Miracle-dz/UniFAR-FTUs huggingface dataset:
Chloroplast SRP54 Was Recruited for Posttranslational Protein Transport via Complex Formation with Chloroplast SRP43 during Land Plant Evolution*

Background: In chloroplasts of higher plants, a heterodimeric cpSRP43·cpSRP54 complex targets LHC proteins to the thylakoid membrane. Results: In green algae, cpSRP43 alone forms a targeting complex with LHC proteins. Conclusion: The coevolution of LHC proteins and cpSRP43 occurred independently of complex formation with cpSRP54. Significance: The results provide new insights into the evolution of cpSRP-dependent protein transport. In bacteria, membrane proteins are targeted cotranslationally via a signal recognition particle (SRP). During the evolution of higher plant chloroplasts from cyanobacteria, the SRP pathway underwent striking adaptations that enable the posttranslational transport of the abundant light-harvesting chlorophyll-a/b-binding proteins (LHCPs). The conserved 54-kDa SRP subunit in higher plant chloroplasts (cpSRP54) is not bound to an SRP RNA, an essential SRP component in bacteria, but forms a stable heterodimer with the chloroplast-specific cpSRP43. This heterodimeric cpSRP recognizes LHCP and delivers it to the thylakoid membrane whereby cpSRP43 plays a central role. This study shows that the cpSRP system in the green alga Chlamydomonas reinhardtii differs significantly from that of higher plants as cpSRP43 is not complexed to cpSRP54 in Chlamydomonas and cpSRP54 is not involved in LHCP recognition. This divergence is attributed to altered residues within the cpSRP54 tail and the second chromodomain of cpSRP43 that are crucial for the formation of the binding interface in Arabidopsis. These changes are highly conserved among chlorophytes, whereas all land plants contain cpSRP proteins with typical interaction motifs. These data demonstrate that the coevolution of LHCPs and cpSRP43 occurred independently of complex formation with cpSRP54 and that the interaction between cpSRP54 and cpSRP43 evolved later during the transition from chlorophytes to land plants. Furthermore, our data show that in higher plants a heterodimeric form of cpSRP is required for the formation of a low molecular weight transit complex with LHCP.
The cerebellar nodulus: Perceptual and ocular processing of graviceptive input

Current concepts postulate a decisive role of the cerebellar nodulus in the processing of otolith input. We hypothesized that nodular lesions abolish otolith‐perceptual integration, predicting alignment of perceived direction of earth vertical with the z‐axis of the head and not with gravity. In an 80‐year‐old patient with acute heminodular infarction, the subjective visual vertical deviated contralesionally by −21.1° when the patient was upright. After subtracting this offset, perceived vertical closely matched the patient's head orientation when the patient was roll‐tilted. Otolith‐ocular reflexes remained normal. This is the first report on abolished earth verticality perception in heminodular stroke and underlines the importance of the nodulus in spatial orientation. Ann Neurol 2015;77:343–347
Identification of the Pharmacophore of the CC Chemokine-binding Proteins Evasin-1 and -4 Using Phage Display*

Background: The selectivity profiles of the closely related chemokine-binding proteins Evasin-1 and -4 differ. Results: Using phage display, we identified the N-terminal region of Evasin-4 as key for the interaction with CC chemokines. Conclusion: Evasin-1 and -4 use different domains for target binding. Significance: Phage display allowed rapid insight into their different selectivities, which could aid rational design of inhibitory proteins. To elucidate the ligand-binding surface of the CC chemokine-binding proteins Evasin-1 and Evasin-4, produced by the tick Rhipicephalus sanguineus, we sought to identify the key determinants responsible for their different chemokine selectivities by expressing Evasin mutants using phage display. We first designed alanine mutants based on the Evasin-1·CCL3 complex structure and an in silico model of Evasin-4 bound to CCL3. The mutants were displayed on M13 phage particles, and binding to chemokine was assessed by ELISA. Selected variants were then produced as purified proteins and characterized by surface plasmon resonance analysis and inhibition of chemotaxis. The method was validated by confirming the importance of Phe-14 and Trp-89 to the inhibitory properties of Evasin-1 and led to the identification of a third crucial residue, Asn-88. Two amino acids, Glu-16 and Tyr-19, were identified as key residues for binding and inhibition of Evasin-4. In a parallel approach, we identified one clone (Y28Q/N60D) that showed a clear reduction in binding to CCL3, CCL5, and CCL8. It therefore appears that Evasin-1 and -4 use different pharmacophores to bind CC chemokines, with the principal binding occurring through the C terminus of Evasin-1, but through the N-terminal region of Evasin-4. However, both proteins appear to target chemokine N termini, presumably because these domains are key to receptor signaling. The results also suggest that phage display may offer a useful approach for rapid investigation of the pharmacophores of small inhibitory binding proteins.
Tissue-type Plasminogen Activator (tPA) Promotes M1 Macrophage Survival through p90 Ribosomal S6 Kinase (RSK) and p38 Mitogen-activated Protein Kinase (MAPK) Pathway*

Background: Macrophages become resistant to apoptosis in response to pathogenic cues. Results: Tissue-type plasminogen activator (tPA) protects the classically activated macrophages from apoptosis. Conclusion: tPA is an endogenous factor that promotes macrophage survival. Significance: tPA modulates inflammation by promoting the survival of polarized macrophages through a new signaling cascade. Macrophage accumulation is one of the hallmarks of progressive kidney disease. Resting macrophages have a finite lifespan, but become resistant to apoptosis in response to pathogenic cues, whereas the underlying mechanism remains unknown. Tissue-type plasminogen activator (tPA), a protease up-regulated in the kidneys with chronic injury, has been shown to promote macrophage accumulation and renal inflammation. We hypothesized that tPA may be the endogenous factor that promotes macrophage survival and extends their lifespan that leads to their accumulation in the injured kidneys. We examined the role of tPA in macrophage survival, and found that tPA protected macrophages from both staurosporine and H2O2-induced apoptosis. tPA promoted the survival of both resting and lipopolysaccharide- or interferon-γ-induced M1 macrophages, but failed to do so in the interleukin 4 (IL4)-induced M2 macrophages. In the kidneys with unilateral ureteral obstruction, there were significantly more apoptotic M1 macrophages in tPA-deficient mice than their wild-type counterparts, and obstruction-induced M1 macrophages accumulation and M1 chemokine expression were markedly reduced in these knock-out mice. The cytoprotective effect of tPA required its receptor, LDL receptor-related protein-1 (LRP-1). tPA induced the phosphorylation of Erk1/2, p90 ribosomal S6 kinase (RSK), and p38 in a temporal order. The tPA-mediated macrophage survival was eliminated by PD98059, BI-D1870, or sc68376, the specific inhibitors for Erk1/2, p90RSK, or p38, respectively. Thus, it is clear that tPA promoted M1 macrophage survival through its receptor LRP-1-mediated novel signaling cascade involving Erk1/2, p90RSK, and p38, which leads to the accumulation of these cells in the injured kidneys.
Brain–computer interface boosts motor imagery practice during stroke recovery

Motor imagery (MI) is assumed to enhance poststroke motor recovery, yet its benefits are debatable. Brain–computer interfaces (BCIs) can provide instantaneous and quantitative measure of cerebral functions modulated by MI. The efficacy of BCI‐monitored MI practice as add‐on intervention to usual rehabilitation care was evaluated in a randomized controlled pilot study in subacute stroke patients.
Huntington’s Disease Does Not Appear to Increase the Risk of Diabetes Mellitus

Huntington’s disease (HD) is an autosomal, dominantly inherited, neurodegenerative disorder characterised by neurological, cognitive and psychiatric symptoms. HD has been associated with diabetes mellitus, which is, to some extent, supported by studies in transgenic HD mice. In transgenic mice, the severity of the diabetic phenotype appears to correlate with the length of a polyglutamine expansion in the protein huntingtin. In the present study, we investigated the association between diabetes mellitus and HD by performing an oral glucose‐tolerance test (OGTT) to evaluate the glucose‐tolerance status and OGTT‐related insulin release in 14 HD patients. Furthermore, we expressed N‐terminal huntingtin fragments with different polyglutamine lengths in an insulinoma‐cell line (INS‐1E) to investigate how mutant huntingtin influences glucose‐stimulated insulin release in vitro. We found no difference between a group of early‐ and middle‐stage HD patients and a large group of control individuals in any of the assessed variables. However, the glucose‐stimulated induction of insulin release was significantly reduced in the insulinoma‐cell line expressing highly expanded huntingtin compared to cells expressing huntingtin with modestly elongated polyglutamine stretches. These data indicate that insulin release from β‐cells expressing mutant huntingtin appears to be polyglutamine length‐dependent, and that polyglutamine lengths within the range normally found in adult onset HD do not influence insulin release. This challenges the assumption of an increased risk of diabetes among HD patients, although our results do not exclude a changed glucose tolerance in end‐stage HD patients or in patients with juvenile onset HD. It also raises the question of which extent transgenic mice models reflect the pathology of human HD in this regard.
Maternal And child health nursing

A guide to maternal and child health nursing. This third edition maintains its strong family focus, emphasizing wellness and illness as family-centred events. Using a nursing process framework, the text presents information for both disciplines. Recurring features that are designed to enhance student learning and promote critical thinking include: "Assessing the Client" boxes; "National Health Goal" boxes; nursing research; two-column nursing procedures; and "Cultural Competence" boxes. Each chapter contains objectives, key terms, key points and critical thinking questions. New to this edition are: dull-colour design and artwork throughout; pain management information; unlicensed assistive personnel management and delegation; and empowering the client and the family. It also contains "Drug Highlight" boxes, "Enhancing Communication" boxes, checkpoint questions, clinical vignettes, "What If? " questions, and two new chapters - "Pain Management in Children" and "Home Care of the Pregnant Client". A free self-study disk tests students' comprehension and focuses study.
Sex Differences in the Expression of Sex Steroid Receptor mRNA in the Quail Brain

In Japanese quail, males will readily exhibit the full sequence of male‐typical sexual behaviors but females never show this response, even after ovariectomy and treatment with male‐typical concentrations of exogenous testosterone. Testosterone aromatisation plays a key‐limiting role in the activation of this behavior but the higher aromatase activity in the brain of males compared to females is not sufficient to explain the behavioural sex difference. The cellular and molecular bases of this prominent sex difference in the functional consequences of testosterone have not been identified so far. We hypothesised that the differential expression of sex steroid receptors in specific brain areas could mediate this behavioural sex difference. Therefore, using radioactive in situ hybridisation histochemistry, we quantified the expression of the mRNA coding for the androgen receptor (AR) and the oestrogen receptors (ER) of the α and β subtypes. All three receptors were expressed in an anatomically discrete manner in various nuclei of the hypothalamus and limbic system and, at usually lower densities, in a few other brain areas. In both sexes, the intensity of the hybridisation signal for all steroid receptors was highest in the medial preoptic nucleus (POM), a major site of testosterone action that is related to the activation of male sexual behaviour. Although no sex difference in the optical density of the AR hybridisation signal could be found in POM, the area covered by AR mRNA was significantly larger in males than in females, indicating a higher overall degree of AR expression in this region in males. By contrast, females tended to have significantly higher levels of AR expression than males in the lateral septum. ERα was more densely expressed in females than males throughout the medial preoptic and hypothalamic areas (including the POM and the medio‐basal hypothalamus), an area implicated in the control of female receptivity) and in the mesencephalic nucleus intercollicularis. ERβ was more densely expressed in the medio‐basal hypothalamus of females but a difference in the reverse direction (males > females) was observed in the nucleus taeniae of the amygdala. These data suggest that a differential expression of steroid receptors in specific brain areas could mediate at least certain aspects of the sex differences in behavioural responses to testosterone, although they do not appear to be sufficient to explain the complete lack of activation by testosterone of male‐typical copulatory behaviour in females.
Value of Rapid Nitrite Screening Test with or without Leukocyte Esterase Test in Detection of Asymptomatic Bacteriuria in Thai Pregnant Women

OBJECTIVE: To determinethe sensitivity, specificity, positive predictive value, and negative predictive value of the rapid dipstick test for detection of asymptomatic bacteriuria (ASB) in pregnancy, and to investigate contributing factors that could relate to having ASB in obstetric patients. STUDY DESIGN: Diagnostic test study MATERIALS AND METHODS: Clean-catch midstream urine samples were collected from 414 pregnant women for bacterial culture and rapid screening tests : the nitrite and leukocyte esterase(LE) dipsticks. RESULTS: Thisstudy showed the sensitivity of the nitrite test being 29%, the LE test being 47%. Wheneither the nitrite or LE test being positive, the sensitivity increased tobe64%. Both the nitrite and LE test had high specificity of 99.2% and 92.4%, respectively, and high negative predictive value of 97.0% and 97.6%, respectively. We did not find any significant differences in contributing factors between patients that had a positive urine culture and those that had a negative urine culture. CONCLUSION: A combination of nitrite and LE testing improved sensitivity for the detection of asymptomatic bacteriuria (ASB), but may not be suitable for screening of ASB. However, the combination of nitrite and LE testing would be useful in monitoring patients after antibiotic treatment for ASB due to the high specificity and high negative predictive value of the combined tests.
Somatostatin Actions on Rat Supraoptic Nucleus Oxytocin and Vasopressin Neurones

Magnocellular neurones in the supraoptic nucleus (SON) receive major afferent inputs from the brainstem that have been implicated in the regulation of oxytocin and vasopressin secretion from the posterior pituitary. Notably, at parturition, some neurones that project from the nucleus tractus solitarii (NTS) in the brainstem directly to the SON are activated. Many of these are noradrenergic and regulate oxytocin secretion during parturition, whereas others contain somatostatin and their role is unclear. In the present study, we report that, at parturition, somatostatin mRNA expression in the NTS is significantly increased compared to pregnancy, suggesting an active role for these neurones at that time. Intracerebroventricular somatostatin infusion significantly increased plasma oxytocin secretion in both virgin female and pregnant rats. Intracerebroventricular somatostatin increased SON oxytocin and vasopressin neurone firing‐rates, and increased Fos expression in the SON and paraventricular nucleus and in the subfornical organ. Retrodialysis of somatostatin onto the ventrally exposed SON also increased vasopressin neurone firing rate but, unexpectedly, decreased oxytocin neurone firing rate. The experiments indicate that somatostatin neurones in the NTS are activated during parturition but, because the direct effects of somatostatin on oxytocin neurones are inhibitory, this direct pathway does not appear to contribute to enhanced oxytocin release at this time, although indirect somatostatin effects may do so.
The neuronal component of gray matter damage in multiple sclerosis: A [11C]flumazenil positron emission tomography study

Using positron emission tomography (PET) with [11C]flumazenil ([11C]FMZ), an antagonist of the central benzodiazepine site located within the GABAA receptor, we quantified and mapped neuronal damage in the gray matter (GM) of patients with multiple sclerosis (MS) at distinct disease stages. We investigated the relationship between neuronal damage and white matter (WM) lesions and evaluated the clinical relevance of this neuronal PET metric.
An Australian Story: Paramedic Education and Practice in Transition

In Australia, western medicine and the majority of allied healthcare professions are regulated via statutory regulation. For most of these allied healthcare professions, education has moved into the higher education (HE) sector and universities. The profession of paramedics is undergoing a transition in terms of scope of practice, and in particular education, moving from a post-employment model characterised by on-the-job training, to a pre-employment model, essentially full time university-based Bachelor degree education, similar to the change that occurred in nursing in Australia many years ago. How to produce work-ready graduates in the healthcare professions is of concern for educators and professional associations. Research into work-readiness in several healthcare fields has yielded important information that may be utilised by paramedic and other allied healthcare educators to improve courses. This paper discusses issues of transition of HE healthcare graduates into the workforce that need to be considered by educators, with a particular focus on the profession of paramedics in Australia. It also summarises key findings of research into work-readiness in a range of healthcare professions.
Developmental and Steroidogenic Effects on the Gene Expression of RFamide Related Peptides and their Receptor in the Rat Brain and Pituitary Gland

RFamide related peptides (RFRPs) have been extensively implicated in the neuroendocrine control of reproduction. While steroid hormones strongly regulate the closely‐related kisspeptin gene and protein expression, the regulation of RFRPs or their receptor by steroid hormones is almost unknown. The present study aimed to quantify relative levels of RFRP and Kiss1 gene expression and their G protein‐coupled receptors (GPR147 and GPR54, respectively) in various brain areas and the pituitary gland, and to determine the effects of differing levels of oestradiol and pubertal development on levels of these gene products. In Experiment 1 , the treatment groups examined were: dioestrus, ovariectomised and ovariectomised with replacement oestradiol to induce a preovulatory‐like luteinising hormone surge. Micropunched brain regions and whole pituitary glands were processed for measurement of RFRP, Kiss1, GPR147 and GPR54 mRNA by quantitative reverse transcriptase‐polymerase chain reaction. As expected, Kiss1 gene expression was low in the rostral periventricular area of the third ventricle of ovariectomised animals, whereas levels were highest in the arcuate nucleus in this situation. No such oestrogenic effects were observed for RFRP gene expression. GPR147 gene expression was highest in the rostral periventricular region of the third ventricle. The levels of GPR147 and GPR54 mRNA were markedly lower in the pituitary gland than in the hypothalamic regions, and RFRP and Kiss1 mRNA were virtually undetectable in the pituitary gland. These data imply that the actions of RFamides are likely to be predominantly central in nature. In Experiment 2 , hypothalamic RFRP and GPR147 mRNA levels were measured in male and female rats aged 2, 4, 6 and 8 weeks. In females, RFRP gene expression increased with developmental age, peaking around the time of puberty, whereas in males gene expression increased between 2 and 4 weeks of age. These results suggest a role in the regulation of adult reproduction rather that prepubertal infertility.
Serum and Cerebrospinal Fluid Prolactin levels in Male and Female Patients with Clinically‐Isolated Syndrome or Relapsing‐Remitting Multiple Sclerosis

There is considerable evidence that prolactin (PRL) exerts immunomodulatory actions, thus being involved in the processes of autoimmune diseases. Animal studies suggest that elevated serum PRL levels may be related to neuroprotection or participate in remyelination after brain injury. To address this question, we estimated PRL levels in both serum and cerebrospinal fluid (CSF) in drug‐free male and female patients with clinically‐isolated syndrome (CIS) suggestive of MS (i.e. after the first episode) as well as in patients with relapsing‐remitting (RR) MS after two or more relapses, and related them to clinical, paraclinical and laboratory data. Seventy two patients with RR MS and 80 patients with CIS in the age range 17–61 years were studied. PRL levels of patients were compared with 74 control subjects, separately for males and females. Significantly higher PRL levels in serum and CSF were found in female RRMS patients but not in males. Patients with CIS had normal PRL levels. No associations were found with disease activity, duration of illness, presence of active lesions or the presence of oligoclonal bands in CSF. The elevated PRL levels observed in female but not in male RRMS patients, or in patients with CIS, could be suggestive of a sexually dimorphic response to central nervous system injury as a result of an increased proneness of females to synthesise and release PRL, which is possibly linked to the relatively more favourable prognosis of MS in women.
A 44‐year‐old man with eye, kidney, and brain dysfunction

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, autosomal dominant condition caused by mutations of TREX1 (3‐prime repair exonuclease‐1). The phenotypic expressions range from isolated retinal involvement to varying degrees of retinopathy, cerebral infarction with calcium depositions, nephropathy, and hepatopathy. We report a case of RVCL caused by a novel TREX1 mutation. This patient's multisystem presentation, retinal involvement interpreted as “retinal vasculitis,” and improvement of neuroimaging abnormalities with dexamethasone led to the accepted diagnosis of a rheumatologic disorder resembling Behçet disease. Clinicians should consider RVCL in any patient with retinal capillary obliterations associated with tumefactive brain lesions or nephropathy. Ann Neurol 2016;79:507–519