The origin of fibonacci phyllotaxis—an analysis of Adler's contact pressure model and Mitchison's expanding apex model

Adler's contact pressure model for Fibonacci phyllotaxis is examined theoretically. It is shown that the model, as it stands, does not account for Fibonacci phyllotaxis, since it requires, but does not provide, a mechanism for initiating new primordia with increasingly greater precision as phyllotaxis rises. Modifications are suggested which remedy this deficiency in the model; one of these modifications involves a combination of Adler's model with Mitchison's model.From a comparison of the ranges of divergence angles permitted by Adler's model against Fujita's measurements of divergence angles in plants with low phyllotaxis, it is shown that the modified contact pressure model, if based on the concept of mechanical pressures between primordia in contact, cannot account for the divergence angles found in low phyllotaxis systems. However it is shown that this deficiency can be overcome if the contact pressure effect is regarded as a chemical phenomenon, mediated by a growth inhibitor produced by the prirnordia and moving more readily in vertical directions than in other directions.Mitchison's model, which is based on the concepts of an expanding apex and primordium initiation by existing primordia, is shown to account for Fibonacci phyllotaxis only if phyllotaxis rises sufficiently slowly; to guarantee that an F_n + F_n+1 system can develop there must already be at least F_n+1 primordia present in an F_n?1 + F_n system, at least F_n primordia in an F_n?2 + F_n?1 system, and so on down to at least three primordia in a 1 + 2 system, making a total of at least F_n+3?5 primordia (where F_n = nth term of the Fibonacci series with F₁ = F₂ = 1). Adler's model, modified, requires only that F_{n + 1} primordia be present with divergence angles in the range 120–180° to guarantee that an F_n + F_{n + 1} system can develop.     

How well does Turing's theory of morphogenesis work?

In 1952 Turing published a paper which showed how under restricted conditions a class of chemical reactions could give biological patterns in diffusion-coupled cells. Although this theory has been much discussed, little has been learnt about the range and type of pattern it can generate. In order to do this and to see how stable the patterns are, we have examined the system in detail and written a computer program to simulate Turing's kinetics for two morphogens over various assemblies of cells. We find that on one-dimensional lines of cells, patterns can indeed be produced and that the chemical wavelengths follow all of Turing's predictions. The results show that stable repeating peaks of chemical concentration of periodicity 2–20 cells can be obtained in embryos in periods of time of less than an hour. We do find however that these patterns are not reliable: small variations in initial conditions give small but significant changes in the number and positions of observed peaks. Similar results are observed in two-dimensional assemblies of cells. On rectangles, random blotches are observed whose position cannot be reliably predicted. On cylinders whose circumference is less than the chemical wavelength, annular stripes are produced. For larger cylinders, blotches that lie very approximately on helices are generated; again sharp prediction of the detailed pattern is impossible.The significance of these results for the developing embryo is discussed. We conclude that Turing kinetics, at least in the simple cases that we have studied, are too unreliable to serve as the generating mechanism for features such as digits which are characterized by a consistent number of units. The theory is however more than adequate by these criteria to specify less well-defined developing patterns such as those of hair follicles or leaf organization. It is emphasized however that the Turing theory is quite unable to generate regulative systems, only mosaicpatterns can be produced.     

The innervation of frog's taste organ “A histochemical study”

Morphological investigations on the fungiform papilla of the frog (Rana pipiens) have shown that this taste organ contains two distinct populations of cells: associate and sensory. Messages received by the sensory cells are believed to be transmitted through the mediation of an adrenergic transmitter. This chemical was shown by fluorescence microscopy and electron histochemistry to be stored in synaptic granular vesicles which accumulate at the membrane of the cytoplasmic processes of the sensory cells in typical chemical synaptic complexes. The sensory cell cytoplasmic processes form the presynaptic component of these complexes whose post synaptic components are the nerve fibres supplying the taste buds. These sensory nerve fibres contain agranular vesticles and are probably cholinergic, since they show positive cholinesterase activity at the light and electron microscopical levels.     

The accumulation of deleterious genes in a population—Muller's Ratchet

A quantitative study of the operation of Muller's Ratchet for the accumulation of deleterious genes in an asexually reproducing population is made. For a population of size N, in which deleterious mutations occur at rate λ/genome/ generation, and the relative fitness of an individual with k mutants is (1 ? s)^k, the most important parameter is $\text{n}{}_0\text{= Ne}{}^{\mathrm{?\theta }}\text{,}\text{where}\text{θ =}\text{λ}\text{s}$. If n₀ is large (?25), deleterious mutations will accumulate very slowly, and independently of each other; if n₀ is small (<1), the rate of accumulation of deleterious mutations will be greater than a natural population could plausibly bear; an estimate of the speed of the Ratchet for intermediate values of n₀ is made. It is pointed out that the frequency distribution for the numbers of individuals carrying k mutants will retain its shape, but will move bodily to the right at the same average speed as the Ratchet. When favourable mutations also occur, the frequency distributions can move right of left; an estimate of the probability that any particular step is right or left is made, and it is shown that, for a given net rate of arrisal of deleterious mutations, the greater the rate of beneficial mutation, the greater the chance that beneficial mutations will accumulate.     

Action de l'ecdystérone sur l'apolysis et l'ecdysis de divers crustacés isopodes

Ecdysterone acts differently according to the period of the moulting cycle when it is applied. In period C it induces apolysis, while at the beginning of apolysis it delays ecdysis. Experiments show that the exoskeleton cannot be rejected in the presence of ecdysterone. The possibility of stopping exuviation or ecdysis with ecdysterone seems to prove that this phenomenon is controlled by a particular factor called the factor of exuviation or the ecdysis factor. Ecdysterone would control only the release of this specific factor but would not prevent its action.     

‘Information parasitism’ in mixed colonies of western grebes and Forster's terns

Of 38 western grebe (Aechmophorus occidentalis) colonies initiated on the Delta Marsh, Lake Manitoba, in 1973 through 1979, over half (53%) included breeding Forster's terns (Sterna forsteri). Tern-associated colonies included 12 of the 13 largest colonies, incorporating 83% of the total nesting effort (N=2821 nests). Such colonies were impossible to approach undetected, because grebes used the tern's aerial alarm system to warn of danger. Playbacks showed that grebes recognized the tern's alarm call, and responded by immediately leaving their nests. This essentially constitutes a form of ‘information parasitism,’ which probably is widespread in many nesting associations. This work suggests a broadening of the ‘information centre’ hypothesis to include transfer of information about any reproductive requisite, not just food.     

Stereochemistry of dihydrofolate reductase inhibitor antitumor acents: Molecular structure of “Baker's antifol” (NSC 139105, triazinate) and “insoluble Baker's antifol” (NSC 113423)

The crystal and molecular structures of 1-[3-chloro-4-($\text{m}$-dimethylcarbamoylbenzyloxy)] phenyl-4,6-diamino-1,2-dihydro-2,2-dimethyl-$\text{s}$-triazine ethanesulfonate, (Baker's antifol), and 1-[4-(N-[3′-methyl-4′-fluorosulfonyl] phenyl) propanamide] phenyl-4,6-diamino-1,2-dihydro-2,2-dimethyl-$\text{s}$-triazine ethanesulfonate dihydrate (insoluble Baker's antifol) have been determined by X-ray crystallography. These compounds are, respectively, reversible and irreversible inhibitors of dihydrofolate reductase and show clinical promise for use in cancer chemotherapy. Both molecules adopt an extended conformation and are protonated at one of the triazine ring nitrogens.     

Heat exchange in the cryosurgery of Menière's disease: Experimental and clinical studies

The temperature course in the lateral semicircular canal and in the facial canal was studied in experiments during freezing of the semicircular canal. The course of the temperature was measured with thermocouples. Concurrently, the heat flow was measured, and also the total heat exchange was measured throughout the freezing period by a thermoelectric heat flowmeter incorporated in the cryotip. The measurements showed correlation between the total amount of heat exchanged, the freezing time, and the temperature in the semicircular canal. This correlation was utilized to assess and calculate (the temperature of the lateral semicircular canal) the course of the cryoprocess in vivo, where it is possible to measure the heat flow and the total heat exchange during the freezing period only.

2. Results upon Vertigo

     

9.

Who's In and Who's Out—Compositional Control of Biomolecular Condensates     

Jonathon A. Ditlev  Lindsay B. Case  Michael K. Rosen 《Journal of molecular biology》2018,430(23):4666-4684

Biomolecular condensates are two- and three-dimensional compartments in eukaryotic cells that concentrate specific collections of molecules without an encapsulating membrane. Many condensates behave as dynamic liquids and appear to form through liquid–liquid phase separation driven by weak, multivalent interactions between macromolecules. In this review, we discuss current models and data regarding the control of condensate composition, and we describe our current understanding of the composition of representative condensates including PML nuclear bodies, P-bodies, stress granules, the nucleolus, and two-dimensional membrane localized LAT and nephrin clusters. Specific interactions, such as interactions between modular binding domains, weaker interactions between intrinsically disorder regions and nucleic acid base pairing, and nonspecific interactions, such as electrostatic interactions and hydrophobic interactions, influence condensate composition. Understanding how specific condensate composition is determined is essential to understanding condensates as biochemical entities and ultimately discerning their cellular and organismic functions.     

10.

PARKIN overexpression in human mesenchymal stromal cells from Wharton's jelly suppresses 6-hydroxydopamine–induced apoptosis: Potential therapeutic strategy in Parkinson's disease     

A.R. Bonilla-Porras  A. Arevalo-Arbelaez  J.F. Alzate-Restrepo  C. Velez-Pardo  M. Jimenez-Del-Rio 《Cytotherapy》2018,20(1):45-61

     

11.

Phg1p: Dictyostelium&#x27;s first ‘fork’ for phagocytosis finger-food     

《Trends in cell biology》2001,11(2):55

     

12.

Disruption of endothelial barrier function is linked with hyposecretion and lymphocytic infiltration in salivary glands of Sjögren's syndrome     

Xin Cong  Xue-Ming Zhang  Yan Zhang  Tai Wei  Qi-Hua He  Li-Wei Zhang  Hong Hua  Sang-Woo Lee  Kyungpyo Park  Guang-Yan Yu  Li-Ling Wu 《生物化学与生物物理学报:疾病的分子基础》2018,1864(10):3154-3163

Sjögren's syndrome (SS) is an inflammatory autoimmune disease that causes hyposecretion in salivary glands. Endothelial tight junctions (TJs) play crucial roles in salivation and barrier function of blood vessels. However, whether the alteration of endothelial TJs were involved in pathogenesis of SS was still unknown. Here, the ultrastructure and function of endothelial TJs in submandibular glands (SMGs) were detected by transmission electron microscopy and in vivo paracellular permeability assay in different aged NOD mouse model for SS. CFSE-labeled lymphocytes were injected into tail vein to trace the infiltration, while claudin-5 expression and distribution were detected by immunofluorescence, qRT-PCR, and western blot. Results showed that the stimulated salivary flow rate was gradually decreased and lymphocytic infiltration was found as age increased in 12- and 21-week-old NOD mice, but not 7-week-old NOD mice. Blood vessels were dilated, while endothelial TJ width and paracellular tracer transport were increased in 12-week-old NOD mice. Moreover, the injected CFSE-labeled lymphocytes were observed in SMGs of 12-week-old NOD mice. Claudin-5 level was increased and relocalized from the apical portion of neighboring endothelial cells to lateral membranes and cytoplasm in 12-week-old NOD mice. Additionally, the alteration of claudin-5 expression and distribution was further confirmed in labial salivary glands and bilateral parotid glands from SS patients. In cultured human microvessel endothelial cell line (HMEC-1), IFN-γ stimulation significantly increased claudin-5 expression. Taken together, we identified that the endothelial TJ barrier was disrupted and contributed to the development of salivary hyposecretion and lymphocytic infiltration in SS.     

13.

C-terminal truncation exacerbates the aggregation and cytotoxicity of α-Synuclein: A vicious cycle in Parkinson's disease     

Liang Ma  Chen Yang  Xia Zhang  Yang Li  Shun Wang  Ling Zheng  Kun Huang 《生物化学与生物物理学报:疾病的分子基础》2018,1864(12):3714-3725

Parkinson's disease (PD) is a common neurodegenerative disease which usually associates with neuroinflammation. The main pathological characteristics of PD are dopaminergic neurons death and the presence of Lewy bodies which are composed of aggregated α-synuclein (α-Syn). Truncated forms of α-Syn are found in the brain of PD patients, and account for 10–30% of total synuclein in Lewy bodies. Caspase-1, which plays an important role in neuroinflammation, cleaves full-length α-Syn (α-Syn FL) to generate a C-terminus 19-residues truncated α-Syn (α-Syn121). However, the role of truncated α-Syn in the onset and/or pathogenesis of PD is unclear. Here, we used α-Syn121 as a model to explore its aggregation, membrane disruption and cytotoxicity properties. Compared with α-Syn FL, α-Syn121 aggregated at an accelerated rate, and formed amorphous aggregates rich in random coil structures rather than β-sheet-rich linear fibrils formed by α-Syn FL. Importantly, higher cytotoxicity with lower membrane disruption capacity was found for α-Syn121 aggregates. Furthermore, α-Syn121 aggregates could activate the apoptosis signaling pathway and stimulate the caspase-1-mediated cleavage of α-Syn FL to generate α-Syn121, which as a result leading to increased levels of endogenous α-Syn121 and intracellular S129 phosphorylated α-Syn inclusions. Together, our data suggests a hidden vicious cycle in PD that α-Syn121 rapidly forms amorphous aggregates, which activate caspase-1 to cleave α-Syn FL and generate more α-Syn121, and this cycle may contribute to the onset and/or pathogenesis of PD.     

14.

How are neuronal thermosensitivity and lack of thermoreception related in the duck's hypothalamus? A tentative answer     

Karin Eissel  E. Simon 《Journal of thermal biology》1980,5(4):219-223

1. 1.|In 15 conscious Pekin ducks, 40 “warm sensitive” hypothalamic neurons were identified according to their discharge rates at 40°C T_hy (F₄₀), local temperature coefficients (Δ/ΔT) and Q₁₀.

2. 2.|Q₁₀ and either F₄₀ or ΔF/ΔT were little or not related.

3. 3.|A positive correlation between F₄₀ and ΔF/ΔT was observed which was particularly close (r = 0.94 and 0.96) when the neurons were classified according to their Q₁₀ of <2 and >2.

4. 4.|The results suggest that neurons with positive temperature coefficients in the duck's hypothalamus mostly exhibit linear to exponential temperature-discharge relationships.

5. 5.|This is an contrast to observations on mammalian hypothalamic thermosensitive neurons and may relate to the absence of the thermosensory function in the duck's rostral brainstem.

Author Keywords: Neuronal thermosensitivity; hypothalamic thermosensory function; Temperature and synaptic transmission; avian thermoregulation; mammalian thermoregulation     

15.

Activité cytokinine de dérivés acylés,alkylés,acyl-alkylés de l'adénine et d'isost`eres azotés de la γ,γ-diméthylallyladénine     

J. Roussaux  M.T. Adeline  P. Adou  N. Dat-Xuong 《Phytochemistry》1977,16(12):1865-1869

The cytokinin activities of various 6-acylaminopurines, 6-alkylaminopurines, 6-acylamino-9-benzyl-purines as well as a series of isosteric-nitrogen derivatives of N⁶-(γ, γ-dimethylallyl)adenine (I⁶Ade) have been tested using the tobacco pith and the pea bud bioassays. The interactions between active, slightly active and inactive compounds have been studied with the last assay. Acylation decreases the biological activity; e.g., N⁶-benzoyl and N⁶-furoyladenines are less active than Na⁶-benzyladenine and kinetin. Substitution at the 9-position reduces (tobacco-pith assay) or suppresses (pea-bud assay) the phytohormonal activity of otherwise active 6-acylaminopurines. In isosteric derivatives, maximum activity occurs when the side chain has the same length as in 1⁶Ade. After the analysis of interactions between more or less active compounds, it is suggested that the differences in cytokinin activity could be related to unequal affinities for a hypothetical receptor site.     

16.

Cournon-les Souméroux: Un nouveau site a vertébrés d'auvergne; Sa place parmi les faunes de l'Oligocène supérieur d'Europe     

Michel Brunet  Marguerite Hugueney  Yves Jehenne 《Geobios》1981,14(3):323-359

     

17.

Serum Albumin's Protective Inhibition of Amyloid-β Fiber Formation Is Suppressed by Cholesterol,Fatty Acids and Warfarin     

David C. Bode  Helen F. Stanyon  Trisha Hirani  Mark D. Baker  Jon Nield  John H. Viles 《Journal of molecular biology》2018,430(7):919-934

Central to Alzheimer's disease (AD) pathology is the assembly of monomeric amyloid-β peptide (Aβ) into oligomers and fibers. The most abundant protein in the blood plasma and cerebrospinal fluid is human serum albumin. Albumin can bind to Aβ and is capable of inhibiting the fibrillization of Aβ at physiological (μM) concentrations. The ability of albumin to bind Aβ has recently been exploited in a phase II clinical trial, which showed a reduction in cognitive decline in AD patients undergoing albumin–plasma exchange. Here we explore the equilibrium between Aβ monomer, oligomer and fiber in the presence of albumin. Using transmission electron microscopy and thioflavin-T fluorescent dye, we have shown that albumin traps Aβ as oligomers, 9 nm in diameter. We show that albumin-trapped Aβ oligomeric assemblies are not capable of forming ion channels, which suggests a mechanism by which albumin is protective in Aβ-exposed neuronal cells. In vivo albumin binds a variety of endogenous and therapeutic exogenous hydrophobic molecules, including cholesterol, fatty acids and warfarin. We show that these molecules bind to albumin and suppress its ability to inhibit Aβ fiber formation. The interplay between Aβ, albumin and endogenous hydrophobic molecules impacts Aβ assembly; thus, changes in cholesterol and fatty acid levels in vivo may impact Aβ fibrillization, by altering the capacity of albumin to bind Aβ. These observations are particularly intriguing given that high cholesterol or fatty acid diets are well-established risk factors for late-onset AD.     

18.

Modalités d'installation et d'évolutiondes Harpocératinés (ammonitina A) au Domérien inférieur dans le sud-Ouest de l'Europe (France,Portugal)     

J.L. Dommergues  R. Mouterde 《Geobios》1980,13(3):289-325

In Mesogea, the Harpoceratinae were known asearly as the end of the Lower Carixian. They later reached the sub-boreal province through the Alps or the South of the Iberic Peninsula. The analysis of the populations met in four crosssections of the Lower Domerian (Causses, Mâconnais, Franche-Comté, Portugal) showed the settling down of the Protogrammoceras isseli group that set up and evoluated in a similar way in the different areas in spite of a certain originality.On the one hand, it gave the cladogenetic groupP. monestieri-nitescens by diminution of the ribing density, strengthening of the ribs and simplification of the suture.On the other hand, a slower evolution give, near the end of the Stokesi zone, P. normanianum in the Paris Basin and in Burgundy, and P. lusitanicum in Portugal. At the same time, a new invader, P. celebratum, arrived in the Causses (and in Portugal).     

19.

Characterization of a new sulfhydryl group reagent: 6,6′-Diselenobis-(3-Nitrobenzoic acid), a selenium analog of Ellman's reagent     

Narender P. Luthra  R.Bruce Dunlap  Jerome D. Odom 《Analytical biochemistry》1981,117(1):94-102

A new reagent, 6,6′-diselenobis-(3-nitrobenzoic acid) (DSNB) has been synthesized and is shown to be useful for quantitative estimation of sulfhydryl groups in proteins. This reagent, which is a selenium analog of Ellman's reagent, reacts specifically and quantitatively with thiol groups of proteins to yield a selenenyl sulfide and the dianion of 3-nitro-6-selenobenzoic acid. The molar absorption coefficient of the chromophoric dianion is 10,000 at 432 nm in dilute aqueous solutions. The titration can best be performed at pH 8.20 where >98% of 3-nitro-6-selenobenzoic acid is in the form of the intensely colored dianion. Sulfhydryl content determinations by this reagent of reduced and denatured ribonuclease, reduced and denatured lysozyme, native papain, and native and denatured thymidylate synthetase are compared with those from corresponding 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) titrations. The reagent was found to inactivate thymidylate synthetase, an enzyme with essential sulfhydryl groups. Unlike DTNB which undergoes alkaline decomposition of pH values greater than 9, DSNB was found to be stable to hydrolysis, even in 0.05 m NaOH.     

20.

Design,synthesis and evaluation of novel bivalent β-carboline derivatives as multifunctional agents for the treatment of Alzheimer's disease     

Yifan Zhao  Feng Ye  Jian Xu  Qinghong Liao  Lei Chen  Weijia Zhang  Haopeng Sun  Wenyuan Liu  Feng Feng  Wei Qu 《Bioorganic & medicinal chemistry》2018,26(13):3812-3824

To develop potent multi-target ligands against Alzheimer's disease (AD), a series of novel bivalent β-carboline derivatives were designed, synthesized, and evaluated. In vitro studies revealed these compounds exhibited good multifunctional activities. In particular, compounds 8f and 8g showed the good selectivity potency on BuChE inhibition (IC₅₀?=?1.7 and 2.7?μM, respectively), Aβ_1-42 disaggregation and neuroprotection. Compared with the positive control resveratrol, 8f and 8g showed better activity in inhibiting Aβ_1-42 aggregation, with inhibitory rate 82.7% and 85.7% at 25?μM, respectively. Moreover, compounds 8e, 8f and 8g displayed excellent neuroprotective activity by ameliorating the impairment induced by H₂O₂, okadaic acid (OA) and Aβ_1-42 without cytotoxicity in SH-SY5Y cells. Thus, the present study evidently showed that compounds 8f and 8g are potent multi-functional agents against AD and might serve as promising lead candidates for further development.     

	No Vertigo	Improved	Unchanged
Number of patients	7	5	3

Who's In and Who's Out—Compositional Control of Biomolecular Condensates

Biomolecular condensates are two- and three-dimensional compartments in eukaryotic cells that concentrate specific collections of molecules without an encapsulating membrane. Many condensates behave as dynamic liquids and appear to form through liquid–liquid phase separation driven by weak, multivalent interactions between macromolecules. In this review, we discuss current models and data regarding the control of condensate composition, and we describe our current understanding of the composition of representative condensates including PML nuclear bodies, P-bodies, stress granules, the nucleolus, and two-dimensional membrane localized LAT and nephrin clusters. Specific interactions, such as interactions between modular binding domains, weaker interactions between intrinsically disorder regions and nucleic acid base pairing, and nonspecific interactions, such as electrostatic interactions and hydrophobic interactions, influence condensate composition. Understanding how specific condensate composition is determined is essential to understanding condensates as biochemical entities and ultimately discerning their cellular and organismic functions.     

Disruption of endothelial barrier function is linked with hyposecretion and lymphocytic infiltration in salivary glands of Sjögren's syndrome

Sjögren's syndrome (SS) is an inflammatory autoimmune disease that causes hyposecretion in salivary glands. Endothelial tight junctions (TJs) play crucial roles in salivation and barrier function of blood vessels. However, whether the alteration of endothelial TJs were involved in pathogenesis of SS was still unknown. Here, the ultrastructure and function of endothelial TJs in submandibular glands (SMGs) were detected by transmission electron microscopy and in vivo paracellular permeability assay in different aged NOD mouse model for SS. CFSE-labeled lymphocytes were injected into tail vein to trace the infiltration, while claudin-5 expression and distribution were detected by immunofluorescence, qRT-PCR, and western blot. Results showed that the stimulated salivary flow rate was gradually decreased and lymphocytic infiltration was found as age increased in 12- and 21-week-old NOD mice, but not 7-week-old NOD mice. Blood vessels were dilated, while endothelial TJ width and paracellular tracer transport were increased in 12-week-old NOD mice. Moreover, the injected CFSE-labeled lymphocytes were observed in SMGs of 12-week-old NOD mice. Claudin-5 level was increased and relocalized from the apical portion of neighboring endothelial cells to lateral membranes and cytoplasm in 12-week-old NOD mice. Additionally, the alteration of claudin-5 expression and distribution was further confirmed in labial salivary glands and bilateral parotid glands from SS patients. In cultured human microvessel endothelial cell line (HMEC-1), IFN-γ stimulation significantly increased claudin-5 expression. Taken together, we identified that the endothelial TJ barrier was disrupted and contributed to the development of salivary hyposecretion and lymphocytic infiltration in SS.     

C-terminal truncation exacerbates the aggregation and cytotoxicity of α-Synuclein: A vicious cycle in Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disease which usually associates with neuroinflammation. The main pathological characteristics of PD are dopaminergic neurons death and the presence of Lewy bodies which are composed of aggregated α-synuclein (α-Syn). Truncated forms of α-Syn are found in the brain of PD patients, and account for 10–30% of total synuclein in Lewy bodies. Caspase-1, which plays an important role in neuroinflammation, cleaves full-length α-Syn (α-Syn FL) to generate a C-terminus 19-residues truncated α-Syn (α-Syn121). However, the role of truncated α-Syn in the onset and/or pathogenesis of PD is unclear. Here, we used α-Syn121 as a model to explore its aggregation, membrane disruption and cytotoxicity properties. Compared with α-Syn FL, α-Syn121 aggregated at an accelerated rate, and formed amorphous aggregates rich in random coil structures rather than β-sheet-rich linear fibrils formed by α-Syn FL. Importantly, higher cytotoxicity with lower membrane disruption capacity was found for α-Syn121 aggregates. Furthermore, α-Syn121 aggregates could activate the apoptosis signaling pathway and stimulate the caspase-1-mediated cleavage of α-Syn FL to generate α-Syn121, which as a result leading to increased levels of endogenous α-Syn121 and intracellular S129 phosphorylated α-Syn inclusions. Together, our data suggests a hidden vicious cycle in PD that α-Syn121 rapidly forms amorphous aggregates, which activate caspase-1 to cleave α-Syn FL and generate more α-Syn121, and this cycle may contribute to the onset and/or pathogenesis of PD.     

How are neuronal thermosensitivity and lack of thermoreception related in the duck's hypothalamus? A tentative answer

1. 1.|In 15 conscious Pekin ducks, 40 “warm sensitive” hypothalamic neurons were identified according to their discharge rates at 40°C T_hy (F₄₀), local temperature coefficients (Δ/ΔT) and Q₁₀.

2. 2.|Q₁₀ and either F₄₀ or ΔF/ΔT were little or not related.

3. 3.|A positive correlation between F₄₀ and ΔF/ΔT was observed which was particularly close (r = 0.94 and 0.96) when the neurons were classified according to their Q₁₀ of <2 and >2.

4. 4.|The results suggest that neurons with positive temperature coefficients in the duck's hypothalamus mostly exhibit linear to exponential temperature-discharge relationships.

5. 5.|This is an contrast to observations on mammalian hypothalamic thermosensitive neurons and may relate to the absence of the thermosensory function in the duck's rostral brainstem.

Activité cytokinine de dérivés acylés,alkylés,acyl-alkylés de l'adénine et d'isost`eres azotés de la γ,γ-diméthylallyladénine

The cytokinin activities of various 6-acylaminopurines, 6-alkylaminopurines, 6-acylamino-9-benzyl-purines as well as a series of isosteric-nitrogen derivatives of N⁶-(γ, γ-dimethylallyl)adenine (I⁶Ade) have been tested using the tobacco pith and the pea bud bioassays. The interactions between active, slightly active and inactive compounds have been studied with the last assay. Acylation decreases the biological activity; e.g., N⁶-benzoyl and N⁶-furoyladenines are less active than Na⁶-benzyladenine and kinetin. Substitution at the 9-position reduces (tobacco-pith assay) or suppresses (pea-bud assay) the phytohormonal activity of otherwise active 6-acylaminopurines. In isosteric derivatives, maximum activity occurs when the side chain has the same length as in 1⁶Ade. After the analysis of interactions between more or less active compounds, it is suggested that the differences in cytokinin activity could be related to unequal affinities for a hypothetical receptor site.     

Serum Albumin's Protective Inhibition of Amyloid-β Fiber Formation Is Suppressed by Cholesterol,Fatty Acids and Warfarin

Central to Alzheimer's disease (AD) pathology is the assembly of monomeric amyloid-β peptide (Aβ) into oligomers and fibers. The most abundant protein in the blood plasma and cerebrospinal fluid is human serum albumin. Albumin can bind to Aβ and is capable of inhibiting the fibrillization of Aβ at physiological (μM) concentrations. The ability of albumin to bind Aβ has recently been exploited in a phase II clinical trial, which showed a reduction in cognitive decline in AD patients undergoing albumin–plasma exchange. Here we explore the equilibrium between Aβ monomer, oligomer and fiber in the presence of albumin. Using transmission electron microscopy and thioflavin-T fluorescent dye, we have shown that albumin traps Aβ as oligomers, 9 nm in diameter. We show that albumin-trapped Aβ oligomeric assemblies are not capable of forming ion channels, which suggests a mechanism by which albumin is protective in Aβ-exposed neuronal cells. In vivo albumin binds a variety of endogenous and therapeutic exogenous hydrophobic molecules, including cholesterol, fatty acids and warfarin. We show that these molecules bind to albumin and suppress its ability to inhibit Aβ fiber formation. The interplay between Aβ, albumin and endogenous hydrophobic molecules impacts Aβ assembly; thus, changes in cholesterol and fatty acid levels in vivo may impact Aβ fibrillization, by altering the capacity of albumin to bind Aβ. These observations are particularly intriguing given that high cholesterol or fatty acid diets are well-established risk factors for late-onset AD.     

Modalités d'installation et d'évolutiondes Harpocératinés (ammonitina A) au Domérien inférieur dans le sud-Ouest de l'Europe (France,Portugal)

In Mesogea, the Harpoceratinae were known asearly as the end of the Lower Carixian. They later reached the sub-boreal province through the Alps or the South of the Iberic Peninsula. The analysis of the populations met in four crosssections of the Lower Domerian (Causses, Mâconnais, Franche-Comté, Portugal) showed the settling down of the Protogrammoceras isseli group that set up and evoluated in a similar way in the different areas in spite of a certain originality.On the one hand, it gave the cladogenetic groupP. monestieri-nitescens by diminution of the ribing density, strengthening of the ribs and simplification of the suture.On the other hand, a slower evolution give, near the end of the Stokesi zone, P. normanianum in the Paris Basin and in Burgundy, and P. lusitanicum in Portugal. At the same time, a new invader, P. celebratum, arrived in the Causses (and in Portugal).     

Characterization of a new sulfhydryl group reagent: 6,6′-Diselenobis-(3-Nitrobenzoic acid), a selenium analog of Ellman's reagent

A new reagent, 6,6′-diselenobis-(3-nitrobenzoic acid) (DSNB) has been synthesized and is shown to be useful for quantitative estimation of sulfhydryl groups in proteins. This reagent, which is a selenium analog of Ellman's reagent, reacts specifically and quantitatively with thiol groups of proteins to yield a selenenyl sulfide and the dianion of 3-nitro-6-selenobenzoic acid. The molar absorption coefficient of the chromophoric dianion is 10,000 at 432 nm in dilute aqueous solutions. The titration can best be performed at pH 8.20 where >98% of 3-nitro-6-selenobenzoic acid is in the form of the intensely colored dianion. Sulfhydryl content determinations by this reagent of reduced and denatured ribonuclease, reduced and denatured lysozyme, native papain, and native and denatured thymidylate synthetase are compared with those from corresponding 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) titrations. The reagent was found to inactivate thymidylate synthetase, an enzyme with essential sulfhydryl groups. Unlike DTNB which undergoes alkaline decomposition of pH values greater than 9, DSNB was found to be stable to hydrolysis, even in 0.05 m NaOH.     

Design,synthesis and evaluation of novel bivalent β-carboline derivatives as multifunctional agents for the treatment of Alzheimer's disease

To develop potent multi-target ligands against Alzheimer's disease (AD), a series of novel bivalent β-carboline derivatives were designed, synthesized, and evaluated. In vitro studies revealed these compounds exhibited good multifunctional activities. In particular, compounds 8f and 8g showed the good selectivity potency on BuChE inhibition (IC₅₀?=?1.7 and 2.7?μM, respectively), Aβ_1-42 disaggregation and neuroprotection. Compared with the positive control resveratrol, 8f and 8g showed better activity in inhibiting Aβ_1-42 aggregation, with inhibitory rate 82.7% and 85.7% at 25?μM, respectively. Moreover, compounds 8e, 8f and 8g displayed excellent neuroprotective activity by ameliorating the impairment induced by H₂O₂, okadaic acid (OA) and Aβ_1-42 without cytotoxicity in SH-SY5Y cells. Thus, the present study evidently showed that compounds 8f and 8g are potent multi-functional agents against AD and might serve as promising lead candidates for further development.