Cancer cells exploit an orphan RNA to drive metastatic progression.

Here we performed a systematic search to identify breast-cancer-specific small noncoding RNAs, which we have collectively termed orphan noncoding RNAs (oncRNAs). We subsequently discovered that one of these oncRNAs, which originates from the 3' end of TERC, acts as a regulator of gene expression and is a robust promoter of breast cancer metastasis. This oncRNA, which we have named T3p, exerts its prometastatic effects by acting as an inhibitor of RISC complex activity and increasing the expression of the prometastatic genes NUPR1 and PANX2. Furthermore, we have shown that oncRNAs are present in cancer-cell-derived extracellular vesicles, raising the possibility that these circulating oncRNAs may also have a role in non-cell autonomous disease pathogenesis. Additionally, these circulating oncRNAs present a novel avenue for cancer fingerprinting using liquid biopsies

Reviewing, indicating, and counting books for modern research evaluation systems

In this chapter, we focus on the specialists who have helped to improve the conditions for book assessments in research evaluation exercises, with empirically based data and insights supporting their greater integration. Our review highlights the research carried out by four types of expert communities, referred to as the monitors, the subject classifiers, the indexers and the indicator constructionists. Many challenges lie ahead for scholars affiliated with these communities, particularly the latter three. By acknowledging their unique, yet interrelated roles, we show where the greatest potential is for both quantitative and qualitative indicator advancements in book-inclusive evaluation systems.Comment: Forthcoming in Glanzel, W., Moed, H.F., Schmoch U., Thelwall, M. (2018). Springer Handbook of Science and Technology Indicators. Springer Some corrections made in subsection 'Publisher prestige or quality

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Comportamentos agressivos em crianças e adolescentes com risco para esquizofrenia: diferenças entre gêneros

OBJECTIVE: This study aimed to investigate whether differences in aggression-related behavioral problems occur between boys and girls at high risk for schizophrenia living in the city of São Paulo, Brazil. METHOD: Using the Child Behavior Checklist, we compared the prevalence of behavioral problems between genders for the offspring (6-18 years) of mothers with diagnosis of schizophrenia and a comparison group of children born to women with no severe mental disorders recruited at the gynecology outpatient clinic of the same hospital. The Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition was applied for the evaluation of diagnostic status of mothers. RESULTS: Male children of women with schizophrenia had a lower prevalence of aggressive behavior compared to females (4% vs. 36%; p = 0.005), whereas no gender differences regarding aggression were detected in the comparison group (24% vs. 32%; p = 0.53). Logistic regression analyses showed that male gender and being a child of women with schizophrenia interacted so as to favor lower prevalence of aggressive behavior (p = 0.03). CONCLUSION: These findings reinforce the notion that behavioral gender differences related to schizophrenia are already detectable in childhood.OBJETIVO: Investigar diferenças da ocorrência de comportamentos agressivos entre crianças e adolescentes do sexo masculino e feminino com risco genético para desenvolver esquizofrenia. MÉTODO: A prevalência de comportamentos agressivos foi medida utilizando o inventário de comportamentos para crianças e adolescentes, Child Behavior Checklist, e comparada entre os gêneros para o grupo de crianças filhas de mulheres com esquizofrenia e para um grupo de crianças filhas de mulheres atendidas no serviço de ginecologia do mesmo hospital. A entrevista clínica estruturada para DSM-IV (The Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) foi utilizada para confirmar o diagnóstico materno. RESULTADOS: Os filhos de mulheres com esquizofrenia do sexo masculino apresentaram prevalência menor de comportamentos agressivos quando comparados às meninas (4% x 36%; p = 0,005), o que não ocorreu para o grupo comparativo (24% x 32%; p = 0,53). A análise de regressão logística mostrou que pertencer ao sexo masculino e ser filho de mulher com esquizofrenia interagiram de forma a favorecer menor prevalência de comportamentos agressivos (p = 0,03). CONCLUSÃO: Esses achados corroboram para a noção que as diferenças comportamentais entre os gêneros na esquizofrenia podem ser detectadas precocemente durante a infância

Inhibition of cervical cancer cell growth in vitro and in vivo with dual shRNAs

RNA interference (RNAi)-based gene silencing is widely used in laboratories for gene function studies and also holds a great promise for developing treatments for diseases. However, in vivo delivery of RNAi therapy remains a key issue. Lentiviral vectors have been employed for stable gene transfer and gene therapy and therefore are expected to deliver a stable and durable RNAi therapy. But this does not seem to be true in some disease models. Here, we showed that lentivirus delivered short-hairpin RNA (shRNA) against human papillomavirus (HPV) E6/E7 oncogenes were effective for only 2 weeks in a cervical cancer model. However, using this vector to carry two copies of the same shRNA or two shRNAs targeting at two different but closely related genes (HPV E6 and vascular endothelial growth factor) was more effective at silencing the gene targets and inhibiting cell or even tumor growth than their single shRNA counterparts. The cancer cells treated with dual shRNA were also more sensitive to chemotherapeutic drugs than single shRNA-treated cells. These results suggest that a multi-shRNA strategy may be a more attractive approach for developing an RNAi therapy for this cancer. Cancer Gene Therapy (2011) 18, 219-227; doi: 10.1038/cgt.2010.72; published online 19 November 201

Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism.National Institute of Mental Health (U.S.) (Intramural Research Program)Simons Foundatio

Febrile seizures and mechanisms of epileptogenesis: insights from an animal model.

Temporal lobe epilepsy (TLE) is the most prevalent type of human epilepsy, yet the causes for its development, and the processes involved, are not known. Most individuals with TLE do not have a family history, suggesting that this limbic epilepsy is a consequence of acquired rather than genetic causes. Among suspected etiologies, febrile seizures have frequently been cited. This is due to the fact that retrospective analyses of adults with TLE have demonstrated a high prevalence (20-->60%) of a history of prolonged febrile seizures during early childhood, suggesting an etiological role for these seizures in the development of TLE. Specifically, neuronal damage induced by febrile seizures has been suggested as a mechanism for the development of mesial temporal sclerosis, the pathological hallmark of TLE. However, the statistical correlation between febrile seizures and TLE does not necessarily indicate a causal relationship. For example, preexisting (genetic or acquired) 'causes' that result independently in febrile seizures and in TLE would also result in tight statistical correlation. For obvious reasons, complex febrile seizures cannot be induced in the human, and studies of their mechanisms and of their consequences on brain molecules and circuits are severely limited. Therefore, an animal model was designed to study these seizures. The model reproduces the fundamental key elements of the human condition: the age specificity, the physiological temperatures seen in fevers of children, the length of the seizures and their lack of immediate morbidity. Neuroanatomical, molecular and functional methods have been used in this model to determine the consequences of prolonged febrile seizures on the survival and integrity of neurons, and on hyperexcitability in the hippocampal-limbic network. Experimental prolonged febrile seizures did not lead to death of any of the seizure-vulnerable populations in hippocampus, and the rate of neurogenesis was also unchanged. Neuronal function was altered sufficiently to promote synaptic reorganization of granule cells, and transient and long-term alterations in the expression of specific genes were observed. The contribution of these consequences of febrile seizures to the epileptogenic process is discussed

Mercury Concentrations in Fish Jerky Snack Food: Marlin, Ahi, and Salmon

<p>Abstract</p> <p>Background</p> <p>Dried meat and fish have served as an important durable nutrition source for humans for centuries. Because omega 3 fatty acids in fish are recognized as having antioxidant and anti inflammatory properties found to be beneficial for good health, many consumers are looking to fish as their main source of protein. Unfortunately, contaminants such as methylmercury can accumulate in some species of fish. The purpose of this research is to test commercially available fish jerky snack foods for mercury contamination.</p> <p>Methods</p> <p>Fifteen bags of marlin jerky, three bags of ahi jerky, and three bags of salmon jerky were purchased from large retail stores in Hawaii and California, and directly from the proprietors' Internet websites. Five individual strips of jerky per bag were analyzed for a total of one hundred and five tests.</p> <p>Results</p> <p>From the seventy-five marlin jerky samples, mercury concentration ranged from 0.052-28.17 μg/g, with an average of 5.53 μg/g, median 4.1 μg/g. Fifty-six (75%) marlin samples had mercury concentrations that exceeded the FDA's current mercury action level of 1.0 μg/g, while six samples had greater than 10 μg/g. Fifteen samples of ahi had mercury concentrations ranging from 0.09-0.55 μg/g, while mercury concentrations in fifteen salmon samples ranged from 0.030-0.17 μg/g.</p> <p>Conclusions</p> <p>This study found that mercury concentrations in some fish jerky can often exceed the FDA's allowable mercury limit and could be a significant source of mercury exposure.</p

DSYB catalyses the key step of dimethylsulfoniopropionate biosynthesis in many phytoplankton

Dimethylsulfoniopropionate (DMSP) is a globally important organosulfur molecule and the major precursor for dimethyl sulfide. These compounds are important info-chemicals, key nutrients for marine microorganisms, and are involved in global sulfur cycling, atmospheric chemistry and cloud formation1,2,3. DMSP production was thought to be confined to eukaryotes, but heterotrophic bacteria can also produce DMSP through the pathway used by most phytoplankton4, and the DsyB enzyme catalysing the key step of this pathway in bacteria was recently identified5. However, eukaryotic phytoplankton probably produce most of Earth’s DMSP, yet no DMSP biosynthesis genes have been identified in any such organisms. Here we identify functional dsyB homologues, termed DSYB, in many phytoplankton and corals. DSYB is a methylthiohydroxybutryate methyltransferase enzyme localized in the chloroplasts and mitochondria of the haptophyte Prymnesium parvum, and stable isotope tracking experiments support these organelles as sites of DMSP synthesis. DSYB transcription levels increased with DMSP concentrations in different phytoplankton and were indicative of intracellular DMSP. Identification of the eukaryotic DSYB sequences, along with bacterial dsyB, provides the first molecular tools to predict the relative contributions of eukaryotes and prokaryotes to global DMSP production. Furthermore, evolutionary analysis suggests that eukaryotic DSYB originated in bacteria and was passed to eukaryotes early in their evolution

Is visual estimation of passive range of motion in the pediatric lower limb valid and reliable

<p>Abstract</p> <p>Background</p> <p>Visual estimation (VE) is an essential tool for evaluation of range of motion. Few papers discussed its validity in children orthopedics' practice. The purpose of our study was to assess validity and reliability of VE for passive range of motions (PROMs) of children's lower limbs.</p> <p>Methods</p> <p>Fifty typically developing children (100 lower limbs) were examined. Visual estimations for PROMs of hip (flexion, adduction, abduction, internal and external rotations), knee (flexion and popliteal angle) and ankle (dorsiflexion and plantarflexion) were made by a pediatric orthopaedic surgeon (POS) and a 5^thyear resident in orthopaedics. A last year medical student did goniometric measurements. Three weeks later, same measurements were performed to assess reliability of visual estimation for each examiner.</p> <p>Results</p> <p>Visual estimations of the POS were highly reliable for hip flexion, hip rotations and popliteal angle (ρ_c≥ 0.8). Reliability was good for hip abduction, knee flexion, ankle dorsiflexion and plantarflexion (ρ_c≥ 0.7) but poor for hip adduction (ρ_c= 0.5). Reproducibility for all PROMs was verified. Resident's VE showed high reliability (ρ_c≥ 0.8) for hip flexion and popliteal angle. Good correlation was found for hip rotations and knee flexion (ρ_c≥ 0.7). Poor results were obtained for ankle PROMs (ρ_c< 0.6) as well as hip adduction and abduction, the results of which not being reproducible. Influence of experience was clearly demonstrated for PROMs of hip rotations, adduction and abduction as well as ankle plantarflexion.</p> <p>Conclusion</p> <p>Accuracy of VE of passive hip flexion and knee PROMs is high regardless of the examiner's experience. Same accuracy can be found for hip rotations and abduction whenever VE is performed by an experienced examiner. Goniometric evaluation is recommended for passive hip adduction and for ankle PROMs.</p