Rai1 frees mice from the repression of active wake behaviors by light.

Besides its role in vision, light impacts physiology and behavior through circadian and direct (aka 'masking') mechanisms. In Smith-Magenis syndrome (SMS), the dysregulation of both sleep-wake behavior and melatonin production strongly suggests impaired non-visual light perception. We discovered that mice haploinsufficient for the SMS causal gene, Retinoic acid induced-1 (Rai1), were hypersensitive to light such that light eliminated alert and active-wake behaviors, while leaving time-spent-awake unaffected. Moreover, variables pertaining to circadian rhythm entrainment were activated more strongly by light. At the input level, the activation of rod/cone and suprachiasmatic nuclei (SCN) by light was paradoxically greatly reduced, while the downstream activation of the ventral-subparaventricular zone (vSPVZ) was increased. The vSPVZ integrates retinal and SCN input and, when activated, suppresses locomotor activity, consistent with the behavioral hypersensitivity to light we observed. Our results implicate Rai1 as a novel and central player in processing non-visual light information, from input to behavioral output

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Abortamento de frutos da nogueira macadâmia sob influência da adubação mineral

Macadamia (Macadamia integrifolia) has a high nut abortion rate. Unbalanced nutrition may be one of the factors that contributes to this problem. The aim of this study was to evaluate the influence of N doses and the split application of NPK fertilizers on fruit abortion of macadamia nut. Two experiments were conducted during three growing seasons on an Oxisol, in Jaboticabal, São Paulo State, Brazil. The first experiment consisted of five N rates (0, 50, 100, 150 and 200 kg ha-1 yr-1) and four replications. The second experiment consisted of four splitting modes of NPK fertilizers (T1: October, T2: October + December, T3: October + December + February and T4: October + December + February + April) and five replications. Most fruits (77.7%) aborted earlier in their development. The N application and the split fertilization of NPK as topdress for at least twice (October and December), did not affect the number of aborted fruits per macadamia tree, but, by increasing the total number of set fruits and reducing the percentage of abortion, provided higher nut productivity.A nogueira macadâmia (Macadamia integrifolia) apresenta elevada taxa de abortamento de frutos. A nutrição desequilibrada pode ser um dos fatores que contribui para isso. Objetivou-se, com esta pesquisa, avaliar a influência de doses de N e do parcelamento da adubação NPK, de cobertura, na redução do abortamento de frutos da nogueira macadâmia. Foram desenvolvidos dois experimentos, durante três anos agrícolas, num Latossolo Vermelho, em Jaboticabal, Estado de São Paulo. O primeiro experimento foi constituído por cinco doses de N (0, 50, 100, 150 e 200 kg ha-1 ano-1) e quatro repetições. O segundo experimento foi constituído por quatro formas de parcelamento da adubação NPK (T1: outubro T2: outubro + dezembro, T3: outubro + dezembro + fevereiro e T4: outubro+dezembro + fevereiro + abril) e cinco repetições. A maior parte dos frutos (77,7 %) foi abortada no início de seu desenvolvimento. A aplicação de N, bem como o parcelamento da adubação NPK de cobertura, pelo menos em duas vezes (outubro e dezembro), não alteraram o número de frutos abortados por planta de macadâmia, mas, por aumentarem o número total de frutos emitidos e reduzirem a percentagem de abortamento, proporcionaram maior produtividade de nozes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Agência Paulista de Tecnologia dos AgronegóciosUniversidade Estadual Paulista Departamento de Produção e Melhoramento VegetalUniversidade Estadual Paulista Departamento de Produção e Melhoramento Vegeta

2-(2-Nitro­anilino)-5,6,7,8-tetra­hydro-4H-cyclo­hepta­[b]thio­phene-3-carbonitrile

The title compound, C16H15N3O2S, was synthesized by the reaction of 2-amino-5,6,7,8-tetra­hydro-4H-cyclo­hepta­[b]thio­phene-3-carbonitrile and o-fluoro­nitro­benzene. The thio­phene and nitro­phenyl rings and amino and carbonitrile groups are coplanar with a maximum deviation of 0.046 (2) Å and a dihedral angle of 0.92 (6)° between the rings. The cyclo­hepta ring adopts a chair conformation. Intra­molecular N—H⋯O and C—H⋯S inter­actions occur. In the crystal, the mol­ecules form layers that are linked by π–π stacking inter­actions between the thio­phene and benzene rings [centroid–centroid distances = 3.7089 (12) and 3.6170 (12) Å]

Measuring the Impact of Conservation : The Growing Importance of Monitoring Fauna, Flora and Funga

Many stakeholders, from governments to civil society to businesses, lack the data they need to make informed decisions on biodiversity, jeopardising efforts to conserve, restore and sustainably manage nature. Here we review the importance of enhancing biodiversity monitoring, assess the challenges involved and identify potential solutions. Capacity for biodiversity monitoring needs to be enhanced urgently, especially in poorer, high-biodiversity countries where data gaps are disproportionately high. Modern tools and technologies, including remote sensing, bioacoustics and environmental DNA, should be used at larger scales to fill taxonomic and geographic data gaps, especially in the tropics, in marine and freshwater biomes, and for plants, fungi and invertebrates. Stakeholders need to follow best monitoring practices, adopting appropriate indicators and using counterfactual approaches to measure and attribute outcomes and impacts. Data should be made openly and freely available. Companies need to invest in collecting the data required to enhance sustainability in their operations and supply chains. With governments soon to commit to the post-2020 global biodiversity framework, the time is right to make a concerted push on monitoring. However, action at scale is needed now if we are to enhance results-based management adequately to conserve the biodiversity and ecosystem services we all depend on.This paper was made possible by funding from the Swiss Network for International Studies to the University of Lausanne (L.F. and P.J.S.) and its partners under the project: "Unblocking the flow of biodiversity data for multi-stakeholder environmental sustainability management". The research was carried out, in part, by GNG at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). PAVB was supported by the project MACRISK-PTDC/BIA-CBI/0625/2021, through the FCT-FundacAo para a Ciencia e a Tecnologia. YNB acknowledges support from the Audemars-Watkins Foundation for the CBCR's protected area monitoring work featured in this paper.info:eu-repo/semantics/publishedVersio

Prevalence of soil transmitted nematodes on Nukufetau, a remote Pacific island in Tuvalu

BACKGROUND: The population of Nukufetau, a remote coral atoll island in Tuvalu in the Western Pacific, received annual mass drug administration (MDA) of diethylcarbamazine and albendazole under the Pacific Elimination of Lymphatic Filariasis program in 2001, 2002 and 2003, with the last MDA occurring six months before a cross-sectional survey of the whole population for soil transmitted helminths (STH). METHODS: A cross-sectional survey in May 2004 recruited 206 residents (35.2% of the population) who provided a single faecal sample that was preserved, concentrated and examined microscopically. RESULTS: Overall prevalence of STH was 69.9%; only hookworm and Trichuris trichiura were diagnosed. Trichuris was present in 68.4% with intensity of infection being light in 56.3%, medium in 11.7% and heavy in 0.5%. Hookworm occurred in 11.7% with intensity of infection 11.2% being light and medium in 0.5%. Twenty individuals (9.7%) had dual infections. The prevalence of Trichuris was constant across all ages while the prevalence of hookworm was significantly lower in residents below 30 years of age. In the age group 5–12 years comparison of results with a 2001 survey [1] suggested that the prevalence of STH has declined minimally, due to sustained high prevalence of Trichuris, while hookworm has declined dramatically from 34.4% to 1.6%. CONCLUSION: The results of this survey suggest that although the MDA appears to have reduced hookworm prevalence in residents below 30 years of age, there has been minimal effect on Trichuris prevalence. An integrated program to control STH is required

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women.The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART.Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm(3) at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit.Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population

Gammaherpesvirus-Driven Plasma Cell Differentiation Regulates Virus Reactivation from Latently Infected B Lymphocytes

Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68) gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency) account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners) that do not directly participate in virus replication, but rather facilitate virus reactivation by manipulating the cellular milieu to provide a reactivation competent environment

Salvage radiotherapy for patients with PSA relapse after radical prostatectomy: a single institution experience

<p>Abstract</p> <p>Background</p> <p>To assess the efficacy of salvage radiotherapy (RT) for persistent or rising PSA after radical prostatectomy and to determine prognostic factors identifying patients who may benefit from salvage RT.</p> <p>Methods</p> <p>Between 1990 and 2003, 59 patients underwent RT for PSA recurrence after radical prostatectomy. Patients received a median of 66 Gy to the prostate bed with 3D or 2D RT. The main end point was biochemical failure after salvage RT, defined as an increase of the serum PSA value >0.2 ng/ml confirmed by a second elevation.</p> <p>Results</p> <p>Median follow-up was 38 months. The 3-year and 5-year bDFS rates were 56.1% and 41.2% respectively. According to multivariate analysis, only preRT PSA ≥1 ng/ml was associated with biochemical relapse.</p> <p>Conclusion</p> <p>When delivered early, RT is an effective treatment after radical prostatectomy. Only preRT PSA ≥1 ng/ml predicted relapse.</p