Pliocene-Pleistocene marine cyclothems, Wanganui Basin, New Zealand: a lithostratigraphic framework

The Rangitikei River valley between Mangaweka and Vinegar Hill and the surrounding Ohingaiti region in eastern Wanganui Basin contains a late Pliocene to early Pleistocene (c. 2.6-1.7 Ma), c. 1100 m thick, southward-dipping (4-9deg.), marine cyclothemic succession. Twenty sedimentary cycles occur within the succession, each of which contains coarse-grained (siliciclastic sandstone and coquina) and fine-grained (siliciclastic siltstone) units. Nineteen of the cycles are assigned to the Rangitikei Group (new). Six new formations are defined within the Rangitikei Group, and their distribution in the Ohingaiti region is represented in a new geologic map. The new formations are named: Mangarere, Tikapu, Makohine, Orangipongo, Mangaonoho, and Vinegar Hill. Each formation comprises one or more cyclothems and includes a previously described and named distinctive basal horizon. Discrete sandstones, siltstones, and coquinas within formations are assigned member status and correspond to systems tracts in sequence stratigraphic nomenclature. The members provide the link between the new formational lithostratigraphy and the sequence stratigraphy of the Rangitikei Group. Base of cycle coquina members accumulated during episodes of sediment starvation associated with stratigraphic condensation on an open marine shelf during sea-level transgressions. Siltstone members accumulated in mid-shelf environments (50-100 m water depth) during sea-level highstands, whereas the overlying sandstone members are ascribed to inner shelf and shoreface environments (0-50 m water depth) and accumulated during falling eustatic sea-level conditions. Repetitive changes in water depth of 50-100 m magnitude are consistent with a glacio-eustatic origin for the cyclothems, which correspond to an interval of Earth history when successive glaciations in the Northern Hemisphere are known to have occurred. Moreover, the chronology of the Rangitikei River section indicates that Rangitikei Group cyclothems accumulated during short duration, 41 ka cycles in continental ice volume attributed to the dominance of the Milankovitch obliquity orbital parameter. The Ohingaiti region has simple postdepositional structure. The late Pliocene formations dip generally to the SSW between 4deg. and 9deg.. Discernible discordances of c. 1deg. between successively younger formations are attributed to synsedimentary tilting of the shelf concomitant with migration of the tectonic hingeline southward into the basin. The outcrop distribution of the Rangitikei Group is strongly influenced by this regional tilt and also by three major northeast-southwest oriented, high-angle reverse faults (Rauoterangi, Pakihikura, and Rangitikei Faults)

PULMONARY TUBERCULOSIS PATIENTS DETECTED DURING MASS SCREENING AND BY REFERRAL TO MEDICAL UNITS

In Russia tuberculosis patients are detected during preventive mass screening and by self referral to medical units with clinical signs of the disease.Goal of the study: to compare pulmonary tuberculosis patients detected during mass screening and by self referral to medical units with clinical signs of the disease.Materials and methods: Data about 446 pulmonary tuberculosis patients treated in Republican TB Dispensary of Saransk in 2012-2014 were retrieved from Rosttsat Forms no. 8 and 33 and Russian Ministry of Health Reporting Forms (Edict 50). Statistica software was used for data processing.Results. Among 446 pulmonary tuberculosis patients detected in 2012-2014, the part of those detected during mass screening made ¾ out of total number, and those detected by self-referral made ¼, however the latter group of patients was significantly more dangerous from epidemiological point of view, since among them the part of those with long period of the disease before treatment start was higher, the positive sputum tests were more often observed as well as pulmonary cavities and primary MDR compared to the patients detected during mass screening.The obtained results point out at the need to focus on mass screening in the targeted groups of population concentrated around sources of infection

ТУБЕРКУЛЕЗ ЛЕГКИХ У ПАЦИЕНТОВ, ВЫЯВЛЕННЫЙ ВО ВРЕМЯ ПЕРИОДИЧЕСКИХ ОСМОТРОВ И ПРИ ОБРАЩЕНИИ В МЕДИЦИНСКИЕ ОРГАНИЗАЦИИ

In Russia tuberculosis patients are detected during preventive mass screening and by self referral to medical units with clinical signs of the disease.Goal of the study: to compare pulmonary tuberculosis patients detected during mass screening and by self referral to medical units with clinical signs of the disease.Materials and methods: Data about 446 pulmonary tuberculosis patients treated in Republican TB Dispensary of Saransk in 2012-2014 were retrieved from Rosttsat Forms no. 8 and 33 and Russian Ministry of Health Reporting Forms (Edict 50). Statistica software was used for data processing.Results. Among 446 pulmonary tuberculosis patients detected in 2012-2014, the part of those detected during mass screening made ¾ out of total number, and those detected by self-referral made ¼, however the latter group of patients was significantly more dangerous from epidemiological point of view, since among them the part of those with long period of the disease before treatment start was higher, the positive sputum tests were more often observed as well as pulmonary cavities and primary MDR compared to the patients detected during mass screening.The obtained results point out at the need to focus on mass screening in the targeted groups of population concentrated around sources of infection. В России выявление больных туберкулезом происходит во время массовых периодических осмотров и при самостоятельном обращении лиц в медицинские организации с клиническими проявлениями болезни.Цель исследования: сравнительная характеристика больных туберкулезом легких, выявленных во время периодических осмотров и при обращении в медицинские организации с клиническими проявлениями болезни.Материалы и методы: сведения о 446 больных туберкулезом легких, лечившихся в ГКУЗ «Республиканский противотуберкулезный диспансер» г. Саранска в 2012-2014 гг., получены из отчетных форм Росттата № 8 и 33 и отчетных форм Минздрава России (приказ № 50). Для обработки данных применены стандартные пакеты статистических программ Statistica.Результаты. Среди 446 больных туберкулезом легких, выявленных в 2012-2014 гг., доля выявленных при периодических осмотрах составляла ¾ от их общего числа, а при обращении в медицинские организации с клиническими проявлениями болезни - ¼, однако именно эти пациенты были значительно опаснее в эпидемическом плане, поскольку среди них была достоверно выше доля лиц с длительными периодами заболевания до начала лечения и достоверно чаще обнаруживались бактериовыделение, полости распада в легких и первичная МЛУ МБТ по сравнению с пациентами, выявленными при периодических осмотрах. Полученные результаты свидетельствуют о необходимости фокусирования массовых периодических осмотров на целевых группах населения, сконцентрированных вокруг очагов инфекции

Role of survivin and its splice variants in tumorigenesis

Survivin, a unique member of the inhibitor of apoptosis (IAP) protein family, is highly expressed in cancer but is undetectable in nonproliferating normal adult tissues, suggesting a potential role in tumorigenesis. Differential splicing of survivin pre-mRNA results in three new survivin variants, survivin-ΔEx3, survivin-2B, and survivin-3B. Loss of survivin-2B expression was found in the later stage of cancer development, while survivin and survivin-ΔEx3 are not, suggesting a differential role of them in tumour development. In this minireview, the author intends to summarise and discuss the current data relevant to the role of survivin and its splicing variants in tumorigenesis, which may facilitate further investigation in this interesting area

Контроль ситуации по туберкулезу на территориях Российской Федерации, курируемых ФГБНУ «Центральный НИИ туберкулеза», за 2014-2015 гг

The article presents the results oftuberculosis epidemic situation analysis in 15 Russian regions supervised by the Institute in 2014-2015. Tuberculosis incidence decreased in 11 regions out of 15 in 2014-2015. 4 regions demonstrated minor increase. Tuberculosis incidence among children in the age from 0-17 years old went down in 10 regions and increased in 5. Tuberculosis mortality decreased butin 3 regions itis higher than the average Russian rate (9.2 per 100,000 pop.). Treatment efficiency among new tuberculosis cases registered for treatment in 2014 with positive sputum microscopy varied from 69.8% in Orel Region down to 32.6% in Ulyanovsk Region, treatment efficiency as persputum conversion by culture – from 70.6% in Orel Region down to 34.2% in Ulyanovsk Region, treatment efficiency as per cavity healing – from 72.3% in Orel Region down to 40.2% in Ulyanovsk Region. The main reasons of low chemotherapy effectiveness are defaults from treatment, multiple drug resistance and insufficient surgical activities. In order to enhance the treatment efficiency, rapid drug susceptibility testing techniques are to be introduced everywhere with susceptibility testing to all anti-tuberculosis drugs and adequate chemotherapy regimens are to be applied consisting only of those drugs to which tuberculous mycobacteria are susceptible, surgical treatment is to be used more often.Представлены результаты анализа эпидемической ситуации по туберкулезу в курируемых институтом 15 регионах РФ за 2014-2015 гг. Снижение показателя заболеваемости туберкулезом за 2014-2015 гг. произошло в 11 из 15 регионов. На 4 территориях отмечен незначительный рост. Показатель заболеваемости туберкулезом детей в возрасте 0-17 лет снизился в 10 регионах, в 5 - отмечен рост. Показатель смертности от туберкулеза снизился, но на 3 территориях он превышает среднестатистический показатель по стране (9,2 на 100 тыс. населения). Эффективность лечения впервые выявленных больных туберкулезом легких, зарегистрированных для лечения в 2014 г. с положительной бактериоскопией мокроты, колебалась от 69,8% в Орловской области до 32,6% в Ульяновской области, по посеву мокроты - от 70,6% в Орловской области до 34,2% в Ульяновской области, по закрытию полостей распада - от 72,3% в Орловской области до 40,2% в Ульяновской области. Основными причинами низкой результативности химиотерапии являются отрыв от лечения, множественная лекарственная устойчивость микобактерий туберкулеза (МБТ), низкая хирургическая активность. Для повышения эффективности лечения необходимо повсеместно внедрить быстрые методы определения лекарственной чувствительности МБТ ко всем противотуберкулезным препаратам и проводить адекватную химиотерапию только теми препаратами, к которым МБТ сохранили чувствительность, активнее применять хирургические методы вмешательства

Two Cellular Protein Kinases, DNA-PK and PKA, Phosphorylate the Adenoviral L4-33K Protein and Have Opposite Effects on L1 Alternative RNA Splicing

Accumulation of the complex set of alternatively processed mRNA from the adenovirus major late transcription unit (MLTU) is subjected to a temporal regulation involving both changes in poly (A) site choice and alternative 3′ splice site usage. We have previously shown that the adenovirus L4-33K protein functions as an alternative splicing factor involved in activating the shift from L1-52,55K to L1-IIIa mRNA. Here we show that L4-33K specifically associates with the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) in uninfected and adenovirus-infected nuclear extracts. Further, we show that L4-33K is highly phosphorylated by DNA-PK in vitro in a double stranded DNA-independent manner. Importantly, DNA-PK deficient cells show an enhanced production of the L1-IIIa mRNA suggesting an inhibitory role of DNA-PK on the temporal switch in L1 alternative RNA splicing. Moreover, we show that L4-33K also is phosphorylated by protein kinase A (PKA), and that PKA has an enhancer effect on L4-33K-stimulated L1-IIIa splicing. Hence, we demonstrate that these kinases have opposite effects on L4-33K function; DNA-PK as an inhibitor and PKA as an activator of L1-IIIa mRNA splicing. Taken together, this is the first report identifying protein kinases that phosphorylate L4-33K and to suggest novel regulatory roles for DNA-PK and PKA in adenovirus alternative RNA splicing

Epigenetic Silencing of Host Cell Defense Genes Enhances Intracellular Survival of the Rickettsial Pathogen Anaplasma phagocytophilum

Intracellular bacteria have evolved mechanisms that promote survival within hostile host environments, often resulting in functional dysregulation and disease. Using the Anaplasma phagocytophilum–infected granulocyte model, we establish a link between host chromatin modifications, defense gene transcription and intracellular bacterial infection. Infection of THP-1 cells with A. phagocytophilum led to silencing of host defense gene expression. Histone deacetylase 1 (HDAC1) expression, activity and binding to the defense gene promoters significantly increased during infection, which resulted in decreased histone H3 acetylation in infected cells. HDAC1 overexpression enhanced infection, whereas pharmacologic and siRNA HDAC1 inhibition significantly decreased bacterial load. HDAC2 does not seem to be involved, since HDAC2 silencing by siRNA had no effect on A. phagocytophilum intracellular propagation. These data indicate that HDAC up-regulation and epigenetic silencing of host cell defense genes is required for A. phagocytophilum infection. Bacterial epigenetic regulation of host cell gene transcription could be a general mechanism that enhances intracellular pathogen survival while altering cell function and promoting disease

Runx Expression Is Mitogenic and Mutually Linked to Wnt Activity in Blastula-Stage Sea Urchin Embryos

The Runt homology domain (Runx) defines a metazoan family of sequence-specific transcriptional regulatory proteins that are critical for animal development and causally associated with a variety of mammalian cancers. The sea urchin Runx gene SpRunt-1 is expressed throughout the blastula stage embryo, and is required globally during embryogenesis for cell survival and differentiation.Depletion of SpRunt-1 by morpholino antisense-mediated knockdown causes a blastula stage deficit in cell proliferation, as shown by bromodeoxyuridine (BrdU) incorporation and direct cell counts. Reverse transcription coupled polymerase chain reaction (RT-PCR) studies show that the cell proliferation deficit is presaged by a deficit in the expression of several zygotic wnt genes, including wnt8, a key regulator of endomesoderm development. In addition, SpRunt-1-depleted blastulae underexpress cyclinD, an effector of mitogenic Wnt signaling. Blastula stage cell proliferation is also impeded by knockdown of either wnt8 or cyclinD. Chromatin immunoprecipitation (ChIP) indicates that Runx target sites within 5′ sequences flanking cyclinD, wnt6 and wnt8 are directly bound by SpRunt-1 protein at late blastula stage. Furthermore, experiments using a green fluorescent protein (GFP) reporter transgene show that the blastula-stage operation of a cis-regulatory module previously shown to be required for wnt8 expression (Minokawa et al., Dev. Biol. 288: 545–558, 2005) is dependent on its direct sequence-specific interaction with SpRunt-1. Finally, inhibitor studies and immunoblot analysis show that SpRunt-1 protein levels are negatively regulated by glycogen synthase kinase (GSK)-3.These results suggest that Runx expression and Wnt signaling are mutually linked in a feedback circuit that controls cell proliferation during development

Marathons and myasthenia gravis: a case report.

The cardinal symptoms of auto-immune myasthenia gravis are fatigue and weakness. Endurance events such as marathon running would seem incompatible with this chronic disease. Many patients stop sport altogether. There is limited literature of patients with auto-immune myasthenia gravis undergoing regular endurance exercise. We report the case of a 36-year-old female who began long-distance running whilst experiencing initial symptoms of myasthenia gravis. She was diagnosed with auto-immune myasthenia gravis and whilst advised to stop all sport, her way of fighting and living with this chronic and unpredictable disease was to continue running to maintain a healthy body and mind. Despite suffering from ocular, bulbar and localized limb fatigability, she managed to complete multiple marathons and achieve disease stability with cholinesterase inhibitors. Marathon and half-marathon running lead to distinct changes in mediators of inflammation in an exercise-dose-dependent manner. Despite symptoms of weakness and fatigue in certain muscles in myasthenia gravis, physical exertion remains possible and may not worsen symptoms as demonstrated in this case and recent studies. The immunomodulatory role of exercise could be considered in this case however this hypothesis remains to be confirmed in future studies with quantitative data