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Abstract The tumour microenvironment is infiltrated by immunosuppressive cells, such as regulatory T cells (Tregs), which contribute to tumour escape and impede immunotherapy outcomes. Soluble fibrinogen-like protein 2 (sFGL2), a Treg effector protein, inhibits immune cell populations, via receptors FcγRIIB and FcγRIII, leading to downregulation of CD86 in antigen presenting cells and limiting T cell activation. Increased FGL2 expression is associated with tumour progression and poor survival in several different cancers, such as glioblastoma multiforme, lung, renal, liver, colorectal, and prostate cancer. Querying scRNA-seq human cancer data shows FGL2 is produced by cells in the tumour microenvironment (TME), particularly monocytes and macrophages as well as T cells and dendritic cells (DCs), while cancer cells have minimal expression of FGL2. We studied the role of FGL2 exclusively produced by cells in the TME, by leveraging Fgl2 knockout mice. We tested two murine models of cancer in which the role of FGL2 has not been previously studied: epithelial ovarian cancer and melanoma. We show that absence of FGL2 leads to a more activated TME, including activated DCs (CD86+, CD40+) and T cells (CD25+, TIGIT+), as well as demonstrating for the first time that the absence of FGL2 leads to more activated natural killer cells (DNAM-1+, NKG2D+) in the TME. Furthermore, the absence of FGL2 leads to prolonged survival in the B16F10 melanoma model, while the absence of FGL2 synergizes with oncolytic virus to prolong survival in the ID8-p53 −/− Brca2 −/− ovarian cancer model. In conclusion, targeting FGL2 is a promising cancer treatment strategy alone and in combination immunotherapies.

The Surface Water and Ocean Topography (SWOT) satellite and AirSWOT airborne instrument are the first imaging radar-altimeters designed with near-nadir and low incidence, 35.75 GHz Ka-band InSAR for mapping terrestrial water storage variability. Remotely sensed surface water extents are crucial for assessing such variability but are confounded by emergent and inundated vegetation along shorelines. However, because SWOT-like measurements are novel, there remains some uncertainty in the ability to detect certain land and water classes. This study examines the likelihood of misclassification between 15 land cover types and develops the Ka-band Phenomenology Scattering (KaPS) model to simulate changes to Ka-band backscatter as a result of changing surface water fraction and surface structure, including vegetation morphology and water surface waves. Using a separability metric, the study finds that water is five times more distinct compared with dry land classes, but has the potential to be confused with littoral zone and wet soil cover types. The KaPS scattering model simulates AirSWOT backscatter for incidence angles 1–27°, identifying the conditions under which open water is likely to be confused with littoral zone and wet soil cover types. KaPS characterization of the sensitivity of near-nadir and low incidence Ka-band SAR to small changes in both wet area fraction and surface structure enables a more nuanced classification of inundation area. These results provide additional confidence in the ability of SWOT to classify water inundation extent and open the door for novel hydrological and ecological applications of future Ka-band SAR missions.

Planar cell polarity (PCP) is critical for tissue-wide coordination and successful development. Here Jussila et al. generate a GFP-Vangl2 fusion for live imaging and discover a surprising directionality to the intercellular propagation of cell polarity, and ultimately link PCP defects with idiopathic scoliosis.

IntroductionAdipocytes in the tumour microenvironment are highly dynamic cells that have an established role in tumour progression, but their impact on anti-cancer therapy resistance is becoming increasingly difficult to overlook.MethodsWe investigated the role of adipose tissue and adipocytes in response to oncolytic virus (OV) therapy in adipose-rich tumours such as breast and ovarian neoplasms.ResultsWe show that secreted products in adipocyte-conditioned medium significantly impairs productive virus infection and OV-driven cell death. This effect was not due to the direct neutralization of virions or inhibition of OV entry into host cells. Instead, further investigation of adipocyte secreted factors demonstrated that adipocyte-mediated OV resistance is primarily a lipid-driven phenomenon. When lipid moieties are depleted from the adipocyte-conditioned medium, cancer cells are re-sensitized to OV-mediated destruction. We further demonstrated that blocking fatty acid uptake by cancer cells, in a combinatorial strategy with virotherapy, has clinical translational potential to overcome adipocyte-mediated OV resistance.DiscussionOur findings indicate that while adipocyte secreted factors can impede OV infection, the impairment of OV treatment efficacy can be overcome by modulating lipid flux in the tumour milieu.

Left ventricular assist devices (LVADs) may be used as bridge therapy or destination therapy in heart failure patients. Total joint arthroplasty may improve the functional status of patients limited by arthritis. This retrospective case series evaluated patients with an implanted LVAD who underwent a total joint arthroplasty at 1 institution from 2012 to present. Five patients underwent 12 surgeries with 7 primary arthroplasties and 5 revisions. Their mortality, length of stay, coagulopathic events, incidence of infection or revision arthroplasty, and heart transplantation were evaluated, and is the largest study to date of this population. Two patients expired from thrombotic events while 3 progressed to heart transplantation. Joint arthroplasty is feasible in patients with an implanted LVAD with expected risk and perioperative multidisciplinary collaboration.

Summary: Matching the treatment to an individual patient’s tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelial/mesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an ex vivo tool for personalized medicine.

Genetic variants in CD36 have been associated with metabolic syndrome. Here, the authors found that lymphatic vessel integrity and lipid transport are influenced by CD36 expression, and lymphatic endothelial cell CD36 deficiency causes visceral obesity and insulin resistance, which are risk factors for metabolic syndrome and diabetes.

Using spheroids as a model, the authors report the molecular signatures of ovarian surface epithelial (OSE) cells exhibiting stemness phenotype under various conditions in vitro, and found that there is a large degree of heterogeneity in the transcriptional profiles of stem cells induced under different conditions. They suggest that maintenance of the OSE may not require a single stem cell population, but heterogeneous stem cells that can be induced transiently under diverse environmental cues.

Optical matter consisting of nanoparticle constituents in solution is of key interest due to the exhibited self-assembling mechanisms. The authors propose a principal components analysis based data-driven approach to determine the collective modes of colloidal clusters mimicking optical binding used in colloidal self-assembly.

Background: Brain size has been associated with intelligence of various orders and families of animals, leading to the concept of encephalization. Brain size scales with body weight between species within mammals to approximately the 0.67 power. However, within species, this scaling exponent appears to be much smaller (approximately 0.27 power). Aim: We examined whether this relationship has persisted in dogs over the 120 years since this was originally observed. Methods: Comparative cross-sectional study of magnetic resonance imaging (MRI) data obtained from 127 dogs, compared to historical data from 157 dogs and 24 non-dog canid species. Results: Brain size in dogs measured by MRI had a scaling exponent virtually identical to that observed previously (0.24 vs 0.26). However, the proportionality constant was smaller, suggesting that dogs in the study cohort had relatively smaller brains than the historical cohort. Absolute brain size appeared to have both a lower and upper limit in dogs. When compared to non-dogs canids, the most appropriate “representative” size for a “typical dog” when examining allometric scaling across Canidae appeared to be approximately 10-15 kg. Conclusions: We interpreted the slight reduction in relative brain size to be a function of increased obesity in the study cohort compared to dogs examined 120 years ago. Further, we suggest that dog brains have a finite lower size limit. Finally, concepts of encephalization should not be applied to dogs.

Abstract Background Degenerative myelopathy (DM) in dogs is a progressive neurodegenerative condition that causes white matter spinal cord lesions. These lesions are undetectable on standard magnetic resonance imaging (MRI), limiting diagnosis and monitoring of the disease. Spinal cord lesions cause disruption to the structural integrity of the axons causing water diffusion to become more random and less anisotropic. These changes are detectable by the technique of diffusion tensor imaging (DTI) which is highly sensitive to diffusion alterations secondary to white matter lesion development. Objective Perform spinal DTI on cohorts of dogs with and without DM to identify if lesions caused by DM will cause a detectable alteration in spinal cord diffusivity that correlates with neurological status. Animals Thirteen dogs with DM and 13 aged‐matched controls. Methods All animals underwent MRI with DTI of the entire spine. Diffusivity parameters fractional anisotropy (FA) and mean diffusivity (MD) were measured at each vertebral level and statistically compared between groups. Results Dogs with DM had significant decreases in FA within the regions of the spinal cord that had high expected lesion load. Decreases in FA were most significant in dogs with severe forms of the disease and correlated with neurological grade. Conclusions and Clinical Importance Findings suggest that FA has the potential to be a biomarker for spinal cord lesion development in DM and could play an important role in improving diagnosis and monitoring of this condition.

Abstract Nanocrystalline cellulose (NCC), which is a known crystal nucleating agent, is utilized to improve poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) thermal properties. Since NCC aggregation in PHBV negatively affects composite properties and processability, NCC crystal nucleation effectiveness was examined at low concentrations (

Summary: The emergence of Homo sapiens in Pleistocene Africa is associated with a profound reconfiguration of technology. Symbolic expression and personal ornamentation, new tool forms, and regional technological traditions are widely recognized as the earliest indicators of complex culture and cognition in humans. Here we describe a bone tool tradition from Contrebandiers Cave on the Atlantic coast of Morocco, dated between 120,000–90,000 years ago. The bone tools were produced for different activities, including likely leather and fur working, and were found in association with carnivore remains that were possibly skinned for fur. A cetacean tooth tip bears what is likely a combination of anthropogenic and non-anthropogenic modification and shows the use of a marine mammal tooth by early humans. The evidence from Contrebandiers Cave demonstrates that the pan-African emergence of complex culture included the use of multiple and diverse materials for specialized tool manufacture.

Abstract Populations of many species of grassland‐associated butterflies, moths, and bumblebees in the Great Plains of North America are experiencing steep declines due to habitat loss and degradation—primarily conversion of grasslands to row‐crop agriculture and invasion of woody plants and exotic cool‐season grasses—and insecticide use. These declines are exacerbated by the generally limited dispersal ability of insects, which make local populations susceptible to extirpation following habitat fragmentation. Interest in pollinator conservation has grown substantially in recent years, but information to guide pollinator conservation across the region is limited. We used pollinator biology along with principles of landscape ecology and metapopulation dynamics to develop a simple decision matrix based on patch size and inter‐patch distances to guide landscape‐scale grassland conservation efforts in the U.S. northern Great Plains. When applied to spatial land cover data depicting potential pollinator habitat, the matrix uses landscape characteristics to guide placement of conservation treatments to help ensure persistence of target pollinator populations. Patch size and connectivity thresholds can be set to match characteristics of target species, but in all cases, local management will be necessary to ensure that fine‐grained features such as nectar sources and host plants are present. Applying the matrix to habitat layers for a nine‐state analysis region showed substantial geographic variation in conservation needs, opportunities, and potential treatments. We also demonstrate that non‐native planted cover such as alfalfa and certain grasslands enrolled in the Conservation Reserve Program can substantially enhance landscape structure by increasing grassland patch size and core area while decreasing distance between patches. Pollinators dependent on native prairie will also benefit from planted cover that provides nectar sources and serves as a buffer from pesticides associated with croplands. Consistent with the principles of strategic habitat conservation, targeted monitoring and research will be necessary to validate and adapt the model to meet local conditions.

Improvement and new technologies for effective poly (lactic acid) (PLA) foaming are still in developing. This study examines the ability of biochar (BC) to assist in PLA foaming through a supercritical CO2 batch process. To determine suitable foaming parameters, process optimization was conducted on neat PLA films. BC particles derived from three different sources – sludge (SLG), pistachio shells (PST) and green waste (GW) were ground, and ball milled to a microscale and then blended with PLA. The PLA/BC blends were extruded into films and then batch foamed. The effect of BC was found to be concentration and source dependent. At 0.25 wt%, BC particles were found to be effective nucleating agents showing an increase up to four orders of magnitude in cell density and 10-fold reduction in the mean pore size compared to the neat PLA foams. An increase in BC content to 0.5 and 1 wt% induced particle aggregation, which resulted in non-homogenous foam densities. BC particles derived from SLG were the most effective nucleating agents due to their narrow size distribution, improved dispersibility and mesoporous surface. This work shows that BC can act as an effective bio-derived nucleating agent for PLA.

Pleistocene aeolianite surfaces on the South African coastline, which occur in national parks, other protected areas, as well as unprotected areas, are of profound scientific, cultural, palaeoenvironmental and heritage importance. A threat is posed to these surfaces by the increasing presence of graffiti, which may deface or destroy fossil tracksites and other evidence of events that transpired on these surfaces when they were composed of unconsolidated sand tens of thousands of years ago. Increased awareness of the importance of this heritage resource is desirable, along with the development of strategies to prevent further damage.

Objective Spontaneous brain microhemorrhages in elderly people are present to some degree in Alzheimer’s disease patients but have been linked to brain atrophy in the absence of obvious cognitive decline. Brain microhemorrhages have recently been described in older dogs, but it is unclear whether these are associated with brain atrophy. Diminution of interthalamic adhesion size-as measured on MRI or CT-has been shown to be a reliable indicator of brain atrophy in dogs with canine cognitive dysfunction (CCD) in comparison with successfully aging dogs. We hypothesized that aging dogs with brain microhemorrhages presenting for neurologic dysfunction but without obvious features of cognitive decline would have small interthalamic adhesion measurements, like dogs with CCD, compared with control dogs. The objective of this study was to compare interthalamic adhesion size between three groups of aging (>9 years) dogs: (1) neurologically impaired dogs with presumptive spontaneous brain microhemorrhages and no clinical evidence of cognitive dysfunction (2) dogs with CCD (3) dogs without clinical evidence of encephalopathy on neurologic examination (control dogs). MR images from 52 aging dogs were reviewed and measurements were obtained of interthalamic adhesion height (thickness) and mid-sagittal interthalamic adhesion area for all dogs, in addition to total brain volume. Interthalamic adhesion measurements, either absolute or normalized to total brain volume were compared between groups. Signalment (age, breed, sex), body weight, presence and number of SBMs, as well as other abnormal MRI findings were recorded for all dogs. Results All interthalamic adhesion measurement parameters were significantly (P < 0.05) different between control dogs and affected dogs. Both dogs with cognitive dysfunction (12/15; 80%) and dogs with isolated brain microhemorrhages had more microhemorrhages than control dogs (3/25; 12%). Affected dogs without cognitive dysfunction had significantly more microhemorrhages than dogs with cognitive dysfunction. In addition to signs of cognitive impairment for the CCD group, main clinical complaints for SBM and CCD dogs were referable to central vestibular dysfunction, recent-onset seizure activity, or both. Geriatric dogs with spontaneous brain microhemorrhages without cognitive dysfunction have similar MRI abnormalities as dogs with cognitive dysfunction but may represent a distinct disease category.

Abstract Objective To investigate the histopathologic characteristics of concurrent splenic and liver masses in dogs undergoing splenectomy and liver mass biopsy/resection. Medical records of 125 client-owned dogs found to have splenic mass or masses and a liver mass or masses during surgery were examined. Signalment (age, sex, breed), body weight, and results of histopathology were recorded for all dogs. Results Twenty-seven percent (34/125) of the dogs in this study had no evidence of malignancy in either the liver or the spleen. Sixty of 125 dogs (48.0%) had malignancy in the spleen and liver, and 56 (56/60, 93.3%) of those dogs had the same malignancy in both organs. Signalment was similar to that in other reports of splenic pathology. In this clinical population of dogs, 27% of dogs with concurrent gross splenic and liver masses discovered intraoperatively had benign lesions in both locations and therefore had a favorable prognosis.

Understanding the impact of different bridging groups in the two-step polymerization of poly(ethylene glycol) (PEG)-incorporated polyimide (PI) materials is significant. It is known that the proton exchange membranes (PEMs) used in industry today can experience performance degradation under rising temperature conditions. Many efforts have been devoted to overcoming this problem by improving the physical and mechanical properties that extend the hygrothermal life of a PEM. This work examines the effect of oxygenated and fluorinated bridging anhydrides in the production of PI-PEG PEMs. It is shown that the dianhydride identity and the amount incorporated in the synthesis influences the properties of the segmented block copolymer (SBC) membranes, such as increased ionic liquid uptake (ILU), enhanced conductivity and higher Young’s modulus favoring stiffness comparable to Nafion 115, an industrial standard. Investigations on the ionic conductivity of PI-PEG membranes were carried out to determine how thermal annealing would affect the material’s performance as an ion-exchange membrane. By applying a thermal annealing process at 60 °C for one hour, the conductivities of synthesized segmented block copolymer membranes values were increased. The effect of thermal annealing on the mechanical properties was also shown for the undoped SBC via measuring the change in the Young’s modulus. These higher ILU abilities and mechanical behavior changes are thought to arise from the interaction between PEG molecules and ethylammonium nitrate (EAN) ionic liquid (IL). In addition, higher interconnected routes provide a better ion-transfer environment within the membrane. It was found that the conductivity was increased by a factor of ten for undoped and a factor of two to seven for IL-doped membranes after thermal annealing.

Proton exchange membranes (PEMs) suffer performance degradation under certain conditions—temperatures greater than 80 °C, relative humidity less than 50%, and water retention less than 22%. Novel materials are needed that have improved water retention, stability at higher temperatures, flexibility, conductivity, and the ability to function at low humidity. This work focuses on polyimide-poly(ethylene glycol) (PI-PEG) segmented block copolymer (SBC) membranes with high conductivity and mechanical strength. Membranes were prepared with one of two ionic liquids (ILs), either ethylammonium nitrate (EAN) or propylammonium nitrate (PAN), incorporated within the membrane structure to enhance the proton exchange capability. Ionic liquid uptake capacities were compared for two different temperatures, 25 and 60 °C. Then, conductivities were measured for a series of combinations of undoped or doped unannealed and undoped or doped annealed membranes. Stress and strain tests were performed for unannealed and thermally annealed undoped membranes. Later, these experiments were repeated for doped unannealed and thermally annealed. Mechanical and conductivity data were interpreted in the context of prior small angle X-ray scattering (SAXS) studies on similar materials. We have shown that varying the compositions of polyimide-poly(ethylene glycol) (PI-PEG) SBCs allowed the morphology in the system to be tuned. Since polyimides (PI) are made from the condensation of dianhydrides and diamines, this was accomplished using components having different functional groups. Dianhydrides having either fluorinated or oxygenated functional groups and diamines having either fluorinated or oxygenated diamines were used as well as mixtures of these species. Changing the morphology by creating macrophase separation elevated the IL uptake capacities, and in turn, increased their conductivities by a factor of three or more compared to Nafion 115. The stiffness of the membranes synthesized in this work was comparable to Nafion 115 and, thus, sufficient for practical applications.

AirSWOT is an experimental airborne Ka-band radar interferometer developed by NASA-JPL as a validation instrument for the forthcoming NASA Surface Water and Ocean Topography (SWOT) satellite mission. In 2017, AirSWOT was deployed as part of the NASA Arctic Boreal Vulnerability Experiment (ABoVE) to map surface water elevations across Alaska and western Canada. The result is the most extensive known collection of near-nadir airborne Ka-band interferometric synthetic aperture radar (InSAR) data and derivative high-resolution (3.6 m pixel) digital elevation models to produce water surface elevation (WSE) maps. This research provides a synoptic assessment of the 2017 AirSWOT ABoVE dataset to quantify regional WSE errors relative to coincident in situ field surveys and LiDAR data acquired from the NASA Land, Vegetation, and Ice Sensor (LVIS) airborne platform. Results show that AirSWOT WSE data can penetrate cloud cover and have nearly twice the swath-width of LVIS as flown for ABoVE (3.2 km vs. 1.8 km nominal swath-width). Despite noise and biases, spatially averaged AirSWOT WSEs can be used to estimate sub-seasonal hydrologic variability, as confirmed with field GPS surveys and in situ pressure transducers. This analysis informs AirSWOT ABoVE data users of known sources of measurement error in the WSEs as influenced by radar parameters including incidence angle, magnitude, coherence, and elevation uncertainty. The analysis also provides recommended best practices for extracting information from the dataset by using filters for these four parameters. Improvements to data handing would significantly increase the accuracy and spatial coverage of future AirSWOT WSE data collections, aiding scientific surface water studies, and improving the platform’s capability as an airborne validation instrument for SWOT.

Cerebrospinal fluid flow is crucial for neurodevelopment and homeostasis of the ventricular system of the brain, with localized flow being established by the polarized beating of the ependymal cell (EC) cilia. Here, we report a homozygous one base-pair deletion, c.1193delT (p.Leu398Glnfs*2), in the Kinesin Family Member 6 (KIF6) gene in a child displaying neurodevelopmental defects and intellectual disability. To test the pathogenicity of this novel human KIF6 mutation we engineered an analogous C-terminal truncating mutation in mouse. These mutant mice display severe, postnatal-onset hydrocephalus. We generated a Kif6-LacZ transgenic mouse strain and report expression specifically and uniquely within the ependymal cells (ECs) of the brain, without labeling other multiciliated mouse tissues. Analysis of Kif6 mutant mice with scanning electron microscopy (SEM) and immunofluorescence (IF) revealed specific defects in the formation of EC cilia, without obvious effect of cilia of other multiciliated tissues. Dilation of the ventricular system and defects in the formation of EC cilia were also observed in adult kif6 mutant zebrafish. Finally, we report Kif6-GFP localization at the axoneme and basal bodies of multi-ciliated cells (MCCs) of the mucociliary Xenopus epidermis. Overall, this work describes the first clinically-defined KIF6 homozygous null mutation in human and defines KIF6 as a conserved mediator of neurological development with a specific role for EC ciliogenesis in vertebrates.

Objective: To describe the pharmacokinetic parameters of oral pregabalin in normal cats after single oral dosing.Animals: Six healthy adult research cats.Procedures: Following sedation and indwelling catheter placement, one oral (4 mg/kg) dose of pregabalin was administered. Blood samples were collected at 0, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 h after administration. Plasma pregabalin concentrations were measured by high-performance liquid chromatography and subjected to pharmacokinetic analysis using commercial software.Results: Four of six cats developed moderate sedation after pregabalin administration. The peak pregabalin concentration was 8.3 ± 1.6 μg/ml which occurred at 2.9 ± 1.2 h. Elimination half-life was 10.4 ± 2.6 h and area under the curve was 133.9 ± 71.5 μg-h/ml. Time above the minimum therapeutic concentration for seizure control in dogs and people (2.8 μg/ml) was 17.6 ± 6.2 h. Using these data, predicted minimum, maximum and average steady state concentrations were calculated for 12 and 24 h dosing intervals.Conclusions and Clinical Relevance: Pregabalin (4 mg/kg) administered orally to cats results in plasma concentrations within the range considered to be efficacious for seizure control in dogs and humans between 1.5 and at least 12 h. Because of moderate sedative side effects in the majority of cats at this dose and high calculated maximum steady state concentrations, a lower dose, given more frequently (1–2 mg/kg q 12 h), should be evaluated in prospective clinical studies.

The HIV-1 Tat protein hijacks P-TEFb kinase to activate paused RNA polymerase II (RNAP II) at the viral promoter. Tat binds additional host factors, but it is unclear how they regulate RNAP II elongation. Here, we identify the cytoplasmic ubiquitin ligase UBE2O as critical for Tat transcriptional activity. Tat hijacks UBE2O to ubiquitinate the P-TEFb kinase inhibitor HEXIM1 of the 7SK snRNP, a fraction of which also resides in the cytoplasm bound to P-TEFb. HEXIM1 ubiquitination sequesters it in the cytoplasm and releases P-TEFb from the inhibitory 7SK complex. Free P-TEFb then becomes enriched in chromatin, a process that is also stimulated by treating cells with a CDK9 inhibitor. Finally, we demonstrate that UBE2O is critical for P-TEFb recruitment to the HIV-1 promoter. Together, the data support a unique model of elongation control where non-degradative ubiquitination of nuclear and cytoplasmic 7SK snRNP pools increases P-TEFb levels for transcriptional activation.

The study of plant remains in archaeological sites, along with a better understanding of the use of plants by prehistoric populations, can help us shed light on changes in survival strategies of hunter-gatherers and consequent impacts on modern human cognition, social organization, and technology. The archaeological locality of Pinnacle Point (Mossel Bay, South Africa) includes a series of coastal caves, rock-shelters, and open-air sites with human occupations spanning the Acheulian through Middle Stone Age (MSA) and Later Stone Age (LSA). These sites have provided some of the earliest evidence for complex human behaviour and technology during the MSA. We used phytoliths-amorphous silica particles that are deposited in cells of plants-as a proxy for the reconstruction of past human plant foraging strategies on the south coast of South Africa during the Middle and Late Pleistocene, emphasizing the use and control of fire as well as other possible plant uses. We analysed sediment samples from the different occupation periods at the rock shelter Pinnacle Point 5-6 North (PP5-6N). We also present an overview of the taphonomic processes affecting phytolith preservation in this site that will be critical to conduct a more reliable interpretation of the original plant use in the rock shelter. Our study reports the first evidence of the intentional gathering and introduction into living areas of plants from the Restionaceae family by MSA hunter-gatherers inhabiting the south coast of South Africa. We suggest that humans inhabiting Pinnacle Point during short-term occupation events during Marine Isotope Stage (MIS) 5 built fast fires using mainly grasses with some wood from trees and/or shrubs for specific purposes, perhaps for shellfish cooking. With the onset of MIS 4 we observed a change in the plant gathering strategies towards the intentional and intensive exploitation of dry wood to improve, we hypothesise, combustion for heating silcrete. This human behaviour is associated with changes in stone tool technology, site occupation intensity and climate change.