A discrete geometric approach for simulating the dynamics of thin viscous threads

We present a numerical model for the dynamics of thin viscous threads based on a discrete, Lagrangian formulation of the smooth equations. The model makes use of a condensed set of coordinates, called the centerline/spin representation: the kinematical constraints linking the centerline's tangent to the orientation of the material frame is used to eliminate two out of three degrees of freedom associated with rotations. Based on a description of twist inspired from discrete differential geometry and from variational principles, we build a full-fledged discrete viscous thread model, which includes in particular a discrete representation of the internal viscous stress. Consistency of the discrete model with the classical, smooth equations is established formally in the limit of a vanishing discretization length. The discrete models lends itself naturally to numerical implementation. Our numerical method is validated against reference solutions for steady coiling. The method makes it possible to simulate the unsteady behavior of thin viscous jets in a robust and efficient way, including the combined effects of inertia, stretching, bending, twisting, large rotations and surface tension

A Novel Heterophilic Antibody Interaction Involves IgG4

IgG4 has been implicated in a diverse set of complex pathologies - e.g. autoimmune pancreatitis (AIP), idiopathic membranous nephropathy - and carries unique features including lack of activation of the classical complement pathway and a dynamic Fab-arm exchange. We recently showed that the rheumatoid factor (RF)-like activity of IgG4 is achieved through a hitherto unknown, Fc-Fc (and not Fab-Fc as is the case in classical RF; CRF) interaction; hence the name, novel RF (NRF). Here, we further explore the resemblance/difference between CRF and NRF. As heterophilic interactions of human IgM RF (CRF) are well known, we checked whether this is the case for IgG4. Human IgG4 showed variable reactivity to animal IgGs: reacting intensely with rabbit and mouse IgGs, but weakly with others. The binding to rabbit IgG was not through the Fab (as in CRF) but via the Fc piece, as was recently shown for human IgG (NRF). This binding correlates with the IgG4 concentration per se and could therefore be of diagnostic usage and incidentally explain some observed interferences in biological assays. In conclusion, here is defined a novel heterophilic antibody interaction and is established the universality of the unique Fc-Fc binding, both involving IgG4.ArticleSCANDINAVIAN JOURNAL OF IMMUNOLOGY. 71(2):109-114 (2010)journal articl

Effects of adverse early-life events on aggression and anti-social behaviours in animals and humans

We review the impact of early adversities on the development of violence and antisocial behaviour in humans, and present three aetiological animal models of escalated rodent aggression, each disentangling the consequences of one particular adverse early-life factor. A review of the human data, as well as those obtained with the animal models of repeated maternal separation, post-weaning social isolation and peripubertal stress, clearly shows that adverse developmental conditions strongly affect aggressive behaviour displayed in adulthood, the emotional responses to social challenges and the neuronal mechanisms activated by conflict. Although similarities between models are evident, important differences were also noted, demonstrating that the behavioural, emotional and neuronal consequences of early adversities are to a large extent dependent on aetiological factors. These findings support recent theories on human aggression, which suggest that particular developmental trajectories lead to specific forms of aggressive behaviour and brain dysfunctions. However, dissecting the roles of particular aetiological factors in humans is difficult because these occur in various combinations; in addition, the neuroscientific tools employed in humans still lack the depth of analysis of those used in animal research. We suggest that the analytical approach of the rodent models presented here may be successfully used to complement human findings and to develop integrative models of the complex relationship between early adversity, brain development and aggressive behaviour. © 2014 British Society for Neuroendocrinology

Detection of Borrelia burgdorferi Sensu Lato and Relapsing Fever Borrelia in Feeding Ixodes Ticks and Rodents in Sarawak, Malaysia: New Geographical Records of Borrelia yangtzensis and Borrelia miyamotoi

Members of the Borrelia burgdorferi sensu lato (Bbsl) complex are etiological agents of Lyme disease (LD), and Borrelia miyamotoi is one of the relapsing fever Borrelia (RFB). Despite the serological evidence of LD in Malaysia, there has been no report from Sarawak, Malaysian Borneo. Thus, this study aimed to detect and characterize Borrelia in rodents and Ixodes ticks from primary forests and an oil palm (OP) plantation in Sarawak. Borrelia yangtzensis (a member of the Bbsl complex) was detected in 43.8% (14/32) of Ixodes granulatus; most of the positive ticks were from the OP plantation (13/14). Out of 56 rodents, B. yangtzensis was detected in four Rattus spp. from the OP plantation and B. miyamotoi was detected in one rodent, Sundamys muelleri, from the primary forest. Further, the positive samples of B. yangtzensis were randomly selected for multilocus sequence analysis (MLSA). The MLSA results of successfully amplified tick samples revealed a clustering with the sequences isolated from Japan and China. This study is the first evidence of B. miyamotoi, a known human pathogen in Malaysia, and B. yangtzensis, which is circulating in ticks and rodents in Sarawak, Malaysian Borneo, and presenting a new geographical record of the Borrelia spp

Development of the paternal brain in expectant fathers during early pregnancy

妊娠初期から発達する父親の「親性」脳の活動を確認 --育児に対する父親の脳と心の発達には個人差がある--. 京都大学プレスリリース. 2020-12-02.The human parenting brain network mediates caregiving behaviors. When exposed to the stimuli of their infants, compared with non-parents, both fathers and mothers exhibit distinct patterns of neural activation. As human males, relative to females, do not undergo robust physiological changes during pregnancy, when and how the paternal brain networks begin to form remains unclear. Thus, using functional MRI, we examined brain activation in response to infant-interaction videos in two groups, childless males and first-time expectant fathers during their partners’ early pregnancy before remarkable changes in their partners’ appearances commenced. Multivoxel pattern analysis revealed that expectant fathers’ left anterior insula and inferior frontal gyrus showed incipient changes in response to parenthood during early pregnancy. Furthermore, these changes were associated with several paternal traits, such as a negative image toward parenting. Such external factors might influence the paternal brain's development during early pregnancy

The dynamics of the microbiome in Ixodidae are shaped by tick ontogeny and pathogens in Sarawak, Malaysian Borneo

Tick-borne diseases have recently been considered a potential emerging public health threat in Malaysia; however, fundamental studies into tick-borne pathogens and microbiome appear limited. In this study, six tick species (Ixodes granulatus, Haemaphysalis hystricis, Haemaphysalis shimoga, Dermacentor compactus, Dermacentor steini and Dermacentor atrosignatus) collected from two primary forests and an oil palm plantation in Sarawak, Malaysian Borneo, were used for microbiome analysis targeting bacterial 16S rDNA using next-generation sequencing (NGS). In addition, bacterial species were further characterized in conventional PCRs to identify potential pathogens. Sequences generated from NGS were first filtered with the Decontam package in R before subsequent microbial diversity analyses. Alpha and beta analyses revealed that the genus Dermacentor had the highest microbial diversity, and H. shimoga significantly differed in microbial composition from other tick species. Alpha and beta diversities were also significantly different between developmental stages of H. shimoga. Furthermore, we observed that some bacterial groups were significantly more abundant in certain tick species and developmental stages of H. shimoga. We tested the relative abundances using pairwise linear discriminant analysis effect size (LEfSe), which also revealed significant microbial composition differences between Borrelia -positive and Borrelia -negative I. granulatus ticks. Finally, pathogenic and potentially pathogenic bacteria circulating in different tick species, such as Rickettsia heilongjiangensis , Ehrlichia sp., Anaplasma sp. and Bartonella spp. were characterized by PCR and sequencing. Moreover, Coxiella and Francisella -like potential symbionts were identified from H. shimoga and D. steini, respectively. More studies are required to unravel the factors associated with the variations observed in this study

The preclinical pharmacology of the high affinity anti-IL-6R Nanobody (R) ALX-0061 supports its clinical development in rheumatoid arthritis

Introduction: The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody (R) with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum albumin. We describe here the relevant aspects of its in vitro and in vivo pharmacology. Methods: ALX-0061 is composed of an affinity-matured IL-6R-targeting domain fused to an albumin-binding domain representing a minimized two-domain structure. A panel of different in vitro assays was used to characterize the biological activities of ALX-0061. The pharmacological properties of ALX-0061 were examined in cynomolgus monkeys, using plasma levels of total soluble (s)IL-6R as pharmacodynamic marker. Therapeutic effect was evaluated in a human IL-6-induced acute phase response model in the same species, and in a collagen-induced arthritis (CIA) model in rhesus monkeys, using tocilizumab as positive control. Results: ALX-0061 was designed to confer the desired pharmacological properties. A 200-fold increase of target affinity was obtained through affinity maturation of the parental domain. The high affinity for sIL-6R (0.19 pM) translated to a concentration-dependent and complete neutralization of sIL-6R in vitro. In cynomolgus monkeys, ALX-0061 showed a dose-dependent and complete inhibition of hIL-6-induced inflammatory parameters, including plasma levels of C-reactive protein (CRP), fibrinogen and platelets. An apparent plasma half-life of 6.6 days was observed after a single intravenous administration of 10 mg/kg ALX-0061 in cynomolgus monkeys, similar to the estimated expected half-life of serum albumin. ALX-0061 and tocilizumab demonstrated a marked decrease in serum CRP levels in a non-human primate CIA model. Clinical effect was confirmed in animals with active drug exposure throughout the study duration. Conclusions: ALX-0061 represents a minimized bispecific biotherapeutic of 26 kDa, nearly six times smaller than monoclonal antibodies. High in vitro affinity and potency was demonstrated. Albumin binding as a half-life extension technology resulted in describable and expected pharmacokinetics. Strong IL-6R engagement was shown to translate to in vivo effect in non-human primates, demonstrated via biomarker deregulation as well as clinical effect. Presented results on preclinical pharmacological properties of ALX-0061 are supportive of clinical development in RA