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Publication Metadata only Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery(American Association for the Advancement of Science (AAAS), 2022) Akolpoglu, Mukrime Birgul; Alapan, Yunus; Dogan, Nihal Olcay; Baltaci, Saadet Fatma; Yasa, Oncay; Tural, Gulsen Aybar; N/A; Department of Mechanical Engineering; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; School of Medicine; College of Engineering; 297104Bacterial biohybrids, composed of self-propelling bacteria carrying micro/nanoscale materials, can deliver their payload to specific regions under magnetic control, enabling additional frontiers in minimally invasive medicine. However, current bacterial biohybrid designs lack high-throughput and facile construction with favorable cargoes, thus underperforming in terms of propulsion, payload efficiency, tissue penetration, and spatiotemporal operation. Here, we report magnetically controlled bacterial biohybrids for targeted localization and multistimuliresponsive drug release in three-dimensional (3D) biological matrices. Magnetic nanoparticles and nanoliposomes loaded with photothermal agents and chemotherapeutic molecules were integrated onto Escherichia coil with similar to 90% efficiency. Bacterial biohybrids, outperforming previously reported E. coli-based microrobots, retained their original motility and were able to navigate through biological matrices and colonize tumor spheroids under magnetic fields for on-demand release of the drug molecules by near-infrared stimulus. Our work thus provides a multifunctional microrobotic platform for guided locomotion in 3D biological networks and stimuli-responsive delivery of therapeutics for diverse medical applications.Publication Metadata only Insectivorous birds consume an estimated 400-500 million tons of prey annually(Springer, 2018) Nyffeler, Martin; Whelan, Christopher J.; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; College of Sciences; 327589In this paper, we present an estimate of the predation impact of the global population of insectivorous birds based on 103 (for the most part) published studies of prey consumption (kg ha(-1) season(-1)) of insectivorous birds in seven biome types. By extrapolation-taking into account the global land cover of the various biomes-an estimate of the annual prey consumption of the world's insectivorous birds was obtained. We estimate the prey biomass consumed by the world's insectivorous birds to be somewhere between 400 and 500 million metric tons year(-1), but most likely at the lower end of this range (corresponding to an energy consumption of ae 2.7 x 10(18) J year(-1) or ae 0.15% of the global terrestrial net primary production). Birds in forests account for > 70% of the global annual prey consumption of insectivorous birds (a 300 million tons year(-1)), whereas birds in other biomes (savannas and grasslands, croplands, deserts, and Arctic tundra) are less significant contributors (a 100 million tons year(-1)). Especially during the breeding season, when adult birds feed their nestlings protein-rich prey, large numbers of herbivorous insects (i.e., primarily in the orders Coleoptera, Diptera, Hemiptera, Hymenoptera, Lepidoptera, and Orthoptera) supplemented by spiders are captured. The estimates presented in this paper emphasize the ecological and economic importance of insectivorous birds in suppressing potentially harmful insect pests on a global scale-especially in forested areas.Publication Metadata only Long-term declines in bird populations in tropical agricultural countryside(Natl Acad Sciences, 2019) Oviedo-Brenes, Federico; Horns, Joshua J.; Ehrlich, Paul R.; Daily, Gretchen C; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; College of Sciences; 327589Tropical agriculture is a major driver of biodiversity loss, yet it can provide conservation opportunities, especially where protected areas are inadequate. To investigate the long-term biodiversity capacity of agricultural countryside, we quantified bird population trends in Costa Rica by mist netting 57,255 birds of 265 species between 1999 and 2010 in sun coffee plantations, riparian corridors, secondary forests, forest fragments, and primary forest reserves. More bird populations (69) were declining than were stable (39) or increasing (4). Declines were common in resident, insectivorous, and more specialized species. There was no relationship between the species richness of a habitat and its conservation value. High-value forest bird communities were characterized by their distinct species composition and habitat and dietary functional signatures. While 49% of bird species preferred forest to coffee, 39% preferred coffee to forest and 12% used both habitats, indicating that coffee plantations have some conservation value. Coffee plantations, although lacking most of the forest specialists, hosted 185 bird species, had the highest capture rates, and supported increasing numbers of some forest species. Coffee plantations with higher tree cover (7% vs. 13%) had more species with increasing capture rates, twice as many forest specialists, and half as many nonforest species. Costa Rican countryside habitats, especially those with greater tree cover, host many bird species and are critical for connecting bird populations in forest remnants. Diversified agricultural landscapes can enhance the biodiversity capacity of tropical countryside, but, for the long-term persistence of all forest bird species, large (> 1,000 ha) protected areas are essential.Publication Metadata only Deep whole-genome ctdna chronology of treatment-resistant prostate cancer(Nature Portfolio, 2022) Herberts, Cameron; Annala, Matti; Sipola, Joonatan; Ng, Sarah W. S.; Chen, Xinyi E.; Nurminen, Anssi; Korhonen, Olga, V; Beja, Kevin; Schonlau, Elena; Bernales, Cecily Q.; Ritch, Elie; Bacon, Jack V. W.; Nykter, Matti; Aggarwal, Rahul; Small, Eric J.; Gleave, Martin E.; Quigley, David A.; Feng, Felix Y.; Chi, Kim N.; Wyatt, Alexander W.; N/A; Lack, Nathan Alan; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 120842Circulating tumour DNA (ctDNA) in blood plasma is an emerging tool for clinical cancer genotyping and longitudinal disease monitoring. However, owing to past emphasis on targeted and low-resolution profiling approaches, our understanding of the distinct populations that comprise bulk ctDNA is incomplete. Here we perform deep whole-genome sequencing of serial plasma and synchronous metastases in patients with aggressive prostate cancer. We comprehensively assess all classes of genomic alterations and show that ctDNA contains multiple dominant populations, the evolutionary histories of which frequently indicate whole-genome doubling and shifts in mutational processes. Although tissue and ctDNA showed concordant clonally expanded cancer driver alterations, most individual metastases contributed only a minor share of total ctDNA. By comparing serial ctDNA before and after clinical progression on potent inhibitors of the androgen receptor (AR) pathway, we reveal population restructuring converging solely on AR augmentation as the dominant genomic driver of acquired treatment resistance. Finally, we leverage nucleosome footprints in ctDNA to infer mRNA expression in synchronously biopsied metastases, including treatment-induced changes in AR transcription factor signalling activity. Our results provide insights into cancer biology and show that liquid biopsy can be used as a tool for comprehensive multi-omic discovery.Publication Metadata only Programmable aniso-electrodeposited modular hydrogel microrobots(American Association for the Advancement of Science (AAAS), 2022) Zheng, Zhiqiang; Wang, Huaping; Demir, Sinan Ozgun; Huang, Qiang; Fukuda, Toshio; N/A; Department of Mechanical Engineering; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; School of Medicine; College of Engineering; 297104Systems with programmable and complex shape morphing are highly desired in many fields wherein sensing, actuation, and manipulation must be performed. Living organisms use nonuniform distributions of their body structural composition to achieve diverse shape morphing, motion, and functionality. However, for the micro -robot fabrication, these designs often involve complicated robotic architectures requiring time-consuming and arduous fabrication processes. This paper proposes a single-step aniso-electrodeposition method for fabricat-ing modular microrobots (MMRs) with distinct functions in each modular segment. By programming the electric field, the microscale stripe-shaped structure can be endowed with diverse shape-morphing capabilities, such as spiraling, twisting, bending, and coiling. The proposed fabrication method can develop MMRs with multiple independent modules onto which cells, drugs, and magnetic nanoparticles can be loaded to achieve multifunc-tionality. Thus, MMRs can perform multiple tasks, such as propulsion, grasping, and object delivery, simultane-under control and ionic and stimuli.Publication Metadata only Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia(American Association for the Advancement of Science (AAAS), 2020) Robinson, Kim S.; Teo, Daniel Eng Thiam; Tan, Kai Sen; Toh, Gee Ann; Ong, Hsiao Hui; Lim, Chrissie Kaishi; Lay, Kenneth; Au, Bijin Veonice; Lew, Tian Sheng; Chu, Justin Jang Hann; Chow, Vincent Tak Kwong; Wang, De Yun; Zhong, Franklin L.; N/A; Reversade, Bruno; Faculty Member; School of Medicine; 274182Immune sensor proteins are critical to the function of the human innate immune system. The full repertoire of cognate triggers for human immune sensors is not fully understood. Here, we report that human NACHT, LRR, and PYD domains-containing protein 1 (NLRP1) is activated by 3C proteases (3Cpros) of enteroviruses, such as human rhinovirus (HRV). 3Cpros directly cleave human NLRP1 at a single site between Glu(130) and Gly(131). This cleavage triggers N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment via the cullin(ZER1/ZYG11B) complex, which liberates the activating C-terminal fragment. Infection of primary human airway epithelial cells by live human HRV triggers NLRP1-dependent inflammasome activation and interleukin-18 secretion. Our findings establish 3Cpros as a pathogen-derived trigger for the human NLRP1 inflammasome and suggest that NLRP1 may contribute to inflammatory diseases of the airway.Publication Metadata only Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly(Nature Publishing Group (NPG), 2020) Wang, Lu; Li, Zhen; Sievert, David; Smith, Desiree E. C.; Mendes, Marisa, I; Chen, Dillon Y.; Stanley, Valentina; Ghosh, Shereen; Wang, Yulu; Kara, Majdi; Rosti, Rasim O.; Houlden, Henry; Salomons, Gajja S.; Gleeson, Joseph G.; N/A; Aslanger, Ayça Dilruba; Doctor; N/A; Koç University Hospital; N/AAsparaginyl-tRNA synthetase1 (NARS1) is a member of the ubiquitously expressed cytoplasmic Class IIa family of tRNA synthetases required for protein translation. Here, we identify biallelic missense and frameshift mutations in NARS1 in seven patients from three unrelated families with microcephaly and neurodevelopmental delay. Patient cells show reduced NARS1 protein, impaired NARS1 activity and impaired global protein synthesis. Cortical brain organoid modeling shows reduced proliferation of radial glial cells (RGCs), leading to smaller organoids characteristic of microcephaly. Single-cell analysis reveals altered constituents of both astrocytic and RGC lineages, suggesting a requirement for NARS1 in RGC proliferation. Our findings demonstrate that NARS1 is required to meet protein synthetic needs and to support RGC proliferation in human brain development. Asparaginyl-tRNA synthetase1 (NARS1) is required for protein synthesis. Here, the authors identify biallelic NARS1 mutations in individuals with microcephaly and neurodevelopmental delay. Cortical brain organoid modeling recapitulates microcephaly characteristics and scRNA-seq reveals a role for NARS1 in radial glial cell proliferation.Publication Metadata only On-demand anchoring of wireless soft miniature robots on soft surfaces(Natl Acad Sciences, 2022) Soon, Ren Hao; Ren, Ziyu; Hu, Wenqi; Bozuyuk, Ugur; Yildiz, Erdost; Li, Meng; N/A; Department of Mechanical Engineering; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; School of Medicine; College of Engineering; 297104Untethered soft miniature robots capable of accessing hard-to-reach regions can enable new, disruptive, and minimally invasive medical procedures. However, once the control input is removed, these robots easily move from their target location because of the dynamic motion of body tissues or fluids, thereby restricting their use in many longterm medical applications. To overcome this, we propose a wireless spring-preloaded barbed needle release mechanism, which can provide up to 1.6 N of force to drive a barbed needle into soft tissues to allow robust on-demand anchoring on threedimensional (3D) surfaces. The mechanism is wirelessly triggered using radio-frequency remote heating and can be easily integrated into existing untethered soft robotic platforms without sacrificing their mobility. Design guidelines aimed at maximizing anchoring over the range of the most biological tissues (kPa range) and extending the operating depth of the device inside the body (up to 75%) are also presented. Enabled by these advances, we achieve robust anchoring on a variety of ex vivo tissues and demonstrate the usage of such a device when integrated with existing soft robotic platforms and medical imaging. Moreover, by simply changing the needle, we demonstrate additional functionalities such as controlled detachment and subsurface drug delivery into 3D cancer spheroids. Given these capabilities, our proposed mechanism could enable the development of a new class of biomedical-related functionalities, such as local drug delivery, disease monitoring, and hyperthermia for future untethered soft medical robots.Publication Metadata only Location-level processes drive the establishment of alien bird populations worldwide(Nature Portfolio, 2019) Redding, David W.; Pigot, Alex L.; Dyer, Ellie E.; Kark, Salit; Blackburn, Tim M.; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; College of Sciences; 327589Human-mediated translocation of species to areas beyond their natural distribution (which results in 'alien' populations(1)) is a key signature of the Anthropocene(2), and is a primary global driver of biodiversity loss and environmental change(3). Stemming the tide of invasions requires understanding why some species fail to establish alien populations, and others succeed. To achieve this, we need to integrate the effects of features of the introduction site, the species introduced and the specific introduction event. Determining which, if any, location-level factors affect the success of establishment has proven difficult, owing to the multiple spatial, temporal and phylogenetic axes along which environmental variation may influence population survival. Here we apply Bayesian hierarchical regression analysis to a global spatially and temporally explicit database of introduction events of alien birds(4) to show that environmental conditions at the introduction location, notably climatic suitability and the presence of other groups of alien species, are the primary determinants of successful establishment. Species-level traits and the size of the founding population (propagule pressure) exert secondary, but important, effects on success. Thus, current trajectories of anthropogenic environmental change will most probably facilitate future incursions by alien species, but predicting future invasions will require the integration of multiple location-, species-and event-level characteristics.Publication Metadata only Response to comment on "children creating core properties of language: evidence from an emerging sign language in nicaragua"(American Association for the Advancement of Science (AAAS), 2005) Senghas, A; Kita, S; Department of Psychology; Department of Psychology; Özyürek, Aslı; Faculty Member; College of Social Sciences and Humanities; N/AN/A