Unveiling the Hidden Language of Extracellular Matrix Deformations: A tale of cellular whispers and unstable fibers

One of the key questions in cellular biology revolves around comprehending the intricate interplay between an individual cell and its neighboring counterparts within a tissue. Beyond the cell’s innate genetic blueprint, external influences, such as those exerted by its microenvironment, drive most of its functions. The main component of this microenvironment is the Extracellular Matrix (ECM), a convoluted network of fibrous proteins which interact directly with cells. The ECM serves as a scaffold that facilitates intercellular signal exchange, including biomechanical forces. Cells actively respond to mechanical action and induce deformation patterns which take the form of bands that interconnect neighbouring cells. These bands include tracts of elevated matrix densification and fiber alignment and orchestrate vital cellular processes like migration, invasion and proliferation, while there is strong evidence of their contribution to intercellular communication. Unraveling the mechanisms underpinning these phenomena equates to deciphering the mechanical properties of ECM and by that, the mechanical traits of its constituent fibers. Prior research into the mechanics of fibers has uncovered unusual mechanical phenomena driven in part by their inherent hierarchical structure. These phenomena encompass unique behaviors such as unstable responses of fibers when subjected to compressive loads. This instability is characterized by transitions from heightened fiber stiffness (in which the fiber becomes harder) to the loss of fiber stiffness (causing the fiber to become less stiff and buckle). In light of these findings, we have developed models that encompass the distinct intrinsic characteristics of fiber structure and mechanics, and investigate deformations of the Extracellular Matrix (ECM) induced by cells. We have analyzed and modelled the mechanical properties of the ECM from a macroscopic perspective. Our fundamental assumption is that individual fibers can withstand tension but buckle and collapse when subjected to compression. We compare two families of fiber mechanics models: Family 1, characterized by stable responses of individual fibers under compression, and Family 2, exhibiting unstable responses of individual fibers under compression. Our simulations expose diverse compression instabilities inherent to each Family. These instabilities lead to the formation of densely packed ECM regions, featuring strongly aligned fibers. These regions emanate either from individual contractile cells or join neighboring cells, mirroring observations from experiments. We show that both fiber alignment and ECM densification are prevented in the absence of elevated compression. Our models demonstrate that material instabilities wield a dominant role in the mechanical behavior of the fibrous ECM. Despite substantial disparities in the responses of the two model families, our research underscores the pivotal role played by compression instabilities in the behavior of fibrous biological tissues. This has implications to a number of cellular and tissue processes, particularly in understanding cancer invasion and metastasis. Our findings introduce novel perspectives for investigating how fibers respond to deformations induced by cells and the ensuing implications for biomechanical interactions between cells.Data-integrated multi-scale modelling of fibrous extracellular matrix materials (DIMMOFEMM

The Role of SATB1 in Medial Ganglionic Eminence-derived Cortical Interneuron Differentiation.

Brain function depends on the activity of cortical γ-aminobutyric acid- producing (GABAergic) interneurons, which participate in the formation of inhibitory circuits and control the activity of excitatory glutamatergic pyramidal neurons. Cortical GABAergic interneurons are extremely diverse in morphology, electrophysiology and molecular marker expression. A plethora of transcription factors that control aspects of this diversity has now been identified. Among them, the LIM-homeodomain transcription factor LHX6 is required for the differentiation of parvalbumin+ (PV+) and somatostatin+ (SST+) cortical interneurons. However, little is known about the molecular cascades operating downstream of LHX6 to control the maturation of these two major interneuron subtypes. With a focus on identifying region- and stage-specific factors regulating interneuron maturation, a genome-wide gene expression analysis was conducted in our laboratory and identified the gene encoding the chromatin organiser protein SATB1 as an LHX6 target in the E15.5 mouse cortex. In this thesis, we investigate the in vivo role of SATB1 in cortical interneuron terminal differentiation. Using a constitutive Satb1-null mouse established in our laboratory we demonstrate that Satb1 regulates multiple aspects of SST+ interneuron maturation. In contrast, by generating mice with a specific deletion of Satb1 in PV+ interneurons (PV-Cre;Satb1-flox) we show that Satb1 is not required for the maturation of this group of inhibitory neurons. Moreover, interneuron-specific deletion of Satb1 with the Nkx2.1-Cre line reveals a disruption of the excitation/inhibition balance in the brain and a significant loss of both SST+ and PV+ interneurons. Finally, we show that SATB1 and the general neuronal maturation marker KCC2 are coexpressed in mature cortical interneurons. By performing overexpression experiments in brain slices we observed regulation of Kcc2 expression by SATB1, but failed to detect any reciprocal regulation of Satb1 by KCC2. Overall, our findings provide a basis for understanding the terminal differentiation of interneurons in the mammalian cortex

Profil masnih kiselina, broj somatskih stanica i mikrobiološka kvaliteta mlijeka dobivenog potpunom strojnom mužnjom i ručnim izmuzivanjem Chios ovaca

The objective of this work was to evaluate the effect of milk fraction on composition, fatty acid profile, somatic cell count and microbiological quality of the milk of Chios ewes sheep breed. Totally forty eight animals were included in the study (16 of the first, 16 of the second and 16 of the third and subsequent lactations, respectively). The animals were fed with 1.06 kg/ewe/day a concentrate mixture and 0.9 kg/ewe/day alfalfa hay. Ewes were milked twice a day for 10 weeks in a milking parlor of “Casse” type 1x24 with 12 milking units and a low milk line and air pipeline. All the variables measured were compared by ANOVA using SPSS. The results of the experiment showed that fat percentage in hand stripped milk was higher than in total machine milk, while protein and lactose were found in the same levels. Despite the higher fat concentration in the hand stripped milk the fatty acid profile in two fractions was found to be similar. Only eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) acid concentrations were found in higher levels in hand stripped milk. Somatic cell count was lower in total machine milk, while microbiological quality was found to be better in hand stripped milk. Lactation stage influenced significantly all measured variables.Ciljevi ovog rada bili su procijeniti učinak izmuzivanja mlijeka na sastav, profil masnih kiselina, broj somatskih stanica i mikrobiološku kvalitetu mlijeka ovaca Chios pasmine. U istraživanje je bilo uključeno ukupno četrdeset osam životinja (16 prve, 16 druge i 16 treće i kasnijih laktacija). Sve su životinje hranjene sa 1,06 kg/ovci/dan koncentrirane smjese i 0,9 kg/ovci/dan sijena lucerne. Ovce su mužene dva puta dnevno tijekom 10 tjedana u izmuzištu tipa «Casse» 1x24 s 12 muznih jedinica. Dobiveni podaci analizirani su ANOVA testom. Rezultati istraživanja pokazali su da je udjel masti ručno izmuženog mlijeka bio veći nego u mlijeku dobivenom cjelokupnom strojnom mužnjom, dok su udjeli proteina i laktoze bili na istim razinama. Unatoč višem udjelu masti u ručno izmuženom mlijeku, profil masnih kiselina u dvije frakcije bio je sličan. Samo su koncentracije eikozapentaenske kiseline (EPA) i dokoheksanoične kiseline (DHA) utvrđene u većim količinama u ručno izmuženom mlijeku. Broj somatskih stanica bio je niži u cjelokupnoj strojnoj mužnji, a mikrobiološka kvaliteta bila je bolja u ručno izmuženom mlijeku. Faza laktacije značajno je utjecala na sve izmjerene varijable

Οι Αφηγηματικές τεχνικές στο πεζογραφικό έργο του Μάνου Κοντολέων: Γεύση πικραμύγδαλου, Μάσκα στο φεγγάρι, Αμαρτωλή πόλη

Η ανάλυση των αφηγηματικών τεχνικών ενός λογοτεχνικού κειμένου έχει τη βάση της στην Αφηγηματολογία. Πρόκειται για έναν κλάδο της Θεωρίας της Λογοτεχνίας, που αναπτύχθηκε κυρίως στη Γαλλία κατά την περίοδο 1965-1975 και, με επιρροή από τον Ρωσικό Φορμαλισμό, υιοθετεί μια κειμενοκεντρική προσέγγιση για τη νοηματοδότηση του κειμένου. Η παρούσα εργασία επιχειρεί, στο πρώτο μέρος της, να κάνει μια ιστορική αναδρομή στις θεωρίες που θεμελίωσαν την Αφηγηματολογία και να παρουσιάσει τις βασικότερες αφηγηματικές τυπολογίες. Στο δεύτερο μέρος γίνεται ερευνητική εφαρμογή των τυπολογιών αυτών, και κυρίως της θεωρίας του G. Genette, σε τρία μυθιστορήματα του συγγραφέα Μάνου Κοντολέων, τα οποία αναλύονται με βάση τις αφηγηματικές τους τεχνικές.The analysis of narrative techniques in a literary text is based on Narratology. Narratology is a branch of Theory of Literature, developed mainly in France during 1965-1975 and, affected by Russian Formalism, adopts a text- centered way of text understanding. In its first part, this thesis attempts to make a historical recursion to the theories Narratology is based on and to present the most well- known narrative typologies. In the second part, these typologies, and mainly the theory of G. Genette, will be applied to three novels, written by Manos Kontoleon. These novels will be analyzed by their narrative techniques

Thermal conductivity enhancement of laser induced graphene foam upon P3HT infiltration

Significant research has been dedicated to the exploration of high thermal conductivity polymer composite materials with conductive filler particles for use in heat transfer applications. However, poor particle dispersibility and interfacial phonon scattering have limited the effective composite thermal conductivity. Three-dimensional foams with high ligament thermal conductivity offer a potential solution to the two aforementioned problems but are traditionally fabricated through expensive and/or complex manufacturing methods. Here, laser induced graphene foams, fabricated through a simple and cost effective laser ablation method, are infiltrated with poly(3-hexylthiophene) in a step-wise fashion to demonstrate the impact of polymer on the thermal conductivity of the composite system. Surprisingly, the addition of polymer results in a drastic (250%) improvement in material thermal conductivity, enhancing the graphene foam's thermal conductivity from 0.68 W/m-K to 1.72 W/m-K for the fully infiltrated composite material. Graphene foam density measurements and theoretical models are utilized to estimate the effective ribbon thermal conductivity as a function of polymer filling. Here, it is proposed that the polymer solution acts as a binding material, which draws graphene ligaments together through elastocapillary coalescence and bonds these ligaments upon drying, resulting in greatly reduced contact resistance within the foam and an effective thermal conductivity improvement greater than what would be expected from the addition of polymer alone