The Rise and Fall of Family Firms in the Process of Development

This paper explores the causes and the consequences of the evolution of family firms in the growth process. The theory suggests that in early stages of development, valuable family specific human capital stimulated the productivity of family firms and the development process. However, in light of the rise in the importance of managerial talents for firms' productivity in later stages, family firms generated a misallocation of managerial talents, curbing productivity and economic growth. Evidence supports the dual impact of family firms in the development process and the role of socio-cultural characteristics in observed variations in the productivity of family firms

Genomic organization and splicing evolution of the doublesex gene, a Drosophila regulator of sexual differentiation, in the dengue and yellow fever mosquito Aedes aegypti

Background: In the model system Drosophila melanogaster, doublesex (dsx) is the double-switch gene at the bottom of the somatic sex determination cascade that determines the differentiation of sexually dimorphic traits. Homologues of dsx are functionally conserved in various dipteran species, including the malaria vector Anopheles gambiae. They show a striking conservation of sex-specific regulation, based on alternative splicing, and of the encoded sex-specific proteins, which are transcriptional regulators of downstream terminal genes that influence sexual differentiation of cells, tissues and organs. Results: In this work, we report on the molecular characterization of the dsx homologue in the dengue and yellow fever vector Aedes aegypti (Aeadsx). Aeadsx produces sex-specific transcripts by alternative splicing, which encode isoforms with a high degree of identity to Anopheles gambiae and Drosophila melanogaster homologues. Interestingly, Aeadsx produces an additional novel female-specific splicing variant. Genomic comparative analyses between the Aedes and Anopheles dsx genes revealed a partial conservation of the exon organization and extensive divergence in the intron lengths. An expression analysis showed that Aeadsx transcripts were present from early stages of development and that sex-specific regulation starts at least from late larval stages. The analysis of the female-specific untranslated region (UTR) led to the identification of putative regulatory cis-elements potentially involved in the sex-specific splicing regulation. The Aedes dsx sex-specific splicing regulation seems to be more complex with the respect of other dipteran species, suggesting slightly novel evolutionary trajectories for its regulation and hence for the recruitment of upstream splicing regulators. Conclusions: This study led to uncover the molecular evolution of Aedes aegypti dsx splicing regulation with the respect of the more closely related Culicidae Anopheles gambiae orthologue. In Aedes aegypti, the dsx gene is sex-specifically regulated and encodes two female-specific and one male-specific isoforms, all sharing a doublesex/mab 3 (DM) domain-containing N-terminus and different C-termini. The sex-specific regulation is based on a combination of exon skipping, 5' alternative splice site choice and, most likely, alternative polyadenylation. Interestingly, when the Aeadsx gene is compared to the Anopheles dsx ortholog, there are differences in the in silico predicted default and regulated sex-specific splicing events, which suggests that the upstream regulators either are different or act in a slightly different manner. Furthermore, this study is a premise for the future development of transgenic sexing strains in mosquitoes useful for sterile insect technique (SIT) programs

IL 17beta-ESTRADIOLO REGOLA L'ESPRESSIONE DEL TRASCRITTO DI fRLX IN Rana esculenta. ISOLAMENTO DA CERVELLO DI RANA DI UN NUOVO MEMBRO DELLA FAMIGLIA DELLE RELAXINE/INSULINE E DI UN RECETTORE fRXFP3

Relaxin and Insulin-like factor (RLX and INSL) are small peptide hormones belonging to the Insulin/IGF/Relaxin superfamily, well characterized in Mammalian and only recently discovered in lower Vertebrates. Human Relaxin family peptides are encoded by seven different genes: RLX1, RLX2, RLX3, INSL3, INSL4, INSL5, and INSL6. Phylogenetic analysis suggests that they could derive from a duplication phenomenon that involved three genetic loci named Relaxin Family Locus (RFL) studied in lower Vertebrates (Park et al., 2008). Although the Relaxins are present in different anatomical districts, they are primarily associated to reproductive roles. Studies on non mammalian vertebrates are mostly recent and generic. Since Relaxin family loci are phylogenetically conserved among lower vertebrates, the existence of further members of RFL has been verified in Rana esculenta through a bioinformatics approach based on the genomic sequence of the amphibious Xenopus tropicalis. This analysis allowed us to identify four preserved putative genes in Xenopus tropicalis, corresponding to the three RFL families (RFLA, RFLB, RFLCI and CII). We designed several degenerate primers, based on the nucleotidic alignment of the identified sequences, then used in RT-PCR experiments on total RNA extracted from some frog tissues. A couple of primers which targeted RLX3 (RFLCI) sequence we managed to amplify a 360 bp cDNA fragment, exclusively expressed in frog encephalon. Its identity was verified by cloning and sequencing. The putative translation of the nucleotidic sequence showed a 120 A.A. open reading frame. Sequence analysis by blastx showed that fRLX3 is homologous to mammalian RLX3 proteins. In particular, 8 there is notable structural similarity in the highly conserved B and A domains, typical of all the members of Relaxin family. It is worth noting that the Relaxin-3 is expressed in the nervous system at the level of nucleus incertus neurons in Variolo bridge, structure present in the encephalic trunk, and it seems to play the role of neuro-peptides or neuro-modulator. In order to understand if the expression profile of frog Relaxin-3 had the same trend than the one found in the mammalian CNS, an RT-PCR experiment was performed on total RNA extracted from different frog encephalic areas: in toto brain, telencephalon, diencephalon and mesencephalon. The first analysis showed that the transcript is highly and specifically expressed in the mesencephalic and diencephalic vesicles, while at telencephalic level the signal resulted lower, as already reported in mammals. In order to gather crucial knowledge about functional implication of fRLX and fRLX3, we had to identify and characterize any potential RLX receptors in the frog. Four relaxin receptors are known so far: RXFP1 (specific Relaxin receptor in mammals), RXFP2 (INSL3 receptor), RXFP3 (RLX3 receptor) and RXFP4 (INSL5 receptor). Using the same approach described earlier we designed degenerate primers for an RT-PCR, in order to isolate the receptors. We were able to amplify, from brain cDNA, a specific 327 nucleotidites band, homologous to mammalian RXFP3. As RXFP3 is the specific receptor to Relaxin-3,we carried out an expression analysis of fRXFP3 in the different encephalic areas of frog. The RT-PCR allowed us to determine that the expression of frxfp3 mRNA is not completely consistent with that of its ligandâs. In fact, while fRLX3 transcript is primarily detectable in the Mesencephal, we could not determine any significant difference in rxfp3 mRNA expression in the three encephalic regions. These data coincides with those about mammals. In fact, as stated previously, anatomical 9 evidences suggest that the RLX3 is produced by GABA neurons soma present in the Variolo bridge and in the mesencephal; it is subsequently transferred through assonal transport and released in the sinaptics or extrasinaptics sites in the forebrain, where it activates its cognate receptor, RXFP3, produced by the postsinaptic neurons.La Relaxina e l’Insulin-like factor (RLX e INSL) sono piccoli ormoni peptidici appartenenti alla superfamiglia dell’Insulina/IGF/Relaxine, ben caratterizzati nei Mammiferi e solo di recente ritrovati in modelli compresi in gruppi tassonomici di bassi Vertebrati. I peptidi appartenenti alla famiglia delle Relaxine sono codificati nell’uomo da sette geni differenti: i geni Relaxina RLX1, RLX2 e RLX3, i geni insulina simile INSL3, INSL4, INSL5, e INSL6 (Halls et al., 2007; Wilkinson et al., 2005b, Olinski, 2007). Analisi filogenetiche suggeriscono che essi possano derivare da un fenomeno di duplicazione che coinvolge tre locus genici denominati Relaxin Family Locus (RFL) evidenziati nei bassi vertebrati (Park et al., 2008). Benché le Relaxine siano presenti in diversi distretti anatomici, ricerche effettuate su Mammiferi ne associano le principali funzioni ai fenomeni riproduttivi. Per quanto concerne i Vertebrati nonmammiferi la ricerca sulle possibili funzioni è ad oggi un campo ancora completamente aperto. Vista la conservazione di locus genici della famiglia delle Relaxine nei bassi vertebrati, è stata verificata l’esistenza di ulteriori forme di RFL in Rana esculenta tramite un approccio bioinformatico analizzando il genoma dell’anfibio Xenopus tropicalis. Quest’analisi ha permesso di identificare quattro geni putativi conservati in Xenopus tropicalis corrispondenti alle tre famiglie RFL (RFLA, RFLB, RFLCI e CII). Sulla base dell’allineamento nucleotidico dei trascritti identificati, è stato dunque possibile disegnare coppie di oligonucleotidi “degenerati” da utilizzare in esperimenti di RT-PCR su RNA totale estratto da diversi tessuti di rana. In questo modo, utilizzando una coppia di primers disegnati sulla sequenza della RLX3 (RFLCI) si è ottenuto un amplificato di circa 360 cb, espresso esclusivamente nell’encefalo di rana. La banda ottenuta è stata, quindi, clonata e sequenziata: la sequenza ottenuta, una volta tradotta, presenta una cornice di lettura aperta di 120 aminoacidi. Tale sequenza, in seguito ad analisi in blastx, ha mostrato un’alta omologia con le proteine della famiglia delle Relaxine 3 depositate in banca dati genomica. In particolare, risultano essere altamente conservati il dominio strutturale della catena B e quello della catena A tipici di tutte le proteine appartenenti a questa famiglia. E’, inoltre, da tener presente che, nei mammiferi, la Relaxina-3 è espressa nel sistema nervoso a livello dei neuroni del nucleo incerto del ponte di Variolo, struttura presente nel tronco encefalico dove sembra svolgere la funzione di neuropeptide o neuromodulatore (Tregear et al., 2005; Sherie Ma. et al., 2009). Per verificare se il profilo di espressione della Relaxina-3 di rana fosse sovrapponibile a quello riscontrato nel SNC di mammifero, è stato effettuato un esperimento di RT-PCR su RNA totali estratti da differenti aree encefaliche di rana: cervello in toto, telencefalo, diencefalo e mesencefalo. Una prima analisi ha mostrato che il trascritto è altamente e specificamente espresso a livello della vescicola mesencefalica e diencefalica, mentre a livello del telencefalo il segnale risulta essere più basso, così come già evidenziato nei mammiferi. Parallelamente, al fine di poter intraprendere un discorso di tipo funzionale sul ruolo svolto da fRLX e fRLX3, si è cercato di identificare e caratterizzare i possibili recettori presenti in rana. Dalla letteratura risultano quattro recettori per le relaxine: RXFP1 (recettore specifico della Relaxina di mammifero), RXFP2 (recettore di INSL3), RXFP3 (RLN3) e RXFP4 (INSL5) (Bathgate et al., 2006) . Attraverso un’analisi di tipo bioinformatica basato sull’allineamento delle putative sequenze dei recettori presenti in banca dati, sono state disegnate delle coppie di primers degenerati che hanno permesso di amplificare dal cDNA di cervello di rana una banda specifica della lunghezza di 327 nucleotidi con sequenza molto conservata rispetto al recettore RXFP3 dei mammiferi. Dal momento che RXFP3 è il recettore specifico della Relaxina 3, si è deciso di effettuare anche un’analisi del profilo di espressione di fRXFP3 nelle diverse aree encefaliche di rana. L’analisi di RT-PCR ha mostrato che l’espressione di tale trascritto non corrisponde perfettamente a quella descritta per il ligando. Infatti, mentre i trascritti per fRLX3 sono maggiormente espressi a livello del Mesencefalo, non si osserva alcuna significativa differenza di espressione per l’mRNA di fRXFP3 a livello del Telencefalo e del Diencefalo. Questo dato coincide con quelli analizzati nei mammiferi. Infatti, come precedentemente affermato, evidenze anatomiche suggeriscono che la RLN3 sia prodotta nel soma dei neuroni GABA presenti nel ponte di Variolo e nel mesencefalo; essa è successivamente trasferita tramite trasporto assonale e rilasciata a livello dei siti sinaptici o extrasinaptici nella parte anteriore del cervello, dove attiva il suo recettore RXFP3 espresso dai neuroni postsinaptici (Tregear et al., 2005; Sherie Ma. et al., 2009)

The rise and fall of family firms in the process of development

This paper explores the causes and the consequences of the evolution of family firms in the growth process. The theory suggests that in early stages of development, valuable family specific human capital stimulated the productivity of family firms and the development process. However, in light of the rise in the importance of managerial talents for firms’ productivity in later stages, family firms generated a misallocation of managerial talents, curbing productivity and economic growth. Evidence supports the dual impact of family firms in the development process and the role of socio-cultural characteristics in observed variations in the productivity of family firms

Family Firms and Entrepreneurial Human Capital in the Process of Development

In this paper we present a new theory accounting for the heterogeneous impact of family firms on economic growth. We develop an overlapping generations model, where agents are heterogeneous in innate talent, and family firms have access to an additional source of managerial capital, family connections, which affects the incentives of the firms' owners to pass on the company within the family and invest in the entrepreneurial human capital of their heirs. Our theory predicts that family firms cluster into heterogeneous groups with different management practices, inducing, at the aggregate level, a misallocation of talent that affects economic growth and the evolution into either a dynamic or a stagnant society, depending on the productivity of family connections in doing business. This heterogeneity in management practices and entrepreneurial human capital explains the different contribution of family firms during industrialization, highlighting the many possible evolutionary patterns for the economy and long-run growth regimes. Consistent with the theory, we provide empirical evidence in favor of the importance of social connectivity among individuals for explaining the difference in management practices between family and non-family firms, and, in turn, the GDP per-capita across countries

Modelling the Maritime Cultural Landscape of the Costiera Amalfitana: The First Three Seasons of Research (2016–2018)

Human activity along the Amalfi coastline in Italy has been tied to the sea for millennia–for sustenance, migration, trade, warfare, and leisure. As a result, this region has an equally rich and extensive maritime cultural landscape composed of tangible and intangible elements. In 2016, a multi-disciplinary project began efforts to model and to understand changes within this landscape, and this essay presents the preliminary results of our first three seasons of work. Some efforts, such as the documentation of maritime cultural heritage in local museums, archival work, and geomorphological research proceeded smoothly. Unexpectedly, however, little material from the pre-modern era was found under water, adding questions to this study that future work in the Marine Protected Area west of Positano may answer