A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules

Abstract: Background: The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure–activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs – including BPP-10c – are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. Results: The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without affecting BTB permeability and the distribution of claudin-1 in the seminiferous epithelium. Interestingly, no morphological or morphometric alterations were observed in animals treated with captopril. Conclusions: The major finding of the present study was that BPP-10c, and not captopril, modifies spermatogenesis by causing hyperplasia of round spermatids in stages I, V, and VII/VIII of the spermatogenic cycle.

The changing politics of preference formation in international trade negotiations: the European Union in the Doha Round

This research seeks to provide an explanation for variations of “politics” of preference formation in international trade negotiations. Building on the ‘policy determines politics’ argument, I hypothesize the existence of a causal relationship between issue-characteristics and their variations with politics dynamics and their variations. More specifically, this study seeks to integrate into a single analytical framework two dimensions along which variations in the “politics of preference formation” can be organized: configurations of power relationships among the relevant actors in the structures within which they interact as well as the logic and the motivations of the actors involved in the policy making process. To do so, I first construct a four-cell typology of ‘politics of preference formation’ and, then, I proceed by specifying that the type of state-society configurations as well as the type of actors’ motivations in the “politics of preference formation” depend, respectively, on the degree to which a policy issue is perceived as politically salient and on the extent to which the distributional implications of such an issue can be calculated by the relevant stakeholders in the policy making process. The empirical yardstick against which the validity of the theoretical argument proposed is tested is drawn from evidence concerning the European Union’s negotiating strategy in four negotiating areas in the context of the so-called WTO’s Doha Development Round of multilateral trade negotiations: agriculture, competition, environment and technical assistance and capacity building.

Sorveglianza dell’infezione da virus dell’epatite E (HEV) in Italia: from farm to table

L'epatite E è una malattia umana con caratteristiche di epatite acuta, causata da un ssRNA virus (HEV). Nel 1997, HEV è stato identificato per la prima volta nei suini (SwHEV). In seguito, diverse evidenze, tra cui la vicinanza genetica tra ceppi umani e suini, suggerirono la trasmissione zoonotica del virus. Nella presente tesi, l’identificazione di SwHEV è stata condotta mediante ricerca di porzioni di genoma virale attraverso RT-PCR. Dal 2011 al 2013, sono stati analizzati 343 campioni fecali (da 19 allevamenti) e 70 bili (da 2 macelli) prelevati da altrettanti suini, in diverse Regioni italiane. E’ stato inoltre condotto uno studio retrospettivo su 78 feci (da 3 allevamenti) raccolte nel 2000. Il virus è stato identificato nel 24,5% e 19,2% delle feci raccolte rispettivamente nel 2011-2013 e nel 2000. Nessuna bile è risultata positiva. Mediante sequenziamento del genoma intero di uno dei virus identificati, è stata condotta l’analisi filogenetica per valutarne il grado di correlazione con alti ceppi suini e umani. La presenza di HEV è stata valutata lungo la filiera di produzione suina, dal macello al punto vendita. Trentaquattro campioni di feci, fegato e muscolo sono stati raccolti in un macello da altrettanti suini sani (età:6-7 mesi). Quattordici feci e 2 fegati, sono risultati positivi per HEV. Sono state prelevate 129 salsicce sia allo stabilimento di trasformazione sia alla vendita, ma nessuna è risultata positiva. La presenza di HEV è stata valutata anche nelle salsicce di fegato, fresche e secche, acquistate presso una macelleria. Il genoma virale è stato rilevato nel 22,2% delle salsicce fresche e nel 4,3 % di quelle secche ma la vitalità del virus non è stata dimostrata. In conclusione, lo studio condotto ha confermato l’ampia circolazione di HEV nei suini e la possibile contaminazione dei prodotti carnei derivati, confermando la necessità di una continua sorveglianza.

Tunnelling induced settlements in soils under the water table.

Tema di questo lavoro sono i cedimenti indotti dallo scavo di gallerie superficiali in terreni coesivi sotto falda. In questi casi la velocità di avanzamento dello scavo v e la permeabilità del mezzo k influenzano molto l'evoluzione della consolidazione. Le ipotesi di risposta non drenata o drenata del mezzo saturo, comunemente adottate, sono valide solo per rapporto v/k estremamente alto o basso. Nei casi intermedi, analisi numeriche accoppiate che tengano conto del processo di consolidazione durante lo scavo sono indispensabili. Ciò nonostante, queste sono molto rare in letteratura viste le notevoli difficoltà teoriche e numeriche ad esse associate. Proprio per non incrementare ulteriormente tali difficoltà, si è deciso di adottare modelli costitutivi semplici quali: il modello elastico perfettamente plastico con criterio di resistenza alla Mohr Coulomb e il Modified Cam Clay. Dopo un' introduzione sulla risposta del terreno nell'intorno dello scavo al variare del modello costitutivo, è stato svolto uno studio parametrico del processo di consolidazione. Ci si è, successivamente, concentrati sulla capacità dei tre modelli costitutivi di predire l'andamento dei cedimenti, mediante confronto con le soluzioni empiriche proposte in letteratura. Infine, sono state effettuate una serie di simulazioni 3D accoppiate passo-passo con il programma agli elementi finiti Abaqus al variare della permeabilità del mezzo e del rivestimento installato, supposto infinitamente permeabile o impermeabile. È emerso che per v/k<100 o v/k>100000 non è necessario esaminare nel dettaglio la dipendenza dal tempo della risposta del suolo e si possono ottenere risultati affidabili assumendo condizioni drenate o non drenate, rispettivamente. Nei casi intermedi, invece, le condizioni sono da ritenersi transienti e l'unico modo per effettuare correttamente le analisi dei cedimenti e lo studio della stabilità del fronte è mediante analisi numeriche 3D idromeccaniche accoppiate.

The floating mass transducer at the round window: direct transmission or bone conduction?

The round window placement of a floating mass transducer (FMT) is a new approach for coupling an implantable hearing system to the cochlea. We evaluated the vibration transfer to the cochlear fluids of an FMT placed at the round window (rwFMT) with special attention to the role of bone conduction. A posterior tympanotomy was performed on eleven ears of seven human whole head specimens. Several rwFMT setups were examined using laser Doppler vibrometry measurements at the stapes and the promontory. In three ears, the vibrations of a bone anchored hearing aid (BAHA) and an FMT fixed to the promontory (pFMT) were compared to explore the role of bone conduction. Vibration transmission to the measuring point at the stapes was best when the rwFMT was perpendicularly placed in the round window and underlayed with connective tissue. Fixation of the rwFMT to the round window exhibited significantly lower vibration transmission. Although measurable, bone conduction from the pFMT was much lower than that of the BAHA. Our results suggest that the rwFMT does not act as a small bone anchored hearing aid, but instead, acts as a direct vibratory stimulator of the round window membrane.

Factors improving the vibration transfer of the floating mass transducer at the round window

With the placement of a floating mass transducer (FMT) at the round window, a new approach of coupling an implantable hearing system to the cochlea has been introduced. The aim of the present experimental study is to examine the influence of different ways of FMT placement at the round window on the vibration energy transfer to the cochlea.

On-table reconstruction of comminuted fractures of the radial head

The most widely accepted treatment for comminuted fractures of the radial head is either the excision or open reduction and internal fixation. The purpose of the present study is to evaluate the value of an 'on-table' reconstruction technique in severely comminuted fractures of the radial head. In this study, two patients with a Mason type-III and four patients with a Mason type-IV radial-head fracture were treated with 'on-table' reconstruction and fixation using low-profile mini-plates. After a mean follow-up of 112 months (47-154 months), the mean elbow motion was 0-6-141 degrees extension flexion with 79 degrees of pronation and 70 degrees of supination. The mean Broberg and Morrey functional rating score was 97.0 points, the Mayo Elbow Performance Index was 99.2 points and the mean Disabilities of the Arm, Shoulder, and Hand (DASH) Outcome Measure score was 1.94 points. One patient had symptoms of degenerative changes, with a slight joint-space narrowing. There were no radiographic signs of devitalisation at final examination. Comminuted fractures of the radial head, which would otherwise require excision, can be successfully treated with an 'on-table' reconstruction technique.

Geophysical Analysis of Seasonal Montandon Gravel Ridge Water Table Fluctuation and Moisture Gradient Variation due to Storm Events

The purpose of this research project is to continue exploring the Montandon Long-Term Hydrologic Research Site(LTHR) by using multiple geophysical methods to obtain more accurate and precise information regarding subsurface hydrologic properties of a local gravel ridge,which are important to both the health of surrounding ecosystems and local agriculture. Through using non-invasive geophysical methods such as seismic refraction, Direct Current resistivity and ground penetrating radar (GPR) instead of invasive methods such as boreholedrilling which displace sediment and may alter water flow, data collection is less likely to bias the data itself. In addition to imaging the gravel ridge subsurface, another important researchpurpose is to observe how both water table elevation and the moisture gradient (moisture content of the unsaturated zone) change over a seasonal time period and directly after storm events. The combination of three types of data collection allows the strengths of each method combine together and provide a relatively strongly supported conclusions compared to previous research. Precipitation and geophysical data suggest that an overall increase in precipitation during the summer months causes a sharp decrease in subsurface resistivity within the unsaturated zone. GPR velocity data indicate significant immediate increase in moisture content within the shallow vadose zone (< 1m), suggesting that rain water was infiltrating into the shallow subsurface. Furthermore, the combination of resistivity and GPR results suggest that the decreased resistivity within the shallow layers is due to increased ion content within groundwater. This is unexpected as rainwater is assumed to have a DC resistivity value of 3.33*105 ohm-m. These results may suggest that ions within the sediment must beincorporated into the infiltrating water.