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1.
Front Pharmacol ; 15: 1387057, 2024.
Article in English | MEDLINE | ID: mdl-38818381

ABSTRACT

The photobiological damage that certain drugs or their metabolites can photosensitize in proteins is generally associated with the nature of the excited species that are generated upon interaction with UVA light. In this regard, the photoinduced damage of the anticancer drug gefitinib (GFT) and its two main photoactive metabolites GFT-M1 and GFT-M2 in cellular milieu was recently investigated. With this background, the photophysical properties of both the drug and its metabolites have now been studied in the presence of the two main transport proteins of human plasma, i.e., serum albumin (HSA) and α1-acid glycoprotein (HAG) upon UVA light excitation. In general, the observed photobehavior was strongly affected by the confined environment provided by the protein. Thus, GFT-M1 (which exhibits the highest phototoxicity) showed the highest fluorescence yield arising from long-lived HSA-bound phenolate-like excited species. Conversely, locally excited (LE) states were formed within HAG, resulting in lower fluorescence yields. The reserve was true for GFT-M2, which despite being also a phenol, led mainly to formation of LE states within HSA, and phenolate-like species (with a minor contribution of LE) inside HAG. Finally, the parent drug GFT, which is known to form LE states within HSA, exhibited a parallel behavior in the two proteins. In addition, determination of the association constants by both absorption and emission spectroscopy revealed that the two metabolites bind stronger to HSA than the parent drug, whereas smaller differences were observed for HAG. This was further confirmed by studying the competing interactions between GFT or its metabolites with the two proteins using fluorescence measurements. These above experimental findings were satisfactorily correlated with the results obtained by means of molecular dynamics (MD) simulations, which revealed the high affinity binding sites, the strength of interactions and the involved amino acid residues. In general, the differences observed in the photobehavior of the drug and its two photoactive metabolites in protein media are consistent with their relative photosensitizing potentials.

2.
Phys Chem Chem Phys ; 26(17): 13489-13496, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38651219

ABSTRACT

The photoinduced cycloreversion of oxetane derivatives is of considerable biological interest since these compounds are involved in the photochemical formation and repair of the highly mutagenic pyrimidine (6-4) pyrimidone DNA photoproducts ((6-4)PPs). Previous reports have dealt with the photoreactivity of heterodimeric oxetanes composed mainly of benzophenone (BP) and thymine (Thy) or uracil (Ura) derivatives. However, these models are far from the non-isolable Thy〈ºã€‰Thy dimers, which are the real precursors of (6-4)PPs. Thus, we have synthesized two chemically stable homodimeric oxetanes through the Paternò-Büchi reaction between two identical enone units, i.e. 1,4-benzoquinone (BQ) and 1,4-naphthoquinone (NQ), that led to formation of BQ-Ox and NQ-Ox, respectively. Their photoreactivity has been studied by means of steady-state photolysis and transient absorption spectroscopy from the femtosecond to the microsecond time scale. Thus, photolysis of BQ-Ox and NQ-Ox led to formation of the monomeric BQ or NQ, respectively, through ring opening in a "non-adiabatic" process. Accordingly, the transient absorption spectra of the triplet excited quinones (3BQ* and 3NQ*) were not observed as a result of direct photolysis of the quinone-derived oxetanes. In the case of NQ-Ox, a minor signal corresponding to 3NQ* was detected; its formation was ascribed to minor photodegradation of the oxetane during acquisitions of the spectra during the laser experiments. These results are supported by computational analyses based on density functional theory and multiconfigurational quantum chemistry (CASSCF/CASPT2); here, an accessible conical intersection between the ground and excited singlet states has been characterized as the main structure leading to deactivation of excited BQ-Ox or NQ-Ox. This behavior contrasts with those previously observed for heterodimeric thymine-derived oxetanes, where a certain degree of ring opening into the excited triplet state is observed.

3.
Emerg Microbes Infect ; 13(1): 2343911, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38618930

ABSTRACT

Malaria remains one of the most important infectious diseases globally due to its high incidence and mortality rates. The influx of infected cases from endemic to non-endemic malaria regions like Europe has resulted in a public health concern over sporadic local outbreaks. This is facilitated by the continued presence of competent Anopheles vectors in non-endemic countries.We modelled the potential distribution of the main malaria vector across Spain using the ensemble of eight modelling techniques based on environmental parameters and the Anopheles maculipennis s.l. presence/absence data collected from 2000 to 2020. We then combined this map with the number of imported malaria cases in each municipality to detect the geographic hot spots with a higher risk of local malaria transmission.The malaria vector occurred preferentially in irrigated lands characterized by warm climate conditions and moderate annual precipitation. Some areas surrounding irrigated lands in northern Spain (e.g. Zaragoza, Logroño), mainland areas (e.g. Madrid, Toledo) and in the South (e.g. Huelva), presented a significant likelihood of A. maculipennis s.l. occurrence, with a large overlap with the presence of imported cases of malaria.While the risk of malaria re-emergence in Spain is low, it is not evenly distributed throughout the country. The four recorded local cases of mosquito-borne transmission occurred in areas with a high overlap of imported cases and mosquito presence. Integrating mosquito distribution with human incidence cases provides an effective tool for the quantification of large-scale geographic variation in transmission risk and pinpointing priority areas for targeted surveillance and prevention.


Subject(s)
Anopheles , Malaria , Mosquito Vectors , Anopheles/parasitology , Animals , Malaria/epidemiology , Malaria/transmission , Spain/epidemiology , Humans , Mosquito Vectors/parasitology , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/transmission , Incidence
4.
Arch Ital Urol Androl ; 96(1): 12214, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38572722

ABSTRACT

INTRODUCTION AND OBJECTIVES: Artificial urinary sphincter (AUS) is a treatment option for women with stress urinary incontinence (SUI) after failure of previous surgery or as a primary procedure in severe intrinsic sphincter deficiency (ISD). The aim of the study was to assess the long-term efficacy and risk factors for surgical revision and definitive explantation of AUS laparoscopic implantation in female patients. METHODS: A retrospective review of all women submitted to AUS implantation between April 2005 and March 2023 was conducted. The AUS was implanted via transperitoneal laparoscopic approach, by two experienced surgeons. The primary endpoint was postoperative continence. Continence was defined as no leakage and no pad usage or leakage and/or pad usage with no impact on social life and failure as leakage and/or pad usage impacting social life. As secondary outcomes, clinical predictive factors for AUS revision and definitive explantation were evaluated. RESULTS: In the last 18 years, females with a mean age of 68±12 years-old were submitted to laparoscopic implantation of AUS. Early overall complication rate was 16%, but only one case was Clavien-Dindo ≥3. After a median follow-up of 67 months, 22.2% of the patients needed a device revision, the majority due to mechanical device dysfunction. AUS definitive explantation was performed in 16%, mainly due to urethral/vaginal erosion (9.9%) and infection (6.2%). Patients with age ≥70 years and follow-up ≥10 years significantly predisposed for device revision. At the time of the last follow-up, 72% of the patients were keeping the urinary continency. CONCLUSIONS: Laparoscopic AUS implantation in females is an effective treatment for SUI due to ISD. Meanwhile, adequate patient selection, multidisciplinary evaluation and careful expectation management are essential to achieving good results, concerning their significant complication rate.


Subject(s)
Laparoscopy , Urethral Diseases , Urinary Incontinence, Stress , Urinary Sphincter, Artificial , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Urinary Sphincter, Artificial/adverse effects , Treatment Outcome , Urinary Incontinence, Stress/surgery , Urinary Incontinence, Stress/etiology , Laparoscopy/adverse effects , Urethra/surgery , Urethral Diseases/surgery , Prosthesis Implantation/methods , Retrospective Studies
5.
Euro Surveill ; 29(14)2024 Apr.
Article in English | MEDLINE | ID: mdl-38577804

ABSTRACT

In February 2023, German public health authorities reported two dengue cases (one confirmed, one probable) and four possible cases who travelled to Ibiza, Spain, in late summer/autumn 2022; the infection was probably acquired through mosquito bites. Case 1 visited Ibiza over 1 week in late August with two familial companions; all three developed symptoms the day after returning home. Only Case 1 was tested; dengue virus (DENV) infection was confirmed by presence of NS1 antigen and IgM antibodies. Case 2 travelled to Ibiza with two familial companions for 1 week in early October, and stayed in the same town as Case 1. Case 2 showed symptoms on the day of return, and the familial companions 1 day before and 3 days after return; Case 2 tested positive for DENV IgM. The most probable source case had symptom onset in mid-August, and travelled to a dengue-endemic country prior to a stay in the same municipality of Ibiza for 20 days, until the end of August. Dengue diagnosis was probable based on positive DENV IgM. Aedes albopictus, a competent vector for dengue, has been present in Ibiza since 2014. This is the first report of a local dengue transmission event on Ibiza.


Subject(s)
Aedes , Dengue Virus , Dengue , Animals , Humans , Dengue/diagnosis , Dengue/epidemiology , Dengue Virus/genetics , Spain/epidemiology , Mosquito Vectors , Disease Outbreaks , Immunoglobulin M
6.
Blood Adv ; 8(11): 2861-2869, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38598745

ABSTRACT

ABSTRACT: The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma without del(17p) were compared using an unanchored matching-adjusted indirect comparison. Individual patient-level data from ELEVATE-TN (acalabrutinib plus obinutuzumab, n = 162; acalabrutinib monotherapy, n = 163) were weighted to match published aggregate baseline data from SEQUOIA cohort 1, which excluded patients with del(17p) (zanubrutinib, n = 241), using variables that were prognostic/predictive of investigator-assessed progression-free survival (INV-PFS) in an exploratory Cox regression analysis of ELEVATE-TN. After matching, INV-PFS was longer with acalabrutinib plus obinutuzumab (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.74) and comparable with acalabrutinib monotherapy (HR, 0.91; 95% CI, 0.53-1.56) vs zanubrutinib. Acalabrutinib monotherapy had significantly lower odds of any grade hypertension vs zanubrutinib (odds ratio [OR], 0.44; 95% CI, 0.20-0.99), whereas acalabrutinib plus obinutuzumab had significantly higher odds of neutropenia (OR, 2.19; 95% CI, 1.33-3.60) and arthralgia (OR, 2.33; 95% CI, 1.37-3.96) vs zanubrutinib. No other significant differences in safety were observed. In summary, acalabrutinib plus obinutuzumab had longer INV-PFS with increased odds of neutropenia and arthralgia than zanubrutinib, whereas acalabrutinib monotherapy had similar INV-PFS with lower odds of any grade hypertension. These trials were registered at www.ClinicalTrials.gov as #NCT02475681 and #NCT03336333.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Benzamides , Leukemia, Lymphocytic, Chronic, B-Cell , Pyrazines , Pyrazoles , Pyrimidines , Humans , Benzamides/therapeutic use , Benzamides/administration & dosage , Benzamides/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Pyrazines/administration & dosage , Pyrazines/therapeutic use , Pyrazines/adverse effects , Female , Male , Aged , Pyrimidines/therapeutic use , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Middle Aged , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aged, 80 and over , Treatment Outcome , Piperidines
7.
Int J Clin Oncol ; 29(6): 780-789, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38528295

ABSTRACT

PURPOSE: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US). METHODS: HER2 + mBC patients initiating 2L treatment (index date) between January 2014 and February 2021 were identified from the Syapse Learning Health Network (LHN) database. Summary statistics for patient characteristics, treatment received, reasons for 2L discontinuation and time to 2L-clinical outcomes are reported. RESULTS: Of the 312 patients initiating 2L treatment, had a median age of 59 years (interquartile range [IQR], 50-66) at the start of 2L. The majority were white (69%) and had de novo mBC (62%). Top three 2L regimens included T-DM1 ± endocrine therapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Around 88% discontinued 2L and 63% received subsequent treatment. Median time-to-next-treatment was 10.6 months (95% CI, 8.8-13.3) and real-world progression-free-survival was 7.9 months (95% CI, 7.0-9.9). Among 274 patients who discontinued 2L, 47% discontinued due to progression and 17% because of intolerance/toxicity, respectively. CONCLUSION: This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression.


Subject(s)
Ado-Trastuzumab Emtansine , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Receptor, ErbB-2 , Trastuzumab , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Middle Aged , Aged , United States , Trastuzumab/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ado-Trastuzumab Emtansine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Retrospective Studies , Neoplasm Metastasis , Progression-Free Survival , Treatment Outcome , Camptothecin/analogs & derivatives , Immunoconjugates
8.
Biotechnol Bioeng ; 121(6): 1961-1972, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38555480

ABSTRACT

Oxygen is essential for tissue regeneration, playing a crucial role in several processes, including cell metabolism and immune response. Therefore, the delivery of oxygen to wounds is an active field of research, and recent studies have highlighted the potential use of photosynthetic biomaterials as alternative oxygenation approach. However, while plants have traditionally been used to enhance tissue regeneration, their potential to produce and deliver local oxygen to wounds has not yet been explored. Hence, in this work we studied the oxygen-releasing capacity of Marchantia polymorpha explants, showing their capacity to release oxygen under different illumination settings and temperatures. Moreover, co-culture experiments revealed that the presence of these explants had no adverse effects on the viability and morphology of fibroblasts in vitro, nor on the viability of zebrafish larvae in vivo. Furthermore, oxygraphy assays demonstrate that these explants could fulfill the oxygen metabolic requirements of zebrafish larvae and freshly isolated skin biopsies ex vivo. Finally, the biocompatibility of explants was confirmed through a human skin irritation test conducted in healthy volunteers following the ISO-10993-10-2010. This proof-of-concept study provides valuable scientific insights, proposing the potential use of freshly isolated plants as biocompatible low-cost oxygen delivery systems for wound healing and tissue regeneration.


Subject(s)
Bandages , Oxygen , Photosynthesis , Zebrafish , Animals , Oxygen/metabolism , Proof of Concept Study , Humans , Wound Healing/drug effects , Skin/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism
9.
Res Vet Sci ; 171: 105206, 2024 May.
Article in English | MEDLINE | ID: mdl-38493661

ABSTRACT

Adult brachycera biting flies can significantly impact livestock through both direct effects (reduction of food intake, disturbance, painful bites, and blood loss) and indirect effects (pathogen transmission), leading to substantial economic losses and production damage. This study aimed to assess the presence of blood-sucking flies in six mixed-animal farm environments on the island of Mallorca (Balearic Islands, Spain) by employing multiple trapping methods. Additionally, distribution maps of brachycera biting fly species recorded in Spain were created, based on data extracted thorough review of scientific literature and citizen digital databases. Investigation of several pathogens, including equine infectious anemia virus (EIAV), Anaplasmataceae bacteria, and piroplasm protozoa, was carried out using different PCR targets (18S rRNA, 16S rRNA, groESL, and tat genes). Citizen science databases and literature review corroborated the consistent distribution trend for two Stomoxyinae species, underscoring the importance of citizen collaboration as a complement to traditional entomological surveillance. Our study confirmed the presence of two biting Stomoxyinae species: the prevalent stable fly Stomoxys calcitrans across all sampled farms, and the horn fly Haematobia irritans, which turned out to be less abundant. DNA barcoding techniques validated the identification of the two species. Neither EIAV nor bacterial/protozoan pathogens were detected using the selected PCR targets in either fly species. However, Wolbachia pipientis (clustered in the supergroup A together with the only sequence of W. pipientis from the USA) was identified through PCR targeting 16S rRNA, groESL and wsp genes in all pools of H. irritans (n = 13) collected from two of the examined farms. This study represents the first attempt to investigate pathogens in Stomoxyinae biting flies in Spain. The discovery of the endosymbiotic Wolbachia organism in H. irritans represents the first record in Spain and the second from Europe. This finding holds significant implications for future research on the applications of this bacterium in biocontrol programs.


Subject(s)
Muscidae , Wolbachia , Animals , Wolbachia/genetics , Spain , RNA, Ribosomal, 16S/genetics , Muscidae/genetics , Muscidae/microbiology , Muscidae/parasitology , Bacteria/genetics
10.
Neurol Sci ; 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38472552

ABSTRACT

Neurolymphomatosis (NL) describes an infiltration of cranial and peripheral nerves by lymphoma cells, most frequently in non-Hodgkin B-cell lymphoma. This clinical entity is rare and poses a challenging diagnosis. We describe a case of a 64-year-old female patient with NL associated with extra-nodal NK/T-cell lymphoma (ENKTL), nasal type, presenting as a painful progressive mononeuropathy multiplex with an oral cavity lesion. ENKTL is usually associated with Epstein-Barr virus (EBV) infection and rarely affects the central and peripheral nervous system. Lumbar puncture, magnetic resonance imaging (MRI), nerve biopsy, and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) help to establish the diagnosis. Thereby, NL should be considered in the differential diagnosis of painful progressive multiple neuropathies, even in patients without previous history of cancer.

11.
Nat Nanotechnol ; 19(4): 514-523, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38212522

ABSTRACT

One of the critical factors determining the performance of neural interfaces is the electrode material used to establish electrical communication with the neural tissue, which needs to meet strict electrical, electrochemical, mechanical, biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin-film technology and its engineering to form flexible neural interfaces. The developed technology allows the fabrication of small microelectrodes (25 µm diameter) while achieving low impedance (∼25 kΩ) and high charge injection (3-5 mC cm-2). In vivo brain recording performance assessed in rodents reveals high-fidelity recordings (signal-to-noise ratio >10 dB for local field potentials), while stimulation performance assessed with an intrafascicular implant demonstrates low current thresholds (<100 µA) and high selectivity (>0.8) for activating subsets of axons within the rat sciatic nerve innervating tibialis anterior and plantar interosseous muscles. Furthermore, the tissue biocompatibility of the devices was validated by chronic epicortical (12 week) and intraneural (8 week) implantation. This work describes a graphene-based thin-film microelectrode technology and demonstrates its potential for high-precision and high-resolution neural interfacing.


Subject(s)
Graphite , Nanopores , Rats , Animals , Microelectrodes , Prostheses and Implants , Electric Stimulation
12.
Vaccine ; 42(7): 1826-1830, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-37271702

ABSTRACT

Vast quantities of open-source data from news reports, social media and other sources can be harnessed using artificial intelligence and machine learning, and utilised to generate valid early warning signals of emerging epidemics. Early warning signals from open-source data are not a replacement for traditional, validated disease surveillance, but provide a trigger for earlier investigation and diagnostics. This may yield earlier pathogen characterisation and genomic data, which can enable earlier vaccine development or deployment of vaccines. Early warning also provides a more feasible prospect of stamping out epidemics before they spread. There are several of such systems currently, but they are not used widely in public health practice, and only some are publicly available. Routine and widespread use of open-source intelligence, as well as training and capacity building in digital surveillance, will improve pandemic preparedness and early response capability.


Subject(s)
Communicable Diseases, Emerging , Epidemics , Humans , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Artificial Intelligence , Population Surveillance/methods , Machine Learning
13.
Front Neural Circuits ; 17: 1253609, 2023.
Article in English | MEDLINE | ID: mdl-37941893

ABSTRACT

While external stimulation can reliably trigger neuronal activity, cerebral processes can operate independently from the environment. In this study, we conceptualize autogenous cerebral processes (ACPs) as intrinsic operations of the brain that exist on multiple scales and can influence or shape stimulus responses, behavior, homeostasis, and the physiological state of an organism. We further propose that the field should consider exploring to what extent perception, arousal, behavior, or movement, as well as other cognitive functions previously investigated mainly regarding their stimulus-response dynamics, are ACP-driven.


Subject(s)
Brain , Head , Brain/physiology , Cognition , Arousal/physiology , Movement/physiology
14.
Front Plant Sci ; 14: 1241576, 2023.
Article in English | MEDLINE | ID: mdl-37881610

ABSTRACT

Introduction: Intelligent monitoring systems must be put in place to practice precision agriculture. In this context, computer vision and artificial intelligence techniques can be applied to monitor and prevent pests, such as that of the olive fly. These techniques are a tool to discover patterns and abnormalities in the data, which helps the early detection of pests and the prompt administration of corrective measures. However, there are significant challenges due to the lack of data to apply state of the art Deep Learning techniques. Methods: This article examines the detection and classification of the olive fly using the Random Forest and Support Vector Machine algorithms, as well as their application in an electronic trap version based on a Raspberry Pi B+ board. Results: The combination of the two methods is suggested to increase the accuracy of the classification results while working with a small training data set. Combining both techniques for olive fly detection yields an accuracy of 89.1%, which increases to 94.5% for SVM and 91.9% for RF when comparing all fly species to other insects. Discussion: This research results reports a successful implementation of ML in an electronic trap system for olive fly detection, providing valuable insights and benefits. The opportunities of using small IoT devices for image classification opens new possibilities, emphasizing the significance of ML in optimizing resource usage and enhancing privacy protection. As the system grows by increasing the number of electronic traps, more data will be available. Therefore, it holds the potential to further enhance accuracy by learning from multiple trap systems, making it a promising tool for effective and sustainable fly population management.

15.
Opt Lett ; 48(20): 5431-5434, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37831885

ABSTRACT

We propose a single-shot, high-repetition rate measurement scheme of the carrier-envelope phase offset of ultrashort laser pulses. The spectral fringes resulting from f-2f nonlinear interferometry, encoding the carrier-envelope-phase, are evaluated completely optically via an optical Fourier transform. For demonstration, the carrier-envelope-phase of a 200 kHz, few-cycle optical parametric chirped-pulse amplification (OPCPA) laser system was measured employing an interferometer as a periodic optical filter. The proposed method shows excellent agreement with simultaneous measurement of the spectral fringes by a fast line-scan camera.

17.
JDS Commun ; 4(5): 406-411, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37727238

ABSTRACT

Two experiments were designed to evaluate the effects of altering body condition score (BCS) and the profile of a fatty acid (FA) supplement on the metabolism of Bos indicus Nellore females. In experiment 1, 16 and 24 B. indicus heifers and nonlactating cows, respectively, were assigned to (1) maintenance diet (MNT-MNT; n = 10), (2) maintenance diet and BCS loss (MNT-LSS; n = 10), (3) maintenance diet supplemented with calcium salts of soybean oil for 30 d and BCS loss for 40 d (MNT+CFA-LSS; n = 10), and (4) maintenance diet for 30 d and BCS loss for 40 d with a diet containing calcium salts of soybean oil (MNT-LSS+CFA; n = 10). Following the BCS loss period, MNT-LSS, MNT+CFA-LSS, and MNT-LSS+CFA were fed a diet to promote the gain of BCS. In experiment 2, 40 Bos indicus nulliparous heifers were assigned to (1) maintenance diet (MNT-MNT; n = 10), (2) BCS loss followed by a BCS gain (LSS-REM; n = 10), (3) BCS loss followed by a BCS gain diet with CFA of palm oil (LSS-REM+PLM; n = 10), and (4) BCS loss followed by a BCS gain diet with CFA of soybean oil (LSS-REM+SOY; n = 10). Blood samples were obtained for serum haptoglobin and fecal samples for pH (experiment 2 only). In experiment 1, a treatment × day interaction was observed for BCS during the 60-d BCS loss and gain period. Animals assigned to MNT-MNT had a greater BCS than the other treatment groups on d 40 and 60 of the experiment, but no other differences were observed. Moreover, a treatment × day interaction was observed for serum haptoglobin, as on d 60, MNT-LSS had a greater mean serum haptoglobin concentration. In experiment 2, a treatment × day interaction was also observed for BCS. From d -4 to 0, LSS-REM and LSS-REM+SOY had a reduced BCS versus MNT-MNT, but also lower for LSS-REM versus MNT-MNT on d 1, and LSS-REM+PLM versus MNT-MNT on d -1 and 0. For serum haptoglobin, no treatment or treatment × day interaction was observed. A treatment × day interaction was observed for fecal pH. From d -10 to 0, MNT often had a lower fecal pH, but during realimentation, LSS-REM heifers had a reduced fecal pH on d 1, 4, and 10. In summary, we failed to demonstrate an increase in serum haptoglobin due to a BCS loss. Still, supplementation with calcium salts of FA alleviated the increase in haptoglobin and maintained fecal pH at more stable values during realimentation, regardless of the FA profile of the supplement.

18.
J Org Chem ; 88(14): 10111-10121, 2023 07 21.
Article in English | MEDLINE | ID: mdl-37437138

ABSTRACT

The quest for simple systems achieving the photoreductive splitting of four-membered ring compounds is a matter of interest not only in organic chemistry but also in biochemistry to mimic the activity of DNA photorepair enzymes. In this context, 8-oxoguanine, the main oxidatively generated lesion of guanine, has been shown to act as an intrinsic photoreductant by transferring an electron to bipyrimidine lesions and provoking their cycloreversion. But, in spite of appropriate photoredox properties, the capacity of guanine to repair cyclobutane pyrimidine dimer is not clearly established. Here, dyads containing the cyclobutane thymine dimer and guanine or 8-oxoguanine are synthesized, and their photoreactivities are compared. In both cases, the splitting of the ring takes place, leading to the formation of thymine, with a quantum yield 3.5 times lower than that for the guanine derivative. This result is in agreement with the more favored thermodynamics determined for the oxidized lesion. In addition, quantum chemistry calculations and molecular dynamics simulations are carried out to rationalize the crucial aspects of the overall cyclobutane thymine dimer photoreductive repair triggered by the nucleobase and its main lesion.


Subject(s)
Cyclobutanes , Pyrimidine Dimers , Pyrimidine Dimers/chemistry , Thymine/chemistry , DNA/chemistry , Guanine
19.
Med Vet Entomol ; 37(4): 871-877, 2023 12.
Article in English | MEDLINE | ID: mdl-37458405

ABSTRACT

Culicoides biting midges (Diptera: Ceratopogonidae) are vectors of pathogens that affect wildlife and livestock. Understanding the composition and distribution of vector species is crucial for implementing control strategies and preventing the spread of infectious diseases. This study provides a morphological and molecular characterisation of Culicoides caucoliberensis, which represents the first record for Spain, increasing the number of Culicoides species in the country to 85. A total of 213 specimens were collected using Onderstepoort-ultraviolet down-draught light traps on a rocky coastline in the Balearic Islands during two sampling periods in 2022. Phylogenetic analysis showed that C. caucoliberensis forms a monophyletic cluster within the Maritimus group. Host preferences were determined for the first time and showed propensity to feed on the European shag (Phalacrocorax aristotelis). The vector role of C. caucoliberensis for haemosporidian transmission remains unclear since molecular detection of Haemosporidians (Haemoproteus and Plasmodium) was negative for all the pools of parous and engorged females analysed. This study emphasises the importance of conducting entomofauna studies in lesser-known Mediterranean islet landscapes and highlights the need for research on vectors within the One Health framework.


Subject(s)
Ceratopogonidae , Haemosporida , Parasites , Female , Animals , Phylogeny , Spain , Insect Vectors/parasitology , Birds/parasitology , Feeding Behavior
20.
PLoS Biol ; 21(7): e3002168, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37410722

ABSTRACT

We know little about mammalian anemotaxis or wind sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how whiskers sense airflow, we first tracked whisker tips in anesthetized rats under low (0.5 m/s) and high (1.5 m/s) airflow. Whisker tips showed increasing movement from low to high airflow conditions, with all whisker tips moving during high airflow. Low airflow conditions-most similar to naturally occurring wind stimuli-engaged whisker tips differentially. Most whiskers moved little, but the long supra-orbital (lSO) whisker showed maximal displacement, followed by the α, ß, and A1 whiskers. The lSO whisker differs from other whiskers in its exposed dorsal position, upward bending, length and thin diameter. Ex vivo extracted lSO whiskers also showed exceptional airflow displacement, suggesting whisker-intrinsic biomechanics mediate the unique airflow-sensitivity. Micro computed tomography (micro-CT) revealed that the ring-wulst-the follicle structure receiving the most sensitive afferents-was more complete/closed in the lSO, and other wind-sensitive whiskers, than in non-wind-sensitive whiskers, suggesting specialization of the supra-orbital for omni-directional sensing. We localized and targeted the cortical supra-orbital whisker representation in simultaneous Neuropixels recordings with D/E-row whisker barrels. Responses to wind-stimuli were stronger in the supra-orbital whisker representation than in D/E-row barrel cortex. We assessed the behavioral significance of whiskers in an airflow-sensing paradigm. We observed that rats spontaneously turn towards airflow stimuli in complete darkness. Selective trimming of wind-responsive whiskers diminished airflow turning responses more than trimming of non-wind-responsive whiskers. Lidocaine injections targeted to supra-orbital whisker follicles also diminished airflow turning responses compared to control injections. We conclude that supra-orbital whiskers act as wind antennae.


Subject(s)
Somatosensory Cortex , Vibrissae , Rats , Animals , Vibrissae/physiology , X-Ray Microtomography , Somatosensory Cortex/physiology , Physical Stimulation , Movement/physiology , Mammals
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