Identification of novel TTN gene variant in a patient exhibiting severe dilated cardiomyopathy co-occurring with acute fibrinoid organizing pneumonia.

OBJECTIVES: Dilated cardiomyopathy (DCM) is often hereditary, with 20% to 40% of nonischemic cases showing familial linkage, yet genetic testing is underused. This report describes an unreported pathogenic nonsense variant in the Titin (TTN) gene (NM_001267550.2:c.92603G>A) in a 24-year-old man with severe DCM and acute fibrinoid organizing pneumonia, highlighting a unique cardiopulmonary pathology. METHODS: We conducted detailed gross, histopathologic, immunophenotypic, and exome-based DNA sequencing analysis in the workup of this case. We also included the patient's clinical and radiologic findings in our study. RESULTS: With rapid clinical deterioration and complex comorbidities, including substance abuse and psychiatric conditions, which precluded transplantation, the patient's cardiac function progressively worsened. Autopsy findings included extreme cardiomegaly, biventricular hypertrophy, and acute and chronic pericarditis. Significant pulmonary pathology consistent with acute fibrinoid organizing pneumonia was also noted. Molecular testing confirmed a deleterious maternally inherited TTN variant that was absent in the sibling of the proband and the extant medical literature, highlighting its rarity and significance. CONCLUSIONS: This case contributes to the ongoing body of work on the impact of TTN variants on DCM. It suggests a potential link between genetic variants and complex cardiac injury patterns, emphasizing the need for further investigation into the interplay between cardiomyopathy and pulmonary pathology.

Joint species distribution modeling reveals a changing prey landscape for North Pacific right whales on the Bering shelf.

The eastern North Pacific right whale (NPRW) is the most endangered population of whale and has been observed north of its core feeding ground in recent years with low sea ice extent. Sea ice and water temperature are important drivers for zooplankton dynamics within the whale's core feeding ground in the southeastern Bering Sea, seasonally forming stable fronts along the shelf that give rise to distinct zooplankton communities. A northward shift in NPRW distribution driven by changing distribution of prey resources could put this species at increased risk of entanglement and vessel strikes. We modeled the abundance of NPRW prey, Calanus glacialis, Neocalanus, and Thysanoessa species, using a dynamic biophysical food web model of nine zooplankton guilds in the Bering shelf zooplankton community during a period of warming (2006-2016). This model is unique among prior zooplankton studies from the region in that it includes density dependence, thereby allowing us to ask whether species interactions influence zooplankton dynamics. Modeling confirmed the importance of sea ice and ocean temperature to zooplankton dynamics in the region. Density-independent growth drove community dynamics, while dependent factors were comparatively minimal. Overall, Calanus responded to environment terms, with the strength and direction of response driven by copepodite stage. Neocalanus and Thysanoessa responses were weaker, likely due to their primary occurrence on the outer shelf. We also modeled the steady-state (equilibrium) abundance of Calanus in conditions with and without wind gusts to test whether advection of outer shelf species might disrupt the steady-state dynamics of Calanus abundance; the results did not support disruption. Given the annual fall sampling design, we interpret our results as follows: low-ice-extent winters induced stronger spring winds and weakened fronts on the shelf, thereby advecting some outer shelf species into the study region; increased development rates in these warm conditions influenced the proportion of C. glacialis copepodite stages over the season. Residual correlation suggests missing drivers, possibly predators, and phytoplankton bloom composition. Given the continued loss of sea ice in the region and projected continued warming, our findings suggest that C. glacialis will move northward, and thus, whales may move northward to continue targeting them.

Song production by the North Pacific right whale, Eubalaena japonica.

This paper describes song production by the eastern North Pacific right whale (NPRW, Eubalaena japonica) in the southeastern Bering Sea. Songs were localized in real-time to individuals using sonobuoys. Singers whose sex could be determined were all males. Autonomous recorder data from 17 year-long deployments were analyzed to document and characterize song types. Four distinct song types were documented over eight years (2009-2017) at five distinct locations. Each song type consists of a hierarchical structure of 1-3 different repeating phrases comprised predominantly of gunshot sounds; three of the four songs contained additional sound types (downsweep, moan, and low-frequency pulsive call). Songs were detected annually (July-January); all song types remained consistent over eight years. Two different songs often occurred simultaneously, produced by different individuals; the same song was never detected simultaneously at the same location. The same song type was detected on the same day and time at two distant locations, indicating multiple individuals can produce the same song. These findings provide support that males produce song; it remains unknown if females also sing. NPRW is the first right whale species documented to produce song. Based on current knowledge about song in mysticetes, it is hypothesized that these songs are reproductive displays.

In situ measurements of phytoplankton fluorescence using low cost electronics.

Chlorophyll a fluorometry has long been used as a method to study phytoplankton in the ocean. In situ fluorometry is used frequently in oceanography to provide depth-resolved estimates of phytoplankton biomass. However, the high price of commercially manufactured in situ fluorometers has made them unavailable to some individuals and institutions. Presented here is an investigation into building an in situ fluorometer using low cost electronics. The goal was to construct an easily reproducible in situ fluorometer from simple and widely available electronic components. The simplicity and modest cost of the sensor makes it valuable to students and professionals alike. Open source sharing of architecture and software will allow students to reconstruct and customize the sensor on a small budget. Research applications that require numerous in situ fluorometers or expendable fluorometers can also benefit from this study. The sensor costs US$150.00 and can be constructed with little to no previous experience. The sensor uses a blue LED to excite chlorophyll a and measures fluorescence using a silicon photodiode. The sensor is controlled by an Arduino microcontroller that also serves as a data logger.

Radiated noise from commercial ships in the Gulf of Maine: implications for whale/vessel collisions.

To understand mysticete acoustic-based detection of ships, radiated noise from high-speed craft, cruise ships, catamarans and fishing vessels was recorded June-September 2009. Calibrated acoustic data (<2500 Hz) from a vertical hydrophone array was combined with ship passage information. A cruise ship had the highest broadband source level, while a fishing vessel had the lowest. Ship noise radiated asymmetrically and varied with depth. Bow null-effect acoustic shadow zones were observed for all ship classes and were correlated with ship-length-to-draft-ratios. These shadow zones may reduce ship detection by near-surface mysticetes.

Mutations in a P-type ATPase gene cause axonal degeneration.

Neuronal loss and axonal degeneration are important pathological features of many neurodegenerative diseases. The molecular mechanisms underlying the majority of axonal degeneration conditions remain unknown. To better understand axonal degeneration, we studied a mouse mutant wabbler-lethal (wl). Wabbler-lethal (wl) mutant mice develop progressive ataxia with pronounced neurodegeneration in the central and peripheral nervous system. Previous studies have led to a debate as to whether myelinopathy or axonopathy is the primary cause of neurodegeneration observed in wl mice. Here we provide clear evidence that wabbler-lethal mutants develop an axonopathy, and that this axonopathy is modulated by Wld(s) and Bax mutations. In addition, we have identified the gene harboring the disease-causing mutations as Atp8a2. We studied three wl alleles and found that all result from mutations in the Atp8a2 gene. Our analysis shows that ATP8A2 possesses phosphatidylserine translocase activity and is involved in localization of phosphatidylserine to the inner leaflet of the plasma membrane. Atp8a2 is widely expressed in the brain, spinal cord, and retina. We assessed two of the mutant alleles of Atp8a2 and found they are both nonfunctional for the phosphatidylserine translocase activity. Thus, our data demonstrate for the first time that mutation of a mammalian phosphatidylserine translocase causes axon degeneration and neurodegenerative disease.