Predicting coding potential from genome sequence: application to betaherpesviruses infecting rats and mice

Prediction of protein-coding regions and other features of primary DNA sequence have greatly contributed to experimental biology. Significant challenges remain in genome annotation methods, including the identification of small or overlapping genes and the assessment of mRNA splicing or unconventional translation signals in expression. We have employed a combined analysis of compositional biases and conservation together with frame-specific G+C representation to reevaluate and annotate the genome sequences of mouse and rat cytomegaloviruses. Our analysis predicts that there are at least 34 protein-coding regions in these genomes that were not apparent in earlier annotation efforts. These include 17 single-exon genes, three new exons of previously identified genes, a newly identified four-exon gene for a lectin-like protein (in rat cytomegalovirus), and 10 probable frameshift extensions of previously annotated genes. This expanded set of candidate genes provides an additional basis for investigation in cytomegalovirus biology and pathogenesis.     

High-throughput microRNA profile in adult and pediatric primary glioblastomas: the role of miR-10b-5p and miR-630 in the tumor aggressiveness

Molecular Biology Reports - Glioblastoma (GBM) is the most common primary malignant neoplasm of the central nervous system and, despite the standard therapy; the patients’ prognoses remain...     

Large-scale chromatin remodeling in germinal vesicle bovine oocytes: interplay with gap junction functionality and developmental competence

In mammals, oocyte acquires a series of competencies sequentially during folliculogenesis that play critical roles at fertilization and early stages of embryonic development. In mouse, chromatin in germinal vesicle (GV) undergoes dynamic changes during oocyte growth and its progressive condensation has been related to the achievement of developmental potential. Cumulus cells are essential for the acquisition of meiotic competence and play a role in chromatin remodeling during oocyte growth. This study is aimed to characterize the chromatin configuration of growing and fully grown bovine oocytes, the status of communications between oocyte and cumulus cells and oocyte developmental potential. Following nuclear staining, we identified four discrete stages of GV, characterized by an increase of chromatin condensation. GV0 stage represented 82% of growing oocytes and it was absent in fully grown oocytes. GV1, GV2, and GV3 represented, respectively, 24, 31, and 45% of fully grown oocytes. Our data indicated a moderate but significant increase in oocyte diameter between GV0 and GV3 stage. By dye coupling assay the 98% of GV0 oocytes showed fully open communications while the number of oocytes with functionally closed communications with cumulus cells was significantly higher in GV3 group than GV1 and GV2. However, GV0 oocytes were unable to progress through metaphase II while GV2 and GV3 showed the highest developmental capability. We conclude that in bovine, the progressive chromatin condensation is related to the sequential achievement of meiotic and embryonic developmental competencies during oocyte growth and differentiation. Moreover, gap-junction-mediated communications between oocyte and cumulus cells could be implicated in modulating the chromatin remodeling process.     

Role of alpha-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation

Inflammatory processes contribute widely to the development of neurodegenerative diseases. The expression of many inflammatory mediators was found to be increased in central nervous system (CNS) disorders suggesting that these molecules are major contributors to neuronal damage. Melanocortins are neuropeptides that have been implicated in a wide range of physiological processes. The melanocortin alpha-melanocyte stimulating hormone (alpha-MSH) has pleiotropic functions and exerts potent anti-inflammatory actions by antagonizing the effects of pro-inflammatory cytokines and by decreasing important inflammatory mediators. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified. Of these, the MC4 receptor is expressed predominantly throughout the CNS. Evidence of effectiveness of selective MC4R agonists in modulating inflammatory processes and their low toxicity suggest that these molecules may be useful in the treatment of CNS disorders with an inflammatory component. This review describes the involvement of the MC4R in central anti-inflammatory effects of melanocortins and discusses the potential value of MC4R agonists for the treatment of inflammatory-related disorders.     

Imidazole-containing ternary complexes of N-benzyloxycarbonyl-aminoacids. Crystal and molecular structure of bis(N-benzyloxycarbonyl-alaninato)bis-(N-methylimidazole)copper(II) ethanol solvate

Mixed ligand complexes of the type Cu(Z-aminoacidato)₂(B₂) (Z = benzyloxycarbonyl group, Z-aminoacidate = Z-glycinate (Zgly), Z-alaninate (Zala); Z-valinate (Zval), Z-leucinate (Zleu) ion, B = imidazole (Im), N-methylimidazole (MeIm)) were synthesized and characterized by means of electronic, infrared and EPR spectroscopies. For one of them, bis(Z-alaninato)bis(N-methylimidazole)copper(II) ethanol solvate, the crystal and molecular structure was also determined by the single crystal X-ray diffraction method. The complex crystallizes in the monoclinic space group P2₁/c, with cell dimensions a = 11.1119(6), b = 18.8398(7), c = 8.9652(5) Å, β = 105.380(2)° and Z = 2. The structure was solved by conventional Patterson and Fourier methods and refined by full-matrix least-squares to an R value of 0.045. The complex has square-planar coordination via two centrosymmetric carboxylic oxygens and two N-methylimidazole nitrogens. The second carboxylate oxygen is 2.731(5) Å from the copper atom in an ‘out of plane’ position. Packing is mainly determined by hydrogen bondings between amide nitrogen and amide carboxyl oxygen. Electronic, infrared and EPR spectra are consistent with this type of coordination geometry for anhydrous complexes, while for hydrate complexes are suggestive of tetragonal bipyramidal geometry.     

A Human Case of Hymenolepis diminuta in a Child from Eastern Sicily

We report a case of Hymenolepis diminuta infection in a 2-year-old child living in a suburban area of Catania, Italy. This case was initially referred to us as Dipylidium caninum infection, which was not cured after being treated twice with mebendazole. However, by analyzing the clinical presentation and stool samples we arrived to the diagnosis of H. diminuta infection. The case presented with atypical allergic manifestations which had never been reported as clinical features of symptomatic H. diminuta infection; remittent fever with abdominal pain, diffuse cutaneous itching, transient thoracic rash, and arthromyalgias. The patient was treated with a 7-day cycle of oral niclosamide, which proved to be safe and effective. This case report emphasizes that a correct parasitological diagnosis requires adequate district laboratories and trained personnel. In addition, we recommend the importance of reporting all H. diminuta infection cases, in order to improve knowledge on epidemiology, clinical presentation, and treatment protocols.     

Treatment of experimental autoimmune prostatitis in nonobese diabetic mice by the vitamin D receptor agonist elocalcitol

On the basis of on the marked inhibitory activity of the vitamin D receptor agonist Elocalcitol on basal and growth factor-induced proliferation of human prostate cells and on its potent anti-inflammatory properties, we have tested its capacity to treat experimental autoimmune prostatitis (EAP) induced by injection of prostate homogenate-CFA in nonobese diabetic (NOD) mice. Administration of Elocalcitol, at normocalcemic doses, for 2 wk in already established EAP significantly inhibits the intraprostatic cell infiltrate, leading to a profound reduction in the number of CD4(+) and CD8(+) T cells, B cells, macrophages, dendritic cells, and I-A(g7)-positive cells. Immunohistological analysis demonstrates reduced cell proliferation and increased apoptosis of resident and infiltrating cells. Significantly decreased production of the proinflammatory cytokines IFN-gamma and IL-17 is observed in prostate-draining lymph node T cells from Elocalcitol-treated NOD mice stimulated by TCR ligation. In addition, Elocalcitol treatment reduces IFN-gamma production by prostate-infiltrating CD4(+) T cells and draining lymph node T cells specific for an immunodominant peptide naturally processed from prostate steroid-binding protein, a prostate-specific autoantigen. Finally, CD4(+) splenic T cells from Elocalcitol-treated NOD mice show decreased ability, upon adoptive transfer into NOD.SCID recipients, to induce autoimmune prostatitis, paralleled by a reduced capacity to produce IFN-gamma in response to prostate steroid-binding protein. The results indicate that Elocalcitol is able to interfere with key pathogenic events in already established EAP in the NOD mouse. These data show a novel indication for vitamin D receptor agonists and indicate that treatment with Elocalcitol may inhibit the intraprostatic inflammatory response in chronic prostatitis/chronic pelvic pain syndrome patients.     

Scent gland apparatus in the Western conifer seed bug Leptoglossus occidentalis Heidemann (Heteroptera: Coreidae)

The coreid Leptoglossus occidentalis is a Nearctic bug responsible for severe seed losses to pine orchards. When disturbed, adults and nymphs emit a defensive secretion deemed an allomone. Here we describe the gross morphology of the scent gland apparatus and the related evaporatory structures in nymphs and adults of L. occidentalis, through light microscopy and scanning electron microscopy. Adults of both sexes possess a metathoracic scent gland complex (MTG) including a central orange‐yellow reservoir and a pair of white lateral glands, connected by ducts to the reservoir. The MTG belongs to the diastomian type, with two ostioles located on the metathorax associated with a microsculptured cuticular accumulation area, i.e. evaporatory area, which can prevent the spread of the secretion on to non‐evaporative cuticle and increase scent fluid evaporation. A high number of male‐specific sternal gland pores were observed. These pores and associated glands are likely the source of an attractant pheromone, which could be extremely useful in monitoring and combating this invasive pest. In nymphs, MTG is replaced by two dorsal abdominal scent glands (DAGs) located between the 4th and the 6th urotergites. DAGs are reddish cuticle‐lined sacs with gland cells forming the gland wall; the scent substances are released through two orifices lying on the mid‐dorsal abdominal line between urotergites IV–V and V–VI. Also in nymphs, peculiar cuticular evaporatory areas surround both orifices.     

Urban expansion and infrastructure development reduce habitat suitability for Asian elephants in southwestern China

Conservation interventions for threatened species must be based on accurate assessments of the effects of anthropogenic pressures on habitat suitability. We used multiscale multivariable species-distribution modeling to evaluate habitat suitability for an Asian elephant (Elephas maximus) population in Shangyong Reserve, Yunnan Province, southwestern China. We investigated the scales at which measurements of environmental variables best reflected elephant habitat selection, and examined whether these responses changed over 2 decades (2000–2010 and 2011–2020) in response to 20 environmental variables, including 14 variables reflecting landscape fragmentation, the extent of buildings, and transport infrastructure. Elephant presence was sensitive to the scale of each variable, and the effects differed among variables within and between decades. More than half of the variables influenced elephant presence at coarse scales of 8 or 16 km, including 12 variables reflecting anthropogenic pressures in 2000–2010 and 10 in 2011–2020. Overall, multivariate models with variables at their optimal scales had higher discrimination than models at uniformly fine scales of 1 km or 2 km. The extent of suitable habitat for elephants declined by 24% over 2 decades. Less than half of elephant habitat was located within Shangyong Reserve (49% in 2000–2010, 40% in 2011–2020), indicating the importance of managing suitable habitat beyond reserve boundaries. Roads and buildings reduced the probability of elephant presence, with effects that extended beyond their immediate footprint. We advocate that infrastructure be planned with buffers, ≥8 km wide, between roads or buildings and core elephant habitat. Multiscale multivariable species-distribution modeling should be employed to ensure that all suitable habitat for the remaining fragmented elephant populations in Yunnan is identified, mapped, and protected.