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Knotted1-like homeobox (KNOX) transcription factors belong to the three amino acid loop extension (TALE) superclass of homeodomain proteins in higher plants (Hay and Tsiantis, 2010; Hamant and Pautot, 2010; Wu and Smith 2012; Di Giacomo et al., 2013). KNOX1 proteins play a key role in several developmental processes by maintaining a proper balance between undifferentiated and differentiated cell state through the modulation of multiple hormonal pathways Besides the homeodomain, KNOX proteins are characterized by the presence of a consensus region called MEINOX that defines this subclass of the TALE family. MEINOX domain is important for protein-protein interactions with a second group of TALE proteins, the BEL-like homeodomain (BLH) family. This interaction modulates KNOX nuclear localization and, likely, target selection . Mutations in KNAT1/BREVIPEDICELLUS (KNAT1/BP), one of the four Arabidopsis KNOX1 genes, result in plants with shorter internodes, downward pointing siliques, altered intra-bundle cell identity and altered lignin deposition (Mele et al., 2004). Recently, KNATM, a novel Arabidopsis KNOX1 gene that encodes a MEINOX domain but lacks the homeodomain was identified and shown to regulate KNAT1/BP (Magnani and Hake, 2008). We identified and characterized a novel isoform of KNAT1/BP transcription factor that arises from an event of alternative splicing and may encode a novel protein (BPhox) that contains the homeodomain but lacks the MEINOX domain. Phenotype and molecular analysis of Arabidopsis lines that overexpress each isoforms under the control of constitutive/inducible promoters and complementation analyses were carried out to unravel the function of BPhox in inflorescence architecture, vascular development and lignin deposition.

Context Laparoscopy has revolutionized abdominal surgery becoming the standard approach for many operations. The “da Vinci” surgical system overcomes most of the inherent technical limitations of laparoscopy. Objective We test whether the robotic approach can improve the outcome of pancreatic resections, which often require challenging dissection and complex digestive reconstructions. Methods One-hundred and six consecutive robotic pancreatic resections were performed between October 2008 and June 2012. There were 40 males and 66 females (62%), with a mean age of 57 years (range 21-80 years) and a mean BMI of 24.6 Kg/m2. Thirty-nine patients underwent pancreaticoduodenectomy (PD) (37%), 47 distal pancreatectomy (DP) (44%), 10 total pancreatectomy (10%), 7 tumor enucleation (6%) and 3 central pancreatectomy (3%). Since our activity spans over about a 4-year period, data were analyzed according to the time of surgery, to verify progress in the learning curve: 17 patients were operated on between October 2008 and September 2009, 22 patients between October 2009 and September 2010, 32 patients between October 2010 and September 2011 and 35 patients during the last 9 months (from October 2011 to June 2012). Results No patient was converted to laparoscopy or open surgery. Mean operative time (OT) was 442.8 minutes. In the first period OT was 512 min for PD and 420 for DP. The mean number of lymph nodes examined (LN) was 16.8; 31.2 for PD and 11.9 for DP. Pancreatic fistula (PF) occurred in 41% of the patients. In the second, OT was 596 min for PD and 402 for DP. The LN was 16.7; 27.2 for PD and 10.0 for DP. PF was amounted 36.3%. In the third, OT was 583 min for PD and 288 for DP. The LN was 28.7; 36.0 for PD and 19.1 for DP. PF was amounted 36.6%. In the fourth, OT was 590 min for PD and 250 for DP. The LN was 30; 32 for PD and 20 for DP. PF was amounted 35%. Fifty-six benign/low-grade tumors and 50 cancers were diagnosed. Surgical margins were all negative. Post-operative mortality was nil, morbidity was 56% and mean hospital stay was 16 days. Conclusions Robot-assisted pancreatic resections can be safely performed in selected patients. Despite the existence of a learning curve, experienced pancreatic surgeons are not expected to pay to robotics the same price that they would have been asked for by laparoscopy., JOP. Journal of the Pancreas, Vol 13, N° 5S (2012): September (Suppl.) - p. 548-650

Context Pancreatic metastases are rare (2% of all pancreatic carcinomas). Very few cases about surgical treatment of colorectal cancer metastases to the pancreas are reported. Case report We report a case of single colorectal cancer metastasis to the pancreas managed by distal splenopancreatectomy in a patient undergone to left hemicolectomy for the primary tumor eight years before and to middle lung lobectomy for metastasis one year before. A 61-year-old asymptomatic woman with a history of colorectal cancer was admitted to our department after that during the oncological imaging follow-up a thoracic-abdominal contrast-enhanced computed tomography (CT) demonstrated a single 25 mm hypodense lesion in the pancreatic tail. She also presented high levels of CEA (61.7 ng/mL) and CA 19-9 (82.9 U/mL) before the admission. Eight years before the patient underwent to left hemicolectomy for a B2-Dukes classification colorectal cancer. The resected margins were free of tumor and no regional lymph nodes were positive. One year before the patient underwent to a lung lobectomy for a single 30 mm pulmonary metastases. Considering history and imaging findings, the pancreatic lesion was suspected a colorectal cancer metastasis. A distal splenopancreatectomy was performed. The patient was discharged in healthy conditions. Final pathology disclosed the pancreatic lesion was a colorectal cancer metastasis (CD20+, CK7-) with infiltration of the peri-pancreatic adipose tissue. The resected margins were free of tumor and no lymph nodes were metastasized. The patient is still alive. Conclusion Metastases to the pancreas are commonly considered rare, especially those from colorectal cancer. The improvement of imaging techniques has led to an increase of diagnoses and surgical procedures for metastases to the pancreas. Secondary tumors may be considered in the differential diagnosis of primitive pancreatic lesions. The diagnosis may be facilitated by clinical history and serum markers assessment. Metastatic colorectal cancer to the pancreas is an indication for pancreatic resection to increase the overall survival and, as palliative procedure, to treat symptoms like jaundice and pain., JOP. Journal of the Pancreas, Vol 13, N° 5S (2012): September (Suppl.) - p. 548-650

Acute lymphoblastic leukemia (ALL) is the most common subtype of leukemia in children. Although ALL and type 1 diabetes appear to be biologically unrelated, there are common threads in both epidemiology and etiology. Rising incidence rates of both ALL (1) and type 1 diabetes (2) observed over recent decades in many Western countries seem to support common etiological factors (3). In the current study, we report on diabetes-related autoantibodies (Abs) in a group of patients with ALL. Thirty-four consecutive children (19 males and 15 females, mean age 6.2 ± 4.6 years) were referred to our institution in 2004 for newly diagnosed ALL. Patients were tested for Abs to islet and thyroid antigens. After the initial investigation and treatment, 31/34 (91%) patients (3 died in the mean time) were followedup for 6 years to evaluate the evolution of the autoimmune markers and progression toward type 1 diabetes. Glutamic acid decarboxylase (GAD) Abs by direct …

Knotted1-like homeobox (KNOX) transcription factors belong to the three amino acid loop extension (TALE) superclass of homeodomain proteins in higher plants. KNOXs play a key role in several developmental processes by maintaining a proper balance between undifferentiated and differentiated cell state through the modulation of multiple hormonal pathways. Besides the homeodomain, KNOX proteins are characterized by the presence of a consensus region called MEINOX that defines this subclass of the TALE family. MEINOX domain is important for protein-protein interactions with a second group of TALE proteins, the BEL-like homeodomain (BLH) family. This interaction modulates KNOX nuclear localization and, likely, target selection. The major goal of our laboratory is to define the molecular mechanisms that underlie KNOX function in cell fate determination and organogenesis using model organisms and transfer the acquired knowledge to non-model plant species including important crops. Our research aims at developing strategies and tools for using KNOX genes, or other components of KNOX developmental pathways, in the selection of plant traits relevant to agriculture production. The traits we are interested in are: leaf morphology and development, vascular differentiation, leaf/stem ratio, lignin content, vegetative-to-reproductive transition, stem architecture, hormone homeostasis, organogenesis, maintenance of indeterminate cell fate, optimization of nitrogen fixation in legumes. Our main research projects regard: post-transcriptional regulation of KNOX1 genes in Arabidopsis thaliana and Medicago truncatula - the role of KNOX1 in the determination of M. truncatula compound leaves - the identification of novel developmental pathways which involve different KNOX transcription factors - the identification of Arabidopsis KNOX functional orthologs in Medicago truncatula for forage legumes, Prunus persica for fruit tree species and Cichorium intybus for cultivated salad species of commercial interest. We will present our latest data on KNOX transcription factors coming from a comparative scientific approach. To gain new insights into the role of alternative splicing in KNOX genes, we will present the functional characterization of a novel isoform of the KNAT1/BP transcription factor (BPhox) that encodes the homeodomain but lacks the MEINOX domain. We will also show data regarding an alternative spliced STM-like gene of M. truncatula (MtKNOX6) that induces novel phenotypes when overexpressed in Arabidopsis thaliana. We will explore the possibility to use the structural polymorphism of KNOX proteins from different species to identify key amino acid residues that are important for functional diversification.

Reduced vitamin D levels may play a significant role in the development of fractures and musculoskeletal pains reported in patients on aromatase inhibitors (AIs) for breast cancer. In this study, we evaluated the vitamin D status in postmenopausal women with non-metastatic breast cancer who were about to start AI therapy. This study was conducted on community dwelling postmenopausal subjects, aged 35-80 years, with early non-metastatic breast cancer (up to stage IIIA), who were about to start therapy using third generation AIs. Symptoms of joint and muscle pains were obtained using a modified Leuven menopausal questionnaire. 25-hydroxyvitamin D [25(OH)D] was evaluated by radioimmunoassay while bone mineral density (BMD) of the lumbar spine and the proximal femur by dual energy x-ray absorptiometry (DXA). Of the 145 participants (mean age = 60.96 ± 0.88 years), 63 of 145 (43.5%) had baseline levels of 25(OH)D of20 ng/mL (deficient), 50 of 145 (34.5%) had levels between 20 and 29 ng/mL (insufficient), and only 32 of 145 (22%) had ≥ 30 ng/mL (sufficient); thus, 113 of 145 (78%) had low 25(OH)D levels (i.e.,30 ng/mL). Arthralgias and myalgias were found in 61.3% and 43% of patients, respectively; and of those, 83.3% and 88.1% had 25(OH)D of30 ng/mL, respectively. Prevalence of vitamin D deficiency is high in breast cancer women and this may increase the risk of bone loss and fractures in those who are going to start AIs. Moreover, musculoskeletal pains are common in breast cancer women, even before the initiation of AIs and in association with low vitamin D in the majority. Future studies may be needed to establish the contribution of low vitamin D, if any, on the prevalence of musculoskeletal pains in women on AIs.