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Bladder tumor recurrence is a serious problem in uro-oncology, as it increases the risk of fatal progression and makes further surgeries necessary. The possibility of intraoperative tissue differentiation can help for diagnostic purposes as well as for ensuring that the entirety of the tumor is removed. The latter not only differ visually from healthy tissue, but also in their mechanical and electrical properties due to an altered physiology. A possible base for intraoperative tissue differentiation are impedance measurements, which are, however, difficult to obtain passing through the limited space of the urethra. This work presents a comparative study of two impedance sensors, which are obtained by laser direct structuring and rely on a four terminal measurement. The miniaturized sensors are suitable for minimally invasive usage. Circular electrodes are placed in a square for a first sensor, whereas a novel combination of one circular electrode and three concentric rings is designed for the second sensor. For each sensor, the specific geometry factor is determined and the impact of sensitivity towards small conductivity changes inside the tissue investigated. Furthermore, multiple ex vivo measurements on fresh pig bladders are carried out with each sensor. It is shown that both sensors reliably determine tissue impedance data that fit empirical tissue models. Conductivity values close to listed data of human urinary bladder are obtained. Ultimately, the novel ring sensor configuration turns out more favorable in terms of sensitivity distribution and yields more reproducible results than the square electrode arrangement.

OBJECTIVES/HYPOTHESIS Identification of parathyroid glands and adjacent tissues intraoperatively can be quite challenging because of their small size, variable locations, and indistinct external features. The objective of this study is to test the efficacy of the dynamic optical contrast imaging (DOCI) technique as a tool in specifically differentiating parathyroid tissue and adjacent structures, facilitating efficient and reliable tissue differentiation. STUDY DESIGN Prospective study. METHODS Both animal and human tissues were included in this study. Fresh specimens were imaged with DOCI and subsequently processed for hematoxylin and eosin (H&E) stain. The DOCI images were analyzed and compared to the H&E results as ground truth. RESULTS In both animal and human experiments, significant DOCI contrast was observed between parathyroid glands and adjacent tissue of all types. Region of interest analysis revealed most distinct DOCI values for each tissue when using 494 and 572 nm-specific band pass filter for signal detection (P

A central challenge of medical imaging studies is to extract quantitative biomarkers that characterize pathology or predict disease outcomes. In high-resolution, high-quality magnetic resonance images (MRI), state-of-the-art approaches have performed well. However, such methods may not translate to low resolution, lower quality images acquired on MRI scanners with lower magnetic field strength. Therefore, in low-resource settings where low field scanners are more common and there is a shortage of available radiologists to manually interpret MRI scans, it is essential to develop automated methods that can accommodate lower quality images and augment or replace manual interpretation. Motivated by a project in which a cohort of children with cerebral malaria were imaged using 0.35 Tesla MRI to evaluate the degree of diffuse brain swelling, we introduce a fully automated framework to translate radiological diagnostic criteria into image-based biomarkers. We integrate multi-atlas label fusion, which leverages high-resolution images from another sample as prior spatial information, with parametric Gaussian hidden Markov models based on image intensities, to create a robust method for determining ventricular cerebrospinal fluid volume. We further propose normalized image intensity and texture measurements to determine the loss of gray-to-white matter tissue differentiation and sulcal effacement. These integrated biomarkers are found to have excellent classification performance for determining severe cerebral edema due to cerebral malaria.

The review presents a brief description of microRNA (miRNA), the mechanism of its formation and functioning. There are also analyzed literature data on miRNA role for diabetes mellitus development. There is generalized the information about participation of various miRNA in insulin production and secretion, tissue differentiation and proliferation, apoptosis genes activation. There is presented the evidence of superior role of miRNA in molecular processes.

Objective Quantitative MRI (qMRI) methods provide versatile neuroradiological applications and are a hot topic in research. The degree of their clinical implementation is however barely known. This survey was created to illuminate which and how qMRI techniques are currently applied across Europe. Methods In total, 4753 neuroradiologists from 27 countries received an online questionnaire. Demographic and professional data, experience with qMRI techniques in the brain and head and neck, usage, reasons for/against application, and knowledge of the QIBA and EIBALL initiatives were assessed. Results Two hundred seventy-two responders in 23 countries used the following techniques clinically (mean values in %): DWI (82.0%, n = 223), DSC (67.3%, n = 183), MRS (64.3%, n = 175), DCE (43.4%, n = 118), BOLD-fMRI (42.6%, n = 116), ASL (37.5%, n = 102), fat quantification (25.0%, n = 68), T2 mapping (16.9%, n = 46), T1 mapping (15.1%, n = 41), PET-MRI (11.8%, n = 32), IVIM (5.5%, n = 15), APT-CEST (4.8%, n = 13), and DKI (3.3%, n = 9). The most frequent usage indications for any qMRI technique were tissue differentiation (82.4%, n = 224) and oncological monitoring (72.8%, n = 198). Usage differed between countries, e.g. ASL: Germany (n = 13/63; 20.6%) vs. France (n = 31/40; 77.5%). Neuroradiologists endorsed the use of qMRI because of an improved diagnostic accuracy (89.3%, n = 243), but 50.0% (n = 136) are in need of better technology, 34.9% (n = 95) wish for more communication, and 31.3% need help with result interpretation/generation (n = 85). QIBA and EIBALL were not well known (12.5%, n = 34, and 11.0%, n = 30). Conclusions The clinical implementation of qMRI methods is highly variable. Beyond the aspect of readiness for clinical use, better availability of support and a wider dissemination of guidelines could catalyse a broader implementation. Key Points • Neuroradiologists endorse the use of qMRI techniques as they subjectively improve diagnostic accuracy. • Clinical implementation is highly variable between countries, techniques, and indications. • The use of advanced imaging could be promoted through an increase in technical support and training of both doctors and technicians.

Many research articles are published on regenerative medicine every year. However, only a small proportion of these articles provide experimental methods on organ/tissue differentiation. Therefore, we developed a database – ATTRACTIVE (An auTo-updating daTabase foR experimentAl protoCols in regeneraTIVe mEdicine) – that collects journal articles with differentiation methods in regenerative medicine and updates itself automatically on a regular basis. Since the number of articles in regenerative medicine was insufficient and unbalanced, which limited the performance of the supervised learning algorithms, we proposed an algorithm that combines cosine similarity and linear discriminant functions to classify articles based on their titles and abstracts more efficiently. The results show that our proposed methods out-performed other machine learning algorithms such as k-nearest neighbors, support vector machine, and long short-term memory methods. The classification accuracy reached 94.62%, even with a small and unbalanced dataset. Lastly, we incorporated our classifier into the database for automatic updates. The database is available at http://attractive.cgm.ntu.edu.tw/ .

Colorectal cancer (CRC) progression is associated with cancer cell dedifferentiation and sternness acquisition. Several methods have been developed to identify sternness signatures in CRCs. However, studies that directly measured the degree of dedifferentiation in CRC tissues are limited. It is unclear how the differentiation states change during CRC progression. To address this, we develop a method to analyze the tissue differentiation spectrum in colorectal cancer using normal gastrointestinal single-cell transcriptome data. Applying this method on 281 tumor samples from The Cancer Genome Atlas Colon Adenocarcinoma dataset, we identified three major CRC subtypes with distinct tissue differentiation pattern. We observed that differentiation states are closely correlated with anti-tumor immune response and patient outcomes in CRC. Highly dedifferentiated CRC samples escaped the immune surveillance and exhibited poor outcomes; mildly dedifferentiated CRC samples showed resistance to anti-tumor immune responses and had a worse survival rate; well-differentiated CRC samples showed sustained anti-tumor immune responses and had a good prognosis. Overall, the spectrum of tissue differentiation observed in CRCs can be used for future clinical risk stratification and subtype-based therapy selection.

Composition of phospholipids was examined in embryogenic and non-embryogenic cell lines of Siberian larch (Larix sibirica Ledeb.). Significant differences in the content and composition of phospholipids were revealed between the cell lines. Phosphatidylcholines (PC) and phosphatidylethanolamines (PE) were predominant phospholipids in embryogenic cell lines, whereas non-embryogenic cell lines featured a high content of phosphatidic acid (>64% of total phospholipids). The PC/PE ratio known to characterize the membrane structure and function was 1.4–3.8 times higher for embryogenic cell lines than for non-embryogenic lines; this was probably caused by the involvement of these phospholipids in tissue differentiation. The content of phosphatidylinositols differed significantly for embryogenic and non-embryogenic cell lines, where it equaled to 0.50–1.06 and 0.17–0.34 mg/g dry wt, respectively. The observed variations in the composition of phospholipids between the cell lines with different embryogenic potential provide evidence for the important role of these lipids in embryogenesis at the stage of embryo formation.

Important roles for reactive oxygen species (ROS) and redox signaling in embryonic development and regenerative processes are increasingly recognized. However, it is difficult to obtain information on spatiotemporal dynamics of ROS production and signaling in vivo. The zebrafish is an excellent model for in vivo bioimaging and possesses a remarkable regenerative capacity upon tissue injury. Here, we review data obtained in this model system with genetically encoded redox-sensors targeting H2O2 and glutathione redox potential. We describe how such observations have prompted insight into regulation and downstream effects of redox alterations during tissue differentiation, morphogenesis and regeneration. We also discuss the properties of the different sensors and their consequences for the interpretation of in vivo imaging results. Finally, we highlight open questions and additional research fields that may benefit from further application of such sensor systems in zebrafish models of development, regeneration and disease.

Study design Experimental in-vivo animal study. Objective The aim of this study was to evaluate an Artificial Intelligence (AI)-enabled ultrasound imaging system's ability to detect, segment, classify, and display neural and other structures during trans-psoas spine surgery. Summary of background data Current methodologies for intraoperatively localizing and visualizing neural structures within the psoas are limited and can impact the safety of lateral lumbar interbody fusion (LLIF). Ultrasound technology, enhanced with AI-derived neural detection algorithms, could prove useful for this task. Methods The study was conducted using an in vivo porcine model (50 subjects). Image processing and machine learning algorithms were developed to detect neural and other anatomic structures within and adjacent to the psoas muscle while using an ultrasound imaging system during lateral lumbar spine surgery (SonoVision,™ Tissue Differentiation Intelligence, USA). The imaging system's ability to detect and classify the anatomic structures was assessed with subsequent tissue dissection. Dice coefficients were calculated to quantify the performance of the image segmentation. Results The AI-trained ultrasound system detected, segmented, classified, and displayed nerve, psoas muscle, and vertebral body surface with high sensitivity and specificity. The mean Dice coefficient score for each tissue type was >80%, indicating that the detected region and ground truth were >80% similar to each other. The mean specificity of nerve detection was 92%; for bone and muscle, it was >95%. The accuracy of nerve detection was >95%. Conclusion This study demonstrates that a combination of AI-derived image processing and machine learning algorithms can be developed to enable real-time ultrasonic detection, segmentation, classification, and display of critical anatomic structures, including neural tissue, during spine surgery. AI-enhanced ultrasound imaging can provide a visual map of important anatomy in and adjacent to the psoas, thereby providing the surgeon with critical information intended to increase the safety of LLIF surgery.Level of Evidence: N/A.

In this paper we aim to improve the understanding of the relationship between unilateral-uniplanar external fixator design parameters and their influences on fixator performance. Stability and strength of bone-fixator construct as well as the quality of healing were defined as our major concerns in order to evaluate the performance of fixator. The roles of six key design parameters were assessed during the early stage of healing by using finite element models. Tissue differentiation within the callus was predicted through the implementation of a mechanoregulation theory of bone healing. Taguchi and ANOVA methods were used to achieve optimal design sets for outputs and to determine contribution percentage of each design parameter on outputs. For improving overall fixator performance, optimal set of design parameters consisting of 2 mm, 8 mm, 120 mm, 20 GPa, 50 mm and 20 mm were determined by Taguchi for pin diameter, rod diameter, rod elevation, fixator Young’s modulus, distance of the nearest pin to fracture site and distance between adjacent pins, respectively. Also, results of ANOVA revealed that rod elevation is the most important design parameter, with 43 % effectiveness on overall fixator performance, which was followed by fixator material and pin diameter with 28 % and 19 %, respectively. Results of this study can assist orthopedic surgeons to achieve an optimal fixator device with respect to the patient’s condition and give insight into the importance of different design parameters.

Biomechanical analysis, numerical and experimental, has been extensively used for more than 3 decades to investigate the mechanical behaviour of bone and implant–bone structures in joint replacement. In this review article, a detailed overview of the state-of-the-art techniques used for the development and pre-clinical testing of orthopaedic implants has been presented, with special focus on the hip-joint and hip implants. The efficacies of biomechanical analysis in analysing failure mechanisms in joint replacement, its clinical relevance, challenges and limitations, and future directions have been highlighted. Finite element (FE) modelling and analysis have contributed immensely towards testing of clinical hypotheses and evaluation of implant designs. Over the last few decades, the size and sophistication of the FE models have increased considerably. A critical analysis of the currently available subject-specific FE modelling techniques has been presented including, development of computed tomography-scan-based FE models of bone and implant, assignment of heterogeneous bone material properties, loading and boundary conditions. The relationship between stress–strain analysis and implant failure needs careful interpretation for clinical relevance. Verification and validation of these models are essential for assessing the validity of the predicted results. The salient features of adaptive simulations including bone remodelling and tissue differentiation and its prominence in investigating potential failure mechanisms and implant design evaluations have been discussed. The key considerations for design and development of orthopaedic implants have been suggested. It is envisaged that the FE simulations would be more holistic in nature, incorporating the complexities and variabilities of the clinical problems.

The coated porous section of stem surface is initially filled with callus that undergoes osseointegration process, which develops a bond between stem and bone, lessens the micromotions and transfers stresses to the bone, proximally. This phenomenon attributes to primary and secondary stabilities of the stems that exhibit trade-off the stem stiffness. This study attempts to ascertain the influence of stem stiffness on peri-prosthetic bone formation and stress shielding when in silico models of solid CoCr alloy and Ti alloy stems, and porous Ti stems (53.8 GPa and 31.5 GPa Young's moduli) were implanted. A tissue differentiation predictive mechanoregulation algorithm was employed to estimate the evolutionary bond between bone and stem interfaces with 0.5-mm- and 1-mm-thick calluses. The results revealed that the high stiffness stems yielded higher stress shielding and lower micromotions than that of low stiffness stems. Contrarily, bone formation around solid Ti alloy stem and porous Ti 53.8 GPa stem was augmented in 0.5-mm- and 1-mm-thick calluses, respectively. All designs of stems exhibited different rates of bone formation, diverse initial micromotions and stress shielding; however, long-term bone formation was coherent with different stress shielding. Therefore, contemplating the secondary stability of the stems, low stiffness stem (Ti 53.8 GPa) gave superior biomechanical performance than that of high stiffness stems. 2020, Springer-Verlag GmbH Germany, part of Springer Nature. This paper was made possible by NPRP grant# NPRP 8-876-2-375 from the Qatar National Research Fund (a member of Qatar Foundation) and seed project# SEED-PSU-23-12-2019 from the Prince Sultan University. The findings achieved herein are solely the responsibility of the authors. Scopus

Запропоновано метод оцінки ефективності компресійної еластографії біологічних тканин в залежності від глибини їх розташування, який дозволяє дослідити якість зображення та диференціацію тканин від глибини розміщення тест-об’єкту, типу датчиків та діапазону частот сканування. Отримані дані розширіють можливості застосування компресійної еластографії. A method is proposed for evaluating the effectiveness of compression elastography of biological tissues depending on the depth of their location, which allows one to study image quality and tissue differentiation from the depth of placement of the test object, the type of sensors and the range of scanning frequencies. The data obtained expand the possibilities of using compression elastography. Предложен метод оценки эффективности компрессионной эластографии биологических тканей в зависимости от глубины их расположения, который позволяет исследовать качество изображения и дифференциацию тканей от глубины размещения тест-объекта, типа датчиков и диапазона частот сканирования. Полученные данные розширяют возможности применения компрессионной эластографии.

MiR396 plays an essential role in various developmental processes. However, the miR396-mRNA molecular network in bamboo vascular tissue differentiation during primary thickening has not been elucidated. Here, we revealed that three of the five members from the miR396 family were overexpressed in the underground thickening shoots collected from Moso bamboo. Furthermore, the predicted target genes were up/down-regulated in the early (S2), middle (S3) and late (S4) developmental samples. Mechanistically, we found that several of the genes encoding protein kinases (PKs), growth-regulating factors (GRF), transcription factors (TFs), and transcription regulators (TRs) were the potential targets of miR396 members. Moreover, we identified QLQ (Gln, Leu, Gln) and WRC (Trp, Arg, Cys) d omains in five PeGRF homologs and a Lipase_3 domain and a K_trans domain in another two potential targets, where the cleavage targets were identified via degradome sequencing (p < 0.05). The sequence alignment indicated many mutations in the precursor sequence of miR396d between Moso bamboo and rice. Our dual-luciferase assay revealed that ped-miR396d-5p binds to a PeGRF6 homolog. Thus, the miR396-GRF module was associated with Moso bamboo shoot development. Fluorescence in situ hybridization localized miR396 in the vascular tissues of the leaves, stems, and roots of pot Moso bamboo seedlings at the age of two months. Collectively, these experiments revealed that miR396 functions as a regulator of vascular tissue differentiation in Moso bamboo. Additionally, we propose that miR396 members are targets for bamboo improvement and breeding.

In vitro studies using human embryonic stem cells (hESCs) are a valuable method to study aspects of embryogenesis, avoiding ethical issues when using embryonic materials and species dissimilarities. The xenograft teratoma assay is often traditionally used to establish pluripotency in putative PSC populations, but also has additional applications, including the study of tissue differentiation. The stem cell field has long sought an alternative due to various well-established issues with the in vivo technique, including significant protocol variability and animal usage. We have established a two-step culture method which combines PSC-derived embryoid bodies (EBs) with porous scaffolds to enhance their viability, prolonging the time these structures can be maintained, and therefore, permitting more complex, mature differentiation. Here, we have utilised human embryonic stem cell-derived EBs, demonstrating the formation of tissue rudiments of increasing complexity over time and the ability to manipulate their differentiation through the application of exogenous morphogens to achieve specific lineages. Crucially, these EB-derived tissues are highly reminiscent of xenograft teratoma samples derived from the same cell line. We believe this in vitro approach represents a reproducible, animal-free alternative to the teratoma assay, which can be used to study human tissue development.

To address the challenge of tissue differentiation during cranial perforation surgery, presented research aims to integrate optical illumination and detection capability into rotating assemblies of surgical tools.

DLK1 is a maternally imprinted, paternally expressed gene coding for the transmembrane protein Delta-like homologue 1 (DLK1), a non-canonical NOTCH ligand with well-described roles during development, and tumor-supportive functions in several aggressive cancer forms. Here, we review the many functions of DLK1 as a regulator of stem cell pools and tissue differentiation in tissues such as brain, muscle, and liver. Furthermore, we review recent evidence supporting roles for DLK1 in the maintenance of aggressive stem cell characteristics of tumor cells, specifically focusing on central nervous system tumors, neuroblastoma, and hepatocellular carcinoma. We discuss NOTCH -dependent as well as NOTCH-independent functions of DLK1, and focus particularly on the complex pattern of DLK1 expression and cleavage that is finely regulated from a spatial and temporal perspective. Progress in recent years suggest differential functions of extracellular, soluble DLK1 as a paracrine stem cell niche-secreted factor, and has revealed a role for the intracellular domain of DLK1 in cell signaling and tumor stemness. A better understanding of DLK1 regulation and signaling may enable therapeutic targeting of cancer stemness by interfering with DLK1 release and/or intracellular signaling.

Aim: To determine whether the promoters of long noncoding RNAs (lncRNAs) undergo dynamic changes in DNA methylation during fetal development. Methods: ANOVA and the tissue specificity index were used to identify and validate tissue-specific methylation sites. Age-associated DNA methylation signatures were identified by applying the elastic net method. Results: The lncRNA methylome landscape was characterized in four types of fetal tissue and at three gestational time points, and specific characteristics relative to the tissue of origin and developmental age were identified. Higher levels of lncRNA methylation might be involved in tissue differentiation. LncRNAs harboring age-associated methylation signatures may participate in the fetal developmental process. Conclusion: This study provides novel insights into the role of lncRNA methylomes in fetal tissue specification and development.

It is well known that, for a particular tissue, the homeostatic and cancer attractors are well apart both in gene expression and in protein expression spaces. By using data for 15 tissues and the corresponding tumors from The Cancer Genome Atlas, and for 49 normal tissues and 20 tumors from The Human Protein Atlas, we show that the set of normal attractors are also well separated from the set of tumors. Roughly speaking, one may say that there is a "cancer progression axis" orthogonal to the normal tissue differentiation and cancer manifolds. This separation suggests that therapies targeting common genes, which define the cancer axis, may be effective, irrespective of the tissue of origin.

Weaning is a critical period for the growth and development of mammals, in which various physiological and biochemical indicators of the body have undergone great changes. The development, differentiation, and maturation of the nervous system are regulated by many proteins. Changes in related proteins affect the physiological functions of the nervous system. However, the regulation of selfrenewal and differentiation of the nervous system at this stage is still poorly understood. The mechanism of differentiation and regulation of the major proteins in the nervous system during this special period of weaning remains to be investigated. Therefore, this paper aims to summarize the alteration of the nervous system during weaning and provide the basis for subsequent research.

La polyploïdie (amplification du génome entier) fait référence à des organismes dont les cellules ont plus de deux jeux complets de chromosomes homologues. La polyploïdie a été observée pour la première fois chez les plantes, il y a plus d'un siècle. Il est dorénavant connu que ce processus se produit chez de nombreux eucaryotes dans diverses circonstances. Chez les mammifères, le développement de cellules polyploïdes peut contribuer à la différenciation des tissus. Il peut donc présenter un gain de fonction. Alternativement, il peut être associé au développement de différentes pathologies comme le cancer. Il existe différents mécanismes qui favorisent la genèse des cellules polyploïdes, dont la fusion cellulaire ou une division cellulaire anormale. Chez les mammifères, la polyploïdie est une des caractéristiques des cellules hépatiques. La polyploïdisation survient en effet principalement au cours du développement du parenchyme hépatique, mais également chez l'adulte, à la suite de différents stress. Des progrès récents ont permis de comprendre les mécanismes de polyploïdisation du tissu hépatique et ses conséquences fonctionnelles dans un contexte physiologique et pathologique.

Orientador: Lúcia Elvira Alvares Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: Os genes da família Dact codificam proteínas multifuncionais que desempenham funções cruciais durante o desenvolvimento embrionário. Em particular, estas proteínas são importantes moduladoras das vias de sinalização Wnt/beta-catenina e TGF-beta, uma vez que elas são requeridas para regular os níveis de sinalização parácrina em diferentes contextos celulares, maximizando a eficiência de vários processos biológicos. Dada a importância das vias Wnt e TGF-beta para a correta formação do corpo do embrião de vertebrado, esta pesquisa visou caracterizar o padrão de expressão dos genes Dact1, Dact2 e Dact3 em membros de camundongos no estádio E14,5, uma etapa do desenvolvimento marcada pela diferenciação tecidual. Em adição, foram estabelecidos os padrões de expressão dos marcadores moleculares Col2a1, Sox9, Runx2, MyoD, Dcx, Bmp2 e Bmp7 visando compará-los com os perfis de expressão dos genes Dact. O padrão de expressão dos genes estudados foi definido por ensaios de hibridação in situ em cortes histológicos de membros, utilizando-se sondas de RNA antisenso gene específicas. Cortes sagitais de embriões de camundongos no estádio E14,5 também foram incluídos nas análises de expressão dos genes Dact. Finalmente, marcações por imunofluorescências foram realizadas para confirmar a expressão das proteínas Sox9 e Runx2 em tecidos específicos dos membros em E14,5. Nossos resultados mostraram que os genes Dact são expressos em um amplo repertório de tecidos nos membros em desenvolvimento de camundongo. A pele, o tecido cartilaginoso, o tecido muscular e o endotélio de vasos sanguíneos de pequeno calibre são os tecidos de maior nível de expressão. Surpreendentemente, a análise dos marcadores moleculares revelou que apenas o gene Col2a1 mostrou um padrão característico de marcador molecular, com sua expressão associada unicamente ao tecido cartilaginoso em desenvolvimento. Os demais genes incluídos neste estudo como marcadores moleculares apresentaram perfis de expressão complexos, abrangendo vários tecidos. Por exemplo, Sox9 e Runx2, marcadores do tecido cartilaginoso e ósseo, respectivamente, são fortemente expressos no músculo esquelético em formação no membro. Esta expressão foi confirmada ao nível proteico por ensaios de imunofluorescência, revelando que não apenas os mRNAs mas também as proteínas codificadas por estes genes estão presentes em células do tecido muscular em desenvolvimento. O estudo dos cortes sagitais dos embriões em E14,5 mostrou que os mesmos tecidos que expressam os genes Dact nos membros também expressam estes genes ao longo do eixo principal do corpo do embrião. Em adição, a análise destes cortes revelou que os genes Dact são expressos em altos níveis no sistema nervoso central e periférico, assim como nos primórdios de vários órgãos do embrião, como pulmões, fígado e rins. Em conjunto, os resultados desta pesquisa mostram que os genes Dact são expressos em múltiplos tecidos, dentre os quais estão vários que requerem sinais Wnt e TGF-beta para se desenvolver corretamente Abstract: The Dact family genes encode multifunctional proteins that play crucial roles during embryonic development. In particular, these proteins are important modulators of the Wnt/beta-catenin and TGF-beta signaling pathways, since they are required to regulate the levels of paracrine signaling in different cellular contexts, maximizing the efficiency of many biological processes. Given the importance of the Wnt and TGF-beta pathways for the correct formation of the vertebrate embryo body, this research aimed to characterize the expression pattern of the Dact1, Dact2 and Dact3 genes in mouse limbs at stage E14.5, a stage of development marked by tissue differentiation. In addition, the expression patterns of the molecular markers Col2a1, Sox9, Runx2, MyoD, Dcx, Bmp2 and Bmp7 were established to make comparisons with the expression profiles of the Dact genes. The expression patterns of the genes studied were defined by in situ hybridization assays in histological sections of limbs, using gene-specific antisense RNA probes. Sagittal sections of mouse embryos at the E14.5 stage were also included in Dact gene expression analyses. Finally, immunofluorescence stainingwas performed to confirm the expression of Sox9 and Runx2 proteins in limb specific tissues at E14.5. Our findings showed that Dact genes are expressed in a broad repertoire of tissues in the developing mouse limbs. Skin, cartilaginous tissue, muscle tissue and endothelium of small-caliber blood vessels are the tissues of highest level of expression. Surprisingly, an analysis of the molecular markers revealed that only Col2a1 gene showed a characteristic pattern of molecular marker, with its expression associated to developing cartilaginous tissue only. The other genes included in this study as molecular markers presented complex expression patterns, encompassing several tissues. For example, Sox9 and Runx2, markers of cartilage and bone tissue, respectively, are strongly expressed during limb skeletal muscles formation. This expression was confirmed at the protein level by immunofluorescence assays, showing that not only the mRNAs but also the proteins encoded by these genes are present in cells of the developing muscle tissue. The study of sagittal sections of embryos at E14.5 showed that the same tissues expressing Dact genes in limbs also express these genes along the main axis of the embryo's body. In addition, analysis of these sections revealed that Dact genes are highly expressed in the central and peripheral nervous system, as well as in the primordia of various organs of the embryo¿s body, such as lungs, liver and kidneys. Together, the results of this research show that Dact genes are expressed in multiple tissues, among which are several that require Wnt and TGF-beta signals to develop properly Mestrado Biologia Tecidual Mestra em Biologia Celular e Estrutural CAPES

Grafting is a means to connect tissues from two individual plants and grow a single chimeric plant through the establishment of both apoplasmic and symplasmic connections. Recent molecular studies using RNA-sequencing data have provided genetic information on the processes involved in tissue reunion, including wound response, cell division, cell–cell adhesion, cell differentiation and vascular formation. Thus, studies on grafting increase our understanding of various aspects of plant biology. Grafting has also been used to study systemic signaling and transport of micromolecules and macromolecules in the plant body. Given that graft viability and molecular transport across graft junctions largely depend on vascular formation, a major focus in grafting biology has been the mechanism of vascular development. In addition, it has been thought that symplasmic connections via plasmodesmata are fundamentally important to share cellular information among newly proliferated cells at the graft interface and to accomplish tissue differentiation correctly. Therefore, this review focuses on plasmodesmata formation during grafting. We take advantage of interfamily grafts for unambiguous identification of the graft interface and summarize morphological aspects of de novo formation of plasmodesmata. Important molecular events are addressed by re-examining the time-course transcriptome of interfamily grafts, from which we recently identified the cell–cell adhesion mechanism. Plasmodesmata-associated genes upregulated during graft healing that may provide a link to symplasm establishment are described. We also discuss future research directions.

Various methods are currently used to investigate human tissue differentiation, including human embryo culture and studies utilising pluripotent stem cells (PSCs) such as in vitro embryoid body formation and in vivo teratoma assays. Each method has its own distinct advantages, yet many are limited due to being unable to achieve the complexity and maturity of tissue structures observed in the developed human. The teratoma xenograft assay allows maturation of more complex tissue derivatives, but this method has ethical issues surrounding animal usage and significant protocol variation. In this study, we have combined three-dimensional (3D) in vitro cell technologies including the common technique of embryoid body (EB) formation with a novel porous scaffold membrane, in order to prolong cell viability and extend the differentiation of PSC derived EBs. This approach enables the formation of more complex morphologically identifiable 3D tissue structures representative of all three primary germ layers. Preliminary in vitro work with the human embryonal carcinoma line TERA2.SP12 demonstrated improved EB viability and enhanced tissue structure formation, comparable to teratocarcinoma xenografts derived in vivo from the same cell line. This is thought to be due to reduced diffusion distances as the shape of the spherical EB transforms and flattens, allowing for improved nutritional/oxygen support to the developing structures over extended periods. Further work with EBs derived from murine embryonic stem cells demonstrated that the formation of a wide range of complex, recognisable tissue structures could be achieved within 2–3 weeks of culture. Rudimentary tissue structures from all three germ layers were present, including epidermal, cartilage and epithelial tissues, again, strongly resembling tissue structure of teratoma xenografts of the same cell line. Proof of concept work with EBs derived from the human embryonic stem cell line H9 also showed the ability to form complex tissue structures within this system. This novel yet simple model offers a controllable, reproducible method to achieve complex tissue formation in vitro. It has the potential to be used to study human developmental processes, as well as offering an animal free alternative method to the teratoma assay to assess the developmental potential of novel stem cell lines.

Dynamization, increasing the interfragmentary movement (IFM) by reducing the fixation stiffness from a rigid to a more flexible condition, is widely used clinically to promote fracture healing. However, it remains unknown how dynamization degree (relative change in fixation stiffness/IFM from a rigid to a flexible fixation) affects bone healing at various stages. To address this issue, we used a fuzzy logic-based mechano-regulated tissue differentiation algorithm on published experimental data from a sheep osteotomy healing model. We applied a varied degree of dynamization, from 0 (fully rigid fixation) to 0.9 (90% reduction in stiffness relative to the rigid fixation) after 1, 2, 3, and 4 weeks of osteotomy (R1wF, R2wF, R3wF, and R4wF) and computationally evaluated bone regeneration and biomechanical integrity over the healing process of 8 weeks. Compared with the constant rigid fixation, early dynamization (R1wF and R2wF) led to delays in bone bridging and biomechanical recovery of the osteotomized bone. However, the effect of early dynamization on healing was dependent of the degree of dynamization. Specifically, a higher dynamization degree (e.g., 0.9 for R1wF) led to a prolonged delay in bone bridging and largely unrecovered bending stiffness (48% relative to the intact bone), whereas a moderate degree of dynamization (e.g., 0.5 or 0.7) significantly enhanced bone formation and biomechanical properties of the osteotomized bone. These results suggest that dynamization degree and timing interactively affect the healing process. A combination of early dynamization with a moderate degree could enhance the ultimate biomechanical recovery of the fractured bone.

The occurrence and development of tumors cannot be separated from the influence of differentiation at different stages and levels. Our study found that E-cadherin was significantly increased in cell model induced by sodium butyrate and cell density, while METTL3, METTL16 and WTAP were decreased during the differentiation of cells. In the clinicopathological tissues, E-cadherin was low expressed in poorly differentiated tumor tissues and above three regulators were highly expressed in poorly differentiated tissues. At the levels of clinicopathological differentiation, tissue differentiation and cell differentiation, the result indicated that the poor prognosis of colorectal cancer (CRC) may be closely related to high expression of total m6A level and high expression of METTL3, METTL16 and WTAP.

This work proposes a new online monitoring method for an assistance during laser osteotomy. The method allows differentiating the type of ablated tissue and the applied dose of laser energy. The setup analyzes the laser-induced acoustic emission, detected by an airborne microphone sensor. The analysis of the acoustic signals is carried out using a machine learning algorithm that is pre-trained in a supervised manner. The efficiency of the method is experimentally evaluated with several types of tissues, which are: skin, fat, muscle, and bone. Several cutting-edge machine learning frameworks are tested for the comparison with the resulting classification accuracy in the range of 84-99%. It is shown that the datasets for the training of the machine learning algorithms are easy to collect in real-life conditions. In the future, this method could assist the doctors during laser osteotomy, minimizing the damage of the nearby healthy tissues and provide cleaner pathologic tissue removal.

Background As far as gastric cancer is concerned, there is a lack of specific early diagnostic biomarkers in clinical diagnosis. Circular RNAs (circRNAs) have been found to be stable in gastric cancer tissues and plasma, so they have the potential to become new type of diagnostic biomarkers for gastric cancer. Materials and Methods The hsa_circ_0001811 expressions in gastric cancer tissues and paired non‐cancer tissues, preoperative and postoperative plasma of patients with gastric cancer, and plasma of healthy volunteers were detected using quantitative reverse transcription‐polymerase chain reaction. The receiver operating characteristic (ROC) curves were drawn; and the combined ROC curves were used to analyze their diagnostic values. The correlation between the plasma or tissue hsa_circ_0001811 levels and the clinicopathological factors of gastric cancer was further analyzed. Results Hsa_circ_0001811 was found to be lowly expressed in gastric cancer tissues and plasma from patients with gastric cancer. The area under the ROC curve (AUC) in the gastric cancer tissues and the plasma of patients with gastric cancer was 0.658 and 0.747, respectively. The AUC increased to 0.824 after combination of both. The expression level of hsa_circ_0001811 in gastric cancer tissue correlated with carcinoembryonic antigen (CEA) (P = .0347), tissue differentiation (P = .0138), and lymph node metastasis (P = .0234), while plasma hsa_circ_0001811 level was related to carbohydrate antigen (CA19‐9) (P = .0278), lymph node metastasis (P = .0469), distant metastasis (P = .0384), and age (P = .0085). Conclusions The above results indicate that hsa_circ_0001811 may become a new biomarker for clinical diagnosis of gastric cancer., Sanger sequence results of qRT‐PCR products of hsa_circ_0001811 are consistent with the sequence of target circRNA. Compared with paired non‐cancer tissues, hsa_circ_0001811 was low expressed in gastric cancer tissues (2A); and the expression of plasma specimens one day before surgery in gastric cancer patients was lower, then those in ten days after surgery and plasma samples of healthy volunteers (2B). The AUC of hsa_circ_0001811 in gastric cancer tissues was 0.658, while the AUC in plasma was 0.747. When tissues and plasma were combined used, the AUC increased to 0.824, further showing the higher diagnostic value of hsa_circ_0001811.

The longerterm secondary stability of an uncemented implant depends primarily on the quality and extent of bone in-growth or on-growth at the bone-implant interface. Investigations are warranted to predict the influences of implant macro-textures on bone on-growth pattern. Mechanoregulatory tissue differentiation algorithms can predict such patterns effectively. There is, however, a dearth of volumetric in silico study to assess the influence of macro-textures on bone growth. The present study investigated the influence of macro-textural grooves/ribs on changes in tissue formation at the bone-implant interface by carrying out a 3D finite element (FE) analysis. Three distinct macro-textures, loosely based on commercially viable hip stem models, were comparatively assessed for varying levels of interfacial micromotion. The study predicted elevated fibrogenesis and chondrogenesis, followed by a suppressed osteogenesis for higher levels of micromotion (60 μm and 100 μm), resulting in weak bone-implant interface strength. However, small judicious modifications in implant surface texture may enhance bone growth to a considerable extent. The numerical scheme can further be used as a template for more rigorous parametric and multi-scale studies.

Mechanoregulatory healing models, bioregulatory healing models, and mechanobioregulatory healing models have been developed to investigate the interaction among the mechanical environment, biological factors, and tissue differentiation during bone fracture healing. However, there are few papers studying the influence of mechanical stability on growth factor activities. In this paper, we set up a computational model to investigate the influence of mechanical stability on growth factor activities. Two kinds of fracture gaps (2 mm: stable group and 3 mm: unstable group) were used in this model. In each group, 7% and 33% interfragmentary strains (IFSs) were used to represent low and high IFSs, respectively. Through the simulation, the spatial and temporal distributions of growth factors within the callus region were predicted. The influence of mechanical stability on growth factor activities was obtained. The computational model contributed to the understanding of the bone fracture healing process, and it can help to optimize the treatment methods.

PurposeReliable intraoperative delineation of tumor from healthy brain tissue is essentially based on the neurosurgeon's visual aspect and tactile impression of the considered tissue, which isdue to inherent low brain consistency contrasta challenging task. Development of an intelligent artificial intraoperative tactile perception will be a relevant task to improve the safety during surgery, especially whenas for neuroendoscopytactile perception will be damped oras for surgical robotic applicationswill not be a priori existent. Here, we present the enhancements and the evaluation of a tactile sensor based on the use of a piezoelectric tactile sensor. MethodsA robotic-driven piezoelectric bimorph sensor was excited using multisine to obtain the frequency response function of the contact between the sensor and fresh ex vivo porcine tissue probes. Based on load-depth, relaxation and creep response tests, viscoelastic parameters E-1 and E-2 for the elastic moduli and for the viscosity coefficient have been obtained allowing tissue classification. Data analysis was performed by a multivariate cluster algorithm.ResultsCluster algorithm assigned five clusters for the assignment of white matter, basal ganglia and thalamus probes. Basal ganglia and white matter have been assigned to a common cluster, revealing a less discriminatory power for these tissue types, whereas thalamus was exclusively delineated; gray matter could even be separated in subclusters.ConclusionsBimorph-based, multisine-excited tactile sensors reveal a high sensitivity in ex vivo tissue-type differentiation. Although, the sensor principle has to be further evaluated, these data are promising.

A field study was established to evaluate symptoms, growth, yield, and nut quality of walnut trees subjected to multiple exposures of simulated bispyribac-sodium drift. Nut yield the year following simulated drift treatment was also evaluated because tissue differentiation for future fruiting position occurs in the prior season. Bispyribac-sodium was applied four times, at weekly intervals, at 0.5% and 3% of the use rate in rice (45 g ai ha-1). Injury from the 0.5% rate exceeded 5% after three applications. In general, the severity of the symptoms peaked 14 d after last application (23% and 40% injury for 0.5% and 3% rate, respectively) and subsequently remained nearly constant over the duration of the study. Growth of shoots treated with the 0.5% rate was initially delayed during the treatment regime but recovered after treatments ended; however, walnut shoots exposed to the higher rate had fewer internodes than nontreated trees at the end of the season. No measurable reduction in walnut yield or average nut weight either in the year of exposure or in the subsequent year was observed. However, both rates negatively affected walnut kernel color in the year of exposure.Nomenclature: Bispyribac-sodium; rice, Oryza sativa L.; walnut, Juglans regia L.

Resurrection plants are a polyphyletic group of angiosperms which display true desiccation tolerance (DT) - the ability to survive near complete loss of cellular water for extended periods while recovering metabolic competence upon watering. This is achieved by employing tailored protection behaviours depending on the relative state of (de)hydration. Recent work has raised interest in desiccation-associated changes related to tissue destiny in desiccation tolerant vegetative tissues. Homoiochlorophyllous species, such as those in the Craterostigma genus, maintain their photosynthetic apparatus during the dehydration process, employing considerable protection thereof. In the current study, detailed phenotypic characterisation and pulse-amplitude modulated chlorophyll fluorometry were used to identify the critical water contents at which key physiological changes occur in leaves of Craterostigma pumilum and how this relates to desiccation-associated differentiation between Tip and Base tissues of leaf blades. This differentiation appeared to be realised only during early rehydration and after initial water movement through the leaf tissues. This work provides strong evidence for the existence of desiccation-associated tissue differentiation in C.pumilum and, potentially, other homoiochlorophyllous resurrection plants.

Distraction osteogenesis (DO) is a mechanobiological process of producing new bone and overlying soft tissues through the gradual and controlled distraction of surgically separated bone segments. The process of bone regeneration during DO is largely affected by distraction parameters. In the present study, a distraction strategy with varying distraction rates (i.e., “rate-varying distraction”) is proposed, with the aim of shortening the distraction time and improving the efficiency of DO. We hypothesized that faster and better healing can be achieved with rate-varying distractions, as compared with constant-rate distractions. A computational model incorporating the viscoelastic behaviors of the callus tissues and the mechano-regulatory tissue differentiation laws was developed and validated to predict the bone regeneration process during DO. The effect of rate-varying distraction on the healing outcomes (bony bridging time and bone formation) was examined. Compared to the constant low-rate distraction, a low-to-high rate-varying distraction provided a favorable mechanical environment for angiogenesis and bone tissue differentiation, throughout the distraction and consolidation phase, leading to an improved healing outcome with a shortened healing time. These results suggest that a rate-varying clinical strategy could reduce the overall treatment time of DO and decrease the risk of complications related to the external fixator.

Sarcandra glabra, a traditional Chinese medicine and herbal tea, has benefits from treating inflammation and fractures to curing cancer. The anti-inflammatory properties of sesquiterpenoids (chloranthalactone A, CTA; atractylenolide II, AT-II) have made S. glabra to a great potential for research and development. Here this study developed S. glabra callus culture to circumvent particular needs of the plant growing seasons and Hardiness zone, with the goal being able to produce sesquiterpenoids in vitro. The half strength Murashige and Skoog (1/2MS) medium supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D, 2.0 mg/L) and 6-benzylaminopurine (6-BA, 1.0 mg/L) was effective for callus induction. The 1/2MS medium supplemented with 2,4-D (2.0 mg/L) and 6-BA (0.5 mg/L) was superior for callus proliferation. The callus was friable, yellowish and rapidly grown without tissue differentiation. Moreover, high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) analysis indicated that the contents of CTA and AT-Ⅱ in multiple subculture S. glabra callus were 3.72 ± 0.51 mg/g and 0.50 ± 0.12 mg/g in fresh weight (FW), respectively. Using abiotic stresses and elicitors, production of CTA (by ultraviolet-B radiation for 48 h) and AT-II (by methyl jasmonate, 100 μmol/L) was enhanced by 2.3-fold. In conclusion, this work not only established the S. glabra callus culture for in vitro production of CTA and AT-II, but also provided the foundation for further development and utilization of S. glabra.

Craniofacial morphogenesis is an intricate developmental process in 3D, which therefore merits visualization and investigation in 3D. To better understand the process, we utilize μCT imaging, and describe a method to calibrate each cone beam μCT individually. Calibration is necessary, because during development, fetuses undergo tissue differentiation, which affects the acquisition process for radiographic images. Additionally, tissue fixation and conservation agents may influence the physical properties of the specimens and may affect image acquisition. After taking a μCT scan from each specimen, we separated a horizontal slice from each neck (which is inconsequential to our question with relation to the whole head). These neck specimens were prepared as horizontal histological serial sections and stained. With these as a reference, the μCT visualization parameters could be adjusted until they matched the selected virtual section planes, which correspond exactly to the planes of the histological sections with a precision (pixel size) of 0.69 μm.

Successfully simulating tissue evolution in bone is of significant importance in predicting various biological processes such as bone remodeling, fracture healing and osseointegration of implants. Each of these processes involves in different ways the permanent or transient formation of different tissue types, namely bone, cartilage and fibrous tissues. The tissue evolution in specific circumstances such as bone remodeling and fracturing healing is currently able to be modeled. Nevertheless, it remains challenging to predict which tissue types and organization can develop without any a priori assumptions. In particular, the role of mechano-biological coupling in this selective tissue evolution has not been clearly elucidated. In this work, a multi-tissue model has been created which simultaneously describes the evolution of bone, cartilage and fibrous tissues. The coupling of the biological and mechanical factors involved in tissue formation has been modeled by defining two different tissue states: an immature state corresponding to the early stages of tissue growth and representing cell clusters in a weakly neo-formed Extra Cellular Matrix (ECM), and a mature state corresponding to well-formed connective tissues. This has allowed for the cellular processes of migration, proliferation and apoptosis to be described simultaneously with the changing ECM properties through strain driven diffusion, growth, maturation and resorption terms. A series of finite element simulations were carried out on idealized cantilever bending geometries. Starting from a tissue composition replicating a mid-diaphysis section of a long bone, a steady-state tissue formation was reached over a statically loaded period of 10,000 h (60 weeks). The results demonstrated that bone formation occurred in regions which are optimally physiologically strained. In two additional 1000 h bending simulations both cartilaginous and fibrous tissues were shown to form under specific geometrical and loading cases and cartilage was shown to lead to the formation of bone in a beam replicating a fracture healing initial tissue distribution. This finding is encouraging in that it is corroborated by similar experimental observations of cartilage leading bone formation during the fracture healing process. The results of this work demonstrate that a multi-tissue mechano-biological model of tissue evolution has the potential for predictive analysis in the design and implementations of implants, describing fracture healing and bone remodeling processes. Funding by the Fédération Francilienne deMécanique (Coup de pouce 2016) is acknowledged.

Bone fracture is a very common body injury. The healing process is physiologically complex, involving both biological and mechanical aspects. Following a fracture, cell migration, cell/tissue differentiation, tissue synthesis, and cytokine and growth factor release occur, regulated by the mechanical environment. Over the past decade, bone healing simulation and modeling has been employed to understand its details and mechanisms, to investigate specific clinical questions, and to design healing strategies. The goal of this effort is to review the history and the most recent work in bone healing simulations with an emphasis on both biological and mechanical properties. Therefore, we provide a brief review of the biology of bone fracture repair, followed by an outline of the key growth factors and mechanical factors influencing it. We then compare different methodologies of bone healing simulation, including conceptual modeling (qualitative modeling of bone healing to understand the general mechanisms), biological modeling (considering only the biological factors and processes), and mechanobiological modeling (considering both biological aspects and mechanical environment). Finally we evaluate different components and clinical applications of bone healing simulation such as mechanical stimuli, phases of bone healing, and angiogenesis., Highlights • Bone fracture healing is a series of biological processes, regulated by the mechanical environment and biological factors. • Conceptual models of bone fracture healing aim to understand the qualitative process and to formulate its general mechanism. • Mechanobiological models consider the effects of both mechanical environment and biological factors. • Mechanobiological regulations and mechanical stimuli effects on growth factors can potentially have clinical applications. • While important, the inflammatory phase in the bone healing process is not included in mechanobiological simulations.

Left-handed helical conformation of a polypeptide chain (PPII) is the third type of the protein backbone structure. This conformation universally exists in fibrous, globular proteins, and biologically active peptides. It has unique physical and chemical properties determining a wide range of biological functions, from the protein folding to the tissue differentiation. New examples of the structure have been appearing in spite of difficulties in their detection and investigation. The annotation and prediction of the PPII was also a challenging task. Recently, many PPII motifs with new and/or unexpected functions are being accumulated in databases. In this review we describe the major structural and dynamic forms of PPII, the diversity of its functions, and the role in different biological processes.

The aim of the article is to analyze the shape of nuclei of various tissues and to assess the tumor differentiation based on morphometric measurements. For this purpose, an experiment was conducted, the results of which determine whether it is possible to determine a tissue’s type based on the mentioned features. The measurements were performed on a publicly available data set containing 1,356 hematoxylin- and eosin-stained images with nucleus segmentations for 14 different human tissues. Morphometric analysis of cell nuclei using ImageJ software took 17 parameters into account. Classification of the obtained results was performed in Matlab R2018b software using the SVM and t-SNE algorithms, which showed that some cancers can be distinguished with an accuracy close to 90% (lung squamous cell cancer vs others; breast cancer vs cervical cancer).

Glandular trichomes found on the surface of many higher plants contain specialized cells that produce and secrete copious amounts of particular secretory products. Leaf glandular trichomes of the non-model plant species Nicotiana tabacum represent a biologically active and stress-responsive tissue that contributes to plant defense response against biotic and abiotic stress and also influences leaf aroma and smoke flavor. Two morphologically different types of tobacco capitate trichomes, long- and short-stalked, with distinct functions, display ultrastructural features that are common to terpene-secreting glands, but only the secretory cells of the tall glandular trichomes are considered to be the site of biosynthesis of certain exudate compounds, including diterpenes and sucrose esters. Ultrastructural and histochemical characterization of tall glandular trichomes is described in an attempt to understand the contribution of these glands to the total secretion produced. Possible roles of distinct cellular compartments involved in the secretory process and secondary metabolite secretion under in vitro conditions are discussed. Gopal RK, Ekiert HM, Goyal S, editors. Plant Cell and Tissue Differentiation and Secondary Metabolites. Springer, Cham; 2020. p. 1–37. (Reference Series in Phytochemistry).

in biomedical and pharmaceutical international markets, there is a huge ambition to use the optical imaging techniques in biological screening and pathogen identification to diagnose abnormal or cancerous cells. Spatial frequency domain imaging is a recent, non-invasive and wide field optical imaging technology developed to quantify a spatial visualization of the tissue absorption and scattering characteristics utilizing the tissue diffuse reflectance dependency on the spatial frequency. In this work, we reveal the capability of Spatial Frequency Domain Imaging method to differentiate biological tissues according to their chromophores concentrations. For this purpose, normal and coagulated samples of chicken liver were experimentally examined with the optical system at different spatial frequency. The presented results showed a quite difference in the reflectance profile and optical properties for each tissue sample providing the ability of implementing the presented technique in medical analysis and identifications.

Spatio‐temporal regulation of signalling pathways plays a key role in generating diverse responses during the development of multicellular organisms. The role of signal dynamics in transferring signalling information in vivo is incompletely understood. Here, we employ genome engineering in Drosophila melanogaster to generate a functional optogenetic allele of the Notch ligand Delta (opto‐Delta), which replaces both copies of the endogenous wild‐type locus. Using clonal analysis, we show that optogenetic activation blocks Notch activation through cis‐inhibition in signal‐receiving cells. Signal perturbation in combination with quantitative analysis of a live transcriptional reporter of Notch pathway activity reveals differential tissue‐ and cell‐scale regulatory modes. While at the tissue‐level the duration of Notch signalling determines the probability with which a cellular response will occur, in individual cells Notch activation acts through a switch‐like mechanism. Thus, time confers regulatory properties to Notch signalling that exhibit integrative digital behaviours during tissue differentiation., An optogenetic method to control endogenous Delta activity with light reveals that the Notch receptor acts as an integrator of analog signals that generates a digital switch‐like behaviour at the level of target gene expression during tissue differentiation.

An introduction of innovative minimally invasive methods like multimodal optical coherence tomography (OCT) with polarization-sensitivity and angiography modes for intrasurgical guidance appears to be a critical challenge for the modern neurooncology. This study aimed to develop a new instrument for targeted stereotactic brain biopsy based on cross-polarization (CP) OCT realized in standard biopsy needle to increase the safety of ongoing neurosurgical procedures. Experimental studies in vivo on the healthy rat’s brain allow detecting blood vessels in the process of moving the biopsy needle along the brain surface and detect tissue type (cerebral cortex or white matter) when the needle went inside the brain. The images was assessed by visual criteria. However, CP OCT signal quantification methods will increase the sensitivity/specificity for the tissue type differentiation and blood vessels detection. The potential of CP OCT as an effective instrument for OCT-guided stereotactic biopsy of brain tumors was demonstrated.

Lasers have become a generally accepted tool for surgery due to their advantages compared to traditional approaches like the scalpel. However, lasers lack a feedback system for safe laser guidance. This problem prevents the potential laser application for a lot of medical cases in the clinical environment. In this work, a new tissue differentiation modality which might be implemented as a feedback system using remote speckle-sensing is presented. This modality is tested on three tissue types and the results are discussed.

Seating a cementless acetabular cup via impaction is a balancing act; good cup fixation must be obtained to ensure adequate bone in‐growth and cup apposition, while acetabular fracture must be avoided. Good impaction technique is essential to the success of hip arthroplasty. Yet little guidance exists in the literature to inform surgeons on ‘how hard’ to hit. A drop rig and synthetic bone model were used to vary the energy of impaction strikes in low and high density synthetic bone, while key parameters such as dynamic strain (quantifying fracture risk), implant fixation and polar gap were measured. For high energy impaction (15 J) in low density synthetic bone a peak tensile strain was observed during impaction that was up to 3.4x as large as post‐strike strain, indicating a high fracture risk. Diminishing returns were observed for pushout fixation with increasing energy. 85% of the pushout fixation achieved using a 15 J impaction strike was attained by using a 7.5 J strike energy. Similarly polar gap was only minimally reduced at high impaction energies. Therefore it is suggested that higher energy strikes increase fracture risk, but do not offer large improvements to fixation or implant‐bone apposition. It may difficult be for surgeons to accurately deliver specific impaction energies, suggesting there is scope for operative tools to manage implant seating.