234 research outputs found
Impact of Oxidation State on Reactivity and Selectivity Differences between Nickel(III) and Nickel(IV) Alkyl Complexes
Described is a systematic comparison of factors impacting the relative rates and selectivities of C(sp3)âC and C(sp3)âO bondâforming reactions at highâvalent Ni as a function of oxidation state. Two Ni complexes are compared: a cationic octahedral NiIV complex ligated by tris(pyrazolyl)borate and a cationic octahedral NiIII complex ligated by tris(pyrazolyl)methane. Key features of reactivity/selectivity are revealed: 1)â
C(sp3)âC(sp2) bondâforming reductive elimination occurs from both centers, but the NiIII complex reacts up to 300âfold faster than the NiIV, depending on the reaction conditions. The relative reactivity is proposed to derive from ligand dissociation kinetics, which vary as a function of oxidation state and the presence/absence of visible light. 2)â
Upon the addition of acetate (AcOâ), the NiIV complex exclusively undergoes C(sp3)âOAc bond formation, while the NiIII analogue forms the C(sp3)âC(sp2) coupled product selectively. This difference is rationalized based on the electrophilicity of the respective MâC(sp3) bonds, and thus their relative reactivity towards outerâsphere SN2âtype bondâforming reactions.The high point: This report describes a systematic comparison of factors impacting the relative rates and selectivities of C(sp3)âC and C(sp3)âO bondâforming reactions at highâvalent Ni centers as a function of oxidation state (NiIII versus NiIV). Two Ni complexes are compared: a cationic octahedral NiIV complex ligated by tris(pyrazolyl)borate and a cationic octahedral NiIII complex ligated by tris(pyrazolyl)methane.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150547/1/anie201903638.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150547/2/anie201903638-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150547/3/anie201903638_am.pd
Effects of flavonoids on glycosaminoglycan synthesis: implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses
Sanfilippo disease (mucopolysaccharidosis type III, MPS III) is a severe metabolic disorder caused by accumulation of heparan sulfate (HS), one of glycosaminoglycans (GAGs), due to a genetic defect resulting in a deficiency of GAG hydrolysis. This disorder is characterized as the most severe neurological form of MPS, revealing rapid deterioration of brain functions. Among therapeutic approaches for MPS III, one of the most promising appears to be the substrate reduction therapy (SRT). Genistein (5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one) is an isoflavone that has been used in SRT for MPS III. In this report, we tested effects of other flavonoids (apigenin, daidzein, kaempferol and naringenin) on GAG synthesis. Their cytotoxicity and anti-proliferation features were also tested. We found that daidzein and kaempferol inhibited GAG synthesis significantly. Moreover, these compounds were able to reduce lysosomal storage in MPS IIIA fibroblasts. Interestingly, although genistein is believed to inhibit GAG synthesis by blocking the tyrosine kinase activity of the epidermal growth factor receptor, we found that effects of other flavonoids were not due to this mechanism. In fact, combinations of various flavonoids resulted in significantly more effective inhibition of GAG synthesis than the use of any of these compounds alone. These results, together with results published recently by others, suggest that combination of flavonoids can be considered as a method for improvement of efficiency of SRT for MPS III
The psychological-type profile of clergywomen in ordained local ministry in the Church of England : pioneers or custodians?
This study employs psychological-type theory to compare the psychological profile of 144 clergywomen serving in ordained local ministry in the Church of England alongside the established profile of 237 professional mobile clergywomen serving in the Church of England published by Francis, Craig, Whinney, Tilley, and Slater. The data found no significant differences between these two groups of clergywomen in terms of orientations (introversion and extraversion) or in terms of the judging process (thinking and feeling). In terms of the perceiving process, there was a significantly higher proportion of sensing types among those serving in ordained local ministry (70% compared with 35%). In terms of the attitudes, there was a significantly higher proportion of judging types among those serving in ordained local ministry (83% compared with 65%). The combined sensing judging (SJ) temperament accounted for 65% of the clergywomen serving in ordained local ministry, compared with 29% of the clergywomen serving in professional mobile ministry in the earlier study. It is argued that the SJ temperament characterises a custodian style of ministry
Environmental variables, habitat discontinuity and life history shaping the genetic structure of Pomatoschistus marmoratus
Coastal lagoons are semi-isolated ecosystems
exposed to wide fluctuations of environmental conditions
and showing habitat fragmentation. These features may
play an important role in separating species into different
populations, even at small spatial scales. In this study, we
evaluate the concordance between mitochondrial (previous
published data) and nuclear data analyzing the genetic
variability of Pomatoschistus marmoratus in five localities,
inside and outside the Mar Menor coastal lagoon (SE
Spain) using eight microsatellites. High genetic diversity
and similar levels of allele richness were observed across
all loci and localities, although significant genic and
genotypic differentiation was found between populations
inside and outside the lagoon. In contrast to the FST values
obtained from previous mitochondrial DNA analyses
(control region), the microsatellite data exhibited significant
differentiation among samples inside the Mar Menor
and between lagoonal and marine samples. This pattern
was corroborated using Cavalli-Sforza genetic distances.
The habitat fragmentation inside the coastal lagoon and
among lagoon and marine localities could be acting as a
barrier to gene flow and contributing to the observed
genetic structure. Our results from generalized additive
models point a significant link between extreme lagoonal
environmental conditions (mainly maximum salinity) and
P. marmoratus genetic composition. Thereby, these environmental
features could be also acting on genetic structure
of coastal lagoon populations of P. marmoratus favoring
their genetic divergence. The mating strategy of P. marmoratus
could be also influencing our results obtained from
mitochondrial and nuclear DNA. Therefore, a special
consideration must be done in the selection of the DNA
markers depending on the reproductive strategy of the
species
Dephosphorylated NSSR1 Is Induced by Androgen in Mouse Epididymis and Phosphorylated NSSR1 Is Increased during Sperm Maturation
NSSR1 (Neural salient serine/arginine rich protein 1, alternatively SRp38) is a newly identified RNA splicing factor and predominantly expressed in neural tissues. Here, by Western blot analysis and immunofluorescent staining, we showed that the expression of dephosphorylated NSSR1 increased significantly during development of the caput epididymis. In adult mice, phosphorylated NSSR1 was mainly expressed in the apical side of epithelial cells, and dephosphorylated NSSR1 in caput epididymis was upregulated in a testosterone dependent manner. In addition, subcellular immunoreactive distribution of NSSR1 varied in different regions of the epididymis. With respect to the sperm, phosphorylated NSSR1 was detected in the mid-piece of the tail as well as the acrosome. Furthermore, NSSR1 was released from the sperm head during the capacitation and acrosome reaction. These findings for the first time provide the evidence for the potential roles of NSSR1 in sperm maturation and fertilization
Effects of fishery protection on biometry and genetic structure of two target sea cucumber species from the Mediterranean Sea
Sea cucumber fisheries are now occurring
in most of the tropical areas of the world, having
expanded from its origin in the central Indo-Pacific.
Due to the overexploitation of these resources and the
increasing demand from Asian countries, new target
species from Mediterranean Sea and northeastern
Atlantic Ocean are being caught. The fishery effects
on biometry and genetic structure of two target species
(Holothuria polii and H. tubulosa) from Turkey, were
assessed. The heaviest and largest individuals of H.
polii were found into the non-fishery area of Kusadasi,
also showing the highest genetic diversity. Similar
pattern was detected in H. tubulosa, but only the
weight was significantly higher in the protected area.
However, the observed differences on the fishery
effects between species, could be explained considering
the different percentage of catches (80% for H.
polii and 20% for H. tubulosa)
Modeling the Spread of Methicillin-Resistant Staphylococcus aureus in Nursing Homes for Elderly
Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in many hospital settings, including nursing homes. It is an important nosocomial pathogen that causes mortality and an economic burden to patients, hospitals, and the community. The epidemiology of the bacteria in nursing homes is both hospital- and community-like. Transmission occurs via hands of health care workers (HCWs) and direct contacts among residents during social activities. In this work, mathematical modeling in both deterministic and stochastic frameworks is used to study dissemination of MRSA among residents and HCWs, persistence and prevalence of MRSA in a population, and possible means of controlling the spread of this pathogen in nursing homes. The model predicts that: without strict screening and decolonization of colonized individuals at admission, MRSA may persist; decolonization of colonized residents, improving hand hygiene in both residents and HCWs, reducing the duration of contamination of HCWs, and decreasing the residentâ¶staff ratio are possible control strategies; the mean time that a resident remains susceptible since admission may be prolonged by screening and decolonization treatment in colonized individuals; in the stochastic framework, the total number of colonized residents varies and may increase when the admission of colonized residents, the duration of colonization, the average number of contacts among residents, or the average number of contacts that each resident requires from HCWs increases; an introduction of a colonized individual into an MRSA-free nursing home has a much higher probability of leading to a major outbreak taking off than an introduction of a contaminated HCW
Kindlins, Integrin Activation and the Regulation of Talin Recruitment to αIIbÎČ3
Talins and kindlins bind to the integrin ÎČ3 cytoplasmic tail and both are required for effective activation of integrin αIIbÎČ3 and resulting high-affinity ligand binding in platelets. However, binding of the talin head domain alone to ÎČ3 is sufficient to activate purified integrin αIIbÎČ3 in vitro. Since talin is localized to the cytoplasm of unstimulated platelets, its re-localization to the plasma membrane and to the integrin is required for activation. Here we explored the mechanism whereby kindlins function as integrin co-activators. To test whether kindlins regulate talin recruitment to plasma membranes and to αIIbÎČ3, full-length talin and kindlin recruitment to ÎČ3 was studied using a reconstructed CHO cell model system that recapitulates agonist-induced αIIbÎČ3 activation. Over-expression of kindlin-2, the endogenous kindlin isoform in CHO cells, promoted PAR1-mediated and talin-dependent ligand binding. In contrast, shRNA knockdown of kindlin-2 inhibited ligand binding. However, depletion of kindlin-2 by shRNA did not affect talin recruitment to the plasma membrane, as assessed by sub-cellular fractionation, and neither over-expression of kindlins nor depletion of kindlin-2 affected talin interaction with αIIbÎČ3 in living cells, as monitored by bimolecular fluorescence complementation. Furthermore, talin failed to promote kindlin-2 association with αIIbÎČ3 in CHO cells. In addition, purified talin and kindlin-3, the kindlin isoform expressed in platelets, failed to promote each other's binding to the ÎČ3 cytoplasmic tail in vitro. Thus, kindlins do not promote initial talin recruitment to αIIbÎČ3, suggesting that they co-activate integrin through a mechanism independent of recruitment
Eating disorders in sport : current status and future directions in the study of the psychological factors
Este trabalho procura atingir dois objetivos. Em primeiro lugar, apresenta-se a situação atual da investigação sobre desordens alimentares no desporto. Neste caso, salientam-se as linhas de investigação dedicadas ao estudo da prevalĂȘncia destes problemas no desporto e analisam-se as diferenças entre atletas e modalidades desportivas. Dadas as dificuldades destas linhas de investigação na compreensĂŁo dos comportamentos alimentares de risco nos atletas, sĂŁo avançadas outras possibilidades de desenvolvimento da investigação. Assim, e enquanto segundo objetivo deste artigo, salientamos a necessidade dos estudos se dirigirem para a compreensĂŁo dos fatores psicolĂłgicos associados aos comportamentos alimentares de risco e implicados no desenvolvimento das desordens alimentares. Esta abordagem tem como vantagem adicional ajudar a prevenir estes problemas atravĂ©s da promoção das competĂȘncias mentais dos atletas no sentido de resistirem melhor aos possĂveis efeitos nocivos da prĂĄtica desportiva, onde se inserem os problemas com a alimentação.This paper focuses on two main goals. In first place, we present the current status on the
research about eating disorders in sport contexts. In this case, we point out studies dedicated to the
analysis of the incidence of eating disorders in sport and studies that observe the differences between athletes and different sports in the tendency for these problems. Second, we proposed new research
directions on this subject, namely the need of analysing the psychological factors that are related with
the development of eating disorders on athletes. This research approach has the advantage of helping
the prevention of eating disorders on athletes through the promotion of psychological skills that protect
athletes from the negative effects of sport practicing, where are included maladaptive eating behaviors.(undefined
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