Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of myosin VI in the differentiation of cochlear hair cells.

The mouse mutant Snell's waltzer (sv) has an intragenic deletion of the Myo6 gene, which encodes the unconventional myosin molecule myosin VI (K. B. Avraham et al., 1995, Nat. Genet. 11, 369-375). Snell's waltzer mutants exhibit behavioural abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tossing, and circling. We have investigated the effects of a lack of myosin VI on the development of the sensory hair cells of the cochlea in these mutants. In normal mice, the hair cells sprout microvilli on their upper surface, and some of these grow to form a crescent or V-shaped array of modified microvilli, the stereocilia. In the mutants, early stages of stereocilia development appear to proceed normally because at birth many stereocilia bundles have a normal appearance, but in places there are signs of disorganisation of the bundles. Over the next few days, the stereocilia become progressively more disorganised and fuse together. Practically all hair cells show fused stereocilia by 3 days after birth, and there is extensive stereocilia fusion by 7 days. By 20 days, giant stereocilia are observed on top of the hair cells. At 1 and 3 days after birth, hair cells of mutants and controls take up the membrane dye FM1-43, suggesting that endocytosis occurs in mutant hair cells. One possible model for the fusion is that myosin VI may be involved in anchoring the apical hair cell membrane to the underlying actin-rich cuticular plate, and in the absence of normal myosin VI this apical membrane will tend to pull up between stereocilia, leading to fusion.
Eye movements and psychiatric disease

Purpose of reviewDuring the past year a number of studies have been published on eye movement dysfunction in patients with psychiatric disease. According to the mainstream of modern neuropsychiatric research, these studies cover either genetic aspects or the results of pharmacological manipulation. Recent findingsA few studies addressed impaired smooth pursuit eye movements (eye tracking dysfunction) in unaffected relatives of psychiatric patients, and were important in excluding non-specific effects (e.g. medication) and isolating genetic predisposition to the disease. This predisposition could be demonstrated in families of schizophrenic patients irrespective of whether the index case was sporadic or familial. One large study demonstrated pathological distributions of various parameters of smooth pursuit eye movement performance in groups of schizophrenic patients and their relatives. However, another study challenged the specificity of eye tracking dysfunction as a trait marker for schizophrenia by showing that its prevalence was identical among relatives of patients with affective disorder and schizophrenia. Eye tracking dysfunction was associated with two gene polymorphisms that interfere with dopamine metabolism and are thus reasonable candidate genes for the predisposition to schizophrenia. The influence of nicotine and neuroleptic drugs on eye movement performance was studied in schizophrenic patients. Nicotine improved smooth pursuit performance in three studies, one of which attributed this finding to enhanced attention. Two groups of schizophrenic patients treated with two different atypical neuroleptic drugs, risperidone and olanzapine, did not differ in a battery of saccadic tasks. SummaryEye movements provide an important tool to measure pharmacological effects in patients and unravel genetic traits in psychiatric disease.
Transport of neurofilaments in growing axons requires microtubules but not actin filaments

Neurofilament (NF) polymers are conveyed from cell body to axon tip by slow axonal transport, and disruption of this process is implicated in several neuronal pathologies. This movement occurs in both anterograde and retrograde directions and is characterized by relatively rapid but brief movements of neurofilaments, interrupted by prolonged pauses. The present studies combine pharmacologic treatments that target actin filaments or microtubules with imaging of NF polymer transport in living axons to examine the dependence of neurofilament transport on these cytoskeletal systems. The heavy NF subunit tagged with green fluorescent protein was expressed in cultured sympathetic neurons to visualize NF transport. Depletion of axonal actin filaments by treatment with 5 μM latrunculin for 6 hr had no detectable effect on directionality or transport rate of NFs, but frequency of movement events was reduced from 1/3.1 min of imaging time to 1/4.9 min. Depolymerization of axonal microtubules using either 5 μM vinblastine for 3 hr or 5 μg/ml nocodazole for 4–6 hr profoundly suppressed neurofilament transport. In 92% of treated neurons, NF transport was undetected. These observations indicate that actin filaments are not required for neurofilament transport, although they may have subtle effects on neurofilament movements. In contrast, axonal transport of NFs requires microtubules, suggesting that anterograde and retrograde NF transport is powered by microtubule‐based motors. © 2005 Wiley‐Liss, Inc.
Role of External and Internal Calcium on Heterocarrier‐Mediated Transmitter Release

Abstract: Release‐regulating heterocarriers exist on brain nerve endings. We have investigated in this study the mechanisms involved in the neurotransmitter release evoked by GABA heterocarrier activation. GABA increased the basal release of [3H]acetylcholine and [3H]noradrenaline from rat hippocampal synaptosomes and of [3H]dopamine from striatal synaptosomes. These GABA effects, insensitive to GABA receptor antagonists, were prevented by inhibiting GABA uptake but not by blocking noradrenaline, choline, or dopamine transport. Lack of extracellular Ca2+ or addition of tetrodotoxin selectively abolished the GABA‐evoked release of [3H]noradrenaline, leaving unaffected that of [3H]acetylcholine or [3H]dopamine. 1,2‐Bis(2‐aminophenoxy)‐ethane‐N,N,N′,N′‐tetraacetic acid acetoxymethyl ester (BAPTA‐AM) or vesamicol attenuated the release of [3H]acetylcholine elicited by GABA. Reserpine, but not BAPTA‐AM, prevented the effect of GABA on [3H]dopamine release. Autoreceptor activation inhibited the GABA‐evoked release of [3H]noradrenaline but not that of [3H]acetylcholine or [3H]dopamine. It is concluded that (a) the release of [3H]noradrenaline consequent to activation of GABA heterocarriers sited on noradrenergic terminals meets the criteria of a conventional exocytotic process, (b) the extracellular [Ca2+]‐independent releases of [3H]acetylcholine and [3H]dopamine appear to occur from vesicles possibly through involvement of intraterminal Ca2+, and (c) autoreceptor activation only affects heterocarrier‐mediated vesicular release linked to entry of extracellular Ca2+.
Nonprofit organizations in Germany

Introduction The term “nonprofit organizations” In Germany the term “nonprofit organizations” is not legally defined, but it is often used in various fields of science (e.g. sociology, economics, political science, and sometimes also law). Although the definitions differ in detail, there is one common finding: nonprofit organizations are subject to a non-distribution constraint, which means that such an organization is barred from distributing its net earnings, if any, to individuals who exercise control over it, such as members, officers, directors or trustees. Empirical information At the moment there are around 600,000 associations and 15,000 foundations in Germany. The number of unincorporated associations and foundations without legal personality is unknown. The same is true for the number of tax-exempt organizations and charitable limited liability companies. Institutional law In Germany there are two basic forms of legal persons for nonprofit organizations: associations ( Vereine ) and foundations ( Stiftungen ). Both legal forms are regulated in the German Civil Code (§§ 21 et seq. for associations and §§ 80 et seq. for foundations). As regards foundations, there are additional laws in the sixteen German provinces ( Lander ) that mainly include provisions for state supervision. The basic difference between an association and a foundation is that while an association must have members, a foundation must not have members. This is the distinction between these two legal forms (cf. the traditional separation under Roman law between universitas personae and universitas bonorum ).
Coordinated process of polarized growth in filamentous fungi

Filamentous fungi are extremely polarized organisms, exhibiting continuous growth at their hyphal tips. The hyphal form is related to their pathogenicity in animals and plants, and their high secretion ability for biotechnology. Polarized growth requires a sequential supply of proteins and lipids to the hyphal tip. This transport is managed by vesicle trafficking via the actin and microtubule cytoskeleton. Therefore, the arrangement of the cytoskeleton is a crucial step to establish and maintain the cell polarity. This review summarizes recent findings unraveling the mechanism of polarized growth with special emphasis on the role of actin and microtubule cytoskeleton and polarity marker proteins. Rapid insertions of membranes via highly active exocytosis at hyphal tips could quickly dilute the accumulated polarity marker proteins. Recent findings by a super-resolution microscopy indicate that filamentous fungal cells maintain their polarity at the tips by repeating transient assembly and disassembly of polarity sites.
Dietary Folate Intake, Alcohol, and Risk of Breast Cancer in a Prospective Study of Postmenopausal Women

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels: <10th, 11th–30th, 31st–50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91–1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78–1.49) among nondrinkers, 1.33 (95% CI = 0.86–2.05) among drinkers of ≤4 gm per day, and 1.59 (95% CI = 1.05–2.41) among drinkers of >4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.
Design and implementation of a cloud-based IoT scheme for precision agriculture

The Internet of Things (IoT) technology is currently shaping different aspects of human life. Precision agriculture is one of the paradigms which can use the IoT advantages to optimize the production efficiency and uniformity across the agriculture fields, optimize the quality of the crops, and minimize the negative environmental impact. In this paper, we present an IoT architecture customized for precision agriculture applications. The proposed three-layer architecture collects the needed data and relays it to a cloud-based back-end where it is processed and analyzed. Feedback actions based on the analyzed data can be sent back to the front-end nodes. We built a prototype of the proposed architecture to demonstrate its performance advantages.
Risk for Nonalcoholic Fatty Liver Disease in Hispanic Youth With BMI ≥95th Percentile

Objectives:To characterize children at risk for nonalcoholic fatty liver disease (NAFLD) and to explore possible mechanisms underlying the development of NAFLD in Hispanic youth with a body mass index ≥95th percentile. Patients and Methods:Hispanic nonoverweight (n = 475) and overweight (n = 517) children, ages 4 to 19 y, were characterized in terms of body composition (dual-energy x-ray absorptiometry), maturation (Tanner stage), diet (24-h recall), physical activity (accelerometry), fitness (maximal oxygen uptake), and biochemical profile (fasting alanine aminotransferase [ALT], glucose, insulin, and lipids; inflammation markers such as adiponectin, leptin, C-reactive protein, and soluble intercellular adhesion molecule-1; and total antioxidants) using standard laboratory techniques. Risk for NAFLD was defined by fasting serum ALT values >97.5th percentile for age- and sex-specific reference values. Results:Fasting serum ALT was elevated in 24% of overweight children and in only 4% of nonoverweight children. Therefore, to identify risk factors associated with elevated ALT, the remaining statistical analysis was restricted to the overweight group. The percentage of overweight children with elevated ALT did not differ by sex, age, or Tanner stage. Weight, body mass index, z score, waist-to-hip ratio, fat-free mass, fat mass, and percent truncal fat mass were higher in the overweight children with elevated ALT. Fasting insulin, glucose, and homeostasis model-insulin resistance were higher in the overweight children with elevated ALT, as were triglycerides, total cholesterol, low-density lipoprotein, thyroid-stimulating hormone, and triiodothyronine. Fasting serum leptin, C-reactive protein, and soluble intercellular adhesion molecule-1 were significantly higher and adiponectin was lower in the overweight children with elevated ALT. Conclusions:The risk for developing NAFLD was high in the overweight Hispanic children. The proportion of “at risk” children was not influenced by gender, age, or maturation. The risk for elevated ALT was predicted by the severity of obesity, central adiposity, hyperinsulinemia, hypertriglyceridemia, elevated thyroid-stimulating hormone, and systemic inflammation.
When the picture is fragmented: Vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) has high mortality and necessitates prompt recognition of microangiopathic hemolytic anemia (MAHA) and initiation of plasmapheresis. We present a challenging diagnostic workup and management of a 42-year-old man who presented with anemia, thrombocytopenia, and schistocytes on peripheral smear, all pointing to MAHA. Plasmapheresis and steroid therapy were promptly initiated, but hemolysis continued. Further workup showed megaloblastic anemia, severe Vitamin B12deficiency, high iron saturation, and absent reticulocytosis, none of which could be explained by TTP. Severe Vitamin B12deficiency can lead to hemolytic anemia from the destruction of red cells in the marrow that have failed the process of maturation. However, this should not cause thrombotic microangiopathy. Previous reports of B12deficiency presenting with MAHA and a TTP-like manifestation have identified acute hyperhomocysteinemia as a missing link between B12deficiency and MAHA, so this possibility was further explored. Our patient similarly had significantly elevated serum homocysteine levels, confirming this suspicion of Vitamin B12deficiency. Vitamin B12replacement led to normalization of the elevated levels of homocysteine, the disappearance of schistocytes on the peripheral smear, and resolution of the microangiopathic hemolysis, thereby confirming the diagnosis. It is pertinent that intensivists not only know the importance of early recognition and treatment of TTP but are also familiar with rare conditions that can present in a similar fashion.
Better Negative than Positive? Evidence of a Bias for Negative Information about Possible Health Dangers

Do the results of a scientific study influence confidence in the study's validity and the magnitude of change in the resulting perceived danger of the health risk investigated? Findings from the three investigations reported here indicate that scientific results that confirm a danger (negative results) do affect confidence in a study's validity and resulting risk assessments differently than results indicating low risk (positive results). Findings of Study 1 revealed that research results indicating a health risk were more trusted than results indicating little health risk. This effect was independent of the credibility of the information source. Study 2 demonstrated that confidence in research results increased with an increasing indication of health risk. Study 3 showed that people have more confidence in the results of animal tests on a food additive indicating negative human health effects than in animal tests indicating that a food additive is harmless. The findings have important practical implications. The observed asymmetry between positive and negative research results may be one reason that people are afraid of many of the hazards they are faced with in modern society.
Genetic variation in NEDD4L, an epithelial sodium channel regulator, is associated with cardiovascular disease and cardiovascular death

Objectives: We have previously shown that genetic variance in NEDD4L, a regulating protein of a sodium channel in the distal nephron, has been associated with marginally higher blood pressure and enhanced salt sensitivity. Here, we tested if the genetic NEDD4L variation previously associated with salt sensitivity is related to population blood pressure, incidence of cardiovascular disease (CVD) and mortality. Method: We genotyped the rs4149601 A→G and rs2288774 T→C NEDD4L variants in 27 564 participants of the Malmö Diet and Cancer Study. The genotype combination previously shown to be associated with salt sensitivity (rs4149601 GG+rs2288774 CC), which was present in 9.6% of participants, was related to cross sectional blood pressure as well as to CVD incidence and mortality during a median follow-up time of 14 years using Cox regression models. Results: Carriers of the NEDD4L salt sensitivity-associated genotype had (mean ± SEM) higher systolic (142 ± 0.4 vs. 141 ± 0.1 mmHg, P = 0.002) and diastolic (86.0 ± 0.5 vs. 85.6 ± 0.2 mmHg, P = 0.025) blood pressure and multivariate adjusted hazards ratio (95% confidence interval) of CVD 1.13 (1.02–1.25, P = 0.018), coronary events 1.20 (1.06–1.37; P = 0.005) and cardiovascular mortality 1.17 (0.99–1.37; P = 0.055) than noncarriers but there was no significant difference in the incidence of stroke and total mortality. Conclusion: The NEDD4L salt sensitivity-associated genotype was associated with higher blood pressure, which may translate into increased risk for CVD morbidity and mortality. Interestingly, there was no association with stroke suggesting that the association is partially blood pressure independent.
Human subtelomeric copy number variations

Copy number variation is a defining characteristic of human subtelomeres. Human subtelomeric segmental duplication regions (‘Subtelomeric Repeats’) comprise about 25% of the most distal 500 kb and 80% of the most distal 100 kb in human DNA. Huge allelic disparities seen in subtelomeric DNA sequence content and organization are postulated to have an impact on the dosage of transcripts embedded within the duplicated sequences, on the transcription of genes in adjacent single copy DNA regions, and on the chromatin structures mediating telomere functions including chromosome stability. In addition to the complex duplicon substructure and huge allelic variations in extended subtelomere regions, both copy number variation and alternative sequence organizations for DNA characterize the sequences immediately adjacent to terminal (TTAGGG)n tracts (‘subterminal DNA’). The structural variation in subterminal DNA is likely to have important consequences for expression of subterminal transcripts such as a newly-discovered gene family encoding actin-interacting proteins and a non-coding telomeric repeat containing RNA (TERRA) transcript family critical for telomere integrity. Major immediate challenges include discovering the full extent and nature of subtelomeric structural and copy number variation in humans, and developing methods for tracking individual allelic variants in the context of total genomic DNA.
A molecular phylogeny of the vataireoid legumes underscores floral evolvability that is general to many early-branching papilionoid lineages.

PREMISE OF STUDY Flowering traits can sometimes be overemphasized in taxonomic classifications. The fused and completely differentiated papilionate floral organs in the neotropical legume trees Vatairea and Vataireopsis were traditionally used in part to ascribe these genera to the tribe Dalbergieae. In contrast, the free and mostly undifferentiated floral parts of Luetzelburgia and Sweetia fit the circumscription of the "primitive" Sophoreae. Such divergent floral morphologies thought to divide deep phylogenetic lineages indeed may be prone to episodic transformation among close papilionoid relatives. METHODS We sampled 26 of 27 known species of Luetzelburgia, Sweetia, Vatairea, and Vataireopsis in parsimony and Bayesian phylogenetic analyses of nuclear ribosomal ITS/5.8S and six plastid (matK, 3'-trnK, psbA-trnH, trnL intron, rps16 intron, and trnD-T) DNA sequence loci. KEY RESULTS The analyses of individual and combined data sets strongly resolved the monophyly of each of Luetzelburgia, Sweetia, Vatairea, and Vataireopsis. Vataireopsis was resolved as sister to the rest and the morphologically divergent Luetzelburgia and Vatairea were strongly resolved as sister clades. Floral morphology was generally not a good predictor of phylogenetic relatedness. CONCLUSIONS Luetzelburgia, Sweetia, Vatairea, and Vataireopsis are unequivocally resolved as the "vataireoid" clade. Fruit and vegetative traits are found to be more phylogenetically conserved than many floral traits. This explains why the identity of the vataireoids has been overlooked or confused. The evolvability of floral traits may also be a general condition among many of the early-branching papilionoid lineages.
Distribution of afaE adhesins in Escherichia coli isolated from Japanese patients with urinary tract infection.

PURPOSE Afimbrial adhesin is known to be one of the most prevalent virulence factors in uropathogenic Escherichia coli. A recent report showed that the new subtype afaE8 predominated in afa positive isolates from patients with pyelonephritis (55.6%), suggesting that this subtype may be an important factor in ascending urinary tract infections. MATERIALS AND METHODS A total of 457 E. coli strains consisting, of 194, 76 and 107 isolates from patients with cystitis, pyelonephritis and prostatitis, respectively, and 80 isolates from the rectal flora of healthy individuals were subjected to polymerase chain reaction to determine the afa operon as well as afaE subtypes. RESULTS We identified 32 afa positive isolates of 377 strains (8.5%) and 2 of 80 strains (2.5%) from urinary tract infection isolates and normal flora, respectively. When afaE subtypes were determined, the afaE3 subtype predominated in afa positive isolates from cystitis (64.7%), pyelonephritis (66.7%) and prostatitis (50%). However, the afaE8 subtype was absent from urinary tract infection isolates, while only 1 isolate from the stool of a healthy adult harbored this subtype. CONCLUSIONS Our data show that the afaE3 subtype predominated in pyelonephritis as well as in other urinary tract infections, indicating that the afa gene may be important in urinary tract infection. However, the distribution of afaE subtypes may be diverse in different areas of the world.