Frontiers in Bioengineering and Biotechnology
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Pietro Morasso

The human “marionette” is extremely complex and multi-articulated: anatomical redundancy (in terms of Degrees of Freedom: DoFs), kinematic redundancy (movements can have different trajectories, velocities, and accelerations and yet achieve the same goal, according to the principle of Motor Equivalence), and neurophysiological redundancy (many more muscles than DoFs and multiple motor units for each muscle). Although it is quite obvious that such abundance is not noxious at all because, in contrast, it is instrumental for motor learning, allowing the nervous system to “explore” the space of feasible actions before settling on an elegant and possibly optimal solution, the crucial question then boils down to figure out how the nervous system “chooses/selects/recruits/modulates” task-dependent subsets of countless assemblies of DoFs as functional motor synergies. Despite this daunting conceptual riddle, human purposive behavior in daily life activities is a proof of concept that solutions can be found easily and quickly by the embodied brain of the human cognitive agent. The point of view suggested in this essay is to frame the question above in the old-fashioned but still seminal observation by Marr and Poggio that cognitive agents should be regarded as Generalized Information Processing Systems (GIPS) and should be investigated according to three nearly independent but complementary levels of analysis: 1) the computational level, 2) the algorithmic level, and 3) the implementation level. In this framework, we attempt to discriminate as well as aggregate the different hypotheses and solutions proposed so far: the optimal control hypothesis, the muscle synergy hypothesis, the equilibrium point hypothesis, or the uncontrolled manifold hypothesis, to mention the most popular ones. The proposed GIPS follows the strategy of factoring out shaping and timing by adopting a force-field based approach (the Passive Motion Paradigm) that is inspired by the Equilibrium Point Hypothesis, extended in such a way to represent covert as well overt actions. In particular, it is shown how this approach can explain spatio-temporal invariances and, at the same time, solve the Degrees of Freedom Problem.

Timothy C. Cairns ◽  
Xiaomei Zheng ◽  
Claudia Feurstein ◽  
Ping Zheng ◽  
Jibin Sun ◽  

Submerged fermentation using filamentous fungal cell factories is used to produce a diverse portfolio of useful molecules, including food, medicines, enzymes, and platform chemicals. Depending on strain background and abiotic culture conditions, different macromorphologies are formed during fermentation, ranging from dispersed hyphal fragments to approximately spherical pellets several millimetres in diameter. These macromorphologies are known to have a critical impact on product titres and rheological performance of the bioreactor. Pilot productivity screens in different macromorphological contexts is technically challenging, time consuming, and thus a significant limitation to achieving maximum product titres. To address this bottleneck, we developed a library of conditional expression mutants in the organic, protein, and secondary metabolite cell factory Aspergillus niger. Thirteen morphology-associated genes transcribed during fermentation were placed via CRISPR-Cas9 under control of a synthetic Tet-on gene switch. Quantitative analysis of submerged growth reveals that these strains have distinct and titratable macromorphologies for use as chassis during strain engineering programs. We also used this library as a tool to quantify how pellet formation is connected with strain fitness and filamentous growth. Using multiple linear regression modelling, we predict that pellet formation is dependent largely on strain fitness, whereas pellet Euclidian parameters depend on fitness and hyphal branching. Finally, we have shown that conditional expression of the putative kinase encoding gene pkh2 can decouple fitness, dry weight, pellet macromorphology, and culture heterogeneity. We hypothesize that further analysis of this gene product and the cell wall integrity pathway in which it is embedded will enable more precise engineering of A. niger macromorphology in future.

Anamar Miranda ◽  
Damien Seyer ◽  
Carla Palomino-Durand ◽  
Houda Morakchi-Goudjil ◽  
Mathilde Massonie ◽  

The success of stable and long-term implant integration implies the promotion, control, and respect of the cell microenvironment at the site of implantation. The key is to enhance the implant–host tissue cross talk by developing interfacial strategies that guarantee an optimal and stable seal of soft tissue onto the implant, while preventing potential early and late infection. Indeed, implant rejection is often jeopardized by lack of stable tissue surrounding the biomaterial combined with infections which reduce the lifespan and increase the failure rate of implants and morbidity and account for high medical costs. Thin films formed by the layer-by-layer (LbL) assembly of oppositely charged polyelectrolytes are particularly versatile and attractive for applications involving cell–material contact. With the combination of the extracellular matrix protein fibronectin (Fn, purified from human plasma) and poly-L-lysine (PLL, exhibiting specific chain lengths), we proposed proactive and biomimetic coatings able to guarantee enhanced cell attachment and exhibiting antimicrobial properties. Fn, able to create a biomimetic interface that could enhance cell attachment and promote extracellular cell matrix remodeling, is incorporated as the anionic polymer during film construction by the LbL technic whereas PLL is used as the cationic polymer for its capacity to confer remarkable antibacterial properties.

Zhipeng Li ◽  
Haoyi Yang ◽  
Chenhua Zheng ◽  
Xiping Du ◽  
Hui Ni ◽  

Astaxanthin is an important natural resource that is widely found in marine environments. Metabolic regulation is an effective method for improving astaxanthin production in Phaffia rhodozyma. Most studies have focused on single regulators, which have limited effects. In this study, 16 metabolic regulators were screened to improve astaxanthin production in high-yield and wild-type strains. Fluconazol and glutamic acid increased astaxanthin volumetric yield in MVP14 by 25.8 and 30.9%, respectively, while ethanol increased astaxanthin volumetric yield in DSM626, 29.3%. Furthermore, six additives that inhibit the competing pathways and promote the main pathway for astaxanthin synthesis were selected for combination treatment. We found that the optimal combination was penicillin, ethanol, triclosan, and fluconazol, which increased astaxanthin cell yield by 51%. Therefore, we suggest that simultaneously promoting the master pathways (mevalonate) and inhibiting competing pathways (fatty acid synthesis and ergosterol) is the best strategy to improve astaxanthin cell yield. Moreover, regulators of the biomass pathway should be avoided to improve cell yield. This study provides a technical basis for the utilisation of astaxanthin in P. rhodozyma.

Xiaoli Zhou ◽  
Zhiqiang Xu ◽  
Yueqiu Li ◽  
Jia He ◽  
Honghui Zhu

Lytic polysaccharide monooxygenases (LPMOs) oxidatively break down the glycosidic bonds of crystalline polysaccharides, significantly improving the saccharification efficiency of recalcitrant biomass, and have broad application prospects in industry. To meet the needs of industrial applications, enzyme engineering is needed to improve the catalytic performance of LPMOs such as enzyme activity and stability. In this study, we engineered the chitin-active CjLPMO10A from Cellvibrio japonicus through a rational disulfide bonds design. Compared with the wild-type, the variant M1 (N78C/H116C) exhibited a 3-fold increase in half-life at 60°C, a 3.5°C higher T5015, and a 7°C rise in the apparent Tm. Furthermore, the resistance of M1 to chemical denaturation was significantly improved. Most importantly, the introduction of the disulfide bond improved the thermal and chemical stability of the enzyme without causing damage to catalytic activity, and M1 showed 1.5 times the specific activity of the wild-type. Our study shows that the stability and activity of LPMOs could be improved simultaneously by selecting suitable engineering sites reasonably, thereby improving the industrial adaptability of the enzymes, which is of great significance for applications.

Yuh-Shan Ho ◽  
A. F. M. Fahad Halim ◽  
Mohammad Tajul Islam

To gain insight into the trend of bacterial nanocellulose research, a bibliometric analysis was performed using the Science Citation Index Expanded database from 2005 to 2020. The study concentrated on the publication’s performance in terms of annual outputs and citations, mainstream journals, categories of the Web of Sciences, leading countries, prominent institutions, and trends in research. Current research priorities and future trends were analyzed after summarizing the most commonly used keywords extracted from words in the paper title analysis, authors’ keyword analysis, and KeyWords Plus. The findings revealed that the annual output in the form of scholarly articles on bacterial nanocellulose research steadily increased during the first quartile of the study period, followed by a very rapid increase in the last five-years of the study. Increasing mechanical strength would remain the main future focus of bacterial nanocellulose research to create its scope in different field of applications.

Yanchun Wang ◽  
Shuli Sang ◽  
Xin Zhang ◽  
Haoxia Tao ◽  
Qing Guan ◽  

A miniature CRISPR-Cas12f has been demonstrated to serve as an effective genome editing tool in gram negative bacteria as well as human cells. Here, we developed an alternative method to edit the genome of Bacillus anthracis based on the AsCas12f1 nuclease from Acidibacillus sulfuroxidans. When the htrA gene on the chromosome and the lef gene on the plasmid pXO1 were selected as targets, the CRISPR-AsCas12f1 system showed very high efficiency (100%). At the same time, a high efficiency was observed for large-fragment deletion. Our results also indicated that the length of the homologous arms of the donor DNA had a close relationship with the editing efficiency. Furthermore, a two-plasmid CRISPR-AsCas12f1 system was also constructed and combined with the endonuclease I-SceI for potential multi-gene modification. This represents a novel tool for mutant strain construction and gene function analyses in B. anthracis and other Bacillus cereus group bacteria.

Jiefei Wang ◽  
W. Seth Childers

The multifaceted and heterogeneous nature of depression presents challenges in pinpointing treatments. Among these contributions are the interconnections between the gut microbiome and neurological function termed the gut-brain axis. A diverse range of microbiome-produced metabolites interact with host signaling and metabolic pathways through this gut-brain axis relationship. Therefore, biosensor detection of gut metabolites offers the potential to quantify the microbiome’s contributions to depression. Herein we review synthetic biology strategies to detect signals that indicate gut-brain axis dysregulation that may contribute to depression. We also highlight future challenges in developing living diagnostics of microbiome conditions influencing depression.

Eddy Saad ◽  
Karl Semaan ◽  
Georges Kawkabani ◽  
Abir Massaad ◽  
Renee Maria Salibv ◽  

Adults with spinal deformity (ASD) are known to have spinal malalignment affecting their quality of life and daily life activities. While walking kinematics were shown to be altered in ASD, other functional activities are yet to be evaluated such as sitting and standing, which are essential for patients’ autonomy and quality of life perception. In this cross-sectional study, 93 ASD subjects (50 ± 20 years; 71 F) age and sex matched to 31 controls (45 ± 15 years; 18 F) underwent biplanar radiographic imaging with subsequent calculation of standing radiographic spinopelvic parameters. All subjects filled HRQOL questionnaires such as SF36 and ODI. ASD were further divided into 34 ASD-sag (with PT > 25° and/or SVA >5 cm and/or PI-LL >10°), 32 ASD-hyperTK (with only TK >60°), and 27 ASD-front (with only frontal malalignment: Cobb >20°). All subjects underwent 3D motion analysis during the sit-to-stand and stand-to-sit movements. The range of motion (ROM) and mean values of pelvis, lower limbs, thorax, head, and spinal segments were calculated on the kinematic waveforms. Kinematics were compared between groups and correlations to radiographic and HRQOL scores were computed. During sit-to-stand and stand-to-sit movements, ASD-sag had decreased pelvic anteversion (12.2 vs 15.2°), hip flexion (53.0 vs 62.2°), sagittal mobility in knees (87.1 vs 93.9°), and lumbar mobility (L1L3-L3L5: −9.1 vs −6.8°, all p < 0.05) compared with controls. ASD-hyperTK showed increased dynamic lordosis (L1L3–L3L5: −9.1 vs −6.8°), segmental thoracic kyphosis (T2T10–T10L1: 32.0 vs 17.2°, C7T2–T2T10: 30.4 vs 17.7°), and thoracolumbar extension (T10L1–L1L3: −12.4 vs −5.5°, all p < 0.05) compared with controls. They also had increased mobility at the thoracolumbar and upper-thoracic spine. Both ASD-sag and ASD-hyperTK maintained a flexed trunk, an extended head along with an increased trunk and head sagittal ROM. Kinematic alterations were correlated to radiographic parameters and HRQOL scores. Even after controlling for demographic factors, dynamic trunk flexion was determined by TK and PI-LL mismatch (adj. R2 = 0.44). Lumbar sagittal ROM was determined by PI-LL mismatch (adj. R2 = 0.13). In conclusion, the type of spinal deformity in ASD seems to determine the strategy used for sitting and standing. Future studies should evaluate whether surgical correction of the deformity could restore sitting and standing kinematics and ultimately improve quality of life.

Simone G.V.S. Smith ◽  
Maiya K. Yokich ◽  
Shawn M. Beaudette ◽  
Stephen H. M. Brown ◽  
Leah R. Bent

Understanding the processing of tactile information is crucial for the development of biofeedback interventions that target cutaneous mechanoreceptors. Mechanics of the skin have been shown to influence cutaneous tactile sensitivity. It has been established that foot skin mechanics are altered due to foot posture, but whether these changes affect cutaneous sensitivity are unknown. The purpose of this study was to investigate the potential effect of posture-mediated skin deformation about the ankle joint on perceptual measures of foot skin sensitivity. Participants (N = 20) underwent perceptual skin sensitivity testing on either the foot sole (N = 10) or dorsum (N = 10) with the foot positioned in maximal dorsiflexion/toe extension, maximal plantarflexion/toe flexion, and a neutral foot posture. Perceptual tests included touch sensitivity, stretch sensitivity, and spatial acuity. Regional differences in touch sensitivity were found across the foot sole (p < 0.001) and dorsum (p < 0.001). Touch sensitivity also significantly increased in postures where the skin was compressed (p = 0.001). Regional differences in spatial acuity were found on the foot sole (p = 0.002) but not dorsum (p = 0.666). Spatial acuity was not significantly altered by posture across the foot sole and dorsum, other than an increase in sensitivity at the medial arch in the dorsiflexion posture (p = 0.006). Posture*site interactions were found for stretch sensitivity on the foot sole and dorsum in both the transverse and longitudinal directions (p < 0.005). Stretch sensitivity increased in postures where the skin was pre-stretched on both the foot sole and dorsum. Changes in sensitivity across locations and postures were believed to occur due to concurrent changes in skin mechanics, such as skin hardness and thickness, which follows our previous findings. Future cutaneous biofeedback interventions should be applied with an awareness of these changes in skin sensitivity, to maximize their effectiveness for foot sole and dorsum input.

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