bluuebunny/crossref_metadata_2025 huggingface dataset:
Raportowanie kwestii zrównoważonego rozwoju oraz integrowanie danych finansowych i pozafinansowych – prawne uwarunkowania w Polsce i na świecie
Authors: Kowalczyk Beata J. , Kowalczyk Wojciech
Published: February 2017

Rozwój idei zrównoważonego rozwoju jest obecnie szeroko propagowany nie tylko w biznesie, lecz także w sektorze non profit. Wraz z wbudowaniem tej idei w strategię rozwoju organizacji sprawozdawczość z tego zakresu wydaje się naturalną konsekwencją, podobnie jak przy raportowaniu danych finansowych. Potrzeba rozwijania sprawozdawczości na rzecz rozwoju zrównoważonego znajduje także swoje udokumentowanie w Agendzie 21. W dokumencie tym zaleca się opracowywanie zintegrowanych systemów rachunkowości środowiskowej (ekologicznej) i gospodarczej (IEEA), które winny stanowić uzupełnienie tradycyjnych zasad rachunkowości. Jedyną formą realizacji tej rekomendacji jest publikowanie przez organizacje raportów zintegrowanych. Wiele z nich upowszechnia takie raporty z własnej inicjatywy, mając świadomość wymiernych korzyści takich działań. Niemniej większość organizacji nie podejmuje tej aktywności, czego przyczyną jest prawdopodobnie brak wiedzy na temat wszystkich istotnych zależności między wynikami finansowymi a niefinansowymi oraz niedostatecznie rozwinięte ustawodawstwo w tym zakresie. Zarówno Unia Europejska, jak i kraje wysoko rozwinięte dostrzegają potrzebę i korzyści płynące z kompleksowego uregulowania prawnego tego obszaru. Stąd też Unia Europejska, a także Dania, Francja czy Brazylia dają temu wyraz w konkretnych aktach prawnych, których podstawowym celem jest zobligowanie do sporządzania raportów zintegrowanych dużych organizacji oraz spółek giełdowych, a także wdrożenie zewnętrznej weryfikacji spójności ujawnianych danych w formie audytów. W Polsce istnieją regulacje w tym zakresie, jednak ciągle niski odsetek podmiotów publikujących raporty zrównoważonego rozwoju oraz raporty zintegrowane skłania do refleksji. Niniejsze opracowanie stanowi przegląd regulacji prawnych obowiązujących w Polsce, w Unii Europejskiej, a także w wybranych krajach Europy i świata, na tle, których autorzy dokonali próby sformułowania uwag de lege ferenda.
Refleksje nad możliwością podjęcia zatrudnienia przez osobę ubezwłasnowolnioną
Authors: Fórmankiewicz Agnieszka
Published: February 2017

Zapewnienie rzeczywistego dostępu do zatrudnienia osobom ubezwłasnowolnionym jest podstawowym warunkiem, by mogły one żyć i pracować w społeczeństwie jak równoprawni obywatele. O ile z przepisów Kodeksu pracy wprost wynika, że ubezwłasnowolnienie częściowe nie stanowi przeszkody w podjęciu zatrudnienia (por. art. 22 § 2 k.p.), o tyle niejasna w tym zakresie wydaje się obowiązująca w Polsce regulacja dotycząca osób ubezwłasnowolnionych całkowicie. Można oczywiście podawać w wątpliwość, czy osoba ubezwłasnowolniona całkowicie jest w stanie podjąć zatrudnienie i wykonywać powierzone jej obowiązki służbowe. Z uwagi jednak na szerokie możliwości i różnorodność pojawiających się obecnie form zatrudnienia oraz działania społeczności międzynarodowej mające na celu aktywizację zawodową osób niepełnosprawnych, kategorycznie negatywna odpowiedź na pytanie dotyczące możliwości podjęcia zatrudnienia przez osobę ubezwłasnowolnioną całkowicie nie wydaje się uzasadniona, tym bardziej że Polska podpisała i ratyfikowała Konwencję ONZ o prawach osób niepełnosprawnych.
Rozwój rynku NewConnect w świetle założeń jego organizatora
Authors: Zygmanowski Piotr
Published: February 2017

Celem niniejszego artykułu jest weryfikacja wybranych początkowych założeń organizatora rynku NewConnect, tj. założeń w zakresie rozmiaru debiutujących emitentów i rodzaju prowadzonej przez nich działalności. W pierwszej z części zasadniczych zaprezentowano podstawy teorii wpływu rozwoju rynku finansowego na wzrost gospodarczy, przesłanki utworzenia rynku NewConnect oraz aktualne kryteria wprowadzenia do obrotu. W drugiej z części zasadniczych zawarto wyniki badań nad wielkością emitentów, którzy zdecydowali się wprowadzić swoje akcje na rynek NewConnect, a także ich charakterystykę. W podsumowaniu zaprezentowano ostateczną weryfikację hipotez towarzyszących badaniu i ogólne wnioski płynące z badania, wskazując jednocześnie obszary wymagające dalszej dogłębnej analizy.Przeprowadzone badania pozwoliły na pełną realizację zakładanego celu artykułu. Wyniki potwierdzają hipotezę główną, mówiącą o tym, że rynek NewConnect jest rynkiem dla mikro-, małych i średnich przedsiębiorstw. Hipoteza ta została potwierdzona uzyskanymi wynikami badań, które świadczą o tym, iż 98,7% emitentów w momencie debiutu kwalifikowało się do grupy mikro-, małych i średnich przedsiębiorstw. Pozytywnie zweryfikowana została także hipoteza cząstkowa. Wykazała ona, że rynek NewConnect jest rynkiem nie tylko dla spółek kwalifikowanych do innowacyjnych branż, które opierają swoją działalność na wartościach niematerialnych i prawnych. Uzyskane wyniki wykazały, że spółki zaliczane do sektorów innowacyjnych odpowiadały za 34,75% debiutantów na rynku NewConnect oraz że tylko w przypadku 7,21% spółek wartości niematerialne i prawne stanowiły ponad 50% ich sumy bilansowej. Uzyskane wyniki wskazują, że rynek NewConnect w latach 2007-2015 tylko częściowo rozwijał się zgodnie z założeniami jego organizatora – większą grupę od małych i średnich przedsiębiorstw stanowiły przedsiębiorstwa mikro, natomiast przedsiębiorstwa zaliczane do sektorów innych niż innowacyjne przewyższały swoją liczebnością te, które oparły swoją działalność na wartościach niematerialnych i prawnych.
Niezależność sądów i niezawisłość sędziów z perspektywy prawa Unii Europejskiej
Authors: Zawistowski Dariusz
Published: February 2017

Niezależność sądów i niezawisłość sędziów stanowią jedną z podstaw państwa prawnego, należącego do podstawowych wartości Unii Europejskiej. Do zasad państwa prawnego należy zasada trójpodziału władz, stanowiąca równocześnie istotną gwarancję niezależności władzy sądowniczej. Zasada podziału władz oznacza, że do wyłącznej kompetencji władzy sądowniczej należy sprawowanie wymiaru sprawiedliwości i organy innych władz nie mogą ingerować w wykonywanie funkcji orzeczniczych przez sądy. W państwach demokratycznych istnieje potrzeba gwarancji niezależności władzy sądowniczej na poziomie norm konstytucyjnych. Podstawową funkcją niezależności sądów i niezawisłości sędziów jest zapewnienie obywatelom prawa do sądu w rozumieniu art. 6 Konwencji o ochronie praw człowieka i podstawowych wolności oraz art. 45 Konstytucji RP. Z punktu widzenia prawa do sądu ważne jest istnienie związku między niezależnością sądów i niezawisłością sędziów a gwarancją bezstronności sądu oraz gwarancją do sprawiedliwego rozpoznania sprawy przez sąd. Niezależność sądów i niezawisłość sędziów są ściśle powiązane z zasadą odpowiedzialności władzy sądowniczej.
Aksjologia źródeł prawa
Authors: Kordela Marzena
Published: February 2017

Wyrażenie „źródło prawa” (fons iuris oriundi) oznacza fakt społeczny, który ze względu na obowiązującą konstytucję i doktrynę prawniczą kwalifikowany jest jako fakt prawotwórczy. Zupełna teoria źródeł prawa powinna charakteryzować się tym, że na podstawie jej elementów o każdej dowolnej normie postępowania można z całą pewnością orzec, czy stanowi czy też nie normę obowiązującego systemu prawnego. Kwestię tę można rozstrzygnąć na podstawie tzw. rozwiniętej normatywnej koncepcji źródeł prawa.Koncepcja ta jako niezbędne swe składniki wymienia: 1) uzasadnienie polityczne podstaw systemu prawnego; 2) kompetencje normodawcze organów władzy publicznej; 3) prawotwórczą rolę zwyczaju i precedensów; 4) dopuszczane w danym systemie reguły interpretacyjne; 5) dopuszczane w danym systemie reguły inferencyjne oraz 6) dopuszczane w danym systemie reguły kolizyjne.Stworzony w ten sposób system źródeł prawa z jednej strony sam jest legitymowany określonymi wartościami, z drugiej zaś ‒ wiele z nich realizuje. Podstawową część aksjologii prawodawcy w sferze źródeł praw tworzą wartości obowiązujące prawnie, tzn. wartości, które sam prawodawca wprowadził do systemu prawa. Do nich należą przede wszystkim wartość państwa prawnego, pewności prawa, zaufania obywateli do państwa i stanowionego przez nie prawa, ale też wartości godności człowieka oraz praw i wolności jednostki. Obok wartości prawnych na ukształtowanie źródeł prawa wpływ mają wartości o charakterze powszechnym stanowiące budulec dominujących doktryn politycznych.
Unijny system rejestrów handlowych i jego implementacja do prawa polskiego po uchwaleniu dyrektywy Parlamentu Europejskiego i Rady 2012/17/UE z 13 czerwca 2012 r.
Authors: Mucha Ariel
Published: February 2017

Opracowanie skupia się na analizie i ocenie dyrektywy 2012/17/UE z 13 czerwca 2012 r. oraz jej implementacji do polskiego prawa, w tym skutków, jakie implementacja niesie dla rodzimych podmiotów gospodarczych. Dyrektywa 2012/17/UE ma na celu stworzenie ram prawnych połączenia rejestrów handlowych funkcjonujących w krajach członkowskich. Służyć to ma usprawnieniu wymiany informacji pomiędzy rejestrami o spółkach kapitałowych oraz oddziałach zagranicznych tych spółek, a także ułatwieniu transgranicznych procesów ich łączenia. Kluczowym elementem wprowadzonych zmian jest utworzenie systemu rejestrów handlowych, składającego się z rejestrów handlowych państw członkowskich, europejskiej centralnej platformy oraz portalu e-Sprawiedliwość (e-Justice). Nadal jednak najistotniejszą rolę odgrywać będą rejestry krajowe, a pozostałe elementy systemu stanowić narzędzia współpracy rejestrów. Stąd w ocenie autora opracowania modyfikacje wprowadzone w dyrektywie 2012/17/UE będą miały ograniczony wpływ na funkcjonowanie podmiotów gospodarczych na unijnym rynku. Nie oznacza to jednak, że implementacja przedmiotowej dyrektywy nie powinna stanowić szczególnego zainteresowania polskiego ustawodawcy. Starannie przeprowadzone zmiany w przepisach prawnych mogą bowiem przyczynić się do zwiększenia konkurencyjności polskiego systemu prawa spółek oraz spółek kapitałowych funkcjonujących w ramach tego systemu.
The Impact of Educational Mismatches on Wages: The Influence of Measurement Error and Unobserved Heterogeneity
Authors: Sellami Sana , Verhaest Dieter , Nonneman Walter , Van Trier Walter
Published: February 2017

We investigate the differential impact of alternative combinations of horizontal and vertical educational mismatches on wages. By using panel data for Belgian graduates, we consider the role of unobserved worker heterogeneity. Random measurement error in both types of mismatches is accounted for by adopting instrumental variable techniques. We consistently find that overeducated individuals without field of study mismatch earn less than adequately educated workers with a similar educational background. However, for individuals who are working outside their field of study, such a wage penalty is not always observed once accounting for unobserved heterogeneity and random measurement error. In some cases, field of study mismatch even seems to be financially beneficial to the worker. These findings contribute to our understanding regarding the extent to which educational mismatches are truly problematic. The results call for policies that focus primarily on combatting vertical mismatches.
Education Outcomes of Children of Asian Intermarriages: Does Gender of the Immigrant Parent Matter?
Authors: Basu Sukanya , Insler Michael
Published: February 2017

Studies about the effects of native and immigrant intermarriage on the human capital of children generally ignore disparate impacts by gender, ethnicity, or other attributes. Using 2000 U.S. Census data, we compare the high school dropout rates of 16–17-year-old children of Asian intermarriages and intra-marriages. We study differences between Asian-father and Asian-mother only families, controlling for observable child, parental and residential characteristics, as well as unobservable selection into intermarriage. Despite the higher average education and income levels of intermarried families, the children of Asian-father-native-mother households have higher dropout rates compared to both Asian intra-married and Asian-mother-native-father households. Children of less-educated fathers do worse, relative to children of less-educated mothers, suggesting the importance of intergenerational paternal transmission of education. Racial self-identity is also important: Children identify as “non-Asian” more often when the mother is native, and their families may under-emphasize education bringing them closer to native levels.
Bubble Motion and Gas-Liquid Mixing in Metallurgical Reactor with a Top Submerged Lance
Authors: Zhao Hongliang , Zhang Lifeng , Yin Pan , Wang Sen
Published: February 2017

The multiphase fluid mixing and bubble motion in a scale-down Isa smelting furnace with a top submerged lance were investigated through cold water model experiments. The mixing time in the liquid bath was determined by a novel criterion, and the bubble formation frequency and gas-liquid contact area were also measured by high-speed photographing. The empirical equations of mixing time (Tm) relating to mixing energy (ε) were

${T_{{\rm{m}},s}} = 913{\varepsilon ^{ - 0.5}}$
for solid tracer and

${T_{{\rm{m}},l}} = 624{\varepsilon ^{ - 0.48}}$
for liquid tracer, respectively. The mixing time trended down with the increasing of bubble formation frequency, affected slightly by the bubbles with small size and decreased obviously when increasing the gas-liquid contact area. The optimal conditions of gas flow rate, bath height, lance submerged height and lance diameter to guarantee high-efficiency mixing and low-level surface fluctuation/splashing were obtained.
Monitoring of vertical deformations by means high-precision geodetic levelling. Test case: The Arenoso dam (South of Spain)
Authors: de Lacy M. Clara , Ramos M. Isabel , Gil Antonio J. , Franco Óscar D. , Herrera Antonio M. , Avilés Manuel , Domínguez Alicia , Chica Juan Carlos
Published: February 2017

The Arenoso reservoir is created by an embankment dam, with central clay core, slates and greywacke shoulders. This kind of engineering structure is subject of deformation due to factors such as changes of water level of the reservoir, seat structure, climate changes, etc. In general, dam monitoring involves measurements both outside (external shell) and inside the structure. A number of control points is established around the area of the dam and the measurements of the displacements of the control points take place at several epochs. In this study high-precision levelling techniques have been used to monitor the vertical deformations. In particular five high-precision levelling profiles were measured in five surveys: February and July 2008, March and July 2013 and August 2014. In this study the design, observations and results are presented. On the one hand the results put in evidence the precision of the observations that are always under 1-mm level. On the other hand these results indicate downstream (southeastward) motion of the thrust block center of the dam probably during the fall and winter. The subsidence reachs here the maximum with a value of −14 cm in 2014 (in respect of February 2008). The displacements observed at the berms of the dam exhibit a similar trend to the displacements observed at the crest but they are significantly smaller, as expected. The accumulative vertical displacements and the settlement index indicate the magnitude of the movements decrease in time, confirming the dam tends to stabilize.
Organo-protective and antioxidant properties of leaf extracts of Syzygium guineense var macrocarpum against ferric nitriloacetate-induced stress of Wistar rats
Authors: Nzufo Francine Tankeu , Pieme Constant Anatole , Njimou Jacques Romain , Nya Prosper Cabral Biapa , Moukette Bruno Moukette , Marco Bravi , Angelo Chianese , Yonkeu Ngogang Jeanne
Published: February 2017

Background

The present study focused on the antioxidant, phenolic profile and free radical scavenging-mediated protective effect of leaves extracts of Syzygium guineense var. macrocarpum against ferric nitriloacetate-induced stress in the liver, heart, kidney and brain tissues of Wistar rats homogenates.

Methods

Spectrophotometric standardized methods were used to determine the free radical scavenging potential, antioxidant and protective properties of plant extracts on rat homogenates.

Results

All the extracts showed a concentration-dependent free radical quenching potential, and the ability to protect all the tested organs by inhibiting the lipid peroxidation and potentiating or restoring the activity of enzymatic and non enzymatic markers. The polyphenolic profile revealed the presence of at least one simple phenolic acid (gallic, caffeic, para-coumaric acid) although the majority (6 out of 14) of the compounds used as standard are present in the aqueous and aqueous–ethanol extracts.

Conclusions

Ethanolic extract of leaves of S. guineense var macrocarpum (SGETOH) exhibited the highest phenol content and appeared as the best extract taking into consideration the antioxidant and organo-protective activities tested.
How to computationally calculate thermochemical properties objectively, accurately, and as economically as possible
Authors: Chan Bun
Published: February 2017

We have developed the WnX series of quantum chemistry composite protocols for the computation of highly-accurate thermochemical quantities with advanced efficiency and applicability. The W1X-type methods have a general accuracy of ~3–4 kJ mol−1 and they can currently be applied to systems with ~20–30 atoms. Higher-level methods include W2X, W3X and W3X-L, with the most accurate of these being W3X-L. It can be applied to molecules with ~10–20 atoms and is generally accurate to ~1.5 kJ mol−1. The WnX procedures have opened up new possibilities for computational chemists in pursue of accurate thermochemical values in a highly-productive manner.
The Economics of Scams
Authors: Miles Stan , Pyne Derek
Published: February 2017

This paper offers one of the first economic analyses of scams. Its major finding is that, unlike other crimes, imperfect enforcement may increase victimization by deterring only low-ability scammers whose failed attempts would otherwise alert potential victims before encounters with high-ability scammers. High-ability scammers may actually benefit from partial enforcement, which reduces their competition. These results may be reinforced when failed attempts are punished.
Film Cooling Mechanism of Combined Hole and Saw-tooth Slot
Authors: Zhang Wei , Zhou Shuai , Wu Zhuang , Li Guangchao , Kou Zhihai
Published: February 2017

Film cooling performance of one row of cylindrical holes integrated with saw-tooth slots was numerically studied at blowing ratios of 0.5, 1.0 1.5 and 2.0 respectively. The saw-tooth slot concept combines the advantages both of easy machining for the slot and of the high film cooling effectiveness caused by the anti-vortex induced by the shaped hole. The film holes have an inclination angles of 30°, length to diameter ratio of 4 and pitch to diameter ratio of 3. The corner angles of the saw-tooth are 60°, 90°, 120°, 150° and 180° respectively. The 180° corner angle corresponds to a standard transverse slot. The emphasis of this other is on the influence of the corner angles of the saw-tooth on film cooling effectiveness. The flow field and thermal field were obtained to explain the mechanism of film cooling performance improvement by the saw-tooth slot. The results show that the numerical data agrees with the experimental values for the cylindrical holes. Relatively small corner angles generate uniform local film cooling effectiveness and high spanwise averaged film cooling effectiveness due to the coolant ejected from the hole smoothly flowing into the slot. The effect of corner angles strongly depends on blowing ratios. The increase of x/D decreases the differences of film cooling effectiveness between various corner angles. At low blowing ratios, an anti-vortex can be found with the spanwise angle of 60° and 120°. At high blowing ratios, an anti-vortex can be found with the spanwise angle of 60°.
The Dendrites of CA2 and CA1 Pyramidal Neurons Differentially Regulate Information Flow in the Cortico-Hippocampal Circuit
Authors: Srinivas Kalyan V. , Buss Eric W. , Sun Qian , Santoro Bina , Takahashi Hiroto , Nicholson Daniel A. , Siegelbaum Steven A.
Published: February 2017

The impact of a given neuronal pathway depends on the number of synapses it makes with its postsynaptic target, the strength of each individual synapse, and the integrative properties of the postsynaptic dendrites. Here we explore the cellular and synaptic mechanisms responsible for the differential excitatory drive from the entorhinal cortical pathway onto mouse CA2 compared with CA1 pyramidal neurons (PNs). Although both types of neurons receive direct input from entorhinal cortex onto their distal dendrites, these inputs produce a 5- to 6-fold larger EPSP at the soma of CA2 compared with CA1 PNs, which is sufficient to drive action potential output from CA2 but not CA1. Experimental and computational approaches reveal that dendritic propagation is more efficient in CA2 than CA1 as a result of differences in dendritic morphology and dendritic expression of the hyperpolarization-activated cation current (Ih). Furthermore, there are three times as many cortical inputs onto CA2 compared with CA1 PN distal dendrites. Using a computational model, we demonstrate that the differences in dendritic properties of CA2 compared with CA1 PNs are necessary to enable the CA2 PNs to generate their characteristically large EPSPs in response to their cortical inputs; in contrast, CA1 dendritic properties limit the size of the EPSPs they generate, even to a similar number of cortical inputs. Thus, the matching of dendritic integrative properties with the density of innervation is crucial for the differential processing of information from the direct cortical inputs by CA2 compared with CA1 PNs.

SIGNIFICANCE STATEMENTRecent discoveries have shown that the long-neglected hippocampal CA2 region has distinct synaptic properties and plays a prominent role in social memory and schizophrenia. This study addresses the puzzling finding that the direct entorhinal cortical inputs to hippocampus, which target the very distal pyramidal neuron dendrites, provide an unusually strong excitatory drive at the soma of CA2 pyramidal neurons, with EPSPs that are 5–6 times larger than those in CA1 pyramidal neurons. We here elucidate synaptic and dendritic mechanisms that account quantitatively for the marked difference in EPSP size. Our findings further demonstrate the general importance of fine-tuning the integrative properties of neuronal dendrites to their density of synaptic innervation.
Acetylcholine Release in Prefrontal Cortex Promotes Gamma Oscillations and Theta–Gamma Coupling during Cue Detection
Authors: Howe William M. , Gritton Howard J. , Lusk Nicholas A. , Roberts Erik A. , Hetrick Vaughn L. , Berke Joshua D. , Sarter Martin
Published: February 2017

The capacity for using external cues to guide behavior (“cue detection”) constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta–gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection.

SIGNIFICANCE STATEMENTThe capacity of learned cues to direct attention and guide responding (“cue detection”) is a key component of goal-directed behavior. Rhythmic neural activity and increases in acetylcholine release in the prefrontal cortex contribute to this process; however, the relationship between these neuronal mechanisms is not well understood. Using a combination ofin vivoneurochemistry, neurophysiology, and pharmacological methods, we demonstrate that cue-evoked acetylcholine release, through distinct actions at both nicotinic and muscarinic receptors, triggers a procession of neural oscillations that map onto the multiple stages of cue detection. Our data offer new insights into cholinergic function by revealing the temporally orchestrated changes in prefrontal network synchrony modulated by acetylcholine release during cue detection.
Muscle Yap Is a Regulator of Neuromuscular Junction Formation and Regeneration
Authors: Zhao Kai , Shen Chengyong , Lu Yisheng , Huang Zhihui , Li Lei , Rand Christopher D. , Pan Jinxiu , Sun Xiang-Dong , Tan Zhibing , Wang Hongsheng , Xing Guanglin , Cao Yu , Hu Guoqing , Zhou Jiliang , Xiong Wen-Cheng , Mei Lin
Published: February 2017

Yes-associated protein (Yap) is a major effector of the Hippo pathway that regulates cell proliferation and differentiation during development and restricts tissue growth in adult animals. However, its role in synapse formation remains poorly understood. In this study, we characterized Yap's role in the formation of the neuromuscular junction (NMJ). InHSA-Yap−/−mice where Yap was mutated specifically in muscle cells, AChR clusters were smaller and were distributed in a broader region in the middle of muscle fibers, suggesting that muscle Yap is necessary for the size and location of AChR clusters. In addition,HSA-Yap−/−mice also exhibited remarkable presynaptic deficits. Many AChR clusters were not or less covered by nerve terminals; miniature endplate potential frequency was reduced, which was associated with an increase in paired-pulse facilitation, indicating structural and functional defects. In addition, muscle Yap mutation prevented reinnervation of denervated muscle fibers. Together, these observations indicate a role of muscle Yap in NMJ formation and regeneration. We found that β-catenin was reduced in the cytoplasm and nucleus of mutant muscles, suggesting compromised β-catenin signaling. Both NMJ formation and regeneration deficits ofHSA-Yap−/−mice were ameliorated by inhibiting β-catenin degradation, further corroborating a role of β-catenin or Wnt-dependent signaling downstream of Yap to regulate NMJ formation and regeneration.

SIGNIFICANCE STATEMENTThis paper explored the role of Yes-associated protein (Yap) in neuromuscular junction (NMJ) formation and regeneration. Yap is a major effector of the Hippo pathway that regulates cell proliferation and differentiation during development and restricts tissue growth in adult animals. However, its role in synapse formation remains poorly understood. We provide evidence that muscle Yap mutation impairs both postsynaptic and presynaptic differentiation and function and inhibits NMJ regeneration after nerve injury, indicating a role of muscle Yap in these events. Further studies suggest compromised β-catenin signaling as a potential mechanism. Both NMJ formation and regeneration deficits ofHSA-Yap−/−mice were ameliorated by inhibiting β-catenin degradation, corroborating a role of β-catenin or Wnt-dependent signaling downstream of Yap to regulate NMJ formation and regeneration.
Amplitude Normalization of Dendritic EPSPs at the Soma of Binaural Coincidence Detector Neurons of the Medial Superior Olive
Authors: Winters Bradley D. , Jin Shan-Xue , Ledford Kenneth R. , Golding Nace L.
Published: February 2017

The principal neurons of the medial superior olive (MSO) encode cues for horizontal sound localization through comparisons of the relative timing of EPSPs. To understand how the timing and amplitude of EPSPs are maintained during propagation in the dendrites, we made dendritic and somatic whole-cell recordings from MSO principal neurons in brain slices from Mongolian gerbils. In somatic recordings, EPSP amplitudes were largely uniform following minimal stimulation of excitatory synapses at visualized locations along the dendrites. Similar results were obtained when excitatory synaptic transmission was eliminated in a low calcium solution and then restored at specific dendritic sites by pairing input stimulation and focal application of a higher calcium solution. We performed dual dendritic and somatic whole-cell recordings to measure spontaneous EPSPs using a dual-channel template-matching algorithm to separate out those events initiated at or distal to the dendritic recording location. Local dendritic spontaneous EPSP amplitudes increased sharply in the dendrite with distance from the soma (length constant, 53.6 μm), but their attenuation during propagation resulted in a uniform amplitude of ∼0.2 mV at the soma. The amplitude gradient of dendritic EPSPs was also apparent in responses to injections of identical simulated excitatory synaptic currents in the dendrites. Compartmental models support the view that these results extensively reflect the influence of dendritic cable properties. With relatively few excitatory axons innervating MSO neurons, the normalization of dendritic EPSPs at the soma would increase the importance of input timing versus location during the processing of interaural time difference cuesin vivo.

SIGNIFICANCE STATEMENTThe neurons of the medial superior olive analyze cues for sound localization by detecting the coincidence of binaural excitatory synaptic inputs distributed along the dendrites. Previous studies have shown that dendritic voltages undergo severe attenuation as they propagate to the soma, potentially reducing the influence of distal inputs. However, using dendritic and somatic patch recordings, we found that dendritic EPSP amplitude increased with distance from the soma, compensating for dendritic attenuation and normalizing EPSP amplitude at the soma. Much of this normalization reflected the influence of dendritic morphology. As different combinations of presynaptic axons may be active during consecutive cycles of sound stimuli, somatic EPSP normalization renders spike initiation more sensitive to synapse timing than dendritic location.
Ultra-High-Field fMRI Reveals a Role for the Subiculum in Scene Perceptual Discrimination
Authors: Hodgetts Carl J. , Voets Natalie L. , Thomas Adam G. , Clare Stuart , Lawrence Andrew D. , Graham Kim S.
Published: February 2017

Recent “representational” accounts suggest a key role for the hippocampus in complex scene perception. Due to limitations in scanner field strength, however, the functional neuroanatomy of hippocampal-dependent scene perception is unknown. Here, we applied 7 T high-resolution functional magnetic resonance imaging (fMRI) alongside a perceptual oddity task, modified from nonhuman primate studies. This task requires subjects to discriminate highly similar scenes, faces, or objects from multiple viewpoints, and has revealed selective impairments during scene discrimination following hippocampal lesions. Region-of-interest analyses identified a preferential response in the subiculum subfield of the hippocampus during scene, but not face or object, discriminations. Notably, this effect was in the anteromedial subiculum and was not modulated by whether scenes were subsequently remembered or forgotten. These results highlight the value of ultra-high-field fMRI in generating more refined, anatomically informed, functional accounts of hippocampal contributions to cognition, and a unique role for the human subiculum in discrimination of complex scenes from different viewpoints.

SIGNIFICANCE STATEMENTThere is increasing evidence that the human hippocampus supports functions beyond just episodic memory, with human lesion studies suggesting a contribution to the perceptual processing of navigationally relevant, complex scenes. While the hippocampus itself contains several small, functionally distinct subfields, examining the role of these in scene processing has been previously limited by scanner field strength. By applying ultra-high-resolution 7 T fMRI, we delineated the functional contribution of individual hippocampal subfields during a perceptual discrimination task for scenes, faces, and objects. This demonstrated that the discrimination of scenes, relative to faces and objects, recruits the anterior subicular region of the hippocampus, regardless of whether scenes were subsequently remembered or forgotten.
Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin
Authors: Ogino Himari , Hisanaga Arisa , Kohno Takao , Kondo Yuta , Okumura Kyoko , Kamei Takana , Sato Tempei , Asahara Hiroshi , Tsuiji Hitomi , Fukata Masaki , Hattori Mitsuharu
Published: February 2017

The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, noninvasive methods that can upregulate Reelin activityin vivohave yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activityin vitro, but it remains controversial as to whether this effect occursin vivo. Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons. This enzyme was identified as a disintegrin and metalloproteinase with thrombospondin motifs-3 (ADAMTS-3). Recombinant ADAMTS-3 cleaved Reelin at the N-t site. ADAMTS-3 was expressed in excitatory neurons in the cerebral cortex and hippocampus. N-t cleavage of Reelin was markedly decreased in the embryonic cerebral cortex of ADAMTS-3 knock-out (KO) mice. Importantly, the amount of Dab1 and the phosphorylation level of Tau, which inversely correlate with Reelin activity, were significantly decreased in the cerebral cortex of ADAMTS-3 KO mice. Conditional KO mice, in which ADAMTS-3 was deficient only in the excitatory neurons of the forebrain, showed increased dendritic branching and elongation in the postnatal cerebral cortex. Our study shows that ADAMTS-3 is the major enzyme that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. Therefore, inhibition of ADAMTS-3 may be an effective treatment for neuropsychiatric and neurodegenerative disorders.

SIGNIFICANCE STATEMENTADAMTS-3 was identified as the protease that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. ADAMTS-3 was expressed in the excitatory neurons of the embryonic and postnatal cerebral cortex and hippocampus. Cleavage by ADAMTS-3 is the major contributor of Reelin inactivationin vivo. Tau phosphorylation was decreased and dendritic branching and elongation was increased in ADAMTS-3-deficient mice. Therefore, inhibition of ADAMTS-3 upregulates Reelin activity and may be a potential therapeutic strategy for the prevention or treatment of neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease.
Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging
Authors: Marks Shawn M. , Lockhart Samuel N. , Baker Suzanne L. , Jagust William J.
Published: February 2017

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Usingin vivohuman Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer's disease-related protein aggregation as an underlying mechanism of age-related memory impairment.

SIGNIFICANCE STATEMENTAlterations in episodic memory and the accumulation of Alzheimer's pathology are common in cognitively normal older adults. However, evidence of pathological effects on episodic memory has largely been limited to β-amyloid (Aβ). Because Aβ and tau often cooccur in older adults, previous research offers an incomplete understanding of the relationship between pathology and episodic memory. With the recent development ofin vivotau PET radiotracers, we show that Aβ and tau are associated with different aspects of memory encoding, leading to aberrant neural activity that is behaviorally detrimental. In addition, our results provide evidence linking Aβ- and tau-associated neural dysfunction to brain atrophy.
Promiscuity among the MRAPs
Authors: Clark Adrian J L , Chan Li F
Published: February 2017

The melanocortin 2 receptor accessory protein (MRAP) was originally discovered to be an essential co-receptor for the ACTH receptor/melanocortin 2 receptor, and it physically interacts with this receptor and is required for receptor trafficking and ligand binding. A related molecule, MRAP2, is mainly expressed in the CNS and appears to have a role with the melanocortin 4 receptor. Consistent with this is the observation that a massively obese phenotype develops when the Mrap2 gene is deleted in mice. However, the characteristics of this phenotype differ from those of Mc4r-deleted mice and suggest that an additional role, possibly resulting from an interaction with other receptors is possible. In support of this, a functional interaction with the prokineticin receptors was recently reported. Evidence for other receptor interactions and aspects of the tissue distribution of MRAP and MRAP2 gene expression may indicate that these accessory proteins have a wider role than with the melanocortin receptors alone.
A Bayesian Approach for Analysis of Whole-Genome Bisulfite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation
Authors: Rackham Owen J L , Langley Sarah R , Oates Thomas , Vradi Eleni , Harmston Nathan , Srivastava Prashant K , Behmoaras Jacques , Dellaportas Petros , Bottolo Leonardo , Petretto Enrico
Published: February 2017

Whole-genome bisulphite sequencing (WGBS) can identify important methylation differences between diseased and healthy samples. However, results from...

DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulfite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome while taking into account the distance between CpG sites as a covariate. Our simulation study shows that ABBA has greater power to detect DMRs than existing methods, providing an accurate identification of DMRs in the large majority of simulated cases. To empirically demonstrate the method’s efficacy in generating biological hypotheses, we performed WGBS of primary macrophages derived from an experimental rat system of glomerulonephritis and used ABBA to identify >1000 disease-associated DMRs. Investigation of these DMRs revealed differential DNA methylation localized to a 600 bp region in the promoter of the Ifitm3 gene. This was confirmed by ChIP-seq and RNA-seq analyses, showing differential transcription factor binding at the Ifitm3 promoter by JunD (an established determinant of glomerulonephritis), and a consistent change in Ifitm3 expression. Our ABBA analysis allowed us to propose a new role for Ifitm3 in the pathogenesis of glomerulonephritis via a mechanism involving promoter hypermethylation that is associated with Ifitm3 repression in the rat strain susceptible to glomerulonephritis.
KALBA BARBARAI: „ISTORIOGRAFINIS TEATRAS“ IR JO POVEIKIS HENRIKO LATVIO LIVONIJOS KRONIKOJE
Authors: Markevičiūtė Ramunė
Published: February 2017

Straipsnyje aptariami draminio pasakojimo, t. y. pasisakymų tiesiogine kalba, paskirtis ir poveikis viduramžių istoriografijoje, ypatingą dėmesį skiriant draminių epizodų pavyzdžiams Henriko Latvio Livonijos kronikoje.Šioje kronikoje minimas Rygos miesto centre surengtas „pranašų spektaklis“ (ludus prophetarum), skirtas miesto krikščioniškajai bendruomenei, taip pat lyvių ir latvių naujakrikštams. Misionieriai teatrą pasitelkdavo katechetiniams tikslams, kai prireikdavo įtaigiai paaiškinti krikščioniškąsias doktrinas neišmanantiems ir naujai pakrikštytiems bendruomenės nariams. Dramos keliamas stiprus emocinis poveikis nuo pat Antikos laikų skatino ir istorikus savo tekstuose įterpti draminių pasakojimų.Remiantis Aristotelio Poetika straipsnyje siekiama parodyti, kad draminis pasakojimas viduramžių istoriografijoje atitinka aristoteliškuosius poetinio žmogaus veiksmų vaizdavimo reikalavimus. Skirdamas poeziją nuo istoriografijos, Aristotelis pabrėžia, kad poetas turi vaizduoti ne tai, kas iš tiesų įvyko tikrovėje, o tai, kas tikėtinai ar būtinai galėjo įvykti. Todėl istoriografinių tekstų dialogai ir kalbos per se kelia istorinės tiesos klausimą. Straipsnyje siekiama parodyti, kad viduramžių istoriografijos prieiga prie istorinės tiesos skiriasi nuo moderniųjų istoriografijos standartų, reikalaujančių nuosaikaus istorinių įvykių aprašymo. Ikimodernistinės minties požiūriu, draminis ar net poetinis įvykių vaizdavimas jų faktiškumui neprieštarauja: pasitelkiant tam tikrą, nors ir fiktyvų scenarijų, apie pavaizduotą asmenį perteikiama žinutė, kurios turinys yra svarbesnis už istorinių aplinkybių detales.Draminio istorinių veikėjų vaizdavimo prasmė ir paskirtis iliustruojama pavyzdžiais iš Livonijos kronikos, kurios autorius, norėdamas išreikšti tam tikras vaizduojamų asmenų savybes, priskiria jiems paradigminius vaidmenis. Pagrindiniai šio teksto, siekiančio pateisinti karinę krikščionių ekspansiją Baltijos kraštuose, veikėjai yra vokiečių kryžiaus kariai ir vietinės tautos, arba barbarai. Skaitant autoriaus aprašomas žiaurias kovas tarp vokiečių ir vietos gyventojų, galima būtų tikėtis ir atitinkamai niūriomis spalvomis tapomo žiauraus ir klastingo barbaro paveikslo; tačiau įdėmiau išanalizavus pagonis vaizduojančius draminius epizodus pasirodo, kad barbaro vaizdavimas nėra toks vienareikšmis. Daroma išvada, kad kronikos autorius naudojo draminį pasakojimą, kad tendencingame tekste išreikštų kitokį požiūrį.
The Child Witness in the Courtroom
Authors: Pantell Robert H. ,   COMMITTEE ON PSYCHOSOCIAL ASPECTS OF CHILD AND FAMILY HEALTH
Published: February 2017

Beginning in the 1980s, children have increasingly served as witnesses in the criminal, civil, and family courts; currently, >100 000 children appear in court each year. This statement updates the 1992 American Academy of Pediatrics (AAP) policy statement “The Child as a Witness” and the subsequent 1999 “The Child in Court: A Subject Review.” It also builds on existing AAP policy on adverse life events affecting children and resources developed to understand and address childhood trauma. The purpose of this policy statement is to provide background information on some of the legal issues involving children testifying in court, including the accuracy and psychological impact of child testimony; to provide suggestions for how pediatricians can support patients who will testify in court; and to make recommendations for policy improvements to minimize the adverse psychological consequences for child witnesses. These recommendations are, for the most part, based on studies on the psychological and physiologic consequences of children witnessing and experiencing violence, as well as appearing in court, that have emerged since the previous AAP publications on the subject. The goal is to reduce the secondary traumatization of and long-term consequences for children providing testimony about violence they have experienced or witnessed. This statement primarily addresses children appearing in court as victims of physical or sexual abuse or as witnesses of violent acts; most of the scientific literature addresses these specific situations. It may apply, in certain situations, to children required to provide testimony in custody disputes, child welfare proceedings, or immigration court. It does not address children appearing in court as offenders or as part of juvenile justice proceedings.
Mit tehet a háziorvos a mammográfiás szűréseken való részvétel javításáért? A prevenciós nővér szerepe
Authors: Móczár Csaba , Ambrózay Éva , Lehoczky Nyina
Published: February 2017

Abstract:

Introduction: In our country the participation rate in screenings, including mammographic screening is very low. Restructuring of primary care system through the development of practice teams is an important task. Aim: The authors examined the effectiveness of prevention nurses’ work as a member of the practice team on the organization of mammographic screening. Method: Prevention nurses looked up women who did not participate in mammographic screening two years before proceeding the reference period according to a protocol. The program was gradually extended to all family doctor practices in Kecskemét. Results: In the author’s own practice is that the turnout could be achieved and sustained over 60% with this method. During the extension of the program on a representative sample respect of Kecskemét 36.7% of patients who did not participate in screening in the previous two years were involved in mammographic screening again. Extending the entire target population of Kecskemét authors found that the 16–20% of non-screened patients participated again and whole screening rate rose above 70% in the city. Conclusions: The program proved that a prevention nurse as a practice team member can coordinate the tasks of screening effectively making a connection among the family doctors, screening centers and patients. Orv. Hetil., 2017, 158(8), 311–315.