFR2 (vascular endothelial growth factor receptor 2) pathway. Intracerebroventricular injection of HS7 improved neurological outcome in ischemic rats without changing infarct volumes. Immunostaining of the compromised cerebrum demonstrated increases in collagen IV/Ki67 and nestin/Ki67 after HS7 exposure, consistent with its ability to promote angiogenesis and neurogenesis, without compromising blood-brain barrier integrity. CONCLUSIONS: A VEGF-activating glycosaminoglycan sugar, by itself, is able to enhance endogenous VEGF165 activity during the post-ischemic recovery phase of stroke.

Bringing Heparan Sulfate Glycomics Together with Proteomics for the Design of Novel Therapeutics: A Historical Perspective.

Increasing knowledge of how peptides bind saccharides, and of how saccharides bind peptides, is starting to revolutionize understanding of cell-extracellular matrix relationships. Here, a historical perspective is taken of the relationship between heparan sulfate glycosaminoglycans and how they interact with peptide growth factors in order to both drive and modulate signaling through the appropriate cognate receptors. Such knowledge is guiding the preparation of targeted sugar mimetics that will impact the treatment of many different kinds of diseases, including cancer.

Small Molecule Antagonist of Cell Surface Glycosaminoglycans Restricts Mouse Embryonic Stem Cells in a Pluripotent State.

Recently, the field of stem cell-based regeneration has turned its attention toward chemical approaches for controlling the pluripotency and differentiation of embryonic stem cells (ESCs) using drug-like small molecule modulators. Growth factor receptors or their associated downstream kinases that regulate intracellular signaling pathways during differentiation are typically the targets for these molecules. The glycocalyx, which plays an essential role in actuating responses to growth factors at the cellular boundary, offers an underexplored opportunity for intervention using small molecules to influence differentiation. Here, we show that surfen, an antagonist of cell-surface glycosaminoglycans required for growth factor association with cognate receptors, acts as a potent and general inhibitor of differentiation and promoter of pluripotency in mouse ESCs. This finding shows that drugging the stem cell Glycome with small molecules to silence differentiation cues can provide a powerful new alternative to existing techniques for controlling stem cell fate. Stem Cells 2018;36:45-54.

Motivations for being informal carers of people living with dementia: a systematic review of qualitative literature.

BACKGROUND: Informal, often family carers play a vital role in supporting people living with dementia in the community. With ageing populations, the part played by these carers is increasing making it important that we understand what motivates them to take on the role. This systematic review aimed to identify and synthesise qualitative literature describing what motivates people to care for someone with dementia. METHODS: The review followed the Centre for Reviews and Dissemination (CRD) guidelines. Six electronic databases were searched from their first records until August 2018. Synthesis was narrative. RESULTS: Twenty-six studies fitting the inclusion criteria were identified. Carers described multiple, inter-related motives for caring for someone with dementia. Caring was generally described as a reflection of long-standing family relationships between carers and the care recipients, whether by blood or marriage. Commonly offered motivations included love, reciprocity, filial piety, duty and obligation. CONCLUSIONS: Perhaps the most striking finding was the similarity in these motivations irrespective of gender or relationship with the care recipient. Family relationship and shared history underlay most motivations. Future research should include more longitudinal studies incorporating within study comparisons between different demographic groups to give greater confidence in identifying similarities and differences between demographic groups.

A qualitative study exploring therapists' experiences of implementing a complex intervention promoting meaningful activity for residents in care homes.

OBJECTIVES:: To explore the experiences of occupational therapists and physiotherapists and to reveal any factors that can facilitate delivering a complex care home intervention promoting meaningful activity. DESIGN:: Qualitative interview study using data from three focus groups conducted longitudinally post intervention implementation. Data were analysed thematically. SETTING:: Three residential care homes in South London, UK. SUBJECTS:: All therapists involved in the implementation of the intervention: three occupational therapists and three physiotherapists. RESULTS:: Three interconnected themes emerged from the analysis: (1) developing trusting relationships, (2) empowering staff and (3) remaining flexible. Therapists described how successfully implementing a complex care home intervention was dependant on developing trusting relationships with care staff. This enabled the therapists to empower care staff to take ownership of the intervention and help embed it in care home culture, facilitating long-term change. The therapists described how remaining flexible in their approach helped keep care staff engaged for the duration of implementation. CONCLUSION:: This study has revealed several important factors that can help facilitate therapists delivering complex interventions in care homes.

Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate.

Peripheral arterial disease is a major cause of limb loss and its prevalence is increasing worldwide. As most standard-of-care therapies yield only unsatisfactory outcomes, more options are needed. Recent cell- and molecular-based therapies that have aimed to modulate vascular endothelial growth factor-165 (VEGF165) levels have not yet been approved for clinical use due to their uncertain side effects. We have previously reported a heparan sulphate (termed HS7) tuned to avidly bind VEGF165. Here, we investigated the ability of HS7 to promote vascular recovery in a murine hindlimb vascular ischaemia model. HS7 stabilised VEGF165 against thermal and enzyme degradation in vitro, and isolated VEGF165 from serum via affinity-chromatography. C57BL6 mice subjected to unilateral hindlimb ischaemia injury received daily intramuscular injections of respective treatments (n = 8) and were assessed over 3 weeks by laser Doppler perfusion, magnetic resonance angiography, histology and the regain of function. Mice receiving HS7 showed improved blood reperfusion in the footpad by day 7. In addition, they recovered hindlimb blood volume two- to fourfold faster compared to the saline group; the greatest rate of recovery was observed in the first week. Notably, 17% of HS7-treated animals recovered full hindlimb function by day 7, a number that grew to 58% and 100% by days 14 and 21, respectively. This was in contrast to only 38% in the control animals. These results highlight the potential of purified glycosaminoglycan fractions for clinical use following vascular insult, and confirm the importance of harnessing the activity of endogenous pro-healing factors generated at injury sites.

Monitoring the sustainable development goals through human rights accountability reviews.

The Universal Periodic Review is a comprehensive, state-to-state peer-review mechanism of the United Nations (UN) Human Rights Council. Created in 2006, the mechanism scrutinizes the human rights record of all UN Member States, including their efforts to realize the right to health. However, the mechanism is relatively under-used in global health governance compared to treaty-based procedures, such as those overseen by the Committee on the Rights of Persons with Disabilities or the Committee on the Elimination of Discrimination against Women. We suggest that the Universal Periodic Review could be used to support the monitoring and review processes of the sustainable development goals (SDGs). The review could offer a unique perspective for other actors on how to ensure accountability for the complex and intertwined SDGs, including their commitments for health. This article provides an overview of how health-related rights have been addressed in the Universal Periodic Review process and how the review can contribute to advancing global commitments to health, including those embodied in the SDGs. We present some of the current limitations in the way health is addressed in the Universal Periodic Review. We also consider what role specialized UN agencies, such as the World Health Organization, might play during the Universal Periodic Review process and how this involvement can contribute towards the comprehensive realization of health and wellbeing for all.

L'Examen périodique universel est un mécanisme complet d'évaluation entre États du Conseil des droits de l'homme des Nations Unies (ONU). Créé en 2006, ce mécanisme passe en revue les réalisations de l'ensemble des États membres de l'ONU dans le domaine des droits de l'homme, et notamment leurs efforts en faveur de l'application du droit à la santé. Ce mécanisme est néanmoins relativement sous-utilisé dans la gouvernance de la santé mondiale par rapport aux procédures fondées sur des traités comme celles supervisées par le Comité des droits des personnes handicapées ou le Comité pour l'élimination de la discrimination à l'égard des femmes. Nous suggérons d'utiliser l'Examen périodique universel pour soutenir les processus de suivi et d'examen des objectifs de développement durable (ODD). L'examen pourrait offrir une perspective unique à d'autres acteurs sur la façon de garantir le principe de responsabilité pour les ODD, complexes et interdépendants, et notamment leurs engagements en matière de santé. Cet article fournit un aperçu de la façon dont les droits liés à la santé sont traités dans le cadre de l'Examen périodique universel et de la façon dont l'examen peut contribuer à faire avancer les engagements mondiaux en faveur de la santé, et notamment ceux inclus dans les ODD. Nous présentons quelques-unes des limites actuelles de l'Examen périodique universel concernant la façon dont il traite de la santé. Nous avons également étudié le rôle que peuvent jouer certaines institutions spécialisées des Nations Unies, telles que l'Organisation mondiale de la Santé, dans le cadre de l'Examen périodique universel, et en quoi ce rôle peut contribuer à l'atteinte de l'objectif de la santé et du bien-être pour tous.

La Revisión periódica universal es un mecanismo integral de revisión entre pares de estado a estado del Consejo de Derechos Humanos de las Naciones Unidas (ONU). Creado en 2006, el mecanismo examina el historial relativo a los derechos humanos de todos los Estados Miembros de las Naciones Unidas, incluidos sus esfuerzos por cumplir el derecho a la salud. Sin embargo, el mecanismo está relativamente infrautilizado en la gobernanza de la salud mundial en comparación con los procedimientos basados en tratados, como los supervisados por el Comité sobre los Derechos de las Personas con Discapacidad o el Comité para la Eliminación de la Discriminación contra la Mujer. Se sugiere que la Revisión periódica universal se utilice para apoyar los procesos de seguimiento y revisión de los objetivos de desarrollo sostenible (ODS). La revisión podría ofrecer una perspectiva única para otros participantes sobre cómo asegurar la responsabilidad de los complejos y vinculados ODS, incluyendo sus compromisos con la salud. Este artículo ofrece una visión general de cómo se han abordado los derechos relacionados con la salud en el proceso de la Revisión periódica universal y cómo la misma puede contribuir al avance de los compromisos mundiales con la salud, incluidos los incorporados en los ODS. Se presentan algunas de las limitaciones actuales en la forma en que se aborda la salud en la Revisión periódica universal. También se valora qué papel podrían desempeñar los organismos especializados de las Naciones Unidas, como la Organización Mundial de la Salud, durante el proceso de la Revisión periódica universal y cómo esta participación puede contribuir a la realización integral de la salud y el bienestar para todos.

The principles and practice of open fracture care, 2018.

The principles of open fracture management are to manage the overall injury and specifically prevent primary contamination becoming frank infection. The surgical management of these complex injuries includes debridement & lavage of the open wound with combined bony and soft tissue reconstruction. Good results depend on early high quality definitive surgery usually with early stable internal fixation and associated soft tissue repair. While all elements of the surgical principles are very important and depend on each other for overall success the most critical element appears to be achieving very early healthy soft tissue cover. As the injuries become more complex this involves progressively more complex soft tissue reconstruction and may even requiring urgent free tissue transfer requiring close co-operative care between orthopaedic and plastic surgeons. Data suggests that the best results are obtained when the whole surgical reconstruction is completed within 48-72 h.

A qualitative study of carers' experiences of dementia cafés: a place to feel supported and be yourself.

BACKGROUND: Unpaid, informal carers or caregivers play an important role in supporting people living with dementia but the role can be challenging and carers themselves may benefit from support. Alzheimer's, dementia or memory cafés are one such form of support . These cafés are usually provided in the voluntary sector and are a place where people with dementia and those supporting them, usually family carers, can meet with others in similar situations. METHODS: Using semi-structured interviews, this qualitative study explored the experiences of 11 carers from five dementia cafés in and around London, England. RESULTS: Thematic analysis resulted in the identification of four key themes. Cafés provide a relaxed, welcoming atmosphere where carers can go where they feel supported and accepted. Café attendance often brought a sense of normality to these carers' lives. Carers and those they care for look forward to going and often enjoy both the activities provided and socialising with others. Other highlighted benefits included peer support from other carers, information provision and support from the volunteer café coordinators. Despite diversity in how the cafés were run and in the activities offered, there were many reported similarities amongst carers in the value ascribed to attending the cafés. CONCLUSIONS: Dementia cafés appear to be a valuable, perhaps unique form of support for carers giving them brief respite from their caring role. Future research incorporating mixed methods is needed to understand the perspectives of those living with dementia.

Mining Available Data from the United States Environmental Protection Agency to Support Rapid Life Cycle Inventory Modeling of Chemical Manufacturing.

Demands for quick and accurate life cycle assessments create a need for methods to rapidly generate reliable life cycle inventories (LCI). Data mining is a suitable tool for this purpose, especially given the large amount of available governmental data. These data are typically applied to LCIs on a case-by-case basis. As linked open data becomes more prevalent, it may be possible to automate LCI using data mining by establishing a reproducible approach for identifying, extracting, and processing the data. This work proposes a method for standardizing and eventually automating the discovery and use of publicly available data at the United States Environmental Protection Agency for chemical-manufacturing LCI. The method is developed using a case study of acetic acid. The data quality and gap analyses for the generated inventory found that the selected data sources can provide information with equal or better reliability and representativeness on air, water, hazardous waste, on-site energy usage, and production volumes but with key data gaps including material inputs, water usage, purchased electricity, and transportation requirements. A comparison of the generated LCI with existing data revealed that the data mining inventory is in reasonable agreement with existing data and may provide a more-comprehensive inventory of air emissions and water discharges. The case study highlighted challenges for current data management practices that must be overcome to successfully automate the method using semantic technology. Benefits of the method are that the openly available data can be compiled in a standardized and transparent approach that supports potential automation with flexibility to incorporate new data sources as needed.

Structural determinants of heparin-transforming growth factor-ß1 interactions and their effects on signaling.

Transforming growth factor-ß1 (TGF-ß1, Uniprot: P01137) is a heparin-binding protein that has been implicated in a number of physiological processes, including the initiation of chondrogenesis by human mesenchymal stem cells (hMSCs). Here, we identify the molecular features in the protein and in heparin required for binding and their effects on the potentiation of TGF-ß1's activity on hMSCs. Using a proteomics "Protect and Label" approach, lysines K291, K304, K309, K315, K338, K373, K375 and K388 were identified as being directly involved in binding heparin (Data are available via ProteomeXchange with identifier PXD002772). Competition assays in an optical biosensor demonstrated that TGF-ß1 does require N- and 6-O-sulfate groups for binding but that 2-O-sulfate groups are unlikely to underpin the interaction. Heparin-derived oligosaccharides as short as degree of polymerization (dp) 4 have a weak ability to compete for TGF-ß1 binding to heparin, which increases with the length of the oligosaccharide to reach a maximum between dp18 and dp24. In cell-based assays, heparin, 2-O-, 6-O- and N-desulfated re-N-acetylated heparin and oligosaccharides 14-24 saccharides (dp14-24) in length all increased the phosphorylation of mothers against decapentaplegic homolog 2 (SMAD2) after 6 h of stimulation with TGF-ß1. The results provide the structural basis for a model of heparin/heparan sulfate binding to TGF-ß1 and demonstrate that the features in the polysaccharide required for binding are not identical to those required for sustaining the signaling by TGF-ß1 in hMSCs.