Global spatial risk assessment of sharks under the footprint of fisheries.

Effective ocean management and the conservation of highly migratory species depend on resolving the overlap between animal movements and distributions, and fishing effort. However, this information is lacking at a global scale. Here we show, using a big-data approach that combines satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space-use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively), and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of fishing effort in marine areas beyond national jurisdictions (the high seas). Our results demonstrate an urgent need for conservation and management measures at high-seas hotspots of shark space use, and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real-time, dynamic management.

The effect of temperature on haemoglobin-oxygen binding affinity in regionally endothermic and ectothermic sharks.

Haemoglobin (Hb)-O2 binding affinity typically decreases with increasing temperature, but several species of ectothermic and regionally endothermic fishes exhibit reduced Hb thermal sensitivity. Regionally endothermic sharks, including the common thresher shark (Alopias vulpinus) and lamnid sharks such as the shortfin mako shark (Isurus oxyrinchus), can maintain select tissues and organs warmer than ambient temperature by retaining metabolic heat with vascular heat exchangers. In the ectothermic bigeye thresher shark (Alopias superciliosus), diurnal movements above and below the thermocline subject the tissues, including the blood, to a wide range of operating temperatures. Therefore, blood-O2 transport must occur across internal temperature gradients in regionally endothermic species, and over the range of environmental temperatures encountered by the ectothermic bigeye thresher shark. While previous studies have shown temperature-independent Hb-O2 affinity in lamnid sharks, including shortfin mako, the Hb-O2 affinity of the common and bigeye thresher sharks is unknown. Therefore, we examined the effect of temperature on whole-blood Hb-O2 affinity in common thresher shark and bigeye thresher shark. For comparison, analyses were also conducted on the shortfin mako shark and two ectothermic species, blue shark (Prionace glauca) and spiny dogfish (Squalus acanthias). Blood-O2 binding affinity was temperature independent for common thresher shark and shortfin mako shark, which should prevent internal temperature gradients from negatively affecting blood-O2 transport. Blue shark and spiny dogfish blood-O2 affinity decreased with increasing temperature, as expected, but bigeye thresher shark blood exhibited both a reduced temperature dependence and a high Hb-O2 affinity, which likely prevents large changes in environment temperature and low environmental oxygen from affecting O2 uptake.

Temperature independence of haemoglobin-oxygen affinity in smalleye Pacific opah (Lampris incognitus) and swordfish (Xiphias gladius).

Smalleye Pacific opah and swordfish can conserve metabolic heat and maintain specific body regions warmer than ambient water temperature (i.e. regional heterothermy). Consequently, blood O2 uptake at the gills occurs at the environmental temperature at which the individual is found, but O2 offloading will occur at different temperatures in different tissues. While several regionally heterothermic fishes (e.g. billfishes, tunas and sharks) show a reduced temperature effect on haemoglobin (Hb)-O2 affinity, the temperature dependence of Hb-O2 affinity in opah and swordfish is unknown. We hypothesized that the Hb of opah and swordfish would also show a reduced temperature dependence. Opah whole-blood-O2 affinity exhibited a reverse temperature dependence above 50% Hb-O2 saturation (10-20°C, pH 7.2-8.0), while the temperature dependence of swordfish blood-O2 affinity (10-25°C) was saturation and pH dependent, becoming temperature independent below 50% Hb-O2 saturation and pH 7.4. Experiments on stripped haemolysates showed that adding ATP ([ATP]/[Hb]=30) decreased the temperature sensitivity of Hb-O2 affinity, changing the overall oxygenation enthalpy (ΔH') values of opah (10-20°C) and swordfish (10-25°C) Hbs at pH 7.4 from -15 and -42 kJ mol-1 O2, respectively, to +84 and -9 kJ mol-1 O2. Swordfish blood-O2 affinity was high compared with that of other large, pelagic, marine teleosts, which may be the result of unusually low ATP/Hb levels, but might also enable swordfish to forage in the potentially low-oxygenated water of the upper reaches of the oxygen minimum layer. The existence of Hbs with reduced temperature sensitivity in regionally heterothermic fishes may prevent marked changes in Hb-O2 affinity between the cold and warm tissues.

Multifactorial control of the expression of a CRISPR-Cas system by an extracytoplasmic function σ/anti-σ pair and a global regulatory complex.

Expression of CRISPR-Cas systems is a prerequisite for their defensive role against invading genetic elements. Yet, much remains unknown about how this crucial step is regulated. We describe a new mechanism controlling CRISPR-cas expression, which requires an extracytoplasmic function (ECF) σ factor (DdvS), its membrane-bound anti-σ (DdvA) and a global regulatory complex (CarD-CarG). Transcriptomic analyses revealed that the DdvS/CarD/CarG-dependent regulon comprises a type III-B CRISPR-Cas system in Myxococcus xanthus. We mapped four DdvS-driven CarD/CarG-dependent promoters, with one lying immediately upstream of the cas cluster. Consistent with direct action, DdvS and CarD-CarG localize at these promoters in vivo. The cas genes are transcribed as a polycistronic mRNA that reads through the leader into the CRISPR array, a putative σA-dependent promoter in the leader having negligible activity in vivo. Consequently, expression of the entire CRISPR-Cas system and mature CRISPR-RNA (crRNA) production is DdvS/CarD/CarG-dependent. DdvA likely uses its large C-terminal domain to sense and transduce the extracytoplasmic signal triggering CRISPR-cas expression, which we show is not starvation-induced multicellular development. An ECF-σ/anti-σ pair and a global regulatory complex provide an effective mechanism to coordinate signal-sensing with production of precursor crRNA, its processing Cas6 endoribonuclease and other Cas proteins for mature crRNA biogenesis and interference.

Thermal effects on red muscle contractile performance in deep-diving, large-bodied fishes.

Bigeye thresher sharks (Alopias superciliosus) and swordfish (Xiphias gladius) are large, pelagic fishes, which make long-duration, diurnal foraging dives from warm, surface waters (18-24 °C) to cold waters beneath the thermocline (5-10 °C). In bigeye thresher sharks, the subcutaneous position of the red, aerobic swimming muscles (RM) suggests that RM temperature mirrors ambient during dives (i.e., ectothermy). In swordfish, the RM is closer to the vertebrae and its associated with vascular counter-current heat exchangers that maintain RM temperature above ambient (i.e., RM endothermy). Here, we sought to determine how exposure to a wide range of ambient temperatures (8, 16, 24 °C) impacted peak power output and optimum cycle (i.e., tailbeat) frequency (0.25, 0.5, 1 Hz) in RM isolated from both species. Bigeye thresher shark RM did not produce substantial power at high cycle frequencies, even at high temperatures; but it did produce relatively high power at slow cycle frequencies regardless of temperature. Swordfish RM produced more power when operating at a combination of fast cycle frequencies and higher temperatures. This suggests that swordfish RM benefits considerably more from warming than bigeye thresher shark RM, while the RM of both species was able to produce power at cold temperatures and slow cycle frequencies. Despite different thermal strategies (i.e., ectothermy vs. RM endothermy), the ability of the RM to power sustained swimming during foraging-related search behaviors may contribute to the unique ability of these fishes to successfully exploit food resources in deep, cold water.

Blood pressure in the Greenland shark as estimated from ventral aortic elasticity.

We conducted in vitro inflations of freshly excised ventral aortas of the Greenland shark, Somniosus microcephalus, and used pressure-diameter data to estimate the point of transition from high to low compliance, which has been shown to occur at the mean blood pressure in other vertebrates including fishes. We also determined the pressure at which the modulus of elasticity of the aorta reached 0.4 MPa, as occurs at the compliance transition in other species. From these analyses, we predict the average ventral aortic blood pressure in S. microcephalus to be about 2.3-2.8 kPa, much lower than reported for other sharks. Our results support the idea that this species is slow moving and has a relatively low aerobic metabolism. Histological investigation of the ventral aorta shows that elastic fibres are present in relatively low abundance and loosely connected, consistent with this aorta having high compliance at a relatively low blood pressure.

Temperature effects on the blood oxygen affinity in sharks.

In fish, regional endothermy (i.e., the capacity to significantly elevate tissue temperatures above ambient via vascular heat exchangers) in the red swimming muscles (RM) has evolved only in a few marine groups (e.g., sharks: Lamnidae, Alopiidae, and teleosts Scombridae). Within these taxa, several species have also been shown to share similar physiological adaptations to enhance oxygen delivery to the working tissues. Although the hemoglobin (Hb) of most fish has a decreased affinity for oxygen with an increase in temperature, some regionally endothermic teleosts (e.g., tunas) have evolved Hbs that have a very low or even an increased affinity for oxygen with an increase in temperature. For sharks, however, blood oxygen affinities remain largely unknown. We examined the effects of temperature on the blood oxygen affinity in two pelagic species (the regionally endothermic shortfin mako shark and the ectothermic blue shark) at 15, 20, and 25 °C, and two coastal ectothermic species (the leopard shark and brown smooth-hound shark) at 10, 15, and 20 °C. Relative to the effects of temperature on the blood oxygen affinity of ectothermic sharks (e.g., blue shark), shortfin mako shark blood was less affected by an increase in temperature, a scenario similar to that documented in some of the tunas. In the shortfin mako shark, this may act to prevent premature oxygen dissociation from Hb as the blood is warmed during its passage through vascular heat exchangers. Even though the shortfin mako shark and blue shark occupy a similar niche, the effects of temperature on blood oxygen affinity in the latter more closely resembled that of the blood in the two coastal shark species examined in this study. The only exception was a small, reverse temperature effect (an increase in blood oxygen affinity with temperature) observed during the warming of the leopard shark blood under simulated arterial conditions, a finding that is likely related to the estuarine ecology of this species. Taken together, we found species-specific differences in how temperature affects blood oxygen affinity in sharks, with some similarities between the regionally endothermic sharks and several regionally endothermic teleost fishes.

The CarD/CarG regulatory complex is required for the action of several members of the large set of Myxococcus xanthus extracytoplasmic function σ factors.

Extracytoplasmic function (ECF) σ factors are critical players in signal transduction networks involved in bacterial response to environmental changes. The Myxococcus xanthus genome reveals ∼45 putative ECF-σ factors, but for the overwhelming majority, the specific signals or mechanisms for selective activation and regulation remain unknown. One well-studied ECF-σ, CarQ, binds to its anti-σ, CarR, and is inactive in the dark but drives its own expression from promoter P(QRS) on illumination. This requires the CarD/CarG complex, the integration host factor (IHF) and a specific CarD-binding site upstream of P(QRS). Here, we show that DdvS, a previously uncharacterized ECF-σ, activates its own expression in a CarD/CarG-dependent manner but is inhibited when specifically bound to the N-terminal zinc-binding anti-σ domain of its cognate anti-σ, DdvA. Interestingly, we find that the autoregulatory action of 11 other ECF-σ factors studied here depends totally or partially on CarD/CarG but not IHF. In silico analysis revealed possible CarD-binding sites that may be involved in direct regulation by CarD/CarG of target promoter activity. CarD/CarG-linked ECF-σ regulation likely recurs in other myxobacteria with CarD/CarG orthologous pairs and could underlie, at least in part, the global regulatory effect of the complex on M. xanthus gene expression.

Postprandial abdominal pain and weight loss as the initial presentation of abdominal neuroendocrine tumor recurrence.

Key Clinical Message: Neuroendocrine tumors, rare and slow-growing, primarily affect the gastrointestinal tract, causing symptoms due to hormone secretion or mass effect. This case image described postprandial abdominal pain as an atypical initial presentation of abdominal neuroendocrine tumor recurrence in a middle-aged male. Abstract: Neuroendocrine tumors are a group of rare, slow-growing neoplasms, most commonly affecting the gastrointestinal tract. Clinical presentations include symptoms related to the mass or hypersecretion of hormones, such as flushing, diarrhea, or bronchoconstriction. Postprandial abdominal pain is most commonly related to chronic mesenteric ischemia from atherosclerotic changes but is rarely linked to external mass compression, including gastrointestinal tumors. Hereby, the authors highlight an uncommon presentation of NET, which is very challenging to diagnose and demands a high index of suspicion.

Type B Lactic Acidosis: A Very Rare but Fatal Complication of Gastrointestinal Solid Tumor.

Type B lactic acidosis, secondary to solid cancer, is very rare. It is mostly seen in patients with hematological malignancies. Although its exact pathogenesis is unknown, it is believed to be caused by overproduction and the inability of tumor cells to remove lactate. In the last 26 years, a systematic review of the literature only identified two previous reports of colorectal cancer-related type B lactic acidosis. Here, we report the third case of severe type B lactic acidosis due to stage IV colorectal with liver metastasis. Besides, this case is unique in that serum lactate levels reaching as high as 24 mmol/L were not reported in association with colorectal cancer. In most cases, the prognosis is still very poor because there are no standardized treatment recommendations. Early chemotherapy is still the only intervention that provides some survival benefits.

A Rare Case of an Elderly Male with Progression to Chronic Myeloid Leukaemia Secondary to Chronic Lymphocytic Leukaemia.

Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disorder characterised by an accumulation of monoclonal B lymphocytes, with an increased risk of secondary cancers. The coexistence of CLL and chronic myeloid leukaemia (CML) is a rare phenomenon, with three main types being classified: CML preceding CLL, CLL preceding CML and simultaneous occurrence. The coexistence of these chronic leukaemias poses a complex clinical challenge, with the underlying mechanisms of their association remaining enigmatic. Here, we present a report of an elderly male with a long history of CLL, who was subsequently diagnosed with secondary CML. LEARNING POINTS: The development of chronic myeloid leukaemia (CML) subsequent to chronic lymphocytic leukaemia (CLL) is an uncommon occurrence, challenging conventional expectations of disease evolution in chronic leukaemia.Extensive and appropriate testing is necessary to promptly identify secondary CML in CLL patients.Targeted therapy with dasatinib, a tyrosine kinase inhibitor, may demonstrate efficacy in reducing leukocytosis and BCR-ABL1 levels in patients with coexisting CLL and CML.

Exploring inter-trial coherence for inner speech classification in EEG-based brain-computer interface.

Objective. In recent years, electroencephalogram (EEG)-based brain-computer interfaces (BCIs) applied to inner speech classification have gathered attention for their potential to provide a communication channel for individuals with speech disabilities. However, existing methodologies for this task fall short in achieving acceptable accuracy for real-life implementation. This paper concentrated on exploring the possibility of using inter-trial coherence (ITC) as a feature extraction technique to enhance inner speech classification accuracy in EEG-based BCIs.Approach. To address the objective, this work presents a novel methodology that employs ITC for feature extraction within a complex Morlet time-frequency representation. The study involves a dataset comprising EEG recordings of four different words for ten subjects, with three recording sessions per subject. The extracted features are then classified using k-nearest-neighbors (kNNs) and support vector machine (SVM).Main results. The average classification accuracy achieved using the proposed methodology is 56.08% for kNN and 59.55% for SVM. These results demonstrate comparable or superior performance in comparison to previous works. The exploration of inter-trial phase coherence as a feature extraction technique proves promising for enhancing accuracy in inner speech classification within EEG-based BCIs.Significance. This study contributes to the advancement of EEG-based BCIs for inner speech classification by introducing a feature extraction methodology using ITC. The obtained results, on par or superior to previous works, highlight the potential significance of this approach in improving the accuracy of BCI systems. The exploration of this technique lays the groundwork for further research toward inner speech decoding.

Immunotherapy-induced colitis in metastatic colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer (CRC) presents significant mortality risks, underscoring the urgency of timely diagnosis and intervention. Advanced stages of CRC are managed through chemotherapy, targeted therapy, immunotherapy, radiotherapy, and surgery. Immunotherapy, while effective in bolstering the immune system against cancer cells, often carries toxic side effects, including colitis. This study aimed to evaluate the incidence of colitis in patients with metastatic CRC (mCRC) undergoing various immunotherapy treatments. Through a systematic search of Google Scholar and PubMed databases from inception until November 2023, nine relevant studies were identified. Subgroup analyses revealed a higher incidence of colitis, particularly in patients treated with anti-cytotoxic T-lymphocyte-associated molecule-4 (anti-CTLA-4) and combination therapies compared to monotherapy with programmed cell death receptor-1 (PD-1) or programmed cell death ligand receptor-1 (PDL-1) inhibitors. Notably, naive-treated metastatic CRC patients exhibited elevated colitis incidences compared to those previously treated. In conclusion, anti-CTLA-4 and combination therapies, such as nivolumab plus ipilimumab, were associated with increased colitis occurrences in metastatic CRC patients, highlighting the need for vigilant monitoring and management strategies, especially in immunotherapy-naive individuals.

Predictive Nomogram and Propensity Score Matching in Neuroendocrine Carcinoma of the Tubular Gastrointestinal Tract: A US Population-Based Clinical Outcome Study.

Background: Neuroendocrine carcinomas (NECs) of the tubular gastrointestinal tract (GI-NECs) are rare and associated with worse clinical outcomes. This population-based study aims to highlight key demographics, clinicopathological factors, and survival outcomes in the US population. Methods: Data from 10,387 patients with GI-NECs were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2000 to 2020. Results: Most patients were >40 years old at the time of presentation with a median age of 63 years old, with almost equal ethnic distribution per US population data. The most common primary tumor site was the small intestine (33.6%). The metastatic spread was localized in 34.8%, regional in 27.8%, and distant in 37.3% of cases, and the liver was the most common site of metastasis (19.9%) in known cases of metastases. Most NEC patients underwent surgery, presenting the highest 5-year overall survival of 73.2% with a 95% confidence interval (CI) (95% CI 72.0-74.4%), while chemotherapy alone had the lowest 5-year survival of 8.0% (95% CI 6.4-10.0%). Compared to men, women had a superior 5-year survival rate of 59.0% (95% CI 57.6-60.5%). On multivariate analysis, age > 65 (HR 2.49, 95% CI 2.36-2.54%, p ≤ 0.001), distant metastasis (HR 2.57, 95% CI 2.52-2.62%, p ≤ 0.001), tumor size > 4 mm (HR 1.98, 95%, CI 1.70-2.31%, p ≤ 0.001), esophageal (HR 1.49, 95% CI 0.86-2.58%, p ≤ 0.001), transverse colon (HR 1.95, 95% CI 1.15-3.33%, p ≤ 0.01), descending colon (HR 2.12, 95% CI 1.12, 3.97%, p = 0.02) anorectal sites, and liver or lung metastases were associated with worse survival. Surgical intervention and tumors located in the small intestine or appendix showed a better prognosis. Conclusion: GI-NECs are a group of rare malignancies associated with a poor prognosis. Therefore, epidemiological studies analyzing national databases may be the best alternative to have a more comprehensive understanding of this condition, assess the impact of current practices, and generate prognosis tools.

Implications of Artificial Intelligence Algorithms in the Diagnosis and Treatment of Motor Neuron Diseases-A Review.

Motor neuron diseases (MNDs) are a group of chronic neurological disorders characterized by the progressive failure of the motor system. Currently, these disorders do not have a definitive treatment; therefore, it is of huge importance to propose new and more advanced diagnoses and treatment options for MNDs. Nowadays, artificial intelligence is being applied to solve several real-life problems in different areas, including healthcare. It has shown great potential to accelerate the understanding and management of many health disorders, including neurological ones. Therefore, the main objective of this work is to offer a review of the most important research that has been done on the application of artificial intelligence models for analyzing motor disorders. This review includes a general description of the most commonly used AI algorithms and their usage in MND diagnosis, prognosis, and treatment. Finally, we highlight the main issues that must be overcome to take full advantage of what AI can offer us when dealing with MNDs.

Complete Genome Sequence Assembly and Annotation for Myxococcus xanthus Strains DK1050 and DK101.

Myxococcus xanthus is a social Gram-negative soil bacterium and the best studied member of the order Myxococcales in the class Deltaproteobacteria, which was recently reclassified as the phylum Myxococcota. Here, we report complete genomes, obtained using Illumina and PacBio sequencing, of M. xanthus strains DK1050 and DK101 (GenBank accession numbers CP104804 and CP104803, respectively).

Genome sequences of Mx1, the first Myxococcus phage isolated, and Mx4, a generalized transducing myxophage.

Myxococcus xanthus is the best-studied member of the phylum Myxococcota, but the bacteriophages infecting it and their characterization remain limited. Here, we present complete genomes of Mx1, the first Myxococcus phage isolated, and of an Mx4 derivative widely used for generalized transduction, both unclassified Caudoviricetes with long, contractile tails.

Hematological indicators of stress in longline-captured sharks.

For many shark species, little information exists about the stress response to capture and release in commercial longline fisheries. Recent studies have used hematological profiling to assess the secondary stress response, but little is known about how, and to what degree, these indicators vary interspecifically. Moreover, there is little understanding of the extent to which the level of relative swimming activity (e.g., sluggish vs. active) or the general ecological classification (e.g., coastal vs. pelagic) correlates to the magnitude of the exercise-induced (capture-related) stress response. This study compared plasma electrolytes (Na(+), Cl(-), Mg(2+), Ca(2+), and K(+)), metabolites (glucose and lactate), blood hematocrit, and heat shock protein (Hsp70) levels between 11 species of longline-captured sharks (n=164). Statistical comparison of hematological parameters revealed species-specific differences in response to longline capture, as well as differences by ecological classification. Taken together, the blood properties of longline-captured sharks appear to be useful indicators of interspecific variation in the secondary stress response to capture, and may prove useful in the future for predicting survivorship of longline-captured sharks where new technologies (i.e., pop-up satellite tags) can verify post-release mortality.