From the editor’s desk

Improving cotton fibre quality is a major breeding goal for Upland cotton in China. To investigate the genetic mechanisms of fibre quality, a diverse panel of 403 Upland cotton accessions was grown, and the fibre quality traits were measured in six different environments. Genotyping was performed with genomewide simple sequence repeats. A total of 201 markers were polymorphic and generated 394 allele loci, and 403 accessions were arranged into two subgroups using Structure software. Of the marker loci, 18.94% showed significant linkage disequilibrium (\(P< 0.05\)). A mixed linear model in association mapping showed that 51 associations were significant between 39 polymorphic loci and five fibre quality traits, according to best linear unbiased prediction, and in at least three of six environments. Of the 39 associated marker loci, 12 were coincident with previous studies. There were 41 typical accessions identified as containing favourable allele loci related to fibre quality traits. The identified favourable QTL alleles and typical accessions for fibre quality are excellent genetic resources for future cotton breeding in China.     

Molecular pharming’s foot in the FDA’s door: Protalix’s trailblazing story

Objectives

This short commentary examines the factors that led to Food and Drug Administration’s approval of the first plant-derived biologic.

Results

In 2012, the first plant-derived protein pharmaceutical (biologic) was approved for commercial use in humans. The product, a recombinant form of human β-glucocerebrosidase marketed as ELELYSO, was developed by Protalix Biotherapeutics (Carmiel, Israel). The foresight to select this particular therapeutic product for development, flawless production pipeline, and serendipity seem to provide the key in explaining how ELELYSO became the first plant-derived biologic to achieve approval by Food and Drug Administration.

Conclusions

While the circumstances that enabled Protalix and its scientists to become the first to arrive at this historic milestone are perhaps unique, it is anticipated that more biologics will follow suit in winning regulatory endorsement.

     

Predicting the Outcome of Sjogren’s Syndrome-Associated Non-Hodgkin’s Lymphoma Patients

BackgroundNon-Hodgkin''s lymphoma (NHL) development in Sjögren’s syndrome (SS) remains a potentially lethal complication and efforts should focus on the identification of predictors that could aid in appropriate therapeutic decisions.MethodsIn order to identify potential prognostic factors for outcome in SS-associated NHL, we retrospectively analyzed a cohort of 77 patients, diagnosed with NHL according to WHO classification criteria and meeting the American-European Consensus Classification (AECC) criteria for SS and examined the effect of SS-activity (defined as the EULAR SS disease activity index-ESSDAI) in the prognosis of SS-related NHLs, as defined in terms of overall and event-free survivals (OS and EFS). An event was defined as lymphoma relapse, treatment failure, disease progression, histological transformation or death. The effect of NHL clinical and laboratory characteristics was also investigated.ResultsMALT lymphomas constituted the majority (66.2%) of lymphomas. During the follow-up (median = 57.93 months), the 5-year OS was 90.91% (95% CI: 82.14–95.80%) and the EFS was 77.92% (95% CI: 67.37–85.82%). Patients with high ESSDAI score at lymphoma diagnosis had a greater risk for death (OR = 5.241, 95% CI: 1.034–26.568) or for event (OR = 4.317, 95% CI: 1.146–9.699, p = 0.008). These patients had also significantly worse EFS (HR = 4.541, 95% CI: 1.772–11.637) and OS (HR = 5.946, 95% CI: 1.259–28.077). In addition, post-chemotherapy ESSDAI improvement was significantly lower in patients who had experienced an event (p = 0.005). An unfavorable International prognostic index (IPI) score (high-intermediate/high) was associated with high risk of death and event (OR = 13.867, 95% CI: 2.656–72.387 and OR = 12.589, 95% CI: 3.911–40.526, respectively), worse EFS (log-rank p<0.001, HR = 8.718, 95% CI: 3.477–21.858), as well as with worse OS (log-rank p<0.001, HR = 11.414, 95% CI: 2.414–53.974). After adjustment for identified risk factors, IPI score retained a significant prognostic role following by a strong effect of ESSDAI in survival outcomes.ConclusionsAt the point of NHL diagnosis, IPI and ESSDAI might be proved useful predictive tools in SS-associated lymphoma prognosis, directing to a more patient-tailored approach.     

Hodgkin’s disease in the spleen

Spleens with proven though small Hodgkin lesions were examined expecially in relation to the lymphoid tissue normally engaged in the immune response. These Hodgkin foci were always very close to small arteries and surrounded by a lymphocyte corona. Most of the red and white pulp seemed normal, but in some instances abnormal looking large and also multinucleated cells were found scattered through the p.a.l.s. and especially through some follicles. It is considered possible that these isolated cellular abnormalities in the white pulp, when associated with pre-existent Hodgkin foci, represent early Hodgkin lesions. The implications for the dissemination of the disease are discussed. Spread of malignant cells to the spleen is only acceptable within the concept of a homing principle. It is also possible that the lesions arise "de novo". The nature of the observed abnormal cells is not clear. An explanation for the origin of these Sternberg-Reed-like cells from B-lymphocytes would be in accordance with recent data, but another possibility still is that they originate from antigen trapping cells.     

Mirror mirror on the ward,who’s the most narcissistic of them all? Pathologic personality traits in health care

Background:

Stereotypes in medicine have become exaggerated for the purpose of workplace amusement. Our objective was to assess the levels of “dark triad” personality traits expressed by individuals working in different health care specialties in comparison with the general population.

Methods:

We conducted a prospective, cross-sectional study within multiple departments of a UK secondary care teaching hospital. A total of 248 health care professionals participated, and 159 members of the general population were recruited as a comparison group. We measured 3 personality traits — narcissism, Machiavellianism and psychopathy — through the validated self-reported personality questionnaires Narcissistic Personality Inventory (NPI), MACH-IV and the Levenson Self-Report Psychopathy Scale (LSRP), respectively.

Results:

Health care professionals scored significantly lower on narcissism, Machiavellianism and psychopathy (mean scores 12.0, 53.0 and 44.7, respectively) than the general population (p < 0.001). Nursing professionals exhibited a significantly higher level of secondary psychopathy than medical professionals (p = 0.04, mean LSRP score 20.3). Within the cohort of medical professionals, surgeons expressed significantly higher levels of narcissism (p = 0.03, mean NPI score 15.0).

Interpretation:

Health care professionals expressed low levels of dark triad personality traits. The suggestion that health care professionals are avaricious and untrustworthy may be refuted, even for surgeons.I was quietly admiring my astonishing good looks in the mirror of the operating theatre changing room when one of my anesthesiologist colleagues brazenly interrupted me: “Typical surgeon — you love yourselves so much we’ll need to have the mirrors removed in here if we are to get any work done!” I was somewhat bemused by the 2 obvious inaccuracies in this comment: first, that all surgeons love themselves and, second, that theatre workflow is ever dependent on the work ethos of the surgical team! I immediately went on the counteroffensive by replying, “Don’t worry, sudoku writers are on strike this week so we should be finished before lunch!”These lighthearted, tongue-in-cheek exchanges between medical professionals occur around the world every day and are based on popular stereotypes that have become exaggerated for the purpose of workplace amusement. One might imagine neanderthalic orthopedic surgeons instinctively reaching for a bigger hammer as the singular solution to any problem, grumpy radiologists growling at anyone who dares disturb their dark sanctuary and dour internists glacially grinding their way through a ward round, which necessitates a packed lunch, comfortable walking shoes and a hospital map.Many stereotypes have filtered into the public domain, where emphasis on negative traits can be misleading for the general public. The callous notion that doctors are self-centred, avaricious and untrustworthy is currently being bandied around the media.^1,2 There is a real danger of these negative stereotypes eroding the high level of regard in which the profession is held. Perhaps the most undesirable personality characteristics are those that form the “dark triad”: a trio of Machiavellianism, narcissism and psychopathy.³Those expressing Machiavellian traits are deceptive, self-interested and succeed through the exploitation of others.^4–6 Narcissism is defined as a “normal” personality trait at low levels and is characterized by the expression of pride, egotism and vanity.^7,8 Psychopathy manifests as antisocial behaviour expressing callousness, remorselessness and selfishness, with little empathy and a high level of impulsivity.^9,10 It has been proposed that 2 variants of psychopathy exist: primary and secondary. Primary psychopathy is believed to be a genetic predisposition to certain behavioural patterns, which include cool, calm, meticulous forward planning and emotional dissociation. Secondary psychopathy, however, is an adaptation to environmental factors and involves impulsivity and emotional instability, which can place others at risk.¹¹It is hypothesized that some of these dark personality traits are present within the health care profession and, more specifically, within certain disciplines. It is not implausible for one to conceive that the self-assured surgeon could display evidence of vanity or that the irrational nurse might exhibit psychopathic tendencies. However, scientific evidence is lacking to support or quantify the existence of such personality traits in the health care profession.The aim of this study was to assess levels of dark triad personality traits among individuals working in health care in comparison with the general population.     

SH3 domain ligand binding: What’s the consensus and where’s the specificity?

An increasing number of SH3 domain-ligand interactions continue to be described that involve the conserved peptide-binding surface of SH3, but structurally deviate substantially from canonical docking of consensus motif-containing SH3 ligands. Indeed, it appears that that the relative frequency and importance of these types of interactions may have been underestimated. Instead of atypical, we propose referring to such peptides as type I or II (depending on the binding orientation) non-consensus ligands. Here we discuss the structural basis of non-consensus SH3 ligand binding and the dominant role of the SH3 domain specificity zone in selective target recognition, and review some of the best-characterized examples of such interactions.     

Look who’s talking—the crosstalk between oxidative stress and autophagy supports exosomal-dependent release of HCV particles

Autophagy is a highly conserved and regulated intracellular lysosomal degradation pathway that is essential for cell survival. Dysregulation has been linked to the development of various human diseases, including neurodegeneration and tumorigenesis, infection, and aging. Besides, many viruses hijack the autophagosomal pathway to support their life cycle. The hepatitis C virus (HCV), a major cause of chronic liver diseases worldwide, has been described to induce autophagy. The autophagosomal pathway can be further activated in response to elevated levels of reactive oxygen species (ROS). HCV impairs the Nrf2/ARE-dependent induction of ROS-detoxifying enzymes by a so far unprecedented mechanism. In line with this, this review aims to discuss the relevance of HCV-dependent elevated ROS levels for the induction of autophagy as a result of the impaired Nrf2 signaling and the described crosstalk between p62 and the Nrf2/Keap1 signaling pathway. Moreover, autophagy is functionally connected to the endocytic pathway as components of the endosomal trafficking are involved in the maturation of autophagosomes. The release of HCV particles is still not fully understood. Recent studies suggest an involvement of exosomes that originate from the endosomal pathway in viral release. In line with this, it is tempting to speculate whether HCV-dependent elevated ROS levels induce autophagy to support exosome-mediated release of viral particles. Based on recent findings, in this review, we will further highlight the impact of HCV-induced autophagy and its interplay with the endosomal pathway as a novel mechanism for the release of HCV particles.     

Huntington’s disease—the sting in the tail

Huntington's disease (HD) is a progressive neurodegenerative condition caused by the abnormal expansion of a polyglutamine tract in the N‐terminus of the huntingtin protein. Over the last 20 years, HD pathogenesis has been explained by the generation of N‐terminal fragments containing the polyglutamine stretch. A new study from Frederic Saudou's group now investigates the function of the C‐terminal fragments generated upon cleavage and shows that these products may also contribute to cellular toxicity in HD (El‐Daher et al, 2015 ).     

A Distinct Boundary between the Higher Brain’s Susceptibility to Ischemia and the Lower Brain’s Resistance

Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O₂/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na⁺/K⁺ pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K⁺]_o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.     

Mango introduction in Florida and the ’haden’ cultivar’s significance to the modern industry

Mango (Mangifera indica L.) introductions to Florida began in 1861 with the importation of ’No. 11’, a polyembryonic, seed-propagated (nucellar) cultivarfrom Cuba. In the 1880s a collection of Cuban mangos was established near Bradenton. One resulting popular cultivar was ’Turpentine’, now widely used as a rootstock. The U. S. Department of Agriculture introduced ’Mulgoba’, an improved cultivarfrom India, in 1889. Other mangos were later brought from India, Vietnam, the Philippines, Thailand, Israel, Australia and Kenya. Related Mangifera species were collected in East Malaysian Borneo in 1990. Inasmuch as the breeding system of Mangifera favors outcrossing, the proximity of numerous genotypes of disparate geographic origin in Florida has made that state a secondary center of diversity for the mango and enabled it to make a unique contribution to the fruit industry.     

Whole-Genome Sequencing of the World’s Oldest People

Supercentenarians (110 years or older) are the world’s oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies.     

On the Mechanism of Brewer’s Yeast Flocculation

Brewer’s yeast appears to flocculate or disperse reversibly in response to the environmental conditions. The yeast and its solubilized cell surface substance show flocculation-dispersion changes according to pH, sugar concentration and flocculation inducing substances. Top fermentative yeasts do not show such a response to the surrounding conditions. Cell surfaces of bottom fermentative yeasts increase in hydrophobicity during a shift from fermentation starting conditions (dispersion of yeast) (high sugar concentration, pH 5.5) to ending conditions ( flocculation) (no sugar, pH 4.2), but this hydrophobicity increase was not seen in the case of top fermentative yeast cells. The contributions of hydrophobic interaction and ionic bonds to flocculence of the yeast were discussed.     

Asperger’s Syndrome,Subjectivity and the Senses

Situated at the intersection of anthropological work on illness narratives and research on the anthropology of autism, this paper is a close reading of an autobiographical narrative recounted by Peter, a young man diagnosed with Asperger’s Syndrome, a type of autism spectrum disorder (ASD). Responding to Solomon’s (2010a:252) call for phenomenologically grounded accounts of “the subjective, sensory, and perceptual experiences of autism … based on personal narratives and practices of being and self-awareness,” this paper calls into question key assumptions in the clinical and popular literature about ASD relating to theory of mind, empathy, capacity for metaphorical thinking, and ASD as a life-long condition.     

Phytotaxonomy in the People’s Republic of China

As three of the members of the delegation of the Botanical Society of America, the authors participated in a 28-day tour of the People’s Republic of China in May and June, 1978. Botanical institutes and universities were visited in nine cities. A list of names and addresses of the collaborators and editors of family treatments for theFlora Reipublicae Popularis Sinicae is supplemented with a bibliography of published floras and significant taxonomic literature issued primarily since the end of the Cultural Revolution. A few observations on herbaria and herbarium practices are included.     

Alzheimer’s Disease: Analyzing the Missing Heritability

Alzheimer’s disease (AD) is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer’s Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer’s Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer’s disease.