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Lyme borreliosis (LB) is a multisystemic tick-borne disease that can affect many organs and have various clinical manifestations in dogs. We attempted to summarise various aspects of Lyme disease: i. e., pathogenesis, epidemiology, benefits and risks of diagnostic approaches, treatment options, and prevention in dogs. Several diagnostic bottlenecks for LB in dogs and humans are compared. Because the occurrence of LB in both humans and dogs is closely related, monitoring its prevalence in dogs as sentinel animals is an excellent aid in assessing the risk of Lyme disease in a given geographic area. Although clinical symptoms in humans help clinicians diagnose LB, they are ineffective in dogs because canines rarely exhibit LB symptoms. Despite significant differences in sensitivity and specificity, sero-logical two-step detection of antibodies against Borrelia spp. (ELISA and Western blot) is the most commonly used method in humans and dogs. The limitations of the assay highlight the need for further research to develop new clinical markers and more accurate diagnostic tests. Due to the lack of a specific all-encompassing LB test, a definitive diagnosis of LB remains a difficult and time-consuming process in human and veterinary medicine. Understanding the disease prevalence and diagnostics, as well as preventing its spread with effective and timely treatment, are fundamental principles of good disease management.

The nucleotides are the building blocks of nucleic acids and determining their sequential arrangement had always been an integral part of biological research. Since the past seven decades, researchers from multi-disciplinary fields has been working together to innovate the best sequencing methods. Various methods had been proposed, from some oligonucleotides to the whole genome sequencing, and the growth had gone through adolescence to the mature phase where it is now capable of sequencing the whole genome at a low cost and within a short time frame. DNA sequencing has become a key technology in every discipline of biology and medicine. This review aims to highlight the evolution of DNA sequencing techniques and the machines used, including their principles and key achievements.

Nickel-binding proteins play an important role in the biological processes and can also be utilized in several fields of biotechnology. This study was focused on analysing the nickel-binding proteins from the blood sera of humans (Homo sapiens), cattle (Bos taurus), sheep (Ovis aries), red deer (Cervus elaphus), mouflon (Ovis orientalis), fallow deer (Dama dama), horses (Equus ferus caballus), pigs (Sus scrofa domesticus), wildboars (Sus scrofa), brown bears (Ursus arctos) and pheasants (Phasianus colchicus). The presence of higher abundance proteins in the blood serum, such as albumins, may mask the detection of lower abundance proteins. The samples were depleted from these higher abundance proteins to facilitate the detection of those with lower abundance. For the characterization of these proteins, nickel cations bound to tetradentate ligand nitrilotriacetic acid(Ni-NTA)immobilized on agarose beads were incubated with animal sera to capture nickel-binding proteins and subsequently the proteins were eluted and fractionated on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The results showed a set of nickel-binding proteins with various molecular weights within different animal species. A unique ~42 kDa nickel-binding protein in the brown bear serum, which was not present in any of the other species, was further characterized and identified by matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry (MALDI-TOF/MS). This protein was identified as ahaptoglobin-like protein. This result may provide some valuable clue for the physiological difference in the metal binding proteins in the serum of Ursus arctos and other animals.

The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid barrier presents animmense challenge for effective delivery of therapeutics to the central nervous system. Many potential drugs, which are effective at their site of action, have failed due to the lack of distribution in sufficient quantity to the central nervous system (CNS). In consequence, many diseases of the central nervous system remain undertreated. Antibodies, IgG for example, are difficult to deliver to the CNS due to their size (~155 kDa), physico-chemical properties and the presence of Fc receptor on the blood-brain barrier. Smaller antibodies, like the recently developed nanobodies, may overcome the obstacle of the BBB and enter into the CNS. The nanobodies are the smallest available antigen-binding fragments harbouring the full antigenbinding capacity of conventional antibodies. They represent a new generation of therapeutics with exceptional properties, such as: recognition of unique epitopes, target specificity, high affinity, high solubility, high stability and high expression yields in cost-effective recombinant production. Their ability to permeate across the BBBmakes thema promising alternative for central nervous system disease therapeutics. In this review, we have systematically presented different aspects of the BBB, drug delivery mechanisms employed to cross the BBB, and finally nanobodies — a potential therapeutic molecule against neuroinfections.

Neisseria meningitidis is a Gram-negative diplococcus responsible for bacterial meningitis and fatal sepsis. Ligand-receptor interactions are one of the main steps in the development of neuroinvasion. Porin B (PorB), neisserial outer membrane protein (ligand), binds to host receptors and triggers many cell signalling cascades allowing the meningococcus to damage the host cells or induce immune cells responses via the TLR2-dependent mechanisms. In this paper, we present a brief review of the structure and function of PorB.

Bacterial meningitis is a devastating worldwide disease. Half of the survivors of meningitis remain with permanent neurological sequelae. The pathogenesis of meningitis is based on a complex host-pathogen interaction. Streptococcus pneumoniae is a life-threatening neuroinvasive pathogen that asymptomatically colonizes the upper respiratory tract. Adherence of pneumococci to the host epithelium is a prerequisite in the onset of streptococcal infections; such adherence is favored by the formation of bacterial pili. In this article, we will describe the pneumococcal pili and its contribution to the onset of meningitis.

The penetration of the blood-brain barrier (BBB) and invasion of the central nervous system (CNS) are important steps for all neuroinvasive pathogens. All of the ways of pathogens passing through the BBB are still unclear. Among known pathways, pathogen traversal can occur paracellularly, transcellularly or using a “Trojan horse” mechanism. The first step of translocation across the BBB is the interactions of the pathogen’s ligands with the receptors of the host brain cells. Lyme disease, the most common vector-borne disease in the temperate zones of Europe and North America, are caused by Borreliella species (former Borrelia burgdorferi sensu lato) that affects the peripheral and the CNS. In this review, we have presented various pathogen interactions with endothelial cells, which allow the disruption of the BBB so that the pathogens can pass across the BBB.

Neuroinfections are difficult and time-consuming to treat. The main bottleneck in therapy is drugs’ inability to enter the central nervous system (CNS) via the blood-brain barrier (BBB). Because the diffusion of conventional antibodies in tissues is limited by their large size (150 kDa), it is necessary to find an antibody fragment that can cross the BBB and treat CNS infections. Camelid heavy chain only antibodies, also known as nanobodies, possess a unique Variable domain of a Heavy chain (VHH). The VHH could be used as an alternative to conventional antibodies and have enormous potential in a wide range of medical and bio-technology fields. The VHH with an average molecular weight of 15 kDa can diffuse nearly four times better in tissues and tumours than common antibodies. A VHH is made up of four framework regions (FR1‒4) and three hypervariable complementarity-determining regions (CDR1‒3), with CDR3 being particularly important in interaction with pathogen epitopes. Experimental results have shown that the CDR3 domain alone can bind to epitopes and may contribute to reduce the size of the antigen-recognizing molecule, allowing it to be used more effectively to diffuse much better in tissues, and as well as to cross the BBB and biodistributed in CNS.

The blood-brain barrier (BBB) is a protective barrier that prevents most substances from entering the brain from the bloodstream, including bacteria and viruses. Unfortunately, this restriction also applies to 99.9 % of therapeutics, posing significant challenges in the treatment of brain diseases. Overcoming this barrier is critical for effective treatment of neurological disorders. Several drug delivery systems are being developed to improve transport of therapeutic agent across the BBB. For example, nanoparticles (liposomes, polymeric nanoparticles, dendrimers), nanocarriers (micelles, nanogels), protein-based delivery (penetrating peptides, exosomes), focused ultrasound, and most recently, a filamentous phage based nanocarriers. Filamentous bacteriophages are viruses that infect bacteria and are not designed to infect eukaryotic cells. Recent evidence suggests that filamentous bacteriophages, such as M13, can cross BBB and enter the central nervous system (CNS). Researchers have been investigating the potential use of M13 as drug carriers, including the delivery of therapeutic agents to the brain. This entails modifying the bacteriophages to carry payloads such as drugs and using them as a delivery system. The BBB’s complexity and the potential risks associated with changing it necessitate careful consideration in the development of such strategies. M13 nanocarrier development is ongoing, and advancements may lead to new therapeutic options for treating infections in the CNS. However, it is important to note that this field is still in its infancy, and more research is needed to assess the feasibility and safety of using modified bacteriophages to cross the BBB. This brief review attempts to compile current research on the potential use of bacteriophages for drug transport across the BBB.

Bacterial meningitis is a serious infection of the central nervous system that affects people all over the world. Streptococcus pneumoniae and Neisseria meningitidis are the most common pathogens causing meningeal inflammation in Europe. Treatment with standard antibiotics is becoming ineffective, not only due to their inability to cross the blood-brain barrier, but also due to rising antibiotic resistance. As a result, novel therapeutics to combat the infection are required. A promising solution could be therapeutic nanomolecules, such as dendrimers, some of which have antimicrobial properties due to their chemical structure. Additionally, they may be decorated with a suitable therapeutic and central nervous system homing peptides to construct nano-drug delivery systems, which can effectively cross the blood-brain barrier. To synthesize safe dendrimeric nano-drug delivery system it is necessary to select the best dendrimer candidates with antimicrobial activity and to understand pharmacosafety, pharmacokinetics and dynamics. This review provides a brief overview of dendrimers and their antimicrobial properties as they have been studied in relation to the blood-brain barrier and existing antibiotics.

Saurabh S Thosar,1– 4 Meera C Bhide,1 Isabel Katlaps,1 Nicole P Bowles,1 Steven A Shea,1,4 Andrew W McHill1,2 1Oregon Institute of Occupational Health Sciences; 2School of Nursing; 3Knight Cardiovascular Institute, School of Medicine; 4OHSU-PSU School of Public Health, Oregon Health and Science University, Portland, OR, 97239, USACorrespondence: Saurabh S ThosarOregon Institute of Occupational Health Sciences, 3181 SW Sam Jackson Park Road, L606/RJH1586, Portland, OR, 97239, USATel +1 503 494-2064Fax +1 503 494-4278Email thosar@ohsu.eduPurpose: Sedentary behavior and suboptimal sleep increase risks for chronic diseases. We hypothesized that sedentary behavior and sleep affect each other and that an underlying sleep disorder would alter these relationships. To test these hypotheses, we studied the bidirectional relationships between sedentary behavior and sleep (duration and efficiency) in healthy controls (HC) and people with untreated obstructive sleep apnea (OSA).Patients and Methods: Fifty-two volunteers (18 HC, 19 mild OSA [apnea/hypopnea index [AHI] range 5– 14.9/hour], 15 moderate OSA [AHI range 15– 29.9/hour]) were studied with actigraphy and sleep diaries across ∼ 9 consecutive nights of self-selected consistent ∼ 8-hour sleep episodes at home (range 4– 21/nights per person). We analyzed whether total time asleep and sleep efficiency affected the subsequent daytime sedentary duration while controlling for body mass index and whether the severity of OSA altered this relationship. We also tested the reverse relationship, namely whether daytime sedentary duration affected the subsequent night’s sleep and if any such relationship differed with OSA severity.Results: Overnight sleep duration and efficiency negatively predicted the subsequent day’s sedentary duration in HC (p< 0.02), but not in people with mild or moderate OSA (p> 0.05). There was no significant reverse relationship between daytime sedentary duration and the subsequent night’s sleep duration or efficiency (p≥ 0.2).Conclusion: In healthy adults, short nighttime sleep predicts a longer duration of sedentary behavior on a subsequent day, but we did not observe this relationship in people with OSA. The mechanisms underlying this association in healthy individuals and its disruption in the presence of OSA need to be studied.Keywords: sitting time, sedentary behavior, cardiometabolic risk, sleep quality, chronic diseases, sleep disorders