Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

Caregiver stress in traumatic brain injury

Aims Many patients experience physical, behavioural, cognitive and emotional problems following traumatic brain injury (TBI). They may require continuing care for many years, most of which is provided by informal caregivers, such as spouses, parents, or other family members. The caregiving role is associated with a range of adverse effects including anxiety, depression, poor physical health and lowered quality of life. This article explores issues around caregiver stress; highlighting interventions for this group and areas for further research. Methods Literature exploring the impact of caregiving, its influencing and alleviating factors and interventions for caregivers of people with TBI is discussed, with brief critical analysis of key studies. Findings Research suggests that caregiver characteristics, coping strategies, their appraisal of the situation and social networks may be associated with the amount of distress experienced. Many caregivers have unmet needs such as respite care and information provision on TBI. Providing information may help to alleviate strain. Community-based family therapies providing education, support and counselling can help to decrease distress and improve aspects of family functioning, although evidence for these is lacking. Conclusions There is a need for more well-designed, controlled studies evaluating the impact of interventions to alleviate caregiver strain

Ethics and biobanks

Biobank research has been the focus of great interest of scholars and regulatory bodies who have addressed different ethical issues. On the basis of a review of the literature it may be concluded that, regarding some major themes in this discussion, a consensus seems to emerge on the international scene after the regular exchange of arguments in scientific journals. Broad or general consent is emerging as the generally preferred solution for biobank studies and straightforward instructions for coding will optimise privacy while facilitating research that may result in new methods for the prevention of disease and for medical treatment. The difficult question regarding the return of information to research subjects is the focus of the current research, but a helpful analysis of some of the issues at stake and concrete recommendations have recently been suggested

Cardiovascular responses to cognitive stress in patients with migraine and tension-type headache

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to investigate the temporal relationship between autonomic changes and pain activation in migraine and tension-type headache induced by stress in a model relevant for everyday office-work.</p> <p>Methods</p> <p>We measured pain, blood pressure (BP), heart rate (HR) and skin blood flow (BF) during and after controlled low-grade cognitive stress in 22 migraineurs during headache-free periods, 18 patients with tension-type headache (TTH) and 44 healthy controls. The stress lasted for one hour and was followed by 30 minutes of relaxation.</p> <p>Results</p> <p>Cardiovascular responses to cognitive stress in migraine did not differ from those in control subjects. In TTH patients HR was maintained during stress, whereas it decreased for migraineurs and controls. A trend towards a delayed systolic BP response during stress was also observed in TTH. Finger BF recovery was delayed after stress and stress-induced pain was associated with less vasoconstriction in TTH during recovery.</p> <p>Conclusion</p> <p>It is hypothesized that TTH patients have different stress adaptive mechanisms than controls and migraineurs, involving delayed cardiovascular adaptation and reduced pain control system inhibition.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT