Angiomatoid fibrous histiocytoma: comparison of fluorescence in situ hybridization and reverse transcription polymerase chain reaction as adjunct diagnostic modalities

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the extremities of children and young adults. Although it has characteristic histologic features of a lymphoid cuff surrounding nodules of ovoid cells with blood-filled cystic cavities, diagnosis is often difficult due to its morphologic heterogeneity and lack of specific immunoprofile. Angiomatoid fibrous histiocytoma is associated with recurrent chromosomal translocations, leading to characteristic EWSR1-CREB1, EWSR1-ATF1, and, rarely, FUS-ATF1 gene fusions; fluorescence in situ hybridization (FISH), detecting EWSR1 or FUS rearrangements, and reverse transcription-polymerase chain reaction (RT-PCR) for EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts have become routine ancillary tools. We present a large comparative series of FISH and RT-PCR for AFH. Seventeen neoplasms (from 16 patients) histologically diagnosed as AFH were assessed for EWSR1 rearrangements or EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts. All 17 were positive for either FISH or RT-PCR or both. Of 16, 14 (87.5%) had detectable EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts by RT-PCR, whereas 13 (76.5%) of 17 had positive EWSR1 rearrangement with FISH. All 13 of 13 non-AFH control neoplasms failed to show EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts, whereas EWSR1 rearrangement was present in 2 of these 13 cases (which were histopathologically myoepithelial neoplasms). This study shows that EWSR1-CREB1 or EWSR1-ATF1 fusions predominate in AFH (supporting previous reports that FUS rearrangement is rare in AFH) and that RT-PCR has a comparable detection rate to FISH for AFH. Importantly, cases of AFH can be missed if RT-PCR is not performed in conjunction with FISH, and RT-PCR has the added advantage of specificity, which is crucial, as EWSR1 rearrangements are present in a variety of neoplasms in the histologic differential diagnosis of AFH, that differ in behavior and treatment.

CLLU1 expression has prognostic value in chronic lymphocytic leukemia after first-line therapy in younger patients and in those with mutated IGHV genes.

CLLU1, located at chromosome 12q22, encodes a transcript specific to chronic lymphocytic leukemia and has potential prognostic value. We assessed the value of CLLU1 expression in the LRF CLL4 randomized trial. Samples from 515 patients with chronic lymphocytic leukemia were collected immediately before the start of treatment. After RNA extraction and cDNA synthesis, CLLU1 expression was assessed by quantitative polymerase chain reaction. In total, 247 and 268 samples were identified as having low and high CLLU1 expression, respectively. The median follow-up was 88 months. High CLLU1 expression was significantly correlated with unmutated IGHV genes, ZAP-70 and CD38 positivity, and absence of 13q deletion (all r>0.2, P

A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value.

To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.

Quantum Otto heat engine based on a multiferroic chain working substance

We study a quantum Otto engine operating on the basis of a helical spin-1/2 multiferroic chain with strongly coupled magnetic and ferroelectric order parameters. The presence of a finite spin chirality in the working substance enables steering of the cycle by an external electric field that couples to the electric polarization. We observe a direct connection between the chirality, the entanglement and the efficiency of the engine. An electric-field dependent threshold temperature is identified, above which the pair correlations in the system, as quantified by the thermal entanglement, diminish. In contrast to the pair correlations, the collective many-body thermal entanglement is less sensitive to the electric field, and in the high temperature limit converges to a constant value. We also discuss the correlations between the threshold temperature of the pair entanglement, the spin chirality and the minimum of the fidelities in relation to the electric and magnetic fields. The efficiency of the quantum Otto cycle shows a saturation plateau with increasing electric field amplitude.

Antiangiogenic potential of yogurts added with extracts rich in apigenin derivatives

Angiogenesis is a biological process through which there is the formation of new blood vessels from preexisting ones [I]. However, in pathological cases, the abnormal growth of new blood vessels promotes the development of various diseases including cancer [2) through the production of atypically large amounts of angiogenesis factors, e.g. the vascular endothelial growth factor (VEGF) [3]. The plant secondary metabolites have been the subject of several studies to evaluate their benefits to human health. In particular, the phenolic compounds have high potential for use in the food industry, including the development of functional foods. Among these, apigenin has been associated with chemopreventive effects related to cancer [4]. In fact, chemoprevention is a present-day concept and contemplates the use of medicines, biological compounds or nutrients as an intervention strategy of cancer prevention. In this work, an Arenaria montana L hydroethanolic extract was prepared and after characterization by HPLC-DAD-ESI/MS showed to be rich in apigenin derivatives. Furthermore, it exhibited ability to inhibit the phosphorylation of VEGFR-2 (vascular endothelium growth factor receptor) through an enzymatic assay. However, for the major protection of bioactive compounds, the extract was microencapsulated by an atomization/coagulation technique with alginate as the matrix material. Posteriorly, the hydroethanolic extract, in free and microencapsulated forms, was incorporated in yogurts in order to develop a novel chemopreventer food in relation to the angiogenesis process. The functionalized yogurts with A. montana extracts (free and microencapsulated) showed a nutritional value similar to the used control (yogurt without extract); however, the samples enriched with extracts revealed added-value regarding the VEGFR-2 phosphorylation inhibition ability. This effect was more effectively preserved over time in the samples functionalized with the protected extract. Overall, this work contributes to the valorization of plants rich in flavonoids, exploring its antiangiogenic potential with VEGFR-2 as target. Moreover, the atomization/coagulation technique allowed the production of viable microspheres enriched with the plant extract. The microspheres were effectively incorporated into yogurts, protecting the extract thus envisaging the development of novel functional foods with chemopreventive effects.

Green supply chain management practices and firm performance: evidence from Finland

In order to address the increasing stakeholder requirements for environmentally sustainable products and processes, firms often need the participation of their supply chain partners. Green supply chain management has emerged as a set of managerial practices that integrate environmental issues into supply chain management. If implemented successfully, green supply chain management can be a way to achieve competitive advantage while enhancing the environmental sustainability of the firm. The overall purpose of this dissertation is to contribute to the discussion on green supply chain management practices from the perspective of their drivers and performance implications. The theoretical background arises from the literature on competitive strategy, firm performance and green supply chain management. The research questions are addressed by analysing firm-level data from manufacturing, trading and logistics firms operating in Finland. The empirical data comes from two consecutive Finland State of Logistics surveys in 2012 and 2014, combined with financial reporting data from external databases. The data is analysed with multiple statistical methods. First, the thesis contributes to the discussion of the drivers of GSCM practices. To enhance the understanding of the relationship between competitive strategy and GSCM practices, a conceptual tool to describe generic competitive strategy approaches was developed. The findings suggest that firms pursuing marketing differentiation are more likely to be able to compete by having only small environmental effects and by adopting a more advanced form of external green supply chain management, such as a combination of strong environmental collaboration and the increased environmental monitoring of suppliers. Furthermore, customer requirements for environmental sustainability are found to be an important driver in the implementation of internal GSCM practices. Firms can respond to this customer pressure by passing environmental requirements on to their suppliers, either through environmental collaboration or environmental monitoring. Second, this thesis adds value to the existing literature on the effects of green supply chain management practices on firm performance. The thesis provides support for the idea that there is a positive relationship between GSCM practices and firm performance and enhances the understanding of how different types of GSCM practices are related to 1) financial, 2) operational and 3) environmental performance in manufacturing and logistics. The empirical results suggest that while internal GSCM practices have the strongest effect on environmentalperformance, environmental collaboration with customers seems to be the most effective way to improve financial performance. In terms of operational performance, the findings were more mixed, suggesting that the operational performance of firms is more likely to be affected by firm characteristics than by the choices they make regarding their environmental collaboration. This thesis is also one of the first attempts to empirically analyse the relationship between GSCM practices and performance among logistics service providers. The findings also have managerial relevance. Management, especially in manufacturing and logistics industries, may benefit by gaining knowledge about which types of GSCM practice could provide the largest benefits in terms of different performance dimensions. This thesis also has implications for policy-makers and regulators regarding how to promote environmentally friendly activities among 1) manufacturing; 2) trading; and 3) logistics firms.

Produtos DOP/IGP de origem animal em trás-os-montes, Portugal: da protecção ao mercado

RESUMO O artigo avalia o desempenho no mercado dos produtos DOP/IGP de origen animal na região de Trás-os-Montes, recorrendo à análise cruzada das variáveis “sucesso observado” e “sucesso calculado”. O “sucesso observado” é estimado pela verificação conjunta de pelo menos três dos seguintes indicadores: 1) produção anual e importância económica crescente; 2) taxas de crescimento superiores às do mercado de referência; 3) notoriedade do nome do produto específico; e 4) preço superior ao do produto standard. O “sucesso calculado” determina-se cruzando as variáveis 1) rapidez na adesão ao processo por parte dos actores; 2) capacidade de coordenação e cooperação dos operadores na gestão colectiva da fileira; 3) especificidade do produto; e 4) relevância do mercado. Os resultados revelam a existência de correlação positiva entre as variáveis referidas. Em geral, a “sucesso calculado” elevado corresponde “sucesso observado” também elevado. Contudo, assumem especial interesse os produtos em que tal correlação não é tão marcada, em particular os casos em que o score da primeira variável é muito superior ao da segunda. Trata-se de situações em que bons ou aceitáveis níveis de organização, dinamismo, capacidade de gestão e de coordenação das Entidades Gestoras não se reflectem em volumes e taxas de crescimento da produção elevados, melhoria de preços e distribuição do valor acrescentado pelos diferentes intervenientes da fileira dos produtos. ABSTRACT The article evaluates the performance of PDO/PGI animal-based products in the region of Trás-os-Montes, northern Portugal, using a cross analysis of the variables “observed success” and “measured success”. The “observed success” was estimated by the simoultaneous verification of at least three of the following indicators: 1) annual production and growing economic importance; 2) growth rates higher than those of the reference market; 3)notoriety of the name of the specif product; and 4) price higher than the one for the standard product. The “measured success” was determined by crossing the variables 1) rapid actor involvement in the process; 2) actor coordination and cooperation capacity in collective chain management; 3) product specificity; and 4) market relevance. The results show a positive correlation between the two mentioned variables. In general, to a high “measured success” corresponds a high “observed success”. However, those products in which such correlation is not so high, particularly those with a higher score of the first variable, assume a special interest. This products, in general, correspond to situations in which with good or acceptable levels of organization, better dynamics, management and coordination capacity of the management bodies, do not reflect in production and high growth rates, price improvements, and distribution of the added value among the different chain actors.

Increasing the value of household appliances by adding a heat pump system

Historically, domestic tasks such as preparing food and washing and drying clothes and dishes were done by hand. In a modern home many of these chores are taken care of by machines such as washing machines, dishwashers and tumble dryers. When the first such machines came on the market customers were happy that they worked at all! Today, the costs of electricity and customers’ environmental awareness are high, so features such as low electricity, water and detergent use strongly influence which household machine the customer will buy. One way to achieve lower electricity usage for the tumble dryer and the dishwasher is to add a heat pump system. The function of a heat pump system is to extract heat from a lower temperature source (heat source) and reject it to a higher temperature sink (heat sink) at a higher temperature level. Heat pump systems have been used for a long time in refrigerators and freezers, and that industry has driven the development of small, high quality, low price heat pump components. The low price of good quality heat pump components, along with an increased willingness to pay extra for lower electricity usage and environmental impact, make it possible to introduce heat pump systems in other household products. However, there is a high risk of failure with new features. A number of household manufacturers no longer exist because they introduced poorly implemented new features, which resulted in low quality and product performance. A manufacturer must predict whether the future value of a feature is high enough for the customer chain to pay for it. The challenge for the manufacturer is to develop and produce a high-performance heat pump feature in a household product with high quality, predict future willingness to pay for it, and launch it at the right moment in order to succeed. Tumble dryers with heat pump systems have been on the market since 2000. Paper I reports on the development of a transient simulation model of a commercial heat pump tumble dryer. The measured and simulated results were compared with good similarity. The influence of the size of the compressor and the condenser was investigated using the validated simulation model. The results from the simulation model show that increasing the cylinder volume of the compressor by 50% decreases the drying time by 14% without using more electricity.  Paper II is a concept study of adding a heat pump system to a dishwasher in order to decrease the total electricity usage. The dishwasher, dishware and water are heated by the condenser, and the evaporator absorbs the heat from a water tank. The majority of the heat transfer to the evaporator occurs when ice is generated in the water tank. An experimental setup and a transient simulation model of a heat pump dishwasher were developed. The simulation results show a 24% reduction in electricity use compared to a conventional dishwasher heated with an electric element. The simulation model was based on an experimental setup that was not optimised. During the study it became apparent that it is possible to decrease electricity usage even more with the next experimental setup.

Applicazione ed implicazioni della Corporate Sustainability Due Diligence nella Supply Chain: caso studio Fincantieri S.p.A.

La richiesta dei consumatori di prodotti sostenibili, le lotte per il cambiamento climatico e l'importanza che viene data alla sostenibilità dal mondo finanziario hanno fatto sì che la politica intraprendesse iniziative sulle tematiche sostenibili e di conseguenza le imprese hanno adottato azioni in linea con i criteri ESG. Anche se per le aziende intraprendere un percorso sostenibile non sia economicamente conveniente e per raggiungere determinati obiettivi servono sforzi e tempi lunghi, sono consapevoli dei benefici nel medio-lungo termine a livello economico, di reputazione e vantaggio competitivo. Queste iniziative però si concentrano prevalentemente sul primo anello della supply chain e le società che operano in un mercato globale fanno difficoltà a rispettare le differenti norme giuridiche non compatibili negli Stati in cui è presente la propria value chain. Per risolvere questi problemi la della Commissione Europea il 23/02/2022 ha proposto la direttiva sulla Corporate Sustainability Due Diligence, che impone l’obbligo per le imprese di implementare un processo di due diligence in tutta la value chain per prevenire effetti negativi e potenziali sui diritti umani e sull’ambiente. L’obiettivo dell'elaborato è di analizzare la direttiva di due diligence per comprendere quanto le aziende di oggi siano pronte al monitoraggio di un’intera catena del valore. Il caso studio scelto per lo scopo è quello dell’azienda Fincantieri S.p.A. la quale ha intrapreso da qualche anno un percorso di sostenibilità. Attraverso il confronto fra le azioni in atto dell'azienda e la direttiva, dalla trattazione emerge che la sfida più grande che Fincantieri dovrà affrontare sarà la condivisione delle pratiche già in atto nei livelli più profondi della supply chain. L’approvazione della direttiva, incentivando anche indirettamente le aziende ad operare in ottica di sostenibilità, aiuterà a perseguire l'obiettivo di due diligence in un percorso di crescita e miglioramento con i fornitori

Stato dell'arte delle tecniche lean per la gestione della supply chain

L’idea di focalizzare la tesi sulla supply chain ed in particolare sulle tecniche lean per la sua ottimizzazione deriva dal fatto che si tratta di un nuovo modo di ragionare, di un approccio moderno perfettamente adattabile al contesto socio-economico attuale, teso ad accrescere la flessibilità e l’efficienza dell’impresa attraverso un ripensamento dell’intero flusso di creazione del valore. Verranno analizzate le caratteristiche generali di questo modello organizzativo, per poi addentrarsi nella sua applicazione ed infine i vantaggi e gli eventuali svantaggi che le organizzazioni devono affrontare per implementare operativamente le tecniche lean. L’analisi effettuata nella tesi è strutturata come segue: La parte iniziale del primo capitolo definisce il concetto generale di supply chain sottolineando il contesto di riferimento in cui oggi operano le attività produttive. Vengono poi riportati l’accezione e il valore della supply chain management e le sue problematiche annesse di gestione e controllo. Nella seconda parte del capitolo vengono analizzati e descritti i modelli letterari esistenti utili per descrivere, impostare e classificare una supply chain. Il secondo capitolo, dopo una breve esposizione storica che descrive le origini della metodologia lean production, è orientato alla raccolta delle definizioni e alle loro differenti visioni tratte dal mondo della letteratura. Segue una parte più analitica, dove vengono analizzati in maniera dettagliata gli obiettivi, gli strumenti ed i principi che la filosofia lean prevede. Nel terzo capitolo viene approfondita la VSM, uno degli strumenti di principale importanza secondo le logiche della lean manufacturing. Vengono analizzati gli step necessari per una corretta implementazione, illustrando prima la simbologia internazionale necessaria per una sua comprensione e realizzazione e poi definiti gli step da applicare non solo per una semplice realizzazione, ma per l’ottenimento di una value stream map in ottica lean.

Greening the Lean Supply Chain: il caso Lush Cosmetics

«La salute degli ecosistemi da cui dipendiamo, noi e tutte le altre specie, si sta aggravando più rapidamente che mai; stiamo compromettendo le stesse basi delle economie, della sussistenza, della sicurezza alimentare, della salute e della qualità della vita in tutto il mondo». Così il chimico R. Watson commentava un diffuso rapporto del 2019 delle Nazioni Unite sulla sconvolgente perdita di flora e fauna a livello globale. In questi anni sono stati infiniti gli appelli che citano l’astratto concetto delle «generazioni a venire», eppure, non tutte le aziende stanno agendo come dovrebbero. I rifiuti prodotti sono ancora molti, soprattutto quelli plastici da packaging. Alcune ideologie snelle, come il Lean Thinking, esistono da decenni e sono strettamente legate a quella che oggi chiamiamo Green Manufacturing. Entrambe propongono diversi strumenti per far fronte alla produzione di massa e agli sprechi: questi verranno trattati nella prima parte, e successivamente saranno impiegati, con il supporto del software «openLCA», per verificare il percorso dell’azienda protagonista dell’analisi, ovvero Lush Cosmetics. L’attenzione all’impatto ambientale che i propri prodotti possono provocare lungo l’intero ciclo di vita ha modellato la gestione interna di ciascun processo e, spontaneamente, si riflette sugli attori dell’intera supply chain: così, il comportamento di uno può ugualmente modificare, in questo caso positivamente, il lavoro di molti. Il seguente elaborato pone l’attenzione sulle problematiche migliorabili, proponendo diverse soluzioni alternative rispetto alla gestione attuale, seppur migliore di altre realtà. Infine, si vuole stimolare il consumatore verso una maggior consapevolezza delle conseguenze delle sue azioni, in fase di acquisto prima ed al momento dello smaltimento poi. I provvedimenti normativi, nazionali ed europei, possono funzionare solo se sostenuti da un consumo responsabile e dalla diffusione di una chiara ed efficace educazione ambientale.

The Value Of The 2005 International Society Of Urological Pathology (isup) Modified Gleason Grading System As A Predictor Of Biochemical Recurrence After Radical Prostatectomy.

To compare time and risk to biochemical recurrence (BR) after radical prostatectomy of two chronologically different groups of patients using the standard and the modified Gleason system (MGS). Cohort 1 comprised biopsies of 197 patients graded according to the standard Gleason system (SGS) in the period 1997/2004, and cohort 2, 176 biopsies graded according to the modified system in the period 2005/2011. Time to BR was analyzed with the Kaplan-Meier product-limit analysis and prediction of shorter time to recurrence using univariate and multivariate Cox proportional hazards model. Patients in cohort 2 reflected time-related changes: striking increase in clinical stage T1c, systematic use of extended biopsies, and lower percentage of total length of cancer in millimeter in all cores. The MGS used in cohort 2 showed fewer biopsies with Gleason score ≤ 6 and more biopsies of the intermediate Gleason score 7. Time to BR using the Kaplan-Meier curves showed statistical significance using the MGS in cohort 2, but not the SGS in cohort 1. Only the MGS predicted shorter time to BR on univariate analysis and on multivariate analysis was an independent predictor. The results favor that the 2005 International Society of Urological Pathology modified system is a refinement of the Gleason grading and valuable for contemporary clinical practice.

Prognostic Value Of Dna And Mrna E6/e7 Of Human Papillomavirus In The Evolution Of Cervical Intraepithelial Neoplasia Grade 2.

This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL). This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months. Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status (P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status (P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant. The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution.

Quantitative Proteomic Analysis Reveals Metabolic Alterations, Calcium Dysregulation, And Increased Expression Of Extracellular Matrix Proteins In Laminin α2 Chain-deficient Muscle.

Congenital muscular dystrophy with laminin α2 chain deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin α2 chain-deficient dy(3K)/dy(3K) mice, using multidimensional protein identification technology combined with tandem mass tags. Out of the approximately 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared with normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium, or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin α2 chain-deficient muscle might help in the design of future anti-fibrotic treatments. All MS data have been deposited in the ProteomeXchange with identifier PXD000978 (http://proteomecentral.proteomexchange.org/dataset/PXD000978).