Networks Underpinning Symbiosis Revealed Through Cross-Species eQTL Mapping.

Organisms engage in extensive cross-species molecular dialog, yet the underlying molecular actors are known for only a few interactions. Many techniques have been designed to uncover genes involved in signaling between organisms. Typically, these focus on only one of the partners. We developed an expression quantitative trait locus (eQTL) mapping-based approach to identify cause-and-effect relationships between genes from two partners engaged in an interspecific interaction. We demonstrated the approach by assaying expression of 98 isogenic plants (Medicago truncatula), each inoculated with a genetically distinct line of the diploid parasitic nematode Meloidogyne hapla With this design, systematic differences in gene expression across host plants could be mapped to genetic polymorphisms of their infecting parasites. The effects of parasite genotypes on plant gene expression were often substantial, with up to 90-fold (P = 3.2 × 10-52) changes in expression levels caused by individual parasite loci. Mapped loci included a number of pleiotropic sites, including one 87-kb parasite locus that modulated expression of >60 host genes. The 213 host genes identified were substantially enriched for transcription factors. We distilled higher-order connections between polymorphisms and genes from both species via network inference. To replicate our results and test whether effects were conserved across a broader host range, we performed a confirmatory experiment using M. hapla-infected tomato. This revealed that homologous genes were similarly affected. Finally, to validate the broader utility of cross-species eQTL mapping, we applied the strategy to data from a Salmonella infection study, successfully identifying polymorphisms in the human genome affecting bacterial expression

Hybrid areas of work between employment and self-employment : emerging challenges and future research directions

The growth of non-standard employment relations has created one of the major challenges in terms of workers\u2019 rights as well as collective representation in European societies. Among non-standard employment relations, so-called \u201csolo self-employed\u201d\u2014self-employed workers without employees\u2014are challenging the very foundations of our labor markets, that is to say the opposition between employers and employees, fostering the development of emerging \u201chybrid\u201d areas of work. The heterogeneity of the solo self-employed is difficult to capture from official statistics, which are still based on traditional classifications, and questions also the legal categories that qualify these workers. Moreover, the fact that solo self-employed workers do not form a homogenous group, and are diverse in terms of their activities, interests and needs, calls for changes in the way trade unions, employer organizations, and new freelancer associations develop collective actions, claims-making activities, and strategies of organizing. With the aim to achieve an in-depth understanding of the increasingly extensive and populated categories of the solo self-employed, this contribution aims at reconstructing the state of the art within different fields of study, such as employment relations, labor law, industrial relations and social movements, and at offering some possible future research directions

Somatic BRCA Mutation in a Cholangiocarcinoma Patient for HBOC Syndrome Detection

BRCA-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk of developing other malignancies including cholangiocarcinoma (CCA). Somatic BRCA mutations have been reported in CCA, but they have yet to be utilized in a proband case to identify HBOC in families. Two healthy daughters of a deceased female patient who had had metachronous breast cancer and CCA received genetic counseling to assess their cancer risk. Somatic BRCA1/2 mutation analysis was performed by next-generation sequencing on the DNA extracted from a formalin-fixed, paraffin-embedded CCA biopsy specimen of their mother. A pathogenic variant was identified (c.6468_6469delTC in a BRCA2 gene mutation). Germline BRCA mutation analysis of the two daughters detected the same pathogenic variant in one of them. For the first time, a CCA somatic BRCA mutation has been used to identify a family with HBOC

Macropinocytotic uptake and infection of human epithelial cells with species B2 adenovirus type 35

The human adenovirus serotype 35 (HAdV-35, short Ad35) causes kidney and urinary tract infections, and infects respiratory organs of immunocompromised individuals. Unlike other adenoviruses, Ad35 has a low seroprevalence which makes Ad35-based vectors promising candidates for gene therapy. Ad35 utilizes CD46 and integrins as receptors for infection of epithelial and hematopoietic cells. Here, we show that infectious entry of Ad35 into HeLa, human kidney HK-2 cells and normal human lung fibroblasts strongly depended on CD46 and integrins but not heparan sulfate, and variably required the large GTPase dynamin. Ad35 infections were independent of expression of the carboxy-terminal domain of AP180 which effectively blocks clathrin-mediated uptake. Ad35 infections were inhibited by small chemicals against the serine/threonine kinase Pak1 (p21-activated kinase), protein kinase C (PKC), sodium-proton exchangers, actin and acidic organelles. Remarkably, the F-actin inhibitor jasplakinolide, the Pak1 inhibitor IPA-3 or the sodium-proton exchange inhibitor EIPA blocked the endocytic uptake of Ad35. Dominant-negative proteins or small interfering RNAs against factors driving macropinocytosis, including the small GTPase Rac1, Pak1 or the Pak1 effector C-terminal binding protein 1 (CtBP1) potently inhibited Ad35 infection. Confocal laser scanning microscopy, electron microscopy and live cell imaging showed that Ad35 colocalized with fluid phase markers in large endocytic structures that were positive for CD46, alpha v integrins and also CtBP1. Our results extend earlier observations with HAdV-3 (Ad3), and establish macropinocytosis as an infectious pathway for species B human adenoviruses in epithelial and hematopoietic cells

Constraint degree in revision total knee replacement: a registry study on 1432 patients

Purpose: Total knee replacement (TKR) failure represents a hard challenge for knee surgeons. TKR failure can be managed in revision with different constraint, related with soft and bone knee damages. The choice of the right constraint for every failure cause represents a not summarized entity. The purpose of this study is identifying distribution of different constraints in revision TKR (rTKR) for failure cause and the overall survival. Methods: A registry study based on the Emilia Romagna Register of the Orthopaedic Prosthetic Implants (called RIPO) was performed with a selection of 1432 implants, in the period between 2000 and 2019. Selection implants including primary surgery constraint, failure cause and constraint revision for every patient, and divided for constraint degrees used during procedures (Cruciate Retaining-CR, Posterior Stabilized-PS, Condylar Constrained Knee-CCK, Hinged). Results: The most common cause of primary TKR failure was aseptic loosening (51,45%), followed by septic loosening (29,12%). Each type of failure was managed with different constraint, the most used was CCK in the most of failure causes, such as to manage aseptic and septic loosening in CR and PS failure. Overall survival of TKA revisions has been calculated at 5 and 10 years for each constraint, with a range of 75.1-90.0% at 5 years and 75.1-87.5% at 10 years. Conclusion: Constraint degree in rTKR is typically higher than primary, CCK is the most used constraint in revision surgery with an overall survival of 87.5% at 10 years

Total knee replacements using rotating hinge implants in polio patients: clinical and functional outcomes

Little evidences are available in the literature concerning the outcomes of total knee replacement (TKR) in poliomyelitis patients with severe knee deformities or degeneration. Encouraging results have been reported concerning the use of constrained implants, i.e., rotating hinge knee prosthesis (RHK), compared to less constrained ones. The purpose of this paper is to report our experience with rotating hinge total knee replacement, using only RHK prosthesis, to determine functional results, complications, and survival of TKR in poliomyelitis patients. We performed a retrospective chart review of 14 patients with a history of knee osteoarthritis following poliomyelitis that underwent primary TKR, for a total of 15 surgical procedure (one bilateral case). Preoperative and postoperative clinical measurements have been conducted for all patients using the Knee Society Score (KSS). Hip-knee angle, recurvatum knee angle, and Insall-Salvati index were evaluated with full weight-bearing panoramic view X-ray preoperatively and postoperatively. The 2-year postoperative clinical KSS significantly improved from the preoperative scores. The average clinical KSS improved from 32,9 (range 3-48) preoperatively to 77,4 (range 60-88) postoperatively (P value < 0.005). The average functional KSS improved from 32,5 (range 10-60) preoperatively to 59,4 (range 30-95) postoperatively (P value < 0.005). TKR is a successful treatment in improving knee function and patient's quality of life. Using constrained implants, especially rotating hinge implants in polio patients with a quadriceps muscle weakness, could be a good alternative to maintain a physiological kinematics and reducing the revision rate due to knee instability

Use of remote sensing‑derived fPAR data in a grapevine simulation model for estimating vine biomass accumulation and yield variability at sub‑field level

Grapevine simulation models are mostly used to estimate plant development, growth and yield at plot scale. However, the spatial variability of pedologic and micro-climatic conditions can influence vine growth, leading to a sub-field heterogeneity in plant vigor and final yield that may be better estimated through the assimilation of high spatial resolution data in crop models. In this study, the spatial variability of grapevine intercepted radiation at fruit-set was used as input for a grapevine simulation model to estimate the variability in biomass accumulation and yield in two Tuscan vineyards (Sites A and B). In Site A, the model, forced with intercepted radiation data as derived from the leaf area index (LAI), measured at canopy level in three main vigor areas of the vineyard, provided a satisfactory simulation of the final pruning weight (r2 = 0.61; RMSE = 19.86 dry matter g m−2). In Site B, Normalized Difference Vegetation Index (NDVI) from Sentinel-2A images was firstly re-scaled to account for canopy fraction cover over the study areas and then used as a proxy for grapevine intercepted radiation for each single pixel. These data were used to drive the grapevine simulation model accounting for spatial variability of plant vigor to reproduce yield variability at pixel scale (r2 = 0.47; RMSE = 75.52 dry matter g m−2). This study represents the first step towards the realization of a decision tool supporting winegrowers in the selection of the most appropriate agronomic practices for reducing the vine vigor and yield variability at sub-field level

Biomarker phenotyping drives clinical management in axillary sentinel node: A retrospective study on women with primary breast cancer in 2002

The current study examined if cancer biomarker phenotyping could predict the clinical/pathological status of axillary nodes in women with primary breast cancer. Primary breast cancers from 2002 were analyzed for tumor size, estrogen receptor (ER), progesterone receptor (PgR), Ki.67MIB expression and Her2/neu amplification. Relationships between the clinical and pathological status of the axilla and the biological subtypes classification were analyzed using univariate, multivariate and regression tree analysis. A total of 65% of women with axillary nodes clinically involved had complete axillary node dissection (ALND) while 705 women with clinically negative axillary underwent sentinel lymph node biopsy (SLNB), 18.5% of the latter had at least one pathologically SLNB involved node. Multivariate analysis revealed that the Luminal A subtype was significantly associated (OR 0.62; P<10-9) with clinical negative axilla while HER2pos/not Luminal was associated with clinical positivity (OR 1.71; P<0.01). No significant association between biological subtypes and SLNB status was demonstrated. Regression tree analysis revealed that subgroups with significantly different probability of SLNB status were separated according to tumor size and PgR values. In conclusion, the current study demonstrated that biomarker breast cancer phenotyping is significantly associated with clinical status of axillary nodes but not with pathological involvement of nodes at SLNB. Regression tree analysis could represent a valid attempt to individualize some patients subgroups candidate to different surgical axilla approaches

Spectrum of germline pathogenic variants in brca1/2 genes in the apulian southern italy population: Geographic distribution and evidence for targeted genetic testing

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects

Improving procedural fidelity of behavioural interventions for people with intellectual and developmental disabilities: A systematic review

Background: Despite its importance within behavioural intervention, it remains unclear how best to achieve high procedural fidelity. This paper reviewed studies on improving procedural fidelity of behavioural interventions for individuals with intellectual and developmental disabilities (IDD). Method: A systematic literature search was conducted, which identified 20 studies meeting inclusion criteria. Data were extracted on study design, participant characteristics, intervention, target behaviours, effect sizes, maintenance, generalisation, and social validity. A quality rating was also applied. Results: A total of 100 participants took part in the included studies. Most participants were teachers working with children in school settings. There was a significant positive correlation between level of procedural fidelity and client outcomes. Feedback was the most commonly employed intervention to improve procedural fidelity. Conclusions: More research should be conducted in environments with high levels of variability such as community homes to determine how to reach and maintain high levels of procedural fidelity