CAR-Expressing Natural Killer Cells for Cancer Retargeting

Since the approval in 2017 and the outstanding success of Kymriah® and Yescarta®, the number of clinical trials investigating the safety and efficacy of chimeric antigen receptormodified autologous T cells has been constantly rising. Currently, more than 200 clinical trials are listed on clinicaltrial. gov. In contrast to CAR-T cells, natural killer (NK) cells can be used from allogeneic donors as an “off the shelf product” and provide alternative candidates for cancer retargeting. This review summarises preclinical results of CAR-engineered NK cells using both primary human NK cells and the cell line NK-92, and provides an overview about the first clinical CAR-NK cell studies targeting haematological malignancies and solid tumours, respectivel

Harpacticoida (Copepoda) in the plankton of Ushuaia and Golondrina Bays, Beagle Channel, Argentina

Harpacticoid copepods form a diverse and abundant group of the meiofauna in marine benthic habitats. Moreover, harpacticoids are frequently found in planktonic samples particularly in shallow and algae-covered coastal waters. Despite their high abundance, little is known about their taxonomy and importance as a component of the food web in the Southern bays of Argentina. Mesozooplankton samples and environmental data were obtained seasonally from Ushuaia and Golondrina Bays (August 2004 to June 2005) and analyzed for the composition and abundance of harpacticoid copepods. Remarkable seasonal changes in the harpacticoid communities were observed. In Ushuaia Bay, nitrogenated nutrients, chlorophyll a, salinity, and temperature were the prevailing environmental parameters that influenced the harpacticoid community, giving rise to different harpacticoid assemblages. The results highlight the importance of the community of Harpacticoida in both bays and provide background data for further studies on zooplankton communities and monitoring programs in marine systems.Fil: Biancalana, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Veit Köhler, G.. German Centre for Integrative Biodiversity Research; AlemaniaFil: Fricke, Anna Lena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Leibniz Centre for Tropical Marine Research; AlemaniaFil: Berasategui, Anabela Anhi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentin

Effect of Narrowband UV-B Irradiation on the Growth Performance of House Crickets

Indoor co-cultivation systems can answer to the need for sustainable and resilient food production systems. Rearing organisms under light-emitting diodes (LEDs) irradiation provides the possibility to control and shape the emitted light spectra. UV-B-irradiation (280–315 nm) can positively affect the nutritional composition of different plants and other organisms, whereas information on edible insects is scarce. To evaluate the potential effect of the photosynthetically active radiation (PAR) and LED-emitting LEDs on the rearing and nutritional quality of edible insects, house crickets (Acheta domesticus) were reared from the age of 21 days under controlled LED spectra, with an additional UV-B (0.08 W/m2) dose of 1.15 KJm2 d−1 (illuminated over a period for 4 h per day) for 34 days. UV-B exposure showed no harm to the weight of the crickets and significantly increased their survival by ca. 10% under narrowband UV-B treatment. The nutritional composition including proteins, fat and chitin contents of the insects was not affected by the UV-B light and reached values of 60.03 ± 10.41, 22.38 ± 2.12 and 9.33 ± 1.21%, respectively, under the LED irradiation. Therefore, house crickets can grow under LED irradiation with a positive effect of narrowband UV-B application on their survival

Doublesex regulates male-specific differentiation during distinct developmental time windows in a parasitoid wasp

Sexually dimorphic traits in insects are subject to sexual selection, but our knowledge of the underlying molecular mechanisms is still scarce. Here we investigate how the highly conserved gene, Doublesex (Dsx), is involved in shaping sexual dimorphism in the model parasitoid wasp Nasonia vitripennis (Hymenoptera: Pteromalidae). First, we present the revised Dsx gene structure including an alternative transcription start, and two additional male NvDsx transcript isoforms. We show sex-specific NvDsx expression and splicing throughout development, and demonstrate that transient NvDsx silencing in different male developmental stages shifts two sexually dimorphic traits from male to female morphology, with the effect being dependent on the timing of silencing. In addition, we determined the effect of NvDsx on the development of reproductive organs. Transient silencing of NvDsx in early male larvae affects the growth and differentiation of the internal and external reproductive tissues. We did not observe phenotypic changes in females after NvDsx silencing. Our results indicate that male NvDsx is required to suppress female-specific traits and/or to promote male-specific traits during distinct developmental windows. This provides new insights into the regulatory activity of Dsx during male wasp development in the Hymenoptera.</p

Chitin determination on marine seston in a shallow temperate estuary (Argentina)

A quitina é um dos biopolímeros mais abundantes no planeta. A quitina foi quantificada em frações do seston, com a finalidade de obter a primeira caracterização deste polímero no Estuário de Bahía Blanca. A amostragem foi realizada durante o inverno e o verão em dois locais: em um canal de maré não impactado (Bahía del Medio, BM) e em um setor de descarga de esgoto (Canal Vieja, CV). Os maiores valores de quitina foram observados na fração seston ; 500 µM) não excederam ~ 1% de quitina total. A maior concentração de quitina no seston < 20 µM sugere que essa fração é um grande reservatório deste biopolímero, contribuindo para a matéria orgânica para os microorganismos na cadeia alimentar do Estuário de Bahía Blanca. Este é o primeiro estudo sobre as possíveis fontes de quitina em ecossistemas marinhos na Argentina.Chitin is one of the most abundant biopolymers in the planet. Chitin was quantified in seston fractions in order to obtain the first characterization of this polymer in the Bahía Blanca Estuary. Sampling was conducted at two sites: a non- impacted tidal channel -Bahía del Medio (BM)- and a sewage discharge sector -Canal Vieja (CV)-, during winter and summer. The highest values of chitin were observed in the seston fraction ;500 µm) did not exceed ~1% of total chitin.. The higher concentration of chitin in sesto

State of knowledge regarding the potential of macroalgae cultivation in providing climate-related and other ecosystem services

Macroalgae (or seaweed) aquaculture can potentially provide many ecosystem services, including climate change mitigation, coastal protection, preservation of biodiversity and improvement of water quality. Nevertheless, there are still many constraints and knowledge gaps that need to be overcome, as well as potential negative impacts or scale-dependent effects that need to be considered, before macroalgae cultivation in Europe can be scaled up successfully and sustainably. To investigate these uncertainties, the Expert Working Group (EWG) on Macroalgae was established. Its role was to determine the state of knowledge regarding the potential of macroalgae culture in providing climate-related and other ecosystem services (ES) and to identify specific knowledge gaps that must be addressed before harvesting this potential. The methodological framework combined a multiple expert consultation with Delphi process and a Quick Scoping Review (QSR). To analyse the outcome of both approaches, the EWG classified the findings under the categories Political, Environmental, Social, Technical, Economic and Legal (PESTEL approach) and categorised the ES based on the CICES 5.1 classification. Although representative stakeholders from many different disciplines were contacted, the majority of responses to the Delphi process were from representatives of academia or research. While the results of each method differed in many ways, both methods identified the following top six ecosystem services provided by seaweed cultivation: i) provisioning food, ii) provisioning hydrocolloids and feed, iii) regulating water quality, iv) provisioning habitats, v) provisioning of nurseries and vi) regulating climate. Diverse technological knowledge gaps were identified by both methods at all scales of the macroalgae cultivation process, followed by economic and environmental knowledge gaps depending on the method used. Based on suggestions from the expert respondents in the Delphi process, there is a clear need for an European-wide strategy for reducing risks for seaweed producers, providing clear standards and guidelines for obtaining permits, and providing financial support to improve technological innovation, that will ensure consistent quality. Legal (e.g., safety regulations), economic (e.g., lack of demand for seaweeds in many countries) and technological (e.g., production at large scale) constraints represented almost 70% of the total responses in the Delphi process, whereas environmental and technical constraints were more dominant in the literature. The most commonly identified potential negative impacts of macroalgae cultivation both among the expert responses and the reviewed articles were unknown environmental impacts, e.g. to deep sea, benthic and pelagic ecosystems. The present study provides an assessment of the state of knowledge regarding ES provided by seaweed cultivation and identifies the associated knowledge gaps, constraints and potential negative impacts. One of the main hurdles recognised by the EWG was the understanding of ES themselves by the different stakeholders, as well as the issue of scale. Studies providing clear evidence of ES provided by seaweed cultivation and/or valorisation of these services were lacking in the literature, and some aspects, like cultural impact etc. were missing in the responses to the questionnaires during the Delphi process. The issue of scale and scaling-up was omnipresent both in assessing the ES provided by seaweed cultivation and in identifying knowledge gaps, constraints and potential negative impacts. For example, the ES provided will depend on the scale of cultivation, the main technological knowledge gaps were often related to scale of cultivation. Likewise at a large scale of operations, there could be multiple associated potential side effects, which need to be further investigated. Based on the outcomes of this investigation, we provide an outlook with open questions that need to be answered to support the sustainable scaling-up of seaweed cultivation in Europe

The Epitope-Specific Anti-human CD4 Antibody MAX.16H5 and Its Role in Immune Tolerance

T cell modulation in the clinical background of autoimmune diseases or allogeneic cell and organ transplantations with concurrent preservation of their natural immunological functions (e.g., pathogen defense) is the major obstacle in immunology. An anti-human CD4 antibody (MAX.16H5) was applied intravenously in clinical trials for the treatment of autoimmune diseases (e.g., rheumatoid arthritis) and acute late-onset rejection after transplantation of a renal allograft. The response rates were remarkable and no critical allergic problems or side effects were obtained. During the treatment of autoimmune diseases with the murine MAX.16H5 IgG1 antibody its effector mechanisms with effects on lymphocytes, cytokines, laboratory and clinical parameters, adverse effects as well as pharmacodynamics and kinetics were studied in detail. However, as the possibility of developing immune reactions against the murine IgG1 Fc-part remains, the murine antibody was chimerized, inheriting CD4-directed variable domains of the MAX.16H5 IgG1 connected to a human IgG4 backbone. Both antibodies were studied in vitro and in specific humanized mouse transplantation models in vivo with a new scope. By ex vivo incubation of an allogeneic immune cell transplant with MAX.16H5 a new therapy strategy has emerged for the first time enabling both the preservation of the graft-vs.-leukemia (GVL) effect and the permanent suppression of the acute graft-vs.-host disease (aGVHD) without conventional immunosuppression. In this review, we especially focus on experimental data and clinical trials obtained from the treatment of autoimmune diseases with the murine MAX.16H5 IgG1 antibody. Insights gained from these trials have paved the way to better understand the effects with the chimerized MAX.16H5 IgG4 as novel therapeutic approach in the context of GVHD prevention

Composite materials for innovative urban farming of alternative food sources (macroalgae and crickets)

Facing an inexorable growth of the human population along with substantial environmental changes, the assurance of food security is a major challenge of the present century. To ensure responsible food consumption and production (SDG 12), new approaches in the food system are required. Thus, environmentally controlled, sustainable production of alternative food sources are of key interest for both urban agriculture and food research. To face the current challenge of integrating food production systems within existing structures, multidisciplinary discourses are required. Here, we bring together novel technologies and indoor farming techniques with the aim of supporting the development of sustainable food production systems. For this purpose, we investigated the feasibility of 10 composite materials for their innovative use as structural support in macroalgal cultivation (settlement substrates) and cricket rearing (housing). Considering material resistance, rigidity, and direct material-organism interactions, the bio-based composite polylactic acid (PLA) was identified as a suitable material for joint farming. For macroalgae cultivation, PLA sustained the corrosive cultivation conditions and provided a suitable substrate without affecting the macroalgal physiology or nutritional composition (carotenoids and chlorophylls). For cricket rearing, PLA provided a suitable and recyclable shelter, which was quickly accepted by the animals without any observed harm. In contrast, other common composite components like phenolic resin or aramid were found to be unsuitable due to being harmful for the cultivated organisms or instable toward the applied sterilization procedure. This multidisciplinary study not only provides profound insights in the developing field of urban indoor food production from a new perspective, but also bridges material science and farming approaches to develop new sustainable and resilient food production systems

Dual-Task Performance in Hearing-Impaired Older Adults—Study Protocol for a Cross-Sectional Mobile Brain/Body Imaging Study

Background: Hearing impairments are associated with reduced walking performance under Dual-task (DT) conditions. Little is known about the neural representation of DT performance while walking in this target group compared to healthy controls or younger adults. Therefore, utilizing the Mobile Brain/Body Imaging approach (MoBI), we aim at gaining deeper insights into the brain dynamics underlying the interaction of cognitive and motor processes during different DT conditions (visual and auditory) controlling for age and the potential performance decrements of older adults with hearing impairments. Methods: The cross-sectional study integrates a multifactorial mixed-measure design. Between-subject factors grouping the sample will be age (younger vs. older adults) and hearing impairment (mild vs. not hearing impaired). The within-subject factors will be the task complexity (single- vs. DT) and cognitive task modality (visual vs. auditory). Stimuli of the cognitive task will vary according to the stimulus modality (visual vs. auditory), presentation side (left vs. right), and presentation-response compatibility (ipsilateral vs. contralateral). Analyses of DT costs and underlying neuronal correlates focus either on gait or cognitive performance. Based on an a priori sample size calculation 96 (48 healthy and 48 mildly hearing impaired) community-dwelling older adults (50–70 years) and 48 younger adults (20–30 years) will be recruited. Gait parameters of speed and rhythm will be captured. EEG activity will be recorded using 64 active electrodes. Discussion: The study evaluates cognitive-motor interference (CMI) in groups of young and older adults as well as older adults with hearing impairment. The underlying processes of the interaction between motor and cognitive tasks will be identified at a behavioral and neurophysiological level comparing an auditory or a visual secondary task. We assume that performance differences are linked to different cognitive-motor processes, i.e., stimulus input, resource allocation, and movement execution. Moreover, for the different DT conditions (auditory vs. visual) we assume performance decrements within the auditory condition, especially for older, hearing-impaired adults. Findings will provide evidence of general mechanisms of CMI (ST vs. DT walking) as well as task-specific effects in dual-task performance while over ground walking.EC/H2020/952401/EU/TWINning the BRAIN with machine learning for neuro-muscular efficiency/TwinBrainDFG, 414044773, Open Access Publizieren 2021 - 2022 / Technische Universität Berli

Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability