Inhibition of apoptotic Bax translocation to the mitochondria is a central function of parkin

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, affecting 1–3% of the population over 65. Mutations in the ubiquitin E3 ligase parkin are the most common cause of autosomal recessive PD. The parkin protein possesses potent cell-protective properties and has been mechanistically linked to both the regulation of apoptosis and the turnover of damaged mitochondria. Here, we explored these two functions of parkin and the relative scale of these processes in various cell types. While biochemical analyses and subcellular fractionation were sufficient to observe robust parkin-dependent mitophagy in immortalized cells, higher resolution techniques appear to be required for primary culture systems. These approaches, however, did affirm a critical role for parkin in the regulation of apoptosis in primary cultured neurons and all other cells studied. Our prior work demonstrated that parkin-dependent ubiquitination of endogenous Bax inhibits its mitochondrial translocation and can account for the anti-apoptotic effects of parkin. Having found a central role for parkin in the regulation of apoptosis, we further investigated the parkin-Bax interaction. We observed that the BH3 domain of Bax is critical for its recognition by parkin, and identified two lysines that are crucial for parkin-dependent regulation of Bax translocation. Last, a disease-linked mutation in parkin failed to influence Bax translocation to mitochondria after apoptotic stress. Taken together, our data suggest that regulation of apoptosis by the inhibition of Bax translocation is a prevalent physiological function of parkin regardless of the kind of cell stress, preventing overt cell death and supporting cell viability during mitochondrial injury and repair

Goal-directed mechanisms that constrain retrieval predict subsequent memory for new "foil" information.

To remember a previous event, it is often helpful to use goal-directed control processes to constrain what comes to mind during retrieval. Behavioral studies have demonstrated that incidental learning of new "foil" words in a recognition test is superior if the participant is trying to remember studied items that were semantically encoded compared to items that were non-semantically encoded. Here, we applied subsequent memory analysis to fMRI data to understand the neural mechanisms underlying the "foil effect". Participants encoded information during deep semantic and shallow non-semantic tasks and were tested in a subsequent blocked memory task to examine how orienting retrieval towards different types of information influences the incidental encoding of new words presented as foils during the memory test phase. To assess memory for foils, participants performed a further surprise old/new recognition test involving foil words that were encountered during the previous memory test blocks as well as completely new words. Subsequent memory effects, distinguishing successful versus unsuccessful incidental encoding of foils, were observed in regions that included the left inferior frontal gyrus and posterior parietal cortex. The left inferior frontal gyrus exhibited disproportionately larger subsequent memory effects for semantic than non-semantic foils, and significant overlap in activity during semantic, but not non-semantic, initial encoding and foil encoding. The results suggest that orienting retrieval towards different types of foils involves re-implementing the neurocognitive processes that were involved during initial encoding.James S. McDonnell Foundation (Scholar Award), Medical Research Council, Wellcome TrustThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.neuropsychologia.2016.07.01

Exploring the Therapeutic Potential of Rosemary: An In-depth Review of its Pharmacological Properties

The pharmacological effects of rosemary plant period a wide range and include anti-inflammatory and antioxidant properties. Rosemary is shown to have its potential on Ischemic stroke because of its Anti-oxidant and Anti-inflammatory properties. It contains strong antioxidants such carnosol, which has anti-inflammatory properties, and Rosmarinus acid, which fights oxidative stress. Rosemary is an attractive possibility for treating disorders like oxidative-related diseases because of its dual activity. Additionally, Rosemary has shown neuroprotective qualities that aid in maintaining brain health and cognitive function. The aromatic components in its essential oil may improve concentration and memory. Rosemary has also been investigated for its potential in hair care, with research indicating that it can encourage hair growth. These rosemary Officinalis also have different chemical substances and compounds like Terpenes, Essential oils, Bicyclic monoterpenes, Monoterpenoids, Ester and also, we have different pharmacological activates they are Anti-oxidative, Anti-inflammatory, Anti-microbial, Anti-obesity, Anti-fungal, Anti-cancer, Anti-diabetic, Cardiovascular activity, Skin health, Neuroprotective, Gastrointestinal, Sperm motility, Anti-depressant, Anti-viral activity

Impaired recollection of visual scene details in adults with autism spectrum conditions.

Subtle memory deficits observed in autism spectrum conditions (ASC) have often been characterized as reflecting impaired recollection and it has been proposed that a relational binding deficit may underlie the recollection impairment. However, subjective recollection and relational binding have not been measured within the same task in ASC to date and it is unclear whether a relational binding deficit can provide a full account of recollection impairments in ASC. Relational memory has also not been compared with item memory when the demands of the 2 tasks are comparable. To assess recollection, relational memory, and item memory within a single task in ASC, 24 adults with ASC and 24 typically developed adults undertook a change detection memory task that assessed recollection of item-specific and spatial details. Participants studied rendered indoor and outdoor scenes and, in a subsequent recognition memory test, distinguished scenes that had not changed from those that had either undergone an item change (a different item exemplar) or a relational (spatial) change, which was followed by a subjective recollection judgment. The ASC group identified fewer item changes and spatial changes, to a similar degree, which was attributable to a specific reduction in recollection-based recognition relative to the control group. These findings provide evidence that recollection deficits in ASC may not be driven entirely by a relational binding deficit.This research was supported by a James S. McDonnell Scholar Award to J.S.S., an Economic and Social Research Council Award to R.A.C., and Leverhulme Trust Visiting Professorship and Parke Davis Exchange Fellowship Awards to C.R.This is the author accepted manuscript. The final version is available from he American Psychological Association via http://dx.doi.org/10.1037/abn000007

Percutaneous tricuspid valvotomy for pacemaker lead-induced tricuspid stenosis

AbstractPermanent pacemaker lead-induced tricuspid regurgitation is extremely uncommon. We report a patient with severe tricuspid stenosis detected 10 years after permanent single chamber pacemaker implantation in surgically corrected congenital heart disease. The loop at the level of the tricuspid valve may have caused endothelial injury and eventually led to stenosis. Percutaneous balloon valvotomy for such stenosis has not been reported from India

Alpha Oscillations during Incidental Encoding Predict Subsequent Memory for New "Foil" Information.

People can employ adaptive strategies to increase the likelihood that previously encoded information will be successfully retrieved. One such strategy is to constrain retrieval toward relevant information by reimplementing the neurocognitive processes that were engaged during encoding. Using EEG, we examined the temporal dynamics with which constraining retrieval toward semantic versus nonsemantic information affects the processing of new "foil" information encountered during a memory test. Time-frequency analysis of EEG data acquired during an initial study phase revealed that semantic compared with nonsemantic processing was associated with alpha decreases in a left frontal electrode cluster from around 600 msec after stimulus onset. Successful encoding of semantic versus nonsemantic foils during a subsequent memory test was related to decreases in alpha oscillatory activity in the same left frontal electrode cluster, which emerged relatively late in the trial at around 1000-1600 msec after stimulus onset. Across participants, left frontal alpha power elicited by semantic processing during the study phase correlated significantly with left frontal alpha power associated with semantic foil encoding during the memory test. Furthermore, larger left frontal alpha power decreases elicited by semantic foil encoding during the memory test predicted better subsequent semantic foil recognition in an additional surprise foil memory test, although this effect did not reach significance. These findings indicate that constraining retrieval toward semantic information involves reimplementing semantic encoding operations that are mediated by alpha oscillations and that such reimplementation occurs at a late stage of memory retrieval, perhaps reflecting additional monitoring processes

Characterization of aerosol hygroscopicity over the Northeast Pacific Ocean: Impacts on prediction of CCN and stratocumulus cloud droplet number concentrations

During the Marine Aerosol Cloud and Wildfire Study (MACAWS) in June and July of 2018, aerosol composition and cloud condensation nuclei (CCN) properties were measured over the N.E. Pacific to characterize the influence of aerosol hygroscopicity on predictions of ambient CCN and stratocumulus cloud droplet number concentrations (CDNC). Three vertical regions were characterized, corresponding to the marine boundary layer (MBL), an above‐cloud organic aerosol layer (AC‐OAL), and the free troposphere (FT) above the AC‐OAL. The aerosol hygroscopicity parameter (κ) was calculated from CCN measurements (κ_(CCN)) and bulk aerosol mass spectrometer (AMS) measurements (κ_(AMS)). Within the MBL, measured hygroscopicities varied between values typical of both continental environments (~0.2) and remote marine locations (~0.7). For most flights, CCN closure was achieved within 20% in the MBL. For five of the seven flights, assuming a constant aerosol size distribution produced similar or better CCN closure than assuming a constant “marine” hygroscopicity (κ = 0.72). An aerosol‐cloud parcel model was used to characterize the sensitivity of predicted stratocumulus CDNC to aerosol hygroscopicity, size distribution properties, and updraft velocity. Average CDNC sensitivity to accumulation mode aerosol hygroscopicity is 39% as large as the sensitivity to the geometric median diameter in this environment. Simulations suggest CDNC sensitivity to hygroscopicity is largest in marine stratocumulus with low updraft velocities (0.6 m s⁻¹), where hygroscopic properties of the Aitken mode dominate hygroscopicity sensitivity

Characterization of aerosol hygroscopicity over the Northeast Pacific Ocean: Impacts on prediction of CCN and stratocumulus cloud droplet number concentrations

During the Marine Aerosol Cloud and Wildfire Study (MACAWS) in June and July of 2018, aerosol composition and cloud condensation nuclei (CCN) properties were measured over the N.E. Pacific to characterize the influence of aerosol hygroscopicity on predictions of ambient CCN and stratocumulus cloud droplet number concentrations (CDNC). Three vertical regions were characterized, corresponding to the marine boundary layer (MBL), an above‐cloud organic aerosol layer (AC‐OAL), and the free troposphere (FT) above the AC‐OAL. The aerosol hygroscopicity parameter (κ) was calculated from CCN measurements (κ_(CCN)) and bulk aerosol mass spectrometer (AMS) measurements (κ_(AMS)). Within the MBL, measured hygroscopicities varied between values typical of both continental environments (~0.2) and remote marine locations (~0.7). For most flights, CCN closure was achieved within 20% in the MBL. For five of the seven flights, assuming a constant aerosol size distribution produced similar or better CCN closure than assuming a constant “marine” hygroscopicity (κ = 0.72). An aerosol‐cloud parcel model was used to characterize the sensitivity of predicted stratocumulus CDNC to aerosol hygroscopicity, size distribution properties, and updraft velocity. Average CDNC sensitivity to accumulation mode aerosol hygroscopicity is 39% as large as the sensitivity to the geometric median diameter in this environment. Simulations suggest CDNC sensitivity to hygroscopicity is largest in marine stratocumulus with low updraft velocities (0.6 m s⁻¹), where hygroscopic properties of the Aitken mode dominate hygroscopicity sensitivity

Market research in the Finnish food industry

This study introduces the important factors of market research and its significancewhen aiming at new foreign markets. Understanding the cultural differences, the consumers and the market itself with the competitors’ actions among other factors, the organization has a better chance to succeed in entering new markets. The case company is a Belgian food industry company which is interested in the Finnish market environment with its consumers and competitors. Currently they are operating in Central European countries with a little market share. An interview was conducted in order to better understand their current situation and expectations on new markets. The company’s products are sold in specialty stores and in bigger hypermarkets due to their higher image which they would like to obtain in Finland. As a small country Finland can not offer big markets but this is no obstacle for the case company since they are not looking to challenge the market leader or even the followers. Instead they are looking for a small market share as in other countries that they already operate in. By using selective distribution focused on the biggest city areas the product availability is guaranteed to the majority of the Finnish population. The thesis emphasizes the different business chains - the different types of stores and their product variety as well as competitors and their product pricing. Among this, the importance of product visibility will be shown as the case company wishes to enter the markets with as little marketing as possible. Regulations on labelling are studied as well as there are little differences from organizations’ home markets. The study also introduces a Finnish importing company that could possibly cooperate with the customer when aiming at the Finnish markets.Tutkimus esittelee markkinatutkimuksen tärkeimmät osa-alueet sekä sen merkityksen tavoiteltaessa uusia markkinoita. Kulttuurillisten eroavaisuuksien, kuluttajien sekä itse markkinoiden ymmärtäminen kilpailijoineen edesauttaa yrityksen menestymistä uudella markkina-alueella. Asiakasyritys on Belgialainen elintarvikeyritys joka kiinnostui Suomen markkinaympäristöstä, kuluttajista sekä kilpailijoista. Tällä hetkellä he toimivat Keski-Euroopan markkinoilla pienin markkinaosuuksin. Haastattelu suoritettiin jotta saataisiin selville heidän nykytilanteensa sekä tulevaisuuden näkymät uusista markkinoista. Yrityksen tuotteet ovat myynnissä erikoisliikkeissä sekä suurimmissa marketeissa korkean imagon vuoksi ja näin he toivoisivat myös tapahtuvan Suomessa. Suomessa ei ole tarjolla suuria markkinoita jo pelkästään maan koon vuoksi. Tämä ei ole kuitenkaan este asiakasyritykselle sillä he eivät lähde haastamaan markkinajohtajaa tai seuraajia, vaan tyytyvät pieneen markkinaosuuteen aivan kuten muillakin markkinoilla. Selektiivisellä tuotejakelulla, keskittyen Suomen suurimpiin kaupunkialueisiin, taataan tuotteiden saatavuus suurimmalle osalle väestöstä. Tutkimus painottuu eri liikeketjuihin, Suomen kauppatyyppeihin ja niiden tuotevalikoiman suuruuteen sekä kilpailijoihin ja heidän tuotehinnoitteluun. Tämän lisäksi tuotteiden näkyvyyden tärkeys osoitetaan, sillä asiakasyritys toivoisi markkinoille tuloa vähäisin markkinointitoiminnoin. Pakkausmerkintäsäännökset tulevat myös esille sillä ne eroavat hieman yrityksen kotimarkkinoiden säännöksistä. Tutkimus esittelee myös suomalaisen maahantuontiyrityksen, joka voisi mahdollisesti toimia asiakasyrityksen yhteistyökumppanina Suomen markkinoille pyrittäessä