Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease.Peer reviewe

The old monastery of Baramus

North of the present Monastery of Virgin Mary of Baramūs in the Wādī al-Naṭrūn (the ancient desert of Sketis) there is a site, formerly known as Dayr Abū Mūsā al-’Aswad (Monastery of Saint Moses the Black). However, certain researchers argued that it could be identified with the Old Monastery of Baramūs. According to the hagiological tradition, this settlement was founded on the topos of the ‘Two Little Strangers’. By the end of the fourth century a laura already existed in its environs, which is regarded as one of the earliest communities organised in the desert of Sketis. The excavations, which were carried out by a team from Leiden University (the Netherlands), under the direction of Dr. Karel C. Innemée, brought to light the remains of a monastic compound. So far, it seems that the nucleus of the compound is the church, which has been remodelled in five different phases. At the south-eastern corner of the site a square-shaped building was uncovered; it has been considered to have been a defence tower, dating back to the fourth/fifth century, namely the earlier period of the settlement. In the western part of the complex, as well as at the north-eastern corner, parts of the living quarters or cells of the monks have been discovered. The pottery finds suggest that these cells were not inhabited before the late sixth to seventh centuries. Throughout the site a ninth century destruction level is evident. This monastic complex was in existence until the sixteenth century.Non UBCUnreviewedResearche

Deir el-Bala’izah, Monastery of Abba Apollo also known as “Dayr al-Balayza”, “Deir el-Balaiza”

The Monastery of Abba Apollo in Deir el-Bala’izah is situated on the left bank of the Nile, circa 18km to the south of Asiut, in Egypt. The first to investigate the site was F. Petrie (1907; 1909) who carried out brief excavation research, mainly in quest for papyri. Much later, P. Grossman conducted fieldwork and provided a more detailed description of the settlement (see: Grossmann 1993). It is considered that the first monastic habitations were adjusted in a pre-existing (presumably Roman?) quarry that was cut into the cliff that carries the desert plateau. Then the settlement extended down the rather steep slope and it was protected by an enclosure wall. The base of the wall is thicker as it was made of large stones connected with mud; the wall itself is constructed of mud-brick. It had a main gate on the east and several side entrances on the sides. The ruins in front of the main gate are interpreted as a guest-house. The entire settlement occupies an almost trapezoid area, where the remains of buildings still stand - some of them at a considerable height. The buildings were constructed of mud-brick and there is evidence that many of them had multiple storeys. They are gathered especially on the upper slope and inside a row of the quarry caves. Two large three-aisled structures are interpreted as refectories. The elongated buildings around them were identified by Grossmann (1993, 190-194) as dormitories. However, Wipszycka (2009, 119-120) argued that they could have been either store rooms either buildings of industrial function. Another building, which is characterised by a number of niches, was considered to be the library of the monastery, yet such an interpretation should be dealt with caution. Remains of two churches were discovered: a small church was built at the south-eastern corner of the site and another one to the west, around and outside a quarry cave. The water was supplied by a rectangular well.Non UBCUnreviewedPostdoctora

Monastery of Apa Apollo in Bawit

The monastic settlement of Apa Apollo in Bawit is situated in middle-Egypt, between the modern cities of al-Minya and Assiut. It lies on the edge of the Nile Valley, on a naturally formed hill (kom). It is a typical ‘monastic village’, with hermitages built close to each other. According to the Historia Monachorum in Aegypto, it was founded by Abba Apollo around 386-388 AD, but no archaeological evidence of such an early date is traced so far. According to inscriptions, the monastery existed until the tenth century, while the site was abandoned in the late eleventh or beginning of the twelfth century. Walter Ewing Crum and Jean Clédat were the first to identify the site as the monastery of Apa Apollo in the early 20th century. Archaeological investigations were first carried out by a French expedition (IFAO) between 1901/1902 and 1913. The site was then researched again in 1976-1985 by the Egyptian Antiquities Organisation. Fieldwork was resumed in 2003 (by IFAO and the Louvre) and continues until nowadays. The excavations have brought to light three churches. The ‘southern’ church was probably built in the seventh century AD. It was excavated in the early twentieth century and after the end of the investigations, it was destroyed by the removal of the architectural sculpture and a selection of wall paintings. The removed finds are nowadays kept in the Coptic Museum in Cairo and in the Louvre Museum. The church of Archangel Michael (also known as ‘northern’ church) is a three-aisled building with a sanctuary at the east, measuring 20.10 x 12.20 m. The walls are made of fired-brick and mud-brick and the floor is of limestone slabs. A wooden screen divides the sanctuary into two parts. The presence of a khurus in the western part is an indication that the church was built after the middle of the seventh century or the beginning of the eighth century. Wallpaintings decorated the walls, the columns and the pillars at the interior of the church. The main church of the complex is a three-aisled basilica with a tripartite sanctuary at the east, measuring 21.2 x 39.6 m (max. dim). Its walls are made of fired bricks with an external facing of limestone blocks. The building underwent various modifications (e.g. reconstruction of south wall with reused blocks, addition of a khurus in the seventh century). The main church was constructed in the late 6th-early seventh century AD. The interior of the entire building was decorated with wall-paintings. Furthermore, the carved architectural decoration in wood and stone would have been quite elaborate, as indicated by the large number of sculpted architectural remains, which are unearthed. In addition to the churches, many buildings were discovered. Some of them were rather impressive, with several barrel-vaulted storeys, and walls decorated with wallpaintings, inscriptions, dipinti, and so on. They were initially identified as chapels, but it is now known that they must have been monastic dwellings. Among them, the so-called 'Building 1' is fully excavated. It consists of several rooms surrounding a courtyard. Access to the building was given from the southwestern room. The walls of a vaulted room, east of the courtyard was richly decorated with wall-paintings. The geophysical survey carried out by T. Herbich showed that the site was densely inhabited, especially in the northern part of the hill. However, it is difficult to know how many of the hermitages were occupied simultaneously. A survey that was conducted in 2005-2006 (IFAO) on the top of the rocky plateau that rises to the west of the hill revealed clusters of hermitages, probably dating to the seventh/ eighth century AD. (Wipszycka 2018, 322-328) Numerous papyri and ostraca written mainly in Coptic, but in Greek as well, provide significant information about the monastic community living in Bawit. They were discovered either during the excavations, or in museum collections. The publications about the site are profuse (only a selection is included below).Non UBCUnreviewedPostdoctora

Skräddarsyd kristallisation av polyhydroxyalkanoater för förbättrade barriäregenskaper hos förpackningsmaterial

På grund av sina gynnsamma egenskaper består förpackningsmaterial till övervägande del sammansatta av petrokemiska plaster, som i hög grad bidrar till miljöföroreningar. Det akuta behovet av hållbara alternativ har ökat intresset för pappersförpackningar, vilka står inför utmaningar på grund av otillräckliga barriäregenskaper. Att utveckla biobaserade barriärer som är både effektiva och nedbrytbara för pappersförpackningar är avgörande. Denna avhandling undersöker potentialen hos naturligt härledda tillsatser som kärnbildande medel för att förbättra kristallisationsegenskaperna hos polyhydroxyalkanoat (PHA)-baserade filmer, i syfte att skapa effektiva barriärer för pappersbaserade förpackningsmaterial. En mängd olika karakteriseringsmetoder användes, och en åldringsstudie genomfördes för några prover för att undersöka om olika lagringsförhållanden skulle påverka kristalliniteten. Nyckelfynd indikerar att vissa kärnbildande medel, såsom behensyra, accelererade kristalliseringen av PHA, vilket resulterade i ökad kristallinitet. Specifikt ökade kristalliniteten med 5% för ett PHA-prov och med 15% för ett annat. Det fanns ingen signifikant effekt på den termiska stabiliteten eller smälttemperaturerna för PHA, vilket gjorde det svårt att avgöra om de kunde förbättra processegenskaperna med ett bredare processfönster. Förändringar i barriäregenskaper observerades, där syre- och vattenångtransmissionshastigheten för filmerna minskade med 70% respektive 40%, vilket indikerar förbättrad barriärprestanda för vissa prover. Åldring visade sig öka kristalliniteten, vilket ledde till förbättringar i barriäregenskaper och mekaniska egenskaper för vissa prover. Ytterligare forskning behövs, med ytterligare termiska analyser för att bedöma potentiella förbättringar i processbarhet.Due to their favourable properties, packaging materials are predominantly composed of petrochemical plastics, which contribute significantly to environmental pollution. The pressing need for sustainable alternatives has led to interest in paper-based packaging, which faces challenges due to inadequate barrier properties. Developing bio-based barriers that are both effective and degradable for fibre-based packaging is crucial. This thesis investigates the potential of naturally derived additives as nucleating agents to enhance the crystallization properties of polyhydroxyalkanoate (PHA)-based films, aiming to create effective barriers for paper-based packaging materials.  A variety of characterization methods were used, and an ageing study was done for some samples to see if different storage conditions would have an impact on the crystallinity. Key findings indicate that certain nucleating agents, such as behenic acid, accelerated the crystallization of PHAs, resulting in increased crystallinity. Specifically, the crystallinity increased by 5% for one PHA sample and by 15% for another. There was no significant effect on the thermal stability or melting temperatures of the PHAs, making it difficult to determine if they could enhance processability with a broader processing window. Changes in barrier properties were observed, with the oxygen and water vapor transmission rate values of the films decreasing by 70% and 40%, respectively, indicating improved barrier performance for some samples. Ageing was found to increase the crystallinity, leading to improvements in barrier and mechanical properties for some samples. Further research is needed, like additional thermal analyses to assess potential improvements in processability

Laserspridning för Snabb Dimensionskarakterisering av Cellulosafilament

Cellulosananofibriller (CNFs) hör till naturens mest fundamentala byggstenar och förser naturliga material, såsom den yttre cellväggen i trä, med en otrolig styrka och styvhet. Genom att imitera träets arkitektur öppnas möjligheter upp för tillverkning av nya, biobaserade och lättviktiga strukturella material med mekaniska egenskaper som överskrider de för glasfiber, metaller och legeringar. Den ingenjörsmässiga utmaningen ligger i att framgångsrikt lyckas överföra de önskade mekaniska egenskaperna hos CNFs till filament som kan användas i material för dagligt bruk. Vid flödesfokuserad spinning av extraherade CNFs påverkar många parametrar den slutgiltiga funktionaliteten och kvaliteten hos de resulterande filamenten. För att optimera dessa processparametrar är mätning av de spunna filamentens dimensioner ett viktigt moment. Av särskilt intresse är filamentbredden, eftersom den är avgörande för de mekaniska egenskaperna. Karakterisering av filamentbredden är i dagsläget en mycket tidskrävande process där varje filament mäts manuellt i optiskt mikroskop. Det huvudsakliga målet med detta projekt är att effektivisera den nuvarande mätprocessen med avseende på både hastighet och noggrannhet med hjälp av laserspridning. I denna rapport visar vi på minst en halvering av nuvarande mättid vid användandet av en 3D-printad laseruppställning istället för ett optiskt mikroskop vid mätning av filamentbredd. Våra resultat indikerar att mätsäkerheten generellt är högre för lasermetoden jämfört med mikroskopin. Genomsnittliga standardavvikelser för mätvärden på tunnaste bredden från mikroskopi samt de två olika kurvanpassningsmetoderna vid lasermätning rapporteras vara 1.62, 0.85 (Curve fit) respektive 1.59 (Minima matching). Standardavvikelserna för tunnaste bredd korrelerar dock inte direkt mot metodernas noggrannhet eftersom de spunna filamenten uppvisar en stor variation i bredd längs med längden. En närmare jämförelse mellan mätvärden för matchade punkter på ideala och defekta filament demonstrerar att icke-uniforma och defekta filament påverkar mätnoggrannheten för laserspridningen negativt. Sammantaget stödjer våra resultat det faktum att ett tunnare filament resulterar i bättre upplösning och mindre mätfel vid mätning med laserspridning. Våra resultat visar på den stora potentialen för laserspridning som en mer effektiv mätmetod vid karakterisering av cellulosafilamentbredd.Cellulose nanofibrils (CNFs) are one of nature’s most fundamental building blocks, providing incredible strength and stiffness to natural materials, such as the outer cell wall layer in wood. By mimicking the architecture of wood, possibilities opens up for the fabrication of new, biobased, light-weight structural materials with mechanical properties exceeding that of glassfibers, metals and alloys. However, the engineering challenge lies in successfully managing to translate the desirable mechanical properties of the CNFs into filaments that can be used in everyday life materials. Throughout the process of spinning the extracted CNFs into filaments, many factors and parameters affect the ultimate functionality and performance of the resulting filaments. Measuring the dimensions of the spun filaments is a crucial step in further optimizing process parameters. The width of the filament especially, impacts its mechanical performance. The characterization of the cellulose filament width is currently very time-consuming as each filament is manually measured using optical microscopy. The primary goal of this project is to make the current characterization process more effective, with respect to both accuracy and speed of measurement, by using laser scattering. In this report, we demonstrate a reduction by more than a half in measurement time using a 3D-printed laser scattering setup instead of an optical microscope when measuring filament width. Our results indicate that the certainty in measurement is generally higher for lase rscattering compared to optical microscopy. The mean standard deviations (SD) for the smallest widths estimated with optical microscopy and the two curve fitting methods used for the laser measurements are reported to be 1.62, 0.85 (Curve fit) and 1.59 (Minima matching) respectively. However, standard deviations for the thinnest width does not correlate directly to the accuracy of the methods since the spun filaments show a large variation in width along the length. A closer comparison between measurement values for matched points at ideal and non-uniform filaments demonstrate that the accuracy of the laser measurements are dependent on the uniformity of the filaments, with non-uniform filaments negatively impacting the accuracy. Our overall results supports the fact that a thinner filament gives a better resolution and smaller error when measuring with laser. Our results provide evidence for the great potential of laser scattering as a more efficient method for cellulose filament width determination

Prevalence of anti-HAV antibodies in multitransfused patients with beta-thalassemia

AIM: To detect the prevalence of anti-HAV IgG antibodies in adult multitransfused beta-thalassemic patients