Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of PINK1 Function Promotes Mitophagy through Effects on Oxidative Stress and Mitochondrial Fission*

Mitochondrial dysregulation is strongly implicated in Parkinson disease. Mutations in PTEN-induced kinase 1 (PINK1) are associated with familial parkinsonism and neuropsychiatric disorders. Although overexpressed PINK1 is neuroprotective, less is known about neuronal responses to loss of PINK1 function. We found that stable knockdown of PINK1 induced mitochondrial fragmentation and autophagy in SH-SY5Y cells, which was reversed by the reintroduction of an RNA interference (RNAi)-resistant plasmid for PINK1. Moreover, stable or transient overexpression of wild-type PINK1 increased mitochondrial interconnectivity and suppressed toxin-induced autophagy/mitophagy. Mitochondrial oxidant production played an essential role in triggering mitochondrial fragmentation and autophagy in PINK1 shRNA lines. Autophagy/mitophagy served a protective role in limiting cell death, and overexpressing Parkin further enhanced this protective mitophagic response. The dominant negative Drp1 mutant inhibited both fission and mitophagy in PINK1-deficient cells. Interestingly, RNAi knockdown of autophagy proteins Atg7 and LC3/Atg8 also decreased mitochondrial fragmentation without affecting oxidative stress, suggesting active involvement of autophagy in morphologic remodeling of mitochondria for clearance. To summarize, loss of PINK1 function elicits oxidative stress and mitochondrial turnover coordinated by the autophagic and fission/fusion machineries. Furthermore, PINK1 and Parkin may cooperate through different mechanisms to maintain mitochondrial homeostasis.
Characterization of Two Activated Mutants of Human pp60c-src That Escape c-Src Kinase Regulation by Distinct Mechanisms (*)

Two activated transforming mutants of human pp60c-src were found to possess single point mutations within the regulatory carboxyl terminus (E527K in CY CST201) and the kinase domain (E381G in WO CST1), respectively, that do not directly interfere with either the regulatory c-Src kinase (CSK) phosphorylation site (Tyr530) or the SH2/3 domains. In vivo, both mutant proteins are hypophosphorylated on their carboxyl-terminal regulatory tyrosines and are hyperactive. In an in vitro Src kinase inactivation assay, both mutant Src proteins exhibited resistance to inactivation by CSK relative to wild-type Src. Under these in vitro conditions, E381G c-Src was found to be phosphorylated by CSK to wild-type levels, while E527K c-Src was not detectably phosphorylated. The ability of CSK to phosphorylate a carboxyl-terminal peptide modelled against E527K c-Src was also impaired, suggesting that CSK is unable to recognize E527K c-Src as an efficient substrate. In the case of E381G c-Src, examination of whether its SH2/3 domains were accessible to the carboxyl-terminal regulatory phosphotyrosine revealed a highly reduced ability of autophosphorylated E381G c-Src to bind to a synthetic phosphopeptide modelled from the SH2-binding region of polyoma middle-T antigen which binds to Src SH2 with high affinity. This suggests that the E381G c-Src mutation results in an altered or reduced accessibility of the SH2 domain of the autophosphorylated form of E381G c-Src and may represent a previously undescribed mode of Src activation. Further study of these and other Src mutants may offer additional new insights into the regulation of “Src family” kinases.
Does Motion Perception Follow Weber's Law?

The subjective strength of a percept often depends on the stimulus intensity in a nonlinear way. Such coding is often reflected by the observation that the just-noticeable difference between two stimulus intensities (JND) is proportional to the absolute stimulus intensity. This behaviour, which is usually referred to as Weber's Law, can be interpreted as a compressive nonlinearity extending the operating range of a sensory system. When the noise superimposed on a motion stimulus is increased along a logarithmic scale (in order to provide linear steps in subjective difference) in motion-coherency measurements, observers often report that the subjective differences between the various noise levels increase together with the absolute level. This observation could indicate a deviation from Weber's Law for variation of motion strength as obtained by changing the signal-to-noise ratio in random-dot kinematograms. Thus JNDs were measured for the superposition of uncorrelated random-dot patterns on static random-dot patterns and three types of motion stimuli realised as random-dot kinematograms, namely large-field and object ‘Fourier’ motion (all or a group of dots move coherently), ‘drift-balanced’ motion (a travelling region of static dots), and paradoxical ‘theta’ motion (the dots on the surface of an object move in opposite direction to the object itself). For all classes of stimuli, the JNDs when expressed as differences in signal-to-noise ratio turned out to increase with the signal-to-noise ratio, whereas the JNDs given as percentage of superimposed noise appear to be similar for all tested noise levels. Thus motion perception is in accordance with Weber's Law when the signal-to-noise ratio is regarded as stimulus intensity, which in turn appears to be coded in a nonlinear fashion. In general the Weber fractions are very large, indicating a poor differential sensitivity in signal-to-noise measurements.
A four-component synthetic attractant for Drosophila suzukii (Diptera: Drosophilidae) isolated from fermented bait headspace.

BACKGROUND A mixture of wine and vinegar is more attractive than wine or vinegar to spotted wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), and ethanol and acetic acid are considered key to that attractiveness. In addition to ethanol and acetic acid, 13 other wine and vinegar volatiles are antennally active to D. suzukii and might be involved in food finding. RESULTS Out of the 13 antennally active chemicals, acetoin, ethyl lactate and methionol increased fly response to a mixture of acetic acid and ethanol in field trapping experiments. A five-component blend of acetic acid, ethanol, acetoin, ethyl lactate and methionol was as attractive as the starting mixture of wine and vinegar in field tests conducted in the states of Oregon and Mississippi. Subtracting ethyl lactate from the five-component blend did not reduce the captures of flies in the trap. However, subtracting any other compound from the blend significantly reduced the numbers of flies captured. CONCLUSION These results indicate that acetic acid, ethanol, acetoin and methionol are key olfactory cues for D. suzukii when attracted to wine and vinegar, which may be food-finding behavior leading flies to fermenting fruit in nature. It is anticipated that this four-component blend can be used as a highly attractive chemical lure for detection and management of D. suzukii. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9

The membrane–cytosol interface is the major locus of control of actin polymerization. At this interface, phosphoinositides act as second messengers to recruit membrane-binding proteins. We show that curved membranes, but not flat ones, can use phosphatidylinositol 3-phosphate [PI(3)P] along with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to stimulate actin polymerization. In this case, actin polymerization requires the small GTPase cell cycle division 42 (Cdc42), the nucleation-promoting factor neural Wiskott–Aldrich syndrome protein (N-WASP) and the actin nucleator the actin-related protein (Arp) 2/3 complex. In liposomes containing PI(4,5)P2 as the sole phosphoinositide, actin polymerization requires transducer of Cdc42 activation-1 (toca-1). In the presence of phosphatidylinositol 3-phosphate, polymerization is both more efficient and independent of toca-1. Under these conditions, sorting nexin 9 (Snx9) can be implicated as a specific adaptor that replaces toca-1 to mobilize neural Wiskott–Aldrich syndrome protein and the Arp2/3 complex. This switch in phosphoinositide and adaptor specificity for actin polymerization from membranes has implications for how different types of actin structures are generated at precise times and locations in the cell.
Vaccinia virus late transcripts generated in vitro have a poly(A) head.

A cell free system mediating accurate transcription of vaccinia virus genes was established using lysates of cells in the late phase of infection. Vaccinia late genes are faithfully transcribed in this extract whereas cellular pol II and pol III promoters are not recognized. The late viral transcripts contain a poly(A) head of approximately 35 nt at the 5′ end which is not co‐linearly encoded in the externally added template. The transcripts obtained in vitro are indistinguishable from the mature in vivo RNAs. The poly(A) head is synthesized de novo and its formation appears to be directly coupled to the transcription of the gene. The synthesis of the poly(A) head transcripts in vitro is consistent with a proposed slippage model.
Mitochondrial and sarcolemmal Ca2+ transport reduce [Ca2+]i during caffeine contractures in rabbit cardiac myocytes.

1. Contraction and intracellular Ca2+ (Ca2+i) transients were measured in isolated rabbit ventricular myocytes during twitches and contractures induced by rapid application of 10 mM‐caffeine. 2. The amplitude of caffeine‐induced contractures and the accompanying Ca2+i transients were larger than during normal twitches and also declined more slowly. This may be because only a fraction of sarcoplasmic reticulum (SR) Ca2+ is released during a normal twitch, or because of a temporal overlap of SR Ca2+ release and uptake during the twitch. 3. When a caffeine contracture was initiated in Na(+)‐free, Ca(2+)‐free medium (to prevent sarcolemmal Na(+)‐Ca2+ exchange) the contracture and Ca2+i transient were larger and decreased much more slowly. Thus, Ca2+ extrusion via Na(+)‐Ca2+ exchange may limit the amplitude of caffeine‐induced contractures. 4. Relaxation half‐time (t1/2) for the twitch (0.17 +/‐ 0.03 s) was increased to 0.54 +/‐ 0.07 s for caffeine contractures in control solution and 8.8 +/‐ 1 s for caffeine‐induced contractures in Na(+)‐free, Ca(2+)‐free solution. These results confirm that the SR Ca2+ pump and Na(+)‐Ca2+ exchange are the predominant mechanisms for cytoplasmic Ca2+ removal during relaxation. However slower mechanisms can still reduce intracellular [Ca2+]. 5. Relaxation of caffeine contractures in Na(+)‐free solution was further slowed when (a) mitochondrial Ca2+ uptake was inhibited with the oxidative phosphorylation uncoupler, FCCP (t1/2 = 19.7 +/‐ 3.2 s), or (b) the sarcolemmal Ca(2+)‐ATPase pumping ability was depressed by a large transmembrane [Ca2+] gradient (t1/2 = 27.5 +/‐ 6.9 s). 6. When the four Ca2+ transport systems were simultaneously inhibited (i.e. SR Ca2+ pump, Na(+)‐Ca2+ exchange, mitochondrial Ca2+ uptake and sarcolemmal Ca2+ pump), relaxation was practically abolished, but the cell could recover quickly when Na+ was reintroduced and caffeine removed. 7. We conclude that, under our experimental conditions, the sarcolemmal Ca2+ pump and mitochondria are approximately 37‐ and 50‐fold slower than the Na(+)‐Ca2+ exchange at removing Ca2+ from the cytoplasm. Additionally, the SR Ca2+ pump is about 3‐4 times faster than Na(+)‐Ca2+ exchange.
Fatty acid acylation of vaccinia virus proteins

Labeling of vaccinia virus-infected cells with [3H]myristic acid resulted in the incorporation of label into two viral proteins with apparent molecular weights of 35,000 and 25,000 (designated M35 and M25, respectively). M35 and M25 were expressed in infected cells after the onset of viral DNA replication, and both proteins were present in purified intracellular virus particles. Virion localization experiments determined M25 to be a constituent of the virion envelope, while M35 appeared to be peripherally associated with the virion core. M35 and M25 labeled by [3H]myristic acid were stable to treatment with neutral hydroxylamine, suggesting an amide-linked acylation of the proteins. Chromatographic identification of the protein-bound fatty acid moieties liberated after acid methanolysis of M25, isolated from infected cells labeled during a 4-h pulse, resulted in the recovery of 25% of the protein-bound fatty acid as myristate-associated label and 75% as palmitate, indicating that interconversion of myristate to palmitate had occurred during the labeling period. Similar analyses of M25 and M35, isolated from infected cells labeled during a 0.5-h pulse, determined that 46 and 43%, respectively, of the protein-bound label had been elongated to palmitate even during this brief labeling period. In contrast, M25 and M35 isolated from purified intracellular virions labeled continuously during 24 h of growth contained 75 and 70%, respectively, myristate-associated label, suggesting greater stability of these proteins or a favored interaction of the proteins containing myristate with the maturing or intracellular virion.
Aberrant topographical organization in gray matter structural network in late life depression: a graph theoretical analysis

ABSTRACT Background: Although previous studies on late life depression (LLD) have shown morphological abnormalities in frontal–striatal–temporal areas, alterations in coordinated patterns of structural brain networks in LLD are still poorly understood. The aim of this study was to investigate differences in gray matter structural brain network between LLD and healthy controls. Methods: We used gray matter volume measurement from magnetic resonance imaging to investigate large-scale structural brain networks in 37 LLD patients and 40 normal controls. Brain networks were constructed by thresholding gray matter volume correlation matrices of 90 regions and analyzed using graph theoretical approaches. Results: Although both LLD and control groups showed a small-world organization of group networks, there were no differences in the clustering coefficient, the path length, and the small-world index across a wide range of network density. Compared with controls, LLD patients showed decreased nodal betweenness in the medial orbitofrontal and angular gyrus regions. In addition, LLD patients showed hub regions in superior temporal gyrus and middle cingulate gyrus, and putamen. On the other hand, the control group showed hub regions in the medial orbitofrontal gyrus, middle cingulate gyrus, and cuneus. Conclusion: Our findings suggest that the gray matter structural networks are not globally but regionally altered in LLD patients. This multivariate structural analysis using graph theory might provide a more appropriate paradigm for understanding complicated neurobiological mechanism of LLD.
Multiple sclerosis and sexual dysfunction: A need for further education and interdisciplinary care.

BACKGROUND Multiple sclerosis (MS) is an autoimmune condition affecting young women and men, resulting in varied disabilities, including sexual dysfunction. OBJECTIVE This narrative review aims to describe the prevalence, pathophysiology, and impact of sexual dysfunction in people with MS (PwMS); provide a review of current assessment and treatment strategies; and offer considerations for future care. METHODS Literature review was performed to identify primary and secondary sources discussing sexual dysfunction in PwMS. RESULTS Sexual dysfunction is common in PwMS and can occur throughout the disease course. Sexual dysfunction is associated with depression, reduced quality of life, and may have broader implications related to relationships, fertility, pregnancy, and parenting. The etiology is often multifactorial and can be classified as primary, secondary, or tertiary dysfunction. Sexual dysfunction in PwMS is underdiagnosed and undertreated; however, many healthcare providers may already have the skills required to care for PwMS with sexual dysfunction. CONCLUSIONS Additional education for providers regarding the approach to assessment and management of sexual dysfunction, their potential role in treatment, and available specialized resources is needed. The role of interdisciplinary care with collaboration among providers should be considered. Further research should evaluate the impact of specific assessment tools and treatments on sexual dysfunction in PwMS.
Possibilités de réduction des rejets chez le poulet par la sélection génétique

Dans un contexte de developpement durable, trouver des moyens de reduire l’impact environnemental de la production avicole est d’une grande importance. L’estimation des parametres genetiques de nombreux caracteres de rejets chez les lignees divergentes D+ et D- nous a permis de definir plusieurs criteres pertinents a prendre en compte dans les schemas de selection pour maitriser l’excretion des poulets. Nous avons egalement montre que l’utilisation de ces criteres n’aurait pas de consequences negatives sur les caracteristiques d’importance economique pour l’industrie avicole. Enfin, nous avons pu montrer que la morphologie du tractus gastro-intestinal etait tres fortement impliquee dans les variations d’excretion des poulets. En effet, un important developpement du proventricule et du gesier et une reduction du developpement de l’intestin grele sont associes aux animaux produisant moins de rejets et presentant une meilleure efficacite digestive.
Regulation of mouse serum amyloid A gene expression in transfected hepatoma cells

Expression of mouse serum amyloid A (SAA1, -2, and -3) mRNAs can be induced up to 1,000-fold in the liver in response to acute inflammation. This large increase is primarily the result of a 200-fold increase in the rates of SAA gene transcription. To analyze the cis-acting regulatory element(s) responsible for regulating transcription, we fused 306 base pairs of the mouse SAA3 promoter to a reporter gene, the chloramphenicol acetyltransferase (CAT) gene, and transfected this chimeric DNA into cultured cells. In transient expression assays, this 5' sequence was sufficient to confer cell-specific expression: CAT activity was readily detectable when the construct was transfected into liver-derived cells but was not detectable in nonliver cells. Furthermore, when liver cells transfected with this construct were treated with conditioned media prepared from activated mixed lymphocyte cultures or with recombinant interleukin-1, a 10- to 15-fold increase in CAT activity was detected. Deletion analyses showed two regions of interest: a proximal region that enhanced CAT expression in a cell-specific manner and a distal region that conferred responsiveness to both conditioned media and recombinant interleukin-1. This distal responsive element had properties of an inducible transcriptional enhancer, and deletion of the proximal cell-specific region rendered the distal element responsive to stimulation by conditioned media in nonliver cells.
Efficacy of early cognitive–linguistic treatment and communicative treatment in aphasia after stroke: a randomised controlled trial (RATS-2)

Background The two main approaches in aphasia treatment are cognitive–linguistic treatment (CLT), aimed at restoring the linguistic levels affected, semantics, phonology or syntax, and communicative treatment, aimed at optimising information transfer by training compensatory strategies and use of residual language skills. The hypothesis that CLT is more effective than communicative treatment in the early stages after stroke was tested in this study. Methods In this multicentre, randomised, parallel group trial with blinded outcome assessment, 80 patients with aphasia after stroke were included within 3 weeks post-stroke. Patients received 6 months of CLT, comprising semantic and/or phonological training, or communicative treatment for at least 2 h per week. They were assessed before treatment and at 3 and 6 months with the Amsterdam–Nijmegen Everyday Language Test (ANELT-A, primary outcome) and semantic and phonological tests (secondary outcomes). The intervention effect was evaluated by means of analysis of covariance, with adjustment for baseline scores. Results There was no difference between the mean ANELT-A score of the CLT group (n=38) and the communicative treatment group (n=42), at 3 months (adjusted difference 1.5, 95% CI −2.6 to 5.6) or at 6 months (adjusted difference 1.6, 95% CI −2.3 to 5.6) post-stroke. On two of six specific semantic and phonological tests, the mean scores differed significantly, both in favour of CLT. Conclusion This study does not confirm the hypothesis that patients with aphasia after stroke benefit more from CLT, aimed at activation of the underlying semantic and phonologic processes, than from general, non-specific communicative treatment (ISRCTN67723958 Current Controlled Trials).
Detection of Trypanosoma cruzi by DNA amplification using the polymerase chain reaction

The polymerase chain reaction was used to amplify a 188-base pair (bp) segment of the repetitive 195-bp nuclear DNA sequence of Trypanosoma cruzi that is the most abundant sequence in this organism. The reaction amplified this repetitive element in four T. cruzi isolates from widely separated geographic regions. No amplification of the 188-bp fragment occurred when DNAs extracted from Leishmania spp. , African trypanosomes, or blood samples from mice and humans were used. Amplification of one-half of the DNA from a single T. cruzi parasite produced an amount of the 188-bp element that was readily visible in a gel stained with ethidium bromide. Hybridization of a radiolabeled probe to membrane-bound amplification products increased the sensitivity to a level at which 1/200 of the DNA in a single parasite could be detected. T. cruzi DNA was readily detected in DNA extracted from the abdominal contents of infected insect vectors reared in the laboratory. No parasite DNA was detected in the blood samples of two individuals known to be infected with T. cruzi, possibly because in such patients the number of circulating parasites are extremely low or because parasitemias are intermittent. These results represent a considerable increase in sensitivity over previously reported methods for the detection of T. cruzi infections. Polymerase chain reaction amplification can be used to evaluate large numbers of samples in a single day and thus should be useful in large-scale studies of the prevalence of T. cruzi in both insect vectors and mammalian hosts.