Network formation and efficiency in linear-quadratic games: An experimental study

We experimentally study effort provision and network formation in the linear-quadratic game characterized by positive externality and complementarity of effort choices among network neighbors. We compare experimental outcomes to the equilibrium and efficient allocations and study the impact of group size and linking costs. We find that individuals overprovide effort relative to the equilibrium level on the network they form. However, their payoffs are lower than the equilibrium payoffs because they create fewer links than it is optimal which limits the beneficial spillovers of effort provision. Reducing the linking costs does not significantly increase the connectedness of the network and the welfare loss is higher in larger groups. Individuals connect to the highest effort providers in the group and ignore links to relative low effort providers, even if those links would be beneficial to form. This effect explains the lack of links in the network

The impact of social status on the formation of collaborative ties and effort provision: An experimental study

We study whether competition for social status induces higher effort provision and efficiency when individuals collaborate with their network neighbors. We consider a laboratory experiment in which individuals choose a costly collaborative effort and their network neighbors. They benefit from their neighbors' effort and effort choices of direct neighbors are strategic complements. We introduce two types of social status in a 2x2 factorial design: 1) individuals receive monetary benefits for incoming links representing popularity; 2) they receive feedback on their relative payoff ranking within the group. We find that link benefits induce higher effort provision and strengthen the collaborative ties relative to the Baseline treatment without social status. In contrast, the ranking information induces lower effort as individuals start competing for higher ranking. Overall, we find that social status has no significant impact on the number of links in the network and the efficiency of collaboration in the group

Whistleblowing and Diffusion of Responsibility: An Experimental Investigation

Societies today are increasingly reliant on whistleblowing to uncover unfair practices. For policy design it is therefore essential to better understand the impact of socio-psychological factors on whistleblowing propensity. We use an experimental setup to explore the role of “Diffusion of Responsibility” (DOR), which posits that individuals are less likely to whistleblow when others could similarly do so. We find that individuals do not shift responsibility to others if they expect an own monetary benefit from the consequences of whistleblowing, even if they could gain even more by freeriding on others who take action. In contrast, DOR affects whistleblowing propensities severely if whistleblowing is motivated solely by altruistic concerns. Our results highlight the fragility of purely altruistic behaviour and suggest that whistleblowing policies should ensure that potential whistleblowers perceive a gain to their in-group, but need not address the free riding problem among the insiders

Transplantacija spermatogonija kao nova metoda u akvakulturi i konzervaciji riba

Poslednjih godina, primena primordijalnih germinativnih ćelija (primordial germ cells - PGCs) i spermatogonijalnih stem ćelija (spermatogonial stem cells - SSCs) riba je postala veoma značajna zbog razvoja metode transplantacije ovih ćelija. Od kada su Brinster i Avarbock (1994) razvili ovu metodu, ona se uspešno koristi za čuvanje genetskog materijala ugroženih vrsta i u stvaranju novih transgenih linija kod miševa i domaćih životinja. Uvođenje ove metode kod riba predstavlja značajan napredak u oblasti reproduktivne biotehnologije, akvakulture, konzervacione biologije, kao i u razvoju novih transgenih linija različitih vrsta riba. Osnovu ove metode predstavlja transplantacija germinativnih ćelija (PGC, SSC) iz donorskog organizma u organizam primaoca. Najinteresantnija u tom smislu je upotreba nediferenciranih spermatogonija A tipa (Aund) koje imaju sposobnost samoobnavljanja ali i proizvodnje ćelija kasnijih faza spermatogeneze. Postoji takođe nekoliko specifičnih osobina SSC koje ih čine pogodnim za transplantaciju: (1) sposobnost da kolonizuju testis primaoca odakle produkuju donorsku spermu, (2) mogućnost da se nakon transplantacije u primaocu muškog pola razviju u spermatogonije, a u primaocu ženskog pola u oogonije i (3) mogućnost genske manipulacije sa ciljem produkcije transgenih riba (Lacerda i sar., 2010). Prilikom transplantacije SSC, posebna pažnja mora biti usmerena ka izboru vrste donora i primaoca. Najbolje bi bilo da donor i primalac ne budu filogenetski previše udaljeni, kao i da primalac ima kratak reproduktivni ciklus i manje dimenzije tela kako bi ekonomski bio pogodniji za gajenje. Donorska vrsta je obično vrsta za koju postoji određneni interes, bilo ekonomski, naučni ili konzervacioni. Tokom transplantacije, kompatibilnost između primaoca i donora može biti ograničavajući faktor u uspehu samog procesa. U najgorem slučaju, primalac, usled imune reakcije, može u potpunosti odbaciti transplantirano tkivo ili ćelije. To je najčešće slučaj ukoliko se vrši transplantacija SSC iz odraslog donora u odraslog primaoca. Kako bi se izbegao problem izazvan transplantacijom između dve odrasle jedinke, koristi se prednost ontogenije primaoca, posebno ontogenije njegovog imunog sistema, tako što se za primaoca koriste embrioni ili larve. Ovi stadijumi kod riba nemaju razvijen imuni sistem niti diferencirane T-ćelije (Takeuchi et al., 2003; Yoshizaki et al., 2011) te s toga nemaju mehanizam pomoću kojeg bi odbacili donorsko tkivo. Takođe, lakše je blokirati razvoj endogenih primordijalnih germinativnih ćelija kod larvi, nego ukloniti SSC iz već razvijenih gonada kod odraslog donora. Pored odabira odgovarajuće vrste donora i primaoca, neophodno je na pravi način izolovati specifične ćelije koje treba da budu transplantirane. Ovaj proces je donekle jednostavniji kada je u pitanju tansplantacija PGC s obzirom na njihov daleko manji broj u odnosu na spermatogonije i na to da one još uvek nisu potpuno razvijene u gonadama. S druge strane, SSC su dobro razvijene u gonadama i najčešće zauzimaju karakteristično mesto unutar pojedinačnih niša u testisu specifičnih za tu vrstu ćelija. Prilikom izolacije nediferenciranih spermatogonija A tipa iz testisa odrasle jedinke, veome je bitno voditi računa od morfologiji tih ćelija kao i specifičnim markerima pomoću kojih ih je moguće razlikovati od ostalih tipova spermatogonija (Adiff, B), spermatocita i spermatida. Osnovne histološke metode u kombinaciji sa imunohistohemijom, in situ hibridizacijom ili in situ PCR metodom se mogu koristiti za identifikaciju spefifičnih molekularnih markera (proteina ili RNK) u ćelijama unutar ćelijskih niša i koji se u daljem toku rada mogu koristiti za izolaciju određenih ćelija. Pre transplantacije PGC ili SSC, neophodno je izolovati željene ćelije iz donorskog tkiva. Nakon multienzimske razgradnje tkiva testisa, ćelije se izoluju na osnovu njihove morfologije i veličine i/ili specifičnih molekularnih markera zbog kojih čitav proces može biti species-specifičan. Kombinacija transplantacije PGS i SSC sa krioprezervacijom daje dodatni značaj ovoj metodi s obzirom da još uvek ne postoji optimizovan protokol za uspešnu krioprezervaciju jaja i embriona riba, pre svega zbog prisustva velike količine žumanceta i masti. Krioprezervacija ćelija kao što su PGS i SSC, koje imaju mogućnost da produkuju spermatozoide ili oocite u zavisnosti od pola jedinke primaoca, ima izuzetno veliku perspektivu primene u konzervacionoj biologiji i akvakulturi. Istraživanja su pokazala da krioprezervirane SSC nakon odmrzavanja i transplantacije u telo primaoca mogu proizvesti spermatozoide i oocite donorske vrste (Kobayashi et al., 2007). Na taj način, čuvanje gameta nije neophodno jer krioprezervacijom germinativnih ćelija i njihovom transplantacijom, moguće je dobiti gamete oba pola.In recent years, the importance of manipulations of primordial germ cells (PGCs) and spermatogonial stem cells (SSCs) in fish has drastically increased due to development of transplantation method of these cells. Since its development by Brinster and Avarbock (1994), this method has been successfully used in the preservation of genetic material of endangered species and in the creation of new transgenic lines of mice and farm animals. Introduction of this method in fish leads to advances in reproductive biotechnology, aquaculture, development of new transgenic lines and conservation biology of fish. The base of this method lies in the transplantation of the germinative cells (PGCs, SSCs) from donor organism into recipient organism. Undifferentiated spermatogonia type A (Aund) which have the ability of self-renewal are the most interesting for transplantation since they have the ability of self-renewal, but can also produce later stage cells. There are several advantages of using SSCs in transplantation process: (1) the capability of SSCs to colonize the testis of the recipients where they are able to produce donor-derived sperm, (2) plasticity in development since SSCs can develop into spermatogonia in male recipients and oogonia in female recipients and (3) the possibility of genetic manipulation in SSCs in order to produce transgenic fish (Lacerda et al., 2010). When transplanting SSCs, special attention must be given to the choice of donors and recipients species. It is best that donor and recipient organisms are phylogenetically not too distant, that recipient organisms have a short reproductive cycle and that they are small for a more economic rearing. Donor species are usually species which attract certain interest, whether its an economic, scientific or conservation interest. During transplantation, compatibility between recipient and donor may be a very limiting factor in transplantation success. In the worst-case scenario, recipients may completely reject the transplanted tissue or cells due to immunological reaction. This is especially the case when transplanting SSCs isolated from adult donors into adult recipients. In order to evade the problems caused by adult-adult transplantations, scientists have taken advantage of the ontogeny of recipients, mainly the ontogeny of their immune system, and used embryos and larvae as recipients. Embryos and larvae do not have a developed immune system nor differentiated T-cells (Takeuchi et al., 2003; Yoshizaki et al., 2011), therefore they do not have mechanisms to reject the donor tissue. Furthermore, it is easier to knock-out larval endogenous PGCs than to deplete SSCs from already developed gonad. Apart from choosing the right donor and recipient organisms, it is necessary to isolate specific cells that need to be transplanted. This is to some extent easier when transplanting PGCs, since there are fewer of them than SSCs, and they have not yet fully developed inside the gonads. On the other hand, SSCs are well developed inside the gonads and usually take their specific place within the spermatogonial stem niche. When isolating undifferentiated spermatogonia type A from adult testis, special attention must be given to their morphology and specific markers that distinguish them from other types of spermatogonia (Adiff, B), spermatocytes and spermatids. Basic histology may be coupled with immunohistochemistry, in situ hybridization or in situ PCR which would enable the identification of specific molecular markers within the cells of the niche (proteins or RNA). All this data can be further used in isolation of particular cells. Prior to transplantation, PGCs and spermatogonia need to be isolated from the donor tissue. After multi-enzymatic digestion it is possible to isolate cells based on their morphology and size, and/or specific molecular markers and the whole process can be species-specific. A great advantage of transplantation of PGCs and SSCs is that this method can be very well combined with cryopreservation. There are still no optimized protocols for cryopreservation of fish eggs and embryos, mostly due to presence of large amount of yolk and fat. Since PGCs and SSCs can develop into both sperm and eggs, cryopreservation of these cells could have a great perspective in conservation biology but also in aquaculture. Studies have shown that frozen/thawed SSCs transplanted into recipients give rise to potent donor sperm and eggs in the recipients (Kobayashi et al., 2007). In this way, there is no need to conserve both sperm and eggs since successful cryopreservation of germ cells can give rise to both sperm and eggs after transplantation

Vitrifikacija mleča grgeča (perca fluviatilis)

Vitrifikacija je proces dovođenja vode ili rastvora u čvrsto stanje, odnosno u amorfno ili staklasto stanje koje može da se dostigne veoma brzom hlađenjem (106-1010 °C/s). Nedavno je objavljeno nekoliko istraživanja o vitrifikaciji mleča različitih vrsta riba, međutim nema dostupnih informacija o vitrifikaciji mleča grgeča (Perca fluviatilis). Mužjaci grgeča su uzorkovani 6 dana posle hormonske injekcije (250 IU kg-1 hCG). Evaluirana je pokretljivost spermatozoida pomoću sistema kompjuterske analize sperme CASA. Za process vitrifikacije mleč je razblažen modifikovanim Tanaka ekstenderom na finalni odnos 1:5 (sa krioprotektantima). Posle preliminarnih testova sa kombinacijom metanola i propilen glikola (PG) u različitim koncentracijama, odlučeno je da se koristi 15% metanola i 15 % PG (ukupno 30% krioprotektanata). Suspenzija mleča je ubačena direktno u tečni azot bez prethodnog hlađenja u njegovoj pari. Za sve eksperimente vitrifikacije za hlađenje su korišćene cevčice Cryotop (Kitazato-Dibimed, za 2 µl rastvora). Za fertilizacioni test su prikupljena jaja ženki grgeča. Vitrifikovane Cryotop cevčice otopljene su direktno u 10 µl rastvora za aktivaciju (50 mm NaCl) u petri šoljama koje su sadržale jaja. Svež mleč služio je za kontrolu. Oplođena jaja su inkubirana u plivajućem sistemu. Izvedena su 3 ogleda da bi se utvrdio odgovarajući broj cevčica Cryotop za svaku seriju jaja: 1, 6 i 18 cevčica Cryotop je isprobano za svaku seriju jajnih ćelija. U 2 µl rastvora mleča jedne Cryotop cevčice bilo je oko 0,33 µl mleča. Na osnovu stepena oplođenja u tri ogleda može se zaključiti da povećanje broja Cryotop cevčica pojačava stepen oplođenja. Dalja sitraživanja su neophodna da bi se razvio metod vitrifikacije sa većim preživljavanjem larvi posle oplođenja vitrifikovanim mlečom. Takođe je potrebno ispitati stepen izvaljenih embriona iz ogleda sa vitrifikovanim mlečom, kao i potencijalni uticaj vitrifikacije na larve, pre svega na deformitete i morfološke promene

The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages

The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF-kappaB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit diminished inflammasome activation, decreased IL-1beta production, and pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli

Proteome-wide landscape of solubility limits in a bacterial cell

Proteins are prone to aggregate when expressed above their solubility limits. Aggregation may occur rapidly, potentially as early as proteins emerge from the ribosome, or slowly, following synthesis. However, in vivo data on aggregation rates are scarce. Here, we classified the Escherichia coli proteome into rapidly and slowly aggregating proteins using an in vivo image-based screen coupled with machine learning. We find that the majority (70%) of cytosolic proteins that become insoluble upon overexpression have relatively low rates of aggregation and are unlikely to aggregate co-translationally. Remarkably, such proteins exhibit higher folding rates compared to rapidly aggregating proteins, potentially implying that they aggregate after reaching their folded states. Furthermore, we find that a substantial fraction (similar to 35%) of the proteome remain soluble at concentrations much higher than those found naturally, indicating a large margin of safety to tolerate gene expression changes. We show that high disorder content and low surface stickiness are major determinants of high solubility and are favored in abundant bacterial proteins. Overall, our study provides a global view of aggregation rates and hence solubility limits of proteins in a bacterial cell.Peer reviewe

Correlative Fluorescence and Raman Microscopy to Define Mitotic Stages at the Single-Cell Level: Opportunities and Limitations in the AI Era

Nowadays, morphology and molecular analyses at the single-cell level have a fundamental role in understanding biology better. These methods are utilized for cell phenotyping and in-depth studies of cellular processes, such as mitosis. Fluorescence microscopy and optical spectroscopy techniques, including Raman micro-spectroscopy, allow researchers to examine biological samples at the single-cell level in a non-destructive manner. Fluorescence microscopy can give detailed morphological information about the localization of stained molecules, while Raman microscopy can produce label-free images at the subcellular level; thus, it can reveal the spatial distribution of molecular fingerprints, even in live samples. Accordingly, the combination of correlative fluorescence and Raman microscopy (CFRM) offers a unique approach for studying cellular stages at the singlecell level. However, subcellular spectral maps are complex and challenging to interpret. Artificial intelligence (AI) may serve as a valuable solution to characterize the molecular backgrounds of phenotypes and biological processes by finding the characteristic patterns in spectral maps. The major contributions of the manuscript are: (I) it gives a comprehensive review of the literature focusing on AI techniques in Raman-based cellular phenotyping; (II) via the presentation of a case study, a new neural network-based approach is described, and the opportunities and limitations of AI, specifically deep learning, are discussed regarding the analysis of Raman spectroscopy data to classify mitotic cellular stages based on their spectral maps

Assessing the Viscoelasticity of Photopolymer Nanowires Using a Three-Parameter Solid Model for Bending Recovery Motion

Photopolymer nanowires prepared by two-photon polymerization direct laser writing (TPP-DLW) are the building blocks of many microstructure systems. These nanowires possess viscoelastic characteristics that define their deformations under applied forces when operated in a dynamic regime. A simple mechanical model was previously used to describe the bending recovery motion of deflected nanowire cantilevers in Newtonian liquids. The inverse problem is targeted in this work; the experimental observations are used to determine the nanowire physical characteristics. Most importantly, based on the linear three-parameter solid model, we derive explicit formulas to calculate the viscoelastic material parameters. It is shown that the effective elastic modulus of the studied nanowires is two orders of magnitude lower than measured for the bulk material. Additionally, we report on a notable effect of the surrounding aqueous glucose solution on the elasticity and the intrinsic viscosity of the studied nanowires made of Ormocomp