Multiple refugia and barriers explain the phylogeography of the Valais shrew, Sorex antinorii (Mammalia: Soricomorpha), Sorex antinorii (Mammalia: Soricomorpha)

The aim of the present study was to investigate the genetic structure of the Valais shrew (Sorex antinorii) by a combined phylogeographical and landscape genetic approach, and thereby to infer the locations of glacial refugia and establish the influence of geographical barriers. We sequenced part of the mitochondrial cytochrome b (cyt b) gene of 179 individuals of S. antinorii sampled across the entire species' range. Six specimens attributed to S. arunchi were included in the analysis. The phylogeographical pattern was assessed by Bayesian molecular phylogenetic reconstruction, population genetic analyses, and a species distribution modelling (SDM)-based hindcasting approach. We also used landscape genetics (including isolation-by-resistance) to infer the determinants of current intra-specific genetic structure. The phylogeographical analysis revealed shallow divergence among haplotypes and no clear substructure within S. antinorii. The starlike structure of the median-joining network is consistent with population expansion from a single refugium, probably located in the Apennines. Long branches observed on the same network also suggest that another refugium may have existed in the north-eastern part of Italy. This result is consistent with SDM, which also suggests several habitable areas for S. antinorii in the Italian peninsula during the LGM. Therefore S. antinorii appears to have occupied disconnected glacial refugia in the Italian peninsula, supporting previous data for other species showing multiple refugia within southern refugial areas. By coupling genetic analyses and SDM, we were able to infer how past climatic suitability contributed to genetic divergence of populations. The genetic differentiation shown in the present study does not support the specific status of S. arunchi.

CD30 in PTCLS: correlation between RNA and protein levels in a large european series from the LYSA

Introduction: CD22 is expressed on most B-non-Hodgkin lymphomas (NHL); inotuzumab ozogamicin (INO) is an anti-CD22 antibody conjugated to calicheamicin. This study evaluated the safety and tolerability of INO plus R-CVP in patients (pts) with relapsed/refractory CD22+ B-NHL. Efficacy data were also collected. Methods: Part 1 of this open-label study identified a maximum tolerated dose (MTD) of INO 0.8mg/m,2 on day 2 plus R-CVP (rituximab 375mg/m,2 cyclophosphamide 750mg/m,2 and vincristine 1.4mg/m,2 on day 1; prednisone 40mg/m,2 on days 1-5) every 21 days. Subsequently, pts were enrolled in the MTD confirmation cohort (part 2, n = 10), which required a dose-limiting toxicity rate of <33% in cycle 1 and <4 pts discontinuing prior to cycle 3 due to an adverse event (AE) in the MTD expansion cohort (part 3, n = 22), which explored preliminary activity. Results: Parts 2 and 3 enrolled 32 pts: 16 pts with diffuse large B-cell lymphoma, 15 with follicular lymphoma and one with mantle cell lymphoma. Median age was 64.5 years (range 44-81 years); 34% of pts had 1 prior regimen, 34% had 2, 28% had ≥3 and 3% had none (median 2; range 0-6).Median treatment duration was five cycles (range 1-6). Part 2 confirmed the MTD as standard dose R-CVP plus INO 0.8mg/m,2; 2/10 pts had a dose-limiting toxicity (grade 3 increased ALT/AST, grade 4 neutropenia requiring G-CSF). One pt discontinued because of an AE prior to cycle 3. Common treatment-related AEs were thrombocytopenia (78%), neutropenia (66%), fatigue (50%), leukopenia (50%), nausea (41%) and lymphopenia (38%); common grade 3/4 AEs were neutropenia (63%), thrombocytopenia (53%), leukopenia (38%) and lymphopenia (31%). There was one case of treatment-related fatal pneumonia with grade 4 neutropenia. Ten pts discontinued treatment due to AEs; thrombocytopenia/delayed platelet recovery was the leading cause (grade 1/2, n = 6; grade 3/4, n = 3). Objective response rate (ORR) was 77% (n = 24/31 evaluable pts), including 26% (n=8/31) with complete response (CR); three pts had stable disease. Of the pts with follicular lymphoma, ORR was 100% (n = 15/15), including seven pts with CR. Of the pts with diffuse large B-cell lymphoma, ORR was 60% (n = 9/16), including one pt with CR. Conclusions: Results suggest that INOplus R-CVP has acceptable toxicity and promising activity in relapsed/refractory CD22+ B-NHL. The most common grade 3/4 AEs were hematologic. Follow-up for progression-free and overall survival is ongoing.

The leishmaniases - survival and expansion in a changing world: a mini-review

The number of cases of visceral and cutaneous leishmaniasis is increasing globally at an alarming rate irrespective of the region and the leishmaniases are amongst the top emergent diseases in spite of control measures. In the present review attention is drawn to some of the reasons for this. The leishmaniases have expanded beyond their natural ecotopes due to the ecological chaos caused by man and this in turn affects the levels of his exposure to the vectors. Examples of how different phenomana (such as war, civilian migration, immuno-suppression caused by medication and viral infections, globalization of work and leisure and transmission outside endemic areas) contribute to the spread and increase of the disease are discussed.

Operator expansion: definition and molecular integral applications

Es defineix l'expansió general d'operadors com una combinació lineal de projectors i s'exposa la seva aplicació generalitzada al càlcul d'integrals moleculars. Com a exemple numèric, es fa l'aplicació al càlcul d'integrals de repulsió electrònica entre quatre funcions de tipus s centrades en punts diferents, i es mostren tant resultats del càlcul com la definició d'escalat respecte a un valor de referència, que facilitarà el procés d'optimització de l'expansió per uns paràmetres arbitraris. Es donen resultats ajustats al valor exacte

The demographic benefits of belligerence and bravery: defeated group repopulation or victorious group size expansion?

Intraspecific coalitional aggression between groups of individuals is a widespread trait in the animal world. It occurs in invertebrates and vertebrates, and is prevalent in humans. What are the conditions under which coalitional aggression evolves in natural populations? In this article, I develop a mathematical model delineating conditions where natural selection can favor the coevolution of belligerence and bravery between small-scale societies. Belligerence increases an actor's group probability of trying to conquer another group and bravery increase the actors's group probability of defeating an attacked group. The model takes into account two different types of demographic scenarios that may lead to the coevolution of belligerence and bravery. Under the first, the fitness benefits driving the coevolution of belligerence and bravery come through the repopulation of defeated groups by fission of victorious ones. Under the second demographic scenario, the fitness benefits come through a temporary increase in the local carrying capacity of victorious groups, after transfer of resources from defeated groups to victorious ones. The analysis of the model suggests that the selective pressures on belligerence and bravery are stronger when defeated groups can be repopulated by victorious ones. The analysis also suggests that, depending on the shape of the contest success function, costly bravery can evolve in groups of any size.

Surface registration from range image fusion

The registration of full 3-D models is an important task in computer vision. Range finders only reconstruct a partial view of the object. Many authors have proposed several techniques to register 3D surfaces from multiple views in which there are basically two aspects to consider. First, poor registration in which some sort of correspondences are established. Second, accurate registration in order to obtain a better solution. A survey of the most common techniques is presented and includes experimental results of some of them

The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches.

The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.

Standardisation of the waist circumference (WC) for each range of body mass index (BMI) in adult outpatients attended to in Endocrinology and Nutrition departments

By this study we seek the expectable range of waist circumference (WC) for every degree of body mass index (BMI), which will serve to studies targeting ascertaining the health risk. We studied 2,932 patients (39.6% men and 60.4% women, between 18 and 96 years ) of the same ethnic group who consecutively attended outpatient departments of our clinics between 2000 and 2004. BMI correlated linearly with the WC (cc: 0.85; p < 0.001). The men, the obese, and diabetics were older (p < 0.001). BMI was greater in women and WC in men. The women had a greater WC if they had diabetes (p < 0.01), being equal to diabetic males. The men had greater WC when they had diabetes (p < 0.001). Waist at risk was detected (men > or = 102 cm and women > or = 88 cm) in 94.3% of the obese, in 32.3% of overweight patients, in 3.8% of patients with BMI < 25, in 84.3% of diabetics, and in 72.6% of patients without diabetes. We made graphic standardisation of WC with regard to BMI, and we calculated the percentiles 10, 25, 50, 75 and 90, grouping in ranges of 2 kg/m(2) of BMI. The diabetic patients are grouped in ranges of 4 kg/m(2). As conclusion we present a standardisation of the WC measurement of patients attended to in our Endocrinology and Nutrition practices distributed in percentiles as a clinically usable tool to define the ranges of WC for every BMI value.

Hippocampal sparing whole brain radiotherapy and simultaneously integrated boost with helical tomotherapy in patients with brain metastases

Materials/Methods: Four patients who underwent whole-brain radiotherapy (WBRT) and simultaneous integrated boost (SIB) between August 2010 and February 2011 were included to this study. Their age were 60, 61, 65, and 70 years. Primary diagnosis was infiltrative ductal breast cancer in two patients, sigmoid adenocarcinoma in one, and transitional bladder cancer in the other patient. All patients underwent cranial surgery but not all of the metastases were operated in 2 patients. All but one (five metastases) patient presented with single brain metastasis. In 2 of the 4 patients, hippocampus was spared contralaterally due to vicinity of the lesions to unilateral hippocampus. Planning irradiation dose was 30 Gy in 10 fractions for WBRT and 40 Gy in 10 fractions for SIB over two weeks in three patients. In one patient, WBRT and boost doses were 36Gy and 50.4 Gy in 18 fractions. Our maximum dose constraints for hippocampus and eyes were 10 and 20 Gy, respectively. All organs were contoured manually. Hippocampi were contoured according to published guidelines, and 5-mm margin expansion was used for hippocampal avoidance volume. All plans utilized a field width of 2.5 cm. Modulation factors ranged between 2 and 3.5. A pitch of 0,287 was used for all patients. All plans were evaluated according to conformity index (CI), homogeneity index (HI), target coverage (TC), and mean normalized total dose (NTDmean). An alpha/beta ratio of 2 was assumed for the hippocampus.Results: Median planning target volume (PTV) for metastases was 17.47 cc.Median hippocampal avoidance volume was 14.73 cc (range, 9.25-16.18 cc). Median average hippocampaldose was 11.84 Gy (range, 10.14-21.01 Gy). PTVs were fully covered with more than 95% of the prescribed dose for all patients. With a median follow-up time of 6 months (range, 3-9 months), all patients were alive without recurrent intracranial disease. To date, no neurocognitive decline reported in any of the patients.Conclusions: Preclinical evidence suggests that hippocampal sparing during cranial irradiation may mitigate neurocognitive decline. Using HT, we significantly reduced the mean dose to the hippocampus without jeopardizing coverage of metastases and whole brain.

MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity.

Pregnancy and obesity are frequently associated with diminished insulin sensitivity, which is normally compensated for by an expansion of the functional β cell mass that prevents chronic hyperglycemia and development of diabetes mellitus. The molecular basis underlying compensatory β cell mass expansion is largely unknown. We found in rodents that β cell mass expansion during pregnancy and obesity is associated with changes in the expression of several islet microRNAs, including miR-338-3p. In isolated pancreatic islets, we recapitulated the decreased miR-338-3p level observed in gestation and obesity by activating the G protein-coupled estrogen receptor GPR30 and the glucagon-like peptide 1 (GLP1) receptor. Blockade of miR-338-3p in β cells using specific anti-miR molecules mimicked gene expression changes occurring during β cell mass expansion and resulted in increased proliferation and improved survival both in vitro and in vivo. These findings point to a major role for miR-338-3p in compensatory β cell mass expansion occurring under different insulin resistance states.

Sandflies (Diptera: Psychodidae) from caves of the quartzite Espinhaço Range, Minas Gerais, Brazil

This study investigated the sandfly fauna of two quartzite caves in the Espinhaço Mountain Range, located in the municipality of Diamantina, state Minas Gerais. From August 2010-July 2011, entomological sampling was performed in the caves of Salitre and Monte Cristo with two HP light traps exposed in the photic and aphotic zones of each cave. The sandfly fauna consisted of 17 species, among which Lutzomyia cipoensis was predominant (54.76%). The male/female ratio in the total captures was 1:2.5. The aphotic zone showed the highest frequency of specimens captured (65%). A greater density of sandflies occurred during the summer (January-February), coinciding with the period of higher temperatures, humidity and rainfall. The presence of Lutzomyia longipalpis, Lutzomyia whitmani and Lutzomyia pessoai, proven or suspected vectors of leishmaniasis, is of concern because the area is visited by many tourists.

In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression.

Via a transcription factor, Foxp3, immunoregulatory CD4(+)CD25(+) T cells (T reg cells) play an important role in suppressing the function of other T cells. Adoptively transferring high numbers of T reg cells can reduce the intensity of the immune response, thereby providing an attractive prospect for inducing tolerance. Extending our previous findings, we describe an in vivo approach for inducing rapid expansion of T reg cells by injecting mice with interleukin (IL)-2 mixed with a particular IL-2 monoclonal antibody (mAb). Injection of these IL-2-IL-2 mAb complexes for a short period of 3 d induces a marked (>10-fold) increase in T reg cell numbers in many organs, including the liver and gut as well as the spleen and lymph nodes, and a modest increase in the thymus. The expanded T reg cells survive for 1-2 wk and are highly activated and display superior suppressive function. Pretreating with the IL-2-IL-2 mAb complexes renders the mice resistant to induction of experimental autoimmune encephalomyelitis; combined with rapamycin, the complexes can also be used to treat ongoing disease. In addition, pretreating mice with the complexes induces tolerance to fully major histocompatibility complex-incompatible pancreatic islets in the absence of immunosuppression. Tolerance is robust and the majority of grafts are accepted indefinitely. The approach described for T reg cell expansion has clinical potential for treating autoimmune disease and promoting organ transplantation.