Augusta Déjerine-Klumpke: the first female neuroanatomist

Augusta Déjerine-Klumpke, the wife of Joseph Jules Dejerine, an eminent French neurologist, was an American and the first woman to intern in a Parisian hospital. She is known for Klumpke's radicular palsy, which is a neuropathy involving the lower nerve roots of the brachial plexus. The neuroanatomical treatise that she wrote together with her husband is considered a masterpiece. Klumpke won several awards in medical science, the first of which was in the field of anatomy when she was a student. She was a pioneer of rehabilitation therapy after spinal cord injuries and contributed much to our current knowledge of spinal cord diseases. We review the current English and French literature regarding this neuroanatomist who was the first woman to directly contribute to the writing of a neuroanatomy textbook.     

Can the sex of the second child be predicted by the birth-weight of the first child?

The reproduction costs to a human mother are different if she has a son as opposed to a daughter. According to the Trivers-Willard hypothesis, evolution should promote those females who, having the ability to invest in the more expensive sex, are also able to adjust the sex of their offspring accordingly. It is therefore possible that a mother's biological condition (which is also connected with her reproductive potential), as measured by the neonatal weight of her first child, can be a good predictor of the second child's sex. From data for 227 healthy mothers from Wroclaw (Poland) we show that the probability of giving birth to a boy in the second pregnancy is higher after a relatively heavier first-born child (ANOVA, F(1,225)=3.79, P<0.053). This relationship, however, is only significant after a first-born daughter (F(1,117)=9.66, P<0.002) and not after a first-born boy. Some possible explanations of the fact that only the birth-weight of a first-born daughter--and not a son--can be a good predictor of the secondary sex ratio are also discussed.     

What came first: PKCtheta or the immune synapse?

Stimulation of T cells by peptide-presenting antigen-presenting cells (APCs) induces formation of a highly organized complex of receptors, signaling molecules and cytoskeleton components at the immune synapse (IS), the contact site between T cells and APCs. Conjugate formation between T cells and APCs initiates the formation of the IS. After this event, micrometer-scale molecular movements occur in the T cell plasma membrane and the actin cytoskeleton undergoes reorganization. Our current knowledge suggests that formation of the IS is an essential step during T cell activation. This is probably related to the proper localization of certain proteins in specific compartments. One of these proteins is protein kinase Ctheta (PKCtheta), which is absolutely required for T cell activation. During the last years we have made great advances in understanding the function and targets of this kinase, and recent reviews have summarized these findings. In contrast, we do not know the exact mechanism that activates PKCtheta after TCR engagement and the role of PKCtheta activation in the formation of the IS. In this review I analyze the mechanism of the translocation of PKCtheta and discuss the function of PKCtheta in the formation of the IS and, vice versa, the role of the IS in the translocation of PKCtheta.     

Which came first,the lectin/classical pathway or the alternative pathway of complement?

It is a widely accepted canon of immunology that the alternative pathway is more primitive and hence older in evolutionary terms than the lectin/classical pathway. This idea has been reinforced by the discovery of “C3” and “factor B” proteins in invertebrate species. However, it is clear that the gene duplications which gave rise to C3/C4/C5 and factor B/C2 occurred in the vertebrate lineage. Hence, the naming of the invertebrate proteins may be based on preconceptions rather than on solid structural or functional evidence. Lectins and associated MASP/C1r/C1s-like proteins have been found in invertebrates, while factor D, the defining component of an alternative pathway, has so far been found only in the bony fish and higher species. It is a principle of Darwinian evolution that complex systems develop through small sequential steps. It is possible to imagine such a series of steps for the evolution of a lectin pathway, involving as it does recognition of non-self. It is difficult to see how the alternative pathway, which lacks a recognition molecule, could have evolved without the prior development of control proteins to protect self from attack.     

Did the first virus self-assemble from self-replicating prion proteins and RNA?

DNA is the molecule responsible for storing and processing genetic information today. In Earth's primeval environmental conditions, RNA was probably more suited for this function, due to its capability to act also as a catalytic enzyme. Some proteins are stable and reliable molecules even in extreme conditions, and under certain circumstances, proteins may play a role in transmitting certain phenotypes that are inherited in a non-Mendelian manner. When the dominant native state of a prion protein is replaced by a misfolded one, the resultant infective protein is associated with several neurological diseases in mammals. The misfolded proteins are remarkably resistant to even the most extreme environments. Prions are also associated with the transmission of certain fungal traits epigenetically, supporting the hypothesis that prions are a possible relic of an early stage of peptide evolution. The primitive world probably contained both self-replicating RNA molecules and prions, and prions attach easily to nucleic acids, and also fold and cause other proteins to fold in the same way. Consequently, a capsid could form from prion protein, enclosing the RNA, and perhaps creating the first RNA virus. A capsid originating from prion proteins would be a versatile and effective protection to RNA and could also explain some characteristics of virus self-assembly that are not well understood.     

How does subchorionic hematoma in the first trimester affect pregnancy outcomes?

IntroductionSubchorionic hematoma (SCH) in pregnancy has been associated with increased risk of adverse pregnancy outcomes. We aimed to investigate the association of SCH with adverse pregnancy outcomes in pregnant women in relation to size of hematoma and control subjects.Material and methodsThis study included 178 pregnant women with sono-graphically detected SCH in the 1^st trimester, and 350 pregnant controls without SCH. Data on maternal age, smoking status, gestational week at diagnosis, location of SCH, medications before diagnosis, gestational week at delivery, delivery route and pregnancy outcomes (first trimester vaginal bleeding, pre-eclampsia, gestational diabetes, intrauterine growth restriction (IUGR), placental abruption, preterm delivery < 37 weeks, early pregnancy loss and intrauterine death) were retrieved retrospectively from hospital records. Pregnant women with SCH were divided into 3 groups according to the size of hematoma including small SCH (SCH-I group, n = 47), medium-size SCH (SCH-II group, n = 110) and large SCH (SCH-III group, n = 21) groups.ResultsSubchorionic hematoma was associated with significantly lower gestational age at delivery (p < 0.001) and higher rate of first trimester bleeding (p < 0.001) compared with the control group, regardless of the size of the hematoma. Placental abruption (p = 0.002) and early pregnancy loss (p < 0.001) were significantly more common in SCH-II and -III groups than in the control group. SCH-III group was associated with a significantly higher rate of < 37 gestational weeks at delivery (p < 0.001), first trimester vaginal bleeding (p < 0.001), early pregnancy loss (p < 0.001), IUGR (p = 0.003) and preterm delivery (p < 0.001) compared to both lesser size hematoma and control groups.ConclusionsOur findings suggest that large SCH might indicate an increased risk of adverse pregnancy outcomes such as 1^st trimester vaginal bleeding, early pregnancy loss, IUGR, placental abruption or preterm delivery. These findings are important to guide the patients with SCH for detailed clinical evaluation.     

Mitochondrial dysfunction: the first domino in brain aging and Alzheimer's disease?

With the increasing average life span of humans and with decreasing cognitive function in elderly individuals, age-related cognitive disorders including dementia have become a major health problem in society. Aging-related mitochondrial dysfunction underlies many common neurodegenerative disorders diseases, including Alzheimer's disease (AD). AD is characterized by two major histopathological hallmarks, initially intracellular and with the progression of the disease extracellular accumulation of oligomeric and fibrillar beta-amyloid (Abeta) peptides and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein. In this review, the authors focus on the latest findings in AD animal models indicating that these histopathological alterations induce deficits in the function of the complexes of the respiratory chain and therefore consecutively result in mitochondrial dysfunction. This parameter is intrinsically tied to oxidative stress. Both are early events in aging and especially in the pathogenesis of aging-related severe neurodegeneration. Ginkgo biloba extract seems to be of therapeutic benefit in the treatment of mild to moderate dementia of different etiology, although the data are quite heterogeneous. Herein, the authors suggest that mitochondrial protection and subsequent reduction of oxidative stress are important components of the neuroprotective activity of Ginkgo biloba extract.     

Marginal zone lymphoma of the lacrimal gland spreading to the lung and the bone marrow 11 years after first symptoms

We report on the case of a 52-year-old male presenting with an extranodal marginal zone lymphoma of the mucosa-associated tissue (MALT lymphoma) in the lung 11 years after radiotherapy for a MALT lymphoma of the lacrimal gland, which was primarily diagnosed as dacryoadenitis. Both tumors were investigated by immunohistochemistry and molecular techniques demonstrating their clonal genetic relationship. Both harbored the t(14;18)(q32;q21) and a trisomy 3 and showed identical immunoglobulin heavy-chain gene rearrangements. At the time of pulmonary relapse, clonal CD20- and CD43-positive bone marrow B lymphocytes were detected as well. The elaboration of this case emphasizes the importance of the combined use of modern diagnostic methods for establishment of correct diagnosis of MALT lymphomas at late relapses, which is essential for proper patient management.     

Regulatory sequences clustered at the 5′ end of the first intron of the human thymidylate synthase gene function in cooperation with the promoter region

A human thymidylate synthase (TS) minigene containing 5- and 3-flanking sequences, all the exons, and only intron 1 showed a normal frequency of stable transformation when transfected into TS-negative mutant cells, whereas minigenes in which intron 1 was replaced by intron 2 or deleted in the above construct showed only a few percent of the above frequency. Introduction of intron 1 into the above intronless or intron 2 minigene restored the transforming activities regardless of its position and orientation. Deletion analysis revealed two positive and one negative regulatory sequences in the 5 end of intron 1, each of which seemed to bind specific proteins as shown by gel shift analysis. Intron 1 also stimulated expression of a TS promoter-CAT gene construct but not that of an SV40 promoter-CAT gene construct. These results indicate that the multiple regulatory sequences clustered in intron 1 stimulate TS gene expression in concert with the 5-flanking sequences.     

Modulating the co-stimulatory signal for T cell activation in rheumatoid arthritis: Could it be the first step of the treatment?

Advances in our understanding of the key mediators of chronic inflammation and tissue damage in rheumatoid arthritis (RA) have fostered the development of targeted therapies and greatly expanded the available treatment options. Abatacept, a soluble human fusion protein that selectively modulates the co-stimulatory signal required for full T-cell activation, is approved for the treatment of moderate to severe RA in the United States, Canada, and the European Union. This review summarises the data on efficacy (disease activity, quality of life, prevention of structural damage) and safety from randomised clinical trials of abatacept plus methotrexate in patients with: i) active RA and an inadequate response to methotrexate who are naïve to biological disease-modifying anti-rheumatic drugs; and ii) methotrexate-naïve early RA with poor prognostic factors. Novel imaging outcomes and biological changes induced by abatacept treatment are also briefly reviewed. Optimal use of abatacept as a first-line biological therapy is discussed in light of the current recommendations and guidelines.     

Laterality of the sleep onset process: Which hemisphere goes to sleep first?

This study aims to assess whether the hemispheric asymmetry inversion observed in the wake-sleep transition can also be revealed by the latency of inter tapping intervals >or= 2.5s for each hand and the latency of theta burst >or= 2.5s in symmetrical loci of the two hemispheres during the sleep onset process. Data collected from 16 right-handed subjects showed a hemispheric asymmetry in the sleep onset latency with both behavioural and EEG indices. For the first time, a hemispheric asymmetry in the sleep onset latency was found considering a visual analysis of EEG. Results suggest that the hemispheric pattern found during sleep onset can be considered a steady characteristic of the transition from wake to sleep, relatively independent of homeostatic and time of night effects. These results are interpreted as being consistent with the hypothesis concerning an advantage of the right hemisphere in sustaining vigilance.