Transmembrane domain–dependent partitioning of membrane proteins within the endoplasmic reticulum

The length and hydrophobicity of the transmembrane domain (TMD) play an important role in the sorting of membrane proteins within the secretory pathway; however, the relative contributions of protein–protein and protein–lipid interactions to this phenomenon are currently not understood. To investigate the mechanism of TMD-dependent sorting, we used the following two C tail–anchored fluorescent proteins (FPs), which differ only in TMD length: FP-17, which is anchored to the endoplasmic reticulum (ER) membrane by 17 uncharged residues, and FP-22, which is driven to the plasma membrane by its 22-residue-long TMD. Before export of FP-22, the two constructs, although freely diffusible, were seen to distribute differently between ER tubules and sheets. Analyses in temperature-blocked cells revealed that FP-17 is excluded from ER exit sites, whereas FP-22 is recruited to them, although it remains freely exchangeable with the surrounding reticulum. Thus, physicochemical features of the TMD influence sorting of membrane proteins both within the ER and at the ER–Golgi boundary by simple receptor-independent mechanisms based on partitioning

The mouse median nerve experimental model in regenerative research

Sciatic nerve crush injury in rat animal model is one of the most common experimental models used in regenerative research. However, the availability of transgenic mouse for nerve regeneration studies is constantly increasing and, therefore, the shift from rat model to mouse model is, in some cases, necessary. Moreover, since most of the human nerve lesions occur in the upper limb, it is also advantageous to shift from sciatic nerve to median nerve. In this study we described an experimental model which involves lesions of the median nerve in the mouse. Data showed that the finger flexor muscle contraction strength, assessed to evaluate the motor function recovery, and reached values not different from the control already 20 days after injury. The degree of nerve regeneration evaluated with stereological methods in light microscopy showed that, 25 days after injury, the number of regenerated myelinated fibers was comparable to the control, but they were smaller with a thinner myelin thickness. Stereological analysis made in electron microscopy confirmed these results, although the total number of fibers quantified was significantly higher compared to light microscopy analysis, due to the very small size of some fibers that can be detected only in electron microscopy

Large outdoor fires and the built environment: summary of kick-off workshop

Presentacions del Workshop celebrat com una part del 11th Asia-Oceania Symposium on Fire Science and Technology (AOSFST) a Taipei, Taiwan.The kickoff workshop of the new permanent working group, sponsored by the International Association for Fire Safety Science (IAFSS), entitled Large Outdoor Fires and the Built Environment was held from 3:00 pm to 4:30 pm on Sunday October 21, 2018. The workshop was held as a part of the 11th Asia-Oceania Symposium on Fire Science and Technology (AOSFST) in Taipei, Taiwan. The working group is co-led by Sara McAllister of the U.S. Forest Service (unable to come to Taiwan), Sayaka Suzuki of National Research Institute of Fire and Disaster, and Samuel L. Manzello of NIST’s Engineering Laboratory. The IAFSS permanent working group consists of three subgroups, with subleaders appointed by Manzello, McAllister, and Suzuki, and these are prioritized into the following topics: Ignition Resistant Communities (IRC – led by Elsa Pastor, UPC, unable to come to Taiwan), Emergency Management and Evacuation (EME, led by Enrico Ronchi, Lund University, unable to come to Taiwan), and Large Outdoor Firefighting (LOFF, led by Raphaele Blanchi, CSIRO). The IRC subgroup is focused on developing the scientific basis for new standard testing methodologies indicative of large outdoor fire exposures, including the development of necessary testing methodologies to characterize wildland fuel treatments adjacent to communities. The EME subgroup is focused on developing the scientific basis for effective emergency management strategies for communities exposed to large outdoor fires. The LOFF subgroup is providing a review of various tactics that are used, as well as the various personal protective equipment (PPE), and suggest pathways for research community engagement, including environmental issues in suppressing these fires. The overall objectives are to bring the full depth of knowledge of the IAFSS community to work on these priority topics. At the kickoff workshop, detailed ideas were presented regarding the planned activities of the working group, especially the large workshop to be held at IAFSS 2020.Peer ReviewedPostprint (published version

Is Stereotactic Body Radiotherapy (SBRT) in lymph node oligometastatic patients feasible and effective?

ObjectivesTo review the available data about stereotactic body-radiotherapy (SBRT) for oligometastatic lymph node cancer recurrence.MethodsThe inclusion criteria for this study were as follows: Medline search for the (1) English language (2) full paper (abstracts were excluded) on (3) adult oligometastatic solid cancer recurrence limited to lymph node that underwent SBRT (4) outcome data available and (5) published up to the 30th April 2014.Results38 papers fulfilling the inclusion criteria have been found: 7 review articles and 31 patient series (20 and 11 retrospective and prospective studies, respectively) including between 1 and 69 patients (636 lymph nodes). Twelve articles reported only lymph node SBRT while in 19 – all types of SBRT including lymph node SBRT were presented. Two-year local control, 4-year progression free survival and overall survival was of up to 100%, 30% and 50%, respectively. The progression was mainly out-field (10–30% of patients had a recurrence in another lymph node/nodes). The toxicity was low with mainly mild acute events and single grade 3–4 late events. When compared to SBRT for any oligometastatic cancer, SBRT for lymph node recurrence carried better prognosis and showed lower toxicity.ConclusionsSBRT is a feasible approach for oligometastatic lymph node recurrence, offering excellent in-field tumor control with low toxicity profile. The potential abscopal effect has been hypothesized as a basis of these findings. Future studies are warranted to identify the patients that benefit most from this treatment. The optimal combination with systemic treatment should also be defined

The Mouse Median Nerve Experimental Model in Regenerative Research

Sciatic nerve crush injury in rat animal model is one of the most common experimental models used in regenerative research. However, the availability of transgenic mouse for nerve regeneration studies is constantly increasing and, therefore, the shift from rat model to mouse model is, in some cases, necessary. Moreover, since most of the human nerve lesions occur in the upper limb, it is also advantageous to shift from sciatic nerve to median nerve. In this study we described an experimental model which involves lesions of the median nerve in the mouse. Data showed that the finger flexor muscle contraction strength, assessed to evaluate the motor function recovery, and reached values not different from the control already 20 days after injury. The degree of nerve regeneration evaluated with stereological methods in light microscopy showed that, 25 days after injury, the number of regenerated myelinated fibers was comparable to the control, but they were smaller with a thinner myelin thickness. Stereological analysis made in electron microscopy confirmed these results, although the total number of fibers quantified was significantly higher compared to light microscopy analysis, due to the very small size of some fibers that can be detected only in electron microscopy

Using simulation as cervical and anal cytology teaching-learning strategy

The current descriptive study is an experience report about the use of gynecological simulators in teaching and research activities developed in the Undergraduate and Postgraduate courses in Health at Cruz Alta University in Southern Brazil. The aim of the present study is to describe the use of gynecological simulator as cervical and anal cytological sample collection teaching-learning strategy, as well as to describe the protocol adopted in such procedure. The gynecological simulator is a useful instrument applied to the sample collection practice for cervical and anal cytological examination purposes, since it is a static dummy anatomically similar to the female body. Simulating the procedure allows students to train and improve skills required to the technique; however, the theoretical contextualization must precede the practice in the simulator in order to stimulate students to reflect on all aspects involved in the exam. The use of gynecological simulator is recommended as complementary tool in cytologic examination teaching-learning scenarios

The impact of particle radiotherapy on the functioning of cardiac implantable electronic devices: a systematic review of in vitro and in vivo studies according to PICO criteria

The number of oncological patients who may benefit from proton beam radiotherapy (PBT) or carbon ion radiotherapy (CIRT), overall referred to as particle radiotherapy (RT), is expected to strongly increase in the next future, as well as the number of cardiological patients requiring cardiac implantable electronic devices (CIEDs). The management of patients with a CIED requiring particle RT deserves peculiar attention compared to those undergoing conventional photon beam RT, mostly due to the potential generation of secondary neutrons by particle beams interactions. Current consensus documents recommend managing these patients as being at intermediate/high risk of RT-induced device malfunctioning regardless of the dose on the CIED and the beam delivery method used, despite the last one significantly affects secondary neutrons generation (very limited neutrons production with active scanning as opposed to the passive scattering technique). The key issues for the current review were expressed in four questions according to the Population, Intervention, Control, Outcome criteria. Three in vitro and five in vivo studies were included. Based on the available data, PBT and CIRT with active scanning have a limited potential to interfere with CIED that has only emerged from in vitro study so far, while a significant potential for neutron-related, not severe, CIED malfunctions (resets) was consistently reported in both clinical and in vitro studies with passive scattering

Oct-4 is highly expressed in stem/progenitor cells and in primordial follicles of the fetal human ovary

Oct-4 (Octamer-binding transcription factor 4) is a member of the POU (Pit-Oct-Unc) family. During development, Oct-4 is expressed in embryonic stem cells and in germ cell precursors. In this study, we investigated the expression of Oct-4 in the ovaries of human fetuses during gestation. The ovaries of 14 human fetuses and newborns, ranging in gestational age from 12 up to 38 weeks of gestation, were formalin-fixed, routinely processed and paraffin-embedded. Paraffin sections were immunostained with an anti-Oct-4 commercial antibody. Oct-4 expression was demonstrated in all the ovaries analyzed. Immunoreactivity for Oct-4 was detected in multiple stem/progenitor cells, including oogonia. Moreover, Oct-4 was expressed in oocytes, in primordial follicles. In ovarian stem/progenitor cells, Oct-4 was expressed in the nucleus, whereas in oocytes reactivity for Oct-4 was restricted to the cytoplasm. In the initial stages of gestation, the majority of Oct-4-positive precursor cells were detected in the external cortex. These preliminary data indicate Oct-4 as a major player in germ cell differentiation in the human ovary and as a useful marker for ovarian stem/progenitor cells. Given the ability of Oct-4 for the detection of ovarian stem/progenitor cells, further studies are needed in order to verify its ability to detect stem cells in adult ovaries

Case report: A novel patient presenting TRIM32-related limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy autosomal recessive 8 (LGMDR8) is a rare clinical manifestation caused by the presence of biallelic variants in the TRIM32 gene. We present the clinical, molecular, histopathological, and muscle magnetic resonance findings of a novel 63-years-old LGMDR8 patient of Italian origins, who went undiagnosed for 24 years. Clinical exome sequencing identified two TRIM32 missense variants, c.1181G > A p.(Arg394His) and c.1781G > A p.(Ser594Asp), located in the NHL1 and NHL4 structural domains, respectively, of the TRIM32 protein. We conducted a literature review of the clinical and instrumental data associated to the so far known 26 TRIM32 variants, carried biallelically by 53 LGMDR8 patients reported to date in 20 papers. Our proband's variants were previously identified only in three independent LGMDR8 patients in homozygosis, therefore our case is the first in literature to be described as compound heterozygous for such variants. Our report also provides additional data in support of their pathogenicity, since p.(Arg394His) is currently classified as a variant of uncertain significance, while p.(Ser594Asp) as likely pathogenic. Taken together, these findings might be useful to improve both the genetic counseling and the diagnostic accuracy of this rare neuromuscular condition

Comunità cooperative. Terzo rapporto sulla cooperazione sociale in Italia

Il terzo rapporto sulla cooperazione sociale fornisce vari elementi conoscitivi che consentono di definire meglio i modelli interpretativi a spiegazione del successo e della grande crescita della cooperazione sociale. Il focus del presente rapporto è pertanto rivolto sia a spiegare lo sviluppo della cooperazione sociale che il differenziarsi dei modelli organizzativi presenti al suo interno.- Indice #4- Prefazione #10- Cap.I I contenuti del terzo rapporto sulla cooperazione sociale, Carlo Borzaga e Flaviano Zandonai #18- Cap.II I dati ministeriali: una fotografia della cooperazione sociale, Gianfranco Marocchi #46- Cap.III Le cooperative sociali nel nonprofit italiano: convergenze e divergenze strutturali, Nereo Zamaro #74- Cap.IV L’inserimento lavorativo nelle cooperative sociali, Gianfranco Marocchi #98- Cap.V La cooperazione sociale a livello locale: il caso della Lombardia, Alessandro Ronchi #120- Cap.VI Peculiarità e modelli delle cooperative sociali, Carlo Borzaga e Sara Depedri #144- Cap.VII Le reti tra cooperative sociali: il fenomeno consortile, Emmanuele Pavolini #188- Cap.VIII Alcune riflessioni sulla natura imprenditoriale della cooperazione sociale, Michele Andreaus #222- Appendice #258- Dentro le regioni #260- Bibliografia #33